Yang Y

References (246)

Title : Complete decomposition of poly(ethylene terephthalate) by crude PET hydrolytic enzyme produced in Pichia pastoris - Chen_2024_Chem.Eng.J_481_148418
Author(s) : Chen CC , Li X , Min J , Zeng Z , Ning Z , He H , Long X , Niu D , Peng R , Liu X , Yang Y , Huang JW , Guo RT
Ref : Chemical Engineering Journal , 481 :148418 , 2024
Abstract : Using enzymes to decompose poly(ethylene terephthalate) (PET) is an attractive strategy to the sustainable utilization of PET, and an effective production platform of PET degrading enzyme is a prerequisite to achieve this goal. Here, we exploited the industrial yeast strain Pichia pastoris to produce a potent PET hydrolase termed FAST-PETase, whose performance was further elevated by removing two N-linked glycosylations through molecular engineering. The expression of the yielded variant, FAST-PETase-212/277, was elevated by antibiotics selection and chaperon co-expression to exceed 3 g/L in a 30-L fermenter. Notably, the crude fermentation product can be directly applied to decompose PET without purification. More than 95 % postconsumer PET can be achieved by 0.5 mgenzyme gPET-1 in 24 h in a 10-L reaction system in a reactor. These results demonstrate the economic viability of producing PET hydrolytic enzyme with modern fermentation facilities for large scale PET decomposition.
ESTHER : Chen_2024_Chem.Eng.J_481_148418
PubMedSearch : Chen_2024_Chem.Eng.J_481_148418
Gene_locus related to this paper: idesa-peth

Title : Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3\/8 activity - Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
Author(s) : Chen YQ , Yang Y , Zhen EY , Beyer TP , Li H , Wen Y , Ehsani M , Jackson N , Xie K , Jung H , Scheithauer JL , Kumari A , Birrane G , Russell AM , Balasubramaniam D , Liao Z , Siegel RW , Qian Y , Ploug M , Young SG , Konrad RJ
Ref : Proc Natl Acad Sci U S A , 121 :e2322332121 , 2024
Abstract : Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5delta35"). We found that wild-type (WT) human APOA5, but not APOA5delta35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5delta40"). Mouse WT-APOA5, but not APOA5delta40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5delta40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5(-/-) mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5delta40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.
ESTHER : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedSearch : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedID: 38625948
Gene_locus related to this paper: human-LPL

Title : Role of uranium toxicity and uranium-induced oxidative stress in advancing kidney injury and endothelial inflammation in rats - Yang_2024_BMC.Pharmacol.Toxicol_25_14
Author(s) : Yang Y , Dai C , Chen X , Zhang B , Li X , Yang W , Wang J , Feng J
Ref : BMC Pharmacol Toxicol , 25 :14 , 2024
Abstract : OBJECTIVE: Uranium exposure may cause serious pathological injury to the body, which is attributed to oxidative stress and inflammation. However, the pathogenesis of uranium toxicity has not been clarified. Here, we evaluated the level of oxidative stress to determine the relationship between uranium exposure, nephrotoxic oxidative stress, and endothelial inflammation. METHODS: Forty male Sprague-Dawley rats were divided into three experimental groups (U-24h, U-48h, and U-72h) and one control group. The three experimental groups were intraperitoneally injected with 2.0 mg/kg uranyl acetate, and tissue and serum samples were collected after 24, 48, and 72 h, respectively, whereas the control group was intraperitoneally injected with 1.0 ml/kg normal saline and samples were collected after 24 h. Then, we observed changes in the uranium levels and oxidative stress parameters, including the total oxidative state (TOS), total antioxidant state (TAS), and oxidative stress index (OSI) in kidney tissue and serum. We also detected the markers of kidney injury, namely urea (Ure), creatine (Cre), cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL). The endothelial inflammatory markers, namely C-reactive protein (CRP), lipoprotein phospholipase A2 (Lp-PLA2), and homocysteine (Hcy), were also quantified. Finally, we analyzed the relationship among these parameters. RESULTS: TOS (z = 3.949; P < 0.001), OSI (z = 5.576; P < 0.001), Ure (z = 3.559; P < 0.001), Cre (z = 3.476; P < 0.001), CysC (z = 4.052; P < 0.001), NGAL (z = 3.661; P < 0.001), and CRP (z = 5.286; P < 0.001) gradually increased after uranium exposure, whereas TAS (z = -3.823; P < 0.001), tissue U (z = -2.736; P = 0.001), Hcy (z = -2.794; P = 0.005), and Lp-PLA2 (z = -4.515; P < 0.001) gradually decreased. The serum U level showed a V-shape change (z = -1.655; P = 0.094). The uranium levels in the kidney tissue and serum were positively correlated with TOS (r = 0.440 and 0.424; P = 0.005 and 0.007) and OSI (r = 0.389 and 0.449; P = 0.013 and 0.004); however, serum U levels were negatively correlated with TAS (r = -0.349; P = 0.027). Partial correlation analysis revealed that NGAL was closely correlated to tissue U (r(partial) = 0.455; P = 0.003), CysC was closely correlated to serum U (r(partial) = 0.501; P = 0.001), and Lp-PLA2 was closely correlated to TOS (r(partial) = 0.391; P = 0.014), TAS (r(partial) = 0.569; P < 0.001), and OSI (r(partial) = -0.494; P = 0.001). Pearson correlation analysis indicated that the Hcy levels were negatively correlated with tissue U (r = -0.344; P = 0.030) and positively correlated with TAS (r = 0.396; P = 0.011). CONCLUSION: The uranium-induced oxidative injury may be mainly reflected in enhanced endothelial inflammation, and the direct chemical toxicity of uranium plays an important role in the process of kidney injury, especially in renal tubular injury. In addition, CysC may be a sensitive marker reflecting the nephrotoxicity of uranium; however, Hcy is not suitable for evaluating short-term endothelial inflammation involving oxidative stress.
ESTHER : Yang_2024_BMC.Pharmacol.Toxicol_25_14
PubMedSearch : Yang_2024_BMC.Pharmacol.Toxicol_25_14
PubMedID: 38308341

Title : Extraction and characterization of polysaccharides from blackcurrant fruits and its inhibitory effects on acetylcholinesterase - Yang_2024_Int.J.Biol.Macromol_262_130047
Author(s) : Yang Y , Zou J , Li M , Yun Y , Li J , Bai J
Ref : Int J Biol Macromol , 262 :130047 , 2024
Abstract : Microwave assisted aqueous two-phase system (MA-ATPS) was used to simultaneously extract two polysaccharides from blackcurrant. Under the suitable ATPS (ethanol/(NH(4))(2)SO(4), 26.75 %/18.98 %) combining with the optimal MA conditions (liquid-to-material ratio 58.5 mL/g, time 9.5 min, temperature 60.5 degreesC, power 587 W) predicted by response surface methodology, the yields of the top/bottom phase polysaccharides were 13.08 +/- 0.37 % and 42.65 +/- 0.89 %, respectively. After purification through column chromatography, the top phase polysaccharide (PRTP) and bottom phase polysaccharide (PRBP) were obtained. FT-IR, methylation and NMR analyses confirmed that the repeating unit in the backbone of PRTP was 2, 5)-alpha-L-Araf-(1 3)-alpha-D-Manp-(1 6)-beta-D-Galp-(1 6)-alpha-D-Glcp-(1 4)-alpha-L-Rhap-(1 4)-alpha-D-GalAp-(1, while the possible unit in PRBP was 4)-alpha-L-Rhap-(1 3)-alpha-D-Manp-(1 6)-beta-D-Galp-(1 6)-alpha-D-Glcp-(1 2, 5)-alpha-L-Araf-(1 4)-alpha-D-GalAp-(1. PRBP with relatively low molecular weight exhibited better stability, rheological property, free radical scavenging and acetylcholinesterase (AChE) inhibitory activities than PRTP. PRTP and PRBP were reversible mixed-type inhibitors for AChE, and the conformation of AChE was changed after binding with the polysaccharides. Molecular docking, fluorescence and isothermal titration calorimetry assays revealed that PRTP and PRBP quenched the fluorescence through static quenching mechanism, and the van der Waals interactions and hydrogen bonding played key roles in the stability of polysaccharide-enzyme complexes. This study provided a theoretical basis for blackcurrant polysaccharides as AChE inhibitors to treat Alzheimer's disease.
ESTHER : Yang_2024_Int.J.Biol.Macromol_262_130047
PubMedSearch : Yang_2024_Int.J.Biol.Macromol_262_130047
PubMedID: 38336315

Title : Novel Flavonol Alkaloids in Green Tea: Synthesis, Detection, and Anti-Alzheimer's Disease Effect in a Transgenic Caenorhabditis elegans CL4176 Model - Chen_2024_J.Agric.Food.Chem__
Author(s) : Chen CH , Yang Y , Ke JP , Yang Z , Li JY , Zhang YX , Liu G , Liu Z , Yao G , Bao GH
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Novel N-ethy-2-pyrrolidinone-substituted flavonols, myricetin alkaloids A-C (1-3), quercetin alkaloids A-C (4a, 4b, and 5), and kaempferol alkaloids A and B (6 and 7), were prepared from thermal reaction products of myricetin, quercetin, kaempferoll-theanine, respectively. We used HPLC-ESI-HRMS/MS to detect 1-7 in 14 cultivars of green tea and found that they were all present in "Shuchazao," "Longjing 43", "Fudingdabai", and "Zhongcha 108" green teas. The structures of 1-4 and 6 were determined by extensive 1D and 2D NMR spectroscopies. These flavonol alkaloids along with their skeletal flavonols were assessed for anti-Alzheimer's disease effect based on molecular docking, acetylcholinesterase inhibition, and the transgenic Caenorhabditis elegans CL4176 model. Compound 7 strongly binds to the protein amyloid beta (Abeta(1-42)) through hydrogen bonds (BE: -9.5 kcal/mol, K(i): 114.3 nM). Compound 3 (100 microM) is the strongest one in significantly extending the mean lifespan (13.4 +/- 0.5 d, 43.0% promotion), delaying the Abeta(1-42)-induced paralysis (PT(50): 40.7 +/- 1.9 h, 17.1% promotion), enhancing the locomotion (140.0% promotion at 48 h), and alleviating glutamic acid (Glu)-induced neurotoxicity (153.5% promotion at 48 h) of CL4176 worms (p < 0.0001).
ESTHER : Chen_2024_J.Agric.Food.Chem__
PubMedSearch : Chen_2024_J.Agric.Food.Chem__
PubMedID: 38324412

Title : Quantification of lipoprotein lipase in mouse plasma with a sandwich enzyme-linked immunosorbent assay - Kimura_2024_J.Lipid.Res_65_100532
Author(s) : Kimura T , Miyashita K , Fukamachi I , Fukamachi K , Ogura K , Yokoyama E , Tsunekawa K , Nagasawa T , Ploug M , Yang Y , Song W , Young SG , Beigneux AP , Nakajima K , Murakami M
Ref : J Lipid Res , 65 :100532 , 2024
Abstract : To support in vivo and in vitro studies of intravascular triglyceride metabolism in mice, we created rat monoclonal antibodies (mAbs) against mouse LPL. Two mAbs, mAbs 23A1 and 31A5, were used to develop a sandwich ELISA for mouse LPL. The detection of mouse LPL by the ELISA was linear in concentrations ranging from 0.31 ng/ml to 20 ng/ml. The sensitivity of the ELISA made it possible to quantify LPL in serum and in both pre-heparin and post-heparin plasma samples (including in grossly lipemic samples). LPL mass and activity levels in the post-heparin plasma were lower in Gpihbp1(-/-) mice than in wild-type mice. In both groups of mice, LPL mass and activity levels were positively correlated. Our mAb-based sandwich ELISA for mouse LPL will be useful for any investigator who uses mouse models to study LPL-mediated intravascular lipolysis.
ESTHER : Kimura_2024_J.Lipid.Res_65_100532
PubMedSearch : Kimura_2024_J.Lipid.Res_65_100532
PubMedID: 38608546
Gene_locus related to this paper: mouse-lipli

Title : Artificial antibody-antigen-directed immobilization of lipase for consecutive catalytic synthesis of ester: Benzyl acetate case study - Yang_2024_Bioresour.Technol_403_130894
Author(s) : Yang Y , Guo M , Guo S , Tian J , Gu D
Ref : Bioresour Technol , 403 :130894 , 2024
Abstract : A strategy based on artificial antibody-antigen recognition was proposed for the specific directed immobilization of lipase. The artificial antibody was synthesized using catechol as a template, alpha-methacrylic acid as a functional monomer, and Fe(3)O(4) as the matrix material. Lipase was modified with 3,4-dihydroxybenzaldehyde as an artificial antigen. The artificial antibody can specifically recognize catechol fragment in the enzyme structure to achieve the immobilization of lipase. The immobilization amount, yield, specific activity, and immobilized enzyme activity were 13.2 +/- 0.2 mg/g, 78.9 +/- 0.4 %, 7.9 +/- 0.2 U/mg(protein), and 104.6 +/- 1.7 U/g(carrier), respectively. Moreover, the immobilized lipase exhibited strong reusability and regeneration ability. Additionally, the immobilized lipase successfully catalyzed the synthesis of benzyl acetate and demonstrated robust continuous catalytic activity. These results fully demonstrate the feasibility of the proposed artificial antibody-antigen-directed immobilization of lipase.
ESTHER : Yang_2024_Bioresour.Technol_403_130894
PubMedSearch : Yang_2024_Bioresour.Technol_403_130894
PubMedID: 38795924

Title : Characterization, Structural Analysis, and Thermal Stability Mutation of a New Zearalenone-Degrading Enzyme Mined from Bacillus subtilis - Shi_2024_J.Agric.Food.Chem__
Author(s) : Shi J , Mwabulili F , Xie Y , Yang Y , Sun S , Li Q , Ma W , Jia H
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : Zearalenone (ZEN) is a widespread mycotoxin that causes serious damage to animal husbandry and poses a threat to human health. A screen of ZEN-degrading soil bacteria yielded Bacillus subtilis YT-4, which yielded 80% ZEN degradation after 6 h and 95% after 36 h. The gene sequence encoding the degradative enzyme ZENY was mined from the genome of YT-4 and expressed in yeast. ZENY is an alpha/beta-hydrolase with an optimal enzyme activity at 37 degreesC and pH 8. By breaking the lactone ring of ZEN, it produces ZENY-C(18)H(24)O(5) with a molecular weight of 320.16 g/mol. Sequence comparison and molecular docking analyses identified the catalytic ZENY triad 99S-245H-123E and the primary ZEN-binding mode within the hydrophobic pocket of the enzyme. To improve the thermal stability of the enzyme for industrial applications, we introduced a mutation at the N-terminus, specifically replacing the fifth residue N with V, and achieved a 25% improvement in stability at 45 degreesC. These findings aim to achieve ZEN biodegradation and provide insight into the structure and function of ZEN hydrolases.
ESTHER : Shi_2024_J.Agric.Food.Chem__
PubMedSearch : Shi_2024_J.Agric.Food.Chem__
PubMedID: 38300990
Gene_locus related to this paper: bacsu-YRAK

Title : Discovery of seven-membered ring berberine analogues as highly potent and specific hCES2A inhibitors - Yang_2023_Chem.Biol.Interact_378_110501
Author(s) : Yang Y , Xiong Y , Zhu G , Sun M , Zou K , Zhao Y , Zhang Y , Xu Z , Li Y , Zhu W , Jia Q , Li B , Ge G
Ref : Chemico-Biological Interactions , 378 :110501 , 2023
Abstract : Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC(50) = 1.66 microM) and excellent selectivity over hCES1A (IC(50) > 100 microM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K(i) value of 1.035 microM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
ESTHER : Yang_2023_Chem.Biol.Interact_378_110501
PubMedSearch : Yang_2023_Chem.Biol.Interact_378_110501
PubMedID: 37080375

Title : Decapentaplegic retards lipolysis during metamorphosis in Bombyx mori and Drosophila melanogaster - Qian_2023_Insect.Biochem.Mol.Biol__103928
Author(s) : Qian W , Guo M , Peng J , Zhao T , Li Z , Yang Y , Li H , Zhang X , King-Jones K , Cheng D
Ref : Insect Biochemistry & Molecular Biology , :103928 , 2023
Abstract : Insect morphogen decapentaplegic (Dpp) functions as one of the key extracellular ligands of the Bone Morphogenetic Protein (BMP) signaling pathway. Previous studies in insects mainly focused on the roles of Dpp during embryonic development and the formation of adult wings. In this study, we demonstrate a new role for Dpp in retarding lipolysis during metamorphosis in both Bombyx mori and Drosophila melanogaster. CRISPR/Cas9-mediated mutation of Bombyx dpp causes pupal lethality, induces an excessive and premature breakdown of lipids in the fat body, and upregulates the expressions of several lipolytic enzyme genes, including brummer (bmm), lipase 3 (lip3), and hormone-sensitive lipase (hsl), and lipid storage droplet 1 (lsd1), a lipid droplets (LD)-associated protein gene. Further investigation in Drosophila reveals that salivary gland-specific knockdown of the dpp gene and fat body-specific knockdown of Mad involved in Dpp signaling phenocopy the effects of Bombyx dpp mutation on pupal development and lipolysis. Taken together, our data indicate that the Dpp-mediated BMP signaling in the fat body maintains lipid homeostasis by retarding lipolysis, which is necessary for pupa-adult transition during insect metamorphosis.
ESTHER : Qian_2023_Insect.Biochem.Mol.Biol__103928
PubMedSearch : Qian_2023_Insect.Biochem.Mol.Biol__103928
PubMedID: 36870515

Title : Rapid detection of carbamate nerve agent analogues using dually functionalized gold nanoclusters - Zhang_2023_Anal.Bioanal.Chem_415_3275
Author(s) : Zhang Q , Lv J , Xia J , Wang L , Qu G , Yang Y , Liu S
Ref : Anal Bioanal Chem , 415 :3275 , 2023
Abstract : Carbamate nerve agents (CMNAs) are a type of lethal cholinesterase inhibitor with one or more quaternary amine centres and aromatic rings. CMNAs have been recently added to the Annex on Chemicals of the Chemical Weapons Convention (CWC) and Schedules of Controlled Chemicals of China. In this study, a rapid, sensitive and selective method was developed for the fluorescence detection of ambenonium chloride (AC) through host-guest and electrostatic dual interactions between AC and cyclodextrin/11-mercaptoundecanoic acid (CD/MUA) dually functionalized gold nanoclusters (AuNCs). Through this method, AC was detected with a limit of detection of 10.0 ng/mL. Method evaluation showed high selectivity towards AC over other related compounds. The practical applicability was verified, as satisfactory recoveries were obtained for AC spiked in river water and urine, as well as Proficiency Test samples from Organisation for the Prohibition of Chemical Weapons (OPCW). In addition, a fluorescence sensing array comprising four AuNCs was designed to distinguish six carbamates and structurally similar compounds. This method provides a potential approach for the rapid, sensitive and selective recognition and detection of CMNAs.
ESTHER : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedSearch : Zhang_2023_Anal.Bioanal.Chem_415_3275
PubMedID: 37266687

Title : Complete bio-degradation of poly(butylene adipate-co-terephthalate) via engineered cutinases - Yang_2023_Nat.Commun_14_1645
Author(s) : Yang Y , Min J , Xue T , Jiang P , Liu X , Peng R , Huang JW , Qu Y , Li X , Ma N , Tsai FC , Dai L , Zhang Q , Liu Y , Chen CC , Guo RT
Ref : Nat Commun , 14 :1645 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT), a polyester made of terephthalic acid (TPA), 1,4-butanediol, and adipic acid, is extensively utilized in plastic production and has accumulated globally as environmental waste. Biodegradation is an attractive strategy to manage PBAT, but an effective PBAT-degrading enzyme is required. Here, we demonstrate that cutinases are highly potent enzymes that can completely decompose PBAT films in 48 h. We further show that the engineered cutinases, by applying a double mutation strategy to render a more flexible substrate-binding pocket exhibit higher decomposition rates. Notably, these variants produce TPA as a major end-product, which is beneficial feature for the future recycling economy. The crystal structures of wild type and double mutation of a cutinase from Thermobifida fusca in complex with a substrate analogue are also solved, elucidating their substrate-binding modes. These structural and biochemical analyses enable us to propose the mechanism of cutinase-mediated PBAT degradation.
ESTHER : Yang_2023_Nat.Commun_14_1645
PubMedSearch : Yang_2023_Nat.Commun_14_1645
PubMedID: 36964144
Gene_locus related to this paper: idesa-peth , thefu-q6a0i4

Title : Strategy of In Situ Electrochemical Regulation for Highly Enhanced Nonenzymatic Sensing of Carbaryl - Lv_2023_Anal.Chem__
Author(s) : Lv Y , Zhang Y , Yang Y , Li J , Wang J , Xiao X , Zhang M
Ref : Analytical Chemistry , : , 2023
Abstract : Specific and sensitive sensing of most pesticide residues relies on enzymes such as acetylcholinesterase and advanced materials, which need to be loaded on the surface of working electrodes, leading to instability, uneven surface, tedious process, and high cost. Meanwhile, employing certain potential or current in electrolyte solution could also modify the surface in situ and overcome these drawbacks. However, this method is only regarded as electrochemical activation widely applied in the pretreatment of electrodes. In this paper, by means of regulating the electrochemical technique and its parameters, we prepared a proper sensing interface and derivatized the carbaryl (a carbamate pesticide) hydrolyzed form (1-naphthol) to enhance sensing by 100 times within several minutes. After regulation I by chronopotentiometry with 0.2 mA for 20 s or chronoamperometry with 2 V for 10 s, abundant oxygen-containing groups form and the ordered carbon structure is destroyed. Sweeping from -0.5 to 0.9 V through cyclic voltammetry for only one segment, following regulation II, the composition of oxygen-containing groups changes and the disordered structure is alleviated. Finally, on the constructed sensing interface, test by regulation III through differential pulse voltammetry from 0.8 to -0.4 V, resulting in derivatization of 1-naphthol during 0.8-0 V, followed by electroreduction of the derivative at around -0.17 V. Compared with the electro-oxidation peak at 0.5 V in previous reports, it is essential to improve specificity, even toward several other carbamate pesticides with similar structures. Hence, the in situ electrochemical regulation strategy has demonstrated great potential for effective sensing of electroactive molecules.
ESTHER : Lv_2023_Anal.Chem__
PubMedSearch : Lv_2023_Anal.Chem__
PubMedID: 36802553

Title : A colorimetric analytical method based on a TCPP-CuCo(2)O(4)-like peroxidase for the detection of trichlorfon - Xiao_2023_Anal.Methods__
Author(s) : Xiao X , Liao W , Ma R , Huang L , Yang Y
Ref : Anal Methods , : , 2023
Abstract : In this work, a highly sensitive colorimetric sensing platform was designed for the detection of trichlorfon based on inhibiting thiocholine (TCh)-induced redox reaction. 5,10,15,20-Tetracarboxyphenylporphyrin (TCPP) functionalized CuCo(2)O(4) (TCPP-CuCo(2)O(4)) was synthesized to construct a colorimetric sensing platform for trichlorfon. In the presence of H(2)O(2), TCPP-CuCo(2)O(4) can oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB, accompanied by a strong absorption peak at 652 nm, while acetylcholinesterase (AChE) can specifically hydrolyze acetylthiocholine (ATCh) into TCh, which can reduce ox-TMB back into colorless TMB, resulting in a lower absorbance at 652 nm. Trichlorfon can irreversibly inhibit the activity of AChE and thus recover the absorption peak. Under the optimized conditions, detection of trichlorfon has a wide linear range of 40-4000 ng mL(-1) with a linear correlation coefficient of 0.9904. The proposed method can be applied to the detection of trichlorfon in vegetables and has good application prospects.
ESTHER : Xiao_2023_Anal.Methods__
PubMedSearch : Xiao_2023_Anal.Methods__
PubMedID: 37609836

Title : Tributyl phosphate can inhibit the feeding behavior of rotifers by altering the axoneme structure, neuronal coordination and energy supply required for motile cilia - Zhang_2023_J.Hazard.Mater_459_132224
Author(s) : Zhang X , Tang X , Yang Y , Tong X , Hu H
Ref : J Hazard Mater , 459 :132224 , 2023
Abstract : Organophosphorus flame retardants (OPFRs) are frequently detected in aquatic environments and can potentially amplify the food chain, posing a potential risk to organisms. Marine invertebrates have primitive nervous systems to regulate behavior, but how they respond to OPFRs that are potentially neurotoxic substances is unclear. This study assessed changes in the feeding behavior of rotifer Brachionus plicatilis exposed to alkyl OPFRs tributyl phosphate (TnBP) (0.376 nM, 3.76 and 22.53 microM) to elucidate the mechanism of behavioral toxicity. TnBP at 22.53 microM reduced the ingestion and filtration rates of rotifers for Chlorella vulgaris and Phaeocystis globosa in a 24-h test and altered rotifer-P. globosa population dynamics in 15-d coculture. Ciliary beat frequency was also reduced, and the expression of genes encoding the cilia axoneme was downregulated. TnBP could inhibit rotifer acetylcholinesterase activity by binding this protein and reduce the expression of the exocytotic membrane protein syntaxin-4, suggesting a disorder in nervous regulation of cilia beat. Moreover, TnBP induced abnormal shape and dysfunction of mitochondria, which caused insufficient energy required for ciliary movement. This study revealed diverse neurotoxicity mechanisms of TnBP, particularly as a potentially competing acetylcholinesterase ligand for aquatic invertebrates. Our research also provides a meaningful reference for OPFR-induced behavioral toxicity assessments.
ESTHER : Zhang_2023_J.Hazard.Mater_459_132224
PubMedSearch : Zhang_2023_J.Hazard.Mater_459_132224
PubMedID: 37557041

Title : Genome-wide identification of CXE and PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit - Qi_2023_Plant.Physiol.Biochem_203_107996
Author(s) : Qi L , Li X , Zang N , Zhang Z , Yang Y , Du Y , Sun J , Mostafa I , Yin Z , Wang A
Ref : Plant Physiol Biochem , 203 :107996 , 2023
Abstract : Volatile esters are the main aromatic components that affect consumer sensory preferences. Aroma is a crucial characteristic of the 'Nanguo' pear (Pyrus ussriensis Maxim). Carboxylesterases (CXEs) are positively correlated with the catabolism of volatile esters in peaches; however, the mechanism of action of CXE family members in 'Nanguo' pear is poorly understood. In this study, 40 PuCXEs were identified in the 'Nanguo' pear and assigned into seven groups. In addition, we found that most PuCXEs were relatively conserved and contained cytoplasmic proteins. This hypothesis was supported by phylogenetic analysis, investigation of conserved domains and gene structures, and prediction of subcellular localization. Based on the content of volatile esters and expression levels of PuCXEs analysis, four PuCXEs, including PuCXE7, PuCXE15, PuCXE20, and PuCXE25, had a significant negative correlation with volatile ester accumulation. Particularly, the correlation of PuCXE15 far exceeded that of the other PuCXEs. The results of the transient expression assay showed that PuCXE15 promoted the degradation of ester in vivo. Subcellular localization experiment revealed that PuCXE15 is located in the plasma membrane and nucleus. These results show that PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit, and provides a foundation for enhancing aroma quality by artificial control in pear.
ESTHER : Qi_2023_Plant.Physiol.Biochem_203_107996
PubMedSearch : Qi_2023_Plant.Physiol.Biochem_203_107996
PubMedID: 37688900

Title : Design, synthesis and biological evaluation of salicylanilides as novel allosteric inhibitors of human pancreatic lipase - Zhao_2023_Bioorg.Med.Chem_91_117413
Author(s) : Zhao Y , Zhang M , Hou X , Han J , Qin X , Yang Y , Song Y , Liu Z , Zhang Y , Xu Z , Jia Q , Li Y , Chen K , Li B , Zhu W , Ge G
Ref : Bioorganic & Medicinal Chemistry , 91 :117413 , 2023
Abstract : Obesity is a growing global health problem and is associated with increased prevalence of many metabolic disorders, including diabetes, hypertension and cardiovascular disease. Pancreatic lipase (PL) has been validated as a key target for developing anti-obesity agents, owing to its crucial role in lipid digestion and absorption. In the past few decades, porcine PL (pPL) is always used as the enzyme source for screening PL inhibitors, which generate numerous pPL inhibitors but the potent inhibitors against human PL (hPL) are rarely reported. Herein, a series of salicylanilide derivatives were designed and synthesized, while their anti-hPL effects were assayed by a fluorescence-based biochemical approach. To investigate the structure-activity relationships of salicylanilide derivatives as hPL inhibitors in detail, structural modifications on three rings (A, B and C) of the salicylanilide skeleton were performed. Among all tested compounds, 2t and 2u were found possessing the most potent anti-PL activity, showing IC(50) values of 1.86 microM and 1.63 microM, respectively. Inhibition kinetic analyses suggested that both 2t and 2u could effectively inhibit hPL in a non-competitive manner, with the k(i) value of 1.67 microM and 1.70 microM, respectively. Fluorescence quenching assays suggested that two inhibitors could quench the fluorescence of hPL via a static quenching procedure. Molecular docking simulations suggested that 2t and 2u could tightly bind on an allosteric site of hPL. Collectively, the structure-activity relationships of salicylanilide derivatives as hPL inhibitors were carefully investigated, while two newly identified reversible hPL inhibitors (2t and 2u) could be used as promising lead compounds to develop novel anti-obesity drugs.
ESTHER : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedSearch : Zhao_2023_Bioorg.Med.Chem_91_117413
PubMedID: 37490786

Title : A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network - Zhang_2023_Adv.Sci.(Weinh)__e2301004
Author(s) : Zhang Z , Liu Z , Wu P , Guo X , Luo X , Yang Y , Chen J , Tian Y
Ref : Adv Sci (Weinh) , :e2301004 , 2023
Abstract : A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.
ESTHER : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedSearch : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedID: 37635166

Title : Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH(2)(Fe) - Zhao_2023_ACS.Appl.Mater.Interfaces__
Author(s) : Zhao D , Liu J , Zhou Y , Zhang L , Zhong Y , Yang Y , Zhao B , Yang M , Wang Y
Ref : ACS Appl Mater Interfaces , : , 2023
Abstract : It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH(2)(Fe) nanoparticles with a size of -100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH(2)(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment.
ESTHER : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedSearch : Zhao_2023_ACS.Appl.Mater.Interfaces__
PubMedID: 36867458

Title : ABHD5-CPT1B: An Important Way of Regulating Placental Lipid Metabolism in Gestational Diabetes Mellitus - Yang_2023_Arch.Med.Res_55_102925
Author(s) : Yang Y , Peng Y , Yu B , Wang H
Ref : Arch Med Res , 55 :102925 , 2023
Abstract : BACKGROUND AND AIM: Gestational diabetes mellitus (GDM) is one of the most common metabolic disorders in pregnancy, and a novel association of maternal lipid profile has been suggested to play an important role. However, the molecular mechanism is not clear. METHODS: Bio-analyzed combined with placental metabonomics and single-cell RNA-sequencing (scRNA-seq) successfully identified a potentially important molecule: alpha-beta hydrolase domain-containing protein 5 (ABHD5). The syncytiotrophoblast (SCT) cell model was adopted as a fusion of BeWo cells in response to forskolin. On this basis, the high glucose-stimulated cell experiment was carried out. 15 women with GDM and 15 normal pregnant women were recruited for validation experiments. RESULTS: ABHD5 was mainly expressed in the trophoblast cells, especially in SCT cells, and significantly decreased in the GDM placenta. After stimulation by high glucose, the expression of ABHD5 was downregulated in a time-dependent manner in BeWo cells treated with forskolin. At the same time, lipid droplets (LDs) were increased in the SCT. LD storage was also increased in the SCT with siABHD5, while it was significantly reduced in SCT cells with high ABHD5 expression. However, this effect could be attenuated by downregulated carnitine palmitoyltransferase 1B (CPT1B). CONCLUSIONS: ABHD5-CPT1B is confirmed as an important regulator of placental lipid metabolism.
ESTHER : Yang_2023_Arch.Med.Res_55_102925
PubMedSearch : Yang_2023_Arch.Med.Res_55_102925
PubMedID: 38042031
Gene_locus related to this paper: human-ABHD5

Title : Ultrasensitive Detection of Organophosphorus Pesticides Using Single-Molecule Conductance Measurement - Dong_2023_Anal.Chem_95_9831
Author(s) : Dong X , Tang Z , Zhang H , Hu Y , Yao Z , Huang R , Bai J , Yang Y , Hong W
Ref : Analytical Chemistry , 95 :9831 , 2023
Abstract : Detection of organophosphorus pesticides (OPs) with high sensitivity in environmental samples is of vital importance for environmental safety and human health. However, it remains a challenge to achieve fM (10(-15) mol/L) sensitivity for detecting OPs. Herein, we developed an acetylcholinesterase sensor based on 3,3',5,5'-tetramethylbenzidine (TMB) combining an enzyme-mediated strategy and scanning tunneling microscopy break junction (STM-BJ). Benefiting from the enzyme inhibition kinetics of OPs and the customized spectral clustering analysis method, our new strategy achieved the detection of methamidophos (MTMP) with a limit of 10 aM (10(-17) mol/L) and 3 times higher selectivity in mixed OPs. As applied to natural lake waters, it also exhibited high reproducibility, high stability, and good recovery. This work paves a new avenue toward the application of single-molecule conductance characterizations for biochemical analysis and environmental monitoring.
ESTHER : Dong_2023_Anal.Chem_95_9831
PubMedSearch : Dong_2023_Anal.Chem_95_9831
PubMedID: 37347983

Title : Effect of Green and Red Thai Kratom (Mitragyna speciosa) on pancreatic digestive enzymes (alpha-glucosidase and lipase) and acetyl-carboxylase 1 activity: A possible therapeutic target for obesity prevention - Janthongkaw_2023_PLoS.One_18_e0291738
Author(s) : Janthongkaw A , Klaophimai S , Khampaya T , Yimthiang S , Yang Y , Ma R , Bumyut A , Pouyfung P
Ref : PLoS ONE , 18 :e0291738 , 2023
Abstract : Regular use of Thai kratom has been linked to reduced blood triglyceride levels and body mass index (BMI) in healthy individuals. We analyzed Green Thai Kratom (GTK) and Red Thai Kratom (RTK) to investigate their effects on pancreatic digestive enzymes. The ethanol extracts of GTK and RTK inhibited lipase activity more strongly than alpha-glucosidase activity, suggesting the presence of lipase inhibitors. Mitragynine, the major compound in GTK, showed potent lipase inhibition and moderate alpha-glucosidase inhibition. Quercetin, found in both extracts, strongly inhibited alpha-glucosidase but had limited effects on lipase. These findings suggest that mitragynine and quercetin may hinder triglyceride and starch digestion. Combination inhibition studies revealed synergistic effects between mitragynine and quercetin on alpha-glucosidase activity. Additionally, both GTK and RTK extracts reduced fat accumulation in 3T3-L1 adipocyte cells, with quercetin specifically inhibiting Acetyl-CoA carboxylase 1 (ACC1), a key enzyme in fatty acid biosynthesis. Thus, GTK and RTK extracts, particularly mitragynine and quercetin, exhibit potential anti-obesity effects. We report the novel finding that Thai kratom inhibits de novo fatty acid synthesis by targeting ACC1, resulting in decreased fat accumulation in adipocytes. Regular use of Thai kratom in specific populations may improve blood triglyceride levels and reduce BMI by inhibiting lipase, alpha-glucosidase, and ACC1 activity. Further clinical trials are needed to determine optimal dosage, duration, toxicity levels, and potential side effects of Kratom use.
ESTHER : Janthongkaw_2023_PLoS.One_18_e0291738
PubMedSearch : Janthongkaw_2023_PLoS.One_18_e0291738
PubMedID: 37733688

Title : Organophosphate Level Evaluation for the Poisoning Treatment by Enzyme Activation Regeneration Strategy with Oxime-Functionalized ZIF-8 Nanoparticles - Shen_2023_Anal.Chem__
Author(s) : Shen A , Hao X , Li M , Zhao Y , Li Z , Hou L , Duan R , Zhang P , Zhang L , Yang Y
Ref : Analytical Chemistry , : , 2023
Abstract : In this work, two nanometal-organic frameworks (NMOFs) of ZIF-8-1 and ZIF-8-2 were designed and synthesized with a "missing linker" defects strategy by using Oxime-1 and Oxime-2 as coligands, respectively. ZIF-8-2 exhibited an excellent performance in comparison to that of ZIF-8-1 in activating and regenerating the activity of BChE suppressed by demeton-S-methyl (DSM) and could rapidly detoxify DSM in poisoned serum samples within 24 min. Additionally, the synthesized fluorescence probe of IND-BChE with high quantum yields, large Stokes shifts, and superior water solubility could be used for the detection of both butyrylcholinesterase (BChE) and DSM in a lower LOD of 0.63 mU/mL (BChE) and 0.086 microg/mL (DSM). By the difference in fluorescent intensity of IND-BChE with and without ZIF-8-2, a highly linear relationship of IND-BChE with DSM concentration was found (R(2) = 0.9889), and the LOD was 0.073 microg/mL. In addition, an intelligent detection platform of ZIF-8-2@IND-BChE@agarose hydrogel combined with a smartphone formed a point-of-care test for DSM -poisoned serum samples and also realized satisfactory results. Unlike other detection methods of nerve agents, this assay first combined an NMOF reactivator for detoxification and detection of BChE enzyme activity and then quantification of OP nerve agents, which was of great significance in treatment of organophosphate poisoning.
ESTHER : Shen_2023_Anal.Chem__
PubMedSearch : Shen_2023_Anal.Chem__
PubMedID: 37358141

