Li S

References (253)

Title : Inhibition of soluble epoxide hydrolase as a therapeutic approach for blood-brain barrier dysfunction - Li_2024_Biochimie__
Author(s) : Li S , Song H , Sun Y , Zhang H , Gao Z
Ref : Biochimie , : , 2024
Abstract : The blood-brain barrier (BBB) is a protective semi-permeable structure that regulates the exchange of biomolecules between the peripheral blood and the central nervous system (CNS). Due to its specialized tight junctions and low vesicle trafficking, the BBB strictly limits the paracellular passage and transcellular transport of molecules to maintain the physiological condition of brain tissues. BBB breakdown is associated with many CNS disorders. Soluble epoxide hydrolase (sEH) is a hydrolase enzyme that converts epoxy-fatty acids (EpFAs) to their corresponding diols and is involved in the onset and progression of multiple diseases. EpFAs play a protective role in the central nervous system via preventing neuroinflammation, making sEH a potential therapeutic target for CNS diseases. Recent studies showed that sEH inhibition prevented BBB impairment caused by stroke, hemorrhage, traumatic brain injury, hyperglycemia and sepsis via regulating the expression of tight junctions. In this review, the protective actions of sEH inhibition on BBB and potential mechanisms are summarized, and some important questions that remain to be resolved are also addressed.
ESTHER : Li_2024_Biochimie__
PubMedSearch : Li_2024_Biochimie__
PubMedID: 38531484
Gene_locus related to this paper: human-EPHX2

Title : Upconversion fluorescence nanosensor based on enzymatic inhibited and copper-triggered o-phenylenediamine oxidation for the detection of dimethoate pesticides - Li_2024_Food.Chem_453_139666
Author(s) : Li S , Zhang S , Wu J , Khan IM , Chen M , Jiao T , Wei J , Chen X , Chen Q
Ref : Food Chem , 453 :139666 , 2024
Abstract : Pesticide residues in agricultural products pose a significant threat to human health. Herein, a sensitive fluorescence method employing upconversion nanoparticles was developed for detecting organophosphorus pesticides (OPs) based on the principle of enzyme inhibition and copper-triggered o-phenylenediamine (OPD) oxidation. Copper ions (Cu(2+)) oxidized the colorless OPD to a yellow 2,3-diaminophenazine (oxOPD). The yellow solution oxOPD quenched the fluorescence of upconversion nanoparticles due to the fluorescence resonance energy transfer. The high affinity of Cu(2+) for thiocholine reduced the level of oxOPD, resulting in almost no fluorescence quenching. The addition of dimethoate led to the inhibition of acetylcholinesterase activity and thus prevented the formation of thiocholine. Subsequently, Cu(2+) oxidized OPD to form oxOPD, which attenuated the fluorescence signal of the system. The detection system has a good linear range of 0.01 ng/mL to 50 ng/mL with a detection limit of 0.008 ng/mL, providing promising applications for rapid detection of dimethoate.
ESTHER : Li_2024_Food.Chem_453_139666
PubMedSearch : Li_2024_Food.Chem_453_139666
PubMedID: 38759443

Title : Biotransformation activities of fungal strain apiotrichum sp. IB-1 to ibuprofen and naproxen - Peng_2024_Arch.Microbiol_206_232
Author(s) : Peng L , Yun H , Ji J , Zhang W , Xu T , Li S , Wang Z , Xie L , Li X
Ref : Arch Microbiol , 206 :232 , 2024
Abstract : Ibuprofen (IBU) and naproxen (NPX), as widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs), are largely produced and consumed globally, leading to frequent and ubiquitous detection in various aqueous environments. Previously, the microbial transformation of them has been given a little attention, especially with the isolated fungus. A yeast-like Apiotrichum sp. IB-1 has been isolated and identified, which could simultaneously transform IBU (5 mg/L) and NPX (2.5 mg/L) with maximum efficiencies of 95.77% and 88.31%, respectively. For mono-substrate, the transformation efficiency of IB-1 was comparable to that of co-removal conditions, higher than most of isolates so far. IBU was oxidized mainly through hydroxylation (m/z of 221, 253) and NPX was detoxified mainly via demethylation (m/z of 215) as shown by UPLC-MS/MS results. Based on transcriptome analysis, the addition of IBU stimulated the basic metabolism like TCA cycle. The transporters and respiration related genes were also up-regulated accompanied with higher expression of several dehydrogenase, carboxylesterase, dioxygenase and oxidoreductase encoding genes, which may be involved in the transformation of IBU. The main functional genes responsible for IBU and NPX transformation for IB-1 should be similar in view of previous studies, which needs further confirmation. This fungus would be useful for potential bioremediation of NSAIDs pollution and accelerate the discovery of functional oxidative genes and enzymes different from those of bacteria.
ESTHER : Peng_2024_Arch.Microbiol_206_232
PubMedSearch : Peng_2024_Arch.Microbiol_206_232
PubMedID: 38658486

Title : Optimizing Nanosuspension Drug Release and Wound Healing Using a Design of Experiments Approach: Improving the Drug Delivery Potential of NDH-4338 for Treating Chemical Burns - Roldan_2024_Pharmaceutics_16_
Author(s) : Roldan TL , Li S , Guillon C , Heindel ND , Laskin JD , Lee IH , Gao D , Sinko PJ
Ref : Pharmaceutics , 16 : , 2024
Abstract : NDH-4338 is a highly lipophilic prodrug comprising indomethacin and an acetylcholinesterase inhibitor. A design of experiments approach was used to synthesize, characterize, and evaluate the wound healing efficacy of optimized NDH-4338 nanosuspensions against nitrogen mustard-induced skin injury. Nanosuspensions were prepared by sonoprecipitation in the presence of a Vitamin E TPGS aqueous stabilizer solution. Critical processing parameters and material attributes were optimized to reduce particle size and determine the effect on dissolution rate and burn healing efficacy. The antisolvent/solvent ratio (A/S), dose concentration (DC), and drug/stabilizer ratio (D/S) were the critical sonoprecipitation factors that control particle size. These factors were subjected to a Box-Behnken design and response surface analysis, and model quality was assessed. Maximize desirability and simulation experiment optimization approaches were used to determine nanosuspension parameters with the smallest size and the lowest defect rate within the 10-50 nm specification limits. Optimized and unoptimized nanosuspensions were prepared and characterized. An established depilatory double-disc mouse model was used to evaluate the healing of nitrogen mustard-induced dermal injuries. Optimized nanosuspensions (A/S = 6.2, DC = 2% w/v, D/S = 2.8) achieved a particle size of 31.46 nm with a narrow size range (PDI = 0.110) and a reduced defect rate (42.2 to 6.1%). The optimized nanosuspensions were stable and re-dispersible, and they showed a ~45% increase in cumulative drug release and significant edema reduction in mice. Optimized NDH-4338 nanosuspensions were smaller with more uniform sizes that led to improved physical stability, faster dissolution, and enhanced burn healing efficacy compared to unoptimized nanosuspensions.
ESTHER : Roldan_2024_Pharmaceutics_16_
PubMedSearch : Roldan_2024_Pharmaceutics_16_
PubMedID: 38675132

Title : Retagliptin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial - Guo_2024_Diabetes.Obes.Metab__
Author(s) : Guo L , Tian F , Liu L , Chen M , Jiang C , Li S , Liu C , Zhang Y , Qin J , Yu D , Zong Y , Dai W
Ref : Diabetes Obes Metab , : , 2024
Abstract : AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
ESTHER : Guo_2024_Diabetes.Obes.Metab__
PubMedSearch : Guo_2024_Diabetes.Obes.Metab__
PubMedID: 38602409

Title : Presence of Multiple Genetic Mutations Related to Insecticide Resistance in Chinese Field Samples of Two Phthorimaea Pest Species - Zhu_2024_Insects_15_
Author(s) : Zhu J , Chen R , Liu J , Lin W , Liang J , Nauen R , Li S , Gao Y
Ref : Insects , 15 : , 2024
Abstract : Potatoes hold the distinction of being the largest non-cereal food crop globally. The application of insecticides has been the most common technology for pest control. The repeated use of synthetic insecticides of the same chemical class and frequent applications have resulted in the emergence of insecticide resistance. Two closely related pests that feed on potato crops are the potato tuber moth, Phthorimaea operculella, and the tomato leafminer, Phthorimaea absoluta (syn. Tuta absoluta). Previous studies indicated the existence of insecticide resistance to various classes of insecticides including organophosphates, carbamates, and pyrethroids in field populations of P. operculella and P. absoluta. However, the exact mechanisms of insecticide resistance in P. operculella and to a lesser extent P. absoluta remain still poorly understood. Detecting resistance genotypes is crucial for the prediction and management of insecticide resistance. In this study, we identified multiple genetic mutations related to insecticide resistance in two species of Phthorimaea. An unexpected genetic divergence on target-site mutations was observed between P. operculella and P. absoluta. Three mutations (A201S, L231V, and F290V) in Ace1 (acetylcholinesterase), four mutations (M918T, L925M, T928I, and L1014F) in VGSC (voltage-gated sodium channel), and one mutation (A301S) in RDL (GABA-gated chloride channel) have been detected with varying frequencies in Chinese P. absoluta field populations. In contrast, P. operculella field populations showed three mutations (F158Y, A201S, and L231V) in Ace1, one mutation (L1014F) in VGSC at a lower frequency, and no mutation in RDL. These findings suggest that pyrethroids, organophosphates, and carbamates are likely to be ineffective in controlling P. absoluta, but not P. operculella. These findings contributed to a deeper understanding of the presence of target-site mutations conferring resistance to commonly used (and cheap) classes of insecticides in two closely related potato pests. It is recommended to consider the resistance status of both pests for the implementation of resistance management strategies in potatoes.
ESTHER : Zhu_2024_Insects_15_
PubMedSearch : Zhu_2024_Insects_15_
PubMedID: 38535389

Title : Phthalate biomarkers composition in relation to fatty liver: evidence from epidemiologic and in vivo studies - Chen_2024_Sci.Total.Environ__171607
Author(s) : Chen S , Liu H , Sun Y , Li S , Shi Y , Cheng Z , Zhu H , Sun H
Ref : Sci Total Environ , :171607 , 2024
Abstract : Phthalates, classified as environmental endocrine disruptors, pose potential toxicity risks to human health. Metabolic dysfunction-associated fatty liver disease is one of the most widespread liver diseases globally. Compared to studies focusing on metabolic disorders in relation to pollutants exposure, the impact of individual factors such as fatty liver on the in vivo metabolism of pollutants is always overlooked. Therefore, this study measured concentrations and composition of phthalate monoesters (mPAEs) in human urine samples, particularly those from fatty liver patients. Furthermore, we induced fatty liver in male Wistar rats by formulating a high-fat diet for twelve weeks. After administering a single dose of DEHP at 500 mg/kg bw through gavage, we compared the levels of di-2-ethylhexyl phthalate (DEHP), its metabolites (mDEHPs) and three hepatic metabolic enzymes, namely cytochrome P450 enzymes (CYP450), UDP glucuronosyltransferase 1 (UGT1), and carboxylesterase 1 (CarE1), between the normal and fatty liver rat groups. Compared to healthy individuals (n = 75), fatty liver patients (n = 104) exhibited significantly lower urinary concentrations of mPAEs (median: 106 vs. 166 ng/mL), but with a higher proportion of mono-2-ethylhexyl phthalate in mDEHPs (25.7 % vs. 9.9 %) (p < 0.05). In the animal experiment, we found that fatty liver in rats prolonged the elimination half-life of DEHP (24.61 h vs. 18.89 h) and increased the contents of CYP450, CarE1, and UGT1, implying the common but differentiated metabolism of DEHP as excess lipid accumulation in liver cells. This study provides valuable information on how to distinguish populations in biomonitoring studies across a diverse population and in assigning exposure classifications of phthalates or similar chemicals in epidemiologic studies.
ESTHER : Chen_2024_Sci.Total.Environ__171607
PubMedSearch : Chen_2024_Sci.Total.Environ__171607
PubMedID: 38461993

Title : Mice with an autism-associated R451C mutation in neuroligin-3 show intact attention orienting but atypical responses to methylphenidate and atomoxetine in the mouse-Posner task - Li_2024_Psychopharmacology.(Berl)__
Author(s) : Li S , May C , Pang TY , Churilov L , Hannan AJ , Johnson KA , Burrows EL
Ref : Psychopharmacology (Berl) , : , 2024
Abstract : RATIONALE: Atypical attention orienting has been associated with some autistic symptoms, but the neural mechanisms remain unclear. The human Posner task, a classic attention orienting paradigm, was recently adapted for use with mice, supporting the investigation of the neurobiological underpinnings of atypical attention orienting in preclinical mouse models. OBJECTIVE: The current study tested mice expressing the autism-associated R451C gene mutation in neuroligin-3 (NL3) on the mouse-Posner (mPosner) task. METHODS: NL3(R451C) and wild-type (WT) mice were trained to respond to a validly or invalidly cued target on a touchscreen. The cue was a peripheral non-predictive flash in the exogenous task and a central spatially predictive image in the endogenous task. The effects of dopaminergic- and noradrenergic-modulating drugs, methylphenidate and atomoxetine, on task performance were assessed. RESULTS: In both tasks, mice were quicker and more accurate in the validly versus invalidly cued trials, consistent with results in the human Posner task. NL3(R451C) and WT mice showed similar response times and accuracy but responded differently when treated with methylphenidate and atomoxetine. Methylphenidate impaired exogenous attention disengagement in NL3(R451C) mice but did not significantly affect WT mice. Atomoxetine impaired endogenous orienting in WT mice but did not significantly affect NL3(R451C) mice. CONCLUSIONS: NL3(R451C) mice demonstrated intact attention orienting but altered responses to the pharmacological manipulation of the dopaminergic and noradrenergic networks. These findings expand our understanding of the NL3(R451C) mutation by suggesting that this mutation may lead to selective alterations in attentional processes.
ESTHER : Li_2024_Psychopharmacology.(Berl)__
PubMedSearch : Li_2024_Psychopharmacology.(Berl)__
PubMedID: 38170320
Gene_locus related to this paper: human-NLGN3 , mouse-3neur

Title : Human umbilical cord mesenchymal stem cells attenuate diet-induced obesity and NASH-related fibrosis in mice - Hu_2024_Heliyon_10_e25460
Author(s) : Hu J , Li S , Zhong X , Wei Y , Sun Q , Zhong L
Ref : Heliyon , 10 :e25460 , 2024
Abstract : Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may progress to cirrhosis and hepatocellular carcinoma but has no available treatment. Mesenchymal stem cells (MSCs) have become increasingly prominent in cell therapy. Human umbilical cord MSCs (hUC-MSCs) are considered superior to other MSCs due to their strong immunomodulatory ability, ease of collection, low immune rejection, and no tumorigenicity. Though hUC-MSCs have received increasing attention in research, they have been rarely applied in any investigations or treatments of NASH and associated fibrosis. Therefore, this study evaluated the therapeutic efficacy of hUC-MSCs in C57BL/6 mice with diet-induced NASH. At week 32, mice were randomized into two groups: phosphate-buffered saline and MSCs, which were injected into the tail vein. At week 40, glucose metabolism was evaluated using glucose and insulin tolerance tests. NASH-related indicators were examined using various biological methods. hUC-MSC administration alleviated obesity, glucose metabolism, hepatic steatosis, inflammation, and fibrosis. Liver RNA-seq showed that the expression of the acyl-CoA thioesterase (ACOT) family members Acot1, Acot2, and Acot3 involved in fatty acid metabolism were altered. The cytochrome P450 (CYP) members Cyp4a10 and Cyp4a14, which are involved in the peroxisome proliferator-activator receptor (PPAR) signaling pathway, were significantly downregulated after hUC-MSC treatment. In conclusion, hUC-MSCs effectively reduced Western diet-induced obesity, NASH, and fibrosis in mice, partly by regulating lipid metabolism and the PPAR signaling pathway.
ESTHER : Hu_2024_Heliyon_10_e25460
PubMedSearch : Hu_2024_Heliyon_10_e25460
PubMedID: 38356602

Title : Inquiry lipaseoring the mechanism of pancreatic lipase inhibition by isovitexin based on multispectral method and enzyme inhibition assay - Yu_2024_Luminescence_39_e4765
Author(s) : Yu H , Xing Z , Jia K , Li S , Xu Y , Zhao P , Zhu X
Ref : Luminescence , 39 :e4765 , 2024
Abstract : Isovitexin is a main natural flavonoid component in various plants. Currently, the inhibitory effect of isovitexin on pancreatic lipase (PL) and its mechanism have not been elucidated yet. In the present study, we investigated the inhibitory effect of isovitexin on PL, as well as its interaction mechanism, using enzyme inhibition methods, spectroscopic analysis, and molecular simulations. Results showed that isovitexin possessed significant PL inhibitory activity, with IC(50) values of 0.26 +/- 0.02 mM. The interaction between isovitexin and PL was dominated by static quenching, and mainly through hydrogen bonding and hydrophobic interaction forces. Analysis of fluorescence spectroscopy confirmed that isovitexin binding altered the conformation of the PL. Circular dichroism (CD) spectrum indicated that isovitexin altered the secondary structure of PL by decreasing the alpha-helix content and increasing the beta-fold content. Molecular simulations further characterize the conformational changes produced by the interaction between isovitexin with PL. The performed study may provide a new insight into the inhibitory mechanism of isovitexin as a novel PL inhibitor.
ESTHER : Yu_2024_Luminescence_39_e4765
PubMedSearch : Yu_2024_Luminescence_39_e4765
PubMedID: 38769927

Title : Co-occurrence, toxicity, and biotransformation pathways of metformin and its intermediate product guanylurea: Current state and future prospects for enhanced biodegradation strategy - Dong_2024_Sci.Total.Environ_921_171108
Author(s) : Dong L , Li S , Huang J , Li WJ , Ali M
Ref : Sci Total Environ , 921 :171108 , 2024
Abstract : Accumulation of metformin and its biotransformation product "guanylurea" are posing an increasing concern due to their low biodegradability under natural attenuated conditions. Therefore, in this study, we reviewed the unavoidable function of metformin in human body and the route of its release in different water ecosystems. In addition, metformin and its biotransformation product guanylurea in aquatic environments caused certain toxic effects on aquatic organisms which include neurotoxicity, endocrine disruption, production of ROS, and acetylcholinesterase disturbance in aquatic organisms. Moreover, microorganisms are the first to expose and deal with the release of these contaminants, therefore, the mechanisms of biodegradation pathways of metformin and guanylurea under aerobic and anaerobic environments were studied. It has been reported that certain microbes, such as Aminobacter sp. and Pseudomonas putida can carry potential enzymatic pathways to degrade the dead-end product "guanylurea", and hence guanylurea is no longer the dead-end product of metformin. However, these microbes can easily be affected by certain geochemical cycles, therefore, we proposed certain strategies that can be helpful in the enhanced biodegradation of metformin and its biotransformation product guanylurea. A better understanding of the biodegradation potential is imperative to improve the use of these approaches for the sustainable and cost-effective remediation of the emerging contaminants of concern, metformin and guanylurea in the near future.
ESTHER : Dong_2024_Sci.Total.Environ_921_171108
PubMedSearch : Dong_2024_Sci.Total.Environ_921_171108
PubMedID: 38395159

Title : Study on the role and mechanism of Tan IIA in Alzheimer's disease based on CREB-BDNF-TrkB pathway - Xiang_2024_Neurosci.Lett_830_137769
Author(s) : Xiang X , Xia S , Li S , Zeng Y , Wang L , Zhou Y
Ref : Neuroscience Letters , 830 :137769 , 2024
Abstract : The occurrence and development of Alzheimer's disease (AD) is closely related to neuronal loss, inflammatory response, cholinergic imbalance, and Tau protein hyperphosphorylation. Previous studies have confirmed that Streptozotocin (STZ) can be used to establish a rat model of AD by injecting it into the rat brain via the lateral ventricle. Our previous research showed that Danshentone IIA (Tan IIA) can improve cognitive dysfunction in rats caused by CC chemokine ligand 2, and network pharmacology results show that Tan IIA is very likely to improve AD symptoms through the cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), and tyrosine kinase receptor protein (TrkB) pathway. The results of the water maze experiment showed that after Tan IIA treatment, the escape latency of AD rats was shortened and the number of platform crossings increased; in the new object recognition experiment, the discrimination index of AD rats significantly increased after treatment; Nissl staining and Tunel staining results showed that Tan IIA increased the number of surviving neurons in the hippocampus of cognitively impaired rats and reduced neuronal apoptosis; Bielschowsky silver staining results showed that Tan IIA reduced neurofibrillary tangles (NFTs) in the AD rats; Tan IIA can reduce the inflammatory response and oxidative stress reaction in the hippocampus of AD rats, and at the same time reduce the activity of acetylcholinesterase. Tan IIA can significantly increase the expression of CREB, BDNF, TrkB in the hippocampal tissue of STZ-injured rats (P < 0.05). These data suggest that Tan IIA may upregulate the expression of the CREB-BDNF-TrkB signaling pathway in the hippocampus of brain tissue, produce anti-neuroinflammatory, antioxidant stress, inhibit neuronal apoptosis effects, and improve cholinergic neurotransmitter disorder induced by STZ, reduce the neuronal damage and learning and memory impairment caused by STZ in rats, and improve the cognitive function of rats.
ESTHER : Xiang_2024_Neurosci.Lett_830_137769
PubMedSearch : Xiang_2024_Neurosci.Lett_830_137769
PubMedID: 38616003

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

Title : Development of Sustainable Insecticide Candidates for Protecting Pollinators: Insight into the Bioactivities, Selective Mechanism of Action and QSAR of Natural Coumarin Derivatives against Aphids - Zhou_2023_J.Agric.Food.Chem_71_18359
Author(s) : Zhou H , Jian Y , Shao Q , Guo F , Zhang M , Wan F , Yang L , Liu Y , Li Y , Yang P , Li Z , Li S , Ding W
Ref : Journal of Agricultural and Food Chemistry , 71 :18359 , 2023
Abstract : Plants employ abundant toxic secondary metabolites to withstand insect attack, while pollinators can tolerate some natural defensive compounds. Coumarins, as promising green alternatives to chemical insecticides, possess wide application prospects in the crop protection field. Herein, the bioactivities of 30 natural coumarin derivatives against Aphis gossypii were assessed and revealed that 6-methylcoumarin exhibited potent aphicidal activity against aphids but displayed no toxicity to honeybees. Additionally, using biochemical, bioinformatic, and molecular assays, we confirmed that the action mode of 6-methylcoumarin against aphids was by inhibiting acetylcholinesterase (AChE). Meanwhile, functional assays revealed that the difference in action site, which located in Lys585 in aphid AChE (equivalent to Val548 in honeybee AChE), was the principal reason for 6-methylcoumarin being toxic to aphids but safe to pollinators. This action site was further validated by mutagenesis data, which uncovered how 6-methylcoumarin was unique selective to the aphid over honeybee or mammalian AChE. Furthermore, a 2D-QSAR model was established, revealing that the central structural feature was H3m, which offers guidance for the future design of more potent coumarin compounds. This work provides a sustainable strategy to take advantage of coumarin analogues for pest management while protecting nontarget pollinators.
ESTHER : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedSearch : Zhou_2023_J.Agric.Food.Chem_71_18359
PubMedID: 37965968

Title : A Dual Fluorescence Assay Enables High-Throughput Screening for Poly(ethylene terephthalate) Hydrolases - Liu_2023_ChemSusChem_16_e202202019
Author(s) : Liu K , Xu Z , Zhao Z , Chen Y , Chai Y , Ma L , Li S
Ref : ChemSusChem , 16 :e202202019 , 2023
Abstract : The drastically increasing consumption of petroleum-derived plastics hasserious environmental impacts and raises public concerns. Poly(ethylene terephthalate) (PET) is amongst the most extensively produced synthetic polymers. Enzymatic hydrolysis of PET recently emerged as an enticing path for plastic degradation and recycling. In-lab directed evolution has revealed the great potential of PET hydrolases (PETases). However, the time-consuming and laborious PETase assays hinder the identification of effective variants in large mutant libraries. Herein, we devise and validate a dual fluorescence-based high-throughput screening (HTS) assay for a representative IsPETase. The two-round HTS of a pilot library consisting of 2850 IsPETase variants yields six mutant IsPETases with 1.3-4.9 folds improved activities. Compared to the currently used structure- or computational redesign-based PETase engineering, this HTS approach provides a new strategy for discovery of new beneficial mutation patterns of PETases.
ESTHER : Liu_2023_ChemSusChem_16_e202202019
PubMedSearch : Liu_2023_ChemSusChem_16_e202202019
PubMedID: 36511949

Title : Variation in the HSL Gene and Its Association with Carcass and Meat Quality Traits in Yak - Wang_2023_Animals.(Basel)_13_
Author(s) : Wang X , Qi Y , Zhu C , Zhou R , Ruo Z , Zhao Z , Liu X , Li S , Zhao F , Wang J , Hu J , Shi B
Ref : Animals (Basel) , 13 : , 2023
Abstract : Hormone-sensitive lipase (HSL) is involved in the breakdown of triacylglycerols in adipose tissue, which influences muscle tenderness and juiciness by affecting the intramuscular fat content (IMF). This study analyzed the association between different genotypes and haplotypes of the yak HSL gene and carcass and meat quality traits. We used hybridization pool sequencing to detect exon 2, exon 8, and intron 3 variants of the yak HSL gene and genotyped 525 Gannan yaks via KASP to analyze the effects of the HSL gene variants on the carcass and meat quality traits in yaks. According to the results, the HSL gene is highly expressed in yak adipose tissue. Three single nucleotide polymorphisms (SNPs) were identified, with 2 of them located in the coding region and one in the intron region. Variants in the 2 coding regions resulted in amino acid changes. The population had 3 genotypes of GG, AG, and AA, and individuals with the AA genotype had lower WBSF values (p < 0.05). The H3H3 haplotype combinations could improve meat tenderness by reducing the WBSF values and the cooking loss rate (CLR) (p < 0.05). H1H1 haplotype combinations were associated with the increased drip loss rate (DLR) (p < 0.05). The presence of the H1 haplotype was associated the increased CLR in yaks, while that of the H2 haplotype was associated with the decreased DLR in yaks (p < 0.05). These results demonstrated that the HSL gene may influence the meat quality traits in yaks by affecting the IMF content in muscle tissues. Consequently, the HSL gene can possibly be used as a biomarker for improving the meat quality traits in yaks in the future.
ESTHER : Wang_2023_Animals.(Basel)_13_
PubMedSearch : Wang_2023_Animals.(Basel)_13_
PubMedID: 38067071

Title : Efficient Combination of Complex Chromatography, Molecular Docking and Enzyme Kinetics for Exploration of Acetylcholinesterase Inhibitors from Poria cocos - Wu_2023_Molecules_28_1228
Author(s) : Wu T , Hou W , Liu C , Li S , Zhang Y
Ref : Molecules , 28 :1228 , 2023
Abstract : Poria cocos (P. cocos) is a traditional Chinese medicinal product with the same origin as medicine and food. It has diuretic, anti-inflammatory and liver protection properties, and has been widely used in a Chinese medicine in the treatment of Alzheimer's disease (AD). This study was conducted to explore the activity screening, isolation of acetylcholinesterase inhibitors (AChEIs), and in vitro inhibiting effect of P. cocos. The aim was to develop a new extraction process optimization method based on the Matlab genetic algorithm combined with a traditional orthogonal experiment. Moreover, bio-affinity ultrafiltration combined with molecular docking was used to screen and evaluate the activity of the AChEIs, which were subsequently isolated and purified using high-speed counter-current chromatography (HSCCC) and semi-preparative high-performance liquid chromatography (semi-preparative HPLC). The change in acetylcholinesterase (AChE) activity was tested using an enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on AChE and explore its mechanism of action. Five potential AChEIs were screened via bio-affinity ultrafiltration. Molecular docking results showed that they had good binding affinity for the active site of AChE. Meanwhile, the five active compounds had reversible inhibitory effects on AChE: Polyporenic acid C and Tumulosic acid were non-competitive inhibitors; 3-Epidehydrotumulosic acid was a mixed inhibitor; and Pachymic acid and Dehydrotrametenolic acid were competitive inhibitors. This study provided a basis for the comprehensive utilization of P. cocos and drug development for the treatment of AD.
ESTHER : Wu_2023_Molecules_28_1228
PubMedSearch : Wu_2023_Molecules_28_1228
PubMedID: 36770895

Title : Antidementia medication acetylcholinesterase inhibitors have therapeutic benefits on osteoporotic bone by attenuating osteoclastogenesis and bone resorption - Li_2023_J.Cell.Physiol__
Author(s) : Li S , Teguh D , Wu D , Liu L , Hu C , Yuan J , Inderjeeth CA , Xu J
Ref : Journal of Cellular Physiology , : , 2023
Abstract : This study was designed to determine whether the use of acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate acetylcholine receptors and are used to treat Alzheimer's disease (AD), is associated with osteoporosis protection and inhibition of osteoclast differentiation and function. Firstly, we examined the effects of AChEIs on RANKL-induced osteoclast differentiation and function with osteoclastogenesis and bone resorption assays. Next, we investigated the impacts of AChEIs on RANKL-induced nuclear factor kappaB and NFATc1 activation and expression of osteoclast marker proteins CA-2, CTSK and NFATc1, and dissected the MAPK signaling in osteoclasts in vitro by using luciferase assay and Western blot. Finally, we assessed the in vivo efficacy of AChEIs using an ovariectomy-induced osteoporosis mouse model, which was analyzed using microcomputed tomography, in vivo osteoclast and osteoblast parameters were assessed using histomorphometry. We found that Donepezil and Rivastigmine inhibited RANKL-induced osteoclastogenesis and impaired osteoclastic bone resorption. Moreover, AChEIs reduced the RANKL-induced transcription of Nfatc1, and expression of osteoclast marker genes to varying degrees (mainly Donepezil and Rivastigmine but not Galantamine). Furthermore, AChEIs variably inhibited RANKL-induced MAPK signaling accompanied by downregulation of AChE transcription. Finally, AChEIs protected against OVX-induced bone loss mainly by inhibiting osteoclast activity. Taken together, AChEIs (mainly Donepezil and Rivastigmine) exerted a positive effect on bone protection by inhibiting osteoclast function through MAPK and NFATc1 signaling pathways through downregulating AChE. Our findings have important clinical implications that elderly patients with dementia who are at risk of developing osteoporosis may potentially benefit from therapy with the AChEI drugs. Our study may influence drug choice in those patients with both AD and osteoporosis.
ESTHER : Li_2023_J.Cell.Physiol__
PubMedSearch : Li_2023_J.Cell.Physiol__
PubMedID: 37334837

Title : Liensinine and neferine exert neuroprotective effects via the autophagy pathway in transgenic Caenorhabditis elegans - Wu_2023_BMC.Complement.Med.Ther_23_386
Author(s) : Wu MC , Gao YH , Zhang C , Ma BT , Lin HR , Jiang JY , Xue MF , Li S , Wang HB
Ref : BMC Complement Med Ther , 23 :386 , 2023
Abstract : BACKGROUND: Liensinine and neferine are the main bisbenzylisoquinoline alkaloids obtained from the seeds of Nelumbo nucifera, which commonly used as edible food and traditional medicine in Asia. It was reported that liensinine and neferine could inhibit the activities of acetylcholinesterase and cross the blood-brain barriers, suggesting their therapeutic potential for the management of Alzheimer's disease. METHODS: Here, we employed SH-SY5Y human neuroblastoma cells stably transfected with the human Swedish amyloid precursor protein (APP) mutation APP695 (APP695swe SH-SY5Y) as an in vitro model and transgenic Caenorhabditis elegans as an in vivo model to investigate the neuroprotective effects and underlying mechanism of liensinine and neferine. RESULTS: We found that liensinine and neferine could significantly improve the viability and reduce ROS levels in APP695swe SH-SY5Y cells, inhibit beta-amyloid and tau-induced toxicity, and enhance stress resistance in nematodes. Moreover, liensinine and neferine had obviously neuroprotective effects by assaying chemotaxis, 5-hydroxytryptamine sensitivity and the integrity of injured neurons in nematodes. Preliminary mechanism studies revealed that liensinine and neferine could upregulate the expression of autophagy related genes (lgg-1, unc-51, pha-4, atg-9 and ced-9) and reduce the accumulation of beta-amyloid induced autophagosomes, which suggested autophagy pathway played a key role in neuroprotective effects of these two alkaloids. CONCLUSIONS: Altogether, our findings provided a certain working foundation for the use of liensinine and neferine to treat Alzheimer's disease based on neuroprotective effects.
ESTHER : Wu_2023_BMC.Complement.Med.Ther_23_386
PubMedSearch : Wu_2023_BMC.Complement.Med.Ther_23_386
PubMedID: 37891552

Title : The preparation of Diacylglycerol-rich soybean oil by acetylated modification of arachin nanoparticles for W\/O Pickering emulsion system - Li_2023_Food.Chem_426_136615
Author(s) : Li W , Faisal S , Guo X , Li S , Shi A , Jiao B , Wang Q
Ref : Food Chem , 426 :136615 , 2023
Abstract : Pickering emulsion catalytic system (PEC) stabilized by nanoparticles is an efficient catalytic platform. Herein, a high-performance PEC was constructed by acetylated modification of arachin nanoparticles (AAPs). The results showed the pI of arachin was decreased from pH 5.5 to pH 3.5. The surface hydrophobicity index was significantly increased (from 56.28 +/- 4.23 to 120.77 +/- 0.79) after acetylated modification. The three-phase contact angle of AAPs was 91.20 +/- 0.98 degrees. AAPs were used as lipase immobilization carriers to increase the activity of free lipase fabricating lipase-AAPs. The immobilization efficiency and activity of lipase-AAPs were 12.95 +/- 0.03% and 1.74 +/- 0.07 U/mg, respectively. Enzymatic reaction kinetics showed that V(m) of lipase-AAPs was twice of free lipase. K(m) was 1/5 of free lipase. The catalytic efficiency of PEC to prepare DAG was 2.36 times of biphasic catalytic system (BCS). This work provided a promising way to promote the efficiency of DAG preparation.
ESTHER : Li_2023_Food.Chem_426_136615
PubMedSearch : Li_2023_Food.Chem_426_136615
PubMedID: 37331136

Title : Investigating the Regulatory Mechanism of the Sesquiterpenol Nerolidol from a Plant on Juvenile Hormone-Related Genes in the Insect Spodoptera exigua - Dai_2023_Int.J.Mol.Sci_24_
Author(s) : Dai H , Liu B , Yang L , Yao Y , Liu M , Xiao W , Li S , Ji R , Sun Y
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Various plant species contain terpene secondary metabolites, which disrupt insect growth and development by affecting the activity of juvenile hormone-degrading enzymes, and the juvenile hormone (JH) titers maintained in insects. Nerolidol, a natural sesquiterpenol belonging to the terpenoid group, exhibits structural similarities to insect JHs. However, the impact of nerolidol on insect growth and development, as well as its underlying molecular mechanism, remains unclear. Here, the effects of nerolidol on Spodoptera exigua were investigated under treatment at various sub-lethal doses (4.0 mg/mL, 1.0 mg/mL, 0.25 mg/mL). We found that a higher dose (4.0 mg/mL) of nerolidol significantly impaired the normal growth, development, and population reproduction of S. exigua, although a relatively lower dose (0.25 mg/mL) of nerolidol had no significant effect on this growth and development. Combined transcriptome sequencing and gene family analysis further revealed that four juvenile hormone esterase (JHE)-family genes that are involved in juvenile hormone degradation were significantly altered in S. exigua larvae after nerolidol treatment (4.0 mg/mL). Interestingly, the juvenile hormone esterase-like (JHEL) gene Sexi006721, a critical element responsive to nerolidol stress, was closely linked with the significant augmentation of JHE activity and JH titer in S. exigua (R(2) = 0.94, p < 0.01). Taken together, we speculate that nerolidol can function as an analog of JH by modulating the expression of the enzyme genes responsible for degrading JH, resulting in JH disorders and ultimately disrupting the development of insect larvae. This study ultimately provides a theoretical basis for the sustainable control of S. exigua in the field whilst proposing a new perspective for the development of novel biological pesticides.
ESTHER : Dai_2023_Int.J.Mol.Sci_24_
PubMedSearch : Dai_2023_Int.J.Mol.Sci_24_
PubMedID: 37686136

Title : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : Identification of Potent and Selective Acetylcholinesterase\/Butyrylcholinesterase Inhibitors by Virtual Screening - Xu_2023_J.Chem.Inf.Model__
Author(s) : Xu T , Li S , Li AJ , Zhao J , Sakamuru S , Huang W , Xia M , Huang R
Ref : J Chem Inf Model , : , 2023
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play important roles in human neurodegenerative disorders such as Alzheimer's disease. In this study, machine learning methods were applied to develop quantitative structure-activity relationship models for the prediction of novel AChE and BChE inhibitors based on data from quantitative high-throughput screening assays. The models were used to virtually screen an in-house collection of -360K compounds. The optimal models achieved good performance with area under the receiver operating characteristic curve values ranging from 0.83 +/- 0.03 to 0.87 +/- 0.01 for the prediction of AChE/BChE inhibition activity and selectivity. Experimental validation showed that the best-performing models increased the assay hit rate by several folds. We identified 88 novel AChE and 126 novel BChE inhibitors, 25% (AChE) and 53% (BChE) of which showed potent inhibitory effects (IC(50) < 5 microM). In addition, structure-activity relationship analysis of the BChE inhibitors revealed scaffolds for chemistry design and optimization. In conclusion, machine learning models were shown to efficiently identify potent and selective inhibitors against AChE and BChE and novel structural series for further design and development of potential therapeutics against neurodegenerative disorders.
ESTHER : Xu_2023_J.Chem.Inf.Model__
PubMedSearch : Xu_2023_J.Chem.Inf.Model__
PubMedID: 37011147

