Sun X

References (101)

Title : Combination of retagliptin and henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, active-controlled, phase 3 trial - Wang_2024_Diabetes.Obes.Metab__
Author(s) : Wang W , Guo X , Zhang C , Ning T , Ma G , Huang Y , Jia R , Zhou D , Cao M , Zhang T , Yao L , Yuan J , Chen L , Wang Y , Jiang C , Dong X , Chen M , Gu Q , Zhang L , Fu Y , Pan T , Bi Y , Song W , Xu J , Lu W , Sun X , Ye Z , Zhang D , Peng L , Lin X , Dai W , Wang Q , Yang W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: This study assessed the efficacy and safety of co-administering retagliptin and henagliflozin versus individual agents at corresponding doses in patients with type 2 diabetes mellitus who were inadequately controlled with metformin. METHODS: This multicentre, phase 3 trial consisted of a 24-week, randomized, double-blind, active-controlled period. Patients with glycated haemoglobin (HbA1c) levels between 7.5% and 10.5% were randomized to receive once-daily retagliptin 100 mg (R100; n = 155), henagliflozin 5 mg (H5; n = 156), henagliflozin 10 mg (H10; n = 156), co-administered R100/H5 (n = 155), or R100/H10 (n = 156). The primary endpoint was the change in HbA1c from baseline to week 24. RESULTS: Based on the primary estimand, the least squares mean reductions in HbA1c at week 24 were significantly greater in the R100/H5 (-1.51%) and R100/H10 (-1.54%) groups compared with those receiving the corresponding doses of individual agents (-0.98% for R100, -0.86% for H5 and -0.95% for H10, respectively; p < .0001 for all pairwise comparisons). Achievement of HbA1c <7.0% at week 24 was observed in 27.1% of patients in the R100 group, 21.2% in the H5 group, 24.4% in the H10 group, 57.4% in the R100/H5 group and 56.4% in the R100/H10 group. Reductions in fasting plasma glucose and 2-h postprandial glucose were also more pronounced in the co-administration groups compared with the individual agents at corresponding doses. Decreases in body weight and systolic blood pressure were greater in the groups containing henagliflozin than in the R100 group. The incidence rates of adverse events were similar across all treatment groups, with no reported episodes of severe hypoglycaemia. CONCLUSIONS: For patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy, the co-administration of retagliptin and henagliflozin yielded more effective glycaemic control through 24 weeks compared with the individual agents at their corresponding doses.
ESTHER : Wang_2024_Diabetes.Obes.Metab__
PubMedSearch : Wang_2024_Diabetes.Obes.Metab__
PubMedID: 38221859 || 38618970

Title : Role of diacylglycerol O-acyltransferase 1 (DGAT1) in lipolysis and autophagy of adipose tissue from ketotic dairy cows - Xu_2024_J.Dairy.Sci__
Author(s) : Xu Q , Fan Y , Mauck J , Loor JJ , Sun X , Jia H , Li X , Xu C
Ref : J Dairy Sci , : , 2024
Abstract : High-yielding dairy cows in early lactation often encounter difficulties in meeting the energy requirements essential for maintaining milk production. This is primarily attributed to insufficient dry matter intake, which consequently leads to sustained lipolysis of adipose tissue. Fatty acids released by lipolysis can disrupt metabolic homeostasis. Autophagy, an adaptive response to intracellular environmental changes, is considered a crucial mechanism for regulating lipid metabolism and maintaining a proper cellular energy status. Despite its close relationship with aberrant lipid metabolism and cyto-lipotoxicity in animal models of metabolic disorders, the precise function of diacylglycerol o-acyltransferase 1 (DGAT1) in bovine adipose tissue during periods of negative energy balance (NEB) is not fully understood. Particularly regarding its involvement in lipolysis and autophagy. The objective of the present study was to assess the impact of DGAT1 on both lipolysis and autophagy in bovine adipose tissue and isolated adipocytes. Adipose tissue and blood samples were collected from cows diagnosed as clinically ketotic (n = 15) or healthy (n = 15) following a veterinary evaluation based on clinical symptoms and serum concentrations of BHB, which were 3.19 mM (interquartile range = 0.20) and 0.50 mM (interquartile range = 0.06), respectively. Protein abundance of DGAT1 and phosphorylation levels of unc-51-like kinase 1 (ULK1), were greater in adipose tissue from cows with ketosis, whereas phosphorylation levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were lower. Furthermore, when adipocytes isolated from the harvested adipose tissue of 15 healthy cows were transfected with DGAT1 overexpression adenovirus or DGAT1 small interfering RNA followed by exposure to epinephrine (EPI), it led to greater ratios and protein abundance of phosphorylated hormone-sensitive triglyceride lipase (LIPE) to total LIPE and adipose triglyceride lipase (ATGL), while inhibiting the protein phosphorylation levels of ULK1, PI3K, AKT and mTOR. Overexpression of DGAT1 in EPI-treated adipocytes reduced lipolysis and autophagy, whereas silencing DGAT1 further exacerbated EPI-induced lipolysis and autophagy. Taken together, these findings indicate that upregulation of DGAT1 may function as an adaptive response to suppress adipocytes lipolysis, highlighting the significance of maintaining metabolic homeostasis in dairy cows during periods of NEB.
ESTHER : Xu_2024_J.Dairy.Sci__
PubMedSearch : Xu_2024_J.Dairy.Sci__
PubMedID: 38395404

Title : Three-in-One Peptide Prodrug with Targeting, Assembly and Release Properties for Overcoming Bacterium-Induced Drug Resistance and Potentiating Anti-Cancer Immune Response - Gao_2024_Adv.Mater__e2312153
Author(s) : Gao G , Jiang YW , Chen J , Xu X , Sun X , Xu H , Liang G , Liu X , Zhan W , Wang M , Xu Y , Zheng J , Wang G
Ref : Adv Mater , :e2312153 , 2024
Abstract : The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate anti-tumor immunity, herein we rationally design a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic ciprofloxacin derivative (Cip-OH) and chemotherapeutic drug camptothecin (CPT) are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment. This article is protected by copyright. All rights reserved.
ESTHER : Gao_2024_Adv.Mater__e2312153
PubMedSearch : Gao_2024_Adv.Mater__e2312153
PubMedID: 38444205

Title : Ameliorative effect of scopolamine-induced cognitive dysfunction by Fufangmuniziqi formula: The roles of alkaloids, saponins, and flavonoids - Zhao_2023_J.Ethnopharmacol__116792
Author(s) : Zhao X , Hu X , Xie Q , Qi S , Xiang Z , Sun X , Xie Z , Dang R , Zhou L , Liu W , Cheng X , Wang C
Ref : J Ethnopharmacol , :116792 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Fufangmuniziqi formula (FFMN), a traditional Uyghur medicine used in China, is derived from an ancient Uyghur medical book and consists of 13 herbs. The herbs of FFMN, such as Peganum harmala L., Glycyrrhiza uralensis Fisch., and Nigella glandulifera, have been demonstrated to have acetylcholinesterase (AChE) inhibitory, anti-neuroinflammatory, or antioxidant effects. Therefore, FFMN may have a good anti-Alzheimer's disease (AD) effect, but its specific action and mechanism need to be further proven. AIM OF THE STUDY: This study aims to investigate the anti-AD effects of FFMN and the role played by alkaloids, flavonoids, and saponins in anti-AD. MATERIALS AND METHODS: The alkaloids, flavonoids, and saponins fractions of FFMN were prepared by macroporous resin chromatography. The absorbed ingredients in the drug-containing serum were identified by UPLC-Q-TOF-MS. An AD mouse model was established by intraperitoneal injection of scopolamine (SCO). The role of different fractions of FFMN in the anti-AD process was examined by Morris water maze (MWM), in-vitro cell, and AChE inhibition assay. RESULTS: A total of 20 ingredients were identified in the serum samples collected after oral administration of FFMN, and seven compounds were selected as candidate active compounds. MWM experiments showed that different fractions of FFMN could significantly improve SCO-induced learning memory impairment in mice. The alkaloids fraction (ALK) regulated cholinergic function by inhibiting AChE activity, activating choline acetyltransferase activity, and protein expression. Flavonoids and saponins were more potent than the ALK in downregulating pro-inflammatory factors or inflammatory mediators, such as TNF-alpha, MPO, and nitric oxide. Western blot results further confirmed that flavonoids and saponins attenuated neuroinflammation by inhibiting the phosphorylation of IkappaB and NF-kappaB p65. This result was also verified by in-vitro cellular assays. FFMN enhanced antioxidant defense by increasing the activity of superoxide dismutase and reducing the production of MDA. Combined with cellular experiments, flavonoids and saponins were proven more protective against oxidative damage. CONCLUSION: FFMN improved cognitive and memory impairment in the SCO-induced AD mouse model. ALK mainly enhanced the function of the cholinergic system. Flavonoid and saponin fractions mainly attenuated neuroinflammation and oxidative stress by modulating the NF-kappaB pathway. All these findings strongly suggested that the combination of alkaloid, flavonoid, and saponin fractions derived from FFMN is a promising anti-AD agent that deserves further development.
ESTHER : Zhao_2023_J.Ethnopharmacol__116792
PubMedSearch : Zhao_2023_J.Ethnopharmacol__116792
PubMedID: 37356745

Title : Introducing Mn into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer for detection of organophosphorus pesticides - Feng_2023_Mikrochim.Acta_190_437
Author(s) : Feng Y , Hu P , Wang M , Sun X , Pan W , Wang J
Ref : Mikrochim Acta , 190 :437 , 2023
Abstract : In order to design and establish a highly efficient and selective nanozyme-based sensing platform for the UV-vis detection of organophosphorus pesticides (OPs), Mn was introduced into ZIF-8 nanozyme for enhancing its catalytic activities and adding specific recognizer. The Mn-doped ZIF-8 (Mn-ZIF-8) nanocomposites were synthesized with a very facile one-pot method by heating the mixture of ZnO, 2-methylimidazole (Hmin) and Mn(CH(3)COO)(2).4H(2)O in a solvent-free system at 180 degreesC for 8 h. The Mn-ZIF-8 nanocomposite showed a higher peroxidase activity and an additional thiocholine (TCh)-degradable property compared to the pristine ZIF-8. OPs could inhibit acetylcholinesterase (AChE) to catalyze the hydrolysis of acetylthiocholine (ATCh) to produce TCh, thus blocking the degradation of Mn-ZIF-8 and protecting the catalysis of the oxidation of colorless 3,3',5,5'-tetramethylbenzydine (TMB) to blue oxidized TMB (ox-TMB). Accordingly, a detection method for OPs with high sensitivity and selectivity was designed and established on the basis of the Mn-ZIF-8 nanozyme with a linear range of 0.1-20 nM and a limit of detection (LOD) as low as 54 pM.
ESTHER : Feng_2023_Mikrochim.Acta_190_437
PubMedSearch : Feng_2023_Mikrochim.Acta_190_437
PubMedID: 37843605

Title : ABHD6 drives endocytosis of AMPA receptors to regulate synaptic plasticity and learning flexibility - Wei_2023_Prog.Neurobiol__102559
Author(s) : Wei M , Yang L , Su F , Liu Y , Zhao X , Luo L , Sun X , Liu S , Dong Z , Zhang Y , Shi YS , Liang J , Zhang C
Ref : Prog Neurobiol , :102559 , 2023
Abstract : Trafficking of alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (AMPARs), mediated by AMPAR interacting proteins, enabled neurons to maintain tuning capabilities at rest or active state. alpha/beta-Hydrolase domain-containing 6 (ABHD6), an endocannabinoid hydrolase, was an AMPAR auxiliary subunit found to negatively regulate the surface delivery of AMPARs. While ABHD6 was found to prevent AMPAR tetramerization in endoplasmic reticulum, ABHD6 was also reported to localize at postsynaptic site. Yet, the role of ABHD6 interacting with AMPAR at postsynaptic site, and the physiological significance of ABHD6 regulating AMPAR trafficking remains elusive. Here, we generated the ABHD6 knockout (ABHD6(KO)) mice and found that deletion of ABHD6 selectively enhanced AMPAR-mediated basal synaptic responses and the surface expression of postsynaptic AMPARs. Furthermore, we found that loss of ABHD6 impaired hippocampal long-term depression (LTD) and synaptic downscaling in hippocampal synapses. AMPAR internalization assays revealed that ABHD6 was essential for neuronal activity-dependent endocytosis of surface AMPARs, which is independent of ABHD6's hydrolase activity. The defects of AMPAR endocytosis and LTD are expressed as deficits in learning flexibility in ABHD6(KO) mice. Collectively, we demonstrated that ABHD6 is an endocytic accessory protein promoting AMPAR endocytosis, thereby contributes to the formation of LTD, synaptic downscaling and reversal learning.
ESTHER : Wei_2023_Prog.Neurobiol__102559
PubMedSearch : Wei_2023_Prog.Neurobiol__102559
PubMedID: 38159878
Gene_locus related to this paper: human-ABHD6 , mouse-ABHD6

Title : Metagenomic exploration of microbial and enzymatic traits involved in microplastic biodegradation - Hu_2023_Chemosphere_348_140762
Author(s) : Hu X , Gu H , Sun X , Wang Y , Liu J , Yu Z , Li Y , Jin J , Wang G
Ref : Chemosphere , 348 :140762 , 2023
Abstract : Agricultural mulch films are frequently applied to achieve high yield, resulting in large quantities of microplastic (MP) pollution in agroecosystem. However, studies focusing specifically on the diversity of MP-degrading enzymes and related microbial communities have yet to be conducted. Here, we established a soil microcosmic incubation with addition of 5% (w/w) conventional (low-density polyethylene (LDPE)) and biodegradable (blend of polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT)) MPs for incubation 90 days. The DNA samples extracted from soils and plastisphere of MPs were examined by metagenomics and genome binning methods, specifically targeting carbohydrate-active enzymes (CAZymes) and plastic-degrading enzymes (PDZymes). The results revealed that plastisphere of MPs exhibited significantly distinct patterns of CAZymes and PDZymes from soils, and abundances of all examined exoenzymes were higher in plastisphere than those in soils. Plastisphere of LDPE-MPs selectively enriched proteases and alkane monooxygenase (alkB), and required families of carbohydrate-binding module (CBM) to increase the binding of CAZymes with MPs. Dissimilarly, diverse CAZymes with high abundances were observed in the plastisphere of PBAT-PLA MPs and esterases were important indicative PDZymes for PBAT-PLA degradation. The enriched exoenzymes in plastisphere of LDPE-MPs were mainly assigned to Actinobacteria while Proteobacteria with higher abundance in plastisphere of PBAT-PLA MPs containing most indicative exoenzymes. Moreover, a high-quality genome classified as Amycolatopsis japonica was reconstructed and found to contain one or more gene copies of indicative exoenzymes for polyethylene. Two novel genomes classified as Sphingomonas were selectively enriched in plastisphere of PBAT-PLA MPs and contained diverse genes encoding degrading exoenzymes. Taken together, our study highlighted the CAZymes and PDZymes can be exploited as potent microbial strategies for solving MPs pollution in croplands.
ESTHER : Hu_2023_Chemosphere_348_140762
PubMedSearch : Hu_2023_Chemosphere_348_140762
PubMedID: 38006912

Title : Integration of clinical demographics and routine laboratory analysis parameters for early prediction of gestational diabetes mellitus in the Chinese population - Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
Author(s) : Zhang H , Dai J , Zhang W , Sun X , Sun Y , Wang L , Li H , Zhang J
Ref : Front Endocrinol (Lausanne) , 14 :1216832 , 2023
Abstract : Gestational diabetes mellitus (GDM) is one of the most common complications in pregnancy, impairing both maternal and fetal health in short and long term. As early interventions are considered desirable to prevent GDM, this study aims to develop a simple-to-use nomogram based on multiple common risk factors from electronic medical health records (EMHRs). A total of 924 pregnant women whose EMHRs were available at Peking University International Hospital from January 2022 to October 2022 were included. Clinical demographics and routine laboratory analysis parameters at 8-12 weeks of gestation were collected. A novel nomogram was established based on the outcomes of multivariate logistic regression. The nomogram demonstrated powerful discrimination (the area under the receiver operating characteristic curve = 0.7542), acceptable agreement (Hosmer-Lemeshow test, P = 0.3214) and favorable clinical utility. The C-statistics of 10-Fold cross validation, Leave one out cross validation and Bootstrap were 0.7411, 0.7357 and 0.7318, respectively, indicating the stability of the nomogram. A novel nomogram based on easily-accessible parameters was developed to predict GDM in early pregnancy, which may provide a paradigm for repurposing clinical data and benefit the clinical management of GDM. There is a need for prospective multi-center studies to validate the nomogram before employing the nomogram in real-world clinical practice.
ESTHER : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedSearch : Zhang_2023_Front.Endocrinol.(Lausanne)_14_1216832
PubMedID: 37900122

Title : Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys - Wang_2023_Mol.Ther.Nucleic.Acids_31_68
Author(s) : Wang J , Zheng W , Zheng S , Yuan Y , Wen W , Cui W , Xue L , Sun X , Shang H , Zhang H , Xiao RP , Gao S , Zhang X
Ref : Mol Ther Nucleic Acids , 31 :68 , 2023
Abstract : Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development.
ESTHER : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedSearch : Wang_2023_Mol.Ther.Nucleic.Acids_31_68
PubMedID: 36618267

Title : Mechanisms of microRNA-132 in central neurodegenerative diseases: A comprehensive review - Mu_2023_Biomed.Pharmacother_170_116029
Author(s) : Mu C , Gao M , Xu W , Sun X , Chen T , Xu H , Qiu H
Ref : Biomed Pharmacother , 170 :116029 , 2023
Abstract : MicroRNA-132 (miR-132) is a highly conserved molecule that plays a crucial regulatory role in central nervous system (CNS) disorders. The expression levels of miR-132 exhibit variability in various neurological disorders and have been closely linked to disease onset and progression. The expression level of miR-132 in the CNS is regulated by a diverse range of stimuli and signaling pathways, including neuronal migration and integration, dendritic outgrowth, and complexity, synaptogenesis, synaptic plasticity, as well as inflammation and apoptosis activation. The aberrant expression of miR-132 in various central neurodegenerative diseases has garnered widespread attention. Clinical studies have revealed altered miR-132 expression levels in both chronic and acute CNS diseases, positioning miR-132 as a potential biomarker or therapeutic target. An in-depth exploration of miR-132 holds the promise of enhancing our understanding of the mechanisms underlying CNS diseases, thereby offering novel insights and strategies for disease diagnosis and treatment. It is anticipated that this review will assist researchers in recognizing the potential value of miR-132 and in generating innovative ideas for clinical trials related to CNS degenerative diseases.
ESTHER : Mu_2023_Biomed.Pharmacother_170_116029
PubMedSearch : Mu_2023_Biomed.Pharmacother_170_116029
PubMedID: 38128185