Title : Network pharmacology-based analysis of Jin-Si-Wei on the treatment of Alzheimer's disease - Zhi_2023_J.Ethnopharmacol__117291
Author(s) : Zhi J , Yin L , Zhang Z , Lv Y , Wu F , Yang Y , Zhang E , Li H , Lu N , Zhou M , Hu Q
Ref : J Ethnopharmacol , :117291 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Jin-Si-Wei (JSW), a traditional Chinese medicine (TCM) formula, have cognitive enhancing effect and delay the memory decline in an animal model of AD which has been reported. However, the therapeutic mechanism of JSW in the treatment of AD remains unclear. AIM OF THE STUDY: This study aimed to verify the pharmacodynamics of JSW in the treatment of AD, and to explore its potential mechanism based on network pharmacology, molecular docking and experimental validation both in vitro and in vivo. MATERIALS AND METHODS: In this study, the underlying mechanism of JSW against AD was investigated by the integration of network pharmacology. Then, the core pathways and biological process of JSW were verified by experiment, including behavioral test and pathological and biochemical assays with 6-month-old APP(swe)/PS1(deltaE9) transgenic (APP/PS1) mice in vivo and verified with Abeta(1-42)-stimulated SH-SY5Y cells in vitro. At last, molecular docking was used to show the binding activity of each active ingredient to the core genes of JSW treatment in AD. RESULTS: A Drug-Ingredient-Target network was established, which included 363 ingredients and 116 targets related to the JSW treatment of AD. The main metabolic pathway of JSW treatment for AD is neuroactive ligand-receptor interaction pathway, and biological processes are mainly involved in Abeta metabolic process. In vivo experiments, compared with APP/PS1 mice, the cognitive and memory ability of mice was significantly improved after JSW administration. In brain tissue of APP/PS1 mice, JSW could increase the contents of low-density lipoprotein receptor-related protein 1 (LRP-1), enkephalinase (NEP) and Acetyl choline (ACh), and decrease the contents of Abeta(1-42), amyloid precursor protein (APP) and receptor for advanced glycation end products (RAGE), decrease the vitality of cholinesterase (AChE) and choline acetyltransferase (ChAT). Besides, JSW could increase alpha-secretase expression and decrease beta/gamma-secretase expression, and improve the number and morphology of synapses in CA1 region of the hippocampus of APP/PS1 mice. In vitro experiments, Drug-Containing Serum (JSW-serum) has a neuroprotective effect by reducing the apoptosis on Abeta(1-42)-stimulated SH-SY5Y cells. Molecular docking results showed that 2-Isopropyl-8-methylphenanthrene-3,4-dione had strong binding activity with PTGS2, which maybe a potential ingredient for the treatment of AD. CONCLUSIONS: JSW improves AD in APP/PS1 mice, and this therapeutic effect may be achieved in part by altering the neuroactive ligand-receptor interaction pathway.
ESTHER : Zhi_2023_J.Ethnopharmacol__117291
PubMedSearch : Zhi_2023_J.Ethnopharmacol__117291
PubMedID: 37925002

Title : A Multifunctional (-)-Meptazinol-Serotonin Hybrid Ameliorates Oxidative Stress-Associated Apoptotic Neuronal Death and Memory Deficits via Activating the Nrf2\/Antioxidant Enzyme Pathway - Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
Author(s) : Zhao F , Zhao L , Zhou Y , Tan X , Yang Y , Ni W , Zheng W , Chen H , Qiu Y , Li J
Ref : Oxid Med Cell Longev , 2023 :6935947 , 2023
Abstract : The pathogenesis of Alzheimer's disease (AD) involves multiple pathophysiological processes. Oxidative stress is a major cause of AD-associated neuronal injury. The current research was designed to examine whether a novel (-)-meptazinol-serotonin hybrid (Mep-S) with potent antioxidant activity and additional inhibitory properties for acetylcholinesterase (AChE) activity could attenuate oxidative neuronal damage and cognitive deficits. In human SH-SY5Y cells, Mep-S suppressed H(2)O(2)-induced apoptosis by restoring mitochondrial membrane potential and inhibiting caspase-3 activation. Meanwhile, it attenuated oxidative stress elicited by H(2)O(2) through lessening generation of reactive oxygen species as well as enhancing production of glutathione (GSH) and activity of superoxide dismutase (SOD). Mechanistically, Mep-S promoted nuclear translocation of a transcription factor nuclear factor E2-related factor-2 (Nrf2) in H(2)O(2)-challenged cells. This effect was accompanied by reduction in Kelch-like ECH-associated protein-1 (Keap1) levels as well as augmentation of Akt phosphorylation and expression of heme oxygenase-1 (HO-1) and NAD(P)H quinine oxidoreductase-1 (NQO-1). Molecular docking analysis revealed that Mep-S may disrupt the protein-protein interactions between Keap1 and Nrf2. In an in vivo mouse model, Mep-S attenuated scopolamine-caused cognitive deficits with inhibition of apoptotic neuronal death and brain AChE activity. Furthermore, the scopolamine-induced impairment of total antioxidant capacity and reduction in SOD1, SOD2, and gamma-glutamate-cysteine ligase expression in the brain were counteracted by Mep-S, accompanied by decreased Keap1 levels, increased Akt catalytic subunit and Nrf2 phosphorylation, and decreased Nrf2, HO-1, and NQO-1 expression. Collectively, our results suggest that Mep-S ameliorates apoptotic neuronal death and memory dysfunction associated with oxidative stress by regulating the Nrf2/antioxidant enzyme pathway through inactivating Keap1 and phosphorylating Nrf2 via Akt activation. Therefore, Mep-S may be a potential lead for multitarget neuroprotective agents to treat AD-like symptoms.
ESTHER : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedSearch : Zhao_2023_Oxid.Med.Cell.Longev_2023_6935947
PubMedID: 36819782

Title : Ultrasensitivity Detecting AChE through "\;Covalent Assembly"\; and Signal Amplification Strategic Approaches and Applied to Screen Its Inhibitor - Zhao_2023_Anal.Chem__
Author(s) : Zhao Y , Shen A , Hao X , Li M , Hou L , Li Z , Duan R , Du M , Li X , Wang X , Zhao X , Yang Y
Ref : Analytical Chemistry , : , 2023
Abstract : An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.
ESTHER : Zhao_2023_Anal.Chem__
PubMedSearch : Zhao_2023_Anal.Chem__
PubMedID: 36812425

Title : Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus - Meng_2023_Lipids.Health.Dis_22_219
Author(s) : Meng J , Yan R , Zhang C , Bai X , Yang X , Yang Y , Feng T , Liu X
Ref : Lipids Health Dis , 22 :219 , 2023
Abstract : BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I(2). Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.
ESTHER : Meng_2023_Lipids.Health.Dis_22_219
PubMedSearch : Meng_2023_Lipids.Health.Dis_22_219
PubMedID: 38082288

Title : Prognostic Factors of Severe Pneumonia in Adult Patients: A Systematic Review - Yang_2023_Altern.Ther.Health.Med__
Author(s) : Yang Y , Wang Q , Yu Z
Ref : Altern Ther Health Med , : , 2023
Abstract : OBJECTIVES: This systematic review aimed to identify independent prognostic factors of severe pneumonia. METHODS: A systematic search was undertaken in Pubmed, Embase, and Web of Science from inception to March 2023 to find cohort studies investigating the association between prognostic factors and adverse outcomes of severe pneumonia in adult patients. The study selection process involved screening the title and abstract of articles to identify relevant studies on severe pneumonia in adult patients. Inclusion criteria included studies with a prospective or retrospective longitudinal design, investigating prognostic factors, and performing multivariate analysis. Exclusion criteria included non-English or non-Chinese studies, studies focusing on severe pneumonia in children, studies conducting only univariate analysis, and conference abstracts, reviews, and case reports. The risk of bias was assessed by the Quality In Prognosis Studies (QUIPS) tool. RESULTS: A total of 27 published studies, including both prospective and retrospective cohort studies, were included. These studies reported on 53 different prognostic factors and covered four unique outcomes. The quality assessment indicated that 59.3% of the studies had a low risk of bias. Age, functional dependence, heart rate, and oxygen saturation/respiratory rate index were found to be associated with mortality. Additionally, various laboratory indexes, such as serum cholinesterase, albumin, and blood urea nitrogen to creatinine ratio, demonstrated either protective or risk factors for prognosis. Injury and comorbidities, including acute renal failure, chronic lung disease, and Glasgow Coma Scale, were identified as risk factors for mortality. Scoring tools like Acute Physiological and Chronic Health Evaluation (APACHE) II score, CURB-65 score, and Pneumonia Severity Index (PSI) score showed associations with mortality. Lastly, certain treatment protocols, such as vasoactive agent use, vasopressor use, and mechanical ventilation, were found to increase the risk of mortality, while invasive mechanical ventilation and the use of remdesivir and steroids had a positive impact on prognosis. These findings provide valuable insights for clinicians in predicting and managing severe pneumonia outcomes. CONCLUSION: This most comprehensive review identified 53 unique prognostic factors of severe pneumonia, which provided a reference for subsequent researchers to construct models to predict clinical outcomes in patients with severe pneumonia for clinical use. By identifying prognostic factors through multivariate analysis, healthcare providers can better assess the severity and prognosis of individual patients. This knowledge can aid in treatment planning, resource allocation, and determining the appropriate level of care for patients with severe pneumonia. Additionally, understanding the prognostic factors can help identify high-risk patients who may require more intensive monitoring or interventions. Overall, this study provides valuable insights that can inform clinical practice and improve patient outcomes in the management of severe pneumonia.
ESTHER : Yang_2023_Altern.Ther.Health.Med__
PubMedSearch : Yang_2023_Altern.Ther.Health.Med__
PubMedID: 37971449

Title : Generic detection of organophosphorus nerve agent adducts to butyrylcholinesterase in plasma using liquid chromatography-tandem mass spectrometry combined with an improved procainamide-gel separation and pepsin digestion method - Liu_2023_J.Chromatogr.A_1697_463990
Author(s) : Liu CC , Liang LH , Yan L , Chen B , Liu XJ , Yang Y , Liu SL , Xi HL
Ref : Journal of Chromatography A , 1697 :463990 , 2023
Abstract : Organophosphorus nerve agent (OPNA) adducts to butyrylcholinesterase (BChE) can be applied to confirm exposure in humans. A sensitive method for generic detection of G- and V-series OPNA adducts to BChE in plasma was developed by combining an improved procainamide-gel separation (PGS) and pepsin digestion protocol with ultra-high-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Residual matrix interferences from prior PGS purification of OPNA-BChE adducts from plasma were found to be a critical cause of significantly reduced UHPLC-MS/MS detection sensitivity. In our developed on-column PGS approach, the matrix interference was successfully removed by adding an appropriate concentration of NaCl to the washing buffer, and it could capture <=92.5% of the BChE in plasma. The lower pH value and the longer digestion time in all previous pepsin digestion methods were found to be a key accelerated aging factor of several adducts such as tabun (GA)-, cyclohexylsarin (GF)-, and soman (GD)-BChE nonapeptide adducts, making them difficult to detect. The aging event of several OPNA-BChE nonapeptide adducts was so successfully addressed that the formic acid level in enzymatic buffer and digestion time were lowered to 0.05% (pH 2.67) and 0.5 h, respectively, and the post-digestion reaction was immediately terminated. The improved condition parameters were optimal for pepsin digestion of all types of OPNA-BChE adducts into their individual unaged nonapeptide adducts with the highest yields, expanding the applicability of the method. The method had a nearly one-fold decrease in sample preparation time through the reduction of digestion time and removal of ultrafiltration procedure after digestion. The limit of identification (LOI) were determined respectively as 0.13 ng mL(-1), 0.28 ng mL(-1), 0.50 ng mL(-1), 0.41 ng mL(-1) and 0.91 ng mL(-1) for VX-, sarin (GB)-, GA-, GF-, and GD-exposed human plasma, being low exposure value compared to previously documented approaches. The approach was utilized to fully characterize the adducted (aged and unaged) BChE levels of five OPNAs in a series of their individual exposed concentration (1.00-400 nM) of plasma sample, and successfully detect OPNA exposure from all unknown plasma samples from OPCW's second and third biomedical proficiency tests. The OPNA-BChE adducts, their aged adducts, and unadducted BChE from OPNA-exposed plasma can simultaneously be measured using the method. The study provides a recommended diagnostic tool for generic verification of any OPNA exposure with high confidence by detecting its corresponding BChE adduct.
ESTHER : Liu_2023_J.Chromatogr.A_1697_463990
PubMedSearch : Liu_2023_J.Chromatogr.A_1697_463990
PubMedID: 37075496

Title : Effects of lipophilic phycotoxin okadaic acid on the early development and transcriptional expression of marine medaka Oryzias melastigma - Yang_2023_Aquat.Toxicol_260_106576
Author(s) : Yang Y , Li A , Qiu J , Yan W , Han L , Li D , Yin C
Ref : Aquat Toxicol , 260 :106576 , 2023
Abstract : The lipophilic okadaic acid (OA)-group toxins produced by some species of Dinophysis spp. and Prorocentrum spp. marine dinoflagellates have been frequently and widely detected in natural seawater environments, e.g. 2.1-1780 ng/L in Spanish sea and 5.63-27.29 ng/L in the Yellow Sea of China. The toxicological effects of these toxins dissolved in seawater on marine fish is still unclear. Effects of OA on the embryonic development and 1-month old larvae of marine medaka (Oryzias melastigma) were explored and discussed in this study. Significantly increased mortality and decreased hatching rates occurred for the medaka embryos exposed to OA at 1.0 microg/mL. Diverse malformations including spinal curvature, dysplasia and tail curvature were also observed in the embryos exposed to OA and the heart rates significantly increased at 11 d post fertilization. The 96 h LC(50) of OA for 1-month old larvae was calculated at 3.80 microg/mL. The reactive oxygen species (ROS) was significantly accumulated in medaka larvae. Catalase (CAT) enzyme activity was significantly increased in 1-month old larvae. Acetylcholinesterase (AChE) activity significantly increased with a dose-dependent pattern in 1-month old larvae. Differentially expressed genes (DEGs) were enriched in 11 KEGG pathways with Q value < 0.05 in 1-month old medaka larvae exposed to OA at 0.38 microg/mL for 96 h, which were mainly related to cell division and proliferation, and nervous system. Most of DEGs involved in DNA replication, cell cycle, nucleotide excision repair, oocyte meiosis, and mismatch repair pathways were significantly up-regulated, while most of DEGs involved in synaptic vesicle cycle, glutamatergic synapse, and long-term potentiation pathways were markedly down-regulated. This transcriptome analysis demonstrated that a risk of cancer developing was possibly caused by OA due to DNA damage in marine medaka larvae. In addition, the neurotoxicity of OA was also testified for marine fish, which potentially cause major depressive disorder (MDD) via the up-regulated expression of NOS1 gene. The genotoxicity and neurotoxicity of OA to marine fish should be paid attention to and explored further in the future.
ESTHER : Yang_2023_Aquat.Toxicol_260_106576
PubMedSearch : Yang_2023_Aquat.Toxicol_260_106576
PubMedID: 37196507

Title : GehB Inactivates Lipoproteins to Delay the Healing of Acute Wounds Infected with Staphylococcus aureus - Wang_2023_Curr.Microbiol_81_36
Author(s) : Wang K , Cai X , Rao Y , Liu L , Hu Z , Peng H , Wang Y , Yang Y , Rao X , Nie K , Shang W
Ref : Curr Microbiol , 81 :36 , 2023
Abstract : Staphylococcus aureus is one of the most prevalent bacteria found in acute wounds. S. aureus produces many virulence factors and extracellular enzymes that contribute to bacterial survival, dissemination, and pathogenicity. Lipase GehB is a glycerol ester hydrolase that hydrolyzes triglycerides to facilitate the evasion of S. aureus from host immune recognition. However, the role and mechanism of lipase GehB in skin acute wound healing after S. aureus infection remain unclear. In this study, we found that the gehB gene deletion mutant (USA300deltagehB) stimulated significantly higher levels of pro-inflammatory cytokines in RAW264.7 and Toll-like receptor 2 (TLR2)-transfected HEK293 cells than the wild-type USA300 strain did. Recombinant GehB-His treated lipoprotein (Lpp) reduced stimulation of TLR2-dependent TNF-alpha production by RAW264.7 macrophages. GehB delayed the skin acute wound healing in BALB/c mice infected with S. aureus, while wound healing was similar in C57BL/6 TLR2(-/-) mice infected with either wild-type USA300 or USA300deltagehB. In BALB/c mice, we also observed more bacterial survival, less leukocyte recruitment, lower IL-8 production, and adipocyte differentiation in USA300-infected skin acute wound tissues than those in USA300deltagehB-challenged ones. Our data indicated that GehB inactivates lipoproteins to shield S. aureus from innate immune killing, resulting in delayed the healing of skin acute wounds infected with S. aureus.
ESTHER : Wang_2023_Curr.Microbiol_81_36
PubMedSearch : Wang_2023_Curr.Microbiol_81_36
PubMedID: 38063939

Title : A type VII-secreted lipase toxin with reverse domain arrangement - Garrett_2023_Nat.Commun_14_8438
Author(s) : Garrett SR , Mietrach N , Deme J , Bitzer A , Yang Y , Ulhuq FR , Kretschmer D , Heilbronner S , Smith TK , Lea SM , Palmer T
Ref : Nat Commun , 14 :8438 , 2023
Abstract : The type VII protein secretion system (T7SS) is found in many Gram-positive bacteria and in pathogenic mycobacteria. All T7SS substrate proteins described to date share a common helical domain architecture at the N-terminus that typically interacts with other helical partner proteins, forming a composite signal sequence for targeting to the T7SS. The C-terminal domains are functionally diverse and in Gram-positive bacteria such as Staphylococcus aureus often specify toxic anti-bacterial activity. Here we describe the first example of a class of T7 substrate, TslA, that has a reverse domain organisation. TslA is widely found across Bacillota including Staphylococcus, Enterococcus and Listeria. We show that the S. aureus TslA N-terminal domain is a phospholipase A with anti-staphylococcal activity that is neutralised by the immunity lipoprotein TilA. Two small helical partner proteins, TlaA1 and TlaA2 are essential for T7-dependent secretion of TslA and at least one of these interacts with the TslA C-terminal domain to form a helical stack. Cryo-EM analysis of purified TslA complexes indicate that they share structural similarity with canonical T7 substrates. Our findings suggest that the T7SS has the capacity to recognise a secretion signal present at either end of a substrate.
ESTHER : Garrett_2023_Nat.Commun_14_8438
PubMedSearch : Garrett_2023_Nat.Commun_14_8438
PubMedID: 38114483
Gene_locus related to this paper: staau-SAV0446

Title : Remodeling the polymer-binding cavity to improve the efficacy of PBAT-degrading enzyme - Yang_2023_J.Hazard.Mater_464_132965
Author(s) : Yang Y , Cheng S , Zheng Y , Xue T , Huang JW , Zhang L , Guo RT , Chen CC
Ref : J Hazard Mater , 464 :132965 , 2023
Abstract : Poly(butylene adipate-co-terephthalate) (PBAT) is among the most widely applied synthetic polyesters that are utilized in the packaging and agricultural industries, but the accumulation of PBAT wastes has posed a great burden to ecosystems. Using renewable enzymes to decompose PBAT is an eco-friendly solution to tackle this problem. Recently, we demonstrated that cutinase is the most effective PBAT-degrading enzyme and that an engineered cutinase termed TfCut-DM could completely decompose PBAT film to terephthalate (TPA). Here, we report crystal structures of a variant of leaf compost cutinase in complex with soluble fragments of PBAT, including BTa and TaBTa. In the TaBTa complex, one TPA moiety was located at a polymer-binding site distal to the catalytic center that has never been experimentally validated. Intriguingly, the composition of the distal TPA-binding site shows higher diversity relative to the one proximal to the catalytic center in various cutinases. We thus modified the distal TPA-binding site of TfCut-DM and obtained variants that exhibit higher activity. Notably, the time needed to completely degrade the PBAT film to TPA was shortened to within 24 h by TfCut-DM Q132Y (5813 mol per mol protein). Taken together, the structural information regarding the substrate-binding behavior of PBAT-degrading enzymes could be useful guidance for direct enzyme engineering.
ESTHER : Yang_2023_J.Hazard.Mater_464_132965
PubMedSearch : Yang_2023_J.Hazard.Mater_464_132965
PubMedID: 37979420
Gene_locus related to this paper: 9bact-g9by57

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

Title : Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures - Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
Author(s) : Song W , Yang Y , Heizer P , Tu Y , Weston TA , Kim JR , Munguia P , Jung H , Fong JL , Tran C , Ploug M , Beigneux AP , Young SG , Fong LG
Ref : Proc Natl Acad Sci U S A , 120 :e2219833120 , 2023
Abstract : Lipoprotein lipase (LPL) is secreted into the interstitial spaces by parenchymal cells and then transported into capillaries by GPIHBP1. LPL carries out the lipolytic processing of triglyceride (TG)-rich lipoproteins (TRLs), but the tissue-specific regulation of LPL is incompletely understood. Plasma levels of TG hydrolase activity after heparin injection are often used to draw inferences about intravascular LPL levels, but the validity of these inferences is unclear. Moreover, plasma TG hydrolase activity levels are not helpful for understanding LPL regulation in specific tissues. Here, we sought to elucidate LPL regulation under thermoneutral conditions (30 degreesC). To pursue this objective, we developed an antibody-based method to quantify (in a direct fashion) LPL levels inside capillaries. At 30 degreesC, intracapillary LPL levels fell sharply in brown adipose tissue (BAT) but not heart. The reduced intracapillary LPL levels were accompanied by reduced margination of TRLs along capillaries. ANGPTL4 expression in BAT increased fourfold at 30 degreesC, suggesting a potential explanation for the lower intracapillary LPL levels. Consistent with that idea, Angptl4 deficiency normalized both LPL levels and TRL margination in BAT at 30 degreesC. In Gpihbp1(-/-) mice housed at 30 degreesC, we observed an ANGPTL4-dependent decrease in LPL levels within the interstitial spaces of BAT, providing in vivo proof that ANGPTL4 regulates LPL levels before LPL transport into capillaries. In conclusion, our studies have illuminated intracapillary LPL regulation under thermoneutral conditions. Our approaches will be useful for defining the impact of genetic variation and metabolic disease on intracapillary LPL levels and TRL processing.
ESTHER : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
PubMedSearch : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
PubMedID: 36787365

Title : Steroids and dihydroisocoumarin glycosides from Xylaria sp. by the one strain many compounds strategy and their bioactivities - Gan_2023_Chin.J.Nat.Med_21_154
Author(s) : Gan D , Li C , Shu Y , Wang J , Wang C , Zhu L , Yang Y , Liu J , He B , Cai L , Ding Z
Ref : Chin J Nat Med , 21 :154 , 2023
Abstract : The fungus Xylaria sp. KYJ-15 was isolated from Illigera celebica. Based on the one strain many compounds (OSMAC) strategy, the strain was fermented on potato and rice solid media, respectively. As a result, two novel steroids, xylarsteroids A (1) and B (2), which are the first examples of C(28)-steroid with an unusual beta- and gamma-lactone ring, respectively, along with two new dihydroisocoumarin glycosides, xylarglycosides A (3) and B (4), were identified. Their structures were elucidated by spectroscopic methods, X-ray diffraction and electronic circular dichroism (ECD) experiments. All isolated compounds were evaluated for cytotoxicity, DPPH radical scavenging activity, acetylcholinesterase inhibitory and antimicrobial effect. Compound 1 exhibited potent AChE inhibitory activity with an IC(50) value of 2.61 +/- 0.05 micromol.L(-1). The beta-lactone ring unit of 1 is critical for its AChE inhibitory activity. The finding was further confirmed through exploring the interaction of 1 with AChE by molecular docking. In addition, both compounds 1 and 2 exhibited obvious antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) of 2 microg.mL(-1). Compounds 3 and 4 exhibited antibacterial activities against Staphylococcus aureus with MICs of 4 and 2 microg.mL(-1), respectively, which also exhibited DPPH radical scavenging activity comparable to the positive control with IC(50) values of 9.2 +/- 0.03 and 13.3 +/- 0.01 micromol.L(-1), respectively.
ESTHER : Gan_2023_Chin.J.Nat.Med_21_154
PubMedSearch : Gan_2023_Chin.J.Nat.Med_21_154
PubMedID: 36871983

Title : The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing - Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
Author(s) : Song W , Beigneux AP , Weston TA , Chen K , Yang Y , Nguyen LP , Guagliardo P , Jung H , Tran AP , Tu Y , Tran C , Birrane G , Miyashita K , Nakajima K , Murakami M , Tontonoz P , Jiang H , Ploug M , Fong LG , Young SG
Ref : Proc Natl Acad Sci U S A , 120 :e2313825120 , 2023
Abstract : Lipoprotein lipase (LPL), the enzyme that carries out the lipolytic processing of triglyceride-rich lipoproteins (TRLs), is synthesized by adipocytes and myocytes and secreted into the interstitial spaces. The LPL is then bound by GPIHBP1, a GPI-anchored protein of endothelial cells (ECs), and transported across ECs to the capillary lumen. The assumption has been that the LPL that is moved into capillaries remains attached to GPIHBP1 and that GPIHBP1 serves as a platform for TRL processing. In the current studies, we examined the validity of that assumption. We found that an LPL-specific monoclonal antibody (mAb), 88B8, which lacks the ability to detect GPIHBP1-bound LPL, binds avidly to LPL within capillaries. We further demonstrated, by confocal microscopy, immunogold electron microscopy, and nanoscale secondary ion mass spectrometry analyses, that the LPL detected by mAb 88B8 is located within the EC glycocalyx, distant from the GPIHBP1 on the EC plasma membrane. The LPL within the glycocalyx mediates the margination of TRLs along capillaries and is active in TRL processing, resulting in the delivery of lipoprotein-derived lipids to immediately adjacent parenchymal cells. Thus, the LPL that GPIHBP1 transports into capillaries can detach and move into the EC glycocalyx, where it functions in the intravascular processing of TRLs.
ESTHER : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
PubMedSearch : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
PubMedID: 37871217

Title : Study on the Expression Significance of Mb, BChE and cTnI in Myocardial Infarction and Their Relationship with Prognosis - Lu_2023_Altern.Ther.Health.Med__
Author(s) : Lu J , Song J , Liu F , Chen B , Dong Y , Yang Y
Ref : Altern Ther Health Med , : , 2023
Abstract : OBJECTIVE: Circulating biomarkers can be used as effective prediction tools for AMI diagnosis and prognosis, but their prediction efficiency is limited and still needs to be explored. The study aimed to investigate the changes of myocardial troponin I (cTn I), myoglobin (Mb), and butyryl cholinesterase (BChE) levels in patients with acute myocardial infarction (AMI) and its clinical predictive efficacy. METHODS: In this prospective cohort study, fifty patients with AMI who received PCI (AMI group) and 50 healthy subjects who underwent physical examination (reference group) during the same period were included. According to the occurrence of short-term major adverse cardiovascular events (MACE) during 6-month follow-up, they were divided into MACE group and non-MACE group . The difference of Mb, BChE, and cTnI levels was compared, and the ROC curve was drawn to analyze the prediction efficiency. RESULTS: Compared with the reference group or non-MACE group, Mb and cTnI significantly increased and BChE significantly decreased inAMI group and MACE group, respectively (P < .05). The AUC of Mb, cTnI and BChE in diagnosing AMI occurrence and prognosis were all > 0.75, and the sensitivity and specificity were all > 85.00%. cTnI, Mb and BChE have good diagnostic efficacy in disease occurrence and prognosis evaluation of AMI patients. CONCLUSIONS: High expression of Mb and cTnI and low expression of BChE can increase the risk of AMI incidence and MACE occurrence and have high diagnostic efficacy, which can be used as sensitive factors in clinical AMI diagnosis and evaluation. Thess provided a theoretical foundation for AMI diagnosis and MACE preventing in AMI patients.
ESTHER : Lu_2023_Altern.Ther.Health.Med__
PubMedSearch : Lu_2023_Altern.Ther.Health.Med__
PubMedID: 37708555

Title : Loss-of-Function Homozygous Variant in LPL Causes Type I Hyperlipoproteinemia and Renal Lipidosis - Wu_2023_Kidney.Int.Rep_8_2428
Author(s) : Wu H , Xu H , Lei S , Yang Z , Yang S , Du J , Zhou Y , Liu Y , Yang Y , Hu Z
Ref : Kidney Int Rep , 8 :2428 , 2023
Abstract : INTRODUCTION: Lipoprotein lipase (LPL) is an important enzyme in lipid metabolism, individuals with LPL gene variants could present type I hyperlipoproteinemia, lipemia retinalis, hepatosplenomegaly, and pancreatitis. To date, there are no reports of renal lipidosis induced by type I hyperlipoproteinemia due to LPL mutation. METHODS: Renal biopsy was conducted to confirm the etiological factor of nephrotic syndrome in a 44-year-old Chinese man. Lipoprotein electrophoresis, apoE genotype detection, and whole-exome sequencing were performed to confirm the dyslipidemia type and genetic factor. Analysis of the 3-dimensional protein structure and in vitro functional study were conducted to verify variant pathogenicity. RESULTS: Renal biopsy revealed numerous CD68 positive foam cells infiltrated in the glomeruli; immunoglobulin and complement staining were negative; and electron microscopy revealed numerous lipid droplets and cholesterol clefts in the cytoplasm of foam cells. Lipoprotein electrophoresis revealed that the patient fulfilled the diagnostic criteria of type I hyperlipoproteinemia. The apoE genotype of the patient was the sigma3/sigma3 genotype. Whole-exome sequencing revealed an LPL (c.292G > A, p.A98T) homozygous variant with alpha-helix instability and reduced post-heparin LPL activity but normal lipid uptake capability compared to the wild-type variant. CONCLUSION: LPL (c.292G > A, p.A98T) is a pathogenic variant that causes renal lipidosis associated with type I hyperlipoproteinemia. This study provides adequate evidence of the causal relationship between dyslipidemia and renal lesions. However, further research is needed to better understand the pathogenetic mechanism of LPL variant-related renal lesions.
ESTHER : Wu_2023_Kidney.Int.Rep_8_2428
PubMedSearch : Wu_2023_Kidney.Int.Rep_8_2428
PubMedID: 38025240
Gene_locus related to this paper: human-LPL

Title : Combined-methods elucidate the multi-organ toxicity of cylindrospermopsin (CYN) on Daphnia magna - He_2023_Environ.Pollut__121250
Author(s) : He Z , Chen Y , Huo D , Gao J , Xu Y , Yang R , Yang Y , Yu G
Ref : Environ Pollut , :121250 , 2023
Abstract : Global water bodies are now at risk from inevitable cyanobacterial blooms and their production of multiple cyanotoxins, in particular cylindrospermopsin (CYN). However, research on the CYN toxicity and its molecular mechanisms is still limited, whilst the responses of aquatic species against CYN are uncovered. By integrating behavioral observations, chemical detections and transcriptome analysis, this study demonstrated that CYN exerted multi-organ toxicity to model species, Daphnia magna. The present study confirmed that CYN could cause protein inhibition by undermining total protein contents, and altered the gene expression related to proteolysis. Meantime, CYN induced oxidative stress by increasing reactive oxidative species (ROS) level, decreasing the glutathione (GSH) concentration, and interfered with protoheme formation process molecularly. Neurotoxicity led by CYN was solidly determined by abnormal swimming patterns, reduced acetylcholinesterase (AChE), and downward expression of muscarinic acetylcholine receptor (CHRM). Importantly, for the first time, this research determined CYN directly interfered with energy metabolism in cladocerans. CYN distinctively reduced filtration and ingestion rate by targeting on heart and thoracic limbs, which declined the energy intake, and could be further displayed by the reduction of motional strength and the trypsin concentration. These phenotypic alterations were supported by transcriptomic profile, including the down-regulation of oxidative phosphorylation and ATP synthesis. Moreover, CYN was speculated to trigger the self-defense responses of D. magna, known as "abandon-ship" by moderating lipid metabolism and distribution. This study, overall, comprehensively demonstrated the CYN toxicity and the responses of D. magna against it, which is of great significance to the advancements of CYN toxicity knowledge.
ESTHER : He_2023_Environ.Pollut__121250
PubMedSearch : He_2023_Environ.Pollut__121250
PubMedID: 36813104

Title : Fungal polyketides produced by an endophytic fungus Phoma sp. associated with Gastrodia elata - Yang_2023_Fitoterapia_173_105793
Author(s) : Yang Y , Li GD , Shao YT , Sun ZW , Li LW , Li W , Li HT
Ref : Fitoterapia , 173 :105793 , 2023
Abstract : Two novel fungal polyketides, phometides A (1) and B (2), together with four known compounds (3-6), were isolated from the endophytic fungus Phoma sp. YUD17001 obtained from Gastrodia elata Blume. The structures were elucidated based on spectroscopic analyses, X-ray crystal diffraction, and time-dependent density functional theory/electronic circular dichroism (TDDFT/ECD) calculations. Structurally, phometide A (1) represented the first example of C(12) polyketide characterized by an unusual tetrahydrobenzofuran-3(2H)-one core with an alpha,beta-unsaturated ketone functionality, while phometide B (2) was an unprecedented molecule containing a 2-pentylcycloheptan-1-one scaffold. In an antimicrobial activity assay, phometide A (1) exhibited significant inhibitory activity against Staphylococcus aureus with MIC value of 4 microg/mL. Phometide B (2) showed moderate antifungal activity against Candida albicans with an MIC value of 16 microg/mL. Furthermore, compounds 1 and 2 were evaluated for their acetylcholinesterase inhibitory and cytotoxic activities.
ESTHER : Yang_2023_Fitoterapia_173_105793
PubMedSearch : Yang_2023_Fitoterapia_173_105793
PubMedID: 38158161

Title : Imaging the ANGPTL3\/8-mediated regulation of lipoprotein lipase in the heart -
Author(s) : Yang Y , Jung H , Konrad RJ , Fong LG , Young SG
Ref : J Lipid Res , :100467 , 2023
PubMedID: 37898405

Title : Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency - Xia_2023_J.Clin.Lipidol__
Author(s) : Xia Y , Zheng W , Du T , Gong Z , Liang L , Wang R , Yang Y , Zhang K , Lu D , Chen X , Sun Y , Xiao B , Qiu W
Ref : J Clin Lipidol , : , 2023
Abstract : BACKGROUND: Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. OBJECTIVE: To describe the manifestations and management of 19 pediatric patients with LPL-FCS. METHODS: LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. RESULTS: Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. CONCLUSIONS: This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy.
ESTHER : Xia_2023_J.Clin.Lipidol__
PubMedSearch : Xia_2023_J.Clin.Lipidol__
PubMedID: 37858495
Gene_locus related to this paper: human-LPL

Title : An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety - Shi_2022_Nanoscale.Adv_4_952
Author(s) : Shi L , Wu X , Li T , Wu Y , Song L , Zhang W , Yin L , Han W , Yang Y
Ref : Nanoscale Adv , 4 :952 , 2022
Abstract : Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (-1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.
ESTHER : Shi_2022_Nanoscale.Adv_4_952
PubMedSearch : Shi_2022_Nanoscale.Adv_4_952
PubMedID: 36131817

Title : Ternary heterostructures of 1D\/2D\/2D CuCo(2)S(4)\/CuS\/Ti(3)C(2) MXene: Boosted amperometric sensing for chlorpyrifos - Mi_2022_J.Hazard.Mater_438_129419
Author(s) : Mi Y , Zhao Y , Chen J , Li X , Yang Y , Gao F
Ref : J Hazard Mater , 438 :129419 , 2022
Abstract : Multicomponent heterogeneous Ti(3)C(2) transition metal carbide (MXene)-based materials are receiving extensive research attention due to their interesting synergistic interactions and catalytic properties. However, the morphology-controllable synthesis of heterostructures as structural stabilizers for Ti(3)C(2) MXene remains a challenge owing the complicated synthesis procedure. In this work, a kind of ternary heterogeneous nanomaterials CuCo(2)S(4)/CuS/Ti(3)C(2) MXene with a nanorod/nanoplate/nanosheet hybrid architecture is constructed through a one-step low-temperature solvothermal method. The well-designed ternary one-dimensional (1D)/two-dimensional (2D)/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterials exhibit synergistic improvements in substrate-catalyzed reactions for electrochemical acetylcholinesterase (AChE) biosensor. The Michaelis-Menten constant for the Nafion/AChE/CuCo(2)S(4)/CuS/Ti(3)C(2) MXene/GCE biosensor is 228 microM, which is smaller than ones reported in previous literatures, indicating a higher affinity of the fabricated enzyme biosensor to acetylthiocholine chloride. The biosensor exhibits a well linear relationship with chlorpyrifos concentration ranging from 2.852 x 10(-12) M to 2.852 x 10(-6) M. The multicomponent 1D/2D/2D CuCo(2)S(4)/CuS/Ti(3)C(2) MXene heteromaterial may shine a light in more electrochemical applications.
ESTHER : Mi_2022_J.Hazard.Mater_438_129419
PubMedSearch : Mi_2022_J.Hazard.Mater_438_129419
PubMedID: 35780734

Title : Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes - Yu_2022_PLoS.Pathog_18_e1010552
Author(s) : Yu X , Tong L , Zhang L , Yang Y , Xiao X , Zhu Y , Wang P , Cheng G
Ref : PLoS Pathog , 18 :e1010552 , 2022
Abstract : Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases.
ESTHER : Yu_2022_PLoS.Pathog_18_e1010552
PubMedSearch : Yu_2022_PLoS.Pathog_18_e1010552
PubMedID: 35679229

Title : Possible Charged Residue Switch for Acylglycerol Selectivity of Lipase MAS1 - Yang_2022_Appl.Biochem.Biotechnol__
Author(s) : Yang Y , Wang J , Yang B , Lan D , Wang Y
Ref : Appl Biochem Biotechnol , : , 2022
Abstract : The amino acid residues lining the substrate binding pocket play quite an important role during the lipase catalytic process. The conversion of those residues might cause a dramatic change in the lipase properties, such as the substrate selectivity of lipase. In our study, T237 residue sitting on the entrance of the catalytic pocket in lipase MAS1 was important for the catalytic performance. When replacing polar Thr with the positively charged Arg, the synthesis ratio of partial glycerides/triglycerides increases to 6.32 rather than 1.21 of MAS1 wild type (WT), as the substrate ratio of glycerol and fatty acids is 1:3. And the fatty acid preference shifted to long-chain substrates for mutant T237R rather than middle-chain substrates for MAS1 WT. Molecular docking analysis revealed that hydrophobic and side chain properties of Arg might contribute to the change of the MAS1 lipase catalytic performance. This work would pave a way for the accurate rational transformation of the lipases to produce value lipid for industrial application.
ESTHER : Yang_2022_Appl.Biochem.Biotechnol__
PubMedSearch : Yang_2022_Appl.Biochem.Biotechnol__
PubMedID: 35695952
Gene_locus related to this paper: 9actn-h0b8d4

Title : Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe - Yang_2022_Anal.Chem__
Author(s) : Yang Y , Zhang L , Wang J , Cao Y , Li S , Qin W , Liu Y
Ref : Analytical Chemistry , : , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.
ESTHER : Yang_2022_Anal.Chem__
PubMedSearch : Yang_2022_Anal.Chem__
PubMedID: 36121878