Title : Combined application of multiple biomarkers for early auxiliary diagnosis of silicosis - Liu_2023_Toxicol.Ind.Health__7482337231154636
Author(s) : Liu K , Sun L , Li S , Xu H
Ref : Toxicol Ind Health , :7482337231154636 , 2023
Abstract : Silicosis is an important industrial health problem for those workers exposed to silica. The present study aimed to investigate the sensitivity and specificity of combined detection of biomarkers in early auxiliary diagnosis of silicosis, the risk factors of silicosis were also studied. The study sample comprised 65 workers who had clinical silicosis and 70 matched control subjects who were exposed to silica but did not have clinical silicosis. The levels of superoxide dismutase, malondialdehyde, interleukin 6 (IL-6), tumor necrosis factor-alpha, and cholinesterases in the serum of 135 subjects were measured. After completing the biochemical assays, a logistic regression model based on the above biochemical determination results was established, and the receiver operating characteristic curve was used for judging the discrimination ability of different statistical indexes. The expression levels of MDA, IL-6, and TNF-alpha in serum samples of patients with stage I silicosis and MDA and IL-6 in serum samples of patients with stage II silicosis were all significantly higher. Results from logistic regression analysis showed that ChEs were protective factors for silicosis, while age, chronic respiratory symptoms, IL-6, and MDA were risk factors. The areas under the ROC curve (AUC) were 0.86 (IL-6), 0.81 (MDA), and 0.65 (TNF-alpha or ChEs). AUC-ROC = 0.90 (95%CI:0.84-0.95). The diagnostic efficiency of IL-6 combined with MDA and TNF-alpha was better than that of any single biomarker.
ESTHER : Liu_2023_Toxicol.Ind.Health__7482337231154636
PubMedSearch : Liu_2023_Toxicol.Ind.Health__7482337231154636
PubMedID: 36734071

Title : Depilatory double-disc mouse model for evaluation of vesicant dermal injury pharmacotherapy countermeasures - Roldan_2023_Animal.Model.Exp.Med_6_57
Author(s) : Roldan TL , Li S , Laskin JD , Gao D , Sinko PJ
Ref : Animal Model Exp Med , 6 :57 , 2023
Abstract : BACKGROUND: Sulfur mustard (SM) is a chemical warfare vesicant that severely injures exposed eyes, lungs, and skin. Mechlorethamine hydrochloride (NM) is widely used as an SM surrogate. This study aimed to develop a depilatory double-disc (DDD) NM skin burn model for investigating vesicant pharmacotherapy countermeasures. METHODS: Hair removal method (clipping only versus clipping followed by a depilatory), the effect of acetone in the vesicant administration vehicle, NM dose (0.5-20 micromol), vehicle volume (5-20 microl), and time course (0.5-21 days) were investigated using male and female CD-1 mice. Edema, an indicator of burn response, was assessed by biopsy skin weight. The ideal NM dose to induce partial-thickness burns was assessed by edema and histopathologic evaluation. The optimized DDD model was validated using an established reagent, NDH-4338, a cyclooxygenase, inducible nitric oxide synthase, and acetylcholinesterase inhibitor prodrug. RESULTS: Clipping/depilatory resulted in a 5-fold higher skin edematous response and was highly reproducible (18-fold lower %CV) compared to clipping alone. Acetone did not affect edema formation. Peak edema occurred 24-48 h after NM administration using optimized dosing methods and volume. Ideal partial-thickness burns were achieved with 5 micromol of NM and responded to treatment with NDH-4338. No differences in burn edematous responses were observed between males and females. CONCLUSION: A highly reproducible and sensitive partial-thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures. This model provides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.
ESTHER : Roldan_2023_Animal.Model.Exp.Med_6_57
PubMedSearch : Roldan_2023_Animal.Model.Exp.Med_6_57
PubMedID: 36872306

Title : Resensitizing Paclitaxel-Resistant Ovarian Cancer via Targeting Lipid Metabolism Key Enzymes CPT1A, SCD and FASN - Ma_2023_Int.J.Mol.Sci_24_
Author(s) : Ma Q , Liu Z , Wang T , Zhao P , Liu M , Wang Y , Zhao W , Yuan Y , Li S
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Epithelial ovarian cancer (EOC) is a lethal gynecological cancer, of which paclitaxel resistance is the major factor limiting treatment outcomes, and identification of paclitaxel resistance-related genes is arduous. We obtained transcriptomic data from seven paclitaxel-resistant ovarian cancer cell lines and corresponding sensitive cell lines. Define genes significantly up-regulated in at least three resistant cell lines, meanwhile they did not down-regulate in the other resistant cell lines as candidate genes. Candidate genes were then ranked according to the frequencies of significant up-regulation in resistant cell lines, defining genes with the highest rankings as paclitaxel resistance-related genes (PRGs). Patients were grouped based on the median expression of PRGs. The lipid metabolism-related gene set and the oncological gene set were established and took intersections with genes co-upregulated with PRGs, obtaining 229 co-upregulated genes associated with lipid metabolism and tumorigenesis. The PPI network obtained 19 highly confidential synergistic targets (interaction score > 0.7) that directly associated with CPT1A. Finally, FASN and SCD were up-stream substrate provider and competitor of CPT1A, respectively. Western blot and qRT-PCR results confirmed the over-expression of CPT1A, SCD and FASN in the A2780/PTX cell line. The inhibition of CPT1A, SCD and FASN down-regulated cell viability and migration, pharmacological blockade of CPT1A and SCD increased apoptosis rate and paclitaxel sensitivity of A2780/PTX. In summary, our novel bioinformatic methods can overcome difficulties in drug resistance evaluation, providing promising therapeutical strategies for paclitaxel-resistant EOC via taregting lipid metabolism-related enzymes.
ESTHER : Ma_2023_Int.J.Mol.Sci_24_
PubMedSearch : Ma_2023_Int.J.Mol.Sci_24_
PubMedID: 38003694

Title : Pancreatic lipase-related protein 2 is selectively expressed by peritubular myoid cells in the murine testis and sustains long-term spermatogenesis - Tao_2023_Cell.Mol.Life.Sci_80_217
Author(s) : Tao HP , Lu TF , Li S , Jia GX , Zhang XN , Yang QE , Hou YP
Ref : Cell Mol Life Sciences , 80 :217 , 2023
Abstract : Spermatogenesis is a complicated process of germ cell differentiation that occurs within the seminiferous tubule in the testis. Peritubular myoid cells (PTMCs) produce major components of the basement membrane that separates and ensures the structural integrity of seminiferous tubules. These cells secrete niche factors to promote spermatogonial stem cell (SSC) maintenance and mediate androgen signals to direct spermatid development. However, the regulatory mechanisms underlying the identity and function of PTMCs have not been fully elucidated. In the present study, we showed that the expression of pancreatic lipase-related protein 2 (Pnliprp2) was restricted in PTMCs in the testis and that its genetic ablation caused age-dependent defects in spermatogenesis. The fertility of Pnliprp2 knockout animals (Pnliprp2(-/-)) was normal at a young age but declined sharply beginning at 9 months. Pnliprp2 deletion impaired the homeostasis of undifferentiated spermatogonia and severely disrupted the development and function of spermatids. Integrated analyses of single-cell RNA-seq and metabolomics data revealed that glyceride metabolism was changed in PTMCs from Pnliprp2(-/-) mice. Further analysis found that 60 metabolites were altered in the sperm of the Pnliprp2(-/-) animals; notably, lipid metabolism was significantly dysregulated. Collectively, these results revealed that Pnliprp2 was exclusively expressed in PTMCs in the testis and played a novel role in supporting continual spermatogenesis in mice. The outcomes of these findings highlight the function of lipid metabolism in reproduction and provide new insights into the regulation of PTMCs in mammals.
ESTHER : Tao_2023_Cell.Mol.Life.Sci_80_217
PubMedSearch : Tao_2023_Cell.Mol.Life.Sci_80_217
PubMedID: 37468762

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : Increased palmitoylation improves estrogen receptor alpha-dependent hippocampal synaptic deficits in a mouse model of synucleinopathy - Moors_2023_Sci.Adv_9_eadj1454
Author(s) : Moors TE , Li S , McCaffery TD , Ho GPH , Bechade PA , Pham LN , Ericsson M , Nuber S
Ref : Sci Adv , 9 :eadj1454 , 2023
Abstract : Parkinson's disease (PD) is characterized by conversion of soluble alpha-synuclein (alphaS) into intraneuronal aggregates and degeneration of neurons and neuronal processes. Indications that women with early-stage PD display milder neurodegenerative features suggest that female sex partially protects against alphaS pathology. We previously reported that female sex and estradiol improved alphaS homeostasis and PD-like phenotypes in E46K-amplified (3K) alphaS mice. Here, we aimed to further dissect mechanisms that drive this sex dimorphism early in disease. We observed that synaptic abnormalities were delayed in females and improved by estradiol, mediated by local estrogen receptor alpha (ERalpha). Aberrant ERalpha distribution in 3K compared to wild-type mice was paired with its decreased palmitoylation. Treatment with ML348, a de-palmitoylation inhibitor, increased ERalpha availability and soluble alphaS homeostasis, ameliorating synaptic plasticity and cognitive and motor phenotypes. Our finding that sex differences in early-disease alphaS-induced synaptic impairment in 3KL mice are in part mediated by palmitoylated ERalpha may have functional and pathogenic implications for clinical PD.
ESTHER : Moors_2023_Sci.Adv_9_eadj1454
PubMedSearch : Moors_2023_Sci.Adv_9_eadj1454
PubMedID: 37976363

Title : Exploration of DPP-IV Inhibitory Peptide Design Rules Assisted by the Deep Learning Pipeline That Identifies the Restriction Enzyme Cutting Site - Guan_2023_ACS.Omega_8_39662
Author(s) : Guan C , Luo J , Li S , Tan ZL , Wang Y , Chen H , Yamamoto N , Zhang C , Lu Y , Chen J , Xing XH
Ref : ACS Omega , 8 :39662 , 2023
Abstract : The mining of antidiabetic dipeptidyl peptidase IV (DPP-IV) inhibitory peptides (DPP-IV-IPs) is currently a costly and laborious process. Due to the absence of rational peptide design rules, it relies on cumbersome screening of unknown enzyme hydrolysates. Here, we present an enhanced deep learning model called bidirectional encoder representation (BERT)-DPPIV, specifically designed to classify DPP-IV-IPs and explore their design rules to discover potent candidates. The end-to-end model utilizes a fine-tuned BERT architecture to extract structural/functional information from input peptides and accurately identify DPP-IV-Ips from input peptides. Experimental results in the benchmark data set showed BERT-DPPIV yielded state-of-the-art accuracy and MCC of 0.894 and 0.790, surpassing the 0.797 and 0.594 obtained by the sequence-feature model. Furthermore, we leveraged the attention mechanism to uncover that our model could recognize the restriction enzyme cutting site and specific residues that contribute to the inhibition of DPP-IV. Moreover, guided by BERT-DPPIV, proposed design rules for DPP-IV inhibitory tripeptides and pentapeptides were validated, and they can be used to screen potent DPP-IV-IPs.
ESTHER : Guan_2023_ACS.Omega_8_39662
PubMedSearch : Guan_2023_ACS.Omega_8_39662
PubMedID: 37901493

Title : Design, synthesis and evaluation of quinoline-O-carbamate derivatives as multifunctional agents for the treatment of Alzheimer's disease - Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
Author(s) : Chen H , Mi J , Li S , Liu Z , Yang J , Chen R , Wang Y , Ban Y , Zhou Y , Dong W , Sang Z
Ref : J Enzyme Inhib Med Chem , 38 :2169682 , 2023
Abstract : A series of novel quinoline-O-carbamate derivatives was rationally designed for treating Alzheimer's disease (AD) by multi-target-directed ligands (MTDLs) strategy. The target compounds were synthesised and evaluated by AChE/BuChE inhibition and anti-inflammatory property. The insvitro activities showed that compound 3f was a reversible dual eeAChE/eqBuChE inhibitor with IC(50) values of 1.3 microM and 0.81 microM, respectively. Moreover, compound 3f displayed good anti-inflammatory property by decreasing the production of IL-6, IL-1beta and NO. In addition, compound 3f presented significant neuroprotective effect on Abeta(25-35)-induced PC12 cell injury. Furthermore, compound 3f presented good stabilities in artificial gastrointestinal fluids, liver microsomes insvitro and plasma. Furthermore, compound 3f could improve AlCl(3)-induced zebrafish AD model by increasing the level of ACh. Therefore, compound 3f was a promising multifunctional agent for the treatment of AD.
ESTHER : Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
PubMedSearch : Chen_2023_J.Enzyme.Inhib.Med.Chem_38_2169682
PubMedID: 36688444

Title : The soluble epoxide hydrolase inhibitor TPPU improves comorbidity of chronic pain and depression via the AHR and TSPO signaling - Luo_2023_J.Transl.Med_21_71
Author(s) : Luo A , Wu Z , Li S , McReynolds CB , Wang D , Liu H , Huang C , He T , Zhang X , Wang Y , Liu C , Hammock BD , Hashimoto K , Yang C
Ref : J Transl Med , 21 :71 , 2023
Abstract : BACKGROUND: Patients suffering from chronic pain often also exhibit depression symptoms. Soluble epoxide hydrolase (sEH) inhibitors can decrease blood levels of inflammatory cytokines. However, whether inhibiting sEH signaling is beneficial for the comorbidity of pain and depression is unknown. METHODS: According to a sucrose preference test (SPT), spared nerve injury (SNI) mice were classified into pain with or without an anhedonia phenotype. Then, sEH protein expression and inflammatory cytokines were assessed in selected tissues. Furthermore, we used sEH inhibitor TPPU to determine the role of sEH in chronic pain and depression. Importantly, agonists and antagonists of aryl hydrocarbon receptor (AHR) and translocator protein (TSPO) were used to explore the pathogenesis of sEH signaling. RESULTS: In anhedonia-susceptible mice, the tissue levels of sEH were significantly increased in the medial prefrontal cortex (mPFC), hippocampus, spinal cord, liver, kidney, and gut. Importantly, serum CYP1A1 and inflammatory cytokines, such as interleukin 1beta (IL-1beta) and the tumor necrosis factor alpha (TNF-alpha), were increased simultaneously. TPPU improved the scores of mechanical withdrawal threshold (MWT) and SPT, and decreased the levels of serum CYP1A1 and inflammatory cytokines. AHR antagonist relieved the anhedonia behaviors but not the algesia behaviors in anhedonia-susceptible mice, whereas an AHR agonist abolished the antidepressant-like effect of TPPU. In addition, a TSPO agonist exerted a similar therapeutic effect to that of TPPU, whereas pretreatment with a TSPO antagonist abolished the antidepressant-like and analgesic effects of TPPU. CONCLUSIONS: sEH underlies the mechanisms of the comorbidity of chronic pain and depression and that TPPU exerts a beneficial effect on anhedonia behaviors in a pain model via AHR and TSPO signaling.
ESTHER : Luo_2023_J.Transl.Med_21_71
PubMedSearch : Luo_2023_J.Transl.Med_21_71
PubMedID: 36732752

Title : Network pharmacology combined with an animal model to reveal the material basis and mechanism of Amomum villosum in alleviating constipation in mice - Liu_2023_Gene_897_148064
Author(s) : Liu S , Zhao Y , Li S , Li Y , Liu L , Sheng J , Tian Y , Gao X
Ref : Gene , 897 :148064 , 2023
Abstract : Constipation is a prevalent gastrointestinal disorder, with its prevalence showing an annual upward trend. There are many factors involved in the occurrence of constipation, such as abnormal smooth muscle contraction and disorders of gastrointestinal hormone secretion. Amomum villosum (A. villosum) has been proven to be effective in improving digestive system diseases, but there is no report on improving constipation. Therefore, we used network pharmacology prediction combined with animal experiments to explore the key active components of A. villosum and their pharmacological mechanisms. The results of network pharmacological prediction showed that beta-sitosterol was the key laxative compound of A. villosum, which may play a laxative role by activating the adrenoceptor alpha 1 A-myosin light chain (ADRA1A-MLC) pathway. Further animal experiments showed that beta-sitosterol could significantly shorten the time to first black stool; increase faecal weight, faecal number, and faecal water content; and promote gastrointestinal motility. beta-sitosterol may promote intestinal motility by upregulating the expression of ADRA1A and myosin light chain 9 (Myl9) mRNA and protein in the colon, thereby activating the ADRA1A-MLC signalling pathway. In addition, it is possible to improve constipation symptoms by regulating serum neurotransmitters and gastrointestinal motility-related factors, such as the serum content of 5-hydroxytryptamine (5-HT) and acetylcholinesterase (AchE) and the mRNA expression of 5-hydroxytryptamine receptor 4 (5-HT4), stem cell factor (SCF), stem cell factor receptor (c-Kit) and smooth muscle myosin light chain kinase (smMLCK) in the colon. These results lay a foundation for the application of A. villosum and beta-sitosterol in constipation.
ESTHER : Liu_2023_Gene_897_148064
PubMedSearch : Liu_2023_Gene_897_148064
PubMedID: 38065427

Title : The preferential utilization of hepatic glycogen as energy substrates in largemouth bass (Micropterus salmoides) under short-term starvation - Zhang_2023_Fish.Physiol.Biochem__
Author(s) : Zhang N , Wang X , Han Z , Gong Y , Huang X , Chen N , Li S
Ref : Fish Physiol Biochem , : , 2023
Abstract : To elucidate the underlying mechanism of the energy metabolism in largemouth bass (Micropterus salmoides), cultured fish (initial body weight: 77.57 +/- 0.75 g) in the present study were starved for 0 h, 12 h, 24 h, 48 h, 96 h and 192 h, respectively. The proximate composition analysis showed that short-term starvation induced a significant up-regulation in crude protein proportion in hepatic of cultured fish (P < 0.05). However, short-term starvation significantly decreased the hepatosomatic index and the viscerosomatic index of cultured fish (P < 0.05). The exact hepatic glycogen content in the group starved for 92 h presented remarkable decrease (P < 0.05). Meanwhile, compared with the weight change of lipid and protein (mg) in hepatic (y = 0.0007x(2) - 0.2827x + 49.402; y = 0.0013x(2) - 0.5666x + 165.31), the decreasing trend of weight in glycogen (mg) was more pronounced (y = 0.0032x(2) - 1.817x + 326.52), which suggested the preferential utilization of hepatic glycogen as energy substrates under short-term starvation. Gene expression analysis revealed that the starvation down-regulated the expression of insulin-like growth factor 1 and genes of TOR pathway, such as target of rapamycin (tor) and ribosomal protein S6 (s6) (P < 0.05). In addition, the starvation significantly enhanced expression of lipolysis-related genes, including hormone-sensitive lipase (hsl) and carnitine palmitoyl transferase I (cpt1), but down-regulated lipogenesis as indicated by the inhibited expression of fatty acids synthase (fas), acetyl-CoA carboxylase 1 (acc1) and acetyl-CoA carboxylase 2 (acc2) (P < 0.05). Starvation of 24 h up-regulated the expression of glycolysis genes, glucokinase (gk), phosphofructokinase liver type (pfkl) and pyruvate kinase (pk), and then their expression returned to the normal level. Meanwhile, the expression of gluconeogenesis genes, such as glucose-6-phosphatase catalytic subunit (g6pc), fructose-1,6-bisphosphatase-1 (fbp1) and phosphoenolpyruvate carboxy kinase (pepck), was significantly inhibited with the short-term starvation (P < 0.05). In conclusion, short-term starvation induced an overall decline in growth performance, but it could deplete the hepatic glycogen accumulation and mobilize glycogen for energy effectively.
ESTHER : Zhang_2023_Fish.Physiol.Biochem__
PubMedSearch : Zhang_2023_Fish.Physiol.Biochem__
PubMedID: 38108936

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection - Wan_2022_Mikrochim.Acta_189_300
Author(s) : Wan Y , Wang H , Zhang L , Chen Y , Li S , Zhou J , Zhang Q , Xia L
Ref : Mikrochim Acta , 189 :300 , 2022
Abstract : A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples.
ESTHER : Wan_2022_Mikrochim.Acta_189_300
PubMedSearch : Wan_2022_Mikrochim.Acta_189_300
PubMedID: 35904635

Title : Neurexin-beta Mediates the Synaptogenic Activity of Amyloid Precursor Protein - Cvetkovska_2022_J.Neurosci__
Author(s) : Cvetkovska V , Ge Y , Xu Q , Li S , Zhang P , Craig AM
Ref : Journal of Neuroscience , : , 2022
Abstract : In addition to its role in Alzheimer's disease, amyloid precursor protein (APP) has physiological roles in synapse development and function. APP induces presynaptic differentiation when presented to axons but the mechanism is unknown. Here we show that APP binds neurexin to mediate this synaptogenic activity. APP specifically binds beta not alpha neurexins modulated by splice site 4. Binding to neurexin heparan sulfate glycan and LNS protein domains is required for high affinity interaction and for full-length APP to recruit axonal neurexin. The synaptogenic activity of APP is abolished by triple knockdown of neurexins in hippocampal neurons pooled from male and female rats. Based on these and previous results, our model is that a dendritic-axonal trans dimer of full-length APP binds to axonal neurexin-beta to promote synaptic differentiation and function. Furthermore, soluble sAPPs also bind neurexin-beta and inhibit its interaction with neuroligin-1, raising the possibility that disruption of neurexin function by altered levels of full-length APP and its cleavage products may contribute to early synaptic deficits in Alzheimer's disease.SIGNIFICANCE STATEMENT:The prevailing model for the basis of Alzheimer's disease is the amyloid cascade triggered by altered cleavage of amyloid precursor protein (APP). APP also has physiological roles at the synapse but the molecular basis for its synaptic functions are not well understood. Here, we show that APP binds the presynaptic organizing protein neurexin-beta and that neurexin is essential for the synaptogenic activity of APP. Furthermore, soluble APP forms generated by APP cleavage also bind neurexin-beta and can block interaction with transmembrane synaptogenic ligands of neurexin. These findings reveal a role for neurexin-APP interaction in synapse development and raise the possibility that disruptions of neurexin function may contribute to synaptic and cognitive deficits in the critical early stage of Alzheimer's disease.
ESTHER : Cvetkovska_2022_J.Neurosci__
PubMedSearch : Cvetkovska_2022_J.Neurosci__
PubMedID: 36261284

Title : Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida) - Li_2022_Environ.Toxicol.Pharmacol_97_104016
Author(s) : Li S , Yuan Y , Wang X , Cai L , Wang J , Zhao Y , Jiang L , Yang X
Ref : Environ Toxicol Pharmacol , 97 :104016 , 2022
Abstract : Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems.
ESTHER : Li_2022_Environ.Toxicol.Pharmacol_97_104016
PubMedSearch : Li_2022_Environ.Toxicol.Pharmacol_97_104016
PubMedID: 36435387

Title : The chromosome-level genome of Chinese praying mantis Tenodera sinensis (Mantodea: Mantidae) reveals its biology as a predator - Yuan_2022_Gigascience_12_
Author(s) : Yuan R , Zheng B , Li Z , Ma X , Shu X , Qu Q , Ye X , Li S , Tang P , Chen X
Ref : Gigascience , 12 : , 2022
Abstract : BACKGROUND: The Chinese praying mantis, Tenodera sinensis (Saussure), is a carnivorous insect that preys on a variety of arthropods and small vertebrates, including pest species. Several studies have been conducted to understand its behavior and physiology. However, there is limited knowledge about the genetic information underlying its genome evolution, digestive demands, and predatory behaviors. FINDINGS: Here we have assembled the chromosome-level genome of T. sinensis, representing the first sequenced genome of the family Mantidae, with a genome size of 2.54 Gb and scaffold N50 of 174.78 Mb. Our analyses revealed that 98.6% of BUSCO genes are present, resulting in a well-annotated assembly compared to other insect genomes, containing 25,022 genes. The reconstructed phylogenetic analysis showed the expected topology placing the praying mantis in an appropriate position. Analysis of transposon elements suggested the Gypsy/Dirs family, which belongs to long terminal repeat (LTR) transposons, may be a key factor resulting in the larger genome size. The genome shows expansions in several digestion and detoxification associated gene families, including trypsin and glycosyl hydrolase (GH) genes, ATP-binding cassette (ABC) transporter, and carboxylesterase (CarE), reflecting the possible genomic basis of digestive demands. Furthermore, we have found 1 ultraviolet-sensitive opsin and 2 long-wavelength-sensitive (LWS) opsins, emphasizing the core role of LWS opsins in regulating predatory behaviors. CONCLUSIONS: The high-quality genome assembly of the praying mantis provides a valuable repository for studying the evolutionary patterns of the mantis genomes and the gene expression profiles of insect predators.
ESTHER : Yuan_2022_Gigascience_12_
PubMedSearch : Yuan_2022_Gigascience_12_
PubMedID: 37882605

Title : Acetylcholinesterase Inhibition Assays for High-Throughput Screening - Li_2022_Methods.Mol.Biol_2474_47
Author(s) : Li S , Li AJ , Zhao J , Santillo MF , Xia M
Ref : Methods Mol Biol , 2474 :47 , 2022
Abstract : Acetylcholinesterase (AChE) hydrolyzes acetylcholine (ACh), a vital neurotransmitter that regulates muscle movement and brain function, including memory, attention, and learning. Inhibition of AChE activity can cause a variety of adverse health effects and toxicity. Identifying AChE inhibitors quickly and efficiently warrants developing AChE inhibition assays in a quantitative, high-throughput screening (qHTS) platform. In this chapter, protocols for multiple homogenous AChE inhibition assays used in a qHTS system are provided. These AChE inhibition assays include a (1) human neuroblastoma (SH-SY5Y) cell-based assay with fluorescence or colorimetric detection; (2) human recombinant AChE with fluorescence or colorimetric detection; and (3) combination of human recombinant AChE and liver microsomes with colorimetric detection, which enables detection of test compounds requiring metabolic activation to become AChE inhibitors. Together, these AChE assays can help identify, prioritize, and predict chemical hazards in large compound libraries using qHTS systems.
ESTHER : Li_2022_Methods.Mol.Biol_2474_47
PubMedSearch : Li_2022_Methods.Mol.Biol_2474_47
PubMedID: 35294755

Title : An artificial self-assembling peptide with carboxylesterase activity and substrate specificity restricted to short-chain acid p-nitrophenyl esters - Liu_2022_Front.Chem_10_996641
Author(s) : Liu Y , Gan L , Feng P , Huang L , Chen L , Li S , Chen H
Ref : Front Chem , 10 :996641 , 2022
Abstract : Natural enzymes possess remarkable catalytic activity and high substrate specificity. Many efforts have been dedicated to construct artificial enzymes with high catalytic activity. However, how to mimic the exquisite substrate specificity of a natural enzyme remains challenging because of the complexity of the enzyme structure. Here, we report artificial carboxylesterases that are specific for short chain fatty acids and were constructed via peptide self-assembly. These artificial systems have esterase-like activity rather than lipase-like activity towards p-nitrophenyl esters. The designer peptides self-assembled into nanofibers with strong beta-sheet character. The extending histidine units and the hydrophobic edge of the fibrillar structure collectively form the active center of the artificial esterase. These artificial esterases show substrate specificity for short-chain acids esters. Moreover, 1-isopropoxy-4-nitrobenzene could function as a competitive inhibitor of hydrolysis of p-nitrophenyl acetate for an artificial esterase.
ESTHER : Liu_2022_Front.Chem_10_996641
PubMedSearch : Liu_2022_Front.Chem_10_996641
PubMedID: 36199662

Title : Rapid screening for acetylcholinesterase inhibitors in Selaginella doederleinii Hieron by using functionalized magnetic Fe(3)O(4) nanoparticles - Zhang_2022_Talanta_243_123284
Author(s) : Zhang F , Li S , Liu C , Fang K , Jiang Y , Zhang J , Lan J , Zhu L , Pang H , Wang G
Ref : Talanta , 243 :123284 , 2022
Abstract : Insufficient acetylcholine (ACh) can cause cognitive and memory dysfunction, clinically known as, Alzheimer's disease (AD). Acetylcholinesterase (AChE) can hydrolyze ACh into acetic acid and inactivate choline. Therefore, inhibiting the activity of AChE would help to improve the effectiveness of AD treatment. Currently, the methods for rapid screening of AChE inhibitors are limited. This study reports the application of AChE-immobilized magnetic nanoparticles as a drug screening tool to screen AChE inhibitors for natural products. First, AChE was immobilized on a surface of amino-modified magnetic nanoparticles using covalent binding and the AChE concentration, and the pH as well as time was optimized to obtain the maximum enzyme immobilization yield (61.4 microg/mg), and the kinetic model indicated that AChE-immobilized magnetic nanoparticles and the substrate had the high affinity and specificity. Then, a ligand fishing experiment was carried out using a mixed model of tacrine (an inhibitor of AChE) and caffeic acid (a non-inhibitor of AChE) to verify the specificity of the immobilized AChE, and the conditions for ligand fishing were further optimized. Finally, the optimized immobilized AChE was combined with UPLC-MS to screen for AChE inhibitors in Selaginella doederleinii Hieron extracts. Four compounds were confirmed to be potent AChE inhibitors. Among the four compounds, amentoflavone had a stronger AChE inhibitory effect than tacrine (positive control) with an IC(50) of 0.73 +/- 0.009 micromol/L. The results showed that AChE-functionalized magnetic nanoparticles can be used in the discovery of target drugs from complex matrices.
ESTHER : Zhang_2022_Talanta_243_123284
PubMedSearch : Zhang_2022_Talanta_243_123284
PubMedID: 35255433

Title : Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection - Pang_2022_Cell.Rep_39_110698
Author(s) : Pang Y , Cheng Z , Zhang S , Li S , Li X , Zhang X , Feng Y , Cui H , Chen Z , Liu L , Li Q , Huang J , Zhang M , Zhu S , Wang L , Feng L
Ref : Cell Rep , 39 :110698 , 2022
Abstract : Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection.
ESTHER : Pang_2022_Cell.Rep_39_110698
PubMedSearch : Pang_2022_Cell.Rep_39_110698
PubMedID: 35443182

Title : The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study - Wu_2022_Food.Res.Int_158_111497
Author(s) : Wu M , Liu M , Wang F , Cai J , Luo Q , Li S , Zhu J , Tang Z , Fang Z , Wang C , Chen H
Ref : Food Res Int , 158 :111497 , 2022
Abstract : The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC(50) values of 0.1974 +/- 0.0047, 0.2589 +/- 0.0131, 1.0905 +/- 0.0598 and 1.503 +/- 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of alpha-helix and reducing beta-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.
ESTHER : Wu_2022_Food.Res.Int_158_111497
PubMedSearch : Wu_2022_Food.Res.Int_158_111497
PubMedID: 35840206

Title : Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe - Yang_2022_Anal.Chem__
Author(s) : Yang Y , Zhang L , Wang J , Cao Y , Li S , Qin W , Liu Y
Ref : Analytical Chemistry , : , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases.
ESTHER : Yang_2022_Anal.Chem__
PubMedSearch : Yang_2022_Anal.Chem__
PubMedID: 36121878

Title : An efficient strategy based on two-stage chromatography and in vitro evaluation for rapid screening and isolation of acetylcholinesterase inhibitors from Scutellaria baicalensis Georgi - Hou_2022_J.Sep.Sci__
Author(s) : Hou W , Liu C , Li S , Zhang Y , Jin Y , Li X , Liu Z , Niu H , Xia J
Ref : J Sep Sci , : , 2022
Abstract : The extraction of Scutellaria baicalensis Georgi was investigated using the response surface methodology-genetic algorithm mathematical regression model, and the extraction variables were optimized to maximize the flavonoid yield. Furthermore, a simple and efficient ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods was developed for the rapid screening and identification of acetylcholinesterase inhibitors present in Scutellaria baicalensis Georgi. Subsequently, four major chemical constituents, namely baicalein, norwogonin, wogonin, and oroxylin A, were identified as potent acetylcholinesterase inhibitors. This novel approach, involving the use of ultrafiltration-liquid chromatography-mass spectrometry and molecular docking methods combined with stepwise flow rate counter-current chromatography and semi-preparative high-performance liquid chromatography, could potentially provide a powerful tool for the screening and extraction of acetylcholinesterase inhibitors from complex matrices and be a useful platform for the production of bioactive and nutraceutical ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Hou_2022_J.Sep.Sci__
PubMedSearch : Hou_2022_J.Sep.Sci__
PubMedID: 34990521

Title : Water-soluble non-conjugated polymer dots with strong green fluorescence for sensitive detection of organophosphate pesticides - Zhang_2022_Anal.Chim.Acta_1206_339792
Author(s) : Zhang C , Li S , Duan Z , Li Q , Zhao M , Chen Y , Zhai X , Mao G , Wang H
Ref : Anal Chim Acta , 1206 :339792 , 2022
Abstract : Water-soluble non-conjugated polymer dots (PDs) have been synthesized using hyperbranched polyethyleneimine (PEI) and dihydroxybenzaldehyde (DHB) for the first time via the Schiff base reaction at room temperature. The yielded non-conjugated PDs of PEI-DHB could display the well-defined spheric structure and good water solubility. In contrast to the common PDs otherwise showing blue emission, the PEI-DHB PDs could give out strong green fluorescence in aqueous media. Especially, the fluorescence of the PEI-DHB PDs could be specifically quenched by MnO(2) nanosheets through the inner filter effects and further restored by the thiocholine that could reduce MnO(2) nanosheets into Mn(2+). Herein, thiocholine could be produced in hydrolysis reaction of acetylthiocholine catalyzed by the acetylcholinesterase (AChE), of which the catalytic activity could be irreversibly inhibitted by the introduction of organophosphates. A highly selective fluorimetric method was thereby been developed for the detection of organophosphorus pesticides using dimethyl-dichloro-vinyl phosphate as a model. The linear concentrations ranges from 0.050 to 2.5 microM. Importantly, the non-conjugated PDs probes with strong green fluorescence and high water solubility may promise the extensive applications in the environmental, food, and clinical analysis fields.
ESTHER : Zhang_2022_Anal.Chim.Acta_1206_339792
PubMedSearch : Zhang_2022_Anal.Chim.Acta_1206_339792
PubMedID: 35473871

Title : Hepatocellular BChE as a therapeutic target to ameliorate hypercholesterolemia through PRMT5 selective degradation to restore LDL receptor transcription - Wang_2022_Life.Sci_293_120336
Author(s) : Wang D , Tan KS , Zeng W , Li S , Wang Y , Xu F , Tan W
Ref : Life Sciences , 293 :120336 , 2022
Abstract : AIMS: Individuals with nonalcoholic hepatosteatosis (NAFLD) have a worse atherogenic lipoprotein profile and are susceptible to cardiovascular diseases. The MEK-ERK signaling cascades are central regulators of the levels of LDL receptor (LDLR), a major determinant of circulating cholesterol. It is elusive how hepatic steatosis contributes to dyslipidemia, especially hypercholesterolemia. MAIN METHODS: The effects of BChE on signaling pathways were determined by immunoblotting in a BChE knockout hepatocyte cell line. DiI-LDL probe was used to explore the effect of BChE expression on LDL internalization. Co-immunoprecipitation and LC-MS were used to explore the interacting proteins with BChE. Finally, a hepatocyte-restricted BChE silencing mouse model was established by AAV8-Tbg-shRNA, and the hypercholesterolemia was induced by 65% kcal% high-fat, high-sucrose diet feeding. MAIN FINDINGS: Here we demonstrate that butyrylcholinesterase (BChE) governs the LDL receptor levels and LDL uptake capacity through the MEK-ERK signaling cascades to promote Ldlr transcription. BChE interacts and co-localizes with PRMT5, a protein methylation modifier controlling the ERK signaling. PRMT5 regulates LDLR-dependent LDL uptake and is a substrate of chaperone-mediated autophagy (CMA). BChE deficiency induces the PRTM5 degradation dependent on CMA activity, possibly through facilitating the HSC70 (Heat shock cognate 71 kDa) recognition of PRMT5. Remarkably, in vivo hepatocyte-restricted BChE silencing reduces plasma cholesterol levels substantially. In contrast, the BChE knockout mice are predisposed to hypercholesterolemia. SIGNIFICANCE: Taken together, these findings outline a regulatory role for the BChE-PRMT5-ERK-LDLR axis in hepatocyte cholesterol metabolism, and suggest that targeting liver BChE is an effective therapeutic strategy to treat hypercholesterolemia.
ESTHER : Wang_2022_Life.Sci_293_120336
PubMedSearch : Wang_2022_Life.Sci_293_120336
PubMedID: 35065166

Title : Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors - Tian_2022_Bioorg.Chem_127_105898
Author(s) : Tian Y , Li S , Dong K , Su X , Fu S , Lv X , Duan M , Yang T , Han Y , Hu G , Liu J , Sun Y , Yue H , Zhang H , Du Z , Miao Z , Tong M , Liu Y , Qin M , Gong P , Hou Y , Gao Z , Zhao Y
Ref : Bioorg Chem , 127 :105898 , 2022
Abstract : The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC(50) value of 0.04 +/- 0.01 nM and a K(i) value of 0.2 +/- 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors.
ESTHER : Tian_2022_Bioorg.Chem_127_105898
PubMedSearch : Tian_2022_Bioorg.Chem_127_105898
PubMedID: 35792317

Title : Genome-wide expression analysis of carboxylesterase (CXE) gene family implies GBCXE49 functional responding to alkaline stress in cotton - Rui_2022_BMC.Plant.Biol_22_194
Author(s) : Rui C , Peng F , Fan Y , Zhang Y , Zhang Z , Xu N , Zhang H , Wang J , Li S , Yang T , Malik WA , Lu X , Chen X , Wang D , Chen C , Gao W , Ye W
Ref : BMC Plant Biol , 22 :194 , 2022
Abstract : BACKGROUND: Carboxylesterase (CXE) is a type of hydrolase with alpha/beta sheet hydrolase activity widely found in animals, plants and microorganisms, which plays an important role in plant growth, development and resistance to stress. RESULTS: A total of 72, 74, 39, 38 CXE genes were identified in Gossypium barbadense, Gossypium hirsutum, Gossypium raimondii and Gossypium arboreum, respectively. The gene structure and expression pattern were analyzed. The GBCXE genes were divided into 6 subgroups, and the chromosome distribution of members of the family were mapped. Analysis of promoter cis-acting elements showed that most GBCXE genes contain cis-elements related to plant hormones (GA, IAA) or abiotic stress. These 6 genes we screened out were expressed in the root, stem and leaf tissues. Combined with the heat map, GBCXE49 gene was selected for subcellular locate and confirmed that the protein was expressed in the cytoplasm. CONCLUSIONS: The collinearity analysis of the CXE genes of the four cotton species in this family indicated that tandem replication played an indispensable role in the evolution of the CXE gene family. The expression patterns of GBCXE gene under different stress treatments indicated that GBCXE gene may significantly participate in the response to salt and alkaline stress through different mechanisms. Through the virus-induced gene silencing technology (VIGS), it was speculated that GBCXE49 gene was involved in the response to alkaline stress in G. barbadense.
ESTHER : Rui_2022_BMC.Plant.Biol_22_194
PubMedSearch : Rui_2022_BMC.Plant.Biol_22_194
PubMedID: 35413814

