He S

References (39)

Title : Molecular basis for the transcriptional regulation of an epoxide-based virulence circuit in Pseudomonas aeruginosa - He_2024_bioRxiv__
Author(s) : He S , Taher NM , Hvorecny KL , Ragusa MJ , Bahl CD , Hickman AB , Dyda F , Madden DR
Ref : Biorxiv , : , 2024
Abstract : The opportunistic pathogen Pseudomonas aeruginosa infects cystic fibrosis (CF) patient airways and produces a virulence factor Cif that is associated with worse outcomes. Cif is an epoxide hydrolase that reduces cell-surface abundance of the cystic fibrosis transmembrane conductance regulator (CFTR) and sabotages pro-resolving signals. Its expression is regulated by a divergently transcribed TetR family transcriptional repressor. CifR represents the first reported epoxide-sensing bacterial transcriptional regulator, but neither its interaction with cognate operator sequences nor the mechanism of activation has been investigated. Using biochemical and structural approaches, we uncovered the molecular mechanisms controlling this complex virulence operon. We present here the first molecular structures of CifR alone and in complex with operator DNA, resolved in a single crystal lattice. Significant conformational changes between these two structures suggest how CifR regulates the expression of the virulence gene cif . Interactions between the N-terminal extension of CifR with the DNA minor groove of the operator play a significant role in the operator recognition of CifR. We also determined that cysteine residue Cys107 is critical for epoxide sensing and DNA release. These results offer new insights into the stereochemical regulation of an epoxide-based virulence circuit in a critically important clinical pathogen.
ESTHER : He_2024_bioRxiv__
PubMedSearch : He_2024_bioRxiv__
PubMedID: 38293063
Gene_locus related to this paper: pseae-PA2934

Title : Improving the Thermostability of Thermomyces lanuginosus Lipase by Restricting the Flexibility of N-Terminus and C-Terminus Simultaneously via the 25-Loop Substitutions - Xiang_2023_Int.J.Mol.Sci_24_
Author(s) : Xiang X , Zhu E , Xiong D , Wen Y , Xing Y , Yue L , He S , Han N , Huang Z
Ref : Int J Mol Sci , 24 : , 2023
Abstract : (1) Lipases are catalysts widely applied in industrial fields. To sustain the harsh treatments in industries, optimizing lipase activities and thermal stability is necessary to reduce production loss. (2) The thermostability of Thermomyces lanuginosus lipase (TLL) was evaluated via B-factor analysis and consensus-sequence substitutions. Five single-point variants (K24S, D27N, D27R, P29S, and A30P) with improved thermostability were constructed via site-directed mutagenesis. (3) The optimal reaction temperatures of all the five variants displayed 5 degreesC improvement compared with TLL. Four variants, except D27N, showed enhanced residual activities at 80 degreesC. The melting temperatures of three variants (D27R, P29S, and A30P) were significantly increased. The molecular dynamics simulations indicated that the 25-loop (residues 24-30) in the N-terminus of the five variants generated more hydrogen bonds with surrounding amino acids; hydrogen bond pair D254-I255 preserved in the C-terminus of the variants also contributes to the improved thermostability. Furthermore, the newly formed salt-bridge interaction (R27...E56) in D27R was identified as a crucial determinant for thermostability. (4) Our study discovered that substituting residues from the 25-loop will enhance the stability of the N-terminus and C-terminus simultaneously, restrict the most flexible regions of TLL, and result in improved thermostability.
ESTHER : Xiang_2023_Int.J.Mol.Sci_24_
PubMedSearch : Xiang_2023_Int.J.Mol.Sci_24_
PubMedID: 38068886

Title : In vivo and in silico toxicity assessment of four common liquid crystal monomers to Daphnia magna: Novel endocrine disrupting chemicals in crustaceans? - He_2023_Sci.Total.Environ__168757
Author(s) : He S , He J , Wu F , Zhao Y , Jin X , Martyniuk CJ
Ref : Sci Total Environ , :168757 , 2023
Abstract : Liquid crystal monomers (LCMs) are widely used in liquid crystal displays (LCDs) and are proposed to be a new generation of environmentally persistent, bioaccumulative and toxic (PBT) substances that are increasingly detected in rivers and seas. However, there is a lack of in vivo data that characterize adverse responses and toxic mechanisms of LCMs on aquatic organisms. The aim of this study was to comprehensively investigate the effect of four typical LCMs on the lethality, growth, molting, and reproductive capacity of Daphnia magna (D. magna), a highly studied aquatic species in environmental toxicology. Whole body and enzymatic biomarkers (i.e., body length, chitobiase, acetylcholinesterase, antioxidant defense) were measured to assess the toxicity of LCMs. The 48 h mortality rate and observations of disrupted thorax development and inhibition of ecdysis indicate that D. magna are sensitive to LCMs exposure. Oxidative stress, impaired neurotransmission, and disruptions in molting were observed in short-term biomarker tests using LCMs. A 21 day exposure of D. magna to LCMs resulted in reduced growth, reproduction, and population intrinsic growth rate. In addition, chitobiase and 20-hydroxyecdysone, enzymes important for the molting process, were altered at 7, 14 and 21 d. This is hypothesized to be related to endocrine imbalance resulting from LCM exposure. Based on molecular docking simulations, there is evidence that LCMs bind directly to ecdysteroid receptors; this may explain the observed endocrine disrupting effects of LCMs. These data support the hypothesis that LCMs are endocrine disrupting chemicals in aquatic species, impacting the process of molting. This may subsequently lead to lower reproduction and unbalanced population dynamics.
ESTHER : He_2023_Sci.Total.Environ__168757
PubMedSearch : He_2023_Sci.Total.Environ__168757
PubMedID: 38008309

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

Title : Peroxidase-like activity of Ru-N-C nanozymes in colorimetric assay of acetylcholinesterase activity - Yan_2022_Anal.Chim.Acta_1191_339362
Author(s) : Yan B , Wang F , He S , Liu W , Zhang C , Chen C , Lu Y
Ref : Anal Chim Acta , 1191 :339362 , 2022
Abstract : Herein, the Ru-N-C nanozymes with abundant active Ru-N(x) sites have been successfully prepared by pyrolyzing Ru(acac)(3) trapped zeolitic-imidazolate-frameworks (Ru(acac)(3)@ZIF-8). Taking advantages of the remarkable peroxidase-mimicking activity, outstanding stability and reusability of Ru-N-C nanozymes, a novel biosensing system with explicit mechanism is strategically fabricated for sensitively determining acetylcholinesterase (AChE) and tacrine. The limit of detection for AChE activity can achieve as low as 0.0433 mU mL(-1), and the IC(50) value of tacrine for AChE is about 0.190 micromol L(-1). The robust analytical performance in serums test verifies the great application potential of this assay in real matrix. Furthermore, "INH" and "IMPLICATION-AND" logic gates are rationally constructed based on the proposed colorimetric sensor. This work not only provides one sustainable and effective avenue to fabricate Ru-N-C-based peroxidase mimic with high catalytic performance, and also gives new impetuses for developing novel biosensors by applying Ru-N-C-based enzyme mimics as substitutes for the natural enzyme.
ESTHER : Yan_2022_Anal.Chim.Acta_1191_339362
PubMedSearch : Yan_2022_Anal.Chim.Acta_1191_339362
PubMedID: 35033267