Title : Simultaneous Inhibitory Effects of All-Trans Astaxanthin on Acetylcholinesterase and Oxidative Stress - Wang_2022_Mar.Drugs_20_
Author(s) : Wang X , Zhang T , Chen X , Xu Y , Li Z , Yang Y , Du X , Jiang Z , Ni H
Ref : Mar Drugs , 20 : , 2022
Abstract : Alzheimers disease is a global neurodegenerative health concern. To prevent the disease, the simultaneous inhibition of acetylcholinesterase and oxidative stress is an efficient approach. In this study, the inhibition effect of all-trans astaxanthin mainly from marine organisms on acetylcholinesterase and oxidative stress was evaluated by a chemical-based method in vitro and cell assay model. The results show that all-trans astaxanthin was a reversible competitive inhibitor and exhibited a strong inhibition effect with half inhibitory concentration (IC(50) value) of 8.64 micromol/L. Furthermore, all-trans astaxanthin inhibited oxidative stress through reducing malondialdehyde content and increasing the activity of superoxide dismutase as well as catalase. All-trans astaxanthin could induce the changes of the secondary structure to reduce acetylcholinesterase activity. Molecular-docking analysis reveals that all-trans astaxanthin prevented substrate from binding to acetylcholinesterase by occupying the space of the active pocket to cause the inhibition. Our finding suggests that all-trans astaxanthin might be a nutraceutical supplement for Alzheimers disease prevention.
ESTHER : Wang_2022_Mar.Drugs_20_
PubMedSearch : Wang_2022_Mar.Drugs_20_
PubMedID: 35447920

Title : Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells - Song_2022_J.Clin.Invest_132_
Author(s) : Song W , Beigneux AP , Winther AL , Kristensen KK , Gronnemose AL , Yang Y , Tu Y , Munguia P , Morales J , Jung H , de Jong PJ , Jung CJ , Miyashita K , Kimura T , Nakajima K , Murakami M , Birrane G , Jiang H , Tontonoz P , Ploug M , Fong LG , Young SG
Ref : J Clinical Investigation , 132 : , 2022
Abstract : GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.
ESTHER : Song_2022_J.Clin.Invest_132_
PubMedSearch : Song_2022_J.Clin.Invest_132_
PubMedID: 35229724

Title : Sitagliptin Alleviates Radiation-Induced Intestinal Injury by Activating NRF2-Antioxidant Axis, Mitigating NLRP3 Inf--lammasome Activation, and Reversing Gut Microbiota Disorder - Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
Author(s) : Huang S , Huang Y , Lin W , Wang L , Yang Y , Li P , Xiao L , Chen Y , Chu Q , Yuan X
Ref : Oxid Med Cell Longev , 2022 :2586305 , 2022
Abstract : Radiation-induced intestinal injury is a common and critical complication of radiotherapy for pelvic or abdominal tumors, with limited therapeutic strategies and effectiveness. Sitagliptin, a dipeptidyl peptidase IV (DPP4) inhibitor, has previously been reported to alleviate total body irradiation- (TBI-) induced damage of hematopoietic system in mice, but its effect on radiation-induced intestinal injury remains unclear. In this study, we confirmed that Sitagliptin could not only protect mice from death and weight loss caused by whole abdominal irradiation (WAI) but also improve the morphological structure of intestine and the regeneration ability of enterocytes. In addition, Sitagliptin significantly inhibited the production of radiation-induced proinflammatory cytokines and reduced the number of apoptotic intestinal epithelial cells and gamma-H2AX expression. In vitro, we demonstrated that Sitagliptin protected HIEC-6 cells from ionizing radiation, resulting in increased cell viability and reduced DNA damage. Mechanistically, the radiation protection of Sitagliptin might be related to the upregulation of NRF2 level and the decrease of NLRP3 inflammasome activity. Importantly, Sitagliptin significantly restored radiation-induced changes in bacterial composition. In conclusion, our results suggested that Sitagliptin could reduce WAI-induced intestinal injury in mice, which may provide novel therapeutic strategy for radiation-induced intestinal injury.
ESTHER : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedSearch : Huang_2022_Oxid.Med.Cell.Longev_2022_2586305
PubMedID: 35620578

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

Title : Tannic acid reduced apparent protein digestibility and induced oxidative stress and inflammatory response without altering growth performance and ruminal microbiota diversity of Xiangdong black goats - Wang_2022_Front.Vet.Sci_9_1004841
Author(s) : Wang Z , Yin L , Liu L , Lan X , He J , Wan F , Shen W , Tang S , Tan Z , Yang Y
Ref : Front Vet Sci , 9 :1004841 , 2022
Abstract : The present study was performed to evaluate the impacts of tannic acid (TA) supplementation at different levels on the growth performance, physiological, oxidative and immunological metrics, and ruminal microflora of Xiangdong black goats. Twenty-four goats were randomly assigned to four dietary treatments: the control (CON, basal diet), the low-dose TA group [TAL, 0.3 % of dry matter (DM)], the mid-dose TA group (TAM, 0.6 % of DM), and the high-dose TA group (TAH, 0.9 % of DM). Results showed that the growth performance was unaffected (P > 0.05) by adding TA, whilst the 0.3 % and 0.6 % TA supplementation significantly decreased (P < 0.05) the apparent digestibility of crude protein (CP) and ruminal NH(3)-N concentration, and raised (P < 0.05) the level of total volatile fatty acid (TVFA) in rumen. The increments of alanine aminotransferase (ALT), triglyceride (TG), cortisol (CORT), total antioxidant capacity (T-AOC), interleukin (IL)-1beta, IL-6, and serumamyloid A (SAA), and decrements of globulin (GLB), immunoglobulin G (IgG), cholinesterase (CHE), glutathione reductase (GR), creatinine (CRE), growth hormone (GH), high-density lipoprotein cholesterol (HDLC), and insulin-like growth factor 1 (IGF-1) to different extents by TA addition were observed. Although the Alpha and Beta diversity of rumen bacterial community remained unchanged by supplementing TA, the relative abundance of the predominant genus Prevotella_1 was significantly enriched (P < 0.05) in TAL. It could hence be concluded that the TA supplementation in the present trial generally decreased CP digestion and caused oxidative stress and inflammatory response without influencing growth performance and ruminal microbiota diversity. More research is needed to explore the premium dosage and mechanisms of effects for TA addition in the diet of goats.
ESTHER : Wang_2022_Front.Vet.Sci_9_1004841
PubMedSearch : Wang_2022_Front.Vet.Sci_9_1004841
PubMedID: 36187804

Title : A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism - Young_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2211136119
Author(s) : Young SG , Song W , Yang Y , Birrane G , Jiang H , Beigneux AP , Ploug M , Fong LG
Ref : Proc Natl Acad Sci U S A , 119 :e2211136119 , 2022
Abstract : GPIHBP1, a protein of capillary endothelial cells (ECs), is a crucial partner for lipoprotein lipase (LPL) in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1, which contains a three-fingered cysteine-rich LU (Ly6/uPAR) domain and an intrinsically disordered acidic domain (AD), captures LPL from within the interstitial spaces (where it is secreted by parenchymal cells) and shuttles it across ECs to the capillary lumen. Without GPIHBP1, LPL remains stranded within the interstitial spaces, causing severe hypertriglyceridemia (chylomicronemia). Biophysical studies revealed that GPIHBP1 stabilizes LPL structure and preserves LPL activity. That discovery was the key to crystallizing the GPIHBP1-LPL complex. The crystal structure revealed that GPIHBP1's LU domain binds, largely by hydrophobic contacts, to LPL's C-terminal lipid-binding domain and that the AD is positioned to project across and interact, by electrostatic forces, with a large basic patch spanning LPL's lipid-binding and catalytic domains. We uncovered three functions for GPIHBP1's AD. First, it accelerates the kinetics of LPL binding. Second, it preserves LPL activity by inhibiting unfolding of LPL's catalytic domain. Third, by sheathing LPL's basic patch, the AD makes it possible for LPL to move across ECs to the capillary lumen. Without the AD, GPIHBP1-bound LPL is trapped by persistent interactions between LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the abluminal surface of ECs. The AD interrupts the HSPG interactions, freeing LPL-GPIHBP1 complexes to move across ECs to the capillary lumen. GPIHBP1 is medically important; GPIHBP1 mutations cause lifelong chylomicronemia, and GPIHBP1 autoantibodies cause some acquired cases of chylomicronemia.
ESTHER : Young_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2211136119
PubMedSearch : Young_2022_Proc.Natl.Acad.Sci.U.S.A_119_e2211136119
PubMedID: 36037340

Title : Preparation, characterization and bioactivities of selenized polysaccharides from Lonicera caerulea L. fruits - Shao_2022_Int.J.Biol.Macromol__
Author(s) : Shao C , Zhong J , Liu J , Yang Y , Li M , YangYu , Xu Y , Wang L
Ref : Int J Biol Macromol , : , 2022
Abstract : Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO(3)-Na(2)SeO(3) method, where the selenium (Se) contents were 228 +/-24 and 353 +/- 36 microg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 10(4), 5.6 10(4), and 5.1 10(4) kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE.
ESTHER : Shao_2022_Int.J.Biol.Macromol__
PubMedSearch : Shao_2022_Int.J.Biol.Macromol__
PubMedID: 36403769

Title : Endothelial lipase promotes acute myeloid leukemia progression through metabolic reprogramming - Shang_2022_Neoplasma__
Author(s) : Shang SQ , Yang Y , Yang XJ , Shi XD , Chen YS , Wang YY
Ref : Neoplasma , : , 2022
Abstract : Metabolic reprogramming occurs in the clonal evolution of acute myeloid leukemia (AML), which contributes to cell survival under metabolic stress and the development of drug resistance. Leukemic cells exhibit various metabolic profiles, which involve multiple metabolic pathways due to the heterogeneity of AML. However, studies on metabolic targets for AML treatment are mostly focused on glycolysis at present. In this work, we established conditional knock-in AML mouse models harboring Dnmt3aR878H/WT, NrasG12D/WT, and both of the mutations, respectively. Transcriptomic analysis of Gr1+ cells from bone marrow was performed afterward to screen interested metabolic pathways and target genes. Candidate genes were studied using the CRISPR/Cas9 technique, quantitative real-time RT-PCR, and flow cytometric analyses. We revealed that multiple metabolic pathways were affected in AML mice, including lipid metabolism. Endothelial lipase (LIPG) was obviously upregulated in leukemic cells from AML mice with Dnmt3a mutation. We performed knockout of LIPG in OCI-AML3 cells carrying DNMT3A R882C mutation by using the CRISPR/Cas9 technique. Depletion of LIPG led to proliferation inhibition, apoptosis, damage of antioxidant capacity, and myeloid differentiation in OCI-AML3 cells. LIPG might serve as a potential metabolic target for the treatment of AML with abnormal lipid metabolism.
ESTHER : Shang_2022_Neoplasma__
PubMedSearch : Shang_2022_Neoplasma__
PubMedID: 35263993

Title : Associations between acetylcholinesterase-1 mutations and chlorpyrifos resistance in beet armyworm, Spodoptera exigua - Teng_2022_Pestic.Biochem.Physiol_184_105105
Author(s) : Teng H , Zuo Y , Jin Z , Wu Y , Yang Y
Ref : Pestic Biochem Physiol , 184 :105105 , 2022
Abstract : Control of the beet armyworm, Spodoptera exigua depends heavily on chemical insecticides. Chlorpyrifos, an acetylcholinesterase (AChE) inhibitor, has been used in beet armyworm control for many years in China. Here we describe high level resistance to chlorpyrifos in a S. exigua strain, FX19-R, which was developed from a field-collected Chinese strain (FX) by selection with chlorpyrifos in the laboratory. FX19-R showed 1001-fold resistance to chlorpyrifos compared with the laboratory reference strain WH-S. The esterase inhibitor triphenyl phosphate (TPP) provided significant but small synergism (only 3.5-fold) for chlorpyrifos and neither of the glutathione s-transferase depletor diethyl maleate and the cytochrome P450s inhibitor piperonyl butoxide provided any detectable synergism, indicating that AChE insensitivity may play the major role in the resistance in FX19-R. Consistent with this, an amino acid substitution, F443Y (F331Y in standard Torpedo californica numbering) in AChE1 was identified in the FX19-R strain and shown to be tightly linked to chlorpyrifos resistance. Precisely homologous substitutions have been associated with organophosphate resistance in other pest species. A novel amino acid substitution, G311S (or G198S in standard numbering), was also identified in the reference strain WH-S. Recombinantly expressed AChE1 proteins carrying the G311S and F443Y substitutions were about 4.2-fold and 210-fold less sensitive to inhibition by chlorpyrifos oxon than wild-type AChE1, respectively. These results enhance our understanding of the mechanisms of chlorpyrifos resistance and provide a basis for resistance management based on monitoring the F443Y and G311S substitutions.
ESTHER : Teng_2022_Pestic.Biochem.Physiol_184_105105
PubMedSearch : Teng_2022_Pestic.Biochem.Physiol_184_105105
PubMedID: 35715044
Gene_locus related to this paper: spolt-ACHE1

Title : Enantioselective bioaccumulation and toxicity of rac-sulfoxaflor in zebrafish (Danio rerio) - Deng_2022_Sci.Total.Environ_817_153007
Author(s) : Deng Y , Wang R , Song B , Yang Y , Hu D , Xiao X , Chen X , Lu P
Ref : Sci Total Environ , 817 :153007 , 2022
Abstract : Sulfoxaflor is a fourth-generation neonicotinoid insecticide mainly used to control sap-feeding pests. In this study, four stereoisomers of sulfoxaflor were separated using HPLC, and the absolute configurations of three stereoisomers were identified via single-crystal X-ray diffraction. First, the stability and isomerization of the four enantiomers and rac-sulfoxaflor in water and seven organic solvents were investigated. All enantiomers were extremely unstable in water with isomerization rates above 20%. The racemate did not isomerize in any of the solutions and was stable in water (degradation rate less than 7%). Therefore, we studied the acute toxicity, enantioselective behavior, and enzymatic activities of rac-sulfoxaflor in zebrafish. The bioaccumulation experiment demonstrated that the bioconcentration of sulfoxaflor in zebrafish was enantioselective, and the four enantiomers accumulated in zebrafish in the order (+)-2S,3S-sulfoxaflor > (-)-2R,3R-sulfoxaflor > (+)-2R,3S-sulfoxaflor > (-)-2S,3R-sulfoxaflor. The effect of rac-sulfoxaflor on the enzymatic activities of zebrafish showed that superoxide dismutase and glutathione-S-transferase activities and malondialdehyde content were significantly enhanced as compared to those in control, whereas acetylcholinesterase was significantly reduced in the sulfoxaflor exposure treatment (p < 0.05), indicating that sulfoxaflor caused oxidative lesions and induced enzymatic activity in zebrafish. This study provides important information on the enantioselective behavior and toxic effects of sulfoxaflor, which can help assess the potential ecological risk of chiral pesticides to aquatic organisms.
ESTHER : Deng_2022_Sci.Total.Environ_817_153007
PubMedSearch : Deng_2022_Sci.Total.Environ_817_153007
PubMedID: 35026276

Title : Site-selective covalently immobilized alpha 1A adrenergic receptor for thermodynamic and extra-thermodynamic study of four ligands binding to the receptor by chromatographic methods - Yuan_2022_J.Chromatogr.A_1665_462827
Author(s) : Yuan X , Shayiranbieke A , Xu R , Jiang H , Yang Y , Zhang Y , Yin G , Zhao X
Ref : Journal of Chromatography A , 1665 :462827 , 2022
Abstract : Immobilized G protein-coupled receptor is a versatile tool to study ligand-receptor interactions. In this work, we synthesized the immobilized alpha 1A adrenergic receptor (alpha(1A)-AR), a GPCR subtype mediating smooth muscle contraction, through a site-selective covalent method that relies on the reaction between haloalkane dehalogenase tagged alpha(1A)-AR and macroporous silica gel coated with 6-chlorohexanoic acid. To investigate thermodynamic and extra-thermodynamic parameters for ligand binding, we utilized the covalently immobilized receptor as stationary phase to perform frontal analysis and injection-amount dependent analysis as well as compared with the random immobilization method. Terazosin gave the association constant of 1.48 x 10(5) M(-1) to alpha(1A)-AR, indicating that the oriented immobilization of alpha(1A)-AR enhances the ligand-binding activity by one order of magnitude in comparison with the random immobilization method (7.9 x 10(4) M(-1)). The binding of phentolamine and tamsulosin to the receptor was accompanied by a large absolute heat capacity (deltaC(p)) of 1.28 +/- 0.23 kJ mol(-1), demonstrating that the binding enthalpy and entropy appear to compensate for one another. These results indicated that the covalent immobilization of the receptor onto solid support has a profound impact on the ligand-binding activity of the receptor and the determination of ligand-receptor binding parameters. The receptor immobilized through the site-selective method will act as a benchmark for chromatographic determination of binding parameters in ligand-receptor interactions and can be used as an effective approach for rapid analysis of drug-protein interactions with high accuracy.
ESTHER : Yuan_2022_J.Chromatogr.A_1665_462827
PubMedSearch : Yuan_2022_J.Chromatogr.A_1665_462827
PubMedID: 35078002

Title : Intact aleurone cells limit the hydrolysis of endogenous lipids in wheat bran during storage - Chen_2022_Food.Res.Int_161_111799
Author(s) : Chen Z , Shen J , Yang Y , Wang H , Xu B
Ref : Food Res Int , 161 :111799 , 2022
Abstract : This work aimed to elucidate the effect of aleurone cell integrity on the hydrolysis of endogenous lipids in wheat bran and flour. The distribution of lipases in the bran dissected layers (aleurone layer, outer pericarp and intermediate layer) and the lipid hydrolysis in the bran fractions and flour containing the aleurone cells with different integrity were investigated. The results indicated that 80% of the lipase activities in bran layers were associated with the aleurone layer. After centrifugal impact milling, the aleurone layer in commercial bran could be detached into the monolayer cell clusters with decreasing integrities as the particle size decreased. In the oil phase, intact aleurone cells did not limit the lipase activities in the bran fractions because the oil could penetrate into aleurone cells. During storage, the hydrolysis rates of endogenous lipids in the bran fractions and their mixed flour increased as the integrity of aleurone cells decreased; while after the aleurone cells were broken, the hydrolysis rates of endogenous lipids increased to be in line with the lipase activities in bran fractions, indicating the limitation of intact aleurone cells on lipid hydrolysis. These results gave a new understanding of the effect of aleurone cell structure on the interaction between lipases and lipids in wheat bran, and will facilitate the production of stable wheat bran and whole wheat flour.
ESTHER : Chen_2022_Food.Res.Int_161_111799
PubMedSearch : Chen_2022_Food.Res.Int_161_111799
PubMedID: 36192945

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

Title : Association of the Cholinergic Anti-Inflammatory Pathway Activity with Proinflammatory Factors and Prognosis of Patients with Acute Respiratory Distress Syndrome - Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
Author(s) : Yang Y , Zhang J , Yang X , Yang J
Ref : Evid Based Complement Alternat Med , 2022 :8302701 , 2022
Abstract : OBJECTIVE: The cholinergic anti-inflammatory pathway (CAP) has been shown to modulate cytokine release by activating alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) in monocytes/macrophages. However, their association with proinflammatory factors and prognosis in patients with acute respiratory distress syndrome (ARDS) has not been clarified. Here, we explored the correlation between CAP activity, proinflammatory factors, and the prognosis of ARDS patients. METHODS: The data of patients with ARDS (n = 65; underwent treatment) and healthy individuals (the control group; n = 65; underwent routine physical examination) at the Chongqing People's Hospital were investigated. Based on the survival status, ARDS patients were divided into a death ARDS group (n = 22) and a survival ARDS group (n = 43), and based on the diagnostic criteria of ARDS, the patients were also divided into a severe ARDS group (n = 30) and a mild-to-moderate ARDS group (n = 35). The levels of acetylcholine (ACh), acetylcholinesterase (AChE), and alpha7nAChR mRNA in peripheral blood monocytes were assessed. The levels of TNF-alpha and IL-6 in peripheral serum and peripheral monocytes were detected by ELISA and Western blot tests. The association between alpha7nAChR and inflammatory factors and prognosis was analyzed. The receiver-operating characteristic (ROC) curve was used to evaluate the reliability of CAP-related factors in predicting the survival status of ARDS patients. RESULTS: Compared with the control group, the levels of ACh, AChE, and alpha7nAChR mRNA of the ARDS group were significantly decreased. And, the ACh, AChE, and alpha7nAChR mRNA levels in the death/severe ARDS group were significantly lower than in the survival/mild-to-moderate ARDS group. However, the levels of TNF-alpha and IL-6 were significantly higher in the severe/death ARDS group. Furthermore, we observed that CAP-related factors were negatively correlated with the levels of IL-6 and TNF-alpha in peripheral serum in the ARDS group. The ROC curve showed that CAP-related factors were reliable markers for predicting the survival status of ARDS patients. CONCLUSION: The related factors of the cholinergic anti-inflammatory pathway were significantly decreased in patients with ARDS, suggesting the ACh, AChE, and alpha7nAChR levels as potential indicators to evaluate the severity and prognosis status of ARDS patients.
ESTHER : Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
PubMedSearch : Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701
PubMedID: 35664939

Title : The Therapeutic Effects of Seven Lycophyte Compounds on Cell Models of Alzheimer's Disease - Guo_2022_J.Alzheimers.Dis__
Author(s) : Guo Q , Cai Q , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : J Alzheimers Dis , : , 2022
Abstract : BACKGROUND: As an acetylcholinesterase inhibitor (AChEI), Huperzine-A (Hup-A) is marketed for treatment of mild to moderate Alzheimer's disease (AD) for decades in China. However, Hup-A causes some side effects. To search for new analogs or derivatives of Hup-A, we produced five Lycophyte alkaloids and two analogues by chemical synthesis: Lyconadins A-E, H-R-NOB, and 2JY-OBZ4. OBJECTIVE: To systematically evaluated the therapeutic effects of the seven compounds on AD cell models. METHODS: We assessed the effects of the seven compounds on cell viability via CCK-8 kit and used HEK293-hTau cells and N2a-hAPP cells as AD cell models to evaluate their potential therapeutic effects. We examined their effects on cholinesterase activity by employing the mice primary neuron. RESULTS: All compounds did not affect cell viability; in addition, Lyconadin A and 2JY-OBZ4 particularly increased cell viability. Lyconadin D and Lyconadin E restored tau phosphorylation at Thr231, and H-R-NOB and 2JY-OBZ4 restored tau phosphorylation at Thr231 and Ser396 in GSK-3beta-transfected HEK293-hTau cells. 2JY-OBZ4 decreased the level of PP2Ac-pY307 and increased the level of PP2Ac-mL309, supporting that 2JY-OBZ4 may activate PP2A. Lyconadin B, Lyconadin D, Lyconadin E, H-R-NOB, and 2JY-OBZ4 increased sAbetaPPalpha level in N2a-hAPP cells. 2JY-OBZ4 decreased the levels of BACE1 and sAbetaPPbeta, thereby reduced Abeta production. Seven compounds exhibited weaker AChE activity inhibition efficiency than Hup-A. Among them, 2JY-OBZ4 showed the strongest AChE inhibition activity with an inhibition rate of 17% at 10microM. CONCLUSION: Among the seven lycophyte compounds, 2JY-OBZ4 showed the most expected effects on promoting cell viability, downregulating tau hyperphosphorylation, and Abeta production and inhibiting AChE in AD.
ESTHER : Guo_2022_J.Alzheimers.Dis__
PubMedSearch : Guo_2022_J.Alzheimers.Dis__
PubMedID: 36189599

Title : Novel small molecular compound 2JY-OBZ4 alleviates AD pathology in cell models via regulating multiple targets - Guo_2022_Aging.(Albany.NY)_14_
Author(s) : Guo Q , Wu G , Huang F , Wei Z , Wang JZ , Zhang B , Liu R , Yang Y , Wang X , Li HL
Ref : Aging (Albany NY) , 14 : , 2022
Abstract : Alzheimer's disease (AD) is the most common form of neurodegenerative dementia, characterized by cognitive deficits and memory dysfunction, which is clinically incurable so far. Novel small molecular compound 2JY-OBZ4 is one of structural analogue of Huperzine A (Hup-A), an anti-AD drug in China. In our previous work, 2JY-OBZ4 exhibited potent effects on tau hyperphosphorylation, Abeta production and acetylcholinesterase (AChE) activity. However, 2JY-OBZ4's anti-AD effects and the underlying molecular mechanisms remain unclear. We here reported that 2JY-OBZ4 resisted tau hyperphosphorylation at Thr181 and Ser396 sites in HEK293-hTau cells transfected with GSK-3beta, decreased tau phosphorylation via upregulating the activity of PP2A in HEK293-hTau cells and reduced Abeta production through regulating protein levels of APP cleavage enzymes in N2a-hAPP cells. Meanwhile, we found that 2JY-OBZ4 had no adverse effects on cell viability of mice primary neuron even at high concentration, and ameliorated synaptic loss induced by human oligomeric Abeta42. 2JY-OBZ4 had moderate AChE inhibitory activity with the half maximal inhibitory concentration (IC50) to be 39.48 microg/ml in vitro, which is more than two times higher than Hup-A. Together, 2JY-OBZ4 showed promising therapeutic effects in AD cell models through regulating multiple targets. The research provides a new candidate for the therapeutic development of AD.
ESTHER : Guo_2022_Aging.(Albany.NY)_14_
PubMedSearch : Guo_2022_Aging.(Albany.NY)_14_
PubMedID: 36227154

Title : The suppression of pancreatic lipase-related protein 2 ameliorates experimental hepatic fibrosis in mice - Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
Author(s) : Ding Z , Cheng R , Liu J , Zhao Y , Ge W , Yang Y , Xu X , Wang S , Zhang J
Ref : Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids , 1867 :159102 , 2022
Abstract : Quiescent hepatic stellate cells (HSCs) store vitamin A as lipid droplets in the cytoplasm. When activated, these cells lose vitamin A and exhibit an increased capacity for proliferation, mobility, contractility, and the synthesis of collagen and other components of the extracellular matrix. Our previous work demonstrated that the lipid hydrolytic gene pancreatic lipase-related protein 2 (mPlrp2) is involved in the hydrolysis of retinyl esters (REs) in the liver. Here, we showed that bile duct ligation (BDL)-induced liver injury triggered the conditional expression of mPlrp2 in livers and describe evidence of a strong relationship between the expression of mPlrp2 and Acta-2, a marker for activated HSCs. RNA interference targeting mPlrp2 inhibited HSC activation and ameliorated hepatic fibrosis induced by BDL in mice. Liver BDL markedly reduced the adenosine level and increased the ratio between S-adenosyl-L-methionine (SAM) and S-adenosyl-L-homocysteine (SAH). Chromatin immunoprecipitation (ChIP) analysis demonstrated an increase in trimethylated histone H3K4 at the mPlrp2 promoter in BDL mice, which was associated with the conditional expression of mPlrp2 in the liver. SAM, a well-known hepatoprotective substance, inhibited mPlrp2 expression and reduced RE hydrolysis in mice with hepatic fibrosis induced by chronic CCl(4) treatment. Liver fibrosis induced by CCl(4) or BDL was improved in Plrp2(-/-) mice. Our results reveal that mPlrp2 suppression is a potential approach for treating hepatic fibrosis.
ESTHER : Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
PubMedSearch : Ding_2022_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids_1867_159102
PubMedID: 34995790
Gene_locus related to this paper: mouse-LIPR2

Title : Substrate-Binding Mode of a Thermophilic PET Hydrolase and Engineering the Enzyme to Enhance the Hydrolytic Efficacy - Zeng_2022_ACS.Catal_12_3033
Author(s) : Zeng W , Li X , Yang Y , Min J , Huang JW , Liu W , Niu D , Yang X , Han X , Zhang L , Dai L , Chen CC , Guo RT
Ref : ACS Catal , 12 :3033 , 2022
Abstract : Polyethylene terephthalate (PET) is among the most extensively produced plastics, but huge amounts of PET wastes that have accumulated in the environment have become a serious threat to the ecosystem. Applying PET hydrolytic enzymes to depolymerize PET is an attractive measure to manage PET pollution, and searching for more effective enzymes is a prerequisite to achieve this goal. A thermostable cutinase that originates from the leaf-branch compost termed ICCG is the most effective PET hydrolase reported so far. Here, we illustrated the crystal structure of ICCG in complex with the PET analogue, mono(2-hydroxyethyl)terephthalic acid, to reveal the enzyme-substrate interaction network. Furthermore, we applied structure-based engineering to modify ICCG and screened for variants that exhibit higher efficacy than the parental enzyme. As a result, several variants with the measured melting temperature approaching 99 C and elevated PET hydrolytic activity were obtained. Finally, crystallographic analyses were performed to reveal the structural stabilization effects mediated by the introduced mutations. These results are of importance in the context of understanding the mechanism of action of the thermostable PET hydrolytic enzyme and shall be beneficial to the development of PET biodegradation platforms.
ESTHER : Zeng_2022_ACS.Catal_12_3033
PubMedSearch : Zeng_2022_ACS.Catal_12_3033
Gene_locus related to this paper: 9bact-g9by57

Title : New fluorescent probe with recognition moiety of bipiperidinyl reveals the rise of hepatocellular carboxylesterase activity during heat shock - Liu_2022_Biosens.Bioelectron_211_114392
Author(s) : Liu Y , He Z , Yang Y , Li X , Li Z , Ma H
Ref : Biosensors & Bioelectronics , 211 :114392 , 2022
Abstract : Heat shock is a heat-related pathology characterized by a high body temperature and an obvious change of many enzymatic activities. Carboxylesterase (CE), as the major hydrolase in liver, is responsible for the hydrolysis of many drugs or the detoxification of various toxins from all organs. However, the correlation between heat shock and the CE activity in cells remains unknown, mainly due to the lack of a suitable research approach. Herein, a new water-soluble fluorescence probe, MYO-CE, with a specific bipiperidinyl recognition moiety has been developed for detecting the CE activity. MYO-CE reacted selectively with CE instead of other esterase, causing a large fluorescence off-on response at 560 nm with a detection limit of 0.39 U/mL. The applicability of MYO-CE for cell imaging was demonstrated by monitoring the alteration of the hepatocellular CE activity under inflammation. More importantly, we investigated the change of the CE activity during heat shock, uncovering a significant increase for the first time. This finding was further validated by a commercial colorimetric kit assay. The proposed probe shows a promising prospect for the CE study in cells under different pathological conditions.
ESTHER : Liu_2022_Biosens.Bioelectron_211_114392
PubMedSearch : Liu_2022_Biosens.Bioelectron_211_114392
PubMedID: 35609457

Title : Different toxicity to liver and gill of zebrafish by selenium nanoparticles derived from bio\/chemical methods - Fan_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : Fan S , Yang Y , Sun L , Yu B , Dai C , Qu Y
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : With the wide application of selenium nanoparticles (SeNPs) in pharmaceutical fields, the toxicity assessment is of great significance. In this study, zebrafish were selected as model organisms to compare the toxicity of SeNPs derived from biological and chemical methods. The results showed that the size of bio-SeNPs was about 5-fold bigger than chem-SeNPs. When exposed to SeNPs for 96 h, LC(50) of bio-SeNPs and chem-SeNPs was 1.668 mg/L and 0.699 mg/L, respectively. Compared with the control, the results showed a significant increase in oxidative toxicity index (P < 0.05), such as glutathione (GSH), superoxide dismutase (SOD) of the liver, and gill in SeNPs-treated group. The neurotoxicity index, such as acetylcholinesterase (AchE) and Na(+)-K(+)-ATP enzyme activity, was significantly decreased both in the liver and gill (P < 0.05). It was found that the toxicity of bio-SeNPs to the liver and gill of zebrafish was lower than chem-SeNPs and the toxicity to the liver was higher than gill. In this study, the toxicity of chem-SeNPs and bio-SeNPs to the target organs of zebrafish were systematically evaluated, which provided the basis for the safe application of SeNPs synthesized by different pathways.
ESTHER : Fan_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Fan_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35445301

Title : Alternative splicing of a carboxyl\/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus - Wei_2022_Insect.Sci__
Author(s) : Wei P , Zeng X , Han H , Yang Y , Zhang Y , He L
Ref : Insect Sci , : , 2022
Abstract : Detoxification plays a crucial role in agricultural pests to withstand the pesticides, and cytochrome P450s, carboxyl/cholinesterases (CCEs), and glutathione-S-transferases are the main proteins responsible for their detoxification ability. The activity of CCEs can be up-regulated, down-regulated, or modified by mutation. However, few studies have examined the role of alternative splicing in altering the properties of CCEs. We identified two variants of TcCCE23 in Tetranychus cinnabarinus: a long version (CCE23-V1) and a short version that is 18 nucleotides shorter than CCE23-V1 (CCE23-V2). Whether splicing affects the activity of TcCCE23 remains unclear. Overexpression of CCE23-V2 in fenpropathrin resistant T. cinnabarinus revealed that splicing affected the detoxification of fenpropathrin by CCE23-V2. The mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down (43.2% +/- 3.3%) via injection of CCE23-dsRNA compared with the control group injected with GFP-dsRNA under fenpropathrin exposure; however, the down-regulation of CCE23-V1 (61.3 +/- 6.3%) by CCE23-siRNA had no such effect, indicating CCE23-V2 plays a greater role in xenobiotic metabolism than CCE23-V1. The tolerance of flies overexpressing CCE23-V2 to fenpropathrin (LD(50) = 19.47 microg/g) was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies (LD(50) = 13.11 microg/g). Molecular docking analysis showed that splicing opened a 'gate' that enlarge the substrate binding cavity of CCE23-V2, which might enhance the ability of CCE23-V2 to harbor fenpropathrin molecules. These findings suggest that splicing might enhance the detoxifying capability of TcCCE23. Generally, our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs. This article is protected by copyright. All rights reserved.
ESTHER : Wei_2022_Insect.Sci__
PubMedSearch : Wei_2022_Insect.Sci__
PubMedID: 36544383

Title : Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals - Yang_2022_ACS.Omega_7_30720
Author(s) : Yang Y , Liu J , Liu L , Zhou Y , Zhang L , Zhong Y , Zhao D , Wang Y
Ref : ACS Omega , 7 :30720 , 2022
Abstract : A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs.
ESTHER : Yang_2022_ACS.Omega_7_30720
PubMedSearch : Yang_2022_ACS.Omega_7_30720
PubMedID: 36092617

Title : SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate - Feng_2021_Mikrochim.Acta_188_280
Author(s) : Feng J , Lu H , Yang Y , Huang W , Cheng H , Kong H , Li L
Ref : Mikrochim Acta , 188 :280 , 2021
Abstract : By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 x 10(-13) mol.L(-1), and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng.mL(-1), the SERS signal intensity of benzidine at 1609 cm(-1) gradually decreases with the increase of hCE 1 concentration (R(2) = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.
ESTHER : Feng_2021_Mikrochim.Acta_188_280
PubMedSearch : Feng_2021_Mikrochim.Acta_188_280
PubMedID: 34331134

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

Title : Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway - Wu_2021_Clin.Transl.Med_11_e428
Author(s) : Wu D , Gao D , Yu H , Pi G , Xiong R , Lei H , Wang X , Liu E , Ye J , Gao Y , He T , Jiang T , Sun F , Su J , Song G , Peng W , Yang Y , Wang JZ
Ref : Clin Transl Med , 11 :e428 , 2021
Abstract : Tau accumulation and cholinergic impairment are characteristic pathologies in Alzheimer's disease (AD). However, the causal role of tau accumulation in cholinergic lesion is elusive. Here, we observed an aberrant tau accumulation in the medial septum (MS) of 3xTg and 5xFAD mice, especially in their cholinergic neurons. Overexpressing hTau in mouse MS (MS(hTau) ) for 6 months but not 3 months induced spatial memory impairment without changing object recognition and anxiety-like behavior, indicating a specific and time-dependent effect of MS-hTau accumulation on spatial cognitive functions. With increasing hTau accumulation, the MS(hTau) mice showed a time-dependent cholinergic neuron loss with reduced cholinergic projections to the hippocampus. Intraperitoneal administration of donepezil, a cholinesterase inhibitor, for 1 month ameliorated the MS-hTau-induced spatial memory deficits with preservation of MS-hippocampal cholinergic pathway and removal of tau load; and the beneficial effects of donepezil was more prominent at low dose. Proteomics revealed that MS-hTau accumulation deregulated multiple signaling pathways with numerous differentially expressed proteins (DEPs). Among them, the vacuolar protein sorting-associated protein 37D (VP37D), an autophagy-related protein, was significantly reduced in MS(hTau) mice; the reduction of VP37D was restored by donepezil, and the effect was more significant at low dose than high dose. These novel evidences reveal a causal role of tau accumulation in linking MS cholinergic lesion to hippocampus-dependent spatial cognitive damages as seen in the AD patients, and the new tau-removal and autophagy-promoting effects of donepezil may extend its application beyond simple symptom amelioration to potential disease modification.
ESTHER : Wu_2021_Clin.Transl.Med_11_e428
PubMedSearch : Wu_2021_Clin.Transl.Med_11_e428
PubMedID: 34185417

Title : General features to enhance enzymatic activity of poly(ethylene terephthalate) hydrolysis - Chen_2021_Nat.Catal_4_425
Author(s) : Chen CC , Han X , Li X , Jiang P , Niu D , Ma L , Liu W , Li S , Qu Y , Hu H , Min J , Yang Y , Zhang L , Zeng W , Huang JW , Dai L , Guo RT , Chen, CC
Ref : Nature Catalysis , 4 :425 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic and a major contributor to plastic pollution. IsPETase, from the PET-assimilating bacterium Ideonella sakaiensis, is a unique PET-hydrolytic enzyme that shares high sequence identity to canonical cutinases, but shows substrate preference towards PET and exhibits higher PET-hydrolytic activity at ambient temperature. Structural analyses suggest that IsPETase harbours a substrate-binding residue, W185, with a wobbling conformation and a highly flexible W185-locating beta6-beta7 loop. Here, we show that these features result from the presence of S214 and I218 in IsPETase, whose equivalents are strictly His and Phe, respectively, in all other homologous enzymes. We found that mutating His/Phe residues to Ser/Ile could enhance the PET-hydrolytic activity of several IsPETase-like enzymes. In conclusion, the Ser/Ile mutations should provide an important strategy to improve the activity of potential PET-hydrolytic enzymes with properties that may be useful for various applications.
ESTHER : Chen_2021_Nat.Catal_4_425
PubMedSearch : Chen_2021_Nat.Catal_4_425
Gene_locus related to this paper: 9burk-a0a1f4jxw8 , idesa-peth

Title : A non-integrated iPSC line (SDQLCHi042-A) from a boy suffering from familial combined hyperlipidemia with compound heterozygous mutations of lipoprotein lipase gene - Li_2021_Stem.Cell.Res_53_102313
Author(s) : Li Z , Zhang X , Li X , Yang Y , Xin H , Yang X , Liu N , Gai Z , Liu Y
Ref : Stem Cell Res , 53 :102313 , 2021
Abstract : In this study, peripheral blood monouclear cells (PBMCs) were donated from a boy suffering from familial combined hyperlipidemia confirmed by clinical and genetic diagnosis, which carried compound heterozygous mutations of lipoprotein lipase (LPL) gene. The induced pluripotent stem cell (iPSC) was generated with non-integrated episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The iPSCs presented the morphology of pluripotent cells, highly expressed mRNA and protein of pluripotent markers, excellent differentiation potency in vitro and normal karyotype, and bore LPL gene mutations.
ESTHER : Li_2021_Stem.Cell.Res_53_102313
PubMedSearch : Li_2021_Stem.Cell.Res_53_102313
PubMedID: 34087978
Gene_locus related to this paper: human-LPL