Title : Acute effects of antimony exposure on adult zebrafish (Danio rerio): From an oxidative stress and intestinal microbiota perspective - Wang_2022_Fish.Shellfish.Immunol_123_1
Author(s) : Wang C , Yuan Z , Li J , Liu Y , Li R , Li S
Ref : Fish Shellfish Immunol , 123 :1 , 2022
Abstract : The rapid development of the textile industry has resulted in a large influx of wastewater production. The "national discharge standards of water pollutants for dyeing and finishing of textile industry (GB4287-2012)" stipulates that the discharge of total Sb from textile industry effluent must be < 0.10 mg/L, but it is difficult to meet the standard at present. Antimony is potentially carcinogenic, and the pathogenic mechanism of antimony is poorly understood. In this study, the acute toxic effects of various concentrations of antimony on adult zebrafish (Danio rerio) were investigated, including effects on oxidative stress, neurotransmitters and intestinal microbiota. The activities of catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and acetylcholinesterase (AChE) were measured in zebrafish muscle and intestine tissue samples. In addition, intestinal microbial community composition and diversity of zebrafish were also analyzed. The results demonstrated that SOD, CAT and GSH-Px activities in the zebrafish gut showed a decreasing and then increasing trend with antimony concentration increasing. SOD, CAT and MDA in zebrafish muscle decreased with increasing exposure time. GSH-Px activities increased with increasing exposure time. T-AOC increased and then decreased. In addition, antimony exposure was neurotoxic to zebrafish, and a significant decrease in AChE activity was found in the intestine with increased exposure time. The neurotoxicity caused by antimony in the high concentration group (40 mg/L) was stronger than that in low concentration groups (10 mg/L and 20 mg/L). Notably, antimony exposure caused increases in the relative abundance of phyla Fusobacteriota and Actinomycetes, but decreases in the relative abundance of the phyla Firmicutes and Proteobacteria in zebrafish intestine. These outcomes will advance our understanding of antimony-induced biotoxicity, environmental problems, and health hazards. In conclusion, this study shows that acute exposure of antimony to zebrafish induces host oxidative stress and neurotoxicity, dysregulates the intestinal microbiota, showing adverse effects on the health and gut microbiota of zebrafish.
ESTHER : Wang_2022_Fish.Shellfish.Immunol_123_1
PubMedSearch : Wang_2022_Fish.Shellfish.Immunol_123_1
PubMedID: 35219828

Title : The Composition and Anti-Aging Activities of Polyphenol Extract from Phyllanthus emblica L. Fruit - Wu_2022_Nutrients_14_
Author(s) : Wu M , Cai J , Fang Z , Li S , Huang Z , Tang Z , Luo Q , Chen H
Ref : Nutrients , 14 : , 2022
Abstract : Phyllanthus emblica L. (PE) is commonly known as a medicine and food homologous plant, which is abundant in natural products polyphenols. In the present study, polyphenols were extracted from PE fruit by response surface method, and the anti-aging ability was determined. PE fruit polyphenols exhibited strong antioxidant capacities in scavenging free radicals, and anti-cholinesterase ability by inhibition of AChE (IC(50) 0.2186 +/- 0.0416 mg/mL) and BuChE (IC(50) 0.0542 +/- 0.0054 mg/mL) in vitro. Moreover, PE fruit polyphenols showed strong protective effect against the aging process in Caenorhabditis elegans model, including increased thermal resistance, extended lifespan by 18.53% (p < 0.05), reduced activity of AChE by 34.71% and BuChE by 45.38% (p < 0.01). This was accompanied by the enhancement in antioxidant enzymes activity of SOD by 30.74% (p < 0.05) and CAT by 8.42% (p > 0.05), while decrease in MDA level by 36.25% (p < 0.05). These properties might be interrelated with the presence of abundant flavonols and phenolic acids identified by UPLC-ESI-QTOF-MS, such as quercetin, myricetin, ellagic, gallic, and chlorogenic acids, together with their glycosides. The remarkable antioxidant and anti-aging potential of PE fruit polyphenols could be implemented in the food and pharmaceutical industry.
ESTHER : Wu_2022_Nutrients_14_
PubMedSearch : Wu_2022_Nutrients_14_
PubMedID: 35215512

Title : Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors - Tian_2022_Bioorg.Med.Chem.Lett_70_128805
Author(s) : Tian Y , Li S , Yang P , Su X , Liu J , Lv X , Dong K , Yang T , Duan M , Hu G , Yue H , Sun Y , Zhang H , Du Z , Miao Z , Tong M , Hou Y , Gao Z , Zhao Y
Ref : Bioorganic & Medicinal Chemistry Lett , 70 :128805 , 2022
Abstract : The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC(50) value of 0.03 +/- 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief.
ESTHER : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedSearch : Tian_2022_Bioorg.Med.Chem.Lett_70_128805
PubMedID: 35598794

Title : MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR - Wang_2022_Front.Vet.Sci_9_948873
Author(s) : Wang J , Hao Z , Hu L , Qiao L , Luo Y , Hu J , Liu X , Li S , Zhao F , Shen J , Li M , Zhao Z
Ref : Front Vet Sci , 9 :948873 , 2022
Abstract : In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep.
ESTHER : Wang_2022_Front.Vet.Sci_9_948873
PubMedSearch : Wang_2022_Front.Vet.Sci_9_948873
PubMedID: 35990270

Title : Extraction and preparation of 5-lipoxygenase and acetylcholinesterase inhibitors from Astragalus membranaceus stems and leaves - Liu_2022_J.Sep.Sci__
Author(s) : Liu R , Zhang Y , Li S , Liu C , Zhuang S , Zhou X , Li Y , Liang J
Ref : J Sep Sci , : , 2022
Abstract : In this study, an efficient method that employs 5-lipoxygenase and acetylcholinesterase as biological target molecules in receptor-ligand affinity ultrafiltration-liquid chromatography was developed for the screening of enzyme inhibitors derived from the Astragalus membranaceus stems and leaves. The effects of the extraction time, number of extraction cycles, ethanol concentration, and liquid-solid ratio on the total yield of the target compounds were investigated using response surface methodology, and the bioactive components were isolated using a combination of semi-preparative high-performance liquid chromatography and high-speed countercurrent chromatography via a two-phase solvent system consisting of n-hexane-ethyl acetate-methanol-water (1:6:2:6, v/v/v/v). Subsequently, ten naturally-occurring bioactive components in the Astragalus membranaceus stems and leaves, including wogonin, ononin, isoquercitrin, calycosin-7-glucoside, 3-hydroxy-9,10-dimethoxyptercarpan, hyperoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, baicalein, calycosin, and soyasaponin, were screened using affinity ultrafiltration to determine their potential effects against Alzheimer's disease. Consequently, all target compounds had purities higher than 95.0%, and the potential anti-Alzheimer's disease effect of the obtained bioactive compounds was verified using molecular docking analysis. Based on the results, the back-to-back screening of complex enzyme inhibitors and separation of the target bioactive compounds using complex chromatography could provide a new approach for the discovery and preparation of natural active ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2022_J.Sep.Sci__
PubMedSearch : Liu_2022_J.Sep.Sci__
PubMedID: 36502278

Title : Characterization of 4 deletion mutants of Pseudomonas plecoglossicida and their potential for live attenuated vaccines in large yellow croaker (Larimichthys crocea) - Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
Author(s) : Li Y , Chi Y , Li S , Jia T , Mao Z
Ref : Fish Shellfish Immunol , : , 2022
Abstract : To search for live attenuated vaccines (LAV) candidates against Pseudomonas plecoglossicida, the causative agent of the visceral granulomas disease in farmed large yellow croaker (Larimichthys crocea), two type VI secretion systems (T6SS) and a predicted alpha/beta fold family hydrolase encoding gene, ORF4885 were targeted to construct deletion mutants. The biological profiles of 4 mutants were characterized; LD50 to the croakers detected, in vivo survival post-infection investigated relative percent of survival (RPS) of the croakers 28d post-vaccination determined, and transcription of five immunity-related genes of the treated fish was quantified. On comparison to the WT, the mutants revealed similar growth curves in 11h; swarming motility of delta4885 declined significantly at 72h post-incubation (P < 0.05); deltaS1delta4885 showed significantly poor biofilm formation and weak resistance to fish serum bactericidal activity (P < 0.05). LD50 of the mutants were much higher than the WT, indication of strong virulence attenuation; in vivo survival test showed the mutant deltaS1delta4885 and deltaS1deltaS3 were eliminated by the host 10d post-infection, demonstration of the safety and potentiality to be LAV candidates. Immunization with the mutant deltaS1delta4885 provided higher RPS than deltaS1deltaS3. Transcription of IgT was significant in all immunized groups while IgM increased only in intraperitoneally injected groups. This study successfully searched a quite safe and strong immunogenic LAV candidate to defeat P. plecoglossicida infection.
ESTHER : Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
PubMedSearch : Li_2022_Fish.Shellfish.Immunol_S1050-4648_00352
PubMedID: 35752370
Gene_locus related to this paper: 9psed-s2k464

Title : A hypothesis-driven study to comprehensively investigate the association between genetic polymorphisms in EPHX2 gene and cardiovascular diseases: findings from the UK Biobank - Zhu_2022_Gene_822_146340
Author(s) : Zhu X , Li Y , Yu T , Li S , Chen M
Ref : Gene , :146340 , 2022
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are protective factors against cardiovascular diseases (CVDs) because of their vasodilatory, cholesterol-lowering, and anti-inflammatory effects. Soluble epoxide hydrolase (sEH), encoded by the EPHX2 gene, degrades EETs into less biologically active metabolites. EPHX2 is highly polymorphic, and genetic polymorphisms in EPHX2 have been linked to various types of CVDs, such as coronary heart disease, essential hypertension, and atrial fibrillation recurrence. METHODS: Based on a priori hypothesis that EPHX2 genetic polymorphisms play an important role in the pathogenesis of CVDs, we comprehensively investigated the associations between 210 genetic polymorphisms in the EPHX2 gene and an array of 118 diseases in the circulatory system using a large sample from the UK Biobank (N=307,516). The diseases in electronic health records were mapped to the phecode system, which was more representative of independent phenotypes. Survival analyses were employed to examine the effects of EPHX2 variants on CVD incidence, and a phenome-wide association study was conducted to study the impact of EPHX2 polymorphisms on 62 traits, including blood pressure, blood lipid levels, and inflammatory indicators. RESULTS: A novel association between the intronic variant rs116932590 and the phenotype "aneurysm and dissection of heart" was identified. In addition, the rs149467044 and rs200286838 variants showed nominal evidence of association with arterial aneurysm and cerebrovascular disease, respectively. Furthermore, the variant rs751141, which was linked with a lower hydrolase activity of sEH, was significantly associated with metabolic traits, including blood levels of triglycerides, creatinine, and urate. CONCLUSIONS: Multiple novel associations observed in the present study highlight the important role of EPHX2 genetic variation in the pathogenesis of CVDs.
ESTHER : Zhu_2022_Gene_822_146340
PubMedSearch : Zhu_2022_Gene_822_146340
PubMedID: 35183688

Title : In Situ Formation of o-Phenylenediamine Cascade Polymers Mediated by Metal-Organic Framework Nanozymes for Fluorescent and Photothermal Dual-Mode Assay of Acetylcholinesterase Activity - Li_2022_Anal.Chem__
Author(s) : Li S , Wei Z , Xiong L , Xu Q , Yu L , Xiao Y
Ref : Analytical Chemistry , : , 2022
Abstract : A fluorescent and photothermal dual-mode assay method was established for the detection of acetylcholinesterase (AChE) activity based on in situ formation of o-phenylenediamine (oPD) cascade polymers. First, copper metal-organic frameworks of benzenetricarboxylic acid (Cu-BTC) were screened out as nanozymes with excellent oxidase-like activity and confinement catalysis effect. Then, an ingenious oPD cascade polymerization strategy was proposed. That is, oPD was oxidized by Cu-BTC to oPD oligomers with strong yellow fluorescence, and oPD oligomers were further catalyzed to generate J-aggregation, which promotes the formation of oPD polymer nanoparticles with a high photothermal effect. By utilizing thiocholine (enzymolysis product of acetylthiocholine) to inhibit the Cu-BTC catalytic effect, AChE activity was detected through the fluorescence-photothermal dual-signal change of oPD oligomers and polymer nanoparticles. Both assay modes have low detection limitation (0.03 U L(-1) for fluorescence and 0.05 U L(-1) for photothermal) and can accurately detect the AChE activity of human serum (recovery 85.0-111.3%). The detection results of real serum samples by fluorescent and photothermal dual modes are consistent with each other (relative error >= 5.2%). It is worth emphasizing that this is the first time to report the high photothermal effect of oPD polymers and the fluorescence-photothermal dual-mode assay of enzyme activity.
ESTHER : Li_2022_Anal.Chem__
PubMedSearch : Li_2022_Anal.Chem__
PubMedID: 36463539

Title : Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA - Liu_2022_Plant.Cell_34_3301
Author(s) : Liu T , Zhang X , Zhang H , Cheng Z , Liu J , Zhou C , Luo S , Luo W , Li S , Xing X , Chang Y , Shi C , Ren Y , Zhu S , Lei C , Guo X , Wang J , Zhao Z , Wang H , Zhai H , Lin Q , Wan J
Ref : Plant Cell , 34 :3301 , 2022
Abstract : Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development.
ESTHER : Liu_2022_Plant.Cell_34_3301
PubMedSearch : Liu_2022_Plant.Cell_34_3301
PubMedID: 35670739

Title : A metabolic CRISPR-Cas9 screen in Chinese hamster ovary cells identifies glutamine-sensitive genes - Karottki_2021_Metab.Eng_66_114
Author(s) : Karottki KJC , Hefzi H , Li S , Pedersen LE , Spahn PN , Joshi C , Ruckerbauer D , Bort JAH , Thomas A , Lee JS , Borth N , Lee GM , Kildegaard HF , Lewis NE
Ref : Metab Eng , 66 :114 , 2021
Abstract : Media and feed optimization have fueled many-fold improvements in mammalian biopharmaceutical production, but genome editing offers an emerging avenue for further enhancing cell metabolism and bioproduction. However, the complexity of metabolism, involving thousands of genes, makes it unclear which engineering strategies will result in desired traits. Here we present a comprehensive pooled CRISPR screen for CHO cell metabolism, including ~16,000 gRNAs against ~2500 metabolic enzymes and regulators. Using this screen, we identified a glutamine response network in CHO cells. Glutamine is particularly important since it is often over-fed to drive increased TCA cycle flux, but toxic ammonia may accumulate. With the screen we found one orphan glutamine-responsive gene with no clear connection to our network. Knockout of this novel and poorly characterized lipase, Abhd11, substantially increased growth in glutamine-free media by altering the regulation of the TCA cycle. Thus, the screen provides an invaluable targeted platform to comprehensively study genes involved in any metabolic trait, and elucidate novel regulators of metabolism.
ESTHER : Karottki_2021_Metab.Eng_66_114
PubMedSearch : Karottki_2021_Metab.Eng_66_114
PubMedID: 33813034
Gene_locus related to this paper: human-ABHD11

Title : Identification of Compounds for Butyrylcholinesterase Inhibition - Li_2021_SLAS.Discov__24725552211030897
Author(s) : Li S , Li AJ , Travers J , Xu T , Sakamuru S , Klumpp-Thomas C , Huang R , Xia M
Ref : SLAS Discov , :24725552211030897 , 2021
Abstract : Butyrylcholinesterase (BChE) is a nonspecific cholinesterase enzyme that hydrolyzes choline-based esters. BChE plays a critical role in maintaining normal cholinergic function like acetylcholinesterase (AChE) through hydrolyzing acetylcholine (ACh). Selective BChE inhibition has been regarded as a viable therapeutic approach in Alzheimer's disease. As of now, a limited number of selective BChE inhibitors are available. To identify BChE inhibitors rapidly and efficiently, we have screened 8998 compounds from several annotated libraries against an enzyme-based BChE inhibition assay in a quantitative high-throughput screening (qHTS) format. From the primary screening, we identified a group of 125 compounds that were further confirmed to inhibit BChE activity, including previously reported BChE inhibitors (e.g., bambuterol and rivastigmine) and potential novel BChE inhibitors (e.g., pancuronium bromide and NNC 756), representing diverse structural classes. These BChE inhibitors were also tested for their selectivity by comparing their IC(50) values in BChE and AChE inhibition assays. The binding modes of these compounds were further studied using molecular docking analyses to identify the differences between the interactions of these BChE inhibitors within the active sites of AChE and BChE. Our qHTS approach allowed us to establish a robust and reliable process to screen large compound collections for potential BChE inhibitors.
ESTHER : Li_2021_SLAS.Discov__24725552211030897
PubMedSearch : Li_2021_SLAS.Discov__24725552211030897
PubMedID: 34269114

Title : Structural basis for substrate specificity of the peroxisomal acyl-CoA hydrolase MpaH' involved in mycophenolic acid biosynthesis - You_2021_FEBS.J_288_5768
Author(s) : You C , Li F , Zhang X , Ma L , Zhang YZ , Zhang W , Li S
Ref : Febs J , 288 :5768 , 2021
Abstract : Mycophenolic acid (MPA) is a fungal natural product and first-line immunosuppressive drug for organ transplantations and autoimmune diseases. In the compartmentalized biosynthesis of MPA, the acyl-coenzyme A (CoA) hydrolase MpaH' located in peroxisomes catalyzes the highly specific hydrolysis of MPA-CoA to produce the final product MPA. The strict substrate specificity of MpaH' not only averts undesired hydrolysis of various cellular acyl-CoAs, but also prevents MPA-CoA from further peroxisomal beta-oxidation catabolism. To elucidate the structural basis for this important property, in this study, we solve the crystal structures of the substrate-free form of MpaH' and the MpaH'(S139A) mutant in complex with the product MPA. The MpaH' structure reveals a canonical alpha/beta-hydrolase fold with an unusually large cap domain and a rare location of the acidic residue D163 of catalytic triad after strand beta6. MpaH' also forms an atypical dimer with the unique C-terminal helices alpha13 and alpha14 arming the cap domain of the other protomer and indirectly participating in the substrate binding. With these characteristics, we propose that MpaH' and its homologues form a new subfamily of alpha/beta hydrolase fold protein. The crystal structure of MpaH'(S139A) /MPA complex and the modelled structure of MpaH'/MPA-CoA, together with the structure-guided mutagenesis analysis and isothermal titration calorimetry (ITC) measurements provide important mechanistic insights into the high substrate specificity of MpaH'.
ESTHER : You_2021_FEBS.J_288_5768
PubMedSearch : You_2021_FEBS.J_288_5768
PubMedID: 33843134
Gene_locus related to this paper: penbr-mpaH

Title : Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota - Zhang_2021_Environ.Pollut_277_116767
Author(s) : Zhang J , Meng H , Kong X , Cheng X , Ma T , He H , Du W , Yang S , Li S , Zhang L
Ref : Environ Pollut , 277 :116767 , 2021
Abstract : Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 microm and 9-Nitroanthracene (9-NAnt, 5 and 500 microg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works.
ESTHER : Zhang_2021_Environ.Pollut_277_116767
PubMedSearch : Zhang_2021_Environ.Pollut_277_116767
PubMedID: 33640823

Title : Carveol Attenuates Seizure Severity and Neuroinflammation in Pentylenetetrazole-Kindled Epileptic Rats by Regulating the Nrf2 Signaling Pathway - Alvi_2021_Oxid.Med.Cell.Longev_2021_9966663
Author(s) : Alvi AM , Al Kury LT , Alattar A , Ullah I , Muhammad AJ , Alshaman R , Shah FA , Khan AU , Feng J , Li S
Ref : Oxid Med Cell Longev , 2021 :9966663 , 2021
Abstract : Epilepsy is a neurodegenerative brain disorder characterized by recurrent seizure attacks. Numerous studies have suggested a strong correlation between oxidative stress and neuroinflammation in several neurodegenerative disorders including epilepsy. This study is aimed at investigating the neuroprotective effects of the natural compound carveol against pentylenetetrazole- (PTZ-) induced kindling and seizure model. Two different doses of carveol (10 mg/kg and 20 mg/kg) were administered to male rats to determine the effects and the effective dose of carveol and to further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in PTZ-induced kindling model. Our results demonstrated reduced levels of innate antioxidants such as superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), and glutathione (GSH), associated with elevated lipid peroxidation (LPO) and inflammatory cytokines level such as tumor necrosis factor-alpha (TNF-alpha), and mediators like cyclooxygenase (COX-2) and nuclear factor kappa B (NFkappaB). These detrimental effects exacerbated oxidative stress and provoked a marked neuronal alteration in the cortex and hippocampus of PTZ-intoxicated animals that were associated with upregulated Nrf2 gene expression. Furthermore, carveol treatment positively modulated the antioxidant gene Nrf2 and its downstream target HO-1. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated PTZ toxicity. Moreover, carveol treatment induced cholinergic system activation by mitigating acetylcholinesterase level which is further linked to attenuated neuroinflammatory cascade. The extent of blood-brain barrier disruption was evaluated based on vascular endothelial growth factor (VEGF) expression. Taken together, our findings suggest that carveol acts as an Nrf2 activator and therefore induces downstream antioxidants and mitigates inflammatory insults through multiple pathways. This eventually alleviates PTZ-induced neuroinflammation and neurodegeneration.
ESTHER : Alvi_2021_Oxid.Med.Cell.Longev_2021_9966663
PubMedSearch : Alvi_2021_Oxid.Med.Cell.Longev_2021_9966663
PubMedID: 34422216

Title : The Enhancement Effect of Acetylcholine and Pyridostigmine on Bone-Tendon Interface Healing in a Murine Rotator Cuff Model - Wang_2021_Am.J.Sports.Med__363546520988680
Author(s) : Wang Z , Chen Y , Xiao H , Li S , Zhang T , Hu J , Lu H , Xie H
Ref : Am J Sports Med , :363546520988680 , 2021
Abstract : BACKGROUND: How to improve rotator cuff healing remains a challenge. Little is known about the effect of the parasympathetic transmitter acetylcholine (ACh) and the acetylcholinesterase inhibitor pyridostigmine (PYR), both of which have anti-inflammatory properties, in the healing process of rotator cuff injury. HYPOTHESIS: ACh and PYR could enhance bone-tendon interface healing in a murine model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 160 C57BL/6 mice underwent unilateral rotator cuff repair surgery. Fibrin gel (FG) was used as a drug carrier. The mice were randomly assigned to 4 groups with 40 mice per group: FG group (received FG alone), 10(-5) M ACh group (received FG containing 10(-5) M ACh), 10(-6) M ACh group (received FG containing 10(-6) M ACh), and PYR group (received FG containing 25 microg of PYR). Ten mice in each group were euthanized at 2, 4, 8, and 12 weeks postoperatively. Histologic, immunohistochemical, and biomechanical evaluations were performed for analysis. RESULTS: Histologically, fibrocartilage-like tissue was shown at the repaired site. The proteoglycan content of the 10(-5) M ACh group was significantly increased compared with the FG group at 4 weeks. M2 macrophages were identified at the repaired site for all groups at 2 and 4 weeks. At 8 weeks, M2 macrophages withdrew back to the tendon in the FG group, but a number of M2 macrophages were retained at the repaired sites in the ACh and PYR groups. Biomechanically, failure load and stiffness of the ACh and PYR groups were significantly higher than those of the FG group at 4 weeks. The stiffness of the ACh and PYR groups was significantly increased compared with the FG group at 8 weeks (P < .001 for all). At 12 weeks, most of the healing properties of the ACh and PYR groups were not significantly different compared with the FG group. CONCLUSION: ACh and PYR enhanced the early stage of bone-tendon insertion healing after rotator cuff repair. CLINICAL RELEVANCE: These findings imply that ACh and PYR could serve as potential therapeutic strategies for rotator cuff healing.
ESTHER : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedSearch : Wang_2021_Am.J.Sports.Med__363546520988680
PubMedID: 33592162

Title : General features to enhance enzymatic activity of poly(ethylene terephthalate) hydrolysis - Chen_2021_Nat.Catal_4_425
Author(s) : Chen CC , Han X , Li X , Jiang P , Niu D , Ma L , Liu W , Li S , Qu Y , Hu H , Min J , Yang Y , Zhang L , Zeng W , Huang JW , Dai L , Guo RT , Chen, CC
Ref : Nature Catalysis , 4 :425 , 2021
Abstract : Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic and a major contributor to plastic pollution. IsPETase, from the PET-assimilating bacterium Ideonella sakaiensis, is a unique PET-hydrolytic enzyme that shares high sequence identity to canonical cutinases, but shows substrate preference towards PET and exhibits higher PET-hydrolytic activity at ambient temperature. Structural analyses suggest that IsPETase harbours a substrate-binding residue, W185, with a wobbling conformation and a highly flexible W185-locating beta6-beta7 loop. Here, we show that these features result from the presence of S214 and I218 in IsPETase, whose equivalents are strictly His and Phe, respectively, in all other homologous enzymes. We found that mutating His/Phe residues to Ser/Ile could enhance the PET-hydrolytic activity of several IsPETase-like enzymes. In conclusion, the Ser/Ile mutations should provide an important strategy to improve the activity of potential PET-hydrolytic enzymes with properties that may be useful for various applications.
ESTHER : Chen_2021_Nat.Catal_4_425
PubMedSearch : Chen_2021_Nat.Catal_4_425
Gene_locus related to this paper: 9burk-a0a1f4jxw8 , idesa-peth

Title : On-line coupling pressurised liquid extraction with two-dimensional counter current chromatography for isolation of natural acetylcholinesterase inhibitors from Astragalus membranaceus - Li_2021_Phytochem.Anal_32_640
Author(s) : Li S , Liu C , Zhang Y , Tsao R
Ref : Phytochem Anal , 32 :640 , 2021
Abstract : INTRODUCTION: Radix Astragali, the dried root of Astragalus membranaceus (Fish.) Bge. (family Fabaceae), which is known as Huangqi in China, has been proven to be an immunostimulant, diuretic, antidiabetic, analgesic, and it has also been used as a health food supplement in some Asian populations and also serves as a lead herb in many traditional Chinese medicine formulations as well as in Chinese ethnic tonifying soups. OBJECTIVE: Screening and purification of bioactive compounds from natural products is challenging work due to their complexity. We present the first report on the use of pressurised liquid extraction and on-line two-dimensional counter current chromatography as an efficient medium for scaled-up extraction and separation of six bioactive compounds from Astragalus membranaceus. METHOD: We applied the established method with ultrafiltration-liquid chromatography to screen acetylcholinesterase inhibitors, which were then evaluated and confirmed for anti-Alzheimer activity using PC12 cell model. RESULTS: Six major compounds, namely, calycosin-7-O-beta-d-glucoside, pratensein-7-O-beta-d-glucoside, formononetin-7-O-beta-d-glucoside, calycosin, genistein, and formononetin, with acetylcholinesterase binding affinities were identified and isolated from the raw plant materials via two sets of n-hexane/ethyl acetate/0.2% acetic acid (first-stage counter current chromatography) and n-hexane/ethyl acetate/methanol/water (second-stage counter current chromatography) solvent systems: 1.87:1.0:1.33 and 5.62:1.0:2.42:5.25, v/v/v/v, which were optimised by a mathematical model. CONCLUSION: Therefore, a useful platform for the large-scale production of bioactive and nutraceutical ingredients was developed herein. With the on-line system developed here, we present a feasible, selective, and effective strategy for rapid screening and identification of enzyme inhibitors from complex mixtures.
ESTHER : Li_2021_Phytochem.Anal_32_640
PubMedSearch : Li_2021_Phytochem.Anal_32_640
PubMedID: 33238329

Title : Enhancing PET hydrolytic enzyme activity by fusion of the cellulose-binding domain of cellobiohydrolase I from Trichoderma reesei - Dai_2021_J.Biotechnol_334_47
Author(s) : Dai L , Qu Y , Huang JW , Hu Y , Hu H , Li S , Chen CC , Guo RT
Ref : J Biotechnol , 334 :47 , 2021
Abstract : The large amounts of polyethylene terephthalate (PET) that enter and accumulate in the environment have posed a serious threat to global ecosystems and human health. A PET hydrolase from PET-assimilating bacterium Ideonella sakaiensis (IsPETase) that exhibits superior PET hydrolytic activity at mild conditions is attracting enormous attention in development of plastic biodegrading strategies. In order to enhance the PET hydrolysis capacity of IsPETase, we selected several polymer-binding domains that can adhere to a hydrophobic polymer surface and fused these to a previously engineered IsPETase(S121E/D186H/R280A) (IsPETase(EHA)) variant. We found that fusing a cellulose-binding domain (CBM) of cellobiohydrolase I from Trichoderma reesei onto the C-terminus of IsPETase(EHA) showed a stimulatory effect on enzymatic hydrolysis of PET. Compared to the parental enzyme, IsPETase(EHA)_CBM exhibited 71.5 % and 44.5 % higher hydrolytic activity at 30 degC and 40 degC, respectively. The catalytic activity of IsPETase(EHA)_CBM was increased by 86 % when the protein concentration was increased from 2.5 microg/mL to 20microg/mL. These findings suggest that the fusion of polymer-binding module to IsPETase is a promising strategy to stimulate the enzymatic hydrolysis of PET.
ESTHER : Dai_2021_J.Biotechnol_334_47
PubMedSearch : Dai_2021_J.Biotechnol_334_47
PubMedID: 34044062
Gene_locus related to this paper: idesa-peth

Title : Strigolactone mimic 2-nitrodebranone is highly active in Arabidopsis growth and development - Li_2021_Plant.J__
Author(s) : Li S , Li Y , Chen L , Zhang C , Wang F , Li H , Wang M , Wang Y , Nan F , Xie D , Yan J
Ref : Plant J , : , 2021
Abstract : Strigolactones play crucial roles in regulating plant architecture and development, as endogenous hormones, and orchestrating symbiotic interactions with fungi and parasitic plants, as components of root exudates. rac-GR24 is currently the most widely used strigolactone analog and serves as a reference compound in investigating the action of strigolactones. In this study, we evaluated a suite of debranones and found that 2-nitrodebranone (2NOD) exhibited higher biological activity than rac-GR24 in various aspects of plant growth and development in Arabidopsis, including hypocotyl elongation inhibition, root hair promotion and senescence acceleration. The enhanced activity of 2NOD in promoting AtD14-SMXL7 and AtD14-MAX2 interactions indicates that the molecular structure of 2NOD is a better match for the ligand perception site pocket of D14. Moreover, 2NOD showed lower activity than rac-GR24 in promoting Orobanche cumana seed germination, suggesting its higher ability to control plant architecture than parasitic interactions. In combination with the improved stability of 2NOD, these results demonstrate that 2NOD is a strigolactone analog that can specifically mimic the activity of strigolactones and that 2NOD exhibits strong potential as a tool for studying the strigolactone signaling pathway in plants.
ESTHER : Li_2021_Plant.J__
PubMedSearch : Li_2021_Plant.J__
PubMedID: 33860570

Title : Decreased carboxylesterase expression associated with increased susceptibility to insecticide in Mythimna separata - Liu_2021_Arch.Insect.Biochem.Physiol__e21859
Author(s) : Liu Y , Li S , Yang H , Chen Y , Fan D
Ref : Archives of Insect Biochemistry & Physiology , :e21859 , 2021
Abstract : Carboxylesterases are one of the three major types of detoxification enzyme in insects. In this study, we screened 12 full-length carboxylesterase cDNA sequences from the oriental armyworm Mythimna separata; they were named MsCarE1-MsCarE12 and registered in GenBank with accession numbers MK440541-MK440552. Treatment of fourth instar larvae of M. separata with the LD(50) of the insecticide chlorantraniliprole increased the expression levels of MsCarE3 and MsCarE4, while treatment with the LD(50) of lambda-cyhalothrin significantly increased the expression levels of MsCarE5 and MsCarE10. Spatiotemporal expression detection showed that MsCarE3, MsCarE4, MsCarE5, and MsCarE10 were expressed at different developmental stages and in different tissues of M. separata and their expression levels were different. Induction using a high dose of chlorantraniliprole resulted in lower expression of MsCarE3 and MsCarE4. LD(50) of lambda-cyhalothrin induced higher expression of MsCarE5 and MsCarE10, while LD(70) induced higher MsCarE10 expression at 3, 6, and 12 h after treatment. RNA interference successfully inhibited the expression of MsCarE3, MsCarE4, MsCarE5, and MsCarE10, to different degrees at different time points. Silencing of MsCarE5, or MsCarE5 and MsCarE10 simultaneously changed carboxylesterase activity and increased the susceptibility of M. separata larvae to lambda-cyhalothrin. This study provides a new method to increase the insect susceptibility to insecticide.
ESTHER : Liu_2021_Arch.Insect.Biochem.Physiol__e21859
PubMedSearch : Liu_2021_Arch.Insect.Biochem.Physiol__e21859
PubMedID: 34881457

Title : Glycerol is Released from a New Path in MGL Lipase Catalytic Process - Lan_2021_J.Chem.Inf.Model__
Author(s) : Lan D , Li S , Tang W , Zhao Z , Luo M , Yuan S , Xu J , Wang Y
Ref : J Chem Inf Model , : , 2021
Abstract : Traditionally, it is believed that the substrate and products of a monoacylglycerol lipase (MGL) share the same path to enter and exit the catalytic site. Glycerol (a product of MGL), however, was recently hypothesized to be released through a different path. In order to improve the catalytic efficacy and thermo-stability of MGL, it is important to articulate the pathways of a MGL products releasing. In this study, with structure biological approaches, biochemical experiments, and in silico methods, we prove that glycerol is released from a different path in the catalytic site indeed. The fatty acid (another product of MGL) does share the same binding path with the substrate. This discovery paves a new road to design MGL inhibitors or optimize MGL catalytic efficacy.
ESTHER : Lan_2021_J.Chem.Inf.Model__
PubMedSearch : Lan_2021_J.Chem.Inf.Model__
PubMedID: 34873908

Title : Molecular cloning and characterization of an atypical butyrylcholinesterase-like protein in zebrafish - Tan_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110590
Author(s) : Tan KS , Zhang Y , Liu L , Li S , Zou X , Zeng W , Cheng G , Wang D , Tan W
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , :110590 , 2021
Abstract : Cholinesterases act as bio scavengers to clear organophosphorus (OP) compounds and prodrugs. The butyrylcholinesterase (BChE) gene has been found in several types of teleost fish but this gene has yet to be identified in cyprinid fish. Indeed, BChE homologs have not been found in the zebrafish (Danio rerio) genomic database. Here, we demonstrate that BChE activity is present in zebrafish, in line with other groups' findings. Using in-gel native-PAGE enzymatic activity staining and LC-MS/MS technique, an atypical BChE-like protein was identified in zebrafish. The si:ch211-93f2.1 gene was cloned, and His-tagged recombinant protein was expressed using the Pichia yeast system. The purified protein (molecular weight ~ 180 kDa) showed BChE activity, and degraded acetylcholinesterase (ACh) at a higher rate than BCh. However, phylogram analysis shows that this novel cholinesterase shared an evolutionary origin with carboxylic esterase rather than BChE. The zebrafish BChE-like protein shares structural characteristics with cholinesterase and carboxylesterase. The 2-arachidonoylglycerol (2-AG), nicosulfuron, and triacetin exhibited a higher binding affinity to the zebrafish BChE-like protein than BCh and ACh. With the identification of BChE-like protein in zebrafish, this study could shed light on the origin of BChE and may contribute towards the development of a BChE knockout zebrafish model for sensitive drug or toxin screening.
ESTHER : Tan_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110590
PubMedSearch : Tan_2021_Comp.Biochem.Physiol.B.Biochem.Mol.Biol__110590
PubMedID: 33662568
Gene_locus related to this paper: danre-a0a0r4iu19.1

Title : Profiling the Tox21 Chemical Collection for Acetylcholinesterase Inhibition - Li_2021_Environ.Health.Perspect_129_47008
Author(s) : Li S , Zhao J , Huang R , Travers J , Klumpp-Thomas C , Yu W , MacKerell AD, Jr. , Sakamuru S , Ooka M , Xue F , Sipes NS , Hsieh JH , Ryan K , Simeonov A , Santillo MF , Xia M
Ref : Environmental Health Perspectives , 129 :47008 , 2021
Abstract : BACKGROUND: Inhibition of acetylcholinesterase (AChE), a biomarker of organophosphorous and carbamate exposure in environmental and occupational human health, has been commonly used to identify potential safety liabilities. So far, many environmental chemicals, including drug candidates, food additives, and industrial chemicals, have not been thoroughly evaluated for their inhibitory effects on AChE activity. AChE inhibitors can have therapeutic applications (e.g., tacrine and donepezil) or neurotoxic consequences (e.g., insecticides and nerve agents). OBJECTIVES: The objective of the current study was to identify environmental chemicals that inhibit AChE activity using in vitro and in silico models. METHODS: To identify AChE inhibitors rapidly and efficiently, we have screened the Toxicology in the 21st Century (Tox21) 10K compound library in a quantitative high-throughput screening (qHTS) platform by using the homogenous cell-based AChE inhibition assay and enzyme-based AChE inhibition assays (with or without microsomes). AChE inhibitors identified from the primary screening were further tested in monolayer or spheroid formed by SH-SY5Y and neural stem cell models. The inhibition and binding modes of these identified compounds were studied with time-dependent enzyme-based AChE inhibition assay and molecular docking, respectively. RESULTS: A group of known AChE inhibitors, such as donepezil, ambenonium dichloride, and tacrine hydrochloride, as well as many previously unreported AChE inhibitors, such as chelerythrine chloride and cilostazol, were identified in this study. Many of these compounds, such as pyrazophos, phosalone, and triazophos, needed metabolic activation. This study identified both reversible (e.g., donepezil and tacrine) and irreversible inhibitors (e.g., chlorpyrifos and bromophos-ethyl). Molecular docking analyses were performed to explain the relative inhibitory potency of selected compounds. CONCLUSIONS: Our tiered qHTS approach allowed us to generate a robust and reliable data set to evaluate large sets of environmental compounds for their AChE inhibitory activity.
ESTHER : Li_2021_Environ.Health.Perspect_129_47008
PubMedSearch : Li_2021_Environ.Health.Perspect_129_47008
PubMedID: 33844597

