Li D

References (139)

Title : Onset of Alzheimer disease in apolipoprotein sigma4 carriers is earlier in butyrylcholinesterase K variant carriers - Lane_2024_BMC.Neurol_24_116
Author(s) : Lane RM , Darreh-Shori T , Junge C , Li D , Yang Q , Edwards AL , Graham DL , Moore K , Mummery CJ
Ref : BMC Neurol , 24 :116 , 2024
Abstract : BACKGROUND: The authors sought to examine the impact of the K-variant of butyrylcholinesterase (BCHE-K) carrier status on age-at-diagnosis of Alzheimer disease (AD) in APOE4 carriers. METHODS: Patients aged 50-74 years with cerebrospinal fluid (CSF) biomarker-confirmed AD, were recruited to clinical trial (NCT03186989 since June 14, 2017). Baseline demographics, disease characteristics, and biomarkers were evaluated in 45 patients according to BCHE-K and APOE4 allelic status in this post-hoc study. RESULTS: In APOE4 carriers (N = 33), the mean age-at-diagnosis of AD in BCHE-K carriers (n = 11) was 6.4 years earlier than in BCHE-K noncarriers (n = 22, P < .001, ANOVA). In APOE4 noncarriers (N = 12) there was no observed influence of BCHE-K. APOE4 carriers with BCHE-K also exhibited slightly higher amyloid and tau accumulations compared to BCHE-K noncarriers. A predominantly amyloid, limited tau, and limbic-amnestic phenotype was exemplified by APOE4 homozygotes with BCHE-K. In the overall population, multiple regression analyses demonstrated an association of amyloid accumulation with APOE4 carrier status (P < .029), larger total brain ventricle volume (P < .021), less synaptic injury (Ng, P < .001), and less tau pathophysiology (p-tau(181), P < .005). In contrast, tau pathophysiology was associated with more neuroaxonal damage (NfL, P = .002), more synaptic injury (Ng, P < .001), and higher levels of glial activation (YKL-40, P = .01). CONCLUSION: These findings have implications for the genetic architecture of prognosis in early AD, not the genetics of susceptibility to AD. In patients with early AD aged less than 75 years, the mean age-at-diagnosis of AD in APOE4 carriers was reduced by over 6 years in BCHE-K carriers versus noncarriers. The functional status of glia may explain many of the effects of APOE4 and BCHE-K on the early AD phenotype. TRIAL REGISTRATION: NCT03186989 since June 14, 2017.
ESTHER : Lane_2024_BMC.Neurol_24_116
PubMedSearch : Lane_2024_BMC.Neurol_24_116
PubMedID: 38594621
Gene_locus related to this paper: human-BCHE

Title : Smartphone-assisted colorimetric biosensor for the determination of organophosphorus pesticides on the peel of fruits - Li_2024_Food.Chem_443_138459
Author(s) : Li D , Li J , Wu C , Liu H , Zhao M , Shi H , Zhang Y , Wang T
Ref : Food Chem , 443 :138459 , 2024
Abstract : Nowadays, the widespread use of organophosphorus pesticides (OPs) in agricultural production leads to varying degrees of residues in crops, which pose a potential threat to human health. Conventional methods used in national standard for the detection of OPs in fruits and vegetables require expensive instruments or cumbersome sample pretreatment steps for the analysis. To address these challenges, in this work, we took advantage of the peroxidase-like activity of PtCu(3) alloy nanocrystals (NCs) for a colorimetric and smartphone assisted sensitive detection of OPs. With the assist of a smartphone, the concentration of OPs on the peel of fruits could be obtained by comparing the B/RG value (the brightness value of blue divided by those of red and green) of a test strip with a calibration curve. This work not only provides a facile and cost-effective method to detect pesticides but also makes a positive contribution to food safety warning.
ESTHER : Li_2024_Food.Chem_443_138459
PubMedSearch : Li_2024_Food.Chem_443_138459
PubMedID: 38306911

Title : Bacterial lipase-responsive polydopamine nanoparticles for detection and synergistic therapy of wound biofilms infection - Jiang_2024_Int.J.Biol.Macromol__132350
Author(s) : Jiang H , Huang X , Li H , Ren F , Li D , Liu Y , Tong Y , Ran P
Ref : Int J Biol Macromol , :132350 , 2024
Abstract : Wound biofilms represent an elusive conundrum in contemporary treatment and diagnostic options, accredited to their escalating antibiotic resistance and interference in chronic wound healing processes. Here, we developed mesoporous polydopamine (mPDA) nanoparticles, and grafted with rhodamine B (Rb) as biofilm lipase responsive detection probe, followed by Pi - Pi stacking mediated ciprofloxacin (CIP) loading to create mP-Rb@CIP nanoparticles. mPDA NPs with a melanin structure could quench fluorescence emissions of Rb. Once encountering biofilm in vivo, the ester bond in Rb and mPDA is hydrolyzed by elevated lipase concentrations, triggering the liberation of Rb and restore fluorescence emissions to achieve real-time imaging of biofilm-infected wounds. Afterwards, the 808 nm near-infrared (NIR) illumination initiates a spatiotemporal controlled antibacterial photothermal therapy (PTT), boosting its effectiveness through photothermal-triggered CIP release for synergistic biofilm eradication. The mP-Rb@CIP platform exhibits dual diagnostic and therapeutic functions, efficaciously treating biofilm-infected wounds in vivo and in vitro. Particularly, the mP-Rb@CIP/NIR procedure expedites wound-healing by alleviating oxidative stress, modulating inflammatory mediators, boosting collagen synthesis, and promoting angiogenesis. Taken together, the theranostic nanosystem strategy holds significant potential for addressing wound biofilm-associated infections.
ESTHER : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedSearch : Jiang_2024_Int.J.Biol.Macromol__132350
PubMedID: 38750839

Title : Molecular basis of the inositol deacylase PGAP1 involved in quality control of GPI-AP biogenesis - Hong_2024_Nat.Commun_15_8
Author(s) : Hong J , Li T , Chao Y , Xu Y , Zhu Z , Zhou Z , Gu W , Qu Q , Li D
Ref : Nat Commun , 15 :8 , 2024
Abstract : The secretion and quality control of glycosylphosphatidylinositol-anchored proteins (GPI-APs) necessitates post-attachment remodeling initiated by the evolutionarily conserved PGAP1, which deacylates the inositol in nascent GPI-APs. Impairment of PGAP1 activity leads to developmental diseases in humans and fatality and infertility in animals. Here, we present three PGAP1 structures (2.66-2.84 A), revealing its 10-transmembrane architecture and product-enzyme interaction details. PGAP1 holds GPI-AP acyl chains in an optimally organized, guitar-shaped cavity with apparent energetic penalties from hydrophobic-hydrophilic mismatches. However, abundant glycan-mediated interactions in the lumen counterbalance these repulsions, likely conferring substrate fidelity and preventing off-target hydrolysis of bulk membrane lipids. Structural and biochemical analyses uncover a serine hydrolase-type catalysis with atypical features and imply mechanisms for substrate entrance and product release involving a drawing compass movement of GPI-APs. Our findings advance the mechanistic understanding of GPI-AP remodeling.
ESTHER : Hong_2024_Nat.Commun_15_8
PubMedSearch : Hong_2024_Nat.Commun_15_8
PubMedID: 38167496
Gene_locus related to this paper: chatd-g0s652 , human-PGAP1

Title : Genome-wide association studies of egg production traits by whole genome sequencing of Laiwu Black chicken - Lei_2024_Poult.Sci_103_103705
Author(s) : Lei Q , Zhang S , Wang J , Qi C , Liu J , Cao D , Li F , Han H , Liu W , Li D , Tang C , Zhou Y
Ref : Poult Sci , 103 :103705 , 2024
Abstract : Compared to high-yield commercial laying hens, Chinese indigenous chicken breeds have poor egg laying capacity due to the lack of intensive selection. However, as these breeds have not undergone systematic selection, it is possible that there is a greater abundance of genetic variations related to egg laying traits. In this study, we assessed 5 egg number (EN) traits at different stages of the egg-laying period: EN1 (from the first egg to 23 wk), EN2 (from 23 to 35 wk), EN3 (from 35 to 48 wk), EN4 (from the first egg to 35 wk), and EN5 (from the first egg to 48 wk). To investigate the molecular mechanisms underlying egg number traits in a Chinese local chicken breed, we conducted a genome-wide association study (GWAS) using data from whole-genome sequencing (WGS) of 399 Laiwu Black chickens. We obtained a total of 3.01 Tb of raw data with an average depth of 7.07 x per individual. A total of 86 genome-wide suggestive or significant single-nucleotide polymorphisms (SNP) contained within a set of 45 corresponding candidate genes were identified and found to be associated with stages EN1-EN5. The genes vitellogenin 2 (VTG2), lipase maturation factor 1 (LMF1), calcium voltage-gated channel auxiliary subunit alpha2delta 3 (CACNA2D3), poly(A) binding protein cytoplasmic 1 (PABPC1), programmed cell death 11 (PDCD11) and family with sequence similarity 213 member A (FAM213A) can be considered as the candidate genes associated with egg number traits, due to their reported association with animal reproduction traits. Noteworthy, results suggests that VTG2 and PDCD11 are not only involved in the regulation of EN3, but also in the regulation of EN5, implies that VTG2 and PDCD11 have a significant influence on egg production traits. Our study offers valuable genomic insights into the molecular genetic mechanisms that govern egg number traits in a Chinese indigenous egg-laying chicken breed. These findings have the potential to enhance the egg-laying performance of chickens.
ESTHER : Lei_2024_Poult.Sci_103_103705
PubMedSearch : Lei_2024_Poult.Sci_103_103705
PubMedID: 38598913

Title : SlCarE054 in Spodoptera litura (Lepidoptera: Noctuidae) showed direct metabolic activity to beta-cypermethrin with stereoselectivity - Xu_2024_Bull.Entomol.Res__1
Author(s) : Xu L , Liu H , Li B , Li G , Liu R , Li D
Ref : Bull Entomol Res , :1 , 2024
Abstract : Carboxylesterases (CarEs) is an important detoxification enzyme system in phase participating in insecticides resistance. In our previous study, SlCarE054, a CarEs gene from lepidoptera class, was screened out to be upregulated in a pyrethroids and organophosphates resistant population. Its overexpression was verified in two field-collected populations of Spodoptera litura (Lepidoptera: Noctuidae) resistant to pyrethroids and organophosphates by qRT-PCR. Spatiotemporal expression results showed that SlCarE054 was highly expressed in the pupae stage and the digestive tissue midgut. To further explore its role in pyrethroids and organophosphates resistance, its metabolism activity to insecticides was determined by UPLC. Its recombinant protein showed significant metabolism activity to cyhalothrin and fenvalerate, but not to phoxim or chlorpyrifos. The metabolic activity of SlCarE054 to beta-cypermethrin showed stereoselectivity, with higher metabolic activity to -cypermethrin than the enantiomer alpha-cypermethrin. The metabolite of beta-cypermethrin was identified as 3-phenoxybenzaldehyde. Further modelling and docking analysis indicated that beta-cypermethrin, cyhalothrin and fenvalerate could bind with the catalytic triad of the 3D structure of SlCarE054. The interaction of beta-cypermethrin with SlCarE054 also showed the lowest binding energy. Our work provides evidence that SlCarE054 play roles in beta-cypermethrin resistance in S. litura.
ESTHER : Xu_2024_Bull.Entomol.Res__1
PubMedSearch : Xu_2024_Bull.Entomol.Res__1
PubMedID: 38708572
Gene_locus related to this paper: spolt-SlCarE054

Title : Identification and characterization of a fungal cutinase-like enzyme CpCut1 from Cladosporium sp. P7 for polyurethane degradation - Liu_2024_Appl.Environ.Microbiol__e0147723
Author(s) : Liu J , Xin K , Zhang T , Wen Y , Li D , Wei R , Zhou J , Cui Z , Dong W , Jiang M
Ref : Applied Environmental Microbiology , :e0147723 , 2024
Abstract : Plastic degradation by biological systems emerges as a prospective avenue for addressing the pressing global concern of plastic waste accumulation. The intricate chemical compositions and diverse structural facets inherent to polyurethanes (PU) substantially increase the complexity associated with PU waste management. Despite the extensive research endeavors spanning over decades, most known enzymes exhibit a propensity for hydrolyzing waterborne PU dispersion (i.e., the commercial Impranil DLN-SD), with only a limited capacity for the degradation of bulky PU materials. Here, we report a novel cutinase (CpCut1) derived from Cladosporium sp. P7, which demonstrates remarkable efficiency in the degrading of various polyester-PU materials. After 12-h incubation at 55 degreesC, CpCut1 was capable of degrading 40.5% and 20.6% of thermoplastic PU film and post-consumer foam, respectively, while achieving complete depolymerization of Impranil DLN-SD. Further analysis of the degradation intermediates suggested that the activity of CpCut1 primarily targeted the ester bonds within the PU soft segments. The versatile performance of CpCut1 against a spectrum of polyester-PU materials positions it as a promising candidate for the bio-recycling of waste plastics.IMPORTANCEPolyurethane (PU) has a complex chemical composition that frequently incorporates a variety of additives, which poses significant obstacles to biodegradability and recyclability. Recent advances have unveiled microbial degradation and enzymatic depolymerization as promising waste PU disposal strategies. In this study, we identified a gene encoding a cutinase from the PU-degrading fungus Cladosporium sp. P7, which allowed the expression, purification, and characterization of the recombinant enzyme CpCut1. Furthermore, this study identified the products derived from the CpCut1 catalyzed PU degradation and proposed its underlying mechanism. These findings highlight the potential of this newly discovered fungal cutinase as a remarkably efficient tool in the degradation of PU materials.
ESTHER : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedSearch : Liu_2024_Appl.Environ.Microbiol__e0147723
PubMedID: 38445906
Gene_locus related to this paper: 9pezi-CpCut1

Title : Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430 - Wu_2024_J.Nat.Prod__
Author(s) : Wu Z , Wang W , Li J , Ma C , Chen L , Che Q , Zhang G , Zhu T , Li D
Ref : Journal of Natural Products , : , 2024
Abstract : Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster (sla) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key alpha,beta-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin (1), characterized by an N-acylated amino acid structure and demonstrating weak anti-Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.
ESTHER : Wu_2024_J.Nat.Prod__
PubMedSearch : Wu_2024_J.Nat.Prod__
PubMedID: 38447096

Title : Effects of age and tissue of Juniperus sabina L. on its phytochemical characteristics, anti-cholinesterase, antidiabetes, and anti-drug resistant bacteria activities - Xu_2023_Front.Plant.Sci_14_1174922
Author(s) : Xu S , Chen Q , Luo N , Yang J , Li D
Ref : Front Plant Sci , 14 :1174922 , 2023
Abstract : Juniperus sabina L. is used in the traditional Chinese medicine (TCM) system to prevent or treat various diseases. However, only the leaves and branches are used as medicinal parts. The aim of this study was to compare the chemical characteristics of different tissues (leaves, branches, stems, and roots) of J. sabina at different ages by HPLC-MS and to evaluate the biological activity (enzyme inhibition, anti-drug-resistant bacteria). Total phenol (TPC) and total lignan (TLC) contents in J. sabina were determined by Folin-Ciocalteu method and UV spectrophotometry, respectively. High levels of total phenols (87.16 mg GAE/g dry weight) and total lignans (491.24 mg PPT/g dry weight) were detected in fifteen annual J. sabina roots and current year leaves, respectively. Eleven compounds, of which six were phenolic compounds and five were lignans, were identified and quantified by HPLC/HPLC-MS. Statistical analysis showed that the distribution and content of the detected compounds showed considerable variation among ages and tissues, and that the current year leaves of fifteen annual J. sabina could be used as a potential application site for the source of podophyllotoxin. Acetylcholinesterase (AChE) inhibitory activity was found to be the highest on the extracts of fifteen annual J. sabina current year leaves (47.37 microg/mL), while the highest inhibition towards butyrylcholinesterase (BChE) was observed for the extracts of seven annual J. sabina previous year leaves (136.3 microg/mL). And the second annual J. sabina current year stem's extracts showed the best antidiabetic activity (anti-alpha-glucosidase, 62.59 microg/mL). In addition, the extracts of fifteen annual J. sabina roots (47.37 microg/mL) showed the highest anti-MRSA activity (31.25 microg/mL). Redundancy analysis (RDA) was conducted to clarify the factors affecting the biological activity of J. sabina, and its results showed that epicatechin and matairesinol showed positive promotion. This study provides a new perspective for understanding the chemical differences and comprehensive utilization of different tissues of J. sabina.
ESTHER : Xu_2023_Front.Plant.Sci_14_1174922
PubMedSearch : Xu_2023_Front.Plant.Sci_14_1174922
PubMedID: 37731973

Title : PROTAC-Mediated Selective Degradation of Cytosolic Soluble Epoxide Hydrolase Enhances ER Stress Reduction - Wang_2023_ACS.Chem.Biol__
Author(s) : Wang Y , Morisseau C , Takamura A , Wan D , Li D , Sidoli S , Yang J , Wolan DW , Hammock BD , Kitamura S
Ref : ACS Chemical Biology , : , 2023
Abstract : Soluble epoxide hydrolase (sEH) is a bifunctional enzyme responsible for lipid metabolism and is a promising drug target. Here, we report the first-in-class PROTAC small-molecule degraders of sEH. Our optimized PROTAC selectively targets the degradation of cytosolic but not peroxisomal sEH, resulting in exquisite spatiotemporal control. Remarkably, our sEH PROTAC molecule has higher potency in cellular assays compared to the parent sEH inhibitor as measured by the significantly reduced ER stress. Interestingly, our mechanistic data indicate that our PROTAC directs the degradation of cytosolic sEH via the lysosome, not through the proteasome. The molecules presented here are useful chemical probes to study the biology of sEH with the potential for therapeutic development. Broadly, our results represent a proof of concept for the superior cellular potency of sEH degradation over sEH enzymatic inhibition, as well as subcellular compartment-selective modulation of a protein by PROTACs.
ESTHER : Wang_2023_ACS.Chem.Biol__
PubMedSearch : Wang_2023_ACS.Chem.Biol__
PubMedID: 36947831
Gene_locus related to this paper: human-EPHX2

Title : Mix-and-Read Nanobody-Based Sandwich Homogeneous Split-Luciferase Assay for the Rapid Detection of Human Soluble Epoxide Hydrolase - He_2023_Anal.Chem__
Author(s) : He Q , McCoy MR , Yang H , Lin M , Cui X , Zhao S , Morisseau C , Li D , Hammock BD
Ref : Analytical Chemistry , : , 2023
Abstract : The soluble epoxide hydrolase (sEH) is possibly both a marker for and target of numerous diseases. Herein, we describe a homogeneous mix-and-read assay for the detection of human sEH based on using split-luciferase detection coupled with anti-sEH nanobodies. Selective anti-sEH nanobodies were individually fused with NanoLuc Binary Technology (NanoBiT), which consists of a large and small portion of NanoLuc (LgBiT and SmBiT, respectively). Different orientations of the LgBiT and SmBiT-nanobody fusions were expressed and investigated for their ability to reform the active NanoLuc in the presence of the sEH. After optimization, the linear range of the assay could reach 3 orders of magnitude with a limit of detection (LOD) of 1.4 ng/mL. The assay has a high sensitivity to human sEH and reached a similar detection limit to our previously reported conventional nanobody-based ELISA. The procedure of the assay was faster (30 min total) and easy to operate, providing a more flexible and simple way to monitor human sEH levels in biological samples. In general, the immunoassay proposed here offers a more efficient detection and quantification approach that can be easily adapted to numerous macromolecules.
ESTHER : He_2023_Anal.Chem__
PubMedSearch : He_2023_Anal.Chem__
PubMedID: 36972550

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

Title : Role of cholinergic innervation in biliary remnants of patients with biliary atresia - Yang_2023_Front.Pediatr_11_1278978
Author(s) : Yang J , Chen X , Wang W , Su Y , Liu K , Abudusalamu A , Li D , He Y , Wang P , Xiong X , Feng J
Ref : Front Pediatr , 11 :1278978 , 2023
Abstract : OBJECTIVE: Biliary innervation is considered important in regulating the function of bile ducts, whereas the role of innervation in the hepatobiliary system of patients with biliary atresia (BA) remains unknown. This current study aims to investigate the role of innervation in biliary remnants and analyze the relationship between the innervation and prognosis of BA after surgery. METHODS: Eighty-seven patients with type III BA who underwent the Kasai procedure were consecutively enrolled from January 2017 to September 2020. Innervation and ductules in remnants were examined by pathologists. Liver function, onset of cholangitis, jaundice clearance, and survival with the native liver were recorded. Patients were followed up for 24 months. The relationship between innervation and prognosis was analyzed. RESULTS: In total, 67 patients had bile drainage postoperatively, and 21 biliary remnants contained neuronal plexuses where there was no neuron but nerve fiber bundles. Acetylcholinesterase staining was positive in all plexuses. In patients with bile drainage, those with plexuses had improved postoperative liver function, significantly better jaundice clearance 3 or 6 months postoperatively (50.0% vs. 19.1%, or 90.0% vs. 63.8%, respectively), fewer episodes of early cholangitis (10.0% vs. 34.0%), and better survival (80.0% vs. 61.7%) compared to those without. In addition, a larger area of plexuses was associated with a larger area of ductules (R(2 )= 0.786, p = 0.000), less frequent (p = 0.000) and later cholangitis onset (p = 0.012), and better jaundice clearance (p = 0.063). CONCLUSIONS: Increased cholinergic innervation in biliary remnants may help reduce the onset of cholangitis and lead to better and earlier jaundice clearance. Thus, it improves the postoperative prognosis of patients with BA.
ESTHER : Yang_2023_Front.Pediatr_11_1278978
PubMedSearch : Yang_2023_Front.Pediatr_11_1278978
PubMedID: 38259596

Title : Hyperoside inhibits pancreatic lipase activity in vitro and reduces fat accumulation in vivo - Zhang_2023_Food.Funct_14_4763
Author(s) : Zhang X , Li D , Wang K , Xie J , Liu Y , Wang T , Liu S , Huang Q , Guo Q , Wang H
Ref : Food Funct , 14 :4763 , 2023
Abstract : Hyperoside, the main component of many anti-obesity plants, might exhibit a lipase inhibition effect to reduce fat accumulation. The anti-obesity effect of hyperoside was investigated by studying its inhibitory effect and mechanism on pancreatic lipase in vitro and evaluating its ability to reduce lipid accumulation in vivo. Hyperoside is a mixed-type inhibitor of lipase with an IC(50) of 0.67 +/- 0.02 mmol L(-)in vitro. Hyperoside changed the secondary conformation of lipase, increased the alpha-helix content, and changed the microenvironment of lipase through static quenching. The interaction between hyperoside and lipase results from a strong binding spontaneous exothermic reaction, mainly through hydrogen bonding, van der Waals force and electrostatic force. Hyperoside protected hepatic lipid accumulation and adipose tissue hypertrophy and reduced the expression of inflammatory factors in high-fat diet-induced rats. Moreover, hyperoside had a good inhibitory effect on lipase activity in serum and increased fecal fat excretion, thereby reducing lipid absorption in vivo. This study provides theoretical support for the research and development of hyperoside in fat-reducing functional foods.
ESTHER : Zhang_2023_Food.Funct_14_4763
PubMedSearch : Zhang_2023_Food.Funct_14_4763
PubMedID: 37128768

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

Title : Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters - Li_2023_Foods_12_1977
Author(s) : Li D , Guo J , Ma H , Pei L , Liu X , Wang H , Chen R , Zhao Z , Gao H
Ref : Foods , 12 :1977 , 2023
Abstract : Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor.
ESTHER : Li_2023_Foods_12_1977
PubMedSearch : Li_2023_Foods_12_1977
PubMedID: 37238795

Title : Lysosome-targeting phenalenones as efficient type I\/II photosensitizers for anticancer photodynamic therapy - Jiang_2023_Eur.J.Med.Chem_255_115418
Author(s) : Jiang Q , Li P , Qiu J , Li D , Li G , Shan G
Ref : Eur Journal of Medicinal Chemistry , 255 :115418 , 2023
Abstract : Development of safe and effective photosensitizers is important for enhancing the efficacy of photodynamic cancer therapy. Phenalenone is a type II photosensitizer with a high singlet oxygen quantum yield; however, its short UV absorption wavelength hinders its application in cancer imaging and in vivo photodynamic therapy. In this study, we report a new redshift phenalenone derivative, 6-amino-5-iodo-1H-phenalen-1-one (SDU Red [SR]), as a lysosome-targeting photosensitizer for triple-negative breast cancer therapy. SDU Red produced singlet oxygen (Type II reactive oxygen species [ROS]) and superoxide anion radicals (Type I ROS) upon light irradiation. It also exhibited good photostability and a remarkable phototherapeutic index (PI > 76) against triple-negative breast cancer MDA-MB-231 cancer cells. Additionally, we designed two amide derivatives, SRE-I and SRE-II, with decreased fluorescence and photosensitizing capabilities based on SDU Red as activatable photosensitizers for photodynamic cancer therapy. SRE-I and SRE-II could be further converted into the active photosensitizer SDU Red via carboxylesterase-catalyzed amide bond cleavage. Moreover, SDU Red and SRE-II induced DNA damage and cell apoptosis in the presence of light. Therefore, SRE-II can act as a promising theranostic agent for triple-negative breast cancer.
ESTHER : Jiang_2023_Eur.J.Med.Chem_255_115418
PubMedSearch : Jiang_2023_Eur.J.Med.Chem_255_115418
PubMedID: 37119664

Title : Cholinergic drugs reduce metabolic inflammation and diabetic myocardial injury by regulating the gut bacterial component lipopolysaccharide-induced ERK\/Egr-1 pathway - Wu_2023_FASEB.J_37_e22917
Author(s) : Wu Q , Zhao M , Li D , He X , Zang W
Ref : FASEB Journal , 37 :e22917 , 2023
Abstract : Autonomic imbalance and metabolic inflammation are important pathological processes in diabetic cardiomyopathy. Gut microbiota dysbiosis and increased levels of bacterial component lipopolysaccharide (LPS) are associated with diabetic myocardial injury, but the mechanism by which gut microbes affect metabolic inflammation and cardiac injury remains unclear. We determined whether pyridostigmine (PYR), which inhibits cholinesterase to improve vagal activity, could regulate the disordered gut microbiota and attenuate gut barrier dysfunction, metabolic endotoxemia, and inflammation in diabetes. Db/db mice exhibited high blood glucose levels, insulin resistance, low vagal activity, and diabetic myocardial injury. Db/db mice also exhibited gut microbiota perturbations and subsequent disruption of gut barrier function, resulting in an influx of LPS, metabolic endotoxemia, and inflammation. PYR ameliorated the dysregulated glucose and lipid metabolism, modulated the overall structure of the gut microbiota, selectively enhanced the abundance of anti-inflammatory bacteria, and reduced the abundance of proinflammatory and potentially pathogenic bacteria in db/db mice. Importantly, PYR enhanced vagal activity, restored gut microbiota homeostasis, and alleviated gut barrier dysfunction. Therefore, the LPS-induced extracellular signal-regulated kinase (ERK)/early growth response-1 (Egr-1) pathway and consequent metabolic inflammation were inhibited, and eventually, cardiac hypertrophy, fibrosis, oxidative stress, and dysfunction were ameliorated in db/db mice. In vitro cardiomyocyte injury was induced by exposing primary neonatal rat ventricular cardiomyocytes to high glucose (HG) and LPS. In vitro analyses showed that HG + LPS induced ERK1/2 phosphorylation, Egr-1 expression, inflammation, and cell apoptosis, which were inhibited by acetylcholine (ACh). Alpha 7 nicotinic ACh receptor but not muscarinic 2 ACh receptor plays an important role in ACh-mediated anti-inflammatory effects and inhibiting the ERK/Egr-1 pathway in HG + LPS-administered neonatal rat ventricular cardiomyocytes. PYR and ACh ameliorated diabetic myocardial injury by inhibiting the LPS-induced ERK/Egr-1 pathway and metabolic inflammation. The vagus-gut-heart axis has provided new insights into the complex mechanisms of diabetes and offers novel therapeutic targets.
ESTHER : Wu_2023_FASEB.J_37_e22917
PubMedSearch : Wu_2023_FASEB.J_37_e22917
PubMedID: 37039813

