Guo Y

References (105)

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 : Chemical characterization, multivariate analysis and comparison of biological activities of different parts of Fraxinus mandshurica - Guo_2024_Biomed.Chromatogr__e5861
Author(s) : Guo J , Liu S , Guo Y , Bai L , Ho CT , Bai N
Ref : Biomedical Chromatography , :e5861 , 2024
Abstract : Fraxinus mandshurica (Oleaceae) is used as a traditional medicinal plant for the treatment of red eyes, menstrual disorders, excessive leucorrhea, chronic bronchitis and psoriasis. To perform chemical characterization of the secondary metabolites of F. mandshurica roots, bark, stems and leaves, 32 samples were collected from eight provinces in this study. A total of 64 chemical components were detected from four different parts of F. mandshurica by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Meanwhile, a total of nine secoiridoids were obtained by natural product chemical extraction, isolation and identification methods. Quantitative analysis by high-performance liquid chromatography-diode array detection-mass spectrometry showed the highest total content of secoiridoids in the bark, which is also consistent with the traditional medicinal parts. The results of methodological validation showed that the correlation coefficient (R(2) ) values were all >0.9993, indicating a good linear range of the standard curve, while the relative standard deviations of precision, reproducibility and stability were <3%, and the spiked recoveries ranged from 98.22 to 102.27%, indicating that the experimental method was reliable and stable. In addition, fingerprinting and a heatmap were established to demonstrate the content trends of F. mandshurica more visually from different origins. Multivariate analysis, including principal component analysis and partial least squares discriminant analysis, was performed to determine the chemical characteristics of different parts of F. mandshurica, and six characteristic secoiridoids that could be used to distinguish different origins were screened. Finally, the inhibition of tyrosinase, alpha-glucosidase, acetylcholinesterase and pancreatic lipase activities by the nine characteristic compounds and extracts from different parts were investigated, and the results showed that they all exhibited different degrees of enzyme activity inhibition and thus have potential applications in whitening and blemish removal, hypoglycemia, anti-Alzheimer's disease and anti-obesity as a new source of natural enzyme activity inhibitors. This study establishes an identification and evaluation method applicable to phytochemistry of different origins, which is a guideline for quality control, origin evaluation and clinical application of traditional medicinal plants. This is also an unprecedented study on the identification of the chemical composition of different parts of F. mandshurica, characteristic compounds and the inhibition of enzyme activity of extracts from different parts.
ESTHER : Guo_2024_Biomed.Chromatogr__e5861
PubMedSearch : Guo_2024_Biomed.Chromatogr__e5861
PubMedID: 38501361

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 : Development of a fluorescent sensor based on TPE-Fc and GSH-AuNCs for the detection of organophosphorus pesticide residues in vegetables - Wang_2023_Food.Chem_431_137067
Author(s) : Wang X , Yu H , Li Q , Tian Y , Gao X , Zhang W , Sun Z , Mou Y , Sun X , Guo Y , Li F
Ref : Food Chem , 431 :137067 , 2023
Abstract : A novel dual-signal fluorescent sensor was developed for detecting organophosphorus pesticides (OPs). It relies on the catalytic activities of acetylcholinesterase (AChE) and choline oxidase (ChOx) to generate hydrogen peroxide (H(2)O(2)) through the conversion of acetylcholine (ACh) to choline.H(2)O(2) then oxidizes ferrocene-modified tetraphenylethylene (TPE-Fc) to its oxidized state (TPE-Fc(+)), resulting in enhanced cyan fluorescence due to aggregation. Simultaneously, ferrocene oxidation generates hydroxyl radicals (OH), causing a decrease in orange fluorescence of glutathione-synthesized gold nanoclusters (GSH-AuNCs). The presence of OPs restricts AChE activity, reducing H(2)O(2) production. Increasing OPs concentration leads to decreased cyan fluorescence and increased orange fluorescence, enabling visual OPs detection. The sensor has a linear dynamic range of 10-2000 ng/mL with a detection limit of 2.05 ng/mL. Smartphone-based color identification and a WeChat mini program were utilized for rapid OPs analysis with successful outcomes.
ESTHER : Wang_2023_Food.Chem_431_137067
PubMedSearch : Wang_2023_Food.Chem_431_137067
PubMedID: 37579609

Title : Genome-wide association study of 17 serum biochemical indicators in a chicken F(2) resource population - Song_2023_BMC.Genomics_24_98
Author(s) : Song H , Li W , Li Y , Zhai B , Guo Y , Chen Y , Han R , Sun G , Jiang R , Li Z , Yan F , Li G , Liu X , Zhang Y , Tian Y , Kang X
Ref : BMC Genomics , 24 :98 , 2023
Abstract : BACKGROUND: Serum biochemical indicators are often regarded as direct reflections of animal metabolism and health. The molecular mechanisms underlying serum biochemical indicators metabolism of chicken (Gallus Gallus) have not been elucidated. Herein, we performed a genome-wide association study (GWAS) to identify the variation associated with serum biochemical indicators. The aim of this research was to broaden the understanding of the serum biochemical indicators in chickens. RESULTS: A GWAS of serum biochemical indicators was carried out on 734 samples from an F2 Gushix Anka chicken population. All chickens were genotyped by sequencing, 734 chickens and 321,314 variants were obtained after quality control. Based on these variants, a total of 236 single-nucleotide polymorphisms (SNPs) on 9 chicken chromosomes (GGAs) were identified to be significantly (-log(10)(P) > 5.72) associated with eight of seventeen serum biochemical indicators. Ten novel quantitative trait locis (QTLs) were identified for the 8 serum biochemical indicator traits of the F2 population. Literature mining revealed that the ALPL, BCHE, GGT2/GGT5 genes at loci GGA24, GGA9 and GGA15 might affect the alkaline phosphatase (AKP), cholinesterase (CHE) and gamma-glutamyl transpeptidase (GGT) traits, respectively. CONCLUSION: The findings of the present study may contribute to a better understanding of the molecular mechanisms of chicken serum biochemical indicator regulation and provide a theoretical basis for chicken breeding programs.
ESTHER : Song_2023_BMC.Genomics_24_98
PubMedSearch : Song_2023_BMC.Genomics_24_98
PubMedID: 36864386

Title : Design and construction of Carboxylesterase 2c Gene knockout Rats by CRISPR\/Cas9 - Liu_2023_Curr.Drug.Metab__
Author(s) : Liu J , Shang X , Yao B , Zhang Y , Huang S , Guo Y , Wang X
Ref : Curr Drug Metab , : , 2023
Abstract : BACKGROUND: Carboxylesterase 2 (CES2) is mainly distributed in the human liver and gut, and plays an active role in the metabolic activation of many prodrugs and lipid metabolism. Although CES2 is of great significance, there are still few animal models related to CES2. OBJECTIVES: This research aims to construct Ces2c gene knockout (KO) rats and further study the function of CES2. METHODS: CRISPR/Cas9 gene editing technology was used to target and cleave the rat Ces2c gene. Compensatory effects of major CES subtypes both in the liver and small intestine of KO rats were detected at mRNA levels. Meanwhile, diltiazem and aspirin were used as substrates to test the metabolic capacity of Ces2c in KO rats. RESULTS: This Ces2c KO rat model showed normal growth and breeding without off-target effects. The metabolic function of Ces2c KO rats was verified by the metabolic study of CES2 substrates in vitro. The results showed that the metabolic capacity of diltiazem in KO rats was weakened, while the metabolic ability of aspirin did not change significantly. In addition, the serum physiological indexes showed that the Ces2c deletion did not affect the liver function of rats. CONCLUSION: The Ces2c KO rat model was successfully constructed by CRISPR/Cas9 system. This rat model can not only be used as an important tool to study the drug metabolism mediated by Ces2, but also as an important animal model to study the physiological function of Ces2.
ESTHER : Liu_2023_Curr.Drug.Metab__
PubMedSearch : Liu_2023_Curr.Drug.Metab__
PubMedID: 36694315
Gene_locus related to this paper: ratno-pbcxe

Title : Molluscicidal activity of Nicotiana tabacum extracts on the invasive snail Pomacea canaliculata - Guo_2023_Sci.Rep_13_11597
Author(s) : Guo J , Zhang S , Zeng J , Chen Y , Guo Y , Liu J , He A
Ref : Sci Rep , 13 :11597 , 2023
Abstract : Botanical molluscicides for controlling the invasive snail Pomacea canaliculata have attracted worldwide attention because of their cost and environmental friendliness. Aqueous extracts from discarded tobacco leaf (Nicotiana tobacum) were evaluated for molluscicidal activity against different-sized P. canaliculata under laboratory conditions. The results showed that over 90% of the snails died in 1 g/L tobacco extract within 4 days, and the survival of P. canaliculata was inversely proportional to the snail size, tobacco extract concentration and length of exposure time. Adult males were more susceptible to tobacco extract than females. The snails had few chances to feed or mate in 0.5 g/L tobacco extract, and reproduction was greatly limited in 0.2 g/L. The growth of juvenile snails was inhibited in 0.2 g/L tobacco extract, but adults were unaffected. The antioxidant capacity of P. canaliculata in response to tobacco extract can be size- and sex-dependent, and the activities of superoxide dismutase, catalase, and acetylcholinesterase and the contents of glutathione and malondialdehyde were increased in adult males. These results suggest that discarded tobacco leaves can be useful as a molluscicide for controlling the invasive snail P. canaliculata based on its effects on survival, behaviour, food intake, growth performance and antioxidant capacity.
ESTHER : Guo_2023_Sci.Rep_13_11597
PubMedSearch : Guo_2023_Sci.Rep_13_11597
PubMedID: 37463929

Title : Inhibition of Th17 cells by donepezil ameliorates experimental lung fibrosis and pulmonary hypertension - Guo_2023_Theranostics_13_1826
Author(s) : Guo Y , He Z , Chen Z , Chen F , Wang C , Zhou W , Liu J , Liu H , Shi R
Ref : Theranostics , 13 :1826 , 2023
Abstract : Rationale: Pulmonary hypertension (PH) secondary to lung fibrosis belongs to WHO Group III, one of the most common subgroups of PH; however, it lacks effective treatment options. Cholinesterase inhibitor donepezil (DON) has been shown to effectively improve Group I PH. However, its effects on Group III PH are unknown. Methods: A lung fibrosis-induced PH mouse model was constructed using a single intratracheal instillation of bleomycin (BLM), after which DON was administered daily. Pulmonary artery and right ventricle (RV) remodeling were evaluated at the end of the study. Lung tissue in each group was analyzed using RNA sequencing, and the results were further verified with datasets from patients with PH. The mechanisms underlying DON-induced effects on PH were verified both in vivo and in vitro. Results: DON effectively improved pulmonary artery and RV remodeling in the BLM-induced mouse model. Transcriptomic profiles of lung tissue indicated that the expression of inflammatory and fibrotic genes was significantly changed in this process. In the animal model and patients with PH, T helper 17 lymphocytes (Th17) were the most common inflammatory cells infiltrating the lung tissue. DON significantly inhibited lung fibroblast activation; thus, preventing lung fibrosis and reducing the inflammatory response and Th17 cell infiltration in the BLM-induced lung tissue. In addition, Th17 cells could activate lung fibroblasts by secreting IL17A, and DON-mediated inhibition of Th17 cell differentiation was found to depend on the alpha7nAchR-JAK2-STAT3 pathway. Conclusion: DON can alleviate lung fibrosis and PH in an experimental mouse model. It inhibited pro-inflammatory Th17 cell differentiation, which is dependent on a cholinergic receptor pathway, thereby regulating fibroblast activation.
ESTHER : Guo_2023_Theranostics_13_1826
PubMedSearch : Guo_2023_Theranostics_13_1826
PubMedID: 37064881

Title : Conocarpus lancifolius (Combretaceae): Pharmacological Effects, LC-ESI-MS\/MS Profiling and In Silico Attributes - Khurm_2023_Metabolites_13_
Author(s) : Khurm M , Guo Y , Wu Q , Zhang X , Ghori MU , Rasool MF , Imran I , Saqib F , Wahid M , Guo Z
Ref : Metabolites , 13 : , 2023
Abstract : In folklore medicine, Conocarpus lancifolius is used to treat various illnesses. The main objective of this study was a comprehensive investigation of Conocarpus lancifolius leaf aqueous extract (CLAE) for its antioxidant, cardioprotective, anxiolytic, antidepressant and memory-enhancing capabilities by using different in vitro, in vivo and in silico models. The in vitro experimentation revealed that CLAE consumed an ample amount of total phenolics (67.70 +/- 0.15 microg GAE/mg) and flavonoids (47.54 +/- 0.45 microg QE/mg) with stronger antiradical effects through DPPH (IC(50) = 16.66 +/- 0.42 microg/mL), TAC (77.33 +/- 0.41 microg AAE/mg) and TRP (79.11 +/- 0.67 microg GAE/mg) assays. The extract also displayed suitable acetylcholinesterase (AChE) inhibitory (IC(50) = 110.13 +/- 1.71 microg/mL) activity through a modified Ellman's method. The toxicology examination presented no mortality or any signs of clinical toxicity in both single-dose and repeated-dose tests. In line with the cardioprotective study, the pretreatment of CLAE was found to be effective in relieving the isoproterenol (ISO)-induced myocardial injury in rats by normalizing the heart weight index, serum cardiac biomarkers, lipid profile and various histopathological variations. In the noise-stress-induced model for behavior attributes, the results demonstrated that CLAE has the tendency to increase the time spent in the central zone and elevated open arms in the open field and elevated plus maze tests (examined for anxiety assessment), reduced periods of immobility in the forced swimming test (for depression) and improved recognition and working memory in the novel object recognition and Morris water maze tests, respectively. Moreover, the LC-ESI-MS/MS profiling predicted 53 phytocompounds in CLAE. The drug-likeness and ADMET analysis exhibited that the majority of the identified compounds have reasonable physicochemical and pharmacokinetic profiles. The co-expression of molecular docking and network analysis indicated that top-ranked CLAE phytoconstituents act efficiently against the key proteins and target multiple signaling pathways to exert its cardiovascular-protectant, anxiolytic, antidepressant and memory-enhancing activity. Hence, this artifact illustrates that the observed biological properties of CLAE elucidate its significance as a sustainable source of bioactive phytochemicals, which appears to be advantageous for pursuing further studies for the development of new therapeutic agents of desired interest.
ESTHER : Khurm_2023_Metabolites_13_
PubMedSearch : Khurm_2023_Metabolites_13_
PubMedID: 37512501

Title : Eco-friendly and efficient extraction of polyphenols from Ligustrum robustum by deep eutectic solvent assisted ultrasound - Qin_2023_Food.Chem_429_136828
Author(s) : Qin G , Zhang F , Ren M , Chen X , Liu C , Li G , Gao Q , Qiao L , Jiang Y , Zhu L , Guo Y , Wang G
Ref : Food Chem , 429 :136828 , 2023
Abstract : An eco-friendly and efficient extraction method using deep eutectic solvents assisted ultrasound extraction (DESs-UAE) for the polyphenols from Ligustrum robustum was developed. Among the 34 kinds of DESs prepared, tetraethyl ammonium bromide: 1,2,4-butanol (Teab: 1,2,4-But) was proved to be a suitable extraction solvent based on the extraction efficiency. The extraction parameters including temperature, water content, liquid-solid ratio were optimized with response surface methodology (RSM). Under the optimal conditions, the total phenolic content (TPC) and total flavonoid content (TFC) were 101.46 +/- 2.96 mg GAE/g DW and 264.17 +/- 5.39 mg RE/g DW, respectively. Furthermore, the extraction mechanism of DESs-UAE was investigated by extraction kinetics, molecular dynamic simulation and theory calculations of interaction. In particular, 9 kinds of polyphenols compounds from Ligustrum robustum were firstly identified by UPLC-Q-TOF-MS. Moreover, the recovered polyphenols exhibited significant antioxidant, alpha-glucosidase inhibition, acetylcholinesterase inhibition and anticancer activity.
ESTHER : Qin_2023_Food.Chem_429_136828
PubMedSearch : Qin_2023_Food.Chem_429_136828
PubMedID: 37478601

Title : Genome-Wide Detection of Copy Number Variations and Evaluation of Candidate Copy Number Polymorphism Genes Associated With Complex Traits of Pigs - Zhang_2022_Front.Vet.Sci_9_909039
Author(s) : Zhang C , Zhao J , Guo Y , Xu Q , Liu M , Cheng M , Chao X , Schinckel AP , Zhou B
Ref : Front Vet Sci , 9 :909039 , 2022
Abstract : Copy number variation (CNV) has been considered to be an important source of genetic variation for important phenotypic traits of livestock. In this study, we performed whole-genome CNV detection on Suhuai (SH) (n = 23), Chinese Min Zhu (MZ) (n = 11), and Large White (LW) (n = 12) pigs based on next-generation sequencing data. The copy number variation regions (CNVRs) were annotated and analyzed, and 10,885, 10,836, and 10,917 CNVRs were detected in LW, MZ, and SH pigs, respectively. Some CNVRs have been randomly selected for verification of the variation type by real-time PCR. We found that SH and LW pigs are closely related, while MZ pigs are distantly related to the SH and LW pigs by CNVR-based genetic structure, PCA, V(ST), and QTL analyses. A total of 14 known genes annotated in CNVRs were unique for LW pigs. Among them, the cyclin T2 (CCNT2) is involved in cell proliferation and the cell cycle. The FA Complementation Group M (FANCM) is involved in defective DNA repair and reproductive cell development. Ten known genes annotated in 47 CNVRs were unique for MZ pigs. The genes included glycerol-3-phosphate acyltransferase 3 (GPAT3) is involved in fat synthesis and is essential to forming the glycerol triphosphate. Glutathione S-transferase mu 4 (GSTM4) gene plays an important role in detoxification. Eleven known genes annotated in 23 CNVRs were unique for SH pigs. Neuroligin 4 X-linked (NLGN4X) and Neuroligin 4 Y-linked (NLGN4Y) are involved with nerve disorders and nerve signal transmission. IgLON family member 5 (IGLON5) is related to autoimmunity and neural activities. The unique characteristics of LW, MZ, and SH pigs are related to these genes with CNV polymorphisms. These findings provide important information for the identification of candidate genes in the molecular breeding of pigs.
ESTHER : Zhang_2022_Front.Vet.Sci_9_909039
PubMedSearch : Zhang_2022_Front.Vet.Sci_9_909039
PubMedID: 35847642

Title : An efficient multi-enzyme cascade platform based on mesoporous metal-organic frameworks for the detection of organophosphorus and glucose - Cao_2022_Food.Chem_381_132282
Author(s) : Cao X , Guo Y , Zhao M , Li J , Wang C , Xia J , Zou T , Wang Z
Ref : Food Chem , 381 :132282 , 2022
Abstract : An efficient colorimetric detection platform based on multi-enzyme cascade has been developed for detection of organophosphorus. Firstly, the dual-enzyme platform was prepared and applied for sensitive glucose detection (detection limit 0.32 microM). And then three enzymes, including acetylcholinesterase, horseradish peroxidase and choline oxidase were encapsulated in cruciate flower-like zeolitic imidazolate framework-8 (CF-ZIF-8) through one-step co-precipitation to construct detection platform with acetylcholine chloride as substrate. The acephate inhibited the activity of acetylcholinesterase, obstructed the cascade reaction and reduced the production of H(2)O(2), resulting in the changes of color intensity for the colorimetric detection. With suitable size and porous structure, CF-ZIF-8 provided a good microenvironment for guaranteeing the activity and spatial proximity of enzymes. The multi-enzyme platform displayed great performances with the detection limit of 0.23 nM for acephate. It was applied to the detection of acephate in Chinese cabbage and romaine, verifying the practicability of this platform.
ESTHER : Cao_2022_Food.Chem_381_132282
PubMedSearch : Cao_2022_Food.Chem_381_132282
PubMedID: 35176684