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

Title : New therapeutics beyond amyloid-beta and tau for the treatment of Alzheimer's disease - Zhang_2021_Acta.Pharmacol.Sin_42_1382
Author(s) : Zhang F , Zhong RJ , Cheng C , Li S , Le WD
Ref : Acta Pharmacol Sin , 42 :1382 , 2021
Abstract : As the population ages, Alzheimer's disease (AD), the most common neurodegenerative disease in elderly people, will impose social and economic burdens to the world. Currently approved drugs for the treatment of AD including cholinesterase inhibitors (donepezil, rivastigmine, and galantamine) and an N-methyl-D-aspartic acid receptor antagonist (memantine) are symptomatic but poorly affect the progression of the disease. In recent decades, the concept of amyloid-beta (Abeta) cascade and tau hyperphosphorylation leading to AD has dominated AD drug development. However, pharmacotherapies targeting Abeta and tau have limited success. It is generally believed that AD is caused by multiple pathological processes resulting from Abeta abnormality, tau phosphorylation, neuroinflammation, neurotransmitter dysregulation, and oxidative stress. In this review we updated the recent development of new therapeutics that regulate neurotransmitters, inflammation, lipid metabolism, autophagy, microbiota, circadian rhythm, and disease-modified genes for AD in preclinical research and clinical trials. It is to emphasize the importance of early diagnosis and multiple-target intervention, which may provide a promising outcome for AD treatment.
ESTHER : Zhang_2021_Acta.Pharmacol.Sin_42_1382
PubMedSearch : Zhang_2021_Acta.Pharmacol.Sin_42_1382
PubMedID: 33268824

Title : Mapping the catalytic conformations of an assembly-line polyketide synthase module - Cogan_2021_Science_374_729
Author(s) : Cogan DP , Zhang K , Li X , Li S , Pintilie GD , Roh SH , Craik CS , Chiu W , Khosla C
Ref : Science , 374 :729 , 2021
Abstract : Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described ""turnstile"" mechanism for transient gating of active sites along the assembly line.
ESTHER : Cogan_2021_Science_374_729
PubMedSearch : Cogan_2021_Science_374_729
PubMedID: 34735239
Gene_locus related to this paper: sacer-ery3

Title : Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr - Zhao_2021_Bioorg.Chem_116_105307
Author(s) : Zhao SS , Li S , Luo ZH , Zhou ZQ , Li N , Wang Y , Yao XS , Gao H
Ref : Bioorg Chem , 116 :105307 , 2021
Abstract : Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, alpha-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed alpha-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).
ESTHER : Zhao_2021_Bioorg.Chem_116_105307
PubMedSearch : Zhao_2021_Bioorg.Chem_116_105307
PubMedID: 34482167

Title : Dammarane Sapogenins Improving Simulated Weightlessness-Induced Depressive-Like Behaviors and Cognitive Dysfunction in Rats - Wang_2021_Front.Psychiatry_12_638328
Author(s) : Wang Q , Dong L , Wang M , Chen S , Li S , Chen Y , He W , Zhang H , Zhang Y , Pires Dias AC , Yang S , Liu X
Ref : Front Psychiatry , 12 :638328 , 2021
Abstract : Background: Our studies demonstrated that the space environment has an impact on the brain function of astronauts. Numerous ground-based microgravity and social isolation showed that the space environment can induce brain function damages in humans and animals. Dammarane sapogenins (DS), an active fraction from oriental ginseng, possesses neuropsychic protective effects and has been shown to improve depression and memory. This study aimed to explore the effects and mechanisms of DS in attenuating depressive-like behaviors and cognitive deficiency induced by simulated weightlessness and isolation [hindlimb suspension and isolation (HLSI)] in rats. Methods: Male rats were orally administered with two different doses of DS (37.5, 75 mg/kg) for 14 days, and huperzine-A (1 mg/kg) served as positive control. Rats were subjected to HLSI for 14 days except the control group during drug administration. The depressive-like behaviors were then evaluated by the open-field test, the novel object recognition test, and the forced swimming test. The spatial memory and working memory were evaluated by the Morris water maze (MWM) test, and the related mechanism was further explored by analyzing the activity of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and superoxide dismutase (SOD) in the hippocampus of rats. Results: The results showed that DS treatment significantly reversed the HLSI-induced depressive-like behaviors in the open-field test, the novel object recognition test, and the forced swimming test and improved the HLSI-induced cognitive impairment in the MWM test. Furthermore, after DS treatment, the ChAT and SOD activities of HLSI rats were increased while AChE activity was significantly suppressed. Conclusions: These findings clearly demonstrated that DS might exert a significant neuropsychic protective effect induced by spaceflight environment, driven in part by the modulation of cholinergic system and anti-oxidation in the hippocampus.
ESTHER : Wang_2021_Front.Psychiatry_12_638328
PubMedSearch : Wang_2021_Front.Psychiatry_12_638328
PubMedID: 33841208

Title : A natural symbiotic bacterium drives mosquito refractoriness to Plasmodium infection via secretion of an antimalarial lipase - Gao_2021_Nat.Microbiol__
Author(s) : Gao H , Bai L , Jiang Y , Huang W , Wang L , Li S , Zhu G , Wang D , Huang Z , Li X , Cao J , Jiang L , Jacobs-Lorena M , Zhan S , Wang S
Ref : Nat Microbiol , : , 2021
Abstract : The stalling global progress in the fight against malaria prompts the urgent need to develop new intervention strategies. Whilst engineered symbiotic bacteria have been shown to confer mosquito resistance to parasite infection, a major challenge for field implementation is to address regulatory concerns. Here, we report the identification of a Plasmodium-blocking symbiotic bacterium, Serratia ureilytica Su_YN1, isolated from the midgut of wild Anopheles sinensis in China that inhibits malaria parasites via secretion of an antimalarial lipase. Analysis of Plasmodium vivax epidemic data indicates that local malaria cases in Tengchong (Yunnan province, China) are significantly lower than imported cases and importantly, that the local vector A. sinensis is more resistant to infection by P. vivax than A. sinensis from other regions. Analysis of the gut symbiotic bacteria of mosquitoes from Yunnan province led to the identification of S. ureilytica Su_YN1. This bacterium renders mosquitoes resistant to infection by the human parasite Plasmodium falciparum or the rodent parasite Plasmodium berghei via secretion of a lipase that selectively kills parasites at various stages. Importantly, Su_YN1 rapidly disseminates through mosquito populations by vertical and horizontal transmission, providing a potential tool for blocking malaria transmission in the field.
ESTHER : Gao_2021_Nat.Microbiol__
PubMedSearch : Gao_2021_Nat.Microbiol__
PubMedID: 33958765

Title : ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis - Ding_2021_ACS.Chem.Neurosci__
Author(s) : Ding Y , Wang X , Ji J , Zhang X , Chen M , Li S , Zhang Q , Liu P
Ref : ACS Chem Neurosci , : , 2021
Abstract : Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects.
ESTHER : Ding_2021_ACS.Chem.Neurosci__
PubMedSearch : Ding_2021_ACS.Chem.Neurosci__
PubMedID: 33517657

Title : Crosstalk of cholinergic pathway on thyroid disrupting effects of the insecticide chlorpyrifos in zebrafish (Danio rerio) - Qiao_2020_Sci.Total.Environ__143769
Author(s) : Qiao K , Hu T , Jiang Y , Huang J , Hu J , Gui W , Ye Q , Li S , Zhu G
Ref : Sci Total Environ , :143769 , 2020
Abstract : Chlorpyrifos is a widely used organophosphate insecticide and ubiquitously detected in the environment. However, little attention has been paid to its endocrine disrupting effect to non-target organisms. In the present study, zebrafish was exposed to 13 and 65 g/L of chlorpyrifos for 7 and 10 days to determine the induced neurotoxicity and the alteration of thyroid metabolism. The 120 h LC(50) and LC(10) of chlorpyrifos was estimated as 1.35 mg/L and 0.62 mg/L based on the acute embryo toxicity assay, respectively. The acetylcholinesterase (AChE) inhibitory was detected by 13 g/L chlorpyrifos and could be reversed by the co-exposure of 100 and 1000 g/L anticholinergic agent atropine. For thyroid hormone level, 13 and 65 g/L of chlorpyrifos induced increased free T(3) levels in 10 dpf (days post-fertilization). The expression of thyroid related genes in 7 and 10 dpf exposed zebrafish were measured by the quantitative Real-Time PCR (qRT-PCR) assay. The mRNA expression of tshba, thrb, crhb, ttr, tpo, ugt1ab and slc5a5 had significant change. However, the alterations of thyroid hormone and mRNA expression could be partly rescued by the addition of atropine. The molecular docking of chlorpyrifos and T(3) to the thyroid receptor beta in zebrafish using homology modelling and CDOCKER procedures shown weaker binding ability of chlorpyrifos compared to T(3). Therefore, we concluded that the disturbance of thyroid signaling in zebrafish might arise from the developmental neurotoxicity induced by chlorpyrifos.
ESTHER : Qiao_2020_Sci.Total.Environ__143769
PubMedSearch : Qiao_2020_Sci.Total.Environ__143769
PubMedID: 33221011
Gene_locus related to this paper: danre-ACHE

Title : GDSL lipase occluded stomatal pore 1 is required for wax biosynthesis and stomatal cuticular ledge formation - Tang_2020_New.Phytol_228_1880
Author(s) : Tang J , Yang X , Xiao C , Li J , Chen Y , Li R , Li S , Lu S , Hu H
Ref : New Phytol , 228 :1880 , 2020
Abstract : The plant leaf surface is coated with a waterproof cuticle layer. Cuticle facing the stomatal pore surface needs to be sculpted to form outer cuticular ledge (OCL) after stomatal maturation for efficient gas exchange. Here, we characterized the roles of Arabidopsis GDSL lipase, Occlusion of Stomatal Pore 1 (OSP1), in wax biosynthesis and stomatal OCL formation. OSP1 mutation results in significant reduction in leaf wax synthesis and occlusion of stomata, leading to increased epidermal permeability, decreased transpiration rate, and enhanced drought tolerance. We demonstrated that OSP1 activity is critical for its role in wax biosynthesis and stomatal function. In vitro enzymatic assays demonstrated that OSP1 possesses thioesterase activity, particularly on C22:0 and C26:0 acyl-CoAs. Genetic interaction analyses with CER1 (ECERIFERUM 1), CER3 (ECERIFERUM 3) and MAH1 (Mid-chain Alkane Hydroxylase 1) in wax biosynthesis and stomatal OCL formation showed that OSP1 may act upstream of CER3 in wax biosynthesis, and implicate that wax composition percentage changes and keeping ketones in a lower level play roles, at least partially, in forming stomatal ledges. Our findings provided insights into the molecular mechanism mediating wax biosynthesis and highlighted the link between wax biosynthesis and the process of stomatal OCL formation.
ESTHER : Tang_2020_New.Phytol_228_1880
PubMedSearch : Tang_2020_New.Phytol_228_1880
PubMedID: 32542680

Title : Application of accelerated solvent extraction coupled with online two-dimensional countercurrent chromatography for continuous extraction and separation of bioactive compounds from Citrus limon peel - Li_2020_J.Sep.Sci_43_3793
Author(s) : Li S , Liu C , Zhang Y , Shi D , Tsao R
Ref : J Sep Sci , 43 :3793 , 2020
Abstract : Drug discovery from complex mixtures, like Chinese herbs, is challenging and extensive false positives make it difficult to obtain compounds with anti-Alzheimer's activity. In this study, a continuous method comprised of accelerated solvent extraction coupled with online two-dimensional countercurrent chromatography was developed for the efficient, scaled-up extraction and separation of six bioactive compounds from Citrus limon peels: neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin, and limonin. These active compounds were isolated and purified from the raw plant materials by two-dimensional countercurrent chromatography separation via two sets of an n-hexane/n-butanol/methanol/water solvent system: 0.23:1.00:0.25:1.13 and 0.47:1.00:0.38:1.46, v/v/v/v. The compounds were collected in yields of 0.22, 0.25, 0.10, 0.31, 0.29, and 0.28 mg/g, respectively, with purities of 95.79, 96.47, 97.69, 97.22, 98.11, and 98.82%, respectively. Subsequently, a simple and efficient in vitro method was developed for rapidly evaluating the acetylcholinesterase inhibitory activities of six bioactive components. Furthermore, the PC12 cell model and the in vitro metabolism of cytochromes P450 were employed to verify the monomers obtained from the continuous method. The results demonstrated that these six bioactive extracts from the C. limon peels were strong acetylcholinesterase inhibitors.
ESTHER : Li_2020_J.Sep.Sci_43_3793
PubMedSearch : Li_2020_J.Sep.Sci_43_3793
PubMedID: 32745365

Title : Colorimetric Differentiation of Flavonoids Based on Effective Reactivation of Acetylcholinesterase Induced by Different Affnities between Flavonoids and Metal Ions - Li_2020_Anal.Chem_92_3361
Author(s) : Li S , Liu X , Liu QY , Chen Z
Ref : Analytical Chemistry , 92 :3361 , 2020
Abstract : Flavonoids are closely related to human health, and the distinguishiment of flavonoids is an important but difficult issue. We herein unveil a novel colorimetric sensor array for the rapid identification of 7 flavonoids (e.g., gallocatechin (GC), morin hydrate (MH), puerarin (Pu), epigallocatechin gallate (EGCG), catechin (C), rac Naringenin (rN), and Flavone (Fla)) for the first time. The colorimetric performances of gold nanoparticles (AuNPs) are characteristically correlated with thiocholine, which is issued from the enzymatic hydrolysis of acetylcholine (AcCh). Therefore, as a proof-of-concept design, three sensors (Cu2+/ acetylcholinesterase (AcChE)/AcCh/AuNPs, Zn2+/AcChE/AcCh/AuNPs, and Mn2+/AcChE/AcCh/AuNPs) were constructed to form our sensor array. The distinct affnities between flavonoids and metal ions would cause varying degrees of effective reactivation of AcChE, leading to unique colorimetric response patterns upon being challenged with the seven flavonoids for their pattern recognition, enabling an excellent identification of the seven flavonoids at a concentration of 20 nM and different concentrations of individual flavonoids, as well as mixtures of them.
ESTHER : Li_2020_Anal.Chem_92_3361
PubMedSearch : Li_2020_Anal.Chem_92_3361
PubMedID: 31983197

Title : miR-96-5p attenuates malathion-induced apoptosis of human kidney cells by targeting the ER stress marker DDIT3 - Li_2020_J.Environ.Sci.Health.B__1
Author(s) : Li S , Yang Y , Shi MH , Wang JF , Ran XQ
Ref : J Environ Sci Health B , :1 , 2020
Abstract : Micro RNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, their functions in organophosphate-induced cytotoxicity remain unclear. This study investigated the involvement of miR-96-5p in the non-cholinergic toxicity of malathion in normal human kidney cells (HK-2 cells). Malathion decreased HK-2 cell viability and the expression of miR-96-5p in a dose- and time-dependent manner. In addition, transfection with miR-96-5p mimics attenuated malathion-induced HK-2 cell apoptosis, whereas transfection with a miR-96-5p inhibitor increased HK-2 cell apoptosis. Luciferase assays indicated that miR-96-5p could bind directly to the 3'-untranslated region of DDIT3, a well-known marker of endoplasmic reticulum stress. Further analyses of the expression of apoptosis-related genes and proteins indicated that miR-96-5p may function to reduce malathion-induced HK-2 cell apoptosis via regulation of the DDIT3/B-cell lymphoma (BCL)-2/caspase-3 signaling pathway. In summary, the results of the present study indicate that miR-96-5p protects HK-2 cells from malathion-induced ER stress-dependent apoptosis by targeting DDIT3.
ESTHER : Li_2020_J.Environ.Sci.Health.B__1
PubMedSearch : Li_2020_J.Environ.Sci.Health.B__1
PubMedID: 32897819

Title : The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike - Li_2020_iScience__101160
Author(s) : Li Y , Zhang Z , Yang L , Lian X , Xie Y , Li S , Xin S , Cao P , Lu J
Ref : iScience , :101160 , 2020
Abstract : The ongoing outbreak of the novel coronavirus pneumonia COVID-19 has caused great number of cases and deaths, but our understanding about the pathogen SARS-CoV-2 remains largely unclear. The attachment of the virus with the cell-surface receptor and a co-factor is the first step for the infection. Here, bioinformatics approaches combining human-virus protein interaction prediction and protein docking based on crystal structures have revealed the high affinity between human dipeptidyl peptidase 4 (DPP4) and the spike (S) receptor-binding domain of SARS-CoV-2. Intriguingly, the crucial binding residues of DPP4 are identical to those as bound to the MERS-CoV-S. Moreover, E484 insertion and adjacent substitutions should be most essential for this DPP4-binding ability acquirement of SARS-CoV-2-S compared with SARS-CoV-S. This potential utilization of DPP4 as a binding target for SARS-CoV-2 may offer novel insight into the viral pathogenesis, and help the surveillance and therapeutics strategy for meeting the challenge of COVID-19.
ESTHER : Li_2020_iScience__101160
PubMedSearch : Li_2020_iScience__101160
PubMedID: 32405622

Title : RMS2 encoding a GDSL lipase mediates lipid homeostasis in anthers to determine rice male fertility - Zhao_2020_Plant.Physiol__
Author(s) : Zhao J , Long T , Wang Y , Tong X , Tang J , Li J , Wang H , Tang L , Li Z , Shu Y , Liu X , Li S , Liu H , Wu Y , Zhang J
Ref : Plant Physiol , : , 2020
Abstract : Plant male gametogenesis is a coordinated effort involving both reproductive tissues and sporophytic tissues, in which lipid metabolism plays an essential role. Although GDSL esterases/lipases have been well known as key enzymes for many plant developmental processes and stress responses, their functions in reproductive development remain unclear. Here, we report the identification of a rice male sterile 2 (rms2) mutant in rice (Oryza sativa), which is completely male sterile due to the defects in tapetum degradation, cuticle formation in sporophytic tissues, and impaired exine and central vacuole development in pollen grains. RMS2 was map-based cloned as an endoplasmic reticulum-localized GDSL lipase gene, which is predominantly transcribed during early anther development. In rms2, a three-nucleotides deletion and one base substitution (TTGT to A) occurred within the GDSL domain, which reduced the lipid hydrolase activity of the resulting protein and led to significant changes in the content of 16 lipid components and numerous other metabolites as revealed by a comparative metabolic analysis. Furthermore, RMS2 is directly targeted by male fertility regulators Undeveloped Tapetum 1 (UDT1) and Persistent Tapetal Cell 1 (PTC1) both in vitro and in vivo, suggesting that RMS2 may serve as a key node in the rice male fertility regulatory network. These findings shed light on the function of GDSLs in reproductive development and provide a promising gene resource for hybrid rice breeding.
ESTHER : Zhao_2020_Plant.Physiol__
PubMedSearch : Zhao_2020_Plant.Physiol__
PubMedID: 32029522

Title : Promoting Active Sites in MOF-Derived Homobimetallic Hollow Nanocages as a High-Performance Multifunctional Nanozyme Catalyst for Biosensing and Organic Pollutant Degradation - Li_2020_ACS.Appl.Mater.Interfaces_12_2581
Author(s) : Li S , Hou Y , Chen Q , Zhang X , Cao H , Huang Y
Ref : ACS Appl Mater Interfaces , 12 :2581 , 2020
Abstract : Nanozymes are one of the ideal alternatives to natural enzymes for various applications. The rational design of nanozymes with improved catalytic activity stimulates increasing attention to address the low activity of current nanozymes. Here, we reported a general strategy to fabricate the Co-based homobimetallic hollow nanocages (HNCs) (C-CoM-HNC, M = Ni, Mn, Cu, and Zn) by ion-assistant solvothermal reaction and subsequent low-temperature calcination from metal-organic frameworks. The C-CoM-HNCs are featured with HNCs composed of interlaced nanosheets with homogeneous bimetallic oxide dispersion. The hierarchical structure and secondary metallic doping endow the C-CoM-HNC highly active sites. In particular, the Cu-doped C-CoCu-HNCs nanostructures exhibit superior performances over the other C-CoM-HNC as both the oxidase mimicking and peroxymonosulfate (PMS) activator. A sensitive bioassay for acetylcholinesterase (AChE) was established based on the excellent oxidase-like activity of C-CoCu-HNC, offering a linear detection range from 0.0001 to 1 mU/mL with an ultralow detection limit of 0.1 mU/L. As the PMS activator, the C-CoCu-HNC was applied for targeted organic pollutant (rhodamine B, RhB) degradation. A highly efficient RhB degradation was realized, along with good adaptability in a wide pH range and good reusability during the eight-cycle run. The results suggest that C-CoCu-HNC holds a practical potential for clinical diagnostics and pollution removal. Further density functional theory calculation reveals that Cu doping leads to a tighter connection and more negative adsorption energy for O2/PMS, as well as an upshifted d-band center in the C-CoCu-HNCs nanostructures. These changes facilitated the adsorption of O2/PMS on the C-CoCu-HNC surface for dissociation. This work not only offers a promising multifunctional nanozyme catalyst for clinical diagnostics and pollution removal but also gives some clues for the further development of novel nanozymes with high catalytic activities.
ESTHER : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedSearch : Li_2020_ACS.Appl.Mater.Interfaces_12_2581
PubMedID: 31854974

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

Title : Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects - Han_2020_Eur.J.Med.Chem__113028
Author(s) : Han Y , Huang D , Xu S , Li L , Tian Y , Li S , Chen C , Li Y , Sun Y , Hou Y , Qin M , Gong P , Gao Z , Zhao Y
Ref : Eur Journal of Medicinal Chemistry , :113028 , 2020
Abstract : Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC(50) value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation.
ESTHER : Han_2020_Eur.J.Med.Chem__113028
PubMedSearch : Han_2020_Eur.J.Med.Chem__113028
PubMedID: 33248848

Title : Extraction and Isolation of Acetylcholinesterase Inhibitors from Citrus limon Peel Using an in vitro Method - Liu_2020_J.Sep.Sci__
Author(s) : Liu C , Hou W , Li S , Tsao R
Ref : J Sep Sci , : , 2020
Abstract : A simple and efficient ultrafiltration-liquid chromatography-mass spectrometry-based method was developed for the rapid screening and identification of ligands from Citrus limon peel, which are suitable acetylcholinesterase inhibitors. Subsequently, the anti-Alzheimer's activity of these compounds was assessed using a PC12 cell model. Six major compounds, viz. neoeriocitrin, isonaringin, naringin, hesperidin, neohesperidin, and limonin, were identified as potent acetylcholinesterase inhibitors. A continuous and efficient online method, which involved the use of a microwave-assisted extraction device, solvent concentration tank, and centrifugal partition chromatography column, was developed for the scale-up of these compounds, and the obtained compounds presented high purity. Next, their bioactivity was evaluated using a PC12 cell model. This novel approach, which was based on ultrafiltration-liquid chromatography-mass spectrometry, microwave-assisted extraction online coupled with solvent concentration tank, and centrifugal partition chromatography along with in vitro evaluation, could represent a powerful tool for the screening and extraction of acetylcholinesterase inhibitors from complex matrices, and could be a useful platform for the large-scale production of bioactive and nutraceutical ingredients. This article is protected by copyright. All rights reserved.
ESTHER : Liu_2020_J.Sep.Sci__
PubMedSearch : Liu_2020_J.Sep.Sci__
PubMedID: 31999045

Title : Fates of dietary sterols in the insect alimentary canal - Li_2020_Curr.Opin.Insect.Sci_41_106
Author(s) : Li S , Jing X
Ref : Curr Opin Insect Sci , 41 :106 , 2020
Abstract : Sterols serve structural and physiological roles in insects. However, insects and other arthropods have lost many genes in the sterol biosynthesis pathway, so they must acquire sterols from their food. Sterols occur naturally as free (unconjugated) molecules, and as conjugated ones (mostly steryl esters). Once sterols are ingested and make their way into the gut, steryl esters can be converted into free sterols by Magro protein, a lipase excreted by enterocytes. Sterols in the free form enter midgut enterocytes through NPC1b and are then transported to the smooth endoplasmic reticulum membrane for possible metabolism. For most insect herbivores, phytosterol dealkylation converts plant sterols into cholesterol. Some ingested sterols may also be consumed by microbiota dwelling inside the insect gut lumen; bacteria use sterols as a source of carbon and energy. Further studies will reveal interesting and exciting discoveries regarding the pathways for the dietary sterols entering the insect alimentary canal.
ESTHER : Li_2020_Curr.Opin.Insect.Sci_41_106
PubMedSearch : Li_2020_Curr.Opin.Insect.Sci_41_106
PubMedID: 32927332

Title : Pediococcus pentosaceus B49 from human colostrum ameliorates constipation in mice - Huang_2020_Food.Funct_11_5607
Author(s) : Huang J , Li S , Wang Q , Guan X , Qian L , Li J , Zheng Y , Lin B
Ref : Food Funct , 11 :5607 , 2020
Abstract : Constipation is a prevalent and burdensome gastrointestinal (GI) disorder that seriously affects the quality of human life. This study evaluated the effects of the P. pentosaceus B49 (from human colostrum) on loperamide (Lop)-induced constipation in mice. Mice were given P. pentosaceus B49 (5 x 109 CFU or 5 x 1010 CFU) by gavage daily for 14 days. The result shows that P. pentosaceus B49 treatment relieved constipation in mice by shortening the defecation time, increasing the GI transit rate and stool production. Compared with the constipation control group, the P. pentosaceus B49-treated groups showed decreased serum levels of inhibitory neurotransmitters (vasoactive intestinal peptide and nitric oxide), increased serum levels of excitatory neurotransmitters (acetylcholinesterase, motilin, and gastrin), and elevated cecal concentration of short chain fatty acids (SCFAs). Analysis of cecal microbiota reveals that P. pentosaceus B49 was colonized in the intestine of constipated mice, and altered the cecal microbiota by increasing beneficial SCFAs-producing bacteria (i.e., Lactobacillus, Ruminococcaceae_UCG-014, and Bacteroidales_S24-7) and decreasing potential pathogenic bacteria (i.e., Staphylococcus and Helicobacter). Moreover, transcriptome analysis of the colon tissue shows that P. pentosaceus B49 partly normalized the expression of genes related to GI peristalsis (i.e., Ache, Chrm2, Slc18a3, Grp, and Vip), water and electrolyte absorption and transport (i.e., Aqp4, Aqp8, and Atp12a), while down-regulating the expression of pro-inflammatory and pro-oncogenic genes (i.e., Lbp, Lgals2, Bcl2, Bcl2l15, Gsdmc2, and Olfm4) in constipated mice. Our findings indicate that P. pentosaceus B49 effectively relieves constipation in mice and is a promising candidate for treating constipation.
ESTHER : Huang_2020_Food.Funct_11_5607
PubMedSearch : Huang_2020_Food.Funct_11_5607
PubMedID: 32525185

Title : A Novel VIII Carboxylesterase with High Hydrolytic Activity Against Ampicillin from a Soil Metagenomic Library - Nan_2019_Mol.Biotechnol_61_892
Author(s) : Nan F , Jiang J , Wu S , Zhang Y , Qiu J , Qiao B , Li S , Xin Z
Ref : Mol Biotechnol , 61 :892 , 2019
Abstract : A novel carboxylesterase gene, named dlfae4, was discovered and sequenced from a soil metagenomic library. The dlfae4 gene was composed of 1017 base pairs encoding 338 amino acid residues with a predicted molecular mass of 37.2 kDa. DLFae4 exhibited strong hydrolytic activity towards methyl ferulate under optimum pH and temperature conditions (pH 8.6, 50 degrees C) and displayed remarkable thermostability, with residual activity as high as 50% after incubation for 3 h at 60 degrees C. A family VIII esterase DLFae4 was found to contain a typical serine residue within the S-X-X-K motif, which serves as a catalytic nucleophile in class C beta-lactamases and family VIII esterases. As a consequence of its high sequence similarity with beta-lactamases, DLFae4 exhibited significant hydrolytic activity towards ampicillin. In addition, DLFae4 was found to be the first known member of family VIII carboxylesterases with phthalate-degrading ability. Site-directed mutagenesis studies revealed that Ser11, Lys14, and Tyr121 residues play an essential catalytic role in DLFae4. These new findings, which are of great importance for further in-depth research and engineering development of carboxylesterases, should advance the implementation of biotechnological applications.
ESTHER : Nan_2019_Mol.Biotechnol_61_892
PubMedSearch : Nan_2019_Mol.Biotechnol_61_892
PubMedID: 31664703

Title : Unprecedented peroxidase-mimicking activity of single-atom nanozyme with atomically dispersed Fe-Nx moieties hosted by MOF derived porous carbon - Niu_2019_Biosens.Bioelectron_142_111495
Author(s) : Niu X , Shi Q , Zhu W , Liu D , Tian H , Fu S , Cheng N , Li S , Smith JN , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 142 :111495 , 2019
Abstract : Due to robustness, easy large-scale preparation and low cost, nanomaterials with enzyme-like characteristics (defined as 'nanozymes') are attracting increasing interest for various applications. However, most of currently developed nanozymes show much lower activity in comparison with natural enzymes, and the deficiency greatly hinders their use in sensing and biomedicine. Single-atom catalysts (SACs) offer the unique feature of maximum atomic utilization, providing a potential pathway to improve the catalytic activity of nanozymes. Herein, we propose a Fe-N-C single-atom nanozyme (SAN) that exhibits unprecedented peroxidase-mimicking activity. The SAN consists of atomically dispersed Fe horizontal line Nx moieties hosted by metal-organic frameworks (MOF) derived porous carbon. Thanks to the 100% single-atom active Fe dispersion and the large surface area of the porous support, the Fe-N-C SAN provided a specific activity of 57.76 U mg(-1), which was almost at the same level as natural horseradish peroxidase (HRP). Attractively, the SAN presented much better storage stability and robustness against harsh environments. As a proof-of-concept application, highly sensitive biosensing of butyrylcholinesterase (BChE) activity using the Fe-N-C SAN as a substitute for natural HRP was further verified.
ESTHER : Niu_2019_Biosens.Bioelectron_142_111495
PubMedSearch : Niu_2019_Biosens.Bioelectron_142_111495
PubMedID: 31310943

Title : Bioaugmentation of Exogenous Strain Rhodococcus sp. 2G Can Efficiently Mitigate Di(2-ethylhexyl) Phthalate Contamination to Vegetable Cultivation - Zhao_2019_J.Agric.Food.Chem_67_6940
Author(s) : Zhao HM , Du H , Huang CQ , Li S , Zeng XH , Huang XJ , Xiang L , Li H , Li YW , Cai QY , Mo CH , He Z
Ref : Journal of Agricultural and Food Chemistry , 67 :6940 , 2019
Abstract : This work developed a bioaugmentation strategy that simultaneously reduced soil di(2-ethylhexyl) phthalate (DEHP) pollution and its bioaccumulation in Brassica parachinensis by inoculating the isolated strain Rhodococcus sp. 2G. This strain could efficiently degrade DEHP at a wide concentration range from 50 to 1600 mg/L and transformed DEHP through a unique biochemical degradation pathway that distinguished it from other Rhodococcus species. Besides, strain 2G colonized well in the rhizosphere soil of the inoculated vegetable without competition with indigenous microbes, resulting in increased removal of DEHP from soil (95%) and reduced DEHP bioaccumulation in vegetables (75% in the edible part) synchronously. Improved enzyme activities and DOC content in the rhizosphere of the planting vegetable and inoculating strain 2G were responsible for the high efficiency in mitigating DEHP contamination to vegetable cultivation. This work demonstrated a great potential application to grow vegetables in contaminated soil for safe food production.
ESTHER : Zhao_2019_J.Agric.Food.Chem_67_6940
PubMedSearch : Zhao_2019_J.Agric.Food.Chem_67_6940
PubMedID: 31021627
Gene_locus related to this paper: rhoso-a0a3g5hne7

Title : CA10 and CA11 negatively regulate neuronal activity-dependent growth of gliomas - Tao_2019_Mol.Oncol_13_1018
Author(s) : Tao B , Ling Y , Zhang Y , Li S , Zhou P , Wang X , Li B , Jun Z , Zhang W , Xu C , Shi J , Wang L
Ref : Mol Oncol , 13 :1018 , 2019
Abstract : Recent studies have revealed that neurons can promote glioma growth through activity-dependent secretion of neurotrophins, especially neuroligin-3. It has therefore been suggested that blocking neuron-derived neurotrophins may serve as a therapeutic intervention for gliomas. Carbonic anhydrase-related proteins 11 and 10 (CA11 and CA10) are secreted synaptic proteins which function as neurexin ligands, and the gene-encoding CA11 is part of a gene signature associated with radiotherapy and prognosis in gliomas. We therefore hypothesized that CA11/CA10 might participate in the neuronal activity-dependent regulation of glioma growth. In this study, we report that CA11 secreted by depolarized cultured neurons within conditioned medium (CM) inhibited the growth of glioma cell lines. CM from depolarized neurons inhibited CA11 expression in glioma cell lines via the Akt signaling pathway. Consistently, CA11 expression was also reduced in clinical glioma samples and negatively associated with high histological grade. Low CA11 expression of gliomas was associated with short survival in four independent datasets [repository of brain neoplasia data (REMBRANDT), The Cancer Genome Atlas (TCGA) lower grade glioma (LGG), GSE4271, and GSE42669]. CA11 knockdown promoted cell growth, clone formation, and migration; inhibited apoptosis; and increased tumor size in xenografted nude mice. Similarly, CA10 and CA10 secreted by depolarized cultured neurons also inhibited the growth of glioma cell lines. Low CA10 expression was associated with short survival in REMBRANDT, TCGA LGG, and GEO GSE4271 datasets. Our results suggest that CA11 and CA10 negatively regulate neuronal activity-dependent glioma growth and inhibit glioma aggression. Thus, CA11/CA10 may represent a potential therapeutic target for the treatment of gliomas.
ESTHER : Tao_2019_Mol.Oncol_13_1018
PubMedSearch : Tao_2019_Mol.Oncol_13_1018
PubMedID: 30636076

Title : Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment - Zhou_2019_J.Proteome.Res_18_1542
Author(s) : Zhou X , Xiao W , Su Z , Cheng J , Zheng C , Zhang Z , Wang Y , Wang L , Xu B , Li S , Yang X , Pui Man Hoi M
Ref : J Proteome Res , 18 :1542 , 2019
Abstract : Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3xTg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3xTg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Abeta1-40 and Abeta1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3xTg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target.
ESTHER : Zhou_2019_J.Proteome.Res_18_1542
PubMedSearch : Zhou_2019_J.Proteome.Res_18_1542
PubMedID: 30484658

Title : Mechanism-based pharmacokinetics-pharmacodynamics studies of harmine and harmaline on neurotransmitters regulatory effects in healthy rats: Challenge on monoamine oxidase and acetylcholinesterase inhibition - Jiang_2019_Phytomedicine_62_152967
Author(s) : Jiang B , Meng L , Zou N , Wang H , Li S , Huang L , Cheng X , Wang Z , Chen W , Wang C
Ref : Phytomedicine , 62 :152967 , 2019
Abstract : BACKGROUND: beta-Carboline alkaloid harmine (HAR) and harmaline (HAL) are monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitors. However, whether HAR and HAL inhibit MAO or AChE selectively and competitively is unclear. PURPOSE: The purpose of this study was to investigate the potential competition inhibition of HAR and HAL on MAO and AChE in brain endothelial cells (RBE4) and in healthy rats to provide a basis for the application of the inhibitors in the treatment of patients with depression and with Parkinson's disease or Alzheimer's disease. STUDY DESIGN/METHODS: The transport properties of HAR and HAL by using blood-brain barrier models constructed with RBE4 were systematically investigated. Then, the modulation effects of HAR and HAL on CNS neurotransmitters (NTs) in healthy rat brains were determined by a microdialysis method coupled with LC-MS/MS. The competition inhibition of HAR and HAL on MAO and AChE was evaluated through real time-PCR, Western blot analysis, and molecular docking experiments. RESULTS: Results showed that HAL and HAR can be detected in the blood and striatum 300min after intravenous injection (1mg/kg). Choline (Ch), gamma-aminobutyric acid (GABA), glutamate (Glu), and phenylalanine (Phe) levels in the striatum decreased in a time-dependent manner after the HAL treatment, with average velocities of 1.41, 0.73, 3.86, and 1.10 (ng/ml)/min, respectively. The Ch and GABA levels in the striatum decreased after the HAR treatment, with average velocities of 1.16 and 0.22ng/ml/min, respectively. The results of the cocktail experiment using the human liver enzyme indicated that the IC50 value of HAL on MAO-A was 0.10 +/- 0.08microm and that of HAR was 0.38 +/- 0.21microm. Their IC50 values on AChE were not obtained. These findings indicated that HAL and HAR selectively acted on MAO in vitro. However, RT-PCR and Western blot analysis results showed that the AChE mRNA and protein expression decreased in a time-dependent manner in RBE4 cells after the HAR and HAL treatments. CONCLUSION: NT analysis results showed that HAL and HAR selectively affect AChE in vivo. HAL and HAR may be highly and suitably developed for the treatment of Alzheimer's disease.
ESTHER : Jiang_2019_Phytomedicine_62_152967
PubMedSearch : Jiang_2019_Phytomedicine_62_152967
PubMedID: 31154274

Title : Potential Pharmacokinetic Drug(-)Drug Interaction Between Harmine, a Cholinesterase Inhibitor, and Memantine, a Non-Competitive N-Methyl-d-Aspartate Receptor Antagonist - Zhang_2019_Molecules_24_
Author(s) : Zhang Y , Li S , Wang Y , Deng G , Cao N , Wu C , Ding W , Cheng X , Wang C
Ref : Molecules , 24 : , 2019
Abstract : Harmine (HAR) is a beta-carboline alkaloid widely distributed in nature. It exhibits psychopharmacological effects of improving learning and memory. However, excessive dose of HAR can cause central tremor toxicity, which may be related to the glutamate system. Memantine (MEM) is a non-competitive N-methyl-d-aspartate receptor antagonist. It can be used for the treatment of Alzheimer's disease and also can block the neurotoxicity caused by glutamate. Therefore, combination of HAR and MEM would be meaningful and the pharmacokinetics investigation of HAR and MEM in combination is necessary. A ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was established and validated for the simultaneous quantitative determination of MEM, HAR and harmol (HOL), a main metabolite of HAR, in rat plasma after oral administration of HAR and MEM in combination (5.0 mg/kg of MEM combined with 20.0, 40.0, 80.0 mg/kg of HAR). The contents of HAR and HOL were determined after oral administration of HAR (20.0, 40.0 and 80.0 mg/kg), and the content of MEM was determined after oral administration of MEM (5.0 mg/kg). Blood samples were collected from each rat at 0 (pre-dose), 0.08, 0.17, 0.25, 0.33, 0.50, 0.75, 1.0, 2.0, 4.0, 8.0, 12.0 and 24.0 h after administration. The maximum peak concentration (Cmax) of MEM was obviously decreased, and the area under the plasma concentration versus time curve from zero to time t (AUC(0-t)) and mean residence time (MRT) were significantly increased after combination with HAR. The Cmax and AUC(0-t) of HAR and its metabolite HOL were increased after combination with MEM. These findings suggested that co-administration of HAR and MEM could extend their residence time in rats, and then might increase the efficacy for treatment of Alzheimer's disease. Therefore, this study will provide a basis for the rational combined application of HAR and MEM.
ESTHER : Zhang_2019_Molecules_24_
PubMedSearch : Zhang_2019_Molecules_24_
PubMedID: 30978991

