Luo X

References (42)

Title : Acetylcholine triggered enzymatic cascade reaction based on Fe(7)S(8) nanoflakes catalysis for organophosphorus pesticides visual detection - Zhu_2024_Anal.Chim.Acta_1301_342464
Author(s) : Zhu S , Qin S , Wei C , Cen L , Xiong L , Luo X , Wang Y
Ref : Anal Chim Acta , 1301 :342464 , 2024
Abstract : BACKGROUND: Organophosphorus pesticides (OPs) play important roles in the natural environment, agricultural fields, and biological prevention. The development of OPs detection has gradually become an effective strategy to avoid the dangers of pesticides abuse and solve the severe environmental and health problems in humans. Although conventional assays for OPs analysis such as the bulky instrument required analytical methods have been well-developed, it still remains the limitation of inconvenient, inefficient and lab-dependence analysis in real samples. Hence, there is an urgent demand to develop efficient detection methods for OPs analysis in real scenarios. RESULTS: Here, by virtue of the highly efficient catalytic performance in Fe(7)S(8) nanoflakes (Fe(7)S(8) NFs), we propose an OPs detection method that rationally integrated Fe(7)S(8) NFs into the acetylcholine (ACh) triggered enzymatic cascade reaction (ATECR) for proceeding better detection performances. In this method, OPs serve as the enzyme inhibitors for inhibiting ATECR among ACh, acetylcholinesterase (AChE), and choline oxidase (CHO), then reduce the generation of H(2)O(2) to suppress the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) that catalyzed by Fe(7)S(8) NFs. Benefiting from the integration of Fe(7)S(8) NFs and ATECR, it enables a sensitive detection for OPs (e.g. dimethoate). The proposed method has presented good linear ranges of OPs detection ranging from 0.1 to 10 microg mL(-1). Compared to the other methods, the comparable limits of detection (LOD) of OPs are as low as 0.05 microg mL(-1). SIGNIFICANCE: Furthermore, the proposed method has also achieved a favorable visual detection performance of revealing OPs analysis in real samples. The visual signals of OPs can be transformed into RGB values and gathered by using smartphones, indicating the great potential in simple, sensitive, instrument-free and on-site analysis of pesticide residues in environmental monitoring and biosecurity research.
ESTHER : Zhu_2024_Anal.Chim.Acta_1301_342464
PubMedSearch : Zhu_2024_Anal.Chim.Acta_1301_342464
PubMedID: 38553122

Title : Simultaneously Predicting the Pharmacokinetics of CES1-Metabolized Drugs and Their Metabolites Using Physiologically Based Pharmacokinetic Model in Cirrhosis Subjects - Luo_2024_Pharmaceutics_16_
Author(s) : Luo X , Zhang Z , Mu R , Hu G , Liu L , Liu X
Ref : Pharmaceutics , 16 : , 2024
Abstract : Hepatic carboxylesterase 1 (CES1) metabolizes numerous prodrugs into active ingredients or direct-acting drugs into inactive metabolites. We aimed to develop a semi-physiologically based pharmacokinetic (semi-PBPK) model to simultaneously predict the pharmacokinetics of CES1 substrates and their active metabolites in liver cirrhosis (LC) patients. Six prodrugs (enalapril, benazepril, cilazapril, temocapril, perindopril and oseltamivir) and three direct-acting drugs (flumazenil, pethidine and remimazolam) were selected. Parameters such as organ blood flows, plasma-binding protein concentrations, functional liver volume, hepatic enzymatic activity, glomerular filtration rate (GFR) and gastrointestinal transit rate were integrated into the simulation. The pharmacokinetic profiles of these drugs and their active metabolites were simulated for 1000 virtual individuals. The developed semi-PBPK model, after validation in healthy individuals, was extrapolated to LC patients. Most of the observations fell within the 5th and 95th percentiles of simulations from 1000 virtual patients. The estimated AUC and C(max) were within 0.5-2-fold of the observed values. The sensitivity analysis showed that the decreased plasma exposure of active metabolites due to the decreased CES1 was partly attenuated by the decreased GFR. Conclusion: The developed PBPK model successfully predicted the pharmacokinetics of CES1 substrates and their metabolites in healthy individuals and LC patients, facilitating tailored dosing of CES1 substrates in LC patients.
ESTHER : Luo_2024_Pharmaceutics_16_
PubMedSearch : Luo_2024_Pharmaceutics_16_
PubMedID: 38399287