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 : Oligomerization of a plant helper NLR requires cell-surface and intracellular immune receptor activation - Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
Author(s) : Feehan JM , Wang J , Sun X , Choi J , Ahn HK , Ngou BPM , Parker JE , Jones JDG
Ref : Proc Natl Acad Sci U S A , 120 :e2210406120 , 2023
Abstract : Plant disease resistance involves both detection of microbial molecular patterns by cell-surface pattern recognition receptors and detection of pathogen effectors by intracellular NLR immune receptors. NLRs are classified as sensor NLRs, involved in effector detection, or helper NLRs required for sensor NLR signaling. TIR-domain-containing sensor NLRs (TNLs) require helper NLRs NRG1 and ADR1 for resistance, and helper NLR activation of defense requires the lipase-domain proteins EDS1, SAG101, and PAD4. Previously, we found that NRG1 associates with EDS1 and SAG101 in a TNL activation-dependent manner [X. Sun et al., Nat. Commun. 12, 3335 (2021)]. We report here how the helper NLR NRG1 associates with itself and with EDS1 and SAG101 during TNL-initiated immunity. Full immunity requires coactivation and mutual potentiation of cell-surface and intracellular immune receptor-initiated signaling [B. P. M. Ngou, H.-K. Ahn, P. Ding, J. D. G. Jones, Nature 592, 110-115 (2021), M. Yuan et al., Nature 592, 105-109 (2021)]. We find that while activation of TNLs is sufficient to promote NRG1-EDS1-SAG101 interaction, the formation of an oligomeric NRG1-EDS1-SAG101 resistosome requires the additional coactivation of cell-surface receptor-initiated defense. These data suggest that NRG1-EDS1-SAG101 resistosome formation in vivo is part of the mechanism that links intracellular and cell-surface receptor signaling pathways.
ESTHER : Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
PubMedSearch : Feehan_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2210406120
PubMedID: 36877846

Title : The MAX2-KAI2 module promotes salicylic acid-mediated immune responses in Arabidopsis - Zheng_2023_J.Integr.Plant.Biol__
Author(s) : Zheng X , Liu F , Yang X , Li W , Chen S , Yue X , Jia Q , Sun X
Ref : J Integr Plant Biol , : , 2023
Abstract : Arabidopsis MORE AXILLARY GROWTH2 (MAX2) is a key component in the strigolactone (SL) and karrikin (KAR) signaling pathways and regulates the degradation of SUPPRESSOR OF MAX2 1/SMAX1-like (SMAX1/SMXL) proteins, which are transcriptional co-repressors that regulate plant architecture, as well as abiotic and biotic stress responses. The max2 mutation reduces resistance against Pseudomonas syringae pv. tomato (Pst). To uncover the mechanism of MAX2-mediated resistance, we evaluated the resistance of various SL and KAR signaling pathway mutants. The resistance of SL-deficient mutants and of dwarf 14 (d14) was similar to that of the wild type, whereas the resistance of the karrikin insensitive 2 (kai2) mutant was compromised, demonstrating that the KAR signaling pathway, not the SL signaling pathway, positively regulates the immune response. We measured the resistance of smax1 and smxl mutants, as well as the double, triple, and quadruple mutants with max2, which revealed that both the smax1 mutant and smxl6/7/8 triple mutant rescue the low resistance phenotype of max2 and that SMAX1 accumulation diminishes resistance. The susceptibility of smax1D, containing a degradation-insensitive form of SMAX1, further confirmed the SMAX1 function in the resistance. The relationship between the accumulation of SMAX1/SMXLs and disease resistance suggested that the inhibitory activity of SMAX1 to resistance requires SMXL6/7/8. Moreover, exogenous application of KAR2 enhanced resistance against Pst, but KAR-induced resistance depended on salicylic acid (SA) signaling. Inhibition of karrikin signaling delayed SA-mediated defense responses and inhibited pathogen-induced protein biosynthesis. Together, we propose that the MAX2-KAI2-SMAX1 complex regulates resistance with the assistance of SMXL6/7/8 and SA signaling and that SMAX1/SMXLs possibly form a multimeric complex with their target transcription factors to fine-tune immune responses. This article is protected by copyright. All rights reserved.
ESTHER : Zheng_2023_J.Integr.Plant.Biol__
PubMedSearch : Zheng_2023_J.Integr.Plant.Biol__
PubMedID: 36738234

Title : N-acylhomoserine lactonase-based hybrid nanoflowers: a novel and practical strategy to control plant bacterial diseases - Chen_2022_J.Nanobiotechnology_20_347
Author(s) : Chen Y , Liu P , Wu J , Yan W , Xie S , Sun X , Ye BC , Chu X
Ref : J Nanobiotechnology , 20 :347 , 2022
Abstract : BACKGROUND: The disease caused by plant pathogenic bacteria in the production, transportation, and storage of many crops has brought huge losses to agricultural production. N-acylhomoserine lactonases (AHLases) can quench quorum-sensing (QS) by hydrolyzing acylhomoserine lactones (AHLs), which makes them the promising candidates for controlling infections of QS-dependent pathogenic bacteria. Although many AHLases have been isolated and considered as a potentially effective preventive and therapeutic agents for bacterial diseases, the intrinsically poor ambient stability has seriously restricted its application. RESULTS: Herein, we showed that a spheroid enzyme-based hybrid nanoflower (EHNF), AhlX@Ni(3)(PO(4))(2), can be easily synthesized, and it exhibited 10 times AHL (3OC8-HSL) degradation activity than that with free AhlX (a thermostable AHL lactonase). In addition, it showed intriguing stability even at the working concentration, and retained ~ 100% activity after incubation at room temperature (25 degreesC) for 40 days and approximately 80% activity after incubation at 60 degreesC for 48 h. Furthermore, it exhibited better organic solvent tolerance and long-term stability in a complicated ecological environment than that of AhlX. To reduce the cost and streamline production processes, CSA@Ni(3)(PO(4))(2), which was assembled from the crude supernatants of AhlX and Ni(3)(PO(4))(2), was synthesized. Both AhlX@Ni(3)(PO(4))(2) and CSA@Ni(3)(PO(4))(2) efficiently attenuated pathogenic bacterial infection. CONCLUSIONS: In this study, we have developed N-acylhomoserine lactonase-based hybrid nanoflowers as a novel and efficient biocontrol reagent with significant control effect, outstanding environmental adaptability and tolerance. It was expected to overcome the bottlenecks of poor stability and limited environmental tolerance that have existed for over two decades and pioneered the practical application of EHNFs in the field of biological control.
ESTHER : Chen_2022_J.Nanobiotechnology_20_347
PubMedSearch : Chen_2022_J.Nanobiotechnology_20_347
PubMedID: 35883097

Title : Acetylcholinesterase-capped mesoporous silica gated switches for selective detection of high-toxicity organophosphate compounds - Zhang_2022_Anal.Chim.Acta_1207_339708
Author(s) : Zhang Y , Li T , Sun X , Liu H , Wang Y , Nie Z
Ref : Anal Chim Acta , 1207 :339708 , 2022
Abstract : Organophosphate (OP) compounds are widely used in agriculture, industry, and even terrorism. It is important to distinguish high-toxicity OP compounds from low-toxicity OP compounds in dealing with chemical accidents. However, there are very few portable and simple detection methods. Mesoporous silica gated switches may provide an effective solution. In this study, a gated switch based on mesoporous silica as an inorganic scaffold loaded with sulforhodamine B and capped with acetylcholinesterase (AChE) was prepared for specific detection of OP compounds. Carbamate derivatives (G1-G6) were designed and synthetized as grafting compounds in consideration of the binding ability with AChE. Through further modification and optimization, grafting compound G6 with phenylpyridine as the substituent showed the best capping capacity, and it achieved excellent blocking of mesoporous silica gated switches for loaded sulforhodamine B. In the presence of high-toxicity OP compounds, low-toxicity OP compounds, AChE substrates and reversible AChE inhibitors respectively, only high-toxicity OP compounds could make the gated switch release loaded sulforhodamine B. The limit of detection for paraoxon-ethyl was 10.6 micro. Furthermore, the preparation process of the gated switch is fast and simple, and the prepared gated switch has good stability and rapid distinguishing ability. The results of this paper provide a new idea for rapidly distinguishing high-toxicity OP compounds from low-toxicity OP compounds and other related compounds on the spot.
ESTHER : Zhang_2022_Anal.Chim.Acta_1207_339708
PubMedSearch : Zhang_2022_Anal.Chim.Acta_1207_339708
PubMedID: 35491047

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : Recent advances of chemosensors for nerve agents - Wang_2022_Chem.Asian.J__
Author(s) : Wang X , Feng R , Fu T , Zhang J , Sun X
Ref : Chem Asian J , : , 2022
Abstract : Nerve agents are a branch of organophosphorus (OP) compounds that chemically cause irreversible inhibition of acetylcholinesterase, thereby failing the hydrolysis of acetylcholine, resulting in severe neurological disease and death in organisms. Thus, the unreasonable use of such compounds threatens public and national security, so it is a high demand to establish portable, low-cost, sensitive, and highly selective methods for their precise detection. In this review, we introduced the recent development of spectroscopy-based optical chemosensors that aimed for the detection of nerve agent, focusing on the progress made in the molecular design, sensing principle and applications. We also conclude this Review by highlighting the current challenges associated with the future development and outlook.
ESTHER : Wang_2022_Chem.Asian.J__
PubMedSearch : Wang_2022_Chem.Asian.J__
PubMedID: 35599234

Title : Analysis of virulence proteins in pathogenic Acinetobacter baumannii to provide early warning of zoonotic risk - Zou_2022_Microbiol.Res_266_127222
Author(s) : Zou D , Chang J , Lu S , Xu J , Hu P , Zhang K , Sun X , Guo W , Li Y , Liu Z , Ren H
Ref : Microbiol Res , 266 :127222 , 2022
Abstract : Acinetobacter baumannii is a ubiquitous opportunistic pathogen usually with low virulence. In recent years, reports of increased pathogenicity of A. baumannii in livestock due to the migratory behaviour of wildlife have attracted public health attention. Our previous study reported that an A. baumannii strain isolated from dead chicks, CCGGD201101, showed enhanced pathogenicity, but the mechanism for increased virulence is not understood. Here, to screen potential virulence factors, the proteomes of the isolated strain CCGGD201101 and the standard strain ATCC19606 of A. baumannii were compared, and the possible virulence-enhancing mechanisms were further analysed. The 50 % lethal dose (LD(50)) values of CCGGD201101 and standard strain ATCC19606 in ICR mice were determined to verify their bacterial toxicity. 2D fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) and quantitative real-time PCR (RTqPCR) were applied to screen and identify differentially expressed proteins or genes that may be related to virulence enhancement. Bioinformatics analyses based on proteinprotein interaction (PPI) networks were used to explore the function of potential virulence proteins. The pathogenicity of potential virulence factors was assessed by phylogenetic analyses and an animal infection model. The results showed that the LD(50) of CCGGD201101 for mice was 1.186 x 10(6) CFU/mL, and the virulence was increased by 180.5-fold compared to ATCC19606. Forty-seven protein spots were significantly upregulated for the A. baumannii CCGGD201101 strain (fold change <=1.5, p < 0.05). In total, 14 upregulated proteins were identified using proteomic analysis, and the mRNA expression levels of these proteins were nearly identical, with few exceptions. According to the PPI network and phylogenetic analyses, the I78 family peptidase inhibitor, 3-oxoacyl-ACP reductase FabG, and glycine zipper were screened as being closely related to the pathogenicity of bacteria. Furthermore, the I78 overexpression strains exhibited higher lethality in mouse infection models, which indicated that the I78 family peptidase inhibitor was a potential new virulence factor to enhance the pathogenicity of the A. baumannii CCGGD201101 strain. The present study helped us to better understand the mechanisms of virulence enhancement and provided a scientific basis for establishing an early warning system for enhanced virulence of A. baumannii from animals.
ESTHER : Zou_2022_Microbiol.Res_266_127222
PubMedSearch : Zou_2022_Microbiol.Res_266_127222
PubMedID: 36306681
Gene_locus related to this paper: aciba-YdeN

Title : Characterization of carboxylesterase PxE8 and its role in multi-insecticide resistance in Plutella xylostella (L.) - Li_2022_J.Integr.Agric_21_1713
Author(s) : Li R , Sun X , Liang P , Gao XW
Ref : J.Integr.Agric , 21 :1714 , 2022
Abstract : Carboxylesterase (CarE) was considered as important phase-I detoxifying enzymes which participated in detoxification of different types of insecticides. Up-regulation of CarE genes has been proved playing a major role in insecticide resistance in many pest insects, but its involvement in resistance to insecticides in Plutella xylostella has been rarely reported. In this study, a CarE cDNA named PxalphaE8 was identified in P. xylostella, which has an open reading frame of 1 599 nucleotides and putatively encodes 532 amino acids. The investigation of spatial expression profiles of PxalphaE8 revealed that it was expressed in all developmental stages, especially in larvae and adults. The body part/tissue-specific expression profiles showed that the PxE8 mainly expressed in fat body, malpighian tubule and hemolymph of larvae. Further, the relative expression of PxalphaE8 in two multi-resistant field populations, Hainan (HN) and Guangdong (GD) populations, was found 24.4- and 15.5-fold higher than that in susceptible population, respectively. Knockdown of PxalphaE8 by RNA interference dramatically increased the mortalities of larvae of HN population treated with LC50 of beta-cypermethrin and phoxim by 25.3 and 18.3%, respectively. These results suggested that up-regulation of PxE8 was involved in resistance to both beta-cypermethrin and phoxim in P. xylostella, which shed light on further understanding of molecular mechanisms of multi-insecticide-resistance in P. xylostella and other pest insects.
ESTHER : Li_2022_J.Integr.Agric_21_1713
PubMedSearch : Li_2022_J.Integr.Agric_21_1713
PubMedID:
Gene_locus related to this paper: pluxy-PxalphaE8

Title : Development of 5-hydroxyl-1-azabenzanthrone derivatives as dual binding site and selective acetylcholinesterase inhibitors - Sun_2022_Eur.J.Med.Chem_234_114210
Author(s) : Sun X , Wang Y , Lei Z , Yue S , Chen L , Sun J
Ref : Eur Journal of Medicinal Chemistry , 234 :114210 , 2022
Abstract : A series of novel 5-hydroxyl-1-azabenzanthrone derivatives were designed, synthesized and evaluated as dual binding site acetylcholinesterase inhibitors for the treatment of Alzheimer's disease (AD). The most effective Compound 16 showed selective inhibition of acetylcholinesterase (eeAChE IC(50) = 0.045 microM; eeBuChE IC(50) = 19.68 microM; SI = 437.33). Most of the compounds showed cytoprotective effects on PC12 cells damaged by hydrogen peroxide, which might be related to their antioxidant activity. Further experiments confirmed that 16 exhibited anti-apoptotic effects at low concentrations and reduced the relative level of ROS generation in PC12 cells. The expression level of proteins related to antioxidant stress pathway in PC12 cells was relatively increased after administrated with 16, which may be beneficial to delay the progression of the disease. Moreover, 16 was evaluated to be safe in vivo and in vitro, and showed good overall pharmacokinetic performance and high bioavailability (Foral = 55.5%). Besides, 16 showed comparable performance in ameliorating the scopolamine-induced cognition impairment to donepezil. In addition, in vitro BBB permeability experiments confirmed that 16 had high BBB permeability.
ESTHER : Sun_2022_Eur.J.Med.Chem_234_114210
PubMedSearch : Sun_2022_Eur.J.Med.Chem_234_114210
PubMedID: 35303485

Title : Characterization of feruloyl esterases from Pecoramyces sp. F1 and the synergistic effect in biomass degradation - Ma_2022_World.J.Microbiol.Biotechnol_39_17
Author(s) : Ma J , Ma Y , Li Y , Sun Z , Sun X , Padmakumar V , Cheng Y , Zhu W
Ref : World J Microbiol Biotechnol , 39 :17 , 2022
Abstract : Feruloyl esterase (FAE; EC 3.1.1.73)cleaves the ester bondbetween ferulic acid (FA) and sugar, to assist the release of FAs and degradation of plant cell walls. In this study, two FAEs (Fae13961 and Fae16537) from the anaerobic fungus Pecoramyces sp. F1 were heterologously expressed in Pichia pastoris (P. pastoris). Compared with Fae16537, Fae13961 had higher catalytic efficiency. The optimum temperature and pH of both the FAEs were 45 and 7.0, respectively. They showed good stability-Fae16537 retained up to 80% activity after incubation at 37 for 24h. The FAEs activity was enhanced by Ca(2+) and reduced by Zn(2+), Mn(2+), Fe(2+) and Fe(3+). Additionally, the effect of FAEs on the hydrolytic efficiency of xylanase and cellulase was also determined. The FAE Fae13961 had synergistic effect with xylanase and it promoted the degradation of xylan substrates by xylanase, but it did not affect the degradation of cellulose substrates by cellulase. When Fae13961 was added in a mixture of xylanase and cellulase to degrade complex agricultural biomass, it significantly enhanced the mixture's ability to disintegrate complex substrates. These FAEs could serve as superior auxiliary enzymes for other lignocellulosic enzymes in the process of degradation of agricultural residues for industrial applications.
ESTHER : Ma_2022_World.J.Microbiol.Biotechnol_39_17
PubMedSearch : Ma_2022_World.J.Microbiol.Biotechnol_39_17
PubMedID: 36409385

Title : Isolation and Mechanistic Characterization of a Novel Zearalenone-Degrading Enzyme - Ji_2022_Foods_11_
Author(s) : Ji J , Yu J , Xu W , Zheng Y , Zhang Y , Sun X
Ref : Foods , 11 : , 2022
Abstract : Zearalenone (ZEN) and its derivatives pose a serious threat to global food quality and animal health. The use of enzymes to degrade mycotoxins has become a popular method to counter this threat. In this study, Aspergillus niger ZEN-S-FS10 extracellular enzyme solution with ZEN-degrading effect was separated and purified to prepare the biological enzyme, FSZ, that can degrade ZEN. The degradation rate of FSZ to ZEN was 7580% (pH = 7.0, 28 degreesC). FSZ can function in a temperature range of 2838 degreesC and pH range of 2.07.0 and can also degrade ZEN derivatives (alpha-ZAL, beta-ZOL, and ZAN). According to the enzyme kinetics fitting, ZEN has a high degradation rate. FSZ can degrade ZEN in real samples of corn flour. FSZ can be obtained stably and repeatedly from the original strain. One ZEN degradation product was isolated: FSZP(C18H26O4), with a relative molecular weight of 306.18 g/mol. Amino-acid-sequencing analysis revealed that FSZ is a novel enzyme (homology < 10%). According to the results of molecular docking, ZEN and ZAN can utilize their end-terminal carbonyl groups to bind FSZ residues PHE307, THR55, and GLU129 for a high-degradation rate. However, alpha-ZAL and beta-ZOL instead contain hydroxyl groups that would prevent binding to GLU129; thus, the degradation rate is low for these derivatives.
ESTHER : Ji_2022_Foods_11_
PubMedSearch : Ji_2022_Foods_11_
PubMedID: 36141036

Title : Enantioselective Metabolic Mechanism and Metabolism Pathway of Pydiflumetofen in Rat Liver Microsomes: In Vitro and In Silico Study - Wang_2022_J.Agric.Food.Chem_70_2520
Author(s) : Wang Z , Li R , Wu Q , Duan J , Tan Y , Sun X , Chen R , Shi H , Wang M
Ref : Journal of Agricultural and Food Chemistry , 70 :2520 , 2022
Abstract : Pydiflumetofen (PYD) has been used worldwide. However, the enantioselective fate of PYD within mammals is not clear. Thus, the enantioselective metabolism and its potential mechanisms of PYD were explored via in vitro and in silico. Consistent results were observed between metabolism and enzyme kinetics experiments, with S-PYD metabolizing faster than R-PYD in rat liver microsomes. Moreover, CYP3A1 and carboxylesterase 1 were found to be major enzymes participating in the metabolism of PYD. Based on the computational results, S-PYD bound with CYP3A1 and carboxylesterase 1 more tightly with lower binding free energy than R-PYD, explaining the mechanism of enantioselective metabolism. Nine phase I metabolites of PYD were identified, and metabolic pathways of PYD were speculated. This study is the first to clarify the metabolism of PYD in mammals, and further research to evaluate the toxicological implications of these metabolites will help in assessing the risk of PYD.
ESTHER : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedSearch : Wang_2022_J.Agric.Food.Chem_70_2520
PubMedID: 35184556