Title : The effect of neostigmine on postoperative delirium after colon carcinoma surgery: a randomized, double-blind, controlled trial - Liu_2022_BMC.Anesthesiol_22_267
Author(s) : Liu F , Lin X , Lin Y , Deng X , Guo Y , Wang B , Dong R , Bi Y
Ref : BMC Anesthesiol , 22 :267 , 2022
Abstract : BACKGROUND: Postoperative delirium (POD) is a critical complication in patients accepting colon carcinoma surgery. Neostigmine, as a cholinesterase inhibitor, can enhance the transmission of cholinergic transmitters in synaptic space, and play an important role in maintaining the normal level of cognition, attention and consciousness. The objective of this study was to investigate the effect of neostigmine on POD and clinical prognosis. METHODS: A randomized, double-blind controlled trial was implemented in Qingdao Municipal Hospital Affiliated to Qingdao University. A total of 454 patients aged 40 to 90 years old accepted colon carcinoma surgery were enrolled between June 7, 2020, and June 7, 2021, with final follow-up on December 8, 2021. Patients were randomly assigned to two groups: the neostigmine group (group N) and the placebo group (group P), the patients in group N were injected with 0.04 mg/kg neostigmine and 0.02 mg/kg atropine intravenously. The primary endpoint was the incidence of POD, researchers evaluated the occurrence of POD by the Confusion Assessment Method (CAM) twice daily (at 10 a.m. and 2 p.m.) during the first 7 postoperative days, POD severity was assessed by the Memorial Delirium Assessment Scale (MDAS). The secondary endpoints were the extubating time, postanesthesia care unit (PACU) time, the incidence of various postoperative complications, length of hospital stays, and 6 months postoperative mortality. RESULTS: The incidence of POD was 20.20% (81/401), including 19.39% (38/196) in group N and 20.98% (43/205) in group P. There was no significant statistical significance in the incidence of POD between group N and group P (P > 0.05); Compared to group P, the extubating time and PACU time in group N were significantly reduced (P < 0.001), the incidence of postoperative pulmonary complications (POPCs) decreased significantly in group N (P < 0.05), while no significant differences were observed in postoperative hospital stay and mortality in 6 months between the two groups (P > 0.05). CONCLUSION: For patients accepted colon carcinoma surgery, neostigmine did not significantly reduce the incidence of POD, postoperative mortality and postoperative hospital stay, while it indeed reduced the extubating time, PACU time and the incidence of POPCs. TRIAL REGISTRATION: The randomized, double-blind, controlled trial was registered retrospectively at on 07/06/2020 (ChiCTR2000033639).
ESTHER : Liu_2022_BMC.Anesthesiol_22_267
PubMedSearch : Liu_2022_BMC.Anesthesiol_22_267
PubMedID: 35996073

Title : A Heterozygous LMF1 Gene Mutation (c.1523C>T), Combined With an LPL Gene Mutation (c.590G>A), Aggravates the Clinical Symptoms in Hypertriglyceridemia - Guo_2022_Front.Genet_13_814295
Author(s) : Guo D , Zheng Y , Gan Z , Guo Y , Jiang S , Yang F , Xiong F , Zheng H
Ref : Front Genet , 13 :814295 , 2022
Abstract : Hypertriglyceridemia is an important contributor to atherosclerotic cardiovascular disease (ASCVD) and acute pancreatitis. Familial hypertriglyceridemia is often caused by mutations in genes involved in triglyceride metabolism. Here, we investigated the disease-causing gene mutations in a Chinese family with hypertriglyceridemia and assessed the functional significance in vitro. Whole-exome sequencing (WES) was performed revealing that the severe hypertriglyceridemic proband carried a missense mutation (c.590G > A) in exon 5 of the LPL gene, as well as a missense mutation (c.1523C > T) in exon 10 of the LMF1 gene. Conservation analysis by Polyphen-2 showed that the 508 locus in the LMF1 protein and 197 locus in the LPL protein were highly conserved between different species. I-TASSER analysis indicated that the LMF1 c.1523C > T mutation and the LPL c.590G > A mutation changed the tertiary structure of the protein. A decrease in mRNA and protein expression was observed in 293T cells transfected with plasmids carrying the LMF1 c.1523C > T mutation. Subcellular localization showed that both wild-type (WT) and mutant LMF1 protein were localized at the cell cytoplasm. In the cell medium and cell lysates, these LMF1 and LPL gene mutations both caused a decreased LPL mass. Moreover, the combination of LMF1 and LPL gene mutations significantly decreased LPL levels compared to their individual effects on the LPL concentration. Both the clinical and in vitro data suggest that severe hypertriglyceridemia was of digenic origin caused by LMF1 and LPL mutation double heterozygosity in this patient.
ESTHER : Guo_2022_Front.Genet_13_814295
PubMedSearch : Guo_2022_Front.Genet_13_814295
PubMedID: 35368694

Title : A sensitive and stable acetylcholinesterase biosensor with TiO(2) nanoparticles anchored on graphitic carbon nanofibers for determination of organophosphate pesticides - Tao_2022_Anal.Methods__
Author(s) : Tao S , Guo Y , Wang S , Xu F , Zhou X , Guo Q
Ref : Anal Methods , : , 2022
Abstract : Electrode materials play a central role in assembling biosensors. In this work, a titanium dioxide nanoparticle loaded graphitized carbon nanofiber (TiO(2)/GNF) composite is prepared for the sensitive detection of organophosphorus pesticide residues (OPs). The TiO(2)/GNF composite with superior conductivity, catalytic activity and biocompatibility offers an extremely hydrophilic surface for the effective immobilization of acetylcholinesterase (AChE). Furthermore, the Ti atoms of TiO(2)/GNFs could coordinate with AChE to improve its stability, and TiO(2) has a strong adsorption on OPs. The developed AChE/TiO(2)/GNFs/GCE biosensor showed a high affinity to acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with an apparent Michaelis-Menten constant (K(m)) of 50 microM. The constructed AChE/TiO(2)/GNFs/GCE biosensor exhibits a wide detection linear range (1.0 x 10(-13) M to 1.0 x 10(-8) M) with a low detection limit (3.3 fM) for paraoxon determination (a model of OPs). In addition, the developed biosensor possesses remarkable anti-interference, acceptable reproducibility and good long-term stability, and is successfully used for the determination of OPs in lake water, providing a new strategy for the analysis of OPs in ecological environments.
ESTHER : Tao_2022_Anal.Methods__
PubMedSearch : Tao_2022_Anal.Methods__
PubMedID: 35666469

Title : Protective effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in aging mice - Guo_2022_Front.Pharmacol_13_992269
Author(s) : Guo Y , Qu Y , Li W , Shen H , Cui J , Liu J , Li J , Wu D
Ref : Front Pharmacol , 13 :992269 , 2022
Abstract : The aging process of human beings is accompanied by the decline of learning and memory ability and progressive decline of brain function, which induces Alzheimer's Disease (AD) in serious cases and seriously affects the quality of patient's life. In recent years, more and more studies have found that natural plant antioxidants can help to improve the learning and memory impairment, reduce oxidative stress injury and aging lesions in tissues. This study aimed to investigate the effect of Monarda didymaL. essential oil and its main component thymol on learning and memory impairment in D-galactose-induced aging mice and its molecular mechanism. The composition of Monarda didymaL. essential oil was analyzed by Gas Chromatography-Mass Spectrometer (GC-MS). A mouse aging model was established by the subcutaneous injection of D-galactose in mice. The behavior changes of the mice were observed by feeding the model mice with essential oil, thymol and donepezil, and the histopathological changes of the hippocampus were observed by HE staining. And the changes of acetylcholinesterase (AchE), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and the content of malondialdehyde (MDA) in hippocampal tissues were detected by corresponding kits. The expression of mitogen activated protein kinase (MAPK) and nuclear factor E2 related factor 2 (Nrf2) pathways related proteins were detected by western blot. Animal experimental results showed that compared with model group, the above indexes in Monarda didymaL. essential oil and thymol groups improved significantly in a dose-dependent manner. Monarda didymaL. essential oil and its main active component thymol can improve the learning and memory impairment of aging mice to some extent, and Nrf2 and MAPK pathways may be involved in its action process.
ESTHER : Guo_2022_Front.Pharmacol_13_992269
PubMedSearch : Guo_2022_Front.Pharmacol_13_992269
PubMedID: 36105199

Title : A highly sensitive and selective enzyme activated fluorescent probe for in vivo profiling of carboxylesterase 2 - Liu_2022_Anal.Chim.Acta_1221_340126
Author(s) : Liu SY , Zou X , Guo Y , Gao X
Ref : Anal Chim Acta , 1221 :340126 , 2022
Abstract : Carboxylesterase 2 (CES2) is a serine-type hydrolase that plays important roles in xenobiotic detoxification and lipid metabolism. Its abnormal expression is highly associated with diseases such as diabetes and carcinoma. To date, intense attention has been attracted to CES2 targeted drug discovery and disease diagnosis. Thus, to further explore the physiological function of CES2 is of great importance. However, until now, most medical research on CES2 function and activity assays is still dependent on conventional methods, which could hardly specify CES2 activity. Therefore, there is an urgent need to develop efficient tools for selective measurement and sensing of endogenous CES2 in complicated biological system. In this study, we report the design and construction of an enzyme-activated fluorescent probe for CES2 activity sensing. The acquired probe DXMB was characterized as a highly specific and sensitive fluorescent probe for CES2 and possessed superior binding affinity, overall catalytic efficiency, and reaction velocity when compared with the reported CES2 probes. By application of DXMB into living system, it was capable of sensing endogenous CES2 in living cells, dynamic monitoring CES2 in zebrafish development, and visualizing tissue distribution of CES2 in nude mice. Most importantly, abnormally elevated CES2 activity in the intestine of diabetic model mice was first revealed, while significantly decreased CES2 activity in the liver was validated by DXMB. These results indicated that DXMB could serve as a vital tool for further CES2-related biological and medical research.
ESTHER : Liu_2022_Anal.Chim.Acta_1221_340126
PubMedSearch : Liu_2022_Anal.Chim.Acta_1221_340126
PubMedID: 35934362

Title : Thyroid endocrine disruption and neurotoxicity of gestodene in adult female mosquitofish (Gambusia affinis) - Tan_2022_Chemosphere__137594
Author(s) : Tan J , Liang C , Guo Y , Zou H , Ye J , Hou L , Wang X
Ref : Chemosphere , :137594 , 2022
Abstract : The frequent detection of progestins in various aquatic environments and their potential endocrine disruptive effects in fish have attracted increasing attention worldwide. However, data on their effects on thyroid function and neurotoxicity in fish are limited, and the underlying mechanisms remain unclear. Here, the effects of gestodene (GES, a common progestin) on the thyroid endocrine and nervous systems of mosquitofish (Gambusia affinis) were studied. Adult female fish were exposed to GES at environmentally relevant concentrations (4.4-378.7 ng/L) for 60 days. The results showed that exposure to 378.7 ng/L GES caused a significant decrease in fish growth compared with the control and a marked reduction in the total distance traveled (50.6%) and swimming velocity (40.1-61.9%). The triiodothyronine (T3) levels were significantly increased by GES in a dose-dependent manner, whereas those of tetraiodothyronine (T4) were significantly decreased only at the G500 concentration. The acetylcholinesterase (AChE) activity was decreased significantly in the 4.42 ng/L GES treatments, but increased significantly at 378.67 ng/L. In the brain, a strong increase in the transcriptional levels of bdnf, trh, and dio2 was observed in fish after the 378.7 ng/L treatment. In addition, chronic exposure to GES caused colloid depletion with a concentration-dependent manner in the thyroid, and angiectasis, congestion, and vacuolar necrosis in the brain. These findings provide a better understanding of the effects of GES and associated underlying mechanisms in G. affinis.
ESTHER : Tan_2022_Chemosphere__137594
PubMedSearch : Tan_2022_Chemosphere__137594
PubMedID: 36538954

Title : Threaded 3D microfluidic paper analytical device-based ratiometric fluorescent sensor for background-free and visual detection of organophosphorus pesticides - Tong_2022_Biosens.Bioelectron_222_114981
Author(s) : Tong X , Cai G , Xie L , Wang T , Zhu Y , Peng Y , Tong C , Shi S , Guo Y
Ref : Biosensors & Bioelectronics , 222 :114981 , 2022
Abstract : With the increasing concerns of food safety and environmental protection, it is desirable to develop reliable, effective, and portable sensors for detection of organophosphorus pesticides (OPs). Here, a cascade reaction system integrated with threaded 3D microfluidic paper analytical device (3D microPAD) was firstly developed for background-free and visual detection of OPs in agricultural samples. Butyrylcholinesterase (BChE) hydrolyzed acetylcholine into thiocholine (TCh), which reduced MnO(2) nanosheets into Mn(2+). With addition of OPs, BChE activity was irreversibly inhibited, and the generation of TCh and the reduction of MnO(2) nanosheets were prevented. Then the remaining MnO(2) nanosheets oxidized o-phenylenediamine into 2,3-diaminophenazine with yellow-emission fluorescence, which quenched the fluorescence intensity of red-emission carbon dots (RCDs) via inner-filter effect. Based on above mechanism, a ratiometric fluorescent system was established for OPs detection. Threaded 3D microPAD consisted of 4 layers, which allowed to load and/or add reagents to trigger the cascade reaction system for OPs detection. The fluorescent images presented distinguishable color variations from red to yellow with dichlorvos concentrations ranging from 2.5 to 120 microgsL(-1), and the limit of detection was 1.0 microgsL(-1). In the practical samples testing, threaded 3D microPAD can eliminate background influence on fluorescent signal for OPs detection. Threaded 3D microPAD integrated with ratiometric sensing platform has merits of accuracy response, facile operation, and background-free detection, which supplies a new alternative approach for on-site pesticide detection.
ESTHER : Tong_2022_Biosens.Bioelectron_222_114981
PubMedSearch : Tong_2022_Biosens.Bioelectron_222_114981
PubMedID: 36473422

Title : A pendant droplet-based sensor for the detection of acetylcholinesterase and its inhibitors - Li_2021_Chem.Commun.(Camb)_57_8909
Author(s) : Li B , Guo Y , Jiang Y , Lin JM , Hu Q , Yu L
Ref : Chem Commun (Camb) , 57 :8909 , 2021
Abstract : In this work, a pendant droplet-based sensor is developed for the rapid and label-free detection of acetylcholinesterase (AChE) and its inhibitors. The detection limit of AChE reaches 0.17 mU mL(-1). The pIC(50) values of AChE inhibitors such as neostigmine, rivastigmine and galantamine are determined to be 0.45 microM, 0.64 microM and 4.93 microM, respectively.
ESTHER : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedSearch : Li_2021_Chem.Commun.(Camb)_57_8909
PubMedID: 35225993

Title : Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer's disease - Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
Author(s) : Zhang J , Liu R , Zhang D , Zhang Z , Zhu J , Xu L , Guo Y
Ref : Colloids Surf B Biointerfaces , 200 :111584 , 2021
Abstract : Nanopeptide assembled from peptide-anchored nanoparticles possess an enormous research potential in the field of cellular medicine and disease treatment. The aim of this study was to explore the neuroprotective effects of maize tetrapeptide anchored gold nanoparticles against l-glutamic acid-induced PC12 cell apoptosis and a murine Alzheimer's disease model induced by aluminum chloride and d-galactose. The results revealed that the nanopeptide antioxidant inhibited intracellular ROS accumulation and promoted cell differentiation than that of maize bioactive tetrapeptide. Compared with untreated Alzheimer's disease model mice, nanopeptide administration shortened the escape latency time in a water maze test and improved the movements in the autonomic activity test. After 16 days of nanopeptide administration, the central cholinergic system function of acetylcholine and cholineacetyltransferase were enhanced, and the level of acetylcholinesterase was reduced. It also increased superoxide dismutase and glutathione peroxidase activity in sera and hypothalami. Moreover, nanopeptide treatment upregulated cerebral nuclear factor erythroid 2-related factor 2 and heme-oxygenase-1 and downregulated kelch-like ECH-associated protein 1 relative to untreated Alzheimer's disease model mice. Thus, the novel nanopeptide is expected to be used as the neuroprotective agent to prevent Alzheimer's disease.
ESTHER : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedSearch : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedID: 33508658

Title : Phlorizin exerts potent effects against aging induced by D-galactose in mice and PC12 cells - Liu_2021_Food.Funct__
Author(s) : Liu Y , Guo Y , Xu L , Wang H
Ref : Food Funct , : , 2021
Abstract : Phlorizin is the main active ingredient of apple peel and has potential utilization value. Some recent studies have suggested that phlorizin may have antioxidant capacity and protect the liver. The injection of a low dose of d-galactose can cause some changes that resemble accelerated aging in mice. This study explored the protective effects of phlorizin on d-galactose-induced mice and PC12 cells. In this study, ICR mice were divided into a normal group (NOR), a d-galactose model group (d-gal) and phlorizin treatment groups (100 mg kg-1, 200 mg kg-1 and 400 mg kg-1). In addition to the NOR group, four other groups were injected with d-galactose (120 mg kg-1) for 12 weeks. The results showed that phlorizin reduced the decline of strength, coordination and spatial memory caused by aging, increased the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), increased total antioxidant capacity (T-AOC), and reduced the content of malondialdehyde (MDA). On the other hand, phlorizin increased the levels of interleukin-2 (IL-2) and acetylcholine (ACh), reduced the release of interleukin-6 (IL-6), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and decreased the activity of acetylcholinesterase (AChE) in the brain, improved the expression of antioxidant genes related to the nuclear factor E2-related factor 2 (Nrf2) pathway, and reduced the occurrence of morphological lesions in the hippocampus and liver. In addition, phlorizin improved cell viability and reduced the cytotoxicity of d-galactose-induced oxidative stress in PC12 cells. Meanwhile, the protective effect of phlorizin was abolished in Nrf2 gene knockdown PC12 cells. Furthermore, molecular docking showed that phlorizin could bind Keap1 protein, which can interact with Nrf2 protein. Therefore, these results suggest that phlorizin may delay senescence and enhance antioxidant capacity through the Nrf2 pathway.
ESTHER : Liu_2021_Food.Funct__
PubMedSearch : Liu_2021_Food.Funct__
PubMedID: 33565551

Title : Determination of methomyl in grain using deep eutectic solvent-based extraction combined with fluorescence-based enzyme inhibition assays - Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
Author(s) : Guo Y , Wang H , Chen Z , Jing X , Wang X
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 266 :120412 , 2021
Abstract : A deep eutectic solvent (DES)-based extraction method is established to facilitate the determination of methomyl in grain via enzyme inhibition fluorescence. The environmentally-friendly DES was synthesized from proline and ethylene glycol and used as a green replacement for traditional extraction solvents that are generally toxic. The DES was added to grain samples and vortex extraction of methomyl, the supernatant was then collected for fluorescence detection. Biomass carbon quantum dots (CQDs) synthesized from millet were used as fluorescent probes. Acetylcholinesterase catalyzes the hydrolysis of acetylthiocholine iodide to thiocholine. The positively-charged thiocholine interacts electrostatically with the negatively-charged quantum dots resulting in the quenching of their fluorescent emission. The pesticide extract solution blocks the enzyme activity and thus recovers the fluorescent from the quantum dots. The fluorescence response was correlated with the amount of methomyl residue in the grain over the range 0.01 to 5 mg kg(-1). The limit of detection was found to be 0.003 mg kg(-1), and the limit of quantification 0.01 mg kg(-1). Recoveries of 86.5% to 107.8% were obtained using real samples, including millet, rice, wheat, and barley, with a relative standard deviation of less than 3.8%. The method is efficient and convenient and has good application prospects for extracting and detecting pesticides in grain samples.
ESTHER : Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
PubMedSearch : Guo_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_266_120412
PubMedID: 34597870

