Li C

References (199)

Title : Design, synthesis, and evaluation of dual-target inhibitors for the treatment of Alzheimer's disease - Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
Author(s) : Zhai J , Hao C , Wang X , Cao Y , Pan Y , Zhou M , Sun J , Li C
Ref : Arch Pharm (Weinheim) , :e2300693 , 2024
Abstract : Abeta(1-42) and acetylcholinesterase (AChE) are two key therapeutic targets for Alzheimer's disease (AD). The purpose of this study is to develop a dual-target inhibitor that inhibits both of these targets by fusing the chemical structure of baicalein and donepezil. Among them, we modified the structure of baicalein to arylcoumarin, synthesized three kinds of structural compounds, and evaluated their biological activities. The results showed that compound 3b had the strongest inhibitory effect on AChE (IC(50) = 0.05 +/- 0.02 microM), which was better than those of donepezil and baicalein. In addition, compound 3b has a strong ability to inhibit the aggregation of Abeta(1-42) and protect nerve cells, and it can also penetrate the blood-brain barrier well. Using a zebrafish behavioral analyzer test, it was found that compound 3b can alleviate the behavioral effects of AlCl(3) -induced zebrafish larval movement retardation, which has a certain guiding significance for simulating the movement disorders of AD patients. In summary, compound 3b is expected to become a multifunctional agent for treating and alleviating the symptoms of AD patients.
ESTHER : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedSearch : Zhai_2024_Arch.Pharm.(Weinheim)__e2300693
PubMedID: 38332316

Title : Characterization of a recombinant Aspergillus niger GZUF36 lipase immobilized by ionic liquid modification strategy - Xing_2024_Appl.Microbiol.Biotechnol_108_233
Author(s) : Xing S , Long J , Xie W , Luo C , He L , Li C , Zeng X
Ref : Applied Microbiology & Biotechnology , 108 :233 , 2024
Abstract : Enzyme immobilized on magnetic nanomaterials is a promising biocatalyst with efficient recovery under applied magnets. In this study, a recombinant extracellular lipase from Aspergillus niger GZUF36 (PEXANL1) expressed in Pichia pastoris GS115 was immobilized on ionic liquid-modified magnetic nano ferric oxide (Fe(3)O(4)@SiO(2)@ILs) via electrostatic and hydrophobic interaction. The morphology, structure, and properties of Fe(3)O(4)@SiO(2)@ILs and immobilized PEXANL1 were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, vibration sample magnetometer, and zeta potential analysis. Under optimized conditions, the immobilization efficiency and activity recovery of immobilized PEXANL1 were 52 +/- 2% and 122 +/- 2%, respectively. The enzymatic properties of immobilized PEXANL1 were also investigated. The results showed that immobilized PEXANL1 achieved the maximum activity at pH 5.0 and 45 degreesC, and the lipolytic activity of immobilized PEXANL1 was more than twice that of PEXANL1. Compared to PEXANL1, immobilized PEXANL1 exhibited enhanced tolerance to temperature, metal ions, surfactants, and organic solvents. The operation stability experiments revealed that immobilized PEXANL1 maintained 86 +/- 3% of its activity after 6 reaction cycles. The enhanced catalytic performance in enzyme immobilization on Fe(3)O(4)@SiO(2)@ILs made nanobiocatalysts a compelling choice for bio-industrial applications. Furthermore, Fe(3)O(4)@SiO(2)@ILs could also benefit various industrial enzymes and their practical uses. KEY POINTS: Immobilized PEXANL1 was confirmed by SEM, FT-IR, and XRD. The specific activity of immobilized PEXANL1 was more than twice that of PEXANL1. Immobilized PEXANL1 had improved properties with good operational stability.
ESTHER : Xing_2024_Appl.Microbiol.Biotechnol_108_233
PubMedSearch : Xing_2024_Appl.Microbiol.Biotechnol_108_233
PubMedID: 38400957

Title : LET-767 determines lipid droplet protein targeting and lipid homeostasis - Fu_2024_J.Cell.Biol_223_
Author(s) : Fu L , Zhang J , Wang Y , Wu H , Xu X , Li C , Li J , Liu J , Wang H , Jiang X , Li Z , He Y , Liu P , Wu Y , Zou X , Liang B
Ref : Journal of Cell Biology , 223 : , 2024
Abstract : Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.
ESTHER : Fu_2024_J.Cell.Biol_223_
PubMedSearch : Fu_2024_J.Cell.Biol_223_
PubMedID: 38551495

Title : Apoptosis signal-regulating kinase 1 (Ask1) deficiency alleviates MPP(+)-induced impairment of evoked dopamine release in the mouse hippocampus - Zhao_2024_Front.Cell.Neurosci_18_1288991
Author(s) : Zhao F , Li C , Zhuang Y , Yan Y , Gao Y , Behnisch T
Ref : Front Cell Neurosci , 18 :1288991 , 2024
Abstract : The dopaminergic system is susceptible to dysfunction in numerous neurological diseases, including Parkinson's disease (PD). In addition to motor symptoms, some PD patients may experience non-motor symptoms, including cognitive and memory deficits. A possible explanation for their manifestation is a disturbed pattern of dopamine release in brain regions involved in learning and memory, such as the hippocampus. Therefore, investigating neuropathological alterations in dopamine release prior to neurodegeneration is imperative. This study aimed to characterize evoked hippocampal dopamine release and assess the impact of the neurotoxin MPP(+) using a genetically encoded dopamine sensor and gene expression analysis. Additionally, considering the potential neuroprotective attributes demonstrated by apoptosis signal-regulating kinase 1 (Ask1) in various animal-disease-like models, the study also aimed to determine whether Ask1 knockdown restores MPP(+)-altered dopamine release in acute hippocampal slices. We applied variations of low- and high-frequency stimulation to evoke dopamine release within different hippocampal regions and discovered that acute application of MPP(+) reduced the amount of dopamine released and hindered the recovery of dopamine release after repeated stimulation. In addition, we observed that Ask1 deficiency attenuated the detrimental effects of MPP(+) on the recovery of dopamine release after repeated stimulation. RNA sequencing analysis indicated that genes associated with the synaptic pathways are involved in response to MPP(+) exposure. Notably, Ask1 deficiency was found to downregulate the expression of Slc5a7, a gene encoding a sodium-dependent high-affinity choline transporter that regulates acetylcholine levels. Respective follow-up experiments indicated that Slc5a7 plays a role in Ask1 deficiency-mediated protection against MPP(+) neurotoxicity. In addition, increasing acetylcholine levels using an acetylcholinesterase inhibitor could exacerbate the toxicity of MPP(+). In conclusion, our data imply that the modulation of the dopamine-acetylcholine balance may be a crucial mechanism of action underlying the neuroprotective effects of Ask1 deficiency in PD.
ESTHER : Zhao_2024_Front.Cell.Neurosci_18_1288991
PubMedSearch : Zhao_2024_Front.Cell.Neurosci_18_1288991
PubMedID: 38414754

Title : Adipocyte HSL is required for maintaining circulating vitamin A and RBP4 levels during fasting - Steinhoff_2024_EMBO.Rep__
Author(s) : Steinhoff JS , Wagner C , Dahnhardt HE , Kosic K , Meng Y , Taschler U , Pajed L , Yang N , Wulff S , Kiefer MF , Petricek KM , Flores RE , Li C , Dittrich S , Sommerfeld M , Guillou H , Henze A , Raila J , Wowro SJ , Schoiswohl G , Lass A , Schupp M
Ref : EMBO Rep , : , 2024
Abstract : Vitamin A (retinol) is distributed via the blood bound to its specific carrier protein, retinol-binding protein 4 (RBP4). Retinol-loaded RBP4 is secreted into the circulation exclusively from hepatocytes, thereby mobilizing hepatic retinoid stores that represent the major vitamin A reserves in the body. The relevance of extrahepatic retinoid stores for circulating retinol and RBP4 levels that are usually kept within narrow physiological limits is unknown. Here, we show that fasting affects retinoid mobilization in a tissue-specific manner, and that hormone-sensitive lipase (HSL) in adipose tissue is required to maintain serum concentrations of retinol and RBP4 during fasting in mice. We found that extracellular retinol-free apo-RBP4 induces retinol release by adipocytes in an HSL-dependent manner. Consistently, global or adipocyte-specific HSL deficiency leads to an accumulation of retinoids in adipose tissue and a drop of serum retinol and RBP4 during fasting, which affects retinoid-responsive gene expression in eye and kidney and lowers renal retinoid content. These findings establish a novel crosstalk between liver and adipose tissue retinoid stores for the maintenance of systemic vitamin A homeostasis during fasting.
ESTHER : Steinhoff_2024_EMBO.Rep__
PubMedSearch : Steinhoff_2024_EMBO.Rep__
PubMedID: 38769419
Gene_locus related to this paper: human-LIPE

Title : A Turn-On Lipid Droplet-Targeted Near-Infrared Fluorescent Probe with a Large Stokes Shift for Detection of Intracellular Carboxylesterases and Cell Viability Imaging - Li_2023_Molecules_28_
Author(s) : Li C , Li S , Li X , Yuan T , Xu J , Gu X , Hua J
Ref : Molecules , 28 : , 2023
Abstract : Carboxylesterases (CEs) play important physiological roles in the human body and are involved in numerous cellular processes. Monitoring CEs activity has great potential for the rapid diagnosis of malignant tumors and multiple diseases. Herein, we developed a new phenazine-based "turn-on" fluorescent probe DBPpys by introducing 4-bromomethyl-phenyl acetate to DBPpy, which can selectively detect CEs with a low detection limit (9.38 x 10(-5) U/mL) and a large Stokes shift (more than 250 nm) in vitro. In addition, DBPpys can also be converted into DBPpy by carboxylesterase in HeLa cells and localized in lipid droplets (LDs), emitting bright near-infrared fluorescence under the irradiation of white light. Moreover, we achieved the detection of cell health status by measuring the intensity of NIR fluorescence after co-incubation of DBPpys with H(2)O(2)-pretreated HeLa cells, indicating that DBPpys has great potential applications for assessing CEs activity and cellular health.
ESTHER : Li_2023_Molecules_28_
PubMedSearch : Li_2023_Molecules_28_
PubMedID: 36903562

Title : A Guanosine-Derived Antitumor Supramolecular Prodrug - Wang_2023_Biomacromolecules__
Author(s) : Wang S , Hu N , Deng B , Wang H , Qiao R , Li C
Ref : Biomacromolecules , : , 2023
Abstract : The prodrug strategy for its potential to enhance the pharmacokinetic and/or pharmacodynamic properties of drugs, especially chemotherapeutic agents, has been widely recognized as an important means to improve therapeutic efficiency. Irinotecan's active metabolite, 7-ethyl-10-hydroxycamptothecin (SN38), a borate derivative, was incorporated into a G-quadruplex hydrogel (GB-SN38) by the ingenious and simple approach. Drug release does not depend on carboxylesterase, thus bypassing the side effects caused by ineffective activation, but specifically responds to the ROS-overexpressed tumor microenvironment by oxidative hydrolysis of borate ester that reduces serious systemic toxicity from nonspecific biodistribution of SN38. Comprehensive spectroscopy was used to define the structural and physicochemical characteristics of the drug-loaded hydrogel. The GB-SN38 hydrogel's high level of biosafety and notable tumor-suppressive properties were proven in in vitro and in vivo tests.
ESTHER : Wang_2023_Biomacromolecules__
PubMedSearch : Wang_2023_Biomacromolecules__
PubMedID: 38065622

Title : Integrative Analysis of Transcriptome and Metabolome to Illuminate the Protective Effects of Didymin against Acute Hepatic Injury - Pang_2023_Mediators.Inflamm_2023_6051946
Author(s) : Pang L , Xiong Y , Feng Z , Li C , Fang B , Huang Q , Lin X
Ref : Mediators Inflamm , 2023 :6051946 , 2023
Abstract : Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-kappaB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-kappaB pathways.
ESTHER : Pang_2023_Mediators.Inflamm_2023_6051946
PubMedSearch : Pang_2023_Mediators.Inflamm_2023_6051946
PubMedID: 36687218

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 : Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis in Rats - Shao_2023_J.Invest.Surg_36_1
Author(s) : Shao Y , Li C , Jiang Y , Li H , Tang X , Gao Z , Zhang D
Ref : J Invest Surg , 36 :1 , 2023
Abstract : Background: Acute kidney injury (AKI) is a common complication in patients with severe acute pancreatitis (SAP). Caspase-11-mediated pyroptosis is essential for the progression of multiple diseases, but its role in SAP-induced AKI remains unknown.Aims: This research investigated whether caspase-11-mediated pyroptosis is involved in SAP-induced AKI and whether inhibiting caspase-11-mediated pyroptosis improves SAP-induced AKI.Methods: A rat model of SAP with AKI was established by slowly injecting 5% sodium taurocholate into the biliopancreatic duct, then wedelolactone (25 or 50 mg/kg), an inhibitor of caspase-11, was injected through the intra-peritoneum 1 and 6 h after SAP induction. Serum biochemical indexes, including serum amylase, lipase, interleukin (IL)-6, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-alpha, and creatinine (Cr) in rats, were evaluated using biochemical test kits. Caspase-11 and gasdermin D (GSDMD) expression in the kidney tissues was evaluated by western blotting and immunohistochemical staining. IL-1 and IL-18 levels in kidney tissues were detected by ELISA kits. Furthermore, histopathological alterations of pancreas and kidney were assessed by H&E staining.Results: The serum biochemical indexes and pyroptosis-related proteins in kidney tissues were significantly increased after SAP induction. Furthermore, wedelolactone decreased the expression of pyroptosis-linked proteins in kidney tissues, reduced serum lipase, amylase, IL-6, TNF-alpha, BUN, and Cr, and ameliorated the renal and pancreatic histological damage in SAP rats.Conclusion: Caspase-11-mediated pyroptosis contributes to SAP-induced AKI, and targeting caspase-11-mediated pyroptosis might be a novel treatment strategy for SAP-induced AKI.
ESTHER : Shao_2023_J.Invest.Surg_36_1
PubMedSearch : Shao_2023_J.Invest.Surg_36_1
PubMedID: 36350036

Title : Lipase-catalyzed ring-opening polymerization of natural compound-based cyclic monomers - Wang_2023_Chem.Commun.(Camb)__
Author(s) : Wang K , Li C , Man L , Zhang M , Jia YG , Zhu XX
Ref : Chem Commun (Camb) , : , 2023
Abstract : The need for sustainable and environment-friendly materials has led to growing interest in the development of biodegradable polymers based on natural compounds. However, metal-based catalysts used in the polymerization process may cause concerns about the toxicity of the resultant polymers. Therefore, polymers derived from natural compounds and synthesized through the use of green catalysts are highly desirable. Lipase-catalyzed ring-opening polymerization (ROP) of biocompound-based cyclic monomers has emerged as a promising and green strategy for the design and synthesis of such polymers. In this review, we summarize reports on the use of ROP catalyzed by lipase for cyclic monomers derived from natural compounds, including bile acid- and porphyrin-based macrocycles, carbonate-based macrocycles, lactones, and cyclic anhydrides, with an emphasis on ring-closure reactions for the synthesis of cyclic monomers, the types of lipases for the ROP and the choice of reaction conditions (temperature, solvent, reaction time, etc.). Moreover, the current challenges and perspectives for the choice and reusability of lipases, ring-closure versus ring-opening reactions, monomer design, and potential applications are discussed.
ESTHER : Wang_2023_Chem.Commun.(Camb)__
PubMedSearch : Wang_2023_Chem.Commun.(Camb)__
PubMedID: 37431654

Title : Nematicidal Coumarins from Cnidium monnieri Fruits and Angelica dahurica Roots and Their Physiological Effect on Pine Wood Nematode (Bursaphelenchus xylophilus) - Feng_2023_Molecules_28_
Author(s) : Feng J , Qin C , Liu X , Li R , Wang C , Li C , Du G , Guo Q
Ref : Molecules , 28 : , 2023
Abstract : Pine wood nematode (PWN), Bursaphelenchus xylophilus, is a major pathogen of pine wilt disease (PWD), which is a devastating disease affecting pine trees. Eco-friendly plant-derived nematicides against PWN have been considered as promising alternatives to control PWD. In this study, the ethyl acetate extracts of Cnidium monnieri fruits and Angelica dahurica roots were confirmed to have significant nematicidal activity against PWN. Through bioassay-guided fractionations, eight nematicidal coumarins against PWN were separately isolated from the ethyl acetate extracts of C. monnieri fruits and A. dahurica roots, and they were identified to be osthol (Compound 1), xanthotoxin (Compound 2), cindimine (Compound 3), isopimpinellin (Compound 4), marmesin (Compound 5), isoimperatorin (Compound 6), imperatorin (Compound 7), and bergapten (Compound 8) by mass and nuclear magnetic resonance (NMR) spectral data analysis. Coumarins 1-8 were all determined to have inhibitory effects on the egg hatching, feeding ability, and reproduction of PWN. Moreover, all eight nematicidal coumarins could inhibit the acetylcholinesterase (AChE) and Ca(2+) ATPase of PWN. Cindimine 3 from C. monnieri fruits showed the strongest nematicidal activity against PWN, with an LC(50) value of 64 microM at 72 h, and the highest inhibitory effect on PWN vitality. In addition, bioassays on PWN pathogenicity demonstrated that the eight nematicidal coumarins could effectively relieve the wilt symptoms of black pine seedlings infected by PWN. The research identified several potent botanical nematicidal coumarins for use against PWN, which could contribute to the development of greener nematicides for PWD control.
ESTHER : Feng_2023_Molecules_28_
PubMedSearch : Feng_2023_Molecules_28_
PubMedID: 37241850

Title : Amelioration of walnut-derived novel peptides against D-galactose-induced cognitive impairment by modulating the gut microbiota composition - Li_2023_Food.Funct__
Author(s) : Li T , Lin L , Li C , Zheng J , Chen B , Shen Y , Ren D
Ref : Food Funct , : , 2023
Abstract : In this work, RLWPF (Arg-Leu-Trp-Pro-Phe) and VLRLF (Val-Leu-Arg-Leu-Phe) were investigated for the effects against D-galactose (D-gal) induced cognitive impairment by modulating the gut microbiota composition. The effects on serum metabolite production were further investigated. The two novel peptides derived from walnut protein alkaline protease hydrolysates were predicted by docking to acetylcholinesterase (AChE) with the highest binding affinities, -10.3 and -9.9 kcal mol(-1), considered as the potential neuroprotective peptides. In behavioral experiments, RLWPF and VLRLF treatment significantly restored spatial learning and memory impairment induced by D-gal. The results showed that RLWPF and VLRLF could alleviate cholinergic dysfunction, oxidative stress, and inflammation to varying degrees caused by D-gal-induced aging. Furthermore, 16S rRNA analysis revealed that RLWPF and VLRLF treatment improved cognitive impairment by regulating the composition of the gut microbiota and the abundance of harmful bacteria, including the ratio of Firmicutes to Bacteroidetes, Helicobacter, Allobaculum, Alistipes, Mucispirillum, and Odoribacter. In addition to the same regulation, RLWPF and VLRLF had their marker and regulatory flora. Studies based on the gut microbiota would allow a better understanding of the neuroprotective effects of walnut-derived peptides, supporting that walnut-derived peptides could be potential functional ingredients in foods and nutraceuticals or drug candidates in the treatment of cognitive dysfunction.
ESTHER : Li_2023_Food.Funct__
PubMedSearch : Li_2023_Food.Funct__
PubMedID: 37067262

Title : Maize resistance to witchweed through changes in strigolactone biosynthesis - Li_2023_Science_379_94
Author(s) : Li C , Dong L , Durairaj J , Guan JC , Yoshimura M , Quinodoz P , Horber R , Gaus K , Li J , Setotaw YB , Qi J , De Groote H , Wang Y , Thiombiano B , Flokova K , Walmsley A , Charnikhova TV , Chojnacka A , Correia de Lemos S , Ding Y , Skibbe D , Hermann K , Screpanti C , De Mesmaeker A , Schmelz EA , Menkir A , Medema M , van Dijk ADJ , Wu J , Koch KE , Bouwmeester HJ
Ref : Science , 379 :94 , 2023
Abstract : Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga-resistant maize.
ESTHER : Li_2023_Science_379_94
PubMedSearch : Li_2023_Science_379_94
PubMedID: 36603079

Title : Discovery selective acetylcholinesterase inhibitors to control Tetranychus urticae (Acari: Tetranychidae) - Wang_2023_J.Insect.Sci_23_19
Author(s) : Wang J , Cao Y , Lai B , Liu Y , Li C , Bu C
Ref : J Insect Sci , 23 :19 , 2023
Abstract : The two-spotted spider mite, Tetranychus urticae Koch, has a broad host plant range and presents an extreme capacity for developing pesticide resistance, becoming a major economic pest in agriculture. Anticholinesterase insecticides still account for a big part of global insecticide sales. However, there is a growing concern about the serious resistance problems of anticholinesterase insecticides and their nontarget toxicity. In this study, structure-based virtual screening was performed to discover selective AChE inhibitors from the ChemBridge database, and 39 potential species-specific AChE inhibitor were obtained targeting T. urticae AChE, but not human AChE. Among them, compound No. 8 inhibited AChE from T. urticae, but not from human, and had an inhibitory activity comparable to that of eserine. Compound No. 8 had dose-dependent toxicity to T. urticae in glass slide-dipping assay and had significant mite control effects in a pot experiment, but required a high concentration to achieve similar control effects to spirodiclofen. The toxicity evaluation suggested that compound No. 8 had no acute toxicity on pollinator honey bees and natural predator N. californicus and did not affect strawberry growth in our assay. Compound No. 8 is a potential lead compound for developing novel acaricides with reduced nontarget toxicity.
ESTHER : Wang_2023_J.Insect.Sci_23_19
PubMedSearch : Wang_2023_J.Insect.Sci_23_19
PubMedID: 37578847
Gene_locus related to this paper: 9acar-m9t420

Title : Effect of substrate composition on physicochemical properties of the medium-long-medium structured triacylglycerol - Tian_2023_J.Sci.Food.Agric__
Author(s) : Tian Y , Zhou Y , Li L , Huang C , Lin L , Li C , Ye Y
Ref : J Sci Food Agric , : , 2023
Abstract : BACKGROUND: Nutritional and functional qualities and applications of structured lipids (SL) depend on the composition and molecular structure of fatty acids in the glycerol backbone of triacylglycerol (TAG). However, the relationship between the substrate composition and physicochemical qualities of SL has not been revealed. The investigation aims to disclose the effect of substrate composition on the physicochemical properties of medium-long-medium structured lipids (MLM-SLs) by enzymatic interesterification of Lipozyme TLIM/RMIM. RESULTS: The medium-long chain triacylglycerol (MLCT) yield could reach 70.32% including 28.98% CaLCa (1,3-dioctonyl-2-linoleoyl glyceride) and 24.34% CaOCa (1,3-didecanoyl-2-oleoyl glyceride). The sn-2 unsaturated fatty acids composition mainly depended on long chain triacylglycerol (LCT) in the substrate. The increased carbon chain length and double bond in triacylglycerol decreased its melting and crystallization temperature. The balanced substrate composition of MCT/LCT increased the size and finer crystals. Molecular docking simulation revealed that the MLCT molecule was mainly interacted with the catalytic triplets of Lipozyme TLIM (Arg81-Ser83-Arg84) and the Lipozyme RMIM (Tyr183-Thr226-Arg262) by O...H bond. The oxygen atom of the ester on the MLCT molecule was primarily bound to the hydrogen of hydroxyl and amino groups on the binding sites of Lipozyme TLIM/RMIM. The intermolecular interplay between MLCT and Lipozyme RMIM is stable than Lipozyme TLIM due to the formation of lower binding affinity energy. CONCLUSION: This research clarifies the interaction mechanism between MLCT molecules and lipases, and provides in-deep understanding the relationship between substrate composition, molecular structure and physicochemical property of MLM-SLs. This article is protected by copyright. All rights reserved.
ESTHER : Tian_2023_J.Sci.Food.Agric__
PubMedSearch : Tian_2023_J.Sci.Food.Agric__
PubMedID: 37708388

Title : Paraoxonase 2 (PON2) plays a limited role in murine lung tumorigenesis - Whitt_2023_Sci.Rep_13_9929
Author(s) : Whitt AG , Neely AM , Sarkar OS , Meng S , Arumugam S , Yaddanapudi K , Li C
Ref : Sci Rep , 13 :9929 , 2023
Abstract : Paraoxonase 2 (PON2) is a multifunctional intracellular enzyme that has received growing attention for its ability to modulate various aspects of normal and malignant cellular physiology. Recent research has revealed that PON2 is upregulated in tissues from patients with various types of solid tumors and hematologic cancers, likely due to its ability to suppress oxidative stress and evade apoptosis. However, the effects of PON2 on pulmonary oncogenesis are unknown. Here, we conducted studies to investigate how PON2 influences lung cancer cell proliferation in vitro and lung tumorigenesis in vivo using a variety of cellular and animal models. It was found that PON2 expression deficiency hampered the proliferation of cultured lung cancer cells with concomitant cell cycle arrest at the G1 phase. In addition, the loss of endogenous PON2 expression impaired key aspects of oxidative metabolism in lung adenocarcinoma cells. Moreover, we investigated how the interplay between PON2 expression in lung tumors and host mice influences lung tumor initiation and progression. PON2 status in both transplanted tumor cells and mice failed to influence the development of subcutaneously grafted Lewis lung carcinoma (LLC) tumors, orthotopically implanted LLC tumors, and oncogenic Kras-driven primary lung adenocarcinoma tumors. Importantly, the frequencies of tumor-infiltrating myeloid subsets that include myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages were not impacted by PON2 expression in LLC tumor-bearing mice. Overall, our studies indicate that PON2 plays a limited role in murine lung tumorigenesis.
ESTHER : Whitt_2023_Sci.Rep_13_9929
PubMedSearch : Whitt_2023_Sci.Rep_13_9929
PubMedID: 37337025

Title : Increased Soluble Epoxide Hydrolase Activity Positively Correlates with Mortality in Heart Failure Patients with Preserved Ejection Fraction: Evidence from Metabolomics - Peng_2023_Phenomics_3_34
Author(s) : Peng L , Song Z , Zhao C , Abuduwufuer K , Wang Y , Wen Z , Ni L , Li C , Yu Y , Zhu Y , Jiang H , Shen J , Jiang X , Chen C , Zhang X , Wang DW
Ref : Phenomics , 3 :34 , 2023
Abstract : Epoxyeicosatrienoic acids (EETs) have pleiotropic endogenous cardiovascular protective effects and can be hydrolyzed to the corresponding dihydroxyeicosatrienoic acids by soluble epoxide hydrolase (sEH). Heart failure with preserved ejection fraction (HFpEF) has shown an increased prevalence and worse prognosis over the decades. However, the role of sEH activity in HFpEF remains unclear. We enrolled 500 patients with HFpEF and 500 healthy controls between February 2010 and March 2016. Eight types of sEH-related eicosanoids were measured according to target metabolomics, and their correlation with clinical endpoints was also analyzed. The primary endpoint was cardiac mortality, and the secondary endpoint was a composite of cardiac events, including heart failure (HF) readmission, cardiogenic hospitalization, and all-cause mortality. Furthermore, the effect of sEH inhibitors on cardiac diastolic function in HFpEF was investigated in vivo and in vitro. Patients with HFpEF showed significantly enhanced EET degradation by the sEH enzyme compared with healthy controls. More importantly, sEH activity was positively correlated with cardiac mortality in patients with HFpEF, especially in older patients with arrhythmia. A consistent result was obtained in the multiple adjusted models. Decreased sEH activity by the sEH inhibitor showed a significant effective effect on the improvement of cardiac diastolic function by ameliorating lipid disorders in cardiomyocytes of HFpEF mouse model. This study demonstrated that increased sEH activity was associated with cardiac mortality in patients with HFpEF and suggested that sEH inhibition could be a promising therapeutic strategy to improve diastolic cardiac function. Clinical trial identifier: NCT03461107 ( SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43657-022-00069-8.
ESTHER : Peng_2023_Phenomics_3_34
PubMedSearch : Peng_2023_Phenomics_3_34
PubMedID: 36939801

Title : Enantioconvergent hydrolysis of racemic 1,2-epoxypentane and 1,2-epoxyhexane by an engineered Escherichia coli strain overexpressing a novel Streptomyces fradiae epoxide hydrolase - Huang_2023_Enzyme.Microb.Technol_166_110228
Author(s) : Huang R , Li C , Zhao SG , Liu QT , Liu Y , Xue ZL
Ref : Enzyme Microb Technol , 166 :110228 , 2023
Abstract : In order to excavate microbial epoxide hydrolases (EHs) with desired catalytic properties, a novel EH, SfEH1, was identified based on the genome annotation of Streptomyces fradiae and sequence alignment analysis with local protein library. The SfEH1-encoding gene, sfeh1, was then cloned and over-expressed in soluble form in Escherichia coli/BL21(DE3). The optimal temperature and pH of recombinant SfEH1 (reSfEH1) and reSfEH1-expressing E. coli (E. coli/sfeh1) were both determined as 30 degC and 7.0, also indicating that the influences of temperature and pH on reSfEH1's activities were more obvious than those of E. coli/sfeh1 whole cells. Subsequently, using E. coli/sfeh1 as catalyst, its catalytic properties towards thirteen common mono-substituted epoxides were tested, in which E. coli/sfeh1 had the highest activity of 28.5 U/g dry cells for rac-1,2-epoxyoctane (rac-6a), and (R)-1,2-pentanediol ((R)-3b) (or (R)-1,2-hexanediol ((R)-4b)) with up to 92.5% (or 94.1%) ee(p) was obtained at almost 100% conversion ratio. Regioselectivity coefficients (alpha(S) and beta(R)) displayed in the enantioconvergent hydrolysis of rac-3a (or rac-4a) were calculated to be 98.7% and 93.8% (or 95.2% and 98.9%). Finally, the reason of the high and complementary regioselectivity was confirmed by both kinetic parameter analysis and molecular docking simulations.
ESTHER : Huang_2023_Enzyme.Microb.Technol_166_110228
PubMedSearch : Huang_2023_Enzyme.Microb.Technol_166_110228
PubMedID: 36940599
Gene_locus related to this paper: strfr-SfEH1

Title : A New Brominated Isocoumarin from the Marine Starfish-Associated Fungus Aspergillus sp. WXF1904 - Li_2023_Chem.Biodivers__e202301706
Author(s) : Li C , Lin X , Wang S , Guan D , Wang X , Yang B , Zhou X , Li J , Xiong B , Liu Y , Sun Y
Ref : Chem Biodivers , :e202301706 , 2023
Abstract : Based on the one strain many compounds strategy, a new brominated isocoumarin, 5-bromo-6,8-dihydroxy-3,7-dimethylisocoumarin (1), along with four new natural products, methyl 3-bromo-2,4-dihydroxy-6-methylbenzoate (2), methyl 2-bromo-4,6-dihydroxybenzoate (3), (E)-3-(3-bromo-4-hydroxyphenyl) acrylic acid (4) and 4-hydroxy-3-methyl-6-phenyl-2H-pyran-2-one (5), and four known compounds, methyl orsellinate (6), 4-hydroxy-3-methyl-6-(1-methyl-1-propenyl)-2H-pyran-2-one (7), pilobolusate (8) and cis-ferulic acid (9), were isolated from the ethyl acetate extract of the fungus Aspergillus sp. WXF1904 under the condition of adding bromine salt to the production medium. The structures of the new compounds were established by analysis of NMR and MS data. Compounds (1-9) were evaluated for inhibitory activity of acetylcholinesterase and pancreatic lipase, the new compound 1, known compounds 6 and 7 displayed weak inhibitory activity against acetylcholinesterase, compounds 257 and 8 showed weak inhibitory activity against pancreatic lipase.
ESTHER : Li_2023_Chem.Biodivers__e202301706
PubMedSearch : Li_2023_Chem.Biodivers__e202301706
PubMedID: 38079052

Title : Population performance and detoxifying and protective enzyme activities of four thrips species feeding on flowers of Magnolia grandiflora (Ranunculales: Magnolia) - Cao_2023_Pest.Manag.Sci__
Author(s) : Cao Y , Qi G , Jiang F , Meng Y , Wang C , Gu Z , Gao Y , Reitz SR , Li C
Ref : Pest Manag Sci , : , 2023
Abstract : BACKGROUND: Different thrips species can co-occur on the same flowers with different dominance degrees. To accurately evaluate the population performance on different thrips species on Magnolia grandiflora flowers, we investigated the diversity of thrips species and their population dynamics both in the field and laboratory. In addition, the activities of detoxifying and protective enzymes in thrips were also measured. RESULTS: Field investigations revealed that four thrips species (Thrips hawaiiensis, Thrips flavidulus, Frankliniella occidentalis, and Thrips coloratus) were coexisted on M. grandiflora flowers. They were ranked, from highest population density to lowest, as follows: T. hawaiiensis > T. flavidulus > F. occidentalis > T. coloratus. In laboratory investigations, the species were ranked, from fastest developmental rates to slowest, as follows: F. occidentalis > T. hawaiiensis > T. flavidulus > T. coloratus; and from largest population size to smallest, as follows: T. hawaiiensis > F. occidentalis > T. flavidulus > T. coloratus. Biochemistry assays showed that the four species differed in their activities of detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and cytochrome P450) and protective enzymes (superoxide dismutase, peroxidase) in both laboratory and field strains. CONCLUSION: Differences in population performance among these four thrips on M. grandiflora may be related to their activity levels of physiological enzymes. The variations in thrips population performance between the field and the laboratory could be due to differences in environmental conditions. T. hawaiiensis showed a strong host preference for M. grandiflora, and thus it has the potential to be a dangerous pest in horticultural plants. This article is protected by copyright. All rights reserved.
ESTHER : Cao_2023_Pest.Manag.Sci__
PubMedSearch : Cao_2023_Pest.Manag.Sci__
PubMedID: 37085951

Title : Individualized regimen of low-dose rituximab monotherapy for new-onset AChR-positive generalized myasthenia gravis - Du_2022_J.Neurol__
Author(s) : Du Y , Li C , Hao YF , Zhao C , Yan Q , Yao D , Li L , Zhang W
Ref : Journal of Neurology , : , 2022
Abstract : BACKGROUND: Generalized AChR-MG is an archetype of B cell-mediated autoimmune disorders, and use of biologic agent rituximab (RTX) for B cell depletion is generally limited to immunosuppressive therapy-refractory cases. However, benefit of RTX monotherapy and individualized regimen with optimal dosage in early stage of new-onset generalized AChR-MG still remains to be elucidated. In this retrospective study, we explore the efficacy and safety of personalized regimen of 100 mg low-dose rituximab monotherapy in treating new-onset generalized AChR-MG. METHODS: Thirteen new-onset generalized AChR-MG patients were enrolled for the study, initiating RTX treatment from November 2017 to August 2020. The individualized low-dose RTX monotherapy protocol consisted of 100 mg induction treatment weekly with no more than three circles, followed by reinfusion (100 mg once) sequentially according to whether achieving primary endpoint and peripheral CD19 + B-cell repopulation <= 1% of total lymphocytes at each visit (every 3 months). Outcome measures included MGFA-PIS Minimal Manifestation (MM) or better status (primary endpoint), changes in QMG, MMT, MG-ADL and MGQOL-15 scores (secondary endpoint), as well as cholinesterase inhibitors dosage. RESULTS: All 13 patients achieved the primary endpoint in parallel with significant improvement of QMG, MMT, MG-ADL MGQOL-15 scores, and reduction of cholinesterase inhibitors dose. A total of 52 visits were performed during follow-up, and only 10 assessments presenting peripheral CD19 + B-cell repopulation (<= 1%) without "MM or better status" were followed by RTX reinfusions (100 mg once) for clinical remission. The total dosage of RTX was only 346.15 +/- 96.74 mg (including 269.23 +/- 63.04 mg for induction and 76.92 +/- 59.91 mg for reinfusion), which seemed to be much lower than those dosages used in new-onset generalized AChR-MG as described previously. Moreover, compared with patients without thymoma, thymectomy markedly delayed initiation of RTX for patients with thymoma (log-rank test, p = 0.0002), but the delaying treatments showed no influence on the time for achieving primary outcome (log-rank test, p = 0.2517). CONCLUSION: Our study firstly showed that individualized regimen of low-dose RTX monotherapy is effective and safe for early treatment of new-onset generalized AChR-MG, and practicable for directing RTX reinfusion and withdrawal. Moreover, the monotherapy protocol was also indicated to be extensively applicable in both new-onset AChR-MG with thymoma (thymectomy) and without thymoma.
ESTHER : Du_2022_J.Neurol__
PubMedSearch : Du_2022_J.Neurol__
PubMedID: 35243555

Title : Aaptamine - a dual acetyl - and butyrylcholinesterase inhibitor as potential anti-Alzheimer's disease agent - Miao_2022_Pharm.Biol_60_1502
Author(s) : Miao S , He Q , Li C , Wu Y , Liu M , Chen Y , Qi S , Gong K
Ref : Pharm Biol , 60 :1502 , 2022
Abstract : CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are promising therapeutic targets for AD. OBJECTIVE: To evaluate the inhibitory effects of aaptamine on two cholinesterases and investigate the in vivo therapeutic effect on AD in a zebrafish model. MATERIALS AND METHODS: Aaptamine was isolated from the sponge Aaptos suberitoides Brondsted (Suberitidae). Enzyme inhibition, kinetic analysis, surface plasmon resonance (SPR) and molecular docking assays were used to determine its inhibitory effect on AChE and BuChE in vitro. Zebrafish were divided into six groups: control, model, 8 microM donepezil, 5 , 10 and 20 microM aaptamine. After three days of drug treatment, the behaviour assay was performed. RESULTS: The IC(50) values of aaptamine towards AChE and BuChE were 16.0 and 4.6 microM. And aaptamine directly inhibited the two cholinesterases in the mixed inhibition type, with K(i) values of 6.96 +/- 0.04 and 6.35 +/- 0.02 microM, with K(d) values of 87.6 and 10.7 microM. Besides, aaptamine interacts with the crucial anionic sites of AChE and BuChE. In vivo studies indicated that the dyskinesia recovery rates of 5 , 10 and 20 microM aaptamine group were 34.8, 58.8 and 60.0%, respectively, and that of donepezil was 63.7%. DISCUSSION AND CONCLUSIONS: Aaptamine showed great potential to exert its anti-AD effects by directly inhibiting the activities of AChE and BuChE. Therefore, this study identified a novel medicinal application of aaptamine and provided a new structural scaffold for the development of anti-AD drugs.
ESTHER : Miao_2022_Pharm.Biol_60_1502
PubMedSearch : Miao_2022_Pharm.Biol_60_1502
PubMedID: 35968601