Title : Mechanisms of Congenital Myasthenia Caused by Three Mutations in the COLQ Gene - Luo_2021_Front.Pediatr_9_679342
Author(s) : Luo X , Wang C , Lin L , Yuan F , Wang S , Wang Y , Wang A , Wu S , Lan X , Xu Q , Yin R , Cheng H , Zhang Y , Xi J , Zhang J , Sun X , Yan J , Zeng F , Chen Y
Ref : Front Pediatr , 9 :679342 , 2021
Abstract : The gene encoding collagen like tail subunit of asymmetric acetylcholinesterase (COLQ) is responsible for the transcription of three strands of collagen of acetylcholinesterase, which is attached to the endplate of neuromuscular junctions. Mutations in the COLQ gene are inherited in an autosomal-recessive manner and can lead to type V congenital myasthenia syndrome (CMS), which manifests as decreased muscle strength at birth or shortly after birth, respiratory failure, restricted eye movements, drooping of eyelids, and difficulty swallowing. Here we reported three variants within COLQ in two unrelated children with CMS. An intronic variant (c.393+1G>A) and a novel missense variant (p.Q381P) were identified as compound heterozygous in a 13-month-old boy, with the parents being carriers of each. An intragenic deletion including exons 14 and 15 was found in a homozygous state in a 12-year-old boy. We studied the relative expression of the COLQ and AChE gene in the probands' families, performed three-dimensional protein structural analysis, and analyzed the conservation of the missense mutation c.1142A>C (p.Q381P). The splicing mutation c.393+1G>A was found to affect the normal splicing of COLQ exon 5, resulting in a 27-bp deletion. The missense mutation c.1142A>C (p.Q381P) was located in a conserved position in different species. We found that homozygous deletion of COLQ exons 14-15 resulted in a 241-bp deletion, which decreased the number of amino acids and caused a frameshift translation. COLQ expression was significantly lower in the probands than in the probands' parents and siblings, while AChE expression was significantly higher. Moreover, the mutations were found to cause significant differences in the predicted three-dimensional structure of the protein. The splicing mutation c.393+1G>A, missense mutation c.1A>C (p.Q381P), and COLQ exon 14-15 deletion could cause CMS.
ESTHER : Luo_2021_Front.Pediatr_9_679342
PubMedSearch : Luo_2021_Front.Pediatr_9_679342
PubMedID: 34912755

Title : An efficient phthalate ester-degrading Bacillus subtilis: Degradation kinetics, metabolic pathway, and catalytic mechanism of the key enzyme - Xu_2021_Environ.Pollut_273_116461
Author(s) : Xu Y , Liu X , Zhao J , Huang H , Wu M , Li X , Li W , Sun X , Sun B
Ref : Environ Pollut , 273 :116461 , 2021
Abstract : Phthalate ester pollution in the environment and food chain is frequently reported. Microbial treatment is a green and efficient method for solving this problem. The isolation and systematic investigation of microorganisms generally recognized as safe (GRAS) will provide useful resources. A GRAS Bacillus subtilis strain, BJQ0005, was isolated from Baijiu fermentation starter and efficiently degraded phthalate esters (PAEs). The half-lives for di-isobutyl phthalate, di-butyl phthalate and di-(2-ethylhexyl) phthalate were 3.93, 4.28, and 25.49 h, respectively, from the initial amount of 10 mg per 10 mL reaction mixture, which are records using wild-type strains. Genome sequencing and metabolic intermediate analysis generated the whole metabolic pathway. Eighteen enzymes from the alpha/beta hydrolase family were expressed. Enzymes GTW28_09400 and GTW28_13725 were capable of single ester bond hydrolysis of PAEs, while GTW28_17760 hydrolyzed di-ester bonds of PAEs. Using molecular docking, a possible mechanism affecting enzymatic ester bond hydrolysis of mono-butyl phthalate was proposed of GTW28_17760. The carboxyl group generated by the first hydrolysis step interacted with histidine in the catalytic active center, which negatively affected enzymatic hydrolysis. Isolation and systematic investigation of the PAE degradation characteristics of B. subtilis will promote the green and safe treatment of PAEs in the environment and food industry.
ESTHER : Xu_2021_Environ.Pollut_273_116461
PubMedSearch : Xu_2021_Environ.Pollut_273_116461
PubMedID: 33485001
Gene_locus related to this paper: bacsu-pnbae

Title : Progesterone activates the cyclic AMP-protein kinase A signalling pathway by upregulating ABHD2 in fertile men - Jiang_2021_J.Int.Med.Res_49_300060521999527
Author(s) : Jiang F , Zhu Y , Chen Y , Tang X , Liu L , Chen G , Liu Y , Sun X
Ref : J Internal Medicine Res , 49 :300060521999527 , 2021
Abstract : OBJECTIVE: This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via alpha/beta hydrolase domain-containing protein 2 (ABHD2). METHODS: Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in ABHD2 were detected by quantitative PCR, western blot, and gene sequencing. The expression of ABHD2 in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively. RESULTS: Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively. CONCLUSION: Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility.
ESTHER : Jiang_2021_J.Int.Med.Res_49_300060521999527
PubMedSearch : Jiang_2021_J.Int.Med.Res_49_300060521999527
PubMedID: 33752482
Gene_locus related to this paper: human-ABHD2

Title : Synthesis and biological evaluation of 2-arylbenzofuran derivatives as potential anti-Alzheimer's disease agents - Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
Author(s) : Yun Y , Miao Y , Sun X , Sun J , Wang X
Ref : J Enzyme Inhib Med Chem , 36 :1346 , 2021
Abstract : Alzheimer's disease (AD) is a type of progressive dementia caused by degeneration of the nervous system. A single target drug usually does not work well. Therefore, multi-target drugs are designed and developed so that one drug can specifically bind to multiple targets to ensure clinical effectiveness and reduce toxicity. We synthesised a series of 2-arylbenzofuran derivatives and evaluated their in vitro activities. 2-Arylbenzofuran compounds have good dual cholinesterase inhibitory activity and beta-secretase inhibitory activity. The IC(50) value of compound 20 against acetylcholinesterase inhibition (0.086 +/- 0.01 micromol.L(-1)) is similar to donepezil (0.085 +/- 0.01 micromol.L(-1)) and is better than baicalein (0.404 +/- 0.04 micromol.L(-1)). And most of the compounds have good BACE1 inhibitory activity, of which 3 compounds (8, 19 and 20) show better activity than baicalein (0.087 +/- 0.03 micromol.L(-1)). According to experimental results, 2-arylbenzofuran compounds provide an idea for drug design to develop prevention and treatment for AD.
ESTHER : Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
PubMedSearch : Yun_2021_J.Enzyme.Inhib.Med.Chem_36_1346
PubMedID: 34134572

Title : Inhibiting Monoacylglycerol Lipase Suppresses RANKL-Induced Osteoclastogenesis and Alleviates Ovariectomy-Induced Bone Loss - Liu_2021_Front.Cell.Dev.Biol_9_640867
Author(s) : Liu H , Zhou C , Qi D , Gao Y , Zhu M , Tao T , Sun X , Xiao J
Ref : Front Cell Developmental Biology , 9 :640867 , 2021
Abstract : Osteoporosis is a common chronic metabolic bone disease characterized by reduced trabecular bone and increased bone fragility. Monoacylglycerol lipase (MAGL) is a lipolytic enzyme to catalyze the hydrolysis of monoglycerides and specifically degrades the 2-arachidonoyl glycerol (2-AG). Previous studies have identified that 2-AG is the mainly source for arachidonic acid and the most abundant endogenous agonist of cannabinoid receptors. Considering the close relationship between inflammatory mediators/cannabinoid receptors and bone metabolism, we speculated that MAGL may play a role in the osteoclast differentiation. In the present study, we found that MAGL protein expression increased during osteoclast differentiation. MAGL knockdown by adenovirus-mediated shRNA in bone marrow-derived macrophages demonstrated the suppressive effects of MAGL on osteoclast formation and bone resorption. In addition, pharmacological inhibition of MAGL by JZL184 suppressed osteoclast differentiation, bone resorption, and osteoclast-specific gene expression. Activation of the Mitogen-activated protein kinase (MAPK) and nuclear factor kappaB (NF-kappaB) pathways was inhibited by JZL184 and deletion of MAGL. Our in vivo study indicated that JZL184 ameliorated bone loss in an ovariectomized mouse model. Furthermore, overexpressing H1 calponin partially alleviated the inhibition caused by JZL184 or MAGL deletion on osteoclastogenesis. Therefore, we conclude that targeting MAGL may be a novel therapeutic strategy for osteoporosis.
ESTHER : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedSearch : Liu_2021_Front.Cell.Dev.Biol_9_640867
PubMedID: 33777947

Title : Pathogen effector recognition-dependent association of NRG1 with EDS1 and SAG101 in TNL receptor immunity - Sun_2021_Nat.Commun_12_3335
Author(s) : Sun X , Lapin D , Feehan JM , Stolze SC , Kramer K , Dongus JA , Rzemieniewski J , Blanvillain-Baufume S , Harzen A , Bautor J , Derbyshire P , Menke FLH , Finkemeier I , Nakagami H , Jones JDG , Parker JE
Ref : Nat Commun , 12 :3335 , 2021
Abstract : Plants utilise intracellular nucleotide-binding, leucine-rich repeat (NLR) immune receptors to detect pathogen effectors and activate local and systemic defence. NRG1 and ADR1 "helper" NLRs (RNLs) cooperate with enhanced disease susceptibility 1 (EDS1), senescence-associated gene 101 (SAG101) and phytoalexin-deficient 4 (PAD4) lipase-like proteins to mediate signalling from TIR domain NLR receptors (TNLs). The mechanism of RNL/EDS1 family protein cooperation is not understood. Here, we present genetic and molecular evidence for exclusive EDS1/SAG101/NRG1 and EDS1/PAD4/ADR1 co-functions in TNL immunity. Using immunoprecipitation and mass spectrometry, we show effector recognition-dependent interaction of NRG1 with EDS1 and SAG101, but not PAD4. An EDS1-SAG101 complex interacts with NRG1, and EDS1-PAD4 with ADR1, in an immune-activated state. NRG1 requires an intact nucleotide-binding P-loop motif, and EDS1 a functional EP domain and its partner SAG101, for induced association and immunity. Thus, two distinct modules (NRG1/EDS1/SAG101 and ADR1/EDS1/PAD4) mediate TNL receptor defence signalling.
ESTHER : Sun_2021_Nat.Commun_12_3335
PubMedSearch : Sun_2021_Nat.Commun_12_3335
PubMedID: 34099661
Gene_locus related to this paper: arath-At5g14930 , arath-eds1 , arath-PAD4

Title : NDRG1 facilitates lytic replication of Kaposi's sarcoma-associated herpesvirus by maintaining the stability of the KSHV helicase - Dong_2021_PLoS.Pathog_17_e1009645
Author(s) : Dong L , Dong J , Xiang M , Lei P , Li Z , Zhang F , Sun X , Niu D , Bai L , Lan K
Ref : PLoS Pathog , 17 :e1009645 , 2021
Abstract : The presumed DNA helicase encoded by ORF44 of Kaposi's sarcoma-associated herpesvirus (KSHV) plays a crucial role in unwinding viral double-stranded DNA and initiating DNA replication during lytic reactivation. However, the regulatory mechanism of KSHV ORF44 has not been fully elucidated. In a previous study, we identified that N-Myc downstream regulated gene 1 (NDRG1), a host scaffold protein, facilitates viral genome replication by interacting with proliferating cell nuclear antigen (PCNA) and the latent viral protein latency-associated nuclear antigen (LANA) during viral latency. In the present study, we further demonstrated that NDRG1 can interact with KSHV ORF44 during viral lytic replication. We also found that the mRNA and protein levels of NDRG1 were significantly increased by KSHV ORF50-encoded replication and transcription activator (RTA). Remarkably, knockdown of NDRG1 greatly decreased the protein level of ORF44 and impaired viral lytic replication. Interestingly, NDRG1 enhanced the stability of ORF44 and inhibited its ubiquitin-proteasome-mediated degradation by reducing the polyubiquitination of the lysine residues at positions 79 and 368 in ORF44. In summary, NDRG1 is a novel binding partner of ORF44 and facilitates viral lytic replication by maintaining the stability of ORF44. This study provides new insight into the mechanisms underlying KSHV lytic replication.
ESTHER : Dong_2021_PLoS.Pathog_17_e1009645
PubMedSearch : Dong_2021_PLoS.Pathog_17_e1009645
PubMedID: 34077484
Gene_locus related to this paper: human-NDRG1

Title : LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p\/CES2 axis - Pei_2020_Mol.Cell.Biochem_475_107
Author(s) : Pei J , Sun X , Yang G , Zhang S
Ref : Molecular & Cellular Biochemistry , 475 :107 , 2020
Abstract : Long noncoding RNAs (lncRNAs) have been shown to be implicated in acetaminophen (APAP)-induced liver injury (AILI). We applied this study to investigate the role and functional mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in AILI. The AILI model was established by APAP treatment in mice. The liver injury was preliminarily evaluated by ALT and AST activities via the detection kits. The quantitative real-time polymerase chain reaction (qRT-PCR) was exploited for detecting the expression of KCNQ1OT1, microRNA-122-5p (miR-122-5p), and carboxylesterase 2 (CES2). Protein levels were analyzed via Western blot. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, and flow cytometry were separately applied to determine cell proliferation and apoptosis rate. Inflammation was assessed by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was implemented to testify the intergenic combination. The function of KCNQ1OT1 in vivo was explored through KCNQ1OT1 knockdown in mice. APAP triggered the downregulation of KCNQ1OT1 and CES2 in mice serums. KCNQ1OT1 upregulation could relieve the AILI in HepaRG cells, which were abrogated by CES2 downregulation. KCNQ1OT1 served as a sponge of miR-122-5p and miR-122-5p directly targeted CES2. KCNQ1OT1 overexpression abated the AILI through the miR-122-5p/CES2 axis in HepaRG cells in vitro and mice in vivo. The collective results clarified that KCNQ1OT1 weakened the AILI in vitro and in vivo by the miR-122-5p/CES2 axis, providing an explicit molecular mechanism and selectable therapeutic strategy of AILI.
ESTHER : Pei_2020_Mol.Cell.Biochem_475_107
PubMedSearch : Pei_2020_Mol.Cell.Biochem_475_107
PubMedID: 32779042

Title : Genomics-driven discovery of the biosynthetic gene cluster of maduramicin and its overproduction in Actinomadura sp. J1-007 - Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
Author(s) : Liu R , Fang F , An Z , Huang R , Wang Y , Sun X , Fu S , Fu A , Deng Z , Liu T
Ref : J Ind Microbiol Biotechnol , 47 :275 , 2020
Abstract : Maduramicin is the most efficient and possesses the largest market share of all anti-coccidiosis polyether antibiotics (ionophore); however, its biosynthetic gene cluster (BGC) has yet to been identified, and the associated strains have not been genetically engineered. Herein, we performed whole-genome sequencing of a maduramicin-producing industrial strain of Actinomadura sp. J1-007 and identified its BGC. Additionally, we analyzed the identified BGCs in silico to predict the biosynthetic pathway of maduramicin. We then developed a conjugation method for the non-spore-forming Actinomadura sp. J1-007, consisting of a site-specific integration method for gene overexpression. The maduramicin titer increased by 30% to 7.16 g/L in shake-flask fermentation following overexpression of type II thioesterase MadTE that is the highest titer at present. Our findings provide insights into the biosynthetic mechanism of polyethers and provide a platform for the metabolic engineering of maduramicin-producing microorganisms for overproduction and development of maduramicin analogs in the future.
ESTHER : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedSearch : Liu_2020_J.Ind.Microbiol.Biotechnol_47_275
PubMedID: 31853778
Gene_locus related to this paper: 9actn-a0a6i4pr03

Title : miR-132 improves the cognitive function of rats with Alzheimer's disease by inhibiting the MAPK1 signal pathway - Deng_2020_Exp.Ther.Med_20_159
Author(s) : Deng Y , Zhang J , Sun X , Ma G , Luo G , Miao Z , Song L
Ref : Exp Ther Med , 20 :159 , 2020
Abstract : Alzheimer's disease (AD) is a common worldwide progressive neurodegenerative disease. The dysregulation of miRNA is crucial in neurodegenerative diseases and neuron apoptosis during AD and is closely associated with the MAPK pathway. By bioinformatic website, we found that there was target inhibiting relationship between microRNA (miR)-132 and MAPK1. Therefore, the current study speculated that miR-132 could improve the cognitive function of rats with AD by inhibiting MAPK1 expression. To verify our hypothesis, 10 normal rats and 60 rats with AD were selected and divided into model, Ad-miR-132 negative control (NC), Ad-miR-132, Ad-small interfering (si)MAPK1 NC, Ad-siMAPK1 and Ad-miR-132 + Ad-MAPK1 groups. Rats were evaluated for learning by performing morris water maze tests and pathological changes of the hippocampus were assessed via HE staining. Additionally, hippocampus cell apoptosis was determined using a TUNEL assay and levels of acetylcholinesterase (AChE), reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were evaluated in sera via ELISA. The mRNA and protein expression of miR-132, iNOS, MAPK1 and phosphorylated (p)-MAPK1 was determined in hippocampus tissues via reverse transcription-quantitative PCR and western blotting, respectively. Compared with normal mice, rats with AD had significantly decreased learning abilities, increased cell apoptosis rates, increased levels of AChE, iNOS, ROS, MDA, MAPK1 and p-MAPK1 and decreased levels of SOD, GSH-Px and miR-132. Upregulation of miR-132 group improved the above indictors and silencing MAKP1 worsened the condition of rats. miR-132 upregulation therefore reversed the negative effects caused by MAPK1 silencing in rats with AD. In conclusion, miR-132 inhibited hippocampal iNOS expression and oxidative stress by inhibiting MAPK1expression to improve the cognitive function of rats with AD.
ESTHER : Deng_2020_Exp.Ther.Med_20_159
PubMedSearch : Deng_2020_Exp.Ther.Med_20_159
PubMedID: 33093897

Title : Identification of a Bacillus amyloliquefaciens H6 Thioesterase Involved in Zearalenone Detoxification by Transcriptomic Analysis - Xu_2020_J.Agric.Food.Chem_68_10071
Author(s) : Xu L , Sun X , Wan X , Li H , Yan F , Han R , Li Z , Tian Y , Liu X , Kang X , Wang Y
Ref : Journal of Agricultural and Food Chemistry , 68 :10071 , 2020
Abstract : Zearalenone (ZEA), a nonsteroidal estrogenic mycotoxin produced by Fusarium graminearum, induces hyperestrogenic responses in mammals and can cause reproductive disorders in farm animals. In this study, a transcriptome analysis of Bacillus amyloliquefaciens H6, which was previously identified as a ZEA-degrading bacterium, was conducted with high-throughput sequencing technology, and the differentially expressed genes were subjected to gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses. Among the 16 upregulated genes, BAMF_RS30125 was predicted to be the key gene responsible for ZEA degradation. The protein encoded by BAMF_RS30125 was then expressed in Escherichia coli, and this recombinant protein (named ZTE138) significantly reduced the ZEA content, as determined by the enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), and decreased the proliferating activity of ZEA in MCF-7 cells. What is more, the liquid chromatography-tandem mass spectrometry (LC-MS/MS) results showed that the relative molecular mass and the structure of ZEA also changed. Sequence alignment of the ZTE138 protein showed that it is a protease that belongs to the YBGC/FADM family of coenzyme A thioesterases, and thus, the protein can presumably cleave the ZEA lactone bond and break down its macrolide ring.
ESTHER : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedSearch : Xu_2020_J.Agric.Food.Chem_68_10071
PubMedID: 32815728