Title : The additive memory and healthspan enhancement effects by the combined treatment of mature silkworm powders and Korean angelica extracts - Nguyen_2021_J.Ethnopharmacol__114520
Author(s) : Nguyen P , Kim KY , Kim AY , Kang S , Osabutey AF , Jin H , Guo Y , Park H , Suh JW , Koh YH
Ref : J Ethnopharmacol , :114520 , 2021
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Silkworm (Bombyx mori) and Korean angelica (KoAg; Angelica gigas Nakai) have been widely used as traditional oriental medicines in Korea, China, and Japan to treat various diseases such as anemia, cold, diabetes, palsy, stroke, etc. Steamed and freeze-dried mature silkworm powder, also known as HongJam (HJ), and extracts of KoAg root (KoAgE) are currently sold in Korea as functional foods to improve memory, cognition, and liver functions. However, the molecular and pharmacological basis for the improvement of brain functions of HJ and KoAgE has not yet been elucidated. AIM OF STUDY: This study aimed to elucidate the molecular basis underlying the memory-enhancing effects of HJ and KoAgE and determine whether administration of HJ and KoAgE complexes (HJ + KoAgC) has additive memory and healthspan-enhancing effects. MATERIALS AND METHODS: The MCI mouse models generated by intraperitoneal injection of Scopolamine (Sco-IP) were orally administered with HJ and KoAgE alone or as complexes. Their memory-enhancing effects were examined on spatial, fear-aggravated, and social memories and compared with control or Donepezil (Dp) treatment. The activities of mitochondria complex (MitoCom) I-IV and acetylcholinesterase (AChE) and the amounts of ATP in the mouse brains were examined. The Drosophila model was used to investigate lifespan- and healthspan-promoting effects of HJ + KoAgC. RESULTS: Administration of HJ + KoAgC produced more memory-enhancing effects than administration of HJ or KoAgE alone or Dp. The increase in MitoCom I-IV activities and ATP amounts and the decrease in AChE activities in the mouse brains were the molecular basis for the memory enhancement. The greatest improvement in memory and mitochondrial function was observed when the mice were administered the 1:0.8 ratio of HJ + KoAgC. Administration of HJ + KoAgC to Drosophila prolonged the lifespan and the healthspan and increased the amounts of ATP. CONCLUSION: HJ + KoAgC had superior effects on memory improvement and healthspan extension by increasing mitochondrial activities and ATP amounts in treated animal models.
ESTHER : Nguyen_2021_J.Ethnopharmacol__114520
PubMedSearch : Nguyen_2021_J.Ethnopharmacol__114520
PubMedID: 34391862

Title : Donepezil Ameliorates Pulmonary Arterial Hypertension by Inhibiting M2-Macrophage Activation - Qiu_2021_Front.Cardiovasc.Med_8_639541
Author(s) : Qiu H , Zhang Y , Li Z , Jiang P , Guo S , He Y , Guo Y
Ref : Front Cardiovasc Med , 8 :639541 , 2021
Abstract : Background: The beneficial effects of parasympathetic stimulation in pulmonary arterial hypertension (PAH) have been reported. However, the specific mechanism has not been completely clarified. Donepezil, an oral cholinesterase inhibitor, enhances parasympathetic activity by inhibiting acetylcholinesterase, whose therapeutic effects in PAH and its mechanism deserve to be investigated. Methods: The PAH model was established by a single intraperitoneal injection of monocrotaline (MCT, 50 mg/kg) in adult male Sprague-Dawley rats. Donepezil was administered via intraperitoneal injection daily after 1 week of MCT administration. At the end of the study, PAH status was confirmed by echocardiography and hemodynamic measurement. Testing for acetylcholinesterase activity and cholinergic receptor expression was used to evaluate parasympathetic activity. Indicators of pulmonary arterial remodeling and right ventricular (RV) dysfunction were assayed. The proliferative and apoptotic ability of pulmonary arterial smooth muscle cells (PASMCs), inflammatory reaction, macrophage infiltration in the lung, and activation of bone marrow-derived macrophages (BMDMs) were also tested. PASMCs from the MCT-treated rats were co-cultured with the supernatant of BMDMs treated with donepezil, and then, the proliferation and apoptosis of PASMCs were evaluated. Results: Donepezil treatment effectively enhanced parasympathetic activity. Furthermore, it markedly reduced mean pulmonary arterial pressure and RV systolic pressure in the MCT-treated rats, as well as reversed pulmonary arterial remodeling and RV dysfunction. Donepezil also reduced the proliferation and promoted the apoptosis of PASMCs in the MCT-treated rats. In addition, it suppressed the inflammatory response and macrophage activation in both lung tissue and BMDMs in the model rats. More importantly, donepezil reduced the proliferation and promoted the apoptosis of PASMCs by suppressing M2-macrophage activation. Conclusion: Donepezil could prevent pulmonary vascular and RV remodeling, thereby reversing PAH progression. Moreover, enhancement of the parasympathetic activity could reduce the proliferation and promote the apoptosis of PASMCs in PAH by suppressing M2-macrophage activation.
ESTHER : Qiu_2021_Front.Cardiovasc.Med_8_639541
PubMedSearch : Qiu_2021_Front.Cardiovasc.Med_8_639541
PubMedID: 33791350

Title : Bioremediation of triphenyl phosphate by Pycnoporus sanguineus: Metabolic pathway, proteomic mechanism and biotoxicity assessment - Feng_2021_J.Hazard.Mater_417_125983
Author(s) : Feng M , Zhou J , Yu X , Wang H , Guo Y , Mao W
Ref : J Hazard Mater , 417 :125983 , 2021
Abstract : So far, no information about the biodegradability of TPhP by white rot fungi has previously been made available, herein, Pycnoporus sanguineus was used as the representative to investigate the potential of white rot fungi in TPhP bioremediation. The results suggested that the biodegradation efficiency of 5 mg/L TPhP by P. sanguineus was 62.84% when pH was adjusted to 6 and initial glucose concentration was 5 g/L. Seven biodegradation products were identified, indicating that TPhP was biotransformed through oxidative cleavage, hydroxylation and methylation. The proteomic analysis revealed that cytochrome P450s, aromatic compound dioxygenase, oxidizing species-generating enzymes, methyltransferases and MFS general substrate transporters might occupy important roles in TPhP biotransformation. Carboxylesterase and glutathione S-transferase were induced to resist TPhP stress. The biotreatment by P. sanguineus contributed to a remarkable decrease of TPhP biotoxicity. Bioaugmentation with P. sanguineus could efficiently promote TPhP biodegradation in the water-sediment system due to the cooperation between P. sanguineus and some putative indigenous degraders, including Sphingobium, Burkholderia, Mycobacterium and Methylobacterium. Overall, this study provided the first insights into the degradation pathway, mechanism and security risk assessment of TPhP biodegradation by P. sanguineus and verified the feasibility of utilizing this fungus for TPhP bioremediation applications.
ESTHER : Feng_2021_J.Hazard.Mater_417_125983
PubMedSearch : Feng_2021_J.Hazard.Mater_417_125983
PubMedID: 33975170

Title : The Impact of ABCB1 and CES1 Polymorphisms on Dabigatran Pharmacokinetics in Healthy Chinese Subjects - Liu_2021_Pharmgenomics.Pers.Med_14_477
Author(s) : Liu Y , Yang C , Qi W , Pei Z , Xue W , Zhu H , Dong M , Guo Y , Cong D , Wang F
Ref : Pharmgenomics Pers Med , 14 :477 , 2021
Abstract : Dabigatran is a novel direct oral anticoagulant agent, whose plasma concentration is closely related to bleeding risk. Genetic polymorphisms can affect the level of plasma dabigatran. The purpose of this study was to understand the relationship between dabigatran-related genes and the plasma level of dabigatran in healthy Chinese subjects after taking a single oral dose. This study was performed with a single-center, single-dose, randomized, open-label, and four-period crossover trial design under both fasting and fed conditions. A total of 106 eligible healthy subjects were enrolled in the study and 104 were genotyped. One-way analysis of variance (ANOVA) was used to compare pharmacokinetic parameters among different genotypes and linear regression was applied to explore the multiplicative interaction between variables. In this study, we found that the genotype frequencies of CES1 rs2244613 and CES1 rs8192935 were significantly different between Chinese and Caucasians, but the genotype frequencies of ABCB1 rs1045642 and ABCB1 rs4148738 were similar in both populations. CES1 rs8192935 were associated with the peak concentration of dabigatran. There was no significant gender difference in the exposure level of dabigatran. Furthermore, food significantly delayed the absorption of dabigatran but had little effect on C(max) and AUC(0-).
ESTHER : Liu_2021_Pharmgenomics.Pers.Med_14_477
PubMedSearch : Liu_2021_Pharmgenomics.Pers.Med_14_477
PubMedID: 33935512

Title : Rational design of a near-infrared fluorescence probe for highly selective sensing butyrylcholinesterase (BChE) and its bioimaging applications in living cell - Ma_2020_Talanta_219_121278
Author(s) : Ma J , Lu X , Zhai H , Li Q , Qiao L , Guo Y
Ref : Talanta , 219 :121278 , 2020
Abstract : In the current work, a near-infrared (NIR) fluorescent probe (CyClCP) was developed for fast (35 min), highly sensitive (LOD of 3.75 U/L) and selective response to BChE in vitro and in vivo. Upon the addition of BChE, CyClCP could be efficiently activated with remarkable NIR ((em) = 708 nm) fluorescence enhancement and obvious absorbance red shift (581 nm-687 nm). Specifically, according to the subtle differences structural features and substrate preference between BChE and its sister enzyme AChE, CyClCP was constructed by introducing chlorine atom at the ortho-position of the phenolic hydroxyl in the previous reported probe (CyCP). Fortunately, CyClCP exhibited better selectivity towards BChE over AChE compared with CyCP. This molecular design strategy was further rationalized by docking molecular of fluorescence probes (CyClCP and CyCP) and enzymes (BChE and AChE). Finally, CyClCP was membrane permeable and successfully applied to image endogenous BChE level in HepG2 and LO2 cells. Therefore, CyClCP could serve as a promising tool for BChE-related physiological function studies in complex biological systems.
ESTHER : Ma_2020_Talanta_219_121278
PubMedSearch : Ma_2020_Talanta_219_121278
PubMedID: 32887168

Title : Bioconcentration and developmental neurotoxicity of novel brominated flame retardants, hexabromobenzene and pentabromobenzene in zebrafish - Chen_2020_Environ.Pollut_268_115895
Author(s) : Chen X , Guo W , Lei L , Guo Y , Yang L , Han J , Zhou B
Ref : Environ Pollut , 268 :115895 , 2020
Abstract : The flame retardants hexabromobenzene (HBB) and pentabromobenzene (PBB) have been extensively used and become ubiquitous pollutants in the aquatic environment and biota, but their potential toxic effects on wildlife remained unknown. In this study, by using zebrafish (Danio rerio) as a model, the bioconcentration and developmental neurotoxicity were investigated. Zebrafish embryos were exposed to HBB and PBB (0, 30, 100 and 300 g/L) from 2 until 144 h post-fertilization (hpf). Chemical analysis showed bioconcentrations of both chemicals, while HBB is readily metabolized to PBB in zebrafish larvae. Embryonic exposure to both chemicals did not cause developmental toxicity, but induced locomotor behavioral anomalies in larvae. Molecular docking results indicated that both chemicals could bind to zebrafish acetylcholinesterase (AChE). Furthermore, HBB and PBB significantly inhibited AChE activities, accompanied by increased contents of acetylcholine and decreased choline in larvae. Downregulation of the genes associated with central nervous system (CNS) development (e.g., mbp, alpha1-tubulin, gfap, shha) as well as the corresponding proteins (e.g., Mbp, alpha1-Tubulin) was observed, but gap-43 was upregulated at both gene and protein levels. Together, our results indicate that both HBB and PBB exhibit developmental neurotoxicity by affecting various parameters related to CNS development and indications for future toxicological research and risk assessment of the novel brominated flame retardants.
ESTHER : Chen_2020_Environ.Pollut_268_115895
PubMedSearch : Chen_2020_Environ.Pollut_268_115895
PubMedID: 33120153

Title : Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial - Wang_2020_Curr.Med.Res.Opin_36_1107
Author(s) : Wang W , Yao J , Guo X , Guo Y , Yan C , Liu K , Zhang Y , Wang X , Li H , Wen Z , Li S , Xiao X , Liu W , Li Z , Zhang L , Shao S , Ye S , Qin G , Li Y , Li F , Zhang X , Li X , Peng Y , Deng H , Xu X , Zhou L , Huang Y , Cao M , Xia X , Shi M , Dou J , Yuan J
Ref : Curr Med Res Opin , 36 :1107 , 2020
Abstract : Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program.
ESTHER : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedSearch : Wang_2020_Curr.Med.Res.Opin_36_1107
PubMedID: 32338063

Title : Hyperbaric oxygen therapy may be effective to improve hypoxemia in patients with severe COVID-2019 pneumonia: two case reports - Guo_2020_Undersea.Hyperb.Med_47_181
Author(s) : Guo D , Pan S , Wang M , Guo Y
Ref : Undersea Hyperb Med , 47 :181 , 2020
Abstract : Objectives: To determine whether hyperbaric oxygen (HBO2) therapy be effective to improve hypoxemia for severe COVID-19 pneumonia patients. Methods: Two male patients ages 57 and 64 years old were treated. Each met at least one of the following criteria: shortness of breath; respiratory rate (RR) >/=30 breaths/minute; finger pulse oxygen saturation (SpO2)
ESTHER : Guo_2020_Undersea.Hyperb.Med_47_181
PubMedSearch : Guo_2020_Undersea.Hyperb.Med_47_181
PubMedID: 32574433

Title : Correlation analysis between CARMEN variants and alcohol-induced osteonecrosis of the femoral head in the Chinese population - Guo_2020_BMC.Musculoskelet.Disord_21_547
Author(s) : Guo Y , Cao Y , Gong S , Zhang S , Hou F , Zhang X , Hu J , Yang Z , Yi J , Luo D , Chen X , Song J
Ref : BMC Musculoskelet Disord , 21 :547 , 2020
Abstract : BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a complicated disease associated with trauma, hormone abuse and excessive alcohol consumption. Polymorphisms of long non-coding RNAs have been also linked with the development of ONFH. Our research aimed to explore the relationship between CARMEN (Cardiac Mesoderm Enhancer-Associated Non-Coding RNA) variants and ONFH risk. METHODS: Our study used Agena MassARRAY Assay to genotype 6 selected single nucleotide polymorphisms (SNPs) in 731 participants (308 alcohol-induced ONFH patients and 423 controls). We used odds ratios (ORs) and 95% confidence intervals (CIs) to calculate the effect of gene polymorphisms on the occurrence of alcohol-induced ONFH by logistic regression analysis and haplotype analysis. RESULTS: Our overall analysis illustrated that rs13177623 and rs12654195 had an association with a reduced risk of ONFH after adjustment for age and gender. We also found that rs13177623, rs12654195 and rs11168100 were associated with a decreased susceptibility to alcohol-induced ONFH in people <=45 years. In addition, the necrotic sites stratification analysis showed that rs12654195 was only found to be related to alcohol-induced ONFH risk in the recessive model. In patients with different clinical stages, rs353300 was observed to be associated with a higher incidence of ONFH. Individuals with different genotypes of rs13177623, rs12654195 and rs11168100 had significantly different clinical parameters (cholinesterase, globulin, percentage of neutrophils and the absolute value of lymphocytes). CONCLUSIONS: Our data provided new light on the association between CARMEN polymorphisms and alcohol-induced ONFH risk in the Chinese Han population.
ESTHER : Guo_2020_BMC.Musculoskelet.Disord_21_547
PubMedSearch : Guo_2020_BMC.Musculoskelet.Disord_21_547
PubMedID: 32799824

Title : Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer's disease - Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330
Author(s) : Mo J , Chen T , Yang H , Guo Y , Li Q , Qiao Y , Lin H , Feng F , Liu W , Chen Y , Liu Z , Sun H
Ref : J Enzyme Inhib Med Chem , 35 :330 , 2020
Abstract : Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer's disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 +/- 0.11 microM; 15j, eqBChE IC50 = 0.16 +/- 0.04 microM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD.
ESTHER : Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330
PubMedSearch : Mo_2020_J.Enzyme.Inhib.Med.Chem_35_330
PubMedID: 31856607

Title : Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish - Ma_2020_ACS.Sens_5_83
Author(s) : Ma J , Si T , Yan C , Li Y , Li Q , Lu X , Guo Y
Ref : ACS Sens , 5 :83 , 2020
Abstract : Acetylcholinesterase (AChE) plays crucial roles in numerous physiological processes such as cell differentiation, cell apoptosis, and nerve tissue developments. Hence, it is highly necessary to design a fluorescent probe for monitoring AChE activity in complex living organisms. In this work, a near-infrared (NIR) off-on probe (CyN) was developed for AChE detection. CyN was exactly synthesized by introducing an N,N-dimethyl carbamyl moiety to hemicyanine (CyOH). AChE can "light up" strong NIR fluorescence through a cleavage special ester bond and transform CyN into CyOH. Moreover, CyN was qualified for imaging the dynamic change of AChE activity in PC12 cells with retinoic acid or hypoxia stimulation. In particular, the probe has been successfully applied for in situ tracing the intact distribution of AChE in living zebrafish. The observations indicate that major occurrence sites of endogenic AChE on zebrafish are the yolk sac and neuromasts. Overall, CyN shows great potential for use in AChE-related physiological studies.
ESTHER : Ma_2020_ACS.Sens_5_83
PubMedSearch : Ma_2020_ACS.Sens_5_83
PubMedID: 31875385
Gene_locus related to this paper: danre-ACHE

Title : Type 2 diabetes mellitus decreases systemic exposure of clopidogrel active metabolite through upregulation of P-glycoprotein in rats - Yao_2020_Biochem.Pharmacol__114142
Author(s) : Yao H , Gu J , Shan Y , Wang Y , Chen X , Sun D , Guo Y
Ref : Biochemical Pharmacology , :114142 , 2020
Abstract : Patients with diabetic mellitus tend to have a poor response to clopidogrel (Clop) due to reduced generation of active metabolite (Clop-AM). However, the underlying mechanism is not elucidated. A type 2 diabetic mellitus (T2DM) rat model was established by combining high-fat diet feeding and low-dose streptozotocin (STZ) injection. The reduced Clop-AM exposure was observed in T2DM rats after oral administration of Clop. However, in vitro liver microsomes incubated with Clop exhibited increased Clop-AM levels in T2DM rats due to a significant decrease in carboxylesterase (CES)1 expression and activity and a significant increase in the expression or activity of CYP1A2 and CYP3A. Interestingly, different from oral administration, the significantly increased Cmax of Clop-AM was observed in T2DM rats after intravenous injection, with no difference in AUC0-t and t1/2 values between the two strains. Meanwhile, in situ single -pass intestinal perfusion study showed lower absorption rate constant (Ka) and effective apparent permeability values (Peff) of Clop in T2DM rats than in control rats. It is explained by the increased expression or function of P-glycoprotein (P-gp) and pregnane X receptor (PXR) in duodenum and jejunum of T2DM rats. Moreover, the decreased Clop-AM level in T2DM rats was eliminated by the pretreatment of cyclosporin A, a P-gp inhibitor. It suggests that intestinal absorption, not hepatic metabolism is responsible for the reduced Clop-AM exposure in T2DM rats. P-gp might be the key factor causing the reduction of Clop absorption, consequently making less Clop available for Clop-AM formation.
ESTHER : Yao_2020_Biochem.Pharmacol__114142
PubMedSearch : Yao_2020_Biochem.Pharmacol__114142
PubMedID: 32653591