Title : Enzyme colorimetric cellulose membrane bioactivity strips based on acetylcholinesterase immobilization for inhibitors preliminary screening - Chen_2023_Colloids.Surf.B.Biointerfaces_223_113184
Author(s) : Chen Y , Zhang X , Luo X
Ref : Colloids Surf B Biointerfaces , 223 :113184 , 2023
Abstract : To quickly screen the active pharmaceutical ingredient that can be used as acetylcholinesterase inhibitors (AChEIs) to treat Alzheimer's disease, an enzyme colorimetric cellulose membrane bioactivity strip (CBS) was developed for simple and rapid screening of AChEIs. The amino group of acetylcholinesterase (AChE) undergoes Schiff base reaction with the aldehyde group on the oxidized cellulose membranes, then the AChE was covalently cross-linking on the surface of cellulose membranes, enabling the screening based on Ellman's enzyme colorimetric method. When the enzyme activity of AChE was inhibited after incubation with inhibitors, the hydrolysis of S-Acetylthiocholine iodide decreased, consequently, the 5-thio-2-nitrobenzoic acid generated by the reaction with 5,5'-dithiobis (2-nitrobenzoic acid) also decreased, leading to a decreased color intensity. In addition, CBSs had fast chromogenic time, excellent specificity, and extraordinary storage stability. Tacrine and Donepezil were used as representative inhibitors during the detection, while their IC(50) and limit of detection were determined. Therefore, our work not only established a platform for effective preliminary screening of AChEIs but also inspired the further development of other cellulose membrane-based biosensors.
ESTHER : Chen_2023_Colloids.Surf.B.Biointerfaces_223_113184
PubMedSearch : Chen_2023_Colloids.Surf.B.Biointerfaces_223_113184
PubMedID: 36739673

Title : Microbial-host-isozyme analyses reveal microbial DPP4 as a potential antidiabetic target - Wang_2023_Science_381_eadd5787
Author(s) : Wang K , Zhang Z , Hang J , Liu J , Guo F , Ding Y , Li M , Nie Q , Lin J , Zhuo Y , Sun L , Luo X , Zhong Q , Ye C , Yun C , Zhang Y , Wang J , Bao R , Pang Y , Wang G , Gonzalez FJ , Lei X , Qiao J , Jiang C
Ref : Science , 381 :eadd5787 , 2023
Abstract : A mechanistic understanding of how microbial proteins affect the host could yield deeper insights into gut microbiota-host cross-talk. We developed an enzyme activity-screening platform to investigate how gut microbiota-derived enzymes might influence host physiology. We discovered that dipeptidyl peptidase 4 (DPP4) is expressed by specific bacterial taxa of the microbiota. Microbial DPP4 was able to decrease the active glucagon like peptide-1 (GLP-1) and disrupt glucose metabolism in mice with a leaky gut. Furthermore, the current drugs targeting human DPP4, including sitagliptin, had little effect on microbial DPP4. Using high-throughput screening, we identified daurisoline-d4 (Dau-d4) as a selective microbial DPP4 inhibitor that improves glucose tolerance in diabetic mice.
ESTHER : Wang_2023_Science_381_eadd5787
PubMedSearch : Wang_2023_Science_381_eadd5787
PubMedID: 37535747
Gene_locus related to this paper: bactn-BT4193