Title : Biodegradation of phthalate esters by Paracoccus kondratievae BJQ0001 isolated from Jiuqu (Baijiu fermentation starter) and identification of the ester bond hydrolysis enzyme - Xu_2020_Environ.Pollut_263_114506
Author(s) : Xu Y , Minhazul K , Wang X , Liu X , Li X , Meng Q , Li H , Zhang C , Sun X , Sun B
Ref : Environ Pollut , 263 :114506 , 2020
Abstract : Phthalate ester (PAE) pollution is an increasing problem globally. Paracoccus kondratievae BJQ0001 was isolated from the fermentation starter of Baijiu and showed an efficient degradation capability toward PAEs. To our poor knowledge, this is the first report of a P. kondratievae strain capable of degrading PAEs. The first complete genome sequence of P. kondratievae was presented without gaps, and composed of two circular chromosomes and one plasmid. The species simultaneously degraded di-methyl phthalate (DMP), di-ethyl phthalate (DEP), di-butyl phthalate (DBP), di-isobutyl phthalate (DIBP) and di-(2-ethylhexyl) phthalate (DEHP), with DMP and DEP as the preferred substrates. The half-life (t(1/2)) of DMP was only 6.34 h with an initial concentration of 200 mg/L. Combined with gene annotation and metabolic intermediate analysis, a metabolic pathway was proposed for the species. Benzoic acid, the intermediate of anaerobic PAE metabolism, was identified in the aerobic degradation process. Two key enzymes for alkyl ester bond hydrolysis were obtained, and belonged to families IV and VI of hydrolases, respectively. These results will promote the investigation of PAE degradation by P. kondratievae, and provide useful information for improving the quality control of food and environmental PAE treatment.
ESTHER : Xu_2020_Environ.Pollut_263_114506
PubMedSearch : Xu_2020_Environ.Pollut_263_114506
PubMedID: 32268225
Gene_locus related to this paper: 9rhob-a0a5p8jcg2 , 9rhob-a0a5p8jaa4

Title : Discovery and development of a novel short-chain fatty acid ester synthetic biocatalyst under aqueous phase from Monascus purpureus isolated from Baijiu - Xu_2020_Food.Chem_338_128025
Author(s) : Xu Y , Wang X , Liu X , Li X , Zhang C , Li W , Sun X , Wang W , Sun B
Ref : Food Chem , 338 :128025 , 2020
Abstract : Short-chain fatty acid esters are important flavor chemicals in Chinese traditional fermented Baijiu. Monascus purpureus was recognized as an important microorganism contributing to ester synthesis. However, the molecular basis for ester synthesis was still lacking. The present work combined genome sequencing, transcriptome sequencing, gene library construction, and enzyme engineering to discover a novel catalyst from M. purpureus (isolated from Baijiu fermentation starter). Enzyme LIP05, belonging to the alpha/beta hydrolase family, was identified to synthesize short-chain fatty acid esters under aqueous phase. After deleting the lid domain of LIP05, the synthesis of ethyl pentanoate, ethyl hexanoate, ethyl octanoate, or ethyl decanoate was achieved. Ethyl octanoate with the highest conversion ratio of 93.7% was obtained with the assistance of ultrasound. The study reveals the molecular basis for synthesizing short-chain fatty acid esters by M. purpureus and will promote the application of the species or the enzyme in food industry.
ESTHER : Xu_2020_Food.Chem_338_128025
PubMedSearch : Xu_2020_Food.Chem_338_128025
PubMedID: 32927200
Gene_locus related to this paper: monpu-a0a507qkl5

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

Title : Integration of lipidomic and transcriptomic profiles reveals novel genes and regulatory mechanisms of Schizochytrium sp. in response to salt stress - Jiang_2019_Bioresour.Technol_294_122231
Author(s) : Jiang JY , Zhu S , Zhang Y , Sun X , Hu X , Huang H , Ren LJ
Ref : Bioresour Technol , 294 :122231 , 2019
Abstract : In this study, the effects of salt stress on the physiological, lipidomic and transcriptomic profiles of halophilic microalga Schizochytrium sp. were investigated. In general, Schizochytrium sp. could survive under high osmotic fermentation medium containing 30g/L NaCl, and showed a significant increase in C14:0 percentage in total fatty acids. In lipidomic analysis, C14:0 was specifically enriched in phosphatidylcholine (PC), and membrane phospholipids participated in the salt stress response mostly. Specially, one novel signal lipid N-acylphosphatidylethanolamine (NAPE) (18:0/20:3/14:0) was upregulated significantly. Transcriptomic analysis revealed glycerol-3-phosphate acyltransferase (GPAT) and phospholipase ABHD3 (PLABDH3) were involved in C14:0 metabolism and NAPE biosynthesis. Signalling pathways they mediated were activated as evident by high expression level of Myristoyl-CoA: protein N-myristoyltransferase (NMT) and NAPE-hydrolyzing PLD (NAPE-PLD). This study gives us an insight in specific responses to salt stress in Schizochytrium sp. and provides a considerable proportion of novel genes that could commendably be used for engineering modification.
ESTHER : Jiang_2019_Bioresour.Technol_294_122231
PubMedSearch : Jiang_2019_Bioresour.Technol_294_122231
PubMedID: 31606596

Title : Novel chromanone-dithiocarbamate hybrids as multifunctional AChE inhibitors with beta-amyloid anti-aggregation properties for the treatment of Alzheimer's disease - Jiang_2019_Bioorg.Chem_89_103027
Author(s) : Jiang N , Ding J , Liu J , Sun X , Zhang Z , Mo Z , Li X , Yin H , Tang W , Xie SS
Ref : Bioorg Chem , 89 :103027 , 2019
Abstract : By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Abeta aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC50=0.10muM) and AChE-induced Abeta aggregation (33.02% at 100muM), and could effectively inhibit self-induced Abeta aggregation (38.25% at 25muM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors.
ESTHER : Jiang_2019_Bioorg.Chem_89_103027
PubMedSearch : Jiang_2019_Bioorg.Chem_89_103027
PubMedID: 31176237

Title : Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease - Zhu_2019_Int.J.Colorectal.Dis_34_255
Author(s) : Zhu T , Sun X , Wei M , Yi B , Zhao X , Wang W , Feng J
Ref : Int J Colorectal Dis , 34 :255 , 2019
Abstract : OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age <= 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR <=3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.
ESTHER : Zhu_2019_Int.J.Colorectal.Dis_34_255
PubMedSearch : Zhu_2019_Int.J.Colorectal.Dis_34_255
PubMedID: 30368570

Title : Copper exposure enhances Spodoptera litura larval tolerance to beta-cypermethrin - Lu_2019_Pestic.Biochem.Physiol_160_127
Author(s) : Lu K , Li W , Cheng Y , Ni H , Chen X , Li Y , Tang B , Sun X , Liu T , Qin N , Chen D , Zeng R , Song Y
Ref : Pestic Biochem Physiol , 160 :127 , 2019
Abstract : Environmental xenobiotics can influence the tolerance of insects to chemical insecticides. Heavy metals are widespread distributed, can be easily bio-accumulated in plants and subsequently within phytophagous insects via the food chains. However, less attention has been paid to the effect of heavy metal exposure on their insecticide tolerance. In this study, pre-exposure of copper (Cu, 25-100mgkg(-1)) significantly enhanced the subsequent tolerance of Spodoptera litura to beta-cypermethrin, a widely used pyrethroid insecticide in crop field. Cytochrome P450 monooxygenases (CYPs) activities were cross-induced in larvae exposed to Cu and beta-cypermethrin, while the activities of glutathione S-transferase (GST) and carboxylesterase (CarE) were not affected. Application of piperonyl butoxide (PBO), a P450 synergist, effectively impaired the tolerance to beta-cypermethrin in Cu-exposed S. litura larvae with a synergistic ratio of 1.72, indicating that P450s contribute to larval tolerance to beta-cypermethrin induced by Cu exposure. Among the four CYP6AB family genes examined, only larval midgut-specific CYP6AB12 was found to be cross-induced by Cu and beta-cypermethrin. RNA interference (RNAi)-mediated silencing of CYP6AB12 effectively decreased the mRNA levels of the target gene, and significantly reduced the larval tolerance to beta-cypermethrin following exposure to Cu. These results showed that pre-exposure of heavy metal Cu enhanced larval tolerance to beta-cypermethrin in S. litura, possibly through the cross-induction of P450s. Our findings provide new insights on the relationship between heavy metals and chemical insecticides that may benefit both the risk evaluation of heavy metal contamination and development of pest management strategies.
ESTHER : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedSearch : Lu_2019_Pestic.Biochem.Physiol_160_127
PubMedID: 31519247

Title : A Coevolved EDS1-SAG101-NRG1 Module Mediates Cell Death Signaling by TIR-Domain Immune Receptors - Lapin_2019_Plant.Cell_31_2430
Author(s) : Lapin D , Kovacova V , Sun X , Dongus JA , Bhandari D , von Born P , Bautor J , Guarneri N , Rzemieniewski J , Stuttmann J , Beyer A , Parker JE
Ref : Plant Cell , 31 :2430 , 2019
Abstract : Plant nucleotide binding/leucine-rich repeat (NLR) immune receptors are activated by pathogen effectors to trigger host defenses and cell death. Toll-interleukin 1 receptor domain NLRs (TNLs) converge on the ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1) family of lipase-like proteins for all resistance outputs. In Arabidopsis (Arabidopsis thaliana) TNL-mediated immunity, AtEDS1 heterodimers with PHYTOALEXIN DEFICIENT4 (AtPAD4) transcriptionally induced basal defenses. AtEDS1 uses the same surface to interact with PAD4-related SENESCENCE-ASSOCIATED GENE101 (AtSAG101), but the role of AtEDS1-AtSAG101 heterodimers remains unclear. We show that AtEDS1-AtSAG101 functions together with N REQUIRED GENE1 (AtNRG1) coiled-coil domain helper NLRs as a coevolved TNL cell death-signaling module. AtEDS1-AtSAG101-AtNRG1 cell death activity is transferable to the Solanaceous species Nicotiana benthamiana and cannot be substituted by AtEDS1-AtPAD4 with AtNRG1 or AtEDS1-AtSAG101 with endogenous NbNRG1. Analysis of EDS1-family evolutionary rate variation and heterodimer structure-guided phenotyping of AtEDS1 variants and AtPAD4-AtSAG101 chimeras identify closely aligned a-helical coil surfaces in the AtEDS1-AtSAG101 partner C-terminal domains that are necessary for reconstituted TNL cell death signaling. Our data suggest that TNL-triggered cell death and pathogen growth restriction are determined by distinctive features of EDS1-SAG101 and EDS1-PAD4 complexes and that these signaling machineries coevolved with other components within plant species or clades to regulate downstream pathways in TNL immunity.
ESTHER : Lapin_2019_Plant.Cell_31_2430
PubMedSearch : Lapin_2019_Plant.Cell_31_2430
PubMedID: 31311833
Gene_locus related to this paper: arath-At5g14930 , arath-eds1 , arath-PAD4

Title : Assessment of phthalate ester residues and distribution patterns in Baijiu raw materials and Baijiu - Dong_2019_Food.Chem_283_508
Author(s) : Dong W , Guo R , Sun X , Li H , Zhao M , Zheng F , Sun J , Huang M , Wu J
Ref : Food Chem , 283 :508 , 2019
Abstract : Phthalate esters (PAEs) are harmful to human health and have been repeatedly identified in Baijiu samples. In our study, the distribution and degradation characteristics of 14 PAEs in Baijiu raw materials (BRMs) and Baijiu during distillation were detected using QuEChERS or vortex-assisted surfactant-enhanced-emulsification liquid-liquid micro-extraction (VSLLME) methods coupled with gas chromatography-mass spectrometry. The same five PAEs were detected in all tested samples, values ranged from 0.003 to 0.292 mg/kg; however, higher concentrations existed in BRMs compared to Baijiu samples. Using multivariate statistical analysis, detailed distinctions between different varieties of Baijiu and BRMs and separation-related PAE markers were revealed. PAEs concentration during Baijiu distillation showed a decreasing trend. The highest concentrations detected in distillate heads, were 1.6-, 2.3-, and 8.1-fold higher than those in heart1, heart2, and tail distillates, respectively. These findings revealed that PAEs may migrate from BRMs; moreover, that PAEs content can be regulated by distillation.
ESTHER : Dong_2019_Food.Chem_283_508
PubMedSearch : Dong_2019_Food.Chem_283_508
PubMedID: 30722905

Title : Effects of two environmental endocrine disruptors di-n-butyl phthalate (DBP) and mono-n-butyl phthalate (MBP) on human sperm functions in vitro - Xie_2019_Reprod.Toxicol_83_1
Author(s) : Xie F , Chen X , Weng S , Xia T , Sun X , Luo T , Li P
Ref : Reprod Toxicol , 83 :1 , 2019
Abstract : Di-n-butyl phthalate (DBP), a plastic-derived, endocrine-disrupting chemical, is regarded as a male reproductive toxicant. In this study, we investigated the in vitro actions of DBP and mono-n-butyl phthalate (MBP, the main metabolite of DBP) on human sperm functions. Human sperm were treated with DBP (2 nM-6 muM), MBP (1 nM-3 muM), and a mixture of DBP and MBP in vitro. The results showed that only DBP at 6 muM, a dose reported in semen of infertile men, MBP at 3 muM (three times of the reported maximum MBP concentration in semen), and their mixture, had obvious adverse effects on sperm motility, penetration ability and capacitation. In addition, these doses of phthalates suppressed human sperm tyrosine phosphorylation, a key signaling pathway that regulates sperm functions. Our findings indicate that DBP and MBP may compromise human sperm functions by inhibiting sperm tyrosine phosphorylation once they accumulate in semen at high levels.
ESTHER : Xie_2019_Reprod.Toxicol_83_1
PubMedSearch : Xie_2019_Reprod.Toxicol_83_1
PubMedID: 30391722

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Comparative proteomic analysis of Ulva prolifera response to high temperature stress - Fan_2018_Proteome.Sci_16_17
Author(s) : Fan M , Sun X , Liao Z , Wang J , Li Y , Xu N
Ref : Proteome Sci , 16 :17 , 2018
Abstract : Background: Ulva prolifera belongs to green macroalgae and is the dominant species of green tide. It is distributed worldwide and is therefore subject to high-temperature stress during the growth process. However, the adaptation mechanisms of the response of U. prolifera to high temperatures have not been clearly investigated yet. Methods: In this study, isobaric tags for relative and absolute quantitation (iTRAQ) labelling was applied in combination with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to conduct comparative proteomic analysis of the response of U. prolifera to high-temperature stress and to elucidate the involvement of this response in adaptation mechanisms. Differentially expressed proteins (DEPs) of U. prolifera under high temperature (denote UpHT) compared with the control (UpC) were identified. Bioinformatic analyses including GO analysis, pathway analysis, and pathway enrichment analysis was performed to analyse the key metabolic pathways that underlie the thermal tolerance mechanism through protein networks. Quantitative real-time PCR and western blot were performed to validate selected proteins. Results: In the present study, 1223 DEPs were identified under high temperature compared with the control, which included 790 up-regulated and 433 down-regulated proteins. The high-temperature stimulus mainly induced the expression of glutathione S-transferase, heat shock protein, ascorbate peroxidase, manganese superoxide dismutase, ubiquitin-related protein, lhcSR, rubisco activase, serine/threonine protein kinase 2, adenylate kinase, Ca(2+)-dependent protein kinase (CDPK), disease resistance protein EDS1, metacaspase type II, NDPK2a, 26S proteasome regulatory subunit, ubiquinone oxidoreductase, ATP synthase subunit, SnRK2s, and cytochrome P450. The down-regulated proteins were photosynthesis-related proteins, glutathione reductase, catalase-peroxidase, thioredoxin, thioredoxin peroxidase, PP2C, and carbon fixation-related proteins. Furthermore, biological index analysis indicated that protein content and SOD activity decreased; the value of Fv/Fm dropped to the lowest point after culture for 96 h. However, APX activity and MDA content increased under high temperature. Conclusion: The present study implied an increase in proteins that were associated with the stress response, oxidative phosphorylation, the cytokinin signal transduction pathway, the abscisic acid signal transduction pathway, and the glutathione metabolism pathway. Proteins that were associated with photosynthesis, carbon fixation in photosynthesis organisms, and the photosynthesis antenna protein pathway were decreased. These pathways played a pivotal role in high temperature regulation. These novel proteins provide a good starting point for further research into their functions using genetic or other approaches. These findings significantly improve the understanding of the molecular mechanisms involved in the tolerance of algae to high-temperature stress.
ESTHER : Fan_2018_Proteome.Sci_16_17
PubMedSearch : Fan_2018_Proteome.Sci_16_17
PubMedID: 30386183

Title : A novel variant associated with HDL-C levels by modifying DAGLB expression levels: An annotation-based genome-wide association study - Zhou_2018_Eur.J.Hum.Genet_26_838
Author(s) : Zhou D , Zhang D , Sun X , Li Z , Ni Y , Shan Z , Li H , Liu C , Zhang S , Liu Y , Zheng R , Pan F , Zhu Y , Shi Y , Lai M
Ref : Eur J Hum Genet , 26 :838 , 2018
Abstract : Although numbers of genome-wide association studies (GWAS) have been performed for serum lipid levels, limited heritability has been explained. Studies showed that combining data from GWAS and expression quantitative trait loci (eQTLs) signals can both enhance the discovery of trait-associated SNPs and gain a better understanding of the mechanism. We performed an annotation-based, multistage genome-wide screening for serum-lipid-level-associated loci in totally 6863 Han Chinese. A serum high-density lipoprotein cholesterol (HDL-C) associated variant rs1880118 (hg19 chr7:g. 6435220G>C) was replicated (Pcombined = 1.4E-10). rs1880118 was associated with DAGLB (diacylglycerol lipase, beta) expression levels in subcutaneous adipose tissue (P = 5.9E-42) and explained 47.7% of the expression variance. After the replication, an active segment covering variants tagged by rs1880118 near 5' of DAGLB was annotated using histone modification and transcription factor binding signals. The luciferase report assay revealed that the segment containing the minor alleles showed increased transcriptional activity compared with segment contains the major alleles, which was consistent with the eQTL analyses. The expression-trait association tests indicated the association between the DAGLB and serum HDL-C levels using gene-based approaches called "TWAS" (P = 3.0E-8), "SMR" (P = 1.1E-4), and "Sherlock" (P = 1.6E-6). To summarize, we identified a novel HDL-C-associated variant which explained nearly half of the expression variance of DAGLB. Integrated analyses established a genotype-gene-phenotype three-way association and expanded our knowledge of DAGLB in lipid metabolism.
ESTHER : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedSearch : Zhou_2018_Eur.J.Hum.Genet_26_838
PubMedID: 29476167