Title : Pseudo toxicity abatement effect of norfloxacin and copper combined exposure on Caenorhabditis elegans - Liu_2022_Chemosphere_287_132019
Author(s) : Liu L , He S , Tang M , Zhang M , Wang C , Wang Z , Sun F , Yan Y , Li H , Lin K
Ref : Chemosphere , 287 :132019 , 2022
Abstract : The coexistence of antibiotics and heavy metals may result in complex ecotoxicological effects on living organisms. In this work, the combined toxic effects of norfloxacin (NOR) and copper (Cu) on Caenorhabditis elegans (C. elegans) were investigated due to the highly possible co-pollution tendency. The results indicated that locomotion behaviors (frequency of head thrash and body bend) of C. elegans were more sensitive as the exposure time of NOR or Cu prolonged. Meanwhile, the physiological indexes (locomotion behaviors, body length) of C. elegans were more sensitive to the combined pollution that with lower Cu dosage (0.0125 microM), in prolonged exposure experiments. In addition, the toxic effects of NOR-Cu on physiological indexes of C. elegans seemed to be alleviated during prolonged exposure when Cu was 1.25 microM. Similarly, the ROS production and apoptosis level almost unchanged with the addition of NOR compared with Cu (1.25 microM) exposure groups, but both significantly higher than the control groups. Furthermore, compared with Cu (0.0125 microM and 1.25 microM) exposure experiments, the addition of NOR had resulted in the genetic expression decrease of hsp-16.1, hsp-16.2, hsp-16.48, and the oxidative stress in C. elegans seems to be alleviated. However, the significantly decreased of ape-1 and sod-3 expression indicated the disruption of ROS defense mechanism. The irregular change in ace-1 and ace-2 gene expressions in NOR-Cu (0.0125 microM) would result in the locomotion behaviors disorders of C. elegans, and this also explains why C. elegans are more sensitive to the combination of NOR and lower concentration of Cu.
ESTHER : Liu_2022_Chemosphere_287_132019
PubMedSearch : Liu_2022_Chemosphere_287_132019
PubMedID: 34450372

Title : Effects of short-term exposure to tralopyril on physiological indexes and endocrine function in turbot (Scophthalmus maximus) - Liu_2022_Aquat.Toxicol_245_106118
Author(s) : Liu B , Li P , He S , Xing S , Cao Z , Cao X , Wang X , Li ZH
Ref : Aquat Toxicol , 245 :106118 , 2022
Abstract : Tralopyril is an emerging marine antifouling agent with potential toxic effects on non-target aquatic organisms. To evaluate the toxicity of tralopyril, to turbot (Scophthalmus maximus), we assessed biomarkers, including oxidative stress, neurotoxicity, and osmotic homeostasis regulation enzymes, after a 7-day exposure to tralopyril (5 microg/L, 15 microg/L, 30 microg/L). Superoxide dismutase activity was significantly decreased at 30 microg/L, and Ca(2+)-Mg(2+)-ATPase activity in the gills was significantly increased at 15 microg/L and 30 microg/L. No statistically significant differences in the responses of acetylcholinesterase and nitric oxide were detected. In addition, 15 microg/L and 30 microg/L tralopyril induced hyperthyroidism, reflected by significantly increased of T3 levels. The expression levels of hypothalamus-pituitary-thyroid axis-related genes were also upregulated. The molecular docking results showed that the thyroid system disruption was not caused by competitive binding to the receptor. In addition, the integrated biomarker response index showed that 15 microg/L tralopyril had the greatest effect on turbot. In general, tralopyril caused oxidative damage, affected energy metabolism, and interfered with the endocrine system. These findings could provide reference data for assessing the ecological risk of tralopyril in marine environments.
ESTHER : Liu_2022_Aquat.Toxicol_245_106118
PubMedSearch : Liu_2022_Aquat.Toxicol_245_106118
PubMedID: 35176693

Title : Comparative Study of the Molecular Characterization, Evolution, and Structure Modeling of Digestive Lipase Genes Reveals the Different Evolutionary Selection Between Mammals and Fishes - Tang_2022_Front.Genet_13_909091
Author(s) : Tang SL , Liang XF , He S , Li L , Alam MS , Wu J
Ref : Front Genet , 13 :909091 , 2022
Abstract : Vertebrates need suitable lipases to digest lipids for the requirement of energy and essential nutrients; however, the main digestive lipase genes of fishes have certain controversies. In this study, two types of digestive lipase genes (pancreatic lipase (pl) and bile salt-activated lipase (bsal)) were identified in mammals and fishes. The neighborhood genes and key active sites of the two lipase genes were conserved in mammals and fishes. Three copies of PL genes were found in mammals, but only one copy of the pl gene was found in most of the fish species, and the pl gene was even completely absent in some fish species (e.g., zebrafish, medaka, and common carp). Additionally, the hydrophobic amino acid residues (Ile and Leu) which are important to pancreatic lipase activity were also absent in most of the fish species. The PL was the main digestive lipase gene in mammals, but the pl gene seemed not to be the main digestive lipase gene in fish due to the absence of the pl gene sequence and the important amino acid residues. In contrast, the bsal gene existed in all fish species, even two to five copies of bsal genes were found in most of the fishes, but only one copy of the BSAL gene was found in mammals. The amino acid residues of bile salt-binding sites and the three-dimensional (3D) structure modeling of Bsal proteins were conserved in most of the fish species, so bsal might be the main digestive lipase gene in fish. The phylogenetic analysis also indicated that pl or bsal showed an independent evolution between mammals and fishes. Therefore, we inferred that the evolutionary selection of the main digestive lipase genes diverged into two types between mammals and fishes. These findings will provide valuable evidence for the study of lipid digestion in fish.
ESTHER : Tang_2022_Front.Genet_13_909091
PubMedSearch : Tang_2022_Front.Genet_13_909091
PubMedID: 35991544

Title : A highly effective and stable butyrylcholinesterase inhibitor with multi-faceted neuroprotection and cognition improvement - Li_2022_Eur.J.Med.Chem_239_114510
Author(s) : Li Q , Xiong B , Wang Y , Lyu W , Xing S , Chen Y , Liao Q , He S , Feng F , Liu W , Sun H
Ref : Eur Journal of Medicinal Chemistry , 239 :114510 , 2022
Abstract : Butyrylcholinesterase (BChE) has been more and more attractive for treating neurodegenerative diseases, especially Alzheimer's disease (AD). In this study, we conducted activity and druggability optimization based on the structures that were previously reported. Most compounds exhibited pronounced BChE inhibitory capacity with nanomolar IC(50) values. Based on the results of inhibiting activity and cyto-safety evaluations, two compounds (7, eqBChE IC(50) = 2.94 nM, hBChE IC(50) = 34.6 nM, and 20, eqBChE IC(50) = 0.15 nM, hBChE IC(50) = 45.2 nM) have been selected as candidates. High stability of compound 20 contributed to significantly improved blood concentration and tissue exposure, resulting in a reduced administration and effective dose in pharmacodynamic experiments. Two candidates exhibited remarkable neuroprotective properties and cognition improving activity, by benefiting cholinergic system, reducing the total Abeta amount and increasing the ghrelin content. Simultaneous modulation in the center and periphery greatly improves the efficiency of BChE inhibitors. Considering the regulation on ghrelin level, BChE inhibition could improve not only symptoms but also nutritional status of AD patients.
ESTHER : Li_2022_Eur.J.Med.Chem_239_114510
PubMedSearch : Li_2022_Eur.J.Med.Chem_239_114510
PubMedID: 35728508

