Gao J

References (61)

Title : Multifunctional Ni-NPC Single-Atom Nanozyme for Removal and Smartphone-Assisted Visualization Monitoring of Carbamate Pesticides - Xu_2024_Inorg.Chem__
Author(s) : Xu X , Ma M , Gao J , Sun T , Guo Y , Feng D , Zhang L
Ref : Inorg Chem , : , 2024
Abstract : A multifunctional single-atom nanozyme, denoted as 3D Ni,N-codoped porous carbon (Ni-NPC), was devised that exhibits remarkable adsorption capabilities and a repertoire of enzyme mimetic functions (oxidase- and peroxidase-like). These attributes stem from the distinctive mesoporous thin-shell structure and well-dispersed Ni sites. The efficient adsorption capacity of Ni-NPC was assessed with respect to three carbamate pesticides (CMPs): metolcarb, carbaryl, and isoprocarb. Moreover, a colorimetric detection method for CMP was established based on its robust peroxidase-like catalytic activity and sequential catalytic interactions with acetylcholinesterase. Furthermore, a portable colorimetric sensor based on a hydrogel sphere integrated with a smartphone platform was devised. This sensor enables rapid, on-site, and quantitative assessment of CMP, boasting an extraordinarily low detection limit of 1.5 ng mL(-1). Notably, this sensor was successfully applied to the analysis of CMP levels in lake water and vegetable samples (pakchoi and rape), propelling the progress of real-time detection technologies in food and environment monitoring.
ESTHER : Xu_2024_Inorg.Chem__
PubMedSearch : Xu_2024_Inorg.Chem__
PubMedID: 38163760

Title : Neuropathy target esterase activity defines phenotypes among PNPLA6 disorders - Liu_2024_Brain__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev YV , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski MR , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent AL , Siskind CE , Traboulsi EI , Blackstone C , Sisk RA , Miraldi Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Brain , : , 2024
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism and hair anomalies. PNPLA6 encodes neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a systematic evidence-based review of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6-associated clinical diagnoses unambiguously reclassified 36 variants as pathogenic and 10 variants as likely pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship, and the generation of a preclinical animal model, pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2024_Brain__
PubMedSearch : Liu_2024_Brain__
PubMedID: 38735647

Title : New Near-Infrared Fluorescence Imaging Platform with Large Stokes Shift for Carboxylesterase 2 Detection in Thyroid Cancer and Inflammatory Diseases Diagnosis - Wang_2024_Anal.Chem__
Author(s) : Wang X , Gao J , Fan C , Gao Y , Yang X , Chen L
Ref : Analytical Chemistry , : , 2024
Abstract : Development of new near-infrared fluorophores is one of the eternal themes in the field of biosensing and biological imaging. In this work, we constructed a novel fluorophore platform MOR by replacing methylindole of hemicyanine fluorophore (CyR) with benzoxazole to acquire better fluorescence characteristics. Based on the platform, a near infrared (NIR) fluorescent probe MOR-CES2 was synthesized for the specific "off-on" response to carboxylesterase 2 (CES2). The probe exhibited excellent properties including near-infrared emission (735 nm), large Stokes shift (105 nm), high sensitivity (LOD, 0.3 ng/mL), and rapid response (15 min). The successful application of MOR-CES2 in biological imaging of CES2 in mice with thyroid cancer and inflammatory bowel disease demonstrated that the probe could identify cancer cells and tissues and sensitively respond to inflammation. The results proved the potency of MOR-CES2 as an efficient imaging tool to assist in the surgical resection of CES2-related tumors.
ESTHER : Wang_2024_Anal.Chem__
PubMedSearch : Wang_2024_Anal.Chem__
PubMedID: 38372636

Title : Biotransformation of HBCDs by the microbial communities enriched from mangrove sediments - Yu_2024_J.Hazard.Mater_469_134036
Author(s) : Yu F , Zhang B , Liu Y , Luo W , Chen H , Gao J , Ye X , Li J , Xie Q , Peng T , Wang H , Huang T , Hu Z
Ref : J Hazard Mater , 469 :134036 , 2024
Abstract : 1,2,5,6,9,10-Hexabromocyclododecanes (HBCDs) are a sort of persistent organic pollutants (POPs). This research investigated 12 microbial communities enriched from sediments of four mangroves in China to transform HBCDs. Six microbial communities gained high transformation rates (27.5-97.7%) after 12 generations of serial transfer. Bacteria were the main contributors to transform HBCDs rather than fungi. Analyses on the bacterial compositions and binning genomes showed that Alcanivorax (55.246-84.942%) harboring haloalkane dehalogenase genes dadAH and dadBH dominated the microbial communities with high transformation rates. Moreover, expressions of dadAH and dadBH in the microbial communities and Alcanivorax isolate could be induced by HBCDs. Further, it was found that purified proteins DadAH and DadBH showed high conversion rates on HBCDs in 36 h (91.9 +/- 7.4 and 101.0 +/- 1.8%, respectively). The engineered Escherichia coli BL21 strains harbored two genes could convert 5.7 +/- 0.4 and 35.1 +/- 0.1% HBCDs, respectively, lower than their cell-free crude extracts (61.2 +/- 5.2 and 56.5 +/- 8.7%, respectively). The diastereoisomer-specific transforming trend by both microbial communities and enzymes were gamma- > alpha- > beta-HBCD, differed from alpha- > beta- > gamma-HBCD by the Alcanivorax isolate. The identified transformation products indicated that HBCDs were dehalogenated via HBr elimination (dehydrobromination), hydrolytic and reductive debromination pathways in the enriched cultures. Two enzymes converted HBCDs via hydrolytic debromination. The present research provided theoretical bases for the biotransformation of HBCDs by microbial community and the bioremediation of HBCDs contamination in the environment.
ESTHER : Yu_2024_J.Hazard.Mater_469_134036
PubMedSearch : Yu_2024_J.Hazard.Mater_469_134036
PubMedID: 38493623

Title : Characterization, multivariate analysis and bioactivity evaluation of coumarins in the bark of Fraxinus mandshurica - Guo_2024_Fitoterapia_174_105865
Author(s) : Guo J , Gao J , Guo Y , Bai L , Ho CT , Bai N
Ref : Fitoterapia , 174 :105865 , 2024
Abstract : The bark of Fraxinus mandshurica is a traditional folk herb used to clear heat and dry dampness. To investigate the differences in coumarins content in the bark of F. mandshurica, 24 batches of samples from four origins were collected and analyzed. Eight coumarins were obtained by traditional natural product extraction, isolation and identification techniques and quantified by high performance liquid chromatography-photodiode array (HPLC-DAD). The quantitative results showed that the overall content of compound 30 (Fraxinol) was higher at 100.23 mg/g, while the overall content of compound 23 (Cichoriin) was lower, which may be related to environmental factors in different regions. The method validation showed that the linear range of the eight standards was between 10 and 2500 microg/mL with correlation coefficient (R(2)) values >0.9991; the relative standard deviation (RSD, %) values of intra-day precision were between 0.35 and 1.38, while the RSD values of inter-day precision were between 0. 29-1.78; the RSD (%) values for the reproducibility experiments ranged from 0.29 to 1.87, while the RSD (%) values for the stability experiments ranged from 0.22 to 2.33; the spiked recovery of the samples ranged from 98.65 to 101.34%, and the RSD (%) values ranged from 0.22 to 1.96. The method validation results showed that the instrument used for the analysis had good precision, the reproducibility and stability of the samples were good, and the accuracy of the experimental method was high. In addition, a total of 54 chemical components were identified from F. mandshurica bark by ultra performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-Q-TOF-MS). Based on this, fingerprinting, heatmap and multivariate analysis, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), were established for 24 batches of samples, and four marker compounds that could be used to distinguish different origins of F. mandshurica were screened. To further investigate the bioactivities of the eight coumarins, in vitro enzyme activity inhibition studies were performed, and the results showed that they all exhibited different degrees of inhibition of acetylcholinesterase, tyrosinase and alpha-glucosidase, thus having potential applications in the treatment of Alzheimer's disease, blemish whitening and anti-diabetes, and becoming a new source of natural enzyme activity inhibitors. This study established an identification and evaluation method applicable to plants of different origins, which provides a strong reference for quality control, origin evaluation and clinical application of traditional medicinal plants.
ESTHER : Guo_2024_Fitoterapia_174_105865
PubMedSearch : Guo_2024_Fitoterapia_174_105865
PubMedID: 38382892

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

Title : Neuropathy target esterase activity predicts retinopathy among PNPLA6 disorders - Liu_2023_bioRxiv__
Author(s) : Liu J , He Y , Lwin C , Han M , Guan B , Naik A , Bender C , Moore N , Huryn LA , Sergeev Y , Qian H , Zeng Y , Dong L , Liu P , Lei J , Haugen CJ , Prasov L , Shi R , Dollfus H , Aristodemou P , Laich Y , Nemeth AH , Taylor J , Downes S , Krawczynski M , Meunier I , Strassberg M , Tenney J , Gao J , Shear MA , Moore AT , Duncan JL , Menendez B , Hull S , Vincent A , Siskind CE , Traboulsi EI , Blackstone C , Sisk R , Utz V , Webster AR , Michaelides M , Arno G , Synofzik M , Hufnagel RB
Ref : Biorxiv , : , 2023
Abstract : Biallelic pathogenic variants in the PNPLA6 gene cause a broad spectrum of disorders leading to gait disturbance, visual impairment, anterior hypopituitarism, and hair anomalies. PNPLA6 encodes Neuropathy target esterase (NTE), yet the role of NTE dysfunction on affected tissues in the large spectrum of associated disease remains unclear. We present a clinical meta-analysis of a novel cohort of 23 new patients along with 95 reported individuals with PNPLA6 variants that implicate missense variants as a driver of disease pathogenesis. Measuring esterase activity of 46 disease-associated and 20 common variants observed across PNPLA6 -associated clinical diagnoses unambiguously reclassified 10 variants as likely pathogenic and 36 variants as pathogenic, establishing a robust functional assay for classifying PNPLA6 variants of unknown significance. Estimating the overall NTE activity of affected individuals revealed a striking inverse relationship between NTE activity and the presence of retinopathy and endocrinopathy. This phenomenon was recaptured in vivo in an allelic mouse series, where a similar NTE threshold for retinopathy exists. Thus, PNPLA6 disorders, previously considered allelic, are a continuous spectrum of pleiotropic phenotypes defined by an NTE genotype:activity:phenotype relationship. This relationship and the generation of a preclinical animal model pave the way for therapeutic trials, using NTE as a biomarker.
ESTHER : Liu_2023_bioRxiv__
PubMedSearch : Liu_2023_bioRxiv__
PubMedID: 37333224