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Molluscicidal activity and mechanism of toxicity of a novel salicylanilide ester derivative against Biomphalaria species - He_2017_Parasit.Vectors_10_383
Author(s) : He P , Wang W , Sanogo B , Zeng X , Sun X , Lv Z , Yuan D , Duan L , Wu Z
Ref : Parasit Vectors , 10 :383 , 2017
Abstract : BACKGROUND: Schistosomiasis mansoni is one of the most important, but often neglected, tropical diseases transmitted by snails of the genus Biomphalaria. Control of the intermediate host snail plays a crucial role in preventing the spread of schistosomiasis. However, there is only one molluscicide, niclosamide, recommended by the World Health Organization. Niclosamide has been used for several decades but is toxic to non-target organisms. Therefore, it is necessary to optimize the scaffold of niclosamide and develop novel molluscicides with enhanced potency and decreased toxicity to non-target organisms.
METHODS: In this study, a candidate compound was analyzed by nuclear magnetic resonance and mass spectrometry. The molluscicidal potential against Biomphalaria species and cercaricidal potential against S. mansoni were evaluated using the immersion method. Furthermore, the preliminary mechanism was studied through cellular enzyme tests and electron microscopy.
RESULTS: 5-chloro-2-[(2-chloro-4-nitrophenyl)carbamoyl]phenyl-4-methoxybenzoate (salicylanilidate), a novel salicylanilide ester derivative, was derived from niclosamide. The 50% lethal concentration to B. glabrata, B. straminea and B. pfeifferi was 0.261 mg/l, 0.172 mg/l and 0.241 mg/l, respectively. The effective dose required to completely kill S. mansoni cercariae was 0.625 mg/l for salicylanilidate and 0.125 mg/l for niclosamide. However, salicylanilidate was approximately 100-fold less toxic to the fish Danio rerio than niclosamide. Furthermore, salicylanilidate reduced the enzymatic activities of nitric oxide synthase (NOS), lactate dehydrogenase (LDH) and acetylcholinesterase (AChE) in the snail, demonstrating that it could affect neurohypophysis transmission and energy metabolism. Severe swelling in the tentacle and deformation of cilia in the tentacle and mantle were observed through scanning electron microscopy. The results of transmission electron microscopy showed that salicylanilidate could damage critical organelles in hepatopancreas tissues, including degeneration of the endoplasmic reticulum and vacuolization in mitochondria. In addition, transcriptional levels of superoxide dismutase (SOD), acid phosphatase (ACP) and NOS in the hepatopancreas were significantly downregulated as shown by real-time quantitative polymerase chain reaction (RT-PCR). These results indicated that the hepatopancreas is a primary target organ of salicylanilidate.
CONCLUSIONS: Salicylanilidate not only had deleterious effects on Biomphalaria species and S. mansoni cercariae but also showed very low toxicity to D. rerio, suggesting that it has broad potential applications.
ESTHER : He_2017_Parasit.Vectors_10_383
PubMedSearch : He_2017_Parasit.Vectors_10_383
PubMedID: 28793917

Title : Severe hypertriglyceridemia due to two novel loss-of-function lipoprotein lipase gene mutations (C310R\/E396V) in a Chinese family associated with recurrent acute pancreatitis - Lun_2017_Oncotarget_8_47741
Author(s) : Lun Y , Sun X , Wang P , Chi J , Hou X , Wang Y
Ref : Oncotarget , 8 :47741 , 2017
Abstract : Lipoprotein lipase (LPL) is widely expressed in skeletal muscles, cardiac muscles as well as adipose tissue and involved in the catabolism of triglyceride. Herein we have systematically characterized two novel loss-of-function mutations in LPL from a Chinese family in which afflicted members were manifested by severe hypertriglyceridemia and recurrent pancreatitis. DNA sequencing revealed that the proband was a heterozygote carrying a novel c.T928C (p.C310R) mutation in exon 6 of the LPL gene. Another member of the family was detected to be a compound heterozygote who along with the c.T928C mutation also carried a novel missense mutation c.A1187T (p.E396V) in exon 8 of the LPL gene. Furthermore, COS-1 cells were transfected with lentiviruses containing the mutant LPL genes. While C310R markedly reduced the overall LPL protein level, COS-1 cells carrying E396V or double mutations contained similar overall LPL protein levels to the wild-type. The specific activity of the LPL mutants remained at comparable magnitude to the wild-type. However, few LPL were detected in the culture medium for the mutants, suggesting that both mutations caused aberrant triglyceride catabolism. More specifically, E396V and double mutations dampened the transport of LPL to the cell surface, while for the C310R mutation, reducing LPL protein level might be involved. By characterizing these two novel LPL mutations, this study has expanded our understanding on the pathogenesis of familial hypertriglyceridemia (FHTG).
ESTHER : Lun_2017_Oncotarget_8_47741
PubMedSearch : Lun_2017_Oncotarget_8_47741
PubMedID: 28548960
Gene_locus related to this paper: human-LPL

Title : Determination of Human Hepatic CYP2C8 and CYP1A2 Age-Dependent Expression to Support Human Health Risk Assessment for Early Ages - Song_2017_Drug.Metab.Dispos_45_468
Author(s) : Song G , Sun X , Hines RN , McCarver DG , Lake BG , Osimitz TG , Creek MR , Clewell HJ , Yoon M
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , 45 :468 , 2017
Abstract : Predicting age-specific metabolism is important for evaluating age-related drug and chemical sensitivity. Multiple cytochrome P450s and carboxylesterase enzymes are responsible for human pyrethroid metabolism. Complete ontogeny data for each enzyme are needed to support in vitro to in vivo extrapolation (IVIVE). This study was designed to determine age-dependent human hepatic CYP2C8 expression, for which only limited ontogeny data are available, and to further define CYP1A2 ontogeny. CYP2C8 and 1A2 protein levels were measured by quantitative Western blotting using liver microsomal samples prepared from 222 subjects with ages ranging from 8 weeks gestation to 18 years after birth. The median CYP2C8 expression was significantly greater among samples from subjects older than 35 postnatal days (n = 122) compared with fetal samples and those from very young infants (fetal to 35 days postnatal, n = 100) (0.00 vs. 13.38 pmol/mg microsomal protein; p < 0.0001). In contrast, the median CYP1A2 expression was significantly greater after 15 months postnatal age (n = 55) than in fetal and younger postnatal samples (fetal to 15 months postnatal, n = 167) (0.0167 vs. 2.354 pmol/mg microsomal protein; p < 0.0001). CYP2C8, but not CYP1A2, protein levels significantly correlated with those of CYP2C9, CYP2C19, and CYP3A4 (p < 0.001), consistent with CYP2C8 and CYP1A2 ontogeny probably being controlled by different mechanisms. This study provides key data for the physiologically based pharmacokinetic model-based prediction of age-dependent pyrethroid metabolism, which will be used for IVIVE to support pyrethroid risk assessment for early life stages.
ESTHER : Song_2017_Drug.Metab.Dispos_45_468
PubMedSearch : Song_2017_Drug.Metab.Dispos_45_468
PubMedID: 28228413

Title : Design, synthesis, biological evaluation, and molecular modeling studies of chalcone-rivastigmine hybrids as cholinesterase inhibitors - Wang_2017_Bioorg.Med.Chem_25_360
Author(s) : Wang L , Wang Y , Tian Y , Shang J , Sun X , Chen H , Wang H , Tan W
Ref : Bioorganic & Medicinal Chemistry , 25 :360 , 2017
Abstract : A series of novel chalcone-rivastigmine hybrids were designed, synthesized, and tested in vitro for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase. Most of the target compounds showed hBChE selective activity in the micro- and submicromolar ranges. The most potent compound 3 exhibited comparable IC50 to the commercially available drug (rivastigmine). To better understand their structure activity relationships (SAR) and mechanisms of enzyme-inhibitor interactions, kinetic and molecular modeling studies including molecular docking and molecular dynamics (MD) simulations were carried out. Furthermore, compound 3 blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells and shows the required druggability and low cytotoxicity, suggesting this hybrid is a promising multifunctional drug candidate for Alzheimer's disease (AD) treatment.
ESTHER : Wang_2017_Bioorg.Med.Chem_25_360
PubMedSearch : Wang_2017_Bioorg.Med.Chem_25_360
PubMedID: 27856236

Title : Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita - Cui_2017_Exp.Parasitol_176_75
Author(s) : Cui R , Zhang L , Chen Y , Huang W , Fan C , Wu Q , Peng D , da Silva W , Sun X
Ref : Experimental Parasitology , 176 :75 , 2017
Abstract : The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant.
ESTHER : Cui_2017_Exp.Parasitol_176_75
PubMedSearch : Cui_2017_Exp.Parasitol_176_75
PubMedID: 28238686
Gene_locus related to this paper: melin-ACHE1 , melin-ACHE2 , melic-a0a0m5m7r8

Title : Association of PON1, P2Y12 and COX1 with Recurrent Ischemic Events in Patients with Extracranial or Intracranial Stenting - Li_2016_PLoS.One_11_e0148891
Author(s) : Li XQ , Ma N , Li XG , Wang B , Sun SS , Gao F , Mo DP , Song LG , Sun X , Liu L , Zhao XQ , Wang YL , Wang YJ , Zhao ZG , Miao ZR
Ref : PLoS ONE , 11 :e0148891 , 2016
Abstract : BACKGROUND AND PURPOSE: Short-term combined use of clopidogrel and aspirin improves cerebrovascular outcomes in patients with symptomatic extracranial or intracranial stenosis. Antiplatelet non-responsiveness is related to recurrent ischemic events, but the culprit genetic variants responsible for the non-responsiveness have not been well studied. We aimed to identify the genetic variants associated with poor clinical outcomes.
METHODS: Patients with symptomatic extracranial or intracranial stenosis scheduled for stenting and receiving dual antiplatelets (clopidogrel 75 mg and aspirin 100 mg daily) for at least 5 days before intervention were enrolled. Ischemic events including recurrent transient ischemic attack, stroke, myocardial infarction, and vascular-related mortality within 12 months follow-up were recorded. We examined the influence of genetic polymorphisms on treatment outcome in our patients.
RESULTS: A total of 268 patients were enrolled into our study and ischemic events were observed in 39 patients. For rs662 of paraoxonase 1 (PON1), allele C was associated with an increased risk of ischemic events (OR = 1.64, 95%CI = 1.03-2.62, P = 0.029). The A-allele carriers of rs2046934 of P2Y12 had a significant association with adverse events (OR = 2.01, 95%CI = 1.10-3.67, P = 0.041). The variant T-allele of cyclooxygenase-1 (COX1) rs1330344 significantly increased the risk of recurrent clinical events (OR = 1.85, 95%CI = 1.12-3.03, P = 0.017). The other single nucleotide polymorphism (SNP) had no association with ischemic events.
CONCLUSIONS: PON1, P2Y12 and COX1 polymorphisms were associated with poorer vascular outcomes. Testing for these polymorphisms may be valuable in the identification of patients at risk for recurrent ischemic events.
ESTHER : Li_2016_PLoS.One_11_e0148891
PubMedSearch : Li_2016_PLoS.One_11_e0148891
PubMedID: 26870959

Title : Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation - Zhang_2016_J.Pharmacol.Exp.Ther_359_374
Author(s) : Zhang J , Zhang L , Sun X , Yang Y , Kong L , Lu C , Lv G , Wang T , Wang H , Fu F
Ref : Journal of Pharmacology & Experimental Therapeutics , 359 :374 , 2016
Abstract : Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP.
ESTHER : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedSearch : Zhang_2016_J.Pharmacol.Exp.Ther_359_374
PubMedID: 27535978

Title : Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population - Wang_2016_Sci.Rep_6_20691
Author(s) : Wang T , Ma X , Peng D , Zhang R , Sun X , Chen M , Yan J , Wang S , Yan D , He Z , Jiang F , Bao Y , Hu C , Jia W
Ref : Sci Rep , 6 :20691 , 2016
Abstract : Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 x 10(-5) and 6.54 x 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 x 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 x 10(-8) and 4.43 x 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 x 10(-4) and 4.65 x 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.
ESTHER : Wang_2016_Sci.Rep_6_20691
PubMedSearch : Wang_2016_Sci.Rep_6_20691
PubMedID: 26848030

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

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

Title : [Role of alpha7 nicotinic acetylcholine receptor in attenuation of endotoxin induced delirium with dexmedetomidine in mice] - Zhang_2016_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_28_127
Author(s) : Zhang X , Li Z , Sun X , Jin F , Liu J , Li J
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 28 :127 , 2016
Abstract : OBJECTIVE: To observe the role of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in the protection against delirium by the use of dexmedetomidine (DEX) in endotoxin derived delirium and its mechanism.
METHODS: 100 male adult C57BL/6 mice were randomly divided into normal saline control group (NS group), DEX control group, lipopolysaccharide (LPS) induced endotoxemia model group (LPS group), DEX protection group (DEX+LPS group), and alpha-bungarotoxin antagonism group (alpha-BGT+DEX+LPS group), with 20 mice in each group. A model of endotoxemia was reproduced by intraperitoneal injection of LPS 20 mg/kg, and the mice in NS group and DEX control group were given equivalent sterile normal saline. The mice in DEX control group, DEX+LPS group, and alpha-BGT+DEX+LPS group were intraperitoneally injected with DEX 40 mug/kg 15 minutes before LPS injection. The mice in alpha-BGT+DEX+LPS group were intraperitoneally injected with alpha7nAChR inhibitor alpha-BGT 1 mug/kg 15 minutes before DEX injection. The mice in NS group were given equivalent sterile normal saline. Ten mice in each group were assigned for open field test before and 24 hours after model reproduction, and the mice were then sacrificed to obtain the specimens. The levels of tumor necrosis factor-alpha (TNF-alpha) and neuron-specific enolase (NSE) in serum were determined by enzyme-linked immune sorbent assay (ELISA). Western Blot method was used to determine the expression of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in hippocampus. Another 10 mice were subjected to new object recognition test to observe the total exploration time during training period and preference index at 3 hours and 24 hours after LPS challenge.
RESULTS: There were no significant differences in all parameters between NS group and DEX control group. (1) It was shown by the open field test results that there were no significant differences in all parameters of open field test before model reproduction among all the groups. Twenty-four hours after model reproduction, when compared with NS group, the mice in LPS group showed that they had the ability of cognition of new environment, but learning and memory abilities were lowered, and tension was increased. DEX could significantly attenuate the degree of delirium, however, the protection of DEX from the delirious syndrome was antagonized partly by alpha-BGT. (2) The new object recognition test results showed that compared with NS group, the ability of exploring new object was decreased in LPS group. DEX could significantly improve the exploration ability. However, DEX failed to control the delirious syndrome in alpha-BGT+DEX+LPS group. (3) The results of ELISA showed that the levels of TNF-alpha and NSE in serum were significantly increased in LPS groups as compared with that in NS group, and the levels of TNF-alpha and NSE were significantly decreased in DEX+LPS group. However, alpha-BGT could antagonise the protective effect of DEX [TNF-alpha (ng/L) in NS, LPS, DEX+LPS and alpha-BGT+DEX+LPS groups was 23.72+/-3.13, 808.78+/-87.86, 192.96+/-31.47, 829.99+/-80.98, respectively, and NSE (mug/L) was 8.70+/-0.74, 25.90+/-3.03, 18.10+/-2.14, and 23.12+/-2.21, respectively, all P < 0.01]. (4) The results of Western Blot showed that compared with NS group, the protein expression of ChAT in LPS group was significantly declined, and the protein expression of AChE was significantly increased. DEX could reverse the expressions of ChAT and AChT, however, alpha-BGT could reverse the protective effect of DEX [ChAT (gray value) in NS, LPS, DEX+LPS and alpha-BGT+DEX+LPS groups was 1.536+/-0.150, 0.381+/-0.138, 0.914+/-0.173, 0.628+/-0.088, respectively, and AChE (gray value) was 0.382+/-0.201, 1.843+/-0.325, 0.898+/-0.155, and 1.470+/-0.220, respectively, P < 0.05 or P<0.01].
CONCLUSIONS: Delirium syndrome may occur in mice with endotoxemia. DEX could attenuate endotoxemia-associated delirium syndrome through transforming central neurotransmitter, and its mechanism maybe related with alpha7nAChR.
ESTHER : Zhang_2016_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_28_127
PubMedSearch : Zhang_2016_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_28_127
PubMedID: 26911944

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 : Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products - Wang_2015_BMC.Genomics_16_28
Author(s) : Wang X , Zhang X , Liu L , Xiang M , Wang W , Sun X , Che Y , Guo L , Liu G , Wang C , Yin WB , Stadler M , Liu X
Ref : BMC Genomics , 16 :28 , 2015
Abstract : BACKGROUND: In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics.
RESULTS: Here, we report the genome sequence of the endophytic fungus of tea Pestalotiopsis fici W106-1/CGMCC3.15140. The abundant carbohydrate-active enzymes especially significantly expanding pectinases allow the fungus to utilize the limited intercellular nutrients within the host plants, suggesting adaptation of the fungus to endophytic lifestyle. The P. fici genome encodes a rich set of secondary metabolite synthesis genes, including 27 polyketide synthases (PKSs), 12 non-ribosomal peptide synthases (NRPSs), five dimethylallyl tryptophan synthases, four putative PKS-like enzymes, 15 putative NRPS-like enzymes, 15 terpenoid synthases, seven terpenoid cyclases, seven fatty-acid synthases, and five hybrids of PKS-NRPS. The majority of these core enzymes distributed into 74 secondary metabolite clusters. The putative Diels-Alderase genes have undergone expansion. CONCLUSION: The significant expansion of pectinase encoding genes provides essential insight in the life strategy of endophytes, and richness of gene clusters for secondary metabolites reveals high potential of natural products of endophytic fungi.
ESTHER : Wang_2015_BMC.Genomics_16_28
PubMedSearch : Wang_2015_BMC.Genomics_16_28
PubMedID: 25623211
Gene_locus related to this paper: 9pezi-w3wud0 , 9pezi-w3xja3 , pesfw-w3wz53 , pesfw-w3x341 , pesfw-w3whp0 , pesfw-w3xc39 , pesfw-w3wrn9 , pesfw-pfmab , pesfw-pfmae

Title : Biphasic photoelectrochemical sensing strategy based on in situ formation of CdS quantum dots for highly sensitive detection of acetylcholinesterase activity and inhibition - Hou_2015_Biosens.Bioelectron_75_359
Author(s) : Hou T , Zhang L , Sun X , Li F
Ref : Biosensors & Bioelectronics , 75 :359 , 2015
Abstract : Herein, we reported a facile and highly sensitive biphasic photoelectrochemical (PEC) sensing strategy based on enzymatic product-mediated in situ formation of CdS quantum dots (QDs), and assayed the activity and inhibition of acetylcholinesterase (AChE) in its optimal state. Upon the hydrolysis of acetylthiocholine catalyzed by AChE, the product thiocholine stabilizes the in situ formation of CdS QDs in homogenous solution. Due to the electrostatic attraction, the resulting tertiary amino group-functionalized CdS QDs are attached to the surface of the negatively charged indium tin oxide (ITO) electrode, generating significant PEC response upon illumination in the presence of electron donors. By taking full advantage of the in situ formation of CdS QDs in homogenous solution, this strategy is capable of detecting AChE activity and inhibition in its optimal state. A directly measured detection limit of 0.01mU/mL for AChE activity is obtained, which is superior to those obtained by some fluorescence methods. The inhibition of AChE activity by aldicarb is successfully detected, and the corresponding IC50 is determined to be 13mug/L. In addition to high sensitivity and good selectivity, this strategy also exhibits additional advantages of simplicity, low cost and easy operation. To the best of our knowledge, the as-proposed strategy is the first example demonstrating the application of CdS QDs formed in situ for biphasic PEC detection of enzyme activity and inhibition. More significantly, it opens up a new horizon for the development of homogenous PEC sensing platforms, and has great potential in probing many other analytes.
ESTHER : Hou_2015_Biosens.Bioelectron_75_359
PubMedSearch : Hou_2015_Biosens.Bioelectron_75_359
PubMedID: 26339933