Title : Design, Synthesis, and Structure-Activity Relationship Study of Pyrazolones as Potent Inhibitors against Pancreatic Lipase - Bao_2021_ChemMedChem__
Author(s) : Bao X , Zhang J , Yang Y , Qian XK , Song PF , Zhao YS , Guan XQ , Zou LW , Wang H
Ref : ChemMedChem , : , 2021
Abstract : Pancreatic lipase (PL), a key target for the prevention and treatment of obesity, plays crucial roles in the hydrolysis and absorption of in dietary fat. In this study, a series of pyrazolones were synthesized and their inhibitory effects against PL were assayed using 4-methylumbelliferyl oleate (4-MUO) as optical substrate for PL. Comprehensive structure-activity relationship analysis of these pyrazolones brought us to design and synthesize a novel compound P32 (5-(naphthalen-2-yl)-2-phenyl-4-(thiophen-2-ylmethyl)-2,4-dihydro-3H-pyrazol-3-one) as a potent mixed-competitive inhibitor against PL (IC50 0.30 microM). In addition, P32 displayed some selectivity over other known serine hydrolase. Molecular docking study for P32 demonstrated that the inhibitory activity of P32 towards PL could be attributed to the Pi-Pi interactions of 2-naphthyl unit (R1) and hydrophobic interactions of phenyl moiety (R3) with the active site of PL, respectively. Thus, P32 could serve as promising lead compound for the development of more efficacious and selective pyrazolones-type PL inhibitors for biomedical applications.
ESTHER : Bao_2021_ChemMedChem__
PubMedSearch : Bao_2021_ChemMedChem__
PubMedID: 33527731

Title : A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China - Qian_2021_Parasit.Vectors_14_169
Author(s) : Qian W , Liu N , Yang Y , Liu J , He J , Chen Z , Li M , Qiu X
Ref : Parasit Vectors , 14 :169 , 2021
Abstract : BACKGROUND: Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides. METHODS: A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing. RESULTS: The G119S mutation in AChE was detected at high frequencies (0.40-0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets. CONCLUSIONS: Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy.
ESTHER : Qian_2021_Parasit.Vectors_14_169
PubMedSearch : Qian_2021_Parasit.Vectors_14_169
PubMedID: 33743789

Title : Cholinesterase level is a predictor of systemic inflammatory response syndrome and complications after cardiopulmonary bypass - Yang_2021_Ann.Palliat.Med_10_11714
Author(s) : Yang Y , Yang X , Yang J
Ref : Ann Palliat Med , 10 :11714 , 2021
Abstract : BACKGROUND: To study the changes of serum cholinesterase (S-ChE) levels in patients with systemic inflammatory response syndrome (SIRS) after cardiopulmonary bypass (CPB) and its predictive value for multiple organ dysfunction syndrome (MODS). METHODS: Forty-two patients with SIRS after CPB were selected as the SIRS group. Another 42 patients who did not develop SIRS after CPB were selected as the control group. The S-ChE levels of patients were compared between the two groups at the time of intensive care unit (ICU) admission and 48 hours after admission to the ICU. The correlation between S-ChE levels and Acute Physiology and Chronic Health EvaluationII (APACHEII) score, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels was compared between the two groups at the time of ICU admission and 48 hours after ICU admission, and receiver operator characteristic (ROC) curve analysis was used to analyze the accuracy of S-ChE level in diagnosing MODS in patients with SIRS after CPB. RESULTS: There was no significant difference in the S-ChE levels among the non-SIRS patients between the time of admission to the ICU and 48 hours later. However, the S-ChE levels in SIRS patients exhibited a decreasing trend from 48 hours after ICU admission compared with those at the time of ICU admission. Meanwhile, the S-ChE levels were obviously lower in SIRS patients than in non-SIRS patients at those two time points. Furthermore, we found that S-ChE levels were negatively correlated with APACHEII scores as well as the levels of TNF-alpha and IL-6 at ICU admission and 48 hours after ICU admission in SIRS patients. Meanwhile, S-ChE levels were associated with the occurrence of MODS of SIRS patients. Subsequent ROC curve analysis revealed that early S-ChE levels could predict the occurrence of SIRS complicated by MODS after CBP. CONCLUSIONS: S-ChE was significantly decreased in patients with SIRS after CPB, and the decrease of S-ChE in the early stage was closely related to the severity of SIRS after CBP and the increase of inflammatory cytokines. Meanwhile, there was a close relationship between S-ChE activity and MODS in the early stage.
ESTHER : Yang_2021_Ann.Palliat.Med_10_11714
PubMedSearch : Yang_2021_Ann.Palliat.Med_10_11714
PubMedID: 34872296

Title : Synthesis and Structure-Activity Relationships of 3-Arylisoquinolone Analogues as Highly Specific hCES2A Inhibitors - Zhao_2021_ChemMedChem_16_388
Author(s) : Zhao Y , Xiong Y , Dong S , Guan X , Song Y , Yang Y , Zou K , Li Z , Zhang Y , Fang S , Li B , Zhu W , Chen K , Jia Q , Ge G
Ref : ChemMedChem , 16 :388 , 2021
Abstract : Mammalian carboxylesterases (CES) are key enzymes that participate in the hydrolytic metabolism of various endogenous and exogenous substrates. Human carboxylesterase 2A (hCES2A), mainly distributed in the small intestine and colon, plays a significant role in the hydrolysis of many drugs. In this study, 3-arylisoquinolones 3h [3-(4-(benzyloxy)-3-methoxyphenyl)-7,8-dimethoxyisoquinolin-1(2H)-one] and 4a [3-(4-(benzyloxy)-3-methoxyphenyl)-4-bromo-7,8-dimethoxyisoquinolin-1(2H)-one] were found to have potent inhibitory effects on hCES2A (IC(50) =0.68microM, K(i) =0.36microM) and excellent specificity (more than 147.05-fold over hCES1A). Moreover, 4a exhibited threefold improved inhibition on intracellular hCES2A in living HepG2 cells relative to 3h, with an IC(50) value of 0.41microM. Results of inhibition kinetics studies and molecular docking simulations demonstrate that both 3h and 4a can bind to multiple sites on hCES2A, functioning as mixed inhibitors. Structure-activity relationship analysis revealed that the lactam moiety on the B ring is crucial for specificity towards hCES2A, while a benzyloxy group is optimal for hCES2A inhibitory potency; the introduction of a bromine atom may enhance cell permeability, thereby increasing the intracellular hCES2A inhibitory activity.
ESTHER : Zhao_2021_ChemMedChem_16_388
PubMedSearch : Zhao_2021_ChemMedChem_16_388
PubMedID: 32935462

Title : Early enteral nutrition combined with PSS-based nursing in the treatment of organophosphorus pesticide poisoning - Sun_2021_Am.J.Transl.Res_13_9315
Author(s) : Sun Y , Yang Y , Zhang Z , Li Y , Hu Y , Wang N
Ref : Am J Transl Res , 13 :9315 , 2021
Abstract : OBJECTIVE: To investigate the administration of early enteral nutrition combined with poisoning severity score (PSS)-based nursing in the treatment of organophosphorus pesticide poisoning (OPP). METHODS: A total of 99 OPP patients treated in our hospital between June 2019 and June 2020 were enrolled in this study and were divided into the conventional group (n=46, early enteral nutrition support + routine care) and the combined group (n=53, PSS-based nursing + early enteral nutrition support + routine care). The nutritional status indicators, the hemoglobin (Hb) and blood glucose levels, the Glasgow coma scale (GCS) scores, and the complications were compared between the two groups. RESULTS: The total protein (TP), albumin (ALB), and prealbumin (PAB) levels were reduced in the conventional group after the intervention (P<0.05) but were significantly lower than they were in the combined group (P<0.05). The Hb and blood glucose levels were decreased in the conventional group after the intervention (P<0.05) and were significantly higher than they were in the combined group (P<0.05). The GCS scores increased significantly as the treatment progressed (P<0.05), and the GCS scores in the combined group were significantly higher than the GCS scores in the conventional group at 3 and 5 days after the treatment (P<0.05). The time to the recovery of 60% cholinesterase (CHE) activity, the durations of the mechanical ventilation, the lengths of the hospital stays, and the hospital costs in the combined group were significantly lower than they were in the conventional group (P<0.05). The complication rate in the combined group (9.43%) was significantly lower than the complication rate in the conventional group (32.61%) (P<0.05). CONCLUSION: Early enteral nutrition combined with PSS-based nursing can effectively control the blood glucose, improve the nutritional disorders, promote recovery, and reduce complications in OPP patients.
ESTHER : Sun_2021_Am.J.Transl.Res_13_9315
PubMedSearch : Sun_2021_Am.J.Transl.Res_13_9315
PubMedID: 34540048

Title : Esterase D stabilizes FKBP25 to suppress mTORC1 - Yang_2021_Cell.Mol.Biol.Lett_26_50
Author(s) : Yang Y , Chen X , Yao W , Cui X , Li N , Lin Z , Zhao B , Miao J
Ref : Cellular & Molecular Biology Lett , 26 :50 , 2021
Abstract : BACKGROUND: Esterase D (ESD) is a nonspecific esterase that detoxifies formaldehyde. Many reports have stated that ESD activity is associated with a variety of physiological and pathological processes. However, the detailed signaling pathway of ESD remains poorly understood. METHODS: Considering the advantages of the small chemical molecule, our recent work demonstrated that 4-chloro-2-(5-phenyl-1-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-3-yl) phenol (FPD5) activates ESD, and will be a good tool for studying ESD further. Firstly, we determined the interaction between ESD and FK506 binding protein 25 (FKBP25) by yeast two-hybrid assay and co-immunoprecipitation (CO-IP) and analyzed the phosphorylation levels of mTORC1, P70S6K and 4EBP1 by western blot. Furthermore, we used the sulforhodamine B (SRB) and chick chorioallantoic membrane (CAM) assay to analyze cell viability in vitro and in vivo after treatment with ESD activator FPD5. RESULTS: We screened FKBP25 as a candidate protein to interact with ESD by yeast two-hybrid assay. Then we verified the interaction between ESD and endogenous FKBP25 or ectopically expressed GFP-FKBP25 by CO-IP. Moreover, the N-terminus (1-90 aa) domain of FKBP25 served as the crucial element for their interaction. More importantly, ESD reduced the K48-linked poly-ubiquitin chains of FKBP25 and thus stabilized cytoplasmic FKBP25. ESD also promoted FKBP25 to bind more mTORC1, suppressing the activity of mTORC1. In addition, ESD suppressed tumor cell growth in vitro and in vivo through autophagy. CONCLUSIONS: These findings provide novel evidence for elucidating the molecular mechanism of ESD and ubiquitination of FKBP25 to regulate autophagy and cancer cell growth. The ESD/FKBP25/mTORC1 signaling pathway is involved in inhibiting tumor cell growth via regulating autophagy.
ESTHER : Yang_2021_Cell.Mol.Biol.Lett_26_50
PubMedSearch : Yang_2021_Cell.Mol.Biol.Lett_26_50
PubMedID: 34875997

Title : A novel biosensor based on multienzyme microcapsules constructed from covalent-organic framework - Liang_2021_Biosens.Bioelectron_193_113553
Author(s) : Liang H , Wang L , Yang Y , Song Y
Ref : Biosensors & Bioelectronics , 193 :113553 , 2021
Abstract : Electrochemical biosensors based on enzymes modified electrode are attracting special attention due to their broad applications. However, the immobilization of enzymes on electrode is always an important challenge because it's not conducive to conformational expansion of enzymes and affects the bioactivity of enzymes accordingly. Although the imobilization of enzymes in micropores of crystalline covalent-organic framework (COF) and metal-organic framework (MOF) to construct electrochemical biosensors based on pore embedding can achive good reuslts, their micropores can still not guarantee that the enzyme's conformation is well extended. Herein, a multienzyme microcapsules (enzymes@COF) containing glucose oxidase, horseradish peroxidase and acetylcholinesterase with a 600 nm-sized cavity and a shell of COF was used to construct electrochemical biosensors. The 600 nm-sized cavity ensures free conformation expansion of encapsulated enzymes and the shell of COF with good chemical stablity protects encapsulated enzymes against external harsh environments. And the specific catalytic substrates of the enzymes can infiltrated into the microcapsule through the pores of COF shell. So, the biosensor based on enzymes@COF microcapsules demonstrated preeminent performances as compared with those of enzymes assembled on electrode. The detection limits were 0.85 microM, 2.81 nM, 3.0x10(-13) g/L, and the detection range were 2.83 microM-8.0 mM, 9.53 nM-7.0 microM, 10(-12) g/L-10(-8) g/L for glucose, H2O2 and malathion detection. This work shows that it is feasible to fabricate electrochemical sensors using enzymes@COF microcapsules.
ESTHER : Liang_2021_Biosens.Bioelectron_193_113553
PubMedSearch : Liang_2021_Biosens.Bioelectron_193_113553
PubMedID: 34385018

Title : Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents - Zhao_2021_Inorg.Chem__
Author(s) : Zhao D , Liu J , Zhang L , Zhou Y , Zhong Y , Yang Y , Huang C , Wang Y
Ref : Inorg Chem , : , 2021
Abstract : Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), -potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning.
ESTHER : Zhao_2021_Inorg.Chem__
PubMedSearch : Zhao_2021_Inorg.Chem__
PubMedID: 34969248

Title : Thifluzamide exposure induced neuro-endocrine disrupting effects in zebrafish (Danio rerio) - Yang_2021_Arch.Toxicol__
Author(s) : Yang Y , Chang J , Wang D , Ma H , Li Y , Zheng Y
Ref : Archives of Toxicology , : , 2021
Abstract : Thifluzamide is widely used fungicide and frequently detected in aquatic system. In this study, the toxicity of fungicide thifluzamide to non-targeted aquatic organisms was investigated for neuroendocrine disruption potentials. Here, zebrafish embryos were exposed to a series of concentrations of thifluzamide for 6 days. The results showed that both the development of embryos/larvae and the behavior of hatched larvae were significantly affected by thifluzamide. Importantly, the decreased activity of acetylcholinesterase (AchE) and the increased contents of neurotransmitters such as serotonin (5-HT) and norepinephrine (NE), along with transcriptional changes of nervous system related genes were observed following 4 days exposure to thifluzamide. Besides, the decreased contents of triiodothyronine (T3) and thyroxine (T4) in whole body, as well as significant expression alteration in hypothalamic-pituitary-thyroid (HPT) axis associated genes were discovered in zebrafish embryos after 4 days of exposure to thifluzamide. Our results clearly demonstrated that zebrafish embryos exposed to thifluzamide could disrupt neuroendocrine, compromise behavior and induce developmental abnormality, suggesting impact of this fungicide on developmental programming in zebrafish.
ESTHER : Yang_2021_Arch.Toxicol__
PubMedSearch : Yang_2021_Arch.Toxicol__
PubMedID: 34635929

Title : Pyridostigmine Protects Against Diabetic Cardiomyopathy by Regulating Vagal Activity, Gut Microbiota, and Branched-Chain Amino Acid Catabolism in Diabetic Mice - Yang_2021_Front.Pharmacol_12_647481
Author(s) : Yang Y , Zhao M , He X , Wu Q , Li DL , Zang WJ
Ref : Front Pharmacol , 12 :647481 , 2021
Abstract : The disruption of gut microbes is associated with diabetic cardiomyopathy, but the mechanism by which gut microbes affect cardiac damage remains unclear. We explored gut microbes and branched-chain amino acid (BCAA) metabolite catabolism in diabetic cardiomyopathy mice and investigated the cardioprotective effect of pyridostigmine. The experiments were conducted using a model of diabetic cardiomyopathy induced by a high-fat diet + streptozotocin in C57BL/6 mice. The results of high-throughput sequencing showed that diabetic cardiomyopathy mice exhibited decreased gut microbial diversity, altered abundance of the diabetes-related microbes, and increased abundance of the BCAA-producing microbes Clostridiales and Lachnospiraceae. In addition, diabetes downregulated tight junction proteins (ZO-1, occludin, and claudin-1) and increased intestinal permeability to impair the intestinal barrier. These impairments were accompanied by reduction in vagal activity that manifested as increased acetylcholinesterase levels, decreased acetylcholine levels, and heart rate variability, which eventually led to cardiac damage. Pyridostigmine enhanced vagal activity, restored gut microbiota homeostasis, decreased BCAA-producing microbe abundance, and improved the intestinal barrier to reduce circulating BCAA levels. Pyridostigmine also upregulated BCAT2 and PP2Cm and downregulated p-BCKDHA/BCKDHA and BCKDK to improve cardiac BCAA catabolism. Moreover, pyridostigmine alleviated abnormal mitochondrial structure; increased ATP production; decreased reactive oxygen species and mitochondria-related apoptosis; and attenuated cardiac dysfunction, hypertrophy, and fibrosis in diabetic cardiomyopathy mice. In conclusion, the gut microbiota, BCAA catabolism, and vagal activity were impaired in diabetic cardiomyopathy mice but were improved by pyridostigmine. These results provide novel insights for the development of a therapeutic strategy for diabetes-induced cardiac damage that targets gut microbes and BCAA catabolism.
ESTHER : Yang_2021_Front.Pharmacol_12_647481
PubMedSearch : Yang_2021_Front.Pharmacol_12_647481
PubMedID: 34084135

Title : Biodegradation of lambda-cyhalothrin through cell surface display of bacterial carboxylesterase - Ding_2021_Chemosphere_289_133130
Author(s) : Ding J , Liu Y , Gao Y , Zhang C , Wang Y , Xu B , Yang Y , Wu Q , Huang Z
Ref : Chemosphere , 289 :133130 , 2021
Abstract : Pyrethroids are the third widespread used insecticides globally which have been extensively applied in agricultural or household environments. Due to continuous applications, pyrethroids have been detected both in living cells and environments. The permanent exposure to pyrethroids have caused substantial health risks and ecosystem concerns. In this work, a lambda-cyhalothrin (one kind of pyrethroid insecticides) degrading bacterium Bacillus velezensis sd was isolated and a carboxylesterase gene, CarCB2 was characterized. A whole cell biocatalyst was developed for lambda-cyhalothrin biodegradation by displaying CarCB2 on the surface of Escherichia coli cells. CarCB2 was successfully displayed and functionally expressed on E. coli cells with optimal pH and temperature of 7.5 and 30 degreesC, using p-NPC(4) as substrate, respectively. The whole cell biocatalyst exhibited better stability than the purified CarCB2, and approximately 120%, 60% or 50% of its original activity at 4 degreesC, 30 degreesC or 37 degreesC over a period of 35 d was retained, respectively. No enzymatic activity was detected when incubated the purified CarCB2 at 30 degreesC for 120 h, or 37 degreesC for 72 h, respectively. Additionally, 30 mg/L of lambda-cyhalothrin was degraded in citrate-phosphate buffer by 10 U of the whole cell biocatalyst in 150 min. This work reveals that the whole cell biocatalyst affords a promising approach for efficient biodegradation of lambda-cyhalothrin, and might have the potential to be applied in further environmental bioremediation of other different kinds of pyrethroid insecticides.
ESTHER : Ding_2021_Chemosphere_289_133130
PubMedSearch : Ding_2021_Chemosphere_289_133130
PubMedID: 34863720
Gene_locus related to this paper: 9baci-MW588803

Title : Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney - Luo_2021_J.Biol.Chem__100667
Author(s) : Luo J , Hu S , Fu M , Luo L , Li Y , Li W , Cai Y , Dong R , Yang Y , Tu L , Xu X
Ref : Journal of Biological Chemistry , :100667 , 2021
Abstract : The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was used to treat mice (1 mg/kg/d) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) were markedly upregulated in the kidneys of mice fed a HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2, and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knock-down or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the IKKalpha/beta/NF-kappaB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by a HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression due to inactivation of the IKKalpha/beta/NF-kappaB-induced inflammatory response.
ESTHER : Luo_2021_J.Biol.Chem__100667
PubMedSearch : Luo_2021_J.Biol.Chem__100667
PubMedID: 33864813

Title : Long-Wavelength Ratiometric Fluorescent Probe for the Early Diagnosis of Diabetes - Wang_2021_Anal.Chem_93_11461
Author(s) : Wang J , Zhang L , Qu Y , Yang Y , Cao T , Cao Y , Iqbal A , Qin W , Liu Y
Ref : Analytical Chemistry , 93 :11461 , 2021
Abstract : Diabetes is a metabolic disease caused by high blood sugar. Patients are often suffering from high blood pressure and arteriosclerosis, which may even evolve into liver disease, kidney disease, and other diabetic complications. Dipeptide peptidase IV (DPP-IV) plays an important role in regulating blood sugar levels and is one of the targets for the diagnosis and treatment of diabetes. Here, a long-wavelength ratiometric fluorescent probe DCDHFNH(2)-dpp4 for detecting DPP-IV was designed and synthesized. DCDHFNH(2)-dpp4 was used to detect DPP-IV in healthy, tumor-bearing, and diabetic mice, and only diabetic mice showed strong fluorescence signals. In organ imaging, it is found that DPP-IV is relatively enriched in the liver of diabetic mice. In addition, probe DCDHFNH(2)-dpp4 also exhibited a significant ratiometric fluorescence signal in the serum of diabetic mice. Therefore, the fluorescent probe DCDHFNH(2)-dpp4 has shown outstanding potential in the early diagnosis of diabetes, and DCDHFNH(2)-dpp4 is hopeful to be applied to actual clinical medicine.
ESTHER : Wang_2021_Anal.Chem_93_11461
PubMedSearch : Wang_2021_Anal.Chem_93_11461
PubMedID: 34369744

Title : The enantioselective toxicity and oxidative stress of dinotefuran on zebrafish (Danio rerio) - Ran_2021_Ecotoxicol.Environ.Saf_226_112809
Author(s) : Ran L , Yang Y , Zhou X , Jiang X , Hu D , Lu P
Ref : Ecotoxicology & Environmental Safety , 226 :112809 , 2021
Abstract : Dinotefuran is a widely used neonicotinoid pesticides in agriculture and it has certain ecological toxicity to aquatic organisms. Studies on the potential toxicological effects of dinotefuran on fish are limited. In the present study, 96 h acute toxicity test indicated that enantiomers of R-(-)-dinotefuran had a greater toxic effect than Rac-dinotefuran on zebrafish, and S-(+)-dinotefuran was the least. In chronic assay, R-(-)-dinotefuran exerted more effects on the development of zebrafish than S-(+)-dinotefuran, and dinotefuran also had enantioselective effect on oxidative stress. Significant changes were observed in the superoxide dismutase (SOD), glutathione S-transferase (GST) and acetylcholinesterase (AChE) activities and malondialdehyde (MDA) contents, which demonstrated dinotefuran induced oxidative stress in zebrafish. Besides, through an ultra-performance liquid chromatography quadrupole-TOF mass spectrometry (UPLC-Q-TOF-MS)-based metabolomics method was used to evaluate the enantioselectivity of dinotefuran enantiomers in zebrafish. The results indicated that R-(-)-dinotefuran caused greater disturbances of endogenous metabolites. Phenylalanine metabolic pathways, glycine, serine and threonine metabolic pathways are only involved in zebrafish exposed to R-(-)-dinotefuran; whereas phenylalanine, tyrosine and tryptophan biosynthesis was only involved in zebrafish exposed to S-(+)-dinotefuran. This study provides a certain reference value for assessing the environmental risks of dinotefuran enantiomers to aquatic organisms, and has practical significance for guiding the ecologically and environmentally safety use of dinotefuran.
ESTHER : Ran_2021_Ecotoxicol.Environ.Saf_226_112809
PubMedSearch : Ran_2021_Ecotoxicol.Environ.Saf_226_112809
PubMedID: 34592523

Title : Differential Effects of 17,18-EEQ and 19,20-EDP Combined with Soluble Epoxide Hydrolase Inhibitor t-TUCB on Diet-Induced Obesity in Mice - Yang_2021_Int.J.Mol.Sci_22_
Author(s) : Yang Y , Xu X , Wu H , Yang J , Chen J , Morisseau C , Hammock BD , Bettaieb A , Zhao L
Ref : Int J Mol Sci , 22 : , 2021
Abstract : 17,18-Epoxyeicosatetraenoic acid (17,18-EEQ) and 19,20-epoxydocosapentaenoic acid (19,20-EDP) are bioactive epoxides produced from n-3 polyunsaturated fatty acid eicosapentaenoic acid and docosahexaenoic acid, respectively. However, these epoxides are quickly metabolized into less active diols by soluble epoxide hydrolase (sEH). We have previously demonstrated that an sEH inhibitor, t-TUCB, decreased serum triglycerides (TG) and increased lipid metabolic protein expression in the brown adipose tissue (BAT) of diet-induced obese mice. This study investigates the preventive effects of t-TUCB (T) alone or combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) on BAT activation in the development of diet-induced obesity and metabolic disorders via osmotic minipump delivery in mice. Both T + EDP and T + EEQ groups showed significant improvement in fasting glucose, serum triglycerides, and higher core body temperature, whereas heat production was only significantly increased in the T + EEQ group. Moreover, both the T + EDP and T + EEQ groups showed less lipid accumulation in the BAT. Although UCP1 expression was not changed, PGC1alpha expression was increased in all three treated groups. In contrast, the expression of CPT1A and CPT1B, which are responsible for the rate-limiting step for fatty acid oxidation, was only increased in the T + EDP and T + EEQ groups. Interestingly, as a fatty acid transporter, CD36 expression was only increased in the T + EEQ group. Furthermore, both the T + EDP and T + EEQ groups showed decreased inflammatory NFkappaB signaling in the BAT. Our results suggest that 17,18-EEQ or 19,20-EDP combined with t-TUCB may prevent high-fat diet-induced metabolic disorders, in part through increased thermogenesis, upregulating lipid metabolic protein expression, and decreasing inflammation in the BAT.
ESTHER : Yang_2021_Int.J.Mol.Sci_22_
PubMedSearch : Yang_2021_Int.J.Mol.Sci_22_
PubMedID: 34361032

Title : Combined use of GABA and sitagliptin promotes human beta-cell proliferation and reduces apoptosis - Liu_2021_J.Endocrinol_248_133
Author(s) : Liu W , Lau HK , Son DO , Jin T , Yang Y , Zhang Z , Li Y , Prud'homme GJ , Wang Q
Ref : J Endocrinol , 248 :133 , 2021
Abstract : gamma-Aminobutyric acid (GABA) and glucagon-like peptide-1 receptor agonist (GLP-1RA) improve rodent beta-cell survival and function. In human beta-cells, GABA exerts stimulatory effects on proliferation and anti-apoptotic effects, whereas GLP-1RA drugs have only limited effects on proliferation. We previously demonstrated that GABA and sitagliptin (Sita), a dipeptidyl peptidase-4 inhibitor which increases endogenous GLP-1 levels, mediated a synergistic beta-cell protective effect in mice islets. However, it remains unclear whether this combination has similar effects on human beta-cell. To address this question, we transplanted a suboptimal mass of human islets into immunodeficient NOD-scid-gamma mice with streptozotocin-induced diabetes, and then treated them with GABA, Sita, or both. The oral administration of either GABA or Sita ameliorated blood glucose levels, increased transplanted human beta-cell counts and plasma human insulin levels. Importantly, the combined administration of the drugs generated significantly superior results in all these responses, as compared to the monotherapy with either one of them. The proliferation and/or regeneration, improved by the combination, were demonstrated by increased Ki67+, PDX-1+, or Nkx6.1+ beta-cell numbers. Protection against apoptosis was also significantly improved by the drug combination. The expression level of alpha-Klotho, a protein with protective and stimulatory effects on beta cells, was also augmented. Our study indicates that combined use of GABA and Sita produced greater therapeutic benefits, which are likely due to an enhancement of beta-cell proliferation and a decrease in apoptosis.
ESTHER : Liu_2021_J.Endocrinol_248_133
PubMedSearch : Liu_2021_J.Endocrinol_248_133
PubMedID: 33258801

Title : Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1 - Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
Author(s) : Hu S , Luo J , Fu M , Luo L , Cai Y , Li W , Li Y , Dong R , Yang Y , Tu L , Xu X
Ref : American Journal of Physiology Heart Circ Physiol , : , 2021
Abstract : Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2(-/-)) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2(-/-) mice without NAM treatment. However, the arterial protective effects were gone in Ephx2(-/-) mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation.
ESTHER : Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
PubMedSearch : Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__
PubMedID: 34142887

Title : Chemical Composition, Antibacterial, Anti-Inflammatory, and Enzyme Inhibitory Activities of Essential Oil from Rhynchanthus beesianus Rhizome - Zhao_2020_Molecules_26_
Author(s) : Zhao X , Chen Q , Lu T , Wei F , Yang Y , Xie D , Wang H , Tian M
Ref : Molecules , 26 : , 2020
Abstract : Rhynchanthus beesianus W. W. Smith, an edible, medicinal, and ornamental plant, is mainly cultivated in China and Myanmar. The essential oil (EO) from R. beesianus rhizome has been used as an aromatic stomachic in China. The chemical composition and biological activities of EO from R. beesianus rhizome were reported for the first time. Based on gas chromatography with flame ionization or mass selective detection (GC-FID/MS) results, the major constituents of EO were 1,8-cineole (47.6%), borneol (15.0%), methyleugenol (11.2%), and bornyl formate (7.6%). For bioactivities, EO showed a significant antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris with the diameter of the inhibition zone (DIZ) (8.66-10.56 mm), minimal inhibitory concentration (MIC) (3.13-6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25-12.5 mg/mL). Moreover, EO (128 microg/mL) significantly inhibited the production of proinflammatory mediators nitric oxide (NO) (92.73 +/- 1.50%) and cytokines tumor necrosis factor-alpha (TNF-alpha) (20.29 +/- 0.17%) and interleukin-6 (IL-6) (61.08 +/- 0.13%) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages without any cytotoxic effect. Moreover, EO exhibited significant acetylcholinesterase (AChE) inhibitory activity (the concentration of the sample that affords a 50% inhibition in the assay (IC(50)) = 1.03 +/- 0.18 mg/mL) and moderate alpha-glucosidase inhibition effect (IC(50) = 11.60 +/- 0.25 mg/mL). Thus, the EO could be regarded as a bioactive natural product and has a high exploitation potential in the cosmetics and pharmaceutical industries.
ESTHER : Zhao_2020_Molecules_26_
PubMedSearch : Zhao_2020_Molecules_26_
PubMedID: 33396533

Title : Evaluation of modes of action of pesticides to Daphnia magna based on QSAR, excess toxicity and critical body residues - Wang_2020_Ecotoxicol.Environ.Saf_203_111046
Author(s) : Wang J , Yang Y , Huang Y , Zhang X , Qin WC , Wen Y , Zhao YH
Ref : Ecotoxicology & Environmental Safety , 203 :111046 , 2020
Abstract : Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna.
ESTHER : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedSearch : Wang_2020_Ecotoxicol.Environ.Saf_203_111046
PubMedID: 32888614

Title : Soluble Epoxide Hydrolase Inhibition by t-TUCB Promotes Brown Adipogenesis and Reduces Serum Triglycerides in Diet-Induced Obesity - Overby_2020_Int.J.Mol.Sci_21_
Author(s) : Overby H , Yang Y , Xu X , Graham K , Hildreth K , Choi S , Wan D , Morisseau C , Zeldin DC , Hammock BD , Wang S , Bettaieb A , Zhao L
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Brown adipose tissue (BAT) is an important target for obesity treatment and prevention. Soluble epoxide hydrolase (sEH) converts bioactive epoxy fatty acids (EpFAs) into less active diols. sEH inhibitors (sEHI) are beneficial in many chronic diseases by stabilizing EpFAs. However, roles of sEH and sEHI in brown adipogenesis and BAT activity in treating diet-induced obesity (DIO) have not been reported. sEH expression was studied in in vitro models of brown adipogenesis and the fat tissues of DIO mice. The effects of the sEHI, trans-4-{4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy-benzoic acid (t-TUCB), were studied in vitro and in the obese mice via mini osmotic pump delivery. sEH expression was increased in brown adipogenesis and the BAT of the DIO mice. t-TUCB promoted brown adipogenesis in vitro. Although t-TCUB did not change body weight, fat pad weight, or glucose and insulin tolerance in the obese mice, it decreased serum triglycerides and increased protein expression of genes important for lipid metabolism in the BAT. Our results suggest that sEH may play a critical role in brown adipogenesis, and sEHI may be beneficial in improving BAT protein expression involved in lipid metabolism. Further studies using the sEHI combined with EpFA generating diets for obesity treatment and prevention are warranted.
ESTHER : Overby_2020_Int.J.Mol.Sci_21_
PubMedSearch : Overby_2020_Int.J.Mol.Sci_21_
PubMedID: 32987880

Title : Characterization of EstZY: A new acetylesterase with 7-aminocephalosporanic acid deacetylase activity from Alicyclobacillus tengchongensis - Ding_2020_Int.J.Biol.Macromol_148_333
Author(s) : Ding J , Zhou Y , Zhu H , Deng M , Gao Y , Yang Y , Huang Z
Ref : Int J Biol Macromol , 148 :333 , 2020
Abstract : Deacetyl-7-aminocephalosporanic acid (D-7-ACA) is required for producing of many semisynthetic beta-lactam antibiotics; therefore, enzymes capable of converting 7-aminocephalosporanic acid (7-ACA) to D-7-ACA present a valuable resource to the pharmaceutical industry. In the present study, a putative acetylesterase, EstZY, was identified and characterized from a thermophilic bacterium Alicyclobacillus tengchongensis. Sequence alignment showed that EstZY was an acetylesterase which belonged to carbohydrate esterase family 7 (CE7), with substrate preference for short-chain acyl esters p-NPC(2) to p-NPC(8). Maximum enzyme activity was recorded at pH 9.0 and 50 degreesC, where K(m) and V(max) were calculated as 1.9 +/- 0.23 mM and 258 +/- 18.5 microM min(-)(1), respectively. The residues Ser185, Asp274, and His303 were identified as the putative catalytic triad by homology modelling, site-directed mutagenesis and molecular docking. Moreover, EstZY can remove the acetyl group at C3' position of 7-ACA to form D-7-ACA; this is the first report of a 7-ACA deacetylase from CE7 family in A. tengchongensis and may represent a new enzyme with industrial values.
ESTHER : Ding_2020_Int.J.Biol.Macromol_148_333
PubMedSearch : Ding_2020_Int.J.Biol.Macromol_148_333
PubMedID: 31954783
Gene_locus related to this paper: 9bacl-a0a6g6c491

Title : Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review - Wang_2020_Curr.Vasc.Pharmacol_18_358
Author(s) : Wang Z , Yang Y , Liu M , Wei Y , Liu J , Pei H , Li H
Ref : Curr Vasc Pharmacol , 18 :358 , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.
ESTHER : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedSearch : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedID: 31291876

Title : Monobutyl phthalate (MBP) can dysregulate the antioxidant system and induce apoptosis of zebrafish liver - Jiao_2020_Environ.Pollut_257_113517
Author(s) : Jiao Y , Tao Y , Yang Y , Diogene T , Yu H , He Z , Han W , Chen Z , Wu P , Zhang Y
Ref : Environ Pollut , 257 :113517 , 2020
Abstract : In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated.
ESTHER : Jiao_2020_Environ.Pollut_257_113517
PubMedSearch : Jiao_2020_Environ.Pollut_257_113517
PubMedID: 31761585

Title : Microbial Degradation and Valorization of Plastic Wastes - Ru_2020_Front.Microbiol_11_442
Author(s) : Ru J , Huo Y , Yang Y
Ref : Front Microbiol , 11 :442 , 2020
Abstract : A growing accumulation of plastic wastes has become a severe environmental and social issue. It is urgent to develop innovative approaches for the disposal of plastic wastes. In recent years, reports on biodegradation of synthetic plastics by microorganisms or enzymes have sprung up, and these offer a possibility to develop biological treatment technology for plastic wastes. In this review, we have comprehensively summarized the microorganisms and enzymes that are able to degrade a variety of generally used synthetic plastics, such as polyethylene (PE), polystyrene (PS), polypropylene (PP), polyvinyl chloride (PVC), polyurethane (PUR), and polyethylene terephthalate (PET). In addition, we have highlighted the microbial metabolic pathways for plastic depolymerization products and the current attempts toward utilization of such products as feedstocks for microbial production of chemicals with high value. Taken together, these findings will contribute to building a conception of bio-upcycling plastic wastes by connecting the biodegradation of plastic wastes to the biosynthesis of valuable chemicals in microorganisms. Last, but not least, we have discussed the challenges toward microbial degradation and valorization of plastic wastes.
ESTHER : Ru_2020_Front.Microbiol_11_442
PubMedSearch : Ru_2020_Front.Microbiol_11_442
PubMedID: 32373075

Title : Improving the production of AHL lactonase AiiO-AIO6 from Ochrobactrum sp. M231 in intracellular protease-deficient Bacillus subtilis - Xia_2020_AMB.Express_10_138
Author(s) : Xia R , Yang Y , Pan X , Gao C , Yao Y , Liu X , Teame T , Zhang F , Hu J , Ran C , Zhang Z , Liu-Clarke J , Zhou Z
Ref : AMB Express , 10 :138 , 2020
Abstract : Quorum quenching (QQ) blocks bacterial cell-to-cell communication (i.e., quorum sensing), and is a promising antipathogenic strategy to control bacterial infection via inhibition of virulence factor expression and biofilm formation. QQ enzyme AiiO-AIO6 from Ochrobactrum sp. M231 has several excellent properties and shows biotherapeutic potential against important bacterial pathogens of aquatic species. AiiO-AIO6 can be secretory expressed in Bacillus subtilis via a non-classical secretion pathway. To improve AiiO-AIO6 production, four intracellular protease-deletion mutants of B. subtilis 1A751 were constructed by individually knocking out the intracellular protease-encoding genes (tepA, ymfH, yrrN and ywpE). The AiiO-AIO6 expression plasmid pWB-AIO6BS was transformed into the B. subtilis 1A751 and its four intracellular protease-deletion derivatives. Results showed that all recombinant intracellular protease-deletion derivatives (BStepA, BSymfH, BSyrrN and BSywpE) had a positive impact on AiiO-AIO6 production. The highest amount of AiiO-AIO6 extracellular production of BSywpE in shake flask reached 1416.47 U/mL/OD(600), which was about 121% higher than that of the wild-type strain. Furthermore, LC-MS/MS analysis of the degrading products of 3-oxo-C8-HSL by purification of AiiO-AIO6 indicated that AiiO-AIO6 was an AHL-lactonase which hydrolyzes the lactone ring of AHLs. Phylogenetic analysis showed that AiiO-AIO6 was classified as a member of the alpha/beta hydrolase family with a conserved "nucleophile-acid-histidine" catalytic triad. In summary, this study showed that intracellular proteases were responsible for the reduced yields of heterologous proteins and provided an efficient strategy to enhance the extracellular production of AHL lactonase AiiO-AIO6.
ESTHER : Xia_2020_AMB.Express_10_138
PubMedSearch : Xia_2020_AMB.Express_10_138
PubMedID: 32757095
Gene_locus related to this paper: ocha4-a6wx49