Title : Correction to Near-Infrared Fluorescence Probe for Evaluating Acetylcholinesterase Activity in PC12 Cells and In Situ Tracing AChE Distribution in Zebrafish -
Author(s) : Ma J , Si T , Yan C , Li Y , Li Q , Lu X , Guo Y
Ref : ACS Sens , : , 2020
PubMedID: 32196313
Gene_locus related to this paper: danre-ACHE

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

Title : Synthesis, physicochemical properties, and health aspects of structured lipids: A review - Guo_2020_Compr.Rev.Food.Sci.Food.Saf_19_759
Author(s) : Guo Y , Cai Z , Xie Y , Ma A , Zhang H , Rao P , Wang Q
Ref : Compr Rev Food Sci Food Saf , 19 :759 , 2020
Abstract : Structured lipids (SLs) refer to a new type of functional lipids obtained by chemically, enzymatically, or genetically modifying the composition and/or distribution of fatty acids in the glycerol backbone. Due to the unique physicochemical characteristics and health benefits of SLs (for example, calorie reduction, immune function improvement, and reduction in serum triacylglycerols), there is increasing interest in the research and application of novel SLs in the food industry. The chemical structures and molecular architectures of SLs define mainly their physicochemical properties and nutritional values, which are also affected by the processing conditions. In this regard, this holistic review provides coverage of the latest developments and applications of SLs in terms of synthesis strategies, physicochemical properties, health aspects, and potential food applications. Enzymatic synthesis of SLs particularly with immobilized lipases is presented with a short introduction to the genetic engineering approach. Some physical features such as solid fat content, crystallization and melting behavior, rheology and interfacial properties, as well as oxidative stability are discussed as influenced by chemical structures and processing conditions. Health-related considerations of SLs including their metabolic characteristics, biopolymer-based lipid digestion modulation, and oleogelation of liquid oils are also explored. Finally, potential food applications of SLs are shortly introduced. Major challenges and future trends in the industrial production of SLs, physicochemical properties, and digestion behavior of SLs in complex food systems, as well as further exploration of SL-based oleogels and their food application are also discussed.
ESTHER : Guo_2020_Compr.Rev.Food.Sci.Food.Saf_19_759
PubMedSearch : Guo_2020_Compr.Rev.Food.Sci.Food.Saf_19_759
PubMedID: 33325163

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

Title : Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer's Diseases - Guo_2020_Molecules_25_
Author(s) : Guo Y , Yang H , Huang Z , Tian S , Li Q , Du C , Chen T , Liu Y , Sun H , Liu Z
Ref : Molecules , 25 : , 2020
Abstract : A series of novel compounds 6a-h, 8i-1, 10s-v, and 16a-d were synthesized and evaluated, together with the known analogs 11a-f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 muM) and BChE (eqBChE IC50 = 0.28 muM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer's disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.
ESTHER : Guo_2020_Molecules_25_
PubMedSearch : Guo_2020_Molecules_25_
PubMedID: 31979317

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

Title : Characterization and Genome Analysis of a Zearalenone-Degrading Bacillus velezensis Strain ANSB01E - Guo_2020_Curr.Microbiol_77_273
Author(s) : Guo Y , Zhou J , Tang Y , Ma Q , Zhang J , Ji C , Zhao L
Ref : Curr Microbiol , 77 :273 , 2020
Abstract : Zearalenone, a nonsteroidal estrogenic mycotoxin mainly produced by Fusarium species, causes reproductive disorders and hyperestrogenic syndromes in animals and humans. The bacterial strain Bacillus velezensis ANSB01E, isolated from chicken cecal content, was capable of effectively degrading zearalenone in both liquid medium and mouldy corn. Moreover, Bacillus velezensis ANSB01E exhibited good antimicrobial activities against animal pathogenic bacteria, including Escherichia coli, Staphylococcus aureus, and Salmonella spp. Genome-based analysis revealed the presence of genes coding peroxiredoxin and alpha/beta hydrolase in Bacillus velezensis ANSB01E, which may be involved in zearalenone degradation. The study on the genome provides insights into the zearalenone degradation mechanisms and advances the potential application of Bacillus velezensis ANSB01E in food and feed industry.
ESTHER : Guo_2020_Curr.Microbiol_77_273
PubMedSearch : Guo_2020_Curr.Microbiol_77_273
PubMedID: 31748861
Gene_locus related to this paper: 9baci-QBK11187

Title : Myasthenia gravis and specific immunotherapy: monoclonal antibodies - Cai_2019_Ann.N.Y.Acad.Sci_1452_18
Author(s) : Cai XJ , Li ZW , Xi JY , Song HZ , Liu J , Zhu WH , Guo Y , Jiao Z
Ref : Annals of the New York Academy of Sciences , 1452 :18 , 2019
Abstract : Myasthenia gravis (MG) is an acquired autoimmune disease affecting the postsynaptic membrane of neuromuscular junctions and characterized by antibody-mediated T cell dependence and complement involvement. Cholinesterase inhibitors (e.g., pyridostigmine bromide), glucocorticoids, and azathioprine are currently recommended as first-line treatments for MG, though they have limitations, including potential toxicity and ineffectiveness in patients with refractory MG. In recent years, owing to an increasing understanding of MG pathogenesis the development and execution of clinical trials with novel biologics, including monoclonal antibodies (mAbs) that have demonstrated higher safety and more specificity, provide new opportunities for the treatment of MG. In this article, we review recent advances in MG pathogenesis and the mAbs that have been used for target-specific MG therapy.
ESTHER : Cai_2019_Ann.N.Y.Acad.Sci_1452_18
PubMedSearch : Cai_2019_Ann.N.Y.Acad.Sci_1452_18
PubMedID: 31393614

Title : A Flexible Acetylcholinesterase-Modified Graphene for Chiral Pesticide Sensor - Zhang_2019_J.Am.Chem.Soc_141_14643
Author(s) : Zhang Y , Liu X , Qiu S , Zhang Q , Tang W , Liu H , Guo Y , Ma Y , Guo X , Liu Y
Ref : Journal of the American Chemical Society , 141 :14643 , 2019
Abstract : Sensors based on graphene are promising devices for chemical and biological detection owing to their high sensitivity, biocompatibility, and low costs. However, for chiral recognition, which is very important in biological systems, graphene sensors remain unable to discriminate enantiomers. Here, using chiral pesticide molecules as an example, we realized a highly sensitive graphene chiral sensor by modification with acetylcholinesterase (AChE). Quantum chemical simulations indicate that the inhibition effect of the enantiomer on AChE was transferred to graphene, which allowed for the electrical detection of chiral molecules. Under an operating voltage of 1 V, the sensitivity of the device reached 0.34 mug/L and 0.32 mug/L for (+)/(-)-methamidophos, respectively, which is much higher than by circular dichroism (6.90 mg/L and 5.16 mg/L, respectively). Furthermore, real-time, rapid detection was realized by combining with smartphones and wireless transmission.
ESTHER : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedSearch : Zhang_2019_J.Am.Chem.Soc_141_14643
PubMedID: 31448915

Title : Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV - Jiang_2019_Viruses_11_
Author(s) : Jiang Y , Li J , Teng Y , Sun H , Tian G , He L , Li P , Chen Y , Guo Y , Zhao G , Zhou Y , Sun S
Ref : Viruses , 11 : , 2019
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection.
ESTHER : Jiang_2019_Viruses_11_
PubMedSearch : Jiang_2019_Viruses_11_
PubMedID: 30634407

Title : Enhanced Platelet Response to Clopidogrel in Zucker Diabetic Fatty Rats due to Impaired Clopidogrel Inactivation by Carboxylesterase 1 and Increased Exposure to Active Metabolite - Yao_2019_Drug.Metab.Dispos_47_794
Author(s) : Yao H , Bai R , Ren T , Wang Y , Gu J , Guo Y
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 47 :794 , 2019
Abstract : Clopidogrel (Clop), a thienopyridine antiplatelet prodrug, is metabolized by cytochrome P450s (CYPs) to an active metabolite, Clop-AM, and hydrolyzed by carboxylesterase (CES)1 to the inactive Clop-acid. Patients with type 2 diabetes (T2DM) tend to have a poor response to Clop due to reduced generation of Clop-AM. Whether a similar response occurs in the Zucker diabetic fatty (ZDF) rat, a commonly used animal model of T2DM, has not been explored. In this work, we compared ZDF and control rats for hepatic CES1- and CYP-mediated Clop metabolism; pharmacokinetics of Clop, Clop-AM, and Clop-acid; and the antiplatelet efficacy of Clop. In contrast to clinical findings, Clop-treated ZDF rats displayed significantly less (50%) maximum platelet aggregation at 4 hours than control rats; the enhanced efficacy was accompanied by higher formation of Clop-AM and lower formation of Clop-acid. In vitro studies showed that hepatic levels of CES1 protein and activity and Ces1e mRNA were significantly lower in ZDF than in control rats, as were the mRNA levels of CYP2B1/2, CYP2C11, and CYP3A2, and levels of CYP2B6-, CYP2C19-, and CYP3A4-related proteins and enzymatic activities in liver microsomes of ZDF rats. Interestingly, liver microsomes of ZDF rats produced higher levels of Clop-AM than that of control rats despite their lower CYP levels, although the addition of fluoride ion, an esterase inhibitor, enhanced Clop-AM formation in control rats more than in ZDF rats. These results suggest that the reduction in CES1-based Clop inactivation indirectly enhances Clop efficacy in ZDF rats by making more Clop available for CYP-mediated Clop-AM formation.
ESTHER : Yao_2019_Drug.Metab.Dispos_47_794
PubMedSearch : Yao_2019_Drug.Metab.Dispos_47_794
PubMedID: 31092394
Gene_locus related to this paper: ratno-Ces1d

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

Title : Ultrasensitive and visible light-responsive photoelectrochemical aptasensor for edifenphos based on Zinc phthalocyanine sensitized MoS2 nanosheets - Ding_2019_Biosens.Bioelectron__111867
Author(s) : Ding L , Jiang D , Wen Z , Xu Y , Guo Y , Ding C , Wang K
Ref : Biosensors & Bioelectronics , :111867 , 2019
Abstract : Developing a simple, rapid detection method for the analysis of edifenphos (EDI) is crucial due to its residue is harmful to acetylcholinesterase on the human cellular system, and cause a lot of complications. Herein, we synthesized visible light-responsive MoS2 nanosheets decorated with Zinc phthalocyanine (ZnPc) nanoparticles (ZnPc/n-MoS2). Due to the sensitization of ZnPc nanoparticles, the resulting ZnPc/n-MoS2 exhibited narrower energy bandgap and efficient charge transfer. Especially, the carrier lifetime of ZnPc/n-MoS2 is 2 more times longer than n-MoS2, and the photocurrent intensity of ZnPc/n-MoS2 is 24 times of n-MoS2 and 22 times of ZnPc nanoparticles under visible light irradiation. Further, a visible light-responsive ultrasensitive photoelectrochemical (PEC) aptasensor for selectivity recognition of EDI was triumphantly established by using EDI aptamer as a biorecognition element, which exhibited a wide linear ranking from 5ngL(-1) to 10mugL(-1) (R(2)=0.996) and a low detection limit of 1.667ngL(-1) (S/N=3). The splendid performance of the ZnPc/n-MoS2 nanosheet ultrasensitive sensing platform can be applied to detect the concentration of EDI in food, biomedical and environmental analysis.
ESTHER : Ding_2019_Biosens.Bioelectron__111867
PubMedSearch : Ding_2019_Biosens.Bioelectron__111867
PubMedID: 31748191

Title : Fast emerging insecticide resistance in Aedes albopictus in Guangzhou, China: Alarm to the dengue epidemic - Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
Author(s) : Su X , Guo Y , Deng J , Xu J , Zhou G , Zhou T , Li Y , Zhong D , Kong L , Wang X , Liu M , Wu K , Yan G , Chen XG
Ref : PLoS Negl Trop Dis , 13 :e0007665 , 2019
Abstract : Dengue is one of the most serious mosquito-borne infectious diseases in the world. Aedes albopictus is the most invasive mosquito and one of the primary vectors of dengue. Vector control using insecticides is the only viable strategy to prevent dengue virus transmission. In Guangzhou, after the 2014 pandemic, massive insecticides have been implemented. Massive insecticide use may lead to the development of resistance, but few reports are available on the status of insecticide resistance in Guangzhou after 2014. In this study, Ae. albopictus were collected from four districts with varied dengue virus transmission intensity in Guangzhou from 2015 to 2017. Adult Ae. albopictus insecticide susceptibility to deltamethrin (0.03%), permethrin(0.25%), DDT(4%), malathion (0.8%) and bendiocarb (0.1%) was determined by the standard WHO tube test, and larval resistance bioassays were conducted using temephos, Bacillus thuringiensis israelensis (Bti), pyriproxyfen (PPF) and hexaflumuron. Mutations at the voltage-gated sodium channel (VGSC) gene and acetylcholinesterase (AChE) gene were analyzed. The effect of cytochrome P450s on the resistance of Ae. albopictus to deltamethrin was tested using the synergistic agent piperonyl butoxide (PBO). The results showed that Ae. albopictus populations have rapidly developed very high resistances to multiple commonly used insecticides at all study areas except malathion, Bti and hexaflumuron. We found 1534 codon mutations in the VGSC gene that were significantly correlated with the resistance to pyrethroids and DDT, and 11 synonymous mutations were also found in the gene. The resistance to deltamethrin can be significantly reduced by PBO but may generated cross-resistance to PPF. Fast emerging resistance in Ae. albopictus may affect mosquito management and threaten the prevention and control of dengue, similar to the resistance in Anopheles mosquitoes has prevented the elimination of malaria and call for timely and guided insecticide management.
ESTHER : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedSearch : Su_2019_PLoS.Negl.Trop.Dis_13_e0007665
PubMedID: 31525199

Title : Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum - Guo_2018_Org.Biomol.Chem_16_8130
Author(s) : Guo Y , Zhang N , Sun W , Duan X , Zhang Q , Zhou Q , Chen C , Zhu H , Luo Z , Liu J , Li XN , Xue Y , Zhang Y
Ref : Org Biomol Chem , 16 :8130 , 2018
Abstract : Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 muM) and simultaneously inhibited BACE1 (at a concentration of 5 muM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
ESTHER : Guo_2018_Org.Biomol.Chem_16_8130
PubMedSearch : Guo_2018_Org.Biomol.Chem_16_8130
PubMedID: 30334059

Title : Dual-Channel Enzymatic Inhibition Measurement (DEIM) Coupling Isotope Substrate via Matrix-Assisted Laser Desorption\/Ionization Time of Flight Mass Spectrometry - Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
Author(s) : Tao M , Zhang L , Guo Y
Ref : J Am Soc Mass Spectrom , 29 :2427 , 2018
Abstract : A novel dual-channel enzymatic inhibition measurement (DEIM) method was developed to improve the repeatability with light/heavy isotope substrates, producing reliable relative standard deviations (< 3%) by employing acetylcholinesterase (AChE) as the model enzyme. The matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was adapted for enzyme-inhibited method due to its good salt-tolerance and high throughput; meanwhile, dual-channel enzymatic reactions were performed to improve the repeatability of each well. The acetylcholinesterase inhibition measurement was conducted by mixing the quenched enzyme reaction solution of blank group (with heavy isotope as substrate) and experimental group (with light isotope as substrate), of which the inhibition rate might be affected by isotope effects. Hence, inverse study and Km measurement were implemented to validate the method. The inverse study shows similar inhibition rate (68.9 and 70.3%) and the Km of isotope substrates are analogous (0.139 and 0.135 mM), which demonstrated that the novel method is feasible to AChE inhibition measurement. Finally, the method was applied to herb extracts, half of which exhibit inhibition to AChE. The precise dual-channel enzymatic inhibition measurement (DEIM) method could be regarded as a promising approach to potential enzyme inhibitor screening. Graphical Abstract .
ESTHER : Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
PubMedSearch : Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427
PubMedID: 30159674

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

Title : Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage - Zou_2018_Aging.Dis_9_51
Author(s) : Zou J , Chen Z , Liang C , Fu Y , Wei X , Lu J , Pan M , Guo Y , Liao X , Xie H , Wu D , Li M , Liang L , Wang P , Wang Q
Ref : Aging Dis , 9 :51 , 2018
Abstract : Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD.
ESTHER : Zou_2018_Aging.Dis_9_51
PubMedSearch : Zou_2018_Aging.Dis_9_51
PubMedID: 29392081

Title : Blockade of the C5a-C5aR axis alleviates lung damage in hDPP4-transgenic mice infected with MERS-CoV - Jiang_2018_Emerg.Microbes.Infect_7_77
Author(s) : Jiang Y , Zhao G , Song N , Li P , Chen Y , Guo Y , Li J , Du L , Jiang S , Guo R , Sun S , Zhou Y
Ref : Emerg Microbes Infect , 7 :77 , 2018
Abstract : The pathogenesis of highly pathogenic Middle East respiratory syndrome coronavirus (MERS-CoV) remains poorly understood. In a previous study, we established an hDPP4-transgenic (hDPP4-Tg) mouse model in which MERS-CoV infection causes severe acute respiratory failure and high mortality accompanied by an elevated secretion of cytokines and chemokines. Since excessive complement activation is an important factor that contributes to acute lung injury after viral infection, in this study, we investigated the role of complement in MERS-CoV-induced lung damage. Our study showed that complement was excessively activated in MERS-CoV-infected hDPP4-Tg mice through observations of increased concentrations of the C5a and C5b-9 complement activation products in sera and lung tissues, respectively. Interestingly, blocking C5a production by targeting its receptor, C5aR, alleviated lung and spleen tissue damage and reduced inflammatory responses. More importantly, anti-C5aR antibody treatment led to decreased viral replication in lung tissues. Furthermore, compared with the sham treatment control, apoptosis of splenic cells was less pronounced in the splenic white pulp of treated mice, and greater number of proliferating splenic cells, particularly in the red pulp, was observed. These data indicate that (1) dysregulated host immune responses contribute to the severe outcome of MERS; (2) excessive complement activation, triggered by MERS-CoV infection, promote such dysregulation; and (3) blockade of the C5a-C5aR axis lead to the decreased tissue damage induced by MERS-CoV infection, as manifested by reduced apoptosis and T cell regeneration in the spleen. Therefore, the results of this study suggest a new strategy for clinical intervention and adjunctive treatment in MERS-CoV cases.
ESTHER : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedSearch : Jiang_2018_Emerg.Microbes.Infect_7_77
PubMedID: 29691378