Title : The Impact of Catalpol on Proliferation, Apoptosis, Migration, and Oxidative Stress of Lung Cancer Cells Based on Nrf2\/ARE Signaling - Wang_2022_Biomed.Res.Int_2022_5621341
Author(s) : Wang H , Wu J , Fan H , Ji Y , Han C , Li C , Jiang S
Ref : Biomed Res Int , 2022 :5621341 , 2022
Abstract : The effects of catalpol on lung cancer cell proliferation, apoptosis, migration, and oxidative stress via the Nrf2/ARE signaling pathway are investigated in this work. Catalpol-12 g/mL group, catalpol-24 g/mL group, catalpol-48 g/mL group, catalpol - 48 g/mL + vector group, catalpol - 48 g/mL + Nrf2 group, si-NC group, and si-Nrf2 group were used to split lung cancer cells A549 into control groups. Proliferation was detected using the CCK-8 assay; apoptosis was detected using flow cytometry; migration was detected using the transwell chamber; ROS was distinguished using the DCFHDA method; MDA, SOD, and GSH were detected using the microvolume method; and Cleaved Caspase-3, Cleaved Caspase-9, Nrf2, HO-1, MMP-9, and MMP-2 were detected using the Western blot method. Catalpol 12 g/mL and 24 g/mL-48 g/mL treatment decreased the proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells when compared to the control group. SOD and GSH levels of lung cancer cells were decreased, and MDA and ROS levels were increased. Cleaved caspase-3, cleaved caspase-9 protein expression levels, and apoptosis were boosted (P < 0.05). The proliferation activity, migration number, and protein levels of Nrf2, HO-1, MMP-9, and MMP-2 in the catalpol - 48 g/mL + Nrf2 group were raised compared to the catalpol - 48 g/mL + vector group, whereas there was an apparent drop in the Cleaved Caspase-3, Cleaved Caspase-9, and apoptosis rate. Similarly, SOD and GSH contents increased, whereas MDA and ROS decreased (P < 0.05). The proliferation activity, migration number, and Nrf2, HO-1, MMP-9, and MMP-2 protein levels of lung cancer cells in the si-Nrf2 group were all decreased when compared to the si-NC and control groups. Cleaved Caspase-3 and Cleaved Caspase-9 protein expression, on the other hand, increased as MDA and ROS levels were raised while SOD and GSH levels dropped (P < 0.05). It reveals that catalpol inhibits the Nrf2/ARE signaling pathway, which causes antiproliferation, migration, apoptosis, and oxidative stress in cancer cells of lungs. The rate of apoptosis was also lowered.
ESTHER : Wang_2022_Biomed.Res.Int_2022_5621341
PubMedSearch : Wang_2022_Biomed.Res.Int_2022_5621341
PubMedID: 35898682

Title : Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus - Gao_2022_Parasit.Vectors_15_353
Author(s) : Gao H , Gu Z , Xing D , Yang Q , Li J , Zhou X , Zhao T , Li C
Ref : Parasit Vectors , 15 :353 , 2022
Abstract : BACKGROUND: Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. METHODS: Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. RESULTS: Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. CONCLUSION: The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences.
ESTHER : Gao_2022_Parasit.Vectors_15_353
PubMedSearch : Gao_2022_Parasit.Vectors_15_353
PubMedID: 36182902

Title : Fluorescence-activated droplet sorting of PET degrading microorganisms - Qiao_2022_J.Hazard.Mater_424_127417
Author(s) : Qiao Y , Hu R , Chen D , Wang L , Wang Z , Yu H , Fu Y , Li C , Dong Z , Weng YX , Du W
Ref : J Hazard Mater , 424 :127417 , 2022
Abstract : Enzymes that can decompose synthetic plastics such as polyethylene terephthalate (PET) are urgently needed. Still, a bottleneck remains due to a lack of techniques for detecting and sorting environmental microorganisms with vast diversity and abundance. Here, we developed a fluorescence-activated droplet sorting (FADS) pipeline for high-throughput screening of PET-degrading microorganisms or enzymes (PETases). The pipeline comprises three steps: generation and incubation of droplets encapsulating single cells, picoinjection of fluorescein dibenzoate (FDBz) as the fluorogenic probe, and screening of droplets to obtain PET-degrading cells. We characterized critical factors associated with this method, including specificity and sensitivity for discriminating PETase from other enzymes. We then optimized its performance and compatibility with environmental samples. The system was used to screen a wastewater sample from a PET textile mill. We successfully obtained PET-degrading species from nine different genera. Moreover, two putative PETases from isolates Kineococcus endophyticus Un-5 and Staphylococcus epidermidis Un-C2-8 were genetically derived, heterologously expressed, and preliminarily validated for PET-degrading activities. We speculate that the FADS pipeline can be widely adopted to discover new plastic-degrading microorganisms and enzymes in various environments and may be utilized in the directed evolution of degrading enzymes using synthetic biology.
ESTHER : Qiao_2022_J.Hazard.Mater_424_127417
PubMedSearch : Qiao_2022_J.Hazard.Mater_424_127417
PubMedID: 34673397

Title : A Fast-Response AIE-Active Ratiometric Fluorescent Probe for the Detection of Carboxylesterase - Xia_2022_Biosensors.(Basel)_12_
Author(s) : Xia M , Li C , Liu L , He Y , Li Y , Jiang G , Wang J
Ref : Biosensors (Basel) , 12 : , 2022
Abstract : Hepatocellular carcinoma (HCC) is associated with a high mortality rate worldwide. The therapeutic outcomes can be significantly improved if diagnosis and treatment are initiated earlier in the disease process. Recently, the carboxylesterase (CaE) activity/level in human plasma was reported to be a novel serological biomarker candidate for HCC. In this article, we fabricated a new fluorescent probe with AIE characteristics for the rapid detection of CaE with a more reliable ratiometric response mode. The TCFISE probe showed high sensitivity (LOD: 93.0 microU/mL) and selectivity toward CaE. Furthermore, the good pH stability, superior resistance against photobleaching, and low cytotoxicity highlight the high potential of the TCFISE probe for application in the monitoring of CaE activity in complex biological samples and in live cells, tissues, and animals.
ESTHER : Xia_2022_Biosensors.(Basel)_12_
PubMedSearch : Xia_2022_Biosensors.(Basel)_12_
PubMedID: 35884287

Title : Maize domestication phenotypes reveal strigolactone networks coordinating grain size evolution with kernel-bearing cupule architecture - Guan_2022_Plant.Cell__
Author(s) : Guan JC , Li C , Flint-Garcia S , Suzuki M , Wu S , Saunders JW , Dong L , Bouwmeester HJ , McCarty DR , Koch KE
Ref : Plant Cell , : , 2022
Abstract : The maize (Zea mays) ear represents one of the most striking domestication phenotypes in any crop species, with the cob conferring an exceptional yield advantage over the ancestral form of teosinte. Remodeling of the grain-bearing surface required profound developmental changes. However, the underlying mechanisms remain unclear and can only be partly attributed to the known domestication gene Teosinte glume architecture 1 (Tga1). Here we show that a more complete conversion involves strigolactones (SLs), and that these are prominent players not only in the Tga1 phenotype, but also other domestication features of the ear and kernel. Genetic combinations of a teosinte tga1 allele with three SL-related mutants progressively enhanced ancestral morphologies. The SL mutants, in addition to modulating the tga1 phenotype, also reshaped kernel-bearing pedicels and cupules in a teosinte-like manner. Genetic and molecular evidence are consistent with SL regulation of TGA1, including direct interaction of TGA1 with components of the SL-signaling system shown here to mediate TGA1 availability by sequestration. Roles of the SL network extend to enhancing maize seed size and, importantly, coordinating increased kernel growth with remodeling of protective maternal tissues. Collectively, our data show that SLs have central roles in releasing kernels from restrictive maternal encasement and coordinating other factors that increase kernel size, physical support, and their exposure on the grain-bearing surface.
ESTHER : Guan_2022_Plant.Cell__
PubMedSearch : Guan_2022_Plant.Cell__
PubMedID: 36573016

Title : Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation - Li_2022_Environ.Sci.Technol__
Author(s) : Li X , Yao Y , Chen H , Zhang Q , Li C , Zhao L , Guo S , Cheng Z , Wang Y , Wang L , Sun H
Ref : Environ Sci Technol , : , 2022
Abstract : The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants.
ESTHER : Li_2022_Environ.Sci.Technol__
PubMedSearch : Li_2022_Environ.Sci.Technol__
PubMedID: 35849551

Title : Biodegradation Pathway and Detoxification of beta-cyfluthrin by the Bacterial Consortium and Its Bacterial Community Structure - Li_2022_J.Agric.Food.Chem_70_7626
Author(s) : Li H , Ma Y , Yao T , Ma L , Zhang J , Li C
Ref : Journal of Agricultural and Food Chemistry , 70 :7626 , 2022
Abstract : In the process of microbial degradation of pyrethroid pesticides, the synergistic effect of the microbial community is more conducive to the complete degradation of toxic compounds than a single strain. At present, the degradation pathway of pyrethroids in a single strain has been well revealed, but the synergistic metabolism at the community level has not been well explained. This study elucidated the bacterial community succession, metabolic pathway, and phytotoxicity assessment during beta-cyfluthrin biodegradation by a novel bacterial consortium enriched from contaminated soil. The results showed that the half-life of beta-cyfluthrin at different initial concentrations of 0.25, 0.5, 0.75, and 1.0 mg mL(-1) were 4.16, 7.34, 12.81, and 22.73 days, respectively. Enterobacter was involved in beta-cyfluthrin degradation metabolism in the initial stage, and other bacterial genera (Microbacterium, Ochrobactrum, Pseudomonas, Hyphomicrobiaceae, Achromobacter, etc.) significantly contribute to the degradation of intermediate metabolites in the later stages. Functional gene prediction and metabolite analysis showed that xenobiotic biodegradation and metabolism, especially benzoate degradation and metabolism by cytochrome P450 were the major means of beta-cyfluthrin degradation. Further, two degradation pathways of beta-cyfluthrin were proposed, which were mainly ester hydrolysis and oxidation to degrade beta-cyfluthrin through the production of carboxylesterase and oxidoreductase. In addition, the inoculated bacterial consortium could degrade beta-cyfluthrin residues in water and soil and reduce its phytotoxicity in Medicago sativa. Hence, this novel bacterial consortium has important application in the remediation environments polluted by beta-cyfluthrin.
ESTHER : Li_2022_J.Agric.Food.Chem_70_7626
PubMedSearch : Li_2022_J.Agric.Food.Chem_70_7626
PubMedID: 35698868

Title : A review of physiological resistance to insecticide stress in Nilaparvata lugens - Tang_2022_3.Biotech_12_84
Author(s) : Tang B , Xu K , Liu Y , Zhou Z , Karthi S , Yang H , Li C
Ref : 3 Biotech , 12 :84 , 2022
Abstract : Insecticides are widely used in agriculture as effective means to control pests. However, pests have not been completely mitigated with the increased use of insecticides. Instead, many side effects have arisen, especially the '3Rs' (resistance, resurgence, and residue). The brown planthopper, Nilaparvata lugens, is one of the most threatening rice pests. The main insecticides for controlling N. lugens belong to organochlorine, organophosphorus, carbamate, neonicotinoid and pyrethroid groups. However, metabolic enzymes, including cytochrome P450s, esterases, glutathione-S-transferases, and ATP-binding cassette transporters, effectively promote the detoxification of insecticides. Besides, mutations of neurological target sites, such as acetylcholinesterase, nicotinic acetylcholine, gamma-aminobutyric acid receptor, and ryanodine receptor, result in insensitivity to insecticides. Here, we review the physiological metabolic resistance in N. lugens under insecticide stress to provide a theoretical basis for identifying and developing more effective and harmless insecticides.
ESTHER : Tang_2022_3.Biotech_12_84
PubMedSearch : Tang_2022_3.Biotech_12_84
PubMedID: 35251886

Title : Phytochemical Properties and In Vitro Biological Activities of Phenolic Compounds from Flower of Clitoria ternatea L - Li_2022_Molecules_27_6336
Author(s) : Li C , Tang W , Chen S , He J , Li X , Zhu X , Li H , Peng Y
Ref : Molecules , 27 :6336 , 2022
Abstract : Phenolic compounds from the flower of Clitoria ternatea L. (PCFCTL) were extracted using a high-speed shearing extraction technique and purified by AB-8 macroporous resins, and the phytochemical composition of the purified phenolic compounds from the flower of Clitoria ternatea L. (PPCFCTL) was then analyzed. Subsequently, its bioactivities including antioxidant properties, enzyme inhibitory activities, and antiproliferative activities against several tumor cell lines were evaluated. Results indicated that the contents of total phenolics, flavonoids, flavonols, flavanols, and phenolic acids in PPCFCTL were increased by 3.29, 4.11, 2.74, 2.43, and 2.96-fold, respectively, compared with those before being purified by AB-8 macroporous resins. The results showed PPCFCTL have significant antioxidant ability (measured by reducing power, RP, and ferric reducing antioxidant power method, FRAP) and good DPPH, ABTS(+), and superoxide anion radical scavenging activities. They can also significantly inhibit lipase, alpha-amylase, and alpha-glucosidase. In addition, morphological changes of HeLa, HepG2, and NCI-H460 tumor cells demonstrated the superior antitumor performance of PPCFCTL. However, the acetylcholinesterase inhibitory activity was relatively weak. These findings suggest that PPCFCTL have important potential as natural antioxidant, antilipidemic, anti-glycemic and antineoplastic agents in health-promoting foods.
ESTHER : Li_2022_Molecules_27_6336
PubMedSearch : Li_2022_Molecules_27_6336
PubMedID: 36234873

Title : Highly Selective Detection of Paraoxon in Food Based on the Platform of Cu Nanocluster\/MnO(2) Nanosheets - Liu_2022_Nanomaterials.(Basel)_12_
Author(s) : Liu S , Zhang P , Miao Y , Li C , Shi YE , Liu J , Lv YK , Wang Z
Ref : Nanomaterials (Basel) , 12 : , 2022
Abstract : Selective and sensitive identification of paraoxon residue in agricultural products is greatly significant for food safety but remains a challenging task. Herein, a detection platform was developed by integrating Cu nanoclusters (Cu NCs) with MnO(2) nanosheets, where the fluorescence of Cu NCs was effectively quenched. Upon introducing butyrylcholinesterase and butyrylcholine into the system, their hydrolysate, thiocholine, leads to the decomposition of the platform through a reaction between the MnO(2) nanosheets and thiol groups on thiocholine. The electron-rich groups on thiocholine can further promote the fluorescence intensity of Cu NCs through host-guest interactions. Adding paraoxon results in the failure of fluorescence recovery and further promotion, which could be utilized for the quantitative detection of paraoxon, and a limit of detection as low as 0.22 ng/mL can be achieved. The detection platform shows strong tolerance to common interference species, which endows its applications for the detection of paraoxon in vegetables and fruit. These presented results not only open a new door for the functionalization of metal nanoclusters but also offer an inspiring strategy for analytic techniques in nanomedicine and environmental science.
ESTHER : Liu_2022_Nanomaterials.(Basel)_12_
PubMedSearch : Liu_2022_Nanomaterials.(Basel)_12_
PubMedID: 35564138

Title : Isorhapontigenin prevents beta-amyloid-associated cognitive impairments through activation of the PI3K\/AKT\/GSK-3beta pathway - Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
Author(s) : Ma Q , Li C , He Y , Liu P , Gong F , Zhang W
Ref : Acta Neurobiol Exp (Wars) , 82 :389 , 2022
Abstract : Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that is the most common cause of dementia in the elderly. Abeta1-42 is significantly associated with memory deficits and it can increase the level of acetylcholine, promote the activity of acetylcholinesterase (AChE), and cause cognitive dysfunction. Isorhapontigenin (ISO) is a stilbene derivative that has antioxidant, anti-tumor, and anti-inflammatory effects. However, it is still unclear whether ISO can affect beta-amyloid-associated cognitive impairments. In this study, we found that ISO improved cognitive dysfunction induced by Abeta1-42 in rats. It inhibited the Abeta-induced activation of M1 microglia and reduced the release of inflammatory cytokines. It alleviated amyloid beta-induced oxidative stress and led to an overall improvement in AD symptoms. Cellularly, we found that ISO alleviated Abeta-induced inflammation and oxidative stress by activating the PI3K/AKT/GSK-3beta pathway and ultimately improved cognitive dysfunction in AD rats.
ESTHER : Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
PubMedSearch : Ma_2022_Acta.Neurobiol.Exp.(Wars)_82_389
PubMedID: 36214721

Title : Strigolactone is involved in nitric oxide-enhanced the salt resistance in tomato seedlings - Liu_2022_J.Plant.Res__
Author(s) : Liu H , Li C , Yan M , Zhao Z , Huang P , Wei L , Wu X , Wang C , Liao W
Ref : J Plant Res , : , 2022
Abstract : Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during stress responses. At present, the interaction and mechanism of SLs and NO in tomato salt tolerance remain unclear. In the current study, tomato 'Micro-Tom' was used to study the roles and interactions of SLs and NO in salinity stress tolerance. The results show that 15 microM SLs synthetic analogs GR24 and 10 microM NO donor S-nitrosoglutathione (GSNO) promoted seedling growth under salt stress. TIS108 (an inhibitor of strigolactone synthesis) suppressed the positive roles of NO in tomato growth under salt stress, indicating that endogenous SLs might be involved in NO-induced salt response in tomato seedlings. Meanwhile, under salt stress, GSNO or GR24 treatment induced the increase of endogenous SLs content in tomato seedlings. Moreover, GR24 or GSNO treatment effectively increased the content of chlorophyll, carotenoids and ascorbic acid (ASA), and enhanced the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), glutathione reductase (GR) and cleavage dioxygenase (CCD) enzyme. Additionally, GSNO or GR24 treatment also up-regulated the expression of SLs synthesis genes (SlCCD7, SlCCD8, SlD27 and SlMAX1) and its signal transduction genes (SlD14 and SlMAX2) in tomato seedlings under salt stress. While, a strigolactone synthesis inhibitor TIS108 blocked the increase of endogenous SLs, chlorophyll, carotenoids and ASA content, and antioxidant enzyme, GR, CCD enzyme activity and SLs-related gene expression levels induced by GSNO. Thus, SLs may play an important role in NO-enhanced salinity tolerance in tomato seedlings by increasing photosynthetic pigment content, enhancing antioxidant capacity and improving endogenous SLs synthesis.
ESTHER : Liu_2022_J.Plant.Res__
PubMedSearch : Liu_2022_J.Plant.Res__
PubMedID: 35106650

Title : Dipeptidyl peptidase IV inhibition delays developmental programming of obesity and metabolic disease in male offspring of obese mothers - Montaniel_2022_J.Dev.Orig.Health.Dis__1
Author(s) : Montaniel KRC , Bucher M , Phillips EA , Li C , Sullivan EL , Kievit P , Rugonyi S , Nathanielsz PW , Maloyan A
Ref : J Dev Orig Health Dis , :1 , 2022
Abstract : Maternal obesity programs the offspring to metabolic diseases later in life; however, the mechanisms of programming are yet unclear, and no strategies exist for addressing its detrimental transgenerational effects. Obesity has been linked to dipeptidyl peptidase IV (DPPIV), an adipokine, and treatment of obese individuals with DPPIV inhibitors has been reported to prevent weight gain and improve metabolism. We hypothesized that DPPIV plays a role in maternal obesity-mediated programming. We measured plasma DPPIV activity in human maternal and cord blood samples from normal-weight and obese mothers at term. We found that maternal obesity increases maternal and cord blood plasma DPPIV activity but only in male offspring. Using two non-human primate models of maternal obesity, we confirmed the activation of DPPIV in the offspring of obese mothers. We then created a mouse model of maternal high-fat diet (HFD)-induced obesity, and found an early-life increase in plasma DPPIV activity in male offspring. Activation of DPPIV preceded the progression of obesity, glucose intolerance and insulin resistance in male offspring of HFD-fed mothers. We then administered sitagliptin, DPPIV inhibitor, to regular diet (RD)- and HFD-fed mothers, starting a week prior to breeding and continuing throughout pregnancy and lactation. We found that sitagliptin treatment of HFD-fed mothers delayed the progression of obesity and metabolic diseases in male offspring and had no effects on females. Our findings reveal that maternal obesity dysregulates plasma DPPIV activity in males and provide evidence that maternal inhibition of DPPIV has potential for addressing the transgenerational effects of maternal obesity.
ESTHER : Montaniel_2022_J.Dev.Orig.Health.Dis__1
PubMedSearch : Montaniel_2022_J.Dev.Orig.Health.Dis__1
PubMedID: 35068408

Title : Prolonged sevoflurane exposure causes abnormal synapse development and dysregulates beta-neurexin and neuroligins in the hippocampus in neonatal rats - Zhang_2022_J.Affect.Disord__
Author(s) : Zhang W , Chen Y , Qin J , Lu J , Fan Y , Shi Z , Song X , Li C , Zhao T
Ref : J Affect Disord , : , 2022
Abstract : BACKGROUND: The underlying molecular mechanisms of the excitatory/inhibitory (E/I) imbalance induced by sevoflurane exposure to neonates remain poorly understood. This study aimed to investigate the long-term effects of prolonged sevoflurane exposure to neonatal rats during the peak period of synaptogenesis on the changes of trans-synaptic neurexin-neuroligin interactions, synaptic ultrastructure in the hippocampus and cognition. METHODS: A total of 30 rat pups at postnatal day (P) 7 was randomly divided into two groups: the control group (exposed to 30 % oxygen balanced with nitrogen) and the sevoflurane group (exposed to 2.5 % sevoflurane plus 30 % oxygen balanced with nitrogen) for 6 h. Neurocognitive behaviors were assessed with the Open field test at P23-25 and the Morris water maze test at P26-30. The expression of beta-neurexin (beta-NRX), N-methyl-d-aspartate receptor 2 subunit (NR2A and NR2B), neuroligin-1 (NLG-1), neuroligin-2 (NLG-2), postsynaptic density protein-95 (PSD-95), alpha1-subunit of the gamma-aminobutyric acid A receptor (GABAAalpha1) and gephyrin in the hippocampus at P30 were measured by Western blot. The ultrastructure of synapses was examined under electron microscope. RESULTS: Prolonged sevoflurane exposure at P7 resulted in cognitive deficiency in adolescence, as well as the downregulation of beta-NRX, NR2A, NR2B, NLG-1, and PSD-95, and the upregulation of GABAAalpha1, NLG-2, and gephyrin in the hippocampal CA3 region. Sevoflurane anesthesia also increased the number of symmetric synapses in the hippocampus. CONCLUSIONS: Prolonged sevoflurane exposure during the brain development leads to cognitive deficiency and disproportion of excitatory/inhibitory synapses which may be caused by dysregulated expression of synaptic adhesion molecules of beta-NRX and neuroligins.
ESTHER : Zhang_2022_J.Affect.Disord__
PubMedSearch : Zhang_2022_J.Affect.Disord__
PubMedID: 35691415

Title : Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt\/beta-catenin Signaling Via p-GSK3beta - Yang_2022_Int.J.Biochem.Cell.Biol__106316
Author(s) : Yang P , Li C , Zhou Q , Zhang X , Kou Y , Feng Q , Wang H , Su R , Hasegawa T , Liu H , Li M
Ref : International Journal of Biochemistryistry & Cell Biology , :106316 , 2022
Abstract : Notum, which belongs to the alpha/beta hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/beta-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC.
ESTHER : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedSearch : Yang_2022_Int.J.Biochem.Cell.Biol__106316
PubMedID: 36280040

Title : Functional characterization of CYP6G4 from the house fly in propoxur metabolism and resistance - Zhu_2022_Pestic.Biochem.Physiol_187_105186
Author(s) : Zhu J , Feng J , Tian K , Li C , Li M , Qiu X
Ref : Pestic Biochem Physiol , 187 :105186 , 2022
Abstract : The house fly (Musca domestica L.) (Diptera: Muscidae) is a global vector that can transmit >250 human and animal diseases. The control of house flies has heavily relied on the application of various chemical insecticides. The carbamate insecticide propoxur has been widely used for the control of house flies, and resistance to propoxur has been documented in many house fly populations worldwide. Previous studies have identified several propoxur resistance-conferring mutations in the target protein acetylcholinesterase; however, the molecular basis for metabolic resistance to propoxur remains unknown. In this study, we investigated the involvement of CYP6G4, a cytochrome P450 overexpressed in many insecticide resistant populations of Musca domestica, in propoxur metabolism and resistance by using combined approaches of recombinant protein-based insecticide metabolism and the Drosophila GAL4/UAS transgenic system. The recombinant CYP6G4 and its redox partners (NADPH-dependent cytochrome P450 reductase and cytochrome b5) were functionally expressed in Escherichia coli. Metabolism experiments showed that CYP6G4 was able to transform propoxur with a turnover rate of around 0.79 min(-1). Six metabolites were putatively identified, suggesting that CYP6G4 could metabolize propoxur via hydroxylation, O-depropylation and N-demethylation. Moreover, bioassay results showed that ectopic overexpression of CYP6G4 in fruit flies significantly increased their tolerance to propoxur. Our in vivo and in vitro data convincingly demonstrate that CYP6G4 contributes to propoxur metabolism and resistance.
ESTHER : Zhu_2022_Pestic.Biochem.Physiol_187_105186
PubMedSearch : Zhu_2022_Pestic.Biochem.Physiol_187_105186
PubMedID: 36127048

Title : Comprehensive Enantioselectivity Evaluation of Insecticidal Activity and Mammalian Toxicity of Fenobucarb - He_2022_J.Agric.Food.Chem__
Author(s) : He Z , Li C , Xia W , Wang Z , Li R , Zhang Y , Wang M
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : To comprehensively evaluate the efficiency and risk of the chiral pesticide fenobucarb, the bioactivity, toxicity, and environmental behavior of fenobucarb (FNC) enantiomers were investigated. The results showed that R-FNC possesses 1.8-2.7 times more bioactivity than S-FNC but 1.3-3.0 times lower toxicity than S-FNC against four nontarget organisms: Chlorella pyrenoidosa, HepG2, and Danio rerio and its embryos. The corresponding enzyme inhibitory activity showed consistent results; the acetylcholinesterase inhibitory activity of target organisms was ordered as R-FNC > rac-FNC > S-FNC, while the reduction in catalase activity after exposure to R-FNC was 2.5 times that after exposure to S-FNC in zebrafish. The enantioselective bioactivity mechanism of FNC enantiomers was further explored in silico. No significant enantioselective degradation was found in soils or rat liver microsomes. In sum, R-FNC possesses higher insecticidal activity and lower toxicity. The development of R-FNC as a commercial agrochemical is beneficial for reducing pesticide inputs.
ESTHER : He_2022_J.Agric.Food.Chem__
PubMedSearch : He_2022_J.Agric.Food.Chem__
PubMedID: 35451821

Title : Structure-guided preparation of functional oil rich in 1,3-diacylglycerols and linoleic acid from Camellia oil by combi-lipase - Huang_2022_J.Sci.Food.Agric__
Author(s) : Huang C , Lin Z , Zhang Y , Liu Z , Tang X , Li C , Lin L , Huang W , Ye Y
Ref : J Sci Food Agric , : , 2022
Abstract : BACKGROUND: The diacylglycerols (DAG) enriched oil has been attracting attention on nutritional benefits and biological functions, but its various free fatty acids (FFA) composition and unclear relationship between substrate and yield make it difficult to be identified and qualified to produce. In this research, the linoleic acid-enriched diacylglycerols (LA-DAG) was synthesized and enriched from Camellia oil by the esterification process using the combi-lipase Lipozyme TL IM/RM IM systems. RESULTS: The relationship between the FFA compositions and the DAG species productivity was revealed. Results showed that heterogeneous FFA with a major constituent (more than 50%) exhibited higher DAG productivity and inhibited TAG productivity than homogeneous constituents. The joint characterization by HPLC-ELSD, GC-MS and UPLC-HESI-MS/MS identified that DAG components contained dilinoleic acid acyl glyceride, linoleyl-oleyl glyceride, and dioleic acid acyl glyceride in esterification products. Under the optimum conditions, 60.4% 1,3-DAG and 61.3% LA-DAG in the crude product at 1 h reaction were obtained, and further purified to 81.7% LA-DAG and 94.7% DAG by the silica column chromatography. CONCLUSION: This research provides a guideline for identification of DAG species, and a structure-guided preparing method of the DAG enriched oils by the cost-effective combi-lipase. This article is protected by copyright. All rights reserved.
ESTHER : Huang_2022_J.Sci.Food.Agric__
PubMedSearch : Huang_2022_J.Sci.Food.Agric__
PubMedID: 35810339

Title : Ratiometric imaging of butyrylcholinesterase activity in mice with nonalcoholic fatty liver using an AIE-based fluorescent probe - Xiang_2022_J.Mater.Chem.B__
Author(s) : Xiang C , Xiang J , Yang X , Li C , Zhou L , Jiang D , Peng Y , Xu Z , Deng G , Zhu B , Zhang P , Cai L , Gong P
Ref : J Mater Chem B , : , 2022
Abstract : Butyrylcholinesterase (BChE) is an essential human biomarker which is related to liver and neurodegenerative diseases. It is of great significance to develop a fluorescent probe that can image BChE in vitro and in vivo. Unfortunately, most fluorescent probes that are based on a single change in fluorescence intensity are susceptible to environmental interference. Therefore, we reported an easily available ratiometric fluorescent probe, TB-BChE, with aggregation-induced emission (AIE) characteristics for ratiometric imaging of BChE. TB-BChE demonstrated excellent sensitivity (LOD = 39.24 ng mL(-1)) and specificity for BChE. Moreover, we have successfully studied the ratiometric imaging of TB-BChE to BChE in a nonalcoholic fatty liver disease model. These results indicated that TB-BChE is expected to become a powerful analysis tool for butyrylcholinesterase research in basic medicine and clinical applications.
ESTHER : Xiang_2022_J.Mater.Chem.B__
PubMedSearch : Xiang_2022_J.Mater.Chem.B__
PubMedID: 35583194

Title : Claulansine F-Donepezil Hybrids as Anti-Alzheimer's Disease Agents with Cholinergic, Free-Radical Scavenging, and Neuroprotective Activities - Zang_2021_Molecules_26_
Author(s) : Zang Y , Liu K , Wang W , Li C , Ma J , Yang J , Chen X , Wang X , Zhang D
Ref : Molecules , 26 : , 2021
Abstract : The multifactorial nature of Alzheimer's disease (AD) calls for the development of multitarget agents addressing key pathogenic processes. A total of 26 Claulansine F-donepezil hybrids were designed and synthesized as multitarget drugs. Among these compounds, six compounds exhibited excellent acetylcholinesterase (AChE) inhibitory activity (half maximal inhibitory concentration (IC(50)) 1.63-4.62 microM). Moreover, (E)-3-(8-(tert-Butyl)-3,3-dimethyl-3,11-dihydropyrano[3,2-a]carbazol-5-yl)-N-((1-(2-chlorobenzyl)piperidin-4-yl)methyl)acrylamide (6bd) exhibited better neuroprotective effects against OGD/R (oxygen-glucose deprivation/reoxygenation) than lead compound Claulansine F. Furthermore, 6bd could cross the blood-brain barrier in vitro. More importantly, compared to edaravone, 6bd had stronger free-radical scavenging activity. Molecular docking studies revealed that 6bd could interact with the catalytic active site of AChE. All of these outstanding in vitro results indicate 6bd as a leading structure worthy of further investigation.
ESTHER : Zang_2021_Molecules_26_
PubMedSearch : Zang_2021_Molecules_26_
PubMedID: 33671020

Title : Acupuncture therapy for Alzheimer's disease: The effectiveness and potential mechanisms - Yin_2021_Anat.Rec.(Hoboken)__
Author(s) : Yin W , Lv G , Li C , Sun J
Ref : Anatomical Record (Hoboken) , : , 2021
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that accounts for approximately 70% of dementia. Following the global escalation of the aging process, the morbidity of AD is increasing rapidly. The current treatment for AD is mainly limited to medications, such as acetylcholinesterase inhibitors. However, the efficacy of acetylcholinesterase inhibitors in improving memory and cognitive functions is not satisfactory. It is a challenge to find an effective alternative therapy for ameliorating AD symptoms. As an important therapeutic technique in traditional Chinese medicine, acupuncture has been proved effective in treating many neurologic diseases including AD. The efficacy of acupuncture is also acknowledged by the National Institutes of Health of the United States. Here, we summarized the effectiveness of acupuncture for treating AD. Especially, the role of acupuncture at certain acupuncture points in modulating the brain function through meridians activity based on Chinese meridian theory is discussed. How acupuncture at a certain acupoint can improve AD symptoms is also described. Furthermore, the possible molecular mechanisms of acupuncture for AD are reviewed, and the role of acupuncture in modulating signaling molecules in neural protection and homeostasis is highlighted. This study may help to understand the theoretical basis and potential molecular mechanisms of acupuncture therapy for AD.
ESTHER : Yin_2021_Anat.Rec.(Hoboken)__
PubMedSearch : Yin_2021_Anat.Rec.(Hoboken)__
PubMedID: 34623030

Title : Adaptation of the parasitic plant lifecycle: germination is controlled by essential host signaling molecules - Bouwmeester_2021_Plant.Physiol_185_1292
Author(s) : Bouwmeester H , Li C , Thiombiano B , Rahimi M , Dong L
Ref : Plant Physiol , 185 :1292 , 2021
Abstract : Parasitic plants are plants that connect with a haustorium to the vasculature of another, host, plant from which they absorb water, assimilates, and nutrients. Because of this parasitic lifestyle, parasitic plants need to coordinate their lifecycle with that of their host. Parasitic plants have evolved a number of host detection/host response mechanisms of which the germination in response to chemical host signals in one of the major families of parasitic plants, the Orobanchaceae, is a striking example. In this update review, we discuss these germination stimulants. We review the different compound classes that function as germination stimulants, how they are produced, and in which host plants. We discuss why they are reliable signals, how parasitic plants have evolved mechanisms that detect and respond to them, and whether they play a role in host specificity. The advances in the knowledge underlying this signaling relationship between host and parasitic plant have greatly improved our understanding of the evolution of plant parasitism and are facilitating the development of more effective control measures in cases where these parasitic plants have developed into weeds.
ESTHER : Bouwmeester_2021_Plant.Physiol_185_1292
PubMedSearch : Bouwmeester_2021_Plant.Physiol_185_1292
PubMedID: 33793901

Title : Enteral Nutrition Combined with Improved-Sijunzi Decoction Shows Positive Effect in Precachexia Cancer Patients: A Retrospective Analysis - Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
Author(s) : Li Y , Chen Y , Zeng Y , Dong J , Li C , Jia Y , Zhao Y , Wang K
Ref : Evid Based Complement Alternat Med , 2021 :7357521 , 2021
Abstract : BACKGROUND: Cancer has been considered as the leading cause of death in the world. In patients with cancer, up to 80% display a cachectic period after diagnosis. Cachexia is known to have a negative impact on function, treatment tolerance, higher rates of hospitalizations, and mortality. Anorexia is often used as a warning sign of precachexia. Long-term anorexia may lead to malnutrition and, then, accelerate the occurrence of cachexia. A safe and effective treatment, which can both improve appetite and assist nutritional support for precachexia cancer patients shows its particular important role. METHODS: A retrospective analysis comparing the different therapeutic effects on precachexia cancer patients with anorexia-malnutrition. We recorded 46 patients with the improved-Sijunzi decoction combined with enteral nutrition emulsion (ISJZ group) and 35 patients with single enteral nutrition emulsion (SEN group). The different therapeutic effects of the two groups were observed by recording indicators before and 2 weeks after treatment, including patient-generated subjective global assessment score, quality of life score, Karnofsky performance status scale, Eastern cooperative oncology group scale standard and traditional Chinese medicine syndrome, daily total dietary intake, red blood cells, hemoglobin, prealbumin, albumin, total protein cholinesterase, C-reactive protein, leukocytes, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea nitrogen, and creatinine. RESULTS: ISJZ group exhibited prominent improvement of traditional Chinese medicine syndrome (TCMS), nutritional condition, and quality of life compared with the SEN group (QOL: p=0.0001, PG-SGA: p=0.019, dietary intake: p=0.0001, TCMS: p=0.0001). The levels of HGB (p=0.006), PAlb (p=0.001), Alb (p=0.0001), TP (p=0.008), and ChE (p=0.0001) in the ISJZ group were higher than the SEN group after treatment. Moreover, the ratios of CRP/ALB (p=0.028) and CRP/PALB (p=0.005) in the two groups have obvious differences; they were lower for the ISJZ group than the SEN group. CONCLUSIONS: Enteral nutrition combined with ISJZ decoction is an effective treatment in precachexia cancer patients for the prevention of cachexia. This treatment therapy can alleviate the inflammatory response, improve malnutrition state, and promote the performance status. Tianjin Medical University Cancer Institute and Hospital approved this study (Trial No. 1913).
ESTHER : Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
PubMedSearch : Li_2021_Evid.Based.Complement.Alternat.Med_2021_7357521
PubMedID: 34603476

Title : Computational redesign of a PETase for plastic biodegradation under ambient condition by the GRAPE strategy - Cui_2021_ACS.Catal_11_1340
Author(s) : Cui Y , Chen Y , Liu X , Dong S , Tian Y , Qiao Y , Mitra R , Han J , Li C , Han X
Ref : ACS Catal , 11 :1340 , 2021
Abstract : Nature has provided a fantastic array of enzymes that are responsible for essential biochemical functions but not usually suitable for technological applications. Not content with the natural repertoire, protein engineering holds promise to extend the applications of improved enzymes with tailored properties. However, engineering of robust proteins remains a difficult task since the positive mutation library may not cooperate to reach the target function in most cases owing to the ubiquity of epistatic effects. The main demand lies in identifying an efficient path of accumulated mutations. Herein, we devised a computational strategy (greedy accumulated strategy for protein engineering, GRAPE) to improve the robustness of a PETase from Ideonella sakaiensis. A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the redesign of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 C and a strikingly enhanced degradation toward semicrystalline poly(ethylene terephthalate) (PET) films (30%) at mild temperatures (over 300-fold). Complete biodegradation of 2 g/L microplastics to water-soluble products under mild conditions is also achieved, opening up opportunities to steer the biological degradation of uncollectable PET waste and further conversion of the resulting monomers to high-value molecules. The crystal structure revealed the individual mutation match with the design model. Concurrently, synergistic effects are captured, while epistatic interactions are alleviated during the accumulation process. We anticipate that our design strategy will provide a broadly applicable strategy for global optimization of enzyme performance.
ESTHER : Cui_2021_ACS.Catal_11_1340
PubMedSearch : Cui_2021_ACS.Catal_11_1340
Gene_locus related to this paper: idesa-peth

Title : Acetylcholinesterase target sites for developing environmentally friendly insecticides against Tetranychus urticae (Acari: Tetranychidae) - Li_2021_Exp.Appl.Acarol__
Author(s) : Li C , Cao Y , Yang J , Li M , Li B , Bu C
Ref : Exp Appl Acarol , : , 2021
Abstract : The non-target toxicity and resistance problems of acetylcholinesterase (AChE) insecticides, such as organophosphates and carbamates, are of growing concern. To explore the potential targets for achieving inhibitor selectivity, the AChE structures at or near the catalytic pocket of Tetranychus urticae (TuAChE), honey bees, and humans were compared. The entrances to the AChE catalytic pocket differ significantly because of their different peripheral sites. The role of these potential mite-specific sites in AChE function was further elucidated by site-directed mutagenesis of these sites and then examining the catalytic activities of TuAChE mutants. The spider mite E(316), H(369), and V(105) active sites are important for AChE function. By further analyzing their physostigmine inhibitory properties and the detailed interaction between physostigmine and TuAChE, the peripheral site H(369) locating near the gorge entrance, and S(154) at the oxyanion hole, affects substrate and inhibitor trafficking. The discovery of conserved mite-specific residues in Tetranychus will enable the development of safer, effective pesticides that target residues present only in mite AChEs, potentially offering effective control against this important agricultural pest.
ESTHER : Li_2021_Exp.Appl.Acarol__
PubMedSearch : Li_2021_Exp.Appl.Acarol__
PubMedID: 33914192