Title : Effects of spinetoram and glyphosate on physiological biomarkers and gut microbes in Bombus terrestris - Tang_2022_Front.Physiol_13_1054742
Author(s) : Tang QH , Li WL , Wang JP , Li XJ , Li D , Cao Z , Huang Q , Li JL , Zhang J , Wang ZW , Guo J
Ref : Front Physiol , 13 :1054742 , 2022
Abstract : The sublethal effects of pesticide poisoning will have significant negative impacts on the foraging and learning of bees and bumblebees, so it has received widespread attention. However, little is known about the physiological effects of sublethal spinetoram and glyphosate exposure on bumblebees. We continuously exposed Bombus terrestris to sublethal (2.5 mg/L) spinetoram or glyphosate under controlled conditions for 10 days. The superoxide dismutase, glutathione-S-transferase, carboxylesterase, prophenoloxidase, alpha-amylase and protease activities, and changes in gut microbes were measured to understand the effects of sublethal pesticide exposure on the physiology and gut microbes of bumblebees. Sublethal pesticide exposure to significantly increased superoxide dismutase activity and significantly decreased gut alpha-amylase activity in bumblebees but had no significant effect on glutathione-S-transferase, carboxylesterase or gut protease activities. In addition, glyphosate increased the activity of prophenoloxidase. Interestingly, we observed that neither of the two pesticides had a significant effect on dominant gut bacteria, but glyphosate significantly altered the structure of the dominant gut fungal community, and reduced the relative abundance of Zygosaccharomyces associated with fat accumulation. These results suggest that sublethal spinetoram and glyphosate do not significantly affect the detoxification system of bumblebees, but may affect bumblebee health by inhibiting energy acquisition. Our results provide information on the sublethal effects of exposure to low concentrations of glyphosate and spinetoram on bumblebees in terms of physiology and gut microbes.
ESTHER : Tang_2022_Front.Physiol_13_1054742
PubMedSearch : Tang_2022_Front.Physiol_13_1054742
PubMedID: 36699673

Title : Soluble Epoxide Hydrolase Is Associated with Postprandial Anxiety Decrease in Healthy Adult Women - Nguyen_2022_Int.J.Mol.Sci_23_
Author(s) : Nguyen N , Morisseau C , Li D , Yang J , Lam E , Woodside DB , Hammock BD , Shih PB
Ref : Int J Mol Sci , 23 : , 2022
Abstract : The metabolism of bioactive oxylipins by soluble epoxide hydrolase (sEH) plays an important role in inflammation, and sEH may be a risk modifier in various human diseases and disorders. The relationships that sEH has with the risk factors of these diseases remain elusive. Herein, sEH protein expression and activity in white blood cells were characterized before and after a high-fat meal in healthy women (HW) and women with anorexia nervosa (AN). sEH expression and sEH activity were significantly correlated and increased in both groups two hours after consumption of the study meal. Fasting sEH expression and activity were positively associated with body mass index (BMI) in both groups, while an inverse association with age was found in AN only (p value < 0.05). sEH was not associated with anxiety or depression in either group at the fasting timepoint. While the anxiety score decreased after eating in both groups, a higher fasting sEH was associated with a lower postprandial anxiety decrease in HW (p value < 0.05). sEH characterization using direct measurements verified the relationship between the protein expression and in vivo activity of this important oxylipin modulator, while a well-controlled food challenge study design using HW and a clinical control group of women with disordered eating elucidated sEH's role in the health of adult women.
ESTHER : Nguyen_2022_Int.J.Mol.Sci_23_
PubMedSearch : Nguyen_2022_Int.J.Mol.Sci_23_
PubMedID: 36233100

Title : Juniperus sabina L. as a Source of Podophyllotoxins: Extraction Optimization and Anticholinesterase Activities - Xu_2022_Int.J.Mol.Sci_23_
Author(s) : Xu S , Li X , Liu S , Tian P , Li D
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Juniperus sabina L. (J. sabina) has been an important plant in traditional medicine since ancient times. Its needles are rich in podophyllotoxin, a precursor compound to anti-tumor drugs. However, no systematic research has been done on J. sabina as a source of podophyllotoxins or their biological action. Hence, extracts of podophyllotoxin and deoxypodophyllotoxin were the main optimization targets using the Box-Behnken design (BBD) and response surface methodology (RSM). The total phenol content and antioxidant activity of J. sabina needle extract were also optimized. Under the optimal process conditions (ratio of material to liquid (RLM) 1:40, 90% methanol, and ultrasonic time 7 min), the podophyllotoxin extraction rate was 7.51 mg/g DW, the highest level reported for Juniperus spp. distributed in China. To evaluate its biological potential, the neuroprotective acetyl- and butyrylcholinease (AChE and BChE) inhibitory abilities were tested. The needle extract exhibited significant anti-butyrylcholinesterase activity (520.15 mg GALE/g extract), which correlated well with the high levels of podophyllotoxin and deoxypodophyllotoxin. This study shows the potential medicinal value of J. sabina needles.
ESTHER : Xu_2022_Int.J.Mol.Sci_23_
PubMedSearch : Xu_2022_Int.J.Mol.Sci_23_
PubMedID: 36142118

Title : Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae - Li_2022_Front.Microbiol_13_853744
Author(s) : Li W , Liu X , Tsui W , Xu A , Li D , Zhang X , Li P , Bian X , Zhang J
Ref : Front Microbiol , 13 :853744 , 2022
Abstract : Klebsiella pneumoniae is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of K. pneumoniae pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of K. pneumoniae have not been fully elucidated. Among these mechanisms, the secretion systems encoded by strains of the bacteria confer adaptive advantages depending on the niche occupied. The type VI secretion system (T6SS) is a multi-protein complex that delivers effector proteins to the extracellular environment or directly to eukaryotic or prokaryotic cells. T6SSs are widely distributed in Gram-negative bacteria and play an important role in bacterial virulence and the interactions between bacteria and other microorganisms or the environment. This study aimed to enhance the understanding of the characteristics of T6SSs in K. pneumoniae through an in-depth comparative genomic analysis of the T6SS in 241 sequenced strains of K. pneumoniae. We identified the T6SS loci, the synteny of the loci in different species, as well as the effectors and core T6SS-related genes in K. pneumoniae. The presence of a T6SS was a common occurrence in K. pneumoniae, and two T6SS clusters are the most prevalent. The variable region downstream of the gene vgrG usually encodes effector proteins. Conserved domain analysis indicated that the identified putative effectors in K. pneumoniae had the functions of lipase, ribonuclease, deoxyribonuclease, and polysaccharide hydrolase. However, some effectors did not contain predicted functional domains, and their specific functions have yet to be elucidated. This in silico study represents a detailed analysis of T6SS-associated genes in K. pneumoniae and provides a foundation for future studies on the mechanism(s) of T6SSs, especially effectors, which may generate new insights into pathogenicity and lead to the identification of proteins with novel antimicrobial properties.
ESTHER : Li_2022_Front.Microbiol_13_853744
PubMedSearch : Li_2022_Front.Microbiol_13_853744
PubMedID: 35633723

Title : Fenpropathrin exposure induces neurotoxicity in zebrafish embryos - Yu_2022_Fish.Physiol.Biochem__
Author(s) : Yu T , Xu X , Mao H , Han X , Liu Y , Zhang H , Lai J , Gu J , Xia M , Hu C , Li D
Ref : Fish Physiol Biochem , : , 2022
Abstract : Fenpropathrin has been a commonly used insecticide to control agricultural and household insects over a few decades. Up to now, fenpropathrin residue in soil and water has been often determined due to its widespread use, which poses serious threat to environment and aquatic organisms. The potential of fenpropathrin to affect aquatic lives is still poorly understood. In this study, we used zebrafish (Danio rerio) embryo as an experimental model system to evaluate the toxicity of fenpropathrin to the development of zebrafish nervous system. Zebrafish embryos were separately exposed to fenpropathrin at the dose of 0.016 mg/L, 0.032 mg/L, 0.064 mg/L, starting at 6 h post-fertilizationhpf (hpf) up to 96 hpf. The results showed that fenpropathrin exposure gives rise to physiological, behavioral, and neurodevelopmental impairments in zebrafish embryos, including enhanced acetylcholinesterase (AChE) activity, abnormal swimming behavior, karyopyknosis in brain cells, increased intercellular space, and uneven migration of neuron in brain area. In addition, the expressions of genes concerning neurodevelopment and neurotransmitter system were inhibited following fenpropathrin exposure. We also found that fenpropathrin exposure distinctly induced oxidative stress by increasing reactive oxygen species (ROS) generation and inhibiting the production of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). Expectedly, some apoptosis-associated genes were induced and the apoptosis appeared in the brain and heart cells of zebrafish embryos. Moreover, fenpropathrin exposure also inhibited the expressions of genes in Nrf2 signaling pathway, such as heme oxygenase-1 (HO-1) and SOD. In summary, the results of this study indicate that oxidative stress-triggered apoptosis may be an underlying fundamental of fenpropathrin-induced neurotoxicity in zebrafish embryos.
ESTHER : Yu_2022_Fish.Physiol.Biochem__
PubMedSearch : Yu_2022_Fish.Physiol.Biochem__
PubMedID: 36266516

Title : Evodiamine-A Privileged Structure with Broad-Ranging Biological Activities - Li_2022_Mini.Rev.Med.Chem__
Author(s) : Li D , Li Y , Jiang X , Liu W , Zhao Q
Ref : Mini Rev Med Chem , : , 2022
Abstract : Evodiamine (EVO) is a natural quinolone alkaloid firstly isolated from the fruit of Evodia rutaecarpa, which is one of the most frequently used traditional Chinese herb for treating a variety of ailments including headaches, abdominal pain, vomiting, diarrhea, amenorrhea difficult menstruation, postpartum hemorrhage, and other diseases. Latest pharmacological studies showed that EVO possesses a broad spectrum of pharmacological activities through different mechanisms. However, its moderate activities and poor physicochemical properties hampered its clinical application. In this regard, the modification of EVO aiming at seeking derivatives with more potency and better physicochemical properties has been extensively emerging. These derivatives exhibit diverse biological activities including antitumor, anti-Alzheimer's disease, anti-pulmonary hypertension, anti-fungi, and thermogenic activities via a variety of mechanisms. Moreover, they were described to act as single, dual, or multiple inhibitors or agonists of many proteins such as topoisomerase I, topoisomerase II, tubulin, histone deacetylase, sirtuins, butyrylcholinesterase, phosphodiesterase 5, and transient receptor potential vanilloid 1. However, hitherto, there is no comprehensive review to systematically summarize the derivatives of EVO. In this perspective, this paper aims to provide a comprehensive description of them focused on their diverse biological activities. For each biological activity, the mechanisms and the main structure-activity relationships (SARs) will be presented in cases where adequate information is available. Finally, future directions of this class of compounds will be discussed. This review will be helpful in understanding and encouraging further exploration of EVO.
ESTHER : Li_2022_Mini.Rev.Med.Chem__
PubMedSearch : Li_2022_Mini.Rev.Med.Chem__
PubMedID: 35379148

Title : Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property - Liu_2022_Bioorg.Chem_126_105875
Author(s) : Liu W , Wu L , Li D , Huang Y , Liu M , Tian C , Liu X , Jiang X , Hu X , Gao X , Xu Z , Lu H , Zhao Q
Ref : Bioorg Chem , 126 :105875 , 2022
Abstract : Tacrine was the first approved drug by the FDA for the treatment of Alzheimer's disease (AD) but was withdrawn from the market due to its dose-dependent hepatotoxicity. Herein, we describe our efforts toward the discovery of a novel series of tacrine derivatives for cancer therapeutics. Intensive structural modifications of tacrine led to the identification of N-(4-{9-[(3S)-3-aminopyrrolidin-1-yl]-5,6,7,8-tetrahydroacridin-2-yl}pyridin-2-yl)cyclopropanecarboxamide hydrochloride ((S)-45, ZLWT-37) as a potent antiproliferative agent (GI(50) = 0.029 microM for HCT116). In addition, ZLWT-37 exhibited lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) compared to tacrine. The in vitro studies demonstrated that ZLWT-37 could significantly induce apoptosis and arrest the cell cycle in the G2/M phase in HCT116 cells. The in vivo studies revealed that compound ZLWT-37 showed excellent antitumor efficacy in HCT116 xenograft tumor model and favorable pharmacokinetics profiles (F% = 28.70%) as well as low toxicity in the acute toxicity test with a median lethal dose (LD(50)) of 380.3 mg/kg. Encouragingly, ZLWT-37 had no obvious hepatotoxicity, nephrotoxicity, and hematologic toxicity. Kinase assay suggested that ZLWT-37 possessed potent cyclin-dependent kinase 9 (CDK9) inhibitory activity (IC(50) = 0.002 microM) and good selectivity over CDK2 (IC(50) = 0.054 microM). Collectively, these findings indicate that compound ZLWT-37 is a promising anti-cancer agent that deserves further preclinical evaluation.
ESTHER : Liu_2022_Bioorg.Chem_126_105875
PubMedSearch : Liu_2022_Bioorg.Chem_126_105875
PubMedID: 35623141

Title : Integrated Proteomic and Metabolomic Analyses of Chicken Ovary Revealed the Crucial Role of Lipoprotein Lipase on Lipid Metabolism and Steroidogenesis During Sexual Maturity - Cui_2022_Front.Physiol_13_885030
Author(s) : Cui Z , Ning Z , Deng X , Du X , Amevor FK , Liu L , Kang X , Tian Y , Wang Y , Li D , Zhao X
Ref : Front Physiol , 13 :885030 , 2022
Abstract : During sexual maturation and ovulatory cycle in chickens, ovaries undergo dynamic morphological and functional changes. The aim of this study was to evaluate the integrated proteome and metabolome analyses of chicken ovaries to characterize the changes in protein and metabolite profiles during sexual maturity. The ovary of Rohman layers before (125 days of age) and after (139 days of age) sexual maturation were collected for proteome and metabolome sequencing. The results showed that a total of 680 differentially expressed proteins (DEPs) and 1,046 differential metabolites (DMs) were identified in the chicken ovary during sexual maturity. Among the DEPs, 595 proteins were up-regulated and 85 were down-regulated, whereas 519 metabolites were up-regulated and 527 were down-regulated. KEGG pathway enrichment analysis showed that DEPs were significantly enriched in glycerolipid metabolism, calcium signaling pathway, folate biosynthesis, fat digestion and absorption, NF-kB signaling pathway, and PPAR signaling pathway. However, DMs were significantly enriched in the metabolism pathways, PPAR signalling pathway, glycerolipid metabolism, ferroptosis, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids. The results of the integrated analyses of DEPs and DMs revealed that the PPAR signaling pathway and glycerolipid metabolism were the most significantly enriched pathways. Among the identified DEPs, lipoprotein lipase (LPL) was upregulated in sexually mature chicken ovaries and was significantly enriched in the glycerolipid metabolism pathway, which may partially explain the possible reasons for steroidogenesis and lipid reserves responsible for oocyte maturation and ovarian follicle development during sexual maturity in chickens. The results further revealed that LPL silencing decreased the content of lipid droplets (LDs), as well as the mRNA expression of lipid metabolism-related genes including; sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FASN); and steroidogenesis-related genes such as; cytochrome P450 11A1 (CYP11A1) and steroidogenic acute regulatory (StAR). The present study revealed that upregulation of LPL in the chicken ovary during sexual maturity promotes granulosa cell (GC) lipid metabolism and steroidogenesis. These findings provide a theoretical support for further studies to elucidate the mechanism of lipid metabolism to regulate the function of avian GCs during sexual maturity in chickens.
ESTHER : Cui_2022_Front.Physiol_13_885030
PubMedSearch : Cui_2022_Front.Physiol_13_885030
PubMedID: 35574488

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

Title : 2.1 A crystal structure of the Mycobacterium tuberculosis serine hydrolase, Hip1, in its anhydro-form (Anhydrohip1) - Brooks_2022_Biochem.Biophys.Res.Commun_630_57
Author(s) : Brooks CL , Ostrov DA , Schumann NC , Kakkad S , Li D , Pena K , Williams BP , Goldfarb NE
Ref : Biochemical & Biophysical Research Communications , 630 :57 , 2022
Abstract : The 2.6s A crystal structure of the apo form of Hip1 (hydrolase important for pathogenesis) has been previously reported. However, very little is known about the active site architecture of this M.stuberculosis (Mtb), serine hydrolase drug target. To begin mapping the active site of Hip1, we cocrystallized Hip1 with the irreversible serine protease inhibitor, 4-(2-aminoethyl)-benzenesulfonylfluoride (AEBSF). We chose AEBSF for cocrystallization with Hip1 since the similar inhibitor, phenylmethylsulfonyl fluoride (PMSF), interestingly exhibited no activity against Hip1. We obtained crystals that diffracted to 2.1sA but to our bewilderment, we did not observe any electron density for the inhibitor in the omit map for the Hip1-AEBSF complex. Rather, in the active site, dehydroalanine (dAla) was found to occupy the expected position of the catalytic Ser228, thus yielding anhydrohip1. Here we present a comparative analysis of the crystal structures of anhydrohip1 and Hip1 and provide a mechanism for the conversion of the enzyme to the anhydro-form through reaction with AEBSF. With the aid of molecular docking, we propose an explanation for the differential inhibition of Hip1 by AEBSF and PMSF. We also present a preliminary definition of the S1 and S2 pockets of the protease's active site and propose a mechanism for a ligand-induced conformational change within the S2 pocket. Finally, we expand upon the previous demarcation of the putative lipid binding pocket in the alpha-domain of the enzyme. We believe that this detailed analysis of the structures of anhydrohip1 and Hip1 provides valuable information useful for the structure-based drug design of novel Hip1-directed Mtb therapeutics.
ESTHER : Brooks_2022_Biochem.Biophys.Res.Commun_630_57
PubMedSearch : Brooks_2022_Biochem.Biophys.Res.Commun_630_57
PubMedID: 36148729
Gene_locus related to this paper: myctu-ym24

Title : Digging and identification of novel microorganisms from the soil environments with high methanol-tolerant lipase production for biodiesel preparation - Tan_2022_Environ.Res_212_113570
Author(s) : Tan Z , Chen G , Zhao Y , Shi H , Wang S , Bilal M , Li D , Li X
Ref : Environ Research , 212 :113570 , 2022
Abstract : Converting renewable biomass into carbon-neutral biofuels is one of the most effective strategies to achieve zero carbon emissions and contribute to environmental protection. Microorganisms from the soil were primarily screened on the rhodamine B-plate for highly-active lipase producing strains and re-screened on a tributyrin-methanol plate using crude lipases produced from the initially screened-out strains. The lipase-producing strains with higher methanol-tolerant lipase were identified based on morphological characteristics and 16S rDNA sequencing. The crude lipases with much higher methanol-tolerance from screened top-4 strains, Stenotrophomonas maltophilia D18, Lysinibacillus fusiformis B23, Acinetobacter junii C69, and A. pittii C95 showed temperature optima of 25 degreesC, 35 degreesC, 30 degreesC, and 30 degreesC at pH 7.0, respectively, while their pH optima were 8.0, 7.0, 7.5, and 7.5 at each optimum temperature, respectively. After 24-h incubation, they retained more than 85% of their original activities in 25%, 15%, 20%, and 20% of methanol, respectively. They catalyzed the conversion of soybean oil into biodiesel by yields of 63.1%, 35.4%, 74.6%, and 78.5% after 24-h reactions, respectively. In conclusion, the as-isolated microorganisms producing high methanol-tolerant lipase are considered promising to provide robust biocatalyst for efficient biodiesel preparation and other industrial applications.
ESTHER : Tan_2022_Environ.Res_212_113570
PubMedSearch : Tan_2022_Environ.Res_212_113570
PubMedID: 35671798

Title : An Enzyme-Mediated Aza-Michael Addition Is Involved in the Biosynthesis of an Imidazoyl Hybrid Product of Conidiogenone B - Hewage_2021_Org.Lett__
Author(s) : Hewage RT , Huang RJ , Lai SJ , Lien YC , Weng SH , Li D , Chen YJ , Wu SH , Chein RJ , Lin HC
Ref : Org Lett , : , 2021
Abstract : Meleagrin B is a terpene-alkaloid hybrid natural product that contains both the conidiogenone and meleagrin scaffold. Their derivatives show diverse biological activities. We characterized the biosynthesis of (-)-conidiogenone B (1), which involves a diterpene synthase and a P450 monooxygenase. In addition, an alpha,beta-hydrolase (Con-ABH) was shown to catalyze an aza-Michael addition between 1 and imidazole to give 3S-imidazolyl conidiogenone B (6). Compound 6 was more potent than 1 against Staphylococcus aureus strains.
ESTHER : Hewage_2021_Org.Lett__
PubMedSearch : Hewage_2021_Org.Lett__
PubMedID: 33570417
Gene_locus related to this paper: pencw-b6hfx7

Title : Expression and kinetic analysis of carboxylesterase LmCesA1 from Locusta migratoria - Yin_2021_Biotechnol.Lett__
Author(s) : Yin F , Ma W , Li D , Zhang X , Zhang J
Ref : Biotechnol Lett , : , 2021
Abstract : OBJECTIVE: To investigate the biochemical characterization of the carboxylesterase LmCesA1 from Locusta migratoria. RESULTS: We expressed recombinant LmCesA1 in Sf9 cells by using the Bac-to-bac baculovirus expression system. Enzyme kinetic assays showed that the K(m) values of LmCesA1 for alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA) were 0.08 +/- 0.01 mM and 0.22 +/- 0.03 mM, respectively, suggesting that LmCesA1 has a higher affinity for alpha-NA. LmCesA1 retained its enzymatic activity during incubations at pH 7-10 and at 10-30 degreesC. In an inhibition experiment, two organophosphate pesticides (malaoxon and malathion) and one pyrethroid pesticide (deltamethrin) showed different inhibition profiles against purified LmCesA1. Recombinant LmCesA1 activity was significantly inhibited by malaoxon in vitro. UPLC analysis showed that no metabolites were detected. CONCLUSIONS: These results suggest that overexpression of LmCesA1 enhances malathion sequestration to confer malathion tolerance in L. migratoria.
ESTHER : Yin_2021_Biotechnol.Lett__
PubMedSearch : Yin_2021_Biotechnol.Lett__
PubMedID: 33511494
Gene_locus related to this paper: locmi-l7su46

Title : The enhancement of rice bran oil quality through a novel moderate biorefining process - Li_2021_LWT_151_112118
Author(s) : Li D , Zhang J , Faiza M , Shi L , Wang W , Liu N , Wang Y
Ref : LWT , 151 :112118 , 2021
Abstract : Edible grade rice bran oil (RBO) rich in ?-oryzanol and phytosterol but without glycidyl esters (GEs) and monochloropropanediol esters (MCPDEs) was obtained from rice bran by moderate biorefining. High-acid RBO (acid value of 51.22mg KOH/g) was firstly extracted from rice bran and was then moderately biorefined by combining improved enzymatic degumming, dewaxing, enzymatic deacidification, bleaching, and low-temperature purification (120C). Through monitoring the refining process, results showed that the improved enzymatic degumming by combining partial glyceride lipase SMG1-F278N and phospholipase A1 enabled the phosphorus content to quickly decrease to 4.56mg/kg after optimization by response surface methodology. After biorefining, the final RBO with the acid and peroxide value of 0.10mg KOH/g and 2.05mmol/kg reached the grade-one standard of edible oil. Additionally, the final RBO contained 20.66mg/kg ?-oryzanol and 20.63mg/kg phytosterol with the retention rate of 71.67% and 59.2% but with undetectable GEs and MCPDEs. The environmental friendliness of the novel moderate biorefining process and superior product quality of the final product point toward a promising viable process for RBO refining in the further.
ESTHER : Li_2021_LWT_151_112118
PubMedSearch : Li_2021_LWT_151_112118
Gene_locus related to this paper: malgo-a8puy1

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

Title : Discovery of novel beta-carboline derivatives as selective AChE inhibitors with GSK-3beta inhibitory property for the treatment of Alzheimer's disease - Liu_2021_Eur.J.Med.Chem_229_114095
Author(s) : Liu W , Liu X , Gao Y , Wu L , Huang Y , Chen H , Li D , Zhou L , Wang N , Xu Z , Jiang X , Zhao Q
Ref : Eur Journal of Medicinal Chemistry , 229 :114095 , 2021
Abstract : The natural product harmine, a representative beta-carboline alkaloid from the seeds of Peganum harmala L. (Zygophyllaceae), possesses a broad spectrum of biological activities. In this study, a novel series of harmine derivatives containing N-benzylpiperidine moiety were identified for the treatment of Alzheimer's disease (AD). The results showed that all the derivatives possessed significant anti-acetylcholinesterase (AChE) activity and good selectivity over butyrylcholinesterase (BChE). In particular, compound ZLWH-23 exhibited potent anti-AChE activity (IC(50) = 0.27 microM) and selective BChE inhibition (IC(50) = 20.82 microM), as well as acceptable glycogen synthase kinase-3 (GSK-3beta) inhibition (IC(50) = 6.78 microM). Molecular docking studies and molecular dynamics simulations indicated that ZLWH-23 could form stable interaction with AChE and GSK-3beta. Gratifyingly, ZLWH-23 exhibited good selectivity for GSK-3beta over multi-kinases and very low cytotoxicity towards SH-SY5Y, HEK-293T, HL-7702, and HepG2 cell lines. Importantly, ZLWH-23 displayed efficient reduction against tau hyperphosphorylation on Ser-396 site in Tau (P301L) 293T cell model. Collectively, harmine-based derivatives could be considered as possible drug leads for the development of AD therapies.
ESTHER : Liu_2021_Eur.J.Med.Chem_229_114095
PubMedSearch : Liu_2021_Eur.J.Med.Chem_229_114095
PubMedID: 34995924

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 : Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder - Zou_2021_Open.Biol_11_200306
Author(s) : Zou M , Liu Y , Xie S , Wang L , Li D , Li L , Wang F , Zhang Y , Xia W , Sun C , Wu L
Ref : Open Biol , 11 :200306 , 2021
Abstract : Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system-endogenous cannabinoids, their receptors and associated enzymes-in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg(-1), which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.
ESTHER : Zou_2021_Open.Biol_11_200306
PubMedSearch : Zou_2021_Open.Biol_11_200306
PubMedID: 33529552

Title : A Network Pharmacology-Based Study on Irritable Bowel Syndrome Prevention and Treatment Utilizing Shenling Baizhu Powder - Meng_2021_Biomed.Res.Int_2021_4579850
Author(s) : Meng M , Bai C , Wan B , Zhao L , Li Z , Li D , Zhang S
Ref : Biomed Res Int , 2021 :4579850 , 2021
Abstract : METHODS: Metabolomics was used to detect the secondary metabolites in SLBZP; the target protein was acquired by target fishing according to the compound's structure. The SymMap database was used to search herbal medicines for the target protein. The target gene of IBS gave rise to the common gene protein which is the potential target of SLBZP in IBS therapy. The interactions between target proteins were analyzed in a STRING database, the protein relationship network was analyzed using Cytoscape software, and the Kyoto Encyclopedia of Genes and Genomes enrichment analysis of the core target gene group was carried out in a DAVID database in order to construct the "compound-traditional Chinese medicine/molecule-target-pathway" network. Molecular docking was used to verify the core protein and its related small molecular compounds. RESULT: There were 129 types of secondary metabolites in SLBZP. 80 target proteins of these metabolites were potential core targets for IBS treatment including acetylcholinesterase (AChE), arachidonate-5-lipoxygenase (ALOX5), B-cell lymphoma-2 (BCL2), recombinant cyclin D1 (CCND1), and catenin-beta1 (CTNNB1), among others. Results from these targets indicated that the most enriched pathway was the tumor necrosis factor (TNF) signaling pathway (p < 0.001) and that the most abundant pathway was signal transduction. In the network nodes of the TNF signaling pathway, the Chinese medicines with the highest aggregation were Lablab semen album and Glycyrrhizae radix et rhizoma (degree = 11). The small molecules with the highest aggregation were oxypeucedanin and 3,5,6,7,8,3',4'-heptamethoxyflavone (degree = 4). Molecular docking results confirmed that daidzein 7-O-glucoside (daidzin) had the highest degree of binding to TNF proteins in the TNF signaling pathway. CONCLUSION: This study shows that SLBZP can treat IBS by influencing multiple targets and pathways, of which the TNF signaling pathway may be the most significant. This typifies the pharmacological characteristics of traditional Chinese medicine, i.e., multiple targets, numerous pathways, and specific therapeutic effects on diseases. SLBZP can therefore be used as a candidate drug for clinical IBS by intervening in human signal transduction.
ESTHER : Meng_2021_Biomed.Res.Int_2021_4579850
PubMedSearch : Meng_2021_Biomed.Res.Int_2021_4579850
PubMedID: 34859100