Title : Use of high-throughput enzyme-based assay with xenobiotic metabolic capability to evaluate the inhibition of acetylcholinesterase activity by organophosphorous pesticides - Li_2019_Toxicol.In.Vitro_56_93
Author(s) : Li S , Zhao J , Huang R , Santillo MF , Houck KA , Xia M
Ref : Toxicol In Vitro , 56 :93 , 2019
Abstract : The inhibition of acetylcholinesterase (AChE) has pharmaceutical applications as well as potential neurotoxic effects. The in vivo metabolites of some chemicals including organophosphorus pesticides can become more potent AChE inhibitors compared to their parental compounds. To account for the effects of biotransformation, we have developed and characterized a high-throughput screening method for identifying AChE inhibitors that become active or more potent following xenobiotic metabolism. In this study, an enzyme-based assay was developed in 1536-well plates using recombinant human AChE combined with human or rat liver microsomes. The AChE activity was measured by two methods with different readouts: colorimetric and fluorescent. The assay exhibited exceptional performance characteristics including large assay signal window, low well-to-well variability and high reproducibility. The performance of the assays with microsomes was characterized by testing a group of known AChE inhibitors including parent compounds and their metabolites. Large potency differences between the parent compounds and the metabolites were observed in the assay with microsome addition. Both assay readouts were required for maximal sensitivity. These results demonstrate that this platform is a promising method to profile large numbers of chemicals that require metabolic activation for inhibiting AChE activity.
ESTHER : Li_2019_Toxicol.In.Vitro_56_93
PubMedSearch : Li_2019_Toxicol.In.Vitro_56_93
PubMedID: 30625376

Title : Compartmentalized biosynthesis of mycophenolic acid - Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
Author(s) : Zhang W , Du L , Qu Z , Zhang X , Li F , Li Z , Qi F , Wang X , Jiang Y , Men P , Sun J , Cao S , Geng C , Wan X , Liu C , Li S
Ref : Proc Natl Acad Sci U S A , 116 :13305 , 2019
Abstract : Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis.
ESTHER : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedSearch : Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305
PubMedID: 31209052
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Acetylcholinesterase-functionalized two-dimensional photonic crystal for the sensing of G-series nerve agents - Qi_2019_Anal.Bioanal.Chem_411_2577
Author(s) : Qi F , Yan C , Meng Z , Li S , Xu J , Hu X , Xue M
Ref : Anal Bioanal Chem , 411 :2577 , 2019
Abstract : G-series nerve agents, such as sarin, tabun, and soman, would cause tremendous harm in military and terrorist attacks, so it is necessary to develop a simple method for the rapid and efficient detection of these hazardous substances. We have developed a tunable acetylcholinesterase (AChE)-functionalized two-dimensional photonic crystal (2D PhC) for the detection of a real nerve agent, sarin. In accordance with the 2D PhC previously prepared by our group, the AChE-functionalized 2D PhC was optimized by adjustment of the amount of monomer in the hydrogel, which not only increased the sensitivity of the 2D PhC, with the detection limit decreasing by two orders of magnitude, but also ensured the structural color spanned the whole visible region in the detection range. A linear relationship between the logarithm of the sarin concentration and the particle spacing of the AChE-functionalized 2D PhC was observed from 7.1 x 10(-17) to 7.1 x 10(-4) mol/L. The AChE-functionalized 2D PhC also responded to mimics of G-series nerve agents, including dimethyl methylphosphonate, diisopropyl methylphosphonate, and isodipropyl methylphosphonate, to various degrees. The proposed 2D-PhC hydrogel has potential for low-cost, trace-level, and on-site monitoring of other G-series nerve agents. Graphical abstract.
ESTHER : Qi_2019_Anal.Bioanal.Chem_411_2577
PubMedSearch : Qi_2019_Anal.Bioanal.Chem_411_2577
PubMedID: 30847569

Title : Toxicity of Chimonanthus nitens flower extracts to the golden apple snail, Pomacea canaliculata - Li_2019_Pestic.Biochem.Physiol_160_136
Author(s) : Li S , Zou Z
Ref : Pestic Biochem Physiol , 160 :136 , 2019
Abstract : We studied the molluscicidal activity of Chimonanthus nitens extracts on Pomacea canaliculata (Ampullariidae). The degree of hepatopancreatic tissue damage, and its physiological and biochemical effects, was evaluated on individuals exposed to petroleum ether extracts (PEEEs). The PEEEs, ethyl acetate extract (EAEE) and water saturated n-butyl extract (SBEE) of C. nitens also had toxic effects on P. canaliculata but PEEE had the greatest molluscicidal activity. After exposure to PEEE for 24h, the hepatopancreas of P. canaliculata had a large necrotic area. The levels of soluble sugar, soluble protein and albumin (Alb) in the hepatopancreas of P. canaliculata decreased with increasing PEEE concentration, while the activities of glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT) and acetylcholinesterase (AchE) increased with increasing PEEE concentration. A total of 29 compounds were identified from the PEEE of C. nitens by gas chromatography-mass spectrometry analysis. The main components were esters (48.13%), alcohols (18.43%) and the compound Chimonanthine (14.70%). The results of the molluscicidal assay, histological experiments and the physiological and biochemical experiments show that the PEEE of C. nitens could potentially be used for P. canaliculata management.
ESTHER : Li_2019_Pestic.Biochem.Physiol_160_136
PubMedSearch : Li_2019_Pestic.Biochem.Physiol_160_136
PubMedID: 31519248

Title : Neuroprotective Effect of Resveratrol via Activation of Sirt1 Signaling in a Rat Model of Combined Diabetes and Alzheimer's Disease - Ma_2019_Front.Neurosci_13_1400
Author(s) : Ma X , Sun Z , Han X , Li S , Jiang X , Chen S , Zhang J , Lu H
Ref : Front Neurosci , 13 :1400 , 2019
Abstract : Background: Alzheimer's disease (AD) and diabetes mellitus (DM) often coexist in patients because having one of these conditions increases risk for the other. These two diseases share several pathophysiological mechanisms, such as specific inflammatory signaling pathways, oxidative stress, and cell apoptosis. It is still unclear exactly which mechanisms associated with DM are responsible for increased AD risk. Studies have found that even transient elevation of brain Abeta levels can allow T2DM to slightly disrupt the neural milieu in a way that encourages pathologies associated with the onset of memory deficits and AD. A recent study argues that a potential common pathogenetic mechanism underlying both DM and AD is evidenced by the cooccurrence of amyloid brain legions and deposits containing both tau and Abeta in pancreatic beta cells. Given these links, an investigation detailing disease mechanisms as well as treatment options for patients with cooccurring DM and AD is urgently needed. The biological effects of resveratrol relevant to DM and AD treatment include its abilities to modulate oxidative stress and reduce inflammation. A rat model of DM and concomitant AD was created for this study using intraperitoneal injection of streptozotocin and hippocampal injection of Abeta1-40 to characterize resveratrol's potential protective action. Results: Resveratrol significantly increased the Sirt1 expression, inhibited the memory impairment, the increased acetylcholinesterase, malondialdehyde, interleukin-1beta and interleukin 6 levels, and the decreased levels of choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione in this rat model of diabetes and concomitant AD. The Sirt 1 inhibitor EX527 partially reversed the effects of resveratrol. Conclusion: This study suggests that resveratrol may have a neuroprotective action through activation of Sirt1 signaling in diabetes and AD with concurrent onset.
ESTHER : Ma_2019_Front.Neurosci_13_1400
PubMedSearch : Ma_2019_Front.Neurosci_13_1400
PubMedID: 32038127

Title : Pharmacological activities of dihydrotanshinone I, a natural product from Salvia miltiorrhiza Bunge - Chen_2019_Pharmacol.Res_145_104254
Author(s) : Chen X , Yu J , Zhong B , Lu J , Lu JJ , Li S , Lu Y
Ref : Pharmacol Res , 145 :104254 , 2019
Abstract : Salvia miltiorrhiza Bunge (Danshen), a famous traditional Chinese herb, has been used clinically for the treatment of various diseases for centuries. Document data showed that tanshinones, a class of lipophilic abietane diterpenes rich in this herb, possess multiple biological effects in vitro and in vivo models. Among which, 15,16-dihydrotanshinone I (DHT) has received much attention in recent years. In this systematical review, we carefully selected, analyzed, and summarized high-quality publications related to pharmacological effects and the underlying mechanisms of DHT. DHT has anti-cancer, cardiovascular protective, anti-inflammation, anti-Alzheimer's disease, and other effects. Furthermore, several molecules such as hypoxia-inducible factor (HIF-1alpha), human antigen R (HuR), acetylcholinesterase (AchE), etc. have been identified as the potential targets for DHT. The diverse pharmacological activities of DHT provide scientific evidence for the local and traditional uses of Salvia miltiorrhiza Bunge. We concluded that DHT might serve as a lead compound for drug discovery in related diseases while further in-depth investigations are still needed.
ESTHER : Chen_2019_Pharmacol.Res_145_104254
PubMedSearch : Chen_2019_Pharmacol.Res_145_104254
PubMedID: 31054311

Title : Molecular cloning, expression and characterization of a novel feruloyl esterase from a soil metagenomic library with phthalate-degrading activity - Wu_2019_Biotechnol.Lett_41_995
Author(s) : Wu S , Nan F , Jiang J , Qiu J , Zhang Y , Qiao B , Li S , Xin Z
Ref : Biotechnol Lett , 41 :995 , 2019
Abstract : OBJECTIVES: To discover novel feruloyl esterases (FAEs) by the function-driven screening procedure from soil metagenome. RESULTS: A novel FAE gene bds4 was isolated from a soil metagenomic library and over-expressed in Escherichia coli. The recombinant enzyme BDS4 was purified to homogeneity with a predicted molecular weight of 38.8 kDa. BDS4 exhibited strong activity (57.05 U/mg) toward methyl ferulate under the optimum pH and temperature of 8.0 and 37 degrees C. Based on its amino acid sequence and model substrates specificity, BDS4 was classified as a type-C FAE. The quantity of the releasing ferulic acid can be enhanced significantly in the presence of xylanase compared with BDS4 alone from de-starched wheat bran. In addition, BDS4 can also hydrolyze several phthalates such as diethyl phthalate, dimethyl phthalate and dibutyl phthalate. CONCLUSION: The current investigation discovered a novel FAE with phthalate-degrading activity and highlighted the usefulness of metagenomic approaches as a powerful tool for discovery of novel FAEs.
ESTHER : Wu_2019_Biotechnol.Lett_41_995
PubMedSearch : Wu_2019_Biotechnol.Lett_41_995
PubMedID: 31102076
Gene_locus related to this paper: pseai-a0a222d555

Title : The Effector AGLIP1 in Rhizoctonia solani AG1 IA Triggers Cell Death in Plants and Promotes Disease Development Through Inhibiting PAMP-Triggered Immunity in Arabidopsis thaliana - Li_2019_Front.Microbiol_10_2228
Author(s) : Li S , Peng X , Wang Y , Hua K , Xing F , Zheng Y , Liu W , Sun W , Wei S
Ref : Front Microbiol , 10 :2228 , 2019
Abstract : Rhizoctonia solani, one of the most detrimental necrotrophic pathogens, causes rice sheath blight and poses a severe threat to production. Focus on the function of effectors secreted by necrotrophic pathogens during infection has grown rapidly in recent years. However, little is known about the virulence and mechanisms of these proteins. In this study, we performed functional studies on putative effectors in R. solani and revealed that AGLIP1 out of 13 putative effectors induced cell death in Nicotiana benthamiana. AGLIP1 was also demonstrated to trigger cell death in rice protoplasts. The predicted lipase active sites and signal peptide (SP) of this protein were required for the cell death-inducing ability. AGLIP1 was greatly induced during R. solani infection in rice sheath. The AGLIP1's virulence function was further demonstrated by transgenic technology. The pathogenesis-related genes induced by pathogen-associated molecular pattern and bacteria were remarkably inhibited in AGLIP1-expressing transgenic Arabidopsis lines. Ectopic expression of AGLIP1 strongly facilitated disease progression in Arabidopsis caused by the type III secretion system-defective mutant from Pseudomonas syringae pv. tomato DC3000. Collectively, these results indicate that AGLIP1 is a possible effector that plays a significant role in pathogen virulence through inhibiting basal defenses and promoting disease development in plants.
ESTHER : Li_2019_Front.Microbiol_10_2228
PubMedSearch : Li_2019_Front.Microbiol_10_2228
PubMedID: 31611861
Gene_locus related to this paper: 9agam-a0a8h2wbw6

Title : Protective role of phenylethanoid glycosides, Torenoside B and Savatiside A, in Alzheimer's disease - Ji_2019_Exp.Ther.Med_17_3755
Author(s) : Ji S , Li S , Zhao X , Kang N , Cao K , Zhu Y , Peng P , Fan J , Xu Q , Yang S , Liu Y
Ref : Exp Ther Med , 17 :3755 , 2019
Abstract : The current study assessed the efficacy of two phenylethanoid glycosides (PhGs), Torenoside B (TB) and Savatiside A (SA), in the treatment of Alzheimer's disease (AD). The effects of TB and SA compounds were first assessed following amyloid beta (Abeta)25-35 induction in SH-SY5Y cells at a range of concentrations. Their effects on cell viability and reactive oxygen species (ROS) were determined by performing MTT and dichlorofluorescin diacetate assays, respectively. The concentration of intracellular Ca(2+) was determined using Fluo-3AM to stain SH-SY5Y cells. SA and TB treatments were also assessed in Abeta25-35-induced mice. Y-maze and Morris water maze methods were utilized to assess murine learning and memory capability. The pathological changes of murine hippocampi was determined using H&E and Nissl staining. In addition, biochemical parameters associated with intracellular reactive oxygen pathways including Maleic dialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE) and Calnexin were also assessed. TB and SA treatment in Abeta25-35-induced SH-SY5Y cells resulted in the restoration of cell morphology, an increase of SOD and GSH-Px activity, a decrease in ROS, Ca(2+) and MDA content, and a decrease in Calnexin expression. Furthermore, SA or TB treatment administered to Abeta25-35-induced mice improved their spatial/non-spatial learning and memory capabilities. The efficacy of treatment was also supported by a marked change in the morphological structure of pyramidal neurons in the CA1 areas of murine hippocampi, as well as an increase of SOD and GSH-Px activity. Treatment also resulted in a decrease in MDA content, AchE activity and Calnexin expression in murine hippocampal tissue. As potential AD treatment drugs, SA and TB compounds have been demonstrated to alleviate the oxidative stress induced by Abeta25-35 via the regulation of intracellular calcium homeostasis and Calnexin, preventing AD development.
ESTHER : Ji_2019_Exp.Ther.Med_17_3755
PubMedSearch : Ji_2019_Exp.Ther.Med_17_3755
PubMedID: 30988761

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

Title : Endoplasmic Reticulum Targeting Ratiometric Fluorescent Probe for Carboxylesterase 2 Detection in Drug-Induced Acute Liver Injury - Tian_2019_Anal.Chem_91_15840
Author(s) : Tian X , Yan F , Zheng J , Cui X , Feng L , Li S , Jin L , James TD , Ma X
Ref : Analytical Chemistry , 91 :15840 , 2019
Abstract : Carboxylesterase 2 (CES2), an endoplasmic reticulum (ER) located phase I enzyme, plays a vital role in the metabolism of various endogenous and exogenous substances, and is regarded as an important target for the design of prodrugs. Unfortunately, superior highly selective ER targeting fluorescent probes for monitoring of CES2 are not currently available. Herein, we report an ER targeting CES2 selective and sensitive ratiometric fluorescent probe ERNB based on the ER localizing group p-toluenesulfonamide. ERNB possessed high specificity, sensitivity, and exhibited excellent subcellular localization when compared to commercial ER tracker, and was used to image CES2 in the ER of living cells. Additionally, using ERNB we evaluated the CES2 regulation under d,l-dithiothreitol and tunicamycin-induced ER stress. Furthermore, we determined the down regulation of CES2 activity and expression in the acetaminophen-induced acute liver injury model. On the basis of these results, we conclude that ERNB is a promising tool for highlighting the role of CES2 in the ER and in exploring the role of CES2 in the development of diseases associated with ER stress.
ESTHER : Tian_2019_Anal.Chem_91_15840
PubMedSearch : Tian_2019_Anal.Chem_91_15840
PubMedID: 31713417
Gene_locus related to this paper: human-CES2

Title : Sequencing of a Wild Apple (Malus baccata) Genome Unravels the Differences Between Cultivated and Wild Apple Species Regarding Disease Resistance and Cold Tolerance - Chen_2019_G3.(Bethesda)_9_2051
Author(s) : Chen X , Li S , Zhang D , Han M , Jin X , Zhao C , Wang S , Xing L , Ma J , Ji J , An N
Ref : G3 (Bethesda) , 9 :2051 , 2019
Abstract : Malus baccata is one of four wild apple species that can hybridize with the cultivated apple species (Malus domestica). It is widely used in high-latitude apple-producing areas as a rootstock and breeding resource because of its disease resistance, and cold tolerance. A lack of a reference genome has limited the application of M. baccata for apple breeding. We present a draft reference genome for M. baccata The assembled sequence consisting of 665 Mb, with a scaffold N50 value of 452 kb, included transposable elements (413 Mb) and 46,114 high-quality protein-coding genes. According to a genetic map derived from 390 sibling lines, 72% of the assembly and 85% of the putative genes were anchored to 17 linkage groups. Many of the M. baccata genes under positive selection pressure were associated with plant-pathogen interaction pathways. We identified 2,345 Transcription factor-encoding genes in 58 families in the M. baccata genome. Genes related to disease defense and cold tolerance were also identified. A total of 462 putative nucleotide-binding site (NBS)-leucine-rich-repeat (LRR) genes, 177 Receptor-like kinase (RLK) and 51 receptor-like proteins (RLP) genes were identified in this genome assembly. The M. baccata genome contained 3978 cold-regulated genes, and 50% of these gene promoter containing DREB motif which can be induced by CBF gene. We herein present the first M. baccata genome assembly, which may be useful for exploring genetic variations in diverse apple germplasm, and for facilitating marker-assisted breeding of new apple cultivars exhibiting resistance to disease and cold stress.
ESTHER : Chen_2019_G3.(Bethesda)_9_2051
PubMedSearch : Chen_2019_G3.(Bethesda)_9_2051
PubMedID: 31126974
Gene_locus related to this paper: malba-a0a540mnd7 , malba-a0a540lct9 , malba-a0a540lik7 , malba-a0a540lik0 , malba-a0a540lri2 , malba-a0a540lr05

Title : A Thermostable Monoacylglycerol Lipase from Marine Geobacillus sp. 12AMOR1: Biochemical Characterization and Mutagenesis Study - Tang_2019_Int.J.Mol.Sci_20_
Author(s) : Tang W , Lan D , Zhao Z , Li S , Li X , Wang Y
Ref : Int J Mol Sci , 20 : , 2019
Abstract : Lipases with unique substrate specificity are highly desired in biotechnological applications. In this study, a putative marine Geobacillus sp. monoacylglycerol lipase (GMGL) encoded gene was identified by a genomic mining strategy. The gene was expressed in Escherichia coli as a His-tag fusion protein and purified by affinity chromatography with a yield of 264 mg per liter fermentation broth. The recombinant GMGL shows the highest hydrolysis activity at 60 degrees C and pH 8.0, and the half-life was 60 min at 70 degrees C. The GMGL is active on monoacylglycerol (MAG) substrate but not diacylglycerol (DAG) or triacylglycerol (TAG), and produces MAG as the single product in the esterification reaction. Modeling structure analysis showed that the catalytic triad is formed by Ser97, Asp196 and His226, and the flexible cap region is constituted by residues from Ala120 to Thr160. A mutagenesis study on Leu142, Ile145 and Ile170 located in the substrate binding tunnel revealed that these residues were related with its substrate specificity. The kcat/Km value toward the pNP-C6 substrate in mutants Leu142Ala, Ile145Ala and Ile170Phe increased to 2.3-, 1.4- and 2.2-fold as compared to that of the wild type, respectively.
ESTHER : Tang_2019_Int.J.Mol.Sci_20_
PubMedSearch : Tang_2019_Int.J.Mol.Sci_20_
PubMedID: 30759774
Gene_locus related to this paper: 9baci-a0a0g3xxb4

Title : Ameliorative effect of deoxyvasicine on scopolamine-induced cognitive dysfunction by restoration of cholinergic function in mice - Deng_2019_Phytomedicine_63_153007
Author(s) : Deng G , Wu C , Rong X , Li S , Ju Z , Wang Y , Ma C , Ding W , Guan H , Cheng X , Liu W , Wang C
Ref : Phytomedicine , 63 :153007 , 2019
Abstract : BACKGROUND: Aerial parts of Peganum harmala Linn is used as a traditional medical herb for treatment of amnesia in Uighur medicine in China. Deoxyvasicine (DVAS) is one of the chief active ingredients in P. harmala, it possesses strong acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities in vitro, but the therapeutic effect and mechanisms on amnesia in vivo are unclear. PURPOSE: The objective of this study was to investigate the improvement effect of DVAS from P. harmala in learning and memory deficits of scopolamine-induced mice and elucidate the underlying mechanisms involved. METHODS: Mice were pretreated with DVAS (5, 15 and 45mg/kg) and huperzine-A (0.2mg/kg) by gavage for 7 days, and subsequently were daily intraperitoneally injected with scopolamine (1mg/kg) to induce learning and memory deficits and behavioral performance was assessed by Morris water maze. To further evaluate the potential mechanisms of DVAS in improving learning and memory capabilities, pathological change, levels of various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation were examined. RESULTS: The results showed that DVAS could alleviate learning and memory deficits in scopolamine-treated mice. DVAS could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities and protein expressions. DVAS could induce brain-derived neurotrophic factor and protect hippocampal pyramidal cells against neuronal damage. DVAS also enhanced antioxidant defense via increasing the antioxidant enzyme level and activity of glutathione peroxidase, and anti-inflammatory function through suppressing tumor necrosis factor-alpha. Additionally, DVAS could regulate the neurotransmitters by elevating acetylcholine, 5-hydroxytryptamine, gamma-aminobutyric acid and reducing 5-hydroxyindole-3-acetic acid and glutamic acid. CONCLUSION: Results illustrated that DVAS may be a promising candidate compound against amnesia via restoration of cholinergic function, regulating neurotransmitters, attenuating neuroinflammation and oxidative stress.
ESTHER : Deng_2019_Phytomedicine_63_153007
PubMedSearch : Deng_2019_Phytomedicine_63_153007
PubMedID: 31301537

Title : Shen-Yuan-Dan Capsule Attenuates Atherosclerosis and Foam Cell Formation by Enhancing Autophagy and Inhibiting the PI3K\/Akt\/mTORC1 Signaling Pathway - Zhou_2019_Front.Pharmacol_10_603
Author(s) : Zhou M , Ren P , Zhang Y , Li S , Li M , Li P , Shang J , Liu W , Liu H
Ref : Front Pharmacol , 10 :603 , 2019
Abstract : Background and Aim: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a crucial role in autophagy and inflammation. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a Chinese medicine used for treating angina pectoris, has anti-atherosclerotic and anti-inflammatory effects in mice. However, its effects on autophagy and the PI3K/Akt/mTORC1 signaling pathway remain unclear. This study aimed to explore the effects of SYDC on autophagy and PI3K/Akt/mTORC1 signaling in the apolipoprotein E knockout (ApoE(-/-)) mouse model and in macrophage-derived foam cells to delineate the underlying mechanism. Methods: After 6 weeks of high-fat diet, ApoE(-/-) mice were randomly grouped into control, Lipitor, low-SYDC (SYDC-L), middle-SYDC (SYDC-M), and high-SYDC (SYDC-H) groups (n = 10). The mice were intragastrically administered the respective treatment for 6 weeks. Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (80 microg/ml) for 24 h and then pretreated with SYDC freeze-dried powder for another 24 h. Cells treated with SYDC were co-cultured for 24 h with LY294002, tricirbine, and rapamycin to investigate the effects on the PI3K/Akt/mTORC1 signaling pathway. Results: SYDC ameliorated blood lipid levels, reduced the atherosclerotic index and plaque areas in the aortic root in mice, and inhibited total cholesterol (TC) levels and cholinesterase (ChE)/TC ratios in ox-LDL stimulated macrophages. Moreover, SYDC up-regulated Beclin1 and LC3II/I proteins in mice and in the ox-LDL-stimulated macrophages. Moreover, SYDC inhibited AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 in mice and in ox-LDL-stimulated macrophages. Furthermore, SYDC's inhibitory of ChE/TC ratios in ox-LDL-stimulated macrophages was not changed by selective inhibition of the PI3K/Akt/mTORC1 pathway. Conclusions: Our results highlight that SYDC treatment attenuates foam cell formation by promoting autophagy via inhibiting activation of the PI3K/Akt/mTORC1 signaling pathway. This study provides new insights into the molecular mechanism underlying SYDC's therapeutic potential for treating atherosclerosis.
ESTHER : Zhou_2019_Front.Pharmacol_10_603
PubMedSearch : Zhou_2019_Front.Pharmacol_10_603
PubMedID: 31214032

Title : New Sesquiterpenoids from the Fermented Broth of Termitomyces albuminosus and their Anti-Acetylcholinesterase Activity - Li_2019_Molecules_24_2980
Author(s) : Li W , Liu Q , Li S , Zheng Y
Ref : Molecules , 24 :2980 , 2019
Abstract : Termitomyces albuminosus is the symbiotic edible mushroom of termites and cannot be artificially cultivated at present. In the project of exploring its pharmaceutical metabolites by microbial fermentation, four new selinane type sesquiterpenoids-teucdiol C (1), D (2), E (3), and F (4), together with two known sesquiterpenoids teucdiol B (5) and epi-guaidiol A (6)-were obtained from its fermented broth of T. albuminosus. Their structures were elucidated by the analysis of NMR data, HR Q-TOF MS spectral data, CD, IR, UV, and single crystal X-ray diffraction. Epi-guaidiol A showed obvious anti-acetylcholinesterase activity in a dose-dependent manner. The experimental results displayed that T. albuminosus possess the pharmaceutical potential for Alzheimer's disease, and it was an effective way to dig new pharmaceutical agent of T. albuminosus with the microbial fermentation technique.
ESTHER : Li_2019_Molecules_24_2980
PubMedSearch : Li_2019_Molecules_24_2980
PubMedID: 31426402

Title : Activatable Near-Infrared Fluorescent Probe for Dipeptidyl Peptidase IV and Its Bioimaging Applications in Living Cells and Animals - Liu_2018_Anal.Chem_90_3965
Author(s) : Liu T , Ning J , Wang B , Dong B , Li S , Tian X , Yu Z , Peng Y , Wang C , Zhao X , Huo X , Sun C , Cui J , Feng L , Ma X
Ref : Analytical Chemistry , 90 :3965 , 2018
Abstract : Visualization of endogenous disease-associated enzymes is of great clinical significance, as it could allow earlier clinical diagnosis and timely intervention. Herein, we first synthesized and characterized an enzyme-activatable near-infrared fluorescent probe, GP-DM, for determining the activity of dipeptidyl peptidase IV (DPP IV), which is associated with various pathological processes, especially in diabetes and malignant tumors. GP-DM emitted significant turn-on NIR fluorescent signals simultaneously in response to DPP IV, making it favorable for accurately and dynamically monitoring DPP IV activity in vitro and in vivo. GP-DM exhibited excellent specificity and sensitivity in DPP IV imaging, as indicated by its higher catalytic activity than other human serine hydrolases and by its strong anti-interference ability to a complex biological matrix, which was fully characterized in a series of phenotyping reactions and inhibition assays. Encouraged by the advantages mentioned above, we successfully used GP-DM to evaluate endogenous DPP IV activity in various biological samples (plasma and tissue preparations) and living tumor cells and performed real-time in vivo bioimaging of DPP IV in zebrafish and tumor-bearing nude mice. All of the results reflected and highlighted the potential application value of GP-DM in the early detection of pathologies, individual tailoring of drug therapy, and image-guided tumor resection. Furthermore, our results revealed that DPP IV, a key target enzyme, is closely associated with the migration and proliferation of cancer cells and regulating the biological activity of DPP IV may be a useful approach for cancer therapy.
ESTHER : Liu_2018_Anal.Chem_90_3965
PubMedSearch : Liu_2018_Anal.Chem_90_3965
PubMedID: 29493228

Title : Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo - Zhu_2018_Eur.J.Pharm.Sci_123_459
Author(s) : Zhu Y , Liu W , Qi S , Wang H , Wang Y , Deng G , Zhang Y , Li S , Ma C , Cheng X , Wang C
Ref : Eur J Pharm Sci , 123 :459 , 2018
Abstract : Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer's disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results, the glucuronidation metabolic rate of l-VAS was faster than d-VAS in human liver microsomes and isoenzymes tests, and it was proved that the UDP-glucuronosyltransferase (UGT) 1A9 and UGT2B15 were the major metabolic enzymes for glucuronidation of l-VAS, while only UGT1A9 for d-VAS, which take responsibility of the significantly less metabolic affinity of d-VAS than l-VAS in HLM and rhUGT1A9. The plasma exposure of d-VAS in rats was 1.3-fold and 1.6-fold higher than that of l-VAS after intravenous and oral administration of d-VAS and l-VAS, respectively. And the plasma exposure of the major glucuronidation metabolite d-VASG was one of tenth of l-VASG or more less, no matter by intravenous or oral administration. Both d-VAS and l-VAS were exhibited promising acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, and the BChE inhibitory activity of d-VAS with IC50 of 0.03+/-0.001muM was significantly stronger than that of l-VAS with IC50 of 0.98+/-0.19muM. The molecular docking results indicated that d-VAS and l-VAS could bind to the catalytic active site (CAS position) either of human AChE and BChE, and the BChE combing ability of d-VAS (the score of GBI/WAS dG -7.398) was stronger than that of l-VAS (the score of GBI/WAS dG -7.135). Both d-VAS and l-VAS could improving the learning and memory on scopolamine-induced memory deficits in mice. The content of acetylcholine (ACh) after oral administration d-VAS increased more than that of l-VAS in mice cortex, through inhibiting cholinesterase (ChE) and increasing choline acetyltransferase (ChAT). In addition, the LD50 value of d-VAS ( was slight lower than l-VAS ( These results indicated that VAS enantiomers displayed significantly stereoselective metabolic, pharmacokinetics, anti-amnesic effect and toxic properties in vitro and in vivo. The d-VAS might be the dominant configuration for treating Alzheimer's disease.
ESTHER : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedSearch : Zhu_2018_Eur.J.Pharm.Sci_123_459
PubMedID: 30077712

Title : Protective effects of evodiamine in experimental paradigm of Alzheimer's disease - Wang_2018_Cogn.Neurodyn_12_303
Author(s) : Wang D , Wang C , Liu L , Li S
Ref : Cogn Neurodyn , 12 :303 , 2018
Abstract : Evodiamine, a major component of Evodia rutaecarpa, has been reported to possess various pharmacological activities, including anti-inflammatory, antioxidative stress, and neuroprotective effects. Our previous study has shown that the potential effects of evodiamine on the learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). The present study was designed to investigate neuroprotective mechanism and therapeutic potential of evodiamine against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic Alzheimer's disease in mice. STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily oral administration with evodiamine (50 or 100 mg/kg per day) starting from the first dose of STZ for 21 days showed an improvement in STZ induced cognitive deficits as assessed by novel object recognition and Morris water maze test. Evodiamine significantly decreased STZ induced elevation in acetylcholinesterase activity and malondialdehyde level, and significantly increased STZ induced reduction in glutathione activities and superoxide dismutase activities in the hippocampus compared to control. Furthermore, evodiamine inhibited significantly glial cell activation and neuroinflammation (TNF-alpha, IL-1beta, and IL-6 levels) in the hippocampus. Moreover, evodiamine increased the activity of AKT/GSK-3beta signalling pathway and inhibited the activity of nuclear factor kappaB. In summary, our study suggests that evodiamine can be a novel therapeutic agent for the management of sporadic AD.
ESTHER : Wang_2018_Cogn.Neurodyn_12_303
PubMedSearch : Wang_2018_Cogn.Neurodyn_12_303
PubMedID: 29765479

Title : Maternal obesity aggravates the abnormality of porcine placenta by increasing N(6)-methyladenosine - Song_2018_Int.J.Obes.(Lond)_42_1812
Author(s) : Song T , Lu J , Deng Z , Xu T , Yang Y , Wei H , Li S , Jiang S , Peng J
Ref : Int J Obes (Lond) , 42 :1812 , 2018
Abstract : BACKGROUND: The growing prevalence of overweight or obese pregnancies shows an increasing risk for aberrant fetal growth and postnatal complications. Maternal obesity is associated with low birth weight (LBW) of piglets. However, the development of LBW from maternal obesity is not well understood. OBJECTIVE: This study attempts to investigate the novel RNA modification N6-methyladenosine (m(6)A) in the placenta tissues by using sows with high backfat thickness as a model for obese pregnancy. SUBJECTS/METHODS: Forty four placentas from eight sows (backfat thickness >/=21 mm) were divided into four groups by piglet weight, with group1 being LBW group (<1.0 kg), group2 (1.0-1.4 kg), group3 (1.4-1.6 kg), and group4 (>1.6 kg) as the comparative groups of normal birth weight. QPCR was used to measure the mRNA levels of the genes and western blot was used to test the content of proteins. At the same time, LC-MS/MS method was built to test the content of m(6)A modification in the placental RNA, and finally MeRIP-QPCR technology was employed to check the specific m(6)A modification in the key genes. RESULTS: Compared with the comparative groups, the expression levels of PPARgamma, VEGFA, ABHD5, and GPR120 in both mRNA and protein decreased noticeably in the LBW group. It was also observed that the density of the H&E stained vessels became attenuated in LBW group. Importantly, for the first time, the increased m(6)A levels were found in LBW placentas. Lower protein level of FTO (the key demethylase of m(6)A) was observed in LBW placentas, whereas no difference was found among the four groups in the expression levels of METTL3, the main methyltransferase of m(6)A. By using MeRIP-QPCR technology, the m(6)A modification in PPARgamma, VEGFA, ABHD5, and GPR120, as well as FTO, was considerably enhanced in the placentas from LBW group. CONCLUSION: We infer that in maternity obesity, the higher m(6)A modification displayed in the genes related to placental development, lipid metabolism and angiogenesis may result in the down regulation of these genes, which could be associated with m(6)A demethylase FTO.
ESTHER : Song_2018_Int.J.Obes.(Lond)_42_1812
PubMedSearch : Song_2018_Int.J.Obes.(Lond)_42_1812
PubMedID: 29795472

Title : Glioblastoma stem cell-derived exosomes induce M2 macrophages and PD-L1 expression on human monocytes - Gabrusiewicz_2018_Oncoimmunology_7_e1412909
Author(s) : Gabrusiewicz K , Li X , Wei J , Hashimoto Y , Marisetty AL , Ott M , Wang F , Hawke D , Yu J , Healy LM , Hossain A , Akers JC , Maiti SN , Yamashita S , Shimizu Y , Dunner K , Zal MA , Burks JK , Gumin J , Nwajei F , Rezavanian A , Zhou S , Rao G , Sawaya R , Fuller GN , Huse JT , Antel JP , Li S , Cooper L , Sulman EP , Chen C , Geula C , Kalluri R , Zal T , Heimberger AB
Ref : Oncoimmunology , 7 :e1412909 , 2018
Abstract : Exosomes can mediate a dynamic method of communication between malignancies, including those sequestered in the central nervous system and the immune system. We sought to determine whether exosomes from glioblastoma (GBM)-derived stem cells (GSCs) can induce immunosuppression. We report that GSC-derived exosomes (GDEs) have a predilection for monocytes, the precursor to macrophages. The GDEs traverse the monocyte cytoplasm, cause a reorganization of the actin cytoskeleton, and skew monocytes toward the immune suppresive M2 phenotype, including programmed death-ligand 1 (PD-L1) expression. Mass spectrometry analysis demonstrated that the GDEs contain a variety of components, including members of the signal transducer and activator of transcription 3 (STAT3) pathway that functionally mediate this immune suppressive switch. Western blot analysis revealed that upregulation of PD-L1 in GSC exosome-treated monocytes and GBM-patient-infiltrating CD14(+) cells predominantly correlates with increased phosphorylation of STAT3, and in some cases, with phosphorylated p70S6 kinase and Erk1/2. Cumulatively, these data indicate that GDEs are secreted GBM-released factors that are potent modulators of the GBM-associated immunosuppressive microenvironment.
ESTHER : Gabrusiewicz_2018_Oncoimmunology_7_e1412909
PubMedSearch : Gabrusiewicz_2018_Oncoimmunology_7_e1412909
PubMedID: 29632728

Title : A reference genome of the Chinese hamster based on a hybrid assembly strategy - Rupp_2018_Biotechnol.Bioeng_115_2087
Author(s) : Rupp O , MacDonald ML , Li S , Dhiman H , Polson S , Griep S , Heffner K , Hernandez I , Brinkrolf K , Jadhav V , Samoudi M , Hao H , Kingham B , Goesmann A , Betenbaugh MJ , Lewis NE , Borth N , Lee KH
Ref : Biotechnol Bioeng , 115 :2087 , 2018
Abstract : Accurate and complete genome sequences are essential in biotechnology to facilitate genome-based cell engineering efforts. The current genome assemblies for Cricetulus griseus, the Chinese hamster, are fragmented and replete with gap sequences and misassemblies, consistent with most short-read-based assemblies. Here, we completely resequenced C. griseus using single molecule real time sequencing and merged this with Illumina-based assemblies. This generated a more contiguous and complete genome assembly than either technology alone, reducing the number of scaffolds by >28-fold, with 90% of the sequence in the 122 longest scaffolds. Most genes are now found in single scaffolds, including up- and downstream regulatory elements, enabling improved study of noncoding regions. With >95% of the gap sequence filled, important Chinese hamster ovary cell mutations have been detected in draft assembly gaps. This new assembly will be an invaluable resource for continued basic and pharmaceutical research.
ESTHER : Rupp_2018_Biotechnol.Bioeng_115_2087
PubMedSearch : Rupp_2018_Biotechnol.Bioeng_115_2087
PubMedID: 29704459
Gene_locus related to this paper: crigr-g3h083 , crigr-a0a3l7ib08 , crigr-g3ifk5 , crigr-g3h7k6