Title : Catalytic Descriptors to Investigate Catalytic Power in the Reaction of Haloalkane Dehalogenase Enzyme with 1,2-Dichloroethane - Xin_2021_Int.J.Mol.Sci_22_
Author(s) : Xin X , Li C , Gao D , Wang D
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Enzymes play a fundamental role in many biological processes. We present a theoretical approach to investigate the catalytic power of the haloalkane dehalogenase reaction with 1,2-dichloroethane. By removing the three main active-site residues one by one from haloalkane dehalogenase, we found two reactive descriptors: one descriptor is the distance difference between the breaking bond and the forming bond, and the other is the charge difference between the transition state and the reactant complex. Both descriptors scale linearly with the reactive barriers, with the three-residue case having the smallest barrier and the zero-residue case having the largest. The results demonstrate that, as the number of residues increases, the catalytic power increases. The predicted free energy barriers using the two descriptors of this reaction in water are 23.1 and 24.2 kcal/mol, both larger than the ones with any residues, indicating that the water solvent hinders the reactivity. Both predicted barrier heights agree well with the calculated one at 25.2 kcal/mol using a quantum mechanics and molecular dynamics approach, and also agree well with the experimental result at 26.0 kcal/mol. This study shows that reactive descriptors can also be used to describe and predict the catalytic performance for enzyme catalysis.
ESTHER : Xin_2021_Int.J.Mol.Sci_22_
PubMedSearch : Xin_2021_Int.J.Mol.Sci_22_
PubMedID: 34072602

Title : Prednisolone induces osteocytes apoptosis by promoting Notum expression and inhibiting PI3K\/AKT\/GSK3beta\/beta-catenin pathway - Li_2021_J.Mol.Histol__
Author(s) : Li C , Yang P , Liu B , Bu J , Liu H , Guo J , Hasegawa T , Si H , Li M
Ref : J Mol Histol , : , 2021
Abstract : The apoptosis of mature osteocytes is the main factor causing damage to the microstructure of cortical bone in glucocorticoid-induced osteoporosis (GIOP). Our previous research found damaged areas and empty osteocytes lacunae in the tibial cortical bone of GIOP mice. However, the specific mechanism has not been clarified. Recently, a study showed that the quality of the cortical bone significantly increased by knocking out Notum, a gene encoding alpha/beta hydrolase. However, it is not clear whether Notum affects cortical bone remodeling by participating in glucocorticoids (GCs)-induced apoptosis of osteocytes. The present study aimed to explore the correlation between Notum, osteocytes apoptosis, and cortical bone quality in GIOP. Prednisolone acetate was intragastrically administered to mice for two weeks. Histochemical staining was applied to evaluate changes in GIOP and Notum expression. Osteocytes were stimulated with prednisolone, and cell viability was assessed via CCK8. Hoechst 33342/PI staining, flow cytometry, RT-PCR, and western blot were used to detect osteocytes apoptosis, siRNA transfection efficiency, and expressions of pathway related factors. The results showed that the number of empty osteocytes lacunae increased in GIOP mice. TUNEL-stained apoptotic osteocytes and Notum immuno-positive osteocytes were also observed. Furthermore, prednisolone was found to promote Notum expression and osteocytes apoptosis in vitro. Knocking down Notum via siRNA partially restored osteocytes apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK3beta)/beta-catenin pathway. These findings showed GCs-induced osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3beta/beta-catenin pathway. Thus, Notum might be a potential therapeutic target for the treatment of GIOP.
ESTHER : Li_2021_J.Mol.Histol__
PubMedSearch : Li_2021_J.Mol.Histol__
PubMedID: 34297260

Title : Effect of cross-linked enzyme aggregate strategy on characterization of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 - Zhu_2021_Appl.Microbiol.Biotechnol__
Author(s) : Zhu R , Li C , Chen C , Xing S , Cai Y , Zeng X , He L
Ref : Applied Microbiology & Biotechnology , : , 2021
Abstract : The sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1) has important potential applications. The cross-linked enzyme aggregate (CLEA) of purified EXANL1 (CLEA-EXANL1) achieved optimum activity recovery (148.5 +/- 0.9%), immobilization yield (100 +/- 0%), and recovered activity (99.7 +/- 0.6%) with 80% tert-butanol as the precipitant, glutaraldehyde (GA) concentration of 30 mM, GA treatment time of 1.5 h, and centrifugal speed of 6000xg. The effect of CLEA strategy on the characterization of EXANL1 was evaluated in this work. CLEA-EXANL1 exhibited a broader optimum pH range (4-6) compared with free EXANL1 (6.5). CLEA-EXANL1 presented optimum activity at 40 degreesC, which was 5 degreesC higher than that of free EXANL1. CLEA strategy decreased the maximum reaction rate and increased the Michaelis-Menten constant of EXANL1 when olive oil emulsion was used as a substrate. Moreover, after 30 days, free EXANL1 lost more than 80.0% of its activity, whereas CLEA-EXANL1 retained more than 90.0% of its activity. CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. Fourier transform infrared spectroscopy results showed that the CLEA technique increased the contents of beta-sheets and beta-turns in EXANL1 and reduced those of alpha-helixes and irregular crimps. CLEA strategy caused no change in the sn-1,3 selectivity of EXANL1. Therefore, EXANL1 in the form of CLEA is a valuable catalyst in the synthesis of 1,3-diacylglycerol. KEY POINTS: Cross-linked enzyme aggregate (CLEA) strategy broadened the optimum pH range of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1). CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. CLEA strategy caused no change in the positional selectivity of EXANL1.
ESTHER : Zhu_2021_Appl.Microbiol.Biotechnol__
PubMedSearch : Zhu_2021_Appl.Microbiol.Biotechnol__
PubMedID: 33559718

Title : Synergistic enhancement of the emergency treatment effect of organophosphate poisoning by a supramolecular strategy - Chen_2021_Chem.Sci_12_5202
Author(s) : Chen J , Zhang Y , Chai Y , Meng Z , Chen L , Quan D , Wang Y , Meng Q , Li C
Ref : Chem Sci , 12 :5202 , 2021
Abstract : Poisoning by organophosphorus agents (OPs) is a serious public health issue across the world. These compounds irreversibly inhibit acetylcholinesterase (AChE), resulting in the accumulation of acetylcholine (ACh) and overstimulation of ACh receptors. A supramolecular detoxification system (SDS) has been designed with a view to deliver pyridine-2-aldoxime methochloride (PAM) with a synergistic inhibition effect on the ACh-induced hyperstimulation through host-guest encapsulation. NMR and fluorescence titration served to confirm the complexation between carboxylatopillar[6]arene (CP6A) and PAM as well as ACh with robust affinities. Patch-clamp studies proved that CP6A could exert an inhibition effect on the ACh-induced hyperstimulation of ACh receptors. Support for the feasibility of this strategy came from fluorescence imaging results. In vivo studies revealed that complexation by CP6A serves to increase the AChE reactivation efficiency of PAM. The formation of the PAM/CP6A complex contributed to enhance in a statistically significant way the ability of PAM not only to relieve symptoms of seizures but also to improve the survival ratio in paraoxon-poisoned model rats. These favorable findings are attributed to synergistic effects that PAM reactivates AChE to hydrolyze ACh and excess ACh is encapsulated in the cavity of CP6A to relieve cholinergic crisis symptoms.
ESTHER : Chen_2021_Chem.Sci_12_5202
PubMedSearch : Chen_2021_Chem.Sci_12_5202
PubMedID: 34163757

Title : Extraction and purification of total flavonoids from Eupatorium lindleyanum DC. and evaluation of their antioxidant and enzyme inhibitory activities - Li_2021_Food.Sci.Nutr_9_2349
Author(s) : Li C , Chen S , Sha J , Cui J , He J , Fu J , Shen Y
Ref : Food Sci Nutr , 9 :2349 , 2021
Abstract : The health benefits and promising medical treatment potential of total flavonoids from Eupatorium lindleyanum DC. (TFELDC) have been recognized. The process parameters of extracting total flavonoids from Eupatorium lindleyanum DC. by ultrasonic-microwave synergistic extraction (UMSE) were optimized, and they were purified by AB-8 macroporous resin in the current study. In addition, the antioxidant and enzyme inhibitory activities of the purified TFELDC (PTFELDC) were evaluated. The results showed that the optimal parameters of UMSE were as follows: ethanol volume fraction 71.5%, L/S ratio 12.2 ml/g, microwave power 318 W, and extraction time 143 s. After TFELDC were purified by AB-8 macroporous resin, the total flavonoid contents of PTFELDC increased from 208.18 +/- 1.60 to 511.19 +/- 3.21 mg RE/g FDS. Compared with TFELDC, the content of total flavonoids in PTFELDC was increased by 2.46 times. The antioxidant activities of PTFELDC were assessed using DPPH radical, superoxide anion radical, reducing power, and ferric reducing antioxidant power assays, and the IC(50) values were found to be 37.13, 19.62, 81.22, and 24.72 microg/ml, respectively. The enzyme inhibitory activities of PTFELDC were measured using lipase, alpha-amylase, alpha-glucosidase, and acetylcholinesterase assays with the IC(50) values 1.38, 2.08, 1.63, and 0.58 mg/ml, respectively. By comparing with their positive controls, it was found that PTFELDC had good antioxidant activities, and lipase, alpha-amylase, and alpha-glucosidase inhibitory activities, However, the acetylcholinesterase inhibitory activity was relatively weaker. These results suggested that PTFELDC have a promising potential as natural antioxidant, antilipidemic, and hypoglycemic drugs used in functional foods or pharmaceuticals.
ESTHER : Li_2021_Food.Sci.Nutr_9_2349
PubMedSearch : Li_2021_Food.Sci.Nutr_9_2349
PubMedID: 34026054

Title : Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects - Issotina_2021_J.Hypertens__
Author(s) : Issotina Zibrila A , Wang Z , Ali MA , Osei JA , Sun Y , Zafar S , Liu K , Li C , Kang Y , Liu J
Ref : J Hypertens , : , 2021
Abstract : OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management.
ESTHER : Issotina_2021_J.Hypertens__
PubMedSearch : Issotina_2021_J.Hypertens__
PubMedID: 34232157

Title : Protection studies of an excretory-secretory protein HcABHD against Haemonchus contortus infection - Lu_2021_Vet.Res_52_3
Author(s) : Lu M , Tian X , Zhang Y , Wang W , Tian AL , Aimulajiang K , Liu L , Li C , Yan R , Xu L , Song X , Li X
Ref : Vet Res , 52 :3 , 2021
Abstract : Unlike the successful immunization of native H. contortus antigens that contributed to the realization of the first commercial vaccine Barbervax, not many studies revealed the encouraging protective efficacies of recombinant H. contortus antigens in laboratory trials or under field conditions. In our preliminary study, H. contortus alpha/beta-hydrolase domain protein (HcABHD) was demonstrated to be an immunomodulatory excretory-secretory (ES) protein that interacts with goat T cells. We herein evaluated the protective capacities of two HcABHD preparations, recombinant HcABHD (rHcABHD) antigen and anti-rHcABHD IgG, against H. contortus challenge via active and passive immunization trials, respectively. Parasitological parameter, antibody responses, hematological pathology and cytokine profiling in unchallenged and challenged goats were monitored and determined throughout both trials. Subcutaneous administration of rHcABHD with Freund adjuvants elicited protective immune responses in challenged goats, diminishing cumulative fecal egg counts (FEC) and total worm burden by 54.0% and 74.2%, respectively, whereas passive immunization with anti-rHcABHD IgG conferred substantial protection to challenged goats by generating a 51.5% reduction of cumulative FEC and a 73.8% reduction of total worm burden. Additionally, comparable changes of mucosal IgA levels, circulating IgG levels, hemoglobin levels, and serum interleukin (IL)-4 and IL-17A levels were observed in rHcABHD protein/anti-rHcABHD IgG immunized goats in both trials. Taken together, the recombinant version of HcABHD might have further application under field conditions in protecting goats against H. contortus infection, and the integrated immunological pipeline of ES antigen identification, screening and characterization may provide new clues for further development of recombinant subunit vaccines to control H. contortus.
ESTHER : Lu_2021_Vet.Res_52_3
PubMedSearch : Lu_2021_Vet.Res_52_3
PubMedID: 33407892
Gene_locus related to this paper: haeco-CDJ88804

Title : Gene Expression, Biochemical Characterization of a sn-1, 3 Extracellular Lipase From Aspergillus niger GZUF36 and Its Model-Structure Analysis - Xing_2021_Front.Microbiol_12_633489
Author(s) : Xing S , Zhu R , Cheng K , Cai Y , Hu Y , Li C , Zeng X , Zhu Q , He L
Ref : Front Microbiol , 12 :633489 , 2021
Abstract : In this study, a sn-1, 3 extracellular lipases from Aspergillus niger GZUF36 (PEXANL1) was expressed in Pichia pastoris, characterized, and the predicted structural model was analyzed. The optimized culture conditions of P. pastoris showed that the highest lipase activity of 66.5 +/- 1.4 U/mL (P < 0.05) could be attained with 1% methanol and 96 h induction time. The purified PEXANL1 exhibited the highest activity at pH 4.0 and 40 degreesC temperature, and its original activity remained unaltered in the majority of the organic solvents (20% v/v concentration). Triton X-100, Tween 20, Tween 80, and SDS at a concentration of 0.01% (w/v) enhanced, and all the metal ions tested inhibited activity of purified PEXANL. The results of ultrasound-assisted PEXANL1 catalyzed synthesis of 1,3-diaglycerides showed that the content of 1,3-diglycerides was rapidly increased to 36.90% with 25 min of ultrasound duration (P < 0.05) and later decreased to 19.93% with 35 min of ultrasound duration. The modeled structure of PEXANL1 by comparative modeling showed alpha/beta hydrolase fold. Structural superposition and molecular docking results validated that Ser162, His274, and Asp217 residues of PEXANL1 were involved in the catalysis. Small-angle X-ray scattering analysis indicated the monomer properties of PEXANL1 in solution. The ab initio model of PEXANL1 overlapped with its modeling structure. This work presents a reliable structural model of A. niger lipase based on homology modeling and small-angle X-ray scattering. Besides, the data from this study will benefit the rational design of suitable crystalline lipase variants in the future.
ESTHER : Xing_2021_Front.Microbiol_12_633489
PubMedSearch : Xing_2021_Front.Microbiol_12_633489
PubMedID: 33776965
Gene_locus related to this paper: aspng-EXANL1

Title : An ultrahigh-throughput screening platform based on flow cytometric droplet sorting for mining novel enzymes from metagenomic libraries - Ma_2021_Environ.Microbiol_23_996
Author(s) : Ma F , Guo T , Zhang Y , Bai X , Li C , Lu Z , Deng X , Li D , Kurabayashi K , Yang GY
Ref : Environ Microbiol , 23 :996 , 2021
Abstract : Uncultivable microbial communities provide enormous reservoirs of enzymes, but their experimental identification by functional metagenomics is challenging, mainly due to the difficulty of screening enormous metagenomic libraries. Here, we propose a reliable and convenient ultrahigh-throughput screening platform based on flow cytometric droplet sorting (FCDS). The FCDS platform employs water-in-oil-in-water double emulsion droplets serving as single-cell enzymatic micro-reactors and a commercially available flow cytometer, and it can efficiently isolate novel biocatalysts from metagenomic libraries by processing single cells as many as 10(8) per day. We demonstrated the power of this platform by screening a metagenomic library constructed from domestic running water samples. The FCDS assay screened 30 million micro-reactors in only 1h, yielding a collection of esterase genes. Among these positive hits, Est WY was identified as a novel esterase with high catalytic efficiency and distinct evolutionary origin from other lipolytic enzymes. Our study manifests that the FCDS platform is a robust tool for functional metagenomics, with the potential to significantly improve the efficiency of exploring novel enzymes from nature.
ESTHER : Ma_2021_Environ.Microbiol_23_996
PubMedSearch : Ma_2021_Environ.Microbiol_23_996
PubMedID: 32985743

Title : Safety and pharmacokinetic interaction between fotagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin in healthy subjects - Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
Author(s) : Ding Y , Zhang H , Li C , Zheng W , Wang M , Li Y , Sun H , Wu M
Ref : Expert Opin Drug Metab Toxicol , 17 :725 , 2021
Abstract : BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have significant clinical efficacy for type 2 diabetes mellitus (T2DM). The combination of fotagliptin (FOT) with metformin (MET) is a promising therapeutic approach in MET-resistant patients. The aim of the present study was to evaluate the pharmacokinetic (PK) interaction between FOT and MET in healthy subjects after multiple-dose administration. METHODS: Eighteen participants received a randomized open-label, three period treatment that included MET 1000 mg alone, co-administration of FOT 24 mg and MET, followed by FOT 24 mg alone. Serial blood samples were collected for PK analysis, which included geometric mean ratios (GMRs) with 90% confidence intervals (CIs), area under the concentration-time curve (AUC), and maximum plasma concentration (C(max)). RESULTS: Analysis results showed that for FOT alone or combination therapy, the 90% CIs of the GMR for AUC(0-24,ss) and C(max,ss) were 102.08% (98.9%, 105.36%) and 110.65% (102.19%, 119.82%), respectively. For MET, they were 113.41% (100.32%, 128.22%) and 97.11% (83.80%, 112.55%) for AUC(0-12,ss) and C(max,ss), respectively. FOT or MET monotherapy and the combination therapy with both drugs were well tolerated. CONCLUSIONS: No PK drug-drug interactions were found in the combination therapy with FOT and MET. Therefore, FOT can be co-administered with MET without dose adjustment. TRIAL REGISTRATION: The trial is registered at No. CTR20190221).
ESTHER : Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
PubMedSearch : Ding_2021_Expert.Opin.Drug.Metab.Toxicol_17_725
PubMedID: 33899649

Title : Binding Mechanism between Acetylcholinesterase and Drugs Pazopanib and Lapatinib: Biochemical and Biophysical Studies - Meira_2021_ACS.Chem.Neurosci__
Author(s) : Meira Menezes T , Assis C , Lacerda Cintra AJ , Silva Dos Santos RC , Martins do Vale WK , Max Gomes Martins R , de Souza Bezerra R , Seabra GM , Li C , Neves JL
Ref : ACS Chem Neurosci , : , 2021
Abstract : Tyrosine kinase inhibitors (TKIs) are antitumor compounds that prevent the phosphorylation of proteins in a biological environment. However, the multitarget performance of TKIs promotes them as possible candidates for drug repositioning. In this work, interaction and inhibition studies through spectroscopic and computational techniques to evaluate the binding effectiveness of lapatinib and pazopanib TKIs to acetylcholinesterase (AChE) are reported. The results indicated potent inhibition at the microM level. The types of inhibition were identified, with pazopanib acting through non-competitive inhibition and lapatinib through acompetitive inhibition. The fluorescence suppression studies indicate a static mechanism for lapatinib-AChE and pazopanib-AChE systems, with a binding constant in the order of 10(5) M(-1). The obtained thermodynamic parameters reveal interactions driven by van der Waals forces and hydrogen bonds in the lapatinib-AChE system (deltaH degrees and deltaS degrees < 0). In contrast, the pazopanib-AChE system shows positive deltaH degrees and deltaS degrees, characteristic of hydrophobic interactions. The Foster resonance energy transfer study supports the fluorescence studies performed. The 3D fluorescence studies suggest changes in the microenvironment of the tryptophan and tyrosine residues of the protein in contact with lapatinib and pazopanib. The results suggest effective inhibition and moderate interaction of the drugs with AChE, making them interesting for conducting more in-depth repositioning studies as AChE inhibitors.
ESTHER : Meira_2021_ACS.Chem.Neurosci__
PubMedSearch : Meira_2021_ACS.Chem.Neurosci__
PubMedID: 34808043

Title : Biodegradation of erythromycin by Delftia lacustris RJJ-61 and characterization of its erythromycin esterase - Ren_2021_J.Basic.Microbiol_61_55
Author(s) : Ren J , Wang Z , Deng L , Niu D , Fan B , Huhe T , Li Z , Zhang J , Li C
Ref : J Basic Microbiol , 61 :55 , 2021
Abstract : The residual erythromycin in fermentation waste can pollute the environment and threaten human health. However, there are no effective approaches to remedy this issue. In this study, an erythromycin-degrading bacterium named RJJ-61 was isolated and identified as a strain of Delftia lacustris based on morphological and phylogenetic analyses. The degradation ability of this strain was also evaluated; it could degrade 45.18% of erythromycin at 35 degreesC in 120h. Furthermore, the key degradation gene ereA was cloned from strain RJJ-61 and expressed in Escherichia coli BL21; the molecular weight of the expressed protein was ~45kDa. The enzyme activity of EreA was 108.0mUml(-1) at 35 degreesC and pH 7.0. Finally, the EreA protein was used to degrade erythromycin from mycelial dregs and 50% diluted solution, and the removal rates in them were 41.42% and 69.78%, respectively. In summary, D. lacustris RJJ-61 is a novel erythromycin-degrading strain that has great potential to remove erythromycin pollutants from the environment.
ESTHER : Ren_2021_J.Basic.Microbiol_61_55
PubMedSearch : Ren_2021_J.Basic.Microbiol_61_55
PubMedID: 33332633

Title : Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology - Li_2021_Drug.Des.Devel.Ther_15_1883
Author(s) : Li S , Wang Y , Li C , Yang N , Yu H , Zhou W , Chen S , Yang S , Li Y
Ref : Drug Des Devel Ther , 15 :1883 , 2021
Abstract : BACKGROUND: Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. METHODS: In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. RESULTS: Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10-13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5'-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. CONCLUSION: These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
ESTHER : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedSearch : Li_2021_Drug.Des.Devel.Ther_15_1883
PubMedID: 33976539

Title : Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt\/Beta catenin signaling pathway - Yang_2021_Arch.Oral.Biol_130_105211
Author(s) : Yang P , Li C , Kou Y , Jiang Y , Li D , Liu S , Lu Y , Hasegawa T , Li M
Ref : Archives of Oral Biology , 130 :105211 , 2021
Abstract : OBJECTIVES: The aims of this study were to explore: (i) the effect of Notum on periodontitis in vivo; (ii) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (iii) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. DESIGN: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. RESULTS: Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. CONCLUSION: These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway.
ESTHER : Yang_2021_Arch.Oral.Biol_130_105211
PubMedSearch : Yang_2021_Arch.Oral.Biol_130_105211
PubMedID: 34352447

Title : Molecular Basis of Binding between Middle East Respiratory Syndrome Coronavirus and CD26 from Seven Bat Species - Yuan_2020_J.Virol_94_e01387
Author(s) : Yuan Y , Qi J , Peng R , Li C , Lu G , Yan J , Wang Q , Gao GF
Ref : J Virol , 94 :e01387 , 2020
Abstract : Continued reports of Middle East respiratory syndrome coronavirus (MERS-CoV) infecting humans have occurred since the identification of this virus in 2012. MERS-CoV is prone to cause endemic disease in the Middle East, with several dozen spillover infections to other continents. It is hypothesized that MERS-CoV originated from bat coronaviruses and that dromedary camels are its natural reservoir. Although gene segments identical to MERS-CoV were sequenced from certain species of bats and one species experimentally shed the virus, it is still unknown whether other bats can transmit the virus. Here, at the molecular level, we found that all purified bat CD26s (bCD26s) from a diverse range of species interact with the receptor binding domain (RBD) of MERS-CoV, with equilibrium dissociation constant values ranging from several to hundreds at the micromolar level. Moreover, all bCD26s expressed in this study mediated the entry of pseudotyped MERS-CoV to receptor-expressing cells, indicating the broad potential engagement of bCD26s as MERS-CoV receptors. Further structural analysis indicated that in the bat receptor, compared to the human receptor, substitutions of key residues and their adjacent amino acids leads to decreased binding affinity to the MERS-RBD. These results add more evidence to the existing belief that bats are the original source of MERS-CoV and suggest that bCD26s in many species can mediate the entry of the virus, which has significant implications for the surveillance and control of MERS-CoV infection.IMPORTANCE In this study, we found that bat CD26s (bCD26s) from different species exhibit large diversities, especially in the region responsible for binding to the receptor binding domain (RBD) of Middle East respiratory syndrome coronavirus (MERS-CoV). However, they maintain the interaction with MERS-RBD at varied affinities and support the entry of pseudotyped MERS-CoV. These bat receptors polymorphisms seem to confer evolutionary pressure for the adaptation of CD26-binding virus, such as the ancestor of MERS-CoV, and led to the generation of diversified CD26-engaging CoV strains. Thus, our data add more evidence to support that bats are the reservoir of MERS-CoV and similar viruses, as well as further emphasize the necessity to survey MERS-CoV and other CoVs among bats.
ESTHER : Yuan_2020_J.Virol_94_e01387
PubMedSearch : Yuan_2020_J.Virol_94_e01387
PubMedID: 31776269
Gene_locus related to this paper: myods-l5lq33

Title : Investigation of the transformation and toxicity of trichlorfon at the molecular level during enzymic hydrolysis of apple juice - Li_2020_Food.Chem__128653
Author(s) : Li C , Zhu H , Guo Y , Xie Y , Cheng Y , Yu H , Qian H , Yao W
Ref : Food Chem , :128653 , 2020
Abstract : Trichlorfon is one of the most widely used organophosphorus pesticides in agriculture. In this study, the extent of transformation of trichlorfon to dichlorvos (DDVP), during the polygalacturonase (PG) treatment of apple pulp was monitored. A transformation pathway is proposed for trichlorfon molecules, based on density functional theory (DFT) calculations. The transformation of trichlorfon involves hydroxyl substitution and cleavage, which was confirmed by molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) theory. In addition, the toxicity of trichlorfon and its transformed products was analyzed using Ecological Structure Activity Relationships (ECOSAR) software. The binding sites of the two pesticides are located in the hydrophobic grooves of the acetylcholinesterase (AChE) active site region and both pesticides form hydrophobic interactions and hydrogen bonds with a large number of surrounding amino acid residues. DDVP binds more strongly with AChE, so it is a better AChE inhibitor and more toxic than trichlorfon.
ESTHER : Li_2020_Food.Chem__128653
PubMedSearch : Li_2020_Food.Chem__128653
PubMedID: 33229164

Title : Dipeptidyl Peptidase-4 Is a Target Protein of Epigallocatechin-3-Gallate - Hou_2020_Biomed.Res.Int_2020_5370759
Author(s) : Hou H , Wang Y , Li C , Wang J , Cao Y
Ref : Biomed Res Int , 2020 :5370759 , 2020
Abstract : Epigallocatechin-3-gallate (EGCG), a major active ingredient in green tea, has various health benefits. It affects glucose metabolism, but the mechanism is not well understood. This study aimed to identify targets of EGCG related to glucose metabolism. The core fragment of EGCG is a flavonoid. The flavonoid scaffold was used as a substructure to find proteins cocrystallized with flavonoids in the Protein Data Bank. The proteins identified were screened in PubMed for known relationships with diabetes. Dipeptidyl peptidase-4 (DPP4; PDB 5J3J) was identified following this approach. By molecular docking, the interactions of EGCG and DPP4 were assessed. To test the stability of the interactions between EGCG and DPP4, molecular dynamics simulation for 100 ns was performed using Desmond software. In vitro, the concentration of EGCG required to inhibit DPP4 activity by 50% (the IC50 value) was 28.42 muM. These data provide a theoretical basis for intervention in glucose metabolism with EGCG.
ESTHER : Hou_2020_Biomed.Res.Int_2020_5370759
PubMedSearch : Hou_2020_Biomed.Res.Int_2020_5370759
PubMedID: 32104696

Title : Manipulating regioselectivity of an epoxide hydrolase for single enzymatic synthesis of (R)-1,2-diols from racemic epoxides - Hu_2020_Chem.Commun.(Camb)__
Author(s) : Hu D , Zong XC , Xue F , Li C , Hu BC , Wu MC
Ref : Chem Commun (Camb) , : , 2020
Abstract : Both the activity and regioselectivity of Phaseolus vulgaris epoxide hydrolase were remarkably improved via reshaping two substrate tunnels based on rational design. The elegant one-step enantioconvergent hydrolysis of seven rac-epoxides was achieved by single mutants, allowing green and efficient access to valuable (R)-1,2 diols with high eep (90.1-98.3%) and yields.
ESTHER : Hu_2020_Chem.Commun.(Camb)__
PubMedSearch : Hu_2020_Chem.Commun.(Camb)__
PubMedID: 32030396

Title : Enantioconvergent hydrolysis of m-nitrostyrene oxide at an elevated concentration by Phaseolus vulgaris epoxide hydrolase in the organic\/aqueous two-phase system - Wen_2020_Lett.Appl.Microbiol_70_181
Author(s) : Wen Z , Zhao J , Liu YY , Zhou JJ , Liu C , Li C , Wu MC
Ref : Lett Appl Microbiol , 70 :181 , 2020
Abstract : (R)-m-Nitrophenyl-1,2-ethanediol (m-NPED) is a versatile and highly value-added chiral building block for the synthesis of some bioactive compounds, such as (R)-Nifenalol. To efficiently produce (R)-m-NPED through the enantioconvergent hydrolysis of racemic (rac-) m-nitrostyrene oxide (m-NSO) using the whole resting cells of Escherichia coli/pCold-pveh2 intracellularly expressing PvEH2, an epoxide hydrolase from Phaseolus vulgaris, two reaction systems were investigated. In the Na2 HPO4 -NaH2 PO4 buffer (50 mmol l(-1) , pH 7.0) system, merely 15 mmol l(-1) rac-m-NSO was successfully subjected to enantioconvergent hydrolysis, producing (R)-m-NPED with 86.0% enantiomeric excess (eep ) and 177.6 mg l(-1) h(-1) space-time yield (STY). The experimental result indicated that there is inhibitory effect of rac-m-NSO at high concentration on PvEH2. To efficiently increase the concentration of rac-m-NSO and the STY of (R)-m-NPED, petroleum ether was first selected to construct an organic/aqueous two-phase system. Then, both the volume ratio (vo /vb ) of petroleum ether to phosphate buffer and the weight ratio (wc /ws ) of E. coli/pCold-pveh2 dry cells to rac-m-NSO were optimized as 2 : 8 and 5 : 1, respectively. In the optimized petroleum ether/phosphate buffer two-phase system, the enantioconvergent hydrolysis of rac-m-NSO at 40 mmol l(-1) (6.6 mg ml(-1) ) was carried out at 25 degrees C for 12 h using 33.0 mg ml(-1) vacuum freeze-dried cells of E. coli/pCold-pveh2, producing (R)-m-NPED with 87.4% eep , 82.3% yield and 502.4 mg l(-1) h(-1) STY. SIGNIFICANCE AND IMPACT OF THE STUDY: Epoxide hydrolases play a crucial role in producing enantiopure epoxides and/or vicinal diols. However, numerous biocatalytic reactions of organic compounds, such as epoxides, in aqueous phase suffered various restrictions. Herein, the enantioconvergent hydrolysis of rac-m-NSO in two reaction systems was investigated using the whole cells of Escherichia coli/pCold-pveh2. As a result, the concentration of rac-m-NSO and the space-time yield of (R)-m-NPED in organic/aqueous two-phase system were significantly increased, when compared with those in aqueous phase. To our knowledge, this is the first report about the production of (R)-m-NPED from rac-m-NSO at an elevated concentration by PvEH2 in the two-phase system.
ESTHER : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedSearch : Wen_2020_Lett.Appl.Microbiol_70_181
PubMedID: 31784998

Title : Near-perfect kinetic resolution of o-methylphenyl glycidyl ether by RpEH, a novel epoxide hydrolase from Rhodotorula paludigena JNU001 with high stereoselectivity - Xu_2020_Appl.Microbiol.Biotechnol__
Author(s) : Xu XF , Hu D , Hu BC , Li C , Liu YY , Wu MC
Ref : Applied Microbiology & Biotechnology , : , 2020
Abstract : In order to provide more alternative epoxide hydrolases for industrial production, a novel cDNA gene Rpeh-encoding epoxide hydrolase (RpEH) of Rhodotorula paludigena JNU001 identified by 26S rDNA sequence analysis was amplified by RT-PCR. The open-reading frame (ORF) of Rpeh was 1236 bp encoding RpEH of 411 amino acids and was heterologously expressed in Escherichia coli BL21(DE3). The substrate spectrum of expressed RpEH showed that the transformant E. coli/Rpeh had excellent enantioselectivity to 2a, 3a, and 5a-10a, among which E. coli/Rpeh had the highest activity (2473 U/g wet cells) and wonderful enantioselectivity (E = 101) for 8a, and its regioselectivity coefficients, alphaR and betaS, toward (R)- and (S)-8a were 99.7 and 83.2%, respectively. Using only 10 mg wet cells/mL of E. coli/Rpeh, the near-perfect kinetic resolution of rac-8a at a high concentration (1000 mM) was achieved within 2.5 h, giving (R)-8a with more than 99% enantiomeric excess (ees) and 46.7% yield and producing (S)-8b with 93.2% eep and 51.4% yield with high space-time yield (STY) for (R)-8a and (S)-8b were 30.6 and 37.3 g/L/h.
ESTHER : Xu_2020_Appl.Microbiol.Biotechnol__
PubMedSearch : Xu_2020_Appl.Microbiol.Biotechnol__
PubMedID: 32462245
Gene_locus related to this paper: rhodp-EPH1

Title : Total flavonoids of Selaginella pulvinata alleviates cognitive impairment in mice - Zhang_2020_Biomed.Rep_13_8
Author(s) : Zhang L , Zhang Y , Hou Y , Li H , Li C , Xin J , Zhou N , Li Q , Song Y , Zhang Z
Ref : Biomed Rep , 13 :8 , 2020
Abstract : Cognitive impairment (CI) refers to dysfunctional cognition, which encompasses a spectrum of disorders, ranging from mild cognitive impairment to dementia. Any factor that results in cortical damage may cause CI. Total flavonoids of Selaginella pulvinata (TFSP), have shown promising antioxidant and protective effects in animal models. In the present study, mice were intraperitoneally treated with scopolamine, sodium nitrite or 45% ethanol to induce memory impairment, and the effects were assessed using a step-down test. After performing the behavioural test, hippocampal sections were collected for anatomical analysis, and the brain and serum levels of memory-related molecules were evaluated. The results showed that TFSP improved memory in a mouse model of CI significantly. Serum data were consistent with the behavioural results: TFSP increased blood acetylcholine levels through modulation of the acetylcholinesterase and choline acetyltransferase levels. It also ameliorated oxidative stress in neurons, increasing superoxide dismutase, glutathione peroxidase and inhibiting nitric oxide synthase levels in the brain. These results suggest that TFSP may exhibit potential as a clinical treatment for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and senile dementia.
ESTHER : Zhang_2020_Biomed.Rep_13_8
PubMedSearch : Zhang_2020_Biomed.Rep_13_8
PubMedID: 32607237

Title : Lipase-Catalyzed Reactive Extrusion: Copolymerization of sigma-Caprolactone and w-Pentadecalactone - Li_2020_Macromol.Rapid.Commun_41_e2000417
Author(s) : Li C , Xu W , Lu Y , Gross RA
Ref : Macromol Rapid Commun , 41 :e2000417 , 2020
Abstract : This study assesses the use of immobilized lipase catalyst N435 during reactive extrusion (REX) versus magnetically stirred bulk and solution reaction conditions for the copolymerization of sigma-caprolactone with omega-pentadecalactone (CL/PDL 1:1 molar). N435-catalyzed REX for reaction times from 1 to 3 h results in total %-monomer conversion, M(n) , and D values increase from 92.7% to 98.8%, 36.1 to 51.3 kDa, and 1.85 to 1.96, respectively. Diad fraction analysis by quantitative (13) C NMR reveals that, after just 1 h, rapid N435-catalyzed transesterification reactions occur that give random copolyesters. In contrast, for bulk polymerization with magnetic stirring in round bottom flasks, reaction times from 1 to 3 h result in the following: M(n) increases from 12.4 to 25.6 kDa, D decreases from 2.98 to 1.87, and the randomness index increases from 0.74 and 0.86 as PDL*-PDL diads are dominant. These results highlight that REX avoids problems associated with internal batch mixing that are encountered in bulk polymerizations. In sharp contrast to a previous study of 1:1 molar PDL/delta-valerolactone (VL) copolymerizations by N435-catalyzed REX, VL %-conversion increases to just 40.1% in 1 h whereas CL reaches 94.7%.
ESTHER : Li_2020_Macromol.Rapid.Commun_41_e2000417
PubMedSearch : Li_2020_Macromol.Rapid.Commun_41_e2000417
PubMedID: 33047442
Gene_locus related to this paper: canar-LipB

Title : Highly regio- and enantio-selective hydrolysis of two racemic epoxides by GmEH3, a novel epoxide hydrolase from Glycine max - Zhang_2020_Int.J.Biol.Macromol_164_2795
Author(s) : Zhang C , Li C , Zhu XX , Liu YY , Zhao J , Wu MC
Ref : Int J Biol Macromol , 164 :2795 , 2020
Abstract : A novel epoxide hydrolase from Glycine max, designated GmEH3, was excavated based on the computer-aided analysis. Then, gmeh3, a GmEH3-encoding gene, was cloned and successfully expressed in E. coli Rosetta(DE3). Among the ten investigated rac-epoxides, GmEH3 possessed the highest and best complementary regioselectivities (regioselectivity coefficients, alpha(S) = 93.7% and beta(R) = 97.2%) in the asymmetric hydrolysis of rac-m-chlorostyrene oxide (5a), and the highest enantioselectivity (enantiomeric ratio, E = 55.6) towards rac-phenyl glycidyl ether (7a). The catalytic efficiency (k(cat)(S)/K(m)(S) = 2.50 mM(-1) s(-1)) of purified GmEH3 for (S)-5a was slightly higher than that (k(cat)(R)/K(m)(R) = 1.52 mM(-1) s(-1)) for (R)-5a, whereas the k(cat)/K(m) (5.16 mM(-1) s(-1)) for (S)-7a was much higher than that (0.09 mM(-1) s(-1)) for (R)-7a. Using 200 mg/mL wet cells of E. coli/gmeh3 as the biocatalyst, the scale-up enantioconvergent hydrolysis of 150 mM rac-5a at 25 degreesC for 1.5 h afforded (R)-5b with 90.2% ee(p) and 95.4% yield(p), while the kinetic resolution of 500 mM rac-7a for 2.5 h retained (R)-7a with over 99% ee(s) and 43.2% yield(s). Furthermore, the sources of high regiocomplementarity of GmEH3 for (S)- and (R)-5a as well as high enantioselectivity towards rac-7a were analyzed via molecular docking (MD) simulation.
ESTHER : Zhang_2020_Int.J.Biol.Macromol_164_2795
PubMedSearch : Zhang_2020_Int.J.Biol.Macromol_164_2795
PubMedID: 32763395
Gene_locus related to this paper: soybn-GmEH3

Title : A Novel alpha\/beta Hydrolase Domain Protein Derived From Haemonchus contortus Acts at the Parasite-Host Interface - Lu_2020_Front.Immunol_11_1388
Author(s) : Lu M , Tian X , Tian AL , Li C , Yan R , Xu L , Song X , Li X
Ref : Front Immunol , 11 :1388 , 2020
Abstract : The alpha/beta-hydrolase domain (ABHD) proteins belonging to alpha/beta-hydrolase (ABH) superfamily are ubiquitously distributed throughout all the organisms, and their functional roles have been implicated in energy metabolism, cell signaling, growth and development. In our preliminary work, we identified a novel ABHD protein derived from Haemonchus contortus excretory-secretory (ES) proteins (HcESPs) that interacted with host T cells. Here, we demonstrated that H. contortus ABHD (HcABHD) protein, expressed in all life-cycle stages of H. contortus, is a mammalian ABHD17 homolog with immunodiagnostic utility and lipase activity. Given its catalytic activities and immunomodulatory potentials, we further investigated the functional diversity of HcABHD as an individual ES protein in parasite-host interactions. HcABHD protein may serve as depalmitoylase or thioesterase to suppress cell viability, inhibit cell proliferation, induce intrinsic and extrinsic T cell apoptosis, and cause cell cycle arrested at G1 phase. Moreover, recombinant HcABHD stimuli exerted critical controls on T cell cytokine production profiles, predominantly by inhibiting the secretions of interleukin (IL)-4, interferon-gamma (IFN-gama) and transforming growth factor-beta (TGF-beta) 1, and promoting IL-10 production. As the immunomodulator acting at the parasite-host interface, HcABHD protein may have potential applications for the vaccine development of therapeutic intervention. Together, these findings may help illuminate the molecular and particularly immunomodulatory aspects of ES proteins and contribute to an enhanced understanding of parasite immune evasion in H. contortus-host biology.
ESTHER : Lu_2020_Front.Immunol_11_1388
PubMedSearch : Lu_2020_Front.Immunol_11_1388
PubMedID: 32695121
Gene_locus related to this paper: haeco-CDJ88804