Title : A supramodal role of the basal ganglia in memory and motor inhibition: Meta-analytic evidence - Guo_2018_Neuropsychologia_108_117
Author(s) : Guo Y , Schmitz TW , Mur M , Ferreira CS , Anderson MC
Ref : Neuropsychologia , 108 :117 , 2018
Abstract : The ability to stop actions and thoughts is essential for goal-directed behaviour. Neuroimaging research has revealed that stopping actions and thoughts engage similar cortical mechanisms, including the ventro- and dorso-lateral prefrontal cortex. However, whether and how these abilities require similar subcortical mechanisms remains unexplored. Specifically of interest are the basal ganglia, subcortical structures long-known for their motor functions, but less so for their role in cognition. To investigate the potential common mechanisms in the basal ganglia underlying action and thought stopping, we conducted meta-analyses using fMRI data from the Go/No-Go, Stop-signal, and Think/No-Think tasks. All three tasks require active stopping of prepotent actions or thoughts. To localise basal ganglia activations, we performed high-resolution manual segmentations of striatal subregions. We found that all three tasks recovered clusters in the basal ganglia, although the specific localisation of these clusters differed. Although the Go/No-Go and Stop-signal tasks are often interchangeably used for measuring action stopping, their cluster locations in the basal ganglia did not significantly overlap. These different localised clusters suggest that the Go/No-Go and Stop-signal tasks may recruit distinct basal ganglia stopping processes, and therefore should not be treated equivalently. More importantly, the basal ganglia cluster recovered from the Think/No-Think task largely co-localised with that from the Stop-signal task, but not the Go/No-Go task, possibly indicating that the Think/No-Think and Stop-signal tasks share a common striatal circuitry involved in the cancellation of unwanted thoughts and actions. The greater similarity of the Think/No-Think task to the Stop-Signal rather than Go/No-Go task also was echoed at the cortical level, which revealed highly overlapping and largely right lateralized set of regions including the anterior DLPFC, VLPFC, Pre-SMA and ACC. Overall, we provide novel evidence suggesting not only that the basal ganglia are critical for thought stopping, but also that they are involved in specific stopping subprocesses that can be engaged by tasks in different domains. These findings raise the possibility that the basal ganglia may be part of a supramodal network responsible for stopping unwanted processes more broadly.
ESTHER : Guo_2018_Neuropsychologia_108_117
PubMedSearch : Guo_2018_Neuropsychologia_108_117
PubMedID: 29199109

Title : A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae - Li_2018_Aquat.Toxicol_199_46
Author(s) : Li R , Zhang L , Shi Q , Guo Y , Zhang W , Zhou B
Ref : Aquat Toxicol , 199 :46 , 2018
Abstract : Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500mug/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100mug/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500mug/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and alpha1-tubulin) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500mug/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1nM) and inhibitor (chloroquine, CQ, 1muM) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and small a, Cyrillic1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500mug/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae.
ESTHER : Li_2018_Aquat.Toxicol_199_46
PubMedSearch : Li_2018_Aquat.Toxicol_199_46
PubMedID: 29605586

Title : A novel mutation in the BCHE gene and phenotype identified in a child with low butyrylcholinesterase activity: a case report - Yu_2018_BMC.Med.Genet_19_58
Author(s) : Yu R , Guo Y , Dan Y , Tan W , Mao Q , Deng G
Ref : BMC Med Genet , 19 :58 , 2018
Abstract : BACKGROUND: Butyrylcholinesterase (BChE), an ester hydrolase produced mainly by the liver, hydrolyzes certain short-acting neuromuscular blocking agents, like succinylcholine and mivacurium that are widely used during anesthesia. Patients with BChE deficiency are possibly in danger of postanesthetic apnea. Hereditary BChE deficiency results from the mutations of BCHE gene located on chromosome 3, 3q26.1-q26.2, between nucleotides 165,490,692-165,555,260. CASE PRESENTATION: This study describes a novel mutation in a child with BChE deficiency. In general, this child appeared healthy and well-developed with a normal appearance. However, the results of Wechsler Intelligence Scale showed that the full-scale intelligence quotient (FIQ) was 53, classified into the group with the minor defect. The BChE activity was 32.0 U/L, considerably lower than the normal lower limit (reference range: 5000-12,000 U/L). Sanger sequencing showed that there were 2 mutations in the exon 2 of BCHE gene of this child. One is a heterozygous mutation rs764588882 (NM_000055.3: c.401_402insA, p.Asn134Lysfs*23). The other one is a heterozygous mutation (NM_000055.3: c.73A > T, p.Lys25Ter) that has never been reported before. The two mutations lead to a premature stop of transcription. CONCLUSIONS: Double heterozygous recessive mutations are the cause of BChE deficiency of this boy in this study, including a novel mutation c.73A > T. Intellectual disability is a new phenotype that is probably associated with this mutation.
ESTHER : Yu_2018_BMC.Med.Genet_19_58
PubMedSearch : Yu_2018_BMC.Med.Genet_19_58
PubMedID: 29631548

Title : A non-competitive surface plasmon resonance immunosensor for rapid detection of triazophos residue in environmental and agricultural samples - Guo_2018_Sci.Total.Environ_613-614_783
Author(s) : Guo Y , Liu R , Liu Y , Xiang D , Gui W , Li M , Zhu G
Ref : Sci Total Environ , 613-614 :783 , 2018
Abstract : The wide application of an organophosphate pesticide triazophos raises concern on the environmental pollution and the potential risk to human health. Thus, it is crucial to regularly monitor triazophos residue in the environment and agro-products. Herein we described a non-competitive immunoassay for trace detection of triazophos using a direct surface plasmon resonance (SPR) biosensor. Two anti-triazophos monoclonal antibodies (mAbs) were immobilized on the sensor chip and characterized by SPR-based kinetic analysis. The mAb with relatively slow dissociation rate was used for direct immunosensing of triazophos. The biosensor assay showed a high specificity and a low detection limit of 0.096ngmL-1 to triazophos, with the linear detection range of 0.98-8.29ngmL-1. Under the optimal condition, the sensor chip could be regenerated for 160cycles at least. Moreover, the sensitive method was applied to determine triazophos in the spiked environmental water and agricultural products, as well as in unknown real-life samples (including Chinese cabbage, cucumber, and apple). Desirable results demonstrated that the newly-developed immunosensor could be used as a rapid, convenient, and reliable tool to regularly monitor triazophos and meet the detection requirement of its maximum residue limits.
ESTHER : Guo_2018_Sci.Total.Environ_613-614_783
PubMedSearch : Guo_2018_Sci.Total.Environ_613-614_783
PubMedID: 28946376

Title : Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae - Shi_2018_Aquat.Toxicol_203_80
Author(s) : Shi Q , Wang M , Shi F , Yang L , Guo Y , Feng C , Liu J , Zhou B
Ref : Aquat Toxicol , 203 :80 , 2018
Abstract : Triphenyl phosphate (TPhP), a typical organophosphate ester, is frequently detected in the environment and biota samples. It has been implicated as a neurotoxin as its structure is similar to neurotoxic organophosphate pesticides. The purpose of the present study was to investigate its potential developmental neurotoxicity in fish by using zebrafish larvae as a model. Zebrafish (Danio rerio) embryos were exposed to 0.8, 4, 20 and 100 mug/L of TPhP from 2 until 144 h post-fertilization. TPhP was found to have high bioconcentrations in zebrafish larvae after exposure. Further, it significantly reduced locomotor activity as well as the heart rate at the 100 mug/L concentration. TPhP exposure significantly altered the content of the neurotransmitters gamma-aminobutyric and histamine. Downregulation of the genes related to central nervous system development (e.g., alpha1-tubulin, mbp, syn2a, shha, and elavl3) as well as the corresponding proteins (e.g., alpha1-tubulin, mbp, and syn2a) was observed, but the gap-43 protein was found to upregulated. Finally, marked inhibition of total acetylcholinesterase activity, which is considered as a biomarker of neurotoxicant exposure, was also observed in the larvae. Our results indicate that exposure to environmentally relevant concentrations of TPhP can affect different parameters related to center nervous system development, and thus contribute to developmental neurotoxicity in early developing zebrafish larvae.
ESTHER : Shi_2018_Aquat.Toxicol_203_80
PubMedSearch : Shi_2018_Aquat.Toxicol_203_80
PubMedID: 30096480

Title : Genomic adaptation to polyphagy and insecticides in a major East Asian noctuid pest - Cheng_2017_Nat.Ecol.Evol_1_1747
Author(s) : Cheng T , Wu J , Wu Y , Chilukuri RV , Huang L , Yamamoto K , Feng L , Li W , Chen Z , Guo H , Liu J , Li S , Wang X , Peng L , Liu D , Guo Y , Fu B , Li Z , Liu C , Chen Y , Tomar A , Hilliou F , Montagne N , Jacquin-Joly E , d'Alencon E , Seth RK , Bhatnagar RK , Jouraku A , Shiotsuki T , Kadono-Okuda K , Promboon A , Smagghe G , Arunkumar KP , Kishino H , Goldsmith MR , Feng Q , Xia Q , Mita K
Ref : Nat Ecol Evol , 1 :1747 , 2017
Abstract : The tobacco cutworm, Spodoptera litura, is among the most widespread and destructive agricultural pests, feeding on over 100 crops throughout tropical and subtropical Asia. By genome sequencing, physical mapping and transcriptome analysis, we found that the gene families encoding receptors for bitter or toxic substances and detoxification enzymes, such as cytochrome P450, carboxylesterase and glutathione-S-transferase, were massively expanded in this polyphagous species, enabling its extraordinary ability to detect and detoxify many plant secondary compounds. Larval exposure to insecticidal toxins induced expression of detoxification genes, and knockdown of representative genes using short interfering RNA (siRNA) reduced larval survival, consistent with their contribution to the insect's natural pesticide tolerance. A population genetics study indicated that this species expanded throughout southeast Asia by migrating along a South India-South China-Japan axis, adapting to wide-ranging ecological conditions with diverse host plants and insecticides, surviving and adapting with the aid of its expanded detoxification systems. The findings of this study will enable the development of new pest management strategies for the control of major agricultural pests such as S. litura.
ESTHER : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedSearch : Cheng_2017_Nat.Ecol.Evol_1_1747
PubMedID: 28963452

Title : Thiolation Protein-Based Transfer of Indolyl to a Ribosomally Synthesized Polythiazolyl Peptide Intermediate during the Biosynthesis of the Side-Ring System of Nosiheptide - Qiu_2017_J.Am.Chem.Soc_139_18186
Author(s) : Qiu Y , Du Y , Zhang F , Liao R , Zhou S , Peng C , Guo Y , Liu W
Ref : Journal of the American Chemical Society , 139 :18186 , 2017
Abstract : Nosiheptide, a potent bicyclic member of the family of thiopeptide antibiotics, possesses a distinctive l-Trp-derived indolyl moiety. The way in which this moiety is incorporated into a ribosomally synthesized and post-translationally modified thiopeptide remains poorly understood. Here, we report that NosK, an alpha/beta-hydrolase fold protein, mediates the transfer of indolyl from NosJ, a discrete thiolation protein, to a linear pentathiazolyl peptide intermediate rather than its genetically encoded untreated precursor. This intermediate results from enzymatic processing of the peptide precursor, in which five of the six l-Cys residues are transformed into thiazoles but Cys4 selectively remains unmodified for indolyl substitution via a thioester exchange. Determining the timing of indolyl incorporation, which expands the chemical space of a thiopeptide framework, facilitates mechanistic access to the unusual logic of post-translational modifications in the biosynthesis of nosiheptide-type thiopeptide members that share a similar compact side-ring system.
ESTHER : Qiu_2017_J.Am.Chem.Soc_139_18186
PubMedSearch : Qiu_2017_J.Am.Chem.Soc_139_18186
PubMedID: 29200275
Gene_locus related to this paper: stras-c6fx50

Title : A pH-responsive colorimetric strategy for DNA detection by acetylcholinesterase catalyzed hydrolysis and cascade amplification - Guo_2017_Biosens.Bioelectron_94_651
Author(s) : Guo Y , Yang K , Sun J , Wu J , Ju H
Ref : Biosensors & Bioelectronics , 94 :651 , 2017
Abstract : A pH-responsive colorimetric strategy was designed for sensitive and convenient biosensing by introducing acetylcholinesterase (AChE) catalyzed hydrolysis of acetylcholine to change solution pH and phenol red as an indicator. Using DNA as a target model, this technique was successfully employed for sensitive DNA analysis by labeling AChE to DNA. The sensitivity could be greatly improved by coupling a newly designed magnetic probe with target DNA-triggered nonenzymatic cascade amplification. In the presence of a help DNA (H) and the functional probe, the cascade assembly via toehold-mediated strand displacement released the AChE-conjugated sequence from magnetic beads, which could be simply separated from the reaction mixture to catalyze the hydrolysis of ACh in detection solution. The color change of detection solution from pink to orange-red, orange-yellow and ultimately yellow could be used for target DNA detection by naked eye and colorimetry with the absorbance ratio of detection solution at 558nm to 432nm as the signal. The nonenzymatically sensitized colorimetric strategy showed a linear range from 50pM to 50nM with a detection limit of 38pM, indicating a promising application in DNA analysis.
ESTHER : Guo_2017_Biosens.Bioelectron_94_651
PubMedSearch : Guo_2017_Biosens.Bioelectron_94_651
PubMedID: 28388529

Title : Enzymatic synthesis of lysophosphatidylcholine with n-3 polyunsaturated fatty acid from sn-glycero-3-phosphatidylcholine in a solvent-free system - Liu_2017_Food.Chem_226_165
Author(s) : Liu Y , Zhang Q , Guo Y , Liu J , Xu J , Li Z , Wang J , Wang Y , Xue C
Ref : Food Chem , 226 :165 , 2017
Abstract : The n-3 polyunsaturated fatty acids (PUFA)-rich lysophosphatidylcholine (LPC) was successfully synthesized by Thermomyces lanuginosus lipase (TL IM)-catalyzed esterification of glycerylphosphorylcholine (GPC) and n-3 PUFA-rich fatty acids in a solvent-free system. Effects of reaction temperature, enzyme loading and substrate mole ratio on the yield of LPC and incorporation of n-3 PUFA were evaluated. The acyl-specificities of five enzymes were tested for direct esterification of n-3 PUFA, and Lipozyme TL IM was found to be more effective than others for production of LPC with n-3 PUFA. Substrate mole ratio and reaction temperature, however, had no significant effect on the incorporation. The maximal yield of LPC was obtained under the following conditions: temperature 45 degC, enzyme loading 15% by weight and substrate mole ratio (GPC/n-3 PUFA) 1:20. Furthermore, the composition of products were further investigated in the study. The 1-acyl-sn-glycero-3-lysophosphatidylcholine (2-LPC) was predominant in the mixtures at early stages of reaction, whereas less increment of 2-acyl-sn-glycero-3-lysophosphatidylcholine (1-LPC) and PC was observed at later stages.
ESTHER : Liu_2017_Food.Chem_226_165
PubMedSearch : Liu_2017_Food.Chem_226_165
PubMedID: 28254008

Title : Tricyclic Polyprenylated Acylphloroglucinols from St John's Wort, Hypericum perforatum - Guo_2017_J.Nat.Prod_80_1493
Author(s) : Guo Y , Zhang N , Chen C , Huang J , Li XN , Liu J , Zhu H , Tong Q , Zhang J , Luo Z , Xue Y , Zhang Y
Ref : Journal of Natural Products , 80 :1493 , 2017
Abstract : The new polyprenylated acylphloroglucinol derivatives 1-15 and the known furohyperforin (16) were isolated from the stems and leaves of Hypericum perforatum. Their structures were determined by analyses of NMR and HRESIMS data. Their absolute configurations were elucidated by a combination of electronic circular dichroism (ECD) and Rh2(OCOCF3)4-induced ECD, as well as X-ray diffraction crystallography. The new hyperforatin F (9) contains a unique acetyl functionality at C-1 of the bicyclo[3.3.1]nonane core. Hyperforatins G (10) and H (11) are similarly the first examples of naturally occurring [3.3.1]-type polycyclic prenylated acylphloroglucinols possessing a carbonyl functionality at C-32. The compounds were tested for their acetylcholinesterase (AChE) inhibitory activities and cytotoxic activities against a panel of human tumor cell lines. Compounds 3, 5, 6, 8, and 9 exerted moderate inhibitory activities (IC50 3.98-9.13 muM) against AChE.
ESTHER : Guo_2017_J.Nat.Prod_80_1493
PubMedSearch : Guo_2017_J.Nat.Prod_80_1493
PubMedID: 28445039

Title : A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults - Millwood_2016_Int.J.Epidemiol_45_1588
Author(s) : Millwood IY , Bennett DA , Walters RG , Clarke R , Waterworth D , Johnson T , Chen Y , Yang L , Guo Y , Bian Z , Hacker A , Yeo A , Parish S , Hill MR , Chissoe S , Peto R , Cardon L , Collins R , Li L , Chen Z
Ref : Int J Epidemiol , 45 :1588 , 2016
Abstract : BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning.
ESTHER : Millwood_2016_Int.J.Epidemiol_45_1588
PubMedSearch : Millwood_2016_Int.J.Epidemiol_45_1588
PubMedID: 27301456
Gene_locus related to this paper: human-PLA2G7

Title : Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease - Wang_2016_Aging.Clin.Exp.Res_28_951
Author(s) : Wang P , Wing YK , Xing J , Liu Y , Zhou B , Zhang Z , Yao H , Guo Y , Shang Y , Zhang X
Ref : Aging Clin Exp Res , 28 :951 , 2016
Abstract : BACKGROUND AND AIMS: Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by alpha-synuclein deposition, including Parkinson's disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer's disease (AD), a non-synucleinopathy.
METHODS: We recruited 105 clinically probable AD patients. Fifteen clinically probable AD patients with suspected RBD underwent a video-polysomnography (vPSG) examination.
RESULTS: Five patients with probable AD exhibited RBD. One of the patients performed repeated touching of the head and the face with his hands and flailed his arms. Three patients exhibited hand twisting, exploring, prominent limb kicking, and jerking. The fifth patient exhibited all of the characteristics of RBD (he recalled a dream about fighting animals), and his wife was awakened by his screaming. Of these five patients, one patient took the acetylcholinesterase inhibitor drug donepezil. The patients with AD + RBD demonstrated increases in both tonic and phasic electromyography activity during REM sleep, but sleep architecture did not differ between the AD + RBD and AD-alone groups. CONCLUSION: RBD can occur in patients with AD. The occurrence of RBD does not change the sleep architecture of AD patients.
ESTHER : Wang_2016_Aging.Clin.Exp.Res_28_951
PubMedSearch : Wang_2016_Aging.Clin.Exp.Res_28_951
PubMedID: 26022447

Title : ace-3 plays an important role in phoxim resistance in Caenorhabditis elegans - Han_2016_Ecotoxicology_25_835
Author(s) : Han Y , Song S , Guo Y , Zhang J , Ma E
Ref : Ecotoxicology , 25 :835 , 2016
Abstract : Organophosphorus and carbamate are widely used in agricultural production. Caenorhabditis elegans is a model organism that is widely used in various toxicology studies. To understand the effects of two types of commonly used pesticides, phoxim (organophosphorus) and carbaryl (carbamate), we determined the activities of acetylcholinesterases (AChEs) and detected the expression of four ace genes by RT-qPCR in C. elegans following treatment with these pesticides. The results showed that phoxim and carbaryl could reduce acetylcholinesterase activities and up-regulate the ace-3 mRNA expression levels. We also detected the toxic effects of these pesticides on the ace-3 deletion mutant dc-2, and found that some characteristics, including LC50, development, movement, reproduction and lifespan, were reduced in the dc-2 mutant. However, the toxic effects of carbaryl were weaker than those of phoxim. Carbaryl treatment did not significantly affect the LC50, movement ability or lifespan. Interestingly, body and brood size increased with carbaryl treatment at low concentrations. These data showed that both phoxim and carbaryl could inhibit AChE but that the ace-3 was necessary for phoxim detoxification. The LC50 of phoxim and carbaryl in wild type N2 and the ace-3 deletion mutant dc-2. **Higher significant differences (P < 0.01).
ESTHER : Han_2016_Ecotoxicology_25_835
PubMedSearch : Han_2016_Ecotoxicology_25_835
PubMedID: 26947509
Gene_locus related to this paper: caeel-ACHE3