Title : Silibinin inhibits acetylcholinesterase activity and amyloid beta peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease - Duan_2015_Neurobiol.Aging_36_1792
Author(s) : Duan S , Guan X , Lin R , Liu X , Yan Y , Zhang T , Chen X , Huang J , Sun X , Li Q , Fang S , Xu J , Yao Z , Gu H
Ref : Neurobiology of Aging , 36 :1792 , 2015
Abstract : Alzheimer's disease (AD) is characterized by amyloid beta (Abeta) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Abeta peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Abeta and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Abeta aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Abeta and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Abeta aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Abeta peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment.
ESTHER : Duan_2015_Neurobiol.Aging_36_1792
PubMedSearch : Duan_2015_Neurobiol.Aging_36_1792
PubMedID: 25771396

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 : Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics - Zhang_2014_Nat.Commun_5_3849
Author(s) : Zhang Y , Zhang K , Fang A , Han Y , Yang J , Xue M , Bao J , Hu D , Zhou B , Sun X , Li S , Wen M , Yao N , Ma LJ , Liu Y , Zhang M , Huang F , Luo C , Zhou L , Li J , Chen Z , Miao J , Wang S , Lai J , Xu JR , Hsiang T , Peng YL , Sun W
Ref : Nat Commun , 5 :3849 , 2014
Abstract : Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U. virens that encodes 8,426 predicted genes. The genome has ~25% repetitive sequences that have been affected by repeat-induced point mutations. Evolutionarily, U. virens is close to the entomopathogenic Metarhizium spp., suggesting potential host jumping across kingdoms. U. virens possesses reduced gene inventories for polysaccharide degradation, nutrient uptake and secondary metabolism, which may result from adaptations to the specific floret infection and biotrophic lifestyles. Consistent with their potential roles in pathogenicity, genes for secreted proteins and secondary metabolism and the pathogen-host interaction database genes are highly enriched in the transcriptome during early infection. We further show that 18 candidate effectors can suppress plant hypersensitive responses. Together, our analyses offer new insights into molecular mechanisms of evolution, biotrophy and pathogenesis of U. virens.
ESTHER : Zhang_2014_Nat.Commun_5_3849
PubMedSearch : Zhang_2014_Nat.Commun_5_3849
PubMedID: 24846013
Gene_locus related to this paper: ustvr-a0a063bxn3

Title : Metabonomics evaluation of urine from rats administered with phorate under long-term and low-level exposure by ultra-performance liquid chromatography-mass spectrometry - Sun_2014_J.Appl.Toxicol_34_176
Author(s) : Sun X , Xu W , Zeng Y , Hou Y , Guo L , Zhao X , Sun C
Ref : J Appl Toxicol , 34 :176 , 2014
Abstract : The purpose of this study was to investigate the toxic effect of long-term and low-level exposure to phorate using a metabonomics approach based on ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Male Wistar rats were given phorate daily in drinking water at low doses of 0.05, 0.15 or 0.45 mg kg(-1) body weight (BW) for 24 weeks consecutively. Rats in the control group were given an equivalent volume of drinking water. Compared with the control group, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TBIL), urea nitrogen (BUN) and creatinine (CR) were increased in the middle- and high-dose groups whereas albumin (ALB) and cholinesterase (CHE) were decreased. Urine metabonomics profiles were analyzed by UPLC-MS. Compared with the control group, 12 metabolites were significantly changed in phorate-treated groups. In the negative mode, metabolite intensities of uric acid, suberic acid and citric acid were significantly decreased in the middle- and high-dose groups, whereas indoxyl sulfic acid (indican) and cholic acid were increased. In the positive mode, uric acid, creatinine, kynurenic acid and xanthurenic acid were significantly decreased in the middle- and high-dose groups, but 7-methylguanine (N(7) G) was increased. In both negative and positive modes, diethylthiophosphate (DETP) was significantly increased, which was considered as a biomarker of exposure to phorate. In conclusion, long-term and low-level exposure to phorate can cause disturbances in energy-related metabolism, liver and kidney function, the antioxidant system, and DNA damage. Moreover, more information can be provided on the evaluation of toxicity of phorate using metabonomics combined with clinical chemistry. Copyright (c) 2012 John Wiley & Sons, Ltd.
ESTHER : Sun_2014_J.Appl.Toxicol_34_176
PubMedSearch : Sun_2014_J.Appl.Toxicol_34_176
PubMedID: 23280859

Title : Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history - Zhou_2014_Nat.Genet_46_1303
Author(s) : Zhou X , Wang B , Pan Q , Zhang J , Kumar S , Sun X , Liu Z , Pan H , Lin Y , Liu G , Zhan W , Li M , Ren B , Ma X , Ruan H , Cheng C , Wang D , Shi F , Hui Y , Tao Y , Zhang C , Zhu P , Xiang Z , Jiang W , Chang J , Wang H , Cao Z , Jiang Z , Li B , Yang G , Roos C , Garber PA , Bruford MW , Li R
Ref : Nat Genet , 46 :1303 , 2014
Abstract : Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
ESTHER : Zhou_2014_Nat.Genet_46_1303
PubMedSearch : Zhou_2014_Nat.Genet_46_1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7 , rhibe-ACHE , rhibe-a0a2k6k3y7 , rhibe-a0a2k6k493 , rhibe-a0a2k6lev4 , rhibe-a0a2k6lfa5 , rhibe-a0a2k6m6k8 , rhiro-a0a2k6p1u8 , rhiro-a0a2k6q1t8 , rhiro-a0a2k6q1w3 , rhibe-a0a2k6n5t9 , rhibe-a0a2k6ju46 , rhibe-a0a2k6kt48 , rhibe-a0a2k6llm5 , rhibe-a0a2k6lnt5 , rhiro-a0a2k6qzp6 , rhiro-a0a2k6q4a6 , rhibe-a0a2k6kn93 , rhibe-a0a2k6lm22 , rhibe-a0a2k6jwp8 , rhiro-a0a2k6qun2 , rhiro-a0a2k6nj56 , rhiro-a0a2k6n885 , rhiro-a0a2k6nnj4 , rhiro-a0a2k6n7n5 , rhibe-a0a2k6jvz4 , rhiro-a0a2k6nfk9 , rhiro-a0a2k6qjv0 , rhibe-a0a2k6jn19 , rhibe-a0a2k6k333 , rhibe-a0a2k6mff5

Title : Valeriana amurensis improves Amyloid-beta 1-42 induced cognitive deficit by enhancing cerebral cholinergic function and protecting the brain neurons from apoptosis in mice - Wang_2014_J.Ethnopharmacol_153_318
Author(s) : Wang Q , Wang C , Shu Z , Chan K , Huang S , Li Y , Xiao Y , Wu L , Kuang H , Sun X
Ref : J Ethnopharmacol , 153 :318 , 2014
Abstract : ETHNOPHAMACOLOGICAL RELEVANCE: Valeriana amurensis, a perennial medicinal herb, has been widely used as anxiolytic, antidepressant, antispasmodic, and sedative in traditional Chinese medicines (TCMs). Moreover, it has been used to treat dementia in Mongolia preparations. In our previous study, we reported that AD-effective fraction of Valeriana amurensis (AD-EFV) has protective effect on Abeta-induced toxicity in PC12 cells. Up to now, however, the therapeutic effect of Valeriana amurensis on Alzheimer disease (AD) has not been explored. This study was designed to determine whether the AD-EFV could improve the Amyloid-beta (Abeta)-induced cognitive deficit and to explore the mechanism of AD-EFV improves cognitive deficit in intact animals. MATERIALS AND
METHODS: The constituents of AD-EFV were isolated with silica gel, octadecyl silica gel (ODS) column chromatography (CC) and preparative HPLC. The structures of compounds were determined by detailed NMR and ESI-MS data analyses. AD mice model was established by injecting Abeta1-42 (1muL, 200mumol) into the bilateral ventricle. Cognitive performance was evaluated by the Morris water maze (MWM) test. The level of cerebral acetylcholine (ACh), the activities of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) were investigated using Enzyme-linked immunoassay (ELISA) kits. Brain sections were processed and neuronal apoptosis in hippocampus were evaluated by Hematoxylin and Eosin (HE), Nissl, and Tunel stainings. The analyses of p-ERK/ERK and Bcl-2/Bax protein expression by western blot assay were used to explore the anti-neuronal apoptosis mechanism of AD-EFV.
RESULTS: Seventeen compounds (15 lignans and two iridoids) were isolated from AD-EFV. A significant improvement in cognitive function was observed in administrated AD-EFV AD model mice. AD-EFV increased the ACh level by enhancing the ChAT activity but has no effect on AChE activity in the cerebral cortex and hippocampus in mice. Moreover, the histological injury in hippocampus CA1 induced by Abeta1-42 was inhibited following administration of the AD-EFV. As well as the expression ratios of Bcl-2 to Bax and p-ERK to ERK were increased significantly in the mice which were administrated AD-EFV. CONCLUSION: These findings suggest that AD-EFV could ameliorate Abeta induced cognitive dysfunction through two underlying mechanisms: AD-EFV enhances the cerebral cholinergic function by increasing the secretion of ACh and enhancing the ChAT activity, and AD-EFV protects the brain neurons from Abeta induced apoptosis via activating the p-ERK and Bcl-2 signaling and suppressing the Bax pathways. Besides, the main constituents of AD-EFV are lignans which might be responsible for the AD-activity of Valeriana amurensis.
ESTHER : Wang_2014_J.Ethnopharmacol_153_318
PubMedSearch : Wang_2014_J.Ethnopharmacol_153_318
PubMedID: 24269774

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 : Destruction of white matter integrity in patients with mild cognitive impairment and Alzheimer disease - Sun_2014_J.Investig.Med_62_927
Author(s) : Sun X , Salat D , Upchurch K , Deason R , Kowall N , Budson A
Ref : J Investig Med , 62 :927 , 2014
Abstract : BACKGROUND: Accumulating evidence shows that gradual loss of white matter integrity plays an important role in the development of Alzheimer disease (AD). OBJECTIVE: The aim of this research was to study the microstructural integrity of white matter in AD in vivo.
METHODS: Global fractional anisotropy, global axial diffusivity (AxD), and global radial diffusivity (RD) were analyzed in subjects with normal controls (NC), mild cognitive impairment (MCI), and AD using Alzheimer's Disease Neuroimaging Initiative data (total N = 210). We further compared specific white matter tracts among the 3 groups.
RESULTS: Compared with the NC group, the MCI group had significantly increased global AxD and global RD. Compared with the NC and MCI groups, the AD group had significantly decreased global fractional anisotropy, increased global AxD, and increased global RD. With regard to specific white matter tracts, in the MCI group, we found increased AxD and increased RD in the external capsule, part of the lateral cholinergic pathway, in addition to the tracts connecting the limbic regions, predominantly in the left hemisphere. In the AD group, white matter abnormalities were widespread, including in the external capsule (cholinergic pathway) and limbic region tracts as well as tracts connecting anterior to posterior regions bilaterally.
CONCLUSIONS: The radiographic manifestation of damaged white matter microstructural integrity in the cholinergic pathway in MCI patients may provide a rational basis for the use of cholinesterase inhibitor drugs in the MCI stage of AD.
ESTHER : Sun_2014_J.Investig.Med_62_927
PubMedSearch : Sun_2014_J.Investig.Med_62_927
PubMedID: 25046178

Title : Determination of tacrine-6-ferulic acid in rat plasma by LC-MS\/MS and its application to pharmacokinetics study - Sun_2014_Biomed.Chromatogr_28_1352
Author(s) : Sun X , Zhang P , Pi R , Zhou Y , Deng X , Xie Z , Liao Q
Ref : Biomedical Chromatography , 28 :1352 , 2014
Abstract : Tacrine, as a drug for treating Alzheimer's disease (AD), has low efficacy owing to its single function and serious side effects. However, tacrine-6-ferulic acid (T6FA), the dimer which added ferulic acid to tacrine, has been found to be a promising multifunctional drug candidate for AD and much more potent and selective on acetylcholinesterase (AChE) than tacrine. The aim of the present work was to develop and validate an LC-MS/MS method with electrospray ionization for the quantification of T6FA in rat plasma using tacrine-3-ferulic acid (T3FA) as internal standard and to examine its application for pharmacokinetic study in rats. Following a single liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved at 25 degrees C on a BDS Hypersil C18 column with a mobile phase composed of 1% formic acid and methonal (30:70, v/v) at a flow rate of 0.2 mL/min. Quantification was achieved by monitoring the selected ions at m/z 474.2 --> 298.1 for T6FA and m/z 432.2 --> 199.0 for T3FA. The method was validated to be rapid, specific, accurate and precise over the concentration range of 0.5-1000.0 ng/mL in rat samples. Furthermore, it was successfully applied for the pharmacokinetic measurement of T6FA with an oral administration at 40 mg/kg to rats. Copyright (c) 2014 John Wiley & Sons, Ltd.
ESTHER : Sun_2014_Biomed.Chromatogr_28_1352
PubMedSearch : Sun_2014_Biomed.Chromatogr_28_1352
PubMedID: 24706520

Title : Evidences for B6C3-Tg (APPswe\/PSEN1dE9) Double-Transgenic Mice Between 3 and 10 Months as an Age-Related Alzheimer's Disease Model - Zhong_2014_J.Mol.Neurosci_53_370
Author(s) : Zhong Z , Yang L , Wu X , Huang W , Yan J , Liu S , Sun X , Liu K , Lin H , Kuang S , Tang X
Ref : Journal of Molecular Neuroscience , 53 :370 , 2014
Abstract : Transgenic mouse has shown great advantages in the study of Alzheimer's disease (AD) and drug screening as AD develops rapidly resent years, while more detail information of these transgenic mice and experience of application are needed. To obtain the basic background information of the B6C3-Tg (APPswe/PSEN1dE9) double-transgenic mouse, which was reported with early onset AD, three- to ten-month-old B6C3-Tg AD mice and normal C57BL/6 mice were selected randomly to test the ability of learning memory by Morris water maze, the brain acetylcholinesterase (AChE) activity by AChE kit, and beta amyloid protein level by immunohistochemistry staining. Compared with the control group, the escape latency time of B6C3-Tg AD mice at 9 and 10 months of age is significantly longer (P < 0.05) in Morris maze test, and the activity of brain AChE is higher. beta-Amyloid plaques were observed at 3 months of age and developed rapidly. Statistical analysis showed a positive correlation between the area of these plaques and the ages of B6C3-Tg AD mouse (y = 0.0355e(0.5557x), R = 0.9557). The model's behavior is conformed to simulate behaviors of human Alzheimer's disease at the early stage and may provide detail background information a new choice when transgenic mice are needed in the research of AD.
ESTHER : Zhong_2014_J.Mol.Neurosci_53_370
PubMedSearch : Zhong_2014_J.Mol.Neurosci_53_370
PubMedID: 24362678

Title : Identification of differentially expressed proteins related to organophosphorus-induced delayed neuropathy in the brains of hens - Jiang_2014_J.Appl.Toxicol_34_1352
Author(s) : Jiang Y , Liu X , Li S , Zhang Y , Piao F , Sun X
Ref : J Appl Toxicol , 34 :1352 , 2014
Abstract : Some organophosphorus compounds can cause organophosphate-induced delayed neuropathy (OPIDN). Incidents have been documented for decades, however, little is known about which proteins contribute to the initiation, progression and development of OPIDN. In this study, 51 hens were divided into three groups. The tri-ortho-cresyl-phosphate (TOCP) group was treated with 1000 mg kg(-1) TOCP whereas the control group was treated with an equivalent volume of vehicle. The PMSF + TOCP group was treated subcutaneously with 40 mg kg(-1) phenylmethylsulfonyl fluoride (PMSF), followed by 1000 mg kg(-1) TOCP 24 h later. Proteins in the brains of hens were separated by two-dimensional polyacrylamide gel electrophoresis on day 5 after TOCP administration. Mass spectrometry identified eight differentially expressed proteins. Among these proteins, downregulated expression of glutamine synthetase (GS) in the brains of hens after TOCP treatment was further confirmed by real time RT-PCR and ELISA. Moreover, the brains of hens exposed to TOCP exhibited increased levels of glutamate (Glu) and cytosolic calcium concentration ([Ca(2+) ]i ), and a decreased level of glutamine (Gln). However, there were no significant differences in GS expression or levels of Glu, Gln, and [Ca(2+) ]i in the brains of hens among the groups on day 21 after TOCP administration. These results indicate that TOCP exposure downregulates GS expression in the brains of hens, and that downregulation of GS is accompanied by increased levels of Glu and [Ca(2+) ]i in the early stage after TOCP administration. It is also suggested that the downregulated expression of GS might be associated with OPIDN through the disruption of homeostasis of the Glu-Gln cycle and [Ca(2+) ]i . Copyright (c) 2013 John Wiley & Sons, Ltd.
ESTHER : Jiang_2014_J.Appl.Toxicol_34_1352
PubMedSearch : Jiang_2014_J.Appl.Toxicol_34_1352
PubMedID: 24338829

Title : Acetylcholinesterase-catalyzed hydrolysis allows ultrasensitive detection of pathogens with the naked eye - Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
Author(s) : Liu D , Wang Z , Jin A , Huang X , Sun X , Wang F , Yan Q , Ge S , Xia N , Niu G , Liu G , Hight Walker AR , Chen X
Ref : Angew Chem Int Ed Engl , 52 :14065 , 2013
Abstract : Seeing is believing: A rapid diagnostic platform for pathogen detection based on the acetylcholinesterase-catalyzed hydrolysis reaction has been developed. Owing to signal amplification strategies, the sensitivity of this assay is comparable to that of PCR. In addition, the readout of the assay is based on solution color change, which can be easily observed by the naked eye alone.
ESTHER : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedSearch : Liu_2013_Angew.Chem.Int.Ed.Engl_52_14065
PubMedID: 24155243