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 : Physiological and transcriptomic changes of zebrafish (Danio rerio) embryos-larvae in response to 2-MIB exposure - Zhou_2021_J.Hazard.Mater_416_126142
Author(s) : Zhou W , Li X , Wang Y , Wang J , Zhang J , Wei H , Peng C , Wang Z , Li G , Li D
Ref : J Hazard Mater , 416 :126142 , 2021
Abstract : 2-Methylisoborneol (2-MIB), a natural odorous substance, is widely distributed in water environment, but there is a paucity of information concerning its systemic toxicity. Herein, we investigated the effects of 2-MIB exposure on developmental parameters, locomotive behavior, oxidative stress, apoptosis and transcriptome of zebrafish. Zebrafish embryos exposed to different concentrations (0, 0.5, 5 and 42.8 microg/L) of 2-MIB showed no changes in mortality, hatchability, and malformation rate, but the body length of zebrafish larvae was significantly increased in a dose-dependent manner, and accompanied by the changes of growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis genes. Moreover, the swimming activity of zebrafish larvae increased, which may be due to the increase of acetylcholinesterase (AChE) activity. Meanwhile, 2-MIB caused oxidative stress and apoptosis in zebrafish larvae by altering the NF-E2-related factor 2 (Nrf2) and mitochondrial signaling pathways, respectively. Transcriptome sequencing assay showed that the phototransduction signaling pathway was significantly enriched, and most of the genes in this pathway exhibited enhanced expression after exposure to 2-MIB. These findings provide an important reference for risk assessment and early warning to 2-MIB exposure.
ESTHER : Zhou_2021_J.Hazard.Mater_416_126142
PubMedSearch : Zhou_2021_J.Hazard.Mater_416_126142
PubMedID: 34492931

Title : Morphine increases myocardial triacylglycerol through regulating adipose triglyceride lipase S406 phosphorylation - Li_2021_Life.Sci_283_119866
Author(s) : Li L , Wang J , Li D , Zhang H
Ref : Life Sciences , 283 :119866 , 2021
Abstract : AIMS: Morphine, a commonly used drug for anesthesia, affects lipid metabolism in different tissues, but the mechanism is currently unclear. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme responsible for the first step of triglyceride (TG) hydrolysis. Here we aim to investigate whether ATGL phosphorylation is involved in morphine-induced TG accumulation. MAIN METHODS: Oil red O staining and TG content analysis were used to detect the effect of morphine on lipid storage. A series of ATGL phosphoamino acid site mutant plasmids were constructed by gene synthesis and transfected to HL-1 cells to evaluate the phosphorylation levels of ATGL phosphoamino acid in morphine-treated HL-1 cells with immunoprecipitation and immunoblotting assay. KEY FINDINGS: Morphine acute treatment induced excessive accumulation of TG and decreased the phosphorylation level of ATGL Ser406 in HL-1 cells. Of note, the phosphorylation positive mutation of ATGL Ser406 to aspartic acid effectively reversed morphine-induced excessive accumulation of TG in HL-1 cells. SIGNIFICANCE: This discovery will help to fully understand the lipid regulation function of morphine in a new scope. In addition, it will expand the phosphorylation research of ATGL more comprehensively and provide powerful clues for lipid metabolism regulation.
ESTHER : Li_2021_Life.Sci_283_119866
PubMedSearch : Li_2021_Life.Sci_283_119866
PubMedID: 34352257

Title : Pharmacological effects of harmine and its derivatives: a review - Zhang_2020_Arch.Pharm.Res_43_1259
Author(s) : Zhang L , Li D , Yu S
Ref : Arch Pharm Res , 43 :1259 , 2020
Abstract : Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure-activity relationship of harmine derivatives has been summarized.
ESTHER : Zhang_2020_Arch.Pharm.Res_43_1259
PubMedSearch : Zhang_2020_Arch.Pharm.Res_43_1259
PubMedID: 33206346

Title : Biochemical Mechanisms, Cross-resistance and Stability of Resistance to Metaflumizone in Plutella xylostella - Shen_2020_Insects_11_
Author(s) : Shen J , Li Z , Li D , Wang R , Zhang S , You H , Li J
Ref : Insects , 11 : , 2020
Abstract : The diamondback moth, Plutella xylostella (L.) is an important pest of cruciferous crops worldwide. It has developed resistance to many conventional and novel insecticide classes. Metaflumizone belongs to the new chemical class of semicarbazone insecticides. To delay the development of metaflumizone resistance in P. xylostella and to guide insecticide use in the field, the biochemical mechanisms, cross-resistance spectrum, and stability of resistance to metaflumizone were studied in a laboratory-selected resistant strain (metaflu-SEL). Synergism tests with the carboxylesterase inhibitor triphenyl phosphate (TPP), the glutathione S-transferase depletor diethyl maleate (DEM), and the P450 inhibitor piperonyl butoxide(PBO) had no obvious effect on metaflumizone in the metaflu-SEL strain and the susceptible strain (SS) of P. xylostella, with synergism ratios that ranged from 1.02 to 1.86. Biochemical studies revealed that the cytochrome P450-dependent monooxygenase increased only 1.13-fold in the metaflu-SEL strain compared with the UNSEL stain; meanwhile, carboxylesterase and glutathione S-transferase activity showed no difference. These results suggest that these detoxification enzymes may be not actively involved in metaflumizone resistance. Furthermore, the metaflu-SEL population showed a moderate level of cross-resistance to indoxacarb (11.63-fold), but only very low cross-resistance to spinosad (1.75-fold), spinetoram (3.52-fold), abamectin (2.81-fold), beta-cypermethrin (0.71-fold), diafenthiuron (0.79-fold), chlorantraniliprole (2.16-fold), BT (WG-001) (3.34-fold), chlorfenapyr (0.49-fold), and chlorfluazuron (0.97-fold). Moreover, metaflumizone resistance decreased from 1087.85- to 1.23-fold in the metaflu-SEL strain after 12 generations without exposure to metaflumizone. These results are useful for formulating insecticide resistance management strategies to control P. xylostella and to delay the development of metaflumizone resistance in the field.
ESTHER : Shen_2020_Insects_11_
PubMedSearch : Shen_2020_Insects_11_
PubMedID: 32429053

Title : Development of a Highly Sensitive Enzyme-Linked Immunosorbent Assay for Mouse Soluble Epoxide Hydrolase Detection by Combining a Polyclonal Capture Antibody with a Nanobody Tracer - Li_2020_Anal.Chem_92_11654
Author(s) : Li D , Cui Y , Morisseau C , Wagner KM , Cho YS , Hammock BD
Ref : Analytical Chemistry , 92 :11654 , 2020
Abstract : Enzyme-linked immunosorbent assays (ELISA) for the detection of soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of fatty acids and a biomarker, may increasingly represent an important diagnostic tool. However, there is a lack of ELISAs for mouse sEH quantification, thus resulting in a bottleneck in understanding the pathogenesis of many diseases related to sEH based on mouse models. In this work, nanobodies recognizing mouse sEH were obtained through rebiopanning against mouse sEH in the previous phage display library of human sEH. Later, we developed four ELISAs involving a combination of anti-mouse sEH polyclonal antibodies (pAbs) and nanobodies. It was found that the double antibodies worked as dual filters and had a huge impact on both the sensitivity and selectivity of sandwich immunoassays. The switch from anti-human sEH pAbs to anti-mouse sEH pAbs led to over a 100-fold increase in the sensitivity and a dramatic decrease of the limit of detection to a picogram per milliliter range in format B (pAb/biotin-VHH/streptavidin-poly-horseradish peroxidase). Moreover, we found that the four sandwich ELISAs might demonstrate excellent selectivities to mouse sEH, despite the antibodies alone showing significant cross-reactivity to the matrix, indicating the enhanced selectivity of double antibodies as dual filters. Eventually, for the first time, the ELISA (format B) was successfully used to measure the mouse sEH level in cancer cells with ultralow abundances. The ELISAs proposed here represent a sensitive tool for tracking sEH in various biological processes and also provide deep insights into developing sandwich immunoassays against various targets in terms of both the sensitivity and selectivity.
ESTHER : Li_2020_Anal.Chem_92_11654
PubMedSearch : Li_2020_Anal.Chem_92_11654
PubMedID: 32786492

Title : Functional Characterization of two Carboxylesterase Genes Involved in Pyrethroid Detoxification in Helicoverpa armigera - Li_2020_J.Agric.Food.Chem_68_3390
Author(s) : Li Y , Bai L , Zhao C , Xu J , Sun Z , Dong Y , Li D , Liu XL , Ma ZQ
Ref : Journal of Agricultural and Food Chemistry , 68 :3390 , 2020
Abstract : Insect carboxylesterases are major enzymes involved in metabolism of xenobiotics including insecticides. Two carboxylesterase genes, CarE001A and CarE001H, were cloned from the destructive agricultural pest Helicoverpa armigera. Quantitative Real-Time PCR showed that CarE001A and CarE001H were predominantly expressed in fat body and midgut, respectively; developmental expression analyses found that the expression levels of both CarEs were significantly higher in fifth- instar larvae than in other life stages. Recombinant CarE001A and CarE001H expressed in the Escherichia coli exhibited high enzymatic activity toward alpha-naphthyl acetate. Inhibition assays showed that organophosphates had strong inhibition on CarEs activity compared to pyrethroids. Metabolism assays indicated that CarE001A and CarE001H were able to metabolize beta-cypermethrin and lambda-cyhalothrin. Homology modeling and molecular docking analyses demonstrated that beta-cypermethrin could fit nicely into the active pocket of both carboxylesterases. These results suggested that CarE001A and CarE001H could play important roles in the detoxification of pyrehtroids in H. armigera.
ESTHER : Li_2020_J.Agric.Food.Chem_68_3390
PubMedSearch : Li_2020_J.Agric.Food.Chem_68_3390
PubMedID: 32096985
Gene_locus related to this paper: helam-d5g3d5 , helam-d9iv61

Title : Enhanced anti-amnestic effect of donepezil by Ginkgo biloba extract (EGb 761) via further improvement in pro-cholinergic and antioxidative activities - Zhao_2020_J.Ethnopharmacol__113711
Author(s) : Zhao J , Li K , Wang Y , Li D , Wang Q , Xie S , Wang J , Zuo Z
Ref : J Ethnopharmacol , :113711 , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: EGb 761 is a standardized dry extract of Ginkgo biloba L. leaves traditionally used by Eastern Asia and has been associated with beneficial effects on neurodegeneration disorders, including Alzheimer's disease. AIM OF THE STUDY: Since beneficial interactions between EGb 761 and donepezil have been observed in previous clinical studies, the current study was proposed aiming to further explore related mechanisms from both pharmacokinetics and pharmacodynamics aspects. MATERIALS AND METHODS: Pharmacodynamic interactions were studied in scopolamine-induced cognitive impairment rats received two-weeks treatment of vehicle, EGb 761 and/or donepezil by the Morris water maze test and ex vivo evaluation of biomarkers of cholinergic transmission and oxidative stress in rat brain. In the meantime, pharmacokinetic profiles of donepezil and bilobalide were obtained and compared among all treatment groups. In addition, impact of the bioavailable EGb 761 components on donepezil brain penetration was evaluated with the hCMEC/D3 cell monolayer model. RESULTS: Scopolamine-induced rats with co-treatment of EGb 761 and donepezil had significantly improved cognitive function in the Morris water maze test with increased brain levels of superoxide dismutase and decreased brain levels of acetylcholinesterase and malondialdehyde than that with treatment of only EGb 761 or donepezil. Despite such beneficial pharmacodynamics outcomes, the two-week co-treatment of EGb 761 and donepezil did not alter the plasma pharmacokinetics and brain uptake of donepezil or bilobalide, which was further verified in the hCMEC/D3 monolayer model. CONCLUSION: Co-administration of EGb 761 and donepezil exerted better anti-amnestic effect via further enhanced pro-cholinergic and antioxidative effects of EGb 761 or donepezil in scopolamine-induced cognitive impairment rat without alteration in their systemic/brain exposure.
ESTHER : Zhao_2020_J.Ethnopharmacol__113711
PubMedSearch : Zhao_2020_J.Ethnopharmacol__113711
PubMedID: 33352242

Title : Protective effects of chondroitin sulphate nano-selenium on a mouse model of Alzheimer's disease - Ji_2020_Int.J.Biol.Macromol__
Author(s) : Ji D , Wu X , Li D , Liu P , Zhang S , Gao D , Gao F , Zhang M , Xiao Y
Ref : Int J Biol Macromol , : , 2020
Abstract : In this study, the effect of chondroitin sulphate nano-selenium (CS@Se) on Alzheimer's disease (AD) in mice was investigated. CS@Se alleviated anxiety and improved the spatial learning and memory impairment in AD mice. CS@Se significantly reduced cell oedema and pyknosis, protected the mitochondria, and improved abnormal changes in the ultrastructure of hippocampal neuron synapses of AD mice. Moreover, CS@Se significantly increased the levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-Px), Na(+)/K(+)-ATPase assay (Na(+)/K(+)-ATPase) and acetyltransferase (ChAT), and decreased the levels of malondialdehyde (MDA) and acetylcholinesterase (ChAE) in AD mice. Western blot results showed that CS@Se can attenuate excessive phosphorylation of tau (Ser396/Ser404) by regulating the expression of glycogen synthase kinase-3 beta (GSK-3beta). In addition, CS@Se can activate the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) signalling pathways to inhibit nuclear transcription factor kappa B (NF-kappaB) nuclear translocation, thereby regulating the expression of pro-inflammatory cytokines. In summary, CS@Se can reduce oxidative stress damage, inhibit excessive tau phosphorylation, reduce inflammation to delay AD development, and increase the learning and memory capacities of AD mice.
ESTHER : Ji_2020_Int.J.Biol.Macromol__
PubMedSearch : Ji_2020_Int.J.Biol.Macromol__
PubMedID: 32171837

Title : Transcriptome analysis of Spodoptera litura reveals the molecular mechanism to pyrethroids resistance - Xu_2020_Pestic.Biochem.Physiol_169_104649
Author(s) : Xu L , Mei Y , Liu R , Chen X , Li D , Wang C
Ref : Pestic Biochem Physiol , 169 :104649 , 2020
Abstract : Spodoptera litura is a destructive agricultural pest and has evolved resistance to multiple insecticides, especially pyrethroids. At present, the resistance mechanism to pyrethroids remains unclear. Four field-collected populations, namely CZ, LF, NJ and JD, were identified to have high resistance to pyrethroids comparing to pyrethroid-susceptible population (GX), with resistant ratio ranging from 11.5- to 9123.5-fold. To characterize pyrethroid resistance mechanism, the transcriptomes between two pyrethroid-resistant (LF and NJ) and a pyrethroid-susceptible (GX) populations were compared by RNA-sequencing. Results showed that multiple differentially expressed genes were enriched in metabolism-related GO terms and KEGG pathways. 35 up-regulated metabolism-related unigenes were selected to verify by qRT-PCR and 15 unigenes, including 4 cytochrome P450s (P450s), 5 glutathione S-transferase (GSTs), 1 UDP-glycosyltransferase (UGT), 4 carboxylesterases (COEs) and 1 and ATP-binding cassette transporters (ABC), were all up-regulated in the four pyrethroid-resistant populations. The expression levels of CYP3 and GST3, which were annotated as CYP6A13 and GSTE1, respectively, showed positive correlation with their pyrethroid resistance levels among the four pyrethroid-resistant populations. While the expression levels of CYP5, CYP12, COE4 and ABC5 showed good correlation with their pyrethroid resistance levels in at least three populations. UGT5 had the highest expression level among the tested UGT genes in the four pyrethroid-resistant populations. RNAi mediated silencing of CYP6 increased the cumulative mortality treated by beta cypermethrin and cyhalothrin significantly, while silencing of GST3 increased the cumulative mortality treated by fenvalerate significantly. CYP3, CYP5, CYP6, CYP12, GST3, COE4, UGT5 and ABC5 play important roles in pyrethroid resistance among the four pyrethroid-resistant populations. Our work provides a valuable clue for further study of pyrethroid resistance mechanisms in S. litura.
ESTHER : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedSearch : Xu_2020_Pestic.Biochem.Physiol_169_104649
PubMedID: 32828367

Title : AGLPM and QMDDQ peptides exert a synergistic action on memory improvement against scopolamine-induced amnesiac mice - Wu_2020_Food.Funct_11_10925
Author(s) : Wu D , Xu X , Sun N , Li D , Zhu B , Lin S
Ref : Food Funct , 11 :10925 , 2020
Abstract : This study aimed to explore the synergistic action of pentapeptides Gln-Met-Asp-Asp-Gln (QMDDQ) and Ala-Gly-Leu-Pro-Met (AGLPM) on memory improvement against scopolamine-induced impairment in mice compared to those of either peptide alone. In behavioral tests, the codelivery of QMDDQ and AGLPM was superior to the individual supplements of either peptide alone not only in enhancing the memory ability at training trials but also in recovering the memory impairment in scopolamine-induced amnesiac mice in test trials. Furthermore, combination treatment with QMDDQ and AGLPM could significantly reduce the acetylcholinesterase (AChE) level and increase the acetylcholine (ACh) level in the hippocampus, and noticeably improve the pathological morphology of the neuron cells in hippocampal regions CA1 and CA2 and dentate gyrus (DG). The findings indicated that the combination treatment with QMDDQ and AGLPM could improve the memory function by regulating the cholinergic system.
ESTHER : Wu_2020_Food.Funct_11_10925
PubMedSearch : Wu_2020_Food.Funct_11_10925
PubMedID: 33242042

Title : Simple analogues of natural product chelerythrine: Discovery of a novel anticholinesterase 2-phenylisoquinolin-2-ium scaffold with excellent potency against acetylcholinesterase - Zhou_2020_Eur.J.Med.Chem_200_112415
Author(s) : Zhou B , Li H , Cui Z , Li D , Geng H , Gao J , Zhou L
Ref : Eur Journal of Medicinal Chemistry , 200 :112415 , 2020
Abstract : As simple analogues of the natural compound chelerythrine, a novel anti-cholinesterase 2-phenylisoquinolin-2-ium scaffold was designed by structure imitation. The activity evaluation led to the discovery of seven compounds with potent anti-acetylcholinesterase activity with IC50 values of
ESTHER : Zhou_2020_Eur.J.Med.Chem_200_112415
PubMedSearch : Zhou_2020_Eur.J.Med.Chem_200_112415
PubMedID: 32454229

Title : Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties - Zhang_2020_Nat.Commun_11_3719
Author(s) : Zhang W , Zhang Y , Qiu H , Guo Y , Wan H , Zhang X , Scossa F , Alseekh S , Zhang Q , Wang P , Xu L , Schmidt MH , Jia X , Li D , Zhu A , Guo F , Chen W , Ni D , Usadel B , Fernie AR , Wen W
Ref : Nat Commun , 11 :3719 , 2020
Abstract : Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds.
ESTHER : Zhang_2020_Nat.Commun_11_3719
PubMedSearch : Zhang_2020_Nat.Commun_11_3719
PubMedID: 32709943
Gene_locus related to this paper: camsi-a0a7j7g2i2 , camsi-a0a7j7hil4

Title : Seladelicatulasine A-G, C(27) steroidal glycosides with cholinesterase inhibitory activities from Selaginella delicatula - Yao_2020_Phytochemistry_180_112514
Author(s) : Yao CP , Li J , Liu JF , Zou ZX , Kang FH , Li XM , Li D , Xu KP , Xu PS , Tan GS
Ref : Phytochemistry , 180 :112514 , 2020
Abstract : Seven undescribed C(27) steroidal glycosides, Seladelicatulasine A-G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC(50) values of 0.31, 0.09, and 0.04 muM, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC(50) values of 0.37 and 0.65 muM, respectively.
ESTHER : Yao_2020_Phytochemistry_180_112514
PubMedSearch : Yao_2020_Phytochemistry_180_112514
PubMedID: 32950771

Title : [1,5]-Hydride Shift-Cyclization versus C(sp(2))-H Functionalization in the Knoevenagel-Cyclization Domino Reactions of 1,4- and 1,5-Benzoxazepines - Szaloki_2020_Molecules_25_
Author(s) : Szaloki Vargane D , Toth L , Buglyo B , Kiss-Szikszai A , Mandi A , Matyus P , Antus S , Chen Y , Li D , Tao L , Zhang H , Kurtan T
Ref : Molecules , 25 : , 2020
Abstract : Domino cyclization reactions of N-aryl-1,4- and 1,5-benzoxazepine derivatives involving [1,5]-hydride shift or C(sp(2))-H functionalization were investigated. Neuroprotective and acetylcholinesterase activities of the products were studied. Domino Knoevenagel-[1,5]-hydride shift-cyclization reaction of N-aryl-1,4-benzoxazepine derivatives with 1,3-dicarbonyl reagents having active methylene group afforded the 1,2,8,9-tetrahydro-7bH-quinolino [1,2-d][1,4]benzoxazepine scaffold with different substitution pattern. The C(sp(3))-H activation step of the tertiary amine moiety occurred with complete regioselectivity and the 6-endo cyclization took place in a complete diastereoselective manner. In two cases, the enantiomers of the chiral condensed new 1,4-benzoxazepine systems were separated by chiral HPLC, HPLC-ECD spectra were recorded, and absolute configurations were determined by time-dependent density functional theory- electronic circular dichroism (TDDFT-ECD) calculations. In contrast, the analogue reaction of the regioisomeric N-aryl-1,5-benzoxazepine derivative did not follow the above mechanism but instead the Knoevenagel intermediate reacted in an SEAr reaction [C(sp(2))-H functionalization] resulting in a condensed acridane derivative. The AChE inhibitory assays of the new derivatives revealed that the acridane derivative had a 6.98 muM IC50 value.
ESTHER : Szaloki_2020_Molecules_25_
PubMedSearch : Szaloki_2020_Molecules_25_
PubMedID: 32168821

Title : Focused rational iterative site-specific mutagenesis (FRISM) - Li_2020_Methods.Enzymol_643_225
Author(s) : Li D , Wu Q , Reetz MT
Ref : Methods Enzymol , 643 :225 , 2020
Abstract : Directed evolution has emerged as the most productive enzyme engineering method, with stereoselectivity playing a crucial role when evolving mutants for application in synthetic organic chemistry and biotechnology. In order to reduce the screening effort (bottleneck of directed evolution), improved methods for the creation of small and smart mutant libraries have been developed, including the combinatorial active-site saturation test (CAST) which involves saturation mutagenesis at appropriate residues surrounding the binding pocket, and iterative saturation mutagenesis (ISM). Nevertheless, even CAST/ISM mutant libraries require a formidable screening effort. Thus far, rational design as the alternative protein engineering technique has had only limited success when aiming for stereoselectivity. Here, we highlight a recent methodology dubbed focused rational iterative site-specific mutagenesis (FRISM), in which mutant libraries are not involved. It makes use of the tools that were previously employed in traditional rational enzyme design, but, inspired by CAST/ISM, the process is performed in an iterative manner. Only a few predicted mutants need to be screened, a fast process which leads to the identification of highly enantioselective and sufficiently active mutants.
ESTHER : Li_2020_Methods.Enzymol_643_225
PubMedSearch : Li_2020_Methods.Enzymol_643_225
PubMedID: 32896283

Title : Development of benzimidazole-based derivatives as antimicrobial agents and their synergistic effect with colistin against gram-negative bacteria - Dokla_2020_Eur.J.Med.Chem_186_111850
Author(s) : Dokla EME , Abutaleb NS , Milik SN , Li D , El-Baz K , Shalaby MW , Al-Karaki R , Nasr M , Klein CD , Abouzid KAM , Seleem MN
Ref : Eur Journal of Medicinal Chemistry , 186 :111850 , 2020
Abstract : Gram-negative bacteria pose a distinctive risk worldwide, especially with the evolution of major resistance to carbapenems, fluoroquinolones and colistin. Therefore, development of new antibacterial agents to target Gram-negative infections is of utmost importance. Using phenotypic screening, we synthesized and tested thirty-one benzimidazole derivatives against E. coli JW55031 (TolC mutant strain). Compound 6c showed potent activity with MIC value of 2 g/ml, however, it lacked activity against several Gram-negative microbes with intact efflux systems, including E. coli BW25113 (wild-type strain). Combination of 6c with colistin partially restored its antibacterial activity against wild strains (MIC range, 8-16 g/ml against E. coli, K. pneumoniae, A. baumannii, and P. aeruginosa). 6c exhibited no cytotoxicity against two mammalian cell lines. Therefore, compound 6c represents a promising lead for further optimization to overcome Gram-negative resistance alone or in combination therapy.
ESTHER : Dokla_2020_Eur.J.Med.Chem_186_111850
PubMedSearch : Dokla_2020_Eur.J.Med.Chem_186_111850
PubMedID: 31735572

Title : Development of Improved Double Nanobody Sandwich ELISAs for Human Soluble Epoxide Hydrolase Detection in PBMCs of Diabetic and Pre-frontal Cortex of Multiple Sclerosis Patients - Li_2020_Anal.Chem_92_7334
Author(s) : Li D , Morisseau C , McReynolds CB , Duflot T , Bellien J , Nagra RM , Taha AY , Hammock BD
Ref : Analytical Chemistry , 92 :7334 , 2020
Abstract : Nanobodies have been progressively replacing traditional antibodies in various immunological methods. However, the use of nanobodies as capture antibodies is greatly hampered by their poor performance after passive adsorption to polystyrene microplates, and this restricts the full use of double nanobodies in sandwich ELISAs. Herein, using the human soluble epoxide hydrolase (sEH) as a model analyte, we found both the immobilization format and blocking agent have a significant influence on the performance of capture nanobodies immobilized on polystyrene and the subsequent development of double nanobody sandwich ELISAs. We first conducted epitope mapping for pairing nanobodies and then prepared a horseradish peroxidase labeled nanobody using a mild conjugation procedure as detection antibody throughout the work. The resulting sandwich ELISA using capture nanobody (A9, 1.25 mug/mL) after passive adsorption and BSA as blocking agent generated a moderate sensitivity of 0.0164 OD*mL/ng and a LOD of 0.74 ng/mL. However, the introduction of streptavidin as a linker to the capture nanobody at the same working concentration demonstrated a dramatic 16-fold increase in sensitivity (0.262 OD*mL/ng) and 25-fold decrease in the LOD for sEH (0.03 ng/mL). The streptavidin bridged double nanobody ELISA was then applied successfully to tests for recovery, cross-reactivity, and real samples. Meanwhile, we accidentally found that blocking with skim milk could severely damage the performance of the capture nanobody by an order of magnitude, compared to BSA. This work provides guideline to retain the high effectiveness of capture nanobody and thus to further develop double nanobody ELISA for various analytes.
ESTHER : Li_2020_Anal.Chem_92_7334
PubMedSearch : Li_2020_Anal.Chem_92_7334
PubMedID: 32253910

Title : Chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species - Zhang_2020_Nat.Prod.Res_34_3531
Author(s) : Zhang Y , Wu D , Kuang S , Qing M , Ma Y , Yang T , Wang T , Li D
Ref : Nat Prod Res , 34 :3531 , 2020
Abstract : The chemical composition, antioxidant, antibacterial and cholinesterase inhibitory activities of three Juniperus species were studied. The contents of total phenolic and 10 phenolic compounds were highest in Juniperus rigida Zucc., of which catechin and cumaric acid were the predominant phenolic compounds, but were lowest in Juniperus sibirica Burgsd. GC-MS analysis showed the highest contents of essential oils were in J. rigida (92.61%), followed by Juniperus formosana Hayata (87.30%) and J. sibirica (84.89%). The a-pinene was the most dominant compound in J. rigida (23.99%) and J. formosana (9.71%), however, it has not been detected in J. sibirica. Ethanol extracts showed the higher radical scavenging capacity in ABTS, FRAP and DPPH assays than essential oils. The essential oils and ethanol extracts of J.sibirica showed the strong antibacterial activity against Salmonella typhimurium and Escherichia coli. Three Juniperus species showed certain acetylcholinesterase and butyrylcholinesterase inhibitions and J. formosana showed better cholinesterase inhibitory.
ESTHER : Zhang_2020_Nat.Prod.Res_34_3531
PubMedSearch : Zhang_2020_Nat.Prod.Res_34_3531
PubMedID: 30822132