Title : miR-140-3p Inhibits Cutaneous Melanoma Progression by Disrupting AKT\/p70S6K and JNK Pathways through ABHD2 - He_2020_Mol.Ther.Oncolytics_17_83
Author(s) : He Y , Yang Y , Liao Y , Xu J , Liu L , Li C , Xiong X
Ref : Mol Ther Oncolytics , 17 :83 , 2020
Abstract : Because cutaneous melanoma (CM) is one of the most lethal human tumors, major treatment advances are vital. miR-140-3p has been suggested to act as a suppressor in a range of malignant tumors, implying its possible use as a biomarker for effective antineoplastic treatment. However, the potential role of miR-140-3p in CM and the underlying mechanism remain unclear. In the present study, we identified lower levels of miR-140-3p in both CM tissues and cell lines; this downregulation was strongly associated with worse CM survival. Additionally, overexpression of miR-140-3p significantly inhibited cell proliferation, migration, and invasion in CM cells with different cell line origins. Importantly, by means of both bioinformatics analysis and luciferase reporter assay, we revealed abhydrolase domain containing 2 (ABHD2) to be a target of miR-140-3p in CM cells. Upregulation of ABHD2 reversed the tumor-suppressive effects of miR-140-3p in CM cells. Furthermore, miR-140-3p-targeted ABHD2 played a role in both activation of JNK signaling and inhibition of the AKT/p70S6K pathway in CM cells. Finally, in vivo results strongly suggested the suppressive effects of miR-140-3p on CM growth and metastasis. Collectively, our findings highlight a novel antineoplastic function for miR-140-3p in CM through ABHD2.
ESTHER : He_2020_Mol.Ther.Oncolytics_17_83
PubMedSearch : He_2020_Mol.Ther.Oncolytics_17_83
PubMedID: 32322665
Gene_locus related to this paper: human-ABHD2

Title : Decreased T-cell mediated hepatic injury in concanavalin A-treated PLRP2-deficient mice - Ge_2020_Int.Immunopharmacol_85_106604
Author(s) : Ge W , Gao Y , Zhao Y , Yang Y , Sun Q , Yang X , Xu X , Zhang J
Ref : Int Immunopharmacol , 85 :106604 , 2020
Abstract : Concanavalin A (Con A) activates innate immunity and causes liver damage mediated by cytotoxic T lymphocytes (CTL) in mice. The Pancreatic lipase-related protein 2 (PLRP2) is induced by interleukin (IL)-4 in vitro in CTLs and associated with CTL functions. We examined the role of PLRP2 in a mouse model of Con A-induced T cell-mediated hepatitis. PLRP2-knockout and wild-type (WT) mice were inoculated with 20 mg/kg Con A. Mice lacking PLRP2 reduced Con A-induced hepatitis, which was manifested by a decrease in serum aminotransferase and histopathological assessment. The expression and secretion of cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon (IFN)-gamma, IL-6, and IL-1beta were suppressed in Con A-treated PLRP2-knockout mice. In PLRP2 knockout mice, Con A-induced liver chemokines and adhesion molecules (such as MIP-1alpha, MIP-1beta, ICAM-1 and MCP-1) were also down regulated. In the WT liver treated with Con A, the number of T cells (CD4(+) and CD8(+)) and macrophages (CD11b(+) F4/80(+)) increased significantly, while the lack of PLRP2 reduced the number of T cells in the liver, but had no effect on macrophages. The shift of the metabolic profiles was impaired in Con A-treated PLRP2-knockout mice compared to WT mice. In conclusion, these results indicate that PLRP2 deficiency reduces T-cell mediated Con A-induced hepatitis, and suggest PLRP2 is a potential target of anti-inflammatory and immunomodulatory drugs to treat immune-mediated hepatitis.
ESTHER : Ge_2020_Int.Immunopharmacol_85_106604
PubMedSearch : Ge_2020_Int.Immunopharmacol_85_106604
PubMedID: 32428799
Gene_locus related to this paper: mouse-LIPR2

Title : sEH Inhibitor Tppu Ameliorates Cecal Ligation and Puncture-Induced Sepsis by Regulating Macrophage Functions - Chen_2020_Shock_53_761
Author(s) : Chen Z , Tang Y , Yu J , Dong R , Yang Y , Fu M , Luo J , Hu S , Wang DW , Tu L , Xu X
Ref : Shock , 53 :761 , 2020
Abstract : BACKGROUND: Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. METHODS: A polymicrobial sepsis model induced by CLP was used in our study. C57BL/6 mice were divided into four groups: sham+ phosphate buffer saline (PBS), sham+TPPU, CLP+PBS, CLP+TPPU. Mice were observed 48h after surgery to assess the survival rate. For other histological examinations, mice were sacrificed 6h after surgery. Macrophage cell line RAW264.7 was used for in vitro studies. RESULTS: TPPU treatment, accompanied with increased EETs levels, markedly improved the survival of septic mice induced by CLP surgery, which was associated with alleviated organ damage and dysfunction triggered by systemic inflammatory response. Moreover, TPPU treatment significantly inhibited systemic inflammatory response via EETs-induced inactivation of mitogen-activated protein kinase signaling due to enhanced macrophage phagocytic ability and subsequently reduced bacterial proliferation and dissemination, and decreased inflammatory factors release. CONCLUSION: sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis.
ESTHER : Chen_2020_Shock_53_761
PubMedSearch : Chen_2020_Shock_53_761
PubMedID: 31318834

Title : ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis - Liu_2020_Front.Cell.Dev.Biol_8_570
Author(s) : Liu G , Ruan Y , Zhang J , Wang X , Wu W , He P , Wang J , Xiong J , Cheng Y , Liu L , Yang Y , Tian Y , Jian R
Ref : Front Cell Developmental Biology , 8 :570 , 2020
Abstract : Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function.
ESTHER : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedSearch : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedID: 32733886
Gene_locus related to this paper: human-ABHD11

Title : miR-96-5p attenuates malathion-induced apoptosis of human kidney cells by targeting the ER stress marker DDIT3 - Li_2020_J.Environ.Sci.Health.B__1
Author(s) : Li S , Yang Y , Shi MH , Wang JF , Ran XQ
Ref : J Environ Sci Health B , :1 , 2020
Abstract : Micro RNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, their functions in organophosphate-induced cytotoxicity remain unclear. This study investigated the involvement of miR-96-5p in the non-cholinergic toxicity of malathion in normal human kidney cells (HK-2 cells). Malathion decreased HK-2 cell viability and the expression of miR-96-5p in a dose- and time-dependent manner. In addition, transfection with miR-96-5p mimics attenuated malathion-induced HK-2 cell apoptosis, whereas transfection with a miR-96-5p inhibitor increased HK-2 cell apoptosis. Luciferase assays indicated that miR-96-5p could bind directly to the 3'-untranslated region of DDIT3, a well-known marker of endoplasmic reticulum stress. Further analyses of the expression of apoptosis-related genes and proteins indicated that miR-96-5p may function to reduce malathion-induced HK-2 cell apoptosis via regulation of the DDIT3/B-cell lymphoma (BCL)-2/caspase-3 signaling pathway. In summary, the results of the present study indicate that miR-96-5p protects HK-2 cells from malathion-induced ER stress-dependent apoptosis by targeting DDIT3.
ESTHER : Li_2020_J.Environ.Sci.Health.B__1
PubMedSearch : Li_2020_J.Environ.Sci.Health.B__1
PubMedID: 32897819

Title : Determination of Genetic Effects of LIPK and LIPJ Genes on Milk Fatty Acids in Dairy Cattle - Shi_2019_Genes.(Basel)_10_
Author(s) : Shi L , Han B , Liu L , Lv X , Ma Z , Li C , Xu L , Li Y , Zhao F , Yang Y , Sun D
Ref : Genes (Basel) , 10 : , 2019
Abstract : In our previous genome-wide association study (GWAS) on milk fatty acids (FAs) in Chinese Holstein, we discovered 83 genome-wide significant single nucleotide polymorphisms (SNPs) associated with milk FAs. Two of them were close to lipase family member K (LIPK) and lipase family member J (LIPJ), respectively. Hence, this study is a follow-up to verify whether the LIPK and LIPJ have significant genetic effects on milk FAs in dairy cattle. By re-sequencing the entire exons, and 3 kb of 5' and 3' flanking regions, two and seven SNPs were identified in LIPK and LIPJ, respectively, including a novel SNP, ss158213049726. With the Haploview 4.1 software, we found that five of the SNPs in LIPJ formed a haplotype block (D' = 0.96 ~ 1.00). Single-locus association analyses revealed that each SNP in LIPK and LIPJ was significantly associated with at least one milk FA (p = < 1.00x10(-4) ~ 4.88x10(-2)), and the haplotype-based association analyses showed significant genetic effects on nine milk FAs (p = < 1.00x10(-4) ~ 3.98x10(-2)). Out of these SNPs, the missense mutation in LIPK gene, rs42774527, could change the protein secondary structure and function predicted by SOPMA, SIFT, and PROVEAN softwares. With the Genomatix software, we predicted that two SNPs, rs110322221 in LIPK and rs211373799 in LIPJ, altered the transcription factors binding sites (TFBSs), indicating their potential regulation on promoter activity of the genes. Furthermore, we found that both LIPK and LIPJ had relatively high expressions in the mammary gland. In conclusion, our research is the first to demonstrate that LIPK and LIPJ genes have significant associations with milk FAs, and the identified SNPs might be served as genetic markers to optimize breeding programs for milk FAs in dairy cattle. This research deserves in-depth verification.
ESTHER : Shi_2019_Genes.(Basel)_10_
PubMedSearch : Shi_2019_Genes.(Basel)_10_
PubMedID: 30696079
Gene_locus related to this paper: bovin-e1bnt1 , bovin-f1msa3 , human-LIPJ , human-LIPK

Title : Identification of a Novel Feruloyl Esterase by Functional Screening of a Soil Metagenomic Library - Li_2019_Appl.Biochem.Biotechnol_187_424
Author(s) : Li X , Guo J , Hu Y , Yang Y , Jiang J , Nan F , Wu S , Xin Z
Ref : Appl Biochem Biotechnol , 187 :424 , 2019
Abstract : A cosmid metagenomic library containing 1.3 x 10(5) clones was created from a soil sample. A novel gene (fae-xuan) encoding a feruloyl esterase was identified through functional screening. Primary sequence analysis showed that the gene consisted of 759 base pairs and encoded a protein of 252 amino acids. The gene was expressed in Escherichia coli BL21 (DE3) and the corresponding purified recombinant enzyme exhibited a molecular weight of 29 kDa. The FAE-Xuan showed high activity (40.0 U/mg) toward methyl ferulate with an optimal temperature and pH of 30 degreesC and 5.0, respectively. Besides methyl ferulate, FAE-Xuan can also hydrolyze methyl sinapate and methyl p-coumarate. The substrate utilization preferences and phylogenetic analysis indicated that FAE-Xuan belongs to type A FAE. FAE-Xuan was quite stable over a broad pH range from 3.0 to 10.0. The activity reduced remarkably in presence of Cu(2+). FAE-Xuan can enhance the quantity of ferulic acid from de-starched wheat bran in presence of xylanase. The work presented here highlighted the effectiveness of metagenomic strategy in identifying novel FAEs with diverse properties for potential use in industrial production.
ESTHER : Li_2019_Appl.Biochem.Biotechnol_187_424
PubMedSearch : Li_2019_Appl.Biochem.Biotechnol_187_424
PubMedID: 29968147

Title : First Genome-wide Association Analysis for Growth Traits in the Largest Coral Reef-Dwelling Bony Fishes, the Giant Grouper (Epinephelus lanceolatus) - Wu_2019_Mar.Biotechnol.(NY)_21_707
Author(s) : Wu L , Yang Y , Li B , Huang W , Wang X , Liu X , Meng Z , Xia J
Ref : Mar Biotechnol (NY) , 21 :707 , 2019
Abstract : The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.
ESTHER : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedSearch : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedID: 31392592

Title : Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations - Zhou_2019_Molecules_24_
Author(s) : Zhou Y , Lu X , Yang H , Chen Y , Wang F , Li J , Tang Z , Cheng X , Yang Y , Xu L , Xia Q
Ref : Molecules , 24 : , 2019
Abstract : As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 muM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.
ESTHER : Zhou_2019_Molecules_24_
PubMedSearch : Zhou_2019_Molecules_24_
PubMedID: 31757047

Title : Fluoride reactivation-enabled sensitive quantification of tabun adducts on human serum albumin by GC-MS\/MS via isotope dilution - Li_2019_Bioanalysis_11_2145
Author(s) : Li XS , Wu JN , Yan L , Xing ZF , Liu CC , Chen B , Yuan L , Yang Y
Ref : Bioanalysis , 11 :2145 , 2019
Abstract : Organophosphorus nerve agents inhibit the cholinesterase activity by phosphylation of the active site serine. The resulting phosphylated cholinesterase and adducts on human serum albumin (HSA) are appropriate biomarkers for nerve agents exposure. Several methods have been developed for the detection of nerve agents, including fluoride reactivation or alkaline cleavage. It was previously thought that some nerve agents adducts to HSA could not be detected via fluoride regeneration. In our study, the results showed that tabun (GA) adducts of HSA could be detected by fluoride regeneration. The sample preparation included acetone precipitation, washing and SPE. Deuterated tabun (d5-GA) was applied as the internal standard. The product of regenerated fluorotabun is detected with a good linearity (R(2) > 0.997) in the concentration range from 0.02 to 100.0 ng/ml, small relative standard deviation (
ESTHER : Li_2019_Bioanalysis_11_2145
PubMedSearch : Li_2019_Bioanalysis_11_2145
PubMedID: 31729243

Title : Identification and characterization of an acetyl esterase from Paenibacillus sp. XW-6-66 and its novel function in 7-aminocephalosporanic acid deacetylation - Ding_2019_Biotechnol.Lett_41_1059
Author(s) : Ding J , Zhou Y , Zhu H , Deng M , Long L , Yang Y , Wu Q , Huang Z
Ref : Biotechnol Lett , 41 :1059 , 2019
Abstract : OBJECTIVES: To obtain a new acetyl esterase from Paenibacillus sp. XW-6-66 and apply the enzyme to 7-aminocephalosporanic acid (7-ACA) deacetylation. RESULTS: The acetyl esterase AesZY was identified from Paenibacillus sp. XW-6-66, and its enzymatic properties were investigated. With the putative catalytic triad Ser114-Asp203-His235, AesZY belongs to the Acetyl esterase (Aes) family which is included in the alpha/beta hydrolase superfamily and contains the consensus Gly-X-Ser-X-Gly motif. The maximum activity of AesZY was detected at pH 8.0 and 40 degrees C. AesZY was stable at different pH values ranging from 5.0 to 12.0, and was tolerant to several metal ions. Furthermore, the deacetylation activity of AesZY toward 7-ACA was approximately 7.5 U/mg, and the Kcat/Km value was 2.04 s(-1) mM(-1). CONCLUSIONS: Our results demonstrate the characterization of a new acetyl esterase belonging to the Aes family with potential biotechnological applications.
ESTHER : Ding_2019_Biotechnol.Lett_41_1059
PubMedSearch : Ding_2019_Biotechnol.Lett_41_1059
PubMedID: 31302814
Gene_locus related to this paper: 9bacl-7ACAaes

Title : Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis - Sun_2019_Ann.Gen.Psychiatry_18_6
Author(s) : Sun H , Yang Y , Zhang L , Wu H , Zhang H , Li H
Ref : Ann Gen Psychiatry , 18 :6 , 2019
Abstract : Background: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD.
ESTHER : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedSearch : Sun_2019_Ann.Gen.Psychiatry_18_6
PubMedID: 31139237
Gene_locus related to this paper: human-NLGN4X

Title : Genetic Data from Nearly 63,000 Women of European Descent Predicts DNA Methylation Biomarkers and Epithelial Ovarian Cancer Risk - Yang_2019_Cancer.Res_79_505
Author(s) : Yang Y , Wu L , Shu X , Lu Y , Shu XO , Cai Q , Beeghly-Fadiel A , Li B , Ye F , Berchuck A , Anton-Culver H , Banerjee S , Benitez J , Bjorge L , Brenton JD , Butzow R , Campbell IG , Chang-Claude J , Chen K , Cook LS , Cramer DW , deFazio A , Dennis J , Doherty JA , Dork T , Eccles DM , Edwards DV , Fasching PA , Fortner RT , Gayther SA , Giles GG , Glasspool RM , Goode EL , Goodman MT , Gronwald J , Harris HR , Heitz F , Hildebrandt MA , Hogdall E , Hogdall CK , Huntsman DG , Kar SP , Karlan BY , Kelemen LE , Kiemeney LA , Kjaer SK , Koushik A , Lambrechts D , Le ND , Levine DA , Massuger LF , Matsuo K , May T , McNeish IA , Menon U , Modugno F , Monteiro AN , Moorman PG , Moysich KB , Ness RB , Nevanlinna H , Olsson H , Onland-Moret NC , Park SK , Paul J , Pearce CL , Pejovic T , Phelan CM , Pike MC , Ramus SJ , Riboli E , Rodriguez-Antona C , Romieu I , Sandler DP , Schildkraut JM , Setiawan VW , Shan K , Siddiqui N , Sieh W , Stampfer MJ , Sutphen R , Swerdlow AJ , Szafron LM , Teo SH , Tworoger SS , Tyrer JP , Webb PM , Wentzensen N , White E , Willett WC , Wolk A , Woo YL , Wu AH , Yan L , Yannoukakos D , Chenevix-Trench G , Sellers TA , Pharoah PDP , Zheng W , Long J
Ref : Cancer Research , 79 :505 , 2019
Abstract : DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high-density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N = 1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P < 7.94 x 10(-7). Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27, and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression. SIGNIFICANCE: Identification of novel DNA methylation markers associated with EOC risk suggests that methylation at multiple CpG may affect EOC risk through regulation of gene expression.
ESTHER : Yang_2019_Cancer.Res_79_505
PubMedSearch : Yang_2019_Cancer.Res_79_505
PubMedID: 30559148

Title : Screening and determination for potential acetylcholinesterase inhibitory constituents from ginseng stem-leaf saponins using ultrafiltration (UF)-LC-ESI-MS(2) - Yang_2019_Phytochem.Anal_30_26
Author(s) : Yang Y , Liang X , Jin P , Li N , Zhang Q , Yan W , Zhang H , Sun J
Ref : Phytochem Anal , 30 :26 , 2019
Abstract : INTRODUCTION: Previous studies have demonstrated that several ginsenosides have remarkable inhibitory effect on acetylcholinesterase (AChE). In the present study, ginseng stem-leaf saponins (GSLS) can improve learning and memory of Alzheimer's disease patients. However, much comprehensive information regarding AChE inhibition of GSLS and its metabolites is yet unknown. OBJECTIVE: The present study aims to screen and determine the potential of AChE inhibitors (AChEIs) from GSLS. METHODOLOGY: The active fraction of the GSLS detected in vitro AChE inhibition assays was selected as a starting material for the screening of the potential of AChEIs using ultrafiltration liquid chromatography coupled to electrospray ionisation tandem mass spectrometry (UF-LC-ESI-MS(2) ). RESULTS: The results showed that 31 ginsenosides were identified with analysis using rapid resolution liquid chromatography with a diode array detector combined with electrospray ionisation tandem mass spectrometry (RRLC-DAD-ESI-MS(2) ) from the active fraction, and there are 27 compounds with AChE binding activity. Among them, 11 ginsenosides were evaluated and confirmed using in vitro enzymatic assay, and ginsenosides F1 , Rd, Rk3 , 20(S)-Rg3 , F2 and Rb2 were found to possess strong AChE inhibitory activities. CONCLUSION: The proposed UF-LC-ESI-MS(2) method was a powerful tool for the discovery of AChEIs from traditional Chinese medicine (TCM).
ESTHER : Yang_2019_Phytochem.Anal_30_26
PubMedSearch : Yang_2019_Phytochem.Anal_30_26
PubMedID: 30159954

Title : Effect and Safety of Huannao Yicong Formula () in Patients with Mild-to-Moderate Alzheimer's Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial - Yang_2019_Chin.J.Integr.Med_25_574
Author(s) : Yang Y , Liu JP , Fang JY , Wang HC , Wei Y , Cao Y , Liu JG , Liu LT , Li H
Ref : Chin J Integr Med , 25 :574 , 2019
Abstract : OBJECTIVE: To assess the effect and safety of Huannao Yicong Formula (, HYF) in the treatment of patients with mild-to-moderate Alzheimer's disease (AD). METHODS: Sixty patients with mild-tomoderate AD were evenly randomized into HYF group and donepezil group with the random number method. Patients in the HYF group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g placebo of HYF granules twice daily. The intervention lasted for 6 months. Clinical researchers, participants and statisticians were blinded to the treatment assignment throughout the study. The primary outcomes were scores of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum levels of acetylcholinesterase (AchE) and amyloid-beta protein 42 (Abeta42) were detected with enzymelinked immunosorbent assay kits. The scale assessments were conducted at baseline, the 3rd and 6th months of treatment, respectively. Biochemistry tests were conducted at baseline and the 6th month of treatment. RESULTS: A total of 52 patients completed the trial, 28 in HYF group and 24 in donepezil group. Compared with the baseline, HYF and donepezil signifificantly decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments remarkably reduced the serum levels of AchE and Abeta42 (both P<0.05). The CM-SS total effective rate of HYF was signifificantly higher than donepezil [75.00% (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in both groups. CONCLUSION: HYF is effective and safe for improving the cognitive function in mildto-moderate AD patients. [Trial registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-IOR-17011746)].
ESTHER : Yang_2019_Chin.J.Integr.Med_25_574
PubMedSearch : Yang_2019_Chin.J.Integr.Med_25_574
PubMedID: 30109588

Title : Graphene oxide disrupts the protein-protein interaction between Neuroligin\/NLG-1 and DLG-1 or MAGI-1 in nematode Caenorhabditis elegans - Zhao_2019_Sci.Total.Environ_700_134492
Author(s) : Zhao Y , Chen H , Yang Y , Wu Q , Wang D
Ref : Sci Total Environ , 700 :134492 , 2019
Abstract : Graphene oxide (GO) is a carbon-based engineered nanomaterial (ENM). Using Caenorhabditis elegans as an animal model, we investigated the effect of GO exposure on protein-protein interactions. In nematodes, NLG-1/Neuroligin, a postsynaptic protein, acted only in the neurons to regulate the GO toxicity. In the neurons, DLG-1, a PSD-95 protein, and MAGI-1, a S-SCAM protein, were identified as the downstream targets of NLG-1 in the regulation of GO toxicity. PKC-1, a serine/threonine protein kinase C, further acted downstream of neuronal DLG-1 and MAGI-1 to regulate the GO toxicity. Co-immunoprecipitation analysis demonstrated the protein-protein interaction between NLG-1 and DLG-1 or MAGI-1. After GO expression, this protein-protein interaction between NLG-1 and DLG-1 or MAGI-1 was significantly inhibited. Therefore, our data raised the evidence to suggest the potential of GO exposure in disrupting protein-protein interactions in organisms.
ESTHER : Zhao_2019_Sci.Total.Environ_700_134492
PubMedSearch : Zhao_2019_Sci.Total.Environ_700_134492
PubMedID: 31627046
Gene_locus related to this paper: caeel-NLGN1 , human-NLGN1

Title : Characterization of a novel thermostable carboxylesterase from thermoalkaliphilic bacterium Bacillus thermocloaceae - Yang_2019_Biosci.Biotechnol.Biochem__1
Author(s) : Yang Y , Ghatge S , Hur HG
Ref : Biosci Biotechnol Biochem , :1 , 2019
Abstract : A novel thermostable carboxylesterase (Est5250) of thermoalkaliphilic bacterium Bacillus thermocloaceae was heterologously expressed in Escherichia coli and its biochemical properties were investigated. Est5250 showed optimum esterase activity at 60 degrees C and pH 8.0. The enzyme was highly thermostable at 60 degrees C, interestingly, the thermostability was enhanced in the presence of Ca(2+), retaining more than 60% of its original activity after 12 h of pre-incubation. Est5250 was active in the presence of 1% (v/v) of organic solvents and 0.1% (v/v) of non-ionic detergents. The enzyme activity was significantly enhanced up to 167% and 159% in the presence of 2-mercaptoethanol and dithiothreitol, respectively. Est5250 showed high substrate specificity for short-chain p-nitrophenyl-esters. Kinetic constants, Km and kcat, for p-nitrophenyl-acetate were 185.8 muM and 186.6 s(-1), respectively. Est5250 showed outstanding thermostability and tolerance to various organic solvents under thermoalkaliphilic conditions, suggesting that it would be a highly suitable biocatalyst for various biotechnological applications. Abbreviations: B. thermocloaceae sp.: Bacillus thermocloaceae; E. coli: Escherichia coli; NP: nitrophenyl; DMSO: dimethyl sulfoxide; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; DMF: dimethyl formamide; EGTA: ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid; CTAB: cetrimonium bromide; PMSF: phenylmethylsulfonyl fluoride; DEPC: diethyl pyrocarbonate; 2-ME: 2-mercaptoethanol; DTT: dithiothreitol.
ESTHER : Yang_2019_Biosci.Biotechnol.Biochem__1
PubMedSearch : Yang_2019_Biosci.Biotechnol.Biochem__1
PubMedID: 30739541
Gene_locus related to this paper: 9baci-Est5250

Title : Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats - Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
Author(s) : Wu Q , Cao Y , Liu M , Liu F , Brantner AH , Yang Y , Wei Y , Zhou Y , Wang Z , Ma L , Wang F , Pei H , Li H
Ref : Neuropsychiatr Dis Treat , 15 :3167 , 2019
Abstract : Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.
ESTHER : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedSearch : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedID: 31814724

Title : A Simple 3D-Printed Enzyme Reactor Paper Spray Mass Spectrometry Platform for Detecting BuChE Activity in Human Serum - Yang_2019_Anal.Chem_91_12874
Author(s) : Yang Y , Liu H , Chen Z , Wu T , Jiang Z , Tong L , Tang B
Ref : Analytical Chemistry , 91 :12874 , 2019
Abstract : To achieve personalized healthcare, a quick, accurate, and high-throughput method to detect disease biomarkers is essential. In the traditional practice, mass spectrometry is one of the most powerful tools and is widely studied. However, the test of human serum usually requires complicated sample pretreatment, tedious operations, and precise condition control, especially for the detection of enzymes as biomarkers. As butyrylcholinesterase (BuChE) has an indicative significance in detecting degenerative disease, liver injury, and organophosphate poisoning, the quick quantification of BuChE is of vital importance to the clinic. In this paper, we report the design and fabrication of a portable 3D-printed enzyme reactor paper spray cartridge (3D ER-PS) with integrated functions: temperature control, enzyme reaction, analyte transfer, and paper spray ionization. Coupled with mass spectrometry, quantitative testing of BuChE activity in human serum was realized conveniently and accurately. While it only requires very simple sample preparation, the results from current 3D ER-PS approach are well consistent with those obtained using Ellman's method. This 3D ER-PS platform not only provides a novel solution for the liquid biopsy of BuChE in clinics but also contributes to the development of quick and targeted medical approaches for analyzing other types of serum biomarker molecules in the field of disease diagnosis.
ESTHER : Yang_2019_Anal.Chem_91_12874
PubMedSearch : Yang_2019_Anal.Chem_91_12874
PubMedID: 31518111

Title : Musa balbisiana genome reveals subgenome evolution and functional divergence - Wang_2019_Nat.Plants_5_810
Author(s) : Wang Z , Miao H , Liu J , Xu B , Yao X , Xu C , Zhao S , Fang X , Jia C , Wang J , Zhang J , Li J , Xu Y , Ma W , Wu Z , Yu L , Yang Y , Liu C , Guo Y , Sun S , Baurens FC , Martin G , Salmon F , Garsmeur O , Yahiaoui N , Hervouet C , Rouard M , Laboureau N , Habas R , Ricci S , Peng M , Guo A , Xie J , Li Y , Ding Z , Yan Y , Tie W , D'Hont A , Hu W , Jin Z
Ref : Nat Plants , 5 :810 , 2019
Abstract : Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.
ESTHER : Wang_2019_Nat.Plants_5_810
PubMedSearch : Wang_2019_Nat.Plants_5_810
PubMedID: 31308504
Gene_locus related to this paper: musam-m0tuu7 , musam-a0a804kav5

Title : Design, synthesis and evaluation of a novel metal chelator as multifunctional agents for the treatment of Alzheimer's disease - Wang_2019_Bioorg.Chem_87_720
Author(s) : Wang Y , Yang Y , Hong KH , Ning Y , Yu P , Ren J , Ji M , Cai J
Ref : Bioorg Chem , 87 :720 , 2019
Abstract : A series of compounds following the lead compounds including deferasirox and tacrine were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). In vitro studies showed that most synthesized compounds exhibited good multifunctional activities in inhibiting acetylcholinesterase (bAChE), and chelating metal ions. Especially, compound TDe demonstrated significant metal chelating property, a moderate acetylcholinesterase (AChE) inhibitory activity and an antioxidant activity. Results from the molecular modeling indicated that TD compounds were mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of TcAChE. Moreover, TDe showed a low cytotoxicity but a good protective activity against the injury caused by H2O2. These results suggest that TD compounds might be considered as attractive multi-target cholinesterase inhibitor and will play important roles in the treatment of AD.
ESTHER : Wang_2019_Bioorg.Chem_87_720
PubMedSearch : Wang_2019_Bioorg.Chem_87_720
PubMedID: 30954836

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

Title : Intestinal damage, neurotoxicity and biochemical responses caused by tris (2-chloroethyl) phosphate and tricresyl phosphate on earthworm - Yang_2018_Ecotoxicol.Environ.Saf_158_78
Author(s) : Yang Y , Xiao Y , Chang Y , Cui Y , Klobucar G , Li M
Ref : Ecotoxicology & Environmental Safety , 158 :78 , 2018
Abstract : Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity. Hameatoxylin and eosin (H&E) demonstrated that intestinal cells suffered serious damage, and the observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it. Both TCEP and TCP significantly increased the DNA damage when the concentrations exceeded 1mg/kg (p<0.01), and a dose-response relationship was observed. In addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and expression of genes associated with neurotoxic effects in earthworms even under exposure to low OPEs concentration (0.1mg/kg). Moreover, genes associated with nicotinic acetylcholine receptors (nAChR) and carrier protein further demonstrated that highest concentration of TCEP (10mg/kg) may have an overloading impact on the cholinergic system of E. fetida. Integrated Biological Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under the same concentrations. We deduced that the observed intestinal damage, oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP and TCP toxicity. This study provides insight into the toxicological effects of OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil ecosystems.
ESTHER : Yang_2018_Ecotoxicol.Environ.Saf_158_78
PubMedSearch : Yang_2018_Ecotoxicol.Environ.Saf_158_78
PubMedID: 29660616

Title : Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy - Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
Author(s) : Wang Q , Liang Y , Qiao Y , Zhao X , Yang Y , Yang S , Li B , Zhao Q , Dong L , Quan S , Tian R , Liu Z
Ref : American Journal of Physiology Renal Physiol , 315 :F915 , 2018
Abstract : Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis.
ESTHER : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedSearch : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedID: 29717935

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

Title : Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry - Zhang_2018_Pharmacogn.Mag_14_248
Author(s) : Zhang H , Guo Y , Meng L , Sun H , Yang Y , Gao Y , Sun J
Ref : Pharmacogn Mag , 14 :248 , 2018
Abstract : Background: At present, approximately 17-25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY: A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry; (AChEIs): acetylcholinesterase inhibitors.
ESTHER : Zhang_2018_Pharmacogn.Mag_14_248
PubMedSearch : Zhang_2018_Pharmacogn.Mag_14_248
PubMedID: 29720840

Title : Association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed workers - Ding_2018_Ecotoxicol.Environ.Saf_161_563
Author(s) : Ding M , Yang Y , Duan X , Wang S , Feng X , Wang T , Wang P , Liu S , Li L , Liu J , Tang L , Niu X , Zhang Y , Li G , Yao W , Cui L , Wang W
Ref : Ecotoxicology & Environmental Safety , 161 :563 , 2018
Abstract : Omethoate, an organophosphorous pesticide, can cause a variety of health effects, especially the decrease of cholinesterase activity. The aim of this study is to explore the association of genetic polymorphisms of telomere binding proteins with cholinesterase activity in omethoate-exposed population. Cholinesterase activities in whole blood, red blood cell and plasma were detected using acetylthiocholine and dithio-bis-(nitrobenzoic acid) method; Genetic Genotyping of POT1 rs1034794, POT1 rs10250202, TERF1 rs3863242 and TERT rs2736098 were performed with PCR-RFLP. The cholinesterase activities of whole blood, red blood cells and plasma in exposure group are significantly lower than that of the control group (P<0.001). Multivariate analysis indicates that exposure group (b=-1.016, P<0.001), agender (b=0.365, P<0.001), drinking (b=0.271, P=0.004) and TERF1rs3863242 (b=-0.368, P=0.016) had an impact on cholinesterase activities. The results suggest that individual carrying AG+GG genotypes in TERF1 gene rs3863242 polymorphism were susceptible to damage in cholinesterase induced by omethoate.
ESTHER : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedSearch : Ding_2018_Ecotoxicol.Environ.Saf_161_563
PubMedID: 29929132

Title : Observational Study of Clinical and Functional Progression Based on Initial Brain MRI Characteristics in Patients with Alzheimer's Disease - Choi_2018_J.Alzheimers.Dis_66_1721
Author(s) : Choi H , Yang Y , Han HJ , Jeong JH , Park MY , Kim YB , Jo KD , Choi JY , Kang KH , Kang H , Kwon DY , Yoo BG , Lee HJ , Shin BS , Jeon SM , Kwon OD , Kim JS , Lee SJ , Kim Y , Park TH , Kim YJ , Yang HJ , Park HY , Shin HE , Lee JS , Jung YH , Lee AY , Shin DI , Shin KJ , Park KH
Ref : J Alzheimers Dis , 66 :1721 , 2018
Abstract : BACKGROUND: Magnetic resonance imaging (MRI) is a useful tool to predict the diagnosis and progression of Alzheimer's disease (AD), especially for primary physicians. However, the correlation between baseline MRI findings and AD progression has not been fully established. OBJECTIVE: To investigate the correlation between hippocampal atrophy (HA) and white matter hyperintensities (WMH) on initial brain MRI images and the degree of cognitive decline and functional changes over 1 year. METHODS: In this prospective, 12-month observational study, dementia outpatients were recruited from 29 centers across South Korea. Baseline assessments of HA and WMH on baseline brain MRI were derived as well as cognitive function, dementia severity, activities of daily living, and acetylcholinesterase inhibitor (AChEI) use. Follow-up assessments were conducted at 6 and 12 months. RESULTS: Among 899 enrolled dementia patients, 748 were diagnosed with AD of whom 654 (87%) were taking AChEIs. Baseline WMH showed significant correlations with age, current alcohol consumption, and Clinical Dementia Rating score; baseline HA was correlated with age, family history, physical exercise, and the results of cognitive assessments. Among the AChEI group, changes in the Korean version of the Instrumental Activities of Daily Living (K-IADL) were correlated with the severity of HA on baseline brain MRI, but not with the baseline severity of WMH. In the no AChEI group, changes in K-IADL were correlated with the severity of WMH and HA at baseline. CONCLUSION: Baseline MRI findings could be a useful tool for predicting future clinical outcomes by primary physicians, especially in relation to patients' functional status.
ESTHER : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedSearch : Choi_2018_J.Alzheimers.Dis_66_1721
PubMedID: 30452413

Title : Interaction between polymorphisms in cell-cycle genes and environmental factors in regulating cholinesterase activity in people with exposure to omethoate - Duan_2018_R.Soc.Open.Sci_5_172357
Author(s) : Duan X , Yang Y , Wang S , Feng X , Wang T , Wang P , Yao W , Cui L , Wang W
Ref : R Soc Open Sci , 5 :172357 , 2018
Abstract : Cholinesterase activity (ChA), the effective biomarker for organophosphate pesticide exposure, is possibly affected by single nucleotide polymorphisms (SNPs) in cell-cycle-related genes. One hundred and eighty workers with long-term exposure to omethoate and 115 healthy controls were recruited to explore the gene-gene and gene-environment interactions. The acetylthiocholine and dithio-bis-(nitrobenzoic acid) method was used to detect the cholinesterase activities in whole blood, erythrocytes and plasma. Genetic polymorphisms were determined by the PCR-RFLP and direct PCR electrophoresis methods. Statistical results showed that the cholinesterase activities of whole blood, erythrocytes and plasma in the exposure group were significantly lower than those in the control group (p < 0.001), and erythrocyte cholinesterase activities were associated with gender, smoking and drinking in the exposure group (p < 0.05). Single-locus analyses showed that there is a statistically significant difference in the ChA among the genotypes CC, CA and AA of the p21 rs1801270 locus in the control group (p = 0.033), but not in the exposure group. A significant interaction between genes and environmental factors (i.e. p53, p21, mdm2, gender, smoking and drinking) affecting ChA was found through a generalized multifactor dimensionality reduction analysis. These obtained markers will be useful in further marker-assisted selection in workers with exposure to omethoate.
ESTHER : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedSearch : Duan_2018_R.Soc.Open.Sci_5_172357
PubMedID: 29892419