Title : Comparative analysis of bat genomes provides insight into the evolution of flight and immunity - Zhang_2013_Science_339_456
Author(s) : Zhang G , Cowled C , Shi Z , Huang Z , Bishop-Lilly KA , Fang X , Wynne JW , Xiong Z , Baker ML , Zhao W , Tachedjian M , Zhu Y , Zhou P , Jiang X , Ng J , Yang L , Wu L , Xiao J , Feng Y , Chen Y , Sun X , Zhang Y , Marsh GA , Crameri G , Broder CC , Frey KG , Wang LF , Wang J
Ref : Science , 339 :456 , 2013
Abstract : Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world's most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related species, fruit bat Pteropus alecto and insectivorous bat Myotis davidii. We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor kappaB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.
ESTHER : Zhang_2013_Science_339_456
PubMedSearch : Zhang_2013_Science_339_456
PubMedID: 23258410
Gene_locus related to this paper: myods-l5mij9 , pteal-l5k8f5 , pteal-l5kjy3 , pteal-l5k6f0 , pteal-l5kxe2 , myods-l5m0a8 , myods-l5lvb4 , pteal-l5k7h7 , myods-l5lm42 , pteal-l5jz73 , pteal-l5kvh1.1 , pteal-l5kvh1.2 , pteal-l5kw21 , myods-l5lug5 , pteal-l5kv18 , myods-l5lbf8 , pteal-l5kwh0 , myods-l5lfh8 , myods-l5lfr7 , myods-l5lu20 , pteal-l5jzi4 , pteal-l5kib7 , pteal-l5kyq5 , myods-l5lf36 , myods-l5lnh7 , myods-l5lu25 , pteal-l5k0u1 , pteal-l5k2g6 , pteal-l5l3r3 , myods-l5mdx5 , pteal-l5k220 , myolu-g1pdp2 , pteal-l5l5n3 , pteal-l5k1s7 , myolu-g1nth4 , pteal-l5l7w7 , pteal-l5l537 , myods-l5lwe4 , pteal-l5klr9 , pteal-l5k670 , pteal-l5jr94 , pteal-l5kvb4 , myolu-g1q4e3 , pteal-l5jrl1

Title : Xenobiotic metabolism of plant secondary compounds in the English grain aphid, Sitobion avenae (F.) (Hemiptera: Aphididae) - Zhang_2013_Pestic.Biochem.Physiol_107_44
Author(s) : Zhang M , Fang T , Pu G , Sun X , Zhou X , Cai Q
Ref : Pestic Biochem Physiol , 107 :44 , 2013
Abstract : Plant secondary compounds have been documented to be deleterious to insects and other herbivores in diverse ways. In this study, the effect of catechol (phenolics), gramine (alkaloid) and L-ornithine-HCI (non-protein amino acid) on the activities of xenobiotic metabolizing enzymes in English grain aphid, Sitobion avenae, was evaluated. Phase I enzymes investigated in this study included carboxylesterase (CarE), and oxidoreductase, whereas Phase II enzymes were represented by glutathione S-transferase (GST). In general, CarE and GST activities in S. avenae were positively correlated with the concentration of plant secondary compounds in artificial diets. Oxidoreductase activity, however, displayed a different profile. Specifically, peroxidase (POD) and polyphenol oxidase (PPO) activities in S. avenae were positively correlated with concentrations of dietary catechol and gramine, respectively, whereas catalase (CAT) activity was significantly suppressed by the higher concentration of catechol, gramine and L-ornithine-HCl. These combined results suggest that CarE and GST in S. avenae are key enzymes to breakdown a broad spectrum of plant secondary compounds, whereas oxidoreductase, including PPO and POD, degrades specific groups of plant secondary compounds.
ESTHER : Zhang_2013_Pestic.Biochem.Physiol_107_44
PubMedSearch : Zhang_2013_Pestic.Biochem.Physiol_107_44
PubMedID: 25149234

Title : A novel and highly sensitive acetyl-cholinesterase biosensor modified with hollow gold nanospheres - Sun_2013_Bioprocess.Biosyst.Eng_36_273
Author(s) : Sun X , Zhai C , Wang X
Ref : Bioprocess Biosyst Eng , 36 :273 , 2013
Abstract : In this work, a highly sensitive acetylcholinesterase (AChE) inhibition-based amperometric biosensor has been developed. Firstly, a glassy carbon electrode (GCE) was modified with chitosan (Chits). Then, hollow gold nanospheres (HGNs) were absorbed onto the surface of chitosan based on the strong affinity through electrostatic adsorption. After that, L-cysteine (L-cys) was assembled on HGNs through Au-S bond. The hollow gold nanospheres were prepared by using Co nanoparticles as sacrificial templates and characterized by scanning electron microscopy, transmission electron microscopy and ultraviolet spectra, respectively. Finally, AChE was immobilized with covalent binding via -COOH groups of L-cysteine onto the modified GCE. The AChE biosensor fabrication process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy methods with the use of ferricyanide as an electrochemical redox indicator. Under optimum conditions, the inhibition rates of pesticides were proportional to their concentrations in the range of 0.1-150 and 0.1-200 mug L for chlorpyrifos and carbofuran, respectively, the detection limits were 0.06 mug L for chlorpyrifos and 0.08 mug L for carbofuran. Moreover, the biosensor exhibited a good stability and reproducibility and was suitable for trace detection of pesticide residues in vegetables and fruits.
ESTHER : Sun_2013_Bioprocess.Biosyst.Eng_36_273
PubMedSearch : Sun_2013_Bioprocess.Biosyst.Eng_36_273
PubMedID: 22829062

Title : A New Anti-acetylcholinesterase alpha-Pyrone Meroterpene, Arigsugacin I, from Mangrove Endophytic Fungus Penicillium sp. sk5GW1L of Kandelia candel - Huang_2013_Planta.Med_79_1572
Author(s) : Huang X , Sun X , Ding B , Lin M , Liu L , Huang H , She Z
Ref : Planta Med , 79 :1572 , 2013
Abstract : Arigsugacin I (1), a new alpha-pyrone meroterpene, along with two known compounds, arigsugacins F (2) and territrem B (3), were isolated from the mangrove endophytic fungus Penicillium sp. sk5GW1L from Kandelia candel. Their structures were identified through mass spectrometry and NMR experiments, and the absolute configuration of compound 1 was further confirmed by low-temperature (100 K) single crystal X-ray diffraction with Cu Kalpha radiation. The absolute configuration of compound 2 was first reported by using X-ray copper radiation. Compounds 1-3 showed inhibitory activities against acetylcholinesterase with IC50 values of 0.64 +/- 0.08 microM, 0.37 +/- 0.11 microM, and 7.03 +/- 0.20 nM, respectively.
ESTHER : Huang_2013_Planta.Med_79_1572
PubMedSearch : Huang_2013_Planta.Med_79_1572
PubMedID: 24081685

Title : Metabonomics analysis of urine and plasma from rats given long-term and low-dose dimethoate by ultra-performance liquid chromatography-mass spectrometry - Feng_2012_Chem.Biol.Interact_199_143
Author(s) : Feng Z , Sun X , Yang J , Hao D , Du L , Wang H , Xu W , Zhao X , Sun C
Ref : Chemico-Biological Interactions , 199 :143 , 2012
Abstract : This study assessed the effects of long-term low-dose dimethoate administration to rats by ultra-performance liquid chromatography-mass spectrometry UPLC-MS Dimethoate 0.04 0.12 and 0.36mg/kg body weight/day was administered daily to male Wistar rats through their drinking water for 24weeks Significant changes in serum clinical chemistry were observed in the middle and high-dose groups UPLC-MS revealed evident separate clustering among the different dose groups using global metabolic profiling by supervised partial least squares-discriminant analysis Metabonomic analysis showed alterations in a number of metabolites 12 from urine and 13 from plasma such as l-tyrosine dimethylthiophosphate DMTP dimethyldithiophosphate DMDTP citric acid uric acid suberic acid glycylproline allantoin isovalerylglutamic acid and kinds of lipids The results suggest that long-term low-dose exposure to dimethoate can cause disturbances in liver function antioxidant and nervous systems as well as the metabolisms of lipids glucose fatty acids amino acids and collagen in rats DMTP and DMDTP which had the most significant changes among all other studied biomarkers were considered as early sensitive biomarkers of exposure to dimethoate The other aforementioned proposed toxicity biomarkers in metabonomic analysis may be useful in the risk assessment of the toxic effects of dimethoate Metabonomics as a systems toxicology approach was able to provide comprehensive information on the dynamic process of dimethoate induced toxicity In addition the results indicate that metabonomic approach could detect systemic toxic effects at an earlier stage compared to clinical chemistry The combination of metabonomics and clinical chemistry made the toxicity of dimethoate on rats more comprehensive.
ESTHER : Feng_2012_Chem.Biol.Interact_199_143
PubMedSearch : Feng_2012_Chem.Biol.Interact_199_143
PubMedID: 22884955

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Acetylcholinesterase biosensor based on chitosan\/prussian blue\/multiwall carbon nanotubes\/hollow gold nanospheres nanocomposite film by one-step electrodeposition - Zhai_2012_Biosens.Bioelectron_42C_124
Author(s) : Zhai C , Sun X , Zhao W , Gong Z , Wang X
Ref : Biosensors & Bioelectronics , 42C :124 , 2012
Abstract : In this paper, chitosan-prussian blue-multiwall carbon nanotubes-hollow gold nanospheres (Chit-PB-MWNTs-HGNs) film was fabricated onto the gold electrode surface by one-step electrodeposition method; and then acetylcholinesterase (AChE) and Nafion were modified onto the film to prepare an AChE biosensor. Incorporating MWNTs and HGNs into Chit-PB hybrid film promoted electron transfer reaction, enhanced the electrochemical response and improved the microarchitecture of the electrode surface. The morphologies and electrochemistry properties of the composite were investigated by using scanning electron microscopy, transmission electron microscopy, cyclic voltammetry and electrochemical impedance spectroscopy, respectively. Parameters affecting the biosensor response such as pH, enzyme loading and inhibition time were optimized. Based on the inhibition of pesticides on the AChE activity, using malathion, chlorpyrifos, monocrotophos and carbofuran as model compounds, this biosensor showed a wide range, low detection limit, good reproducibility and high stability. Moreover, AChE/Chit-PB-MWNTs-HGNs/Au biosensor can also be used for direct analysis of practical samples, which would be a new promising tool for pesticide analysis.
ESTHER : Zhai_2012_Biosens.Bioelectron_42C_124
PubMedSearch : Zhai_2012_Biosens.Bioelectron_42C_124
PubMedID: 23202341

Title : Insights from the first putative biosynthetic gene cluster for a lichen depside and depsidone - Armaleo_2011_Mycologia_103_741
Author(s) : Armaleo D , Sun X , Culberson C
Ref : Mycologia , 103 :741 , 2011
Abstract : The genes for polyketide synthases (PKSs), enzymes that assemble the carbon backbones of many secondary metabolites, often cluster with other secondary pathway genes. We describe here the first lichen PKS cluster likely to be implicated in the biosynthesis of a depside and a depsidone, compounds in a class almost exclusively produced by lichen fungi (mycobionts). With degenerate PCR with primers biased toward presumed PKS genes for depsides and depsidones we identified among the many PKS genes in Cladonia grayi four (CgrPKS13-16) potentially responsible for grayanic acid (GRA), the orcinol depsidone characteristic of this lichen. To single out a likely GRA PKS we compared mRNA and GRA induction in mycobiont cultures using the four candidate PKS genes plus three controls; only CgrPKS16 expression closely matched GRA induction. CgrPKS16 protein domains were compatible with orcinol depside biosynthesis. Phylogenetically CgrPKS16 fell in a new subclade of fungal PKSs uniquely producing orcinol compounds. In the C. grayi genome CgrPKS16 clustered with a CytP450 and an o-methyltransferase gene, appropriately matching the three compounds in the GRA pathway. Induction, domain organization, phylogeny and cluster pathway correspondence independently indicated that the CgrPKS16 cluster is most likely responsible for GRA biosynthesis. Specifically we propose that (i) a single PKS synthesizes two aromatic rings and links them into a depside, (ii) the depside to depsidone transition requires only a cytochrome P450 and (iii) lichen compounds evolved early in the radiation of filamentous fungi.
ESTHER : Armaleo_2011_Mycologia_103_741
PubMedSearch : Armaleo_2011_Mycologia_103_741
PubMedID: 21289108
Gene_locus related to this paper: clagr-gra1

Title : Increased fat mass and insulin resistance in mice lacking pancreatic lipase-related protein 1 - Ren_2011_J.Nutr.Biochem_22_691
Author(s) : Ren J , Chen Z , Zhang W , Li L , Sun R , Deng C , Fei Z , Sheng Z , Wang L , Sun X , Wang Z , Fei J
Ref : J Nutr Biochem , 22 :691 , 2011
Abstract : Pancreatic triglyceride lipase (PTL) and its cofactor, colipase, are required for efficient dietary triglyceride digestion. In addition to PTL, pancreatic acinar cells synthesize two pancreatic lipase-related proteins (PLRP1 and PLRP2), which have a high degree of sequence and structural homology with PTL. The lipase activity of PLRP2 has been confirmed, whereas no known triglyceride lipase activity has been detected with PLRP1 up to now. To explore the biological functions of PLRP1 in vivo, we generated Plrp1 knockout (KO) mice in our laboratory. Here we show that the Plrp1 KO mice displayed mature-onset obesity with increased fat mass, impaired glucose clearance and the resultant insulin resistance. When fed on high-fat (HF) diet, the Plrp1 KO mice exhibited an increased weight gain, fat mass and severe insulin resistance compared with wild-type mice. Pancreatic juice extracted from Plrp1 KO mice had greater ability to hydrolyze triglyceride than that from the wild-type littermates. We propose that PLRP1 may function as a metabolic inhibitor in vivo of PLT-colipase-mediated dietary triglyceride digestion and provides potential anti-obesity targets for developing new drugs.
ESTHER : Ren_2011_J.Nutr.Biochem_22_691
PubMedSearch : Ren_2011_J.Nutr.Biochem_22_691
PubMedID: 21115337
Gene_locus related to this paper: human-PNLIPRP1 , mouse-1plrp

Title : Genome sequencing reveals insights into physiology and longevity of the naked mole rat - Kim_2011_Nature_479_223
Author(s) : Kim EB , Fang X , Fushan AA , Huang Z , Lobanov AV , Han L , Marino SM , Sun X , Turanov AA , Yang P , Yim SH , Zhao X , Kasaikina MV , Stoletzki N , Peng C , Polak P , Xiong Z , Kiezun A , Zhu Y , Chen Y , Kryukov GV , Zhang Q , Peshkin L , Yang L , Bronson RT , Buffenstein R , Wang B , Han C , Li Q , Chen L , Zhao W , Sunyaev SR , Park TJ , Zhang G , Wang J , Gladyshev VN
Ref : Nature , 479 :223 , 2011
Abstract : The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
ESTHER : Kim_2011_Nature_479_223
PubMedSearch : Kim_2011_Nature_479_223
PubMedID: 21993625
Gene_locus related to this paper: hetga-g5amh8 , hetga-g5an68 , hetga-g5anw7 , hetga-g5as32 , hetga-g5atg6 , hetga-g5b5b7 , hetga-g5b9m6 , hetga-g5bdh8 , hetga-g5bmv3 , hetga-g5bp66 , hetga-g5bp67 , hetga-g5bp68 , hetga-g5bpp3 , hetga-g5bsd4 , hetga-g5bul0 , hetga-g5bw29 , hetga-g5bze3 , hetga-g5c6q5 , hetga-g5bfw4 , hetga-g5b832 , hetga-g5c6q8 , hetga-g5bj87 , hetga-a0a0p6jix7 , hetga-g5c108 , hetga-g5c109 , hetga-g5c110 , hetga-g5arh0 , hetga-g5aua1 , hetga-g5are8 , hetga-g5ax31 , hetga-a0a0p6jud6 , hetga-g5b7v3 , hetga-a0a0p6jw61 , hetga-a0a0p6jdl4 , hetga-g5bg83 , hetga-g5bcu5 , hetga-g5bvp0 , hetga-g5b8m7 , hetga-g5b709 , hetga-g5bt99 , hetga-g5b4q4

Title : A sensitive and regenerable biosensor for organophosphate pesticide based on self-assembled multilayer film with CdTe as fluorescence probe - Sun_2011_Luminescence_26_616
Author(s) : Sun X , Liu B , Xia K
Ref : Luminescence , 26 :616 , 2011
Abstract : A fluorescence biosensor for organophosphorus pesticides was developed. A pH indicator, CdTe quantum dots, were used as an optical transducer of the inhibition of enzyme by analyte. Through the intervening agency of chitosan, the recognition elements (acetylcholinesterase and CdTe) were immobilized onto the surface of quartz by electrostatic attraction to form a self-assembled multilayer film. In the absence of pesticide, acetylcholine was biocatalytically hydrolysed to yield acetic acid and choline. The released acid resulted in pH decrease, which was sensed by the immobilized pH indicator (CdTe). In the presence of pesticide, the action of acetylcholine was reduced; the fluorescence intensity of the film changed and was related to the concentration of pesticide. This multilayer film could be used as the biosensor for monocrotophos, with a detection limit of 3.20 x 10(-8) mol/L; the sensitivity was 100 times higher than that of CdTe in aqueous solution. The sensor was easily regenerated, and had good stability and selectivity for organophosphorus pesticides.
ESTHER : Sun_2011_Luminescence_26_616
PubMedSearch : Sun_2011_Luminescence_26_616
PubMedID: 21567885

Title : Complete genome of Pseudomonas mendocina NK-01, which synthesizes medium-chain-length polyhydroxyalkanoates and alginate oligosaccharides - Guo_2011_J.Bacteriol_193_3413
Author(s) : Guo W , Wang Y , Song C , Yang C , Li Q , Li B , Su W , Sun X , Song D , Yang X , Wang S
Ref : Journal of Bacteriology , 193 :3413 , 2011
Abstract : Pseudomonas mendocina NK-01 can synthesize medium-chain-length polyhydroxyalkanoate (PHA(MCL)) and alginate oligosaccharides (AO) simultaneously from glucose under conditions of limited nitrogen. Here, we report the complete sequence of the 5.4-Mbp genome of Pseudomonas mendocina NK-01, which was isolated from farmland soil in Tianjin, China.
ESTHER : Guo_2011_J.Bacteriol_193_3413
PubMedSearch : Guo_2011_J.Bacteriol_193_3413
PubMedID: 21551299
Gene_locus related to this paper: pseme-PHAZ , psemn-f4dpi6 , psemn-f4dyl0 , psemn-f4dqg5 , pseme-a0a081x852 , psemn-f4dv64

Title : Metabolomic analysis of the toxic effects of chronic exposure to low-level dichlorvos on rats using ultra-performance liquid chromatography-mass spectrometry - Yang_2011_Toxicol.Lett_206_306
Author(s) : Yang J , Sun X , Feng Z , Hao D , Wang M , Zhao X , Sun C
Ref : Toxicol Lett , 206 :306 , 2011
Abstract : The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6 mg/kg body weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography-mass spectrometry (UPLC-MS). Dimethyl phosphate (DMP), which was exclusively detected in the treated groups, can be an early, sensitive biomarker for DDVP exposure. Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid, suberic acid, gulonic acid, urea, creatinine, and uric acid. These results suggest that chronic exposure to low-level DDVP can cause a disturbance in carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore, an analysis of the metabolic profiles can contribute to the understanding of the adverse effects of long-term exposure to low doses of DDVP.
ESTHER : Yang_2011_Toxicol.Lett_206_306
PubMedSearch : Yang_2011_Toxicol.Lett_206_306
PubMedID: 21889581

Title : Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression - Wang_2010_Mol.Biol.Cell_21_1991
Author(s) : Wang H , Wei E , Quiroga AD , Sun X , Touret N , Lehner R
Ref : Mol Biology of the cell , 21 :1991 , 2010
Abstract : Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes.
ESTHER : Wang_2010_Mol.Biol.Cell_21_1991
PubMedSearch : Wang_2010_Mol.Biol.Cell_21_1991
PubMedID: 20410140