Title : Nos2 deficiency enhances carbon tetrachloride-induced liver injury in aged mice - Li_2020_Iran.J.Basic.Med.Sci_23_600
Author(s) : Li D , Song Y , Wang Y , Guo Y , Zhang Z , Yang G , Wang G , Xu C
Ref : Iran J Basic Med Sci , 23 :600 , 2020
Abstract : OBJECTIVES: As a multifunctional molecule, NO has different effects on liver injury. The present work aimed to investigate the effects of Nos2 knockout (KO) on acute liver injury in aged mice treated with carbon tetrachloride (CCl(4)). MATERIALS AND METHODS: The acute liver injury model was produced by CCl(4) at 10 ml/kg body weight in 24-month-old Nos2 KO mice and wild type (WT) mice groups. The histological changes, transaminase and glutathione (GSH) contents, and the expressions of liver function genes superoxide dismutase (SOD2) and butyrylcholinesterase (BCHE), as well as apoptosis- and inflammation-associated genes were detected at 0, 6, 16, 20, 28, and 48 hr, respectively. RESULTS: Compared with WT aged mice, there are more fat droplets in liver tissues of Nos2 KO aged mice, and the serum levels of ALT and AST were elevated in the KO group; in addition, there was a decrease in the expression of SOD2 and BCHE and GSH content at multiple time-points. Furthermore, the expression of apoptosis protein CASPASE-3 was elevated from 20 to 48 hr, the same as CASPASE-9 at 28 and 48 hr and pro-apoptotic protein BAX at 6 and 28 hr, while the expression of apoptosis inhibitory protein BCL2 declined at 6 and 28 hr; at the same time the mRNA expressions of genes related to inflammation were increased at different extents in liver extracts of Nos2 KO aged mice. CONCLUSION: Nos2 KO exacerbated liver injury probably by elevated oxidative stress, apoptosis and inammation response in CCl(4)-induced aged mice liver intoxication model.
ESTHER : Li_2020_Iran.J.Basic.Med.Sci_23_600
PubMedSearch : Li_2020_Iran.J.Basic.Med.Sci_23_600
PubMedID: 32742597

Title : An efficient LSPR method to quantitatively detect dimethoate: Development, characterization and evaluation - Li_2020_PLoS.One_15_e0239632
Author(s) : Li D , Zhang Y , Guo Q , Sun X , Zhang H , Wang S , Birech Z , Hu J
Ref : PLoS ONE , 15 :e0239632 , 2020
Abstract : In recent years, there has been growing concern among consumers about pesticide contamination in fruits. Therefore, rapid, reliable, and consistent detection methods for OPPs, especially dimethoate, are crucially needed. The existing quantitative methods for detecting dimethoate are not suitable for rapid measuring system such as the dimethoate samples from two channels. Hence this paper examines the utilization of a dual-channel system for utilize the absorption variations of the Localized Surface Plasmon Resonance (LSPR) bands of gold nanoparticles (AuNPs) were investigate for detection of dimethoate. Under optimized conditions, the relationship between concentrations of dimethoate and absorbance ratios (A(520)/A(640)) was linearly found in the concentration range of 10-100 nM. Result from the experiment shows that both channels exhibit a linear correlation coefficient as high as 0.97 and a limit of detection (LOD) as low as 5.5 nM. This LSPR detection system was characterized by testing the dimethoate in apple samples and the recovery rates were found to be in the range of 85.90% to 107.37%. The proposed dual-channel LSPR system for detecting dimethoate creating a new approach for detecting organophosphate insecticide in agricultural fields. It could lay the foundation for designing a high-throughput analysis of the insecticides using a wavelength division multiplexing switch (WDMS).
ESTHER : Li_2020_PLoS.One_15_e0239632
PubMedSearch : Li_2020_PLoS.One_15_e0239632
PubMedID: 32970749

Title : Anti-cholinesterase activities of constituents isolated from Lycopodiastrum casuarinoides - Liu_2019_Fitoterapia__104366
Author(s) : Liu Y , Li J , Li D , Li XM , Zhou G , Xu KP , Kang FH , Zou ZX , Xu PS , Tan GS
Ref : Fitoterapia , :104366 , 2019
Abstract : Phytochemical investigation of the ethyl acetate extract of Lycopodiastrum casuarinoides (Spring) Holub (Lycopodiaceae) led to the isolation of nine compounds, including two new serratene triterpenoids, serrat-14-en-3alpha,21alpha-diol (1), 26-nor-8-oxo-21-one-alpha-onocerin (6), one new abietane diterpenoid, lycocasuarinone A (7), one new sesquiterpene acid, 7, 9-diene-1,4-epoxy-2-hydroxy-10-carboxylic acid (8) and one new chromone derivative, 5,7-dihydroxy-2-methyl esterchromone (9), together with four known serratene triterpenoids (2-5). Abietane diterpenoid (7) and sesquiterpene acid (8) from Lycopodiastrum casuarinoides are reported for the first time. Their structures and stereochemistry were unambiguously elucidated by spectroscopic analysis and comparison with known ones. All the compounds were tested for acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities. Bioactivity assays revealed that compound 6 exhibited the most potent AChE inhibitory effect.
ESTHER : Liu_2019_Fitoterapia__104366
PubMedSearch : Liu_2019_Fitoterapia__104366
PubMedID: 31629868

Title : The genome of broomcorn millet - Zou_2019_Nat.Commun_10_436
Author(s) : Zou C , Li L , Miki D , Li D , Tang Q , Xiao L , Rajput S , Deng P , Peng L , Jia W , Huang R , Zhang M , Sun Y , Hu J , Fu X , Schnable PS , Chang Y , Li F , Zhang H , Feng B , Zhu X , Liu R , Schnable JC , Zhu JK
Ref : Nat Commun , 10 :436 , 2019
Abstract : Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology.
ESTHER : Zou_2019_Nat.Commun_10_436
PubMedSearch : Zou_2019_Nat.Commun_10_436
PubMedID: 30683860
Gene_locus related to this paper: panmi-a0a3l6qvl9 , 9poal-a0a2s3hbt0 , panmi-a0a3l6sxg5 , 9poal-a0a2t7cdl4 , panmi-a0a3l6ta96 , panmi-a0a3l6qv47 , panmi-a0a3l6s688 , panmi-a0a3l6tph0

Title : Altered bioavailability of epoxyeicosatrienoic acids is associated with conduit artery endothelial dysfunction in type 2 diabetic patients - Duflot_2019_Cardiovasc.Diabetol_18_35
Author(s) : Duflot T , Moreau-Grange L , Roche C , Iacob M , Wils J , Remy-Jouet I , Cailleux AF , Leuillier M , Renet S , Li D , Morisseau C , Lamoureux F , Richard V , Prevost G , Joannides R , Bellien J
Ref : Cardiovasc Diabetol , 18 :35 , 2019
Abstract : BACKGROUND: This pathophysiological study addressed the hypothesis that soluble epoxide hydrolase (sEH), which metabolizes the vasodilator and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), contributes to conduit artery endothelial dysfunction in type 2 diabetes. METHODS AND RESULTS: Radial artery endothelium-dependent flow-mediated dilatation in response to hand skin heating was reduced in essential hypertensive patients (n = 9) and type 2 diabetic subjects with (n = 19) or without hypertension (n = 10) compared to healthy subjects (n = 36), taking into consideration cardiovascular risk factors, flow stimulus and endothelium-independent dilatation to glyceryl trinitrate. Diabetic patients but not non-diabetic hypertensive subjects displayed elevated whole blood reactive oxygen species levels and loss of NO release during heating, assessed by measuring local plasma nitrite variation. Moreover, plasma levels of EET regioisomers increased during heating in healthy subjects, did not change in hypertensive patients and decreased in diabetic patients. Correlation analysis showed in the overall population that the less NO and EETs bioavailability increases during heating, the more flow-mediated dilatation is reduced. The expression and activity of sEH, measured in isolated peripheral blood mononuclear cells, was elevated in diabetic but not hypertensive patients, leading to increased EETs conversion to DHETs. Finally, hyperglycemic and hyperinsulinemic euglycemic clamps induced a decrease in flow-mediated dilatation in healthy subjects and this was associated with an altered EETs release during heating. CONCLUSIONS: These results demonstrate that an increased EETs degradation by sEH and altered NO bioavailability are associated with conduit artery endothelial dysfunction in type 2 diabetic patients independently from their hypertensive status. The hyperinsulinemic and hyperglycemic state in these patients may contribute to these alterations. Trial registration NCT02311075. Registered December 8, 2014.
ESTHER : Duflot_2019_Cardiovasc.Diabetol_18_35
PubMedSearch : Duflot_2019_Cardiovasc.Diabetol_18_35
PubMedID: 30885203

Title : Anti-inflammatory treatment with a soluble epoxide hydrolase inhibitor attenuates seizures and epilepsy-associated depression in the LiCl-pilocarpine post-status epilepticus rat model - Shen_2019_Brain.Behav.Immun_81_535
Author(s) : Shen Y , Peng W , Chen Q , Hammock BD , Liu J , Li D , Yang J , Ding J , Wang X
Ref : Brain Behavior & Immunity , 81 :535 , 2019
Abstract : PURPOSE: This study aimed to investigate whether 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), a soluble epoxide hydrolase inhibitor with anti-inflammatory effects, could alleviate spontaneous recurrent seizures (SRS) and epilepsy-associated depressive behaviours in the lithium chloride (LiCl)-pilocarpine-induced post-status epilepticus (SE) rat model. METHODS: The rats were intraperitoneally (IP) injected with LiCl (127mg/kg) and pilocarpine (40mg/kg) to induce SE. A video surveillance system was used to monitor SRS in the post-SE model for 6weeks (from the onset of the 2nd week to the end of the 7th week after SE induction). TPPU (0.1mg/kg/d) was intragastrically given for 4weeks from the 21st day after SE induction in the SRS+0.1 TPPU group. The SRS+PEG 400 group was given the vehicle (40% polyethylene glycol 400) instead, and the control group was given LiCl and PEG 400 but not pilocarpine. The sucrose preference test (SPT) and forced swim test (FST) were conducted to evaluate the depression-like behaviours of rats. Immunofluorescent staining, enzyme-linked immunosorbent assay, and western blot analysis were performed to measure astrocytic and microglial gliosis, neuronal loss, and levels of soluble epoxide hydrolase (sEH), cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6], and cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB). RESULTS: The frequency of SRS was significantly decreased at 6weeks and 7weeks after SE induction in the 0.1TPP U group compared with the SRS+PEG 400 group. The immobility time (IMT) evaluated by FST was significantly decreased, whereas the climbing time (CMT) was increased, and the sucrose preference rate (SPR) evaluated by SPT was in an increasing trend. The levels of sEH, TNF-alpha, IL-1beta, and IL-6 in the hippocampus (Hip) and prefrontal cortex (PFC) were all significantly increased in the SRS+PEG 400 group compared with the control group; neuronal loss, astrogliosis, and microglial activation were also observed. The astrocytic and microglial activation and levels of the pro-inflammatory cytokines in the Hip and PFC were significantly attenuated in the TPPU group compared with the SRS+PEG 400 group; moreover, neuronal loss and the decreased CREB expression were significantly alleviated as well. CONCLUSION: TPPU treatment after SE attenuates SRS and epilepsy-associated depressive behaviours in the LiCl-pilocarpine induced post-SE rat model, and it also exerts anti-inflammatory effects in the brain. Our findings suggest a new therapeutic approach for epilepsy and its comorbidities, especially depression.
ESTHER : Shen_2019_Brain.Behav.Immun_81_535
PubMedSearch : Shen_2019_Brain.Behav.Immun_81_535
PubMedID: 31306773

Title : Discovery of a Natural-Product-Derived Preclinical Candidate for Once-Weekly Treatment of Type 2 Diabetes - Li_2019_J.Med.Chem_62_2348
Author(s) : Li S , Qin C , Cui S , Xu H , Wu F , Wang J , Su M , Fang X , Li D , Jiao Q , Zhang M , Xia C , Zhu L , Wang R , Li J , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 62 :2348 , 2019
Abstract : Poor medication adherence is one of the leading causes of suboptimal glycaemic control in approximately half of the patients with type 2 diabetes mellitus (T2DM). Long-acting antidiabetic drugs are clinically needed for improving patients' compliance. Dipeptidyl peptidase-4 (DPP-4) inhibitors play an increasingly important role in the treatment of T2DM because of their favorable properties of weight neutrality and hypoglycemia avoidance. Herein, we report the successful discovery and scale-up synthesis of compound 5, a structurally novel, potent, and long-acting DPP-4 inhibitor for the once-weekly treatment of T2DM. Inhibitor 5 has fast-associating and slow-dissociating binding kinetics profiles as well as slow clearance rate and long terminal half-life pharmacokinetic properties. A single-dose oral administration of 5 (3 mg/kg) inhibited >80% of DPP-4 activity for more than 7 days in diabetic mice. The long-term antidiabetic efficacies of 5 (10 mg/kg, qw) were better than those of the once-weekly trelagliptin and omarigliptin, especially in decreasing the hemoglobin A1c level.
ESTHER : Li_2019_J.Med.Chem_62_2348
PubMedSearch : Li_2019_J.Med.Chem_62_2348
PubMedID: 30694668
Gene_locus related to this paper: human-DPP4

Title : Subchronic effects of dietary selenium yeast and selenite on growth performance and the immune and antioxidant systems in Nile tilapia Oreochromis niloticus - Chen_2019_Fish.Shellfish.Immunol_97_283
Author(s) : Chen H , Li J , Yan L , Cao J , Li D , Huang GY , Shi WJ , Dong W , Zha J , Ying GG , Zhong H , Wang Z , Huang Y , Luo Y , Xie L
Ref : Fish Shellfish Immunol , 97 :283 , 2019
Abstract : Selenium is an essential element but toxic at high levels in animals. The effects of Se on growth performance and the immune system in Nile tilapia remain inconclusive. In this study, Nile tilapia Oreochromis niloticus was fed on selenium yeast (Se(Y))- and selenite (Se(IV))-enriched feed at 0, 3, 6, and 12 mug/g (dry wt) for 45 and 90 d. The growth, bioaccumulation, biochemical markers related to antioxidant, immunological, nervous and digestive systems were evaluated in various fish tissues (liver, intestine, kidney, muscle, brain, spleen, gills). The results showed that the accumulation of Se(Y) was 1.3-2 folds of Se(IV) in most tissues. The growth of tilapia was enhanced by both Se(Y) and Se(IV) at 3 mug/g after 90 d, with Se(Y) better than Se(IV) in tilapia feed. After 45 d, the levels of lipid peroxidation, the activity of the antioxidant enzymes, and the transcriptional levels of the immune related genes (IL-1beta, IFN-gamma and TNF-alpha) and stress proteins (HSP70 and MT) were enhanced in all treatments, except that of MT in the 12 mug/g Se(Y) group. In addition, both Se species inhibited the activity of acetylcholinesterase (AChE) in the brain and one digestive enzyme alpha-glucosidase (alpha-Glu) in the intestine at 12 mug/g. However, after 90 d, the effects on most biochemical markers were less pronounced, implying a possible acclimation after prolonged duration. The results demonstrate Se is beneficial to O. niloticus at low levels and toxic at elevated levels. The immunostimulation by Se might be greatly weakened after long term feeding Se-enriched feed. This study helps to better understand the effects of Se on the antioxidant and immune systems and to establish the optimal Se levels in the feed and duration for O. niloticus.
ESTHER : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedSearch : Chen_2019_Fish.Shellfish.Immunol_97_283
PubMedID: 31863904

Title : Bisphenol A Exposure and Sperm ACHE Hydroxymethylation in Men - Song_2019_Int.J.Environ.Res.Public.Health_16_
Author(s) : Song X , Miao M , Zhou X , Li D , Tian Y , Liang H , Li R , Yuan W
Ref : Int J Environ Research Public Health , 16 : , 2019
Abstract : Exposure to bisphenol A (BPA) has been shown to impact human sperm quality. The epigenetic mechanisms underlying the effect remain unknown. The acetylcholinesterase (ACHE) gene is a sperm-expressed gene encoding the acetylcholine hydrolyzing enzyme acetylcholinesterase and participates in the apoptosis of cells, including sperm. This study aimed to examine whether BPA exposure is associated with the hydroxymethylation level of the sperm ACHE gene. A total of 157 male factory workers were studied, among whom 74 had BPA exposure in the workplace (BPA exposure group) and 83 had no BPA exposure in the workplace (control group). Urine samples were collected for BPA measurement and semen samples were collected to assay for ACHE hydroxymethylation. Sperm ACHE hydroxymethylation level was higher in the BPA exposure group (p = 0.041) compared to the control group. When subjects were categorized according to tertiles of detected BPA level, higher ACHE hydroxymethylation levels were observed for the lowest, middle, and top tertiles compared to those with BPA below the limit of detection (LOD). In a linear regression analysis adjusted for confounders, a positive linear association between urine BPA concentration and 5-hydroxymethylcytosine (5hmC) rate of the sperm ACHE gene was observed, although the association did not reach statistical significance in all categories after being stratified by the BPA tertile. In conclusion, 5hmC of the sperm ACHE gene was positively associated with BPA exposure, which may provide supportive evidence for BPA's effects on male fertility or other health endpoints.
ESTHER : Song_2019_Int.J.Environ.Res.Public.Health_16_
PubMedSearch : Song_2019_Int.J.Environ.Res.Public.Health_16_
PubMedID: 30626059

Title : Pharmaceutical Effects of Inhibiting the Soluble Epoxide Hydrolase in Canine Osteoarthritis - McReynolds_2019_Front.Pharmacol_10_533
Author(s) : McReynolds CB , Hwang SH , Yang J , Wan D , Wagner K , Morisseau C , Li D , Schmidt WK , Hammock BD
Ref : Front Pharmacol , 10 :533 , 2019
Abstract : Osteoarthritis (OA) is a degenerative joint disease that causes pain and bone deterioration driven by an increase in prostaglandins (PGs) and inflammatory cytokines. Current treatments focus on inhibiting prostaglandin production, a pro-inflammatory lipid metabolite, with NSAID drugs; however, other lipid signaling targets could provide safer and more effective treatment strategies. Epoxides of polyunsaturated fatty acids (PUFAs) are anti-inflammatory lipid mediators that are rapidly metabolized by the soluble epoxide hydrolase (sEH) into corresponding vicinal diols. Interestingly, diol levels are increased in the synovial fluid of humans with OA, warranting further research on the biological role of this lipid pathway in the progression of OA. sEH inhibitors (sEHI) stabilize these biologically active, anti-inflammatory lipid epoxides, resulting in analgesia in both neuropathic, and inflammatory pain conditions. Most experimental studies testing the analgesic effects of sEH inhibitors have used experimental rodent models, which do not completely represent the complex etiology of painful diseases. Here, we tested the efficacy of sEHI in aged dogs with natural arthritis to provide a better representation of the clinical manifestations of pain. Two sEHI were administered orally, once daily for 5 days to dogs with naturally occurring arthritis to assess efficacy and pharmacokinetics. Blinded technicians recorded the behavior of the arthritic dogs based on pre-determined criteria to assess pain and function. After 5 days, EC1728 significantly reduced pain at a dose of 5 mg/kg compared to vehicle controls. Pharmacokinetic evaluation showed concentrations exceeding the enzyme potency in both plasma and synovial fluid. In vitro data showed that epoxyeicosatrienoic acid (EETs), epoxide metabolites of arachidonic acid, decreased inflammatory cytokines, IL-6 and TNF-alpha, and reduced cytotoxicity in canine chondrocytes challenged with IL1beta to simulate an arthritic environment. These results provide the first example of altering lipid epoxides as a therapeutic target for OA potentially acting by protecting chondrocytes from inflammatory induced cytotoxicity. Considering the challenges and high variability of naturally occurring disease in aged dogs, these data provide initial proof of concept justification that inhibiting the sEH is a non-NSAID, non-opioid, disease altering strategy for treating OA, and warrants further investigation.
ESTHER : McReynolds_2019_Front.Pharmacol_10_533
PubMedSearch : McReynolds_2019_Front.Pharmacol_10_533
PubMedID: 31214021

Title : Combined toxicity of organophosphate flame retardants and cadmium to Corbicula fluminea in aquatic sediments - Li_2018_Environ.Pollut_243_645
Author(s) : Li D , Wang P , Wang C , Fan X , Wang X , Hu B
Ref : Environ Pollut , 243 :645 , 2018
Abstract : Organophosphate flame retardants (OPFRs), as alternatives to polybrominated biphenyl ethers (PBDEs), are frequently detected in various environmental matrices. Owing to urbanization and industrial pollution, co-contamination of OPFRs and heavy metals is ubiquitous in the environment. The toxicity of OPFRs in aqueous phase is a significant concern, but uncertainty still exists regarding the co-toxicity to benthic organisms of OPFRs and metals in sediments. Hence, we explored the physiological response of Corbicula fluminea to OPFRs and Cd in sediments. The results indicated that the antioxidant system in the clams was stimulated in the presence of OPFRs and Cd, and the oxidative stress increased with increasing concentrations of OPFRs. In contrast, the cytochrome P450 (CYP450) content and acetylcholinesterase (AChE) activity were reduced by exposure to both OPFRs and Cd. The cytochrome P450 4 family (CYP4) mRNA expression and OPFR toxicity were lower than those in previously reported experiments conducted in the water phase. Moreover, the expression levels of metallothionein (MT) and AChE mRNA decreased when OPFRs and Cd were present together. The highest integrated biomarker response (IBR) index (IBR=15.41) was observed in the presence of 45mgkg(-1) Cd + 200 mg kg(-1) OPFRs, rather than the 45mgkg(-1) Cd + 400 mg kg(-1) OPFRs treatment (IBR=9.48). In addition, CYP450 and AChE in the digestive glands of C. fluminea exhibited significant correlations with the concentration of the OPFR/Cd mixture (p<0.01) and could be effective biomarkers for OPFR and Cd co-contamination. The results potentially contribute to more realistic predictions and evaluations of the environmental risks posed by OPFRs in aquatic sediments contaminated with heavy metals, particularly with respect to the risk to benthic organisms.
ESTHER : Li_2018_Environ.Pollut_243_645
PubMedSearch : Li_2018_Environ.Pollut_243_645
PubMedID: 30219590

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 : Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their cholinesterase inhibitory activities - Liu_2018_Fitoterapia_130_203
Author(s) : Liu Y , Xu PS , Ren Q , Chen X , Zhou G , Li D , Li XM , Xu KP , Yu X , Tan GS
Ref : Fitoterapia , 130 :203 , 2018
Abstract : Four new trace alkaloids with lycodine-related structures, Lycocasuarinines A-D (1-4), together with seven known analogues (5-11), were isolated from the chloroform extract of Lycopodiastrum casuarinoides. The structures and stereochemistry of 1-4 were elucidated by spectroscopic analysis (IR, UV, MS, NMR, HRESIMS and CD) and comparison with known ones. The acetylcholinesterase (AChE) and butyrocholinesterase (BuChE) inhibitory activities of nine isolates were evaluated. Lycocasuarinine D (4) showed the most potent AChE inhibitory effect. In addition, a plausible biogenetic pathway of compound 4 was proposed.
ESTHER : Liu_2018_Fitoterapia_130_203
PubMedSearch : Liu_2018_Fitoterapia_130_203
PubMedID: 30213757

Title : Highly Efficient Deacidification of High-Acid Rice Bran Oil Using Methanol as a Novel Acyl Acceptor - Li_2018_Appl.Biochem.Biotechnol_184_1061
Author(s) : Li D , Faiza M , Ali S , Wang W , Tan CP , Yang B , Wang Y
Ref : Appl Biochem Biotechnol , 184 :1061 , 2018
Abstract : A highly efficient process for reducing the fatty acid (FA) content of high-acid rice bran oil (RBO) was developed by immobilized partial glycerides-selective lipase SMG1-F278N-catalyzed esterification/transesterification using methanol as a novel acyl acceptor. Molecular docking simulation indicated that methanol was much closer to the catalytic serine (Ser-171) compared with ethanol and glycerol, which might be one of the reasons for its high efficiency in the deacidification of high-acid RBO. Additionally, the reaction parameters were optimized to minimize the FA content of high-acid RBO. Under the optimal conditions (substrate molar ratio of methanol to FAs of 1.8:1, enzyme loading of 40sU/g, and at 30s degreesC), FA content decreased from 25.14 to 0.03% after 6sh of reaction. Immobilized SMG1-F278N exhibited excellent methanol tolerance and retained almost 100% of its initial activity after being used for ten batches. After purification by molecular distillation, the final product contained 97.86% triacylglycerol, 2.10% diacylglycerol, and 0.04% FA. The acid value of the final product was 0.09smg KOH/g, which reached the grade one standard of edible oil. Overall, methanol was a superior acyl acceptor for the deacidification of high-acid RBO and the high reusability of immobilized SMG1-F278N indicates an economically attractive process.
ESTHER : Li_2018_Appl.Biochem.Biotechnol_184_1061
PubMedSearch : Li_2018_Appl.Biochem.Biotechnol_184_1061
PubMedID: 28948493
Gene_locus related to this paper: malgo-a8puy1

Title : Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality - Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
Author(s) : Wei C , Yang H , Wang S , Zhao J , Liu C , Gao L , Xia E , Lu Y , Tai Y , She G , Sun J , Cao H , Tong W , Gao Q , Li Y , Deng W , Jiang X , Wang W , Chen Q , Zhang S , Li H , Wu J , Wang P , Li P , Shi C , Zheng F , Jian J , Huang B , Shan D , Shi M , Fang C , Yue Y , Li F , Li D , Wei S , Han B , Jiang C , Yin Y , Xia T , Zhang Z , Bennetzen JL , Zhao S , Wan X
Ref : Proc Natl Acad Sci U S A , 115 :E4151 , 2018
Abstract : Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to approximately 0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred approximately 30 to 40 and approximately 90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.
ESTHER : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedSearch : Wei_2018_Proc.Natl.Acad.Sci.U.S.A_115_E4151
PubMedID: 29678829
Gene_locus related to this paper: camsi-a0a4s4dr18 , camsi-a0a4s4etg9 , camsi-a0a4s4e3j5 , camsi-a0a4s4d2s5 , camsi-a0a4s4duc4 , camsi-a0a4v3wr80 , camsi-a0a4v3wpu4

Title : New 2-Aryl-9-methyl-beta-carbolinium salts as Potential Acetylcholinesterase Inhibitor agents: Synthesis, Bioactivity and Structure-Activity Relationship - Zhou_2018_Sci.Rep_8_1559
Author(s) : Zhou B , Zhang B , Li X , Liu X , Li H , Li D , Cui Z , Geng H , Zhou L
Ref : Sci Rep , 8 :1559 , 2018
Abstract : A series of 2-aryl-9-methyl-beta-carbolinium bromides (B) were synthesized and explored for anti-acetylcholinesterase (AChE) activities in vitro, action mechanism and structure-activity relationship. All the compounds B along with their respective 3,4-dihydro intermediates (A) presented anti-AChE activity at 10 muM. Thirteen compounds B showed the excellent activity with IC50 values of 0.11-0.76 muM and high selectivity toward AChE relative to butyrylcholinesterase (BChE), superior to galantamine (IC50 = 0.79 muM), a selective AChE inhibitor drug. Kinetic analysis showed that the action mechanisms of both compounds B and A are a competitive inhibition model. Structure-activity relationship analyses showed that the C = N(+) moiety is a determinant for the activity. Substituents at 6, 7 or 4' site, the indole-N-alkyl and the aromatization of the C-ring can significantly improve the activity. Molecular docking studies showed that the compounds could combine with the active site of AChE by the pi-pi or cation-pi action between the carboline ring and the phenyl rings of the residues, and the beta-carboline moiety is embedded in a cavity surrounded by four aromatic residues of Trp86, Tyr337, Trp439 and Tyr449. The present results strongly suggest that the para-position of the D-ring should be a preferred modification site for further structural optimization design. Thus, 2-aryl-9-methyl-beta-carboliniums emerged as novel and promising tool compounds for the development of new AChE inhibitor agents.
ESTHER : Zhou_2018_Sci.Rep_8_1559
PubMedSearch : Zhou_2018_Sci.Rep_8_1559
PubMedID: 29367595