Title : Highly Potent and Selective Butyrylcholinesterase Inhibitors for Cognitive Improvement and Neuroprotection - Li_2021_J.Med.Chem__
Author(s) : Li Q , Chen Y , Xing S , Liao Q , Xiong B , Wang Y , Lu W , He S , Feng F , Liu W , Sun H
Ref : Journal of Medicinal Chemistry , : , 2021
Abstract : Butyrylcholinesterase (BChE) has been considered as a potential therapeutic target for Alzheimer's disease (AD) because of its compensation capacity to hydrolyze acetylcholine (ACh) and its close association with Abeta deposit. Here, we identified S06-1011 (hBChE IC(50) = 16 nM) and S06-1031 (hBChE IC(50) = 25 nM) as highly effective and selective BChE inhibitors, which were proved to be safe and long-acting. Candidate compounds exhibited neuroprotective effects and the ability to improve cognition in scopolamine- and Abeta(1-42) peptide-induced cognitive deficit models. The best candidate S06-1011 increased the level of ghrelin, a substrate of BChE, which can function as improving the mental mood appetite. The weight gain of the S06-1011-treated group remarkably increased. Hence, BChE inhibition not only plays a protective role against dementia but also exerts a great effect on treating and nursing care.
ESTHER : Li_2021_J.Med.Chem__
PubMedSearch : Li_2021_J.Med.Chem__
PubMedID: 33973470

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

Title : Effects of elevated CO(2) on activities of protective and detoxifying enzymes in Frankliniella occidentalis and Frankliniella intonsa under spinetoram stress1 - Fan_2021_Pest.Manag.Sci__
Author(s) : Fan Z , Qian L , Chen Y , Fan R , He S , Gao Y , Gui F
Ref : Pest Manag Sci , : , 2021
Abstract : BACKGROUND: Elevated CO(2) can directly affect toxicity of insecticides to insects and the physiological response of insects to insecticides. Frankliniella occidentalis and Frankliniella intonsa are highly destructive pests that target horticultural crops. Spinetoram is an effective pesticide against thrips. This study sought to explore the effect of elevated CO(2) on efficacy of spinetoram against F. occidentalis and F. intonsa and effect of the spinetoram on activities of protective and detoxifying enzymes under elevated CO(2) . Notably, these enzymes can be exploited in further studies to develop interventions for thrips resistance management. RESULTS: Toxicity bioassay showed that the LC(50) values of F. occidentalis and F. intonsa exposed to spinetoram at elevated CO(2) (800 microL.L(-1) concentration) for 48 h was 0.08 and 0.006 mg.L(-1) , respectively, they are 0.62 and 0.75 times of those at ambient CO(2) (400 microL.L(-1) concentration). The findings showed that elevated CO(2) decreased activities of the superoxide dismutase and acetylcholinesterase in thrips, while increased the activities of carboxylesterase and glutathione-S-transferase. However, spinetoram increased activities of protective and detoxifying enzymes in both thrips under the two CO(2) levels. It has synergistic effect of elevated CO(2) and spinetoram treatment on the physiological enzyme activity of thrips, and the activities of analyzed enzymes were generally higher in F. occidentalis than those in F. intonsa. CONCLUSION: Elevated CO(2) amplifies the efficacy of spinetoram on thrips, F. intonsa is more susceptibility to spinetoram than F. occidentalis, and the latter showed better adaptation to adverse conditions than the former. This article is protected by copyright. All rights reserved.
ESTHER : Fan_2021_Pest.Manag.Sci__
PubMedSearch : Fan_2021_Pest.Manag.Sci__
PubMedID: 34480397

Title : Protein liposomes-mediated targeted acetylcholinesterase gene delivery for effective liver cancer therapy - Wang_2021_J.Nanobiotechnology_19_31
Author(s) : Wang K , Shang F , Chen D , Cao T , Wang X , Jiao J , He S , Liang X
Ref : J Nanobiotechnology , 19 :31 , 2021
Abstract : BACKGROUND: Effective methods to deliver therapeutic genes to solid tumors and improve their bioavailability are the main challenges of current medical research on gene therapy. The development of efficient non-viral gene vector with tumor-targeting has very important application value in the field of cancer therapy. Proteolipid integrated with tumor-targeting potential of functional protein and excellent gene delivery performance has shown potential for targeted gene therapy. RESULTS: Herein, we prepared transferrin-modified liposomes (Tf-PL) for the targeted delivery of acetylcholinesterase (AChE) therapeutic gene to liver cancer. We found that the derived Tf-PL/AChE liposomes exhibited much higher transfection efficiency than the commercial product Lipo 2000 and shown premium targeting efficacy to liver cancer SMMC-7721 cells in vitro. In vivo, the Tf-PL/AChE could effectively target liver cancer, and significantly inhibit the growth of liver cancer xenografts grafted in nude mice by subcutaneous administration. CONCLUSIONS: This study proposed a transferrin-modified proteolipid-mediated gene delivery strategy for targeted liver cancer treatment, which has a promising potential for precise personalized cancer therapy.
ESTHER : Wang_2021_J.Nanobiotechnology_19_31
PubMedSearch : Wang_2021_J.Nanobiotechnology_19_31
PubMedID: 33482834

Title : Design and synthesis of novel tacrine-dipicolylamine dimers that are multiple-target-directed ligands with potential to treat Alzheimer's disease - Zhang_2021_Bioorg.Chem_116_105387
Author(s) : Zhang P , Wang Z , Mou C , Zou J , Xie Y , Liu Z , Benjamin Naman C , Mao Y , Wei J , Huang X , Dong J , Yang M , Wang N , Jin H , Liu F , Lin D , Liu H , Zhou F , He S , Zhang B , Cui W
Ref : Bioorg Chem , 116 :105387 , 2021
Abstract : Alzheimer's disease (AD) is a prevalent neurodegenerative disorder that has multiple causes. Therefore, multiple-target-directed ligands (MTDLs), which act on multiple targets, have been developed as a novel strategy for AD therapy. In this study, novel drug candidates were designed and synthesized by the covalent linkings of tacrine, a previously used anti-AD acetylcholinesterase (AChE) inhibitor, and dipicolylamine, an beta-amyloid (Abeta) aggregation inhibitor. Most tacrine-dipicolylamine dimers potently inhibited AChE and Abeta(1-42) aggregation in vitro, and 13a exhibited nanomolar level inhibition. Molecular docking analysis suggested that 13a could interact with the catalytic active sites and the peripheral anion site of AChE, and bind to Abeta(1-42) pentamers. Moreover, 13a effectively attenuated Abeta(1-42) oligomers-induced cognitive dysfunction in mice by activating the cAMP-response element binding protein/brain-derived neurotrophic factor signaling pathway, decreasing tau phosphorylation, preventing synaptic toxicity, and inhibiting neuroinflammation. The safety profile of 13a in mice was demonstrated by acute toxicity experiments. All these results suggested that novel tacrine-dipicolylamine dimers, especially 13a, have multi-target neuroprotective and cognitive-enhancing potentials, and therefore might be developed as MTDLs to combat AD.
ESTHER : Zhang_2021_Bioorg.Chem_116_105387
PubMedSearch : Zhang_2021_Bioorg.Chem_116_105387
PubMedID: 34628225