Title : Novel N(1) or N(9) modified alpha-carboline analogues as potential ligands in Alzheimer's disease therapy: Synthesis and neurobiological activity evaluation - Dan_2023_Bioorg.Chem_133_106378
Author(s) : Dan W , Cao Y , Sun Y , Zhang J , Liu J , Gao J , Han R , Dai J
Ref : Bioorg Chem , 133 :106378 , 2023
Abstract : A series of new alpha-carboline analogues modified at N(1) or N(9) positions by alkyl, benzyl and phenyl were synthesized and characterized as potential ligands for AD therapy. These compounds exhibited multifunctional neurobiological activities including anti-neuroinflammatory, neuroprotective and cholinesterase inhibition. Among them, compound 5d with good drug-like properties and no cytotoxicity, showed potent inhibitory activity against NO production (IC(50) = 1.45 microM), which could suppress the expression levels of iNOS and COX-2 in a dose-dependent manner. Further mechanism exploration indicated that compound 5d could regulate the NF-kappaB signaling pathway by decreasing the phosphorylation of IkappaB-alpha and p65. Notably, compound 5d could effectively decrease the LPS-induced aberrations in zebrafish. Compounds 3b, 4f, 5c, 5g, 5m and 6i exhibited potential neuroprotective activity (cell viability > 70 %) in the H(2)O(2)-induced PC-12 neuronal death model and rescued the SOD activity. In particular, compounds 3b, 4f, and 5g activated the Nrf2 signaling pathway, and improved the expressions of antioxidant proteins NQO-1 and HO-1, which alleviated the head cell apoptosis in zebrafish. Additionally, compound 6i exhibited potential inhibitory activity against BuChE with IC(50) of 0.77 microM. Overall, this work provided some lead compounds based on alpha-carboline used for AD therapy.
ESTHER : Dan_2023_Bioorg.Chem_133_106378
PubMedSearch : Dan_2023_Bioorg.Chem_133_106378
PubMedID: 36736035

Title : Characterization of a PBAT Degradation Carboxylesterase from Thermobacillus composti KWC4 - Wu_2023_Catalysts_13_340
Author(s) : Wu P , Li Z , Gao J , Zhao Y , Wang H , Qin H , Gu Q , Wei R , Liu W , Han X
Ref : Catalysts , 13 :340 , 2023
Abstract : The large amount of waste synthetic polyester plastics has complicated waste management and also endangering the environment due to improper littering. In this study, a novel carboxylesterase from Thermobacillus composti KWC4 (Tcca) was identified, heterologously expressed in Escherichia coli, purified and characterized with various plastic substrates. Irregular grooves were detected on polybutylene adipate terephthalate (PBAT) film by scanning electron microscopy (SEM) after Tcca treatment, and Tcca can also hydrolyze short-chain diester bis(hydroxyethyl) terephthalate (BHET). The optimal pH and temperature for Tcca were 7.0 and 40 C, respectively. In order to explore its catalytic mechanism and improve its potential for plastic hydrolysis, we modeled the protein structure of Tcca and compared it with its homologous structures, and we identified positions that might be crucial for the binding of substrates. We generated a variety of Tcca variants by mutating these key positions; the variant F325A exhibited a more than 1.4-fold improvement in PBAT hydrolytic activity, and E80A exhibited a more than 4.1-fold increase in BHET activity when compared to the wild type. Tcca and its variants demonstrated future applicability for the recycling of bioplastic waste containing a PBAT fraction.
ESTHER : Wu_2023_Catalysts_13_340
PubMedSearch : Wu_2023_Catalysts_13_340
PubMedID:
Gene_locus related to this paper: theck-l0ef70

Title : A chloroplast diacylglycerol lipase modulates glycerolipid pathway balance in Arabidopsis - Yu_2023_Plant.J__
Author(s) : Yu L , Shen W , Fan J , Sah SK , Mavraganis I , Wang L , Gao P , Gao J , Zheng Q , Meesapyodsuk D , Yang H , Li Q , Zou J , Xu C
Ref : Plant J , : , 2023
Abstract : Two parallel pathways compartmentalized in the chloroplast and the endoplasmic reticulum (ER) contribute to thylakoid lipid synthesis in plants, but how these two pathways are coordinated during thylakoid biogenesis and remodeling remain unknown. We report here the molecular characterization of a homologous ADIPOSE TRIGLYCERIDE LIPASE-LIKE gene, previously referred to as ATGLL. The ATGLL gene is ubiquitously expressed throughout development and rapidly upregulated in response to a wide range of environmental cues. We show that ATGLL is a chloroplast non-regioselective lipase with a hydrolytic activity preferentially towards 16:0 of diacylglycerol (DAG). Comprehensive lipid profiling and radiotracer labeling studies revealed negative correlation of ATGLL expression and the relative contribution of the chloroplast lipid pathway to thylakoid lipid biosynthesis. Additionally, we show that genetic manipulation of ATGLL expression resulted in changes in triacylglycerol levels in leaves. We propose that ATGLL, through affecting the level of prokaryotic DAG in the chloroplast, plays important roles in balancing the two glycerolipid pathways and in maintaining lipid homeostasis in plants.
ESTHER : Yu_2023_Plant.J__
PubMedSearch : Yu_2023_Plant.J__
PubMedID: 37006186

Title : Complete Depolymerization of PET Wastes by an Evolved PET Hydrolase from Directed Evolution - Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
Author(s) : Shi L , Liu P , Tan Z , Zhao W , Gao J , Gu Q , Ma H , Liu H , Zhu L
Ref : Angew Chem Int Ed Engl , 62 :e202218390 , 2023
Abstract : PETase displays great potential in PET depolymerization. Directed evolution has been limited to engineer PETase due to the lack of high-throughput screening assay. In this study, a novel fluorescence-based high-throughput screening assay employing a newly designed substrate, bis (2-hydroxyethyl) 2-hydroxyterephthalate (termed BHET-OH), was developed for PET hydrolases. The best variant DepoPETase produced 1407-fold more products towards amorphous PET film at 50 degreesC and showed a 23.3 degreesC higher T(m) value than the PETase WT. DepoPETase enabled complete depolymerization of seven untreated PET wastes and 19.1g PET waste (0.4 % W(enzyme) /W(PET) ) in liter-scale reactor, suggesting that it is a potential candidate for industrial PET depolymerization processes. The molecular dynamic simulations revealed that the distal substitutions stabilized the loops around the active sites and transmitted the stabilization effect to the active sites through enhancing inter-loop interactions network.
ESTHER : Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
PubMedSearch : Shi_2023_Angew.Chem.Int.Ed.Engl_62_e202218390
PubMedID: 36751696
Gene_locus related to this paper: idesa-peth

Title : Enhancement of neural regeneration as a therapeutic strategy for Alzheimer's disease (Review) - Gao_2023_Exp.Ther.Med_26_444
Author(s) : Gao J , Li L
Ref : Exp Ther Med , 26 :444 , 2023
Abstract : Alzheimer's disease (AD), the most common cause of dementia worldwide, has gradually become a global health concern for society and individuals with the process of global ageing. Although extensive research has been carried out on AD, the etiology and pathological mechanism of the disease are still unclear, and there is no specific drug to cure or delay AD progression. The exploration of enhancing nerve regeneration in AD has gradually attracted increasing attention. In the current review, the existing therapeutic strategies were summarized to induce nerve regeneration which can increase the number of neurons, and improve the survival of neurons, the plasticity of synapses and synaptic activity. The strategies include increasing neurotrophic expression (such as brain-derived neurotrophic factor and nerve growth factor), inhibiting acetylcholinesterase (such as donepezil, tacrine, rivastigmine and galanthamine), elevating histone deacetylase levels (such as RGFP-966, Tasquinimod, CM-414 and 44B), stimulating the brain by physiotherapy (such as near-infrared light, repetitive transcranial magnetic stimulation, and transcranial direct current stimulation) and transplanting exogenous neural stem cells. However, further evaluations need to be performed to determine the optimal treatment. The present study reviews recent interventions for enhancing adult neurogenesis and attempts to elucidate their mechanisms of action, which may provide a theoretical basis for inducing nerve regeneration to fight against AD.
ESTHER : Gao_2023_Exp.Ther.Med_26_444
PubMedSearch : Gao_2023_Exp.Ther.Med_26_444
PubMedID: 37614437

Title : Using a Battery of Bioassays to Assess the Toxicity of Wastewater Treatment Plant Effluents in Industrial Parks - Yang_2023_Toxics_11_702
Author(s) : Yang B , Cui H , Gao J , Cao J , Klobucar G , Li M
Ref : Toxics , 11 :702 , 2023
Abstract : Bioassays, as an addition to physico-chemical water quality evaluation, can provide information on the toxic effects of pollutants present in the water. In this study, a broad evaluation of environmental health risks from industrial wastewater along the Yangtze River, China, was conducted using a battery of bioassays. Toxicity tests showed that the wastewater treatment processes were effective at lowering acetylcholinesterase (AChE) inhibition, HepG2 cells' cytotoxicity, the estrogenic effect in T47D-Kbluc cells, DNA damage of Euglena gracilis and the mutagenicity of Salmonella typhimurium in the analyzed wastewater samples. Polycyclic aromatic hydrocarbons (PAHs) were identified as potential major toxic chemicals of concern in the wastewater samples of W, J and T wastewater treatment plants; thus, the potential harm of PAHs to aquatic organisms has been investigated. Based on the health risk assessment model, the risk index of wastewater from the industrial parks along the Yangtze River was below one, indicating that the PAHs were less harmful to human health through skin contact or respiratory exposure. Overall, the biological toxicity tests used in this study provide a good basis for the health risk assessment of industrial wastewater and a scientific reference for the optimization and operation of the treatment process.
ESTHER : Yang_2023_Toxics_11_702
PubMedSearch : Yang_2023_Toxics_11_702
PubMedID: 37624206

Title : The Conformational Transitions and Dynamics of Burkholderia cepacia Lipase Regulated by Water-Oil Interfaces - Liang_2023_J.Chem.Inf.Model__
Author(s) : Liang K , Dong W , Gao J , Liu Z , Zhou R , Shu Z , Duan M
Ref : J Chem Inf Model , : , 2023
Abstract : Structural dynamics and conformational transitions are crucial for the activities of enzymes. As one of the most widely used industrial biocatalysts, lipase could be activated by the water-oil interfaces. The interface activations were believed to be dominated by the close-to-open transitions of the lid subdomains. However, the detailed mechanism and the roles of structure transitions are still under debate. In this study, the dynamic structures and conformational transitions of Burkholderia cepacia lipase (LipA) were investigated by combining all-atom molecular dynamics simulations, enhanced sampling simulation, and spectrophotometric assay experiments. The conformational transitions between the lid-open and lid-closed states of LipA in aqueous solution are directly observed by the computational simulation methods. The interactions between the hydrophobic residues on the two lid-subdomains are the driven forces for the LipA closing. Meanwhile, the hydrophobic environment provided by the oil interfaces would separate the interactions between the lid-subdomains and promote the structure opening of LipA. Moreover, our studies demonstrate the opening of the lids structure is insufficient to initiate the interfacial activation, providing explanations for the inability of interfacial activation of many lipases with lid structures.
ESTHER : Liang_2023_J.Chem.Inf.Model__
PubMedSearch : Liang_2023_J.Chem.Inf.Model__
PubMedID: 37307245

Title : Microbial gatekeepers: unraveling the role of the gut microbiota enzyme DPP4 in diabetes management - Liao_2023_Trends.Biochem.Sci__
Author(s) : Liao L , Lin F , Gao J
Ref : Trends in Biochemical Sciences , : , 2023
Abstract : Wang et al. identified dipeptidyl peptidase 4 (DPP4) as a gut microbe-derived enzyme that impacts on host glucose metabolism. They further introduced a novel therapeutic, daurisoline-d4 (Dau-d4), a selective microbial DPP4 (mDPP4) inhibitor that shows promise in improving glucose tolerance, highlighting the potential of therapies that target both host enzymes and gut microbial enzymes.
ESTHER : Liao_2023_Trends.Biochem.Sci__
PubMedSearch : Liao_2023_Trends.Biochem.Sci__
PubMedID: 37770288