Title : Soluble epoxide hydrolase inhibitors, t-AUCB, downregulated miR-133 in a mouse model of myocardial infarction - Gui_2018_Lipids.Health.Dis_17_129
Author(s) : Gui Y , Li D , Chen J , Wang Y , Hu J , Liao C , Deng L , Xiang Q , Yang T , Du X , Zhang S , Xu D
Ref : Lipids Health Dis , 17 :129 , 2018
Abstract : BACKGROUND: It has been demonstrated that soluble epoxide hydrolase inhibitors (sEHIs) are protective against ischemia-induced lethal arrhythmias, but the mechanisms involved are unknown. Previously, we showed that sEHIs might reduce the incidence of ischemic arrhythmias by suppressing microRNA-1 (miR-1) in the myocardium. As miR-1 and miR-133 have the same proarrhythmic effects in the heart, we assumed that the beneficial effects of sEHIs might also relate to the regulation of miR-133. METHODS: A mouse model of myocardial infarction (MI) was established by ligating the coronary artery. The sEHI t-AUCB (trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) was administered daily for 7 days before MI. Myocardial infarct size and cardiac function was assessed at 24 h post-MI. The miRNA expression profiles of sham and MI mice treated with or without t-AUCB were determined by microarray and verified by real-time PCR. The incidence of arrhythmias was assessed by in vivo electrophysiologic studies. The mRNA levels of miR-133, its target genes (KCNQ1 [potassium voltage-gated channel subfamily Q member 1] and KCNH2 [potassium voltage-gated channel subfamily H member 2]), and serum response factor (SRF) were measured by real-time PCR; KCNQ1, KCNH2, and SRF protein levels were assessed by western blotting. RESULTS: We demonstrated that the treatment with sEHIs could reduce infarct size, improve cardia function, and prevent the development of cardiac arrhythmias in MI mice. The expression levels of 14 miRNAs differed between the sham and MI groups. t-AUCB treatment altered the expression of eight miRNAs: two were upregulated and six were downregulated. Of these, the muscle-specific miR-133 was downregulated in the ischemic myocardium. In line with this, up-regulation of miR-133 and down-regulation of KCNQ1 and KCNH2 mRNA/protein were observed in ischemic myocaridum, whereas administration of sEHIs produced an opposite effect. In addition, miR-133 overexpression inhibited expression of the target mRNA, whereas t-AUCB reversed the effects. Furthermore, SRF might participate in the negative regulation of miR-133 by t-AUCB. CONCLUSIONS: In MI mice, sEHI t-AUCB can repress miR-133, consequently stimulating KCNQ1 and KCNH2 mRNA and protein expression, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmias.
ESTHER : Gui_2018_Lipids.Health.Dis_17_129
PubMedSearch : Gui_2018_Lipids.Health.Dis_17_129
PubMedID: 29843720

Title : Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations - Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
Author(s) : Zhang L , Li D , Cao F , Xiao W , Zhao L , Ding G , Wang ZZ
Ref : Comb Chem High Throughput Screen , 21 :41 , 2018
Abstract : AIM AND OBJECTIVE: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. MATERIAL AND METHOD: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. RESULTS: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e. Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. CONCLUSION: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD.
ESTHER : Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
PubMedSearch : Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41
PubMedID: 29173156

Title : A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants - Pilkington_2018_BMC.Genomics_19_257
Author(s) : Pilkington SM , Crowhurst R , Hilario E , Nardozza S , Fraser L , Peng Y , Gunaseelan K , Simpson R , Tahir J , Deroles SC , Templeton K , Luo Z , Davy M , Cheng C , McNeilage M , Scaglione D , Liu Y , Zhang Q , Datson P , De Silva N , Gardiner SE , Bassett H , Chagne D , McCallum J , Dzierzon H , Deng C , Wang YY , Barron L , Manako K , Bowen J , Foster TM , Erridge ZA , Tiffin H , Waite CN , Davies KM , Grierson EP , Laing WA , Kirk R , Chen X , Wood M , Montefiori M , Brummell DA , Schwinn KE , Catanach A , Fullerton C , Li D , Meiyalaghan S , Nieuwenhuizen N , Read N , Prakash R , Hunter D , Zhang H , McKenzie M , Knabel M , Harris A , Allan AC , Gleave A , Chen A , Janssen BJ , Plunkett B , Ampomah-Dwamena C , Voogd C , Leif D , Lafferty D , Souleyre EJF , Varkonyi-Gasic E , Gambi F , Hanley J , Yao JL , Cheung J , David KM , Warren B , Marsh K , Snowden KC , Lin-Wang K , Brian L , Martinez-Sanchez M , Wang M , Ileperuma N , Macnee N , Campin R , McAtee P , Drummond RSM , Espley RV , Ireland HS , Wu R , Atkinson RG , Karunairetnam S , Bulley S , Chunkath S , Hanley Z , Storey R , Thrimawithana AH , Thomson S , David C , Testolin R , Huang H , Hellens RP , Schaffer RJ
Ref : BMC Genomics , 19 :257 , 2018
Abstract : BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models. RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models. CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.
ESTHER : Pilkington_2018_BMC.Genomics_19_257
PubMedSearch : Pilkington_2018_BMC.Genomics_19_257
PubMedID: 29661190
Gene_locus related to this paper: actde-CXE3 , actde-CXE5 , actch-a0a2r6p9v4 , actch-a0a2r6phk8 , actch-a0a2r6pty2 , actch-q0zpu6 , actcc-a0a2r6q553 , actcc-a0a2r6quq2 , actcc-a0a2r6q2m9 , actcc-a0a2r6q2n7 , actcc-a0a2r6ru97 , actcc-a0a2r6r3e8 , actcc-a0a2r6qy24 , actcc-a0a2r6pzy5 , actcc-a0a2r6p5n3 , actcc-a0a2r6qdp0 , actcc-a0a2r6qgs9

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract : Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.
ESTHER : Qi_2018_Org.Biomol.Chem_16_9046
PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

Title : Design, synthesis and evaluation of 2-arylethenyl-N-methylquinolinium derivatives as effective multifunctional agents for Alzheimer's disease treatment - Xia_2017_Eur.J.Med.Chem_130_139
Author(s) : Xia CL , Wang N , Guo QL , Liu ZQ , Wu JQ , Huang SL , Ou TM , Tan JH , Wang HG , Li D , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 130 :139 , 2017
Abstract : A series of 2-arylethenyl-N-methylquinolinium derivatives were designed and synthesized based on our previous research of 2-arylethenylquinoline analogues as multifunctional agents for the treatment of Alzheimer's disease (AD) (Eur. J. Med. Chem. 2015, 89, 349-361). The results of in vitro biological activity evaluation, including beta-amyloid (Abeta) aggregation inhibition, cholinesterase inhibition, and antioxidant activity, showed that introduction of N-methyl in quinoline ring significantly improved the anti-AD potential of compounds. The optimal compound, compound a12, dramatically attenuated the cell death of glutamate-induced HT22 cells by preventing the generation of ROS and increasing the level of GSH. Most importantly, intragastric administration of a12*HAc was well tolerated at doses up to 2000 mg/kg and could traverse blood-brain barrier.
ESTHER : Xia_2017_Eur.J.Med.Chem_130_139
PubMedSearch : Xia_2017_Eur.J.Med.Chem_130_139
PubMedID: 28242549

Title : Immobilized MAS1 lipase showed high esterification activity in the production of triacylglycerols with n-3 polyunsaturated fatty acids - Wang_2017_Food.Chem_216_260
Author(s) : Wang X , Li D , Qu M , Durrani R , Yang B , Wang Y
Ref : Food Chem , 216 :260 , 2017
Abstract : Immobilization of lipase MAS1 from marine Streptomyces sp. strain W007 and its application in catalyzing esterification of n-3 polyunsaturated fatty acids (PUFA) with glycerol were investigated. The resin XAD1180 was selected as a suitable support for the immobilization of lipase MAS1, and its absorption ability was 75mg/g (lipase/resin ratio) with initial buffer pH value of 8.0. The thermal stability of immobilized MAS1 was improved significantly compared with that of the free lipase. Immobilized MAS1 had no regiospecificity in the hydrolysis of triolein. The highest esterification degree (99.31%) and TAG content (92.26%) by immobilized MAS1-catalyzed esterification were achieved under the optimized conditions, which were significantly better than those (82.16% and 47.26%, respectively) by Novozym 435. More than 92% n-3 PUFA was incorporated into TAG that had similar fatty acids composition to the substrate (n-3 PUFA). The immobilized MAS1 exhibited 50% of its initial activity after being used for five cycles.
ESTHER : Wang_2017_Food.Chem_216_260
PubMedSearch : Wang_2017_Food.Chem_216_260
PubMedID: 27596418
Gene_locus related to this paper: 9actn-h0b8d4

Title : Imaging and Detection of Carboxylesterase in Living Cells and Zebrafish Pretreated with Pesticides by a New Near-Infrared Fluorescence Off-On Probe - Li_2017_J.Agric.Food.Chem_65_4209
Author(s) : Li D , Li Z , Chen W , Yang X
Ref : Journal of Agricultural and Food Chemistry , 65 :4209 , 2017
Abstract : A new near-infrared fluorescence off-on probe was developed and applied to fluorescence imaging of carboxylesterase in living HepG-2 cells and zebrafish pretreated with pesticides (carbamate, organophosphorus, and pyrethroid). The probe was readily prepared by connecting (4-acetoxybenzyl)oxy as a quenching and recognizing moiety to a stable hemicyanine skeleton that can be formed via the decomposition of IR-780. The fluorescence off-on response of the probe to carboxylesterase is based on the enzyme-catalyzed spontaneous hydrolysis of the carboxylic ester bond, followed by a further fragmentation of the phenylmethyl unit and thereby the fluorophore release. Compared with the only existing near-infrared carboxylesterase probe, the proposed probe exhibits superior analytical performance, such as near-infrared fluorescence emission over 700 nm as well as high selectivity and sensitivity, with a detection limit of 4.5 x 10-3 U/mL. More importantly, the probe is cell membrane permeable, and its applicability has been successfully demonstrated for monitoring carboxylesterase activity in living HepG-2 cells and zebrafish pretreated with pesticides, revealing that pesticides can effectively inhibit the activity of carboxylesterase. The superior properties of the probe make it of great potential use in indicating pesticide exposure.
ESTHER : Li_2017_J.Agric.Food.Chem_65_4209
PubMedSearch : Li_2017_J.Agric.Food.Chem_65_4209
PubMedID: 28475833

Title : Individual and binary mixture effects of bisphenol A and lignin-derived bisphenol in Daphnia magna under chronic exposure - Li_2017_Chemosphere_191_779
Author(s) : Li D , Chen H , Bi R , Xie H , Zhou Y , Luo Y , Xie L
Ref : Chemosphere , 191 :779 , 2017
Abstract : In recent years, many new chemicals have been synthesized from biomass with an aim for sustainable development by replacing the existing toxic chemicals with those having similar properties and applications. However, the effects of these new chemicals on aquatic organisms remain relatively unknown. In this study, the effects of bisphenol A (BPA) and lignin-derived bisphenol (LD-BP, a BPA analogue) on Daphnia magna were evaluated. The animals were exposed to BPA, LD-BP, and their binary mixture at concentrations (2-2000 mug L-1) for 21 days. The expression of various biochemical markers and the effects on growth, molting, and reproduction parameters were examined. The results showed that the weight of daphnids significantly increased after exposure to BPA, LD-BP, and the binary mixture relative to that of the control animals. The activity of superoxide dismutase was significantly inhibited by LD-BP and the binary mixture. At the highest exposure concentration of the binary mixture, the activities of acetylcholinesterase and alpha-glucosidase, fecundity, and the number of neonates per brood were significantly altered. Our results showed that the effects of BPA and LD-BP on D. magna were generally comparable, except for the effect on the weight at their environmentally relevant concentrations (e.g., <20 mug L-1). The effects on the reproduction of D. magna could be mainly due to the shift in energy redistribution under BPA and LD-BP exposures. Our results implied that exposures to both BPA and LD-BP could potentially cause deleterious effects at the population level in D. magna.
ESTHER : Li_2017_Chemosphere_191_779
PubMedSearch : Li_2017_Chemosphere_191_779
PubMedID: 29080539

Title : MicroRNA-132 attenuates neurobehavioral and neuropathological changes associated with intracerebral hemorrhage in mice - Zhang_2017_Neurochem.Int_107_182
Author(s) : Zhang Y , Han B , He Y , Li D , Ma X , Liu Q , Hao J
Ref : Neurochem Int , 107 :182 , 2017
Abstract : Recent studies suggest that microRNA-132 (miR-132) potentiates the cholinergic blockade of inflammatory reactions by targeting acetylcholinesterase (AChE) and affords robust protection against ischemia-induced neuronal death. However, the role of miR-132 in intracerebral hemorrhage (ICH) remains unexplored. This study aimed to determine whether miR-132 participates in the process and launches an anti-inflammatory response in a mouse model of ICH. To establish a relationship between miR-132 and ICH-induced neuronal inflammation and death, we used unilateral stereotaxic injections to deliver lentiviruses encoding miR-132, anti-miR-132 or an empty lentiviral vector directly into the right caudate nuclei of 192 living male C57BL/6 mice. Fourteen days later, ICH was induced by injection of autologous blood into these three groups. Neurodeficits, brain edema, blood-brain barrier (BBB) integrity, inflammatory reactions, together with cell death were assessed after ICH. Compared with the control group, the mice overexpressing miR-132 in the brain responded with attenuated neurological deficits and brain edema. The counts of activated microglia and the expression of proinflammatory cytokines were also decreased in these mice. Additionally, BBB integrity improved, and the extent of neuronal death decreased in ICH mice injected with lentivirus encoding miR-132. On the contrary, a decrease of miR-132 expression aggravated the severity of inflammation and increased cell apoptosis. Overall, these findings support a protective role of miR-132 in a mouse model of ICH, providing new opportunities for therapeutic intervention.
ESTHER : Zhang_2017_Neurochem.Int_107_182
PubMedSearch : Zhang_2017_Neurochem.Int_107_182
PubMedID: 27940326

Title : Simplified Enzymatic Upgrading of High-Acid Rice Bran Oil Using Ethanol as a Novel Acyl Acceptor - Li_2016_J.Agric.Food.Chem_64_6730
Author(s) : Li D , Wang W , Durrani R , Li X , Yang B , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 64 :6730 , 2016
Abstract : One of the major challenges in the upgrading of high-acid rice bran oil (RBO) is to efficiently reduce the amount of free fatty acids. Here we report a novel method for upgrading high-acid RBO using ethanol as a novel acyl acceptor in combination with a highly selective lipase from Malassezia globosa (SMG1-F278N). This process enabled an unprecedented deacidification efficiency of up to 99.80% in a short time (6 h); the immobilized SMG1-F278N used in deacidification exhibited excellent operational stability and could be used for at least 10 consecutive batches without detectable loss in activity. Scale-up was performed under optimized conditions to verify the applicability of this process, and low-acid (0.08%) RBO with a high level of gamma-oryzanol (27.8 g/kg) and gamma-oryzanol accumulation fold (1.5) was obtained after molecular distillation at lower temperature (120 degreesC). Overall, we report a simplified and efficient procedure for the production of edible RBO from high-acid RBO.
ESTHER : Li_2016_J.Agric.Food.Chem_64_6730
PubMedSearch : Li_2016_J.Agric.Food.Chem_64_6730
PubMedID: 27571030
Gene_locus related to this paper: malgo-a8puy1

Title : A Novel Process for the Synthesis of Highly Pure n-3 Polyunsaturated Fatty Acid (PUFA)-Enriched Triglycerides by Combined Transesterification and Ethanolysis - Li_2016_J.Agric.Food.Chem_64_6533
Author(s) : Li D , Wang W , Qin X , Li X , Yang B , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 64 :6533 , 2016
Abstract : In this study, a novel two-step enzymatic reaction was developed for the synthesis of highly pure triacylglycerols (TAGs) with a high content of n-3 polyunsaturated fatty acids (PUFAs). Glyceride mixtures were primarily synthesized by Novozym 435-catalyzed transesterification of glycerol and DHA/EPA-rich ethyl esters (EEs), followed by removal of partial glycerides, for the first time, by immobilized mono- and diacylglycerol lipase SMG1-F278N-catalyzed ethanolysis. TAG yield as high as 98.66% was achieved under the optimized conditions, and highly pure (98.75%) n-3 PUFA-enriched TAGs with 88.44% of n-3 PUFA was obtained after molecular distillation at lower temperature (140 degreesC). In addition, the EEs produced during ethanolysis had a FA composition similar to that of the original EEs, making them feasible for cyclic utilization. This was the first study reporting removal of partial glycerides by ethanolysis. Through ethanolysis, a higher purity product could be easily obtained at a relatively low temperature compared with the conventional high-temperature molecular distillation.
ESTHER : Li_2016_J.Agric.Food.Chem_64_6533
PubMedSearch : Li_2016_J.Agric.Food.Chem_64_6533
PubMedID: 27540752
Gene_locus related to this paper: malgo-a8puy1

Title : Lid mobility in lipase SMG1 validated using a thiol\/disulfide redox potential probe - Guo_2016_FEBS.Open.Bio_6_477
Author(s) : Guo S , Popowicz GM , Li D , Yuan D , Wang Y
Ref : FEBS Open Bio , 6 :477 , 2016
Abstract : Most lipases possess a lid domain above the catalytic site that is responsible for their activation. Lipase SMG1 from Malassezia globose CBS 7966 (Malassezia globosa LIP1), is a mono- and diacylglycerol lipase with an atypical loop-like lid domain. Activation of SMG1 was proposed to be solely through a gating mechanism involving two residues (F278 and N102). However, through disulfide bond cross-linking of the lid, this study shows that full activation also requires mobility of the lid domain, contrary to a previous proposal. The newly introduced disulfide bond makes lipase SMG1 eligible as a ratiometric thiol/disulfide redox potential probe, when it is coupled with chromogenic substrates. This redox-switch lipase could also be of potential use in cascade biocatalysis.
ESTHER : Guo_2016_FEBS.Open.Bio_6_477
PubMedSearch : Guo_2016_FEBS.Open.Bio_6_477
PubMedID: 27419053
Gene_locus related to this paper: malgo-a8puy1

Title : Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing monocyte infiltration in Ldlr(-\/-) mice - Li_2016_J.Mol.Cell.Cardiol_98_128
Author(s) : Li D , Liu Y , Zhang X , Lv H , Pang W , Sun X , Gan LM , Hammock BD , Ai D , Zhu Y
Ref : Journal of Molecular & Cellular Cardiology , 98 :128 , 2016
Abstract : RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition in atherogenesis. METHODS AND
RESULTS: Mice with low-density lipoprotein receptor deficiency (Ldlr(-/-)) with or without sEH inhibitor, and Ldlr/sEH double-knockout (DK) mice were fed a Western-type diet (WTD) for 6weeks to induce arteriosclerosis. Both sEH inhibition and gene depletion decreased the WTD-induced hyperlipidemia, plaque area and macrophage infiltration in mice arterial wall. Ly6C(hi) infiltration of monocytes remained similar in blood, spleen and bone marrow of DK mice, but was decreased in aortic lesions. To further assess the role of sEH or EETs in monocyte/macrophage infiltration in atherogenesis, we transplanted DK bone marrow into Ldlr(-/-) recipients, and then fed mice the WTD. Aortic lesions and Ly6C(hi) monocyte infiltration were reduced in mice with transplanted bone marrow of DK mice without diminishing the cholesterol level. Furthermore, sEH inhibition or gene depletion increased the ratio of EETs/DHETs and diminished the expression of P-selectin glycoprotein ligand 1 (PSGL-1) in mice peripheral-blood mononuclear cells. Monocyte adhesion to P-selectin and to tumor necrosis factor alpha-activated endothelial cells was also diminished by sEH inhibition. CONCLUSION: sEH inhibition and gene depletion attenuated atherosclerosis in mice by decreasing the infiltration of monocytes into the artery wall. EET and PSGL-1 may play pivotal roles in monocyte/macrophage infiltration and atherogenesis.
ESTHER : Li_2016_J.Mol.Cell.Cardiol_98_128
PubMedSearch : Li_2016_J.Mol.Cell.Cardiol_98_128
PubMedID: 27496380

Title : Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet - Zhang_2016_Int.J.Mol.Sci_17_
Author(s) : Zhang L , Cai Y , Wei S , Ling Y , Zhu L , Li D , Cai Z
Ref : Int J Mol Sci , 17 : , 2016
Abstract : Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency.
ESTHER : Zhang_2016_Int.J.Mol.Sci_17_
PubMedSearch : Zhang_2016_Int.J.Mol.Sci_17_
PubMedID: 27999286

Title : Psoriasis Skin Inflammation-Induced microRNA-26b Targets NCEH1 in Underlying Subcutaneous Adipose Tissue - Cheung_2016_J.Invest.Dermatol_136_640
Author(s) : Cheung L , Fisher RM , Kuzmina N , Li D , Li X , Werngren O , Blomqvist L , Stahle M , Landen NX
Ref : Journal of Investigative Dermatology , 136 :640 , 2016
Abstract : Psoriasis is an immune-mediated inflammatory disease, which is associated with a high risk of developing systemic comorbidities, such as obesity, cardiovascular disease, and diabetes mellitus. However, the mechanistic links between psoriatic skin inflammation and systemic comorbidities remain largely unknown. MicroRNAs (miRNAs) are recently discovered gene regulators that play important roles in psoriasis skin inflammation. In this study we aimed to explore whether the skin inflammation in psoriasis affects miRNA expression of the underlying subcutaneous adipose tissue and whether this may be a link between psoriasis and comorbidities. To this end, we compared the miRNA expression profile of subcutaneous adipose tissue underneath lesional and nonlesional psoriatic skin. We further validated the differential expression of several miRNAs and characterized their expression patterns in different cell types present in subcutaneous adipose tissue. We focused on miR-26b-5p, which was highly up-regulated in subcutaneous adipose tissue underneath lesional psoriasis skin. We showed that it targets and down-regulates neutral cholesterol ester hydrolase 1, an enzyme essential for cholesterol efflux, in monocytes/macrophages, adipocytes, vascular endothelial cells, and fibroblasts. We conclude that this miRNA may serve as a mechanistic link between psoriatic skin inflammation and its systemic comorbidities.
ESTHER : Cheung_2016_J.Invest.Dermatol_136_640
PubMedSearch : Cheung_2016_J.Invest.Dermatol_136_640
PubMedID: 27015452
Gene_locus related to this paper: human-NCEH1

Title : Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication - Li_2016_Mol.Immunol_75_112
Author(s) : Li W , Zhu Z , Cao W , Yang F , Zhang X , Li D , Zhang K , Li P , Mao R , Liu X , Zheng H
Ref : Mol Immunol , 75 :112 , 2016
Abstract : The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-beta promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection.
ESTHER : Li_2016_Mol.Immunol_75_112
PubMedSearch : Li_2016_Mol.Immunol_75_112
PubMedID: 27267271

Title : High-throughput proteomics integrated with gene microarray for discovery of colorectal cancer potential biomarkers - Yu_2016_Oncotarget_7_75279
Author(s) : Yu J , Li X , Zhong C , Li D , Zhai X , Hu W , Guo C , Yuan Y , Zheng S
Ref : Oncotarget , 7 :75279 , 2016
Abstract : Proteins, as executives of genes' instructions, are responsible for cellular phenotypes. Integratingproteomics with gene microarray, we conducted this study to identify potential protein biomarkers of colorectal cancer (CRC). Isobaric tags with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between paired CRC and adjacent normal mucosa. Meanwhile, Affymetrix U133plus2.0 microarrays were used to perform gene microarray analysis. Verification experiments included immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay (ELISA) of selected proteins. Overall, 5469 differentially expressed proteins were detected with iTRAQ-MS from 24 matched CRC and adjacent normal tissues. And gene microarray identified 39859 differential genes from 52 patients. Of these, 3083 differential proteins had corresponding differentially expressed genes, with 245 proteins and their genes showed >1.5-fold change in expression level. Gene ontology enrichment analysis revealed that up-regulated proteins were more involved in cell adhesion and motion than down-regulated proteins. In addition, up-regulated proteins were more likely to be located in nucleus and vesicles. Further verification experiments with IHC confirmed differential expression levels of 5 proteins (S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1) between CRC and normal tissues. Besides, western blot showed a stepwise increase of annexin A3 abundance in normal colorectal mucosa, adenoma and CRC tissues. ELISAresults revealed significantly higher serum levels of S100 calcium-binding protein A9 and annexin A3 in CRC patients than healthy controls, validating diagnostic value of these proteins. Cell experiments showed that inhibition of annexin A3 could suppress CRC cell proliferation and aggressiveness. S100 calcium-binding protein A9, annexin A3, nicotinamide phosphoribosyltransferase, carboxylesterase 2 and calcium activated chloride channel A1 were probably potential biomarkers of colorectal cancer. Annexin A3 was a potentially valuable therapeutic target of CRC.
ESTHER : Yu_2016_Oncotarget_7_75279
PubMedSearch : Yu_2016_Oncotarget_7_75279
PubMedID: 27661117

Title : Ionic liquids as novel solvents for biosynthesis of octenyl succinic anhydride-modified waxy maize starch - Li_2016_Int.J.Biol.Macromol_86_119
Author(s) : Li D , Zhang X , Tian Y
Ref : Int J Biol Macromol , 86 :119 , 2016
Abstract : Biosynthesis of octenyl succinic anhydride (OSA) starch was investigated using ionic liquids (ILs) as reaction media. Waxy maize starch was pretreated in 1-butyl-3-methylimidazolium chlorine and then esterified with OSA in 1-octyl-3-methylimidazolium nitrate by using Novozyme 435as catalyst. The degree of substitution of OSA starch reached 0.0130 with 5wt% starch concentration and 1wt% lipase dosage based on ILs weight at 50 degrees C for 3h. The formation of OSA starch was confirmed by fourier transform infrared spectroscopy. Scanning electron microscopy and X-ray diffraction revealed that the morphology and crystal structure of starch were significantly destroyed. Thermogravimetric analysis showed that esterification decreased the thermal stability of starch. The successful lipase-catalyzed synthesis of OSA starch in ILs suggests that ILs are potential replacement of traditional organic solvents for starch ester biosynthesis.
ESTHER : Li_2016_Int.J.Biol.Macromol_86_119
PubMedSearch : Li_2016_Int.J.Biol.Macromol_86_119
PubMedID: 26797225

Title : Monoacylglycerol lipase (MGLL) polymorphism rs604300 interacts with childhood adversity to predict cannabis dependence symptoms and amygdala habituation: Evidence from an endocannabinoid system-level analysis - Carey_2015_J.Abnorm.Psychol_124_860
Author(s) : Carey CE , Agrawal A , Zhang B , Conley ED , Degenhardt L , Heath AC , Li D , Lynskey MT , Martin NG , Montgomery GW , Wang T , Bierut LJ , Hariri AR , Nelson EC , Bogdan R
Ref : J Abnorm Psychol , 124 :860 , 2015
Abstract : Despite evidence for heritable variation in cannabis involvement and the discovery of cannabinoid receptors and their endogenous ligands, no consistent patterns have emerged from candidate endocannabinoid (eCB) genetic association studies of cannabis involvement. Given interactions between eCB and stress systems and associations between childhood stress and cannabis involvement, it may be important to consider childhood adversity in the context of eCB-related genetic variation. We employed a system-level gene-based analysis of data from the Comorbidity and Trauma Study (N = 1,558) to examine whether genetic variation in six eCB genes (anabolism: DAGLA, DAGLB, NAPEPLD; catabolism: MGLL, FAAH; binding: CNR1; SNPs N = 65) and childhood sexual abuse (CSA) predict cannabis dependence symptoms. Significant interactions with CSA emerged for MGLL at the gene level (p = .009), and for rs604300 within MGLL (DeltaR2 = .007, p < .001), the latter of which survived SNP-level Bonferroni correction and was significant in an additional sample with similar directional effects (N = 859; DeltaR2 = .005, p = .026). Furthermore, in a third sample (N = 312), there was evidence that rs604300 genotype interacts with early life adversity to predict threat-related basolateral amygdala habituation, a neural phenotype linked to the eCB system and addiction (DeltaR2 = .013, p = .047). Rs604300 may be related to epigenetic modulation of MGLL expression. These results are consistent with rodent models implicating 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid metabolized by the enzyme encoded by MGLL, in the etiology of stress adaptation related to cannabis dependence, but require further replication.
ESTHER : Carey_2015_J.Abnorm.Psychol_124_860
PubMedSearch : Carey_2015_J.Abnorm.Psychol_124_860
PubMedID: 26595473