Title : High specific immobilization of His-tagged recombinant Microbacterium esterase by Ni-NTA magnetic chitosan microspheres for efficient synthesis of key chiral intermediate of d-biotin - He_2021_Bioprocess.Biosyst.Eng__
Author(s) : He S , Wu X , Ma B , Xu Y
Ref : Bioprocess Biosyst Eng , : , 2021
Abstract : The novel Ni-NTA-functionalized magnetic chitosan microspheres (MCS-NTA-Ni) were prepared via amino functionalization of MCS with epichlorohydrin and ethylenediamine, followed by the introduction of the aldehyde groups and NTA in turn, and nickel (II) ions were chelated in the end. MCS-NTA-Ni contained numerous long-armed NTA-Ni surface groups, ensuring high enzyme loading and providing more space and flexibility to attach enzymes and maintain their activity. This microsphere can have highly selective adsorption of his-tagged recombinant protein. The his-tagged recombinant Microbacterium esterase of E. coli BL21 (DE3)/pET21a-EstSIT01 was first immobilized on MCS-NTA-Ni by affinity fixation, giving high immobilization yield (90.1%) and enzyme loading (120 mg/g). Compared with free esterase, the immobilized esterase was found to exhibit higher pH stability and thermal stability. In addition, the immobilized esterase had excellent reusability for the synthesis of key chiral intermediate of d-biotin and the substrate conversion could still keep 100% after 8 cycles continuously.
ESTHER : He_2021_Bioprocess.Biosyst.Eng__
PubMedSearch : He_2021_Bioprocess.Biosyst.Eng__
PubMedID: 34089090

Title : PubChem in 2021: new data content and improved web interfaces - Kim_2021_Nucleic.Acids.Res_49_D1388
Author(s) : Kim S , Chen J , Cheng T , Gindulyte A , He J , He S , Li Q , Shoemaker BA , Thiessen PA , Yu B , Zaslavsky L , Zhang J , Bolton EE
Ref : Nucleic Acids Research , 49 :D1388 , 2021
Abstract : PubChem (https://pubchem.ncbi.nlm.nih.gov) is a popular chemical information resource that serves the scientific community as well as the general public, with millions of unique users per month. In the past two years, PubChem made substantial improvements. Data from more than 100 new data sources were added to PubChem, including chemical-literature links from Thieme Chemistry, chemical and physical property links from SpringerMaterials, and patent links from the World Intellectual Properties Organization (WIPO). PubChem's homepage and individual record pages were updated to help users find desired information faster. This update involved a data model change for the data objects used by these pages as well as by programmatic users. Several new services were introduced, including the PubChem Periodic Table and Element pages, Pathway pages, and Knowledge panels. Additionally, in response to the coronavirus disease 2019 (COVID-19) outbreak, PubChem created a special data collection that contains PubChem data related to COVID-19 and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
ESTHER : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedSearch : Kim_2021_Nucleic.Acids.Res_49_D1388
PubMedID: 33151290

Title : Inhibition of acetylcholinesterase activity and beta-amyloid oligomer formation by 6-bromotryptamine A, a multi-target anti-Alzheimer's molecule - Jin_2020_Oncol.Lett_19_1593
Author(s) : Jin X , Wang M , Shentu J , Huang C , Bai Y , Pan H , Zhang D , Yuan Z , Zhang H , Xiao X , Wu X , Ding L , Wang Q , He S , Cui W
Ref : Oncol Lett , 19 :1593 , 2020
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and beta-amyloid (Abeta) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Abeta oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Abeta oligomer formation.
ESTHER : Jin_2020_Oncol.Lett_19_1593
PubMedSearch : Jin_2020_Oncol.Lett_19_1593
PubMedID: 31966085

Title : Discovery and Biological Evaluation of a Novel Highly Potent Selective Butyrylcholinsterase Inhibitor - Li_2020_J.Med.Chem_63_10030
Author(s) : Li Q , Xing S , Chen Y , Liao Q , Xiong B , He S , Lu W , Liu Y , Yang H , Feng F , Liu W , Sun H
Ref : Journal of Medicinal Chemistry , 63 :10030 , 2020
Abstract : To discover novel BChE inhibitors, a hierarchical virtual screening protocol followed by biochemical evaluation was applied. The most potent compound 8012-9656 (eqBChE IC(50) = 0.18 +/- 0.03 M, hBChE IC(50) = 0.32 +/- 0.07 M) was purchased and synthesized. It inhibited BChE in a noncompetitive manner and could occupy the binding pocket forming diverse interactions with the target. 8012-9656 was proven to be safe in vivo and in vitro and showed comparable performance in ameliorating the scopolamine-induced cognition impairment to tacrine. Additionally, treatment with 8012-9656 could almost entirely recover the Abeta(1-42) (icv)-impaired cognitive function to the normal level and showed better behavioral performance than donepezil. The evaluation of the Abeta(1-42) total amount confirmed its anti-amyloidogenic profile. Moreover, 8012-9656 possessed blood-brain barrier (BBB) penetrating ability, a long T(1/2), and low intrinsic clearance. Hence, the novel potential BChE inhibitor 8012-9656 can be considered as a promising lead compound for further investigation of anti-AD agents.
ESTHER : Li_2020_J.Med.Chem_63_10030
PubMedSearch : Li_2020_J.Med.Chem_63_10030
PubMedID: 32787113

Title : Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases - Li_2020_Eur.J.Med.Chem_185_111862
Author(s) : Li Q , Xing S , Chen Y , Liao Q , Liu Y , He S , Feng F , Zhang J , Liu W , Guo Q , Sun Y , Sun H
Ref : Eur Journal of Medicinal Chemistry , 185 :111862 , 2020
Abstract : Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases.
ESTHER : Li_2020_Eur.J.Med.Chem_185_111862
PubMedSearch : Li_2020_Eur.J.Med.Chem_185_111862
PubMedID: 31735576

Title : Carboxylesterase genes in nitenpyram-resistant brown planthoppers, Nilaparvata lugens - Mao_2020_Insect.Sci__
Author(s) : Mao K , Ren Z , Li W , Cai T , Qin X , Wan H , Jin BR , He S , Li J
Ref : Insect Sci , : , 2020
Abstract : Carboxylesterases (CarEs) represent one of the major detoxification enzyme families involved in insecticide resistance. However, the function of specific CarE genes in insecticide resistance is still unclear in the insect Nilaparvata lugens (Stal), a notorious rice crop pest in Asia. In this study, a total of 29 putative CarE genes in N. lugens were identified, and they were divided into seven clades; further, the beta-esterase clade was significantly expanded. Tissue-specific expression analysis found that seventeen CarE genes were abundantly distributed in the midgut and fat body, while twelve CarE genes were highly expressed in the head. The expression of most CarE genes was significantly induced in response to the challenge of nitenpyram, triflumezopyrim, chlorpyrifos, isoprocarb and etofenprox. Among these, the expression levels of NlCarE2, NlCarE4, NlCarE9, NlCarE17 and NlCarE24 were increased by each insecticide. RT-qPCR and RNAi assays revealed the NlCarE1 gene to be a candidate gene mainly involved in nitenpyram resistance, while simultaneously silencing NlCarE1 and NlCarE19 produced a stronger effect than silencing either one individually, suggesting a cooperative relationship in resistance formation. These findings lay the foundation for further clarification of insecticide resistance mediated by CarE in N. lugens. This article is protected by copyright. All rights reserved.
ESTHER : Mao_2020_Insect.Sci__
PubMedSearch : Mao_2020_Insect.Sci__
PubMedID: 32495409