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 : Near-perfect kinetic resolution of racemic p-chlorostyrene oxide by SlEH1, a novel epoxide hydrolase from Solanum lycopersicum with extremely high enantioselectivity - Hu_2020_Int.J.Biol.Macromol_147_1213
Author(s) : Hu BC , Hu D , Li C , Xu XF , Wen Z , Wu MC
Ref : Int J Biol Macromol , 147 :1213 , 2020
Abstract : An open reading frame of sleh1, a gene encoding for a novel epoxide hydrolase from Solanum lycopersicum (SlEH1), was amplified by RT-PCR and expressed in E. coli BL21(DE3). The substrate spectrum assay showed that E. coli/sleh1 had EH activities towards all tested substrates except for racemic (rac-) 5a, and the highest enantiomeric ratio (E > 200) towards rac-2a, retaining (R)-2a with 99.1% ees and 49.2% yields and affording (R)-2b with 89.8% eep and 46.7% yieldp. Besides, E. coli/sleh1 also hydrolyzed of rac-7a-9a with moderate regioselectivities, producing (S)- or (R)-7b-9b with 40.5-51.3% eep and 69.4-75.2% yieldp. The pH optimum and stability of the purified SlEH1 were 7.5 and at a range of 6.5-8.5, and it was thermostable at or below 40 degrees C. Its catalytic efficiency (kcat(S)/Km(S) = 7.49 mM(-1) s(-1)) for (S)-2a was much higher than that for (R)-2a. The gram-scale kinetic resolution of 150 mM rac-2a was carried out by E. coli/sleh1 at 20 degrees C for 8 h, producing (R)-2a with 98.2% ees and 45.3% overall yields after purification by silica gel column chromatography. Furthermore, the source of extremely high enantioselectivity of SlEH1 towards rac-2a was analyzed by molecular docking simulations.
ESTHER : Hu_2020_Int.J.Biol.Macromol_147_1213
PubMedSearch : Hu_2020_Int.J.Biol.Macromol_147_1213
PubMedID: 31739010
Gene_locus related to this paper: aspng-q1ktb5

Title : Gene cloning, expression, purification and characterization of a sn-1,3 extracellular lipase from Aspergillus niger GZUF36 - Xing_2020_J.Food.Sci.Technol_57_2669
Author(s) : Xing S , Zhu R , Li C , He L , Zeng X , Zhang Q
Ref : J Food Sci Technol , 57 :2669 , 2020
Abstract : Sn-1,3 extracellular Aspergillus niger GZUF36 lipase (EXANL1) has wide application potential in the food industry. However, the A. niger strain has defects such as easy degradation and instability in the expression of sn-1,3 lipase. To obtain a stable expression of this lipase and its subsequent enzymatic properties, the gene encoding EXANL1 was cloned and expressed in Escherichia coli BL21 (DE3) cells using pET-28a as the expression vector. The temperature-induced conditions were optimized, and we successfully achieved its active expression in E. coli. These conditions significantly influenced the active expression of EXANL1 (P < 0.05), and the highest enzyme activity of the supernatant of lysis cells expressed at 20 degreesC was at 7.02 +/- 0.05 U/mL. The expressed recombinant EXANL1 was purified using Ni-NTA, showing an estimated relative molecular mass of 35 kDa. The recombinant EXANL1 exhibited maximum activity at 35 degreesC and pH 4.0, with a wide acid pH range. Thin-layer chromatography analysis showed that the enzyme displayed sn-1,3 positional selectivity toward triolein. The recombinant EXANL1 could maintain its relative activities (> 80%) after 24 h of incubation at pH 3-10, suggesting its suitability for a wide range of industrial applications. After comparing these properties with those of the other A. niger lipases, we found that some key amino acids may play a decisive role in enzymology. This work laid a foundation for the stable expression of the EXANL1 gene and its potential industrial application.
ESTHER : Xing_2020_J.Food.Sci.Technol_57_2669
PubMedSearch : Xing_2020_J.Food.Sci.Technol_57_2669
PubMedID: 32549617
Gene_locus related to this paper: aspng-EXANL1

Title : Greatly enhancing the enantioselectivity of PvEH2, a Phaseolus vulgaris epoxide hydrolase, towards racemic 1,2-epoxyhexane via replacing its partial cap-loop - Li_2020_Int.J.Biol.Macromol_156_225
Author(s) : Li C , Hu BC , Wen Z , Hu D , Liu YY , Chu Q , Wu MC
Ref : Int J Biol Macromol , 156 :225 , 2020
Abstract : To achieve the kinetic resolution and enantioconvergent hydrolysis of rac-1,2-epoxyhexane, the E value of PvEH2 was enhanced by substituting its partial cap-loop. Based on the experimental results reported previously and computer-aided analysis, the flexible and variable cap-loop, especially its middle segment, was speculated to be related to the catalytic properties of PvEH2. In view of this, four PvEH2's hybrids, Pv2St, Pv2Pv1, Pv2Vr1 and Pv2Vr2, were designed by substituting the middle segment ((190)EGMGSNLNTSMP(201)) of a cap-loop in PvEH2 with the corresponding ones in StEH, PvEH1, VrEH1 and VrEH2, respectively. Then, the hybrid-encoding genes, pv2st, pv2pv1, pv2vr1 and pv2vr2, were constructed by fusion PCR, and expressed in E. coli Rosetta(DE3). The expressed hybrid, Pv2St, displayed the highest specific activity of 35.3 U/mg protein towards rac-1,2-epoxyhexane. The corresponding transformant, E. coli/pv2st, exhibited the largest E value of 24.2, which was 11.5-fold that of E. coli/pveh2 expressing PvEH2. The scale-up kinetic resolution of 280 mM rac-1,2-epoxyhexane was carried out using 40 mg dry cells/mL of E. coli/pv2st at 25 degrees C for 4.5 h, retaining (S)-1,2-epoxyhexane with >99.5% ees and 36.9% yield. Additionally, the chemo-enzymatic enantioconvergent hydrolysis of rac-1,2-epoxyhexane using E. coli/pv2st followed by sulfuric acid produced (R)-hexane-1,2-diol with 73.0% eep and 86.5% yield.
ESTHER : Li_2020_Int.J.Biol.Macromol_156_225
PubMedSearch : Li_2020_Int.J.Biol.Macromol_156_225
PubMedID: 32294502
Gene_locus related to this paper: phavu-v7bpm3

Title : Significant improvement in catalytic activity and enantioselectivity of a Phaseolus vulgaris epoxide hydrolase, PvEH3, towards ortho-cresyl glycidyl ether based on the semi-rational design - Zhang_2020_Sci.Rep_10_1680
Author(s) : Zhang C , Liu Y , Li C , Xu Y , Su Y , Li J , Zhao J , Wu M
Ref : Sci Rep , 10 :1680 , 2020
Abstract : The investigation of substrate spectrum towards five racemic (rac-) aryl glycidyl ethers (1a-5a) indicated that E. coli/pveh3, an E. coli BL21(DE3) transformant harboring a PvEH3-encoding gene pveh3, showed the highest EH activity and enantiomeric ratio (E) towards rac-3a. For efficiently catalyzing the kinetic resolution of rac-3a, the activity and E value of PvEH3 were further improved by site-directed mutagenesis of selected residues. Based on the semi-rational design of an NC-loop in PvEH3, four single-site variants of pveh3 were amplified by PCR, and intracellularly expressed in E. coli BL21(DE3), respectively. E. coli/pveh3(E134K) and /pveh3(T137P) had the enhanced EH activities of 15.3 +/- 0.4 and 16.1 +/- 0.5 U/g wet cell as well as E values of 21.7 +/- 1.0 and 21.2 +/- 1.1 towards rac-3a. Subsequently, E. coli/pveh3(E134K/T137P) harboring a double-site variant gene was also constructed, having the highest EH activity of 22.4 +/- 0.6 U/g wet cell and E value of 24.1 +/- 1.2. The specific activity of the purified PvEH3(E134K/T137P) (14.5 +/- 0.5 U/mg protein) towards rac-3a and its catalytic efficiency (k(cat)/K(m) of 5.67 mM(-1) s(-1)) for (S)-3a were 1.7- and 3.54-fold those (8.4 +/- 0.3 U/mg and 1.60 mM(-1) s(-1)) of PvEH3. The gram-scale kinetic resolution of rac-3a using whole wet cells of E. coli/pveh3(E134K/T137P) was performed at 20 degC for 7.0 h, producing (R)-3a with 99.4% ee(s) and 38.5 +/- 1.2% yield. Additionally, the mechanism of PvEH3(E134K/T137P) with remarkably improved E value was analyzed by molecular docking simulation.
ESTHER : Zhang_2020_Sci.Rep_10_1680
PubMedSearch : Zhang_2020_Sci.Rep_10_1680
PubMedID: 32015448
Gene_locus related to this paper: phavu-PvEH3

Title : Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis - Shang_2019_Cancer.Res_79_5513
Author(s) : Shang S , Ji X , Zhang L , Chen J , Li C , Shi R , Xiang W , Kang X , Zhang D , Yang F , Dai R , Chen P , Chen S , Chen Y , Li Y , Miao H
Ref : Cancer Research , 79 :5513 , 2019
Abstract : Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract:
ESTHER : Shang_2019_Cancer.Res_79_5513
PubMedSearch : Shang_2019_Cancer.Res_79_5513
PubMedID: 31439546
Gene_locus related to this paper: human-ABHD5

Title : Functional analysis of four upregulated carboxylesterase genes associated with fenpropathrin resistance in Tetranychus cinnabarinus (Boisduval) - Wei_2019_Pest.Manag.Sci_75_252
Author(s) : Wei P , Li J , Liu X , Nan C , Shi L , Zhang Y , Li C , He L
Ref : Pest Manag Sci , 75 :252 , 2019
Abstract : BACKGROUND: Carboxylesterases (CarEs) are important in pesticide resistance. Four overexpressed CarE genes with inducible character were screened out in fenpropathrin-resistant Tetranychus cinnabarinus, but their functional roles remained to be further analyzed by RNAi and protein expression. RESULTS: Feeding a single double-stranded (ds)RNA of each of four genes led to gene-specific downregulation of mRNA, decreased esterase activity and diminished resistance in T. cinnabarinus. More interestingly, feeding four dsRNAs simultaneously led to a more significant decrease in enzymatic activity and fold resistance than feeding a single dsRNA individually, suggesting that these CarE genes were involved in fenpropathrin-resistance and had cooperative roles. The gene CarE6 was regarded as the primary and representative candidate to be functionally expressed, because silencing of CarE6 led to the most significant decrease in resistance level. The activity of CarE6 protein was competitively inhibited by fenpropathrin. It could effectively decompose 41.7 +/- 0.09% of fenpropathrin within 3 h, proving that CarE6 protein was capable of metabolizing fenpropathrin effectively in T. cinnabarinus. CONCLUSION: The results confirm that four CarE genes are cooperatively involved in fenpropathrin resistance and the metabolic enzymes encoded by these overexpressed genes do indeed metabolize acaricide in resistant T. cinnabarinus in the evolution of acaricide resistance. (c) 2018 Society of Chemical Industry.
ESTHER : Wei_2019_Pest.Manag.Sci_75_252
PubMedSearch : Wei_2019_Pest.Manag.Sci_75_252
PubMedID: 29877064
Gene_locus related to this paper: tetur-t1k786

Title : Carboxylesterase, a de-esterification enzyme, catalyzes the degradation of chlorimuron-ethyl in Rhodococcus erythropolis D310-1 - Zang_2019_J.Hazard.Mater__121684
Author(s) : Zang H , Wang H , Miao L , Cheng Y , Zhang Y , Liu Y , Sun S , Wang Y , Li C
Ref : J Hazard Mater , :121684 , 2019
Abstract : Microbial degradation is considered to be the most acceptable method for degradation of chlorimuron-ethyl, a typical long-term residual sulfonylurea herbicide, but the underlying mechanism at the genetic and biochemical levels is unclear. In this work, the genome sequence of the chlorimuron-ethyl-degrading bacterium Rhodococcus erythropolis D310-1 was completed, and the gene clusters responsible for the degradation of chlorimuron-ethyl in D310-1 were predicted. A carboxylesterase gene, carE, suggested to be responsible for carboxylesterase de-esterification, was cloned from D310-1. CarE was expressed in Escherichia coli BL21 and purified to homogeneity. The active site of the chlorimuron-ethyl-degrading enzyme CarE and the biochemical activities of CarE were elucidated. The results demonstrated that CarE is involved in catalyzing the de-esterification of chlorimuron-ethyl. A carE deletion mutant strain, D310-1DeltacarE, was constructed, and the chlorimuron-ethyl degradation rate in the presence of 100mgL(-1) chlorimuron-ethyl within 120h decreased from 86.5 % (wild-type strain D310-1) to 58.2 % (mutant strain D310-1DeltacarE). Introduction of the plasmid pNit-carE restored the ability of the mutant strain to utilize chlorimuron-ethyl. This study is the first to demonstrate that carboxylesterase can catalyze the de-esterification reaction of chlorimuron-ethyl and provides new insights into the mechanism underlying the degradation of sulfonylurea herbicides and a theoretical basis for the utilization of enzyme resources.
ESTHER : Zang_2019_J.Hazard.Mater__121684
PubMedSearch : Zang_2019_J.Hazard.Mater__121684
PubMedID: 31784128
Gene_locus related to this paper: rhoe4-c1a280

Title : Evaluation of potential herb-drug interactions between oseltamivir and commonly used anti-influenza Chinese medicinal herbs - Zhang_2019_J.Ethnopharmacol__112097
Author(s) : Zhang Y , Lyu C , Fong S , Wang Q , Li C , Ho NJ , Chan KS , Yan X , Zuo Z
Ref : J Ethnopharmacol , :112097 , 2019
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: According to Traditional Chinese Medicine theory, influenza is categorized as a warm disease or Wen Bing. The Wen Bing formulas, such as Yin-Qiao-San and Sang-Ju-Yin, are still first-line herbal therapies in combating variant influenza virus. To continue our study on the pharmacokinetic and pharmacodynamic interactions between Wen Bing formulas and oseltamivir (OS), the first-line western drug for the treatment of influenza, further interactions between OS and the eight single herbs and their relevant marker components from Wen Bing formulas were investigated in the current study. AIM OF STUDY: To establish an in-vitro screening platform for investigation of the potential anti-influenza herbs/herbal components that may have pharmacokinetic and pharmacodynamic interactions with OS. MATERIALS AND METHODS: To screen potential inhibition on OS hydrolysis, 1mug/mL of OS is incubated with herbs/herbal components in diluted rat plasma, microsomes and human recombinant carboxylesterase 1(hCE1) under optimized conditions. MDCK-WT and MDCK-MDR1 cell lines are utilized to identify potential modification on P-gp mediated transport of OS by herbs/herbal components. Caco-2cells with and without Gly-Sar inhibition are performed to study the uptake of OS via PEPT1 transporters. Modification on OAT3 mediated transport is verified by the uptake of OS on HEK293-MOCK/HEK293-OAT3 cells. Anti-virus effects were evaluated using plaque reduction assay on H1N1 and H3N2 viruses. Potential pharmacokinetic and pharmacodynamic interaction between OS (30mg/kg) and the selected herb, Radix Scutellariae (RS), at 300-600mg/kg were carried out on rats. All samples are analyzed by an LC/MS/MS method for the contents of OS and OSA. A mechanistic PK model was developed to interpret the HDI between OS and RS in rats. RESULTS: Our developed platform was successfully applied to screen the eight herbal extracts and their ten marker components on metabolic inhibition of OS and modification of OS transport mediated by P-gp, OAT3 and PEPT1. Results from six in-vitro experiments were analyzed after converting raw data from each experiment to corresponding fold-change (FC) values, based on which Radix Scutellariae (RS) were selected to have the most HDI potential with OS. By analyzing the plasma and urine pharmacokinetic data after co-administration of OS with a standardized RS extract in rats using an integrated population pharmacokinetics model, it is suggested that RS could inhibit OS hydrolysis during absorption and increase the absorbed fraction of OS, which leads to the increased ratio of OS concentration versus that of OSA in both rat plasma and urine. Never the less, the anti-virus effects of 2.5h post-dose rat plasma were not influenced by co-administration of OS with RS. CONCLUSION: A six-dimension in-vitro screening platform has been developed and successfully applied to find RS as a potential herb that would influence the co-administrated OS in rats. Although co-administered RS could inhibit OS hydrolysis during absorption and increase the absorbed fraction of OS, which lead to the increased ratio of OS concentration versus that of OSA in both rat plasma and urine, the anti-virus effect of OS was not influenced by co-administered RS.
ESTHER : Zhang_2019_J.Ethnopharmacol__112097
PubMedSearch : Zhang_2019_J.Ethnopharmacol__112097
PubMedID: 31325600

Title : Safety, efficacy, and pharmacokinetics of pradefovir for the treatment of chronic hepatitis B infection - Zhang_2019_Antiviral.Res__104693
Author(s) : Zhang H , Liu J , Zhu X , Li X , Jin W , Chen H , Wu M , Li C , Liu C , JunqiNiu , Ding Y
Ref : Antiviral Res , :104693 , 2019
Abstract : BACKGROUND & AIMS: Pradefovir is a liver targeted novel prodrug of adefovir (PMEA) developed to provide higher antiviral activity with reduced systemic toxicities. This study evaluated the tolerability, pharmacokinetics, and antiviral activity of pradefovir in patients with chronic hepatitis B (CHB) virus infection. METHODS: Non-cirrhotic, treatment-naive subjects with CHB were divided into five groups (10 patients each) and randomized within each group in a ratio of 6:2:2 to receive an ascending dose of 30, 60, 75, 90, or 120mg pradefovir, 10mg adefovir dipivoxil (ADV), or 300mg tenofovir disoproxil fumarate (TDF) once a day for 28 days. RESULTS: A total of 51 subjects were randomized and 49 subjects completed the study. The groups were well matched and included 39 males, of whom 71% were hepatitis B e-antigen-negative with a mean hepatitis B virus (HBV) DNA level of 6.4-7.16 log10 IU/mL. No subject experienced a serious adverse event or nephrotoxicity. The most frequently reported adverse event was asymptomatic reduction in blood cholinesterase levels in the pradefovir group which recovered without any treatment about 13+/-7 days after drug discontinuation. This adverse event was not observed in the ADV and TDF groups. The mean changes in serum HBV DNA were -2.78, -2.77, -3.08, -3.18, -3.44, -2.34, and -3.07 log10 IU/mL at 30, 60, 75, 90, and 120mg pradefovir, 10mg ADV and 300mg TDF, respectively, with plateau levels reached with 60mg pradefovir. Pradefovir and its metabolite PMEA showed linear pharmacokinetics proportional to the dose. The half-life of PMEA in the pradefovir group was 11.47-17.63h. CONCLUSIONS: Short-term use of pradefovir was well tolerated. A decline in HBV DNA levels was superior to TDF at higher doses of pradefovir. 30-60mg pradefovir is recommended for CHB treatment. CLINICAL TRIAL NUMBER: CTR20150224.
ESTHER : Zhang_2019_Antiviral.Res__104693
PubMedSearch : Zhang_2019_Antiviral.Res__104693
PubMedID: 31838002

Title : Improving the activity and enantioselectivity of PvEH1, a Phaseolus vulgaris epoxide hydrolase, for o-methylphenyl glycidyl ether by multiple site-directed mutagenesis on the basis of rational design - Li_2019_Mol.Catal_476_110517
Author(s) : Li C , Kan T-T , Hu D , Wang T-T , Su Y-J , Zhang C , Cheng J-Q , Wu M-C
Ref : Molecular Catalysis , 476 :110517 , 2019
Abstract : Substrate spectrum assay exhibited that PvEH1, which is an epoxide hydrolase from P. vulgaris, had the highest specific activity and enantiomeric ratio (E) for racemic o-methylphenyl glycidyl ether (rac-1) among tested aryl glycidyl ethers (1-5). To produce (R)-1 via kinetic resolution of rac-1 efficiently, the catalytic properties of PvEH1 were further improved on the basis of rational design. Firstly, the seven single-site variants of PvEH1-encoding gene (pveh1) were PCR-amplified as designed, and expressed in E. coli BL21(DE3). Among all expressed single-site mutants, PvEH1L105I and PvEH1V106I had the highest specific activities of 17.6 and 16.4 U/mg protein, respectively, while PvEH1L196D had an enhanced E value of 9.2. Secondly, to combine their respective merits, one triple-site variant, pveh1L105I/V106I/L196D, was also amplified, and expressed. The specific activity, E value, and catalytic efficiency of PvEH1L105I/V106I/L196D were 23.1 U/mg, 10.9, and 6.65 mM1 s1, respectively, which were 2.0-, 1.8- and 2.4-fold higher than those of wild-type PvEH1. The source of PvEH1L105I/V106I/L196D with enhanced E value for rac-1 was preliminarily analyzed by molecular docking simulation. Finally, the scale-up kinetic resolution of 100 mM rac-1 was conducted using 5 mg wet cells/mL E. coli/pveh1L105I/V106I/L196D at 25 degreesC for 1.5 h, producing (R)-1 with 95.0% ees, 32.1% yield and 3.52 g/L/h space-time yield.
ESTHER : Li_2019_Mol.Catal_476_110517
PubMedSearch : Li_2019_Mol.Catal_476_110517
Gene_locus related to this paper: phavu-PvEH1

Title : Substantially improving the enantioconvergence of PvEH1, a Phaseolus vulgaris epoxide hydrolase, towards m-chlorostyrene oxide by laboratory evolution - Zong_2019_Microb.Cell.Fact_18_202
Author(s) : Zong XC , Li C , Xu YH , Hu D , Hu BC , Zang J , Wu MC
Ref : Microb Cell Fact , 18 :202 , 2019
Abstract : BACKGROUND: Epoxide hydrolase can regioselectively catalyze the oxirane ring-opening hydrolysis of rac-epoxides producing the corresponding chiral diols. In our laboratory, a gene named pveh1 encoding an EH from Phaseolus vulgaris was cloned. Although the directed modification of PvEH1 was carried out, the mutant PvEH1(Y3) showed a limited degree of enantioconvergence towards racemic (rac-) m-chlorostyrene oxide (mCSO). RESULTS: PvEH1 and PvEH1(Y3) were combinatively subjected to laboratory evolution to further enhance the enantioconvergence of PvEH1(Y3) towards rac-mCSO. Firstly, the substrate-binding pocket of PvEH1 was identified using a CAVER 3.0 software, and divided into three zones. After all residues in zones 1 and 3 were subjected to leucine scanning, two E. coli transformants, E. coli/pveh1(Y149L) and /pveh1(P184L), were selected, by which rac-mCSO was transformed into (R)-m-chlorophenyl-1,2-ethanediol (mCPED) having 55.1% and 27.2% ee(p). Secondly, two saturation mutagenesis libraries, E. coli/pveh1(Y149X) and /pveh1(P184X) (X: any one of 20 residues) were created at sites Y149 and P184 of PvEH1. Among all transformants, both E. coli/pveh1(Y149L) (65.8% alpha(S) and 55.1% ee(p)) and /pveh1(P184W) (66.6% alpha(S) and 59.8% ee(p)) possessed the highest enantioconvergences. Finally, the combinatorial mutagenesis was conducted by replacements of both Y149L and P184W in PvEH1(Y3), constructing E. coli/pveh1(Y3Z2), whose alpha(S) reached 97.5%, higher than that (75.3%) of E. coli/pveh1(Y3). In addition, the enantioconvergent hydrolysis of 20 mM rac-mCSO was performed by E. coli/pveh1(Y3Z2), giving (R)-mCPED with 95.2% ee(p) and 97.2% yield. CONCLUSIONS: In summary, the enantioconvergence of PvEH1(Y3Z2) was successfully improved by laboratory evolution, which was based on the study of substrate-binding pocket by leucine scanning. Our present work introduced an effective strategy for the directed modification of enantioconvergence of PvEH1.
ESTHER : Zong_2019_Microb.Cell.Fact_18_202
PubMedSearch : Zong_2019_Microb.Cell.Fact_18_202
PubMedID: 31739786
Gene_locus related to this paper: phavu-PvEH1

Title : Multiple site-directed mutagenesis of a Phaseolus vulgaris epoxide hydrolase to improve its catalytic performance towards p-chlorostyrene oxide based on the computer-aided re-design - Li_2019_Int.J.Biol.Macromol_121_326
Author(s) : Li C , Zhao J , Hu D , Hu BC , Wang R , Zang J , Wu MC
Ref : Int J Biol Macromol , 121 :326 , 2019
Abstract : To improve the activity and regioselectivity of a Phaseolus vulgaris epoxide hydrolase (PvEH3) towards p-chlorostyrene oxide (pCSO), the site-directed mutagenesis was conducted based on the computer-aided re-design. Firstly, seven single-site variants of a PvEH3-encoding gene (pveh3) were constructed as designed theoretically and expressed in E. coli BL21(DE3), respectively. One transformant, E. coli/pveh3(G170E), had the higher EH activity towards racemic pCSO, while both E. coli/pveh3(F187L) and /pveh3(P237L) with enhanced regioselectivity coefficient alphaS values. Secondly, to combine their respective merits, the double- and triple-site variants, pveh3(G170E/F187L), pveh3(G170E/P237L) and pveh3(G170E/F187L/P237L), were also constructed. Among all E. coli transformants, E. coli/pveh3(G170E/F187L/P237L) simultaneously had the highest EH activity of 20.3U/g wet cell and alphaS value of 95.2%, by which the hydrolysis of rac-pCSO enantioconvergently produced (R)-p-chlorophenylethane-1,2-diol with an enantiomeric excess of 93.2%. Furthermore, PvEH3(G170E/F187L/P237L) expressed in E. coli/pveh3(G170E/F187L/P237L) was purified. Its specific activity and catalytic efficiency towards rac-pCSO were 4.1U/mg protein and 1.81mM(-1)s(-1), which were 3.0- and 3.1-fold those of PvEH3. Finally, the molecular docking simulation analysis indicated that PvEH3(G170E/F187L/P237L) preferentially attacks the more hindered benzylic carbon of (S)-pCSO over PvEH3, which was consistent with their alphaS values measured experimentally.
ESTHER : Li_2019_Int.J.Biol.Macromol_121_326
PubMedSearch : Li_2019_Int.J.Biol.Macromol_121_326
PubMedID: 30308283
Gene_locus related to this paper: phavu-PvEH3

Title : Network pharmacology study on the active components of Pterocypsela elata and the mechanism of their effect against cerebral ischemia - Niu_2019_Drug.Des.Devel.Ther_13_3009
Author(s) : Niu B , Zhang H , Li C , Yan F , Song Y , Hai G , Jiao Y , Feng Y
Ref : Drug Des Devel Ther , 13 :3009 , 2019
Abstract : Objective: The aim of this study was to identify the active anti-ischemic components of Pterocypsela elata (P. elata) using a network pharmacology approach to construct an effective component anti-cerebral ischemic target network and systematically analyze this medicinal material. Methods: Pharmacological studies have shown that P. elata has an obvious effect against cerebral ischemia. To identify the potential targets, 14 components of P. elata were docked to each structural element of the targets in the DRAR-CPI database by reverse docking technology. We then compared the identified potential targets with FDA-approved targets for stroke/cerebral infarction treatment in the DrugBank database and identified the active components of P. elata and their potential targets for stroke/cerebral infarction treatment. The active component-target networks were constructed using Cytoscape 3.5.1 software. The target protein-protein interactions were analyzed using the STRING database. KEGG pathway analysis and gene ontology (GO) enrichment analysis were performed through the Database for Annotation, Visualization and Integrated Discovery (DAVID). Results: There were 14 active components identified from P. elata and 21 potential targets identified for cerebral ischemia treatment, including carbonic anhydrase 2, ribosyldihydronicotinamide dehydrogenase, cholinesterase, and glutathione S-transferase P. The main involved pathways include metabolic pathways, complement and coagulation cascades and steroid hormone biosynthesis. Conclusion: Through a network pharmacology approach, we predicted the active components of P. elata and their potential targets for cerebral ischemia treatment. Our results provide new perspectives and clues for further studies on the anti-cerebral ischemia mechanism of P. elata.
ESTHER : Niu_2019_Drug.Des.Devel.Ther_13_3009
PubMedSearch : Niu_2019_Drug.Des.Devel.Ther_13_3009
PubMedID: 31564827

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 : Global transcriptomic analysis of Rhodococcus erythropolis D310-1 in responding to chlorimuron-ethyl - Cheng_2018_Ecotoxicol.Environ.Saf_157_111
Author(s) : Cheng Y , Zang H , Wang H , Li D , Li C
Ref : Ecotoxicology & Environmental Safety , 157 :111 , 2018
Abstract : Chlorimuron-ethyl is a typical long-term residual sulfonylurea herbicide whose long period of residence poses a serious hazard to rotational crops. Microbial degradation is considered to be the most acceptable method for its removal, but the degradation mechanism is not clear. In this work, we investigated gene expression changes during the degradation of chlorimuron-ethyl by an effective chlorimuron-ethyl-degrading bacterium, Rhodococcus erythropolis D310-1. The genes that correspond to this degradation and their mode of action were identified using RNA-Seq and qRT-PCR. The RNA-Seq results revealed that 500 genes were up-regulated during chlorimuron-ethyl degradation by strain D310-1. KEGG annotation showed that the dominant metabolic pathways were "Toluene degradation" and "Aminobenzoate degradation". Combining GO and KEGG classification with the relevant literature, we predicted that cytochrome P-450, carboxylesterase, and monooxygenase were involved in metabolic chlorimuron-ethyl biodegradation and that the enzyme active site and mode of action coincided with the degradation pathway proposed in our previous study. qRT-PCR experiments suggested that the R. erythropolis D310-1 carboxylesterase, cytochrome P-450 and glycosyltransferase genes were the key genes expressed during chlorimuron-ethyl biodegradation. To the best of our knowledge, this report is the first to describe the transcriptome analysis of a Rhodococcus species during the degradation of chlorimuron-ethyl.
ESTHER : Cheng_2018_Ecotoxicol.Environ.Saf_157_111
PubMedSearch : Cheng_2018_Ecotoxicol.Environ.Saf_157_111
PubMedID: 29614448

Title : Design, synthesis and biological evaluation of novel pyrimidinedione derivatives as DPP-4 inhibitors - Li_2018_Bioorg.Med.Chem.Lett_28_2131
Author(s) : Li N , Wang LJ , Jiang B , Guo SJ , Li XQ , Chen XC , Luo J , Li C , Wang Y , Shi DY
Ref : Bioorganic & Medicinal Chemistry Lett , 28 :2131 , 2018
Abstract : A series of novel pyrimidinedione derivatives were designed and evaluated for in vitro dipeptidyl peptidase-4 (DPP-4) inhibitory activity and in vivo anti-hyperglycemic efficacy. Among them, the representative compounds 11, 15 and 16 showed excellent inhibitory activity of DPP-4 with IC50 values of 64.47nM, 188.7nM and 65.36nM, respectively. Further studies revealed that compound 11 was potent in vivo hypoglycemic effect. The structure-activity relationships of these pyrimidinedione derivatives had been discussed, which would be useful for developing novel DPP-4 inhibitors as treating type 2 diabetes.
ESTHER : Li_2018_Bioorg.Med.Chem.Lett_28_2131
PubMedSearch : Li_2018_Bioorg.Med.Chem.Lett_28_2131
PubMedID: 29773502

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 : Plasma exosome levels in non-small-cell lung cancer: Correlation with clinicopathological features and prognostic implications - Liu_2018_Cancer.Biomark_22_267
Author(s) : Liu Q , Xiang Y , Yuan S , Xie W , Li C , Hu Z , Wu N , Wu L , Yu Z , Bai L , Li Y
Ref : Cancer Biomark , 22 :267 , 2018
Abstract : BACKGROUND: Biomarker studies revealed important clinical significance of exosome for cancer patients. However, there is currently no consensus on exosome quantification methods. METHODS: Bicinchoninic acid (BCA) method, acetylcholinesterase (AChE) method and nanoparticle tracking analysis (NTA) were utilized to quantify 20 plasma exosome samples, and interrelations between these three methods were explored. Associations of plasma exosome levels with characteristics and prognosis of 208 non-small-cell lung cancer (NSCLC) patients were investigated. RESULTS: Results of the three methods for exosome quantification were significantly correlated with each other. Correlation coefficient between AChE and NTA (r= 0.79, P< 0.001) was greater than that between BCA and NTA (r= 0.64, P= 0.003). Plasma exosome levels of 208 NSCLC patients were then quantified with AChE method. Exosome level was significantly associated with tumour stage (P< 0.001) and the history of chronic obstructive pulmonary disease (P= 0.023). Cox proportional hazard analysis demonstrated that higher exosome level was independently associated with poorer overall survival (P= 0.033; hazard ratio = 1.72, 95% confidence interval: 1.05-2.83). CONCLUSIONS: Plasma exosome level correlates with tumor stage and the history of chronic obstructive pulmonary disease, and may serve as a prognostic factor for NSCLC.
ESTHER : Liu_2018_Cancer.Biomark_22_267
PubMedSearch : Liu_2018_Cancer.Biomark_22_267
PubMedID: 29660899

Title : Induction of hepatic miR-34a by perfluorooctanoic acid regulates metabolism-related genes in mice - Cui_2018_Environ.Pollut_244_270
Author(s) : Cui R , Li C , Wang J , Dai J
Ref : Environ Pollut , 244 :270 , 2018
Abstract : Perfluorooctanoic acid (PFOA) is a widespread organic pollutant with various toxicological impacts on the liver. Members of the miR-34 family are P53-targeted growth suppressors. We found that PFOA exposure (5mg/kg/d PFOA for 28d) resulted in a significant increase of miR-34a in the livers of mice but had no effect on either miR-34b or miR-34c. We knocked out miR-34a in mice to explore the role of elevated miR-34a in PFOA-induced liver toxicity. Compared with the corresponding untreated control, significant increases in liver weight as well as serum alanine transaminase, aspartate aminotransferase, and cholinesterase levels were observed in miR-34a(-/-) and wild-type mice after PFOA exposure. Hepatic cells showed similar swelling in both miR-34a(-/-) and wild-type mice after PFOA treatment. Hepatic RNA-sequencing (RNA-seq) showed that PFOA led to significant alteration in lipid metabolism genes, especially those involved in the peroxisome proliferator-activated receptor pathway, in both wild-type and miR-34a null mice. With or without PFOA treatment, relatively fewer genes were altered in miR-34a(-/-) livers compared to wild-type livers. Among the changed genes by miR-34a, the most dominant were metabolism-related genes, such as Fabp3, Cyp7a1, and Apoa4. Our in vivo study indicated that miR-34a mainly exerts a metabolic regulation role, rather than the pro-apoptosis and cell cycle arrest role reported previously by many in vitro studies. In addition, although hepatic P53 was unchanged, the active type of P53 (acetylated P53 (acetyl-p53, Lys379)) was markedly altered under PFOA treatment. Therefore, the increase in acetylated P53 may have activated the transcription of miR-34a in mouse livers after PFOA treatment.
ESTHER : Cui_2018_Environ.Pollut_244_270
PubMedSearch : Cui_2018_Environ.Pollut_244_270
PubMedID: 30342367

Title : Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides - Li_2018_Nat.Commun_9_4951
Author(s) : Li C , Cao YX , Wang R , Wang YN , Lan Q , Wang XS
Ref : Nat Commun , 9 :4951 , 2018
Abstract : The selective incorporation of gem-difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp(3))-CF2 bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer's disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery.
ESTHER : Li_2018_Nat.Commun_9_4951
PubMedSearch : Li_2018_Nat.Commun_9_4951
PubMedID: 30470757

Title : Purification and characterization of a hydroxynitrile lyase from Amygdalus pedunculata Pall - Yao_2018_Int.J.Biol.Macromol_118_189
Author(s) : Yao L , Li H , Yang J , Li C , Shen Y
Ref : Int J Biol Macromol , 118 :189 , 2018
Abstract : Hydroxynitrile lyases (HNLs) are widely used in the asymmetric synthesis of cyanohydrins which are organic compounds used in the production of fine chemicals and pharmaceuticals, because these enzymes exhibit high catalytic efficiency and are very economical. In the present study, seeds of A. pedunculata Pall were identified as new potential source of HNLs. The HNL from A. pedunculata Pall (APHNL) was purified 138 fold and 4.20% yield with a specific activity of 661U/mg. SDS-PAGE result showed the enzyme to be present as a monomer and the relative molecular mass determined by MALDI-TOF MS was 61kDa. APHNL owned highest activity at pH6.0 and at 60 degrees C temperature, showing activity up to 80 degrees C and stable up to 60 degrees C. APHNL has a Km of 0.5mM, Vmax of 665.9mumolmg(-1)min(-1), Kcat of 676.5s(-1) and Kcat/Km of 1353s(-1)mM(-1) using mandelonitrile as substrate. Syntheses of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were carried out using APHNL and molar conversion of (R)-mandelonitrile and (R)-2-Hydroxy-2-(3-phenoxy-phenyl)-acetonitrile were 90% and 98% with 94% and 93% ee, respectively. These results indicated that APHNL was an excellent biocatalyst and has very high potential for synthesis of enantiopure cyanohydrins.
ESTHER : Yao_2018_Int.J.Biol.Macromol_118_189
PubMedSearch : Yao_2018_Int.J.Biol.Macromol_118_189
PubMedID: 29890248

Title : Protein Crystallography and Site-Direct Mutagenesis Analysis of the Poly(ethylene terephthalate) Hydrolase PETase from Ideonella sakaiensis - Liu_2018_Chembiochem_19_1471
Author(s) : Liu B , He L , Wang L , Li T , Li C , Liu H , Luo Y , Bao R
Ref : Chembiochem , 19 :1471 , 2018
Abstract : Unlike traditional recycling strategies, biodegradation is a sustainable solution for disposing of poly(ethylene terephthalate) (PET) waste. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET and is, thus, a prominent candidate for PET degradation. On the basis of biochemical analysis, we propose that a wide substrate-binding pocket is critical for its excellent ability to hydrolyze crystallized PET. Structure-guided site-directed mutagenesis revealed an improvement in PETase catalytic efficiency, providing valuable insight into how the molecular engineering of PETase can optimize its application in biocatalysis.
ESTHER : Liu_2018_Chembiochem_19_1471
PubMedSearch : Liu_2018_Chembiochem_19_1471
PubMedID: 29603535
Gene_locus related to this paper: idesa-peth