Title : Fibroblast growth factor 21 protects mouse brain against d-galactose induced aging via suppression of oxidative stress response and advanced glycation end products formation - Yu_2015_Pharmacol.Biochem.Behav_133_122
Author(s) : Yu Y , Bai F , Wang W , Liu Y , Yuan Q , Qu S , Zhang T , Tian G , Li S , Li D , Ren G
Ref : Pharmacol Biochem Behav , 133 :122 , 2015
Abstract : Fibroblast growth factor 21 (FGF21) is a hormone secreted predominantly in the liver, pancreas and adipose tissue. Recently, it has been reported that FGF21-Transgenic mice can extend their lifespan compared with wild type counterparts. Thus, we hypothesize that FGF21 may play some roles in aging of organisms. In this study d-galactose (d-gal)-induced aging mice were used to study the mechanism that FGF21 protects mice from aging. The three-month-old Kunming mice were subcutaneously injected with d-gal ( for 8weeks and administered simultaneously with FGF21 (1, 2 or Our results showed that administration of FGF21 significantly improved behavioral performance of d-gal-treated mice in water maze task and step-down test, reduced brain cell damage in the hippocampus, and attenuated the d-gal-induced production of MDA, ROS and advanced glycation end products (AGEs). At the same time, FGF21 also markedly renewed the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and total anti-oxidation capability (T-AOC), and decreased the enhanced total cholinesterase (TChE) activity in the brain of d-gal-treated mice. The expression of aldose reductase (AR), sorbitol dehydrogenase (SDH) and member-anchored receptor for AGEs (RAGE) declined significantly after FGF21 treatment. Furthermore, FGF21 suppressed inflamm-aging by inhibiting IkappaBalpha degradation and NF-kappaB p65 nuclear translocation. The expression levels of pro-inflammatory cytokines, such as TNF-alpha and IL-6, decreased significantly. In conclusion, these results suggest that FGF21 protects the aging mice brain from d-gal-induced injury by attenuating oxidative stress damage and decreasing AGE formation.
ESTHER : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedSearch : Yu_2015_Pharmacol.Biochem.Behav_133_122
PubMedID: 25871519

Title : Characterization of large structural genetic mosaicism in human autosomes - Machiela_2015_Am.J.Hum.Genet_96_487
Author(s) : Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD, 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF, Jr. , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , Lacroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ
Ref : American Journal of Human Genetics , 96 :487 , 2015
Abstract : Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
ESTHER : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedSearch : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedID: 25748358

Title : The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis - Li_2015_Chemosphere_135_387
Author(s) : Li D , Huang Q , Lu M , Zhang L , Yang Z , Zong M , Tao L
Ref : Chemosphere , 135 :387 , 2015
Abstract : The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, gammaH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of gammaH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis.
ESTHER : Li_2015_Chemosphere_135_387
PubMedSearch : Li_2015_Chemosphere_135_387
PubMedID: 26002045

Title : Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect - Guo_2015_Neuromuscul.Disord_25_257
Author(s) : Guo Y , Menezes MJ , Menezes MP , Liang J , Li D , Riley LG , Clarke NF , Andrews PI , Tian L , Webster R , Wang F , Liu X , Shen Y , Thorburn DR , Keating BJ , Engel A , Hakonarson H , Christodoulou J , Xu X
Ref : Neuromuscular Disorders , 25 :257 , 2015
Abstract : Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p.Arg410Trp) and c.679C > T (p.Arg227*) in collagen-like tail subunit (single strand of homotrimer) of asymmetric acetylcholinesterase (COLQ). In patient 2, in whom a deletion of exon 52 in Dystrophin gene was previously detected by multiplex ligation-dependent probe amplification, Sanger sequencing revealed an additional homozygous mutation c.1511_1513delCTT (p.Pro504Argfs*183) in docking protein7 (DOK7). These case reports highlight the need for careful diagnosis of clinically heterogeneous syndromes like congenital myasthenic syndromes, which are treatable, and for which delayed diagnosis is likely to have implications for patient health. The report also demonstrates that whole exome sequencing is an effective diagnostic tool in providing molecular diagnosis in patients with complex phenotypes.
ESTHER : Guo_2015_Neuromuscul.Disord_25_257
PubMedSearch : Guo_2015_Neuromuscul.Disord_25_257
PubMedID: 25557462

Title : The chronic effects of lignin-derived bisphenol and bisphenol A in Japanese medaka Oryzias latipes - Li_2015_Aquat.Toxicol_170_199
Author(s) : Li D , Chen Q , Cao J , Chen H , Li L , Cedergreen N , Xie H , Xie L
Ref : Aquat Toxicol , 170 :199 , 2015
Abstract : One of the ultimate goals of green chemistry is to produce greener and more environmentally friendly chemicals to replace the existing toxic chemicals. In this study, Japanese medaka were exposed to 1.5mg/L of bisphenol A or lignin-derived bisphenol for 60 days, and the expressions of various biochemical markers, effects on reproduction, and histopathology were evaluated. The results showed that concentrations of liver vitellogenin of LD-BP exposed males were approximately 125% higher compared to the control males. Total number of eggs from the BPA and LD-BP exposed fish was approximately 47% (p<0.001) and 25% (p<0.05) less than the control fish, respectively. Total number of brood was lower from the BPA (46%, p<0.05) and LD-BP (17%, p<0.05) exposed fish than that of the control fish. Relative to the control fish, catalase and glutathione-S-transferase were significantly affected by the two chemicals in all tested tissues. BPA and LD-BP caused lipid peroxidation in all the tested tissues. Furthermore, acetylcholinesterase and alpha-glucosidase activity were significantly inhibited. Histopathological analysis showed that both the testis and ovary were mildly damaged by both chemicals. LD-BP affected medaka slightly more severe than BPA except on the reproduction, which was most likely due to different uptake, translocation, binding to targets and metabolism. Our results demonstrated that chronic exposure to both chemicals caused several adverse effects to medaka. Further research on the toxicity of LD-BP to other aquatic organisms is needed before substitution of traditional BPA with LD-BP can be recommended.
ESTHER : Li_2015_Aquat.Toxicol_170_199
PubMedSearch : Li_2015_Aquat.Toxicol_170_199
PubMedID: 26674368

Title : Heavy chain single-domain antibodies to detect native human soluble epoxide hydrolase - Cui_2015_Anal.Bioanal.Chem_407_7275
Author(s) : Cui Y , Li D , Morisseau C , Dong JX , Yang J , Wan D , Rossotti MA , Gee SJ , Gonzalez-Sapienza GG , Hammock BD
Ref : Anal Bioanal Chem , 407 :7275 , 2015
Abstract : The soluble epoxide hydrolase (sEH) is a potential pharmacological target for treating hypertension, vascular inflammation, pain, cancer, and other diseases. However, there is not a simple, inexpensive, and reliable method to estimate levels of active sEH in tissues. Toward developing such an assay, a polyclonal variable domain of heavy chain antibody (VHH) sandwich immunoassay was developed. Ten VHHs, which are highly selective for native human sEH, were isolated from a phage-displayed library. The ten VHHs have no significant cross-reactivity with human microsomal epoxide hydrolase, rat and mouse sEH, and denatured human sEH. There is a high correlation between protein levels of the sEH determined by the enzyme-linked immunosorbent assay (ELISA) and the catalytic activity of the enzyme in S9 fractions of human tissues (liver, kidney, and lung). The VHH-based ELISA appears to be a new reliable method for monitoring the sEH and may be useful as a diagnostic tool for diseases influenced by sEH. This study also demonstrates the broad utility of VHH in biochemical and pharmacological research.
ESTHER : Cui_2015_Anal.Bioanal.Chem_407_7275
PubMedSearch : Cui_2015_Anal.Bioanal.Chem_407_7275
PubMedID: 26229025

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

Title : [Anti-inflammatory effect of acetylcholine on lipopolysaccharide induced inflammatory response of alveolar macrophages] - Liu_2015_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_27_811
Author(s) : Liu F , Zhao N , Li D , Zeng Z , Shao Q , Peng F , Wang Y , Qian K
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 27 :811 , 2015
Abstract : OBJECTIVE: To observe the effect of acetylcholine (ACh) on lipopolysaccharide (LPS) induced inflammatory model of rat alveolar macrophages, and to observe the effect of the acetylcholinesterase inhibitor physostigmine (Phy) on the anti-inflammatory effect of ACh.
METHODS: The rat alveolar macrophages NR8383 were cultured in vitro, which were divided into five groups: blank control group, LPS group (stimulated with 1 mg/L LPS for 12 hours), LPS + ACh group (0.01, 0.1, 1, 10, 100 mumol/L of ACh were added for 5 minutes before LPS stimulation), LPS + Phy group (1 mmol/L Phy was added for 5 minutes before LPS stimulation), and LPS + ACh + Phy group (1 mmol/L Phy and 10 mumol/L ACh were added for 5 minutes before LPS stimulation). The supernatants were collected in each group, the enzyme-linked immunosorbent assay (ELISA) was used to assay the contents of tumor necrosis factor-alpha (TNF-alpha), interleukins (IL-1beta, and IL-6). The activity of acetylcholine esterase (AChE ) in the supernatant was also determined.
RESULTS: (1) The contents of TNF-alpha (ng/L: 605.09 +/- 57.13 vs. 34.07 +/- 8.62), IL-1beta (ng/L: 377.09 +/- 28.55 vs. 32.33 +/- 10.62) and IL-6 (ng/L: 558.04 +/- 77.45 vs. 42.62 +/- 11.21) in the LPS group were significantly higher than those in the blank control group (all P < 0.05). These results indicated that the inflammatory model of rat alveolar macrophages was constructed successfully. (2) ACh with the final concentrations of 0.01, 0.1, and 1 mumol/L had less influence on the production of TNF-alpha, IL-1beta and IL-6 in the culture supernatants of alveolar macrophages stimulated with LPS compared with LPS group (all P > 0.05). Nevertheless, 10 mumol/L and 100 mumol/L ACh notably reduced the production of TNF-alpha (ng/L: 451.19 +/- 30.67, 332.19 +/- 32.19 vs. 604.96 +/- 22.56), IL-1beta (ng/L: 261.08 +/- 24.78, 143.98 +/- 28.39 vs. 367.06 +/- 10.44) and IL-6 (ng/L: 342.75 +/- 54.60, 235.48 +/- 29.75 vs. 562.69 +/- 63.34) in the culture supernatants compared with the LPS group (all P < 0.05). (3) The activity of AChE in the LPS group was significantly higher than that in the blank control group (kU/L: 5.21 +/- 0.63 vs. 3.09 +/- 0.10, P < 0.05). The activity of AChE was successfully inhibited by 1 mmol/L acetylcholinesterase inhibitor Phy pretreatment compared with that in the LPS group (1.51 +/- 0.12 vs. 5.21 +/- 0.63, P < 0.05). (4) The level of TNF-alpha (ng/L: 183.17 +/- 35.44 vs. 451.19 +/- 30.67), IL-1beta (ng/L: 91.49 +/- 12.27 vs. 261.08 +/- 24.78) and IL-6 (ng/L: 108.17 +/- 22.82 vs. 342.75 +/- 54.60) in the culture supernatants of LPS + ACh + Phy group was significantly decreased as compared with LPS + ACh group (all P < 0.05).
CONCLUSIONS: ACh with the final concentrations of 10 mumol/L and 100 mumol/L can inhibit the LPS induced inflammatory reaction in alveolar macrophages. The acetylcholinesterase inhibitor Phy can reinforce the ACh-mediated anti-inflammatory effect on alveolar macrophages inflammatory model.
ESTHER : Liu_2015_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_27_811
PubMedSearch : Liu_2015_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_27_811
PubMedID: 27132443

Title : Two homologous carboxylesterase genes from Locusta migratoria with different tissue expression patterns and roles in insecticide detoxification - Zhang_2015_J.Insect.Physiol_77_1
Author(s) : Zhang J , Ge P , Li D , Guo Y , Zhu KY , Ma E
Ref : J Insect Physiol , 77 :1 , 2015
Abstract : Carboxylesterases (CarEs) play a crucial role in detoxification of xenobiotics and resistance to insecticides in insects. In this study, two cDNAs of CarE genes (LmCesA4 and LmCesA5) were sequenced from the migratory locust, Locusta migratoria. The cDNAs of LmCesA4 and LmCesA5 putatively encoded 538 and 470 amino acid residues, respectively. The deduced amino acid sequences of the two CarE genes showed 45.0% identities, possessed highly conserved catalytic triads (Ser-Glu-His), and clustered in phylogenetic analysis. These results suggest that they are homologous genes. Both CarE genes were expressed throughout the developmental stages. However, LmCesA4 was predominately expressed in the midgut (including the gastric caeca) and fat bodies, whereas LmCesA5 was mainly expressed in the gastric caeca. The in situ hybridization results showed that the transcripts of the two genes were localized in apical and basal regions of the columnar cells in the gastric caeca. Gene silencing followed by insecticide bioassay increased the mortalities of deltamethrin-, malathion-, and carbaryl-treated locusts by 29.5%, 31.0% and 20.4%, respectively, after the locusts were injected with LmCesA4 double-stranded RNA (dsRNA). In contrast, the injection of LmCesA5 dsRNA did not significantly increase the susceptibility of the locusts to any of these insecticides. These results suggest that these genes not only show different tissue expression patterns but also play different roles in insecticide detoxification.
ESTHER : Zhang_2015_J.Insect.Physiol_77_1
PubMedSearch : Zhang_2015_J.Insect.Physiol_77_1
PubMedID: 25840107
Gene_locus related to this paper: locmi-t1vxw3 , locmi-t1vxb0

Title : Design, synthesis, and biological evaluation of 2-arylethenylquinoline derivatives as multifunctional agents for the treatment of Alzheimer's disease - Wang_2014_Eur.J.Med.Chem_89C_349
Author(s) : Wang XQ , Xia CL , Chen SB , Tan JH , Ou TM , Huang SL , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 89C :349 , 2014
Abstract : A series of new 2-arylethenylquinoline derivatives (4a1-4a12, 4b1-4b8, 4c1-4c4, 4d1-4d3 and 4e1-4e9) were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). In vitro studies showed that these synthetic compounds inhibited self-induced Abeta1-42 aggregation effectively ranged from 23.6% to 83.9% at the concentration of 20 muM, and acted as potential antioxidants and biometal chelators. Their structure-activity relationships were obtained and discussed. In particular, compound 4b1, the most active compound, displayed strong inhibitory activity with an IC50 value of 9.7 muM for self-induced Abeta1-42 aggregation, good antioxidative activity with a value of 3.9-fold of Trolox, potent inhibitory activity for cholinesterase with IC50 values of 0.2 muM and 64.1 muM against butyrylcholinesterase (BCHE) and acetylcholinesterase (AChE), respectively. Besides, 4b1 was also capable of disassembling the self-induced Abeta1-42 aggregation fibrils with a ratio of 59.8% at 20 muM concentration, and had a good metal chelating activity. Taken together, these results suggest that compound 4b1 might be a promising lead compound for AD treatment.
ESTHER : Wang_2014_Eur.J.Med.Chem_89C_349
PubMedSearch : Wang_2014_Eur.J.Med.Chem_89C_349
PubMedID: 25462251

Title : Synthesis and characterization of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for treatment of Alzheimer's disease - Liu_2014_Biochim.Biophys.Acta_1840_2886
Author(s) : Liu J , Qiu J , Wang M , Wang L , Su L , Gao J , Gu Q , Xu J , Huang SL , Gu LQ , Huang ZS , Li D
Ref : Biochimica & Biophysica Acta , 1840 :2886 , 2014
Abstract : BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder that is characterized by dementia, cognitive impairment, and memory loss. Diverse factors are related to the development of AD, such as increased level of beta-amyloid (Abeta), acetylcholine, metal ion deregulation, hyperphosphorylated tau protein, and oxidative stress.
METHODS: The following methods were used: organic syntheses of 1H-phenanthro[9,10-d]imidazole derivatives, inhibition of self-mediated and metal-induced Abeta1-42 aggregation, inhibition studies for acetylcholinesterase and butyrylcholinesterase, anti-oxidation activity studies, CD, MTT assay, transmission electron microscopy, dot plot assay, gel electrophoresis, Western blot, and molecular docking studies.
RESULTS: We synthesized and characterized a new type of 1H-phenanthro[9,10-d]imidazole derivatives as multifunctional agents for AD treatment. Our results showed that most of these derivatives exhibited strong Abeta aggregation inhibitory activity. Compound 9g had 74% Abeta1-42 aggregation inhibitory effect at 10muM concentration with its IC50 value of 6.5muM for self-induced Abeta1-42 aggregation. This compound also showed good inhibition of metal-mediated (Cu2+ and Fe2+) and acetylcholinesterase-induced Abeta1-42 aggregation, as indicated by using thioflavin T assay, transmission electron microscopy, gel electrophoresis, and Western blot. Besides, compound 9g exhibited cholinesterase inhibitory activity, with its IC50 values of 0.86muM and 0.51muM for acetylcholinesterase and butyrylcholinesterase, respectively. In addition, compound 9g showed good anti-oxidation effect with oxygen radical absorbance capacity (ORAC) value of 2.29.
CONCLUSIONS: Compound 9g was found to be a potent multi-target-directed agent for Alzheimer's disease. GENERAL SIGNIFICANCE: Compound 9g could become a lead compound for further development as a multi-target-directed agent for AD treatment.
ESTHER : Liu_2014_Biochim.Biophys.Acta_1840_2886
PubMedSearch : Liu_2014_Biochim.Biophys.Acta_1840_2886
PubMedID: 24821011

Title : Complete genome sequencing and comparative analysis of the linezolid-resistant Enterococcus faecalis strain DENG1 - Yu_2014_Arch.Microbiol_196_513
Author(s) : Yu Z , Chen Z , Cheng H , Zheng J , Li D , Deng X , Pan W , Yang W , Deng Q
Ref : Arch Microbiol , 196 :513 , 2014
Abstract : Genome level analysis of bacterial strains provides information on genetic composition and resistance mechanisms to clinically relevant antibiotics. To date, whole genome characterization of linezolid-resistant Enterococcus faecalis isolated in the clinic is lacking. In this study, we report the entire genome sequence, genomic characteristics and virulence factors of a pathogenic E. faecalis strain, DENG1. Our results showed considerable differences in genomic characteristics and virulence factors compared with other E. faecalis strains (V583 and OG1RF). The genome of this LZD-resistant E. faecalis strain can be used as a reference to study the mechanism of LZD resistance and the phylogenetic relationship of E. faecalis strains worldwide.
ESTHER : Yu_2014_Arch.Microbiol_196_513
PubMedSearch : Yu_2014_Arch.Microbiol_196_513
PubMedID: 24800692

Title : Genome sequencing of the high oil crop sesame provides insight into oil biosynthesis - Wang_2014_Genome.Biol_15_R39
Author(s) : Wang L , Yu S , Tong C , Zhao Y , Liu Y , Song C , Zhang Y , Zhang X , Wang Y , Hua W , Li D , Li F , Yu J , Xu C , Han X , Huang S , Tai S , Wang J , Xu X , Li Y , Liu S , Varshney RK
Ref : Genome Biol , 15 :R39 , 2014
Abstract : BACKGROUND: Sesame, Sesamum indicum L., is considered the queen of oilseeds for its high oil content and quality, and is grown widely in tropical and subtropical areas as an important source of oil and protein. However, the molecular biology of sesame is largely unexplored. RESULTS: Here, we report a high-quality genome sequence of sesame assembled de novo with a contig N50 of 52.2 kb and a scaffold N50 of 2.1 Mb, containing an estimated 27,148 genes. The results reveal novel, independent whole genome duplication and the absence of the Toll/interleukin-1 receptor domain in resistance genes. Candidate genes and oil biosynthetic pathways contributing to high oil content were discovered by comparative genomic and transcriptomic analyses. These revealed the expansion of type 1 lipid transfer genes by tandem duplication, the contraction of lipid degradation genes, and the differential expression of essential genes in the triacylglycerol biosynthesis pathway, particularly in the early stage of seed development. Resequencing data in 29 sesame accessions from 12 countries suggested that the high genetic diversity of lipid-related genes might be associated with the wide variation in oil content. Additionally, the results shed light on the pivotal stage of seed development, oil accumulation and potential key genes for sesamin production, an important pharmacological constituent of sesame. CONCLUSIONS: As an important species from the order Lamiales and a high oil crop, the sesame genome will facilitate future research on the evolution of eudicots, as well as the study of lipid biosynthesis and potential genetic improvement of sesame.
ESTHER : Wang_2014_Genome.Biol_15_R39
PubMedSearch : Wang_2014_Genome.Biol_15_R39
PubMedID: 24576357
Gene_locus related to this paper: sesin-a0a6i9snr9

Title : A lifespan observation of a novel mouse model: in vivo evidence supports abeta oligomer hypothesis - Zhang_2014_PLoS.One_9_e85885
Author(s) : Zhang Y , Lu L , Jia J , Jia L , Geula C , Pei J , Xu Z , Qin W , Liu R , Li D , Pan N
Ref : PLoS ONE , 9 :e85885 , 2014
Abstract : Transgenic mouse models are powerful tools in exploring the mechanisms of AD. Most current transgenic models of AD mimic the memory impairment and the main pathologic features, among which the formation of beta-amyloid (Abeta) plaques is considered a dominant pathologic event. Recently, Abeta oligomers have been identified as more neurotoxic than Abeta plaques. However, no ideal transgenic mouse model directly support Abeta oligomers as a neurotoxic species due to the puzzling effects of amyloid plaques in the more widely-used models. Here, we constructed a single-mutant transgenic (Tg) model harboring the PS1V97L mutation and used Non-Tg littermates as a control group. Employing the Morris water maze, electrophysiology, immunohistochemistry, biochemistry, and electron microscopy, we investigated behavioral changes and pathology progression in our single-mutant transgenic model. We discovered the pathological alteration of intraneuronal accumulation of Abeta oligomers without Abeta plaques in the PS1V97L-Tg mouse model, which might be the result of PS1 gene mutation. Following Abeta oligomers, we detected synaptic alteration, tau hyperphosphorylation and glial activation. This model supports an initial role for Abeta oligomers in the onset of AD and suggests that Abeta plaques may not be the only prerequisite. This model provides a useful tool for studying the role of Abeta oligomers in AD pathogenesis.
ESTHER : Zhang_2014_PLoS.One_9_e85885
PubMedSearch : Zhang_2014_PLoS.One_9_e85885
PubMedID: 24465766

Title : Acetylcholine secretion by motor neuron-like cells from umbilical cord mesenchymal stem cells - Liu_2013_Neural.Regen.Res_8_2086
Author(s) : Liu X , Li D , Jiang D , Fang Y
Ref : Neural Regen Res , 8 :2086 , 2013
Abstract : Umbilical cord mesenchymal stem cells were isolated by a double enzyme digestion method. The third passage of umbilical cord mesenchymal stem cells was induced with heparin and/or basic fibroblast growth factor. Results confirmed that cell morphology did not change after induction with basic fibroblast growth factor alone. However, neuronal morphology was visible, and microtubule-associated protein-2 expression and acetylcholine levels increased following induction with heparin alone or heparin combined with basic fibroblast growth factor. Hb9 and choline acetyltransferase expression was high following inductive with heparin combined with basic fibroblast growth factor. Results indicate that the inductive effect of basic fibroblast growth factor alone was not obvious. Heparin combined with basic fibroblast growth factor noticeably promoted the differentiation of umbilical cord mesenchymal stem cells into motor neuron-like cells. Simultaneously, umbilical cord mesenchymal stem cells could secrete acetylcholine.
ESTHER : Liu_2013_Neural.Regen.Res_8_2086
PubMedSearch : Liu_2013_Neural.Regen.Res_8_2086
PubMedID: 25206517

Title : 3D-QSAR studies of azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives as anti-AChE and anti-AD agents by the CoMFA method - Li_2013_J.Mol.Graph.Model_41C_61
Author(s) : Li YP , Weng X , Ning FX , Ou JB , Hou JQ , Luo HB , Li D , Huang ZS , Huang SL , Gu LQ
Ref : J Mol Graph Model , 41C :61 , 2013
Abstract : In the present study, a series of novel azaoxoisoaporphine derivatives were reported and their inhibitory activities toward acetylcholinesterase (AChE), butyrylcholinesterase (BCHE), and Abeta aggregation were evaluated. The new compounds remained high inhibitory potency on Abeta aggregation, with inhibitory activity from 29.42% to 89.63% at a concentration of 10muM, but had no action on AChE or BCHE, which was very different from our previously reported oxoaporphine and oxoisoaporphine derivatives. By 3D-QSAR studies, we constructed a reliable CoMFA model (q2=0.856 and r2=0.986) based on the inhibitory activities toward AChE and discovered key information on structure and anti-AChE activities among the azaoxoisoaporphine, oxoaporphine, and oxoisoaporphine derivatives. The model was further confirmed by the test-set validation (q2=0.873, r2=0.937, and slope k=0.902) and Y-randomization examination. The statistically significant and physically meaningful 3D-QSAR/CoMFA model provided better insight into understanding the inhibitory behaviors of those chemicals, which may provide useful information for the rational molecular design of azaoxoisoaporphine derivatives anti-AChE and anti-AD agents.
ESTHER : Li_2013_J.Mol.Graph.Model_41C_61
PubMedSearch : Li_2013_J.Mol.Graph.Model_41C_61
PubMedID: 23500628

Title : Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease - He_2013_Eur.J.Med.Chem_63C_299
Author(s) : He Y , Yao PF , Chen SB , Huang ZH , Huang SL , Tan JH , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 63C :299 , 2013
Abstract : A series of 7,8-dehydrorutaecarpine derivatives were synthesized and characterized as potential multifunctional agents for treatment of Alzheimer's disease (AD). All of these synthetic compounds showed high acetylcholinesterase (AChE) inhibitory activity with IC50 values ranged from 0.60 to 196.7 nM, and good selectivity for AChE over butyrylcholinesterase (BCHE) (125- to 3225-fold). A Lineweaver-Burk plot and molecular modeling study indicated these compounds could bind to both catalytic active site and the peripheral anionic site of AChE. Besides, compounds showed higher activity of inhibiting AChE-induced amyloid-beta (Abeta) aggregation than curcumin, higher anti-oxidative activity than Trolox, and could also be good metal chelators. Considering their low cytotoxicity, our results indicated that these derivatives provide good templates for developing new multifunctional agents for AD treatment.
ESTHER : He_2013_Eur.J.Med.Chem_63C_299
PubMedSearch : He_2013_Eur.J.Med.Chem_63C_299
PubMedID: 23501115

Title : RNA interference revealed the roles of two carboxylesterase genes in insecticide detoxification in Locusta migratoria - Zhang_2013_Chemosphere_93_1207
Author(s) : Zhang J , Li D , Ge P , Yang M , Guo Y , Zhu KY , Ma E
Ref : Chemosphere , 93 :1207 , 2013
Abstract : Carboxylesterases (CarEs) play key roles in metabolism of specific hormones and detoxification of dietary and environmental xenobiotics in insects. We sequenced and characterized CarE cDNAs putatively derived from two different genes named LmCesA1 and LmCesA2 from the migratory locust, Locusta migratoria, one of the most important agricultural pests in the world. The full-length cDNAs of LmCesA1 (1892bp) and LmCesA2 (1643bp) encode 543 and 501 amino acid residues, respectively. The two deduced CarEs share a characteristic alpha/beta-hydrolase structure, including a catalytic triad composed of Ser-Glu (Asp)-His and a consensus sequence GQSAG, which suggests that both CarEs are biologically active. Phylogenetic analysis grouped both LmCesA1 and LmCesA2 into clade A which has been suggested to be involved in dietary detoxification. Both transcripts were highly expressed in all the nymphal and adult stages, but only slightly expressed in eggs. Analyses of tissue-dependent expression and in situ hybridization revealed that both transcripts were primarily expressed in gastric caeca. RNA interference (RNAi) of LmCesA1 and LmCesA2 followed by a topical application of carbaryl or deltamethrin did not lead to a significantly increased mortality with either insecticide. However, RNAi of LmCesA1 and LmCesA2 increased insect mortalities by 20.9% and 14.5%, respectively, when chlorpyrifos was applied. These results suggest that these genes might not play a significant role in detoxification of carbaryl and deltamethrin but are most likely to be involved in detoxification of chlorpyrifos in L. migratoria.
ESTHER : Zhang_2013_Chemosphere_93_1207
PubMedSearch : Zhang_2013_Chemosphere_93_1207
PubMedID: 23899922
Gene_locus related to this paper: locmi-l7szt8 , locmi-l7su46