Title : Rescuing yeast from cell death enables overproduction of fatty acids from sole methanol - Gao_2022_Nat.Metab__
Author(s) : Gao J , Li Y , Yu W , Zhou YJ
Ref : Nat Metab , : , 2022
Abstract : Methanol is an ideal feedstock for biomanufacturing that can be beneficial for global carbon neutrality; however, the toxicity of methanol limits the efficiency of methanol metabolism toward biochemical production. We here show that engineering production of free fatty acids from sole methanol results in cell death with decreased cellular levels of phospholipids in the methylotrophic yeast Ogataea polymorpha, and cell growth is restored by adaptive laboratory evolution. Whole-genome sequencing of the adapted strains reveals that inactivation of LPL1 (encoding a putative lipase) and IZH3 (encoding a membrane protein related to zinc metabolism) preserve cell survival by restoring phospholipid metabolism. Engineering the pentose phosphate pathway and gluconeogenesis enables high-level production of free fatty acid (15.9 g l(-1)) from sole methanol. Preventing methanol-associated toxicity underscores the link between lipid metabolism and methanol tolerance, which should contribute to enhancing methanol-based biomanufacturing.
ESTHER : Gao_2022_Nat.Metab__
PubMedSearch : Gao_2022_Nat.Metab__
PubMedID: 35817856

Title : Structural Insights into (Tere)phthalate-Ester Hydrolysis by a Carboxylesterase and Its Role in Promoting PET Depolymerization - von Haugwitz_2022_ACS.Catal_12_15259
Author(s) : von Haugwitz G , Han X , Pfaff L , Li Q , Wei H , Gao J , Methling K , Ao Y , Brack Y , Jan Mican J , Feiler CG , Weiss MS , Bednar D , Palm GJ , Lalk M , Lammers M , Damborsky J , Weber G , Liu W , Bornscheuer UT , Wei R
Ref : ACS Catal , 12 :15259 , 2022
Abstract : TfCa, a promiscuous carboxylesterase from Thermobifida fusca, was found to hydrolyze polyethylene terephthalate (PET) degradation intermediates such as bis(2-hydroxyethyl) terephthalate (BHET) and mono-(2-hydroxyethyl)-terephthalate (MHET). In this study, we elucidated the structures of TfCa in its apo form, as well as in complex with a PET monomer analogue and with BHET. The structurefunction relationship of TfCa was investigated by comparing its hydrolytic activity on various ortho- and para-phthalate esters of different lengths. Structure-guided rational engineering of amino acid residues in the substrate-binding pocket resulted in the TfCa variant I69W/V376A (WA), which showed 2.6-fold and 3.3-fold higher hydrolytic activity on MHET and BHET, respectively, than the wild-type enzyme. TfCa or its WA variant was mixed with a mesophilic PET depolymerizing enzyme variant [Ideonella sakaiensis PETase (IsPETase) PM] to degrade PET substrates of various crystallinity. The dual enzyme system with the wild-type TfCa or its WA variant produced up to 11-fold and 14-fold more terephthalate (TPA) than the single IsPETase PM, respectively. In comparison to the recently published chimeric fusion protein of IsPETase and MHETase, our system requires 10% IsPETase and one-fourth of the reaction time to yield the same amount of TPA under similar PET degradation conditions. Our simple dual enzyme system reveals further advantages in terms of cost-effectiveness and catalytic efficiency since it does not require time-consuming and expensive cross-linking and immobilization approaches.
ESTHER : von Haugwitz_2022_ACS.Catal_12_15259
PubMedSearch : von Haugwitz_2022_ACS.Catal_12_15259
PubMedID: 36570084
Gene_locus related to this paper: thefu-1831

Title : Multiple Substrate Binding Mode-Guided Engineering of a Thermophilic PET Hydrolase - Pfaff_2022_ACS.Catalysis_12_9790
Author(s) : Pfaff L , Gao J , Li Z , Jackering A , Weber G , Mican J , Chen Y , Dong W , Han X , Feiler CG , Ao YF , Badenhorst CPS , Bednar D , Palm GJ , Lammers M , Damborsky J , Strodel B , Liu W , Bornscheuer UT , Wei R
Ref : ACS Catal , 12 :9790 , 2022
Abstract : Thermophilic polyester hydrolases (PES-H) have recently enabled biocatalytic recycling of the mass-produced synthetic polyester polyethylene terephthalate (PET), which has found widespread use in the packaging and textile industries. The growing demand for efficient PET hydrolases prompted us to solve high-resolution crystal structures of two metagenome-derived enzymes (PES-H1 and PES-H2) and notably also in complex with various PET substrate analogues. Structural analyses and computational modeling using molecular dynamics simulations provided an understanding of how product inhibition and multiple substrate binding modes influence key mechanistic steps of enzymatic PET hydrolysis. Key residues involved in substratebinding and those identified previously as mutational hotspots in homologous enzymes were subjected to mutagenesis. At 72 C, the L92F/Q94Y variant of PES-H1 exhibited 2.3-fold and 3.4-fold improved hydrolytic activity against amorphous PET films and pretreated real-world PET waste, respectively. The R204C/S250C variant of PES-H1 had a 6.4 C higher melting temperature than the wild-type enzyme but retained similar hydrolytic activity. Under optimal reaction conditions, the L92F/Q94Y variant of PES-H1 hydrolyzed low-crystallinity PET materials 2.2-fold more efficiently than LCC ICCG, which was previously the most active PET hydrolase reported in the literature. This property makes the L92F/ Q94Y variant of PES-H1 a good candidate for future applications in industrial plastic r"cycling processes.
ESTHER : Pfaff_2022_ACS.Catalysis_12_9790
PubMedSearch : Pfaff_2022_ACS.Catalysis_12_9790
PubMedID: 35966606
Gene_locus related to this paper: 9firm-PHL7

Title : Rapid Screening of Lipase Inhibitors in Scutellaria baicalensis by Using Porcine Pancreatic Lipase Immobilized on Magnetic Core-Shell Metal-Organic Frameworks - Xu_2022_Molecules_27_3475
Author(s) : Xu J , Cao P , Fan Z , Luo X , Yang G , Qu T , Gao J
Ref : Molecules , 27 :3475 , 2022
Abstract : As for ligand fishing, the current immobilization approaches have some potential drawbacks such as the small protein loading capacity and difficult recycle process. The core-shell metal-organic frameworks composite (Fe(3)O(4)-COOH@UiO-66-NH(2)), which exhibited both magnetic characteristics and large specific surface area, was herein fabricated and used as magnetic support for the covalent immobilization of porcine pancreatic lipase (PPL). The resultant composite Fe(3)O(4)-COOH@UiO-66-NH(2)@PPL manifested a high loading capacity (247.8 mg/g) and relative activity recovery (101.5%). In addition, PPL exhibited enhanced tolerance to temperature and pH after immobilization. Then, the composite Fe(3)O(4)-COOH@UiO-66-NH(2)@PPL was incubated with the extract of Scutellaria baicalensis to fish out the ligands. Eight lipase inhibitors were obtained and identified by UPLC-Q-TOF-MS/MS. The feasibility of the method was further confirmed through an in vitro inhibitory assay and molecular docking. The proposed ligand fishing technique based on Fe(3)O(4)-COOH@UiO-66-NH(2)@PPL provided a feasible, selective, and effective platform for discovering enzyme inhibitors from natural products.
ESTHER : Xu_2022_Molecules_27_3475
PubMedSearch : Xu_2022_Molecules_27_3475
PubMedID: 35684413

Title : Molecular and Biochemical Differences of the Tandem and Cold-Adapted PET Hydrolases Ple628 and Ple629, Isolated From a Marine Microbial Consortium - Meyer-Cifuentes_2022_Front.Bioeng.Biotechnol_10_930140
Author(s) : Meyer-Cifuentes IE , Wu P , Zhao Y , Liu W , Neumann-Schaal M , Pfaff L , Barys J , Li Z , Gao J , Han X , Bornscheuer UT , Wei R , Ozturk B
Ref : Front Bioeng Biotechnol , 10 :930140 , 2022
Abstract : Polybutylene adipate terephthalate (PBAT) is a biodegradable alternative to polyethylene and can be broadly used in various applications. These polymers can be degraded by hydrolases of terrestrial and aquatic origin. In a previous study, we identified tandem PETase-like hydrolases (Ples) from the marine microbial consortium I1 that were highly expressed when a PBAT blend was supplied as the only carbon source. In this study, the tandem Ples, Ple628 and Ple629, were recombinantly expressed and characterized. Both enzymes are mesophilic and active on a wide range of oligomers. The activities of the Ples differed greatly when model substrates, PBAT-modified polymers or PET nanoparticles were supplied. Ple629 was always more active than Ple628. Crystal structures of Ple628 and Ple629 revealed a structural similarity to other PETases and can be classified as member of the PETases IIa subclass, alpha/beta hydrolase superfamily. Our results show that the predicted functions of Ple628 and Ple629 agree with the bioinformatic predictions, and these enzymes play a significant role in the plastic degradation by the consortium.
ESTHER : Meyer-Cifuentes_2022_Front.Bioeng.Biotechnol_10_930140
PubMedSearch : Meyer-Cifuentes_2022_Front.Bioeng.Biotechnol_10_930140
PubMedID: 35935485
Gene_locus related to this paper: 9zzzz-Ple628 , 9zzzz-Ple629

Title : Correlation of lipoprotein lipase gene polymorphism and mRNA expression with intramuscular fat content in Baicheng-Oil chicken - Wang_2022_J.Anim.Physiol.Anim.Nutr.(Berl)__
Author(s) : Wang Y , Chen H , Hang C , Chen Y , Gao J , Qiu D
Ref : J Anim Physiol Anim Nutr (Berl) , : , 2022
Abstract : Lipoprotein lipase (LPL) was often taken as a candidate gene for investigating fat metabolism. However, there are few studies on the effect of LPL on intramuscular fat (IMF) deposition in Baicheng oil chicken (BOC) and Three-yellow Chicken (TYC). In this study, we studied the relationship between polymorphism and messenger RNA (mRNA) expression of LPL with IMF deposition in the chest muscle (CM) and leg muscle (LM) of TYC and BOC. Sixty TYCs and 60 BOCs were raised from 1 d and slaughtered by avascularization at their slaughtering age. IMF contents of the CM and LM in the BOC were markedly higher than those in the TYC. Three genotypes following AA, AB and BB were found by the method of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The synonymous mutation C12315T was detected. The content of IMF with the AA genotype was significantly higher than the AB genotype in the LM of TYC. The mRNA expression both of CM and LM in BOC was prominently higher than those in TYC, and there was a positive significant correlation between LM and CM in both BOC and TYC. These results suggested that the SNPs polymorphism and mRNA expression of the LPL gene might be helpful for selective breeding in IMF of the chicken.
ESTHER : Wang_2022_J.Anim.Physiol.Anim.Nutr.(Berl)__
PubMedSearch : Wang_2022_J.Anim.Physiol.Anim.Nutr.(Berl)__
PubMedID: 35267203