Title : Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present) - Wang_2019_Curr.Med.Chem_26_5684
Author(s) : Wang N , Qiu P , Cui W , Yan X , Zhang B , He S
Ref : Curr Med Chem , 26 :5684 , 2019
Abstract : Since the last century, when scientists proposed the lock-and-key model, the discovery of drugs has focused on the development of drugs acting on single target. However, single-target drug therapies are not effective to complex diseases with multi-factorial pathogenesis. Moreover, the combination of single-target drugs readily causes drug resistance and side effects. In recent years, multi-target drugs have increasingly been represented among FDA-approved drugs. Alzheimer's Disease (AD) is a complex and multi-factorial disease for which the precise molecular mechanisms are still not fully understood. In recent years, rational multi-target drug design methods, which combine the pharmacophores of multiple drugs, have been increasingly applied in the development of anti-AD drugs. In this review, we give a brief description of the pathogenesis of AD and provide detailed discussions about the recent development of chemical structures of anti-AD agents (2013 up to present) that have multiple targets, such as amyloid-beta peptide, Tau protein, cholinesterases, monoamine oxidase, beta-site amyloid-precursor protein-cleaving enzyme 1, free radicals, metal ions (Fe2+, Cu2+, Zn2+) and so on. In this paper, we also added some novel targets or possible pathogenesis which have been reported in recent years for AD therapy. We hope that these findings may provide new perspectives for the pharmacological treatment of AD.
ESTHER : Wang_2019_Curr.Med.Chem_26_5684
PubMedSearch : Wang_2019_Curr.Med.Chem_26_5684
PubMedID: 30501591

Title : The influence of temperature on the toxicity of insecticides to Nilaparvata lugens (Stal) - Mao_2019_Pestic.Biochem.Physiol_156_80
Author(s) : Mao K , Jin R , Li W , Ren Z , Qin X , He S , Li J , Wan H
Ref : Pestic Biochem Physiol , 156 :80 , 2019
Abstract : The toxicity of insecticides is associated with a variety of factors including temperature, and global warming is bound to lead to the outbreak of pests; therefore, it is important to study the influence of temperature on insecticide toxicity and pest control. In this study, the influence of temperature on the toxicity of insecticides to Nilaparvata lugens (BPH) was determined. The results showed that the sensitivity of BPH to cycloxaprid (LC50=42.5-0.388mg/L), nitenpyram (LC50=3.49-0.187mg/L), triflumezopyrim (LC50=0.354-0.0533mg/L) and chlorpyrifos (LC50=36.3-7.41mg/L) increased significantly when the temperature changed from 18 degrees C to 36 degrees C. BPH sensitivity to etofenprox (LC50=9.04-54.2mg/L) was also affected by temperature. Additionally, the feeding amount and the activities of three detoxification enzymes [cytochrome P450 (P450), glutathione S-transferase (GST) and carboxylesterase (CarE)] of BPH at different temperatures were also measured. The feeding amounts were positively correlated with temperature increases while the activities of P450 and GST were significantly inhibited. The correlation analysis showed that changes in P450 activity (but not GST activity) were closely related to the sensitivity of BPH to cycloxaprid, nitenpyram, chlorpyrifos, and etofenprox according to the variation in temperatures. This study provides a theoretical basis for the rational use of chemical pesticides under the global warming trend and provides a reference for the integrated management of BPH in the field.
ESTHER : Mao_2019_Pestic.Biochem.Physiol_156_80
PubMedSearch : Mao_2019_Pestic.Biochem.Physiol_156_80
PubMedID: 31027584

Title : 9-Methylfascaplysin Is a More Potent Abeta Aggregation Inhibitor than the Marine-Derived Alkaloid, Fascaplysin, and Produces Nanomolar Neuroprotective Effects in SH-SY5Y Cells - Sun_2019_Mar.Drugs_17_
Author(s) : Sun Q , Liu F , Sang J , Lin M , Ma J , Xiao X , Yan S , Naman CB , Wang N , He S , Yan X , Cui W , Liang H
Ref : Mar Drugs , 17 : , 2019
Abstract : beta-Amyloid (Abeta) is regarded as an important pathogenic target for Alzheimer's disease (AD), the most prevalent neurodegenerative disease. Abeta can assemble into oligomers and fibrils, and produce neurotoxicity. Therefore, Abeta aggregation inhibitors may have anti-AD therapeutic efficacies. It was found, here, that the marine-derived alkaloid, fascaplysin, inhibits Abeta fibrillization in vitro. Moreover, the new analogue, 9-methylfascaplysin, was designed and synthesized from 5-methyltryptamine. Interestingly, 9-methylfascaplysin is a more potent inhibitor of Abeta fibril formation than fascaplysin. Incubation of 9-methylfascaplysin with Abeta directly reduced Abeta oligomer formation. Molecular dynamics simulations revealed that 9-methylfascaplysin might interact with negatively charged residues of Abeta42 with polar binding energy. Hydrogen bonds and pi(-)pi interactions between the key amino acid residues of Abeta42 and 9-methylfascaplysin were also suggested. Most importantly, compared with the typical Abeta oligomer, Abeta modified by nanomolar 9-methylfascaplysin produced less neuronal toxicity in SH-SY5Y cells. 9-Methylfascaplysin appears to be one of the most potent marine-derived compounds that produces anti-Abeta neuroprotective effects. Given previous reports that fascaplysin inhibits acetylcholinesterase and induces P-glycoprotein, the current study results suggest that fascaplysin derivatives can be developed as novel anti-AD drugs that possibly act via inhibition of Abeta aggregation along with other target mechanisms.
ESTHER : Sun_2019_Mar.Drugs_17_
PubMedSearch : Sun_2019_Mar.Drugs_17_
PubMedID: 30781608

Title : New Dihydroisocoumarin Root Growth Inhibitors From the Sponge-Derived Fungus Aspergillus sp. NBUF87 - Huang_2019_Front.Microbiol_10_2846
Author(s) : Huang L , Ding L , Li X , Wang N , Cui W , Wang X , Naman CB , Lazaro JEH , Yan X , He S
Ref : Front Microbiol , 10 :2846 , 2019
Abstract : Six new dihydroisocoumarins, aspergimarins A-F (1-6), were discovered together with five known analogs (7-11) from a monoculture of the sponge-derived fungus Aspergillus sp. NBUF87. The structures of these compounds were elucidated through comprehensive spectroscopic methods, and absolute configurations were assigned after X-ray crystallography, use of the modified Mosher's method, and comparison of electronic circular dichroism (ECD) data with literature values for previously reported analogs. Compounds 1-11 were evaluated in a variety of bioassays, and at 100 muM, both 1 and 5 showed significant inhibitory effects on the lateral root growth of Arabidopsis thaliana Columbia-0 (Col-0). Moreover, at 100 muM, 5 also possessed notable inhibition against the primary root growth of Col-0. Meanwhile, 1-11 were all found to be inactive in vitro against acetylcholinesterase (AChE) (IC50 > 100 muM), four different types of human-derived cancer cell lines (IC50 > 50 muM), as well as methicillin-resistant Staphylococcus aureus and Escherichia coli (MIC > 50 mug/mL), and Plasmodium falciparum W2 (EC50 > 100 mug/mL), in phenotypic tests.
ESTHER : Huang_2019_Front.Microbiol_10_2846
PubMedSearch : Huang_2019_Front.Microbiol_10_2846
PubMedID: 31921029