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

Title : 2-(2-indolyl-)-4(3H)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling - Li_2013_J.Enzyme.Inhib.Med.Chem_28_583
Author(s) : Li Z , Wang B , Hou JQ , Huang SL , Ou TM , Tan JH , An LK , Li D , Gu LQ , Huang ZS
Ref : J Enzyme Inhib Med Chem , 28 :583 , 2013
Abstract : We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BCHE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BCHE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.
ESTHER : Li_2013_J.Enzyme.Inhib.Med.Chem_28_583
PubMedSearch : Li_2013_J.Enzyme.Inhib.Med.Chem_28_583
PubMedID: 22380775

Title : Highly sensitive detection of organophosphorus pesticides by acetylcholinesterase-coated thin film bulk acoustic resonator mass-loading sensor - Chen_2013_Biosens.Bioelectron_41_163
Author(s) : Chen D , Wang J , Xu Y , Li D , Zhang L , Li Z
Ref : Biosensors & Bioelectronics , 41 :163 , 2013
Abstract : An acetylcholinesterase-coated thin film bulk acoustic resonator has been developed for the detection of organophosphorus pesticides. The thin film bulk acoustic resonator acts as a robust mass-sensitive transducer for bio-sensing. This device works in thickness shear mode with a resonance at 1.97GHz. The detection is based on the inhibitory effects of organophosphorus compounds on the enzymatic activity of the acetylcholinesterase immobilized on one of the faces of the acoustic resonator. The enzyme reaction in the substrate solution and the inhibitory effect is observed are real time by measuring the frequency shift. The presence of organophosphorus pesticides can be detected from the diminution of the frequency shift compared with the levels found in their absence. The device exhibits linear responses, good reproducibility, simple operation, portability and a low detection limit of 5.3x10(-11)M for paraoxon. The detection results of organophosphorus pesticide residues in practical samples show that the proposed sensor has the feasibility and sensing accuracy comparable to gas chromatography.
ESTHER : Chen_2013_Biosens.Bioelectron_41_163
PubMedSearch : Chen_2013_Biosens.Bioelectron_41_163
PubMedID: 23017678

Title : Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation - Yan_2012_Bioorg.Med.Chem_20_2527
Author(s) : Yan JW , Li YP , Ye WJ , Chen SB , Hou JQ , Tan JH , Ou TM , Li D , Gu LQ , Huang ZS
Ref : Bioorganic & Medicinal Chemistry , 20 :2527 , 2012
Abstract : A series of isaindigotone derivatives and analogues were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced beta-amyloid (Abeta) aggregation. The synthetic compounds had IC(50) values at micro or nano molar range for cholinesterase inhibition, and some compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE, which were much better than the isaindigotone derivatives previously reported by our group. Most of these compounds showed higher self-induced Abeta aggregation inhibitory activity than a reference compound curcumin. The structure-activity relationship studies revealed that the derivatives with higher inhibition activity on AChE also showed higher selectivity for AChE over BuChE. Compound 6c exhibiting excellent inhibition for both AChE and self-induced Abeta aggregation was further studied using CD, EM, molecular docking and kinetics.
ESTHER : Yan_2012_Bioorg.Med.Chem_20_2527
PubMedSearch : Yan_2012_Bioorg.Med.Chem_20_2527
PubMedID: 22444876

Title : Antibacterial bisabolane-type sesquiterpenoids from the sponge-derived fungus Aspergillus sp - Li_2012_Mar.Drugs_10_234
Author(s) : Li D , Xu Y , Shao CL , Yang RY , Zheng CJ , Chen YY , Fu XM , Qian PY , She ZG , de Voogd NJ , Wang CY
Ref : Mar Drugs , 10 :234 , 2012
Abstract : Four new bisabolane-type sesquiterpenoids, aspergiterpenoid A (1), (-)-sydonol (2), (-)-sydonic acid (3), and (-)-5-(hydroxymethyl)-2-(2',6',6'-trimethyltetrahydro-2H- pyran-2-yl)phenol (4) together with one known fungal metabolite (5) were isolated from the fermentation broth of a marine-derived fungus Aspergillus sp., which was isolated from the sponge Xestospongia testudinaria collected from the South China Sea. Four of them (1-4) are optically active compounds. Their structures and absolute configurations were elucidated by using NMR spectroscopic techniques and mass spectrometric analysis, and by comparing their optical rotations with those related known analogues. Compounds 1-5 showed selective antibacterial activity against eight bacterial strains with the MIC (minimum inhibiting concentrations) values between 1.25 and 20.0 microM. The cytotoxic, antifouling, and acetylcholinesterase inhibitory activities of these compounds were also examined.
ESTHER : Li_2012_Mar.Drugs_10_234
PubMedSearch : Li_2012_Mar.Drugs_10_234
PubMedID: 22363233

Title : Inhibition of soluble epoxide hydrolase attenuates high-fat-diet-induced hepatic steatosis by reduced systemic inflammatory status in mice - Liu_2012_PLoS.One_7_e39165
Author(s) : Liu Y , Dang H , Li D , Pang W , Hammock BD , Zhu Y
Ref : PLoS ONE , 7 :e39165 , 2012
Abstract : Non-alcoholic fatty liver disease is associated with obesity and considered an inflammatory disease. Soluble epoxide hydrolase (sEH) is a major enzyme hydrolyzing epoxyeicosatrienoic acids and attenuates their cardiovascular protective and anti-inflammatory effects. We examined whether sEH inhibition can protect against high-fat (HF)-diet-induced fatty liver in mice and the underlying mechanism. Compared with wild-type littermates, sEH-null mice showed lower diet-induced lipid accumulation in liver, as seen by Oil-red O staining and triglycerides levels. We studied the effect of sEH inhibition on diet-induced fatty liver by feeding C57BL/6 mice an HF diet for 8 weeks (short-term) or 16 weeks (long-term) and administering t-AUCB, a selective sEH inhibitor. sEH inhibition had no effect on the HF-diet-increased body and adipose tissue weight or impaired glucose tolerance but alleviated the diet-induced hepatic steatosis. Adenovirus-mediated overexpression of sEH in liver increased the level of triglycerides in liver and the hepatic inflammatory response. Surprisingly, the induced expression of sEH in liver occurred only with the long-term but not short-term HF diet, which suggests a secondary effect of HF diet on regulating sEH expression. Furthermore, sEH inhibition attenuated the HF-diet-induced increase in plasma levels of proinflammatory cytokines and their mRNA upregulation in adipose tissue, which was accompanied by increased macrophage infiltration. Therefore, sEH inhibition could alleviate HF-diet-induced hepatic steatosis, which might involve its anti-inflammatory effect in adipose tissue and direct inhibition in liver. sEH may be a therapeutic target for HF-diet-induced hepatic steatosis in inhibiting systemic inflammation.
ESTHER : Liu_2012_PLoS.One_7_e39165
PubMedSearch : Liu_2012_PLoS.One_7_e39165
PubMedID: 22720061

Title : Autism-Associated Mutations in ProSAP2\/Shank3 Impair Synaptic Transmission and Neurexin-Neuroligin-Mediated Transsynaptic Signaling - Arons_2012_J.Neurosci_32_14966
Author(s) : Arons MH , Thynne CJ , Grabrucker AM , Li D , Schoen M , Cheyne JE , Boeckers TM , Montgomery JM , Garner CC
Ref : Journal of Neuroscience , 32 :14966 , 2012
Abstract : Mutations in several postsynaptic proteins have recently been implicated in the molecular pathogenesis of autism and autism spectrum disorders ASDs including Neuroligins Neurexins and members of the ProSAP/Shank family thereby suggesting that these genetic forms of autism may share common synaptic mechanisms Initial studies of ASD-associated mutations in ProSAP2/Shank3 support a role for this protein in glutamate receptor function and spine morphology but these synaptic phenotypes are not universally penetrant indicating that other core facets of ProSAP2/Shank3 function must underlie synaptic deficits in patients with ASDs In the present study we have examined whether the ability of ProSAP2/Shank3 to interact with the cytoplasmic tail of Neuroligins functions to coordinate pre/postsynaptic signaling through the Neurexin-Neuroligin signaling complex in hippocampal neurons of Rattus norvegicus Indeed we find that synaptic levels of ProSAP2/Shank3 regulate AMPA and NMDA receptor-mediated synaptic transmission and induce widespread changes in the levels of presynaptic and postsynaptic proteins via Neurexin-Neuroligin transsynaptic signaling ASD-associated mutations in ProSAP2/Shank3 disrupt not only postsynaptic AMPA and NMDA receptor signaling but also interfere with the ability of ProSAP2/Shank3 to signal across the synapse to alter presynaptic structure and function These data indicate that ASD-associated mutations in a subset of synaptic proteins may target core cellular pathways that coordinate the functional matching and maturation of excitatory synapses in the CNS.
ESTHER : Arons_2012_J.Neurosci_32_14966
PubMedSearch : Arons_2012_J.Neurosci_32_14966
PubMedID: 23100419

Title : Synthesis and evaluation of heterobivalent tacrine derivatives as potential multi-functional anti-Alzheimer agents - Luo_2011_Eur.J.Med.Chem_46_2609
Author(s) : Luo W , Li YP , He Y , Huang SL , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 46 :2609 , 2011
Abstract : A new series of heterobivalent tacrine derivatives were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents for their inhibitory activity on cholinesterases, antioxidant activity and self-induced beta-amyloid (Abeta) aggregation. All these synthesized compounds had potent inhibition activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) at nanomolar range. A Lineweaver-Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. The compounds containing hydroxyl group showed potent peroxyl radical absorbance activity. In addition, compound 5j exhibited higher self-induced Abeta aggregation inhibitory activity than curcumin, which could become a multi-functional agent for further development for the treatment of AD.
ESTHER : Luo_2011_Eur.J.Med.Chem_46_2609
PubMedSearch : Luo_2011_Eur.J.Med.Chem_46_2609
PubMedID: 21497959

Title : Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as dual inhibitors for cholinesterases and amyloid beta aggregation - Luo_2011_Bioorg.Med.Chem_19_763
Author(s) : Luo W , Li YP , He Y , Huang SL , Tan JH , Ou TM , Li D , Gu LQ , Huang ZS
Ref : Bioorganic & Medicinal Chemistry , 19 :763 , 2011
Abstract : A new series of tacrine-multialkoxybenzene hybrids (9a-9n) were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced beta-amyloid (Abeta) aggregation. All the synthesized compounds had high acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activity with IC(5)(0) values at the nanomolar range, which were much better than tacrine alone. A Lineweaver-Burk plot and molecular modeling study showed that these hybrids targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compounds 9a-9f with methylenedioxybenzene moiety showed higher self-induced Abeta aggregation inhibitory activity than a reference compound, curcumin. These compounds could be selected as multi-potent agents for further investigation to treat AD.
ESTHER : Luo_2011_Bioorg.Med.Chem_19_763
PubMedSearch : Luo_2011_Bioorg.Med.Chem_19_763
PubMedID: 21211982

Title : Syntheses and characterization of novel oxoisoaporphine derivatives as dual inhibitors for cholinesterases and amyloid beta aggregation - Li_2011_Eur.J.Med.Chem_46_1572
Author(s) : Li YP , Ning FX , Yang MB , Li YC , Nie MH , Ou TM , Tan JH , Huang SL , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 46 :1572 , 2011
Abstract : A series of 3-substituted (5c-5f, 6c-6f) and 4-substituted (10a-10g) oxoisoaporphine derivatives were synthesized. It was found that all these synthetic compounds had IC50 values at micro or nano molar range for cholinesterase inhibition, and most of them could inhibit amyloid beta (Abeta) self-induced aggregation with inhibition ratio from 31.8% to 57.6%. The structure-activity relationship studies revealed that the derivatives with higher selectivity on AChE also showed better inhibition on Abeta self-induced aggregation. The results from cell toxicity study indicated that most quaternary methiodide salts had higher IC50 values than the corresponding non-quaternary compounds. This study provided potentially important information for further development of oxoisoaporphine derivatives as lead compounds for the treatment of Alzheimer's disease.
ESTHER : Li_2011_Eur.J.Med.Chem_46_1572
PubMedSearch : Li_2011_Eur.J.Med.Chem_46_1572
PubMedID: 21367493

Title : Rates of mutation and host transmission for an Escherichia coli clone over 3 years - Reeves_2011_PLoS.One_6_e26907
Author(s) : Reeves PR , Liu B , Zhou Z , Li D , Guo D , Ren Y , Clabots C , Lan R , Johnson JR , Wang L
Ref : PLoS ONE , 6 :e26907 , 2011
Abstract : Although over 50 complete Escherichia coli/Shigella genome sequences are available, it is only for closely related strains, for example the O55:H7 and O157:H7 clones of E. coli, that we can assign differences to individual evolutionary events along specific lineages. Here we sequence the genomes of 14 isolates of a uropathogenic E. coli clone that persisted for 3 years within a household, including a dog, causing a urinary tract infection (UTI) in the dog after 2 years. The 20 mutations observed fit a single tree that allows us to estimate the mutation rate to be about 1.1 per genome per year, with minimal evidence for adaptive change, including in relation to the UTI episode. The host data also imply at least 6 host transfer events over the 3 years, with 2 lineages present over much of that period. To our knowledge, these are the first direct measurements for a clone in a well-defined host community that includes rates of mutation and host transmission. There is a concentration of non-synonymous mutations associated with 2 transfers to the dog, suggesting some selection pressure from the change of host. However, there are no changes to which we can attribute the UTI event in the dog, which suggests that this occurrence after 2 years of the clone being in the household may have been due to chance, or some unknown change in the host or environment. The ability of a UTI strain to persist for 2 years and also to transfer readily within a household has implications for epidemiology, diagnosis, and clinical intervention.
ESTHER : Reeves_2011_PLoS.One_6_e26907
PubMedSearch : Reeves_2011_PLoS.One_6_e26907
PubMedID: 22046404
Gene_locus related to this paper: ecoli-ybff , ecoli-ycfp , ecoli-YFBB , ecoli-yqia

Title : Production of diacylglycerols from glycerol monooleate and ethyl oleate through free and immobilized lipase-catalyzed consecutive reactions - Jin_2011_N.Biotechnol_28_190
Author(s) : Jin J , Li D , Zhu XM , Adhikari P , Lee KT , Lee JH
Ref : N Biotechnol , 28 :190 , 2011
Abstract : The ability of free and immobilized lipase on the production of diacylglycerols (DAG) by transesterification of glycerol monooleate (GMO) and ethyl oleate was investigated. Among three free lipases such as lipase G (Penicillium cyclopium), lipase AK (Pseudomonas fluorescens) and lipase PS (Pseudomonas cepacia), lipase PS exhibited the highest DAG productivity, and the DAG content gradually increased up to 24 hours reaction and then remained steady. The comparative result for DAG productivity between free lipase PS and immobilized lipases (lipase PS-D and Lipozyme RM IM) during nine times of 24 hours reaction indicated that total DAG production was higher in immobilized lipase PS-D (183.5mM) and Lipozyme RM IM (309.5mM) than free lipase PS (122.0mM) at the first reaction, and that the DAG production rate was reduced by consecutive reactions, in which more sn-1,3-DAG was synthesized than sn-1,2-DAG. During the consecutive reactions, the activity of lipase PS was relatively steady by showing similar DAG content, whereas DAG production of lipase PS-D and Lipozyme RM IM was gradually decreased to 69.9 and 167.1mM at 9th reaction, respectively, resulting in 62% and 46% reduced production when compared with 1st reaction. Interestingly, from 7th reaction lipase PS produced more DAG than immobilized lipase PS-D, and exhibited a stable activity for DAG production. Therefore, the present study suggested that DAG productivity between GMO and ethyl oleate was higher in immobilized lipases than free lipases, but the activity was reduced with repeated uses.
ESTHER : Jin_2011_N.Biotechnol_28_190
PubMedSearch : Jin_2011_N.Biotechnol_28_190
PubMedID: 20951847

Title : Genome analysis and characterization of zinc efflux systems of a highly zinc-resistant bacterium, Comamonas testosteroni S44 - Xiong_2011_Res.Microbiol_162_671
Author(s) : Xiong J , Li D , Li H , He M , Miller SJ , Yu L , Rensing C , Wang G
Ref : Res Microbiol , 162 :671 , 2011
Abstract : A novel and multiple metal(loid)-resistant strain Comamonas testosteroni S44 with a high Zn(2+) resistance level (10 mM) was isolated. To understand the molecular basis for the high zinc resistance, whole genome sequencing was performed and revealed a large number of genes encoding putative metal(loid) resistance proteins, mobile genetic elements (MGEs) and horizontal gene transfer (HGT) events that may have occurred to adapt to a metal(loid)-contaminated environment. In particular, 9 putative Zn(2+) transporters [4 znt operons encoding putative Zn(2+)-translocating P-type ATPases and 5 czc operons encoding putative RND-driven (resistance, nodulation, cell division protein family)] tripartite protein complexes were identified. Real-time RT-PCR analysis revealed that the four zntA-like genes were all induced by Zn(2+), while czcA genes were either Zn(2+)-induced or downregulated by Zn(2+). Furthermore, a zntR1A1 operon encoding a ZntR-type regulator and a P-type ATPase was studied in detail. The zntR1 deletion strain (S44DeltazntR1) displayed intermediate resistance to Zn(2+) (6 mM) and accumulated more intracellular Zn(2+). Reporter gene expression assays indicated that ZntR1 responded to Zn(2+), Cd(2+) and Pb(2+), with Zn(2+) being the best inducer. Gene transcription analysis indicated that ZntR1 was a regulator for transcription of zntA1, while other putative ZntR-type regulators may also regulate the transcription expression of zntA1.
ESTHER : Xiong_2011_Res.Microbiol_162_671
PubMedSearch : Xiong_2011_Res.Microbiol_162_671
PubMedID: 21704702
Gene_locus related to this paper: comt2-d0iyk2 , comt2-d0j233 , comte-b7wz02 , comte-b7x2b9 , comte-d8d186 , comte-b7wth6 , comte-d8d685 , comte-d8d7u8

Title : The glycobiome of the rumen bacterium Butyrivibrio proteoclasticus B316(T) highlights adaptation to a polysaccharide-rich environment - Kelly_2010_PLoS.One_5_e11942
Author(s) : Kelly WJ , Leahy SC , Altermann E , Yeoman CJ , Dunne JC , Kong Z , Pacheco DM , Li D , Noel SJ , Moon CD , Cookson AL , Attwood GT
Ref : PLoS ONE , 5 :e11942 , 2010
Abstract : Determining the role of rumen microbes and their enzymes in plant polysaccharide breakdown is fundamental to understanding digestion and maximising productivity in ruminant animals. Butyrivibrio proteoclasticus B316(T) is a gram-positive, butyrate-forming rumen bacterium with a key role in plant polysaccharide degradation. The 4.4 Mb genome consists of 4 replicons; a chromosome, a chromid and two megaplasmids. The chromid is the smallest reported for all bacteria, and the first identified from the phylum Firmicutes. B316 devotes a large proportion of its genome to the breakdown and reassembly of complex polysaccharides and has a highly developed glycobiome when compared to other sequenced bacteria. The secretion of a range of polysaccharide-degrading enzymes which initiate the breakdown of pectin, starch and xylan, a subtilisin family protease active against plant proteins, and diverse intracellular enzymes to break down oligosaccharides constitute the degradative capability of this organism. A prominent feature of the genome is the presence of multiple gene clusters predicted to be involved in polysaccharide biosynthesis. Metabolic reconstruction reveals the absence of an identifiable gene for enolase, a conserved enzyme of the glycolytic pathway. To our knowledge this is the first report of an organism lacking an enolase. Our analysis of the B316 genome shows how one organism can contribute to the multi-organism complex that rapidly breaks down plant material in the rumen. It can be concluded that B316, and similar organisms with broad polysaccharide-degrading capability, are well suited to being early colonizers and degraders of plant polysaccharides in the rumen environment.
ESTHER : Kelly_2010_PLoS.One_5_e11942
PubMedSearch : Kelly_2010_PLoS.One_5_e11942
PubMedID: 20689770
Gene_locus related to this paper: butpb-e0rxq6 , butpb-e0ryg8 , butpb-e0ryt2 , butpb-e0s1b3 , butpb-e0s2z7 , butpb-e0rxr0 , butpb-e0rxg9

Title : Regulation of gene expression by FSP27 in white and brown adipose tissue - Li_2010_BMC.Genomics_11_446
Author(s) : Li D , Zhang Y , Xu L , Zhou L , Wang Y , Xue B , Wen Z , Li P , Sang J
Ref : BMC Genomics , 11 :446 , 2010
Abstract : BACKGROUND: Brown and white adipose tissues (BAT and WAT) play critical roles in controlling energy homeostasis and in the development of obesity and diabetes. The mouse Fat-Specific protein 27 (FSP27), a member of the cell death-inducing DFF45-like effector (CIDE) family, is expressed in both BAT and WAT and is associated with lipid droplets. Over-expression of FSP27 promotes lipid storage, whereas FSP27 deficient mice have improved insulin sensitivity and are resistant to diet-induced obesity. In addition, FSP27-deficient white adipocytes have reduced lipid storage, smaller lipid droplets, increased mitochondrial activity and a higher expression of several BAT-selective genes. To elucidate the molecular mechanism by which FSP27 controls lipid storage and gene expression in WAT and BAT, we systematically analyzed the gene expression profile of FSP27-deficient WAT by microarray analysis and compared the expression levels of a specific set of genes in WAT and BAT by semi-quantitative real-time PCR analysis.
RESULTS: BAT-selective genes were significantly up-regulated, whereas WAT-selective genes were down-regulated in the WAT of FSP27-deficient mice. The expression of the BAT-selective genes was also dramatically up-regulated in the WAT of leptin/FSP27 double deficient mice. In addition, the expression levels of genes involved in multiple metabolic pathways, including oxidative phosphorylation, the TCA cycle, fatty acid synthesis and fatty acid oxidation, were increased in the FSP27-deficient WAT. In contrast, the expression levels for genes involved in extracellular matrix remodeling, the classic complement pathway and TGF-beta signaling were down-regulated in the FSP27-deficient WAT. Most importantly, the expression levels of regulatory factors that determine BAT identity, such as CEBP alpha/beta, PRDM16 and major components of the cAMP pathway, were markedly up-regulated in the WAT of FSP27-deficient mice. The expression levels of these regulatory factors were also up-regulated in leptin/FSP27 double deficient mice. Interestingly, distinct gene expression profiles were observed in the BAT of FSP27-deficient mice. Taken together, these data suggest that the WAT of FSP27-deficient mice have a gene expression profile similar to that of BAT.
CONCLUSIONS: FSP27 acts as a molecular determinant that controls gene expression for a diversity of metabolic and signaling pathways and, in particular, the expression of regulatory factors, including CEBP alpha/beta, PRDM16 and components of the cAMP signaling pathway, that control the identity of WAT and BAT.
ESTHER : Li_2010_BMC.Genomics_11_446
PubMedSearch : Li_2010_BMC.Genomics_11_446
PubMedID: 20649970

Title : Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors - Wang_2010_Eur.J.Med.Chem_45_1415
Author(s) : Wang B , Mai YC , Li Y , Hou JQ , Huang SL , Ou TM , Tan JH , An LK , Li D , Gu LQ , Huang ZS
Ref : Eur Journal of Medicinal Chemistry , 45 :1415 , 2010
Abstract : A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.
ESTHER : Wang_2010_Eur.J.Med.Chem_45_1415
PubMedSearch : Wang_2010_Eur.J.Med.Chem_45_1415
PubMedID: 20079560

Title : The sequence and de novo assembly of the giant panda genome - Li_2010_Nature_463_311
Author(s) : Li R , Fan W , Tian G , Zhu H , He L , Cai J , Huang Q , Cai Q , Li B , Bai Y , Zhang Z , Zhang Y , Wang W , Li J , Wei F , Li H , Jian M , Nielsen R , Li D , Gu W , Yang Z , Xuan Z , Ryder OA , Leung FC , Zhou Y , Cao J , Sun X , Fu Y , Fang X , Guo X , Wang B , Hou R , Shen F , Mu B , Ni P , Lin R , Qian W , Wang G , Yu C , Nie W , Wang J , Wu Z , Liang H , Min J , Wu Q , Cheng S , Ruan J , Wang M , Shi Z , Wen M , Liu B , Ren X , Zheng H , Dong D , Cook K , Shan G , Zhang H , Kosiol C , Xie X , Lu Z , Li Y , Steiner CC , Lam TT , Lin S , Zhang Q , Li G , Tian J , Gong T , Liu H , Zhang D , Fang L , Ye C , Zhang J , Hu W , Xu A , Ren Y , Zhang G , Bruford MW , Li Q , Ma L , Guo Y , An N , Hu Y , Zheng Y , Shi Y , Li Z , Liu Q , Chen Y , Zhao J , Qu N , Zhao S , Tian F , Wang X , Wang H , Xu L , Liu X , Vinar T , Wang Y , Lam TW , Yiu SM , Liu S , Huang Y , Yang G , Jiang Z , Qin N , Li L , Bolund L , Kristiansen K , Wong GK , Olson M , Zhang X , Li S , Yang H
Ref : Nature , 463 :311 , 2010
Abstract : Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.
ESTHER : Li_2010_Nature_463_311
PubMedSearch : Li_2010_Nature_463_311
PubMedID: 20010809
Gene_locus related to this paper: ailme-ABH15 , ailme-ACHE , ailme-BCHE , ailme-d2gtv3 , ailme-d2gty9 , ailme-d2gu87 , ailme-d2gu97 , ailme-d2gve7 , ailme-d2gwu1 , ailme-d2gx08 , ailme-d2gyt0 , ailme-d2gz36 , ailme-d2gz37 , ailme-d2gz38 , ailme-d2gz39 , ailme-d2gz40 , ailme-d2h5r9 , ailme-d2h7b7 , ailme-d2h9c9 , ailme-d2h794 , ailme-d2hau7 , ailme-d2hau8 , ailme-d2hcd9 , ailme-d2hdi6 , ailme-d2heu6 , ailme-d2hga4 , ailme-d2hqw5 , ailme-d2hs98 , ailme-d2hsx4 , ailme-d2hti6 , ailme-d2htv3 , ailme-d2htz6 , ailme-d2huc7 , ailme-d2hwj8 , ailme-d2hwy7 , ailme-d2hxm1 , ailme-d2hyc8 , ailme-d2hyv2 , ailme-d2hz11 , ailme-d2hza3 , ailme-d2hzr4 , ailme-d2i1l4 , ailme-d2i2g8 , ailme-g1l7m3 , ailme-g1lu36 , ailme-g1m769 , ailme-g1mc29 , ailme-g1mdj8 , ailme-g1mdr5 , ailme-g1mfp4 , ailme-g1mfx5 , ailme-g1lj41 , ailme-g1lm28 , ailme-g1l3u1 , ailme-g1l7l1 , ailme-g1m5i3 , ailme-g1l2f6 , ailme-g1lji5 , ailme-g1lqk3 , ailme-g1l8s9 , ailme-d2h717 , ailme-d2h718 , ailme-d2h719 , ailme-d2h720 , ailme-g1m5v0 , ailme-g1m5y7 , ailme-g1lkt7 , ailme-g1l2a1 , ailme-g1lsc8 , ailme-g1lrp4 , ailme-d2gv02 , ailme-g1mik5 , ailme-g1ljr1 , ailme-g1lxw7 , ailme-d2h8b5 , ailme-d2h2r2 , ailme-d2h9w7 , ailme-g1meh3 , ailme-g1m719