Title : AND-Logic Strategy for Accurate Analysis of Alzheimer's Disease via Fluorescent Probe Lighted Up by Two Specific Biomarkers - Zhang_2021_Anal.Chem__
Author(s) : Zhang P , Fu C , Liu H , Guo X , Zhang Q , Gao J , Chen W , Yuan W , Ding C
Ref : Analytical Chemistry , : , 2021
Abstract : Alzheimer's disease (AD) has become a global threat to the elderly health with a short survival time after diagnosis. Due to the asymptomatic stage during the early development, patients are usually diagnosed at the middle or late stage. Therefore, an efficient tool for AD early diagnosis deserves considerable attention, which could make a significant contribution to the treatment intervention. A fluorescent probe has been widely applied for detecting and visualizing species of interest in vitro and in vivo, and the proper reaction between the probe and analytes is responsible for the fluorescence change to provide a lighting-on or ratiometric responsive pattern with satisfactory sensing behavior. In this work, we report the first attempt to build up an AND-logic probe P2 for AD accuracy diagnosis taking butyrylcholinesterase (BChE) and reactive oxygen species (ROSs) as dual targets. Upon the co-stimulation by these two factors through enzymatic hydrolysis and redox reaction, the NIR emission could be readily turned on. This AND sensing pattern avoided the false-positive response effectively, and other diseases sharing one biomarker could hardly induce a NIR fluorescence response. The sensing assay has also been confirmed to be feasible in vitro and in vivo with good sensibility and selectivity. It is worth mentioning that the probe structure has been optimized in terms of the linkage length. This study shows that probe P2 with a connecting arm of medium length (one methylene, n = 1) has superior sensing performance, promising to provide a reference for the relative structure design.
ESTHER : Zhang_2021_Anal.Chem__
PubMedSearch : Zhang_2021_Anal.Chem__
PubMedID: 34353021

Title : The Role of Clt1-Regulated Xylan Metabolism in Melanin and Toxin Formation for the Pathogenicity of Curvularia lunata in Maize - Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
Author(s) : Gao J , Chen J
Ref : Mol Plant Microbe Interact , :MPMI08200235R , 2021
Abstract : We previously reported that the BTB (brica-brac, tramtrack, and broad) domain-containing protein Clt1 regulates melanin and toxin synthesis, conidiation, and pathogenicity in Curvularia lunata, but the interacting proteins and regulative mechanism of Clt1 are unclear. In this research, we identified two proteins, which respectively correspond to xylanase (Clxyn24) and acetyl xylan esterase (Claxe43) from C. lunata, that were regulated by Clt1. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation assays were conducted to verify the interaction of Clt1 with full-length Clxyn24 and Claxe43. Furthermore, the Y2H assay revealed that Clt1 physically interacted with Clxyn24 and Claxe43 through its BTB domain to degrade xylan, which was used as a carbon source for C. lunata growth. The utilization of xylan provides acetyl-CoA for the synthesis of melanin and toxin as well as energy and other intermediate metabolites for conidiation. Furthermore, transcriptome analysis revealed that PKS18 and its 13 flanking genes found clustered in a region spanning 57.89 kb on scaffold 9 of the C. lunata CX-3 genome were down-regulated in toxin production-deficient mutant T806, and this cluster is possibly responsible for toxin biosynthesis of C. lunata. [Formula: see text] Copyright 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
ESTHER : Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
PubMedSearch : Gao_2021_Mol.Plant.Microbe.Interact__MPMI08200235R
PubMedID: 33417477

Title : Nitrogen-Doped Graphdiyne as a Robust Electrochemical Biosensing Platform for Ultrasensitive Detection of Environmental Pollutants - Niu_2021_Anal.Chem__
Author(s) : Niu K , Gao J , Wu L , Lu X , Chen J
Ref : Analytical Chemistry , : , 2021
Abstract : Owing to its unique chemical structure, natural pores, high structure defects, good surface hydrophilicity and biocompatibility, and favorable electrical conductivity, nitrogen-doped graphdiyne (NGDY) has been attracting attention in the application of electrochemical sensing. Taking advantage of these fascinating electrochemical properties, for the first time, two types of electrochemical enzymatic biosensors were fabricated for the respective detection of organophosphorus pesticides (OPs) and phenols based on the immobilization of acetylcholinesterase or tyrosinase with NGDY. Results revealed that the sensitivities of the NGDY-based enzymatic biosensors were almost twice higher than that of the matching biosensor in the absence of NGDY, proving that NGDY plays a vital role in immobilizing the enzymes and improving the performance of the fabricated biosensors. The effects of nitrogen doping on improving the biosensing performance were studied in depth. Graphitic N atoms can enhance the electrical conductivity, while imine N and pyridinic N can help to adsorb and accumulate the substance molecules to the electrode surface, all of which contribute to the significantly improved performance. Furthermore, these two types of biosensors also demonstrated excellent reproducibility, high stability, and good recovery rate in real environmental samples, which showed a valuable way for the rapid detection of OPs and phenols in the environment. With these excellent performances, it is strongly anticipated that NGDY has tremendous potential to be applied to many other biomedical and environmental fields.
ESTHER : Niu_2021_Anal.Chem__
PubMedSearch : Niu_2021_Anal.Chem__
PubMedID: 34110153

Title : Fluorescent Determination of Butyrylcholinesterase Activity and Its Application in Biological Imaging and Pesticide Residue Detection - Zhang_2021_ACS.Sens__
Author(s) : Zhang Q , Fu C , Guo X , Gao J , Zhang P , Ding C
Ref : ACS Sens , : , 2021
Abstract : Butyrylcholinesterase (BChE) is an essential human cholinesterase relevant to liver conditions and neurodegenerative diseases, which makes it a pivotal biomarker of health. It therefore remains challenging and highly desired to elaborate efficient chemical tools for BChE with simple operations and satisfactory working performance. In this work, a background-free detection strategy was built by virtue of the judicious coupling of a specific BChE-enzymatic reaction and in situ cyclization. High sensitivity with a low limit of detection (LOD) of 0.075 microg/mL could be readily achieved from the blank background and the as-produced emissive indicators, and the specific reaction site contributed to the high selectivity over other bio-species even acetylcholinesterase (AChE). In addition to the multifaceted spectral experiments to verify the sensing mechanism, this work assumed comprehensive studies on the application. The bio-investigation ranged from cells to an organism, declaring a noteworthy prospect in disease diagnosis, especially for Alzheimer's disease (AD), a common neurodegenerative disease with over-expressed BChE. Moreover, its excellent work for inhibition efficacy elucidation was also proved with the accuracy IC(50) of tacrine for BChE (8.6 nM), giving rise to an expanded application for trace pesticide determination.
ESTHER : Zhang_2021_ACS.Sens__
PubMedSearch : Zhang_2021_ACS.Sens__
PubMedID: 33503372

Title : Design and Synthesis of Ranitidine Analogs as Multi-Target Directed Ligands for the Treatment of Alzheimer's Disease - Gao_2021_Int.J.Mol.Sci_22_
Author(s) : Gao J , Suo C , Tseng JH , Moss MA , Terry AV, Jr. , Chapman J
Ref : Int J Mol Sci , 22 : , 2021
Abstract : The aggregation of amyloid beta (Abeta) peptides and deposition of amyloid plaques are implicated in the pathogenesis of Alzheimer's disease (AD). Therefore, blocking Abeta aggregation with small molecules has been proposed as one therapeutic approach for AD. In the present study, a series of ranitidine analogs containing cyclic imide isosteres were synthesized and their inhibitory activities toward Abeta aggregation were evaluated using in vitro thioflavin T assays. The structure-activity relationship revealed that the 1,8-naphthalimide moiety provided profound inhibition of Abeta aggregation and structural modifications on the other parts of the parent molecule (compound 6) maintained similar efficacy. Some of these ranitidine analogs also possessed potent inhibitory activities of acetylcholinesterase (AChE), which is another therapeutic target in AD. These ranitidine analogs, by addressing both Abeta aggregation and AChE, offer insight into the key chemical features of a new type of multi-target directed ligands for the pharmaceutical treatment of AD.
ESTHER : Gao_2021_Int.J.Mol.Sci_22_
PubMedSearch : Gao_2021_Int.J.Mol.Sci_22_
PubMedID: 33803769

Title : Efficacy and Safety of Neostigmine and Decompressive Colonoscopy for Acute Colonic Pseudo-Obstruction: A Single-Center Analysis - Liu_2021_Gastroenterology.Res_14_157
Author(s) : Liu JJ , Venkatesh V , Gao J , Adler E , Brenner DM
Ref : Gastroenterology Res , 14 :157 , 2021
Abstract : BACKGROUND: Acute colonic pseudo-obstruction (ACPO) is characterized by acute colonic dilation in the absence of anatomical obstruction. Neostigmine is an acetylcholinesterase inhibitor recommended as first-line salvage therapy for uncomplicated ACPO. Decompressive colonoscopy is recommended if neostigmine is contraindicated or unsuccessful. There is a need to better characterize relative efficacy and factors impacting treatment choice. The aim of the study was to examine the use, efficacy, and safety of neostigmine and decompressive colonoscopy in the management of ACPO at a single academic center. METHODS: Patients <= 18 years of age meeting established criteria for uncomplicated ACPO and with cecal diameter <= 10 cm on imaging between 1999 and 2019 were identified. Individuals were categorized as having received supportive care alone or subsequent trials of neostigmine or decompressive colonoscopy. Demographics and pre- and post-intervention data were collected, including indication and contraindication to intervention used, time to intervention, initial response, and adverse events. RESULTS: In 46 cases of ACPO (N = 42 patients), all but one individual received initial supportive care. Seven responded to conservative measures alone. Of the patients failing supportive care, 15 cases were initially treated with neostigmine (response rate 86.7%) and 24 initially underwent decompressive colonoscopy (response rate 95.8%) (P = 0.390). One episode of transient bradycardia, resolved with atropine, occurred in the neostigmine group. One patient experienced respiratory instability during colonoscopy. CONCLUSIONS: Both neostigmine and decompressive colonoscopy appear effective for treating uncomplicated ACPO in individuals failing conservative therapy. Adverse events were infrequent in both cohorts. Future prospective studies examining treatment for ACPO should focus on whether either intervention is superior to the other.
ESTHER : Liu_2021_Gastroenterology.Res_14_157
PubMedSearch : Liu_2021_Gastroenterology.Res_14_157
PubMedID: 34267830

Title : Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach - Huang_2020_J.Med.Chem_63_7052
Author(s) : Huang F , Hu H , Wang K , Peng C , Xu W , Zhang Y , Gao J , Liu Y , Zhou H , Huang R , Li M , Shen J , Xu Y
Ref : Journal of Medicinal Chemistry , 63 :7052 , 2020
Abstract : Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases.
ESTHER : Huang_2020_J.Med.Chem_63_7052
PubMedSearch : Huang_2020_J.Med.Chem_63_7052
PubMedID: 32459096
Gene_locus related to this paper: human-PLA2G7

Title : ABHD12 and LPCAT3 Interplay Regulates a Lyso-phosphatidylserine-C20:4 Phosphatidylserine Lipid Network Implicated in Neurological Disease - Ichu_2020_Biochemistry_59_1793
Author(s) : Ichu TA , Reed A , Ogasawara D , Ulanovskaya O , Roberts A , Aguirre CA , Bar-Peled L , Gao J , Germain J , Barbas S , Masuda K , Conti B , Tontonoz P , Cravatt BF
Ref : Biochemistry , 59 :1793 , 2020
Abstract : PHARC (polyneuropathy, hearing loss, cerebellar ataxia, retinitis pigmentosa, and cataract) is a human neurological disorder caused by deleterious mutations in the ABHD12 gene, which encodes an integral membrane lyso-phosphatidylserine (lyso-PS) lipase. Pharmacological or genetic disruption of ABHD12 leads to higher levels of lyso-PS lipids in human cells and the central nervous system (CNS) of mice. ABHD12 loss also causes rapid rewiring of PS content, resulting in selective increases in the level of arachidonoyl (C20:4) PS and decreases in the levels of other PS species. The biochemical basis for ABHD12-dependent PS remodeling and its pathophysiological significance remain unknown. Here, we show that genetic deletion of the lysophospholipid acyltransferase LPCAT3 blocks accumulation of brain C20:4 PS in mice lacking ABHD12 and concurrently produces hyper-increases in the level of lyso-PS in these animals. These lipid changes correlate with exacerbated auditory dysfunction and brain microgliosis in mice lacking both ABHD12 and LPCAT3. Taken together, our findings reveal that ABHD12 and LPCAT3 coordinately regulate lyso-PS and C20:4 PS content in the CNS and point to lyso-PS lipids as the likely bioactive metabolites contributing to PHARC-related neuropathologies.
ESTHER : Ichu_2020_Biochemistry_59_1793
PubMedSearch : Ichu_2020_Biochemistry_59_1793
PubMedID: 32364701
Gene_locus related to this paper: human-ABHD12