Title : Impact of Fabp1 Gene Ablation on Uptake and Degradation of Endocannabinoids in Mouse Hepatocytes - McIntosh_2018_Lipids_53_561
Author(s) : McIntosh AL , Huang H , Landrock D , Martin GG , Li S , Kier AB , Schroeder F
Ref : Lipids , 53 :561 , 2018
Abstract : Liver fatty-acid-binding protein (FABP1, L-FABP) is the major cytosolic binding/chaperone protein for both precursor arachidonic acid (ARA) and the endocannabinoid (EC) products N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). Although FABP1 regulates hepatic uptake and metabolism of ARA, almost nothing is known regarding FABP1's impact on AEA and 2-AG uptake, intracellular distribution, and targeting of AEA and 2-AG to degradative hepatic enzymes. In vitro assays revealed that FABP1 considerably enhanced monoacylglycerol lipase hydrolysis of 2-AG but only modestly enhanced AEA hydrolysis by fatty-acid amide hydrolase. Conversely, liquid chromatography-mass spectrometry of lipids from Fabp1 gene-ablated (LKO) hepatocytes confirmed that loss of FABP1 markedly diminished hydrolysis of 2-AG. Furthermore, the real-time imaging of novel fluorescent NBD-labeled probes (NBD-AEA, NBD-2-AG, and NBD-ARA) resolved FABP1's impact on uptake vs intracellular targeting/hydrolysis. FABP1 bound NBD-ARA with 2:1 stoichiometry analogous to ARA, but bound NBD-2-AG and NBD-AEA with 1:1 stoichiometry-apparently at different sites in FABP1's binding cavity. All three probes were taken up, but NBD-2-AG and NBD-AEA were targeted to lipid droplets. LKO reduced the uptake of NBD-ARA as expected, significantly enhanced that of NBD-AEA, but had little effect on NBD-2-AG. These data indicated that FABP1 impacts hepatocyte EC levels by binding EC and differentially impacts their intracellular hydrolysis (2-AG) and uptake (AEA).
ESTHER : McIntosh_2018_Lipids_53_561
PubMedSearch : McIntosh_2018_Lipids_53_561
PubMedID: 30203570

Title : Use of low-dose neostigmine intravenously in the treatment of thyroid storm-induced severe tachycardia in patient during huge pelvic mass resection: A case report and review of literature - Zhang_2018_Medicine.(Baltimore)_97_e0300
Author(s) : Zhang X , Jiang H , Li S , Luo A , Zhao Y
Ref : Medicine (Baltimore) , 97 :e0300 , 2018
Abstract : RATIONALE: Thyroid storm is a rare and life-threatening metabolic crisis because of an emergent release of excess thyroid hormone. Sinus tachycardia induced by excess thyroid hormone may result in congestive heart failure due to decreased diastolic filling time. PATIENT CONCERNS: A controlled hyperthyroidism patient with severe sinus tachycardia. DIAGNOSES: A controlled hyperthyroidism patient was induced thyroid storm during huge pelvic mass resection. INTERVENTIONS: Application of low-dose neostigmine and beta-antagonist esmolol to control the heart rate (HR) avoided hemodynamic collapse. OUTCOMES: The patient improved dramatically following application of low-dose neostigmine instead of esmolol to control the HR avoided hemodynamic collapse. LESSONS: Our case suggests that neostigmine, an acetylcholinesterase inhibitor, may warrant further investigation in patients with thyroid storm-induced severe sinus tachycardia.
ESTHER : Zhang_2018_Medicine.(Baltimore)_97_e0300
PubMedSearch : Zhang_2018_Medicine.(Baltimore)_97_e0300
PubMedID: 29620652

Title : Rice DWARF14 acts as an unconventional hormone receptor for strigolactone - Yao_2018_J.Exp.Bot_69_2355
Author(s) : Yao R , Wang L , Li Y , Chen L , Li S , Du X , Wang B , Yan J , Li J , Xie D
Ref : J Exp Bot , 69 :2355 , 2018
Abstract : Strigolactones (SLs) act as an important class of phytohormones to regulate plant shoot branching, and also serve as rhizosphere signals to mediate interactions of host plants with soil microbes and parasitic weeds. SL receptors in dicots, such as DWARF14 in Arabidopsis (AtD14), RMS3 in pea, and ShHTL7 in Striga, serve as unconventional receptors that hydrolyze SLs into a D-ring-derived intermediate CLIM and irreversibly bind CLIM to trigger SL signal transduction. Here, we show that D14 from the monocot rice can complement Arabidopsis d14 mutant and interact with the SL signaling components in Arabidopsis. Our results further reveal that rice D14, similar to SL receptors in dicots, also serves as an unconventional hormone receptor that generates and irreversibly binds the active form of SLs. These findings uncover the conserved functions of D14 proteins in monocots and dicots.
ESTHER : Yao_2018_J.Exp.Bot_69_2355
PubMedSearch : Yao_2018_J.Exp.Bot_69_2355
PubMedID: 29365172

Title : The molecular basis for lipase stereoselectivity - Chen_2018_Appl.Microbiol.Biotechnol_102_3487
Author(s) : Chen H , Meng X , Xu X , Liu W , Li S
Ref : Applied Microbiology & Biotechnology , 102 :3487 , 2018
Abstract : Lipases are among the most applied biocatalysts in organic synthesis to catalyze the kinetic resolution of a wide range of racemic substrates to yield optically pure compounds. Due to the rapidly increased demands for optically pure compounds, deep understanding of the molecular basis for lipase stereoselectivity and how to obtain lipases with excellent asymmetric selectivity have become one of primary research goals in this field. This review is focused on the molecular factors that have impacts on the stereoselectivity of lipases including the steric complementarity between the lipase topological structure and its substrate, the regional structural flexibility, the hydrogen bonds between the residues around the catalytic site and the tetrahedral intermediates, and the electrostatic interactions between surface residues. Moreover, the synergistic effects of these structural factors on the catalytic properties including stereoselectivity, activity, and stability are also discussed.
ESTHER : Chen_2018_Appl.Microbiol.Biotechnol_102_3487
PubMedSearch : Chen_2018_Appl.Microbiol.Biotechnol_102_3487
PubMedID: 29500755

Title : Protective effects of taurine against inflammation, apoptosis, and oxidative stress in brain injury - Niu_2018_Mol.Med.Rep_18_4516
Author(s) : Niu X , Zheng S , Liu H , Li S
Ref : Mol Med Rep , 18 :4516 , 2018
Abstract : The protective effect of taurine against inflammation, apoptosis and oxidative stress in traumatic brain injury was investigated in the present study. Taurine is a nonproteogenic and essential amino acid in animals. It plays a critical nutritional role in brain cell growth, differentiation, and development. Taurine is involved in regeneration and neuroprotection in the injured nervous system, and is an effective antioxidant against lead, cadmium, and exerciseinduced oxidative stress. Astrocytes and neuron cells were cocultured and cells were treated with different concentrations of taurine (100, 200 and 300 mg/l) for 72 h, and the levels of reactive oxygen species, malondialdehyde, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, acetylcholinesterase, tumor necrosis factoralpha, interleukin6, caspase3, p53, Bcell lymphoma 2 and Bcl2associated X protein were determined. These inflammatory, apoptotic, and oxidative stress markers were substantially increased in injured cells, and returned to normal levels following taurine supplementation. Thus, taurine supplementation may be effective against oxidative stress, apoptosis, and inflammation in injured brain cells.
ESTHER : Niu_2018_Mol.Med.Rep_18_4516
PubMedSearch : Niu_2018_Mol.Med.Rep_18_4516
PubMedID: 30221665

Title : Effects of high temperature on insecticide tolerance in whitefly Bemisia tabaci (Gennadius) Q biotype - Guo_2018_Pestic.Biochem.Physiol_150_97
Author(s) : Guo L , Su M , Liang P , Li S , Chu D
Ref : Pestic Biochem Physiol , 150 :97 , 2018
Abstract : Bemisia tabaci (Gennadius) Q biotype (BTQ) has spread to many tropical and subtropical regions over the past several decades. This may reflect an advantage biotype Q has over closely related forms in having greater thermal and/or insecticide resistance, although the effects of higher temperatures on insecticide tolerance of BTQ has, to date, been largely ignored. In this study, the effects of elevated temperatures on BTQ's tolerance to the insecticide thiamethoxam were investigated. The effect on the activities of detoxifying enzymes [carboxylesterase (CarE), glutathione S-transferase (GST), and cytochrome P450 monooxygenase (P450)] and expression profiling of eleven genes of detoxifying enzymes were also determined. In addition, RNA interference (RNAi) and bioassay methods were used to further identify the function of CYP6CM1 in tolerance to thiamethoxam following exposure to higher temperatures. The results showed that elevated temperatures were responsible for causing different outcomes in the tolerance of BTQ to thiamethoxam: Temperatures of 35 degrees C or higher decreased the tolerance of BTQ to thiamethoxam, while a moderately high temperature of 31 degrees C increased the tolerance. The high temperature influenced the tolerance of BTQ by affecting the activity of P450. Quantitative real-time PCR (qPCR) showed that CYP6CM1 was significantly up-regulated in most treatments at 31 degrees C, but was suppressed at 35 degrees C, which was closely associated with the mortality rates. Feeding on double-stranded RNA (dsRNA) of CYP6CM1 significantly reduced the mRNA levels of the target gene in the adults, and dramatically decreased tolerance to thiamethoxam induced by a temperature of 31 degrees C for 6h. Our finding provides useful information to better understand the invasion mechanism of BTQ.
ESTHER : Guo_2018_Pestic.Biochem.Physiol_150_97
PubMedSearch : Guo_2018_Pestic.Biochem.Physiol_150_97
PubMedID: 30195394

Title : Tat-Independent Secretion of Polyethylene Terephthalate Hydrolase PETase in Bacillus subtilis 168 Mediated by Its Native Signal Peptide - Huang_2018_J.Agric.Food.Chem_66_13217
Author(s) : Huang X , Cao L , Qin Z , Li S , Kong W , Liu Y
Ref : Journal of Agricultural and Food Chemistry , 66 :13217 , 2018
Abstract : Widespread utilization of polyethylene terephthalate (PET) has caused critical environmental pollution. The enzymatic degradation of PET is a promising solution to this problem. In this study, PETase, which exhibits much higher PET-hydrolytic activity than other enzymes, was successfully secreted into extracellular milieu from Bacillus subtilis 168 under the direction of its native signal peptide (named SP(PETase)). SP(PETase) is predicted to be a twin-arginine signal peptide. Intriguingly, inactivation of twin-arginine translocation (Tat) complexes improved the secretion amount by 3.8-fold, indicating that PETase was exported via Tat-independent pathway. To the best of our knowledge, this is the first report on the improvement of Tat-independent secretion by inactivating Tat components of B. subtilis 168 in LB medium. Furthermore, PET film degradation assay showed that the secreted PETase was fully active. This study paves the first step to construct an efficient engineered strain for PET degradation.
ESTHER : Huang_2018_J.Agric.Food.Chem_66_13217
PubMedSearch : Huang_2018_J.Agric.Food.Chem_66_13217
PubMedID: 30465427

Title : An alkaline and surfactant-tolerant lipase from Trichoderma lentiforme ACCC30425 with high application potential in the detergent industry - Wang_2018_AMB.Express_8_95
Author(s) : Wang Y , Ma R , Li S , Gong M , Yao B , Bai Y , Gu J
Ref : AMB Express , 8 :95 , 2018
Abstract : Alkaline lipases with adaptability to low temperatures and strong surfactant tolerance are favorable for application in the detergent industry. In the present study, a lipase-encoding gene, TllipA, was cloned from Trichoderma lentiforme ACCC30425 and expressed in Pichia pastoris GS115. The purified recombinant TlLipA was found to have optimal activities at 50 degreesC and pH 9.5 and retain stable over the pH range of 6.0-10.0 and 40 degreesC and below. When using esters of different lengths as substrates, TlLipA showed preference for the medium length p-nitrophenyl octanoate. In comparison to commercial lipases, TlLipA demonstrated higher tolerance to various surfactants (SDS, Tween 20, and Triton X100) and retained more activities after incubation with Triton X100 for up to 24 h. These favorable characteristics make TlLipA prospective as an additive in the detergent industry.
ESTHER : Wang_2018_AMB.Express_8_95
PubMedSearch : Wang_2018_AMB.Express_8_95
PubMedID: 29873028
Gene_locus related to this paper: 9hypo-a0a2z2qj16

Title : Complete biosynthesis of noscapine and halogenated alkaloids in yeast - Li_2018_Proc.Natl.Acad.Sci.U.S.A_115_E3922
Author(s) : Li Y , Li S , Thodey K , Trenchard I , Cravens A , Smolke CD
Ref : Proc Natl Acad Sci U S A , 115 :E3922 , 2018
Abstract : Microbial biosynthesis of plant natural products from simple building blocks is a promising approach toward scalable production and modification of high-value compounds. The pathway for biosynthesis of noscapine, a potential anticancer compound, from canadine was recently elucidated as a 10-gene cluster from opium poppy. Here we demonstrate the de novo production of noscapine in Saccharomyces cerevisiae, through the reconstruction of a biosynthetic pathway comprising over 30 enzymes from plants, bacteria, mammals, and yeast itself, including 7 plant endoplasmic reticulum (ER)-localized enzymes. Optimization directed to tuning expression of pathway enzymes, host endogenous metabolic pathways, and fermentation conditions led to an over 18,000-fold improvement from initial noscapine titers to -2.2 mg/L. By feeding modified tyrosine derivatives to the optimized noscapine-producing strain we further demonstrated microbial production of halogenated benzylisoquinoline alkaloids. This work highlights the potential for microbial biosynthetic platforms to support the synthesis of valuable and novel alkaloid compounds, which can advance alkaloid-based drug discovery and development.
ESTHER : Li_2018_Proc.Natl.Acad.Sci.U.S.A_115_E3922
PubMedSearch : Li_2018_Proc.Natl.Acad.Sci.U.S.A_115_E3922
PubMedID: 29610307
Gene_locus related to this paper: papso-cxe1

Title : Identification and characterization of a novel carboxylesterase (FpbH) that hydrolyzes aryloxyphenoxypropionate herbicides - Wang_2017_Biotechnol.Lett_39_553
Author(s) : Wang C , Qiu J , Yang Y , Zheng J , He J , Li S
Ref : Biotechnol Lett , 39 :553 , 2017
Abstract : OBJECTIVE: To identify and characterize a novel aryloxyphenoxypropionate (AOPP) herbicide-hydrolyzing carboxylesterase from Aquamicrobium sp. FPB-1.
RESULTS: A carboxylesterase gene, fpbH, was cloned from Aquamicrobium sp. FPB-1. The gene is 798 bp long and encodes a protein of 265 amino acids. FpbH is smaller than previously reported AOPP herbicide-hydrolyzing carboxylesterases and shares only 21-35% sequence identity with them. FpbH was expressed in Escherichia coli BL21(DE3) and the product was purified by Ni-NTA affinity chromatography. The purified FpbH hydrolyzed a wide range of AOPP herbicides with catalytic efficiency in the order: haloxyfop-P-methyl > diclofop-methyl > fenoxaprop-P-ethyl > quizalofop-P-ethyl > fluazifop-P-butyl > cyhalofop-butyl. The optimal temperature and pH for FpbH activity were 37 degrees C and 7, respectively.
CONCLUSIONS: FpbH is a novel AOPP herbicide-hydrolyzing carboxylesterase; it is a good candidate for mechanistic study of AOPP herbicide-hydrolyzing carboxylesterases and for bioremediation of AOPP herbicide-contaminated environments.
ESTHER : Wang_2017_Biotechnol.Lett_39_553
PubMedSearch : Wang_2017_Biotechnol.Lett_39_553
PubMedID: 28058522
Gene_locus related to this paper: burvg-a4jl51

Title : Conjugates of salicylaldoximes and peripheral site ligands: Novel efficient nonquaternary reactivators for nerve agent-inhibited acetylcholinesterase - Wei_2017_Bioorg.Med.Chem_25_4497
Author(s) : Wei Z , Liu YQ , Wang SZ , Yao L , Nie HF , Wang YA , Liu XY , Zheng ZB , Li S
Ref : Bioorganic & Medicinal Chemistry , 25 :4497 , 2017
Abstract : A new family of nonquaternary reactivators for nerve agent-inhibited human acetylcholinesterase (hAChE) were designed, synthesized and tested in this paper. It was found that salicylaldoximes were able to quickly cleave the P-S bond of organophosphate and avoid the reinhibition phenomenon in the reactivation process, but they lacked reactivating ability due to poor affinity for AChE. Based on a dual site binding strategy, different peripheral site ligands of AChE were introduced to achieve extra affinity. The in vitro reactivation experiments demonstrated that some of the yielding conjugates exhibited similar or even superior ability to reactivate sarin-, VX- or tabun-inhibited hAChE in comparison with the mono- and bis-pyridinium aldoximes currently used. Moreover, due to greatly improved lipophilicity, these nonquaternary conjugates hold promise for the development of efficient centrally activating reactivators.
ESTHER : Wei_2017_Bioorg.Med.Chem_25_4497
PubMedSearch : Wei_2017_Bioorg.Med.Chem_25_4497
PubMedID: 28684009

Title : Crystal structure of Pelagibacterium halotolerans PE8: New insight into its substrate-binding pattern - Huo_2017_Sci.Rep_7_4422
Author(s) : Huo YY , Li S , Huang J , Rong Z , Wang Z , Li Z , Ji R , Kuang S , Cui HL , Li J , Xu XW
Ref : Sci Rep , 7 :4422 , 2017
Abstract : Lysophospholipase_carboxylesterase (LPCE) has highly conserved homologs in many diverse species ranging from bacteria to humans, as well as substantial biological significance and potential therapeutic implications. However, its biological function and catalytic mechanism remain minimally investigated because of the lack of structural information. Here, we report the crystal structure of a bacterial esterase PE8 belonging to the LPCE family. The crystal structure of PE8 was solved with a high resolution of 1.66 A. Compared with other homologs in the family, significant differences were observed in the amino acid sequence, three-dimensional structure, and substrate-binding pattern. Residue Arg79 undergoes configuration switching when binding to the substrate and forms a unique wall, leading to a relatively closed cavity in the substrate-binding pocket compared with the relatively more open and longer clefts in other homologs. Moreover, the mutant Met122Ala showed much stronger substrate affinity and higher catalytic efficiency because less steric repulsion acted on the substrates. Taken together, these results showed that, in PE8, Arg79 and Met122 play important roles in substrate binding and the binding pocket shaping, respectively. Our study provides new insight into the catalytic mechanism of LPCE, which may facilitate the development of structure-based therapeutics and other biocatalytic applications.
ESTHER : Huo_2017_Sci.Rep_7_4422
PubMedSearch : Huo_2017_Sci.Rep_7_4422
PubMedID: 28667306
Gene_locus related to this paper: pelhb-g4rfi7

Title : The sea cucumber genome provides insights into morphological evolution and visceral regeneration - Zhang_2017_PLoS.Biol_15_e2003790
Author(s) : Zhang X , Sun L , Yuan J , Sun Y , Gao Y , Zhang L , Li S , Dai H , Hamel JF , Liu C , Yu Y , Liu S , Lin W , Guo K , Jin S , Xu P , Storey KB , Huan P , Zhang T , Zhou Y , Zhang J , Lin C , Li X , Xing L , Huo D , Sun M , Wang L , Mercier A , Li F , Yang H , Xiang J
Ref : PLoS Biol , 15 :e2003790 , 2017
Abstract : Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs.
ESTHER : Zhang_2017_PLoS.Biol_15_e2003790
PubMedSearch : Zhang_2017_PLoS.Biol_15_e2003790
PubMedID: 29023486
Gene_locus related to this paper: stija-a0a2g8k9s2 , stija-a0a2g8ka54 , stija-a0a2g8jd52 , stija-a0a2g8l0w8

Title : Genomic innovations, transcriptional plasticity and gene loss underlying the evolution and divergence of two highly polyphagous and invasive Helicoverpa pest species - Pearce_2017_BMC.Biol_15_63
Author(s) : Pearce SL , Clarke DF , East PD , Elfekih S , Gordon KHJ , Jermiin LS , McGaughran A , Oakeshott JG , Papanicolaou A , Perera OP , Rane RV , Richards S , Tay WT , Walsh TK , Anderson A , Anderson CJ , Asgari S , Board PG , Bretschneider A , Campbell PM , Chertemps T , Christeller JT , Coppin CW , Downes SJ , Duan G , Farnsworth CA , Good RT , Han LB , Han YC , Hatje K , Horne I , Huang YP , Hughes DST , Jacquin-Joly E , James W , Jhangiani S , Kollmar M , Kuwar SS , Li S , Liu NY , Maibeche MT , Miller JR , Montagne N , Perry T , Qu J , Song SV , Sutton GG , Vogel H , Walenz BP , Xu W , Zhang HJ , Zou Z , Batterham P , Edwards OR , Feyereisen R , Gibbs RA , Heckel DG , McGrath A , Robin C , Scherer SE , Worley KC , Wu YD
Ref : BMC Biol , 15 :63 , 2017
Abstract : BACKGROUND: Helicoverpa armigera and Helicoverpa zea are major caterpillar pests of Old and New World agriculture, respectively. Both, particularly H. armigera, are extremely polyphagous, and H. armigera has developed resistance to many insecticides. Here we use comparative genomics, transcriptomics and resequencing to elucidate the genetic basis for their properties as pests. RESULTS: We find that, prior to their divergence about 1.5 Mya, the H. armigera/H. zea lineage had accumulated up to more than 100 more members of specific detoxification and digestion gene families and more than 100 extra gustatory receptor genes, compared to other lepidopterans with narrower host ranges. The two genomes remain very similar in gene content and order, but H. armigera is more polymorphic overall, and H. zea has lost several detoxification genes, as well as about 50 gustatory receptor genes. It also lacks certain genes and alleles conferring insecticide resistance found in H. armigera. Non-synonymous sites in the expanded gene families above are rapidly diverging, both between paralogues and between orthologues in the two species. Whole genome transcriptomic analyses of H. armigera larvae show widely divergent responses to different host plants, including responses among many of the duplicated detoxification and digestion genes. CONCLUSIONS: The extreme polyphagy of the two heliothines is associated with extensive amplification and neofunctionalisation of genes involved in host finding and use, coupled with versatile transcriptional responses on different hosts. H. armigera's invasion of the Americas in recent years means that hybridisation could generate populations that are both locally adapted and insecticide resistant.
ESTHER : Pearce_2017_BMC.Biol_15_63
PubMedSearch : Pearce_2017_BMC.Biol_15_63
PubMedID: 28756777
Gene_locus related to this paper: helam-a0a2w1bn75 , helam-a0a2w1bp69 , helam-a0a2w1bvf3

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

Title : Cell therapy could be a potential way to improve lipoprotein lipase deficiency - Wu_2017_Lipids.Health.Dis_16_189
Author(s) : Wu W , Yin Y , Zhong J , Peng Y , Li S , Zheng L , Cao H , Zhang J
Ref : Lipids Health Dis , 16 :189 , 2017
Abstract : BACKGROUND: Lipoprotein lipase (LPL) deficiency is an autosomal recessive genetic disorder characterized by extreme hypertriglyceridemia, with no cure presently available. The purpose of this study was to test the possibility of using cell therapy to alleviate LPL deficiency.
METHODS: The LPL coding sequence was cloned into the MSCV retrovirus vector, after which MSCV-hLPL and MSCV (empty construct without LPL coding sequence) virion suspensions were made using the calcium chloride method. A muscle cell line (C2C12), kidney cell line (HEK293T) and pre-adipocyte cell line (3 T3-L1) were transfected with the virus in order to express recombinant LPL in vitro. Finally, each transfected cell line was injected subcutaneously into nude mice to identify the cell type which could secret recombinant LPL in vivo. Control cells were transfected with the MSCV empty vector. LPL activity was analyzed using a radioimmunoassay.
RESULTS: After virus infection, the LPL activity at the cell surface of each cell type was significantly higher than in the control cells, which indicates that all three cell types can be used to generate functional LPL. The transfected cells were injected subcutaneously into nude mice, and the LPL activity of the nearby muscle tissue at the injection site in mice injected with 3 T3-L1 cells was more than 5 times higher at the injection sites than at non-injected control sites. The other two types of cells did not show this trend. CONCLUSION: The subcutaneous injection of adipocytes overexpressing LPL can improve the LPL activity of the adjacent tissue of nude mice. This is a ground-breaking preliminary study for the treatment of LPL deficiency, and lays a good foundation for using cell therapy to correct LPL deficiency.
ESTHER : Wu_2017_Lipids.Health.Dis_16_189
PubMedSearch : Wu_2017_Lipids.Health.Dis_16_189
PubMedID: 28969646

Title : A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the genus Peganum - Li_2017_J.Ethnopharmacol_203_127
Author(s) : Li S , Cheng X , Wang C
Ref : J Ethnopharmacol , 203 :127 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Peganum have a long history as a Chinese traditional medicine for the treatment of cough, hypertension, diabetes, asthma, jaundice, colic, lumbago, and many other human ailments. Additionally, the plants can be used as an amulet against evil-eye, dye and so on, which have become increasingly popular in Asia, Iran, Northwest India, and North Africa. AIM OF THE REVIEW: The present paper reviewed the ethnopharmacology, phytochemistry, analytical methods, biological activities, metabolism, pharmacokinetics, toxicology, and drug interaction of the genus Peganum in order to assess the ethnopharmacological use and to explore therapeutic potentials and future opportunities for research. MATERIALS AND
METHODS: Information on studies of the genus Peganum was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pudmed, Web of Science, CNKI and EMBASE) and libraries. Additionally, information was also obtained from some local books, PhD and MS's dissertations.
RESULTS: The genus Peganum has played an important role in traditional Chinese medicine. The main bioactive metabolites of the genus include alkaloids, flavonoids, volatile oils, etc. Scientific studies on extracts and formulations revealed a wide range of pharmacological activities, such as cholinesterase and monoamine oxidase inhibitory activities, antitumor, anti-hypertension, anticoagulant, antidiabetic, antimicrobial, insecticidal, antiparasidal, anti-leishmaniasis, antioxidant, and anti-inflammatory.
CONCLUSIONS: Based on this review, there is some evidence for extracts' pharmacological effects on Alzheimer's and Parkinson's diseases, cancer, diabetes, hypertension. Some indications from ethnomedicine have been confirmed by pharmacological effects, such as the cholinesterase, monoamine oxidase and DNA topoisomerase inhibitory activities, hypoglycemic and vasodilation effects of this genus. The available literature showed that most of the activities of the genus Peganum can be attributed to the active alkaloids. Data regarding many aspects of the genus such as mechanisms of actions, metabolism, pharmacokinetics, toxicology, potential drug interactions with standard-of-care medications is still limited which call for additional studies particularly in humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices.
ESTHER : Li_2017_J.Ethnopharmacol_203_127
PubMedSearch : Li_2017_J.Ethnopharmacol_203_127
PubMedID: 28359849

Title : Extraction and in vitro screening of potential acetylcholinesterase inhibitors from the leaves of Panax japonicus - Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
Author(s) : Li S , Liu C , Zhang Y
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1061-1062 :139 , 2017
Abstract : Ultrafiltration liquid chromatography-mass spectrometry (UFLC-MS) is an efficient method that can be applied to rapidly screen and identify ligands for acetylcholinesterase (AChE) from the leaves of Panax japonicus. Using this method, we identified 5 major compounds, chikusetsusaponins V, Ib, IV, IVa, and IVa ethyl ester, as potent AChE inhibitors, which were assessed for anti-Alzheimer disease activity using the PC12 cell model. A continuous online method, which consisted of microwave-assisted extraction, a solvent concentration tank, and centrifugal partition chromatography (MAE-SCT-CPC), was newly developed for scaled up production of these compounds with high purity and efficiency. The bioactivities of the compounds separated were assessed by the PC12 cell model. This novel approach of using UFLC-MS coupled with MAE-SCT-CPC and a PC12 cell model could be applied to efficiently screen, extract, and separate AChE inhibitors from complex samples, and could serve as an important platform for the large-scale production of functional food and nutraceutical ingredients.
ESTHER : Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
PubMedSearch : Li_2017_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1061-1062_139
PubMedID: 28734162

Title : Synthesis and characterization of biodegradable poly(ether-ester) urethane acrylates for controlled drug release - Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
Author(s) : Feng X , Wang G , Neumann K , Yao W , Ding L , Li S , Sheng Y , Jiang Y , Bradley M , Zhang R
Ref : Mater Sci Eng C Mater Biol Appl , 74 :270 , 2017
Abstract : Three polyether-ester triblock diols, with various molecular weights, were synthesized from sigma-caprolactone and polyethylene glycol and used, with diisocyanates, as soft segments for the preparation of polyurethane acrylate oligomers. The polyurethane acrylates were used to generate cross-linked polyurethane films via UV initiated polymerization with and without cargo incorporation. Degradation experiment indicated that in PBS/H(2)O(2)/CoCl(2) the films degraded rapidly compared to PBS alone or with lipase. The polyurethane membrane loaded with the antibiotic tetracycline, demonstrated prolonged release over 200h, suggesting that the polymers could be used as an implant coating for controlled drug release.
ESTHER : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedSearch : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedID: 28254295

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

Title : Anti-amnesic effect of extract and alkaloid fraction from aerial parts of Peganum harmala on scopolamine-induced memory deficits in mice - Liu_2017_J.Ethnopharmacol_204_95
Author(s) : Liu W , Zhu Y , Wang Y , Qi S , Ma C , Li S , Jiang B , Cheng X , Wang Z , Xuan Z , Wang C
Ref : J Ethnopharmacol , 204 :95 , 2017
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Peganum harmala Linn (APP) is used as traditional medical herb for treatment of forgetfulness in Uighur medicine in China. But, the active ingredients and underlying mechanisms are unclear. AIM OF THE STUDY: The present study was undertaken to investigate the improvement effects of extract and alkaloid fraction from APP on scopolamine-induced cognitive dysfunction and to elucidate their underlying mechanisms of action, and to support its folk use with scientific evidence, and lay a foundation for its further researches. MATERIALS AND
METHODS: The acetylcholinesterase (AChE) inhibitory activities of extract (EXT), alkaloid fraction (ALK) and flavonoid fraction (FLA) from APP were evaluated in normal male C57BL/6 mice. The anti-amnesic effects of EXT and ALK from APP were measured in scopolamine-induced memory deficits mice by the Morris water maze (MWM) tasks. The levels of biomarkers, enzyme activity and protein expression of cholinergic system were determined in brain tissues.
RESULTS: The AChE activity was significantly decreased and the content of neurotransmitter acetylcholine (ACh) was significantly increased in normal mice cortex and hippocampus by treatment with donepezil at dosage of 8mg/kg, EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), and the AChE activity and the content of ACh were not significantly changed in cortex and hippocampus after treatment with FLA at dosages of 10, 30, 90mg/kg (P>0.05). In the MWM task, scopolamine-induced a decrease in both the swimming time within the target zone and the number of crossings where the platform had been placed were significantly reversed by treatment with EXT at dosages of 550, 1650mg/kg and ALK at dosages of 30, 90mg/kg (P<0.05). Moreover, the activity and protein expression of AChE was significantly decreased and the content of neurotransmitter ACh was significantly increased in cerebral cortex of scopolamine-induced mice by treatment with EXT at dosages of 183, 550, 1650mg/kg and ALK at dosages of 10, 30, 90mg/kg (P<0.05), compared with scopolamine-treated group.
CONCLUSIONS: EXT and ALK from APP exert beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. APP is an effective traditional folk medicine and the ALK fraction is proved to be the main effective components for the treatment of forgetfulness. The ALK may be valuable source for lead compounds discovery and drug development for treatment of memory impairment such as in Alzheimer's disease.
ESTHER : Liu_2017_J.Ethnopharmacol_204_95
PubMedSearch : Liu_2017_J.Ethnopharmacol_204_95
PubMedID: 28442406

Title : The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure - Ren_2017_J.Toxicol_2017_3265727
Author(s) : Ren Q , Zhao R , Wang C , Li S , Zhang T , Ren Z , Yang M , Pan H , Xu S , Zhu J , Wang X
Ref : J Toxicol , 2017 :3265727 , 2017
Abstract : The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE) in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The behavior responses of D. magna in DM (13.36 mug/L and 33.40 mug/L) and MT (19.66 mug/L and 49.15 mug/L) suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.
ESTHER : Ren_2017_J.Toxicol_2017_3265727
PubMedSearch : Ren_2017_J.Toxicol_2017_3265727
PubMedID: 29201050
Gene_locus related to this paper: dapul-ACHE1

Title : Does time difference of the acetylcholinesterase (AChE) inhibition in different tissues exist? A case study of zebra fish (Danio rerio) exposed to cadmium chloride and deltamethrin - Zhang_2017_Chemosphere_168_908
Author(s) : Zhang T , Yang M , Pan H , Li S , Ren B , Ren Z , Xing N , Qi L , Ren Q , Xu S , Song J , Ma J
Ref : Chemosphere , 168 :908 , 2017
Abstract : In order to illustrate time difference in toxic effects of cadmium chloride (CdCl2) and deltamethrin (DM), AChE activities were measured in different tissues, liver, muscle, brain, and gill, of Zebra fish (Danio rerio) across different concentrations in this research. The average AChE activity decreased comparing to 0.0 TU with DM (82.81% in 0.1 TU, 56.14% in 1.0 TU and 44.68% in 2.0 TU) and with CdCl2 (74.68% in 0.1 TU, 52.05% in 1.0 TU and 50.14% in 2.0 TU) showed an overall decrease with the increase of exposure concentrations. According to Self-Organizing Map (SOM), the AChE activities were characterized in relation with experimental conditions, showing an inverse relationship with exposure time. As the exposure time was longer, the AChE activities were correspondingly lower. The AChE inhibition showed time delay in sublethal treatments (0.1 TU) in different tissues: the AChE was first inhibited in brain by chemicals followed by gill, muscle and liver (brain > gill > muscle > liver). The AChE activity was almost inhibited synchronously in higher environmental stress (1.0 TU and 2.0 TU). As the AChE inhibition can induce abnormal of behavior movement, these results will be helpful to the mechanism of stepwise behavior responses according to the time difference in different tissues rather than the whole body AChE activity.
ESTHER : Zhang_2017_Chemosphere_168_908
PubMedSearch : Zhang_2017_Chemosphere_168_908
PubMedID: 27825714

Title : A comprehensive draft genome sequence for lupin (Lupinus angustifolius), an emerging health food: insights into plant-microbe interactions and legume evolution - Hane_2017_Plant.Biotechnol.J_15_318
Author(s) : Hane JK , Ming Y , Kamphuis LG , Nelson MN , Garg G , Atkins CA , Bayer PE , Bravo A , Bringans S , Cannon S , Edwards D , Foley R , Gao LL , Harrison MJ , Huang W , Hurgobin B , Li S , Liu CW , McGrath A , Morahan G , Murray J , Weller J , Jian J , Singh KB
Ref : Plant Biotechnol J , 15 :318 , 2017
Abstract : Lupins are important grain legume crops that form a critical part of sustainable farming systems, reducing fertilizer use and providing disease breaks. It has a basal phylogenetic position relative to other crop and model legumes and a high speciation rate. Narrow-leafed lupin (NLL; Lupinus angustifolius L.) is gaining popularity as a health food, which is high in protein and dietary fibre but low in starch and gluten-free. We report the draft genome assembly (609 Mb) of NLL cultivar Tanjil, which has captured >98% of the gene content, sequences of additional lines and a dense genetic map. Lupins are unique among legumes and differ from most other land plants in that they do not form mycorrhizal associations. Remarkably, we find that NLL has lost all mycorrhiza-specific genes, but has retained genes commonly required for mycorrhization and nodulation. In addition, the genome also provided candidate genes for key disease resistance and domestication traits. We also find evidence of a whole-genome triplication at around 25 million years ago in the genistoid lineage leading to Lupinus. Our results will support detailed studies of legume evolution and accelerate lupin breeding programmes.
ESTHER : Hane_2017_Plant.Biotechnol.J_15_318
PubMedSearch : Hane_2017_Plant.Biotechnol.J_15_318
PubMedID: 27557478
Gene_locus related to this paper: lupan-a0a1j7h2u5 , lupan-a0a4p1r201 , lupan-a0a4p1rve4 , lupan-a0a1j7inr2 , lupan-a0a4p1rbl4 , lupan-a0a1j7ifk4 , lupan-a0a4p1rs77 , lupan-a0a1j7h5s4

Title : Identification of acetylcholinesterase inhibitors using homogenous cell-based assays in quantitative high-throughput screening platforms - Li_2017_Biotechnol.J_12_
Author(s) : Li S , Huang R , Solomon S , Liu Y , Zhao B , Santillo MF , Xia M
Ref : Biotechnol J , 12 : , 2017
Abstract : Acetylcholinesterase (AChE) is an enzyme responsible for metabolism of acetylcholine, a neurotransmitter associated with muscle movement, cognition, and other neurobiological processes. Inhibition of AChE activity can serve as a therapeutic mechanism, but also cause adverse health effects and neurotoxicity. In order to efficiently identify AChE inhibitors from large compound libraries, homogenous cell-based assays in high-throughput screening platforms are needed. In this study, a fluorescent method using Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine) and the Ellman absorbance method were both developed in a homogenous format using a human neuroblastoma cell line (SH-SY5Y). An enzyme-based assay using Amplex Red was also optimized and used to confirm the potential inhibitors. These three assays were used to screen 1368 compounds, which included a library of pharmacologically active compounds (LOPAC) and 88 additional compounds from the Tox21 program, at multiple concentrations in a quantitative high-throughput screening (qHTS) format. All three assays exhibited exceptional performance characteristics including assay signal quality, precision, and reproducibility. A group of inhibitors were identified from this study, including known (e.g. physostigmine and neostigmine bromide) and potential novel AChE inhibitors (e.g. chelerythrine chloride and cilostazol). These results demonstrate that this platform is a promising means to profile large numbers of chemicals that inhibit AChE activity.
ESTHER : Li_2017_Biotechnol.J_12_
PubMedSearch : Li_2017_Biotechnol.J_12_
PubMedID: 28294544