Title : Enrichment of pinolenic acid at the sn-2 position of triacylglycerol molecules through lipase-catalyzed reaction - Zhu_2010_Int.J.Food.Sci.Nutr_61_138
Author(s) : Zhu XM , Hu JN , Shin JA , Li D , Jin J , Adhikari P , Akoh CC , Lee JH , Choi SW , Lee KT
Ref : Int J Food Sci Nutr , 61 :138 , 2010
Abstract : Reports have shown that Delta-5 polyunsaturated fatty acids (-5 PUFA) are enriched at sn-1,3 positions of triacylglycerols (TAG) in pine (Pinus koraiensis) nut oil (Pn). As a major Delta-5 PUFA, pinolenic acid (Pi) is about 14.2% in the oil, while the percentage of Pi at the sn-1 and/or sn-3 positions in TAG was found more than 20%. In this current study, the enhancement of Pi at the sn-2 position has been achieved by acyl migration during the lipase-catalyzed inter-esterification between Pn and palm stearin (Ps). After reaction, the proportion of Pi increased at sn-2 positional fatty acid even is similar to that in total fatty acid; for example, in the inter-esterified product of 50:50 (Pn:Ps), the same amount of Pi (7.1%) present was detected both at the sn-2 and sn-1,3 positions. However, the reduction of phytosterols and tocopherols are observed in the inter-esterified products.
ESTHER : Zhu_2010_Int.J.Food.Sci.Nutr_61_138
PubMedSearch : Zhu_2010_Int.J.Food.Sci.Nutr_61_138
PubMedID: 20001760

Title : The genome sequence of the rumen methanogen Methanobrevibacter ruminantium reveals new possibilities for controlling ruminant methane emissions - Leahy_2010_PLoS.One_5_e8926
Author(s) : Leahy SC , Kelly WJ , Altermann E , Ronimus RS , Yeoman CJ , Pacheco DM , Li D , Kong Z , McTavish S , Sang C , Lambie SC , Janssen PH , Dey D , Attwood GT
Ref : PLoS ONE , 5 :e8926 , 2010
Abstract : BACKGROUND: Methane (CH(4)) is a potent greenhouse gas (GHG), having a global warming potential 21 times that of carbon dioxide (CO(2)). Methane emissions from agriculture represent around 40% of the emissions produced by human-related activities, the single largest source being enteric fermentation, mainly in ruminant livestock. Technologies to reduce these emissions are lacking. Ruminant methane is formed by the action of methanogenic archaea typified by Methanobrevibacter ruminantium, which is present in ruminants fed a wide variety of diets worldwide. To gain more insight into the lifestyle of a rumen methanogen, and to identify genes and proteins that can be targeted to reduce methane production, we have sequenced the 2.93 Mb genome of M. ruminantium M1, the first rumen methanogen genome to be completed. METHODOLOGY/PRINCIPAL FINDINGS: The M1 genome was sequenced, annotated and subjected to comparative genomic and metabolic pathway analyses. Conserved and methanogen-specific gene sets suitable as targets for vaccine development or chemogenomic-based inhibition of rumen methanogens were identified. The feasibility of using a synthetic peptide-directed vaccinology approach to target epitopes of methanogen surface proteins was demonstrated. A prophage genome was described and its lytic enzyme, endoisopeptidase PeiR, was shown to lyse M1 cells in pure culture. A predicted stimulation of M1 growth by alcohols was demonstrated and microarray analyses indicated up-regulation of methanogenesis genes during co-culture with a hydrogen (H(2)) producing rumen bacterium. We also report the discovery of non-ribosomal peptide synthetases in M. ruminantium M1, the first reported in archaeal species. CONCLUSIONS/SIGNIFICANCE: The M1 genome sequence provides new insights into the lifestyle and cellular processes of this important rumen methanogen. It also defines vaccine and chemogenomic targets for broad inhibition of rumen methanogens and represents a significant contribution to worldwide efforts to mitigate ruminant methane emissions and reduce production of anthropogenic greenhouse gases.
ESTHER : Leahy_2010_PLoS.One_5_e8926
PubMedSearch : Leahy_2010_PLoS.One_5_e8926
PubMedID: 20126622
Gene_locus related to this paper: metrm-metxa

Title : Isolation and biochemical characterization of two lipases from a metagenomic library of China Holstein cow rumen - Liu_2009_Biochem.Biophys.Res.Commun_385_605
Author(s) : Liu K , Wang J , Bu D , Zhao S , McSweeney C , Yu P , Li D
Ref : Biochemical & Biophysical Research Communications , 385 :605 , 2009
Abstract : Two novel lipase genes RlipE1 and RlipE2 which encoded 361- and 265-amino acid peptides, respectively, were recovered from a metagenomic library of the rumen microbiota of Chinese Holstein cows. A BLAST search revealed a high similarity (90%) between RlipE2 and a carboxylesterase from Thermosinus carboxydivorans Nor1, while there was a low similarity (below 50%) between RlipE1 and other lipases. Phylogenetic analysis indicated that RlipE2 clustered with the lipolytic enzymes from family V while RlipE1 clustered with six other putative bacterial lipases which might constitute a new subfamily. The recombinant lipases were thermally unstable and retained 60% activity over a pH range of 6.5-8.5. Substrate specificity assay indicated that both enzymes had higher hydrolytic activity toward laurate (C(12)), palmitate (C(16)) and stearate (C(18)). The novel phylogenetic affiliation and high specificity of both enzymes for long-chain fatty acid make them interesting targets for manipulation of rumen lipid metabolism.
ESTHER : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedSearch : Liu_2009_Biochem.Biophys.Res.Commun_385_605
PubMedID: 19486892
Gene_locus related to this paper: 9bact-c0k075 , 9bact-c0k085

Title : A recalibrated molecular clock and independent origins for the cholera pandemic clones - Feng_2008_PLoS.One_3_e4053
Author(s) : Feng L , Reeves PR , Lan R , Ren Y , Gao C , Zhou Z , Cheng J , Wang W , Wang J , Qian W , Li D , Wang L
Ref : PLoS ONE , 3 :e4053 , 2008
Abstract : Cholera, caused by Vibrio cholerae, erupted globally from South Asia in 7 pandemics, but there were also local outbreaks between the 6(th) (1899-1923) and 7(th) (1961-present) pandemics. All the above are serotype O1, whereas environmental or invertebrate isolates are antigenically diverse. The pre 7th pandemic isolates mentioned above, and other minor pathogenic clones, are related to the 7(th) pandemic clone, while the 6(th) pandemic clone is in the same lineage but more distantly related, and non-pathogenic isolates show no clonal structure. To understand the origins and relationships of the pandemic clones, we sequenced the genomes of a 1937 prepandemic strain and a 6(th) pandemic isolate, and compared them with the published 7(th) pandemic genome. We distinguished mutational and recombinational events, and allocated these and other events, to specific branches in the evolutionary tree. There were more mutational than recombinational events, but more genes, and 44 times more base pairs, changed by recombination. We used the mutational single-nucleotide polymorphisms and known isolation dates of the prepandemic and 7(th) pandemic isolates to estimate the mutation rate, and found it to be 100 fold higher than usually assumed. We then used this to estimate the divergence date of the 6(th) and 7(th) pandemic clones to be about 1880. While there is a large margin of error, this is far more realistic than the 10,000-50,000 years ago estimated using the usual assumptions. We conclude that the 2 pandemic clones gained pandemic potential independently, and overall there were 29 insertions or deletions of one or more genes. There were also substantial changes in the major integron, attributed to gain of individual cassettes including copying from within, or loss of blocks of cassettes. The approaches used open up new avenues for analysing the origin and history of other important pathogens.
ESTHER : Feng_2008_PLoS.One_3_e4053
PubMedSearch : Feng_2008_PLoS.One_3_e4053
PubMedID: 19115014
Gene_locus related to this paper: vibch-VC1974 , vibch-VC2610 , vibch-VC2718 , vibch-y1892 , vibch-y2276

Title : Encapsulated in silica: genome, proteome and physiology of the thermophilic bacterium Anoxybacillus flavithermus WK1 - Saw_2008_Genome.Biol_9_R161
Author(s) : Saw JH , Mountain BW , Feng L , Omelchenko MV , Hou S , Saito JA , Stott MB , Li D , Zhao G , Wu J , Galperin MY , Koonin EV , Makarova KS , Wolf YI , Rigden DJ , Dunfield PF , Wang L , Alam M
Ref : Genome Biol , 9 :R161 , 2008
Abstract : BACKGROUND: Gram-positive bacteria of the genus Anoxybacillus have been found in diverse thermophilic habitats, such as geothermal hot springs and manure, and in processed foods such as gelatin and milk powder. Anoxybacillus flavithermus is a facultatively anaerobic bacterium found in super-saturated silica solutions and in opaline silica sinter. The ability of A. flavithermus to grow in super-saturated silica solutions makes it an ideal subject to study the processes of sinter formation, which might be similar to the biomineralization processes that occurred at the dawn of life. RESULTS: We report here the complete genome sequence of A. flavithermus strain WK1, isolated from the waste water drain at the Wairakei geothermal power station in New Zealand. It consists of a single chromosome of 2,846,746 base pairs and is predicted to encode 2,863 proteins. In silico genome analysis identified several enzymes that could be involved in silica adaptation and biofilm formation, and their predicted functions were experimentally validated in vitro. Proteomic analysis confirmed the regulation of biofilm-related proteins and crucial enzymes for the synthesis of long-chain polyamines as constituents of silica nanospheres. CONCLUSIONS: Microbial fossils preserved in silica and silica sinters are excellent objects for studying ancient life, a new paleobiological frontier. An integrated analysis of the A. flavithermus genome and proteome provides the first glimpse of metabolic adaptation during silicification and sinter formation. Comparative genome analysis suggests an extensive gene loss in the Anoxybacillus/Geobacillus branch after its divergence from other bacilli.
ESTHER : Saw_2008_Genome.Biol_9_R161
PubMedSearch : Saw_2008_Genome.Biol_9_R161
PubMedID: 19014707
Gene_locus related to this paper: anofw-b7ghw8 , anofw-b7gk10 , anofw-b7gk45 , anofw-b7gln5 , anofw-b7glx5 , anofw-b7gm70

Title : The Genomes of Oryza sativa: a history of duplications - Yu_2005_PLoS.Biol_3_e38
Author(s) : Yu J , Wang J , Lin W , Li S , Li H , Zhou J , Ni P , Dong W , Hu S , Zeng C , Zhang J , Zhang Y , Li R , Xu Z , Li X , Zheng H , Cong L , Lin L , Yin J , Geng J , Li G , Shi J , Liu J , Lv H , Li J , Deng Y , Ran L , Shi X , Wang X , Wu Q , Li C , Ren X , Li D , Liu D , Zhang X , Ji Z , Zhao W , Sun Y , Zhang Z , Bao J , Han Y , Dong L , Ji J , Chen P , Wu S , Xiao Y , Bu D , Tan J , Yang L , Ye C , Xu J , Zhou Y , Yu Y , Zhang B , Zhuang S , Wei H , Liu B , Lei M , Yu H , Li Y , Xu H , Wei S , He X , Fang L , Huang X , Su Z , Tong W , Tong Z , Ye J , Wang L , Lei T , Chen C , Chen H , Huang H , Zhang F , Li N , Zhao C , Huang Y , Li L , Xi Y , Qi Q , Li W , Hu W , Tian X , Jiao Y , Liang X , Jin J , Gao L , Zheng W , Hao B , Liu S , Wang W , Yuan L , Cao M , McDermott J , Samudrala R , Wong GK , Yang H
Ref : PLoS Biol , 3 :e38 , 2005
Abstract : We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family.
ESTHER : Yu_2005_PLoS.Biol_3_e38
PubMedSearch : Yu_2005_PLoS.Biol_3_e38
PubMedID: 15685292
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q852M6 , orysa-Q8GSE8 , orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q8H5P9 , orysa-Q8H5P5 , orysa-Q7F1Y5 , orysa-Q949C9 , orysa-cbp1 , orysa-cbp3 , orysa-cbpx , orysa-Q33B71 , orysa-Q8GSJ3 , orysa-LPL1 , orysa-Q6YSZ8 , orysa-Q8S5X5 , orysa-Q8LIG3 , orysa-Q6K7F5 , orysa-Q7F1B1 , orysa-Q8H4S9 , orysa-Q69UB1 , orysa-Q9FW17 , orysa-Q337C3 , orysa-Q7F959 , orysa-Q84QZ6 , orysa-Q84QY7 , orysa-Q851E3 , orysa-Q6YTH5 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q0JCY4 , orysa-Q8GTK2 , orysa-B9EWJ8 , orysa-Q8H3K6 , orysa-Q6ZDG8 , orysa-Q6ZDG6 , orysa-Q6ZDG5 , orysa-Q6ZDG4 , orysa-Q5NAI4 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q8RYV9 , orysa-Q8H3R3 , orysa-Q5SNH3 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-q2qlm4 , orysa-q2qm78 , orysa-q2qm82 , orysa-q2qn31 , orysa-q2qnj4 , orysa-q2qnt9 , orysa-q2qur1 , orysa-q2qx94 , orysa-q2qyi1 , orysa-q2qyj1 , orysa-q2r051 , orysa-q2r077 , orysa-q2ram0 , orysa-q2rat1 , orysa-q2rbb3 , orysa-Q4VWY7 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5smv5 , orysa-Q5VP27 , orysa-q5vrt2 , orysa-q5w6c5 , orysa-q5z5a3 , orysa-q5z9i2 , orysa-q5z417 , orysa-q5z901 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-Q5ZCR3 , orysa-q6atz0 , orysa-q6ave2 , orysa-q6f358 , orysa-q6h6s1 , orysa-q6h7i6 , orysa-q6i5q3 , orysa-q6i5u7 , orysa-q6j657 , orysa-q6k3d9 , orysa-q6k4q2 , orysa-q6k880 , orysa-q6l5b6 , orysa-Q6L5F5 , orysa-q6l556 , orysj-q6yse8 , orysa-q6yy42 , orysa-q6yzk1 , orysa-q6z8b1 , orysa-q6z995 , orysa-q6zc62 , orysa-q6zia4 , orysa-q6zjq6 , orysa-q7x7y5 , orysa-Q7XC50 , orysa-q7xej4 , orysa-q7xem8 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-q7xts6 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q8L562 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q8SAY7 , orysa-Q8SAY9 , orysa-Q8W3C6 , orysa-Q8W3F2 , orysa-Q8W3F4 , orysa-Q8W3F6 , orysa-Q9LHX5 , orysa-q33aq0 , orysa-q53lh1 , orysa-q53m20 , orysa-q53nd8 , orysa-q60e79 , orysa-q60ew8 , orysa-q67iz2 , orysa-q67iz3 , orysa-q67iz7 , orysa-q67iz8 , orysa-q67j02 , orysa-q67j05 , orysa-q67j07 , orysa-q67j09 , orysa-q67j10 , orysa-q67tr6 , orysa-q67tv0 , orysa-q67uz1 , orysa-q67v34 , orysa-q67wz5 , orysa-q69j38 , orysa-q69k08 , orysa-q69md7 , orysa-q69me0 , orysa-q69pf3 , orysa-q69ti3 , orysa-q69xr2 , orysa-q69y12 , orysa-q69y21 , orysa-q75hy2 , orysa-q75i01 , orysa-Q94JD7 , orysa-Q0J0A4 , orysa-q651a8 , orysa-q651z3 , orysa-q652g4 , orysa-q688m0 , orysa-q688m8 , orysa-q688m9 , orysa-Q6H8G1 , orysi-a2wn01 , orysi-a2xc83 , orysi-a2yh83 , orysi-a2z179 , orysi-a2zef2 , orysi-b8a7e6 , orysi-b8a7e7 , orysi-b8bfe5 , orysi-b8bhp9 , orysj-a3b9l8 , orysj-b9eub8 , orysj-b9eya5 , orysj-b9fi05 , orysj-b9fkb0 , orysj-b9fn42 , orysj-b9gbb7 , orysj-cgep , orysj-PLA7 , orysj-q0d4u5 , orysj-q0djj0 , orysj-q0jaf0 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q5z419 , orysj-q6h7q9 , orysj-q6yvk6 , orysj-q6z6i1 , orysj-q7f8x1 , orysj-q7xcx3 , orysj-q9fwm6 , orysj-q10j20 , orysj-q10ss2 , orysj-q69uw6 , orysj-q94d71 , orysj-q338c0 , orysi-b8bly4 , orysj-b9gbs4 , orysi-a2zb88 , orysj-b9gbs1 , orysi-b8b698 , orysj-pla4 , orysj-pla1

Title : Molecular evidence that the extracellular cutinase Pbc1 is required for pathogenicity of Pyrenopeziza brassicae on oilseed rape - Li_2003_Mol.Plant.Microbe.Interact_16_545
Author(s) : Li D , Ashby AM , Johnstone K
Ref : Mol Plant Microbe Interact , 16 :545 , 2003
Abstract : Recent evidence has suggested that cutinase is required for cuticular penetration and, therefore, is essential for pathogenicity of Pyrenopeziza brassicae, the causal organism of light leaf spot disease of oilseed rape and other brassicas. In order to acquire molecular evidence for the role of cutinase in pathogenesis, the single-copy P. brassicae cutinase gene Pbc1 was disrupted by a transformation-mediated approach. Southern hybridization analysis revealed that in one mutant, NH10-1224, the disruption was due to a tandem insertion of two copies of the disruption vector into the 5' coding region of Pbc1. In contrast to the wild type, no expression of Pbc1 was detected during in planta growth or in cutin-induced mycelium of NH10-1224 and no cutinase activity was detected in culture supernatants from NH10-1224 using p-nitrophenyl butyrate as substrate. Scanning electron microscopy of Brassica napus cotyledons infected with wild-type P. brassicae confirmed that entry into the host is by direct penetration of the cuticle. In contrast, the cutinase-deficient mutant NH10-1224 failed to penetrate the cuticular layer and was unable to develop disease symptoms. This evidence is consistent with the hypothesis that Pbc1 is required for P. brassicae to penetrate the plant cuticle. Demonstration that complementation of NH10-1224 with the Pbc1 wild-type gene restores both cutinase activity and pathogenicity will be required to definitively establish that cutinase is required for successful pathogenesis of brassicas by P. brassicae.
ESTHER : Li_2003_Mol.Plant.Microbe.Interact_16_545
PubMedSearch : Li_2003_Mol.Plant.Microbe.Interact_16_545
PubMedID: 12795380
Gene_locus related to this paper: pyrbr-Q9Y7G8

Title : Regulation of constitutively expressed and induced cutinase genes by different zinc finger transcription factors in Fusarium solani f. sp. pisi (Nectria haematococca) - Li_2002_J.Biol.Chem_277_7905
Author(s) : Li D , Sirakova T , Rogers L , Ettinger WF , Kolattukudy PE
Ref : Journal of Biological Chemistry , 277 :7905 , 2002
Abstract : Cutin monomers, generated by the low levels of constitutively expressed cutinase, induce high levels of cutinase that can help pathogenic fungi to penetrate into the host through the cuticle whose major structural polymer is cutin. We cloned three highly homologous cutinase genes, cut1, cut2, and cut3, from Fusarium solani f. pisi (Nectria haematococca). Amino acid sequence deduced from the nucleotide sequence of cut1 and cut2/3 matched with that of the peptides from cutinase 1 and cutinase 2, respectively, isolated from F. solani pisi grown on cutin as the sole carbon source. Induction of beta-glucuronidase gene fused to the promoters of the cutinases integrated into F. solani pisi genome indicates that cut2 is constitutively expressed and induced under starvation, whereas cut1 is highly induced by cutin monomers. A palindrome binding protein (PBP) previously cloned binds only to palindrome 1 of cut1 promoter but not palindrome 1 of cut2/3 which contains two base substitutions. PBP is thought to interfere with the binding of CTF1 alpha, the transcription factor involved in induction, to cut1 promoter and thus keep cut1 gene repressed until induced by cutin monomers. Because PBP cannot bind palindrome 1 of cut2, this gene is not repressed. CTF1 alpha does not transactivate cut2 promoter. A new Cys(6)Zn(2) motif-containing transcription factor, CTF1 beta, that binds palindrome 2 was cloned and sequenced. In yeast, CTF1 beta transactivates cut2 promoter but not cut1 promoter unless its palindrome 1 is mutated, unlike CTF1 alpha which transactivates cut1. Thus, CTF1 beta is involved in the constitutive expression of cut2 that causes production of low levels of cutin monomers that strongly induce cut1 using CTF1 alpha as the transcription factor.
ESTHER : Li_2002_J.Biol.Chem_277_7905
PubMedSearch : Li_2002_J.Biol.Chem_277_7905
PubMedID: 11756444
Gene_locus related to this paper: fusso-CUT2 , fusso-CUT3

Title : Detection of anatoxin-a(s) in environmental samples of cyanobacteria by using a biosensor with engineered acetylcholinesterases - Devic_2002_Appl.Environ.Microbiol_68_4102
Author(s) : Devic E , Li D , Dauta A , Henriksen P , Codd GA , Marty JL , Fournier D
Ref : Applied Environmental Microbiology , 68 :4102 , 2002
Abstract : Bioassays are little used to detect individual toxins in the environment because, compared to analytical methods, these assays are still limited by several problems, such as the sensitivity and specificity of detection. We tentatively solved these two drawbacks for detection of anatoxin-a(s) by engineering an acetylcholinesterase to increase its sensitivity and by using a combination of mutants to obtain increased analyte specificity. Anatoxin-a(s), a neurotoxin produced by some freshwater cyanobacteria, was detected by measuring the inhibition of acetylcholinesterase activity. By using mutated enzyme, the sensitivity of detection was brought to below the nanomole-per-liter level. However, anatoxin-a(s) is an organophosphorous compound, as are several synthetic molecules which are widely used as insecticides. The mode of action of these compounds is via inhibition of acetylcholinesterase, which makes the biotest nonspecific. The use of a four-mutant set of acetylcholinesterase variants, two mutants that are sensitive to anatoxin-a(s) and two mutants that are sensitive to the insecticides, allows specific detection of the cyanobacterial neurotoxin.
ESTHER : Devic_2002_Appl.Environ.Microbiol_68_4102
PubMedSearch : Devic_2002_Appl.Environ.Microbiol_68_4102
PubMedID: 12147513

Title : Exploring the potential for subtype-selective muscarinic agonists in glaucoma - Gil_2001_Life.Sci_68(22-23)_2601
Author(s) : Gil DW , Spalding TA , Kharlamb A , Skjaerbaek N , Uldam A , Trotter C , Li D , WoldeMussie E , Wheeler L , Brann M
Ref : Life Sciences , 68 :2601 , 2001
Abstract : Pilocarpine has been used to lower intraocular pressure (IOP) in glaucoma patients for more than 100 years. Since the identification of five muscarinic receptor subtypes, there has been an interest in separating the IOP-lowering effects from the ocular side effects of pupil constriction and lens accommodation. However, all these actions seem to be mediated by the M3 receptor. A novel muscarinic receptor agonist, AGN 199170, that has no activity on the M3 subtype was compared to pilocarpine in a monkey glaucoma model. This compound lowered IOP suggesting that muscarinic agonists targeted at muscarinic receptors other than the M3 subtype may be able to selectively lower IOP.
ESTHER : Gil_2001_Life.Sci_68(22-23)_2601
PubMedSearch : Gil_2001_Life.Sci_68(22-23)_2601
PubMedID: 11392632

Title : Cloning of cutinase transcription factor 1, a transactivating protein containing Cys6Zn2 binuclear cluster DNA-binding motif - Li_1997_J.Biol.Chem_272_12462
Author(s) : Li D , Kolattukudy PE
Ref : Journal of Biological Chemistry , 272 :12462 , 1997
Abstract : Hydroxy fatty acids from plant cutin were shown previously to induce the expression of the cutinase gene via a palindromic sequence located at -159 base pairs of the cutinase gene in Fusarium solani f. sp. pisi (Nectria hematococca mating type VI). Of the two overlapping palindromes in this sequence, palindrome 2 was found to be essential for the inducibility of cutinase by hydroxy fatty acids. Screening of a phage expression library with the concatenated palindrome 2 as probe detected a distinct cDNA clone encoding a polypeptide designated cutinase transcription factor 1alpha (CTF1alpha) with a calculated molecular weight of 101,109. This protein contains a Cys6Zn2 binuclear cluster motif sharing homology to the Cys6Zn2 binuclear cluster DNA-binding domains of transcription factors from Saccharomyces cerevisiae, S. carlsbergensis, Kluyveromyces lactis, Neurospora crassa, Aspergillus nidulans, and A. flavus. CTF1alpha, expressed in Escherichia coli, showed specific binding to the palindrome 2 DNA fragment but not to palindrome 1 or mutant palindrome 2 DNA fragments, suggesting specific binding of CTF1alpha to palindrome 2. When CTF1alpha was expressed as a fusion protein with the nuclear localization sequence of SV40 in yeast, it transactivated the native cutinase promoter fused to the chloramphenicol acetyl transferase (cat) gene. Mutation of palindrome 2 but not palindrome 1 abolished this transactivation. Thus, CTF1alpha positively acts in vivo by binding selectively to palindrome 2 of the cutinase gene promoter.
ESTHER : Li_1997_J.Biol.Chem_272_12462
PubMedSearch : Li_1997_J.Biol.Chem_272_12462
PubMedID: 9139694

Title : Cloning and expression of cDNA encoding a protein that binds a palindromic promoter element essential for induction of fungal cutinase by plant cutin - Li_1995_J.Biol.Chem_270_11753
Author(s) : Li D , Kolattukudy PE
Ref : Journal of Biological Chemistry , 270 :11753 , 1995
Abstract : Previous studies showed that a palindromic sequence located at -159 base pairs is essential for induction of cutinase gene in Fusarium solani f. sp. pisi (Nectria haematococca mating type VI) by the hydroxy fatty acids from plant cutin and that a 50-kDa nuclear protein binds to a promoter that contains this element. Screening of a phage lambda gt11 expression library with the concatenated palindromic sequence as the probe identified a cDNA encoding a palindrome-binding protein (PBP). Nucleotide sequence of this cDNA revealed an open reading frame that would code for PBP with a calculated molecular weight of 49,847. This PBP contains a putative nuclear localization signal and a zinc finger motif sharing homology with the zinc finger DNA binding domains of transcription factors from mammals, Saccharomyces cerevisiae, Neurospora crassa, and Ustilago maydis. A highly basic region immediately adjacent to the carboxyl side of the zinc finger was also observed. PBP expressed in Escherichia coli showed specific binding to the palindromic DNA fragment.
ESTHER : Li_1995_J.Biol.Chem_270_11753
PubMedSearch : Li_1995_J.Biol.Chem_270_11753
PubMedID: 7744822

Title : Surface signaling in pathogenesis - Kolattukudy_1995_Proc.Natl.Acad.Sci.U.S.A_92_4080
Author(s) : Kolattukudy PE , Rogers LM , Li D , Hwang CS , Flaishman MA
Ref : Proceedings of the National Academy of Sciences of the United States of America , 92 :4080 , 1995
Abstract : Surface signaling plays a major role in fungal infection. Topographical features of the plant surface and chemicals on the surface can trigger germination of fungal spores and differentiation of the germ tubes into appressoria. Ethylene, the fruit-ripening hormone, triggers germination of conidia, branching of hyphae, and multiple appressoria formation in Colletotrichum, thus allowing fungi to time their infection to coincide with ripening of the host. Genes uniquely expressed during appressoria formation induced by topography and surface chemicals have been isolated. Disruption of some of them has been shown to decrease virulence on the hosts. Penetration of the cuticle by the fungus is assisted by fungal cutinase secreted at the penetration structure of the fungus. Disruption of cutinase gene in Fusarium solani pisi drastically decreased its virulence. Small amounts of cutinase carried by spores of virulent pathogens, upon contact with plant surface, release small amounts of cutin monomers that trigger cutinase gene expression. The promoter elements involved in this process in F. solani pisi were identified, and transcription factors that bind these elements were cloned. One of them, cutinase transcription factor 1, expressed in Escherichia coli, is phosphorylated. Several protein kinases from F. solani pisi were cloned. The kinase involved in phosphorylation of specific transcription factors and the precise role of phosphorylation in regulating cutinase gene transcription remain to be elucidated.
ESTHER : Kolattukudy_1995_Proc.Natl.Acad.Sci.U.S.A_92_4080
PubMedSearch : Kolattukudy_1995_Proc.Natl.Acad.Sci.U.S.A_92_4080
PubMedID: 7753774