Title : Biopanning of allergens from wasp sting patients - Chai_2018_Biosci.Rep_38_
Author(s) : Chai L , Yang X , Liu M , Liu C , Han L , Guo H , Li C , Sun Y , Li X , Xiao M , Fang Z
Ref : Bioscience Reports , 38 : , 2018
Abstract : OBJECTIVE: Wasp venom is a potentially important natural drug, but it can cause hypersensitivity reactions. The purpose of the present study was to systematically study the epitopes of wasp venom. METHODS: Using a random 12-peptide phage library, we performed antibody-binding epitope panning on ten serum samples from wasp sting victims at 3 h and 4 days after the sting. The panning epitopes were identified by high-throughput sequencing and matched with wasp venom proteins by BLAST. The panned antibody-binding epitopes were verified by ELISA. RESULTS: A total of 35 specific potential wasp venom epitopes in 4 days were identified. Amongst them, twelve peptide epitopes were matched with nine wasp venom proteins, namely, vitellogenin precursor, hexamerin 70b precursor, venom carboxylesterase-6 precursor, MRJP5, major royal jelly protein 8 precursor, venom acid phosphatase Acph-1 precursor, phospholipase A2, venom serine protease 34 precursor, and major royal jelly protein 9 precursor. The changes in serum IgM antibodies induced by wasp venom were confirmed by ELISA based on the 12 peptide epitopes. CONCLUSION: The nine wasp venom proteins are potential allergens, which should be excluded or modified in the potential biomedical applications of wasp venom.
ESTHER : Chai_2018_Biosci.Rep_38_
PubMedSearch : Chai_2018_Biosci.Rep_38_
PubMedID: 30249752

Title : Bioinformatics Analysis and Characterization of Highly Efficient Polyvinyl Alcohol (PVA)-Degrading Enzymes from the Novel PVA Degrader Stenotrophomonas rhizophila QL-P4 - Wei_2018_Appl.Environ.Microbiol_84_
Author(s) : Wei Y , Fu J , Wu J , Jia X , Zhou Y , Li C , Dong M , Wang S , Zhang J , Chen F
Ref : Applied Environmental Microbiology , 84 : , 2018
Abstract : Polyvinyl alcohol (PVA) is used widely in industry, and associated environmental pollution is a serious problem. Herein, we report a novel, efficient PVA degrader, Stenotrophomonas rhizophila QL-P4, isolated from fallen leaves from a virgin forest in the Qinling Mountains. The complete genome was obtained using single-molecule real-time (SMRT) technology and corrected using Illumina sequencing. Bioinformatics analysis revealed eight PVA/vinyl alcohol oligomer (OVA)-degrading genes. Of these, seven genes were predicted to be involved in the classic intracellular PVA/OVA degradation pathway, and one (BAY15_3292) was identified as a novel PVA oxidase. Five PVA/OVA-degrading enzymes were purified and characterized. One of these, BAY15_1712, a PVA dehydrogenase (PVADH), displayed high catalytic efficiency toward PVA and OVA substrate. All reported PVADHs only have PVA-degrading ability. Most importantly, we discovered a novel PVA oxidase (BAY15_3292) that exhibited higher PVA-degrading efficiency than the reported PVADHs. Further investigation indicated that BAY15_3292 plays a crucial role in PVA degradation in S. rhizophila QL-P4. Knocking out BAY15_3292 resulted in a significant decline in PVA-degrading activity in S. rhizophila QL-P4. Interestingly, we found that BAY15_3292 possesses exocrine activity, which distinguishes it from classic PVADHs. Transparent circle experiments further proved that BAY15_3292 greatly affects extracellular PVA degradation in S. rhizophila QL-P4. The exocrine characteristics of BAY15_3292 facilitate its potential application to PVA bioremediation. In addition, we report three new efficient secondary alcohol dehydrogenases (SADHs) with OVA-degrading ability in S. rhizophila QL-P4; in contrast, only one OVA-degrading SADH was reported previously.IMPORTANCE With the widespread application of PVA in industry, PVA-related environmental pollution is an increasingly serious issue. Because PVA is difficult to degrade, it accumulates in aquatic environments and causes chronic toxicity to aquatic organisms. Biodegradation of PVA, as an economical and environment-friendly method, has attracted much interest. To date, effective and applicable PVA-degrading bacteria/enzymes have not been reported. Herein, we report a new efficient PVA degrader (S. rhizophila QL-P4) that has five PVA/OVA-degrading enzymes with high catalytic efficiency, among which BAY15_1712 is the only reported PVADH with both PVA- and OVA-degrading abilities. Importantly, we discovered a novel PVA oxidase (BAY15_3292) that is not only more efficient than other reported PVA-degrading PVADHs but also has exocrine activity. Overall, our findings provide new insight into PVA-degrading pathways in microorganisms and suggest S. rhizophila QL-P4 and its enzymes have the potential for application to PVA bioremediation to reduce or eliminate PVA-related environmental pollution.
ESTHER : Wei_2018_Appl.Environ.Microbiol_84_
PubMedSearch : Wei_2018_Appl.Environ.Microbiol_84_
PubMedID: 29079625

Title : Heme scavenging reduces pulmonary endoplasmic reticulum stress, fibrosis, and emphysema - Aggarwal_2018_JCI.Insight_3_
Author(s) : Aggarwal S , Ahmad I , Lam A , Carlisle MA , Li C , Wells JM , Raju SV , Athar M , Rowe SM , Dransfield MT , Matalon S
Ref : JCI Insight , 3 : , 2018
Abstract : Pulmonary fibrosis and emphysema are irreversible chronic events after inhalation injury. However, the mechanism(s) involved in their development remain poorly understood. Higher levels of plasma and lung heme have been recorded in acute lung injury associated with several insults. Here, we provide the molecular basis for heme-induced chronic lung injury. We found elevated plasma heme in chronic obstructive pulmonary disease (COPD) (GOLD stage 4) patients and also in a ferret model of COPD secondary to chronic cigarette smoke inhalation. Next, we developed a rodent model of chronic lung injury, where we exposed C57BL/6 mice to the halogen gas, bromine (Br2) (400 ppm, 30 minutes), and returned them to room air resulting in combined airway fibrosis and emphysematous phenotype, as indicated by high collagen deposition in the peribronchial spaces, increased lung hydroxyproline concentrations, and alveolar septal damage. These mice also had elevated pulmonary endoplasmic reticulum (ER) stress as seen in COPD patients; the pharmacological or genetic diminution of ER stress in mice attenuated Br2-induced lung changes. Finally, treating mice with the heme-scavenging protein, hemopexin, reduced plasma heme, ER stress, airway fibrosis, and emphysema. This is the first study to our knowledge to report elevated heme in COPD patients and establishes heme scavenging as a potential therapy after inhalation injury.
ESTHER : Aggarwal_2018_JCI.Insight_3_
PubMedSearch : Aggarwal_2018_JCI.Insight_3_
PubMedID: 30385726

Title : Controllable Growth of Core-Shell Nanogels via Esterase-Induced Self-Assembly of Peptides for Drug Delivery - Wu_2018_J.Biomed.Nanotechnol_14_354
Author(s) : Wu C , Hu W , Wei Q , Qiao L , Gao Y , Lv Y , Liu M , Li C , Wang X , Wang Q
Ref : J Biomed Nanotechnol , 14 :354 , 2018
Abstract : In this work, we developed an unexplored enzyme-responsive core-shell nanogel via the assembly of hydrogelators at the surface of silicon nanoparticles. The immobilized carboxylesterase at the surface of silicon nanoparticles can catalyse precursors into hydrogelators, self-assembling around the surface of silicon nanoparticles owing to its surface confinement effect. These novel phenomena can be confirmed by observation of their morphology and increased diameters through scanning electron microscopy, transmission electron microscopy and dynamic light scattering. Moreover, these resulting core-shell nanogels can achieve controlled growth of the gel layer by means of changing the concentrations of precursors. Because of their good biocompatibility, these nanogels can realize applications in enzyme-specific drug delivery as nanocarriers.
ESTHER : Wu_2018_J.Biomed.Nanotechnol_14_354
PubMedSearch : Wu_2018_J.Biomed.Nanotechnol_14_354
PubMedID: 31352931

Title : The dual DPP4 inhibitor and GPR119 agonist HBK001 regulates glycemic control and beta cell function ex and in vivo - Huan_2017_Sci.Rep_7_4351
Author(s) : Huan Y , Jiang Q , Li G , Bai G , Zhou T , Liu S , Li C , Liu Q , Sun S , Yang M , Guo N , Wang X , Wang S , Liu Y , Wang G , Huang H , Shen Z
Ref : Sci Rep , 7 :4351 , 2017
Abstract : Glucagon like peptide-1 (GLP-1) plays a vital role in glucose homeostasis and sustaining beta-cell function. Currently there are two major methods to enhance endogenous GLP-1 activity; inhibiting dipeptidyl peptidase-4 (DPP4) or activating G protein-coupled receptor 119 (GPR119). Here we describe and validate a novel dual-target compound, HBK001, which can both inhibit DPP4 and activate GPR119 ex and in vivo. We show that HBK001 can promote glucose-stimulated insulin secretion in mouse and human primary islets. A single administration of HBK001 in ICR mice can increase plasma incretins levels much more efficiently than linagliptin, a classic DPP4 inhibitor. Long-term treatment of HBK001 in KKAy mice can ameliorate hyperglycemia as well as improve glucose tolerance, while linagliptin fails to achieve such glucose-lowing effects despite inhibiting 95% of serum DPP4 activity. Moreover, HBK001 can increase first-phase insulin secretion in KKAy mice, suggesting a direct effect on islet beta-cells via GPR119 activation. Furthermore, HBK001 can improve islet morphology, increase beta-cell proliferation and up-regulate genes involved in improved beta-cell function. Thus, we have identified, designed and synthesized a novel dual-target compound, HBK001, which represents a promising therapeutic candidate for type 2 diabetes, especially for patients who are insensitive to current DPP4 inhibitors.
ESTHER : Huan_2017_Sci.Rep_7_4351
PubMedSearch : Huan_2017_Sci.Rep_7_4351
PubMedID: 28659588

Title : Granularity and Laxative Effect of Ultrafine Powder of Dendrobium officinale - Luo_2017_J.Med.Food_20_180
Author(s) : Luo D , Qu C , Zhang Z , Xie J , Xu L , Yang H , Li C , Lin G , Wang H , Su Z
Ref : J Med Food , 20 :180 , 2017
Abstract : Constipation is a common disorder that is a significant source of morbidity among people around the world ranging from 2% to 28%. Dendrobium officinale Kimura et Migo is a traditional herbal medicine and health food used for tonicity of the stomach and promotion of body fluid production in China. This study aimed to prepare the ultrafine powder of Dendrobium officinale (UDO) and investigate its laxative effect and potential mechanism in mice with diphenoxylate-induced constipation. Results indicated that the mean diameter (d50) of UDO obtained by ball milling was 6.56 mum. UDO (62.5, 125, and 250 mg/kg, p.o.) could significantly enhance the gastrointestinal transit ratio and promote fecal output. Moreover, UDO treatment resulted in significant increases in the serum levels of acetylcholinesterase (AChE), gastrin (Gas), motilin (MTL), and substance P (SP), and obviously decreased serum contents of somatostatin (SS). Taken together, UDO, which can be easily obtained through milling to a satisfactory particle size, exhibited obvious laxative effect in diphenoxylate-induced constipated mice, and the mechanism might be associated with elevated levels of AChE, Gas, MTL, SP, and reduced production of SS. UDO has the potential for further development into an alternative effective diet therapy for constipation.
ESTHER : Luo_2017_J.Med.Food_20_180
PubMedSearch : Luo_2017_J.Med.Food_20_180
PubMedID: 28146409

Title : Characterization and function of Mycobacterium tuberculosis H37Rv Lipase Rv1076 (LipU) - Li_2017_Microbiol.Res_196_7
Author(s) : Li C , Li Q , Zhang Y , Gong Z , Ren S , Li P , Xie J
Ref : Microbiol Res , 196 :7 , 2017
Abstract : Lipids and lipases/esterases are essential for Mycobacterium tuberculosis (Mtb) survival and persistence, even virulence. Mycobacterium tuberculosis H37Rv Rv1076 (LipU), a member of lipase family, is homologous to the human Hormone Sensitive Lipase (HSL) based on the presence of conserved motif 'GXSXG'. To define the enzymatic characteristics of rv1076, the gene was cloned, and expressed in Escherichia coli. The protein was purified for enzymatic characterization. LipU showed high specific activity for the hydrolysis of short carbon chain substrates with optimal activity at 40 degrees C/pH 8.0 and stability at low temperature and near-neutral pH. The specific activity, Km and Vmax of LipU was calculated to 176.7U/mg, 1.73muM and 62.24muM/min respectively. Ionic detergents can inhibit its activity. The active-site residues of LipU were determined to be Ser140, Asp244 and His269 by site-directed mutagenesis. The upregulation of Mycobacterium tuberculosis rv1076 under nutritive stress implicates a role in starvation.
ESTHER : Li_2017_Microbiol.Res_196_7
PubMedSearch : Li_2017_Microbiol.Res_196_7
PubMedID: 28164792
Gene_locus related to this paper: myctu-Rv1076

Title : Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus - Zhou_2017_Sci.Adv_3_eaao4966
Author(s) : Zhou J , Li C , Zhao G , Chu H , Wang D , Yan HH , Poon VK , Wen L , Wong BH , Zhao X , Chiu MC , Yang D , Wang Y , Au-Yeung RKH , Chan IH , Sun S , Chan JF , To KK , Memish ZA , Corman VM , Drosten C , Hung IF , Zhou Y , Leung SY , Yuen KY
Ref : Sci Adv , 3 :eaao4966 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
ESTHER : Zhou_2017_Sci.Adv_3_eaao4966
PubMedSearch : Zhou_2017_Sci.Adv_3_eaao4966
PubMedID: 29152574

Title : Metabolism of KO143, an ABCG2 inhibitor - Liu_2017_Drug.Metab.Pharmacokinet_32_193
Author(s) : Liu K , Zhu J , Huang Y , Li C , Lu J , Sachar M , Li S , Ma X
Ref : Drug Metab Pharmacokinet , 32 :193 , 2017
Abstract : The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice. K1 is an analog of KO143 without the ester group. We found that the metabolic stability of K1 was significantly improved in HLM when compared to KO143. These data suggest that the ester group in KO143 is the major cause of the poor metabolic stability of KO143. The data from this study can be used to guide the development of KO143 analogs with better metabolic properties.
ESTHER : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedSearch : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedID: 28619281

Title : Stereoselective Hydrolysis of Epoxides by reVrEH3, a Novel Vigna radiata Epoxide Hydrolase with High Enantioselectivity or High and Complementary Regioselectivity - Hu_2017_J.Agric.Food.Chem_65_9861
Author(s) : Hu D , Tang C , Li C , Kan T , Shi X , Feng L , Wu M
Ref : Journal of Agricultural and Food Chemistry , 65 :9861 , 2017
Abstract : To provide more options for the stereoselective hydrolysis of epoxides, an epoxide hydrolase (VrEH3) gene from Vigna radiata was cloned and expressed in Escherichia coli. Recombinant VrEH3 displayed the maximum activity at pH 7.0 and 45 degrees C and high stability at pH 4.5-7.5 and 55 degrees C. Notably, reVrEH3 exhibited high and complementary regioselectivity toward styrene oxides 1a-3a and high enantioselectivity (E = 48.7) toward o-cresyl glycidyl ether 9a. To elucidate these interesting phenomena, the interactions of the three-dimensional structure between VrEH3 and enantiomers of 1a and 9a were analyzed by molecular docking simulation. Using E. coli/vreh3 whole cells, gram-scale preparations of (R)-1b and (R)-9a were performed by enantioconvergent hydrolysis of 100 mM rac-1a and kinetic resolution of 200 mM rac-9a in the buffer-free water system at 25 degrees C. These afforded (R)-1b with >99% eep and 78.7% overall yield after recrystallization and (R)-9a with >99% ees, 38.7% overall yield, and 12.7 g/L/h space-time yield.
ESTHER : Hu_2017_J.Agric.Food.Chem_65_9861
PubMedSearch : Hu_2017_J.Agric.Food.Chem_65_9861
PubMedID: 29058432
Gene_locus related to this paper: vigra-Vreh3

Title : Thyroglobulin gene mutations in Chinese patients with congenital hypothyroidism - Hu_2016_Mol.Cell.Endocrinol_423_60
Author(s) : Hu X , Chen R , Fu C , Fan X , Wang J , Qian J , Yi S , Li C , Luo J , Su J , Zhang S , Xie B , Zheng H , Lai Y , Chen Y , Li H , Gu X , Chen S , Shen Y
Ref : Mol Cell Endocrinol , 423 :60 , 2016
Abstract : Mutations in Thyroglobulin (TG) are common genetic causes of congenital hypothyroidism (CH). But the TG mutation spectrum and its frequency in Chinese CH patients have not been investigated. Here we conducted a genetic screening of TG gene in a cohort of 382 Chinese CH patients. We identified 22 rare non-polymorphic variants including six truncating variants and 16 missense variants of unknown significance (VUS). Seven patients carried homozygous pathogenic variants, and three patients carried homozygous or compound heterozygous VUS. 48 out of 382 patients carried one of 18 heterozygous VUS which is significantly more often than their occurrences in control cohort (P < 0.0001). Unique to Asian population, the c.274+2T>G variant is the most common pathogenic variant with an allele frequency of 0.021. The prevalence of CH due to TG gene defect in Chinese population was estimated to be approximately 1/101,000. Our study uncovered ethnicity specific TG mutation spectrum and frequency.
ESTHER : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedSearch : Hu_2016_Mol.Cell.Endocrinol_423_60
PubMedID: 26777470
Gene_locus related to this paper: human-TG

Title : Identification and Biochemical Properties of Two New Acetylcholinesterases in the Pond Wolf Spider (Pardosa pseudoannulata) - Meng_2016_PLoS.One_11_e0158011
Author(s) : Meng X , Li C , Xiu C , Zhang J , Li J , Huang L , Zhang Y , Liu Z
Ref : PLoS ONE , 11 :e0158011 , 2016
Abstract : Acetylcholinesterase (AChE), an important neurotransmitter hydrolase in both invertebrates and vertebrates, is targeted by organophosphorus and carbamate insecticides. In this study, two new AChEs were identified in the pond wolf spider Pardosa pseudoannulata, an important predatory natural enemy of several insect pests. In total, four AChEs were found in P. pseudoannulata (including two AChEs previously identified in our laboratory). The new putative AChEs PpAChE3 and PpAChE4 contain most of the common features of the AChE family, including cysteine residues, choline binding sites, the conserved sequence 'FGESAG' and conserved aromatic residues but with a catalytic triad of 'SDH' rather than 'SEH'. Recombinant enzymes expressed in Sf9 cells showed significant differences in biochemical properties compared to other AChEs, such as the optimal pH, substrate specificity, and catalytic efficiency. Among three test substrates, PpAChE1, PpAChE3 and PpAChE4 showed the highest catalytic efficiency (Vmax/KM) for ATC (acetylthiocholine iodide), with PpAChE3 exhibiting a clear preference for ATC based on the VmaxATC/VmaxBTC ratio. In addition, the four PpAChEs were more sensitive to the AChE-specific inhibitor BW284C51, which acts against ATC hydrolysis, than to the BChE-specific inhibitor ISO-OMPA, which acts against BTC hydrolysis, with at least a 8.5-fold difference in IC50 values for each PpAChE. PpAChE3, PpAChE4, and PpAChE1 were more sensitive than PpAChE2 to the tested Carb insecticides, and PpAChE3 was more sensitive than the other three AChEs to the tested OP insecticides. Based on all the results, two new functional AChEs were identified from P. pseudoannulata. The differences in AChE sequence between this spider and insects enrich our knowledge of invertebrate AChE diversity, and our findings will be helpful for understanding the selectivity of insecticides between insects and natural enemy spiders.
ESTHER : Meng_2016_PLoS.One_11_e0158011
PubMedSearch : Meng_2016_PLoS.One_11_e0158011
PubMedID: 27337188
Gene_locus related to this paper: 9arac-KU501290 , 9arac-KU501289 , 9arac-KU501288 , 9arac-KU501287 , 9arac-v5qqc6 , 9arac-v5qqr1

Title : Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways - Chu_2016_J.Infect.Dis_213_904
Author(s) : Chu H , Zhou J , Wong BH , Li C , Chan JF , Cheng ZS , Yang D , Wang D , Lee AC , Yeung ML , Cai JP , Chan IH , Ho WK , To KK , Zheng BJ , Yao Y , Qin C , Yuen KY
Ref : J Infect Dis , 213 :904 , 2016
Abstract : Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.
ESTHER : Chu_2016_J.Infect.Dis_213_904
PubMedSearch : Chu_2016_J.Infect.Dis_213_904
PubMedID: 26203058

Title : De novo transcriptome analysis in radish (Raphanus sativus L.) and identification of critical genes involved in bolting and flowering - Nie_2016_BMC.Genomics_17_389
Author(s) : Nie S , Li C , Xu L , Wang Y , Huang D , Muleke EM , Sun X , Xie Y , Liu L
Ref : BMC Genomics , 17 :389 , 2016
Abstract : BACKGROUND: The appropriate timing of bolting and flowering is pivotal for reproductive success in Brassicaceae crops including radish (Raphanus sativus L.). Although several flowering regulatory pathways had been described in some plant species, no study on genetic networks of bolting and flowering regulation was performed in radish. In this study, to generate dataset of radish unigene sequences for large-scale gene discovery and functional pathway identification, a cDNA library from mixed radish leaves at different developmental stages was subjected to high-throughput RNA sequencing (RNA-seq). RESULTS: A total of 54.64 million clean reads and 111,167 contigs representing 53,642 unigenes were obtained from the radish leaf transcriptome. Among these, 50,385 unigenes were successfully annotated by BLAST searching against the public protein databases. Functional classification and annotation indicated that 42,903 and 15,382 unique sequences were assigned to 55 GO terms and 25 COG categories, respectively. KEGG pathway analysis revealed that 25,973 unigenes were classified into 128 functional pathways, among which 24 candidate genes related to plant circadian rhythm were identified. Moreover, 142 potential bolting and flowering-related genes involved in various flowering pathways were identified. In addition, seven critical bolting and flowering-related genes were isolated and profiled by T-A cloning and RT-qPCR analysis. Finally, a schematic network model of bolting and flowering regulation and pathways was put forward in radish. CONCLUSIONS: This study is the first report on systematic identification of bolting and flowering-related genes based on transcriptome sequencing and assembly in radish. These results could provide a foundation for further investigating bolting and flowering regulatory networks in radish, and facilitate dissecting molecular genetic mechanisms underlying bolting and flowering in Brassicaceae vegetable crops.
ESTHER : Nie_2016_BMC.Genomics_17_389
PubMedSearch : Nie_2016_BMC.Genomics_17_389
PubMedID: 27216755
Gene_locus related to this paper: rapsa-a0a6j0lzs2

Title : Molecular Modeling on Berberine Derivatives toward BuChE: An Integrated Study with Quantitative Structure-Activity Relationships Models, Molecular Docking, and Molecular Dynamics Simulations - Fang_2016_Chem.Biol.Drug.Des_87_649
Author(s) : Fang J , Pang X , Wu P , Yan R , Gao L , Li C , Lian W , Wang Q , Liu AL , Du GH
Ref : Chemical Biology Drug Des , 87 :649 , 2016
Abstract : A dataset of 67 berberine derivatives for the inhibition of butyrylcholinesterase (BuChE) was studied based on the combination of quantitative structure-activity relationships models, molecular docking, and molecular dynamics methods. First, a series of berberine derivatives were reported, and their inhibitory activities toward butyrylcholinesterase (BuChE) were evaluated. By 2D- quantitative structure-activity relationships studies, the best model built by partial least-square had a conventional correlation coefficient of the training set (R(2) ) of 0.883, a cross-validation correlation coefficient (Qcv2) of 0.777, and a conventional correlation coefficient of the test set (Rpred2) of 0.775. The model was also confirmed by Y-randomization examination. In addition, the molecular docking and molecular dynamics simulation were performed to better elucidate the inhibitory mechanism of three typical berberine derivatives (berberine, C2, and C55) toward BuChE. The predicted binding free energy results were consistent with the experimental data and showed that the van der Waals energy term (DeltaEvdw ) difference played the most important role in differentiating the activity among the three inhibitors (berberine, C2, and C55). The developed quantitative structure-activity relationships models provide details on the fine relationship linking structure and activity and offer clues for structural modifications, and the molecular simulation helps to understand the inhibitory mechanism of the three typical inhibitors. In conclusion, the results of this study provide useful clues for new drug design and discovery of BuChE inhibitors from berberine derivatives.
ESTHER : Fang_2016_Chem.Biol.Drug.Des_87_649
PubMedSearch : Fang_2016_Chem.Biol.Drug.Des_87_649
PubMedID: 26648584

Title : Biosynthesis of LL-Z1272beta: Discovery of a New Member of NRPS-like Enzymes for Aryl-Aldehyde Formation - Li_2016_Chembiochem_17_904
Author(s) : Li C , Matsuda Y , Gao H , Hu D , Yao XS , Abe I
Ref : Chembiochem , 17 :904 , 2016
Abstract : LL-Z1272beta (1) is a prenylated aryl-aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identified the biosynthetic gene cluster for 1 from Stachybotrys bisbyi PYH05-7, and elucidated the biosynthetic route to 1. The biosynthesis involves a polyketide synthase, a prenyltransferase, and a nonribosomal peptide synthetase (NRPS)-like enzyme, which is responsible for the generation of the aldehyde functionality. Interestingly, the NRPS-like enzyme only accepts the farnesylated substrate to catalyze the carboxylate reduction; this represents a new example of a substrate for adenylation domains.
ESTHER : Li_2016_Chembiochem_17_904
PubMedSearch : Li_2016_Chembiochem_17_904
PubMedID: 26972702
Gene_locus related to this paper: stabi-stba

Title : Discovery of Multitarget-Directed Ligands against Alzheimer's Disease through Systematic Prediction of Chemical-Protein Interactions - Fang_2015_J.Chem.Inf.Model_55_149
Author(s) : Fang J , Li Y , Liu R , Pang X , Li C , Yang R , He Y , Lian W , Liu AL , Du GH
Ref : J Chem Inf Model , 55 :149 , 2015
Abstract : To determine chemical-protein interactions (CPI) is costly, time-consuming, and labor-intensive. In silico prediction of CPI can facilitate the target identification and drug discovery. Although many in silico target prediction tools have been developed, few of them could predict active molecules against multitarget for a single disease. In this investigation, naive Bayesian (NB) and recursive partitioning (RP) algorithms were applied to construct classifiers for predicting the active molecules against 25 key targets toward Alzheimer's disease (AD) using the multitarget-quantitative structure-activity relationships (mt-QSAR) method. Each molecule was initially represented with two kinds of fingerprint descriptors (ECFP6 and MACCS). One hundred classifiers were constructed, and their performance was evaluated and verified with internally 5-fold cross-validation and external test set validation. The range of the area under the receiver operating characteristic curve (ROC) for the test sets was from 0.741 to 1.0, with an average of 0.965. In addition, the important fragments for multitarget against AD given by NB classifiers were also analyzed. Finally, the validated models were employed to systematically predict the potential targets for six approved anti-AD drugs and 19 known active compounds related to AD. The prediction results were confirmed by reported bioactivity data and our in vitro experimental validation, resulting in several multitarget-directed ligands (MTDLs) against AD, including seven acetylcholinesterase (AChE) inhibitors ranging from 0.442 to 72.26 muM and four histamine receptor 3 (H3R) antagonists ranging from 0.308 to 58.6 muM. To be exciting, the best MTDL DL0410 was identified as an dual cholinesterase inhibitor with IC50 values of 0.442 muM (AChE) and 3.57 muM (BCHE) as well as a H3R antagonist with an IC50 of 0.308 muM. This investigation is the first report using mt-QASR approach to predict chemical-protein interaction for a single disease and discovering highly potent MTDLs. This protocol may be useful for in silico multitarget prediction of other diseases.
ESTHER : Fang_2015_J.Chem.Inf.Model_55_149
PubMedSearch : Fang_2015_J.Chem.Inf.Model_55_149
PubMedID: 25531792

Title : Construction of an immobilised acetylcholinesterase column and its application in screening insecticidal constituents from Magnolia officinalis - Ye_2015_Pest.Manag.Sci_71_607
Author(s) : Ye YH , Li C , Yang J , Ma L , Xiao Y , Hu J , Rajput NA , Gao CF , Zhang YY , Wang MH
Ref : Pest Manag Sci , 71 :607 , 2015
Abstract : BACKGROUND: Application of a matrix-immobilised target enzyme for screening inhibitors is widely used in drug development, but there are few studies in insecticide discovery. In this paper, an economical and effective immobilised acetylcholinesterase (AChE) column was prepared using the sol-gel embedment method, which was further combined with high-performance liquid chromatography for screening the AChE inhibitors and insecticidal compounds from complex natural products.
RESULTS: AChE inhibitory constituents magnolol and honokiol were isolated from the ethanol extract of Magnolia officinalis, with IC50 values of 0.069 and 0.057 mM respectively. In an in vivo bioassay, magnolol and honokiol showed insecticidal activity against Nilaparvata lugens, with LC50 values of 0.324 and 0.137 mM, which are comparable with that of commonly used insecticide chlorpyrifos (0.233 mM). Moreover, molecular docking was carried out against a homology model of N. lugens AChE. The complexes showed that magnolol and honokiol placed themselves nicely into the active site of the enzyme and exhibited an interaction energy that was in accordance with our activity profile data. CONCLUSION: These results demonstrate that magnolol and honokiol have great applied potential to be developed as natural insecticides, and an immobilised AChE column is very useful as a rapid screening tool for target enzymes towards potent inhibitors. (c) 2014 Society of Chemical Industry.
ESTHER : Ye_2015_Pest.Manag.Sci_71_607
PubMedSearch : Ye_2015_Pest.Manag.Sci_71_607
PubMedID: 25228142

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

Title : Complete genome sequences of one human respiratory syncytial antigenic group a virus from china and its four mouse-adapted isolates - Zhang_2015_Genome.Announc_3_0
Author(s) : Zhang K , He J , Li C , Bose ME , Henrickson KJ , Zhou J , Zheng BJ
Ref : Genome Announc , 3 : , 2015
Abstract : In this study, one human respiratory syncytial antigenic group A virus (HRSV-A-GZ08-0) and its four BALB/c mouse-adapted isolates were sequenced and elucidated. Nineteen nucleotides were mutated between HRSV-A-GZ08-0 and the four mouse-adapted isolates.
ESTHER : Zhang_2015_Genome.Announc_3_0
PubMedSearch : Zhang_2015_Genome.Announc_3_0
PubMedID: 25744999
Gene_locus related to this paper: 9noca-a0a0d5aa12 , 9noca-a0a0d5abi2

Title : Validating the importance of two acetylcholinesterases in insecticide sensitivities by RNAi in Pardosa pseudoannulata, an important predatory enemy against several insect pests - Meng_2015_Pestic.Biochem.Physiol_125_26
Author(s) : Meng X , Li C , Bao H , Fang J , Liu Z , Zhang Y
Ref : Pestic Biochem Physiol , 125 :26 , 2015
Abstract : The pond wolf spider (Pardosa pseudoannulata) is an important predatory enemy against several insect pests and showed relative different sensitivities to organophosphate and carbamate insecticides compared to insect pests. In our previous studies, two acetylcholinesterases were identified in P. pseudoannulata and played important roles in insecticide sensitivities. In order to understand the contributions of the two acetylcholinesterases to insecticide sensitivities, we firstly employed the RNAi technology in the spider. For a suitable microinjection RNAi method, the injection site, injection volume and interference time were optimized, which then demonstrated that the injection RNAi method was applicable in this spider. With the new RNAi method, it was revealed that both Pp-AChE1 and Pp-AChE2, encoded by genes Ppace1 and Ppace2, were the targets of organophosphate insecticides, but Pp-AChE1 would be more important. In contrast, the carbamate acted selectively on Pp-AChE1. The results showed that Pp-AChE1 was the major catalytic enzyme in P. pseudoannulata and the major target of organophosphate and carbamate insecticides. In a word, an RNAi method was established in the pond wolf spider, which further validated the importance of two acetylcholinesterases in insecticide sensitivities in this spider.
ESTHER : Meng_2015_Pestic.Biochem.Physiol_125_26
PubMedSearch : Meng_2015_Pestic.Biochem.Physiol_125_26
PubMedID: 26615147

Title : DL0410 can reverse cognitive impairment, synaptic loss and reduce plaque load in APP\/PS1 transgenic mice - Yang_2015_Pharmacol.Biochem.Behav_139_15
Author(s) : Yang RY , Zhao G , Wang DM , Pang XC , Wang SB , Fang JS , Li C , Liu AL , Wu S , Du GH
Ref : Pharmacol Biochem Behav , 139 :15 , 2015
Abstract : Cholinesterase inhibitors are first-line therapy for Alzheimer's disease (AD). DL0410 is an AChE/BuChE dual inhibitor with a novel new structural scaffold. It has been demonstrated that DL0410 could improve memory deficits in both Abeta1-42-induced and scopolamine-induced amnesia in mice. In the present study, the therapeutic effect of DL0410 and its action mechanism were investigated in APP/PS1 transgenic mice. Six-month old APP/PS1 transgenic mice were orally administered with DL0410 (3, 10, 30mg/kg/day). After 60days, several behavioural tests, including the Morris water maze and step-down tests, were used to investigate the effects of DL0410 on mice behaviours. All the behavioural experimental results showed that DL0410 significantly ameliorated memory deficits. Meanwhile, DL0410 attenuated neural cell damage and reduced senile plaques significantly in the hippocampus of APP/PS1 transgenic mice. In addition, DL0410 significantly decreased Abeta plaques, while increasing the number of synapses and the thickness of PSD in the hippocampus. We also found DL0410 decreased the expression of APP, NMDAR1B and the phosphorylation level of NMDAR2B, and increased the phosphorylation level of CAMKII and the expression of PSD-95. In this study, the results of behavioural tests demonstrated for the first time that DL0410 could improve learning and memory dysfunction in APP/PS1 transgenic mice. The mechanism of its beneficial effects might be related to cholinesterase inhibition, Abeta plaques inhibition, improvement of synapse loss by regulating of expression of proteins related to synapses. As a result, DL0410 could be considered as a candidate drug for the therapy of AD.
ESTHER : Yang_2015_Pharmacol.Biochem.Behav_139_15
PubMedSearch : Yang_2015_Pharmacol.Biochem.Behav_139_15
PubMedID: 26476132

Title : Chemical and enzymatic synthesis of a library of 2-phenethyl esters and their sensory attributes - Li_2014_Food.Chem_154_205
Author(s) : Li C , Sun J , Li T , Liu SQ , Huang D
Ref : Food Chem , 154 :205 , 2014
Abstract : We report a simple enzymatic approach to synthesise phenethyl esters as natural flavouring materials. Chemical and lipase-catalysed esterification reactions between fatty acids of C4-C18 and 2-phenethyl alcohol were studied. Both methods were compared qualitatively and quantitatively by GC-MS/FID. The acid and thermal stabilities of 2-phenethyl esters were excellent and can meet the requirements of food matrices under most processing conditions. Sensory evaluation showed that each 2-phenethyl ester with a different carbon-chain-length fatty acid had unique sensory notes. Moreover, through Lipozyme TL IM-mediated transesterification, valuable 2-phenethyl alcohol-derived esters were synthesised from butter oil and 2-phenethyl alcohol. The influence of several physicochemical parameters (temperature, substrate molar ratio, enzyme loading, shaking speed and time) on the transesterification reaction was investigated to give optimal reaction conditions, leading to a high yield of 80.0%.
ESTHER : Li_2014_Food.Chem_154_205
PubMedSearch : Li_2014_Food.Chem_154_205
PubMedID: 24518334

Title : Pseudomonas aeruginosa homoserine lactone triggers apoptosis and Bak\/Bax-independent release of mitochondrial cytochrome C in fibroblasts - Schwarzer_2014_Cell.Microbiol_16_1094
Author(s) : Schwarzer C , Fu Z , Shuai S , Babbar S , Zhao G , Li C , Machen TE
Ref : Cell Microbiol , 16 :1094 , 2014
Abstract : Pseudomonas aeruginosa use N-(3-oxododecanoyl)-homoserine lactone (C12) as a quorum-sensing molecule to regulate gene expression in the bacteria. It is expected that in patients with chronic infections with P. aeruginosa, especially as biofilms, local [C12] will be high and, since C12 is lipid soluble, diffuse from the airways into the epithelium and underlying fibroblasts, capillary endothelia and white blood cells. Previous work showed that C12 has multiple effects in human host cells, including activation of apoptosis. The present work tested the involvement of Bak and Bax in C12-triggered apoptosis in mouse embryo fibroblasts (MEF) by comparing MEF isolated from embryos of wild-type (WT) and Bax(-/-) /Bak(-/-) (DKO) mice. In WT MEF C12 rapidly triggered (minutes to 2 h): activation of caspases 3/7 and 8, depolarization of mitochondrial membrane potential (Deltapsimito ), release of cytochrome C from mitochondria into the cytosol, blebbing of plasma membranes, shrinkage/condensation of cells and nuclei and, subsequently, cell killing. A DKO MEF line that was relatively unaffected by the Bak/Bax-dependent proapoptotic stimulants staurosporine and etoposide responded to C12 similarly to WT MEF: activation of caspase 3/7, depolarization of Deltapsimito and release of cytochrome C and cell death. Re-expression of Bax or Bak in DKO MEF did not alter the WT-like responses to C12 in DKO MEF. These data showed that C12 triggers novel, rapid proapoptotic Bak/Bax-independent responses that include events commonly associated with activation of both the intrinsic pathway (depolarization of Deltapsimito and release of cytochrome C from mitochondria into the cytosol) and the extrinsic pathway (activation of caspase 8). Unlike the proapoptotic agonists staurosporine and etoposide that release cytochrome C from mitochondria, C12's effects do not require participation of either Bak or Bax.
ESTHER : Schwarzer_2014_Cell.Microbiol_16_1094
PubMedSearch : Schwarzer_2014_Cell.Microbiol_16_1094
PubMedID: 24438098

Title : Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation - Fang_2014_Acta.Pharm.Sin.B_4_430
Author(s) : Fang J , Wu P , Yang R , Gao L , Li C , Wang D , Wu S , Liu AL , Du GH
Ref : Acta Pharm Sin B , 4 :430 , 2014
Abstract : In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (DeltaE ele+DeltaG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.
ESTHER : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedSearch : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedID: 26579414

Title : Determination of nerve agent metabolites in human urine by isotope-dilution gas chromatography-tandem mass spectrometry after solid phase supported derivatization - Lin_2014_Anal.Bioanal.Chem_406_5213
Author(s) : Lin Y , Chen J , Yan L , Guo L , Wu B , Li C , Feng J , Liu Q , Xie J
Ref : Anal Bioanal Chem , 406 :5213 , 2014
Abstract : A simple and sensitive method has been developed and validated for determining ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), and pinacolyl methylphosphonic acid (PMPA) in human urine using gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with solid phase derivatization (SPD). These four alkyl methylphosphonic acids (AMPAs) are specific hydrolysis products and biomarkers of exposure to classic organophosphorus (OP) nerve agents VX, sarin, RVX, and soman. The AMPAs in urine samples were directly derivatized with pentafluorobenzyl bromide on a solid support and then extracted by liquid-liquid extraction. The analytes were quantified with isotope-dilution by negative chemical ionization (NCI) GC-MS/MS in a selected reaction monitoring (SRM) mode. This method is highly sensitive, with the limits of detection of 0.02 ng/mL for each compound in a 0.2 mL sample of human urine, and an excellent linearity from 0.1 to 50 ng/mL. It is proven to be very suitable for the qualitative and quantitative analyses of degradation markers of OP nerve agents in biomedical samples.
ESTHER : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedSearch : Lin_2014_Anal.Bioanal.Chem_406_5213
PubMedID: 24633564