Title : Effects of monocrotophos pesticide on cholinergic and dopaminergic neurotransmitter systems during early development in the sea urchin Hemicentrotus pulcherrimus - Zhang_2017_Toxicol.Appl.Pharmacol_328_46
Author(s) : Zhang X , Li S , Wang C , Tian H , Wang W , Ru S
Ref : Toxicol Appl Pharmacol , 328 :46 , 2017
Abstract : During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae. At the blastula stages, MCP disrupted DA metabolism but not 5-HT metabolism, resulting in abnormal development. High ChAT and AChE activity were observed at the gastrulation-completed stage and the two-armed pluteus stage, respectively, MCP inhibited ChAT activity and AChE activity/distribution and resulted in developmental defects of the plutei. From the gastrula stage to the two-armed pluteus stage, we found ubiquitous disrupting effects of MCP on ACh, DA, and 5-HT metabolism, particularly at critical periods during the development of these neurotransmitter systems. Therefore, we propose that this disruption is one of the main mechanisms of MCP-related developmental neurotoxicity, which would contribute better understanding insight into the mechanism of MCP pesticide's toxic effects.
ESTHER : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedSearch : Zhang_2017_Toxicol.Appl.Pharmacol_328_46
PubMedID: 28479505

Title : Genome and Transcriptome Sequences Reveal the Specific Parasitism of the Nematophagous Purpureocillium lilacinum 36-1 - Xie_2016_Front.Microbiol_7_1084
Author(s) : Xie J , Li S , Mo C , Xiao X , Peng D , Wang G , Xiao Y
Ref : Front Microbiol , 7 :1084 , 2016
Abstract : Purpureocillium lilacinum is a promising nematophagous ascomycete able to adapt diverse environments and it is also an opportunistic fungus that infects humans. A microbial inoculant of P. lilacinum has been registered to control plant parasitic nematodes. However, the molecular mechanism of the toxicological processes is still unclear because of the relatively few reports on the subject. In this study, using Illumina paired-end sequencing, the draft genome sequence and the transcriptome of P. lilacinum strain 36-1 infecting nematode-eggs were determined. Whole genome alignment indicated that P. lilacinum 36-1 possessed a more dynamic genome in comparison with P. lilacinum India strain. Moreover, a phylogenetic analysis showed that the P. lilacinum 36-1 had a closer relation to entomophagous fungi. The protein-coding genes in P. lilacinum 36-1 occurred much more frequently than they did in other fungi, which was a result of the depletion of repeat-induced point mutations (RIP). Comparative genome and transcriptome analyses revealed the genes that were involved in pathogenicity, particularly in the recognition, adhesion of nematode-eggs, downstream signal transduction pathways and hydrolase genes. By contrast, certain numbers of cellulose and xylan degradation genes and a lack of polysaccharide lyase genes showed the potential of P. lilacinum 36-1 as an endophyte. Notably, the expression of appressorium-formation and antioxidants-related genes exhibited similar infection patterns in P. lilacinum strain 36-1 to those of the model entomophagous fungi Metarhizium spp. These results uncovered the specific parasitism of P. lilacinum and presented the genes responsible for the infection of nematode-eggs.
ESTHER : Xie_2016_Front.Microbiol_7_1084
PubMedSearch : Xie_2016_Front.Microbiol_7_1084
PubMedID: 27486440
Gene_locus related to this paper: purli-a0a2u3dwt4 , purli-lcse

Title : Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of Hirschsprung' disease - Jiang_2016_Am.J.Transl.Res_8_3159
Author(s) : Jiang M , Li K , Li S , Yang L , Yang D , Zhang X , Fang M , Cao G , Wang Y , Chen W , Tang S
Ref : Am J Transl Res , 8 :3159 , 2016
Abstract : Evaluation of rectal suction biopsies for the ganglion cells and neural hypertrophy is the basic modality for the diagnosis of Hirschsprung's disease (HD). However, the traditional hematoxylin and eosin staining coupled with acetylcholinesterase histochemistry remain challenging, especially in newborns. Thus we conducted a prospective study to evaluate the usefulness of calretinin combined with S100 and protein gene product 9.5 (PGP9.5) immunostaining of rectal suction biopsies for the diagnosis of HD. A total of 195 patients were enrolled in our study. Of the 195 patients 69% had ganglion cells on the initial diagnostic protocol. Sixty cases were devoid of ganglion cells, and of these, 90% and 91% showed submucosal neural hypertrophy on S-100 staining and PGP9.5 staining, respectively. Eighty-one patients underwent a colonic resection, and of these, 59 had confirmed aganglionic segment, the other 22 patients were diagnosed as intestinal neuronal dysplasia type B (n=13) and isolated hypoganglionosis (n=9). Of the rest 114 patients, 51 cases underwent a full-thickness biopsy, and HD was excluded; sixty-three patients were thoroughly followed-up with no evidence of HD. We encountered two false-negatives and they were proved to be short segment HD after the surgery. The sensitivity and specificity rates of our diagnostic protocol was 96.49% (95% CI, 0.88-0.99) and 100% (95% CI, 0.97-1.00), respectively, excluding 5 patients with inconclusive results. Our findings demonstrated that calretinin coupled with S100 and PGP9.5 immunostaining on suction rectal biopsies is sensitive and specific for diagnosing HD.
ESTHER : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedSearch : Jiang_2016_Am.J.Transl.Res_8_3159
PubMedID: 27508037

Title : Novel nonquaternary reactivators showing reactivation efficiency for soman-inhibited human acetylcholinesterase - Wei_2016_Toxicol.Lett_246_1
Author(s) : Wei Z , Liu YQ , Wang YA , Li WH , Zhou XB , Zhao J , Huang CQ , Li XZ , Liu J , Zheng ZB , Li S
Ref : Toxicol Lett , 246 :1 , 2016
Abstract : Soman is a highly toxic nerve agent with strong inhibition of acetylcholinesterase (AChE), but of the few reactivators showing antidotal efficiency for soman-inhibited AChE presently are all permanently charged cationic oximes with poor penetration of the blood-brain barrier. To overcome this problem, uncharged reactivators have been designed and synthesized, but few of them were efficient for treating soman poisoning. Herein, we used a dual site biding strategy to develop more efficient uncharged reactivators. The ortho-hydroxylbenzaldoximes were chosen as reactivation ligands of AChE to prevent the secondary poisoning of AChE, and simple aromatic groups were used as peripheral site ligands of AChE, which were linked to the oximes in a similar way as that found in the reactivator HI-6. The in vitro experiment demonstrated that some of the resulting conjugates have robust activity against soman-inhibited AChE, and oxime 8b was highlighted as the most efficient one. Although not good as HI-6 in vitro, these new compounds hold promise for development of more efficient centrally acting reactivators for soman poisoning due to their novel nonquaternary structures, which are predicted to be able to cross the blood-brain barrier.
ESTHER : Wei_2016_Toxicol.Lett_246_1
PubMedSearch : Wei_2016_Toxicol.Lett_246_1
PubMedID: 26809136

Title : alpha\/beta-Hydrolase domain-containing 6 (ABHD6) negatively regulates the surface delivery and synaptic function of AMPA receptors - Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
Author(s) : Wei M , Zhang J , Jia M , Yang C , Pan Y , Li S , Luo Y , Zheng J , Ji J , Chen J , Hu X , Xiong J , Shi Y , Zhang C
Ref : Proc Natl Acad Sci U S A , 113 :E2695 , 2016
Abstract : In the brain, AMPA-type glutamate receptors are major postsynaptic receptors at excitatory synapses that mediate fast neurotransmission and synaptic plasticity. alpha/beta-Hydrolase domain-containing 6 (ABHD6), a monoacylglycerol lipase, was previously found to be a component of AMPA receptor macromolecular complexes, but its physiological significance in the function of AMPA receptors (AMPARs) has remained unclear. The present study shows that overexpression of ABHD6 in neurons drastically reduced excitatory neurotransmission mediated by AMPA but not by NMDA receptors at excitatory synapses. Inactivation of ABHD6 expression in neurons by either CRISPR/Cas9 or shRNA knockdown methods significantly increased excitatory neurotransmission at excitatory synapses. Interestingly, overexpression of ABHD6 reduced glutamate-induced currents and the surface expression of GluA1 in HEK293T cells expressing GluA1 and stargazin, suggesting a direct functional interaction between these two proteins. The C-terminal tail of GluA1 was required for the binding between of ABHD6 and GluA1. Mutagenesis analysis revealed a GFCLIPQ sequence in the GluA1 C terminus that was essential for the inhibitory effect of ABHD6. The hydrolase activity of ABHD6 was not required for the effects of ABHD6 on AMPAR function in either neurons or transfected HEK293T cells. Thus, these findings reveal a novel and unexpected mechanism governing AMPAR trafficking at synapses through ABHD6.
ESTHER : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedSearch : Wei_2016_Proc.Natl.Acad.Sci.U.S.A_113_E2695
PubMedID: 27114538
Gene_locus related to this paper: human-ABHD6

Title : Arsenicitalea aurantiaca gen. nov., sp. nov., a new member of the family Hyphomicrobiaceae, isolated from high-arsenic sediment - Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
Author(s) : Mu Y , Zhou L , Zeng XC , Liu L , Pan Y , Chen X , Wang J , Li S , Li WJ , Wang Y
Ref : Int J Syst Evol Microbiol , 66 :5478 , 2016
Abstract : A novel arsenic-resistant bacterium, designated 42-50T, was isolated from the high-arsenic sediment of Jianghan Plain, Hubei Province, China. Phylogenetic and biochemical analysis indicated that this bacterium represents the first species of a novel genus belonging to the family Hyphomicrobiaceae. The 16S rRNA gene of strain 42-50T shares 96.3-94.2, 96.3, 96.2 and 94.9-93.8 % sequence identities to those of species from the genera Devosia, Youhaiella, Paradevosia and Pelagibacterium, respectively. The major cellular fatty acids are C16 : 0, C18 : 0, C18 : 1omega7c 11-methyl and summed feature 8 (comprising C18 : 1omega7c and C18 : 1omega6c). The predominant polar lipids are diphosphatidylglycerol, phosphatidylglycerol and two unidentified glycolipids. The predominant respiratory quinone is ubiquinone-10 (Q-10). The DNA G+C content of strain 42-50T is 73.7 mol%. The distinct phylogenetic lineage and unique cellular fatty acids suggest that strain 42-50T represents a novel species of a new genus affiliated with the family Hyphomicrobiaceae, for which the name Arsenicitalea aurantiaca gen. nov., sp. nov. is proposed. The type strain is 42-50T (=CCTCC AB 2014325T=KCTC 42825T).
ESTHER : Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
PubMedSearch : Mu_2016_Int.J.Syst.Evol.Microbiol_66_5478
PubMedID: 27902179
Gene_locus related to this paper: 9rhiz-a0a433xfq5

Title : Discovery and Rational Design of Natural-Product-Derived 2-Phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine Analogs as Novel and Potent Dipeptidyl Peptidase 4 (DPP-4) Inhibitors for the Treatment of Type 2 Diabetes - Li_2016_J.Med.Chem_59_6772
Author(s) : Li S , Xu H , Cui S , Wu F , Zhang Y , Su M , Gong Y , Qiu S , Jiao Q , Qin C , Shan J , Zhang M , Wang J , Yin Q , Xu M , Liu X , Wang R , Zhu L , Li J , Xu Y , Jiang H , Zhao Z , Li H
Ref : Journal of Medicinal Chemistry , 59 :6772 , 2016
Abstract : Starting from the lead isodaphnetin, a natural product inhibitor of DPP-4 discovered through a target fishing docking based approach, a series of novel 2-phenyl-3,4-dihydro-2H-benzo[f]chromen-3-amine derivatives as potent DPP-4 inhibitors are rationally designed utilizing highly efficient 3D molecular similarity based scaffold hopping as well as electrostatic complementary methods. Those ingenious drug design strategies bring us approximate 7400-fold boost in potency. Compounds 22a and 24a are the most potent ones (IC50 approximately 2.0 nM) with good pharmacokinetic profiles. Compound 22a demonstrated stable pharmacological effect. A 3 mg/kg oral dose provided >80% inhibition of DPP-4 activity within 24 h, which is comparable to the performance of the long-acting control omarigliptin. Moreover, the efficacy of 22a in improving the glucose tolerance is also comparable with omarigliptin. In this study, not only promising DPP-4 inhibitors as long acting antidiabetic that are clinically on demand are identified, but the target fish docking and medicinal chemistry strategies were successfully implemented.
ESTHER : Li_2016_J.Med.Chem_59_6772
PubMedSearch : Li_2016_J.Med.Chem_59_6772
PubMedID: 27396490
Gene_locus related to this paper: human-DPP4

Title : Functionalized photonic crystal for the sensing of Sarin agents - Yan_2016_Talanta_159_412
Author(s) : Yan C , Qi F , Li S , Xu J , Liu C , Meng Z , Qiu L , Xue M , Lu W , Yan Z
Ref : Talanta , 159 :412 , 2016
Abstract : The indiscriminate use of nerve agents by terrorist groups has attracted attention of the scientific communities toward the development of novel sensor technique for these deadly chemicals. A photonic crystal (PhC) hydrogel immobilized with butyrylcholinesterase (BuChE) was firstly prepared for the sensing of Sarin agents. Periodic polystyrene colloidal (240nm) array was embedded inside an acrylamide hydrogel, and then BuChE was immobilized inside the hydrogel matrix via condensation with 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3h)-one (DEPBT). It indicated that a total of 3.7 units of BuChE were immobilized onto the PhC hydrogel. The functionalized hydrogel recognized the Sarin agent and then shrunk, thus the diffraction of PhC hydrogel blue shifted significantly, and a limit of detection (LOD) of 10(-15)molL(-1) was achieved.
ESTHER : Yan_2016_Talanta_159_412
PubMedSearch : Yan_2016_Talanta_159_412
PubMedID: 27474325

Title : Anti-phytopathogen, multi-target acetylcholinesterase inhibitory and antioxidant activities of metabolites from endophytic Chaetomium globosum - Li_2016_Nat.Prod.Res__1
Author(s) : Li W , Yang X , Yang Y , Duang R , Chen G , Li X , Li Q , Qin S , Li S , Zhao L , Ding Z
Ref : Nat Prod Res , :1 , 2016
Abstract : Fourteen metabolites with various structure types were isolated from endophytic Chaetomium globosum. Five compounds were separated from genus Chaetomium for the first time. Some compounds exhibited remarkable inhibition against phytopathogenic fungi causing root rot of Panax notoginseng. Compounds 1-5 had significant DPPH-free radical-scavenging activity. Compounds 3 and 5 indicated significant inhibitions against the acetylcholinesterase (AChE). From preliminary structure-activity relationship, it was found that the oxygenic five-membered ring of 3 and 5 was crucial in the anti-AChE activity. These structures provide new templates for the potential treatment and management of plant diseases and Alzheimer disease.
ESTHER : Li_2016_Nat.Prod.Res__1
PubMedSearch : Li_2016_Nat.Prod.Res__1
PubMedID: 26744178

Title : DWARF14 is a non-canonical hormone receptor for strigolactone - Yao_2016_Nature_536_469
Author(s) : Yao R , Ming Z , Yan L , Li S , Wang F , Ma S , Yu C , Yang M , Chen L , Li Y , Yan C , Miao D , Sun Z , Yan J , Sun Y , Wang L , Chu J , Fan S , He W , Deng H , Nan F , Li J , Rao Z , Lou Z , Xie D
Ref : Nature , 536 :469 , 2016
Abstract : Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone.
ESTHER : Yao_2016_Nature_536_469
PubMedSearch : Yao_2016_Nature_536_469
PubMedID: 27479325
Gene_locus related to this paper: arath-AtD14

Title : Immobilization of Lipase from Pseudomonas fluorescens on Porous Polyurea and Its Application in Kinetic Resolution of Racemic 1-Phenylethanol - Han_2016_ACS.Appl.Mater.Interfaces_8_25714
Author(s) : Han H , Zhou Y , Li S , Wang Y , Kong XZ
Ref : ACS Appl Mater Interfaces , 8 :25714 , 2016
Abstract : A porous polyurea (PPU) was prepared through a simple protocol by reacting toluene diisocyanate with water in binary solvent of water-acetone. Its amine group was determined through spectrophotometric absorbance based on its iminization with p-nitrobenzaldehyde amines. PPU was then used as a novel polymer support for enzyme immobilization, through activation by glutaraldehyde followed by immobilization of an enzyme, lipase from Pseudomonas fluorescens (PFL), via covalent bonding with the amine groups of lipase molecules. Influences of glutaraldehyde and enzyme concentration and pH in the process were studied. The results revealed that the activity of the immobilized PFL reached a maximum at GA concentration of 0.17 mol/L and at pH 8. Immobilization rate of 60% or higher for PFL was obtained under optimized condition with an enzyme activity of 283 U/mg. The porous structure of PPU, prior to and after GA activation and PFL immobilization, was characterized. The activity of the immobilized PFL at different temperature and pH and its stability at 40 degrees C as well as its reusability were tested. The immobilized enzyme was finally used as enantioselective catalyst in kinetic resolution of racemic 1-phenylethanol (1-PEOH), and its performance compared with the free PFL. The results demonstrate that the enzyme activity and stability were greatly improved for the immobilized PFL, and highly pure enantiomers from racemic 1-PEOH were effectively achieved using the immobilized PFL. Noticeable deactivation of PFL in the resolution was observed by acetaldehyde in situ formed. In addition, the immobilized PFL was readily recovered from the reaction system for reuse. A total of 73% of the initial activity was retained after 5 repeated reuse cycles. This work provides a novel route to preparation of a polyurea porous material and its enzyme immobilization, leading to a novel type of immobilized enzyme for efficient kinetic resolution of racemic molecules.
ESTHER : Han_2016_ACS.Appl.Mater.Interfaces_8_25714
PubMedSearch : Han_2016_ACS.Appl.Mater.Interfaces_8_25714
PubMedID: 27618157

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

Title : Destabilization of strigolactone receptor DWARF14 by binding of ligand and E3-ligase signaling effector DWARF3 - Zhao_2015_Cell.Res_25_1219
Author(s) : Zhao LH , Zhou XE , Yi W , Wu Z , Liu Y , Kang Y , Hou L , de Waal PW , Li S , Jiang Y , Scaffidi A , Flematti GR , Smith SM , Lam VQ , Griffin PR , Wang Y , Li J , Melcher K , Xu HE
Ref : Cell Res , 25 :1219 , 2015
Abstract : Strigolactones (SLs) are endogenous hormones and exuded signaling molecules in plant responses to low levels of mineral nutrients. Key mediators of the SL signaling pathway in rice include the alpha/beta-fold hydrolase DWARF 14 (D14) and the F-box component DWARF 3 (D3) of the ubiquitin ligase SCF(D3) that mediate ligand-dependent degradation of downstream signaling repressors. One perplexing feature is that D14 not only functions as the SL receptor but is also an active enzyme that slowly hydrolyzes diverse natural and synthetic SLs including GR24, preventing the crystallization of a binary complex of D14 with an intact SL as well as the ternary D14/SL/D3 complex. Here we overcome these barriers to derive a structural model of D14 bound to intact GR24 and identify the interface that is required for GR24-mediated D14-D3 interaction. The mode of GR24-mediated signaling, including ligand recognition, hydrolysis by D14, and ligand-mediated D14-D3 interaction, is conserved in structurally diverse SLs. More importantly, D14 is destabilized upon the binding of ligands and D3, thus revealing an unusual mechanism of SL recognition and signaling, in which the hormone, the receptor, and the downstream effectors are systematically destabilized during the signal transduction process.
ESTHER : Zhao_2015_Cell.Res_25_1219
PubMedSearch : Zhao_2015_Cell.Res_25_1219
PubMedID: 26470846
Gene_locus related to this paper: orysj-Q10QA5

Title : Behavioral and biochemical responses in freshwater fish Carassius auratus exposed to sertraline - Xie_2015_Chemosphere_135_146
Author(s) : Xie Z , Lu G , Li S , Nie Y , Ma B , Liu J
Ref : Chemosphere , 135 :146 , 2015
Abstract : Sertraline is one of the most commonly prescribed selective serotonin reuptake inhibitors and is frequently detected in the aquatic environment. However, knowledge regarding relationships among molecular or biochemical endpoints involved in modes of action (MOAs) of sertraline and ecologically important behavioral responses of fish is insufficient. The present study aimed to investigate the bioconcentration and possible adverse outcomes pathways (AOPs) in crucian carp (Carassius auratus) exposed to various concentrations of sertraline (4.36, 21.3 and 116mugL-1) for 7d. Bioconcentration factor values were in the range of 19.5-626 in liver, 6.94-285 in brain, 4.01-146 in gill and 0.625-43.1 in muscle during the entire period of exposure. Liver superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) activities and brain acetylcholinesterase (AChE) activity were selected as biochemical endpoints associated with MOAs. Swimming activity, shoaling, feeding rate and food consumption were determined to assess behavioral responses. Fish plasma levels of sertraline exceeding human therapeutic doses were also predicted from external exposure concentrations. Significant enhancements in CAT, GPx, AChE and swimming activities and decreases in shoaling tendency, feeding rate and food consumption were observed when fish plasma levels exceeded human therapeutic thresholds. Shoaling, feeding rate and food consumption were correlated with the activities of SOD, CAT and GST. A significant positive correlation between swimming activity and AChE activity was also observed. As such, our study provides important AOPs linking biochemical responses with ultimate ecologically relevant behavioral endpoints.
ESTHER : Xie_2015_Chemosphere_135_146
PubMedSearch : Xie_2015_Chemosphere_135_146
PubMedID: 25950408

Title : Functional characterization of MpaG', the O-methyltransferase involved in the biosynthesis of mycophenolic acid - Zhang_2015_Chembiochem_16_565
Author(s) : Zhang W , Cao S , Qiu L , Qi F , Li Z , Yang Y , Huang S , Bai F , Liu C , Wan X , Li S
Ref : Chembiochem , 16 :565 , 2015
Abstract : Mycophenolic acid (MPA, 1) is a clinically important immunosuppressant. In this report, a gene cluster mpa' responsible for the biosynthesis of 1 was identified from Penicillium brevicompactum NRRL 864. The S-adenosyl-L-methionine-dependent (SAM-dependent) O-methyltransferase encoded by the mpaG' gene was functionally and kinetically characterized in vitro. MpaG' catalyzes the methylation of demethylmycophenolic acid (DMMPA, 6) to form 1. It also showed significant substrate flexibility by methylating two structural derivatives of 6 prepared by organic synthesis.
ESTHER : Zhang_2015_Chembiochem_16_565
PubMedSearch : Zhang_2015_Chembiochem_16_565
PubMedID: 25630520
Gene_locus related to this paper: penbr-mpaH , penbr-mpac

Title : Outbred genome sequencing and CRISPR\/Cas9 gene editing in butterflies - Li_2015_Nat.Commun_6_8212
Author(s) : Li X , Fan D , Zhang W , Liu G , Zhang L , Zhao L , Fang X , Chen L , Dong Y , Chen Y , Ding Y , Zhao R , Feng M , Zhu Y , Feng Y , Jiang X , Zhu D , Xiang H , Feng X , Li S , Wang J , Zhang G , Kronforst MR , Wang W
Ref : Nat Commun , 6 :8212 , 2015
Abstract : Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system.
ESTHER : Li_2015_Nat.Commun_6_8212
PubMedSearch : Li_2015_Nat.Commun_6_8212
PubMedID: 26354079
Gene_locus related to this paper: papxu-a0a194pj15 , papxu-a0a194q254 , papma-a0a194rdx2 , papxu-a0a194q858 , papxu-a0a194pyl3 , papxu-a0a194q337 , papma-a0a194r1p9 , papma-a0a194r6h1 , papxu-a0a194q1w8 , papma-a0a194ql80 , papma-a0a0n1ipl3 , papma-a0a194qm14

Title : Increased permeability of the blood-brain barrier and Alzheimer's disease-like alterations in slit-2 transgenic mice - Li_2015_J.Alzheimers.Dis_43_535
Author(s) : Li JC , Han L , Wen YX , Yang YX , Li S , Li XS , Zhao CJ , Wang TY , Chen H , Liu Y , Qi CL , He XD , Gu QL , Ye YX , Zhang Y , Huang R , Wu YE , He RR , Kurihara H , Song XY , Cao L , Wang LJ
Ref : J Alzheimers Dis , 43 :535 , 2015
Abstract : Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-beta (Abeta) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD.
ESTHER : Li_2015_J.Alzheimers.Dis_43_535
PubMedSearch : Li_2015_J.Alzheimers.Dis_43_535
PubMedID: 25114073

Title : Alleviating effects of bushen-yizhi formula on ibotenic Acid-induced cholinergic impairments in rat - Hou_2015_Rejuvenation.Res_18_111
Author(s) : Hou XQ , Zhang L , Yang C , Rong CP , He WQ , Zhang CX , Li S , Su RY , Chang X , Qin JH , Chen YB , Xian SX , Wang Q
Ref : Rejuvenation Res , 18 :111 , 2015
Abstract : This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases.
ESTHER : Hou_2015_Rejuvenation.Res_18_111
PubMedSearch : Hou_2015_Rejuvenation.Res_18_111
PubMedID: 25482164

Title : Baicalein alters PI3K\/Akt\/GSK3beta signaling pathway in rats with diabetes-associated cognitive deficits - Qi_2015_Int.J.Clin.Exp.Med_8_1993
Author(s) : Qi Z , Xu Y , Liang Z , Li S , Wang J , Wei Y , Dong B
Ref : Int J Clin Exp Med , 8 :1993 , 2015
Abstract : Our present investigation focused on assessing the neuroprotective potential of baicalein (BAC) against diabetes-associated cognitive deficit (DACD) using a diabetic model and further figure out the potential molecular mechanisms. Diabetic rat model was established by streptozotocin (STZ). Vehicle or BAC by the doses of 2 and 4 mg/kg was intraperitoneally injected once a day for seven consecutive weeks. Memory function was evaluated by Morris water maze test and avoidance passive test. The activities of acetylcholinesterase (AChE), choline acetylase (ChAT), caspase-9 and caspase-3 in STZ-induced diabetic rats' hippocampus were detected via responsive commercial kits. Western blot assay were used to determine the protein levels of phospho-phosphatidylinositol 3-kinase (p-PI3K), phospho-Akt (p-Akt), and phospho-glycogen synthase kinase-3beta (p-GSK3beta). Our results showed that BAC remarkably increased body weight and ChAT activity, decreased blood glucose level and AChE activity as well as improved cognitive deficits in diabetic rats. Additionally, it was also found that treatment with BAC to diabetes obviously stimulated the p-PI3K and p-Akt and inhibited the level of p-GSK3beta. Furthermore, the neuronal apoptosis was also prevented after BAC treatment by decreasing caspase-9 and caspase-3 activities in diabetic rats' hippocampus. It is concluded that BAC exerted beneficial effects against DACD in rats and its neuroprotection might be linked with activating PI3K and Akt phosphorylation accompanied with suppressing the phosphorylated level of GSK3beta. These results hint that BAC is likely to be served as an adjuvant therapy to conventional anti-hyperglycemic regimens as well as DACD.
ESTHER : Qi_2015_Int.J.Clin.Exp.Med_8_1993
PubMedSearch : Qi_2015_Int.J.Clin.Exp.Med_8_1993
PubMedID: 25932128

Title : Lack of association between EPHX1 polymorphism and esophageal cancer risk: evidence from meta-analysis - Yan_2015_Dis.Esophagus_28_164
Author(s) : Yan YL , Chen X , Liang HJ , Wang J , Li TJ , Li RL , Li S , Qin X
Ref : Dis Esophagus , 28 :164 , 2015
Abstract : The microsomal epoxide hydrolase 1 (EPHX1) Tyr113His and His139Arg polymorphisms have been reported to be associated with esophageal cancer (EC) risk, yet the results of these previous results have been inconsistent or controversial. The objective of this study was to explore whether the EPHX1 Tyr113His and His139Arg polymorphisms confer risk to EC. The relevant studies were identified through a search of PubMed, Excerpta Medica Database (Embase), Elsevier Science Direct, and Chinese Biomedical Literature Database until May 2013. The association between the EPHX1 Tyr113His and His139Arg polymorphisms and EC risk was pooled by odds ratios (ORs) together with their 95% confidence intervals (95%CIs). A total of eight case-control studies with 1163 EC patients and 1868 controls (seven studies for both Tyr113His and His139Arg polymorphisms, one study only for Tyr113His polymorphism) were eventually identified. We found no association between EPHX1 Tyr113His and His139Arg polymorphisms and EC risk in overall population (For Tyr113His: His vs. Tyr: OR = 1.05, 95%CI = 0.95-1.15, P = 0.379; His/His vs. Tyr/Tyr: OR = 1.04, 95%CI = 0.88-1.22, P = 0.208; His/Tyr vs. Tyr/Tyr: OR = 0.96, 95%CI = 0.80-1.15, P = 0.577; His/His vs. His/Tyr + Tyr/Tyr: OR = 1.10, 95%CI = 0.96-1.26, P = 0.164; His/His + His/Tyr vs. Tyr/Tyr: OR = 1.01, 95%CI = 0.90-1.12, P = 0.543. For His139Arg: Arg vs. His: OR = 1.04, 95%CI = 0.94-1.14, P = 0.465; Arg/Arg vs. His/His: OR = 1.06, 95%CI = 0.91-1.24, P = 0.470; Arg/His vs. His/His: OR = 1.03, 95%CI = 0.91-1.16, P = 0.673; Arg/Arg vs. Arg/His + His/His: OR = 1.04, 95%CI = 0.85-1.27, P = 0.708; Arg/Arg + Arg/His vs. His/His: OR = 1.02, 95%CI = 0.93-1.13, P = 0.617). In subgroup analysis based on ethnicity, significant association has been found in neither EPHX1 Tyr113His nor His139Arg polymorphism. The current meta-analysis suggests no evidence of association between the EPHX1 polymorphism and EC risk.
ESTHER : Yan_2015_Dis.Esophagus_28_164
PubMedSearch : Yan_2015_Dis.Esophagus_28_164
PubMedID: 25714851

Title : Relationship between plasma phospholipase A2 concentrations and lipoprotein subfractions in patients with stable coronary artery disease - Xu_2015_Clin.Chim.Acta_446_195
Author(s) : Xu RX , Zhang Y , Li XL , Li S , Guo YL , Dong Q , Liu G , Li JJ
Ref : Clinica Chimica Acta , 446 :195 , 2015
Abstract : BACKGROUND: Both increased lipoprotein-associated phospholipase A2 (Lp-PLA2) concentrations and atherogenic lipoprotein subfractions have been shown to reflect unfavourable cardiovascular risk. However, the correlation between Lp-PLA2 and lipoprotein subfractions in patients with coronary artery disease (CAD) has not been assessed yet. METHODS: A total of 324 consecutive subjects who were not treated with lipid-lowering drugs were enrolled (angiographically proven CAD: n = 253; non-CAD: n = 71). Plasma Lp-PLA2 concentrations were measured using ELISA. The low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions were determined by Lipoprint System. RESULTS: Plasma Lp-PLA2 concentrations were higher in patients with CAD compared with those without CAD (153.61 +/- 78.73 vs. 131.41 +/- 65.49 ng/ml, p = 0.028). The univariable correlation analysis revealed that Lp-PLA2 concentrations were positively correlated with the cholesterol concentrations of each LDL subfractions and the intermediate as well as small HDL subfractions, while negatively linked with the LDL particle size and large HDL-cholesterol (HDL-C) concentrations in CAD group. However, no similar results were observed in the non-CAD group. Furthermore, multivariable regression analysis was performed in patients with CAD and showed that plasma Lp-PLA2 concentrations were independently correlated with the cholesterol concentrations of each LDL subfractions [large LDL-cholesterol (LDL-C): beta = 0.263, p < 0.001; intermediate LDL-C: beta = 0.327, p < 0.001; small LDL-C: beta = 0.135, p = 0.033] and small HDL-C (beta = 0.133, p = 0.034). CONCLUSION: Lp-PLA2 concentrations were positively associated with all LDL subfractions and small HDL subfraction, suggesting an interaction between Lp-PLA2 and lipoprotein subfraction phenotypes in the status of CAD.
ESTHER : Xu_2015_Clin.Chim.Acta_446_195
PubMedSearch : Xu_2015_Clin.Chim.Acta_446_195
PubMedID: 25934512
Gene_locus related to this paper: human-PLA2G7

Title : Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases - Zhang_2015_Forensic.Sci.Med.Pathol_11_570
Author(s) : Zhang L , Ma J , Li S , Xue R , Jin M , Zhou Y
Ref : Forensic Science Med Pathol , 11 :570 , 2015
Abstract : Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 microg/ml in heart blood, 39 microg/ml in femoral vein blood, 141 microg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning.
ESTHER : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedSearch : Zhang_2015_Forensic.Sci.Med.Pathol_11_570
PubMedID: 26481789

Title : Pharmacokinetic and Metabolic Studies of ADTM: A Novel Danshensu Derivative Confers Cardioprotection by HPLC-UV and LC-MS\/MS - Li_2015_J.Chromatogr.Sci_53_872
Author(s) : Li S , Shan L , Zhang Z , Li W , Liao K , Sheng X , Yu P , Wang Y
Ref : Journal of Chromatography Sci , 53 :872 , 2015
Abstract : (R)-(3,5,6-Trimethylpyrazinyl) methyl-2-acetoxy-3-(3,4-diacetoxyphenyl) propanoate (ADTM) is a novel Danshensu (DSS) derivative regarded as a potential new agent for the treatment of myocardial ischemia. A validated high performance liquid chromatography (HPLC) approach with a detection limit of 5 ng/mL was used for pharmacokinetic evaluation of ADTM in rat plasma. The intra- and interday precision in terms of relative standard deviation were <4.98 and 4.84%, respectively, at concentration levels of 0.02, 0.20 and 0.80 microg/mL. ADTM's absolute oral bioavailability value was 30.4% and t1/2 was 34.33 +/- 11.51 and 29.94 +/- 8.19 min after oral and intravenous administration of 20 mg/kg. In addition, the major metabolites both in vitro and in vivo were 2-hydroxymethy-3,5,6-trimethylpyrazin and DSS. The results indicated that the hydrolysis was the main metabolic pathway of ADTM, and carboxylesterase may play an important role in ADTM's metabolism. The present work provides basic information for ADTM's further preclinical research and DSS's chemical structure modification.
ESTHER : Li_2015_J.Chromatogr.Sci_53_872
PubMedSearch : Li_2015_J.Chromatogr.Sci_53_872
PubMedID: 25609599

Title : Expression, purification and characterization of a functional, recombinant, cold-active lipase (LipA) from psychrotrophic Yersinia enterocolitica - Ji_2015_Protein.Expr.Purif_115_125
Author(s) : Ji X , Li S , Wang B , Zhang Q , Lin L , Dong Z , Wei Y
Ref : Protein Expr Purif , 115 :125 , 2015
Abstract : A novel cold-active lipase gene encoding 294 amino acid residues was obtained from the Yersinia enterocolitica strain KM1. Sequence alignment and phylogenetic analysis revealed that this novel lipase is a new member of the bacterial lipase family I.1. The lipase shares the conserved GXSXG motif and catalytic triad Ser85-Asp239-His261. The recombinant protein LipA was solubly and heterogeneously expressed in Escherichia coli, purified by Ni-affinity chromatography, and then characterized. LipA was active over a broad range spanning 15-60 degrees C with an optimum activity at 25 degrees C and across a wide pH range from 5.0 to 11.0 with an optimum activity at pH 7.5. The molecular weight was estimated to be 34.2KDa. The lipase could be activated by Mg(2+) and a low concentration (10%) of ethanol, dimethyl sulfoxide, methanol and acetonitrile, whereas it was strongly inhibited by Zn(2+), Cu(2+) and Mn(2+). This cold-active lipase may be a good candidate for detergents and biocatalysts at low temperature.
ESTHER : Ji_2015_Protein.Expr.Purif_115_125
PubMedSearch : Ji_2015_Protein.Expr.Purif_115_125
PubMedID: 26256062

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 : A novel angular dioxygenase gene cluster encoding 3-phenoxybenzoate 1',2'-dioxygenase in Sphingobium wenxiniae JZ-1 - Wang_2014_Appl.Environ.Microbiol_80_3811
Author(s) : Wang C , Chen Q , Wang R , Shi C , Yan X , He J , Hong Q , Li S
Ref : Applied Environmental Microbiology , 80 :3811 , 2014
Abstract : Sphingobium wenxiniae JZ-1 utilizes a wide range of pyrethroids and their metabolic product, 3-phenoxybenzoate, as sources of carbon and energy. A mutant JZ-1 strain, MJZ-1, defective in the degradation of 3-phenoxybenzoate was obtained by successive streaking on LB agar. Comparison of the draft genomes of strains JZ-1 and MJZ-1 revealed that a 29,366-bp DNA fragment containing a putative angular dioxygenase gene cluster (pbaA1A2B) is missing in strain MJZ-1. PbaA1, PbaA2, and PbaB share 65%, 52%, and 10% identity with the corresponding alpha and beta subunits and the ferredoxin component of dioxin dioxygenase from Sphingomonas wittichii RW1, respectively. Complementation of pbaA1A2B in strain MJZ-1 resulted in the active 3-phenoxybenzoate 1',2'-dioxygenase, but the enzyme activity in Escherichia coli was achieved only through the coexpression of pbaA1A2B and a glutathione reductase (GR)-type reductase gene, pbaC, indicating that the 3-phenoxybenzoate 1',2'-dioxygenase belongs to a type IV Rieske non-heme iron aromatic ring-hydroxylating oxygenase system consisting of a hetero-oligomeric oxygenase, a [2Fe-2S]-type ferredoxin, and a GR-type reductase. The pbaC gene is not located in the immediate vicinity of pbaA1A2B. 3-Phenoxybenzoate 1',2'-dioxygenase catalyzes the hydroxylation in the 1' and 2' positions of the benzene moiety of 3-phenoxybenzoate, yielding 3-hydroxybenzoate and catechol. Transcription of pbaA1A2B and pbaC was induced by 3-phenoxybenzoate, but the transcriptional level of pbaC was far less than that of pbaA1A2B, implying the possibility that PbaC may not be the only reductase that can physiologically transfer electrons to PbaA1A2B in strain JZ-1. Some GR-type reductases from other sphingomonad strains could also transfer electrons to PbaA1A2B, suggesting that PbaA1A2B has a low specificity for reductase.
ESTHER : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedSearch : Wang_2014_Appl.Environ.Microbiol_80_3811
PubMedID: 24747891
Gene_locus related to this paper: 9sphn-q0kjt3 , sphwj-a0a059u2z8