Title : Detoxification of Fumonisins by Three Novel Transaminases with Diverse Enzymatic Characteristics Coupled with Carboxylesterase - Wang_2023_Foods_12_
Author(s) : Wang Y , Sun J , Zhang M , Pan K , Liu T , Zhang T , Luo X , Zhao J , Li Z
Ref : Foods , 12 : , 2023
Abstract : Fumonisin (FB) is one of the most common mycotoxins contaminating feed and food, causing severe public health threat to human and animals worldwide. Until now, only several transaminases were found to reduce FB toxicity, thus, more fumonisin detoxification transaminases with excellent catalytic properties required urgent exploration for complex application conditions. Herein, through gene mining and enzymatic characterization, three novel fumonisin detoxification transaminases-FumTSTA, FumUPTA, FumPHTA-were identified, sharing only 61-74% sequence identity with reported fumonisin detoxification transaminases. Moreover, the recombinant proteins shared diverse pH reaction ranges, good pH stability and thermostability, and the recombinant protein yields were also improved by condition optimum. Furthermore, the final products were analyzed by liquid chromatography-mass spectrometry. This study provides ideal candidates for fumonisin detoxification and meets diverse required demands in food and feed industries.
ESTHER : Wang_2023_Foods_12_
PubMedSearch : Wang_2023_Foods_12_
PubMedID: 36673508

Title : A High-Density Raman Photometry for Tracking and Quantifying of AchE Activity in The Brain of Freely Moving Animals with Network - Zhang_2023_Adv.Sci.(Weinh)__e2301004
Author(s) : Zhang Z , Liu Z , Wu P , Guo X , Luo X , Yang Y , Chen J , Tian Y
Ref : Adv Sci (Weinh) , :e2301004 , 2023
Abstract : A high-density Raman photometry based on a dual-recognition strategy is created for accurately quantifying acetylcholinesterase (AchE) activity in 24 brain regions of free-moving animals with network. A series of 5-ethynyl-1,2,3,3-tetramethyl-based molecules with different conjugated structures and substitute groups are designed and synthesized for specific recognition of AchE by Raman spectroscopy. After systematically evaluating the recognition ability toward AchE, 2-(4-((4-(dimethylamino)benzoyl)oxy)styryl)-5-ethynyl-1,3,3-trimethyl-3H-indol-1-ium (ET-5) is finally optimized for AchE determination, which shows the highest selectivity, the greatest sensitivity, and the fastest response time among the investigated seven molecules. More interestingly, using the developed probe for AchE with high accuracy and sensitivity, the optimized AchE regulated by nitric oxide (NO) is discovered for promoting the neurogenesis of neural stem cells (NSCs). Benefiting from the high-density photometry, it is found that the activity and distribution of AchE varied in 24 brain regions, and the levels of AchE activity in 24 brain regions of Alzheimer's mice (AD) are lower than those of normal mice. It is the first time that a functional network of AchE in 24 brain regions is established. It is also found that the loss of AchE functional network in AD mice is restored and reconstructed by the controlled release of AchE regulated by NO.
ESTHER : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedSearch : Zhang_2023_Adv.Sci.(Weinh)__e2301004
PubMedID: 37635166

Title : Hormetic effects of EGC and EGCG on CES1 activity and its rescue from oxidative stress in rat liver S9 - Luo_2023_Chem.Biol.Interact__110612
Author(s) : Luo X , Lu F , Yin Z , Zhou Z , Wang Z , Zhang H
Ref : Chemico-Biological Interactions , :110612 , 2023
Abstract : Carboxylesterase 1 (CES1) is a hydrolytic enzyme that plays an important role in the activation or deactivation of many therapeutic agents, thus affecting their pharmacokinetic and pharmacodynamic outcomes. Using rat liver S9 as an enzyme source and enalapril as a CES1 substrate, the present study examined effects of a number of flavonoids on the formation of enalaprilat (the active form of enalapril) produced by CES1-mediated hydrolysis. While a majority of flavonoids tested showed inhibition on CES1, an unexpected hormetic effect was observed for epigallocatechin (EGC) and epigallocatechin gallate (EGCG), i.e., stimulatory effect at low concentrations and enzyme inhibition at high concentrations. Further experiments revealed that oxidative stress caused by hydrogen peroxide, arachidonic acid plus iron, and oxidized low density lipoproteins (oxLOL) reduced CES1 activity in rat liver S9 and the loss of CES1 enzyme activity could be rescued largely by EGC or EGCG. In contrast, such effects were minimal in human liver S9, probably due to the presence of a higher ratio of reduced vs oxidized forms of glutathione. The above findings suggest that the polyphenolic nature of EGC or EGCG might be responsible for rescuing CES1 activity under oxidative stress. Because of the importance of CES1 in drug activation or deactivation and rat liver S9 as a versatile in vitro system used for drug metabolism studies and drug safety assessment, caution should be exercised to avoid potential biases for data interpretation and decision making when CES1 activity in rat liver S9 is evaluated with dependency on experimental conditions.
ESTHER : Luo_2023_Chem.Biol.Interact__110612
PubMedSearch : Luo_2023_Chem.Biol.Interact__110612
PubMedID: 37353134