Title : Should we pay attention to the aberrant nerve communication between the lingual and mylohyoid nerves? - Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
Author(s) : Zhan C , Yuan Z , Qu R , Zou L , He S , Li Z , Liu C , Xiao Z , Ouyang J , Dai J
Ref : Br J Oral Maxillofac Surg , 57 :317 , 2019
Abstract : An unusual communication between the lingual and mylohyoid nerves has been identified as one reason for incomplete mandibular anaesthesia, and for neuropathy. However, its anatomical features and function are poorly understood and its relations with neighbouring structures, which are valuable in reducing the side effects of surgical operations, have not been sufficiently described. The aim of this study, therefore, was to describe the communication between the nerves and to assess the implications for oral and maxillofacial surgery. We explored the communication between the mylohyoid nerves of 62 embalmed, and 16 fresh, hemifaces. The diameter, length of the communication, and other variables were measured, and the junctions with the two nerves microdissected. The nervous communications of fresh specimens and relative nerves were stained histochemically for acetylcholinesterase. Of the 62 embalmed specimens, 19 had a communication that pierced the mylohyoid muscle, and staining showed that this was a sensory nerve. Our results suggest that the sensory communication between the lingual and mylohyoid nerves pierces the mylohyoid muscle and connects these otherwise unrelated nerves, thereby contributing to the likelihood of operative side effects.
ESTHER : Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
PubMedSearch : Zhan_2019_Br.J.Oral.Maxillofac.Surg_57_317
PubMedID: 30940405

Title : Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease - Li_2018_Eur.J.Med.Chem_158_463
Author(s) : Li Q , He S , Chen Y , Feng F , Qu W , Sun H
Ref : Eur Journal of Medicinal Chemistry , 158 :463 , 2018
Abstract : Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in elderly people. Considering the multifactorial nature of AD, the concept of multi-target-directed ligands (MTDLs) has recently emerged as a new strategy for designing therapeutic agents on AD. MTDLs are confirmed to simultaneously affect diverse targets which contribute to etiology of AD. As the most potent approved drug, donepezil affects various events of AD, like inhibiting cholinesterases activities, anti-Abeta aggregation, anti-oxidative stress et al. Modifications of donepezil or hybrids with pharmacophores of donepezil in recent five years are summarized in this article. On the basis of case studies, our concerns and opinions about development of donepezil derivatives, designing of MTDLs, and perspectives for AD treatments are discussed in final part.
ESTHER : Li_2018_Eur.J.Med.Chem_158_463
PubMedSearch : Li_2018_Eur.J.Med.Chem_158_463
PubMedID: 30243151

Title : Biodegradation of pyraclostrobin by two microbial communities from Hawaiian soils and metabolic mechanism - Chen_2018_J.Hazard.Mater_354_225
Author(s) : Chen X , He S , Liang Z , Li QX , Yan H , Hu J , Liu X
Ref : J Hazard Mater , 354 :225 , 2018
Abstract : Pyraclostrobin has been widely and long-termly applicated to agricultural fields. The removal of pyraclostrobin from ecological environment has received wide attention. In this study, using sequential enrichments with pyraclostrobin as a sole carbon source, two microbial communities (HI2 and HI6) capable of catabolizing pyraclostrobin were obtained from Hawaiian soils. The microfloras analysis indicated that only Proteobacteria and Bacteroides could survive in HI2-soil after acclimatization, whereas the number of Proteobacteria in HI6-soil accounted for more than 99%. The percentages of Pseudomonas in the HI2 and HI6 microfloras were 69.3% and 59.3%, respectively. More than 99% of pyraclostrobin (C0=100mgL(-1)) was degraded by the HI2 and HI6 microorganisms within five days. A unique metabolite was identified by high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (HPLC-QTOF-MS/MS). A metabolic pathway involving carbamate hydrolysis was proposed. The tertiary amine group of pyraclostrobin was hydrolyzed to primary amine group with the decarboxylation, which facilitated pyraclostrobin detoxification because carboxylester was an important functional group. The metabolic mechanism suggested that Pseudomonas expressing carboxylesterase might be able to degrade carbamate chemicals. Therefore, Pseudomonas might be an ideal candidate for expression and cloning of carbamate-degrading gene in genomics studies. The current study would have important implications in detoxification and bioremediation of carbamates through the CN bond cleavage of methyl carbamate.
ESTHER : Chen_2018_J.Hazard.Mater_354_225
PubMedSearch : Chen_2018_J.Hazard.Mater_354_225
PubMedID: 29753191

Title : Involvement of pregnane X receptor in the suppression of carboxylesterases by metformin in vivo and in vitro, mediated by the activation of AMPK and JNK signaling pathway - Shan_2017_Eur.J.Pharm.Sci_102_14
Author(s) : Shan E , Zhu Z , He S , Chu D , Ge D , Zhan Y , Liu W , Yang J , Xiong J
Ref : Eur J Pharm Sci , 102 :14 , 2017
Abstract : Type 2 diabetes mellitus (T2D) is a complex metabolic disorder requiring polypharmacy treatment in clinic, with metformin being widely used antihyperglycemic drug. However, the mechanisms of metformin as a perpetrator inducing potential drug-drug interactions and adverse drug reactions are scarcely known to date. Carboxylesterases (CESs) are major hydrolytic enzymes highly expressed in the liver, including mouse carboxylesterase 1d (Ces1d) and Ces1e. In the present study, experiments are designed to investigate the effects and mechanisms of metformin on Ces1d and Ces1e in vivo and in vitro. In results, metformin suppresses the expression and activity of Ces1d and Ces1e in a dose- and time-dependent manner. The decreased expression of nuclear receptor PXR and its target gene P-gp indicates the involvements of PXR in the suppressed expression of carboxylesterases by metformin. Furthermore, metformin significantly suppresses the phosphorylation of AMPK and JNK, and the suppression of carboxylesterases induced by metformin is repeatedly abolished by AMPK inhibitor Compound C and JNK inhibitor SP600125. It implies that the activation of AMPK and JNK pathways mediates the suppression of carboxylesterases by metformin. The findings deserve further elucidation including clinical trials and have a potential to make contribution for the rational medication in the treatment of T2D patients.
ESTHER : Shan_2017_Eur.J.Pharm.Sci_102_14
PubMedSearch : Shan_2017_Eur.J.Pharm.Sci_102_14
PubMedID: 28238946

Title : Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro - Lin_2016_Mar.Drugs_14_
Author(s) : Lin J , Huang L , Yu J , Xiang S , Wang J , Zhang J , Yan X , Cui W , He S , Wang Q
Ref : Mar Drugs , 14 : , 2016
Abstract : Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 muM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer's disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression.
ESTHER : Lin_2016_Mar.Drugs_14_
PubMedSearch : Lin_2016_Mar.Drugs_14_
PubMedID: 27023569