Title : Crystal structure of juvenile hormone epoxide hydrolase from the silkworm Bombyx mori - Zhou_2014_Proteins_82_3224
Author(s) : Zhou K , Jia N , Hu C , Jiang YL , Yang JP , Chen Y , Li S , Li WF , Zhou CZ
Ref : Proteins , 82 :3224 , 2014
Abstract : The juvenile hormone (JH) epoxide hydrolase (JHEH) catalyzes the degradation of JH, which regulates the metamorphosis development of insects. Here we report the 2.30 A crystal structure of JHEH from the silkworm Bombyx mori (BmJHEH). The overall structure of BmJHEH is composed of an N-terminal segment followed by a core hydrolase domain, which is interrupted by an all-alpha lid domain. Structural analyses together with molecular simulation reveal insights into the conservation and specificity of the active-site pocket. These findings increase our understanding of the substrate recognition and catalysis of microsomal epoxide hydrolase family and might help the design of JH-derived pesticides. (c) Proteins 2014;. (c) 2014 Wiley Periodicals, Inc.
ESTHER : Zhou_2014_Proteins_82_3224
PubMedSearch : Zhou_2014_Proteins_82_3224
PubMedID: 25143157
Gene_locus related to this paper: bommo-q6u6j0

Title : Complete Genome Sequence of Paenibacillus polymyxa SQR-21, a Plant Growth-Promoting Rhizobacterium with Antifungal Activity and Rhizosphere Colonization Ability - Li_2014_Genome.Announc_2_e00281
Author(s) : Li S , Yang D , Qiu M , Shao J , Guo R , Shen B , Yin X , Zhang R , Zhang N , Shen Q
Ref : Genome Announc , 2 : , 2014
Abstract : Here we report the complete genome sequence of a plant growth-promoting rhizobacterium (PGPR), Paenibacillus polymyxa SQR-21, which consists of one circular chromosome of 5,828,438 bp with 5,024 coding sequences (CDS). The data presented highlight multiple sets of functional genes associated with its plant-beneficial characteristics.
ESTHER : Li_2014_Genome.Announc_2_e00281
PubMedSearch : Li_2014_Genome.Announc_2_e00281
PubMedID: 24723719
Gene_locus related to this paper: paep6-e0rmc7

Title : Rapid and sensitive detection of the inhibitive activities of acetyl- and butyryl-cholinesterases inhibitors by UPLC-ESI-MS\/MS - Liu_2014_J.Pharm.Biomed.Anal_94_215
Author(s) : Liu W , Yang Y , Cheng X , Gong C , Li S , He D , Yang L , Wang Z , Wang C
Ref : J Pharm Biomed Anal , 94 :215 , 2014
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are legitimate therapeutic targets for Alzheimer's disease. The classical approach for screening potential AChE/BChE inhibitors was developed by Ellman. However, the background color of compounds or plant extracts remained uncertain and frequently interfered with the detection of the secondary reaction, thereby easily yielding false positive or false negative results. Rapid, selective, and sensitive ultra-performance liquid chromatography combined with electrospray ionization tandem mass spectrometry method was developed and used for the detection of AChE and BChE inhibition by directly determining the common product, choline (Ch). Proper separation was achieved for choline and chlormequat (internal standard) within 1.2min via isocratic elution (0.1% fromic acid:methanol=98:2) on an HSS T3 column following a simple precipitation of proteins for sample treatment. The relative standard deviations of the intra- and inter-day precisions were below 7.34 and 9.09%, respectively, whereas the mean accuracy for the quality control samples was 100.31+/-10.93%. The method exhibited the advantages of small total reaction volume (100muL), short analysis time (1.2min), high sensitivity (LOQ of 0.036muM for Ch), and low cost (little consumption enzymes of 0.0035 and 0.008unitmL(-1) for AChE and BChE, and substrates of 5.505 and 7.152muM for ACh and BCh in individual inhibition, respectively), and without matrix effect (90.00-105.03%). The developed method was successfully applied for detecting the AChE and BChE inhibitive activities for model drugs, including galanthamine, tacrine, neostigmine methylsulfate, eserine, as well as beta-carboline and quinazoline alkaloids from Peganum harmala.
ESTHER : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedSearch : Liu_2014_J.Pharm.Biomed.Anal_94_215
PubMedID: 24631841

Title : Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites - Zhou_2014_BMC.Genomics_15_42
Author(s) : Zhou D , Zhang D , Ding G , Shi L , Hou Q , Ye Y , Xu Y , Zhou H , Xiong C , Li S , Yu J , Hong S , Yu X , Zou P , Chen C , Chang X , Wang W , Lv Y , Sun Y , Ma L , Shen B , Zhu C
Ref : BMC Genomics , 15 :42 , 2014
Abstract : BACKGROUND: Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan.
RESULTS: We performed 454 next-generation sequencing and obtained a draft sequence of A. sinensis assembled into scaffolds spanning 220.8 million base pairs. Analysis of this genome sequence, we observed expansion and contraction of several immune-related gene families in anopheline relative to culicine mosquito species. These differences suggest that species-specific immune responses to Plasmodium invasion underpin the biological differences in susceptibility to Plasmodium infection that characterize these two mosquito subfamilies.
CONCLUSIONS: The A. sinensis genome produced in this study, provides an important resource for analyzing the genetic basis of susceptibility and resistance of mosquitoes to Plasmodium parasites research which will ultimately facilitate the design of urgently needed interventions against this debilitating mosquito-borne disease.
ESTHER : Zhou_2014_BMC.Genomics_15_42
PubMedSearch : Zhou_2014_BMC.Genomics_15_42
PubMedID: 24438588
Gene_locus related to this paper: anoga-Q7PVF9 , 9dipt-a0a084vlt1 , 9dipt-a0a084vdq2 , 9dipt-sime3xf.a , 9dipt-sime3xf.b , 9dipt-a0a084vbj8 , 9dipt-a0a084wan7 , 9dipt-a0a084wik4 , 9dipt-a0a084wk64 , 9dipt-a0a084wez8 , 9dipt-a0a084vji7 , 9dipt-a0a084vlc2 , 9dipt-a0a084vsa5 , 9dipt-a0a084wlk0 , 9dipt-a0a084wah8 , 9dipt-a0a084wln4 , 9dipt-a0a084we78 , 9dipt-a0a084wjm6 , 9dipt-a0a084wjm7 , 9dipt-a0a084we77 , 9dipt-a0a084wlk1 , 9dipt-a0a084we80 , 9dipt-a0a084wjm4 , 9dipt-a0a084w1n7 , 9dipt-a0a084we79 , 9dipt-a0a084wev9 , 9dipt-a0a084vlc3 , 9dipt-a0a084vdq4 , 9dipt-a0a084vdq5 , 9dipt-a0a084vdq1 , 9dipt-a0a084wah9 , 9dipt-a0a084wan6 , 9dipt-a0a084wlj8 , 9dipt-a0a084wk45 , 9dipt-a0a084wk46 , 9dipt-a0a084wlj9 , 9dipt-a0a084vsa4 , 9dipt-a0a084vs93 , 9dipt-a0a084wl93 , anosi-a0a0f7kyf5 , anosi-a0a0f7l1f2 , anosi-a0a084wum0 , anost-a0a182xxz0 , anosi-a0a084vn28 , anosi-a0a084vpt0 , anoga-q7q887

Title : Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1 - Wang_2014_Genome.Announc_2_e00171
Author(s) : Wang X , Wang Q , Zhang W , Wang Y , Li L , Wen T , Zhang T , Zhang Y , Xu J , Hu J , Li S , Liu L , Liu J , Jiang W , Tian J , Li Y , Schuler D , Wang L , Li J
Ref : Genome Announc , 2 : , 2014
Abstract : We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and "domestication" by accelerated evolution of the strain upon repeated passaging.
ESTHER : Wang_2014_Genome.Announc_2_e00171
PubMedSearch : Wang_2014_Genome.Announc_2_e00171
PubMedID: 24625872
Gene_locus related to this paper: maggm-v6ezc0

Title : A novel cephalosporin deacetylating acetyl xylan esterase from Bacillus subtilis with high activity toward cephalosporin C and 7-aminocephalosporanic acid - Tian_2014_Appl.Microbiol.Biotechnol_98_2081
Author(s) : Tian Q , Song P , Jiang L , Li S , Huang H
Ref : Applied Microbiology & Biotechnology , 98 :2081 , 2014
Abstract : A cephalosporin deacetylating acetyl xylan esterase was cloned from the genomic DNA of Bacillus subtilis CICC 20034 and functionally expressed in Escherichia coli. Its gene contained an open reading frame of 957 bp encoding 318 amino acids with a calculated mass of 35,607 Da, and it displayed significant identity to acetyl xylan esterases from Bacillus sp. 916, B. subtilis 168, and Bacillus pumilus Cect5072. The enzyme was a native homohexamer but a trimer under the condition of 1% sodium dodecyl sulfate (SDS); both forms were active and could transit to each other by incubating in or removing SDS. The enzyme belongs to carbohydrate esterase family 7 and had a double specificity on both the acetylated oligosaccharide and cephalosporin C (CPC) and 7-aminocephalosporanic acid (7-ACA). The activity of this purified enzyme toward CPC and 7-ACA was highest among all the acetyl xylan esterase from CE family 7, which were 484 and 888 U/mg, respectively, and endowed itself with great industrial interest on semi-synthetic beta-lactam antibiotics. The optimum pH of the purified enzyme was 8.0, and the optimum temperature was 50 degrees C, and the enzyme had high thermal stability, broad range of pH tolerance, and extremely organic solvent tolerance.
ESTHER : Tian_2014_Appl.Microbiol.Biotechnol_98_2081
PubMedSearch : Tian_2014_Appl.Microbiol.Biotechnol_98_2081
PubMedID: 23828600

Title : Lactobacillus casei-01 Facilitates the Ameliorative Effects of Proanthocyanidins Extracted from Lotus Seedpod on Learning and Memory Impairment in Scopolamine-Induced Amnesia Mice - Xiao_2014_PLoS.One_9_e112773
Author(s) : Xiao J , Li S , Sui Y , Wu Q , Li X , Xie B , Zhang M , Sun Z
Ref : PLoS ONE , 9 :e112773 , 2014
Abstract : Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (109 cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice.
ESTHER : Xiao_2014_PLoS.One_9_e112773
PubMedSearch : Xiao_2014_PLoS.One_9_e112773
PubMedID: 25396737

Title : Specialist versus generalist life histories and nucleotide diversity in Caenorhabditis nematodes - Li_2014_Proc.Biol.Sci_281_20132858
Author(s) : Li S , Jovelin R , Yoshiga T , Tanaka R , Cutter AD
Ref : Proc Biol Sci , 281 :20132858 , 2014
Abstract : Species with broad ecological amplitudes with respect to a key focal resource, niche generalists, should maintain larger and more connected populations than niche specialists, leading to the prediction that nucleotide diversity will be lower and more subdivided in specialists relative to their generalist relatives. This logic describes the specialist-generalist variation hypothesis (SGVH). Some outbreeding species of Caenorhabditis nematodes use a variety of invertebrate dispersal vectors and have high molecular diversity. By contrast, Caenorhabditis japonica lives in a strict association and synchronized life cycle with its dispersal host, the shield bug Parastrachia japonensis, itself a diet specialist. Here, we characterize sequence variation for 20 nuclear loci to investigate how C. japonica's life history shapes nucleotide diversity. We find that C. japonica has more than threefold lower polymorphism than other outbreeding Caenorhabditis species, but that local populations are not genetically disconnected. Coupled with its restricted range, we propose that its specialist host association contributes to a smaller effective population size and lower genetic variation than host generalist Caenorhabditis species with outbreeding reproductive modes. A literature survey of diverse organisms provides broader support for the SGVH. These findings encourage further testing of ecological and evolutionary hypotheses with comparative population genetics in Caenorhabditis and other taxa.
ESTHER : Li_2014_Proc.Biol.Sci_281_20132858
PubMedSearch : Li_2014_Proc.Biol.Sci_281_20132858
PubMedID: 24403340
Gene_locus related to this paper: caeja-h2wj36

Title : Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization - Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
Author(s) : Qin C , Yu C , Shen Y , Fang X , Chen L , Min J , Cheng J , Zhao S , Xu M , Luo Y , Yang Y , Wu Z , Mao L , Wu H , Ling-Hu C , Zhou H , Lin H , Gonzalez-Morales S , Trejo-Saavedra DL , Tian H , Tang X , Zhao M , Huang Z , Zhou A , Yao X , Cui J , Li W , Chen Z , Feng Y , Niu Y , Bi S , Yang X , Cai H , Luo X , Montes-Hernandez S , Leyva-Gonzalez MA , Xiong Z , He X , Bai L , Tan S , Liu D , Liu J , Zhang S , Chen M , Zhang L , Zhang Y , Liao W , Wang M , Lv X , Wen B , Liu H , Luan H , Yang S , Wang X , Xu J , Li X , Li S , Wang J , Palloix A , Bosland PW , Li Y , Krogh A , Rivera-Bustamante RF , Herrera-Estrella L , Yin Y , Yu J , Hu K , Zhang Z
Ref : Proc Natl Acad Sci U S A , 111 :5135 , 2014
Abstract : As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs.
ESTHER : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedSearch : Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135
PubMedID: 24591624
Gene_locus related to this paper: capch-q75qh4 , capan-a0a1u8fuf5 , capan-a0a1u8gmz3 , capan-a0a1u8f879 , capan-a0a1u8ftr2 , capan-a0a1u8g8s6

Title : miR-124 represses ROCK1 expression to promote neurite elongation through activation of the PI3K\/Akt signal pathway - Gu_2014_J.Mol.Neurosci_52_156
Author(s) : Gu X , Meng S , Liu S , Jia C , Fang Y , Li S , Fu C , Song Q , Lin L , Wang X
Ref : Journal of Molecular Neuroscience , 52 :156 , 2014
Abstract : Recent studies have demonstrated an important role for miR-124, the most abundant and well-conserved brain-specific microRNA(miRNA), in promoting neurite outgrowth and elongation during neuronal differentiation. This miRNA's target genes and the mechanisms that execute this role remain unclear. In this study, we identified ROCK1, a small GTPase Rho kinase, as a direct target of miR-124 for regulating neurite elongation. miR-124 significantly inhibited ROCK1 expression in M17 cells. Inhibiting ROCK1 promoted neurite elongation, and the overexpression of ROCK1 strongly repressed the neurite elongation-enhancing effect of miR-124 in M17 cells. We determined that Akt functions as a novel ROCK1 downstream effector in regulating neurite outgrowth and elongation.
ESTHER : Gu_2014_J.Mol.Neurosci_52_156
PubMedSearch : Gu_2014_J.Mol.Neurosci_52_156
PubMedID: 24338057

Title : Lab-on-a-drop: biocompatible fluorescent nanoprobes of gold nanoclusters for label-free evaluation of phosphorylation-induced inhibition of acetylcholinesterase activity towards the ultrasensitive detection of pesticide residues - Zhang_2014_Analyst_139_4620
Author(s) : Zhang N , Si Y , Sun Z , Li S , Lin Y , Wang H
Ref : Analyst , 139 :4620 , 2014
Abstract : A simple, sensitive, selective, and "lab-on-a-drop"-based fluorimetric protocol has been proposed using biocompatible fluorescent nanoprobes of gold nanoclusters (AuNCs) for the label-free evaluation of the catalytic activity and phosphorylation of acetylcholinesterase (AChE) under physiologically simulated environments. Protein-stabilized AuNCs were prepared and mixed with acetylthiocholine (ATC) serving as "a drop" of fluorimetric reaction substrate. The AChE-catalyzed hydrolysis of ATC releases thiocholine to cause the aggregation of the AuNCs towards a dramatic decrease in fluorescence intensities, which could be curbed by the phosphorylation-induced inhibition of AChE activity when exposed to organophosphorus compounds (OPs). The reaction procedures and conditions of AChE catalysis and phosphorylation were monitored by fluorimetric measurements and electron microscopy imaging. Moreover, a selective and ultrasensitive fluorimetric assay has been tailored for the detection of pesticide residues using dimethyl-dichloro-vinyl phosphate (DDVP) as an example. Investigation results indicate that the specific catalysis and irreversible OP-induced phosphorylation of AChE, in combination with sensitive fluorimetric outputs could facilitate the detection of total free OPs with high selectivity and sensitivity. A linear concentration of DDVP ranging from 0.032 nM to 20 nM could be obtained with a detection limit of 13.67 pM. Particularly, pesticide residues of DDVP in vegetable samples were quantified down to approximately 36 pM. Such a label-free "lab-on-a drop"-based fluorimetry may promise wide applications for the evaluation of the physiological catalytic activity of various enzymes (i.e., cholinesterase), and especially for monitoring the direct phosphorylation biomarkers of free OPs towards rapid and early warning, and accurate diagnosis of OP exposure.
ESTHER : Zhang_2014_Analyst_139_4620
PubMedSearch : Zhang_2014_Analyst_139_4620
PubMedID: 25050413

Title : New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase - Wei_2014_Bioorg.Med.Chem.Lett_24_5743
Author(s) : Wei Z , Liu YQ , Zhou XB , Luo Y , Huang CQ , Wang YA , Zheng ZB , Li S
Ref : Bioorganic & Medicinal Chemistry Lett , 24 :5743 , 2014
Abstract : Herein, we described a new class of uncharged non-pyridinium reactivators for nerve agent-inhibited acetylcholinesterase (AChE). Based on a dual site binding strategy, we conjugated the imidazolium aldoxime to different peripheral site ligands (PSLs) of AChE through alkyl chains. Compared with the known quaternary pyridinium reactivators, two of the resulting conjugates (7g and 7h) were highlighted to be the first efficient non-pyridinium oxime conjugates exhibiting similar or superior ability to reactivate sarin-, VX- and tabun-inhibited AChE. Moreover, they were more broad-spectrum reactivators.
ESTHER : Wei_2014_Bioorg.Med.Chem.Lett_24_5743
PubMedSearch : Wei_2014_Bioorg.Med.Chem.Lett_24_5743
PubMedID: 25453812

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 : Crystal structures of two phytohormone signal-transducing alpha\/beta hydrolases: karrikin-signaling KAI2 and strigolactonesignaling DWARF14 -
Author(s) : Zhao LH , Zhou XE , Wu ZS , Yi W , Xu Y , Li S , Xu TH , Liu Y , Chen RZ , Kovach A , Kang Y , Hou L , He Y , Xie C , Song W , Zhong D , Wang Y , Li J , Zhang C , Melcher K , Xu HE
Ref : Cell Res , 23 :436 , 2013
PubMedID: 23381136
Gene_locus related to this paper: orysj-Q10QA5

Title : Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat - Blackett_2013_J.Clin.Lipidol_7_132
Author(s) : Blackett P , Tryggestad J , Krishnan S , Li S , Xu W , Alaupovic P , Quiroga C , Copeland K
Ref : J Clin Lipidol , 7 :132 , 2013
Abstract : BACKGROUND: The treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis. OBJECTIVE: To report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition.
METHODS: Serial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample.
RESULTS: The affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk. CONCLUSION: The data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis.
ESTHER : Blackett_2013_J.Clin.Lipidol_7_132
PubMedSearch : Blackett_2013_J.Clin.Lipidol_7_132
PubMedID: 23415432

Title : Alterations in activity and mRNA expression of acetylcholinesterase in the liver, kidney and gill of common carp exposed to atrazine and chlorpyrifos - Xing_2013_Environ.Toxicol.Pharmacol_35_47
Author(s) : Xing H , Wu H , Sun G , Zhang Z , Xu S , Li S
Ref : Environ Toxicol Pharmacol , 35 :47 , 2013
Abstract : Insecticides and herbicides are widely used in modern agricultural production. The intensive use of insecticide chlorpyrifos (CPF) and herbicide atrazine (ATR) has resulted in serious environmental problems. Herein, we investigated alteration in activity and mRNA levels of AChE in the liver, kidney and gill from common carp after 40d exposure to CPF and ATR alone or in combination and 20d recovery treatment. Results indicated that activity and mRNA levels of AChE at all high-dose groups have been significantly decreased after CPF and ATR alone or ATR/CPF mixture exposure, and the changes were improved in the end of recovery tests in varying degrees, the activity and gene expression of AChE in the joint toxicity of ATR and CPF groups were significantly lower than that in the single toxicant group. Our study suggests that the decrease of AChE activity observed at all high-dose groups (CPF and ATR alone or in combination) may be directly related to a lower AChE expression, and the joint toxicity of ATR and CPF is higher than ATR and CPF alone.
ESTHER : Xing_2013_Environ.Toxicol.Pharmacol_35_47
PubMedSearch : Xing_2013_Environ.Toxicol.Pharmacol_35_47
PubMedID: 23237783

Title : Comparative analyses of lipoprotein lipase, hepatic lipase, and endothelial lipase, and their binding properties with known inhibitors - Wang_2013_PLoS.One_8_e72146
Author(s) : Wang Z , Li S , Sun L , Fan J , Liu Z
Ref : PLoS ONE , 8 :e72146 , 2013
Abstract : The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investigated the kinetic characteristics for the catalytic residues using a molecular dynamics simulation strategy. To elucidate the molecular interactions and determine potential key residues involved in the binding to lipase inhibitors, we analyzed the binding pockets and binding poses of known inhibitors of the three lipases. We identified the spatial consensus catalytic triad "Ser-Asp-His", a characteristic motif in all three lipases. Furthermore, we found that the spatial characteristics of the binding pockets of the lipase molecules play a key role in ligand recognition, binding poses, and affinities. To the best of our knowledge, this is the first report that systematically builds homology models of all the triglyceride lipase gene subfamily members. Our data provide novel insights into the molecular structures of lipases and their structure-function relationship, and thus provides groundwork for functional probe design towards lipase-based therapeutic inhibitors for the treatment of hyperlipidemia and atherosclerosis.
ESTHER : Wang_2013_PLoS.One_8_e72146
PubMedSearch : Wang_2013_PLoS.One_8_e72146
PubMedID: 23991054

Title : The evolution and pathogenic mechanisms of the rice sheath blight pathogen - Zheng_2013_Nat.Commun_4_1424
Author(s) : Zheng A , Lin R , Zhang D , Qin P , Xu L , Ai P , Ding L , Wang Y , Chen Y , Liu Y , Sun Z , Feng H , Liang X , Fu R , Tang C , Li Q , Zhang J , Xie Z , Deng Q , Li S , Wang S , Zhu J , Wang L , Liu H , Li P
Ref : Nat Commun , 4 :1424 , 2013
Abstract : Rhizoctonia solani is a major fungal pathogen of rice (Oryza sativa L.) that causes great yield losses in all rice-growing regions of the world. Here we report the draft genome sequence of the rice sheath blight disease pathogen, R. solani AG1 IA, assembled using next-generation Illumina Genome Analyser sequencing technologies. The genome encodes a large and diverse set of secreted proteins, enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, which probably reflect an exclusive necrotrophic lifestyle. We find few repetitive elements, a closer relationship to Agaricomycotina among Basidiomycetes, and expand protein domains and families. Among the 25 candidate pathogen effectors identified according to their functionality and evolution, we validate 3 that trigger crop defence responses; hence we reveal the exclusive expression patterns of the pathogenic determinants during host infection.
ESTHER : Zheng_2013_Nat.Commun_4_1424
PubMedSearch : Zheng_2013_Nat.Commun_4_1424
PubMedID: 23361014
Gene_locus related to this paper: thaca-l8wvp3 , thaca-l8wv47 , thaca-l8wp17 , thaca-l8x532

Title : First report of a sequence type 239 vancomycin-intermediate Staphylococcus aureus isolate in Mainland China - Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
Author(s) : Zhang X , Hu Q , Yuan W , Shang W , Cheng H , Yuan J , Zhu J , Hu Z , Li S , Chen W , Hu X , Rao X
Ref : Diagn Microbiol Infect Dis , 77 :64 , 2013
Abstract : Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that causes a wide range of both hospital- and community-acquired infections. The high prevalence of MRSA and the extensive use of vancomycin in Mainland China may lead to the emergence of vancomycin-intermediate S. aureus (VISA) isolates. In this case, we report a VISA isolate from a 34-year-old male patient with steam burn. The isolate was determined to be sequence type 239 staphylococcal cassette chromosome mec type III, the most prevalent MRSA clone in Mainland China.
ESTHER : Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
PubMedSearch : Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
PubMedID: 23876353

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

Title : 6-acetyl-5H-thiazolo[3,2-a]pyrimidine derivatives as the novel acetylcholinesterase inhibitors: design, synthesis, and biological activity - Zhi_2013_Med.Chem_9_703
Author(s) : Zhi H , Zhang C , Cheng Z , Jin Z , Huang E , Li S , Lin H , Wan DC , Hu C
Ref : Med Chem , 9 :703 , 2013
Abstract : Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer's drugs. A series of 6-acetyl- 5H-thiazolo[3,2-a]pyrimidine derivatives as the novel acetylcholinesterase inhibitors were designed based on virtual screening methods. The target compounds which are not reported in the literature were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, 1H-NMR and 13C-NMR. The biological evaluation against human acetylcholinesterase in vitro showed most of the target compounds exhibited varying inhibition at 10 microM using the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer's disease, and a foundation in search for improved acetylcholinesterase inhibitors with the novel scaffolds. The preliminary structure-activity relationships were the 2-hydroxyethoxy group at the phenyl ring at C4 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.
ESTHER : Zhi_2013_Med.Chem_9_703
PubMedSearch : Zhi_2013_Med.Chem_9_703
PubMedID: 23270368

Title : Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis - Chen_2013_BMC.Genomics_14_339
Author(s) : Chen L , Yue Q , Zhang X , Xiang M , Wang C , Li S , Che Y , Ortiz-Lopez FJ , Bills GF , Liu X , An Z
Ref : BMC Genomics , 14 :339 , 2013
Abstract : BACKGROUND: The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868.
RESULTS: The pneumocandin biosynthetic gene cluster contains a NRPS (GLNRPS4) and a PKS (GLPKS4) arranged in tandem, two cytochrome P450 monooxygenases, seven other modifying enzymes, and genes for L-homotyrosine biosynthesis, a component of the peptide core. Thus, the pneumocandin biosynthetic gene cluster is significantly more autonomous and organized than that of the recently characterized echinocandin B gene cluster. Disruption mutants of GLNRPS4 and GLPKS4 no longer produced the pneumocandins (A0 and B0), and the Deltaglnrps4 and Deltaglpks4 mutants lost antifungal activity against the human pathogenic fungus Candida albicans. In addition to pneumocandins, the G. lozoyensis genome encodes a rich repertoire of natural product-encoding genes including 24 PKSs, six NRPSs, five PKS-NRPS hybrids, two dimethylallyl tryptophan synthases, and 14 terpene synthases.
CONCLUSIONS: Characterization of the gene cluster provides a blueprint for engineering new pneumocandin derivatives with improved pharmacological properties. Whole genome estimation of the secondary metabolite-encoding genes from G. lozoyensis provides yet another example of the huge potential for drug discovery from natural products from the fungal kingdom.
ESTHER : Chen_2013_BMC.Genomics_14_339
PubMedSearch : Chen_2013_BMC.Genomics_14_339
PubMedID: 23688303
Gene_locus related to this paper: glal2-s3cg73 , glal2-s3d2r4 , glal2-s3dmm6 , glal2-s3e306 , glal2-s3dl45 , glal2-s3d1r9 , glal2-s3e4a7 , glal2-s3ddr1 , glal2-s3ctz6 , glal2-s3dy35 , glal2-s3dws5 , glal2-s3df31 , glal2-s3d7q5 , glal2-s3cwz5 , glal2-s3dcn7 , glal2-s3dhj7 , glal2-s3dm96 , glal2-s3d6q1 , glal2-s3cv25 , glal2-s3e8v9 , glal2-s3crh2 , glal2-s3dde8 , glal2-s3cxt6 , glal2-s3da89 , glal2-s3ckn8 , glal2-s3d4y3 , glal2-s3ddw6 , glal2-s3dk02 , glal2-s3d048 , glal2-s3de12

Title : Draft Genome Sequence of Strain JLT2015T, Belonging to the Family Sphingomonadaceae of the Alphaproteobacteria - Tang_2013_Genome.Announc_1_e00226
Author(s) : Tang K , Liu K , Li S , Jiao N
Ref : Genome Announc , 1 : , 2013
Abstract : Strain JLT2015(T) was isolated from the southeastern Pacific, as a representative of a new genus of the family Sphingomonadaceae of the Alphaproteobacteria. Here, we present the draft genome sequence of strain JLT2015(T), which provides insight into the oligotrophic strategy of this organism.
ESTHER : Tang_2013_Genome.Announc_1_e00226
PubMedSearch : Tang_2013_Genome.Announc_1_e00226
PubMedID: 23661488
Gene_locus related to this paper: 9prot-m2u802 , 9prot-m2u3z8 , 9prot-m2u526

Title : LovG: the thioesterase required for dihydromonacolin L release and lovastatin nonaketide synthase turnover in lovastatin biosynthesis -
Author(s) : Xu W , Chooi YH , Choi JW , Li S , Vederas JC , Da Silva NA , Tang Y
Ref : Angew Chem Int Ed Engl , 52 :6472 , 2013
PubMedID: 23653178
Gene_locus related to this paper: asptn-LOVG

Title : Nanosized sustained-release pyridostigmine bromide microcapsules: process optimization and evaluation of characteristics - Tan_2013_Int.J.Nanomedicine_8_737
Author(s) : Tan Q , Jiang R , Xu M , Liu G , Li S , Zhang J
Ref : Int J Nanomedicine , 8 :737 , 2013
Abstract : BACKGROUND: Pyridostigmine bromide (3-[[(dimethylamino)-carbonyl]oxy]-1-methylpyridinium bromide), a reversible inhibitor of cholinesterase, is given orally in tablet form, and a treatment schedule of multiple daily doses is recommended for adult patients. Nanotechnology was used in this study to develop an alternative sustained-release delivery system for pyridostigmine, a synthetic drug with high solubility and poor oral bioavailability, hence a Class III drug according to the Biopharmaceutics Classification System. Novel nanosized pyridostigmine-poly(lactic acid) microcapsules (PPNMCs) were expected to have a longer duration of action than free pyridostigmine and previously reported sustained-release formulations of pyridostigmine.
METHODS: The PPNMCs were prepared using a double emulsion-solvent evaporation method to achieve sustained-release characteristics for pyridostigmine. The preparation process for the PPNMCs was optimized by single-factor experiments. The size distribution, zeta potential, and sustained-release behavior were evaluated in different types of release medium.
RESULTS: The optimal volume ratio of inner phase to external phase, poly(lactic acid) concentration, polyvinyl alcohol concentration, and amount of pyridostigmine were 1:10, 6%, 3% and 40 mg, respectively. The negatively charged PPNMCs had an average particle size of 937.9 nm. Compared with free pyridostigmine, PPNMCs showed an initial burst release and a subsequent very slow release in vitro. The release profiles for the PPNMCs in four different types of dissolution medium were fitted to the Ritger-Peppas and Weibull models. The similarity between pairs of dissolution profiles for the PPNMCs in different types of medium was statistically significant, and the difference between the release curves for PPNMCs and free pyridostigmine was also statistically significant. CONCLUSION: PPNMCs prepared by the optimized protocol described here were in the nanometer range and had good uniformity, with significantly slower pyridostigmine release than from free pyridostigmine. This novel sustained-release delivery nanosystem for pyridostigmine might alleviate the need to identify new acetylcholinesterase inhibitors.
ESTHER : Tan_2013_Int.J.Nanomedicine_8_737
PubMedSearch : Tan_2013_Int.J.Nanomedicine_8_737
PubMedID: 23459707

Title : 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism - Zhang_2013_Biomaterials_34_7552
Author(s) : Zhang J , Cao Q , Li S , Lu X , Zhao Y , Guan JS , Chen JC , Wu Q , Chen GQ
Ref : Biomaterials , 34 :7552 , 2013
Abstract : Alzheimer's disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-beta deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages.
ESTHER : Zhang_2013_Biomaterials_34_7552
PubMedSearch : Zhang_2013_Biomaterials_34_7552
PubMedID: 23849878

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Altered quantities and in vivo activities of cholinesterase from Daphnia magna in sub-lethal exposure to organophosphorus insecticides - Liu_2012_Ecotoxicol.Environ.Saf_80_118
Author(s) : Liu H , Yuan B , Li S
Ref : Ecotoxicology & Environmental Safety , 80 :118 , 2012
Abstract : For investigating relationship between activity of cholinesterase (ChE) and ambient concentration of anticholinesterases, Daphnia magna had been exposed for 21 day to sub-lethal concentrations, i.e. 1/6 EC(50), 1/36 EC(50), and 1/216 EC(50), of either triazophos or chlorpyrifos. Samples were taken at different points of time for measuring total activity and immunoreactive content of ChE and actual concentrations of the anticholinesterases. A type of antigen formerly developed by immunizing mice with purified ChE was utilized in this study to establish an indirect non-competitive ELISA for measuring immunoreactive content of ChE in Daphnia. Studies showed that for apparent activity, i.e. activity that was scaled with total protein, the insecticides caused 5.2-6.9 percent inhibition and 17.0-17.7 percent inductions during the 21 d exposure, whereas for inherent activity, i.e. activity that was scaled with immunoreactive protein, no induction was detected during the exposure. Accompanied by up to 65.9 percent and 68.0 percent promotion in terms of the immunoreactive content, up to 42.8 percent and 44.6 percent inhibition in terms of the inherent activity was indicated, respectively, for triazophos and chlopyrifos. Judged by measured concentrations, the inherent activity recovered faster than the rate of dissipation of the anticholinesterases. Result of the study suggested that the inherent activity was more sensitive than the apparent one in predicting sub-lethal and/or long-term stress of anticholinesterases. It also suggested that apart from promotion in terms of content of the ChE, the Daphnia developed capacities to block bio-concentration of anticholinesterases, and these capacities would make it liable to underestimate ambient concentration of anticholinesterases along with the time of exposure.
ESTHER : Liu_2012_Ecotoxicol.Environ.Saf_80_118
PubMedSearch : Liu_2012_Ecotoxicol.Environ.Saf_80_118
PubMedID: 22436861

Title : Enzyme-catalyzed degradation of biodegradable polymers derived from trimethylene carbonate and glycolide by lipases from Candida antarctica and Hog pancreas - Liu_2012_J.Biomater.Sci.Polym.Ed_23_1355
Author(s) : Liu F , Yang J , Fan Z , Li S , Kasperczyk J , Dobrzynski P
Ref : J Biomater Sci Polym Ed , 23 :1355 , 2012
Abstract : Enzyme-catalyzed degradation of poly(trimethylene carbonate) homo-polymer (PTMC) and poly(trimethylene carbonate-co-glycolide) co-polymer (PTGA) was investigated in the presence of lipases from Candida antarctica and Hog pancreas. Degradation was monitored by gravimetry, size-exclusion chromatography (SEC), nuclear magnetic resonance (NMR), tensiometry and environmental scanning electron microscopy (ESEM). PTMC can be rapidly degraded by Candida antarctica lipase with 98% mass loss after 9 days, while degradation by Hog pancreas lipase leads to 27% mass loss. Introduction of 16% glycolide units in PTMC chains strongly affects the enzymatic degradation. Hog pancreas lipase becomes more effective to PTGA co-polymer with a mass loss of 58% after 9 days, while Candida antarctica lipase seems not able to degrade PTGA. Bimodal molecular weight distributions are observed during enzymatic degradation of both PTMC and PTGA, which can be assigned to the fact that the surface is largely degraded while the internal part remains intact. The composition of the PTGA co-polymer remains constant, and ESEM shows that the polymers are homogeneously eroded during enzymatic degradation. Contact angle measurements confirm the enzymatic degradation mechanism, i.e., enzyme adsorption on the polymer surface followed by enzyme-catalyzed chain cleavage.
ESTHER : Liu_2012_J.Biomater.Sci.Polym.Ed_23_1355
PubMedSearch : Liu_2012_J.Biomater.Sci.Polym.Ed_23_1355
PubMedID: 21722422

Title : Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1beta and activation of fibroblast growth factor receptor-1 - Gjorlund_2012_Faseb.J_26_4174
Author(s) : Gjorlund MD , Nielsen J , Pankratova S , Li S , Korshunova I , Bock E , Berezin V
Ref : FASEB Journal , 26 :4174 , 2012
Abstract : Neurexin-1 NRXN1 and neuroligin-1 NLGN1 are synaptic cell adhesion molecules that connect pre and postsynaptic neurons at synapses and mediate signaling across the synapse which modulates synaptic activity and determines the properties of neuronal networks Defects in the genes encoding NLGN1 have been linked to cognitive diseases such as autism The roles of both NRXN1 and NLGN1 during synaptogenesis have been studied extensively but little is known about the role of these molecules in neuritogenesis which eventually results in neuronal circuitry formation The present study investigated the neuritogenic effect of NLGN1 in cultures of hippocampal neurons Our results show that NLGN1 both in soluble and membrane-bound forms induces neurite outgrowth that depends on the interaction with NRXN1beta and on activation of fibroblast growth factor receptor-1 In addition we demonstrate that a synthetic peptide termed neurolide which is modeled after a part of the binding interface of NLGN1 for NRXN1beta can bind to NRXN1beta and mimic the biological properties of NLGN1 in vitro.-Gjorlund M D Nielsen J Pankratova S Li S Korshunova I Bock B Berezin V Neuroligin-1 induces neurite outgrowth through interaction with neurexin-1beta and activation of fibroblast growth factor receptor-1.
ESTHER : Gjorlund_2012_Faseb.J_26_4174
PubMedSearch : Gjorlund_2012_Faseb.J_26_4174
PubMedID: 22750515

Title : A screen-printed, amperometric biosensor for the determination of organophosphorus pesticides in water samples - Dou_2012_J.Environ.Sci.(China)_24_956
Author(s) : Dou J , Fan F , Ding A , Cheng L , Sekar R , Wang H , Li S
Ref : J Environ Sci (China) , 24 :956 , 2012
Abstract : An amperometric biosensor based on screen-printed electrodes (SPEs) was developed for the determination of organophosphorus pesticides in water samples. The extent of acetylcholinesterase (AChE) deactivation was determined and quantified for pesticide concentrations in water samples. An enzyme immobilization adsorption procedure and polyacrylamide gel matrix polymerization were used for fabrication of the biosensor, with minimal losses in enzyme activity. The optimal conditions for enzyme catalytic reaction on the SPEs surfaces were acetylthiocholine chloride (ATChCl) concentration of 5 mmol/L, pH 7 and reaction time of 4 min. The detection limits for three organophosphorus pesticides (dichlorvos, monocrotophs and parathion) were in the range of 4 to 7 microg/L when an AChE amount of 0.1 U was used for immobilization.
ESTHER : Dou_2012_J.Environ.Sci.(China)_24_956
PubMedSearch : Dou_2012_J.Environ.Sci.(China)_24_956
PubMedID: 22893976

Title : Effects of dietary isoleucine on growth, the digestion and absorption capacity and gene expression in hepatopancreas and intestine of juvenile Jian carp (Cyprinus carpio var. Jian) - Zhao_2012_Aquaculture_368-369_117
Author(s) : Zhao J , Liu Y , Jiang J , Wu P , Chen G , Jiang W ,