Title : Insecticide resistance of Anopheles sinensis and An. vagus in Hainan Island, a malaria-endemic area of China - Qin_2014_Parasit.Vectors_7_92
Author(s) : Qin Q , Li Y , Zhong D , Zhou N , Chang X , Li C , Cui L , Yan G , Chen XG
Ref : Parasit Vectors , 7 :92 , 2014
Abstract : BACKGROUND: Malaria is one of the most important public health problems in Southeast Asia, including Hainan Island, China. Vector control is the main malaria control measure, and insecticide resistance is a major concern for the effectiveness of chemical insecticide control programs. The objective of this study is to determine the resistance status of the main malaria vector species to pyrethroids and other insecticides recommended by the World Health Organization (WHO) for indoor residual sprays.
METHODS: The larvae and pupae of Anopheles mosquitoes were sampled from multiple sites in Hainan Island, and five sites yielded sufficient mosquitoes for insecticide susceptibility bioassays. Bioassays of female adult mosquitoes three days after emergence were conducted in the two most abundant species, Anopheles sinensis and An. vagus, using three insecticides (0.05% deltamethrin, 4% DDT, and 5% malathion) and following the WHO standard tube assay procedure. P450 monooxygenase, glutathione S-transferase and carboxylesterase activities were measured. Mutations at the knockdown resistance (kdr) gene and the ace-1 gene were detected by DNA sequencing and PCR-RFLP analysis, respectively.
RESULTS: An. sinensis and An. vagus were the predominant Anopheles mosquito species. An. sinensis was found to be resistant to DDT and deltamethrin. An. vagus was susceptible to deltamethrin but resistant to DDT and malathion. Low kdr mutation (L1014F) frequency (<10%) was detected in An. sinensis, but no kdr mutation was detected in An. vagus populations. Modest to high (45%-75%) ace-1 mutation frequency was found in An. sinensis populations, but no ace-1 mutation was detected in An. vagus populations. Significantly higher P450 monooxygenase and carboxylesterase activities were detected in deltamethrin-resistant An. sinensis, and significantly higher P450 monooxygenase, glutathione S-transferase and carboxylesterase activities were found in malathion-resistant An. vagus mosquitoes.
CONCLUSIONS: Multiple insecticide resistance was found in An. sinensis and An. vagus in Hainan Island, a malaria-endemic area of China. Cost-effective integrated vector control programs that go beyond synthetic insecticides are urgently needed.
ESTHER : Qin_2014_Parasit.Vectors_7_92
PubMedSearch : Qin_2014_Parasit.Vectors_7_92
PubMedID: 24589247
Gene_locus related to this paper: anoga-ACHE1

Title : Molecular traces of alternative social organization in a termite genome - Terrapon_2014_Nat.Commun_5_3636
Author(s) : Terrapon N , Li C , Robertson HM , Ji L , Meng X , Booth W , Chen Z , Childers CP , Glastad KM , Gokhale K , Gowin J , Gronenberg W , Hermansen RA , Hu H , Hunt BG , Huylmans AK , Khalil SM , Mitchell RD , Munoz-Torres MC , Mustard JA , Pan H , Reese JT , Scharf ME , Sun F , Vogel H , Xiao J , Yang W , Yang Z , Zhou J , Zhu J , Brent CS , Elsik CG , Goodisman MA , Liberles DA , Roe RM , Vargo EL , Vilcinskas A , Wang J , Bornberg-Bauer E , Korb J , Zhang G , Liebig J
Ref : Nat Commun , 5 :3636 , 2014
Abstract : Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.
ESTHER : Terrapon_2014_Nat.Commun_5_3636
PubMedSearch : Terrapon_2014_Nat.Commun_5_3636
PubMedID: 24845553
Gene_locus related to this paper: zoone-a0a067r283 , zoone-a0a067qst6 , zoone-a0a067rbc7 , zoone-a0a067qz43 , zoone-a0a067qn94 , zoone-a0a067rbw9 , zoone-a0a067qx93 , zoone-a0a067rcf4 , zoone-a0a067r8q8 , zoone-a0a067rh81 , zoone-a0a067r506 , zoone-a0a067qxd4 , zoone-a0a067qy86 , zoone-a0a067qsw2 , zoone-a0a067qfp9 , zoone-a0a067ru91 , zoone-a0a067rwu7 , zoone-a0a067rmu8 , zoone-a0a067r773 , zoone-a0a067qlt8 , zoone-a0a067qhm6 , zoone-a0a067qjz2 , zoone-a0a067qs20 , zoone-a0a067rmu4 , zoone-a0a067qty7 , zoone-a0a067rk35 , zoone-a0a067rk64 , zoone-a0a067rj74 , zoone-a0a067rp97 , zoone-a0a067rjm1

Title : Hyphomonas beringensis sp. nov. and Hyphomonas chukchiensis sp. nov., isolated from surface seawater of the Bering Sea and Chukchi Sea - Li_2014_Antonie.Van.Leeuwenhoek_106_657
Author(s) : Li C , Lai Q , Li G , Dong C , Wang J , Liao Y , Shao Z
Ref : Antonie Van Leeuwenhoek , 106 :657 , 2014
Abstract : Two Gram-negative, non-spore-forming, oval to pear shaped motile strains, designated 25B14_1(T) and BH-BN04-4(T), isolated from surface seawater from the Bering Sea and Chukchi Sea, respectively, were subjected to polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences demonstrated that strains 25B14_1(T) and BH-BN04-4(T) clustered together with Hyphomonas atlanticus 22II1-22F38(T) and Hyphomonas oceanitis DSM 5155(T), respectively, within genus Hyphomonas. Based on whole genome sequence analysis, the calculated DDH and ANIm values between strain 25B14_1(T) and BH-BN04-4(T) are 18.8 and 83.19% respectively. The calculated DDH values of strain 25B14_1(T) and BH-BN04-4(T) with seven type strains ranged from 18.2 to 19.9% and from 18.4 to 40.4%, respectively. The ANIm values of strain 25B14_1(T) and BH-BN04-4(T) with seven type strains ranged from 83.00 to 84.67% and from 83.14 to 90.58%, respectively. Both isolates were found to contain Q-11 as the predominant respiratory quinone. The major fatty acids of strain 25B14_1(T) were identified as C(16:0), C(17:0), C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c as defined by MIDI), while in the case of strain BH-BN04-4(T) they were identified as C(16:0), C(18:1)omega7c-methyl and Summed Feature 8 (C(18:1)omega6c/omega7c). The G+C contents of 25B14_1(T) and BH-BN04-4(T) were determined to be 58.4 and 61.0 mol%, respectively. The combined phenotypic and genotypic data show that the two isolates each represent novel species of the genus Hyphomonas, for which the names Hyphomonas beringensis sp. nov. and Hyphomonas chukchiensis sp. nov. are proposed, with the type strain 25B14_1(T) (=MCCC 1A07321(T) = LMG 27914(T)) and BH-BN04-4(T) (=MCCC 1A07481(T) = LMG 27915(T)), respectively.
ESTHER : Li_2014_Antonie.Van.Leeuwenhoek_106_657
PubMedSearch : Li_2014_Antonie.Van.Leeuwenhoek_106_657
PubMedID: 25070064
Gene_locus related to this paper: 9rhob-a0a059fvx5 , 9rhob-a0a062ve25 , 9rhob-a0a059e3y9 , 9rhob-a0a062tww8 , 9rhob-a0a062u829 , 9rhob-a0a059e1b7 , 9rhob-a0a059g4l9 , 9rhob-a0a059f7b2 , 9rhob-a0a069e8d0 , 9rhob-a0a059g313 , 9rhob-a0a059g3u2 , 9rhob-a0a059fuw7 , 9rhob-a0a062ui03 , 9rhob-a0a059fgt4 , 9rhob-a0a059dz53 , 9rhob-a0a069e7i5 , 9rhob-a0a059fgq3 , 9rhob-a0a069e822 , 9rhob-a0a062vhu5 , 9rhob-a0a062uj80 , 9rhob-a0a062udx1 , 9rhob-a0a059eck3 , 9rhob-a0a062u513 , 9rhob-a0a062vh83 , 9rhob-a0a062u677 , 9rhob-a0a069e9p2 , 9rhob-a0a062ui16 , 9rhob-a0a059g4x1 , 9rhob-a0a062u908 , 9rhob-a0a062uqj8 , 9rhob-a0a062u917 , 9rhob-a0a059fty9 , 9rhob-a0a062uq79 , 9rhob-a0a059g214 , 9rhob-a0a062uez6 , 9rhob-a0a062v9r9 , 9rhob-a0a059g243 , 9rhob-a0a059fbn4 , 9rhob-a0a069e4q5 , 9rhob-a0a069e8h3 , 9rhob-a0a059dyu6 , 9rhob-a0a059fva5 , 9rhob-a0a059g4g8 , 9rhob-a0a059f9m8 , 9rhob-a0a062vgs9

Title : Point Mutations Associated with Organophosphate and Carbamate Resistance in Chinese Strains of Culex pipiens quinquefasciatus (Diptera: Culicidae) - Zhao_2014_PLoS.One_9_e952607
Author(s) : Zhao M , Dong Y , Ran X , Wu Z , Guo X , Zhang Y , Xing D , Yan T , Wang G , Zhu X , Zhang H , Li C , Zhao T
Ref : PLoS ONE , 9 :e95260 , 2014
Abstract : Acetylcholinesterase resistance has been well documented in many insects, including several mosquito species. We tested the resistance of five wild, Chinese strains of the mosquito Culex pipiens quinquefasciatus to two kinds of pesticides, dichlorvos and propoxur. An acetylcholinesterase gene (ace1) was cloned and sequenced from a pooled sample of mosquitoes from these five strains and the amino acids of five positions were found to vary (V185M, G247S, A328S, A391T, and T682A). Analysis of the correlation between mutation frequencies and resistance levels (LC50) suggests that two point mutations, G247S (r2 = 0.732, P = 0.065) and A328S (r2 = 0.891, P = 0.016), are associated with resistance to propoxur but not to dichlorvos. Although the V185M mutation was not associated with either dichlorvos or propoxur resistance, its RS genotype frequency was correlated with propoxur resistance (r2 = 0.815, P = 0.036). And the HWE test showed the A328S mutation is linked with V185M, also with G247S mutation. This suggested that these three mutations may contribute synergistically to propoxur resistance. The T682A mutation was negatively correlated with propoxur (r2 = 0.788, P = 0.045) resistance. Knowledge of these mutations may help design strategies for managing pesticide resistance in wild mosquito populations.
ESTHER : Zhao_2014_PLoS.One_9_e952607
PubMedSearch : Zhao_2014_PLoS.One_9_e952607
PubMedID: 24788312
Gene_locus related to this paper: culpi-ACHE1

Title : Potential mechanisms of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose VOCs - Wang_2014_Inhal.Toxicol_26_250
Author(s) : Wang F , Li C , Liu W , Jin Y
Ref : Inhal Toxicol , 26 :250 , 2014
Abstract : Abstract To investigate effects of neurobehavioral disturbances in mice caused by sub-chronic exposure to low-dose volatile organic compounds (VOCs) and the possible mechanism for these effects, 60 male Kunming mice were exposed in 5 similar static chambers, 0 (control) and 4 different doses of VOCs mixture (G1-4) for consecutively 90 d at 2 h/d. The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.05 + 0.05 + 0.10 + 0.10 mg/m(3), 0.10 + 0.11 + 0.20 + 0.20 mg/m(3), 0.50 + 0.55 + 1.00 + 1.00 mg/m(3), 1.00 +1.10 + 2.00 + 2.00 mg/m(3), respectively, which corresponded to 1/2, 1, 5, and 10 times of indoor air quality standard in China. Morris water maze (MWM) and Grip strength (GS) test were performed in the last 7 weeks. One day following VOCs exposure, oxidative stress markers, neurotransmitters, and cholinergic system enzymes in brain were examined. In addition, the expressions of N-methyl-d-aspartate (NMDA) receptor in hippocampus were determined. VOCs exposure induced behavioral impairment of mice in MWM and GS test. The levels of reactive oxygen species (ROS), malondialdehyde (MDA) and glutamic acid (Glu) were significantly increased, while the acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and acetylcholine (ACh) levels, and the expression of NMDA receptor were significantly decreased in VOCs exposed groups. Results showed that sub-chronic exposure to low-dose VOCs induced damage on physique and motor function, as well as impairment on learning and memory capacity of mice. Oxidative damage, abnormal metabolism of neurotransmitters and cholinergic system enzymes, and the alternation of NMDA receptor expression may be the possible mechanism for VOCs-induced neurotoxicity.
ESTHER : Wang_2014_Inhal.Toxicol_26_250
PubMedSearch : Wang_2014_Inhal.Toxicol_26_250
PubMedID: 24568580

Title : Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins - Liu_2014_Acta.Pharm.Sin.B_4_135
Author(s) : Liu J , Huan Y , Li C , Liu M , Shen Z
Ref : Acta Pharm Sin B , 4 :135 , 2014
Abstract : Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2 mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors.
ESTHER : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedSearch : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedID: 26579375

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

Title : The genome of the clonal raider ant Cerapachys biroi - Oxley_2014_Curr.Biol_24_451
Author(s) : Oxley PR , Ji L , Fetter-Pruneda I , McKenzie SK , Li C , Hu H , Zhang G , Kronauer DJ
Ref : Current Biology , 24 :451 , 2014
Abstract : Social insects are important models for social evolution and behavior. However, in many species, experimental control over important factors that regulate division of labor, such as genotype and age, is limited. Furthermore, most species have fixed queen and worker castes, making it difficult to establish causality between the molecular mechanisms that underlie reproductive division of labor, the hallmark of insect societies. Here we present the genome of the queenless clonal raider ant Cerapachys biroi, a powerful new study system that does not suffer from these constraints. Using cytology and RAD-seq, we show that C. biroi reproduces via automixis with central fusion and that heterozygosity is lost extremely slowly. As a consequence, nestmates are almost clonally related (r = 0.996). Workers in C. biroi colonies synchronously alternate between reproduction and brood care, and young workers eclose in synchronized cohorts. We show that genes associated with division of labor in other social insects are conserved in C. biroi and dynamically regulated during the colony cycle. With unparalleled experimental control over an individual's genotype and age, and the ability to induce reproduction and brood care, C. biroi has great potential to illuminate the molecular regulation of division of labor.
ESTHER : Oxley_2014_Curr.Biol_24_451
PubMedSearch : Oxley_2014_Curr.Biol_24_451
PubMedID: 24508170
Gene_locus related to this paper: solin-e9ige7 , cerbi-a0a026whr6 , cerbi-a0a026wk96 , cerbi-a0a026vw30 , cerbi-a0a026wfw0 , cerbi-a0a026w5f6 , cerbi-a0a026wt53 , cerbi-a0a026vug0 , cerbi-a0a026x3b8 , cerbi-a0a026we54 , cerbi-a0a026wla0 , cerbi-a0a026wis7 , cerbi-a0a026wrn0 , cerbi-a0a026wi21 , cerbi-a0a026wec0 , cerbi-a0a026wvz8 , cerbi-a0a026w8e0 , oocbi-a0a026wtb1 , oocbi-a0a026wvq6 , oocbi-a0a026w0p3 , oocbi-a0a026w634

Title : Comparative genomic analysis and virulence differences in closely related salmonella enterica serotype heidelberg isolates from humans, retail meats, and animals - Hoffmann_2014_Genome.Biol.Evol_6_1046
Author(s) : Hoffmann M , Zhao S , Pettengill J , Luo Y , Monday SR , Abbott J , Ayers SL , Cinar HN , Muruvanda T , Li C , Allard MW , Whichard J , Meng J , Brown EW , McDermott PF
Ref : Genome Biol Evol , 6 :1046 , 2014
Abstract : Salmonella enterica subsp. enterica serovar Heidelberg (S. Heidelberg) is one of the top serovars causing human salmonellosis. Recently, an antibiotic-resistant strain of this serovar was implicated in a large 2011 multistate outbreak resulting from consumption of contaminated ground turkey that involved 136 confirmed cases, with one death. In this study, we assessed the evolutionary diversity of 44 S. Heidelberg isolates using whole-genome sequencing (WGS) generated by the 454 GS FLX (Roche) platform. The isolates, including 30 with nearly indistinguishable (one band difference) Xbal pulsed-field gel electrophoresis patterns (JF6X01.0032, JF6X01.0058), were collected from various sources between 1982 and 2011 and included nine isolates associated with the 2011 outbreak. Additionally, we determined the complete sequence for the chromosome and three plasmids from a clinical isolate associated with the 2011 outbreak using the Pacific Biosciences (PacBio) system. Using single-nucleotide polymorphism (SNP) analyses, we were able to distinguish highly clonal isolates, including strains isolated at different times in the same year. The isolates from the recent 2011 outbreak clustered together with a mean SNP variation of only 17 SNPs. The S. Heidelberg isolates carried a variety of phages, such as prophage P22, P4, lambda-like prophage Gifsy-2, and the P2-like phage which carries the sopE1 gene, virulence genes including 62 pathogenicity, and 13 fimbrial markers and resistance plasmids of the incompatibility (Inc)I1, IncA/C, and IncHI2 groups. Twenty-one strains contained an IncX plasmid carrying a type IV secretion system. On the basis of the recent and historical isolates used in this study, our results demonstrated that, in addition to providing detailed genetic information for the isolates, WGS can identify SNP targets that can be utilized for differentiating highly clonal S. Heidelberg isolates.
ESTHER : Hoffmann_2014_Genome.Biol.Evol_6_1046
PubMedSearch : Hoffmann_2014_Genome.Biol.Evol_6_1046
PubMedID: 24732280

Title : Identification of a novel salt tolerance gene in wild soybean by whole-genome sequencing - Qi_2014_Nat.Commun_5_4340
Author(s) : Qi X , Li MW , Xie M , Liu X , Ni M , Shao G , Song C , Kay-Yuen Yim A , Tao Y , Wong FL , Isobe S , Wong CF , Wong KS , Xu C , Li C , Wang Y , Guan R , Sun F , Fan G , Xiao Z , Zhou F , Phang TH , Tong SW , Chan TF , Yiu SM , Tabata S , Wang J , Xu X , Lam HM
Ref : Nat Commun , 5 :4340 , 2014
Abstract : Using a whole-genome-sequencing approach to explore germplasm resources can serve as an important strategy for crop improvement, especially in investigating wild accessions that may contain useful genetic resources that have been lost during the domestication process. Here we sequence and assemble a draft genome of wild soybean and construct a recombinant inbred population for genotyping-by-sequencing and phenotypic analyses to identify multiple QTLs relevant to traits of interest in agriculture. We use a combination of de novo sequencing data from this work and our previous germplasm re-sequencing data to identify a novel ion transporter gene, GmCHX1, and relate its sequence alterations to salt tolerance. Rapid gain-of-function tests show the protective effects of GmCHX1 towards salt stress. This combination of whole-genome de novo sequencing, high-density-marker QTL mapping by re-sequencing and functional analyses can serve as an effective strategy to unveil novel genomic information in wild soybean to facilitate crop improvement.
ESTHER : Qi_2014_Nat.Commun_5_4340
PubMedSearch : Qi_2014_Nat.Commun_5_4340
PubMedID: 25004933
Gene_locus related to this paper: soybn-i1k636 , soybn-i1j4c6 , glyso-a0a0b2sjw6 , soybn-a0a0r0i9y7 , soybn-a0a0r0j241 , soybn-i1kfz9 , glyso-a0a0b2rre9 , soybn-i1jx17

Title : Synthesis and evaluation of odour-active methionyl esters of fatty acids via esterification and transesterification of butter oil - Li_2014_Food.Chem_145_796
Author(s) : Li C , Sun J , Fu C , Yu B , Liu SQ , Li T , Huang D
Ref : Food Chem , 145 :796 , 2014
Abstract : Methionol-derived fatty acid esters were synthesised by both chemical and lipase catalysed esterification between fatty acids and methionol. Beneficial effects of both methods were compared qualitatively and quantitatively by GC-MS/GC-FID results. And the high acid and heat stability of our designed methionyl esters meet the requirement of the food industry. Most importantly, the sensory test showed that fatty acid carbon-chain length had an important effect on the flavour attributes of methionyl esters. Moreover, through Lipozyme TL IM-mediated transesterification, valuable methionol-derived esters were synthesised from the readily available natural material butter oil as the fatty acid source. The conversion of methionol and yield of each methionyl ester were also elucidated by GC-MS-FID.
ESTHER : Li_2014_Food.Chem_145_796
PubMedSearch : Li_2014_Food.Chem_145_796
PubMedID: 24128547

Title : Contamination of bananas with beauvericin and fusaric acid produced by Fusarium oxysporum f. sp. cubense - Li_2013_PLoS.One_8_e70226
Author(s) : Li C , Zuo C , Deng G , Kuang R , Yang Q , Hu C , Sheng O , Zhang S , Ma L , Wei Y , Yang J , Liu S , Biswas MK , Viljoen A , Yi G
Ref : PLoS ONE , 8 :e70226 , 2013
Abstract : BACKGROUND: Fusarium wilt, caused by the fungal pathogen Fusarium oxysporum f. sp. cubense (Foc), is one of the most destructive diseases of banana. Toxins produced by Foc have been proposed to play an important role during the pathogenic process. The objectives of this study were to investigate the contamination of banana with toxins produced by Foc, and to elucidate their role in pathogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Twenty isolates of Foc representing races 1 and 4 were isolated from diseased bananas in five Chinese provinces. Two toxins were consistently associated with Foc, fusaric acid (FA) and beauvericin (BEA). Cytotoxicity of the two toxins on banana protoplast was determined using the Alamar Blue assay. The virulence of 20 Foc isolates was further tested by inoculating tissue culture banana plantlets, and the contents of toxins determined in banana roots, pseudostems and leaves. Virulence of Foc isolates correlated well with toxin deposition in the host plant. To determine the natural occurrence of the two toxins in banana plants with Fusarium wilt symptoms, samples were collected before harvest from the pseudostems, fruit and leaves from 10 Pisang Awak 'Guangfen #1' and 10 Cavendish 'Brazilian' plants. Fusaric acid and BEA were detected in all the tissues, including the fruits. CONCLUSIONS/SIGNFICANCE: The current study provides the first investigation of toxins produced by Foc in banana. The toxins produced by Foc, and their levels of contamination of banana fruits, however, were too low to be of concern to human and animal health. Rather, these toxins appear to contribute to the pathogenicity of the fungus during infection of banana plants.
ESTHER : Li_2013_PLoS.One_8_e70226
PubMedSearch : Li_2013_PLoS.One_8_e70226
PubMedID: 23922960
Gene_locus related to this paper: gibf5-fub5

Title : The draft genomes of soft-shell turtle and green sea turtle yield insights into the development and evolution of the turtle-specific body plan - Wang_2013_Nat.Genet_45_701
Author(s) : Wang Z , Pascual-Anaya J , Zadissa A , Li W , Niimura Y , Huang Z , Li C , White S , Xiong Z , Fang D , Wang B , Ming Y , Chen Y , Zheng Y , Kuraku S , Pignatelli M , Herrero J , Beal K , Nozawa M , Li Q , Wang J , Zhang H , Yu L , Shigenobu S , Liu J , Flicek P , Searle S , Kuratani S , Yin Y , Aken B , Zhang G , Irie N
Ref : Nat Genet , 45 :701 , 2013
Abstract : The unique anatomical features of turtles have raised unanswered questions about the origin of their unique body plan. We generated and analyzed draft genomes of the soft-shell turtle (Pelodiscus sinensis) and the green sea turtle (Chelonia mydas); our results indicated the close relationship of the turtles to the bird-crocodilian lineage, from which they split approximately 267.9-248.3 million years ago (Upper Permian to Triassic). We also found extensive expansion of olfactory receptor genes in these turtles. Embryonic gene expression analysis identified an hourglass-like divergence of turtle and chicken embryogenesis, with maximal conservation around the vertebrate phylotypic period, rather than at later stages that show the amniote-common pattern. Wnt5a expression was found in the growth zone of the dorsal shell, supporting the possible co-option of limb-associated Wnt signaling in the acquisition of this turtle-specific novelty. Our results suggest that turtle evolution was accompanied by an unexpectedly conservative vertebrate phylotypic period, followed by turtle-specific repatterning of development to yield the novel structure of the shell.
ESTHER : Wang_2013_Nat.Genet_45_701
PubMedSearch : Wang_2013_Nat.Genet_45_701
PubMedID: 23624526
Gene_locus related to this paper: chemy-m7c042 , chemy-m7bp40 , chemy-m7cgq9 , chemy-m7bs15 , chemy-m7c0b2 , chemy-m7bkv2 , chemy-m7bnk5 , chemy-m7bzy6

Title : Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci - Schardl_2013_PLoS.Genet_9_e1003323
Author(s) : Schardl CL , Young CA , Hesse U , Amyotte SG , Andreeva K , Calie PJ , Fleetwood DJ , Haws DC , Moore N , Oeser B , Panaccione DG , Schweri KK , Voisey CR , Farman ML , Jaromczyk JW , Roe BA , O'Sullivan DM , Scott B , Tudzynski P , An Z , Arnaoudova EG , Bullock CT , Charlton ND , Chen L , Cox M , Dinkins RD , Florea S , Glenn AE , Gordon A , Guldener U , Harris DR , Hollin W , Jaromczyk J , Johnson RD , Khan AK , Leistner E , Leuchtmann A , Li C , Liu J , Liu M , Mace W , Machado C , Nagabhyru P , Pan J , Schmid J , Sugawara K , Steiner U , Takach JE , Tanaka E , Webb JS , Wilson EV , Wiseman JL , Yoshida R , Zeng Z
Ref : PLoS Genet , 9 :e1003323 , 2013
Abstract : The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloe and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.
ESTHER : Schardl_2013_PLoS.Genet_9_e1003323
PubMedSearch : Schardl_2013_PLoS.Genet_9_e1003323
PubMedID: 23468653
Gene_locus related to this paper: clap2-m1w2a8 , clap2-m1w555 , clap2-m1wa31 , clap2-m1whd2 , clap2-m1weh2 , clap2-m1w5y7 , clap2-m1wh11 , clap2-m1vyn7 , clap2-m1w670

Title : On the evolutionary history, population genetics and diversity among isolates of Salmonella Enteritidis PFGE pattern JEGX01.0004 - Allard_2013_PLoS.One_8_e55254
Author(s) : Allard MW , Luo Y , Strain E , Pettengill J , Timme R , Wang C , Li C , Keys CE , Zheng J , Stones R , Wilson MR , Musser SM , Brown EW
Ref : PLoS ONE , 8 :e55254 , 2013
Abstract : Facile laboratory tools are needed to augment identification in contamination events to trace the contamination back to the source (traceback) of Salmonella enterica subsp. enterica serovar Enteritidis (S. Enteritidis). Understanding the evolution and diversity within and among outbreak strains is the first step towards this goal. To this end, we collected 106 new S. Enteriditis isolates within S. Enteriditis Pulsed-Field Gel Electrophoresis (PFGE) pattern JEGX01.0004 and close relatives, and determined their genome sequences. Sources for these isolates spanned food, clinical and environmental farm sources collected during the 2010 S. Enteritidis shell egg outbreak in the United States along with closely related serovars, S. Dublin, S. Gallinarum biovar Pullorum and S. Gallinarum. Despite the highly homogeneous structure of this population, S. Enteritidis isolates examined in this study revealed thousands of SNP differences and numerous variable genes (n = 366). Twenty-one of these genes from the lineages leading to outbreak-associated samples had nonsynonymous (causing amino acid changes) changes and five genes are putatively involved in known Salmonella virulence pathways. While chromosome synteny and genome organization appeared to be stable among these isolates, genome size differences were observed due to variation in the presence or absence of several phages and plasmids, including phage RE-2010, phage P125109, plasmid pSEEE3072_19 (similar to pSENV), plasmid pOU1114 and two newly observed mobile plasmid elements pSEEE1729_15 and pSEEE0956_35. These differences produced modifications to the assembled bases for these draft genomes in the size range of approximately 4.6 to 4.8 mbp, with S. Dublin being larger ( approximately 4.9 mbp) and S. Gallinarum smaller (4.55 mbp) when compared to S. Enteritidis. Finally, we identified variable S. Enteritidis genes associated with virulence pathways that may be useful markers for the development of rapid surveillance and typing methods, potentially aiding in traceback efforts during future outbreaks involving S. Enteritidis PFGE pattern JEGX01.0004.
ESTHER : Allard_2013_PLoS.One_8_e55254
PubMedSearch : Allard_2013_PLoS.One_8_e55254
PubMedID: 23383127
Gene_locus related to this paper: salty-STY1441 , salty-ycfp , salen-l6rcw4

Title : Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity - Dai_2013_Mol.Cell.Endocrinol_377_123
Author(s) : Dai Z , Qi W , Li C , Lu J , Mao Y , Yao Y , Li L , Zhang T , Hong H , Li S , Zhou T , Yang Z , Yang X , Gao G , Cai W
Ref : Mol Cell Endocrinol , 377 :123 , 2013
Abstract : Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL.
ESTHER : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedSearch : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedID: 23850519

Title : Genomic diversity and evolution of the head crest in the rock pigeon - Shapiro_2013_Science_339_1063
Author(s) : Shapiro MD , Kronenberg Z , Li C , Domyan ET , Pan H , Campbell M , Tan H , Huff CD , Hu H , Vickrey AI , Nielsen SC , Stringham SA , Willerslev E , Gilbert MT , Yandell M , Zhang G , Wang J
Ref : Science , 339 :1063 , 2013
Abstract : The geographic origins of breeds and the genetic basis of variation within the widely distributed and phenotypically diverse domestic rock pigeon (Columba livia) remain largely unknown. We generated a rock pigeon reference genome and additional genome sequences representing domestic and feral populations. We found evidence for the origins of major breed groups in the Middle East and contributions from a racing breed to North American feral populations. We identified the gene EphB2 as a strong candidate for the derived head crest phenotype shared by numerous breeds, an important trait in mate selection in many avian species. We also found evidence that this trait evolved just once and spread throughout the species, and that the crest originates early in development by the localized molecular reversal of feather bud polarity.
ESTHER : Shapiro_2013_Science_339_1063
PubMedSearch : Shapiro_2013_Science_339_1063
PubMedID: 23371554
Gene_locus related to this paper: colli-r7vnu6 , colli-r7vv16 , colli-a0a2i0m6q6 , colli-a0a2i0mey7 , colli-a0a2i0mey8 , colli-a0a2i0mez3 , colli-a0a2i0ms89 , colli-a0a160dr48 , colli-a0a2i0m6c1 , colli-a0a2i0lic2 , colli-a0a2i0mlj2 , colli-r7vwj5 , nipni-a0a091w0t8 , fical-u3jnn0 , colli-a0a2i0mwb1 , colli-a0a2i0mwb4 , colli-a0a2i0mwd0

Title : Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors - Shi_2013_Bioorg.Med.Chem_21_1064
Author(s) : Shi DH , Huang W , Li C , Wang LT , Wang SF
Ref : Bioorganic & Medicinal Chemistry , 21 :1064 , 2013
Abstract : A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC(50)=0.09 muM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.
ESTHER : Shi_2013_Bioorg.Med.Chem_21_1064
PubMedSearch : Shi_2013_Bioorg.Med.Chem_21_1064
PubMedID: 23380475

Title : Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals - Hu_2013_Acta.Pharmacol.Sin_34_1437
Author(s) : Hu ZY , Li XX , Du FF , Yang JL , Niu W , Xu F , Wang FQ , Li C , Sun Y
Ref : Acta Pharmacol Sin , 34 :1437 , 2013
Abstract : Aim:To investigate the pharmacokinetics and disposition of simmitecan (L-P) that was a water-soluble ester prodrug of chimmitecan (L-2-Z) with potent anti-tumor activities in different experimental animals, and to assess its drug-drug interaction potential.Methods:SD rats were injected with a single iv bolus doses of L-P (3.75, 7.5 and 15 mg/kg). The pharmacokinetics, tissue distribution, excretion and metabolism of L-P and its active metabolite L-2-Z were studied through quantitative measurements and metabolite profiling with LC/MS. The binding of L-P and L-2-Z to rat plasma proteins was examined using an ultrafiltration method. Systemic exposures of beagle dogs to L-P as well as drug distribution in tumors of the nude mice xenograft model of human hepatic cancer SMMC-7721 cells were also examined. The metabolism of L-P by liver mcirosomal carboxylesterase in vitro was investigated in different species. The effects of L-P and L-2-Z on cytochrome P450 enzymes were examined using commercial screening kits.Results:The in vivo biotransformation of L-P to L-2-Z showed a significant species difference, with a mean elimination half-life t1/2 of approximately 1.4 h in rats and 1.9 h in dogs. The systemic exposure levels of L-P and L-2-Z were increased in a dose-dependent manner. In rats, approximately 66% of L-P and 79% of L-2-Z were bound to plasma proteins. In rats and the nude mice bearing human hepatic cancers, most organ tissues had significantly higher concentrations of L-P than the corresponding plasma levels. In the tumor tissues, the L-P levels were comparable to those of plasma, whereas the L-2-Z levels were lower than the L-P levels. In rats, L-P was eliminated mainly via biliary excretion, but metabolism played an important role in elimination of the intact L-P. Finally, L-P and L-2-Z exerted moderate inhibition on the activity of CYP3A4 in vitro.Conclusion:L-P and L-2-Z have relatively short elimination half-lives and L-P is mainly eliminated via biliary excretion. The species difference in the conversion of L-P to L-2-Z and potential drug-drug interactions due to inhibition of CYP3A4 should be considered in further studies.
ESTHER : Hu_2013_Acta.Pharmacol.Sin_34_1437
PubMedSearch : Hu_2013_Acta.Pharmacol.Sin_34_1437
PubMedID: 24056706

Title : Discovery of benzamide analogs as negative allosteric modulators of human neuronal nicotinic receptors: pharmacophore modeling and structure-activity relationship studies - Yi_2013_Bioorg.Med.Chem_21_4730
Author(s) : Yi B , Long S , Gonzalez-Cestari TF , Henderson BJ , Pavlovicz RE , Werbovetz K , Li C , McKay DB
Ref : Bioorganic & Medicinal Chemistry , 21 :4730 , 2013
Abstract : The present study describes our ongoing efforts toward the discovery of drugs that selectively target nAChR subtypes. We exploited knowledge on nAChR ligands and their binding site that were previously identified by our laboratory through virtual screenings and identified benzamide analogs as a novel chemical class of neuronal nicotinic receptor (nAChR) ligands. The lead molecule, compound 1 (4-(allyloxy)-N-(6-methylpyridin-2-yl)benzamide) inhibits nAChR activity with an IC(5)(0) value of 6.0 (3.4-10.6) muM on human alpha4beta2 nAChRs with a approximately 5-fold preference against human alpha3beta4 nAChRs. Twenty-six analogs of compound 1 were also either synthesized or purchased for structure-activity relationship (SAR) studies and provided information relating the chemical/structural properties of the molecules to their ability to inhibit nAChR activity. The discovery of subtype-selective ligands of nAChRs described here should contribute significantly to our understanding of the involvement of specific nAChR subtypes in normal and pathophysiological states.
ESTHER : Yi_2013_Bioorg.Med.Chem_21_4730
PubMedSearch : Yi_2013_Bioorg.Med.Chem_21_4730
PubMedID: 23757208

Title : Biruloquinone, an Acetylcholinesterase Inhibitor Produced by Lichen-Forming Fungus Cladonia macilenta - Luo_2013_J.Microbiol.Biotechnol_23_161
Author(s) : Luo H , Li C , Kim JC , Liu Y , Jung JS , Koh YJ , Hur JS
Ref : J Microbiol Biotechnol , 23 :161 , 2013
Abstract : At present, acetylcholinesterase (AChE) inhibitors are the first group of drugs to treat mild to moderate Alzheimer's disease (AD). Although beneficial in improving cognitive and behavioral symptoms, the effectiveness of AChE inhibitors has been questioned since they do not delay or prevent neurodegeneration in AD patients. Therefore, in the present study, in order to develop new and effective anti-AD agents from lichen products, both the AChE inhibitory and the neuroprotective effects were evaluated. The AChE inhibitory assay was performed based on Ellman's reaction, and the neuroprotective effect was evaluated by using the MTT method on injured PC12 cells. One AChE inhibitor (IC50 = 27.1 microg/ml) was isolated by means of bioactivity-guided isolation from the extract of lichen-forming fungus Cladonia macilenta, which showed the most potent AChE inhibitory activity in previous screening experiment. It was then identified as biruloquinone by MS, and 1H- and 13C-NMR analyses. The inhibitory kinetic assay suggested that biruloquinone is a mixed-II inhibitor on AChE. Meanwhile, biruloquinone improved the viability of the H2O2- and beta-amyloid-injured PC12 cells at 1 to 25 microg/ml. The protective effects are proposed to be related to the potent antioxidant activities of biruloquinone. These results imply that biruloquinone has the potential to be developed as a multifunctional anti- AD agent.
ESTHER : Luo_2013_J.Microbiol.Biotechnol_23_161
PubMedSearch : Luo_2013_J.Microbiol.Biotechnol_23_161
PubMedID: 23412057

Title : High resolution clustering of Salmonella enterica serovar Montevideo strains using a next-generation sequencing approach - Allard_2012_BMC.Genomics_13_32
Author(s) : Allard MW , Luo Y , Strain E , Li C , Keys CE , Son I , Stones R , Musser SM , Brown EW
Ref : BMC Genomics , 13 :32 , 2012
Abstract : BACKGROUND: Next-Generation Sequencing (NGS) is increasingly being used as a molecular epidemiologic tool for discerning ancestry and traceback of the most complicated, difficult to resolve bacterial pathogens. Making a linkage between possible food sources and clinical isolates requires distinguishing the suspected pathogen from an environmental background and placing the variation observed into the wider context of variation occurring within a serovar and among other closely related foodborne pathogens. Equally important is the need to validate these high resolution molecular tools for use in molecular epidemiologic traceback. Such efforts include the examination of strain cluster stability as well as the cumulative genetic effects of sub-culturing on these clusters. Numerous isolates of S. Montevideo were shot-gun sequenced including diverse lineage representatives as well as numerous replicate clones to determine how much variability is due to bias, sequencing error, and or the culturing of isolates. All new draft genomes were compared to 34 S. Montevideo isolates previously published during an NGS-based molecular epidemiological case study.
RESULTS: Intraserovar lineages of S. Montevideo differ by thousands of SNPs, that are only slightly less than the number of SNPs observed between S. Montevideo and other distinct serovars. Much less variability was discovered within an individual S. Montevideo clade implicated in a recent foodborne outbreak as well as among individual NGS replicates. These findings were similar to previous reports documenting homopolymeric and deletion error rates with the Roche 454 GS Titanium technology. In no case, however, did variability associated with sequencing methods or sample preparations create inconsistencies with our current phylogenetic results or the subsequent molecular epidemiological evidence gleaned from these data.
CONCLUSIONS: Implementation of a validated pipeline for NGS data acquisition and analysis provides highly reproducible results that are stable and predictable for molecular epidemiological applications. When draft genomes are collected at 15x-20x coverage and passed through a quality filter as part of a data analysis pipeline, including sub-passaged replicates defined by a few SNPs, they can be accurately placed in a phylogenetic context. This reproducibility applies to all levels within and between serovars of Salmonella suggesting that investigators using these methods can have confidence in their conclusions.
ESTHER : Allard_2012_BMC.Genomics_13_32
PubMedSearch : Allard_2012_BMC.Genomics_13_32
PubMedID: 22260654
Gene_locus related to this paper: salen-OPDB , salti-q8z717 , salty-DLHH , salty-ENTF , salty-FES , salty-IROD , salty-IROE , salty-PLDB , salty-STY1441 , salty-yafa , salty-YBFF , salty-ycfp , salty-YFBB , salty-YQIA