Title : Exploring the Inhibition of Quercetin on Acetylcholinesterase by Multispectroscopic and In Silico Approaches and Evaluation of Its Neuroprotective Effects on PC12 Cells - Liao_2022_Molecules_27_
Author(s) : Liao Y , Mai X , Wu X , Hu X , Luo X , Zhang G
Ref : Molecules , 27 : , 2022
Abstract : This study investigated the inhibitory mechanism of quercetin in acetylcholinesterase (AChE) and its neuroprotective effects on beta-amyloid(25-35)-induced oxidative stress injury in PC12 cells. Quercetin inhibited AChE in a reversible mixed manner with an IC(50) of 4.59 +/- 0.27 microM. The binding constant of quercetin with AChE at 25 degreesC was (5.52 +/- 0.05) x 10(4) L mol(-1). Hydrogen bonding and van der Waals forces were the main interactions in forming the stable quercetin-AChE complex. Computational docking revealed that quercetin was dominant at the peripheral aromatic site in AChE and induced enzymatic allosterism; meanwhile, it extended deep into the active center of AChE and destabilized the hydrogen bond network, which caused the constriction of the gorge entrance and prevented the substrate from entering the enzyme, thus resulting in the inhibition of AChE. Molecular dynamics (MD) simulation emphasized the stability of the quercetin-AChE complex and corroborated the previous findings. Interestingly, a combination of galantamine hydrobromide and quercetin exhibited the synergistic inhibition effect by binding to different active sites of AChE. In a beta-amyloid(25-35)-induced oxidative stress injury model in PC12 cells, quercetin exerted neuroprotective effects by increasing the glutathione level and reducing the malondialdehyde content and reactive oxygen species levels. These findings may provide novel insights into the development and application of quercetin in the dietary treatment of Alzheimer's disease.
ESTHER : Liao_2022_Molecules_27_
PubMedSearch : Liao_2022_Molecules_27_
PubMedID: 36432070