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 : Metagenomic analysis exploring microbial assemblages and functional genes potentially involved in di (2-ethylhexyl) phthalate degradation in soil - Zhu_2020_Sci.Total.Environ_715_137037
Author(s) : Zhu F , Doyle E , Zhu C , Zhou D , Gu C , Gao J
Ref : Sci Total Environ , 715 :137037 , 2020
Abstract : Widespread use of di (2-ethylhexyl) phthalate (DEHP) as a plasticizer has caused considerable soil pollution; however, little is known about indigenous microbial communities involved in its degradation in soil. In this study, metagenomic sequencing combined with metabolite determination was used to explore microorganisms and genes potentially involved in DEHP degradation in aerobic and anaerobic soils. The results showed that under both dryland aerobic and flooded anaerobic conditions, DEHP was initially hydrolyzed into mono (2-ethylhexyl) phthalate which was then hydrolyzed into phthalic acid; benzoic acid was the central intermediate during further metabolism steps. Bacteria were more responsive to DEHP presence than fungi/archaea, and potential degradative genes stimulated by DEHP were predominantly associated with bacteria, reflecting the dominant role of bacteria in DEHP degradation. Members of the Actinomycetales seemed to be the dominant degraders under aerobic conditions, while a number of phyla i.e. Gemmatimonadetes, Proteobacteria, Acidobacteria and Bacteroidetes appeared to be involved under anaerobic conditions. Interestingly, ~50% of esterase/lipase/cytochrome P450 genes enriched by DEHP under aerobic conditions were from Nocardioides, a bacterial genus that has not been previously directly linked to phthalate ester degradation. The results indicate that novel degraders may play an important role in DEHP degradation in natural soil environments. This study provides a better understanding of the phthalate ester biodegradation processes occurring in soil.
ESTHER : Zhu_2020_Sci.Total.Environ_715_137037
PubMedSearch : Zhu_2020_Sci.Total.Environ_715_137037
PubMedID: 32041058

Title : Near-infrared emission tracks inter-individual variability of carboxylesterase-2 via a novel molecular substrate - Liu_2020_Mikrochim.Acta_187_313
Author(s) : Liu X , Li X , Dong P , Wu Z , Gao J , Wang Q
Ref : Mikrochim Acta , 187 :313 , 2020
Abstract : A low-molecular-weight molecule (4-(2-(3-(dicyanomethyl)-5,5-dimethylcyclohex-1-en-1-yl)vinyl)phenyl-benzoate, DDPB) has been developed. The organic framework possesses very weak fluorescence . The feasibility of the signal transduction has been performed via fluorometric titrations in solution. DDPB gives rise to responses to carboxylesterase 2 (CES2) based on "off-on" responses. The red emission at 670 nm has been derived from the enzyme-induced hydrolysis of ester linkages, thus suppressing the intramolecular charge transfer (ICT) effect and thereby generating the fluorescent segment. The optical excitation window for this probe is extended to the visible light range (lambdaex = 516 nm), and it will induce less harmful influence on biological substances. The detection limit for the measurement of CES2 concentration is as low as 2.33 mU/mL. The conventional studies concerning the activation process are generally performed within only a single liveing cell system. In this study, it is the first time that expression of carboxylesterase 2 in five kinds of cell lines (HeLa > C1498 > active T cell > Jurkat > unactive T cell) has been clarified by flow cytometry, Western blotting, and confocal microscopy analysis. The elucidation of CES2 and its variability in a variety of cells will open new ways for drug metabolism and disease prevention. Graphical abstract We reported a new "substrate-mediated light-on" strategy based on an ester bond cleavage reaction. Most of prepared nanomaterials and organic fluorophores possessed short wavelength emissions in the blue or green region which will not be difficult for cellular imaging. In this study, a novel functional molecule (DDPB) was considered as the substrate for CES2 and the optical "off-on" response was realized. DDPB was cell permeable and possessed very low cytotoxicity. Moreover, the identification of CES2 and their subtle changes in five different cells afforded the sequence for carboxylesterase-2 as Hela > C1498 > Active T cell > Jurkat > Unactive T cell. Inhibition studies showed that the hydrolysis of DDPB was effectively suppressed by bis-p-nitrophenyl phosphate and the cellular tracking results firmly supported this point. To our knowledge, the inter-individual variability for the CES2 expressions in five different cell lines has never been reported via the substrate induced optical changes.
ESTHER : Liu_2020_Mikrochim.Acta_187_313
PubMedSearch : Liu_2020_Mikrochim.Acta_187_313
PubMedID: 32377952

Title : The toxicity assessment of extract of Peganum harmala L. seeds in Caenorhabditis elegans - Miao_2020_BMC.Complement.Med.Ther_20_256
Author(s) : Miao X , Zhang X , Yuan Y , Zhang Y , Gao J , Kang N , Liu X , Wu J , Liu Y , Tan P
Ref : BMC Complement Med Ther , 20 :256 , 2020
Abstract : BACKGROUND: Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. METHODS: In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 degC in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P < 0.01), and the mean lifespan was significantly decreased (P < 0.01). We also observed that PHS exposure could induce the toxicity on body length, brood size, and locomotion behavior. CONCLUSION: Our study shows that the ethanol extract of PHS exerts obvious toxic effects on C. elegans, which would provide new ideas and methods for the biological evaluation of the toxicity of Chinese medicinal materials.
ESTHER : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedSearch : Miao_2020_BMC.Complement.Med.Ther_20_256
PubMedID: 32807143

Title : Applanaic acids A-C, three new highly oxygenated lanostane triterpenoids from the fruiting bodies of Ganoderma applanatum - Chen_2020_Nat.Prod.Res__1
Author(s) : Chen Y , Gao J , Chen Q , Liu W , Qi Y , Aisa HA , Yuan T
Ref : Nat Prod Res , :1 , 2020
Abstract : Three new highly oxygenated lanostane triterpenoids, applanaic acids A-C (1-3), were isolated from the fruiting bodies of the basidiomycete Ganoderma applanatum. Among them, applanaic acid B (2) possessed the Delta(17(20))-double bond connection between the side chain and the tetracyclic skeleton, which was not common in the natural lanostane triterpenoids. Their structures were determined by 1D, 2D NMR and HRESIMS spectroscopic analysis. Compound 3 showed a weak acetylcholinesterase (AchE) inhibitory activity with 33.5% inhibition rate at 50 muM.
ESTHER : Chen_2020_Nat.Prod.Res__1
PubMedSearch : Chen_2020_Nat.Prod.Res__1
PubMedID: 32252566

Title : Buyang Huanwu Tang alleviates inflammation and improves motor endplate functions in DSMA rat models by activating several biological molecules and associated signaling pathways - Zhou_2019_Am.J.Transl.Res_11_3056
Author(s) : Zhou L , Huang YF , Xie H , Mei XY , Gao J
Ref : Am J Transl Res , 11 :3056 , 2019
Abstract : Denervated-dependent skeletal muscle atrophy (DSMA) is considered to be the neuro-disconnection of skeletal muscle. This study aimed to investigate the protective effects of Buyang Huanwu Tang (BYHWT) on the DSMA and clarify associated molecular and genetic mechanisms. DSMA rat models were established according to the previously published study and divided into Model group and BYHWT group. Meanwhile, normal rats were assigned as Normal control (NC) group. Hematoxylin and eosin (HE) staining was used to examine inflammatory responses. Motor endplate activity was evaluated with wholemount acetylcholinesterase (AChE) staining. Mass-spectrometry analysis was conducted to compare differentially expressed proteins. RNAs were prepared and applied to gene functional analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze biological functions. The results indicated that BYHWT remarkably alleviated inflammatory responses and significantly improved motor endplate function, compared to that in DSMA Model rats (P<0.05). In BYHWT group, there were 393 differentially up-regulated and 576 differentially down-regulated molecules compared to that in Model group. Comparing to Model group, the cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes in BYHWT group were the most biological process (BP), cellular component (CC) and molecular function (MF) differential genes, respectively. Fructose/mannose metabolism and glycerolipid metabolism KEGG signaling pathways illustrated the most significant enrichment of differentially expressed genes. In conclusion, BYHWT alleviated the inflammations and improved the motor endplate function of DSMA rats by activating cellular response to interferon-gamma, integral component of plasma membrane and voltage-gated potassium channel activity genes and associated signaling pathways.
ESTHER : Zhou_2019_Am.J.Transl.Res_11_3056
PubMedSearch : Zhou_2019_Am.J.Transl.Res_11_3056
PubMedID: 31217875

Title : Hierarchical nanocomposites with an N-doped carbon shell and bimetal core: Novel enzyme nanocarriers for electrochemical pesticide detection - Ma_2018_Biosens.Bioelectron_121_166
Author(s) : Ma L , Zhou L , He Y , Wang L , Huang Z , Jiang Y , Gao J
Ref : Biosensors & Bioelectronics , 121 :166 , 2018
Abstract : Core-shell structured nanocomposites (named PtPd@NCS) with N-doped carbon shell and bimetal core (Pt and Pd) were fabricated through a facile strategy for the first time. The PtPd@NCS nanocomposites were obtained through reduction of K2PtCl4, H2PtCl6 and Na2PdCl4 species, self-polymerization of dopamine (DA) and co-assembly of Pluronic F127 using a one-pot approach. DA serves as a reductant, as well as a carbon and nitrogen source. The core-shell structure of the PtPd@NCS nanocomposites was characterized and the result indicated that Pt-Pd nanoparticle core with a diameter of approximately 15nm was encased in the N-doped carbon shells with a thickness of approximately 35nm. The PtPd@NCS nanocomposites were used as an electrode material to prepare acetylcholinesterase (AChE) biosensors for detecting organophosphate pesticides. The obtained AChE biosensor exhibited a linear range of 1x10(-14) to 1x10(-10) M and 1x10(-9) to 1x10(-5) M within the detection limit of 7.9x10(-15) M for malathion, 1x10(-13) to 1x10(-6) within the detection limit of 7.1x10(-14) M for chlopyrifos, and 1x10(-14) to 1x10(-11) M and 1x10(-10) to 1x10(-5) M within the detection limit of 8.6x10(-15) M for parathion methyl. The proposed biosensor also exhibited high selectivity, reproducibility and stability. The AChE biosensor was also applied in real samples for detecting organophosphate pesticides and exhibited acceptable recovery. This work demonstrated that the PtPd@NCS had great potential in constructing biosensors to detect organophosphate pesticides and other analytes.
ESTHER : Ma_2018_Biosens.Bioelectron_121_166
PubMedSearch : Ma_2018_Biosens.Bioelectron_121_166
PubMedID: 30218924