Title : Sodium aescinate ameliorates liver injury induced by methyl parathion in rats - Du_2012_Exp.Ther.Med_3_818
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Li C , Li CK , Fu FH
Ref : Exp Ther Med , 3 :818 , 2012
Abstract : Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural pest control for several years. The present study investigated the protective effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg) poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and antioxidative parameters were measured. Histopathological examination of the liver was also performed. The results revealed that SA had no effect on AChE. Treatment with SA decreased the activities of ALT and AST, and the levels of malondialdehyde and NO. Treatment with SA also increased the level of glutathione and the activities of superoxide dismutase and glutathione peroxidase. SA administration also ameliorated liver injury induced by methyl parathion poisoning. The findings indicate that SA protects against liver injury induced by methyl parathion and that the mechanism of action is related to the antioxidative and anti-inflammatory effects of SA.
ESTHER : Du_2012_Exp.Ther.Med_3_818
PubMedSearch : Du_2012_Exp.Ther.Med_3_818
PubMedID: 22969975

Title : Defining the putative inhibitory site for a selective negative allosteric modulator of human alpha4beta2 neuronal nicotinic receptors - Henderson_2012_ACS.Chem.Neurosci_3_682
Author(s) : Henderson BJ , Gonzalez-Cestari TF , Yi B , Pavlovicz RE , Boyd RT , Li C , Bergmeier SC , McKay DB
Ref : ACS Chem Neurosci , 3 :682 , 2012
Abstract : Neuronal nicotinic receptors (nAChRs) have been implicated in several diseases and disorders such as autism spectrum disorders, Alzheimer's disease, Parkinson's disease, epilepsy, and nicotine addiction. To understand the role of nAChRs in these conditions, it would be beneficial to have selective molecules that target specific nAChRs in vitro and in vivo. Our laboratory has previously identified a novel allosteric site on human alpha4beta2 nAChRs using a series of computational and in vitro approaches. At this site, we have identified negative allosteric modulators that selectively inhibit human alpha4beta2 nAChRs, a subtype implicated in nicotine addiction. This study characterizes the allosteric site via site-directed mutagenesis. Three amino acids (Phe118, Glu60, and Thr58) on the beta2 subunit were shown to participate in the inhibitory properties of the selective antagonist KAB-18 and provided insights into its antagonism of human alpha4beta2 nAChRs. SAR studies with KAB-18 analogues and various mutant alpha4beta2 nAChRs also provided information concerning how different physiochemical features influence the inhibition of nAChRs through this allosteric site. Together, these studies identify the amino acids that contribute to the selective antagonism of human alpha4beta2 nAChRs at this allosteric site. Finally, these studies define the physiochemical features of ligands that influence interaction with specific amino acids in this allosteric site.
ESTHER : Henderson_2012_ACS.Chem.Neurosci_3_682
PubMedSearch : Henderson_2012_ACS.Chem.Neurosci_3_682
PubMedID: 23019495

Title : Genome sequence of Galbibacter marinum type strain ck-I2-15 - Lai_2012_J.Bacteriol_194_6973
Author(s) : Lai Q , Li C , Shao Z
Ref : Journal of Bacteriology , 194 :6973 , 2012
Abstract : Galbibacter marinum strain ck-I2-15(T) was isolated from an arsenite-resistant consortium enriched from the deep sea sediment of a hydrothermal vent field on the Southwest Indian Ocean Ridge. Here, we present the draft genome of strain ck-I2-15(T), which contains 3,572,447 bp with a G+C content of 37.04% and contains 3,099 protein-coding genes and 38 tRNA genes.
ESTHER : Lai_2012_J.Bacteriol_194_6973
PubMedSearch : Lai_2012_J.Bacteriol_194_6973
PubMedID: 23209227
Gene_locus related to this paper: 9flao-k2pua7 , 9flao-k2q643 , 9flao-k2qni2

Title : Genome sequences of five Salmonella enterica serovar Heidelberg isolates associated with a 2011 multistate outbreak in the United States - Hoffmann_2012_J.Bacteriol_194_3274
Author(s) : Hoffmann M , Zhao S , Luo Y , Li C , Folster JP , Whichard J , Allard MW , Brown EW , McDermott PF
Ref : Journal of Bacteriology , 194 :3274 , 2012
Abstract : Salmonella enterica serovar Heidelberg has caused numerous outbreaks in humans. Here, we report draft genomes of five isolates of serovar Heidelberg associated with the recent (2011) multistate outbreak linked to ground turkey in the United States. Isolates 2011K-1110 and 2011K-1132 were recovered from humans, while isolates 2011K-1138, 2011K-1224, and 2011K-1225 were recovered from ground turkey. Whole-genome sequence analysis of these isolates provides a tool for studying the short-term evolution of these epidemic clones.
ESTHER : Hoffmann_2012_J.Bacteriol_194_3274
PubMedSearch : Hoffmann_2012_J.Bacteriol_194_3274
PubMedID: 22628505
Gene_locus related to this paper: salty-STY1441 , salty-YFBB

Title : Draft genome sequences of 21 Salmonella enterica serovar enteritidis strains - Timme_2012_J.Bacteriol_194_5994
Author(s) : Timme RE , Allard MW , Luo Y , Strain E , Pettengill J , Wang C , Li C , Keys CE , Zheng J , Stones R , Wilson MR , Musser SM , Brown EW
Ref : Journal of Bacteriology , 194 :5994 , 2012
Abstract : Salmonella enterica subsp. enterica serovar Enteritidis is a common food-borne pathogen, often associated with shell eggs and poultry. Here, we report draft genomes of 21 S. Enteritidis strains associated with or related to the U.S.-wide 2010 shell egg recall. Eleven of these genomes were from environmental isolates associated with the egg outbreak, and 10 were reference isolates from previous years, unrelated to the outbreak. The whole-genome sequence data for these 21 human pathogen strains are being released in conjunction with the newly formed 100K Genome Project.
ESTHER : Timme_2012_J.Bacteriol_194_5994
PubMedSearch : Timme_2012_J.Bacteriol_194_5994
PubMedID: 23045502
Gene_locus related to this paper: salty-STY1441

Title : Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors - Wu_2012_Chem.Biol.Drug.Des_79_897
Author(s) : Wu D , Jin F , Lu W , Zhu J , Li C , Wang W , Tang Y , Jiang H , Huang J , Liu G , Li J
Ref : Chemical Biology Drug Des , 79 :897 , 2012
Abstract : Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design.
ESTHER : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedSearch : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedID: 22381062

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

Title : Steady and fluctuant methods of inhibition of acetylcholinesterase differentially regulate neurotrophic factors in the hippocampus of juvenile mice - Li_2012_Exp.Ther.Med_3_269
Author(s) : Li C , Wang T , Jiang N , Yu P , Du Y , Ren R , Fu F
Ref : Exp Ther Med , 3 :269 , 2012
Abstract : The present study was designed to evaluate the effects of steady and fluctuant inhibition of acetylcholinesterase (AChE) activity on neurotrophic factors in the hippocampus of juvenile mice. Steady inhibition of AChE activity was induced by an intramuscular injection of huperizine A (HupA) sustained-release microspheres. Fluctuant inhibition of AChE activity was induced by an intragastric administration of HupA tablets. Six days after cessation of steady AChE inhibition, there was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In contrast, fluctuant AChE inhibition had no effect on BDNF and NGF levels. Additionally, neither steady nor fluctuant inhibition of AChE activity altered the choline acetyltransferase activity or spatial learning in juvenile mice. These findings indicate that steady and fluctuant methods of inhibition of AChE have different effects on the levels of BDNF and NGF in the hippocampus. In addition, the effects of AChE inhibitors may not improve learning in normal juvenile animals.
ESTHER : Li_2012_Exp.Ther.Med_3_269
PubMedSearch : Li_2012_Exp.Ther.Med_3_269
PubMedID: 22969880

Title : Comparative analysis of the genomes of two field isolates of the rice blast fungus Magnaporthe oryzae - Xue_2012_PLoS.Genet_8_e1002869
Author(s) : Xue M , Yang J , Li Z , Hu S , Yao N , Dean RA , Zhao W , Shen M , Zhang H , Li C , Liu L , Cao L , Xu X , Xing Y , Hsiang T , Zhang Z , Xu JR , Peng YL
Ref : PLoS Genet , 8 :e1002869 , 2012
Abstract : Rice blast caused by Magnaporthe oryzae is one of the most destructive diseases of rice worldwide. The fungal pathogen is notorious for its ability to overcome host resistance. To better understand its genetic variation in nature, we sequenced the genomes of two field isolates, Y34 and P131. In comparison with the previously sequenced laboratory strain 70-15, both field isolates had a similar genome size but slightly more genes. Sequences from the field isolates were used to improve genome assembly and gene prediction of 70-15. Although the overall genome structure is similar, a number of gene families that are likely involved in plant-fungal interactions are expanded in the field isolates. Genome-wide analysis on asynonymous to synonymous nucleotide substitution rates revealed that many infection-related genes underwent diversifying selection. The field isolates also have hundreds of isolate-specific genes and a number of isolate-specific gene duplication events. Functional characterization of randomly selected isolate-specific genes revealed that they play diverse roles, some of which affect virulence. Furthermore, each genome contains thousands of loci of transposon-like elements, but less than 30% of them are conserved among different isolates, suggesting active transposition events in M. oryzae. A total of approximately 200 genes were disrupted in these three strains by transposable elements. Interestingly, transposon-like elements tend to be associated with isolate-specific or duplicated sequences. Overall, our results indicate that gain or loss of unique genes, DNA duplication, gene family expansion, and frequent translocation of transposon-like elements are important factors in genome variation of the rice blast fungus.
ESTHER : Xue_2012_PLoS.Genet_8_e1002869
PubMedSearch : Xue_2012_PLoS.Genet_8_e1002869
PubMedID: 22876203
Gene_locus related to this paper: maggr-q0pnd2 , mago7-g4mk92 , mago7-g4mkc6 , mago7-g4mkk9 , mago7-g4mns9 , mago7-g4ms19 , mago7-g4mvm8 , mago7-g4mvw5 , mago7-g4mvw6 , mago7-g4n6j4 , mago7-g4nal1 , mago7-g4nba0 , mago7-g4nbs0 , mago7-g4nc41 , mago7-g4ncz9 , mago7-g4nhn9 , mago7-g4nil3 , mago7-g4nky6 , mago7-g5ehg6 , mago7-g5ehv6 , mago7-g4msm5 , magoy-l7il05 , magoy-l7i6m7 , magoy-l7ic25

Title : Cardiac abnormalities in severe acute dichlorvos poisoning - He_2011_Crit.Care.Med_39_1906
Author(s) : He X , Li C , Wei D , Wu J , Shen L , Wang T
Ref : Critical Care Medicine , 39 :1906 , 2011
Abstract : OBJECTIVE: Patients with organophosphorus poisoning sometimes die suddenly during rigorous treatment, possibly from myocardial injury. This study sought to elucidate the mechanisms underlying organophosphorus poisoning-induced cardiotoxicity. DESIGN: Prospective observational study. SETTING: Urban, tertiary teaching hospital emergency intensive care unit with 10 beds. PATIENTS: Forty-one patients with severe acute dichlorvos poisoning were consecutively enrolled (n = 92) at emergency intensive care unit and followed for 3 months. MEASUREMENTS AND MAIN RESULTS: Levels of serum creatine kinase isoenzyme myocardium, cardiac troponin I, acetylcholinesterase, acetylcholine, epinephrine, and norepinephrine were tested on hospital days 1, 3, and 5 and on discharge day. Electrocardiography was recorded on admission and then every other day. Transthoracic echocardiography was performed at admission, in the acute phase, before discharge, and during follow-up. Technetium 99m-sestamibi myocardial single photon emission computed tomography was conducted in four patients. Thirty-seven (90.2%) patients survived and four (9.8%) patients died during treatment. We observed sinus tachycardia in 37 (90.2%) patients and ST-T changes in 33 (80.4%) patients. Creatine kinase isoenzyme myocardium and cardiac troponin I levels peaked at day 3 postadmission and then decreased to normal levels. Serum acetylcholine, epinephrine, and norepinephrine peaked at day 1 after admission and then decreased. Echocardiography revealed marked decreases in wall motion of the interventricular septum and left ventricle in the acute phase but returned to normal in the recovery phase. The left ventricular ejection fraction improved significantly from 42 +/- 5% to 59 +/- 4% (p = .001). Single photon emission computed tomography showed abnormal left ventricle perfusion. CONCLUSION: Severe acute dichlorvos poisoning is associated with reversible myocardial dysfunction, possibly through an increase in catecholamine levels.
ESTHER : He_2011_Crit.Care.Med_39_1906
PubMedSearch : He_2011_Crit.Care.Med_39_1906
PubMedID: 21516037

Title : Structure-activity relationship studies of sulfonylpiperazine analogues as novel negative allosteric modulators of human neuronal nicotinic receptors - Henderson_2011_J.Med.Chem_54_8681
Author(s) : Henderson BJ , Carper DJ , Gonzalez-Cestari TF , Yi B , Mahasenan K , Pavlovicz RE , Dalefield ML , Coleman RS , Li C , McKay DB
Ref : Journal of Medicinal Chemistry , 54 :8681 , 2011
Abstract : Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer's disease, Parkinson's disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human alpha4beta2 (Halpha4beta2) and human alpha3beta4 (Halpha3beta4) nicotinic receptors. The effects of novel sulfonylpiperazine analogues that act as negative allosteric modulators on both Halpha4beta2 nAChRs and Halpha3beta4 nAChRs were investigated. This work, through structure-activity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on Halpha4beta2 nAChRs.
ESTHER : Henderson_2011_J.Med.Chem_54_8681
PubMedSearch : Henderson_2011_J.Med.Chem_54_8681
PubMedID: 22060139

Title : Discovery of Novel alpha4beta2 Neuronal Nicotinic Receptor Modulators through Structure-Based Virtual Screening - Mahasenan_2011_ACS.Med.Chem.Lett_2_855
Author(s) : Mahasenan KV , Pavlovicz RE , Henderson BJ , Gonzalez-Cestari TF , Yi B , McKay DB , Li C
Ref : ACS Med Chem Lett , 2 :855 , 2011
Abstract : We performed a hierarchical structure-based virtual screening utilizing a comparative model of the human alpha4beta2 neuronal nicotinic acetylcholine receptor (nAChR) extracellular domain. Compounds were selected for experimental testing based on structural diversity, binding pocket location, and standard error of the free energy scoring function used in the screening. Four of the eleven in silico hit compounds showed promising activity with low micromolar IC50 values in a calcium accumulation assay. Two of the antagonists were also proven to be selective for human alpha4beta2 vs human alpha3beta4 nAChRs. This is the first report of successful discovery of novel nAChR antagonists through the use of structure-based virtual screening with a human nAChR homology model. These compounds may serve as potential novel scaffolds for further development of selective nAChR antagonists.
ESTHER : Mahasenan_2011_ACS.Med.Chem.Lett_2_855
PubMedSearch : Mahasenan_2011_ACS.Med.Chem.Lett_2_855
PubMedID: 24936233

Title : Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases - Hu_2011_J.Chromatogr.A_1218_6646
Author(s) : Hu Z , Sun Y , Du F , Niu W , Xu F , Huang Y , Li C
Ref : Journal of Chromatography A , 1218 :6646 , 2011
Abstract : Simmitecan (L-P) is an anticancer ester prodrug, which involves activation to chimmitecan (L-2-Z). In the current study, a liquid chromatography/tandem mass spectrometry-based method was developed for simultaneous determination of L-P and L-2-Z in various plasma samples. Because L-P is rapidly converted to L-2-Z by blood carboxylesterase during and after sampling, which hampers accurate determination of L-P and L-2-Z in the biological samples, different carboxylesterase inhibitors were tested. As a result, bis(4-nitrophenyl)phosphate gave the best results with respect to inhibitory capability, hemolysis, and matrix effects and was used to deactivate blood carboxylesterases when sampling. The plasma samples were precipitated with acetonitrile and the resulting supernatants were separated using a pulse gradient method on a C18 column. Irinotecan and camptothecin were used as internal standards for quantification of L-P and L-2-Z, respectively. Protonated L-P, L-2-Z and their internal standards were generated by electrospray ionization and their precursor-product ion pairs (m/z 599-->124, 405-->361, 587-->195, and 349-->305, respectively) were used for measurement. The newly developed bioanalytical assay processed favorable accuracy and precision with lower limits of quantification of 2.1 nM for L-P and 3.4 nM for L-2-Z, and was successfully applied to pharmacokinetic studies in tumor-bearing nude mice, rats, and dogs. There are substantial species differences in the ester activity. The experimental strategies illustrated in our report may be adopted for measurement of other prodrugs (including irinotecan) or drugs subject to ester hydrolysis, as well as their metabolites, in biological matrices.
ESTHER : Hu_2011_J.Chromatogr.A_1218_6646
PubMedSearch : Hu_2011_J.Chromatogr.A_1218_6646
PubMedID: 21839460

Title : Colorimetric assays for acetylcholinesterase activity and inhibitor screening based on the disassembly-assembly of a water-soluble polythiophene derivative - Li_2011_ACS.Appl.Mater.Interfaces_3_1306
Author(s) : Li Y , Bai H , Li C , Shi G
Ref : ACS Appl Mater Interfaces , 3 :1306 , 2011
Abstract : A complex between an anionic polythiophene derivative (PT-COO(-)) and a cationic surfactant, myristoylcholine, has been prepared and applied to be colorimetric probe for acetylcholinesterase (AChE) assays. The complex formation process, AChE activity assay and inhibitor screening has been studied by absorption spectroscopy. It was confirmed that the introduction of myristoylcholine into PT-COO(-) phosphate buffer solution resulted in the disassembly of PT-COO(-) aggregates, and further addition of AChE into the above solution led to the reassembly of PT-COO(-) due to the catalyzed hydrolysis of myristoylcholine and the collapse of the complex. The colorimetric assay for AChE can be readily realized with the concentration of AChE as low as 0.2 U/mL. The results also demonstrate that the colorimetric approach can be applied for screening inhibitors of AChE.
ESTHER : Li_2011_ACS.Appl.Mater.Interfaces_3_1306
PubMedSearch : Li_2011_ACS.Appl.Mater.Interfaces_3_1306
PubMedID: 21438627

Title : The genome of the leaf-cutting ant Acromyrmex echinatior suggests key adaptations to advanced social life and fungus farming - Nygaard_2011_Genome.Res_21_1339
Author(s) : Nygaard S , Zhang G , Schiott M , Li C , Wurm Y , Hu H , Zhou J , Ji L , Qiu F , Rasmussen M , Pan H , Hauser F , Krogh A , Grimmelikhuijzen CJ , Wang J , Boomsma JJ
Ref : Genome Res , 21 :1339 , 2011
Abstract : We present a high-quality (>100x depth) Illumina genome sequence of the leaf-cutting ant Acromyrmex echinatior, a model species for symbiosis and reproductive conflict studies. We compare this genome with three previously sequenced genomes of ants from different subfamilies and focus our analyses on aspects of the genome likely to be associated with known evolutionary changes. The first is the specialized fungal diet of A. echinatior, where we find gene loss in the ant's arginine synthesis pathway, loss of detoxification genes, and expansion of a group of peptidase proteins. One of these is a unique ant-derived contribution to the fecal fluid, which otherwise consists of "garden manuring" fungal enzymes that are unaffected by ant digestion. The second is multiple mating of queens and ejaculate competition, which may be associated with a greatly expanded nardilysin-like peptidase gene family. The third is sex determination, where we could identify only a single homolog of the feminizer gene. As other ants and the honeybee have duplications of this gene, we hypothesize that this may partly explain the frequent production of diploid male larvae in A. echinatior. The fourth is the evolution of eusociality, where we find a highly conserved ant-specific profile of neuropeptide genes that may be related to caste determination. These first analyses of the A. echinatior genome indicate that considerable genetic changes are likely to have accompanied the transition from hunter-gathering to agricultural food production 50 million years ago, and the transition from single to multiple queen mating 10 million years ago.
ESTHER : Nygaard_2011_Genome.Res_21_1339
PubMedSearch : Nygaard_2011_Genome.Res_21_1339
PubMedID: 21719571
Gene_locus related to this paper: acrec-f4we58 , acrec-f4wfr0 , acrec-f4wwr9 , acrec-f4x396 , acrec-f4wlq1 , acrec-f4wk97 , acrec-f4wdb2 , acrec-f4wdb3 , acrec-f4x1t2

Title : Identification of a negative allosteric site on human alpha4beta2 and alpha3beta4 neuronal nicotinic acetylcholine receptors - Pavlovicz_2011_PLoS.One_6_e24949
Author(s) : Pavlovicz RE , Henderson BJ , Bonnell AB , Boyd RT , McKay DB , Li C
Ref : PLoS ONE , 6 :e24949 , 2011
Abstract : Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human alpha4beta2 and alpha3beta4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the beta2 subunit were independently mutated to the corresponding residues found on the beta4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human alpha4beta2 over alpha3beta4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 microM. These results demonstrate the selectivity of KAB-18 for human alpha4beta2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders.
ESTHER : Pavlovicz_2011_PLoS.One_6_e24949
PubMedSearch : Pavlovicz_2011_PLoS.One_6_e24949
PubMedID: 21949802

Title : Hydrophobic surface induced activation of Pseudomonas cepacia lipase immobilized into mesoporous silica - Jin_2011_Langmuir_27_12016
Author(s) : Jin Q , Jia G , Zhang Y , Yang Q , Li C
Ref : Langmuir , 27 :12016 , 2011
Abstract : Lipase from Pseudomonas cepacia (PCL) was successfully immobilized into siliceous mesocellular foams (MCFs) with various hydrophobic/hydrophilic surfaces. The catalytic performances of immobilized PCL were investigated using the transesterification reaction and hydrolytic reaction as model reactions. The specific activity of immobilized PCL greatly increased with enhanced surface hydrophobicity of MCFs, mainly because of lipase activation via hydrophobic interaction between alkyl groups in MCFs and the surface loop (so-called "lid") of PCL. Conformational changes of immobilized PCL were further investigated using time-resolved fluorescence spectroscopy with Trp as an intrinsic probe. When the immobilized PCL was suspended in phosphate buffer, short-lived tau(1) shortened and the fractional contribution of tau(1) significantly increased with the increasing level of surface hydrophobicity of MCFs. These results revealed that Trp(s) of the immobilized PCL were surrounded by a hydrophilic microenvironment because of the fact that the opened "lid" permitted the diffusion of water to the active site cleft. However, for the immobilized PCL suspended in n-hexane, long-lived tau(3) increased with the increase of surface hydrophobicity of MCFs. The reduced interaction between Trp(s) and the surrounding protein matrix was due to intercalation of n-hexane into the active site cleft when the lipase was in open conformation. The above results demonstrated that PCL immobilized into MCF with hydrophobic surfaces were in an activated open conformation.
ESTHER : Jin_2011_Langmuir_27_12016
PubMedSearch : Jin_2011_Langmuir_27_12016
PubMedID: 21851086

Title : Possible ligand release pathway of dipeptidyl peptidase IV investigated by molecular dynamics simulations - Li_2011_Proteins_79_1800
Author(s) : Li C , Shen J , Li W , Lu C , Liu G , Tang Y
Ref : Proteins , 79 :1800 , 2011
Abstract : Dipeptidyl peptidase IV (DPP4) is an important target for the treatment of Type II diabetes mellitus. The crystal structure of DPP4 demonstrates that there are two possible pathways to the active site, a side opening and a beta propeller opening. However, it still lacks quantitative evidence to illustrate which pathway is more favorable for inhibitor to enter into or release from the active site. In this study, conventional and steered molecular dynamics simulations were performed to explore the details of inhibitor Q448 release from the active site of DPP4 via the two potential pathways. The comparisons of force and work together with potentials of mean force results suggested that the side opening might be more favorable for the inhibitor to pass through. Moreover, Glu205-Glu206 and Phe357 were recognized as two "key residues" in the active site for inhibitor binding. Accordingly, suggestions for further inhibitor design were provided.
ESTHER : Li_2011_Proteins_79_1800
PubMedSearch : Li_2011_Proteins_79_1800
PubMedID: 21465558

Title : Genome sequencing and comparison of two nonhuman primate animal models, the cynomolgus and Chinese rhesus macaques - Yan_2011_Nat.Biotechnol_29_1019
Author(s) : Yan G , Zhang G , Fang X , Zhang Y , Li C , Ling F , Cooper DN , Li Q , Li Y , van Gool AJ , Du H , Chen J , Chen R , Zhang P , Huang Z , Thompson JR , Meng Y , Bai Y , Wang J , Zhuo M , Wang T , Huang Y , Wei L , Li J , Wang Z , Hu H , Yang P , Le L , Stenson PD , Li B , Liu X , Ball EV , An N , Huang Q , Fan W , Zhang X , Wang W , Katze MG , Su B , Nielsen R , Yang H , Wang X
Ref : Nat Biotechnol , 29 :1019 , 2011
Abstract : The nonhuman primates most commonly used in medical research are from the genus Macaca. To better understand the genetic differences between these animal models, we present high-quality draft genome sequences from two macaque species, the cynomolgus/crab-eating macaque and the Chinese rhesus macaque. Comparison with the previously sequenced Indian rhesus macaque reveals that all three macaques maintain abundant genetic heterogeneity, including millions of single-nucleotide substitutions and many insertions, deletions and gross chromosomal rearrangements. By assessing genetic regions with reduced variability, we identify genes in each macaque species that may have experienced positive selection. Genetic divergence patterns suggest that the cynomolgus macaque genome has been shaped by introgression after hybridization with the Chinese rhesus macaque. Macaque genes display a high degree of sequence similarity with human disease gene orthologs and drug targets. However, we identify several putatively dysfunctional genetic differences between the three macaque species, which may explain functional differences between them previously observed in clinical studies.
ESTHER : Yan_2011_Nat.Biotechnol_29_1019
PubMedSearch : Yan_2011_Nat.Biotechnol_29_1019
PubMedID: 22002653
Gene_locus related to this paper: macfa-BCHE , macfa-g7nzc0 , macfa-g7nze2 , macfa-g7p4b9 , macfa-g7pa87 , macfa-g7pd01 , macfa-g7q259 , macfa-3neur , macfa-g8f585 , macfa-KANSL3 , macfa-q4r8p0 , macfa-SPG21 , macfa-TEX30 , macmu-3neur , macmu-ACHE , macmu-BCHE , macmu-f6sz31 , macmu-f6the6 , macmu-f6zkq5 , macmu-f7buk8 , macmu-f7cfi8 , macmu-f7flv1 , macmu-f7ggk1 , macmu-f7hir7 , macmu-g7n054 , macmu-g7npb8 , macmu-g7nq39 , macmu-KANSL3 , macmu-TEX30 , macfa-g7pgg6 , macmu-g7n4x3 , macfa-g7nzx2 , macfa-g8f4f7 , macmu-f7ba84 , macfa-g7psx7 , macmu-h9er02 , macfa-g8f3k0 , macfa-a0a2k5w1n7 , macmu-g7mxj6 , macfa-g7pbk1 , macfa-a0a2k5urk5 , macfa-a0a2k5wye4 , macfa-g7pe14 , macmu-f7hkw9 , macmu-f7hm08 , macmu-g7mke4 , macfa-g7nxn9 , macmu-a0a1d5rh04 , macmu-h9fud6 , macfa-g8f3e1 , macfa-i7gcw6 , macmu-f6qwx1 , macmu-f7h4t2 , macfa-a0a2k5wkd0 , macfa-a0a2k5v7v4 , macfa-g7p7y3 , macfa-a0a2k5uqq3 , macmu-i2cu80 , macfa-g8f5i1 , macmu-f7h550 , macmu-f7gkb9 , macfa-a0a2k5tui1

Title : Integrated transcriptional and proteomic analysis with in vitro biochemical assay reveal the important role of CYP3A46 in T-2 toxin hydroxylation in porcine primary hepatocytes - Wang_2011_Mol.Cell.Proteomics_10_M111 008748
Author(s) : Wang J , Jiang J , Zhang H , Cai H , Li C , Li K , Liu J , Guo X , Zou G , Wang D , Deng Y , Dai J
Ref : Mol Cell Proteomics , 10 :M111 008748 , 2011
Abstract : Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3'-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions.
ESTHER : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedSearch : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedID: 21685020

Title : Protective effect of sodium aescinate on lung injury induced by methyl parathion - Du_2011_Hum.Exp.Toxicol_30_1584
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Zhao DL , Li C , Fu FH
Ref : Hum Exp Toxicol , 30 :1584 , 2011
Abstract : Methyl parathion (MP) is a high venenosus insecticide. It has been used in pest control of agriculture for several years. The present study is performed to investigate the protective effect of sodium aescinate (SA) on lung injury induced by MP. Forty male Sprague-Dawley rats are randomly divided into five groups, with 8 animals in each group: control group, MP administration group, MP plus SA at doses of 0.45 mg/kg, 0.9 mg/kg and 1.8 mg/kg groups. Acetylcholinesterase (AChE) activity and nitric oxide (NO) level in plasma, myeloperoxidase (MPO) activity, NO level, and antioxidative parameters in lung tissue are assayed. Histopathological examination of lung is also performed. The results show that SA has no effect on AChE. Treatment with SA decreases the activity of MPO in lung and the level of NO in plasma and lung. The level of malondialdehyde in lung is decreased after SA treatments. SA increases the activities of superoxide dismutase, glutathione peroxidase and the content of glutathione in lung. SA administration also ameliorates lung injury induced by MP. The findings indicate that SA could protect lung injury induced by MP and the mechanism of action is related to the anti-inflammatory and anti-oxidative effect of SA.
ESTHER : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedSearch : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedID: 21177729

Title : A subpopulation of neuronal M4 muscarinic acetylcholine receptors plays a critical role in modulating dopamine-dependent behaviors - Jeon_2010_J.Neurosci_30_2396
Author(s) : Jeon J , Dencker D , Wortwein G , Woldbye DP , Cui Y , Davis AA , Levey AI , Schutz G , Sager TN , Mork A , Li C , Deng CX , Fink-Jensen A , Wess J
Ref : Journal of Neuroscience , 30 :2396 , 2010
Abstract : Acetylcholine (ACh) regulates many key functions of the CNS by activating cell surface receptors referred to as muscarinic ACh receptors (M(1)-M(5) mAChRs). Like other mAChR subtypes, the M(4) mAChR is widely expressed in different regions of the forebrain. Interestingly, M(4) mAChRs are coexpressed with D(1) dopamine receptors in a specific subset of striatal projection neurons. To investigate the physiological relevance of this M(4) mAChR subpopulation in modulating dopamine-dependent behaviors, we used Cre/loxP technology to generate mutant mice that lack M(4) mAChRs only in D(1) dopamine receptor-expressing cells. The newly generated mutant mice displayed several striking behavioral phenotypes, including enhanced hyperlocomotor activity and increased behavioral sensitization following treatment with psychostimulants. These behavioral changes were accompanied by a lack of muscarinic inhibition of D(1) dopamine receptor-mediated cAMP stimulation in the striatum and an increase in dopamine efflux in the nucleus accumbens. These novel findings demonstrate that a distinct subpopulation of neuronal M(4) mAChRs plays a critical role in modulating several important dopamine-dependent behaviors. Since enhanced central dopaminergic neurotransmission is a hallmark of several severe disorders of the CNS, including schizophrenia and drug addiction, our findings have substantial clinical relevance.
ESTHER : Jeon_2010_J.Neurosci_30_2396
PubMedSearch : Jeon_2010_J.Neurosci_30_2396
PubMedID: 20147565

Title : Negative allosteric modulators that target human alpha4beta2 neuronal nicotinic receptors - Henderson_2010_J.Pharmacol.Exp.Ther_334_761
Author(s) : Henderson BJ , Pavlovicz RE , Allen JD , Gonzalez-Cestari TF , Orac CM , Bonnell AB , Zhu MX , Boyd RT , Li C , Bergmeier SC , McKay DB
Ref : Journal of Pharmacology & Experimental Therapeutics , 334 :761 , 2010
Abstract : Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. We have previously reported on the pharmacological activity of several compounds that act as negative allosteric modulators (NAMs) of nAChRs. In the following studies, the effects of 30 NAMs from our small chemical library on both human alpha4beta2 (Halpha4beta2) and human alpha3beta4 (Halpha3beta4) nAChRs expressed in human embryonic kidney ts201 cells were investigated. During calcium accumulation assays, these NAMs inhibited nAChR activation with IC(50) values ranging from 2.4 microM to more than 100 microM. Several NAMs showed relative selectivity for Halpha4beta2 nAChRs with IC(50) values in the low micromolar range. A lead molecule, KAB-18, was identified that shows relative selectivity for Halpha4beta2 nAChRs. This molecule contains three phenyl rings, one piperidine ring, and one ester bond linkage. Structure-activity relationship (SAR) analyses of our data revealed three regions of KAB-18 that contribute to its relative selectivity. Predictive three-dimensional quantitative SAR (comparative molecular field analysis and comparative molecular similarity indices analysis) models were generated from these data, and a pharmacophore model was constructed to determine the chemical features that are important for biological activity. Using docking approaches and molecular dynamics on a Halpha4beta2 nAChR homology model, a binding mode for KAB-18 at the alpha/beta subunit interface that corresponds to the predicted pharmacophore is described. This binding mode was supported by mutagenesis studies. In summary, these studies highlight the importance of SAR, computational, and molecular biology approaches for the design and synthesis of potent and selective antagonists targeting specific nAChR subtypes.
ESTHER : Henderson_2010_J.Pharmacol.Exp.Ther_334_761
PubMedSearch : Henderson_2010_J.Pharmacol.Exp.Ther_334_761
PubMedID: 20551292

Title : A novel GLP-1 analog, BPI3006, with potent DPP IV resistance and good glucoregulatory effect - Li_2010_Biochem.Biophys.Res.Commun_400_563
Author(s) : Li C , Huan Y , Shen N , Ji L , Sun S , Liu S , Liu Q , Gao L , Tan F , Wang Y , Shen Z
Ref : Biochemical & Biophysical Research Communications , 400 :563 , 2010
Abstract : Glucagon-like peptide-1 (GLP-1) is an incretin hormone that decreases postprandial glycemic excursions by enhancing insulin secretion but with short half-life due to rapid inactivation by enzymatic N-terminal truncation. Therefore, efforts are being made to improve the stability of GLP-1 via modifying its structure or inhibiting dipeptidyl-peptidase IV (DPP IV), which is responsible for its degradation. Here we report a novel GLP-1 analog BPI3006 with -NHCO- of Ala(8) replaced by -CH(CF(3))NH- and features of its metabolic stability, GLP-1 receptor trans-activation and in vivo biological activity. BPI3006 is highly resistant to DPP IV-mediated degradation with 91.1% of parental peptide left after 24h exposure to the enzyme. BPI3006 also effectively activates its target gene promoter through GLP-1 receptor activation by measuring the transiently transfected reporter gene green fluorescence protein (GFP) expression in NIT-1 cells. Furthermore, BPI3006 could well restrain the glycemia variation in fasted normal ICR mice after a single administration followed by an oral glucose loading. In spontaneous type 2 diabetic KKA(y) mice, BPI3006 injected twice daily could significantly improve the oral glucose tolerance and hyperinsulinemia, as well as ameliorate the food and water consumption. In conclusion, BPI3006 has enhanced resistance to DPP IV leading to improved stability, and shows excellent in vivo biological activity. Thus it may be a new candidate for T2DM treatment and its novel modification may provide valuable guidance for the future development of long-acting GLP-1 analogs.
ESTHER : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedSearch : Li_2010_Biochem.Biophys.Res.Commun_400_563
PubMedID: 20804731

Title : Cannabinoid receptors are coupled to stimulation of insulin secretion from mouse MIN6 beta-cells - Li_2010_Cell.Physiol.Biochem_26_187
Author(s) : Li C , Jones PM , Persaud SJ
Ref : Cell Physiol Biochem , 26 :187 , 2010
Abstract : Endocannabinoid lipids are known to exert orexigenic effects via central cannabinoid CB1 and CB2 receptors, which have also been identified in islet endocrine cells. However, there is no consensus on whether the receptors are expressed by beta-cells, nor what effect CB1 and CB2 receptor agonists have on insulin secretion. In the current study we have therefore used the mouse MIN6 beta-cell line rather than primary islets, which are heterogeneous clusters of endocrine cells. Cannabinoid receptor and diacylglycerol lipase isoform mRNAs were detected in MIN6 cells by RT-PCR and immunocytochemistry was used to identify cannabinoid receptor expression by MIN6 cells. Changes in cyclic AMP and intracellular calcium were measured by immunoassay and microfluorimetry, respectively, and insulin secretion from perifused MIN6 pseudoislets was determined by radioimmunoassay. MIN6 beta-cells express the cannabinoid synthesising enzyme diacylglycerol lipase and CB1 and CB2 receptors, which are coupled to inhibition of beta-cell cyclic AMP generation and stimulation of intracellular calcium levels. Cannabinoid receptor activation with pharmacological agonists resulted in reversible elevations in insulin secretion at both 2 mM and 20 mM glucose. Synthesis of endocannabinoids by beta-cells may provide an additional mechanism for stimulation of insulin secretion through activation of beta-cell CB1 and/or CB2 cannabinoid receptors.
ESTHER : Li_2010_Cell.Physiol.Biochem_26_187
PubMedSearch : Li_2010_Cell.Physiol.Biochem_26_187
PubMedID: 20798502

Title : Analysis of the conformational stability and activity of Candida antarctica lipase B in organic solvents: insight from molecular dynamics and quantum mechanics\/simulations - Li_2010_J.Biol.Chem_285_28434
Author(s) : Li C , Tan T , Zhang H , Feng W
Ref : Journal of Biological Chemistry , 285 :28434 , 2010
Abstract : The conformational stability and activity of Candida antarctica lipase B (CALB) in the polar and nonpolar organic solvents were investigated by molecular dynamics and quantum mechanics/molecular mechanics simulations. The conformation change of CALB in the polar and nonpolar solvents was examined in two aspects: the overall conformation change of CALB and the conformation change of the active site. The simulation results show that the overall conformation of CALB is stable in the organic solvents. In the nonpolar solvents, the conformation of the active site keeps stable, whereas in the polar solvents, the solvent molecules reach into the active site and interact intensively with the active site. This interaction destroys the hydrogen bonding between Ser(105) and His(224). In the solvents, the activation energy of CALB and that of the active site region were further simulated by quantum mechanics/molecular mechanics simulation. The results indicate that the conformation change in the region of active sites is the main factor that influences the activity of CALB.
ESTHER : Li_2010_J.Biol.Chem_285_28434
PubMedSearch : Li_2010_J.Biol.Chem_285_28434
PubMedID: 20601697

Title : Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism - Zhao_2010_Cell.Res_20_1096
Author(s) : Zhao W , Zhong Y , Yuan H , Wang J , Zheng H , Wang Y , Cen X , Xu F , Bai J , Han X , Lu G , Zhu Y , Shao Z , Yan H , Li C , Peng N , Zhang Z , Zhang Y , Lin W , Fan Y , Qin Z , Hu Y , Zhu B , Wang S , Ding X , Zhao GP
Ref : Cell Res , 20 :1096 , 2010
Abstract : Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimycobacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10,236,715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9,228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel 'quasi-core' with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.
ESTHER : Zhao_2010_Cell.Res_20_1096
PubMedSearch : Zhao_2010_Cell.Res_20_1096
PubMedID: 20567260
Gene_locus related to this paper: amyme-ester , amymu-d8hj63 , amymu-d8hka5 , amymu-d8hl19 , amymu-d8hp99 , amymu-d8hpp2 , amymu-d8htc9 , amymu-d8hu68 , amymu-d8hu87 , amymu-d8hy40 , amymu-d8hy73 , amymu-d8i2j5 , amymu-d8i4g6 , amymu-d8i8i8 , amymu-d8hri1 , amymu-d8hsx7 , amymu-d8hzu8 , amymu-d8i5g7 , amyms-g0g7f0 , amymu-a0a0h3cwx4 , amymu-a0a0h3d2a5 , amymu-a0a0h3d6r8