Title : Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages - He_2015_Circ.Heart.Fail_8_980
Author(s) : He S , Chousterman BG , Fenn A , Anzai A , Nairz M , Brandt M , Hilgendorf I , Sun Y , Ye YX , Iwamoto Y , Tricot B , Weissleder R , Macphee C , Libby P , Nahrendorf M , Swirski FK
Ref : Circ Heart Fail , 8 :980 , 2015
Abstract : BACKGROUND: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Elevated Lp-PLA2 levels associate with increased risk of cardiovascular events across diverse patient populations, but the mechanisms by which the enzyme elicits its effects remain unclear. This study tested the role of Lp-PLA2 in healing after MI. METHODS AND
RESULTS: In response to MI, Lp-PLA2 levels markedly increased in the circulation. To test the functional importance of Lp-PLA2, we generated chimeric mice whose bone marrow-derived leukocytes were Lp-PLA2-deficient (bmLp-PLA2 (-/-)). Compared with wild-type controls, bmLp-PLA2 (-/-) mice subjected to MI had lower serum levels of inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1beta, and IL-6, and decreased number of circulating inflammatory myeloid cells. Accordingly, bmLp-PLA2 (-/-) mice developed smaller and less inflamed infarcts with reduced numbers of infiltrating neutrophils and inflammatory Ly-6C(high) monocytes. During the later, reparative phase, infarcts of bmLp-PLA2 (-/-) mice contained Ly-6C(low) macrophages with a skewed M2-prone gene expression signature, increased collagen deposition, fewer inflammatory cells, and improved indices of angiogenesis. Consequently, the hearts of bmLp-PLA2 (-/-) mice healed more efficiently, as determined by improved left ventricle remodeling and ejection fraction.
CONCLUSIONS: Lp-PLA2 augments the inflammatory response after MI and antagonizes healing by disrupting the balance between inflammation and repair, providing a rationale for focused study of ventricular function and heart failure after targeting this enzyme acutely in MI.
ESTHER : He_2015_Circ.Heart.Fail_8_980
PubMedSearch : He_2015_Circ.Heart.Fail_8_980
PubMedID: 26232205

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

Title : A highly sensitive gold-nanoparticle-based assay for acetylcholinesterase in cerebrospinal fluid of transgenic mice with Alzheimer's disease - Liu_2012_Adv.Healthc.Mater_1_90
Author(s) : Liu D , Chen W , Tian Y , He S , Zheng W , Sun J , Wang Z , Jiang X
Ref : Adv Healthc Mater , 1 :90 , 2012
Abstract : A highly sensitive, selective, and dual-readout (colorimetric and fluorometric) assay for acetylcholinesterase (AChE) based on Rhodamine B-modified gold nanoparticle is reported. Due to its good sensitivity and selectivity, the assay can be used for monitoring AChE levels in the cerebrospinal fluid of transgenic mice with Alzheimer's disease.
ESTHER : Liu_2012_Adv.Healthc.Mater_1_90
PubMedSearch : Liu_2012_Adv.Healthc.Mater_1_90
PubMedID: 23184691

Title : Reversible and persistent decreases in cocaine self-administration after cholinesterase inhibition: different effects of donepezil and rivastigmine - Grasing_2011_Behav.Pharmacol_22_58
Author(s) : Grasing K , Yang Y , He S
Ref : Behav Pharmacol , 22 :58 , 2011
Abstract : We recently observed that pretreatment with the cholinesterase inhibitor, tacrine can produce long-lasting reductions in cocaine-reinforced behavior, described as persistent attenuation. In addition to inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase, tacrine can potentiate actions of dopamine. This study was carried out to evaluate the effects of donepezil (which selectively inhibits AChE) and rivastigmine (which inhibits both AChE and butyrylcholinesterase) on cocaine self-administration. High self-administration rats self-administered different doses of cocaine under a fixed ratio-5 schedule. Over a 4-day period, vehicle, donepezil, or rivastigmine was infused as animals were maintained in home cages (21 h per day), with signs of cholinergic stimulation (fasciculation, vacuous jaw movements, yawning, and diarrhea) scored by a blinded observer. Both compounds dose-dependently decreased cocaine self-administration, but differed in the potency and temporal pattern of their effects. Self-administration of low-dose cocaine was decreased to a greater degree by rivastigmine than donepezil (50% effective doses of 2.33 and 6.21 mg/kg/day, respectively), but this early effect did not continue beyond sessions immediately after treatment with rivastigmine. Group means for cocaine self-administration were decreased at some time points occurring between 1 and 3 days after the treatment with 10 mg/kg/day of donepezil (late effects), with decreases of more than 80% observed in some individual rats that persisted for 1 week or longer. Early, but not late, effects were correlated with signs of cholinergic stimulation. In summary, pretreatment with donepezil, but not rivastigmine produced persistent reductions in cocaine-reinforced behavior, which were not associated with signs of cholinergic stimulation.
ESTHER : Grasing_2011_Behav.Pharmacol_22_58
PubMedSearch : Grasing_2011_Behav.Pharmacol_22_58
PubMedID: 22173266

Title : Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution - Pope_2011_PLoS.One_6_e16329
Author(s) : Pope WH , Jacobs-Sera D , Russell DA , Peebles CL , Al-Atrache Z , Alcoser TA , Alexander LM , Alfano MB , Alford ST , Amy NE , Anderson MD , Anderson AG , Ang AA , Ares M, Jr. , Barber AJ , Barker LP , Barrett JM , Barshop WD , Bauerle CM , Bayles IM , Belfield KL , Best AA , Borjon A, Jr. , Bowman CA , Boyer CA , Bradley KW , Bradley VA , Broadway LN , Budwal K , Busby KN , Campbell IW , Campbell AM , Carey A , Caruso SM , Chew RD , Cockburn CL , Cohen LB , Corajod JM , Cresawn SG , Davis KR , Deng L , Denver DR , Dixon BR , Ekram S , Elgin SC , Engelsen AE , English BE , Erb ML , Estrada C , Filliger LZ , Findley AM , Forbes L , Forsyth MH , Fox TM , Fritz MJ , Garcia R , George ZD , Georges AE , Gissendanner CR , Goff S , Goldstein R , Gordon KC , Green RD , Guerra SL , Guiney-Olsen KR , Guiza BG , Haghighat L , Hagopian GV , Harmon CJ , Harmson JS , Hartzog GA , Harvey SE , He S , He KJ , Healy KE , Higinbotham ER , Hildebrandt EN , Ho JH , Hogan GM , Hohenstein VG , Holz NA , Huang VJ , Hufford EL , Hynes PM , Jackson AS , Jansen EC , Jarvik J , Jasinto PG , Jordan TC , Kasza T , Katelyn MA , Kelsey JS , Kerrigan LA , Khaw D , Kim J , Knutter JZ , Ko CC , Larkin GV , Laroche JR , Latif A , Leuba KD , Leuba SI , Lewis LO , Loesser-Casey KE , Long CA , Lopez AJ , Lowery N , Lu TQ , Mac V , Masters IR , McCloud JJ , McDonough MJ , Medenbach AJ , Menon A , Miller R , Morgan BK , Ng PC , Nguyen E , Nguyen KT , Nguyen ET , Nicholson KM , Parnell LA , Peirce CE , Perz AM , Peterson LJ , Pferdehirt RE , Philip SV , Pogliano K , Pogliano J , Polley T , Puopolo EJ , Rabinowitz HS , Resiss MJ , Rhyan CN , Robinson YM , Rodriguez LL , Rose AC , Rubin JD , Ruby JA , Saha MS , Sandoz JW , Savitskaya J , Schipper DJ , Schnitzler CE , Schott AR , Segal JB , Shaffer CD , Sheldon KE , Shepard EM , Shepardson JW , Shroff MK , Simmons JM , Simms EF , Simpson BM , Sinclair KM , Sjoholm RL , Slette IJ , Spaulding BC , Straub CL , Stukey J , Sughrue T , Tang TY , Tatyana LM , Taylor SB , Taylor BJ , Temple LM , Thompson JV , Tokarz MP , Trapani SE , Troum AP , Tsay J , Tubbs AT , Walton JM , Wang DH , Wang H , Warner JR , Weisser EG , Wendler SC , Weston-Hafer KA , Whelan HM , Williamson KE , Willis AN , Wirtshafter HS , Wong TW , Wu P , Yang Y , Yee BC , Zaidins DA , Zhang B , Zuniga MY , Hendrix RW , Hatfull GF
Ref : PLoS ONE , 6 :e16329 , 2011
Abstract : Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.
ESTHER : Pope_2011_PLoS.One_6_e16329
PubMedSearch : Pope_2011_PLoS.One_6_e16329
PubMedID: 21298013
Gene_locus related to this paper: 9caud-g1jvt5 , 9caud-e0ypf9