Title : Acetylcholinesterase biosensor based on Prussian blue-modified electrode for detecting organophosphorous pesticides - Sun_2010_Biosens.Bioelectron_25_2611
Author(s) : Sun X , Wang X
Ref : Biosensors & Bioelectronics , 25 :2611 , 2010
Abstract : In this study, a novel acetylcholinesterase (AChE) biosensor was developed based on dual-layer membranes (chitosan membrane and prussian blue membrane) modifying glassy carbon electrode (GCE). A chitosan membrane was used for immobilizing AChE through glutaraldehyde cross-linking attachment to recognize pesticides selectively. A prussian blue (PB) membrane was electrodeposited on the surface of GCE to enhance electron transfer. Before the detection, the chitosan enzyme membrane was quickly fixed on the surface of PB/GCE with O-ring to prepare an amperometric AChE-PB/GCE sensor for organophosphorus (OP) pesticides. The electrochemical behaviour of AChE-PB/GCE was studied, and the results showed that the chitosan membrane as carrier can absorb a large amount of enzyme, and PB has a significant synergistic effect towards enzymatic catalysis. As a result of these two important enhancement factors, the proposed biosensor exhibited extreme sensitivity to OP pesticides compared to the other kinds of AChE biosensor. The influences of phosphate buffer pH, substrate concentration, incubation time of pesticide on the response of the fabricated biosensor were investigated. Under optimum conditions, the inhibition rates of these pesticides were proportional to their concentrations in the range of 0.01-10 microg l(-1), 0.05-10 microg l(-1), 0.03-5 microg l(-1), and 0.05-10 microg l(-1), respectively. The detection limits were found to be 2.5 ng l(-1) for dichlorvos, 15 ng l(-1) for omethoate, 5 ng l(-1) for trichlorfon and 10 ng l(-1) for phoxim. Moreover, the biosensor exhibited good reproducibility and stability, and it was suitable for trace detection of OP pesticide residue.
ESTHER : Sun_2010_Biosens.Bioelectron_25_2611
PubMedSearch : Sun_2010_Biosens.Bioelectron_25_2611
PubMedID: 20466535

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 : [Effects of tumor necrosis factor-alpha induced insulin resistance on adipose triglyceride lipase in mice] - Cheng_2008_Zhonghua.Yi.Xue.Za.Zhi_88_2417
Author(s) : Cheng YL , Li L , Yang GY , Shi SC , Chen Y , Zhu W , Sun X
Ref : Zhonghua Yi Xue Za Zhi , 88 :2417 , 2008
Abstract : OBJECTIVE: To investigate the effects of tumor necrosis factor (TNF)-alpha induced insulin resistance (IR) on glucose and lipid metabolism and adipose triglyceride lipase (ATGL).
METHODS: Forty male C57BL/6J mice were randomly divided into 2 equal groups: TNF-alpha group with undergoing intraperitoneal injection of TNF-alpha 6 microg x kg(-1) x d(-1) for 7 days and normal control (NC) group with saline injection. Hyperinsulinemic-euglycemic clamp technique combined with 2-deoxy-[(3)H] glucose as a tracer was used on 20 mice, 10 from each group, to examine the fasting blood glucose (FBG), plasma insulin (INS), total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA). The glucose infusion rate (GIR) was recorded. Other 20 mice, 10 in each group, were killed with their adipose and/or muscle tissues taken out. RT-PCR was used to detect the mRNA expression of ATGL, hormone-sensitive lipase (HSL), carnitine palmitoyl transferase-1 (CPT-1), and peroxisome proliferator activated receptor-gamma (PPARgamma). Western blotting was used to measure the protein expression of ATGL. Muscle glucose uptake (MGU) was measured.
RESULTS: After TNF-alpha treatment, the FBG, plasma INS, and FFA were significantly elevated in the TNF group compared with the NC group (all P < 0.05). During the steady-state of clamp test, the plasma INS level of the TNF group was (341.7 +/- 17.7) mU/L, significantly higher than that of the NC group [(84.7 +/- 5.5) mU/L, P < 0.01]. The FFA level of the TNF group was (0.82 +/- 0.03) mmol/L, significantly higher than that of the NC group [(0.43 +/- 0.07) mmol/L, P < 0.01]. The GIR of the TNF group was (39.1 +/- 2.3) mg x kg(-1)x min(-1), significantly lower than that of the NC group [(54.2 +/- 2.2) mg x kg(-1) x min(-1), P < 0.01]. The MGU level of the TNF group was (15.8 +/- 1.7) micromol.100 g(-1) x min(-1), significantly lower than that of the NC group [(20.9 +/- 2.5) micromol.100 g(-1) x min(-1), P < 0.01]. The ATGL mRNA expression level in adipose tissues of the TNF group was (0.85 +/- 0.09), significantly lower than that of the NC group (1.37 +/- 0.12, P < 0.01). The ATGL protein expression level of the TNF group was 0.53 +/- 0.03, significantly lower than that of the NC group (0.65 +/- 0.05, P < 0.05). The PPARgamma mRNA expression level in adipose tissues of the TNF group was 0.83 +/- 0.07, significantly lower than that of the NC group (1.07 +/- 0.07, P < 0.05).
CONCLUSION: In TNF-alpha induced insulin resistance, AGTL may be involved in the pathways of lipid metabolism.
ESTHER : Cheng_2008_Zhonghua.Yi.Xue.Za.Zhi_88_2417
PubMedSearch : Cheng_2008_Zhonghua.Yi.Xue.Za.Zhi_88_2417
PubMedID: 19087720

Title : Desensitized nicotinic receptors in brain - Wang_2005_Brain.Res.Brain.Res.Rev_48_420
Author(s) : Wang H , Sun X
Ref : Brain Research Brain Res Rev , 48 :420 , 2005
Abstract : Desensitization is an intriguing characteristic of ligand-gated channels, whereby a decrease or loss of biological response occurs following prolonged or repetitive stimulation. Nicotinic acetylcholine receptors (nAChRs), as a member of transmitter gated ion channels family, also can be desensitized by continuous or repeated exposure to agonist. Desensitization of nicotinic receptors can occur as a result of extended nicotine exposure during smoking or prolonged acetylcholine when treatment of Alzheimer's disease (AD) with cholinesterase inhibitors, or anticholinesterase agent poisoning. Studies from our lab have shown that nAChRs desensitization is not a nonfunctional state and we proposed that desensitized nAChRs could increase sensitivity of brain muscarinic receptor to its agonists. Here, we will review the regulation of nicotinic receptor desensitization and discuss the important biological function of desensitized nicotinic receptors in light of our previous studies. These studies provide the critical information for understanding the importance of nicotinic receptors desensitization in both normal physiological processing and in various disease states.
ESTHER : Wang_2005_Brain.Res.Brain.Res.Rev_48_420
PubMedSearch : Wang_2005_Brain.Res.Brain.Res.Rev_48_420
PubMedID: 15914250

Title : Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer - Wang_2005_Mol.Pharmacol_67_2173
Author(s) : Wang D , Sun X , Bohn LM , Sadee W
Ref : Molecular Pharmacology , 67 :2173 , 2005
Abstract : Opioid receptors have been shown to dimerize or oligomerize among themselves and each other, affecting their functional properties. This study used bioluminescence resonance energy transfer (BRET) between the mu, delta, and kappa opioid receptors to study opioid receptor aggregation in transfected human embryonic kidney 293 cells. Titration of receptor levels indicated that all three opioid receptors have a similar affinity to form homo- or hetero-oligomers in combination with any other opioid receptor type. In contrast, none of the opioid receptors formed detectable oligomers with the muscarinic M2 receptor, indicating that interactions among opioid receptors are selective. The formation of opioid receptor dimers, rather than higher order oligomers, is supported by binding kinetics in competition experiments between labeled and unlabeled receptors. Opioid receptor dimerization occurred at physiological temperatures upon receptor biosynthesis, before trafficking to the plasma membrane. Moreover, using BRET, coimmunoprecipitation, receptor binding, and G protein coupling, we demonstrate for the first time functional mu opioid receptor-kappa opioid receptor heterodimerization. These combined results demonstrate that opioid receptors can undergo homo- and heterodimerization, a process with potential implications for opioid physiology and pharmacology.
ESTHER : Wang_2005_Mol.Pharmacol_67_2173
PubMedSearch : Wang_2005_Mol.Pharmacol_67_2173
PubMedID: 15778451

Title : N-Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents - Sun_2001_Bioorg.Med.Chem.Lett_11_1875
Author(s) : Sun X , Zeckner DJ , Current WL , Boyer R , McMillian C , Yumibe N , Chen S
Ref : Bioorganic & Medicinal Chemistry Lett , 11 :1875 , 2001
Abstract : We describe herein the synthesis, bioconversion, antifungal activity, and preliminary toxicology evaluation of a series of N-acyloxymethyl carbamate linked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) were achieved via simple N-acylation of PSB (1) or PSC' (2) with various prodrug linkers (7-9). As expected, upon incubation with mouse and/or human plasma, many of these prodrugs (3, 5, and 6) were converted to the parent compound within a few hours. Of particular significance, two pseudomycin triprodrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidiasis without tail vein irritation being observed.
ESTHER : Sun_2001_Bioorg.Med.Chem.Lett_11_1875
PubMedSearch : Sun_2001_Bioorg.Med.Chem.Lett_11_1875
PubMedID: 11459651

Title : Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents - Sun_2001_Bioorg.Med.Chem.Lett_11_1881
Author(s) : Sun X , Zeckner D , Zhang Y , Sachs RK , Current W , Rodriguez M , Chen S
Ref : Bioorganic & Medicinal Chemistry Lett , 11 :1881 , 2001
Abstract : With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.
ESTHER : Sun_2001_Bioorg.Med.Chem.Lett_11_1881
PubMedSearch : Sun_2001_Bioorg.Med.Chem.Lett_11_1881
PubMedID: 11459652

Title : Upregulation of tyrosine hydroxylase and downregulation of choline acetyltransferase in lead-exposed PC12 cells: the role of PKC activation - Tian_2000_Toxicol.Appl.Pharmacol_167_246
Author(s) : Tian X , Sun X , Suszkiw JB
Ref : Toxicol Appl Pharmacol , 167 :246 , 2000
Abstract : The effects of lead (Pb) on the expression of tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) were compared in relation to Pb-activation of cPKC in the PC12 cells. Exposure to 0.53 microM Pb (0.1094 ppm) increased TH but reduced ChAT activity and mRNA levels. The increase of TH activity was detectable as early as 0.5 h of exposure, reached a maximum 150% of control after 2 h, and then diminished to a steady state 135% of control between 12 and 48 h of exposure. The decrease of ChAT activity was first detectable after 2 h of Pb exposure, reached a 45% reduction after 6 h, and remained stable thereafter through 48 h of exposure. PKC activity increased 200% after 2 h and then reverted to control levels by 48 h of Pb exposure. The increase of TH activity after 2 h but not 48 h of exposure exceeded that of its mRNA. PKC inhibitor Ro32-0342 suppressed TH activity increase after 2 h of Pb exposure by 80% without affecting TH mRNA. The decrease of ChAT activity correlated with the reductions in steady-state ChAT mRNA levels at 2 and 48 h of Pb exposure and Ro32-0342 had no effect on the Pb-induced decrease of either ChAT activity or mRNA. These results demonstrate that Pb alters TH and ChAT expression in PC12 cells in a reciprocal manner, i.e., upregulates the former but downregulates the latter. PKC is not involved in Pb-induced downregulation of ChAT but does mediate the early phase of Pb-induced augmentation of TH activity, presumably through postranslational modification (phosphorylation) of the enzyme. However, this effect is short-lived due to downregulation of PKC in the course of prolonged (48 h) Pb exposure. It is concluded that, in the course of prolonged exposure, both upregulation of TH and downregulation of ChAT reflect primarily the effects of Pb at the level of gene expression through mechanisms that are not related to Pb activation of PKC.
ESTHER : Tian_2000_Toxicol.Appl.Pharmacol_167_246
PubMedSearch : Tian_2000_Toxicol.Appl.Pharmacol_167_246
PubMedID: 10986016

Title : Effects of low concentrations of paraoxon on Ca(2+) mobilization in a human parotid salivary cell-line HSY - Sun_2000_Arch.Oral.Biol_45_621
Author(s) : Sun X , Liu XB , Martinez JR , Zhang GH
Ref : Archives of Oral Biology , 45 :621 , 2000
Abstract : The salivary gland is a target organ of organophosphate pesticides (OPs). Inhibition of acetylcholinesterase (AChE) by OPs leads to a decrease in acetylcholine (ACh) breakdown that results in overstimulation of muscarinic cholinergic receptors (mChR). However, OPs may also directly interact with downstream elements of the phosphoinositide (PI) signalling pathway coupled with mChR. The present study examined the effects of exposure to low concentrations of the OP paraoxon on inositol 1,4,5-trisphosphate (IP(3)) formation and Ca(2+) mobilization in response to ACh or ATP in the human parotid cell-line HSY. Exposure to 0.1 and 1 nM, but not 10 nM, paraoxon for 24 hr significantly elevated the basal cytosolic free Ca(2+) ([Ca(2+)](i)). This increase was abolished by atropine. Ca(2+) release from the IP(3)-sensitive store in response to ACh or ATP, a P2Y-nucleotide agonist, was significantly increased in cells pre-exposed to 0.1 nM paraoxon. However, IP(3) formation was inhibited by paraoxon but mChR expression was not altered. Although IP(3) receptor expression was not changed, Ca(2+) release elicited by IP(3) in streptolysin O toxin-permeabilized cells was significantly larger in cells pre-exposed to 0.1 nM paraoxon, suggesting that paraoxon increases the sensitivity of IP(3) receptors. Paraoxon exposure also induced a concentration-dependent reduction in the total capacity of intracellular Ca(2+) stores, whereas the capacity of the IP(3)-sensitive Ca(2+) store was not altered by paraoxon, as judged by discharging of the IP(3)-sensitive Ca(2+) store with thapsigargin (TG). Ca(2+) influx stimulated by ACh or ATP was also enhanced by 0.1 nM, but not 1 and 10 nM, paraoxon. On the other hand, Ca(2+) influx activated by TG was enhanced by exposure to all concentrations of paraoxon, indicating that paraoxon modulates the Ca(2+) entry pathway. These results suggest that low concentrations of paraoxon interact with elements of the PI pathway, enhancing Ca(2+) release and influx mechanisms.
ESTHER : Sun_2000_Arch.Oral.Biol_45_621
PubMedSearch : Sun_2000_Arch.Oral.Biol_45_621
PubMedID: 10869474

Title : Reduction of choline acetyltransferase mRNA in the septum of developing rat exposed to inorganic lead - Sun_1997_Neurotoxicol_18_201
Author(s) : Sun X , Tian X , Suszkiw JB
Ref : Neurotoxicology , 18 :201 , 1997
Abstract : We previously reported that perinatal exposure to low levels of lead (Pb) results in a pronounced reduction of choline acetyltransferase (ChAT) activity in the septohippocampal pathway of the rat. In the present study we employed a ChAT specific 43-base oligonucleotide hybridization probe to compare the developmental expression of ChAT mRNA and ChAT activity in the septum of normal and Pb-exposed rats. Rats were exposed to Pb via maternal administration of 0.2% solution of Pb acetate in drinking water from one week before birth through postnatal day 21 (PN21). In normal animals, the developmental changes in the ChAT mRNA and activity levels were temporally correlated and approached adult levels by PN21. In the Pb-exposed pups, ChAT mRNA and activity levels were reduced respectively by 69% and 50% at PN7, 47% and 33% at PN14, and 47% and 22% at PN21. In contrast, Pb exposure had no significant effect on either ChAT mRNA or ChAT activity in the dams. These results indicate that cholinotoxicity of Pb in the septohippocampal pathway of the rat involves developmental stage-dependent disruption of ChAT gene expression.
ESTHER : Sun_1997_Neurotoxicol_18_201
PubMedSearch : Sun_1997_Neurotoxicol_18_201
PubMedID: 9216002

Title : Reduction of vesicular acetylcholine transporter mRNA in the rat septum following lead exposure - Sun_1997_Neuroreport_8_891
Author(s) : Sun X , Tian X , Suszkiw JB
Ref : Neuroreport , 8 :891 , 1997
Abstract : We have previously observed that maternal exposure to lead (Pb) results in a reduction of levels of mRNA coding for cholineacetyltransferase (ChAT) in the septum of developing rat without affecting the dams. Here we report that Pb similarly affects the expression of vesicular acetylcholine transporter (VAChT) mRNA in the rat septum. In close agreement with the time course of ChAT mRNA expression, septal VAChT mRNA levels increased from 30% at postnatal day 7 to 78% and 100% of adult levels at days 14 and 21, respectively. Maternal exposure to 0.2% lead acetate in drinking water from gestational day 16 resulted in an approximately 30% reduction of VAChT in 7 and 21-day-old rat pups without affecting VAChT mRNA levels in the dams. These results indicate a developmental stage-dependent interference by Pb with ChAT/VAChT gene expression in the rat septum.
ESTHER : Sun_1997_Neuroreport_8_891
PubMedSearch : Sun_1997_Neuroreport_8_891
PubMedID: 9141059

Title : Developmental age-dependent upregulation of choline acetyltransferase and vesicular acetylcholine transporter mRNA expression in neonatal rat septum by nerve growth factor - Tian_1996_Neurosci.Lett_209_134
Author(s) : Tian X , Sun X , Suszkiw JB
Ref : Neuroscience Letters , 209 :134 , 1996
Abstract : We examined the effect of intraventricular injection of nerve growth factor (NGF) on the choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT) mRNA expression in the septa of neonatal rats. Rat pups were injected with 2.5 S NGF or cytochrome-c (control) on postnatal days (PN) 4 and 18, and sacrificed 3 days after injections for analysis of ChAT and VAChT mRNA levels by dot-blot hybridization of total septal RNA. In the NGF-treated pups, the ChAT and VAChT mRNA levels were elevated 3- and 2-fold, respectively, at PN7, and 1.8- and 1.3-fold at PN21. These results indicate that (1) NGF upregulates the expression of both ChAT and VAChT genes, (2) NGF has a greater effect on the expression of ChAT mRNA than VAChT mRNA, and (3) the effect of exogenous NGF on the expression of both genes diminishes with developmental age.
ESTHER : Tian_1996_Neurosci.Lett_209_134
PubMedSearch : Tian_1996_Neurosci.Lett_209_134
PubMedID: 8762000

Title : Endogenous acetylcholine-induced Fos expression in magnocellular neurosecretory neurons in the supraoptic nucleus of the rat hypothalamus - Shen_1995_Neurosci.Lett_195_191
Author(s) : Shen E , Sun X
Ref : Neuroscience Letters , 195 :191 , 1995
Abstract : Induction of c-Fos expression in the supraoptic nucleus (SON) of the rat hypothalamus by endogenous acetylcholine was examined by microinfusion of neostigmine, a cholinesterase inhibitor, into the nucleus to locally accumulate the spontaneously released acetylcholine from the cholinergic terminals in the SON. Double staining of the neurosecretory neurons with antiserum to Fos, the protein product of c-Fos, and antiserum to vasopressin or oxytocin was performed. Fos-like immunoreactivity was manifested in both the vasopressin neurons and oxytocin neurons following the microinfusion of neostigmine. Microinfusion of nicotinic agonist, nicotine, to the SON also induced Fos expression, but mainly in the vasopressin neurons. Microinfusion of muscarinic agonist, carbachol, induced Fos expression as well, but mostly in the oxytocin neurons.
ESTHER : Shen_1995_Neurosci.Lett_195_191
PubMedSearch : Shen_1995_Neurosci.Lett_195_191
PubMedID: 8584207