Title : Biosynthetic and antimicrobial potential of actinobacteria isolated from bulrush rhizospheres habitat in Zhalong Wetland, China - Li_2018_Arch.Microbiol_200_695
Author(s) : Li Y , Li Q , Gao J , Wang J , Luo Y , Fan X , Gu P
Ref : Arch Microbiol , 200 :695 , 2018
Abstract : The wetland ecosystem is known to possess unique vegetation and serves multiple functions within the environment. In this study, bacterial bioprospecting of bulrush rhizospheres in the Zhalong Wetland, China, was performed using comprehensive methods, including strain isolation and phylogenetic analysis, PCR detection of biosynthetic gene clusters, assessment of antimicrobial activity, metabolite profiling and genome analysis. A total of 27 actinobacterial strains were isolated, and their biosynthetic gene clusters (NRPS, PKS-I and PKS-II) were investigated; all of the tested strains had at least one of the three aforementioned biosynthetic gene clusters. Furthermore, fermentation broth extracts produced by these strains showed antimicrobial activities against certain pathogens, and ten of the extracts exhibited broad-spectrum antimicrobial activity. Liquid chromatography-mass spectrometry (LC-MS) analysis indicated chemical diversity of secondary metabolites from these extracts. Among these strains, ZLSD-24 generated the largest amounts and types of secondary metabolites. Subsequent genome analysis showed that 41 secondary metabolite biosynthetic gene clusters were present in the strain ZLSD-24, which was in accordance with the LC-MS data. Taken together, the results of this study reveal that bulrush rhizosphere habitat in the Zhalong wetland is a promising source of novel natural products.
ESTHER : Li_2018_Arch.Microbiol_200_695
PubMedSearch : Li_2018_Arch.Microbiol_200_695
PubMedID: 29368168
Gene_locus related to this paper: 9actn-a0a2s3y543

Title : Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons - Gao_2017_Neurotoxicol_62_111
Author(s) : Gao J , Naughton SX , Beck WD , Hernandez CM , Wu G , Wei Z , Yang X , Bartlett MG , Terry AV, Jr.
Ref : Neurotoxicology , 62 :111 , 2017
Abstract : Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide that has recently come under increasing scrutiny due to environmental health concerns particularly its association with neurodevelopmental defects. While the insecticidal actions and acute toxicity of CPF are attributed to its oxon metabolite (CPO) which potently inhibits the cholinergic enzyme acetylcholinesterase (AChE), there is significant evidence that CPF, CPO, and other organophosphates may affect a variety of neuronal targets and processes that are not directly related to AChE. Previously, in adult rat sciatic nerves ex vivo and postnatal neurons from rats in vitro we observed that CPF and CPO impaired the movements of vesicles and mitochondria in axons. Here, in embryonic neurons from rats in culture, we evaluated 24h exposures to CPF and CPO across picomolar to micromolar concentrations for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). The most notable observations of this study were concentration-dependent decreases in the velocity and percentage of MBOs moving in the anterograde direction, an increase in the number of stationary MBOs, and an increased frequency of pauses associated with both CPF and CPO. These effects occurred at concentrations that did not significantly inhibit AChE activity, they were not blocked by cholinergic receptor antagonists, and they were not associated with compromised cell viability. These effects of CPF and CPO may be significant given the importance of axonal transport to neuronal development as well the function of fully developed neurons.
ESTHER : Gao_2017_Neurotoxicol_62_111
PubMedSearch : Gao_2017_Neurotoxicol_62_111
PubMedID: 28600141

Title : Prunella vulgaris L., an Edible and Medicinal Plant, Attenuates Scopolamine-Induced Memory Impairment in Rats - Qu_2017_J.Agric.Food.Chem_65_291
Author(s) : Qu Z , Zhang J , Yang H , Gao J , Chen H , Liu C , Gao W
Ref : Journal of Agricultural and Food Chemistry , 65 :291 , 2017
Abstract : Prunella vulgaris L. is as a major plant in the Chinese traditional functional beverage Guangdong herbal tea for the treatment of fevers, diarrhea, and sore mouth. In this study, ethyl acetate parts of aqueous extracts from P. vulgaris L. (EtOAc-APV) were found to demonstrate potent acetylcholinesterase (AChE) inhibition in vitro. Therefore, this study was designed to further investigate the effects of EtOAc-APV on scopolamine (SCOP)-induced aging rats. Male Wistar rats were randomly divided into four groups (n = 12) and given orally by gavage EtOAc-APV (100 mg/kg) for 3 weeks. SCOP (1 mg/kg, ip) was administered to rats 30 min before starting behavioral tests consecutively for 3 days. EtOAc-APV could attenuate SCOP-induced brain senescence in rats by improving behavioral performance and decreasing brain cell damage, which was associated with a notable reduction in AChE activity and MDA level, as well as an increase in SOD and GPx activities. Additionally, EtOAc-APV administration could reduce the expression of NF-kappaB and GFAP, which showed an anti-neuroinflammatory effect on the SCOP-treated rat. Overall, the current study highlights P. vulgaris L. as an antidementia dietary supplement.
ESTHER : Qu_2017_J.Agric.Food.Chem_65_291
PubMedSearch : Qu_2017_J.Agric.Food.Chem_65_291
PubMedID: 28001065

Title : The asparagus genome sheds light on the origin and evolution of a young Y chromosome - Harkess_2017_Nat.Commun_8_1279
Author(s) : Harkess A , Zhou J , Xu C , Bowers JE , Van der Hulst R , Ayyampalayam S , Mercati F , Riccardi P , McKain MR , Kakrana A , Tang H , Ray J , Groenendijk J , Arikit S , Mathioni SM , Nakano M , Shan H , Telgmann-Rauber A , Kanno A , Yue Z , Chen H , Li W , Chen Y , Xu X , Zhang Y , Luo S , Gao J , Mao Z , Pires JC , Luo M , Kudrna D , Wing RA , Meyers BC , Yi K , Kong H , Lavrijsen P , Sunseri F , Falavigna A , Ye Y , Leebens-Mack JH , Chen G
Ref : Nat Commun , 8 :1279 , 2017
Abstract : Sex chromosomes evolved from autosomes many times across the eukaryote phylogeny. Several models have been proposed to explain this transition, some involving male and female sterility mutations linked in a region of suppressed recombination between X and Y (or Z/W, U/V) chromosomes. Comparative and experimental analysis of a reference genome assembly for a double haploid YY male garden asparagus (Asparagus officinalis L.) individual implicates separate but linked genes as responsible for sex determination. Dioecy has evolved recently within Asparagus and sex chromosomes are cytogenetically identical with the Y, harboring a megabase segment that is missing from the X. We show that deletion of this entire region results in a male-to-female conversion, whereas loss of a single suppressor of female development drives male-to-hermaphrodite conversion. A single copy anther-specific gene with a male sterile Arabidopsis knockout phenotype is also in the Y-specific region, supporting a two-gene model for sex chromosome evolution.
ESTHER : Harkess_2017_Nat.Commun_8_1279
PubMedSearch : Harkess_2017_Nat.Commun_8_1279
PubMedID: 29093472
Gene_locus related to this paper: aspof-a0a5p1ew48

Title : Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons - Gao_2016_J.Pharmacol.Exp.Ther_356_645
Author(s) : Gao J , Naughton SX , Wulff H , Singh V , Beck WD , Magrane J , Thomas B , Kaidery NA , Hernandez CM , Terry AV, Jr.
Ref : Journal of Pharmacology & Experimental Therapeutics , 356 :645 , 2016
Abstract : The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs.
ESTHER : Gao_2016_J.Pharmacol.Exp.Ther_356_645
PubMedSearch : Gao_2016_J.Pharmacol.Exp.Ther_356_645
PubMedID: 26718240

Title : Effects of pharmacological treatments on hippocampal NCAM1 and ERK2 expression in epileptic rats with cognitive dysfunction - Kong_2016_Oncol.Lett_12_1783
Author(s) : Kong Q , Min X , Sun R , Gao J , Liang R , Li L , Chu X
Ref : Oncol Lett , 12 :1783 , 2016
Abstract : The present study aimed to investigate the effects of various pharmacological agents on the hippocampal expression of neural cell adhesion molecule 1 (NCAM1) and extracellular signal-regulated kinase 2 (ERK2) in epileptic rats with cognitive dysfunction. The experiments were conducted using 120 Wistar rats: 20 controls and 100 with pilocarpine-induced status epilepticus (SE). The SE rats were randomly assigned to 5 groups (n=20/group) that received daily treatments for 1 month with one of the following: (i) saline (no effect on epilepsy); (ii) carbamazepine (an anticonvulsant); (iii) oxcarbazepine (an anticonvulsant); (iv) aniracetam (a nootropic); or (v) donepezil (an acetylcholinesterase inhibitor). Spatial learning and memory were assessed using a Morris Water Maze (MWM). Hippocampal tissue was assessed for NCAM1 and ERK2 messenger RNA (mRNA) expression by reverse transcription polymerase chain reaction, and protein expression by immunochemistry. The results revealed that SE rats had significantly poorer MWM performances compared with controls (P<0.01). Performance in SE rats was improved with donepezil treatment (P<0.01), but declined with carbamazepine (P<0.01). Compared with controls, saline-treated SE rats exhibited increased hippocampal NCAM1 mRNA expression (P<0.01). Among SE rats, NCAM1 mRNA expression was highest in those treated with donepezil, followed by aniracetam-, saline-, oxcarbazepine- and carbamazepine-treated rats. Compared to controls, saline-treated SE rats exhibited decreased hippocampal ERK2 mRNA expression (P<0.01). Among SE rats, ERK2 mRNA expression was highest in those treated with donepezil, followed by aniracetam, saline, oxcarbazepine and carbamazepine. NCAM1 and ERK2 protein expression levels were parallel to those of the mRNA. In saline-treated SE rats, hippocampal ERK2 expression was decreased and NCAM1 expression was increased; thus, these two molecules may be involved in the impairment of spatial memory. Carbamazepine augmented this impairment, whereas donepezil was found to ameliorate the dysfunction associated with epilepsy. In conclusion, ERK2 and NCAM1 have significant roles in impairment of spatial memory in SE rats. Carbamazepine may increase this impairment, while donepezil may decrease this impairment.
ESTHER : Kong_2016_Oncol.Lett_12_1783
PubMedSearch : Kong_2016_Oncol.Lett_12_1783
PubMedID: 27588125

Title : Independent Prognostic Factors for Acute Organophosphorus Pesticide Poisoning - Tang_2016_Respir.Care_61_965
Author(s) : Tang W , Ruan F , Chen Q , Chen S , Shao X , Gao J , Zhang M
Ref : Respir Care , 61 :965 , 2016
Abstract : BACKGROUND: Acute organophosphorus pesticide poisoning (AOPP) is becoming a significant problem and a potential cause of human mortality because of the abuse of organophosphate compounds. This study aims to determine the independent prognostic factors of AOPP by using multivariate logistic regression analysis.
METHODS: The clinical data for 71 subjects with AOPP admitted to our hospital were retrospectively analyzed. This information included the Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, admission blood cholinesterase levels, 6-h post-admission blood cholinesterase levels, cholinesterase activity, blood pH, and other factors. Univariate analysis and multivariate logistic regression analyses were conducted to identify all prognostic factors and independent prognostic factors, respectively. A receiver operating characteristic curve was plotted to analyze the testing power of independent prognostic factors.
RESULTS: Twelve of 71 subjects died. Admission blood lactate levels, 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, blood pH, and APACHE II scores were identified as prognostic factors for AOPP according to the univariate analysis, whereas only 6-h post-admission blood lactate levels, post-admission 6-h lactate clearance rates, and blood pH were independent prognostic factors identified by multivariate logistic regression analysis. The receiver operating characteristic analysis suggested that post-admission 6-h lactate clearance rates were of moderate diagnostic value.
CONCLUSIONS: High 6-h post-admission blood lactate levels, low blood pH, and low post-admission 6-h lactate clearance rates were independent prognostic factors identified by multivariate logistic regression analysis.
ESTHER : Tang_2016_Respir.Care_61_965
PubMedSearch : Tang_2016_Respir.Care_61_965
PubMedID: 27048625