Title : Transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformintreated SpragueDawley rats with type 2 diabetes mellitus - Chen_2018_Int.J.Mol.Med_41_3327
Author(s) : Chen Y , Wu Y , Yang Y , Xu Z , Tong J , Li Z , Zhou X , Li C
Ref : Int J Mol Med , 41 :3327 , 2018
Abstract : The main actions of metformin are as follows: To reduce hyperglycemia via the suppression of gluconeogenesis, improve glucose uptake and insulin sensitivity, and stimulate activation of adenosine monophosphateactivated protein kinase during the treatment of diabetes mellitus. It is well known that metformin acts via complex mechanisms, including multitarget and multipathway mechanisms; however, the multitargeted antidiabetic genes of metformin remain obscure. The present study aimed to perform transcriptomic and proteomic analysis of potential therapeutic target genes in the liver of metformintreated SpragueDawley rats with type 2 diabetes mellitus. The type 2 diabetes rat model was established using streptozotocin. Fasting blood glucose, hemoglobin A1c, serum insulin and biological parameters were subsequently measured. Differentially expressed genes (DEGs) and proteins were identified in the rat livers by expression profile analysis and isobaric tags for relative and absolute quantitation (iTRAQ). A 1.5fold alteration in gene expression, as determined using chipbased expression profile analysis, and a 1.2fold alteration in protein expression, as determined using iTRAQ, were considered physiologically significant benchmarks, which were used to identify DEGS in metformintreated rats with type 2 diabetes mellitus. The DEGs were verified using quantitative polymerase chain reaction (qPCR) and western blot analysis. Numerous hepatic genes involved in various metabolic pathways were affected by metformin; in particular, genes associated with lipid metabolism were markedly affected. Expression profile analysis and iTRAQ analysis suggested that carboxylesterase 1C subunit (Ces1C) and cholesterol 7alphahydroxylyase (Cyp7a1) may serve as important DEGs, which were validated by qPCR and western blot analysis. Ces1C and Cyp7a1 are the main enzymes in cholesterol metabolism, yet the result of western blotting was not consistent with qPCR. The present study demonstrated that metformin may affect the expression of numerous hepatic genes involved in metabolic pathways, particularly the lipid and cholesterol metabolic pathways. Ces1C and Cyp7a1 may be considered novel therapeutic target genes in the liver, which are involved in the antidiabetic effects of metformin.
ESTHER : Chen_2018_Int.J.Mol.Med_41_3327
PubMedSearch : Chen_2018_Int.J.Mol.Med_41_3327
PubMedID: 29512687

Title : Midgut transcriptomal response of the rice leaffolder, Cnaphalocrocis medinalis (Guenee) to Cry1C toxin - Yang_2018_PLoS.One_13_e0191686
Author(s) : Yang Y , Xu H , Lu Y , Wang C , Lu Z
Ref : PLoS ONE , 13 :e0191686 , 2018
Abstract : Cnaphalocrocis medinalis (Guenee) is one of the important insect pests in rice field. Bt agents were recommended in the C. medinalis control and Bt rice is bred as a tactic to control this insect. However, the tolerance or resistance of insect to Bt protein is a main threat to the application of Bt protein. In order to investigate the response of C. medinalis transcriptome in defending a Cry1C toxin, high-through RNA-sequencing was carried in the C. medinalis larvae treated with and without Cry1C toxin. A total of 35,586 high-quality unigenes was annotated in the transcriptome of C. medinalis midgut. The comparative analysis identified 6,966 differently expressed unigenes (DEGs) between the two treatments. GO analysis showed that these genes involved in proteolysis and extracellular region. Among these DEGs, carboxylesterase, glutathione S-transferase and P450 were differently expressed in the treated C. medinalis midgut. Furthermore, trypsin, chymotrypsin, and carboxypeptidase were identified in DEGs, and most of them up-regulated. In addition, thirteen ABC transporters were downregulated and three upregulated in Cry1C-treated C. medinalis midgut. Based on the pathway analysis, antigen processing and presentation pathway, and chronic myeloid leukemia pathway were significant in C. medinalis treated with Cry1C toxin. These results indicated that serine protease, detoxification enzymes and ABC transporter, antigen processing and presentation pathway, and chronic myeloid leukemia pathway may involved in the response of C. medinalis to Cry1C toxin. This study provides a transcriptomal foundation for the identification and functional characterization of genes involved in the toxicity of Bt Cry protein against C. medinalis, and provides potential clues to the studies on the tolerance or resistance of an agriculturally important insect pest C. medinalis to Cry1C toxin.
ESTHER : Yang_2018_PLoS.One_13_e0191686
PubMedSearch : Yang_2018_PLoS.One_13_e0191686
PubMedID: 29360856

Title : Maternal obesity aggravates the abnormality of porcine placenta by increasing N(6)-methyladenosine - Song_2018_Int.J.Obes.(Lond)_42_1812
Author(s) : Song T , Lu J , Deng Z , Xu T , Yang Y , Wei H , Li S , Jiang S , Peng J
Ref : Int J Obes (Lond) , 42 :1812 , 2018
Abstract : BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m(6)A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. SUBJECTS/METHODS: Forty four placentas from eight sows (backfat thickness >/=21 mm) were divided into four groups by piglet weight, with group1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m(6)A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m(6)A modification in the key genes. RESULTS: Compared with the comparative groups, the expression levels of PPARgamma, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m(6)A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m(6)A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m(6)A. By using MeRIP-QPCR technology, the m(6)A modification in PPARgamma, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. CONCLUSION: We infer that in maternity obesity, the higher m(6)A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m(6)A demethylase FTO.
ESTHER : Song_2018_Int.J.Obes.(Lond)_42_1812
PubMedSearch : Song_2018_Int.J.Obes.(Lond)_42_1812
PubMedID: 29795472

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 : Expression of Cellulolytic Enzyme as a Fusion Protein That Reacts Specifically With a Polymeric Scaffold - Katyal_2017_Methods.Enzymol_590_259
Author(s) : Katyal P , Yang Y , Vinogradova O , Lin Y
Ref : Methods Enzymol , 590 :259 , 2017
Abstract : The formation of higher-order assemblies of multiple proteins or enzymes is a general mechanism to achieve more sophisticated biological function in biological systems. For example, cellulosomes are large complexes consisting of multiple cellulolytic enzymes that rely on the concerted actions of different enzymes built onto a common protein scaffold to facilitate the breakdown of the polymeric substrate, cellulose. One strategy for mimicking these highly effective nanomachines may involve the use of synthetic scaffolds that can react to and organize multiple engineered enzymes to promote synergistic action between the enzymes on the scaffold. As an example of the earlier strategy, we describe here an approach for the expression of cellulolytic enzymes with a serine esterase tag, and the rapid reaction between the tag and the end-functionalized polymers to form enzyme-polymer-enzyme multienzyme conjugates. In principle, this general and versatile supramolecular approach may be used to organize specific cellulolytic enzymes onto synthetic scaffolds to form multienzyme complexes to potentially work in synergy for enhanced biological activities. Best reaction conditions, good activities of the armored cellulolytic enzymes and the design of optimal protein linker in the fusion protein are discussed in detail. If other reactive tags are included on the enzyme in future, multiple types of synergistic enzymes may be positioned at specific sites on a designed polymer scaffold that mimics the complex structure and enhanced function of natural cellulosomes. This type of nanoarmoring of multiple enzymes on a nanoscale might also enhance enzyme stability, when compared to the unprotected enzymes.
ESTHER : Katyal_2017_Methods.Enzymol_590_259
PubMedSearch : Katyal_2017_Methods.Enzymol_590_259
PubMedID: 28411640

Title : Identification and characterization of a novel carboxylesterase (FpbH) that hydrolyzes aryloxyphenoxypropionate herbicides - Wang_2017_Biotechnol.Lett_39_553
Author(s) : Wang C , Qiu J , Yang Y , Zheng J , He J , Li S
Ref : Biotechnol Lett , 39 :553 , 2017
Abstract : OBJECTIVE: To identify and characterize a novel aryloxyphenoxypropionate (AOPP) herbicide-hydrolyzing carboxylesterase from Aquamicrobium sp. FPB-1.
RESULTS: A carboxylesterase gene, fpbH, was cloned from Aquamicrobium sp. FPB-1. The gene is 798 bp long and encodes a protein of 265 amino acids. FpbH is smaller than previously reported AOPP herbicide-hydrolyzing carboxylesterases and shares only 21-35% sequence identity with them. FpbH was expressed in Escherichia coli BL21(DE3) and the product was purified by Ni-NTA affinity chromatography. The purified FpbH hydrolyzed a wide range of AOPP herbicides with catalytic efficiency in the order: haloxyfop-P-methyl > diclofop-methyl > fenoxaprop-P-ethyl > quizalofop-P-ethyl > fluazifop-P-butyl > cyhalofop-butyl. The optimal temperature and pH for FpbH activity were 37 degrees C and 7, respectively.
CONCLUSIONS: FpbH is a novel AOPP herbicide-hydrolyzing carboxylesterase; it is a good candidate for mechanistic study of AOPP herbicide-hydrolyzing carboxylesterases and for bioremediation of AOPP herbicide-contaminated environments.
ESTHER : Wang_2017_Biotechnol.Lett_39_553
PubMedSearch : Wang_2017_Biotechnol.Lett_39_553
PubMedID: 28058522
Gene_locus related to this paper: burvg-a4jl51

Title : Molecular cloning, characterization and expression analysis of two juvenile hormone esterase-like carboxylesterase cDNAs in Chinese mitten crab, Eriocheir sinensis - Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
Author(s) : Xu Y , Zhao M , Deng Y , Yang Y , Li X , Lu Q , Ge J , Pan J , Xu Z
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 205 :46 , 2017
Abstract : Precise regulation of methyl farnesoate (MF) titer is of prime importance throughout the crustacean life-cycle. Although the synthetic pathway of MF is well-documented, little is known about its degradation and recycling in crustaceans. Juvenile hormone esterase-like (JHE-like) carboxylesterase (CXE) is a key enzyme in MF degradation, thus playing a significant role in regulating the MF titer. We identified and characterized two cDNAs, Es-CXE1 and Es-CXE2, encoding JHE-like CXEs in Chinese mitten crab. Full-length cDNAs of Es-CXE1 and Es-CXE2 encode proteins composed of 584 and 597 amino acids, respectively, both of which contain a typical carboxylesterase domain. Alignment and phylogenetic analyses revealed that the Es-CXEs are highly similar to those of other crustaceans. To further validate their functions, we evaluated the mRNA expression patterns of the Es-CXEs in various tissues and in different physiological conditions. Tissue-specific expression analysis showed that the two Es-CXEs were predominantly expressed in the hepatopancreas and ovaries, which are the major tissues for MF metabolism. Es-CXE2 expression levels in the hepatopancreas and ovaries were about 100 and 25-fold higher, than the respective Es-CXE1 expressions. During ovarian rapid development stage, the global expressions of Es-CXEs were up-regulated in the hepatopancreas and down-regulated in the ovaries. After eyestalk ablation (ESA), the mRNA expressions of the two Es-CXEs were up-regulated in the hepatopancreas, further indicating their potential in degrading MF. Taken together, our results suggest that Es-CXEs, the key component of the juvenile hormone degradation pathway, may play vital roles in the development and reproduction of the Chinese mitten crab.
ESTHER : Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
PubMedSearch : Xu_2017_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_205_46
PubMedID: 28077333
Gene_locus related to this paper: erisi-a0a1l5jht6

Title : Development of tacrine-bifendate conjugates with improved cholinesterase inhibitory and pro-cognitive efficacy and reduced hepatotoxicity - Cen_2017_Eur.J.Med.Chem_144_128
Author(s) : Cen J , Guo H , Hong C , Lv J , Yang Y , Wang T , Fang D , Luo W , Wang C
Ref : Eur Journal of Medicinal Chemistry , 144 :128 , 2017
Abstract : A novel series of tacrine-bifendate (THA-DDB) conjugates (7a-e) were synthesized and evaluated as potential anti-Alzheimer's agents. These compounds showed potent cholinesterase and self-induced beta-amyloid (Abeta) aggregation inhibitory activities. A Lineweaver-Burk plot and molecular modeling study showed that these compounds can target both catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE). The cytotoxicity of the conjugate 7d against PC12 and HepG2 cells and hepatotoxicity against human hepatocyte cell line (HL-7702) were found to be considerably less compared to THA. Moreover, treatment with 7d did not exhibit significant hepatotoxicity in mice. Finally, in vivo studies confirmed that 7d significantly ameliorates the cognitive performances of scopolamine-treated ICR mice. Therefore, 7d has high potential for the treatment of Alzheimer's disease and warrants further investigation.
ESTHER : Cen_2017_Eur.J.Med.Chem_144_128
PubMedSearch : Cen_2017_Eur.J.Med.Chem_144_128
PubMedID: 29268129

Title : The Synergistic Effect of Microwave Radiation and Hypergravity on Rats and the Intervention Effect of Rana Sylvatica Le Conte Oil - Sun_2017_Dose.Response_15_1559325817711511
Author(s) : Sun W , Yang Y , Yu H , Wang L , Pan S
Ref : Dose Response , 15 :1559325817711511 , 2017
Abstract : AIM: The phenomena of hypergravity and microwave radiation are widespread, which cause more and more concern for the hazards to human health. The aim of this study was to investigate the synergistic effect of microwave radiation and hypergravity on rats and observe the protective effect of Rana sylvatica Le conte oil.
METHODS: Rats were exposed to microwave radiation and hypergravity, and the rat weight, the climbing pole height, serum enzyme activities, blood urea nitrogen concentration, and total antioxidant capacity were detected.
RESULTS: The climbing pole height, the activities of choline acetyl transferase and cholinesterase, and the total antioxidant capacity decreased, whereas the activities of alanine aminotransferase, aspartate aminotransferase, areatine kinase, isocitric dehydrogenase, hydroxybutyrate dehydrogenase, and the blood urea nitrogen concentration increased in the hypergravity irradiation group as compared with the others. CONCLUSION: These results imply that the motion and nervous system of rats might be affected critically by the synergistic effect of microwave radiation and hypergravity, and it causes damage to most rat organs, such as the bone, skeletal muscle, liver, heart, and kidney, and the antioxidant effect is also damaged, while the injury resulted from it could be protected by Rana sylvatica Le conte oil.
ESTHER : Sun_2017_Dose.Response_15_1559325817711511
PubMedSearch : Sun_2017_Dose.Response_15_1559325817711511
PubMedID: 28717348

Title : MERS-CoV spike protein: a key target for antivirals - Du_2017_Expert.Opin.Ther.Targets_21_131
Author(s) : Du L , Yang Y , Zhou Y , Lu L , Li F , Jiang S
Ref : Expert Opin Ther Targets , 21 :131 , 2017
Abstract : INTRODUCTION: The continual Middle East respiratory syndrome (MERS) threat highlights the importance of developing effective antiviral therapeutics to prevent and treat MERS coronavirus (MERS-CoV) infection. A surface spike (S) protein guides MERS-CoV entry into host cells by binding to cellular receptor dipeptidyl peptidase-4 (DPP4), followed by fusion between virus and host cell membranes. MERS-CoV S protein represents a key target for developing therapeutics to block viral entry and inhibit membrane fusion. Areas covered: This review illustrates MERS-CoV S protein's structure and function, particularly S1 receptor-binding domain (RBD) and S2 heptad repeat 1 (HR1) as therapeutic targets, and summarizes current advancement on developing anti-MERS-CoV therapeutics, focusing on neutralizing monoclonal antibodies (mAbs) and antiviral peptides. Expert opinion: No anti-MERS-CoV therapeutic is approved for human use. Several S-targeting neutralizing mAbs and peptides have demonstrated efficacy against MERS-CoV infection, providing feasibility for development. Generally, human neutralizing mAbs targeting RBD are more potent than those targeting other regions of S protein. However, emergence of escape mutant viruses and mAb's limitations make it necessary for combining neutralizing mAbs recognizing different neutralizing epitopes and engineering them with improved efficacy and reduced cost. Optimization of the peptide sequences is expected to produce next-generation anti-MERS-CoV peptides with improved potency.
ESTHER : Du_2017_Expert.Opin.Ther.Targets_21_131
PubMedSearch : Du_2017_Expert.Opin.Ther.Targets_21_131
PubMedID: 27936982

Title : N-myc downstream regulated gene 1(NDRG1) promotes the stem-like properties of lung cancer cells through stabilized c-Myc - Wang_2017_Cancer.Lett_401_53
Author(s) : Wang Y , Zhou Y , Tao F , Chai S , Xu X , Yang Y , Xu H , Wang K
Ref : Cancer Letters , 401 :53 , 2017
Abstract : Tumor-initiating cells (TICs) play an important role in tumorigenesis and development for many various tissue origin cancers including non-small cell lung cancer (NSCLC). However, the mechanism to maintain TICs in NSCLC is still largely unknown. Here, we evaluated differences of mRNA expression between parental and oncosphere cells that enriched TICs. We found that N-myc downstream regulated gene 1(NDRG1) was upregulated in oncosphere cells derived from human NSCLC cell lines and primary NSCLC cells. NDRG1 promoted stem-like properties of LTICs in NSCLC including iPSC (induced pluripotent stem cell) factors (OCT4, SOX2, KLF4, and C-MYC), the spheres-forming ability and the tumorigenicity of NSCLC. NDRG1 prevented the degradation of c-Myc through Skp2-mediated ubiquitination. NDRG1 directly interacted with Skp2, and decreased phosphorylation of Skp2 through inactivation of CDK2. Finally, we confirmed that NDRG1 was negatively correlated with survival and prognosis. Thus, our findings indicate that NDRG1 is a potential target for eradicating TICs in NSCLC.
ESTHER : Wang_2017_Cancer.Lett_401_53
PubMedSearch : Wang_2017_Cancer.Lett_401_53
PubMedID: 28456659
Gene_locus related to this paper: human-NDRG1

Title : Four new bi-2-(2-phenylethyl)chromone derivatives of agarwood from Aquilaria crassna - Yang_2017_Fitoterapia_119_20
Author(s) : Yang Y , Mei WL , Kong FD , Chen HQ , Li W , Chen ZB , Dai HF
Ref : Fitoterapia , 119 :20 , 2017
Abstract : Four new bi-2-(2-phenylethyl)chromone derivatives, crassins A-D (1-4), were isolated from the EtOAc extract of agarwood originating from Aquilaria crassna. The structures including the absolute configurations of compounds were unambiguously elucidated by extensive spectroscopic methods (1D and 2D NMR, UV, ECD, IR, MS), and by comparison with the literature. The isolated compounds were tested for their acetylcholinesterase (AChE) and alpha-glucosidase inhibitory activities, as well as cytotoxic activities. All the compounds showed weak inhibitory activity against AChE, while compounds 3 and 4 also displayed weak cytotoxicity against human myeloid leukemia cell line (K562).
ESTHER : Yang_2017_Fitoterapia_119_20
PubMedSearch : Yang_2017_Fitoterapia_119_20
PubMedID: 28300702

Title : Design, synthesis and evaluation of novel ferulic acid-O-alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - Sang_2017_Eur.J.Med.Chem_130_379
Author(s) : Sang Z , Pan W , Wang K , Ma Q , Yu L , Yang Y , Bai P , Leng C , Xu Q , Li X , Tan Z , Liu W
Ref : Eur Journal of Medicinal Chemistry , 130 :379 , 2017
Abstract : A series of novel ferulic acid-O-alkylamines derivatives were designed, synthesized, and evaluated as multitarget-directed ligands against Alzheimer's disease. In vitro studies displayed that all the synthesized target compounds showed impressive inhibitory activity against butyrylcholinesterase (BuChE), significant inhibition/disaggregation of self-induced beta-amyloid (Abeta) aggregation and acted as potential antioxidants. Particularly, compound 7f, one of the most potent BuChE inhibitor (IC50 value of 0.021 muM for equine serum BuChE, 8.63 muM for ratBuChE and 0.07 muM for human serum BuChE), was found to be a good acetylcholinesterase (AChE) inhibitor (IC50 = 2.13 muM for electric eel AChE, 1.8 muM for ratAChE and 3.82 muM for human erythrocytes AChE), and the result of molecular docking provided an explanation for its selective BuChE inhibitory activity. Compound 7f also had noteworthy inhibitory effects on self-induced Abeta1-42 aggregation (50.8 +/- 0.82%) and was found to disaggregate self-induced Abeta1-42 aggregation (38.7 +/- 0.65%), which was further elucidated by the transmission electron microscopy. Meanwhile, compound 7f showed the modest antioxidant activity (0.55 eq of Trolox), good protective effect against H2O2-induced PC12 cell injury, with low toxicity. Moreover, compound 7f could cross the blood-brain barrier (BBB) in vitro. Significantly, compound 7f did not exhibit any acute toxicity in mice at doses up to 1000 mg/kg, and the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. Taken together, the results indicated that compound 7f is a very promising multifunctional agent in the treatment of Alzheimer's disease, particularly the advanced stages of AD.
ESTHER : Sang_2017_Eur.J.Med.Chem_130_379
PubMedSearch : Sang_2017_Eur.J.Med.Chem_130_379
PubMedID: 28279845

Title : The genome draft of coconut (Cocos nucifera) - Xiao_2017_Gigascience_6_1
Author(s) : Xiao Y , Xu P , Fan H , Baudouin L , Xia W , Bocs S , Xu J , Li Q , Guo A , Zhou L , Li J , Wu Y , Ma Z , Armero A , Issali AE , Liu N , Peng M , Yang Y
Ref : Gigascience , 6 :1 , 2017
Abstract : Coconut palm (Cocos nucifera,2n = 32), a member of genus Cocos and family Arecaceae (Palmaceae), is an important tropical fruit and oil crop. Currently, coconut palm is cultivated in 93 countries, including Central and South America, East and West Africa, Southeast Asia and the Pacific Islands, with a total growth area of more than 12 million hectares [1]. Coconut palm is generally classified into 2 main categories: "Tall" (flowering 8-10 years after planting) and "Dwarf" (flowering 4-6 years after planting), based on morphological characteristics and breeding habits. This Palmae species has a long growth period before reproductive years, which hinders conventional breeding progress. In spite of initial successes, improvements made by conventional breeding have been very slow. In the present study, we obtained de novo sequences of the Cocos nucifera genome: a major genomic resource that could be used to facilitate molecular breeding in Cocos nucifera and accelerate the breeding process in this important crop. A total of 419.67 gigabases (Gb) of raw reads were generated by the Illumina HiSeq 2000 platform using a series of paired-end and mate-pair libraries, covering the predicted Cocos nucifera genome length (2.42 Gb, variety "Hainan Tall") to an estimated x173.32 read depth. A total scaffold length of 2.20 Gb was generated (N50 = 418 Kb), representing 90.91% of the genome. The coconut genome was predicted to harbor 28 039 protein-coding genes, which is less than in Phoenix dactylifera (PDK30: 28 889), Phoenix dactylifera (DPV01: 41 660), and Elaeis guineensis (EG5: 34 802). BUSCO evaluation demonstrated that the obtained scaffold sequences covered 90.8% of the coconut genome and that the genome annotation was 74.1% complete. Genome annotation results revealed that 72.75% of the coconut genome consisted of transposable elements, of which long-terminal repeat retrotransposons elements (LTRs) accounted for the largest proportion (92.23%). Comparative analysis of the antiporter gene family and ion channel gene families between C. nucifera and Arabidopsis thaliana indicated that significant gene expansion may have occurred in the coconut involving Na+/H+ antiporter, carnitine/acylcarnitine translocase, potassium-dependent sodium-calcium exchanger, and potassium channel genes. Despite its agronomic importance, C. nucifera is still under-studied. In this report, we present a draft genome of C. nucifera and provide genomic information that will facilitate future functional genomics and molecular-assisted breeding in this crop species.
ESTHER : Xiao_2017_Gigascience_6_1
PubMedSearch : Xiao_2017_Gigascience_6_1
PubMedID: 29048487
Gene_locus related to this paper: cocnu-a0a8k0hu18

Title : The Protective Effect of Lavender Essential Oil and Its Main Component Linalool against the Cognitive Deficits Induced by D-Galactose and Aluminum Trichloride in Mice - Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
Author(s) : Xu P , Wang K , Lu C , Dong L , Gao L , Yan M , Aibai S , Yang Y , Liu X
Ref : Evid Based Complement Alternat Med , 2017 :7426538 , 2017
Abstract : Lavender essential oil (LO) is a traditional medicine used for the treatment of Alzheimer's disease (AD). It was extracted from Lavandula angustifolia Mill. This study was designed to investigate the effects of lavender essential oil (LO) and its active component, linalool (LI), against cognitive impairment induced by D-galactose (D-gal) and AlCl3 in mice and to explore the related mechanisms. Our results revealed that LO (100 mg/kg) or LI (100 mg/kg) significantly protected the cognitive impairments as assessed by the Morris water maze test and step-though test. The mechanisms study demonstrated that LO and LI significantly protected the decreased activity of superoxide dismutase (SOD), glutathione peroxidase (GPX), and protected the increased activity of acetylcholinesterase (AChE) and content of malondialdehyde (MDA). Besides, they protected the suppressed nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression significantly. Moreover, the decreased expression of synapse plasticity-related proteins, calcium-calmodulin-dependent protein kinase II (CaMKII), p-CaMKII, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were increased with drug treatment. In conclusion, LO and its active component LI have protected the oxidative stress, activity of cholinergic function and expression of proteins of Nrf2/HO-1 pathway, and synaptic plasticity. It suggest that LO, especially LI, could be a potential agent for improving cognitive impairment in AD.
ESTHER : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedSearch : Xu_2017_Evid.Based.Complement.Alternat.Med_2017_7426538
PubMedID: 28529531

Title : Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer - Yang_2016_Tumour.Biol_37_1183
Author(s) : Yang Y , Shao Y , Zhu M , Li Q , Yang F , Lu X , Xu C , Xiao B , Sun Y , Guo J
Ref : Tumour Biol , 37 :1183 , 2016
Abstract : Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer.
ESTHER : Yang_2016_Tumour.Biol_37_1183
PubMedSearch : Yang_2016_Tumour.Biol_37_1183
PubMedID: 26280398
Gene_locus related to this paper: human-ABHD11

Title : Characterization of DWARF14 Genes in Populus - Zheng_2016_Sci.Rep_6_21593
Author(s) : Zheng K , Wang X , Weighill DA , Guo HB , Xie M , Yang Y , Yang J , Wang S , Jacobson DA , Guo H , Muchero W , Tuskan GA , Chen JG
Ref : Sci Rep , 6 :21593 , 2016
Abstract : Strigolactones are a new class of plant hormones regulating shoot branching and symbiotic interactions with arbuscular mycorrhizal fungi. Studies of branching mutants in herbaceous plants have identified several key genes involved in strigolactone biosynthesis or signaling. The strigolactone signal is perceived by a member of the alpha/beta-fold hydrolase superfamily, known as DWARF14 (D14). However, little is known about D14 genes in the woody perennial plants. Here we report the identification of D14 homologs in the model woody plant Populus trichocarpa. We showed that there are two D14 homologs in P. trichocarpa, designated as PtD14a and PtD14b that are over 95% similar at the amino acid level. Expression analysis indicated that the transcript level of PtD14a is generally more abundant than that of PtD14b. However, only PtD14a was able to complement Arabidopsis d14 mutants, suggesting that PtD14a is the functional D14 ortholog. Amino acid alignment and structural modeling revealed substitutions of several highly conserved amino acids in the PtD14b protein including a phenylalanine near the catalytic triad of D14 proteins. This study lays a foundation for further characterization of strigolactone pathway and its functions in the woody perennial plants.
ESTHER : Zheng_2016_Sci.Rep_6_21593
PubMedSearch : Zheng_2016_Sci.Rep_6_21593
PubMedID: 26875827

Title : Identification and Characterization of a New Alkaline SGNH Hydrolase from a Thermophilic Bacterium Bacillus sp. K91 - Yu_2016_J.Microbiol.Biotechnol_26_730
Author(s) : Yu T , Ding J , Zheng Q , Han N , Yu J , Yang Y , Li J , Mu Y , Wu Q , Huang Z
Ref : J Microbiol Biotechnol , 26 :730 , 2016
Abstract : est19 is a gene from Bacillus sp. K91 that encodes a new esterase. A comparison of the amino acid sequence showed that Est19 has typical Ser-Gly-Asn-His (SGNH) family motifs and could be grouped into the SGNH hydrolase family. The Est19 protein was functionally cloned, and expressed and purified from Escherichia coli BL21(DE3). The enzyme activity was optimal at 60 degrees C and pH 9.0, and displayed esterase activity towards esters with short-chain acyl esters (C(2)-C(6)). A structural model of Est19 was constructed using phospholipase A1 from Streptomyces albidoflavus NA297 as a template. The structure showed an alpha/beta-hydrolase fold and indicated the presence of the typical catalytic triad Ser49-Asp227-His230, which were further investigated by site-directed mutagenesis. To the best of our knowledge, Est19 is a new member of the SGNH hydrolase family identified from thermophiles, which may be applicable in the industrial production of semisynthetic beta-lactam antibiotics after modification.
ESTHER : Yu_2016_J.Microbiol.Biotechnol_26_730
PubMedSearch : Yu_2016_J.Microbiol.Biotechnol_26_730
PubMedID: 26699742

Title : Biosynthesis of Antibiotic Leucinostatins in Bio-control Fungus Purpureocillium lilacinum and Their Inhibition on Phytophthora Revealed by Genome Mining - Wang_2016_PLoS.Pathog_12_e1005685
Author(s) : Wang G , Liu Z , Lin R , Li E , Mao Z , Ling J , Yang Y , Yin WB , Xie B
Ref : PLoS Pathog , 12 :e1005685 , 2016
Abstract : Purpureocillium lilacinum of Ophiocordycipitaceae is one of the most promising and commercialized agents for controlling plant parasitic nematodes, as well as other insects and plant pathogens. However, how the fungus functions at the molecular level remains unknown. Here, we sequenced two isolates (PLBJ-1 and PLFJ-1) of P. lilacinum from different places Beijing and Fujian. Genomic analysis showed high synteny of the two isolates, and the phylogenetic analysis indicated they were most related to the insect pathogen Tolypocladium inflatum. A comparison with other species revealed that this fungus was enriched in carbohydrate-active enzymes (CAZymes), proteases and pathogenesis related genes. Whole genome search revealed a rich repertoire of secondary metabolites (SMs) encoding genes. The non-ribosomal peptide synthetase LcsA, which is comprised of ten C-A-PCP modules, was identified as the core biosynthetic gene of lipopeptide leucinostatins, which was specific to P. lilacinum and T. ophioglossoides, as confirmed by phylogenetic analysis. Furthermore, gene expression level was analyzed when PLBJ-1 was grown in leucinostatin-inducing and non-inducing medium, and 20 genes involved in the biosynthesis of leucionostatins were identified. Disruption mutants allowed us to propose a putative biosynthetic pathway of leucinostatin A. Moreover, overexpression of the transcription factor lcsF increased the production (1.5-fold) of leucinostatins A and B compared to wild type. Bioassays explored a new bioactivity of leucinostatins and P. lilacinum: inhibiting the growth of Phytophthora infestans and P. capsici. These results contribute to our understanding of the biosynthetic mechanism of leucinostatins and may allow us to utilize P. lilacinum better as bio-control agent.
ESTHER : Wang_2016_PLoS.Pathog_12_e1005685
PubMedSearch : Wang_2016_PLoS.Pathog_12_e1005685
PubMedID: 27416025
Gene_locus related to this paper: metcm-a0a179g1m3 , metcm-a0a179g2w0 , metcm-a0a4q7js68 , purli-lcse

Title : Anti-phytopathogen, multi-target acetylcholinesterase inhibitory and antioxidant activities of metabolites from endophytic Chaetomium globosum - Li_2016_Nat.Prod.Res__1
Author(s) : Li W , Yang X , Yang Y , Duang R , Chen G , Li X , Li Q , Qin S , Li S , Zhao L , Ding Z
Ref : Nat Prod Res , :1 , 2016
Abstract : Fourteen metabolites with various structure types were isolated from endophytic Chaetomium globosum. Five compounds were separated from genus Chaetomium for the first time. Some compounds exhibited remarkable inhibition against phytopathogenic fungi causing root rot of Panax notoginseng. Compounds 1-5 had significant DPPH-free radical-scavenging activity. Compounds 3 and 5 indicated significant inhibitions against the acetylcholinesterase (AChE). From preliminary structure-activity relationship, it was found that the oxygenic five-membered ring of 3 and 5 was crucial in the anti-AChE activity. These structures provide new templates for the potential treatment and management of plant diseases and Alzheimer disease.
ESTHER : Li_2016_Nat.Prod.Res__1
PubMedSearch : Li_2016_Nat.Prod.Res__1
PubMedID: 26744178

Title : Comment on A bacterium that degrades and assimilates poly(ethylene terephthalate) - Yang_2016_Science_353_759
Author(s) : Yang Y , Yang J , Jiang L
Ref : Science , 353 :759 , 2016
Abstract : Yoshida et al (Report, 11 March 2016, p. 1196) reported that the bacterium Ideonella sakaiensis 201-F6 can degrade and assimilate poly(ethylene terephthalate) (PET). However, the authors exaggerated degradation efficiency using a low-crystallinity PET and presented no straightforward experiments to verify depolymerization and assimilation of PET. Thus, the authors' conclusions are rather misleading.
ESTHER : Yang_2016_Science_353_759
PubMedSearch : Yang_2016_Science_353_759
PubMedID: 27540159
Gene_locus related to this paper: idesa-peth

Title : Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting - Ma_2016_Atherosclerosis_251_305
Author(s) : Ma W , Liang Y , Zhu J , Chen T , Feng G , Yang Y , Liu X , Wang X
Ref : Atherosclerosis , 251 :305 , 2016
Abstract : BACKGROUND AND AIMS: Asians have very different genotype distributions of cytochrome P450 2C19 (CYP2C19), ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase-1 (PON1), in whom relevant studies based on large samples are scarce. The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in Chinese patients after coronary stenting.
METHODS: A total of 2569 acute coronary syndrome (ACS) patients were enrolled in a gene database study. Among the 1674 patients receiving coronary stenting, 504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort.
RESULTS: The prevalence of the CYP2C19 loss-of-function carriers (had at least 1 allele of *2, *3 and *4) was considerable high (52.2%). During re-angiography, in-stent restenosis occurred in 106 (21.0%) out of the 504 patients; the mean restenosis degree was 71.3% and 152 (30.2%) patients received re-stenting treatment. In multivariate regression, only age and left ventricular ejection fraction (LVEF) were significantly associated with in-stent restenosis. As for predictors of re-stenting, multivariate regression identified variables of LVEF, coronary artery lesions, and PON1 Q192R genotype. Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR (OR 1.95, 95% CI 1.30-2.93, p = 0.001). The genotypes of CYP2C19, ABCB1 C3435T, and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting.
CONCLUSIONS: Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.
ESTHER : Ma_2016_Atherosclerosis_251_305
PubMedSearch : Ma_2016_Atherosclerosis_251_305
PubMedID: 27450784

Title : Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation - Zhang_2016_J.Pharmacol.Exp.Ther_359_374
Author(s) : Zhang J , Zhang L , Sun X , Yang Y , Kong L , Lu C , Lv G , Wang T , Wang H , Fu F
Ref : Journal of Pharmacology & Experimental Therapeutics , 359 :374 , 2016
Abstract : Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.
ESTHER : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedSearch : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedID: 27535978

Title : Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer - Gui_2016_Int.Urol.Nephrol_48_701
Author(s) : Gui SL , Teng LC , Wang SQ , Liu S , Lin YL , Zhao XL , Liu L , Sui HY , Yang Y , Liang LC , Wang ML , Li XY , Cao Y , Li FY , Wang WQ
Ref : International Urology & Nephrology , 48 :701 , 2016
Abstract : PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis.
ESTHER : Gui_2016_Int.Urol.Nephrol_48_701
PubMedSearch : Gui_2016_Int.Urol.Nephrol_48_701
PubMedID: 26837773

Title : Chemical Constituents of Plants from the Genus Phlegmariurus - Yang_2016_Chem.Biodivers_13_269
Author(s) : Yang Y , Wang Z , Wu J , Chen Y
Ref : Chem Biodivers , 13 :269 , 2016
Abstract : Phlegmariurus is a genus of ca. 200 species in the family Huperziaceae. Up to now, six species of the Phlegmariurus genus have been chemically investigated, and 89 compounds, including Lycopodium alkaloids possessing diverse structures and serratane-type triterpenes, have been isolated. These compounds show potent bioactivities, such as acetylcholinesterase inhibitory and cytotoxic activities.
ESTHER : Yang_2016_Chem.Biodivers_13_269
PubMedSearch : Yang_2016_Chem.Biodivers_13_269
PubMedID: 26916276

Title : Genomic and proteomic characterization of Candidatus Nitrosopelagicus brevis: an ammonia-oxidizing archaeon from the open ocean - Santoro_2015_Proc.Natl.Acad.Sci.U.S.A_112_1173
Author(s) : Santoro AE , Dupont CL , Richter RA , Craig MT , Carini P , McIlvin MR , Yang Y , Orsi WD , Moran DM , Saito MA
Ref : Proc Natl Acad Sci U S A , 112 :1173 , 2015
Abstract : Thaumarchaeota are among the most abundant microbial cells in the ocean, but difficulty in cultivating marine Thaumarchaeota has hindered investigation into the physiological and evolutionary basis of their success. We report here a closed genome assembled from a highly enriched culture of the ammonia-oxidizing pelagic thaumarchaeon CN25, originating from the open ocean. The CN25 genome exhibits strong evidence of genome streamlining, including a 1.23-Mbp genome, a high coding density, and a low number of paralogous genes. Proteomic analysis recovered nearly 70% of the predicted proteins encoded by the genome, demonstrating that a high fraction of the genome is translated. In contrast to other minimal marine microbes that acquire, rather than synthesize, cofactors, CN25 encodes and expresses near-complete biosynthetic pathways for multiple vitamins. Metagenomic fragment recruitment indicated the presence of DNA sequences >90% identical to the CN25 genome throughout the oligotrophic ocean. We propose the provisional name "Candidatus Nitrosopelagicus brevis" str. CN25 for this minimalist marine thaumarchaeon and suggest it as a potential model system for understanding archaeal adaptation to the open ocean.
ESTHER : Santoro_2015_Proc.Natl.Acad.Sci.U.S.A_112_1173
PubMedSearch : Santoro_2015_Proc.Natl.Acad.Sci.U.S.A_112_1173
PubMedID: 25587132

Title : Biodegradation and Mineralization of Polystyrene by Plastic-Eating Mealworms: Part 1. Chemical and Physical Characterization and Isotopic Tests - Yang_2015_Environ.Sci.Technol_49_12080
Author(s) : Yang Y , Yang J , Wu WM , Zhao J , Song Y , Gao L , Yang R , Jiang L
Ref : Environ Sci Technol , 49 :12080 , 2015
Abstract : Polystyrene (PS) is generally considered to be durable and resistant to biodegradation. Mealworms (the larvae of Tenebrio molitor Linnaeus) from different sources chew and eat Styrofoam, a common PS product. The Styrofoam was efficiently degraded in the larval gut within a retention time of less than 24 h. Fed with Styrofoam as the sole diet, the larvae lived as well as those fed with a normal diet (bran) over a period of 1 month. The analysis of fecula egested from Styrofoam-feeding larvae, using gel permeation chromatography (GPC), solid-state (13)C cross-polarization/magic angle spinning nuclear magnetic resonance (CP/MAS NMR) spectroscopy, and thermogravimetric Fourier transform infrared (TG-FTIR) spectroscopy, substantiated that cleavage/depolymerization of long-chain PS molecules and the formation of depolymerized metabolites occurred in the larval gut. Within a 16 day test period, 47.7% of the ingested Styrofoam carbon was converted into CO2 and the residue (ca. 49.2%) was egested as fecula with a limited fraction incorporated into biomass (ca. 0.5%). Tests with alpha (13)C- or beta (13)C-labeled PS confirmed that the (13)C-labeled PS was mineralized to (13)CO2 and incorporated into lipids. The discovery of the rapid biodegradation of PS in the larval gut reveals a new fate for plastic waste in the environment.
ESTHER : Yang_2015_Environ.Sci.Technol_49_12080
PubMedSearch : Yang_2015_Environ.Sci.Technol_49_12080
PubMedID: 26390034