Title : A recombinant receptor-binding domain of MERS-CoV in trimeric form protects human dipeptidyl peptidase 4 (hDPP4) transgenic mice from MERS-CoV infection - Tai_2016_Virology_499_375
Author(s) : Tai W , Zhao G , Sun S , Guo Y , Wang Y , Tao X , Tseng CK , Li F , Jiang S , Du L , Zhou Y
Ref : Virology , 499 :375 , 2016
Abstract : Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif. It bound strongly to the receptor of MERS-CoV, dipeptidyl peptidase 4 (DPP4), and elicited robust RBD-specific neutralizing antibodies in mice, maintaining long-term neutralizing activity against MERS-CoV infection. RBD-Fd potently protected hDPP4 transgenic mice from lethal MERS-CoV challenge. These results suggest that MERS-CoV RBD in its trimeric form maintains native conformation and induces protective neutralizing antibodies, making it a candidate for further therapeutic development.
ESTHER : Tai_2016_Virology_499_375
PubMedSearch : Tai_2016_Virology_499_375
PubMedID: 27750111

Title : Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives - Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
Author(s) : Wang Y , Sun Y , Guo Y , Wang Z , Huang L , Li X
Ref : J Enzyme Inhib Med Chem , 31 :389 , 2016
Abstract : Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound 10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 muM, respectively. Further studies revealed that compound 10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that 10 was a promising dual functional agent for the treatment of AD.
ESTHER : Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
PubMedSearch : Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389
PubMedID: 25798687

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

Title : Multi-Organ Damage in Human Dipeptidyl Peptidase 4 Transgenic Mice Infected with Middle East Respiratory Syndrome-Coronavirus - Zhao_2015_PLoS.One_10_e0145561
Author(s) : Zhao G , Jiang Y , Qiu H , Gao T , Zeng Y , Guo Y , Yu H , Li J , Kou Z , Du L , Tan W , Jiang S , Sun S , Zhou Y
Ref : PLoS ONE , 10 :e0145561 , 2015
Abstract : The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe acute respiratory failure and considerable extrapumonary organ dysfuction with substantial high mortality. For the limited number of autopsy reports, small animal models are urgently needed to study the mechanisms of MERS-CoV infection and pathogenesis of the disease and to evaluate the efficacy of therapeutics against MERS-CoV infection. In this study, we developed a transgenic mouse model globally expressing codon-optimized human dipeptidyl peptidase 4 (hDPP4), the receptor for MERS-CoV. After intranasal inoculation with MERS-CoV, the mice rapidly developed severe pneumonia and multi-organ damage, with viral replication being detected in the lungs on day 5 and in the lungs, kidneys and brains on day 9 post-infection. In addition, the mice exhibited systemic inflammation with mild to severe pneumonia accompanied by the injury of liver, kidney and spleen with neutrophil and macrophage infiltration. Importantly, the mice exhibited symptoms of paralysis with high viral burden and viral positive neurons on day 9. Taken together, this study characterizes the tropism of MERS-CoV upon infection. Importantly, this hDPP4-expressing transgenic mouse model will be applicable for studying the pathogenesis of MERS-CoV infection and investigating the efficacy of vaccines and antiviral agents designed to combat MERS-CoV infection.
ESTHER : Zhao_2015_PLoS.One_10_e0145561
PubMedSearch : Zhao_2015_PLoS.One_10_e0145561
PubMedID: 26701103

Title : Bioconcentration and Transfer of the Organophorous Flame Retardant 1,3-Dichloro-2-propyl Phosphate Causes Thyroid Endocrine Disruption and Developmental Neurotoxicity in Zebrafish Larvae - Wang_2015_Environ.Sci.Technol_49_5123
Author(s) : Wang Q , Lai NL , Wang X , Guo Y , Lam PK , Lam JC , Zhou B
Ref : Environ Sci Technol , 49 :5123 , 2015
Abstract : Organophosphate flame retardants are emerging environmental contaminants, although knowledge of their health risks is limited. Here, thyroid hormone homeostasis and neuronal development was studied in the progeny of adult zebrafish exposed to tris(1,3-dichloro-2-propyl) phosphate (TDCPP). Adult zebrafish were exposed to TDCPP (0, 4, 20, and 100 mug/L) for 3 months. Increased generation of reactive oxygen species and reduced survival rates was observed in exposed F1 larvae. We also observed a significant decrease in plasma thyroxine and 3,5,3'-triiodothyronine levels in F0 females and F1 eggs/larvae. The mRNA and protein expression of factors associated with neuronal development (e.g., alpha1-tubulin, myelin basic protein, and synapsin IIa) were significantly downregulated in exposed F1 larvae, as was the level of the neurotransmitters dopamine, serotonin, gamma amino butyric acid, and histamine. Larval locomotion was significantly decreased in exposed fish, but there was no effect on acetylcholinesterase activity. Bioconcentration of TDCPP was observed in F0 fish. TDCPP was also detected in F1 eggs following parental exposure, indicating maternal transfer of this compound. This study uniquely shows that TDCPP can be transferred to the offspring of exposed adults, causing thyroid endocrine disruption and developmental neurotoxicity.
ESTHER : Wang_2015_Environ.Sci.Technol_49_5123
PubMedSearch : Wang_2015_Environ.Sci.Technol_49_5123
PubMedID: 25826601

Title : Acetylcholinesterase biosensor based on multi-walled carbon nanotubes-SnO2-chitosan nanocomposite - Chen_2015_Bioprocess.Biosyst.Eng_38_315
Author(s) : Chen D , Sun X , Guo Y , Qiao L , Wang X
Ref : Bioprocess Biosyst Eng , 38 :315 , 2015
Abstract : A sensitive amperometric acetylcholinesterase (AChE) biosensor was developed based on the nanocomposite of multi-walled carbon nanotubes (MWCNTs), tin oxide (SnO2) nanoparticles and chitosan (CHIT). Acetylcholinesterase (AChE) and Nafion were immobilized onto the nanocomposite film to prepare AChE biosensor for pesticide residues detection. The morphologies and electrochemistry properties of the surface modification were investigated using cyclic voltammetry, differential pulse voltammetry, and scanning electron microscopy, respectively. Compared with individual MWCNTs-CHIT, SnO2-CHIT and bare gold electrode, this nanocomposite showed the most obvious electrochemical signal in the presence of [Fe(CN)6](3-/4-) as a redox couple. Incorporating MWCNTs and SnO2 into 0.2 % CHIT solution can promote electron transfer, enhance the electrochemical response, and improve the microarchitecture of the electrode surface. All variables involved in the preparation process and analytical performance of the biosensor were optimized. Under optimized conditions, the AChE biosensor exhibited a wide linear range from 0.05 to 1.0 x 10(5 )mug/L and with a detection limit for chlorpyrifos was 0.05 mug/L. Based on the inhibition of pesticides on the AChE activity, using chlorpyrifos as model pesticide, the proposed biosensor exhibited a wide range, low detection limit, good reproducibility, and high stability. Using cabbages, lettuces, leeks, and pakchois as model samples, acceptable recovery of 98.7-105.2 % was obtained. The proposed method was proven to be a feasible quantitative method for chlorpyrifos analysis, which may open a new door ultrasensitive detection of chlorpyrifos residues in vegetables and fruits.
ESTHER : Chen_2015_Bioprocess.Biosyst.Eng_38_315
PubMedSearch : Chen_2015_Bioprocess.Biosyst.Eng_38_315
PubMedID: 25147124

Title : Safety, tolerability and pharmacokinetics of doravirine, a novel HIV non-nucleoside reverse transcriptase inhibitor, after single and multiple doses in healthy subjects - Anderson_2015_Antivir.Ther_20_397
Author(s) : Anderson MS , Gilmartin J , Cilissen C , De Lepeleire I , Van Bortel L , Dockendorf MF , Tetteh E , Ancona JK , Liu R , Guo Y , Wagner JA , Butterton JR
Ref : Antivir Ther , 20 :397 , 2015
Abstract : BACKGROUND: Doravirine is a novel non-nucleoside inhibitor of HIV-1 reverse transcriptase with potent activity against wild-type virus (95% inhibitory concentration 19 nM, 50% human serum). Doravirine has low potential to cause drug-drug interactions since it is primarily eliminated by oxidative metabolism and does not inhibit or significantly induce drug-metabolizing enzymes.
METHODS: The pharmacokinetics and safety of doravirine were investigated in two double-blind, dose-escalation studies in healthy males. Thirty-two subjects received single doses of doravirine (6-1,200 mg) or matching placebo tablets; 40 subjects received doravirine (30-750 mg) or matching placebo tablets once daily for 10 days. In addition, the effect of doravirine (120 mg for 14 days) on single-dose pharmacokinetics of the CYP3A substrate midazolam was evaluated (10 subjects).
RESULTS: The maximum plasma concentration (Cmax) of doravirine was achieved within 1-5 h with an apparent terminal half-life of 12-21 h. Consistent with single-dose pharmacokinetics, steady state was achieved after approximately 7 days of once daily administration, with accumulation ratios (day 10/day 1) of 1.1-1.5 in the area under the plasma concentration-time curve during the dosing interval (AUC0-24 h), Cmax and trough plasma concentration (C24 h). All dose levels produced C24 h>19 nM. Administration of 50 mg doravirine with a high-fat meal was associated with slight elevations in AUC time zero to infinity (AUC0-infinity) and C24 h with no change in Cmax. Midazolam AUC0-infinity was slightly reduced by coadministration of doravirine (geometric mean ratio 0.82, 90% CI 0.70, 0.97). There was no apparent relationship between adverse event frequency or intensity and doravirine dose. No rash or significant central nervous system events other than headache were reported.
CONCLUSIONS: Doravirine is generally well tolerated in single doses up to 1,200 mg and multiple doses up to 750 mg once daily for up to 10 days, with a pharmacokinetic profile supportive of once-daily dosing. Doravirine at steady state slightly reduced the exposure of coadministered midazolam, to a clinically unimportant extent.
ESTHER : Anderson_2015_Antivir.Ther_20_397
PubMedSearch : Anderson_2015_Antivir.Ther_20_397
PubMedID: 25470746

Title : Production of Structured Triacylglycerols Containing Palmitic Acids at sn-2 Position and Docosahexaenoic Acids at sn-1, 3 Positions - Liu_2015_J.Oleo.Sci_64_1227
Author(s) : Liu Y , Guo Y , Sun Z , Jie X , Li Z , Wang J , Wang Y , Xue C
Ref : J Oleo Sci , 64 :1227 , 2015
Abstract : Docosahexaenoic acid supplementation has been shown well-established health benefits that justify their use as functional ingredients in healthy foods and nutraceutical products. Structured triacylglycerols rich in 1,3-docosahexenoyl-2-palmitoyl-sn-glycerol were produced from algal oil (Schizochytrium sp) which was prepared by a two-step process. Novozym 435 lipase was used to produce tripalmitin. Tripalmitin was then used to produce the final structured triacylglycerol (STAG) through interesterification reactions using Lipozyme RM IM. The optimum conditions for the enzymatic reaction were a mole ratio of tripalmitin/fatty acid ethyl esters 1:9, 60 degC, 10% enzyme load (wt % of substrates), 10 h; the enzymatic product contained 51.6% palmitic acid (PA), 30.13% docosahexaenoic acid (DHA, C22:6 n-3) and 5.33% docosapentanoic acid (DPA, C22:5 n-3), 12.15% oleic acid (OLA). This STAG can be used as a functional ingredient in dietary supplementation to provide the benefits of DHA.
ESTHER : Liu_2015_J.Oleo.Sci_64_1227
PubMedSearch : Liu_2015_J.Oleo.Sci_64_1227
PubMedID: 26521813

Title : A cationic surfactant-decorated liquid crystal sensing platform for simple and sensitive detection of acetylcholinesterase and its inhibitor - Wang_2015_Biosens.Bioelectron_72_25
Author(s) : Wang Y , Hu Q , Guo Y , Yu L
Ref : Biosensors & Bioelectronics , 72 :25 , 2015
Abstract : In this paper, construction of the liquid crystal (LC)-based sensing platform for simple and sensitive detection of acetylcholinesterase (AChE) and its inhibitor using a cationic surfactant-decorated LC interface was demonstrated. A change of the optical images of LCs from bright to dark appearance was observed when the cationic surfactant, myristoylcholine chloride (Myr), was transferred onto the aqueous/LC interface, due to the formation of a stable surfactant monolayer at the interface. A dark-to-bright change of the optical appearance was then observed when AChE was transferred onto the Myr-decorated LC interface. The sensitivity of this new type of LC-based sensor is 3 orders of magnitude higher in the serum albumin solution than that only in the buffer solution. Noteworthy is that the AChE LC sensor shows a very high sensitivity for the detection of the enzyme inhibitor, which is around 1fM. The constructed low-cost LC-based sensor is quite simple and convenient, showing high promise for label-free detection of AChE and its inhibitors.
ESTHER : Wang_2015_Biosens.Bioelectron_72_25
PubMedSearch : Wang_2015_Biosens.Bioelectron_72_25
PubMedID: 25957073

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

Title : An acetylcholinesterase biosensor based on graphene-gold nanocomposite and calcined layered double hydroxide - Zhai_2014_Enzyme.Microb.Technol_58-59_8
Author(s) : Zhai C , Guo Y , Sun X , Zheng Y , Wang X
Ref : Enzyme Microb Technol , 58-59 :8 , 2014
Abstract : In this study, a novel acetylcholinesterase-based biosensor was fabricated. Acetylcholinesterase (AChE) was immobilized onto a glassy carbon electrode (GCE) with the aid of Cu-Mg-Al calcined layered double hydroxide (CLDH). CLDH can provide a bigger effective surface area for AChE loading, which could improve the precision and stability of AChE biosensor. However, the poor electroconductibility of CLDHs could lead to the low sensitivity of AChE biosensor. In order to effectively compensate the disadvantages of CLDHs, graphene-gold nanocomposites were used for improving the electron transfer rate. Thus, the graphene-gold nanocomposite (GN-AuNPs) was firstly modified onto the GCE, and then the prepared CLDH-AChE composite was immobilized onto the modified GCE to construct a sensitive AChE biosensor for pesticides detection. Relevant parameters were studied in detail and optimized, including the pH of the acetylthiocholine chloride (ATCl) solution, the amount of AChE immobilized on the biosensor and the inhibition time governing the analytical performance of the biosensor. The biosensor detected chlorpyrifos at concentrations ranging from 0.05 to 150mug/L. The detection limit for chlorpyrifos was 0.05mug/L.
ESTHER : Zhai_2014_Enzyme.Microb.Technol_58-59_8
PubMedSearch : Zhai_2014_Enzyme.Microb.Technol_58-59_8
PubMedID: 24731819

Title : Selective and sensitive detection of acetylcholinesterase activity using denatured protein-protected gold nanoclusters as a label-free probe - Li_2014_Analyst_139_285
Author(s) : Li H , Guo Y , Xiao L , Chen B
Ref : Analyst , 139 :285 , 2014
Abstract : Based on the fluorescence quenching of novel denatured protein-protected gold nanoclusters, a label-free detection method of acetylcholinesterase (AChE) activity has been developed. Using denatured bovine serum albumin (dBSA), in which 35 cysteine residues can interact polyvalently with Au nanoclusters (AuNCs) as a stabilizing agent, water-soluble and stable fluorescent gold nanoclusters were synthesized. The fluorescence of the AuNCs was quenched by thiocholine that was produced from the AChE hydrolysis of S-acetylthiocholine iodide (ACTI) to detect the AChE activity. The linear range of the method was 0.005-0.15 U mL(-1). The limit of detection (LOD) was 0.02 mU mL(-1). Other enzymes and metal ions, i.e., GPT, gamma-GT, GOx, K(+), Ca(2+) and Na(+), showed minimal interference. Using the fluorescence probe, satisfactory results for the detection of the AChE activity in human serum were obtained.
ESTHER : Li_2014_Analyst_139_285
PubMedSearch : Li_2014_Analyst_139_285
PubMedID: 24251311

Title : Acetylcholinesterase biosensor for carbaryl detection based on interdigitated array microelectrodes - Gong_2014_Bioprocess.Biosyst.Eng_37_1929
Author(s) : Gong Z , Guo Y , Sun X , Cao Y , Wang X
Ref : Bioprocess Biosyst Eng , 37 :1929 , 2014
Abstract : In this study, an acetylcholinesterase (AChE) biosensor with superior accuracy and sensitivity was successfully developed based on interdigitated array microelectrodes (IAMs). IAMs have a series of parallel microband electrodes with alternating microbands connected together. Chitosan was used as the enzyme immobilization material, and AChE was used as the model enzyme for carbaryl detection to fabricate AChE biosensor. Electrochemical impedance spectroscopy was used in conjunction with the fabricated biosensor to detect pesticide residues. Based on the inhibition of pesticides on the AChE activity, using carbaryl as model compounds, the biosensor exhibited a wide range, low detection limit, and high stability. Moreover, the biosensor can also be used as a new promising tool for pesticide residue analysis.
ESTHER : Gong_2014_Bioprocess.Biosyst.Eng_37_1929
PubMedSearch : Gong_2014_Bioprocess.Biosyst.Eng_37_1929
PubMedID: 24770986

Title : Hyperthermia-induced NDRG2 upregulation inhibits the invasion of human hepatocellular carcinoma via suppressing ERK1\/2 signaling pathway - Guo_2013_PLoS.One_8_e61079
Author(s) : Guo Y , Ma J , Wu L , Wang Q , Li X , Zhang Y , Zhang J , Yao L , Liu W
Ref : PLoS ONE , 8 :e61079 , 2013
Abstract : Hyperthermia (HT) has been proven to be able to alter the invasion capacity of cancer cells. However, the detailed mechanisms responsible for the anti-metastasis effects of HT have not been elucidated. N-myc downstream-regulated gene 2 (NDRG2), as a member of the NDRG family, has been suggested to be highly responsive to various stresses and is associated with tumor suppression. The present study aimed to investigate the biological role of NDRG2 in the invasion of human hepatocellular carcinoma (HCC) cells exposed to HT. We found that NDRG2 could be induced by HT at 45 degrees C. In addition, NDRG2 overexpression inhibited the expression of matrix metallo proteinases-2 (MMP-2) and MMP-9 as well as the invasion of HCC cells, whereas knockingdown NDRG2 reversed the anti-invasion effect of HT in vivo. Further investigation revealed that the phosphorylation level of ERK1/2, but not that of JNK and p38MAPK, was reduced in NDRG2 overexpressing cells. Moreover, the knockdown of NDRG2 expression resulted in increased cell invasion, which was rescued by treating the HepG2 cells with the ERK1/2 inhibitor PD98059, but not with the p38MAPK inhibitor SB203580 or the JNK inhibitor SP600125. Finally, the synergistic cooperation of HT at 43 degrees C and NDRG2 expression effectively reduced cytotoxicity and promoted the anti-invasion effect of HT at 45 degrees C. Taken together, these data suggest that NDRG2 can be induced by HT and that it mediates the HT-caused inhibition of invasion in HCC cells by suppressing the ERK1/2 signaling pathway. The combined application of constitutive NDRG2 expression with HT may yield an optimized therapeutic benefit.
ESTHER : Guo_2013_PLoS.One_8_e61079
PubMedSearch : Guo_2013_PLoS.One_8_e61079
PubMedID: 23630579