Title : Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat - Qu_2016_Physiol.Behav_154_114
Author(s) : Qu Z , Zhang J , Yang H , Huo L , Gao J , Chen H , Gao W
Ref : Physiol Behav , 154 :114 , 2016
Abstract : Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor kappa (NF-kappaB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy.
ESTHER : Qu_2016_Physiol.Behav_154_114
PubMedSearch : Qu_2016_Physiol.Behav_154_114
PubMedID: 26592138

Title : Acetylcholinesterase inhibitory dimeric indole derivatives from the marine actinomycetes Rubrobacter radiotolerans - Li_2015_Fitoterapia_102_203
Author(s) : Li JL , Huang L , Liu J , Song Y , Gao J , Jung JH , Liu Y , Chen G
Ref : Fitoterapia , 102 :203 , 2015
Abstract : Investigation of the bioactive secondary metabolites of the marine actinomycetes Rubrobacter radiotolerans led to the isolation and characterization of two naturally rare dimeric indole derivatives (1 and 2). The structures of these new compounds were elucidated by spectroscopic data interpretation, and the absolute configurations were assigned by CD calculations. The acetylcholinesterase (AchE) inhibitory activity of compounds 1 and 2 was evaluated, both of which showed moderate activity with IC50 values of 11.8 and 13.5muM, respectively.
ESTHER : Li_2015_Fitoterapia_102_203
PubMedSearch : Li_2015_Fitoterapia_102_203
PubMedID: 25655350

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 : Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease - Gao_2014_Bioorg.Med.Chem.Lett_24_1472
Author(s) : Gao J , Adam BL , Terry AV, Jr.
Ref : Bioorganic & Medicinal Chemistry Lett , 24 :1472 , 2014
Abstract : The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies.
ESTHER : Gao_2014_Bioorg.Med.Chem.Lett_24_1472
PubMedSearch : Gao_2014_Bioorg.Med.Chem.Lett_24_1472
PubMedID: 24581918

Title : The effects of CES1A2 A(-816)C and CYP2C19 loss-of-function polymorphisms on clopidogrel response variability among Chinese patients with coronary heart disease - Xie_2014_Pharmacogenet.Genomics_24_204
Author(s) : Xie C , Ding X , Gao J , Wang H , Hang Y , Zhang H , Zhang J , Jiang B , Miao L
Ref : Pharmacogenet Genomics , 24 :204 , 2014
Abstract : OBJECTIVE: Carboxylesterase 1 hydrolyzes the majority of clopidogrel to the inactive metabolite. The aim of this study was to assess the effects of the CES1A2 A(-816)C polymorphism and other genetic and clinical factors on clopidogrel response variability. An additional aim was to investigate the relationship between genetic variations and development of stent thrombosis (ST).
METHODS: We recruited 162 coronary heart disease patients treated with aspirin and clopidogrel, and we genotyped them for the CES1A2 A(-816)C, CYP2C19 *2/*3, PON1 Q192R, and ABCB1 C3435T polymorphisms. Platelet reactivity was analyzed using the VASP-PRI assay. We also carried out a case-control study in which 22 patients undergoing stent implantation who had ST were matched with 86 ST-free controls.
RESULTS: The VASP-PRI values were significantly higher in the carriers of the CES1A2 -816C allele (P=0.014) and CYP2C19 loss of function (LOF) alleles (P=0.004). Furthermore, the patients with CYP2C19 LOF alleles showed an increased risk of ST (ORadj=4.28, P=0.033). However, there was no significant association between the CES1A2 -816C allele and the development of ST. The CYP2C19 and CES1A2 genotypes alone could explain 6.1 and 3.7% of the interindividual variability in the VASP-PRI results, respectively. The value increased to 12.5% when clinical factors (e.g. BMI and triglycerides) were also considered. The PON1 Q192R and ABCB1 C3435T genetic variations produced no significant impact. CONCLUSION: The CES1A2 -816C and the CYP2C19 LOF alleles were associated with attenuated platelet reactivity to clopidogrel. CYP2C19 LOF was also predictive of ST; however, the association between the CES1A2 -816C allele and development of ST requires further study.
ESTHER : Xie_2014_Pharmacogenet.Genomics_24_204
PubMedSearch : Xie_2014_Pharmacogenet.Genomics_24_204
PubMedID: 24535487

Title : Molecular Cloning and Characterization of a Novel Cold-Adapted Family VIII Esterase from a Biogas Slurry Metagenomic Library - Cheng_2014_J.Microbiol.Biotechnol_24_1484
Author(s) : Cheng X , Wang X , Qiu T , Yuan M , Sun J , Gao J
Ref : J Microbiol Biotechnol , 24 :1484 , 2014
Abstract : A novel esterase gene, est01, was successfully unearthed from a biogas digester microbiota metagenomic library. The 1,194 bp est01 gene encodes a protein of 44,804 Da (designated Est01). The amino acid sequence of Est01 shows only moderate (33%) identity to a lipase/ esterase. Phylogenetic analysis and biochemical characterization confirmed that Est01 is a new member of family VIII esterases. The purified Est01 from recombinant Escherichia coli BL21 (DE3) showed high hydrolytic activity against short-chain fatty acid esters, suggesting that it is a typical carboxylesterase rather than a lipase. Furthermore, the Est01 was even active at 10 degrees C (43% activity remained), with the optimal temperature at 20 degrees C, and had a broad pH range from 5.0 to 10.0, with the optimal pH of 8.0. These properties suggest that Est01 is a cold-adaptive esterase and could have good potential for low-temperature hydrolysis application.
ESTHER : Cheng_2014_J.Microbiol.Biotechnol_24_1484
PubMedSearch : Cheng_2014_J.Microbiol.Biotechnol_24_1484
PubMedID: 25394508

Title : Purification and characterization of an extracellular poly(3-hydroxybutyrate-co-3-hydroxyvalerate) depolymerase from Acidovorax sp. HB01 - Wang_2012_World.J.Microbiol.Biotechnol_28_2395
Author(s) : Wang Z , Gao J , Li L , Jiang H
Ref : World J Microbiol Biotechnol , 28 :2395 , 2012
Abstract : The poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV)-degrading strain Acidovorax sp. HB01 was isolated from an activated sludge sample. A novel PHBV depolymerase with a molecular weight of 43.4 kDa was purified to homogeneity from the culture supernatant of the HB01 strain. The optimum pH and temperature of the PHBV depolymerase were 7.0 and 50 degreesC, respectively. The PHBV depolymerase can also degrade polyhydroxybutyrate, poly (3-hydroxybutyrate-co-4-hydroxybutyrate), and poly(caprolactone); however, the PHBV degradation activity of the depolymerase is higher than its activity against the other polymers. Effect of metal ions and various inhibitors on the PHBV depolymerase activity was examined. The addition of Na(+), K(+), and Ca(2+) markedly increased the hydrolysis rate, whereas the enzyme activity was inhibited by Zn(2+), Mg(2+), Mn(2+), and particularly by Cu(2+) and Fe(2+). Ethylenediaminetetraacetic acid was found to have a significant inhibitory effect. The main degradation product of depolymerase was identified as the 3-hydroxybutyric acid monomer and 3-hydroxyvaleric acid monomers via mass spectrometry.
ESTHER : Wang_2012_World.J.Microbiol.Biotechnol_28_2395
PubMedSearch : Wang_2012_World.J.Microbiol.Biotechnol_28_2395
PubMedID: 22806113

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

Title : Identification of carboxylesterases expressed in rat intestine and effects of their hydrolyzing activity in predicting first-pass metabolism of ester prodrugs - Liu_2011_Pharmazie_66_888
Author(s) : Liu D , Gao J , Zhang C , Ren X , Liu Y , Xu Y
Ref : Pharmazie , 66 :888 , 2011
Abstract : Carboxylesterases (CESs) located in the intestine play an unique role in the absorption of many drugs especially ester prodrugs. In order to determine the expression and hydrolyzing activity of CESs isozymes (CES1 and CES2) located in rat intestine, the activities of CES1 and CES2 were evaluated by the intestinal S9 incubation with imidapril and irinotecan (CPT-11), the substrates of CES1 and CES2, respectively. The distribution characteristics of CES1, CES2, Pregnane X Receptor (PXR) and Constitutive Androstane Receptor were analyzed by real-time polymerase chain reaction (RT-PCR) or Western blot. Imidaprilat metabolized from imidapril by CES1 was too low to be detected in rat intestinal S9 fractions, while there was little and even no expression of CES1 mRNA in intestinal segments. In contrast, Vmax values for CPT-11 diminished gradually from proximal to distal segments within the rat intestine which was consistent with the mRNA expression level of CES2. These results indicated that CES2 represents the major CESs isoform in the rat complete intestine and decreased from duodenum to colon, whereas the expression of CES1 was too low to influence the metabolism of ester prodrugs. The expression of PXR and CAR decreased slightly along the entire intestine on both mRNA and protein levels which indicated that PXR and CAR may be one of the major factors which contribute to the expression of CES1 and CES2. Thus, the knowledge about the characteristic and site-specific expression of CES1 and CES2 in rat intestine will help to predict the oral bioavailability of ester prodrugs.
ESTHER : Liu_2011_Pharmazie_66_888
PubMedSearch : Liu_2011_Pharmazie_66_888
PubMedID: 22204136

Title : Immobilization of Candida antarctica lipase B by adsorption in organic medium - Sun_2010_N.Biotechnol_27_53
Author(s) : Sun J , Jiang Y , Zhou L , Gao J
Ref : N Biotechnol , 27 :53 , 2010
Abstract : Candida antarctica lipase B (CALB) was immobilized on the macroporous resin by physical adsorption in organic medium. The immobilization was performed in 5 mL isooctane, and the immobilization conditions were optimized. The results were achieved with the mass ratio of lipase to support 1:80, the buffer of pH 6.0, initial addition of PBS 75 microL, and immobilization time of two hours at 30 degrees C. Under the optimal conditions, the activity recovery was 83.3%. IM-CALB presented enhanced pH and thermal stability compared to the free lipase, and showed comparable stability with the commercial Novozym 435, after 7 times repeated use for catalyzing the synthesis of ethyl lactate, 56.9% of its initial activity was retained, and only 24.7% was retained when used for catalyzing the hydrolysis of olive oil.
ESTHER : Sun_2010_N.Biotechnol_27_53
PubMedSearch : Sun_2010_N.Biotechnol_27_53
PubMedID: 20004754