Title : Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus - Yang_2015_J.Virol_89_9119
Author(s) : Yang Y , Liu C , Du L , Jiang S , Shi Z , Baric RS , Li F
Ref : J Virol , 89 :9119 , 2015
Abstract : To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts.
ESTHER : Yang_2015_J.Virol_89_9119
PubMedSearch : Yang_2015_J.Virol_89_9119
PubMedID: 26063432

Title : A point mutation in the acetylcholinesterase-1 gene is associated with chlorpyrifos resistance in the plant bug Apolygus lucorum - Wu_2015_Insect.Biochem.Mol.Biol_65_75
Author(s) : Wu S , Zuo K , Kang Z , Yang Y , Oakeshott JG , Wu Y
Ref : Insect Biochemistry & Molecular Biology , 65 :75 , 2015
Abstract : Control of Chinese Apolygus lucorum relies heavily on organophosphate insecticides. Here we describe resistance to the organophosphate chlorpyrifos in an A. lucorum strain, BZ-R, which was developed from a field-collected strain (BZ) by selection with chlorpyrifos in the laboratory. BZ-R showed 21-58 fold resistance to chlorpyrifos compared with the laboratory reference strain LSF and another susceptible strain, BZ-S, derived from BZ. BZ-R also showed several fold resistance to two other organophosphates and a carbamate. No synergism of chlorpyrifos by metabolic enzyme inhibitors nor any increase in detoxifying enzyme activities were observed in BZ-R. No sequence differences in acetylcholinesterase-2 were found to be associated with the resistance but the frequency of an alanine to serine substitution at position 216 of acetylcholinesterase-1 was 100% in BZ-R, approximately 21-23% in SLF and BZ, and 0% in BZ-S. A single generation treatment of chlorpyrifos on the BZ strain also increased its frequency of the serine substitution to 64%. Recombinantly expressed acetylcholinesterase-1 carrying the serine substitution was about five fold less sensitive to inhibition by chlorpyrifos oxon than the wild-type enzyme. Quantitative real-time PCR found no differences in ace1 or ace2 expression levels among the strains tested. Thus the chlorpyrifos resistance is strongly associated with the serine substituted acetylcholinesterase-1. An equivalent substitution has been found to confer resistance to many organophosphate and carbamate insecticides in four other insect species.
ESTHER : Wu_2015_Insect.Biochem.Mol.Biol_65_75
PubMedSearch : Wu_2015_Insect.Biochem.Mol.Biol_65_75
PubMedID: 26363297
Gene_locus related to this paper: apolu-ACHE1

Title : Inhibition of osteoclast differentiation by overexpression of NDRG2 in monocytes - Kang_2015_Biochem.Biophys.Res.Commun_468_611
Author(s) : Kang K , Nam S , Kim B , Lim JH , Yang Y , Lee MS , Lim JS
Ref : Biochemical & Biophysical Research Communications , 468 :611 , 2015
Abstract : N-Myc downstream-regulated gene 2 (NDRG2), a member of the NDRG family of differentiation-related genes, has been characterized as a regulator of dendritic cell differentiation from monocytes, CD34(+) progenitor cells, and myelomonocytic leukemic cells. In this study, we show that NDRG2 overexpression inhibits the differentiation of U937 cells into osteoclasts in response to stimulation with a combination of macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-kappaB ligand (RANKL). U937 cells stably expressing NDRG2 are unable to differentiate into multinucleated osteoclast-like cells and display reduced tartrate-resistant acid phosphatase (TRAP) activity and resorption pit formation. Furthermore, NDRG2 expression significantly suppresses the expression of genes that are crucial for the proliferation, survival, differentiation, and function of osteoclasts, including c-Fos, Atp6v0d2, RANK, and OSCAR. The activation of ERK1/2 and p38 is also inhibited by NDRG2 expression during osteoclastogenesis, and the inhibition of osteoclastogenesis by NDRG2 correlates with the down-regulation of the expression of the transcription factor PU.1. Taken together, our results suggest that the expression of NDRG2 potentially inhibits osteoclast differentiation and plays a role in modulating the signal transduction pathway responsible for osteoclastogenesis.
ESTHER : Kang_2015_Biochem.Biophys.Res.Commun_468_611
PubMedSearch : Kang_2015_Biochem.Biophys.Res.Commun_468_611
PubMedID: 26546825

Title : Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro - Liu_2015_Sci.Rep_5_17108
Author(s) : Liu JJ , Huang N , Lu Y , Zhao M , Yu XJ , Yang Y , Yang YH , Zang WJ
Ref : Sci Rep , 5 :17108 , 2015
Abstract : Cardiac remodeling is characterized by overactivity of the renin-angiotensin system (RAS) and withdrawal of vagal activity. We hypothesized that improving vagal activity could attenuate cardiac fibrosis induced by angiotensin II (Ang II) in vivo and in vitro. Rats were subjected to abdominal aorta constriction (AAC) with or without pyridostigmine (PYR) (31 mg/kg/d). After 8 weeks, PYR significantly decreased Ang II level, AT1 protein expression, and collagen deposition in cardiac tissue and improved heart rate variability, baroreflex sensitivity and cardiac function, which were abolished by atropine. In vitro, treatment of cardiac fibroblasts (CFs) with Ang II (10(-7) M) increased cell proliferation, migration, transformation, and secretory properties, which were significantly diminished by acetylcholine (ACh, 10(-6) M). Subsequently, Ang II significantly increased collagen type I expression as well as metalloproteinase (MMP)-2 expression and activity. Transforming growth factor (TGF)-beta1 expression and Smad3 phosphorylation presented a similar trend. Notably, the knockdown of the acetylcholine M2 receptor by siRNA could abolish ACh anti-fibrotic action. These data implicated cholinesterase inhibitor can increase vagal activity and reduce local Ang II level, and ACh inhibit Ang II pro-fibrotic effects. Our findings suggested that the parasympathetic nervous system can serve as a promising target for cardiac remodeling treatment.
ESTHER : Liu_2015_Sci.Rep_5_17108
PubMedSearch : Liu_2015_Sci.Rep_5_17108
PubMedID: 26596640

Title : Genome sequence of the Asian Tiger mosquito, Aedes albopictus, reveals insights into its biology, genetics, and evolution - Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
Author(s) : Chen XG , Jiang X , Gu J , Xu M , Wu Y , Deng Y , Zhang C , Bonizzoni M , Dermauw W , Vontas J , Armbruster P , Huang X , Yang Y , Zhang H , He W , Peng H , Liu Y , Wu K , Chen J , Lirakis M , Topalis P , Van Leeuwen T , Hall AB , Thorpe C , Mueller RL , Sun C , Waterhouse RM , Yan G , Tu ZJ , Fang X , James AA
Ref : Proc Natl Acad Sci U S A , 112 :E5907 , 2015
Abstract : The Asian tiger mosquito, Aedes albopictus, is a highly successful invasive species that transmits a number of human viral diseases, including dengue and Chikungunya fevers. This species has a large genome with significant population-based size variation. The complete genome sequence was determined for the Foshan strain, an established laboratory colony derived from wild mosquitoes from southeastern China, a region within the historical range of the origin of the species. The genome comprises 1,967 Mb, the largest mosquito genome sequenced to date, and its size results principally from an abundance of repetitive DNA classes. In addition, expansions of the numbers of members in gene families involved in insecticide-resistance mechanisms, diapause, sex determination, immunity, and olfaction also contribute to the larger size. Portions of integrated flavivirus-like genomes support a shared evolutionary history of association of these viruses with their vector. The large genome repertory may contribute to the adaptability and success of Ae. albopictus as an invasive species.
ESTHER : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedSearch : Chen_2015_Proc.Natl.Acad.Sci.U.S.A_112_E5907
PubMedID: 26483478
Gene_locus related to this paper: aedae-q177c7 , aedal-a0a182gwe3 , aedal-a0a182gwt8 , aedal-a0a023eq67

Title : Enduring effects of tacrine on cocaine-reinforced behavior: Analysis by conditioned-place preference, temporal separation from drug reward, and reinstatement - Grasing_2015_Pharmacol.Res_97_40
Author(s) : Grasing K , Yang Y , He S
Ref : Pharmacol Res , 97 :40 , 2015
Abstract : Previous work by our laboratory has shown that tacrine can produce long-lasting reductions in cocaine-reinforced behavior, when administered to rats as daily intravenous infusions over four days. Tacrine causes dose-related liver toxicity in different species, and its manufacture for human use was recently discontinued. This study was conducted to further characterize its actions on cocaine reward. Cocaine-experienced animals that had no contact with drug over one week resumed self-administration at levels similar to their initial baseline. When tacrine was administered over four days which were preceded and followed by washout periods to allow elimination of cocaine and tacrine respectively, subsequent cocaine self-administration was attenuated by more than one-half. Tacrine administered at 10mg/kg-day as a chronic infusion by osmotic pump did not modify cocaine-induced increases in locomotor activity or conditioned-place preference. In rats that exhibited persistent attenuation of cocaine-self-administration after receiving tacrine, cocaine-induced reinstatement was also attenuated. No changes in plasma measures of renal or hepatic function were observed in rats receiving tacrine. In conclusion, pretreatment with tacrine can decrease cocaine-motivated behavior measured by self-administration or reinstatement, but not conditioned-place preference. Reductions in cocaine self-administration following pretreatment with tacrine do not require direct interaction with cocaine and are not secondary to either liver or kidney toxicity.
ESTHER : Grasing_2015_Pharmacol.Res_97_40
PubMedSearch : Grasing_2015_Pharmacol.Res_97_40
PubMedID: 25890194

Title : Functional characterization of MpaG', the O-methyltransferase involved in the biosynthesis of mycophenolic acid - Zhang_2015_Chembiochem_16_565
Author(s) : Zhang W , Cao S , Qiu L , Qi F , Li Z , Yang Y , Huang S , Bai F , Liu C , Wan X , Li S
Ref : Chembiochem , 16 :565 , 2015
Abstract : Mycophenolic acid (MPA, 1) is a clinically important immunosuppressant. In this report, a gene cluster mpa' responsible for the biosynthesis of 1 was identified from Penicillium brevicompactum NRRL 864. The S-adenosyl-L-methionine-dependent (SAM-dependent) O-methyltransferase encoded by the mpaG' gene was functionally and kinetically characterized in vitro. MpaG' catalyzes the methylation of demethylmycophenolic acid (DMMPA, 6) to form 1. It also showed significant substrate flexibility by methylating two structural derivatives of 6 prepared by organic synthesis.
ESTHER : Zhang_2015_Chembiochem_16_565
PubMedSearch : Zhang_2015_Chembiochem_16_565
PubMedID: 25630520
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Properties of a newly identified esterase from Bacillus sp. K91 and its novel function in diisobutyl phthalate degradation - Ding_2015_PLoS.One_10_e0119216
Author(s) : Ding J , Wang C , Xie Z , Li J , Yang Y , Mu Y , Tang X , Xu B , Zhou J , Huang Z
Ref : PLoS ONE , 10 :e0119216 , 2015
Abstract : The widely used plasticizer phthalate esters (PAEs) have become a public concern because of their effects on environmental contamination and toxicity on mammals. However, the biodegradation of PAEs, especially diisobutyl phthalate (DiBP), remains poorly understood. In particular, genes involved in the hydrolysis of these compounds were not conclusively identified. In this study, the CarEW gene, which encodes an enzyme that is capable of hydrolyzing ro-nitrophenyl esters of fatty acids, was cloned from a thermophilic bacterium Bacillus sp. K91 and heterologously expressed in Escherichia coli BL21 using the pEASY-E2 expression system. The enzyme showed a monomeric structure with a molecular mass of approximately 53.76 kDa and pI of 4.88. The enzyme exhibited maximal activity at pH 7.5 and 45 degreesC, with ro-NP butyrate as the best substrate. The enzyme was fairly stable within the pH range from 7.0 to 8.5. High-pressure liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS) were employed to detect the catabolic pathway of DiBP. Two intermediate products were identified, and a potential biodegradation pathway was proposed. Altogether, our findings present a novel DiBP degradation enzyme and indicate that the purified enzyme may be a promising candidate for DiBP detoxification and for environmental protection.
ESTHER : Ding_2015_PLoS.One_10_e0119216
PubMedSearch : Ding_2015_PLoS.One_10_e0119216
PubMedID: 25746227
Gene_locus related to this paper: bacsu-pnbae

Title : Obesity associated Lyplal1 gene is regulated in diet induced obesity but not required for adipocyte differentiation - Lei_2015_Mol.Cell.Endocrinol_411_207
Author(s) : Lei X , Callaway M , Zhou H , Yang Y , Chen W
Ref : Mol Cell Endocrinol , 411 :207 , 2015
Abstract : Obesity and its associated morbidities represent one of the major and most rapidly expanding health epidemics in the world. Recent genome-wide association studies (GWAS) have identified several variants in LYPLAL1 gene that are significantly associated with central obesity preferentially in females. However, the exact function of this gene in adipose tissue development and obesity remains completely uncharacterized. We found murine Lyplal1 gene demonstrated a depot and sex-specific expression profile in white adipose tissues (WAT), and was significantly reduced in the epididymal and retroperitoneal fats in a murine model of high fat diet induced obesity (DIO). Lyplal1 mRNA was mildly up-regulated during adipogenesis and enriched in mature adipocytes through a PPARgamma-independent mechanism. However, overexpression and knockdown of Lyplal1 did not significantly perturb adipocyte differentiation, triacylglycerol accumulation and/or insulin signaling. These data highlight a depot-specific marked reduction of Lyplal1 transcripts in diet induced obesity but a dispensable role of Lyplal1 in adipose tissue development.
ESTHER : Lei_2015_Mol.Cell.Endocrinol_411_207
PubMedSearch : Lei_2015_Mol.Cell.Endocrinol_411_207
PubMedID: 25958046
Gene_locus related to this paper: human-LYPLAL1 , mouse-lypl1

Title : A Novel Lipase as Aquafeed Additive for Warm-Water Aquaculture - Ran_2015_PLoS.One_10_e0132049
Author(s) : Ran C , He S , Yang Y , Huang L , Zhou Z
Ref : PLoS ONE , 10 :e0132049 , 2015
Abstract : A novel Acinetobacter lipase gene lipG1was cloned from DNA extracted from intestinal sample of common carp (Cyprinus carpio), and expressed in E. coli BL21. The encoded protein was 406 amino acids in length. Phylogenetic analysis indicated that LipG1 and its relatives comprised a novel group of true lipases produced by Gram-negative bacteria. LipG1 showed maximal activity at 40 and pH 8.0 when pNP decanoate (C10) was used as the substrate, and remained high activity between 20 and 35. Activity of the lipase was promoted by Ca2+ and Mg2+, and inhibited by Zn2+ and Cu2+. Moreover, LipG1 is stable with proteases, most commercial detergents and organic solvents. Substrate specificity test indicated that LipG1can hydrolyse pNP esters with acyl chain length from C2 to C16, with preference for medium-chain pNP esters (C8, C10). Lastly, LipG1was evaluated as an aquafeed additive for juvenile common carp (Cyprinus carpio). Results showed that supplementation of LipG1significantly improved the gut and heptaopancreas lipase activity of fish fed with palm oil diet. Consistently, improved feed conversion ratio and growth performance were recorded in the LipG1 feeding group, to levels comparable to the group of fish fed with soybean oil diet. Collectively, LipG1 exhibited good potential as an aquafeed additive enzyme, and deserves further characterization as the representative of a novel group of lipases.
ESTHER : Ran_2015_PLoS.One_10_e0132049
PubMedSearch : Ran_2015_PLoS.One_10_e0132049
PubMedID: 26147311

Title : Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida - Wang_2015_Bull.Environ.Contam.Toxicol_95_475
Author(s) : Wang K , Qi S , Mu X , Chai T , Yang Y , Wang D , Li D , Che W , Wang C
Ref : Bulletin of Environmental Contamination & Toxicology , 95 :475 , 2015
Abstract : Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.
ESTHER : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedSearch : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedID: 26293707

Title : Distribution and frequency of G119S mutation in ace-1 gene within Anopheles sinensis populations from Guangxi, China - Feng_2015_Malar.J_14_470
Author(s) : Feng X , Yang C , Yang Y , Li J , Lin K , Li M , Qiu X
Ref : Malar J , 14 :470 , 2015
Abstract : BACKGROUND: Malaria is one of the most serious vector-borne diseases in the world. Vector control is an important measure for malaria prevention and elimination. However, this strategy is under threat as disease vectors are developing resistance to insecticides. Therefore, it is important to monitor mechanisms responsible for insecticide resistance. In this study, the presence of G119S mutation in the acetyl cholinesterase-encoding gene (ace-1) was investigated in nine Anopheles sinensis populations sampled across Guangxi Zhuang Autonomous Region China.
METHODS: PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method was used to genotype each individual adult of An. sinensis. Direct sequencing of PCR products was performed to verify the accuracy of PCR-RFLP genotyping result. Population genetics analysis was conducted using Genepop programme.
RESULTS: The frequencies of susceptible homozygotes, heterozygotes and resistant homozygotes in the nine populations ranged between 0-0.296, 0.143-0.500 and 0.333-0.857, respectively. Overall, a high frequency (0.519-0.929) of mutant 119S allele was observed and the genotype frequency of the ace-1 gene of An. sinensis was at Hardy-Weinberg equilibrium in each of the nine examined populations. CONCLUSION: The G119S mutation has become fixed and is widespread in An. sinensis field populations in Guangxi, China. These findings are useful in helping design strategies for An. sinensis control.
ESTHER : Feng_2015_Malar.J_14_470
PubMedSearch : Feng_2015_Malar.J_14_470
PubMedID: 26608572
Gene_locus related to this paper: anoga-ACHE1

Title : Anticancer drugs induce hypomethylation of the acetylcholinesterase promoter via a phosphorylated-p38-DNMT1-AChE pathway in apoptotic hepatocellular carcinoma cells - Xi_2015_Int.J.Biochem.Cell.Biol_68_21
Author(s) : Xi Q , Gao N , Yang Y , Ye W , Zhang B , Wu J , Jiang G , Zhang X
Ref : International Journal of Biochemistryistry & Cell Biology , 68 :21 , 2015
Abstract : Apoptosis, also known as programmed cell death, plays an essential role in eliminating excessive, damaged or harmful cells. Previous work has demonstrated that anticancer drugs induce cell apoptosis by inducing cytotoxicity. In recent years, several reports demonstrated modulated expression of DNA methyltransferases 1 (DNMT1) and acetylcholinesterase (AChE) in a variety of tumors. In this study, we showed that the expression of DNMT1 was decreased and the methylation of CpGs in the promoter of AChE was reduced in anticancer drugs-induced apoptotic hepatocellular carcinoma cells. Silencing of DNMT1 expression by AZA or RNA interference (RNAi) restored AChE production and inhibition of AChE expression by RNAi protected HCC cells from anticancer drugs-induced apoptosis. Furthermore, we demonstrated that the regulation of AChE by DNMT1 was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis. In addition, immunohistochemical staining showed that P-p38, DNMT1 and AChE were aberrantly expressed in a subset of HCC tumors. Taken together, we demonstrated the regulation of AChE by DNMT1 and further, we found that this regulation was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis.
ESTHER : Xi_2015_Int.J.Biochem.Cell.Biol_68_21
PubMedSearch : Xi_2015_Int.J.Biochem.Cell.Biol_68_21
PubMedID: 26299326

Title : A Phase 3 Trial of Sebelipase Alfa in Lysosomal Acid Lipase Deficiency - Burton_2015_N.Engl.J.Med_373_1010
Author(s) : Burton BK , Balwani M , Feillet F , Baric I , Burrow TA , Camarena Grande C , Coker M , Consuelo-Sanchez A , Deegan P , Di Rocco M , Enns GM , Erbe R , Ezgu F , Ficicioglu C , Furuya KN , Kane J , Laukaitis C , Mengel E , Neilan EG , Nightingale S , Peters H , Scarpa M , Schwab KO , Smolka V , Valayannopoulos V , Wood M , Goodman Z , Yang Y , Eckert S , Rojas-Caro S , Quinn AG
Ref : N Engl J Med , 373 :1010 , 2015
Abstract : BACKGROUND: Lysosomal acid lipase is an essential lipid-metabolizing enzyme that breaks down endocytosed lipid particles and regulates lipid metabolism. We conducted a phase 3 trial of enzyme-replacement therapy in children and adults with lysosomal acid lipase deficiency, an underappreciated cause of cirrhosis and severe dyslipidemia.
METHODS: In this multicenter, randomized, double-blind, placebo-controlled study involving 66 patients, we evaluated the safety and effectiveness of enzyme-replacement therapy with sebelipase alfa (administered intravenously at a dose of 1 mg per kilogram of body weight every other week); the placebo-controlled phase of the study was 20 weeks long and was followed by open-label treatment for all patients. The primary end point was normalization of the alanine aminotransferase level. Secondary end points included additional disease-related efficacy assessments, safety, and side-effect profile.
RESULTS: Substantial disease burden at baseline included a very high level of low-density lipoprotein cholesterol (>/=190 mg per deciliter) in 38 of 66 patients (58%) and cirrhosis in 10 of 32 patients (31%) who underwent biopsy. A total of 65 of the 66 patients who underwent randomization completed the double-blind portion of the trial and continued with open-label treatment. At 20 weeks, the alanine aminotransferase level was normal in 11 of 36 patients (31%) in the sebelipase alfa group and in 2 of 30 (7%) in the placebo group (P=0.03), with mean changes from baseline of -58 U per liter versus -7 U per liter (P<0.001). With respect to prespecified key secondary efficacy end points, we observed improvements in lipid levels and reduction in hepatic fat content (P<0.001 for all comparisons, except P=0.04 for triglycerides). The number of patients with adverse events was similar in the two groups; most events were mild and were considered by the investigator to be unrelated to treatment.
CONCLUSIONS: Sebelipase alfa therapy resulted in a reduction in multiple disease-related hepatic and lipid abnormalities in children and adults with lysosomal acid lipase deficiency. (Funded by Synageva BioPharma and others; ARISE ClinicalTrials.gov number, NCT01757184.).
ESTHER : Burton_2015_N.Engl.J.Med_373_1010
PubMedSearch : Burton_2015_N.Engl.J.Med_373_1010
PubMedID: 26352813
Gene_locus related to this paper: human-LIPA

Title : Toxicity of a neonicotinoid insecticide, guadipyr, in earthworm (Eisenia fetida) - Wang_2015_Ecotoxicol.Environ.Saf_114C_17
Author(s) : Wang K , Mu X , Qi S , Chai T , Pang S , Yang Y , Wang C , Jiang J
Ref : Ecotoxicology & Environmental Safety , 114C :17 , 2015
Abstract : Neonicotinoid insecticides are new class of pesticides and it is very meaningful to evaluate the toxicity of guadipyr to earthworm (Eisenia fetida). In the present study, effects of guadipyr on reproduction, growth, catalase(CAT), superoxide dismutase (SOD), acetylcholinesterase (AChE) and DNA damage in earthworm were assessed using an artificial soil medium. Guadipyr showed low toxicity to earthworms and did not elicit an effect on earthworm reproduction or growth in artificial soils at concentrations <100mg/kg. However, after exposure to guadipyr, the activity of SOD and CAT in earthworm increased and then decreased to control level. AChE activity decreased at day 3 at 50 and 100mg/kg and then increased to control level. Our data indicate that guadipyr did not induce DNA damage in earthworms at concentration of <100mg/kg.
ESTHER : Wang_2015_Ecotoxicol.Environ.Saf_114C_17
PubMedSearch : Wang_2015_Ecotoxicol.Environ.Saf_114C_17
PubMedID: 25594687

Title : Probing the role of amino acids in oxime-mediated reactivation of nerve agent-inhibited human acetylcholinesterase - Chambers_2015_Toxicol.In.Vitro_29_408
Author(s) : Chambers C , Luo C , Tong M , Yang Y , Saxena A
Ref : Toxicol In Vitro , 29 :408 , 2015
Abstract : In this study, we employed site-directed mutagenesis to understand the role of amino acids in the gorge in oxime-induced reactivation of nerve agent-inhibited human (Hu) acetylcholinesterase (AChE). The organophosphorus (OP) nerve agents studied included GA (tabun), GB (sarin), GF (cyclosarin), VX, and VR. The kinetics of reactivation were examined using both the mono-pyridinium oxime 2-PAM and bis-pyridinium oximes MMB4, HI-6, and HLo-7. The second-order reactivation rate constants were used to compare reactivation of nerve agent-inhibited wild-type (WT) and mutant enzymes. Residues including Y72, Y124 and W286 were found to play important roles in reactivation by bis-pyridinium, but not by mono-pyridinium oximes. Residue Y124 also was found to play a key role in reactivation by HI-6 and HLo-7, while E202 was important for reactivation by all oximes. Residue substitutions of F295 by Leu and Y337 by Ala showed enhanced reactivation by bis-pyridinium oximes MMB4, HI-6, and HLo-7, possibly by providing more accessibility of the OP moiety associated at the active-site serine to the oxime. These results are similar to those observed previously with bovine AChE and demonstrate that there is significant similarity between human and bovine AChEs with regard to oxime reactivation.
ESTHER : Chambers_2015_Toxicol.In.Vitro_29_408
PubMedSearch : Chambers_2015_Toxicol.In.Vitro_29_408
PubMedID: 25451328

Title : Protection against beta-amyloid-induced synaptic and memory impairments via altering beta-amyloid assembly by bis(heptyl)-cognitin - Chang_2015_Sci.Rep_5_10256
Author(s) : Chang L , Cui W , Yang Y , Xu S , Zhou WH , Fu HJ , Hu SQ , Mak SH , Hu JW , Wang Q , Pui-Yan Ma V , Chung-Lit Choi T , Dik-Lung Ma E , Tao L , Pang YP , Rowan MJ , Anwyl R , Han YF
Ref : Sci Rep , 5 :10256 , 2015
Abstract : beta-amyloid (Abeta) oligomers have been closely implicated in the pathogenesis of Alzheimer's disease (AD). We found, for the first time, that bis(heptyl)-cognitin, a novel dimeric acetylcholinesterase (AChE) inhibitor derived from tacrine, prevented Abeta oligomers-induced inhibition of long-term potentiation (LTP) at concentrations that did not interfere with normal LTP. Bis(heptyl)-cognitin also prevented Abeta oligomers-induced synaptotoxicity in primary hippocampal neurons. In contrast, tacrine and donepezil, typical AChE inhibitors, could not prevent synaptic impairments in these models, indicating that the modification of Abeta oligomers toxicity by bis(heptyl)-cognitin might be attributed to a mechanism other than AChE inhibition. Studies by using dot blotting, immunoblotting, circular dichroism spectroscopy, and transmission electron microscopy have shown that bis(heptyl)-cognitin altered Abeta assembly via directly inhibiting Abeta oligomers formation and reducing the amount of preformed Abeta oligomers. Molecular docking analysis further suggested that bis(heptyl)-cognitin presumably interacted with the hydrophobic pockets of Abeta, which confers stabilizing powers and assembly alteration effects on Abeta. Most importantly, bis(heptyl)-cognitin significantly reduced cognitive impairments induced by intra-hippocampal infusion of Abeta oligomers in mice. These results clearly demonstrated how dimeric agents prevent Abeta oligomers-induced synaptic and memory impairments, and offered a strong support for the beneficial therapeutic effects of bis(heptyl)-cognitin in the treatment of AD.
ESTHER : Chang_2015_Sci.Rep_5_10256
PubMedSearch : Chang_2015_Sci.Rep_5_10256
PubMedID: 26194093

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

Title : Potent AChE and BChE inhibitors isolated from seeds of Peganum harmala Linn by a bioassay-guided fractionation - Yang_2015_J.Ethnopharmacol_168_279
Author(s) : Yang Y , Cheng X , Liu W , Chou G , Wang Z , Wang C
Ref : J Ethnopharmacol , 168 :279 , 2015
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Peganum harmala Linn are traditionally used as folk medical herb in Uighur medicine in China to treat disorders of hemiplegia and amnesia. Previously studies have proved that dominating alkaloids in P. harmala show significant inhibitory activities on the cholinesterase. AIM OF THE STUDY: The aim of the present study is to isolate trace ingredients from seeds of P. harmala and evaluate its inhibitory activities on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). MATERIALS AND
METHODS: For sake of screening effective cholinesterase inhibitors, trace compounds were isolated from seeds of P. harmala through a bioassay-guided fractionation and their structures were determined via detailed spectral analysis. The inhibitory activities on AChE and BChE were assessed using an improved Ellman method by UPLC-ESI-MS/MS to determine the common final product choline.
RESULTS: The activity-guided fractionation led to the isolation of two new alkaloids 2-aldehyde-tetrahydroharmine (10), 2-carboxyl-3,4-dihydroquinazoline (19), one syringin structure analog 1-O-beta-D-xylopyranose sinapyl alcohol (22), and along with 19 known compounds. Compounds acetylnorharmine (6), harmic acid methy ester (7), harmine N-oxide (13), 6-methoxyindoline (14), syringin (21) were first found from genus Peganum and compounds 3-hydroxylated harmine (4), 1-hydroxy-7-methoxy-beta-carboline (5) were new natural products. The results showed that the 2-aldehyde-tetrahydroharmine (10) has a potential inbibitive effect on both AChE and BChE with IC50 values of 12.35+/-0.24 and 5.51+/-0.33microM, respectively. Deoxyvasicine (15) and vasicine (16) showed the strongest BChE inhibitory activity with IC50 values of 0.04+/-0.01 and 0.1+/-0.01microM. The analysis of the structure-activity relationship indicated that the saturation of pyridine ring and the presence of substitution at indole ring, C-1, C-3, C-7 and N-2, for beta-carbolines, were essential for effective inhibition of both AChE and BChE and the five-membered ring between C-2 and N-3 as well as the substituent groups sited at C-4 and C-9, for quinazolines, were important to both the AChE/BChE-inhibitory activity.
CONCLUSIONS: Bioassay-guided fractionation has led to the isolation of AChE and BChE inhibitors from the seeds of P. harmala. These results are in agreement with the traditional uses of the seeds of P. harmala.
ESTHER : Yang_2015_J.Ethnopharmacol_168_279
PubMedSearch : Yang_2015_J.Ethnopharmacol_168_279
PubMedID: 25862961

Title : Organelle-Specific Nitric Oxide Detection in Living Cells via HaloTag Protein Labeling - Wang_2015_PLoS.One_10_e0123986
Author(s) : Wang J , Zhao Y , Wang C , Zhu Q , Du Z , Hu A , Yang Y
Ref : PLoS ONE , 10 :e0123986 , 2015
Abstract : Nitric oxide (NO) is a membrane-permeable signaling molecule that is constantly produced, transferred, and consumed in vivo. NO participates and plays important roles in multiple biological processes. However, spatiotemporal imaging of NO in living cells is challenging. To fill the gap in currently used techniques, we exploited the versatility of HaloTag technology and synthesized a novel organelle-targetable fluorescent probe called HTDAF-2DA. We demonstrate the utility of the probe by monitoring subcellular NO dynamics. The developed strategy enables precise determination of local NO function.
ESTHER : Wang_2015_PLoS.One_10_e0123986
PubMedSearch : Wang_2015_PLoS.One_10_e0123986
PubMedID: 25923693

Title : Next generation digital PCR measurement of hepatitis B virus copy number in formalin-fixed paraffin-embedded hepatocellular carcinoma tissue - Huang_2015_Clin.Chem_61_290
Author(s) : Huang JT , Liu YJ , Wang J , Xu ZG , Yang Y , Shen F , Liu XH , Zhou X , Liu SM
Ref : Clinical Chemistry , 61 :290 , 2015
Abstract : BACKGROUND: Hepatocellular carcinoma (HCC) is strongly associated with hepatitis B virus (HBV) infection. False-negative results are common in routine serological tests and quantitative real-time PCR because of HBV surface antigen (HBsAg) variation and low HBV copy number. Droplet digital PCR (ddPCR), a next generation digital PCR, is a novel, sensitive, and specific platform that can be used to improve HBV detection.
METHODS: A total of 131 HCC cases with different tumor stages and clinical features were initially classified with a serological test as HBsAg positive (n = 107) or negative (n = 24) for HBV infection. Next, DNA templates were prepared from the corresponding formalin-fixed paraffin-embedded (FFPE) tissues to determine HBV copy number by ddPCR.
RESULTS: HBV copy numbers, successfully determined for all clinical FFPE tissues (n = 131), ranged from 1.1 to 175.5 copies/muL according to ddPCR. The copy numbers of HBV were positively correlated with tumor-nodes-metastasis (P = 0.008) and Barcelona-Clinic Liver Cancer (P = 0.045) classification. Moreover, serum cholinesterase correlated with hepatitis B viral load (P = 0.006).
CONCLUSIONS: HBV infection is a key factor that influences tumorigenesis in HCC by regulating tumor occurrence and development. ddPCR improves the analytical sensitivity and specificity of measurements in nucleic acids at a single-molecule level and is suitable for HBV detection.
ESTHER : Huang_2015_Clin.Chem_61_290
PubMedSearch : Huang_2015_Clin.Chem_61_290
PubMedID: 25361948

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : Biochemical characterization and high-level production of oxidized polyvinyl alcohol hydrolase from Sphingopyxis sp. 113P3 expressed in methylotrophic Pichia pastoris - Yang_2014_Bioprocess.Biosyst.Eng_37_777
Author(s) : Yang Y , Liu L , Li J , Du G , Chen J
Ref : Bioprocess Biosyst Eng , 37 :777 , 2014
Abstract : The Sphingopyxis sp. 113P3 gene oph, encoding oxidized polyvinyl alcohol hydrolase (OPH), was optimized with the preferred codons of Pichia pastoris and ligated into the pPIC9K vector behind the alpha-factor signal sequence. The vector was then transfected into P. pastoris GS115 and genomic integration was confirmed. Large-scale production of recombinant protein was performed by induction with 14.4 g/L methanol at 22 degrees C in a 3-L bioreactor. The maximal OPH activity obtained was 68.4 U/mL, which is the highest activity reported. The optimal pH and temperature of recombinant OPH were 8.0 and 45 degrees C, respectively. OPH activity was stable over a pH range of 5.0-8.5, and at a maximal temperature of 45 degrees C. The K cat /K m of recombinant OPH was 598 mM(-1) s(-1), which was 4.27-fold higher than that of recombinant OPH derived from Escherichia coli. The improved catalytic efficiency of OPH expressed in recombinant P. pastoris makes it favorable for industrial applications.
ESTHER : Yang_2014_Bioprocess.Biosyst.Eng_37_777
PubMedSearch : Yang_2014_Bioprocess.Biosyst.Eng_37_777
PubMedID: 24068496

Title : Evidence of polyethylene biodegradation by bacterial strains from the guts of plastic-eating waxworms - Yang_2014_Environ.Sci.Technol_48_13776
Author(s) : Yang J , Yang Y , Wu WM , Zhao J , Jiang L
Ref : Environ Sci Technol , 48 :13776 , 2014
Abstract : Polyethylene (PE) has been considered nonbiodegradable for decades. Although the biodegradation of PE by bacterial cultures has been occasionally described, valid evidence of PE biodegradation has remained limited in the literature. We found that waxworms, or Indian mealmoths (the larvae of Plodia interpunctella), were capable of chewing and eating PE films. Two bacterial strains capable of degrading PE were isolated from this worm's gut, Enterobacter asburiae YT1 and Bacillus sp. YP1. Over a 28-day incubation period of the two strains on PE films, viable biofilms formed, and the PE films' hydrophobicity decreased. Obvious damage, including pits and cavities (0.3-0.4 mum in depth), was observed on the surfaces of the PE films using scanning electron microscopy (SEM) and atomic force microscopy (AFM). The formation of carbonyl groups was verified using X-ray photoelectron spectroscopy (XPS) and microattenuated total reflectance/Fourier transform infrared (micro-ATR/FTIR) imaging microscope. Suspension cultures of YT1 and YP1 (10(8) cells/mL) were able to degrade approximately 6.1 +/- 0.3% and 10.7 +/- 0.2% of the PE films (100 mg), respectively, over a 60-day incubation period. The molecular weights of the residual PE films were lower, and the release of 12 water-soluble daughter products was also detected. The results demonstrated the presence of PE-degrading bacteria in the guts of waxworms and provided promising evidence for the biodegradation of PE in the environment.
ESTHER : Yang_2014_Environ.Sci.Technol_48_13776
PubMedSearch : Yang_2014_Environ.Sci.Technol_48_13776
PubMedID: 25384056

Title : Acetylcholinesterase biosensor based on a gold nanoparticle-polypyrrole-reduced graphene oxide nanocomposite modified electrode for the amperometric detection of organophosphorus pesticides - Yang_2014_Analyst_139_3055
Author(s) : Yang Y , Asiri AM , Du D , Lin Y
Ref : Analyst , 139 :3055 , 2014
Abstract : A nanohybrid of gold nanoparticles, polypyrrole, and reduced graphene oxide sheets (named as Au-PPy-rGO) was achieved by electrochemical deposition of reduced graphene oxide with pyrrole and the introduction of gold nanoparticles. Acetylcholinesterase (AChE) was further encapsulated in a silica matrix and immobilized on the Au-PPy-rGO nanocomposite by co-deposition with (NH4)2SiF6. The presence of PPy helped to avoid the aggregation of rGO caused by van der Waals interactions between individual sheets and significantly increased the surface area of the modified electrode. The obtained Au-PPy-rGO nanocomposite not only showed excellent conductivity but also exhibited a high electrocatalytic activity and specific affinity for thiocholine, the hydrolysis product of the enzyme, and thus an improved detection sensitivity. Since AChE molecules were protected by the circumambient silica matrix, which provided a biocompatible environment and facilitated mass transport, the fabricated AChE biosensor displayed high stability and excellent activity together with a fast response to organophosphorus pesticides. Under optimum conditions, the biosensor led to the rapid and sensitive detection of paraoxon-ethyl from 1.0 nM to 5 muM with a detection limit of 0.5 nM.
ESTHER : Yang_2014_Analyst_139_3055
PubMedSearch : Yang_2014_Analyst_139_3055
PubMedID: 24770670

Title : Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus - Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
Author(s) : Yang Y , Du L , Liu C , Wang L , Ma C , Tang J , Baric RS , Jiang S , Li F
Ref : Proc Natl Acad Sci U S A , 111 :12516 , 2014
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes approximately 36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5. We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5. Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences. First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells. Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes' capability to adapt to human cells for cross-species transmissions.
ESTHER : Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
PubMedSearch : Yang_2014_Proc.Natl.Acad.Sci.U.S.A_111_12516
PubMedID: 25114257