Title : Remote brain network changes after unilateral cortical impact injury and their modulation by acetylcholinesterase inhibition - Holschneider_2013_J.Neurotrauma_30_907
Author(s) : Holschneider DP , Guo Y , Wang Z , Roch M , Scremin OU
Ref : Journal of Neurotrauma , 30 :907 , 2013
Abstract : We explored whether cerebral cortical impact injury (CCI) effects extend beyond direct lesion sites to affect remote brain networks, and whether acetylcholinesterase (AChE) inhibition elicits discrete changes in functional activation of motor circuits following CCI. Adult male rats underwent unilateral motor-sensory CCI or sham injury. Physostigmine (AChE inhibitor) or saline were administered subcutaneously continuously via implanted minipumps (1.6 micromoles/kg/day) for 3 weeks, followed by cerebral perfusion mapping during treadmill walking using [(14)C]-iodoantipyrine. Quantitative autoradiographs were analyzed by statistical parametric mapping and functional connectivity (FC) analysis. CCI resulted in functional deficits in the ipsilesional basal ganglia, with increased activation contralesionally. Recruitment was also observed, especially contralesionally, of the red nucleus, superior colliculus, pedunculopontine tegmental nucleus, thalamus (ventrolateral n., central medial n.), cerebellum, and sensory cortex. FC decreased significantly within ipsi- and contralesional motor circuits and between hemispheres, but increased between midline cerebellum and select regions of the basal ganglia within each hemisphere. Physostigmine significantly increased functional brain activation in the cerebellar thalamocortical pathway (midline cerebellum-->ventrolateral thalamus-->motor cortex), subthalamic nucleus/zona incerta, and red nucleus and bilateral sensory cortex. In conclusion, CCI resulted in increased functional recruitment of contralesional motor cortex and bilateral subcortical motor regions, as well as recruitment of the cerebellar-thalamocortical circuit and contralesional sensory cortex. This phenomenon, augmented by physostigmine, may partially compensate motor deficits. FC decreased inter-hemispherically and in negative, but not positive, intra-hemispherical FC, and it was not affected by physostigmine. Circuit-based approaches into functional brain reorganization may inform future behavioral or molecular strategies to augment targeted neurorehabilitation.
ESTHER : Holschneider_2013_J.Neurotrauma_30_907
PubMedSearch : Holschneider_2013_J.Neurotrauma_30_907
PubMedID: 23343118

Title : Smoke-derived karrikin perception by the alpha\/beta-hydrolase KAI2 from Arabidopsis - Guo_2013_Proc.Natl.Acad.Sci.U.S.A_110_8284
Author(s) : Guo Y , Zheng Z , La Clair JJ , Chory J , Noel JP
Ref : Proc Natl Acad Sci U S A , 110 :8284 , 2013
Abstract : Genetic studies in Arabidopsis implicate an alpha/beta-hydrolase, KARRIKIN-INSENSITIVE 2 (KAI2) as a receptor for karrikins, germination-promoting butenolide small molecules found in the smoke of burned plants. However, direct biochemical evidence for the interaction between KAI2 and karrikin and for the mechanism of downstream signaling by a KAI2-karrikin complex remain elusive. We report crystallographic analyses and ligand-binding experiments for KAI2 recognition of karrikins. The karrikin-1 (KAR1) ligand sits in the opening to the active site abutting a helical domain insert but distal from the canonical catalytic triad (Ser95-His246-Asp217) of alpha/beta-hydrolases, consistent with the lack of detectable hydrolytic activity by purified KAI2. The closest approach of KAR1 to Ser95-His246-Asp217 is 3.8 A from His246. Six aromatic side chains, including His246, encapsulate KAR1 through geometrically defined aromatic-aromatic interactions. KAR1 binding induces a conformational change in KAI2 at the active site entrance. A crevice of hydrophobic residues linking the polar edge of KAR1 and the helical domain insert suggests that KAI2-KAR1 creates a contiguous interface for binding signaling partners in a ligand-dependent manner.
ESTHER : Guo_2013_Proc.Natl.Acad.Sci.U.S.A_110_8284
PubMedSearch : Guo_2013_Proc.Natl.Acad.Sci.U.S.A_110_8284
PubMedID: 23613584
Gene_locus related to this paper: arath-AtD14

Title : Association of the G-250A promoter polymorphism in the hepatic lipase gene with the risk of type 2 diabetes mellitus - Ou_2013_Ann.Endocrinol.(Paris)_74_45
Author(s) : Ou L , Yao L , Guo Y , Fan S
Ref : Ann Endocrinol (Paris) , 74 :45 , 2013
Abstract : OBJECTIVE: Variants in hepatic lipase (HL) gene which is a lipolytic enzyme involved in the metabolism of plasma lipoprotein and regulating lipid and lipoprotein metabolism are potential candidate genes for type 2 diabetes. Association of the polymorphisms in the promoter region of the HL gene (LIPC) to the plasma HDL-C concentration has been investigated. In this study, we investigated whether the G-250A polymorphism of LIPC is associated with type 2 diabetes in Chinese Han population. SUBJECTS AND
METHODS: A total of 130 patients with type 2 diabetes and 133 healthy subjects as control were randomly selected from January 2008 to January 2011 in endocrine wards of Zhengzhou People's Hospital. The G-250A polymorphisms were studied by polymerase chain reaction and restriction fragment length polymorphism. A logistic regression analysis was performed to determine the association between the rare allele and type 2 diabetes mellitus.
RESULTS: The frequency of the -250A allele was 0.297 in the T2DM group and 0.388 in the control group (P<0.05), with the difference remaining significant.
CONCLUSIONS: Patients who are carrying of the -250A allele in the promoter of the LIPC gene are susceptible to type 2 diabetes mellitus in Chinese Han population.
ESTHER : Ou_2013_Ann.Endocrinol.(Paris)_74_45
PubMedSearch : Ou_2013_Ann.Endocrinol.(Paris)_74_45
PubMedID: 23351562

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

Title : Genome of Helicobacter pylori strain XZ274, an isolate from a tibetan patient with gastric cancer in China - Guo_2012_J.Bacteriol_194_4146
Author(s) : Guo Y , Wang H , Li Y , Song Y , Chen C , Liao Y , Ren L , Guo C , Tong W , Shen W , Chen M , Mao X , Guo G , Zou Q
Ref : Journal of Bacteriology , 194 :4146 , 2012
Abstract : The infection rate of Helicobacter pylori is high all over the world, especially in the Chinese Tibetan Plateau. Here, we report the genome sequence of Helicobacter pylori strain XZ274 isolated from a Tibetan patient with gastric cancer. The strain contains 1,634,138 bp with 1,654 coding sequences and a pXZ274 plasmid of 22,406 bp with 26 coding sequences. This is the first complete genome sequence of Helicobacter pylori from the Tibetan Plateau in China.
ESTHER : Guo_2012_J.Bacteriol_194_4146
PubMedSearch : Guo_2012_J.Bacteriol_194_4146
PubMedID: 22815458
Gene_locus related to this paper: helpy-o25061

Title : Draft genome sequence of Rahnella aquatilis strain HX2, a plant growth-promoting rhizobacterium isolated from vineyard soil in Beijing, China - Guo_2012_J.Bacteriol_194_6646
Author(s) : Guo Y , Jiao Z , Li L , Wu D , Crowley DE , Wang Y , Wu W
Ref : Journal of Bacteriology , 194 :6646 , 2012
Abstract : Rahnella aquatilis strain HX2 is a plant growth-promoting, disease-suppressive rhizobacterium that was isolated from a vineyard soil in Beijing, China. Here, we report the genome sequence of this strain, which provides a valuable resource for future research examining the mechanisms of traits associated with plant growth promotion and biocontrol.
ESTHER : Guo_2012_J.Bacteriol_194_6646
PubMedSearch : Guo_2012_J.Bacteriol_194_6646
PubMedID: 23144397
Gene_locus related to this paper: rahaq-h8nn14 , rahac-h2iui7 , rahaq-h8nx59

Title : Emergent decarboxylase activity and attenuation of alpha\/beta-hydrolase activity during the evolution of methylketone biosynthesis in tomato - Auldridge_2012_Plant.Cell_24_1596
Author(s) : Auldridge ME , Guo Y , Austin MB , Ramsey J , Fridman E , Pichersky E , Noel JP
Ref : Plant Cell , 24 :1596 , 2012
Abstract : Specialized methylketone-containing metabolites accumulate in certain plants, in particular wild tomatoes in which they serve as toxic compounds against chewing insects. In Solanum habrochaites f. glabratum, methylketone biosynthesis occurs in the plastids of glandular trichomes and begins with intermediates of de novo fatty acid synthesis. These fatty-acyl intermediates are converted via sequential reactions catalyzed by Methylketone Synthase2 (MKS2) and MKS1 to produce the n-1 methylketone. We report crystal structures of S. habrochaites MKS1, an atypical member of the alpha/beta-hydrolase superfamily. Sequence comparisons revealed the MKS1 catalytic triad, Ala-His-Asn, as divergent to the traditional alpha/beta-hydrolase triad, Ser-His-Asp. Determination of the MKS1 structure points to a novel enzymatic mechanism dependent upon residues Thr-18 and His-243, confirmed by biochemical assays. Structural analysis further reveals a tunnel leading from the active site consisting mostly of hydrophobic residues, an environment well suited for fatty-acyl chain binding. We confirmed the importance of this substrate binding mode by substituting several amino acids leading to an alteration in the acyl-chain length preference of MKS1. Furthermore, we employ structure-guided mutagenesis and functional assays to demonstrate that MKS1, unlike enzymes from this hydrolase superfamily, is not an efficient hydrolase but instead catalyzes the decarboxylation of 3-keto acids.
ESTHER : Auldridge_2012_Plant.Cell_24_1596
PubMedSearch : Auldridge_2012_Plant.Cell_24_1596
PubMedID: 22523203
Gene_locus related to this paper: solha-e0ycs2

Title : The genomes of the fungal plant pathogens Cladosporium fulvum and Dothistroma septosporum reveal adaptation to different hosts and lifestyles but also signatures of common ancestry - de Wit_2012_PLoS.Genet_8_E1003088
Author(s) : de Wit PJ , van der Burgt A , Okmen B , Stergiopoulos I , Abd-Elsalam KA , Aerts AL , Bahkali AH , Beenen HG , Chettri P , Cox MP , Datema E , de Vries RP , Dhillon B , Ganley AR , Griffiths SA , Guo Y , Hamelin RC , Henrissat B , Kabir MS , Jashni MK , Kema G , Klaubauf S , Lapidus A , Levasseur A , Lindquist E , Mehrabi R , Ohm RA , Owen TJ , Salamov A , Schwelm A , Schijlen E , Sun H , van den Burg HA , van Ham RC , Zhang S , Goodwin SB , Grigoriev IV , Collemare J , Bradshaw RE
Ref : PLoS Genet , 8 :e1003088 , 2012
Abstract : We sequenced and compared the genomes of the Dothideomycete fungal plant pathogens Cladosporium fulvum (Cfu) (syn. Passalora fulva) and Dothistroma septosporum (Dse) that are closely related phylogenetically, but have different lifestyles and hosts. Although both fungi grow extracellularly in close contact with host mesophyll cells, Cfu is a biotroph infecting tomato, while Dse is a hemibiotroph infecting pine. The genomes of these fungi have a similar set of genes (70% of gene content in both genomes are homologs), but differ significantly in size (Cfu >61.1-Mb; Dse 31.2-Mb), which is mainly due to the difference in repeat content (47.2% in Cfu versus 3.2% in Dse). Recent adaptation to different lifestyles and hosts is suggested by diverged sets of genes. Cfu contains an alpha-tomatinase gene that we predict might be required for detoxification of tomatine, while this gene is absent in Dse. Many genes encoding secreted proteins are unique to each species and the repeat-rich areas in Cfu are enriched for these species-specific genes. In contrast, conserved genes suggest common host ancestry. Homologs of Cfu effector genes, including Ecp2 and Avr4, are present in Dse and induce a Cf-Ecp2- and Cf-4-mediated hypersensitive response, respectively. Strikingly, genes involved in production of the toxin dothistromin, a likely virulence factor for Dse, are conserved in Cfu, but their expression differs markedly with essentially no expression by Cfu in planta. Likewise, Cfu has a carbohydrate-degrading enzyme catalog that is more similar to that of necrotrophs or hemibiotrophs and a larger pectinolytic gene arsenal than Dse, but many of these genes are not expressed in planta or are pseudogenized. Overall, comparison of their genomes suggests that these closely related plant pathogens had a common ancestral host but since adapted to different hosts and lifestyles by a combination of differentiated gene content, pseudogenization, and gene regulation.
ESTHER : de Wit_2012_PLoS.Genet_8_E1003088
PubMedSearch : de Wit_2012_PLoS.Genet_8_E1003088
PubMedID: 23209441
Gene_locus related to this paper: mycpj-q30dw8 , mycp1-n1pnd6 , mycp1-n1per0 , mycp1-n1pg49 , mycp1-n1pwj1 , mycp1-n1pcl8 , mycp1-m2y2b1 , mycp1-n1pwu7 , mycp1-n1ppa8 , mycp1-m2yk59 , mycp1-n1pps5 , mycp1-n1pw13 , mycp1-n1pe19 , mycp1-m2xhl1 , mycp1-n1pnh6 , mycp1-n1psn5 , mycp1-n1puh9 , mycp1-n1phf7 , mycp1-m2y2h4 , mycp1-n1q523 , dotsn-n1q1b1 , dotsn-n1q415 , dotsn-est1

Title : Assisted inhibition effect of acetylcholinesterase with n-octylphosphonic acid and application in high sensitive detection of organophosphorous pesticides by matrix-assisted laser desorption\/ionization Fourier transform mass spectrometry - Cai_2011_Anal.Chim.Acta_706_291
Author(s) : Cai T , Zhang L , Wang H , Zhang J , Guo Y
Ref : Anal Chim Acta , 706 :291 , 2011
Abstract : A simple and practical approach to improve the sensitivity of acetylcholinesterase (AChE)-inhibited method has been developed for monitoring organophosphorous (OP) pesticide residues. In this work, matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) was used to detect AChE activity. Due to its good salt-tolerance and low sample consumption, MALDI-FTMS facilitates rapid and high-throughput screening of OP pesticides. Here we describe a new method to obtain low detection limits via employing external reagents. Among candidate compounds, n-octylphosphonic acid (n-Octyl-PA) displays assistant effect to enhance AChE inhibition by OP pesticides. In presence of n-Octyl-PA, the percentages of AChE inhibition still kept correlation with OP pesticide concentrations. The detection limits were improved significantly even by 10(2)-10(3) folds in comparison with conventional enzyme-inhibited methods. Different detection limits of OP pesticides with different toxicities were as low as 0.005 mug L(-1) for high toxic pesticides and 0.05 mug L(-1) for low toxic pesticides. Besides, the reliability of results from this method to analyze cowpea samples had been demonstrated by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The application of this commercial available assistant agent shows great promise to detect OP compounds in complicated biological matrix and broadens the mind for high sensitivity detection of OP pesticide residues in agricultural products.
ESTHER : Cai_2011_Anal.Chim.Acta_706_291
PubMedSearch : Cai_2011_Anal.Chim.Acta_706_291
PubMedID: 22023864

Title : Genomics-based approaches to screening carboxylesterase-like genes potentially involved in malathion resistance in oriental migratory locust (Locusta migratoria manilensis) - Zhang_2011_Pest.Manag.Sci_67_183
Author(s) : Zhang J , Yang M , Jia Q , Guo Y , Ma E , Zhu KY
Ref : Pest Manag Sci , 67 :183 , 2011
Abstract : BACKGROUND: Previous studies have indicated that increased carboxylesterase (CarE) activity is a major mechanism of malathion resistance in field populations of the oriental migratory locust, Locusta migratoria manilensis (Meyen), in China. The aim of the present study was to screen CarE-like genes from a large locust expressed sequence tag (EST) database and to assess their potential roles in malathion resistance. RESULTS: Twenty-five ESTs derived from different CarE-like genes in the locust EST database were identified, and 12 candidate genes with significantly increased expressions, ranging from 2.6- to 11.6-fold in a field-derived resistant (FR) colony of the locust, were found. These candidate genes were constitutively expressed in all nymph and adult stages, and most of them were predominantly expressed in the gastric caeca and the midgut. Among the 12 genes, two representative genes (LmCarE9 and LmCarE25) were chosen for RNAi followed by malathion bioassay. The nymph mortalities increased from 34.3 to 65.2 and 54.2% respectively after LmCarE9 and LmcarE25 were silenced. These results indicated significant roles of these CarE-like genes in conferring malathion resistance in the locust. CONCLUSION: Multiple CarE-like genes were involved in malathion resistance in the locust. As validated by RNAi followed by malathion bioassay, LmCarE9 and LmcarE25 played a significant role in conferring malathion resistance.
ESTHER : Zhang_2011_Pest.Manag.Sci_67_183
PubMedSearch : Zhang_2011_Pest.Manag.Sci_67_183
PubMedID: 21061277
Gene_locus related to this paper: locmi-l7szt8 , locmi-l7su46

Title : Biochemical effects of acute phoxim administration on antioxidant system and acetylcholinesterase in Oxya chinensis (Thunberg) (Orthoptera: Acrididae) - Wu_2011_Pestic.Biochem.Physiol_100_23
Author(s) : Wu H , Liu J , Zhang R , Zhang J , Guo Y , Ma E
Ref : Pesticide Biochemistry and Physiology , 100 :23 , 2011
Abstract : The study was undertaken to evaluate the effects of different concentrations of phoxim on acetylcholinesterase (AChE) and esterase (EST) activities, and antioxidant system after topical application to Oxya chinensis. The results showed that phoxim inhibited AChE activity, and did not cause significant changes in the EST activity and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). After phoxim administration, superoxide (SOD) and catalase (CAT) activities showed a biphasic response with an initial increase followed by a decline in their activities. Glutathione reductase (GR) and glutathione peroxidase (GPx) activities were inhibited in comparison with the control. Glutathione S-transferase (GST) activity showed irregular changes. Its activity increased significantly at the concentrations of 0.06 and 0.12 ug/uL and decreased at the concentrations of 0.09 and 0.24 ug/uL compared with the control. Changes in SOD, CAT, GST, GPx, and GR activities indicated that phoxim caused oxidative damage in O. chinensis. However, no significant changes in MDA content suggested that these enzymes played important roles in scavenging the oxidative free radicals induced by phoxim in O. chinensis. The formation of oxygen free radicals might be a factor in the toxicity of phoxim.
ESTHER : Wu_2011_Pestic.Biochem.Physiol_100_23
PubMedSearch : Wu_2011_Pestic.Biochem.Physiol_100_23