Title : GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity - Cheng_2010_J.Biol.Chem_285_41541
Author(s) : Cheng S , Li L , He S , Liu J , Sun Y , He M , Grasing K , Premont RT , Suo WZ
Ref : Journal of Biological Chemistry , 285 :41541 , 2010
Abstract : Membrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its precise roles in the disease pathogenesis remain to be delineated. We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of presynaptic M2 autoreceptors, which causes presynaptic M2 hyperactivity and inhibits acetylcholine release. Here we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing beta-amyloid precursor protein (APP) carrying Swedish mutations (Tg2576 or APPsw) resulted in significantly increased beta-amyloid (Abeta) accumulation, including increased Abeta(+) plaque burdens and soluble Abeta in brain lysates and interstitial fluid (ISF). In addition, secreted beta-APP fragment (sAPPbeta) also increased, whereas full-length APP level did not change, suggesting an alteration in favor of beta-amyloidogenic APP processing in these animals. Reversely, perfusion of methoctramine, a selective M2 antagonist, fully corrected the difference between the control and GRK5-deficient APPsw mice for ISF Abeta. In contrast, a cholinesterase inhibitor, eserine, although significantly decreasing the ISF Abeta in both control and GRK5-deficient APPsw mice, failed to correct the difference between them. However, combining eserine with methoctramine additively reduced the ISF Abeta further in both animals. Altogether, these findings indicate that GRK5 deficiency accelerates beta-amyloidogenic APP processing and Abeta accumulation in APPsw mice via impaired cholinergic activity and that presynaptic M2 hyperactivity is the specific target for eliminating the pathologic impact of GRK5 deficiency. Moreover, a combination of an M2 antagonist and a cholinesterase inhibitor may reach the maximal disease-modifying effect for both amyloid pathology and cholinergic dysfunction.
ESTHER : Cheng_2010_J.Biol.Chem_285_41541
PubMedSearch : Cheng_2010_J.Biol.Chem_285_41541
PubMedID: 21041302

Title : Long-lasting decreases in cocaine-reinforced behavior following treatment with the cholinesterase inhibitor tacrine in rats selectively bred for drug self-administration - Grasing_2009_Pharmacol.Biochem.Behav_94_169
Author(s) : Grasing K , He S , Yang Y
Ref : Pharmacol Biochem Behav , 94 :169 , 2009
Abstract : Tacrine is a centrally acting, reversible cholinesterase inhibitor that increases synaptic levels of acetylcholine (ACh) and can potentiate the actions of dopamine (DA). The present study was conducted to evaluate effects of tacrine on cocaine-reinforced responding in a rat line selectively bred for high levels of drug self-administration (the HS line). HS rats self-administered different doses of cocaine under a fixed-ratio-5 (FR-5) schedule. Over a four-day period, vehicle or tacrine (1.0, 3.2, or 10 mg/kg-day) was infused when animals were maintained in home cages (21 h per day). Tacrine dose-dependently decreased cocaine self-administration. Actions of tacrine differed for self-administration that was initiated within 20 min of pretreatment (described as early sessions), and for self-administration that occurred between one and three days after administration of tacrine was discontinued (late sessions). Tacrine's potency for attenuating self-administration during late sessions was greater for cocaine- relative to food-reinforcement in HS rats, and for HS relative to outbred rats. In a subset of tacrine-treated HS rats, cocaine self-administration was persistently attenuated by more than 80% from pretreatment baseline levels over a one-week period during which no further tacrine was administered. In summary, pretreatment with tacrine can produce a long-lasting attenuation of cocaine-reinforced responding.
ESTHER : Grasing_2009_Pharmacol.Biochem.Behav_94_169
PubMedSearch : Grasing_2009_Pharmacol.Biochem.Behav_94_169
PubMedID: 19698738

Title : Dose-related effects of the acetylcholinesterase inhibitor tacrine on cocaine and food self-administration in rats - Grasing_2008_Psychopharmacology.(Berl)_196_133
Author(s) : Grasing K , He S , Yang Y
Ref : Psychopharmacology (Berl) , 196 :133 , 2008
Abstract : RATIONALE: Acetylcholine (ACh) is involved in brain reward and learning functions and contributes to opiate- and psychostimulant-motivated behaviors. Tacrine is a centrally acting, reversible cholinesterase inhibitor that also inhibits monoamine oxidase (MAO) and blocks reuptake of dopamine (DA) and serotonin. OBJECTIVES: To determine the effects of pretreatment with tacrine on self-administration of cocaine and nondrug reinforcers. MATERIALS AND
METHODS: Male Wistar rats were trained to self-administer cocaine under a fixed-ratio-5 (FR-5) schedule during 2-h multiple-component sessions in which 0.1, 0.2, and 0.4 mg/kg per injection of cocaine were each available for 40 min. Other animals self-administered 45 mg food pellets under FR-30 or 20% Ensure (liquid food) under FR-5 in amounts of 30, 60, or 120 microl. Vehicle or tacrine was administered as single intravenous doses 20 min before self-administration of cocaine, food pellets, or liquid food.
RESULTS: Although pretreatment with 0.032 mg/kg of tacrine increased self-administration of food pellets, pretreatment with higher doses of tacrine attenuated self-administration of cocaine, food pellets, or liquid food. Tacrine's ED50 value for attenuating self-administration of 0.1 mg/kg per injection of cocaine was more than sixfold lower than values for attenuating liquid food- or food pellet-reinforced behavior. However, ED50 values for attenuating self-administration of higher doses of cocaine were similar to those observed for 30 or 60 microl of liquid food.
CONCLUSIONS: Tacrine can selectively attenuate self-administration of low-dose cocaine, but its effects on higher doses of cocaine are similar to its ability to decrease self-administration of nondrug reinforcers.
ESTHER : Grasing_2008_Psychopharmacology.(Berl)_196_133
PubMedSearch : Grasing_2008_Psychopharmacology.(Berl)_196_133
PubMedID: 17917719