Title : Lipidomic analyses of female mice lacking hepatic lipase and endothelial lipase indicate selective modulation of plasma lipid species - Yang_2014_Lipids_49_505
Author(s) : Yang Y , Kuwano T , Lagor WR , Albert CJ , Brenton S , Rader DJ , Ford DA , Brown RJ
Ref : Lipids , 49 :505 , 2014
Abstract : Hepatic lipase (HL) and endothelial lipase (EL) share overlapping and complementary roles in lipoprotein metabolism. The deletion of HL and EL alleles in mice raises plasma total cholesterol and phospholipid concentrations. However, the influence of HL and EL in vivo on individual molecular species from each class of lipid is not known. We hypothesized that the loss of HL, EL, or both in vivo may affect select molecular species from each class of lipids. To test this hypothesis, we performed lipidomic analyses on plasma and livers from fasted female wild-type, HL-knockout, EL-knockout, and HL/EL-double knockout mice. Overall, the loss of HL, EL, or both resulted in minimal changes to hepatic lipids; however, select species of CE were surprisingly reduced in the livers of mice only lacking EL. The loss of HL, EL, or both reduced the plasma concentrations for select molecular species of triacylglycerol, diacylglycerol, and free fatty acid. On the other hand, the loss of HL, EL, or both raised the plasma concentrations for select molecular species of phosphatidylcholine, cholesteryl ester, diacylglycerol, sphingomyelin, ceramide, plasmanylcholine, and plasmenylcholine. The increased plasma concentration of select ether phospholipids was evident in the absence of EL, thus suggesting that EL might exhibit a phospholipase A2 activity. Using recombinant EL, we showed that it could hydrolyse the artificial phospholipase A2 substrate 4-nitro-3-(octanoyloxy)benzoic acid. In summary, our study shows for the first time the influence of HL and EL on individual molecular species of several classes of lipids in vivo using lipidomic methods.
ESTHER : Yang_2014_Lipids_49_505
PubMedSearch : Yang_2014_Lipids_49_505
PubMedID: 24777581
Gene_locus related to this paper: human-LIPC , human-LIPG

Title : Toxic effects of HgCl2 on activities of SOD, AchE and relative expression of SOD, AChE, CYP1A1 of zebrafish - Zhen_2014_Ecotoxicology_23_1842
Author(s) : Zhen H , Wen M , Yang Y , Can Z , Hui G , Li X , Deli L
Ref : Ecotoxicology , 23 :1842 , 2014
Abstract : In order to explore the impact of mercury on fish, zebrafish were exposed in various levels of HgCl2 and the superoxide dismutase (SOD), acetylcholinesterase (AChE) activities were measured after 1 and 7 days exposure. Muscle RNA was also extracted for semi-quantitative RT-PCR determination of the expression of AChE, CYP1A1, Cu/Zn-SOD. It indicated that 96 h-LC50 of HgCl2 to zebrafish is 244.06 microg L(-1). The AChE activity was decreased on 1st day and 7th day. The SOD activity was almost unchanged on 1st day, it showed a dose-response effect on 7th day. The expression of AChE was down-regulated on 1st day, it is consistent with the AChE activity, but the expression was showed a significant difference between exposed group and the control group on 7th day. The expression of CYP1A1 was decreased compared with the control group on 1st day. After 7 day exposure, the expression of CYP1A1 was up-regulated in 0.1LC50 group, and down-regulated in 0.4LC50 group, 0.8LC50 group, showing a stimulation effect at low concentration and inhibition at high concentration. The expression of Cu/Zn-SOD was down-regulated on 1st day, also showing an effect of stimulation at low concentration and inhibition at high concentrations. Thus HgCl2 was highly toxic to zebrafish, both the enzymatic activities and the gene transcription were changed significantly. But the change of gene transcription is earlier than enzymes activities. It indicates that gene transcript can be used as an early warning for environmental risk assessment.
ESTHER : Zhen_2014_Ecotoxicology_23_1842
PubMedSearch : Zhen_2014_Ecotoxicology_23_1842
PubMedID: 25240424

Title : A Fluorogenic Probe with Aggregation-Induced Emission Characteristics for Carboxylesterase Assay through Formation of Supramolecular Microfibers - Wang_2014_Chem.Asian.J_9_784
Author(s) : Wang X , Liu H , Li J , Ding K , Lv Z , Yang Y , Chen H , Li X
Ref : Chem Asian J , 9 :784 , 2014
Abstract : Herein, we report a novel fluorescent "light-up" probe useful for carboxylesterase assay that is based on a tetraphenylethylene derivative containing carboxylic ester groups. The specific cleavage of the carboxylic ester bonds by carboxylesterase results in the generation of a relatively hydrophobic moiety that self-assembles into supramolecular microfibers, thus giving rise to "turn-on" fluorescent signals. A high sensitivity towards carboxylesterase was achieved with a detection limit as low as 29 pM, which is much lower than the corresponding assays based on other fluorescent approaches.
ESTHER : Wang_2014_Chem.Asian.J_9_784
PubMedSearch : Wang_2014_Chem.Asian.J_9_784
PubMedID: 24403215

Title : Structural insights into enzymatic degradation of oxidized polyvinyl alcohol - Yang_2014_Chembiochem_15_1882
Author(s) : Yang Y , Ko TP , Liu L , Li J , Huang CH , Chan HC , Ren F , Jia D , Wang AH , Guo RT , Chen J , Du G
Ref : Chembiochem , 15 :1882 , 2014
Abstract : The ever-increasing production and use of polyvinyl alcohol (PVA) threaten our environment. Yet PVA can be assimilated by microbes in two steps: oxidation and cleavage. Here we report novel alpha/beta-hydrolase structures of oxidized PVA hydrolase (OPH) from two known PVA-degrading organisms, Sphingopyxis sp. 113P3 and Pseudomonas sp. VM15C, including complexes with substrate analogues, acetylacetone and caprylate. The active site is covered by a lid-like beta-ribbon. Unlike other esterase and amidase, OPH is unique in cleaving the CC bond of beta-diketone, although it has a catalytic triad similar to that of most alpha/beta-hydrolases. Analysis of the crystal structures suggests a double-oxyanion-hole mechanism, previously only found in thiolase cleaving beta-ketoacyl-CoA. Three mutations in the lid region showed enhanced activity, with potential in industrial applications.
ESTHER : Yang_2014_Chembiochem_15_1882
PubMedSearch : Yang_2014_Chembiochem_15_1882
PubMedID: 25044912
Gene_locus related to this paper: psesp-OPH , sphs1-OPH

Title : The Expanding MEGDEL Phenotype: Optic Nerve Atrophy, Microcephaly, and Myoclonic Epilepsy in a Child with SERAC1 Mutations - Lumish_2014_JIMD.Rep_16_75
Author(s) : Lumish HS , Yang Y , Xia F , Wilson A , Chung WK
Ref : JIMD Rep , 16 :75 , 2014
Abstract : The inborn errors of metabolism associated with 3-methylglutaconic aciduria are a diverse group of disorders characterized by the excretion of 3-methylglutaconic and 3-methylglutaric acids in the urine. Mutations in several genes have been identified in association with 3-methylglutaconic aciduria. We describe a patient of Saudi Arabian descent with 3-methylglutaconic aciduria, sensorineural hearing loss, encephalopathy, and Leigh-like pattern on MRI (MEGDEL syndrome), as well as developmental delay and developmental regression, bilateral optic nerve atrophy, microcephaly, and myoclonic epilepsy. The patient had an earlier age of onset of optic atrophy than previously described in other MEGDEL syndrome patients. Whole exome sequencing revealed two loss-of-function mutations in SERAC1 in trans: c.438delC (p.T147Rfs*22) and c.442C>T (p.R148X), confirmed by Sanger sequencing. One of these mutations is novel (c.438delC). This case contributes to refining the MEGDEL phenotype.
ESTHER : Lumish_2014_JIMD.Rep_16_75
PubMedSearch : Lumish_2014_JIMD.Rep_16_75
PubMedID: 24997715
Gene_locus related to this paper: human-SERAC1

Title : Roles of tryptophan residue and disulfide bond in the variable lid region of oxidized polyvinyl alcohol hydrolase - Yang_2014_Biochem.Biophys.Res.Commun_452_509
Author(s) : Yang Y , Ko TP , Liu L , Li J , Huang CH , Chen J , Guo RT , Du G
Ref : Biochemical & Biophysical Research Communications , 452 :509 , 2014
Abstract : Oxidized polyvinyl alcohol hydrolase (OPH) catalyzes the cleavage of C-C bond in beta-diketone. It belongs to the alpha/beta-hydrolase family and contains a unique lid region that covers the active site. The lid is the most variable region when pOPH from Pseudomonas sp. VM15C and sOPH from Sphingopyxis sp. 113P3 are compared. The wild-type enzymes and the pOPH mutants W255A, W255Y and W255F were analyzed for lipase activity by using p-nitrophenyl (pNP) esters as the substrates. The wild-type enzymes showed increased Km and decreased kcat/Km with the acyl chain length, and the mutants showed reduced kcat/Km for pNP acetate, indicating the importance of Trp255 in sequestering the active site from solvent. The significantly lower activity for pNP butyrate can be a result of product inhibition, as suggested by the complex crystal structures, in which butyric acid, DMSO or PEG occupied the same substrate-binding cleft. The mutant activity was retained with pNP caprylate and pNP laurate as the substrates, reflecting the amphipathic nature of the cleft. Moreover, the disulfide bond formation of Cys257/267 is important for the activity of pOPH, but it is not essential for sOPH, which has a shorter lid structure.
ESTHER : Yang_2014_Biochem.Biophys.Res.Commun_452_509
PubMedSearch : Yang_2014_Biochem.Biophys.Res.Commun_452_509
PubMedID: 25173935
Gene_locus related to this paper: sphs1-OPH

Title : Eucommia ulmoides Oliv.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine - He_2014_J.Ethnopharmacol_151_78
Author(s) : He X , Wang J , Li M , Hao D , Yang Y , Zhang C , He R , Tao R
Ref : J Ethnopharmacol , 151 :78 , 2014
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. (Family Eucommiaceae), also known as Du-zhong (Chinese: ), Tuchong (in Japanese), is the sole species of the genus Eucommia. The leaf, stem, and bark as well as staminate flower of Eucommia ulmoides have been traditionally used to cure many diseases in China, Japan, Korea, among others. The aim of this review is to comprehensively outline the botanical description, ethnopharmacology, phytochemistry, biological activities, and toxicology of Eucommia ulmoides and to discuss possible trends for further study of Eucommia ulmoides. MATERIALS AND
METHODS: Information on Eucommia ulmoides was gathered via the internet (using Pub Med, Elsevier, Baidu Scholar, Google Scholar, Medline Plus, ACS, CNKI, and Web of Science) and from books in local libraries.
RESULTS: One-hundred twelve compounds of Eucommia ulmoides, including the main active constituents, lignans and iridoids, have been isolated and identified. In vitro and in vivo studies indicated that monomer compounds and extracts from Eucommia ulmoides possess wide-ranging pharmacological actions, especially in treating hypertension, hyperlipemia, diabetes, obesity, sexual dysfunction, osteoporosis, Alzheimer's disease, aging, lupus-like syndrome, and immunoregulation.
CONCLUSIONS: Eucommia ulmoides has been used as a source of traditional medicine and as a beneficial health food. Phytochemical and pharmacological studies of Eucommia ulmoides have received much interest, and extracts and active compounds continue to be isolated and proven to exert various effects. Further toxicity and clinical studies are warranted to establish more detailed data on crude extracts and pure compounds, enabling more convenient preparations for patients. Therefore, this review on the ethnopharmacology, phytochemistry, biological activities, and toxicity of Eucommia ulmoides will provide helpful data for further studies as well as the commercial exploitation of this traditional medicine.
ESTHER : He_2014_J.Ethnopharmacol_151_78
PubMedSearch : He_2014_J.Ethnopharmacol_151_78
PubMedID: 24296089

Title : A hydrolase of trehalose dimycolate induces nutrient influx and stress sensitivity to balance intracellular growth of Mycobacterium tuberculosis - Yang_2014_Cell.Host.Microbe_15_153
Author(s) : Yang Y , Kulka K , Montelaro RC , Reinhart TA , Sissons J , Aderem A , Ojha AK
Ref : Cell Host Microbe , 15 :153 , 2014
Abstract : Chronic tuberculosis in an immunocompetent host is a consequence of the delicately balanced growth of Mycobacterium tuberculosis (Mtb) in the face of host defense mechanisms. We identify an Mtb enzyme (TdmhMtb) that hydrolyzes the mycobacterial glycolipid trehalose dimycolate and plays a critical role in balancing the intracellular growth of the pathogen. TdmhMtb is induced under nutrient-limiting conditions and remodels the Mtb envelope to increase nutrient influx but concomitantly sensitizes Mtb to stresses encountered in the host. Consistent with this, a DeltatdmhMtb mutant is more resilient to stress and grows to levels higher than those of wild-type in immunocompetent mice. By contrast, mutant growth is retarded in MyD88(-/-) mice, indicating that TdmhMtb provides a growth advantage to intracellular Mtb in an immunocompromised host. Thus, the effects and countereffects of TdmhMtb play an important role in balancing intracellular growth of Mtb in a manner that is directly responsive to host innate immunity.
ESTHER : Yang_2014_Cell.Host.Microbe_15_153
PubMedSearch : Yang_2014_Cell.Host.Microbe_15_153
PubMedID: 24528862
Gene_locus related to this paper: myctu-cut3 , myctu-RV3452 , mycs2-a0qsm3

Title : Lignin binding to pancreatic lipase and its influence on enzymatic activity - Zhang_2014_Food.Chem_149_99
Author(s) : Zhang J , Xiao L , Yang Y , Wang Z , Li G
Ref : Food Chem , 149 :99 , 2014
Abstract : In this paper, we find that the effect of lignin on pancreatic lipase (PL) is dependent on reaction medium and substrate used. Experimental results reveal that lignin can gradually bind to PL to form a PL-lignin complex, resulting in an increased activity of the enzyme. The binding process is spontaneous and the PL-lignin complex formation is an endothermic reaction induced by hydrophobic and electrostatic interaction. There is a non-radiation energy transfer from PL to lignin during the binding process, and the binding of lignin to PL conforms to a secondary exponential decay function. Moreover, the alpha-helix content of the enzyme will be changed and the rigidity of its side chain will be enhanced due to the formation of lignin-PL complex. This study has not only provided the activation effect of lignin on PL, but also given an insight into the interaction between lignin and the enzyme, which would benefit the application of lignin in the pharmacy and food industry, as well as other fields.
ESTHER : Zhang_2014_Food.Chem_149_99
PubMedSearch : Zhang_2014_Food.Chem_149_99
PubMedID: 24295682

Title : Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect - Xu_2014_BMC.Cancer_14_668
Author(s) : Xu H , Shen Z , Xiao J , Yang Y , Huang W , Zhou Z , Shen J , Zhu Y , Liu XY , Chu L
Ref : BMC Cancer , 14 :668 , 2014
Abstract : BACKGROUND: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
METHODS: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 x 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
RESULTS: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells. CONCLUSION: ZD55-AChE represented potential therapeutic effect for human gastric cancer.
ESTHER : Xu_2014_BMC.Cancer_14_668
PubMedSearch : Xu_2014_BMC.Cancer_14_668
PubMedID: 25220382

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 : Determination of neonicotinoid insecticides residues in eels using subcritical water extraction and ultra-performance liquid chromatography-tandem mass spectrometry - Xiao_2013_Anal.Chim.Acta_777_32
Author(s) : Xiao Z , Yang Y , Li Y , Fan X , Ding S
Ref : Anal Chim Acta , 777 :32 , 2013
Abstract : A rapid, sensitive, and environmental-friendly multi-residue method has been developed for the simultaneous determination of seven neonicotinoid insecticides (dinotefuran, nitenpyram, thiamethoxam, imidacloprid, clothianidin, acetamiprid, and thiacloprid) residues in eel samples. Subcritical water extraction was investigated as a novel and alternative technology for the extraction of neonicotinoids from eel matrices and the results were compared with the conventional ultrasonic and shaking extraction. The target compounds were identified and quantitatively determined by ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-MS/MS) operated in multiple reaction monitoring mode. Under the current optimized chromatographic conditions, each LC run was completed in 5 min. Average recoveries of the seven analytes from fortified samples ranged between 84.6% and 102.0%, with relative standard deviations (RSD) lower than 10.8%. The limits of detection (LODs) and quantification (LOQs) for neonicotinoids were in the ranges of 0.12-0.36 mug kg(-1) and 0.42-1.12 mug kg(-1), respectively. The proposed method is fast, sensitive, easy to perform, water-based thus more environmentally acceptable, making it applicable for high-throughput monitoring of insecticides residues in aquatic products.
ESTHER : Xiao_2013_Anal.Chim.Acta_777_32
PubMedSearch : Xiao_2013_Anal.Chim.Acta_777_32
PubMedID: 23622962

Title : Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus - Chen_2013_J.Virol_87_10777
Author(s) : Chen Y , Rajashankar KR , Yang Y , Agnihothram SS , Liu C , Lin YL , Baric RS , Li F
Ref : J Virol , 87 :10777 , 2013
Abstract : The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans.
ESTHER : Chen_2013_J.Virol_87_10777
PubMedSearch : Chen_2013_J.Virol_87_10777
PubMedID: 23903833

Title : Draft Genome Sequence of Ochrobactrum pseudogrignonense Strain CDB2, a Highly Efficient Arsenate-Resistant Soil Bacterium from Arsenic-Contaminated Cattle Dip Sites - Yang_2013_Genome.Announc_1_e0017313
Author(s) : Yang Y , Yu X , Zhang R
Ref : Genome Announc , 1 :e0017313 , 2013
Abstract : We report the 4.97-Mb draft genome sequence of a highly efficient arsenate-resistant bacterium, Ochrobactrum sp. strain CDB2. It contains a novel arsenic resistance (ars) operon (arsR-arsC1-ACR3-arsC2-arsH-mfs) and two non-operon-associated ars genes, arsC3 and arsB. The genome information will aid in the understanding of the arsenic resistance mechanism of this and other bacterial species.
ESTHER : Yang_2013_Genome.Announc_1_e0017313
PubMedSearch : Yang_2013_Genome.Announc_1_e0017313
PubMedID: 23599296

Title : Hydrolysis products generated by lipoprotein lipase and endothelial lipase differentially impact THP-1 macrophage cell signalling pathways - Essaji_2013_Lipids_48_769
Author(s) : Essaji Y , Yang Y , Albert CJ , Ford DA , Brown RJ
Ref : Lipids , 48 :769 , 2013
Abstract : Macrophages express lipoprotein lipase (LPL) and endothelial lipase (EL) within atherosclerotic plaques; however, little is known about how lipoprotein hydrolysis products generated by these lipases might affect macrophage cell signalling pathways. We hypothesized that hydrolysis products affect macrophage cell signalling pathways associated with atherosclerosis. To test our hypothesis, we incubated differentiated THP-1 macrophages with products from total lipoprotein hydrolysis by recombinant LPL or EL. Using antibody arrays, we found that the phosphorylation of six receptor tyrosine kinases and three signalling nodes--most associated with atherosclerotic processes--was increased by LPL derived hydrolysis products. EL derived hydrolysis products only increased the phosphorylation of tropomyosin-related kinase A, which is also implicated in playing a role in atherosclerosis. Using electrospray ionization-mass spectrometry, we identified the species of triacylglycerols and phosphatidylcholines that were hydrolyzed by LPL and EL, and we identified the fatty acids liberated by gas chromatography-mass spectrometry. To determine if the total liberated fatty acids influenced signalling pathways, we incubated differentiated THP-1 macrophages with a mixture of the fatty acids that matched the concentrations of liberated fatty acids from total lipoproteins by LPL, and we subjected cell lysates to antibody array analyses. The analyses showed that only the phosphorylation of Akt was significantly increased in response to fatty acid treatment. Overall, our study shows that macrophages display potentially pro-atherogenic signalling responses following acute treatments with LPL and EL lipoprotein hydrolysis products.
ESTHER : Essaji_2013_Lipids_48_769
PubMedSearch : Essaji_2013_Lipids_48_769
PubMedID: 23794138
Gene_locus related to this paper: human-LIPG

Title : Nicotinic alpha7 receptors enhance NMDA cognitive circuits in dorsolateral prefrontal cortex - Yang_2013_Proc.Natl.Acad.Sci.U.S.A_110_12078
Author(s) : Yang Y , Paspalas CD , Jin LE , Picciotto MR , Arnsten AF , Wang M
Ref : Proc Natl Acad Sci U S A , 110 :12078 , 2013
Abstract : The cognitive function of the highly evolved dorsolateral prefrontal cortex (dlPFC) is greatly influenced by arousal state, and is gravely afflicted in disorders such as schizophrenia, where there are genetic insults in alpha7 nicotinic acetylcholine receptors (alpha7-nAChRs). A recent behavioral study indicates that ACh depletion from dlPFC markedly impairs working memory [Croxson PL, Kyriazis DA, Baxter MG (2011) Nat Neurosci 14(12):1510-1512]; however, little is known about how alpha7-nAChRs influence dlPFC cognitive circuits. Goldman-Rakic [Goldman-Rakic (1995) Neuron 14(3):477-485] discovered the circuit basis for working memory, whereby dlPFC pyramidal cells excite each other through glutamatergic NMDA receptor synapses to generate persistent network firing in the absence of sensory stimulation. Here we explore alpha7-nAChR localization and actions in primate dlPFC and find that they are enriched in glutamate network synapses, where they are essential for dlPFC persistent firing, with permissive effects on NMDA receptor actions. Blockade of alpha7-nAChRs markedly reduced, whereas low-dose stimulation selectively enhanced, neuronal representations of visual space. These findings in dlPFC contrast with the primary visual cortex, where nAChR blockade had no effect on neuronal firing [Herrero JL, et al. (2008) Nature 454(7208):1110-1114]. We additionally show that alpha7-nAChR stimulation is needed for NMDA actions, suggesting that it is key for the engagement of dlPFC circuits. As ACh is released in cortex during waking but not during deep sleep, these findings may explain how ACh shapes differing mental states during wakefulness vs. sleep. The results also explain why genetic insults to alpha7-nAChR would profoundly disrupt cognitive experience in patients with schizophrenia.
ESTHER : Yang_2013_Proc.Natl.Acad.Sci.U.S.A_110_12078
PubMedSearch : Yang_2013_Proc.Natl.Acad.Sci.U.S.A_110_12078
PubMedID: 23818597

Title : Schizophrenia: a neurodevelopmental disorder--integrative genomic hypothesis and therapeutic implications from a transgenic mouse model - Stachowiak_2013_Schizophr.Res_143_367
Author(s) : Stachowiak MK , Kucinski A , Curl R , Syposs C , Yang Y , Narla S , Terranova C , Prokop D , Klejbor I , Bencherif M , Birkaya B , Corso T , Parikh A , Tzanakakis ES , Wersinger S , Stachowiak EK
Ref : Schizophr Res , 143 :367 , 2013
Abstract : Schizophrenia is a neurodevelopmental disorder featuring complex aberrations in the structure, wiring, and chemistry of multiple neuronal systems. The abnormal developmental trajectory of the brain appears to be established during gestation, long before clinical symptoms of the disease appear in early adult life. Many genes are associated with schizophrenia, however, altered expression of no one gene has been shown to be present in a majority of schizophrenia patients. How does altered expression of such a variety of genes lead to the complex set of abnormalities observed in the schizophrenic brain? We hypothesize that the protein products of these genes converge on common neurodevelopmental pathways that affect the development of multiple neural circuits and neurotransmitter systems. One such neurodevelopmental pathway is Integrative Nuclear FGFR1 Signaling (INFS). INFS integrates diverse neurogenic signals that direct the postmitotic development of embryonic stem cells, neural progenitors and immature neurons, by direct gene reprogramming. Additionally, FGFR1 and its partner proteins link multiple upstream pathways in which schizophrenia-linked genes are known to function and interact directly with those genes. A th-fgfr1(tk-) transgenic mouse with impaired FGF receptor signaling establishes a number of important characteristics that mimic human schizophrenia - a neurodevelopmental origin, anatomical abnormalities at birth, a delayed onset of behavioral symptoms, deficits across multiple domains of the disorder and symptom improvement with typical and atypical antipsychotics, 5-HT antagonists, and nicotinic receptor agonists. Our research suggests that altered FGF receptor signaling plays a central role in the developmental abnormalities underlying schizophrenia and that nicotinic agonists are an effective class of compounds for the treatment of schizophrenia.
ESTHER : Stachowiak_2013_Schizophr.Res_143_367
PubMedSearch : Stachowiak_2013_Schizophr.Res_143_367
PubMedID: 23231877

Title : Exposure to a Cutinase-like Serine Esterase Triggers Rapid Lysis of Multiple Mycobacterial Species - Yang_2013_J.Biol.Chem_288_382
Author(s) : Yang Y , Bhatti A , Ke D , Gonzalez-Juarrero M , Lenaerts A , Kremer L , Guerardel Y , Zhang P , Ojha AK
Ref : Journal of Biological Chemistry , 288 :382 , 2013
Abstract : Mycobacteria are shaped by a thick envelope made of an array of uniquely structured lipids and polysaccharides. However, the spatial organization of these molecules remains unclear. Here, we show that exposure to an esterase from Mycobacterium smegmatis (Msmeg_1529), hydrolyzing the ester linkage of trehalose dimycolate in vitro, triggers rapid and efficient lysis of Mycobacterium tuberculosis, Mycobacterium bovis BCG, and Mycobacterium marinum. Exposure to the esterase immediately releases free mycolic acids, while concomitantly depleting trehalose mycolates. Moreover, lysis could be competitively inhibited by an excess of purified trehalose dimycolate and was abolished by a S124A mutation affecting the catalytic activity of the esterase. These findings are consistent with an indispensable structural role of trehalose mycolates in the architectural design of the exposed surface of the mycobacterial envelope. Importantly, we also demonstrate that the esterase-mediated rapid lysis of M. tuberculosis significantly improves its detection in paucibacillary samples.
ESTHER : Yang_2013_J.Biol.Chem_288_382
PubMedSearch : Yang_2013_J.Biol.Chem_288_382
PubMedID: 23155047

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

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 : Candidate phylum TM6 genome recovered from a hospital sink biofilm provides genomic insights into this uncultivated phylum - McLean_2013_Proc.Natl.Acad.Sci.U.S.A_110_E2390
Author(s) : McLean JS , Lombardo MJ , Badger JH , Edlund A , Novotny M , Yee-Greenbaum J , Vyahhi N , Hall AP , Yang Y , Dupont CL , Ziegler MG , Chitsaz H , Allen AE , Yooseph S , Tesler G , Pevzner PA , Friedman RM , Nealson KH , Venter JC , Lasken RS
Ref : Proc Natl Acad Sci U S A , 110 :E2390 , 2013
Abstract : The "dark matter of life" describes microbes and even entire divisions of bacterial phyla that have evaded cultivation and have yet to be sequenced. We present a genome from the globally distributed but elusive candidate phylum TM6 and uncover its metabolic potential. TM6 was detected in a biofilm from a sink drain within a hospital restroom by analyzing cells using a highly automated single-cell genomics platform. We developed an approach for increasing throughput and effectively improving the likelihood of sampling rare events based on forming small random pools of single-flow-sorted cells, amplifying their DNA by multiple displacement amplification and sequencing all cells in the pool, creating a "mini-metagenome." A recently developed single-cell assembler, SPAdes, in combination with contig binning methods, allowed the reconstruction of genomes from these mini-metagenomes. A total of 1.07 Mb was recovered in seven contigs for this member of TM6 (JCVI TM6SC1), estimated to represent 90% of its genome. High nucleotide identity between a total of three TM6 genome drafts generated from pools that were independently captured, amplified, and assembled provided strong confirmation of a correct genomic sequence. TM6 is likely a Gram-negative organism and possibly a symbiont of an unknown host (nonfree living) in part based on its small genome, low-GC content, and lack of biosynthesis pathways for most amino acids and vitamins. Phylogenomic analysis of conserved single-copy genes confirms that TM6SC1 is a deeply branching phylum.
ESTHER : McLean_2013_Proc.Natl.Acad.Sci.U.S.A_110_E2390
PubMedSearch : McLean_2013_Proc.Natl.Acad.Sci.U.S.A_110_E2390
PubMedID: 23754396
Gene_locus related to this paper: 9bact-a0a0d2je38

Title : Draft Genome Sequence of Ralstonia solanacearum Race 4 Biovar 4 Strain SD54 - Shan_2013_Genome.Announc_1_e00890
Author(s) : Shan W , Yang X , Ma W , Yang Y , Guo X , Guo J , Zheng H , Li G , Xie B
Ref : Genome Announc , 1 : , 2013
Abstract : Ralstonia solanacearum is an important etiological agent that can cause serious bacterial wilt in a very wide range of potential host plants, including ginger. Here, we report the complete genome sequence of R. solanacearum SD54, a race 4 biovar 4 (R4B4) strain from a diseased ginger plant in China.
ESTHER : Shan_2013_Genome.Announc_1_e00890
PubMedSearch : Shan_2013_Genome.Announc_1_e00890
PubMedID: 24356823
Gene_locus related to this paper: ralso-PCAD

Title : Cell debris self-immobilized thermophilic lipase: a biocatalyst for synthesizing aliphatic polyesters - Sun_2013_Appl.Biochem.Biotechnol_170_399
Author(s) : Sun Y , Yang Y , Wang C , Liu J , Shi W , Zhu X , Lu L , Li Q
Ref : Appl Biochem Biotechnol , 170 :399 , 2013
Abstract : The paper explored the catalytic activity of a cell debris self-immobilized thermophilic lipase for polyester synthesis, using the ring-opening polymerization of sigma-caprolactone as model. Effects of biocatalyst concentration, temperature, and reaction medium on monomer conversion and product molecular weight were systematically evaluated. The biocatalyst displayed high catalytic activity at high temperatures (70-90 degreesC), with 100 % monomer conversion. High monomer conversion values (>90 %) were achieved in both hydrophobic and hydrophilic solvents, and also in solvent-free system, with the exception of dichloromethane. Poly(sigma-caprolactone) was obtained in 100 % monomer conversion, with a number-average molecular weight of 1,680 g/mol and a polydispersity index of 1.35 in cyclohexane at 70 degreesC for 72 h. Furthermore, the biocatalyst exhibited excellent operational stability, with monomer conversion values exceeding 90 % over the course of 15 batch reactions.
ESTHER : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedSearch : Sun_2013_Appl.Biochem.Biotechnol_170_399
PubMedID: 23536248

Title : Frequency of the cholesteryl ester storage disease common LIPA E8SJM mutation (c.894G>\;A) in various racial and ethnic groups - Scott_2013_Hepatology_58_958
Author(s) : Scott SA , Liu B , Nazarenko I , Martis S , Kozlitina J , Yang Y , Ramirez C , Kasai Y , Hyatt T , Peter I , Desnick RJ
Ref : Hepatology , 58 :958 , 2013
Abstract : Cholesteryl ester storage disease (CESD) and Wolman disease are autosomal recessive later-onset and severe infantile disorders, respectively, which result from the deficient activity of lysosomal acid lipase (LAL). LAL is encoded by LIPA (10q23.31) and the most common mutation associated with CESD is an exon 8 splice junction mutation (c.894G>A; E8SJM), which expresses only approximately 3%-5% of normally spliced LAL. However, the frequency of c.894G>A is unknown in most populations. To estimate the prevalence of CESD in different populations, the frequencies of the c.894G>A mutation were determined in 10,000 LIPA alleles from healthy African-American, Asian, Caucasian, Hispanic, and Ashkenazi Jewish individuals from the greater New York metropolitan area and 6,578 LIPA alleles from African-American, Caucasian, and Hispanic subjects enrolled in the Dallas Heart Study. The combined c.894G>A allele frequencies from the two cohorts ranged from 0.0005 (Asian) to 0.0017 (Caucasian and Hispanic), which translated to carrier frequencies of 1 in 1,000 to approximately 1 in 300, respectively. No African-American heterozygotes were detected. Additionally, by surveying the available literature, c.894G>A was estimated to account for 60% (95% confidence interval [CI]: 51%-69%) of reported mutations among multiethnic CESD patients. Using this estimate, the predicted prevalence of CESD in the Caucasian and Hispanic populations is approximately 0.8 per 100,000 ( approximately 1 in 130,000; 95% CI: approximately 1 in 90,000 to 1 in 170,000). Conclusion: These data indicate that CESD may be underdiagnosed in the general Caucasian and Hispanic populations, which is important since clinical trials of enzyme replacement therapy for LAL deficiency are currently being developed. Moreover, future studies on CESD prevalence in African and Asian populations may require full-gene LIPA sequencing to determine heterozygote frequencies, since c.894G>A is not common in these racial groups. (HEPATOLOGY 2013;53:958-965).
ESTHER : Scott_2013_Hepatology_58_958
PubMedSearch : Scott_2013_Hepatology_58_958
PubMedID: 23424026

Title : Selective esterase-ester pair for targeting small molecules with cellular specificity - Tian_2012_Proc.Natl.Acad.Sci.U.S.A_109_4756
Author(s) : Tian L , Yang Y , Wysocki LM , Arnold AC , Hu A , Ravichandran B , Sternson SM , Looger LL , Lavis LD
Ref : Proc Natl Acad Sci U S A , 109 :4756 , 2012
Abstract : Small molecules are important tools to measure and modulate intracellular signaling pathways. A longstanding limitation for using chemical compounds in complex tissues has been the inability to target bioactive small molecules to a specific cell class. Here, we describe a generalizable esterase-ester pair capable of targeted delivery of small molecules to living cells and tissue with cellular specificity. We used fluorogenic molecules to rapidly identify a small ester masking motif that is stable to endogenous esterases, but is efficiently removed by an exogenous esterase. This strategy allows facile targeting of dyes and drugs in complex biological environments to label specific cell types, illuminate gap junction connectivity, and pharmacologically perturb distinct subsets of cells. We expect this approach to have general utility for the specific delivery of many small molecules to defined cellular populations.
ESTHER : Tian_2012_Proc.Natl.Acad.Sci.U.S.A_109_4756
PubMedSearch : Tian_2012_Proc.Natl.Acad.Sci.U.S.A_109_4756
PubMedID: 22411832

Title : Intranasal administration of TAT-haFGF(14-154) attenuates disease progression in a mouse model of Alzheimer's disease - Lou_2012_Neurosci_223_225
Author(s) : Lou G , Zhang Q , Xiao F , Xiang Q , Su Z , Zhang L , Yang P , Yang Y , Zheng Q , Huang Y
Ref : Neuroscience , 223 :225 , 2012
Abstract : Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 ug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress.
ESTHER : Lou_2012_Neurosci_223_225
PubMedSearch : Lou_2012_Neurosci_223_225
PubMedID: 22885230

Title : Chlorpyrifos resistance is associated with mutation and amplification of the acetylcholinesterase-1 gene in the tomato red spider mite, Tetranychus evansi - Carvalho_2012_Pestic.Biochem.Physiol_104_143
Author(s) : Carvalho RA , Yang Y , Field LM , Gorman K , Moores GD , Williamson MS , Bass C
Ref : Pesticide Biochemistry and Physiology , 104 :143 , 2012
Abstract : The tomato red spider mite, Tetranychus evansi is an invasive pest of many African countries where it causes significant damage to a range of solanaceous crops. In Malawi the control of T. evansi relies heavily on the use of chemical pesticides and this species has evolved resistance to members of the pyrethroid and organophosphate (OP) classes. In this study the molecular mechanisms underlying resistance to the organophosphate chlorpyrifos were investigated in two resistant strains of T. evansi from Malawi and France. Cloning and sequencing of the gene encoding the OP target (ace-1) revealed an amino acid substitution at just one of the positions (331) previously implicated in OP resistance across a range of different insect and mite species. The amino acid residue usually found at this position in susceptible insects and mites is a phenylalanine (F) but was a tyrosine (Y) in all sequenced clones of the France strain and a tyrosine or tryptophan (W) in sequenced clones of the Malawi strain. Additionally we found evidence that the ace-1 locus is amplified in the resistant strains, with direct measurement of gene copy number by quantitative PCR showing there are around 8-10 copies of the gene in both the France and the Malawi strain. Sequencing of clones of ace-1 from the Malawi strain indicated that individual mites have fewer copies of the W331 allele than the Y331 allele. The enhanced copy number of the ace-1 gene in T. evansi and copy number variation of the two alleles seen in the Malawi strain may be a mechanism to compensate for fitness costs associated with the mutant alleles as has been proposed for T. urticae.
ESTHER : Carvalho_2012_Pestic.Biochem.Physiol_104_143
PubMedSearch : Carvalho_2012_Pestic.Biochem.Physiol_104_143
Gene_locus related to this paper: 9acar-k9m8p0

Title : No association of five candidate genetic variants with amyotrophic lateral sclerosis in a Chinese population - Chen_2012_Neurobiol.Aging_33_2721 e3
Author(s) : Chen Y , Zeng Y , Huang R , Yang Y , Chen K , Song W , Zhao B , Li J , Yuan L , Shang HF
Ref : Neurobiology of Aging , 33 :2721 e3 , 2012
Abstract : Recently, 5 single nucleotide polymorphisms (SNPs), rs2306677 in the inositol 1,4,5-triphosphate receptor 2 gene (ITPR2), rs1541160 in the kinesin-association protein 3 gene (KIFAP3), rs6690993 and rs6700125 in the FLJ10986 gene, and rs10260404 in the dipeptidyl-peptidase 6 gene (DPP6) have been reported to be associated with the risk of developing sporadic amyotrophic lateral sclerosis (SALS) in Caucasian populations. However, this association is not consistent among different studies and yet to be tested in Chinese SALS patients. We examined the above SNPs in a large cohort consisting of 395 SALS patients and 288 controls from Southwest China. Our results suggest that these SNPs are unlikely to be a common cause of SALS in Chinese populations.
ESTHER : Chen_2012_Neurobiol.Aging_33_2721 e3
PubMedSearch : Chen_2012_Neurobiol.Aging_33_2721 e3
PubMedID: 22795786

Title : Biocatalytic Synthesis of Poly(delta-Valerolactone) Using a Thermophilic Esterase from Archaeoglobus fulgidus as Catalyst - Cao_2012_Int.J.Mol.Sci_13_12232
Author(s) : Cao H , Han H , Li G , Yang J , Zhang L , Yang Y , Fang X , Li Q
Ref : Int J Mol Sci , 13 :12232 , 2012
Abstract : The ring-opening polymerization of delta-valerolactone catalyzed by a thermophilic esterase from the archaeon Archaeoglobus fulgidus was successfully conducted in organic solvents. The effects of enzyme concentration, temperature, reaction time and reaction medium on monomer conversion and product molecular weight were systematically evaluated. Through the optimization of reaction conditions, poly(delta-valerolactone) was produced in 97% m