Title : Comparative functional genomics of the fission yeasts - Rhind_2011_Science_332_930
Author(s) : Rhind N , Chen Z , Yassour M , Thompson DA , Haas BJ , Habib N , Wapinski I , Roy S , Lin MF , Heiman DI , Young SK , Furuya K , Guo Y , Pidoux A , Chen HM , Robbertse B , Goldberg JM , Aoki K , Bayne EH , Berlin AM , Desjardins CA , Dobbs E , Dukaj L , Fan L , Fitzgerald MG , French C , Gujja S , Hansen K , Keifenheim D , Levin JZ , Mosher RA , Muller CA , Pfiffner J , Priest M , Russ C , Smialowska A , Swoboda P , Sykes SM , Vaughn M , Vengrova S , Yoder R , Zeng Q , Allshire R , Baulcombe D , Birren BW , Brown W , Ekwall K , Kellis M , Leatherwood J , Levin H , Margalit H , Martienssen R , Nieduszynski CA , Spatafora JW , Friedman N , Dalgaard JZ , Baumann P , Niki H , Regev A , Nusbaum C
Ref : Science , 332 :930 , 2011
Abstract : The fission yeast clade--comprising Schizosaccharomyces pombe, S. octosporus, S. cryophilus, and S. japonicus--occupies the basal branch of Ascomycete fungi and is an important model of eukaryote biology. A comparative annotation of these genomes identified a near extinction of transposons and the associated innovation of transposon-free centromeres. Expression analysis established that meiotic genes are subject to antisense transcription during vegetative growth, which suggests a mechanism for their tight regulation. In addition, trans-acting regulators control new genes within the context of expanded functional modules for meiosis and stress response. Differences in gene content and regulation also explain why, unlike the budding yeast of Saccharomycotina, fission yeasts cannot use ethanol as a primary carbon source. These analyses elucidate the genome structure and gene regulation of fission yeast and provide tools for investigation across the Schizosaccharomyces clade.
ESTHER : Rhind_2011_Science_332_930
PubMedSearch : Rhind_2011_Science_332_930
PubMedID: 21511999
Gene_locus related to this paper: schjy-b6jxl8 , schjy-b6k0k9 , schjy-b6k7s4 , schjy-b6k575 , schcr-s9vnl9 , schoy-s9q625 , schjy-kex1 , schpo-ykv6

Title : Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury - Holschneider_2011_J.Neurotrauma_28_1909
Author(s) : Holschneider DP , Guo Y , Roch M , Norman KM , Scremin OU
Ref : Journal of Neurotrauma , 28 :1909 , 2011
Abstract : Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 mumol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 mumol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses.
ESTHER : Holschneider_2011_J.Neurotrauma_28_1909
PubMedSearch : Holschneider_2011_J.Neurotrauma_28_1909
PubMedID: 21787180

Title : Enzymatic functions of wild tomato methylketone synthases 1 and 2 - Yu_2010_Plant.Physiol_154_67
Author(s) : Yu G , Nguyen TT , Guo Y , Schauvinhold I , Auldridge ME , Bhuiyan N , Ben-Israel I , Iijima Y , Fridman E , Noel JP , Pichersky E
Ref : Plant Physiol , 154 :67 , 2010
Abstract : The trichomes of the wild tomato species Solanum habrochaites subsp. glabratum synthesize and store high levels of methylketones, primarily 2-tridecanone and 2-undecanone, that protect the plants against various herbivorous insects. Previously, we identified cDNAs encoding two proteins necessary for methylketone biosynthesis, designated methylketone synthase 1 (ShMKS1) and ShMKS2. Here, we report the isolation of genomic sequences encoding ShMKS1 and ShMKS2 as well as the homologous genes from the cultivated tomato, Solanum lycopersicum. We show that a full-length transcript of ShMKS2 encodes a protein that is localized in the plastids. By expressing ShMKS1 and ShMKS2 in Escherichia coli and analyzing the products formed, as well as by performing in vitro assays with both ShMKS1and ShMKS2, we conclude that ShMKS2 acts as a thioesterase hydrolyzing 3-ketoacyl-acyl carrier proteins (plastid-localized intermediates of fatty acid biosynthesis) to release 3-ketoacids and that ShMKS1 subsequently catalyzes the decarboxylation of these liberated 3-ketoacids, forming the methylketone products. Genes encoding proteins with high similarity to ShMKS2, a member of the "hot-dog fold" protein family that is known to include other thioesterases in nonplant organisms, are present in plant species outside the genus Solanum. We show that a related enzyme from Arabidopsis (Arabidopsis thaliana) also produces 3-ketoacids when recombinantly expressed in E. coli. Thus, the thioesterase activity of proteins in this family appears to be ancient. In contrast, the 3-ketoacid decarboxylase activity of ShMKS1, which belongs to the alpha/beta-hydrolase fold superfamily, appears to have emerged more recently, possibly within the genus Solanum.
ESTHER : Yu_2010_Plant.Physiol_154_67
PubMedSearch : Yu_2010_Plant.Physiol_154_67
PubMedID: 20605911
Gene_locus related to this paper: solha-e0ycs2 , sollc-e0ycs4 , sollc-e0ycs5 , sollc-e0ycs6 , sollc-e0ycs7

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

Title : Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China - Qi_2009_Psychiatr.Genet_19_1
Author(s) : Qi H , Xing L , Zhang K , Gao X , Zheng Z , Huang S , Guo Y , Zhang F
Ref : Psychiatr Genet , 19 :1 , 2009
Abstract : OBJECTIVE: Neuroligin-4 is essential for proper brain function. Some studies indicate a close relationship between neuroligin-4 and several human psychiatric conditions. METHODS: The case-control method was used to study the association between nonspecific mental retardation (NSMR) and genetic variants of neuroligin-4 gene (NLGN4). Five single nucleotide polymorphisms (SNPs: rs5916271, rs7049300, rs6638575, rs3810686, and rs1882260) were genotyped by PCR-RFLP/SSCP method in the NLGN4. RESULTS: Individual SNP analysis shows significant differences at SNPs rs3810686 and rs1882260 for allele frequency when NSMR cases and controls [odds ratio (OR)=1.589, 95% confidence interval (CI)=1.035-2.438, chi2=4.53, df=1, P=0.033; OR=2.050, 95% CI=1.211-3.470, chi2=7.38, df=1, P=0.007, respectively] were compared. Further haplotype analysis indicates that there are two haplotype sets, rs3810686-rs1882260 and rs6638575-rs3810686-rs1882260, which show statistical differences between NSMR cases and controls (chi2=6.79, df=2, global P=0.034; chi2=9.29, df=2, global P=0.0096, respectively). CONCLUSION: The results suggest a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region.
ESTHER : Qi_2009_Psychiatr.Genet_19_1
PubMedSearch : Qi_2009_Psychiatr.Genet_19_1
PubMedID: 19125102

Title : Monitoring enzyme reaction and screening of inhibitors of acetylcholinesterase by quantitative matrix-assisted laser desorption\/ionization Fourier transform mass spectrometry - Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
Author(s) : Xu Z , Yao S , Wei Y , Zhou J , Zhang L , Wang C , Guo Y
Ref : J Am Soc Mass Spectrom , 19 :1849 , 2008
Abstract : A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)-based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (K(m)) of acetylcholinesterase (AChE) was determined to be 73.9 micromol L(-1) by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC(50)) value of galantamine obtained for AChE was 2.39 micromol L(-1). Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE.
ESTHER : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedSearch : Xu_2008_J.Am.Soc.Mass.Spectrom_19_1849
PubMedID: 18789720

Title : Increased activity and reduced sensitivity of acetylcholinesterase associated with malathion resistance in a field population of the oriental migratory locust, Locusta migratoria manilensis (Meyen) - Yang_2008_Pestic.Biochem.Physiol_91_32
Author(s) : Yang M , Zhang J , Zhu KY , Xuan T , Liu X , Guo Y , Ma E
Ref : Pesticide Biochemistry and Physiology , 91 :32 , 2008
Abstract : The susceptibility to malathion, and the activity and sensitivity of acetylcholinesterase (AChE, EC were compared between two populations of the oriental migratory locust, Locusta migratoria manilensis (Meyen) collected from Wudi County of Shandong Province in East China and Huangliu County of Hainan Province in South China. Huangliu population showed 8.5-fold resistance to malathion compared with Wudi population. AChE from Huangliu population showed 4.8-fold higher activity than that from Wudi population toward the model substrate acetylthiocholine (ATC). Kinetic studies indicated that AChE from Huangliu population had 2.6-fold lower affinity, but 5.0-fold higher catalytic activity toward ATC than AChE from Wudi population. Significantly increased activity of AChE in Huangliu population was also confirmed by non-denaturing polyacrylamide gel electrophoresis. Inhibition kinetics revealed that AChE from Huangliu population was 9.8-, 2.4-, 8.0- and 7.7-fold less sensitive to inhibition by paraoxon, malaoxon, chlopyrifos oxon, demeton-S-methyl, respectively, than that from Wudi population. Our studies revealed that a mild resistance to malathion in Huangliu population was associated with reduced sensitivity and increased catalytic activity of AChE. Our results suggest that alterations of AChE may play an important role conferring or contribute to malathion resistance in Huangliu population of the locust.
ESTHER : Yang_2008_Pestic.Biochem.Physiol_91_32
PubMedSearch : Yang_2008_Pestic.Biochem.Physiol_91_32
Gene_locus related to this paper: locmi-ACHE1

Title : Effect of polysaccharide from Auricularia auricula on blood lipid metabolism and lipoprotein lipase activity of ICR mice fed a cholesterol-enriched diet - Chen_2008_J.Food.Sci_73_H103
Author(s) : Chen G , Luo YC , Li BP , Li B , Guo Y , Li Y , Su W , Xiao ZL
Ref : J Food Sci , 73 :H103 , 2008
Abstract : Polysaccharides from Auricularia auricula (AAP) extracted in hot water and precipitated by ethanol were chemically well defined, including 42.5% total carbohydrate, 19.6% uronic acids, 15.8% sulfate groups, 1.7% N, and 20.3% ash. Gas chromatography analysis demonstrated that the neutral sugars were mainly composed of rhamnose, xylose, and glucose and smaller amounts of mannose, galactose, and arabinose. The present study was designed to investigate the antioxidant capacity of AAP on blood lipid metabolism and lipoprotein lipase (LPL) activity in ICR mice fed cholesterol-enriched diet (CED) for the 1st time. Furthermore, the relationship between the atherosclerotic index (AI) and LPL activity to total antioxidant capacity (TAC) was studied. Thirty-six ICR mice were randomly assigned to 3 groups (n=12). The mice in control group (NG) received regular diet and the mice in model group (MG) received CED; these 2 groups were provided with distilled water by oral gavage. The experimental group (EG) was fed CED with oral gavage of AAP (120 mg/kg/d body weight) for an 8-wk period. After 2, 4, 6, and 8 wk, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) levels of the serum were determined by enzymatic methods. The results indicated that the polysaccharides significantly lowered the concentrations of serum TC and LDL-C compared with the CED control group (P<0.05). Moreover, oral administration of polysaccharides significantly improved TAC, LPL activity, and decreased MDA level, as well as AI. These conclusions revealed the beneficial effects ofAAP on the preventive actions against hypercholesterolemia.
ESTHER : Chen_2008_J.Food.Sci_73_H103
PubMedSearch : Chen_2008_J.Food.Sci_73_H103
PubMedID: 19241585

Title : Comparisons of malathion susceptibility, target sensitivity, and detoxification enzyme activity in nine field populations of Oxya chinensis (Orthoptera: Acrididae) - Wu_2007_J.Econ.Entomol_100_1409
Author(s) : Wu H , Yang M , Guo Y , Xie Z , Ma E
Ref : J Econ Entomol , 100 :1409 , 2007
Abstract : The malathion susceptibility, acetylcholinesterase (AChE) sensitivity, and the activity of selected detoxification enzymes including general esterase (EST) and glutathione S-transferase (GST) were compared among field populations of the grasshopper Oxya chinensis (Thunberg) (Orthoptera: Acrididae) collected from nine regions of China. Bioassay results showed that these populations had various levels of the susceptibility to malathion with the LDo values ranging from 1.4- to 22.6-fold compared with the most susceptible population (Xiangyuan or XY). The Jinnan (JN) population seemed to be malathion resistant (22.6-fold), whereas other populations exhibited 1.4- to 6.8-fold reduced malathion susceptibility with a rank order of Changan > Baodi > Hanzhong > Xinxiang > Yinchuan > Beidagang > Jinyuan. It seemed that the observed malathion resistance in the JN population was attributed to at least two resistance mechanisms, including increased EST activity (2.2-fold) and reduced sensitivity of AChE to inhibition by malaoxon (4.6-fold) compared with those of the XY population. In contrast, differential malathion susceptibilities in other populations may be due to increased activities of certain detoxification enzymes (e.g., EST and GST), reduced sensitivity of AChE, or other factors, which were not consistent across the populations examined. Such differential susceptibilities to malathion were likely due to different population habitats (e.g., grasslands, rice [Oryza sativa L.]-producing regions) with very different insecticide application histories and pest management practices.
ESTHER : Wu_2007_J.Econ.Entomol_100_1409
PubMedSearch : Wu_2007_J.Econ.Entomol_100_1409
PubMedID: 17849895

Title : Lipase-catalysed enantioselective ammonolysis of phenylglycine methyl ester in organic solvent - Du_2003_Biotechnol.Appl.Biochem_38_107
Author(s) : Du W , Zong M , Guo Y , Liu D
Ref : Biotechnol Appl Biochem , 38 :107 , 2003
Abstract : Ammonium, provided by ammonium carbamate as a novel acyl acceptor, was adopted for enzymic enantioselective ammonolysis of racemic phenylglycine methyl ester in this paper and it has been found that the reaction conditions have profound effects on enzymic activity and enantioselectivity: the optimal concentration of ammonium carbamate was 80 mM; t-butanol was the most suitable reaction medium and the optimum initial water activity was found to be 0.75; relatively high reaction rate and enantioselectivity could be attained within the temperature range of 30-40 degrees C. Compared with the corresponding hydrolysis and alcoholysis, enzymic ammonolysis expressed rather high enzymic activity and enantioselectivity and 95% of enzymic activity remained after 10 batches of ammonolysis, which demonstrates that lipase-catalysed ammonolysis is a promising method for the preparation of optically pure (R)-phenylglycine and its derivatives.
ESTHER : Du_2003_Biotechnol.Appl.Biochem_38_107
PubMedSearch : Du_2003_Biotechnol.Appl.Biochem_38_107
PubMedID: 12749767

Title : G protein-coupled receptor-induced sensitization of phospholipase C stimulation by receptor tyrosine kinases - Schmidt_2000_J.Biol.Chem_275_32603
Author(s) : Schmidt M , Frings M , Mono ML , Guo Y , Weernink PA , Evellin S , Han L , Jakobs KH
Ref : Journal of Biological Chemistry , 275 :32603 , 2000
Abstract : Activation of stably expressed M(2) and M(3) muscarinic acetylcholine receptors (mAChRs) as well as of endogenously expressed lysophosphatidic acid and purinergic receptors in HEK-293 cells can induce a long lasting potentiation of phospholipase C (PLC) stimulation by these and other G protein-coupled receptors (GPCRs). Here, we report that GPCRs can induce an up-regulation of PLC stimulation by receptor tyrosine kinases (RTKs) as well and provide essential mechanistic characteristics of this sensitization process. Pretreatment of HEK-293 cells for 2 min with carbachol, a mAChR agonist, lysophosphatidic acid, or ATP, followed by agonist washout, strongly increased (by 2-3-fold) maximal PLC stimulation (measured >/=40 min later) by epidermal growth factor and platelet-derived growth factor, but not insulin, and largely enhanced PLC sensitivity to these RTK agonists. The up-regulation of RTK-induced PLC stimulation was cycloheximide-insensitive and was observed for up to approximately 90 min after removal of the GPCR agonist. Sensitization of receptor-induced PLC stimulation caused by prior M(2) mAChR activation was fully prevented by pertussis toxin and strongly reduced by expression of Gbetagamma scavengers. Furthermore, inhibition of conventional protein kinase C (PKC) isoenzymes and chelation of intracellular Ca(2+) suppressed the sensitization process, while overexpression of PKC-alpha, but not PKC-betaI, further enhanced the M(2) mAChR-induced sensitization of PLC stimulation. None of these treatments affected acute PLC stimulation by either GPCR or RTK agonists. Taken together, short term activation of GPCRs can induce a strong and long lasting sensitization of PLC stimulation by RTKs, a process apparently involving G(i)-derived Gbetagammas as well as increases in intracellular Ca(2+) and activation of a PKC isoenzyme, most likely PKC-alpha.
ESTHER : Schmidt_2000_J.Biol.Chem_275_32603
PubMedSearch : Schmidt_2000_J.Biol.Chem_275_32603
PubMedID: 10908568

Title : [Morphological observations of the medial olivocochlear efferents in gerbils with chronic gentamicin ototoxicity] - Xie_1999_Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi_34_157
Author(s) : Xie D , Guo Y , Wu W
Ref : Zhonghua Er Bi Yan Hou Ke Za Zhi , 34 :157 , 1999
Abstract : OBJECTIVE: To determine the possible involvement of the medial olivocochlear efferents (MOC) in chronic aminoglycoside ototoxicity, the morphological changes of the MOC efferents in the cochlea of Mongolian gerbils and their correlations with the impairment of the outer hair cells (OHCs) were observed.
METHODS: The animals were given gentamicin in a dose of 150 mg/kg a day for 10 days. The distributions and densities of the MOC efferents were examined using the modified histochemical staining for acetylcholinesterase (AChE) and the numbers of OHCs were numerated with toluidine blue and Ehrlich haematoxylin staining on the surface preparation.
RESULTS: Significant damage to the MOC fibers and terminals as well as OHCs was noted in the basal turn of the cochlea, especially in those animals examined in 7th and 11th week after the gentamicin administration. The site of the greatest impairment of OHCs was consistent with that of the MOC efferents. CONCLUSION: The results suggested that damage to the MOC efferents might play an important role in gentamicin-induced impairment of OHCs.
ESTHER : Xie_1999_Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi_34_157
PubMedSearch : Xie_1999_Zhonghua.Er.Bi.Yan.Hou.Ke.Za.Zhi_34_157
PubMedID: 12764807

Title : Role of sphingosine kinase in Ca(2+) signalling by epidermal growth factor receptor - Meyer_1999_FEBS.Lett_461_217
Author(s) : Meyer zu Heringdorf D , Lass H , Kuchar I , Alemany R , Guo Y , Schmidt M , Jakobs KH
Ref : FEBS Letters , 461 :217 , 1999
Abstract : Contribution of sphingosine kinase (SPK)-catalyzed production of sphingosine-1-phosphate (SPP), in comparison to phospholipase C (PLC), to Ca(2+) signalling by epidermal growth factor (EGF) was studied in two HEK-293 cell clones (HEK2 and HEK3), expressing functional EGF receptors and exhibiting release of stored Ca(2+) by intracellular SPP. In HEK3 cells, EGF increased [Ca(2+)](i) and stimulated both, SPK and PLC. [Ca(2+)](i) increase, but not PLC stimulation, was strongly reduced by SPK inhibition. In HEK2 cells, EGF similarly stimulated PLC, but did not increase [Ca(2+)](i) or stimulate SPK, suggesting that intracellular SPP production plays a major role for Ca(2+) signalling by EGF in HEK-293 cells.
ESTHER : Meyer_1999_FEBS.Lett_461_217
PubMedSearch : Meyer_1999_FEBS.Lett_461_217
PubMedID: 10567700