Title : Genomic comparison of the ants Camponotus floridanus and Harpegnathos saltator - Bonasio_2010_Science_329_1068
Author(s) : Bonasio R , Zhang G , Ye C , Mutti NS , Fang X , Qin N , Donahue G , Yang P , Li Q , Li C , Zhang P , Huang Z , Berger SL , Reinberg D , Wang J , Liebig J
Ref : Science , 329 :1068 , 2010
Abstract : The organized societies of ants include short-lived worker castes displaying specialized behavior and morphology and long-lived queens dedicated to reproduction. We sequenced and compared the genomes of two socially divergent ant species: Camponotus floridanus and Harpegnathos saltator. Both genomes contained high amounts of CpG, despite the presence of DNA methylation, which in non-Hymenoptera correlates with CpG depletion. Comparison of gene expression in different castes identified up-regulation of telomerase and sirtuin deacetylases in longer-lived H. saltator reproductives, caste-specific expression of microRNAs and SMYD histone methyltransferases, and differential regulation of genes implicated in neuronal function and chemical communication. Our findings provide clues on the molecular differences between castes in these two ants and establish a new experimental model to study epigenetics in aging and behavior.
ESTHER : Bonasio_2010_Science_329_1068
PubMedSearch : Bonasio_2010_Science_329_1068
PubMedID: 20798317
Gene_locus related to this paper: 9hyme-e1zye4 , 9hyme-e2a0n6 , 9hyme-e2a3j7 , 9hyme-e2a4n5 , 9hyme-e2a4n6 , 9hyme-e2a8v4 , 9hyme-e2a9y2 , 9hyme-e2acx6 , 9hyme-e2adw2 , 9hyme-e2adw3 , 9hyme-e2adw4 , 9hyme-e2adw5 , 9hyme-e2adw7 , 9hyme-e2adw9 , 9hyme-e2adx0 , 9hyme-e2ai90 , 9hyme-e2ajl7 , 9hyme-e2ajl8 , 9hyme-e2ajl9 , 9hyme-e2am67 , 9hyme-e2am68 , 9hyme-e2any0 , 9hyme-e2ara9 , 9hyme-e2axr7 , 9hyme-e2b2q4 , 9hyme-e2b493 , 9hyme-e2bc53 , 9hyme-e2bft9 , 9hyme-e2bfu1 , 9hyme-e2bfu2 , 9hyme-e2bi28 , 9hyme-e2bn41 , 9hyme-e2by80 , 9hyme-e2c2j5 , camfo-e1zwv0 , camfo-e1zxk2 , camfo-e1zze7 , camfo-e2a1a9 , camfo-e2a6b9 , camfo-e2a925 , camfo-e2af07 , camfo-e2af09 , camfo-e2ahe1 , camfo-e2am62 , camfo-e2ap71 , camfo-e2aqx6 , camfo-e2ar09 , camfo-e2arj6 , camfo-e2ask6 , camfo-e2av24 , camfo-e2axp8 , camfo-e2az30 , camfo-e2b0g1 , camfo-e2b1u7 , camfo-e2b1v1 , harsa-e2b4e6 , harsa-e2b4y5 , harsa-e2b5u0 , harsa-e2b6u3 , harsa-e2b8w0 , harsa-e2b8w2 , harsa-e2b370 , harsa-e2b563 , harsa-e2bfn3 , harsa-e2bh58 , harsa-e2bh77 , harsa-e2bnc8 , harsa-e2bng4 , harsa-e2bnh3 , harsa-e2btb0 , harsa-e2buf0 , harsa-e2bva8 , harsa-e2bwj6 , harsa-e2bwn1 , harsa-e2c1r6 , harsa-e2c1r7 , harsa-e2c5m6 , harsa-e2c6m2 , harsa-e2c618 , camfo-e2ad05 , harsa-e2ca28 , camfo-e2a8t9 , harsa-e2blx5 , camfo-e1zxe8 , harsa-e2bmi6 , harsa-e2c8h0 , camfo-e2a7b9 , camfo-e1zyd7 , camfo-e1zyd8 , harsa-e2c2j9 , harsa-e2bmu7 , camfo-e2ax69 , camfo-e2a482 , harsa-e2c147

Title : Biocatalytic synthesis and in vitro release of biodegradable linear polyesters with pendant ketoprofen - Wang_2010_Biomacromolecules_11_3290
Author(s) : Wang HY , Zhang WW , Wang N , Li C , Li K , Yu XQ
Ref : Biomacromolecules , 11 :3290 , 2010
Abstract : Enzyme-catalyzed polycondensation for the synthesis of polyester prodrugs of ketoprofen was reported. Lipase acrylic resin from Candida antarctica (CAL-B) was used to synthesize the linear polyesters with pendent ketoprofen groups based on ketoprofen glycerol ester, poly(ethylene glycol), and divinyl sebacate. The products were characterized by GPC and (1)H NMR. The results indicated that the molecular weight and yields of the polyesters depend on experimental conditions such as temperature and feed ratio. The in vitro study showed that the drug release from the polyester was slow under physiological conditions, which indicated that the polyester could be a promising prodrug with extended pharmacological effects by delayed release of ketoprofen.
ESTHER : Wang_2010_Biomacromolecules_11_3290
PubMedSearch : Wang_2010_Biomacromolecules_11_3290
PubMedID: 21053944

Title : Pathologically activated neuroprotection via uncompetitive blockade of N-methyl-D-aspartate receptors with fast off-rate by novel multifunctional dimer bis(propyl)-cognitin - Luo_2010_J.Biol.Chem_285_19947
Author(s) : Luo J , Li W , Zhao Y , Fu H , Ma DL , Tang J , Li C , Peoples RW , Li F , Wang Q , Huang P , Xia J , Pang Y , Han Y
Ref : Journal of Biological Chemistry , 285 :19947 , 2010
Abstract : Uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonists with fast off-rate (UFO) may represent promising drug candidates for various neurodegenerative disorders. In this study, we report that bis(propyl)-cognitin, a novel dimeric acetylcholinesterase inhibitor and gamma-aminobutyric acid subtype A receptor antagonist, is such an antagonist of NMDA receptors. In cultured rat hippocampal neurons, we demonstrated that bis(propyl)-cognitin voltage-dependently, selectively, and moderately inhibited NMDA-activated currents. The inhibitory effects of bis(propyl)-cognitin increased with the rise in NMDA and glycine concentrations. Kinetics analysis showed that the inhibition was of fast onset and offset with an off-rate time constant of 1.9 s. Molecular docking simulations showed moderate hydrophobic interaction between bis(propyl)-cognitin and the MK-801 binding region in the ion channel pore of the NMDA receptor. Bis(propyl)-cognitin was further found to compete with [(3)H]MK-801 with a K(i) value of 0.27 mum, and the mutation of NR1(N616R) significantly reduced its inhibitory potency. Under glutamate-mediated pathological conditions, bis(propyl)-cognitin, in contrast to bis(heptyl)-cognitin, prevented excitotoxicity with increasing effectiveness against escalating levels of glutamate and much more effectively protected against middle cerebral artery occlusion-induced brain damage than did memantine. More interestingly, under NMDA receptor-mediated physiological conditions, bis(propyl)-cognitin enhanced long-term potentiation in hippocampal slices, whereas MK-801 reduced and memantine did not alter this process. These results suggest that bis(propyl)-cognitin is a UFO antagonist of NMDA receptors with moderate affinity, which may provide a pathologically activated therapy for various neurodegenerative disorders associated with NMDA receptor dysregulation.
ESTHER : Luo_2010_J.Biol.Chem_285_19947
PubMedSearch : Luo_2010_J.Biol.Chem_285_19947
PubMedID: 20404346

Title : Esterification activity and conformation studies of Burkholderia cepacia lipase in conventional organic solvents, ionic liquids and their co-solvent mixture media - Pan_2010_Bioresour.Technol_101_9822
Author(s) : Pan S , Liu X , Xie Y , Yi Y , Li C , Yan Y , Liu Y
Ref : Bioresour Technol , 101 :9822 , 2010
Abstract : In this work, experiments were carried out to evaluate the esterification activity and conformation of lipase from Burkholderia cepacia in the selected conventional organic solvents, ionic liquids and their co-solvent mixture media. The results revealed that the activity of esterification of B. cepacia lipase was mostly highest in co-solvent mixture of ionic liquids-organic solvents, followed by conventional organic solvents and ionic liquids. Hence, co-solvent mixture was a high-effective strategy to enhance the activity of B. cepacia lipase for non-aqueous enzymology reaction. Conformational studies via circular dichroism spectroscopy indicated that the secondary structure of B. cepacia lipase was variant in the above-mentioned media, especially the content of alpha-helix, which was probably responsible for lipase activity difference.
ESTHER : Pan_2010_Bioresour.Technol_101_9822
PubMedSearch : Pan_2010_Bioresour.Technol_101_9822
PubMedID: 20713309

Title : Protective effect of reduced glutathione on the respiratory muscle injury induced by acute omethoate poisoning - Lu_2009_Pestic.Biochem.Physiol_95_135
Author(s) : Lu L , Fu F , Wang T , He P , Xin W , Li C
Ref : Pesticide Biochemistry and Physiology , 95 :135 , 2009
Abstract : The aim of this work was to investigate whether reduced glutathione (GSH) could protect rats from the respiratory muscle injury induced by omethoate. Three groups named as control, OM (omethoate poisoning) and OM + GSH (omethoate poisoning treated with GSH) were arranged. The cholinesterase (ChE) activity was assayed and the pathological observation of respiratory muscles was carried out. Furthermore, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and the free organophosphate (FOP) remained in the respiratory muscles were measured. The results indicated that ChE activity was significantly inhibited by omethoate and not be changed by GSH. GSH could attenuate the respiratory muscle injury after omethoate poisoning. No changes of SOD, GPx, CAT and FOP were found after GSH was given. The findings suggested that GSH could protect the respiratory muscle against injury induced by omethoate, which was not the result of GSH to reactivate ChE or regulate the antioxidant enzymes.
ESTHER : Lu_2009_Pestic.Biochem.Physiol_95_135
PubMedSearch : Lu_2009_Pestic.Biochem.Physiol_95_135

Title : Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery - Gonzalez-Cestari_2009_J.Pharmacol.Exp.Ther_328_504
Author(s) : Gonzalez-Cestari TF , Henderson BJ , Pavlovicz RE , McKay SB , El-Hajj RA , Pulipaka AB , Orac CM , Reed DD , Boyd RT , Zhu MX , Li C , Bergmeier SC , McKay DB
Ref : Journal of Pharmacology & Experimental Therapeutics , 328 :504 , 2009
Abstract : Allosteric modulation of nAChRs is considered to be one of the most promising approaches for drug design targeting nicotinic acetylcholine receptors (nAChRs). We have reported previously on the pharmacological activity of several compounds that seem to act noncompetitively to inhibit the activation of alpha3beta4(*) nAChRs. In this study, the effects of 51 structurally similar molecules on native and recombinant alpha3beta4 nAChRs are characterized. These 51 molecules inhibited adrenal neurosecretion activated via stimulation of native alpha3beta4(*) nAChR, with IC(50) values ranging from 0.4 to 13.0 microM. Using cells expressing recombinant alpha3beta4 nAChRs, these molecules inhibited calcium accumulation (a more direct assay to establish nAChR activity), with IC(50) values ranging from 0.7 to 38.2 microM. Radiolabeled nAChR binding studies to orthosteric sites showed no inhibitory activity on either native or recombinant nAChRs. Correlation analyses of the data from both functional assays suggested additional, non-nAChR activity of the molecules. To test this hypothesis, the effects of the drugs on neurosecretion stimulated through non-nAChR mechanisms were investigated; inhibitory effects ranged from no inhibition to 95% inhibition at concentrations of 10 microM. Correlation analyses of the functional data confirmed this hypothesis. Several of the molecules (24/51) increased agonist binding to native nAChRs, supporting allosteric interactions with nAChRs. Computational modeling and blind docking identified a binding site for our negative allosteric modulators near the orthosteric binding site of the receptor. In summary, this study identified several molecules for potential development as negative allosteric modulators and documented the importance of multiple screening assays for nAChR drug discovery.
ESTHER : Gonzalez-Cestari_2009_J.Pharmacol.Exp.Ther_328_504
PubMedSearch : Gonzalez-Cestari_2009_J.Pharmacol.Exp.Ther_328_504
PubMedID: 18984653

Title : Thiostrepton biosynthesis: prototype for a new family of bacteriocins - Kelly_2009_J.Am.Chem.Soc_131_4327
Author(s) : Kelly WL , Pan L , Li C
Ref : Journal of the American Chemical Society , 131 :4327 , 2009
Abstract : Thiopeptide antibiotics are a group of highly modified peptide metabolites. The defining scaffold for the thiopeptides is a macrocycle containing a dehydropiperidine or pyridine ring, dehydrated amino acids, and multiple thiazole or oxazole rings. Some members of the thiopeptides, such as thiostrepton, also contain either a quinaldic acid or indolic acid substituent derived from tryptophan. Although the amino acid precursors of these metabolites are well-established, the biogenesis of these complex peptides has remained elusive. Whole-genome scanning of Streptomyces laurentii permitted identification of a thiostrepton prepeptide, TsrA, and involvement of TsrA in thiostrepton biosynthesis was confirmed by mutagenesis. A gene cluster responsible for thiostrepton biosynthesis is reported, and the encoded gene products are discussed. The disruption of a gene encoding an amidotransferase, tsrT, led to the loss of thiostrepton production and the detection of a new metabolite, contributing further support to the identification of the tsr cluster. The tsr locus also appears to possess the gene products needed to convert tryptophan to the quinaldic acid moiety, and an aminotransferase was found to catalyze an early step in this pathway. This work establishes that the thiopeptides are a type of bacteriocin, a family of genetically encoded antimicrobial peptides, and are subjected to extensive posttranslational modification during maturation of the prepeptide.
ESTHER : Kelly_2009_J.Am.Chem.Soc_131_4327
PubMedSearch : Kelly_2009_J.Am.Chem.Soc_131_4327
PubMedID: 19265401
Gene_locus related to this paper: strlu-c0jry1 , strlu-c0l0l7

Title : Selective alpha7 nicotinic receptor activation by AZD0328 enhances cortical dopamine release and improves learning and attentional processes - Sydserff_2009_Biochem.Pharmacol_78(7)_880
Author(s) : Sydserff S , Sutton EJ , Song D , Quirk MC , Maciag C , Li C , Jonak G , Gurley D , Gordon JC , Christian EP , Doherty JJ , Hudzik T , Johnson E , Mrzljak L , Piser T , Smagin GN , Wang Y , Widzowski D , Smith JS
Ref : Biochemical Pharmacology , 78 :880 , 2009
Abstract : AZD0328, a novel spirofuropyridine neuronal nicotinic receptor partial agonist, was used to investigate the role of alpha7 neuronal nicotinic receptor (NNR) activation in the modulation of midbrain dopamine neuron function, cortical dopamine release and on two behavioral tasks known to be dependent on optimal levels of cortical dopamine. In vivo recordings from area 10 (ventral tegmental area) in rat brain showed an increased firing of putative dopamine neurons in response to low (0.00138 mg/kg) doses of AZD0328. Bursting patterns of dopamine neuron activity remained largely unchanged by application of AZD0328. In vivo microdialysis in awake rats showed an increase in extracellular prefrontal cortical dopamine in response to low doses of AZD0328. Compound-stimulated dopamine release showed an inverted dose effect relation that was maximal at the lowest dose tested (0.00178 mg/kg). Peak extracellular dopamine levels were reached 2h after dosing with AZD0328. Acquisition of operant responding with delayed reinforcement in rats was dose dependently enhanced by AZD0328 with a plateau effect measured at 0.003 mg/kg. This effect was blocked by pre-treatment of animals with the selective alpha7 antagonist methyllycaconitine. AZD0328 improved novel object recognition in mice over a broad range of doses (0.00178-1.78 mg/kg) and the compound effect was found to be absent in homozygous alpha7 KO animals. Together, these data indicate that selective interaction with alpha7 NNRs by AZD0328 selectively enhances midbrain dopaminergic neuronal activity causing an enhancement of cortical dopamine levels; these neurochemical changes likely, underlie the positive behavioral responses observed in two different animal models. Our results suggest selective alpha7 NNR agonists may have significant therapeutic utility in neurologic and psychiatric indications where cognitive deficits and dopamine neuron dysfunction co-exist.
ESTHER : Sydserff_2009_Biochem.Pharmacol_78(7)_880
PubMedSearch : Sydserff_2009_Biochem.Pharmacol_78(7)_880
PubMedID: 19615981

Title : Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes - Mu_2009_Eur.J.Pharmacol_623_148
Author(s) : Mu J , Petrov A , Eiermann GJ , Woods J , Zhou YP , Li Z , Zycband E , Feng Y , Zhu L , Roy RS , Howard AD , Li C , Thornberry NA , Zhang BB
Ref : European Journal of Pharmacology , 623 :148 , 2009
Abstract : Inhibition of dipeptidyl peptidase-4 (DPP-4) activity has been shown to improve glycemic control in patients with type 2 diabetes by prolonging and potentiating the actions of incretin hormones. This study is designed to determine the effects of the DPP-4 inhibitor sitagliptin on improving islet function in a mouse model of insulin resistance and insulin secretion defects. ICR mice were pre-treated with high fat diet and a low dose of streptozotocin to induce insulin resistance and impaired insulin secretion, respectively. Diabetic mice were treated with sitagliptin or the sulfonylurea agent glipizide as admixture to high fat diet for ten weeks. Sustained reduction of blood glucose, HbA(1c), circulating glucagon and improvement in oral glucose tolerance were observed in mice treated with sitagliptin. In contrast, glipizide improved glycemic control only during the early weeks and to a lesser degree compared to sitagliptin, and had no effect on circulating glucagon levels or glucose tolerance. The improvement in glycemic control in sitagliptin-treated mice was associated with a significant increase in glucose-dependent insulin secretion in both perfused pancreas and isolated islets. Importantly, in contrast to the lack of effect by glipizide, sitagliptin significantly restored beta and alpha cell mass as well as alpha/beta cell ratio. These data indicate that DPP-4 inhibition by sitagliptin provided better overall improvement of glycemic control compared to glipizide in the high fat diet/streptozotocin induced diabetic mouse model. The ability of sitagliptin to enhance islet cell function may offer insight into the potential for disease modification.
ESTHER : Mu_2009_Eur.J.Pharmacol_623_148
PubMedSearch : Mu_2009_Eur.J.Pharmacol_623_148
PubMedID: 19765579

Title : The genome sequence of taurine cattle: a window to ruminant biology and evolution - Elsik_2009_Science_324_522
Author(s) : Elsik CG , Tellam RL , Worley KC , Gibbs RA , Muzny DM , Weinstock GM , Adelson DL , Eichler EE , Elnitski L , Guigo R , Hamernik DL , Kappes SM , Lewin HA , Lynn DJ , Nicholas FW , Reymond A , Rijnkels M , Skow LC , Zdobnov EM , Schook L , Womack J , Alioto T , Antonarakis SE , Astashyn A , Chapple CE , Chen HC , Chrast J , Camara F , Ermolaeva O , Henrichsen CN , Hlavina W , Kapustin Y , Kiryutin B , Kitts P , Kokocinski F , Landrum M , Maglott D , Pruitt K , Sapojnikov V , Searle SM , Solovyev V , Souvorov A , Ucla C , Wyss C , Anzola JM , Gerlach D , Elhaik E , Graur D , Reese JT , Edgar RC , McEwan JC , Payne GM , Raison JM , Junier T , Kriventseva EV , Eyras E , Plass M , Donthu R , Larkin DM , Reecy J , Yang MQ , Chen L , Cheng Z , Chitko-McKown CG , Liu GE , Matukumalli LK , Song J , Zhu B , Bradley DG , Brinkman FS , Lau LP , Whiteside MD , Walker A , Wheeler TT , Casey T , German JB , Lemay DG , Maqbool NJ , Molenaar AJ , Seo S , Stothard P , Baldwin CL , Baxter R , Brinkmeyer-Langford CL , Brown WC , Childers CP , Connelley T , Ellis SA , Fritz K , Glass EJ , Herzig CT , Iivanainen A , Lahmers KK , Bennett AK , Dickens CM , Gilbert JG , Hagen DE , Salih H , Aerts J , Caetano AR , Dalrymple B , Garcia JF , Gill CA , Hiendleder SG , Memili E , Spurlock D , Williams JL , Alexander L , Brownstein MJ , Guan L , Holt RA , Jones SJ , Marra MA , Moore R , Moore SS , Roberts A , Taniguchi M , Waterman RC , Chacko J , Chandrabose MM , Cree A , Dao MD , Dinh HH , Gabisi RA , Hines S , Hume J , Jhangiani SN , Joshi V , Kovar CL , Lewis LR , Liu YS , Lopez J , Morgan MB , Nguyen NB , Okwuonu GO , Ruiz SJ , Santibanez J , Wright RA , Buhay C , Ding Y , Dugan-Rocha S , Herdandez J , Holder M , Sabo A , Egan A , Goodell J , Wilczek-Boney K , Fowler GR , Hitchens ME , Lozado RJ , Moen C , Steffen D , Warren JT , Zhang J , Chiu R , Schein JE , Durbin KJ , Havlak P , Jiang H , Liu Y , Qin X , Ren Y , Shen Y , Song H , Bell SN , Davis C , Johnson AJ , Lee S , Nazareth LV , Patel BM , Pu LL , Vattathil S , Williams RL, Jr. , Curry S , Hamilton C , Sodergren E , Wheeler DA , Barris W , Bennett GL , Eggen A , Green RD , Harhay GP , Hobbs M , Jann O , Keele JW , Kent MP , Lien S , McKay SD , McWilliam S , Ratnakumar A , Schnabel RD , Smith T , Snelling WM , Sonstegard TS , Stone RT , Sugimoto Y , Takasuga A , Taylor JF , Van Tassell CP , Macneil MD , Abatepaulo AR , Abbey CA , Ahola V , Almeida IG , Amadio AF , Anatriello E , Bahadue SM , Biase FH , Boldt CR , Carroll JA , Carvalho WA , Cervelatti EP , Chacko E , Chapin JE , Cheng Y , Choi J , Colley AJ , de Campos TA , De Donato M , Santos IK , de Oliveira CJ , Deobald H , Devinoy E , Donohue KE , Dovc P , Eberlein A , Fitzsimmons CJ , Franzin AM , Garcia GR , Genini S , Gladney CJ , Grant JR , Greaser ML , Green JA , Hadsell DL , Hakimov HA , Halgren R , Harrow JL , Hart EA , Hastings N , Hernandez M , Hu ZL , Ingham A , Iso-Touru T , Jamis C , Jensen K , Kapetis D , Kerr T , Khalil SS , Khatib H , Kolbehdari D , Kumar CG , Kumar D , Leach R , Lee JC , Li C , Logan KM , Malinverni R , Marques E , Martin WF , Martins NF , Maruyama SR , Mazza R , McLean KL , Medrano JF , Moreno BT , More DD , Muntean CT , Nandakumar HP , Nogueira MF , Olsaker I , Pant SD , Panzitta F , Pastor RC , Poli MA , Poslusny N , Rachagani S , Ranganathan S , Razpet A , Riggs PK , Rincon G , Rodriguez-Osorio N , Rodriguez-Zas SL , Romero NE , Rosenwald A , Sando L , Schmutz SM , Shen L , Sherman L , Southey BR , Lutzow YS , Sweedler JV , Tammen I , Telugu BP , Urbanski JM , Utsunomiya YT , Verschoor CP , Waardenberg AJ , Wang Z , Ward R , Weikard R , Welsh TH, Jr. , White SN , Wilming LG , Wunderlich KR , Yang J , Zhao FQ
Ref : Science , 324 :522 , 2009
Abstract : To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
ESTHER : Elsik_2009_Science_324_522
PubMedSearch : Elsik_2009_Science_324_522
PubMedID: 19390049
Gene_locus related to this paper: bovin-2neur , bovin-a0jnh8 , bovin-a5d7b7 , bovin-ACHE , bovin-balip , bovin-dpp4 , bovin-dpp6 , bovin-e1bi31 , bovin-e1bn79 , bovin-est8 , bovin-f1mbd6 , bovin-f1mi11 , bovin-f1mr65 , bovin-f1n1l4 , bovin-g3mxp5 , bovin-q0vcc8 , bovin-q2kj30 , bovin-q3t0r6 , bovin-thyro

Title : Template enhanced activity of lipase accommodated in siliceous mesocellular foams - Zhang_2008_Biochem.Biophys.Res.Commun_372_650
Author(s) : Zhang Y , Zhao L , Li J , Zhang H , Zheng L , Cao S , Li C
Ref : Biochemical & Biophysical Research Communications , 372 :650 , 2008
Abstract : Lipases were adsorbed in siliceous mesocellular foams containing different amounts of residual template in the nanopores. It is found that the hydrolytic activities of the adsorbed lipases are increased with increasing the contents of template in the mesopores. The triacetin hydrolytic activity of the lipase adsorbed in the foam containing 46% of template can be 13 times higher than that of the lipase adsorbed in the foam without template in the nanopores, and its specific activity is about three times higher than that of the free lipase, showing the hyperactivation effect on lipase resulting from the interaction between the lipase and the surfactant in the nanopores. The immobilized lipase cross-linked with glutaraldehyde can retain up to 88% of its original activity after six hydrolysis reaction test. This work provides a new strategy to enhance the activity of immobilized lipase in mesoporous materials.
ESTHER : Zhang_2008_Biochem.Biophys.Res.Commun_372_650
PubMedSearch : Zhang_2008_Biochem.Biophys.Res.Commun_372_650
PubMedID: 18510948

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

Title : Efficacy and safety of donepezil in patients with schizophrenia or schizoaffective disorder: significant placebo\/practice effects in a 12-week, randomized, double-blind, placebo-controlled trial - Keefe_2008_Neuropsychopharmacology_33_1217
Author(s) : Keefe RS , Malhotra AK , Meltzer HY , Kane JM , Buchanan RW , Murthy A , Sovel M , Li C , Goldman R
Ref : Neuropsychopharmacology , 33 :1217 , 2008
Abstract : Altered expression of central muscarinic and nicotinic acetylcholine receptors in hippocampal and cortical regions may contribute to the cognitive impairment exhibited in patients with schizophrenia. Increasing cholinergic activity through the use of a cholinesterase inhibitor (ChEI) therefore represents a possible strategy for cognitive augmentation in schizophrenia. We examined the efficacy and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive impairment in schizophrenia or schizoaffective disorder in a prospective, 12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 patients (18-55 years) with schizophrenia or schizoaffective disorder who were clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The primary outcome measure was the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) neurocognitive battery composite score. In the intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed improvement in the composite score from baseline to week 12. At week 12, cognitive improvement with donepezil was similar to that with placebo (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and statistically significantly inferior for the observed-cases analysis (0.257 vs 0.450; p=0.044). There was statistically significant improvement in the Positive and Negative Syndrome Assessment Scale negative symptoms score for placebo compared with donepezil, while total and positive symptom scores were similar between both treatments. Statistically significant improvements in positive symptoms score and Clinical Global Impression-Improvement for donepezil compared with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs were rated as mild to moderate in severity. Donepezil was safe and well-tolerated but was not effective compared with placebo as a cotreatment for the improvement of cognitive impairment in this patient population. A significant and surprisingly large placebo/practice effect was observed among placebo-treated patients, and is a serious consideration in future clinical trial study designs for potential cognitive enhancing compounds in schizophrenia.
ESTHER : Keefe_2008_Neuropsychopharmacology_33_1217
PubMedSearch : Keefe_2008_Neuropsychopharmacology_33_1217
PubMedID: 17625502

Title : Catalytic promiscuity in the alpha\/beta-hydrolase superfamily: hydroxamic acid formation, C--C bond formation, ester and thioester hydrolysis in the C--C hydrolase family - Li_2008_Chembiochem_9_71
Author(s) : Li C , Hassler M , Bugg TD
Ref : Chembiochem , 9 :71 , 2008
Abstract : The haloperoxidase family of alpha/beta-hydrolases contains enzymes of several different catalytic activities, including esterases, C--C hydrolases and cofactor-independent haloperoxidases (perhydrolases), but the molecular basis of this catalytic promiscuity is not fully understood. The C--C hydrolase enzyme MhpC from E. coli is shown to possess esterase and thioesterase activity, and the ability to activate hydroxylamine as a nucleophile to form hydroxamic acid products. The ratio of these activities was examined for nine site-directed mutant enzymes that contained mutations at nonessential residues in the enzyme active site. Higher levels of esterase and thioesterase activity were found in mutants Phe173Gly and Trp264Gly; this might be due to increased amounts of space in the active site. Higher levels of hydroxamic acid formation activity were found in mutant Asn109His-a mutation found in many haloperoxidase enzymes. Wild-type and mutant MhpC enzymes were also capable of C--C bond formation in organic solvents, and the highest activity was observed in nonpolar solvents. The results provide experimental support for the catalytic promiscuity shown in this family of enzymes, and indicate that differences in catalytic function can be introduced by point mutations.
ESTHER : Li_2008_Chembiochem_9_71
PubMedSearch : Li_2008_Chembiochem_9_71
PubMedID: 18058773
Gene_locus related to this paper: ecoli-mhpc

Title : Evolution of the aging brain transcriptome and synaptic regulation - Loerch_2008_PLoS.One_3_e3329
Author(s) : Loerch PM , Lu T , Dakin KA , Vann JM , Isaacs A , Geula C , Wang J , Pan Y , Gabuzda DH , Li C , Prolla TA , Yankner BA
Ref : PLoS ONE , 3 :e3329 , 2008
Abstract : Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes.
ESTHER : Loerch_2008_PLoS.One_3_e3329
PubMedSearch : Loerch_2008_PLoS.One_3_e3329
PubMedID: 18830410

Title : Effectiveness of open-label donepezil treatment in patients with Alzheimer's disease discontinuing memantine monotherapy - Sakka_2007_Curr.Med.Res.Opin_23_3153
Author(s) : Sakka P , Tsolaki M , Hort J , Hager K , Soininen H , Lopez Pousa S , Li C , Schwam E
Ref : Curr Med Res Opin , 23 :3153 , 2007
Abstract : OBJECTIVE: To evaluate the efficacy and safety of donepezil in patients with Alzheimer's disease (AD) who discontinue memantine due to a lack of efficacy or not being well tolerated.
METHODS: This study enrolled patients with moderate-to-severe AD (Mini-Mental State Examination [MMSE] score 5-17) who had a history of treatment with memantine monotherapy (10 mg/BID) for > or = 3 months prior to screening and maintained until study baseline. For inclusion in this study, the patient's memantine treatment had to have been judged as lacking efficacy or not well tolerated at the screening visit. Information on previous memantine use was also obtained with regard to dose and duration of treatment. At the baseline visit, patients were switched to open-label donepezil 5 mg/day for 4 weeks, and 10 mg/day thereafter. The primary efficacy measure was a change in MMSE at week 12 using a last observation carried forward (LOCF) analysis. Secondary measures included Physician and Caregiver Satisfaction Questionnaires (PSQ, CSQ), the Clinical Global Impression-Improvement (CGI-I), Neuropsychiatric Inventory (NPI), and a Caregiver Diary (CD).
RESULTS: At week 12-LOCF, MMSE scores increased by a mean of 1.55 points from baseline (p < 0.0001). At end point, the PSQ and CSQ indicated consistent improvements in satisfaction/ease of use with donepezil; 60.2% of patients improved on the CGI-I; and 44.4-55.6% improved on each of three components of the CD. Improvements on the MMSE, CSQ, and CGI-I were apparent, irrespective of previous cholinesterase (ChE) inhibitor use. No significant effects were seen for the total score on the NPI. Withdrawal rates (8.7% due to adverse events [AEs]) and AEs were consistent with the known donepezil safety profile. CONCLUSION: Donepezil was effective and well tolerated in moderate-to-severe AD patients who discontinued memantine monotherapy, including those with previous exposure to ChE inhibitors.
ESTHER : Sakka_2007_Curr.Med.Res.Opin_23_3153
PubMedSearch : Sakka_2007_Curr.Med.Res.Opin_23_3153
PubMedID: 17988434

Title : Imprinting analysis of the porcine MEST gene in 75 and 90 day placentas and prenatal tissues - Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
Author(s) : Xu C , Su L , Zhou Q , Li C , Zhao S
Ref : Acta Biochim Biophys Sin (Shanghai) , 39 :633 , 2007
Abstract : Imprinted genes play important roles in mammalian growth, development and behavior. Mouse mesoderm-specific transcript (MEST) has been identified as an imprinted gene and mapped to an imprinted region of mouse chromosome 6 (MMU6). It plays essential roles in embryonic and placental growth, and it is required for maternal behavior in adult female mouse. Here, we isolated the porcine MEST gene and detected a single nucleotide polymorphism in the 3 -untranslated region. The RsaI polymorphism was used to investigate the allele frequencies in different pig breeds and the imprinting status in prenatal porcine tissues. Allele frequencies were significantly different between the native Chinese and Landrace breeds, except that most of the native Yushan pigs (21/26) are heterozygous at this locus. The results indicate that MEST was imprinted in placentas on days 75 and 90 of gestation as well as in the 75 d fetal heart, muscle, kidney, lung and liver.
ESTHER : Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
PubMedSearch : Xu_2007_Acta.Biochim.Biophys.Sin.(Shanghai)_39_633
PubMedID: 17687499

Title : Preconditioning ischemia attenuates increased neurexin-neuroligin1-PSD-95 interaction after transient cerebral ischemia in rat hippocampus - Li_2007_Neurosci.Lett_426_192
Author(s) : Li C , Han D , Zhang F , Zhou C , Yu HM , Zhang GY
Ref : Neuroscience Letters , 426 :192 , 2007
Abstract : In this study, we investigated the interactions between synapse adhesion molecules neurexin, neuroligin1, neuroligin2 and postsynaptic density protein 95 (PSD-95) in transient cerebral ischemia and possible regulatory mechanism of these interactions. Our data show that preconditioning ischemia can down-regulate the increased neurexin-neuroligin1-PSD-95 interaction induced by ischemia injury and exerts a neuroprotective effect. Pre-treatment of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can demolish this neuroprotective effect of preconditioning by increasing neurexin-neuroligin1-PSD-95 interaction. These results indicate that the neurexin-neuroligin1-PSD-95 is an important signalling module in ischemic injury and a novel possible target in therapeutics of brain ischemia.
ESTHER : Li_2007_Neurosci.Lett_426_192
PubMedSearch : Li_2007_Neurosci.Lett_426_192
PubMedID: 17904739

Title : Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes - Mu_2006_Diabetes_55_1695
Author(s) : Mu J , Woods J , Zhou YP , Roy RS , Li Z , Zycband E , Feng Y , Zhu L , Li C , Howard AD , Moller DE , Thornberry NA , Zhang BB
Ref : Diabetes , 55 :1695 , 2006
Abstract : Inhibitors of dipeptidyl peptidase-4 (DPP-4), a key regulator of the actions of incretin hormones, exert antihyperglycemic effects in type 2 diabetic patients. A major unanswered question concerns the potential ability of DPP-4 inhibition to have beneficial disease-modifying effects, specifically to attenuate loss of pancreatic beta-cell mass and function. Here, we investigated the effects of a potent and selective DPP-4 inhibitor, an analog of sitagliptin (des-fluoro-sitagliptin), on glycemic control and pancreatic beta-cell mass and function in a mouse model with defects in insulin sensitivity and secretion, namely high-fat diet (HFD) streptozotocin (STZ)-induced diabetic mice. Significant and dose-dependent correction of postprandial and fasting hyperglycemia, HbA(1c), and plasma triglyceride and free fatty acid levels were observed in HFD/STZ mice following 2-3 months of chronic therapy. Treatment with des-fluoro-sitagliptin dose dependently increased the number of insulin-positive beta-cells in islets, leading to the normalization of beta-cell mass and beta-cell-to-alpha-cell ratio. In addition, treatment of mice with des-fluoro-sitagliptin, but not glipizide, significantly increased islet insulin content and improved glucose-stimulated insulin secretion in isolated islets. These findings suggest that DPP-4 inhibitors may offer long-lasting efficacy in the treatment of type 2 diabetes by modifying the courses of the disease.
ESTHER : Mu_2006_Diabetes_55_1695
PubMedSearch : Mu_2006_Diabetes_55_1695
PubMedID: 16731832

Title : Catalytic role for arginine 188 in the C-C hydrolase catalytic mechanism for Escherichia coli MhpC and Burkholderia xenovorans LB400 BphD - Li_2006_Biochemistry_45_12470
Author(s) : Li C , Li JJ , Montgomery MG , Wood SP , Bugg TD
Ref : Biochemistry , 45 :12470 , 2006
Abstract : The alpha/beta-hydrolase superfamily, comprised mainly of esterase and lipase enzymes, contains a family of bacterial C-C hydrolases, including MhpC and BphD which catalyze the hydrolytic C-C cleavage of meta-ring fission intermediates on the Escherichia coli phenylpropionic acid pathway and Burkholderia xenovorans LB400 biphenyl degradation pathway, respectively. Five active site amino acid residues (Arg-188, Asn-109, Phe-173, Cys-261, and Trp-264) were identified from sequence alignments that are conserved in C-C hydrolases, but not in enzymes of different function. Replacement of Arg-188 in MhpC with Gln and Lys led to 200- and 40-fold decreases, respectively, in k(cat); the same replacements for Arg-190 of BphD led to 400- and 700-fold decreases, respectively, in k(cat). Pre-steady-state kinetic analysis of the R188Q MhpC mutant revealed that the first step of the reaction, keto-enol tautomerization, had become rate-limiting, indicating that Arg-188 has a catalytic role in ketonization of the dienol substrate, which we propose is via substrate destabilization. Mutation of nearby residues Phe-173 and Trp-264 to Gly gave 4-10-fold reductions in k(cat) but 10-20-fold increases in K(m), indicating that these residues are primarily involved in substrate binding. The X-ray structure of a succinate-H263A MhpC complex shows concerted movements in the positions of both Phe-173 and Trp-264 that line the approach to Arg-188. Mutation of Asn-109 to Ala and His yielded 200- and 350-fold reductions, respectively, in k(cat) and pre-steady-state kinetic behavior similar to that of a previous S110A mutant, indicating a role for Asn-109 is positioning the active site loop containing Ser-110. The catalytic role of Arg-188 is rationalized by a hydrogen bond network close to the C-1 carboxylate of the substrate, which positions the substrate and promotes substrate ketonization, probably via destabilization of the bound substrate.
ESTHER : Li_2006_Biochemistry_45_12470
PubMedSearch : Li_2006_Biochemistry_45_12470
PubMedID: 17029402

Title : Evidence for a gem-diol reaction intermediate in bacterial C-C hydrolase enzymes BphD and MhpC from 13C NMR spectroscopy - Li_2006_Biochemistry_45_12461
Author(s) : Li JJ , Li C , Blindauer CA , Bugg TD
Ref : Biochemistry , 45 :12461 , 2006
Abstract : C-C hydrolase enzymes MhpC and BphD catalyze the hydrolytic C-C cleavage of meta-ring fission intermediates on the Escherichia coli phenylpropionic acid and Burkholderia xenovorans LB400 biphenyl degra