Title : Quantitative and qualitative changes of the carboxylesterase associated with beta-cypermethrin resistance in the housefly, Musca domestica (Diptera: Muscidae) - Zhang_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_156_6
Author(s) : Zhang L , Shi J , Shi X , Liang P , Gao J , Gao X
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 156 :6 , 2010
Abstract : Mechanisms of esterase-mediated pyrethroid resistance were analyzed based on our previous works in a strain of the housefly, Musca domestica. The carboxylesterase gene, MdalphaE7, was cloned and sequenced from susceptible (CSS) and resistant (CRR) strains, and a total of nine amino acid substitutions were found. The mutation, Trp(251)-Ser appeared to play a role in beta-cypermethrin resistance and cross-resistance between organophosphates (OPs) and pyrethroids in the CRR strain. Quantitative real-time PCR showed that MdalphaE7 was over-expressed in the CRR strain, the reciprocal cross progeny F(1) and back-cross progeny BC(2) compared with the CSS strain, respectively. Two alpha-cynaoester substrates as surrogates for beta-cypermethrin and deltamethrin, were synthesized to determine the pyrethroid hydrolase activity. Results showed that carboxylesterases from the CRR strain hydrolyzed cypermethrin/deltamethrin-like substrate 9.05- and 13.53-fold more efficiently than those from the CSS strain, respectively. Our studies suggested that quantitative and qualitative changes in the carboxylesterase might contribute together to pyrethroid resistance in the CRR strain.
ESTHER : Zhang_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_156_6
PubMedSearch : Zhang_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_156_6
PubMedID: 20117228
Gene_locus related to this paper: musdo-EST23aes07

Title : Identification of pancreatic juice proteins as biomarkers of pancreatic cancer - Gao_2010_Oncol.Rep_23_1683
Author(s) : Gao J , Zhu F , Lv S , Li Z , Ling Z , Gong Y , Jie C , Ma L
Ref : Oncol Rep , 23 :1683 , 2010
Abstract : Pancreatic juice is a potential source of proteins associated with pancreatic cancer (PC) due to the proximity of ducts to tumor tissue. Therefore, screening of proteins in pancreatic juice from PC patients may identify new PC biomarkers. We analyzed pancreatic juice from patients with pancreatic diseases including PC, chronic pancreatitis (CP) and simple choledocholithiasis (CDS) by 2-DE. Protein spots from PC patients that changed >2-fold compared with both CP and CDS were selected and identified by mass spectrometry (MS). mRNA levels were measured by QRT-PCR in PC cell lines, PC tissues and adjacent pancreatic normal (PN) tissues. Relationships between mRNA levels in PC tissues and their clinical characteristics and promoter methylation were analyzed in PC cell lines and tissues. We found that four proteins were significantly changed in PC compared to CP and simple CDS. Two proteins were up-regulated, serine proteinase-2 (PRSS2) preproprotein and pancreatic lipase-related protein-1 (PLRP1), and two proteins were down-regulated, chymotrypsinogen B (CTRB) precursor and elastase 3B (ELA3B) preproprotein. In all PC cell lines, PRSS 2 mRNA levels were elevated, while PLRP 1 mRNA was detected in 4/5 cell lines. ELA3B mRNA was undetectable in all cell lines, but CTRB mRNA was detected in 2/5 cell lines. In PC tissues compared to PN, levels of PRSS2 mRNA were significantly higher, ELA3B significantly lower, and PLRP1 and CTRB not significantly different. Elevated PRSS2 mRNA levels correlated with high T stage. The ELA3B gene promoter had higher methylation in PC cell lines and tissues compared with PN tissues, and correlated with low ELA3B gene expression. In conclusion, comparative proteomic analysis of pancreatic juice from PC patients is a powerful method to find new PC biomarkers. Hyperexpression of the PRSS2 gene and hypermethylation of ELA3B gene promoter were associated with PC, raising the possibility of their application as new biomarkers in PC diagnosis and screening.
ESTHER : Gao_2010_Oncol.Rep_23_1683
PubMedSearch : Gao_2010_Oncol.Rep_23_1683
PubMedID: 20428826

Title : Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor - Tian_2010_Endocrinology_151_3049
Author(s) : Tian L , Gao J , Hao J , Zhang Y , Yi H , O'Brien TD , Sorenson R , Luo J , Guo Z
Ref : Endocrinology , 151 :3049 , 2010
Abstract : Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice.
ESTHER : Tian_2010_Endocrinology_151_3049
PubMedSearch : Tian_2010_Endocrinology_151_3049
PubMedID: 20444936

Title : [Immobilized lipase-catalyzed synthesis of biodiesel from crude cottonseed oil] - Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
Author(s) : Liu W , Zhou L , Jiang Y , Gao J
Ref : Sheng Wu Gong Cheng Xue Bao , 25 :1996 , 2009
Abstract : We investigated the transesterification of crude cottonseed oil with methyl acetate to biodiesel, by using Lipozyme TL IM and Novozym 435 as catalysts. Results showed that the biodiesel yield significantly increased with the addition of methanol into the reaction system, and the highest biodiesel yield of 91.83% was achieved with the optimum conditions as follows: n-hexane as solvent, molar ratio of methyl acetate to oil 9:1, 3% methanol based on the oil mass to inhibit the creation of acetic acid, 10% Lipozyme TL IM and 5% Novozym 435 as catalyst based on the oil mass, reaction temperature 55 degrees C and reaction time 8 h. Additionally, we explored the kinetics of lipase-catalyzed crude cottonseed oil to biodiesel, and proposed a kinetic model.
ESTHER : Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
PubMedSearch : Liu_2009_Sheng.Wu.Gong.Cheng.Xue.Bao_25_1996
PubMedID: 20352980

Title : Inhibition of Coix seed extract on fatty acid synthase, a novel target for anticancer activity - Yu_2008_J.Ethnopharmacol_119_252
Author(s) : Yu F , Gao J , Zeng Y , Liu CX
Ref : J Ethnopharmacol , 119 :252 , 2008
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Coix seed has been traditionally used to treat cancers in folk medicine. AIM OF THE STUDY: Study the anticancer action mechanism of Coix seed extract. MATERIALS AND METHODS: After the treatment with Coix seed extract (10 microl/ml), the residual activity of fatty acid synthase (FAS) as overall reaction, beta-ketoacyl reduction, enoyl reduction, and acetyl acetyl coenzyme A (AcAcCoA) reduction was separately detected at 340 nm in the UV-190 spectrophotometer. After rats were administrated Coix seed extract (2.5, 5.0, and 10.0 ml/kg) intragastrically for 10 days consecutively, activities of FAS, malate dehydrogenase (MDH), lipid protein lipase (LPL), hepatic lipase (HL), triglyceride (TG), and glucose-6-phosphate dehydrogenase (G-6-PD) in the plasma, liver and fatty tissues were determined. RESULTS: Experiments in vitro showed that the inhibition of Coix seed extract on FAS activity was significant and dose dependent, and two active sites inhibited were beta-ketoacyl reductases (KR) and enoyl reductase (ER). Experiments in vivo showed that Coix seed extract inhibited FAS activity in the liver, and elevated LPL and HL activity in the plasma, and effected G-6-PD activity. CONCLUSIONS: The study supports that FAS is a novel target for anticancer activity, and provides a theoretical foundation for the wide application of Coix seed extract in traditional medicine.
ESTHER : Yu_2008_J.Ethnopharmacol_119_252
PubMedSearch : Yu_2008_J.Ethnopharmacol_119_252
PubMedID: 18691644

Title : Identification of a novel keratinocyte retinyl ester hydrolase as a transacylase and lipase - Gao_2005_J.Invest.Dermatol_124_1259
Author(s) : Gao J , Simon M
Ref : Journal of Investigative Dermatology , 124 :1259 , 2005
Abstract : Retinoic acid influences epidermal morphology and function through its ability to control transcription. Because the circulation presents the epidermis with micromolar amounts of retinol that can be converted to retinoic acid, regulating retinol access is imperative. In keratinocytes the majority of retinol is sequestered as long chain fatty acid esters. Although much has been learned about the major esterifying enzyme, little is known about the hydrolase that accesses retinol from its storage depot. Murine carboxylesterases and hormone sensitive lipase have been shown to have this activity. We found that their in vitro sensitivity to bis-p-nitrophenyl phosphate (BNPP), however, was not shared by the epidermal hydrolase activity. We therefore produced and screened two keratinocyte cDNA expression libraries and identified a previously sequenced gene (GS2) as a keratinocyte retinyl ester (RE) hydrolase insensitive to BNPP. The enzyme also catalyzes fattyacyl CoA-dependent and -independent retinol esterification. The hydrolysis reaction is greater at neutral pH, whereas the esterification reaction is greater at acidic pH. These activities are consistent with the increased RE content that accompanies epidermal maturation. In addition, this enzyme utilizes triolein as substrate and generates diacylglyceride and free fatty acid.
ESTHER : Gao_2005_J.Invest.Dermatol_124_1259
PubMedSearch : Gao_2005_J.Invest.Dermatol_124_1259
PubMedID: 15955102

Title : Cloning and characterization of Trichophyton rubrum genes encoding actin, Tri r2, and Tri r4 - Gao_2004_J.Clin.Microbiol_42_3298
Author(s) : Gao J , Takashima A
Ref : J Clin Microbiol , 42 :3298 , 2004
Abstract : The three structural genes of Trichophyton rubrum encoding actin (3,429 bp) and two antigens, Tri r2 (2,950 bp) and Tri r4 (3,988 bp), were cloned and characterized. They contained six, four, and five exons, respectively. The T. rubrum actin protein sequence revealed extremely high homology to other fungal actins.
ESTHER : Gao_2004_J.Clin.Microbiol_42_3298
PubMedSearch : Gao_2004_J.Clin.Microbiol_42_3298
PubMedID: 15243098
Gene_locus related to this paper: triru-DPPV

Title : An acetylcholinesterase purified from the greenbug (Schizaphis graminum) with some unique enzymological and pharmacological characteristics - Gao_2001_Insect.Biochem.Mol.Biol_31_1095
Author(s) : Gao J , Zhu KY , Gao JR
Ref : Insect Biochemistry & Molecular Biology , 31 :1095 , 2001
Abstract : An acetylcholinesterase (AChE, EC 3.1.1.7) was purified from the greenbug, Schizaphis graminum (Rondani). The maximum velocities (Vmax) for hydrolyzing acetylthiocholine (ATC), acetyl-(beta-methyl) thiocholine (AbetaMTC), propionylthiocholine, and S-butyrylthiocholine were 78.0, 67.0, 37.4, and 2.3 micromol/min/mg, and the Michaelis constants (Km) were 57.6, 60.6, 31.3, and 33.4 microM, respectively. More than 98% of AChE activity was inhibited by 10 microM eserine or BW284C51, but only 7% of the activity was inhibited by ethopropazine at the same concentration. Based on the substrate and inhibitor specificities, the purified enzyme appeared to be a true AChE. Nondenaturing polyacrylamide gel electrophoresis (PAGE) and isoelectric focusing of the purified AChE revealed three molecular forms. The isoelectric points were 7.3 for the major form and 6.3 and 7.1 for two minor forms. The major form of purified AChE showed molecular masses of 129 kDa for its native protein and 72 kDa for its subunits on SDS-PAGE. However, the purified AChE exhibited some distinctive characteristics including: (1) lack of affinity to the affinity ligand 3-(carboxyphenyl) ethyldimethyl ammonium, which has been used widely in purification of AChE from various insect species; and (2) 20-200-fold higher substrate-inhibition thresholds for ATC and AbetaMTC than AChE from other insect species. These biochemical properties may reflect structural differences of AChE purified from the greenbug compared with that from other insect species.
ESTHER : Gao_2001_Insect.Biochem.Mol.Biol_31_1095
PubMedSearch : Gao_2001_Insect.Biochem.Mol.Biol_31_1095
PubMedID: 11520688