Title : Role of Bmal1 in mediating the cholinergic system to regulate the behavioral rhythm of nocturnal marine molluscs - Gao_2022_Comput.Struct.Biotechnol.J_20_2815
Author(s) : Gao X , Zhang M , Lyu M , Lin S , Luo X , You W , Ke C
Ref : Comput Struct Biotechnol J , 20 :2815 , 2022
Abstract : The circadian rhythm is one of the most general and important rhythms in biological organisms. In this study, continuous 24-h video recordings showed that the cumulative movement distance and duration of the abalone, Haliotis discus hannai, reached their maximum values between 20:00-00:00, but both were significantly lower between 08:00-12:00 than at any other time of day or night (P < 0.05). To investigate the causes of these diel differences in abalone movement behavior, their cerebral ganglia were harvested at 00:00 (group D) and 12:00 (group L) to screen for differentially expressed proteins using tandem mass tagging (TMT) quantitative proteomics. Seventy-five significantly different proteins were identified in group D vs. group L. The differences in acetylcholinesterase (AchE) expression levels between day- and nighttime and the key role in the cholinergic nervous system received particular attention during the investigation. A cosine rhythm analysis found that the concentration of acetylcholine (Ach) and the expression levels of AchE tended to be low during the day and high at night, and high during the day and low at night, respectively. However, the rhythmicity of the diel expression levels of acetylcholine receptor (nAchR) appeared to be insignificant (P > 0.05). Following the injection of three different concentrations of neostigmine methylsulfate, as an AchE inhibitor, the concentration of Ach in the hemolymph, and the expression levels of nAchR in the cerebral ganglia increased significantly (P < 0.05). Four hours after drug injection, the cumulative movement distance and duration of abalones were significantly higher than those in the uninjected control group, and the group injected with saline (P < 0.05). The expression levels of the core diurnal clock Bmal1 over a 24-h period also tended to be high during the day and low at night. First, a co-immunoprecipitation assay demonstrated the binding between Bmal1 and AchE or nAchR. A dual-luciferase gene test and electrophoretic mobility shift assay showed that Bmal1 bound to the promoter regions of AchE and nAchR. Twenty-four hours after silencing the Bmal1 gene, the expression levels of AchE and nAchR decreased significantly compared to those of the dsEGFP and PBS control groups, further showing that Bmal1 mediates the cholinergic system to regulate the behavioral rhythm of abalone. These findings shed light on the endocrine mechanism regulating the rhythmic behavior of abalone, and provide a reference for understanding the life history adaptation strategies of nocturnal organisms and the proliferation and protection of bottom dwelling economically important organisms.
ESTHER : Gao_2022_Comput.Struct.Biotechnol.J_20_2815
PubMedSearch : Gao_2022_Comput.Struct.Biotechnol.J_20_2815
PubMedID: 35765646

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

Title : The Aptamer Ob2, a novel AChE inhibitor, restores cognitive deficits and alleviates amyloidogenesis in 5FAD transgenic mice - Liang_2022_Mol.Ther.Nucleic.Acids_28_114
Author(s) : Liang Z , Li X , Luo X , Luo H , Chen Y , Cai M , Zhong X , Fang Y , Guo T , Shi Y , Zhang X
Ref : Mol Ther Nucleic Acids , 28 :114 , 2022
Abstract : Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5xFAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5xFAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5xFAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Abeta by lowering the expression of beta-secretase (BACE1), and activation of astrocytes in the brains of 5xFAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD.
ESTHER : Liang_2022_Mol.Ther.Nucleic.Acids_28_114
PubMedSearch : Liang_2022_Mol.Ther.Nucleic.Acids_28_114
PubMedID: 35402070

Title : Effects of Flavonoid Supplementation on Nanomaterial-Induced Toxicity: A Meta-Analysis of Preclinical Animal Studies - Xie_2022_Front.Nutr_9_929343
Author(s) : Xie D , Hu J , Wu T , Xu W , Meng Q , Cao K , Luo X
Ref : Front Nutr , 9 :929343 , 2022
Abstract : BACKGROUND: Nanomaterials, widely applied in various fields, are reported to have toxic effects on human beings; thus, preventive or therapeutic measures are urgently needed. Given the anti-inflammatory and antioxidant activities, supplementation with flavonoids that are abundant in the human diet has been suggested as a potential strategy to protect against nanomaterial-induced toxicities. However, the beneficial effects of flavonoids remain inconclusive. In the present study, we performed a meta-analysis to comprehensively explore the roles and mechanisms of flavonoids for animals intoxicated with nanomaterials. METHODS: A systematic literature search in PubMed, EMBASE, and Cochrane Library databases was performed up to April 2022. STATA 15.0 software was used for meta-analyses. RESULTS: A total of 26 studies were identified. The results showed that flavonoid supplementation could significantly increase the levels of antioxidative enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione-S-transferase), reduce the production of oxidative agents (malonaldehyde) and pro-inflammatory mediators (tumor necrosis factor-alpha, interleukin-6, IL-1beta, C-reactive protein, immunoglobulin G, nitric oxide, vascular endothelial growth factor, and myeloperoxidase), and alleviate cell apoptosis (manifested by decreases in the mRNA expression levels of pro-apoptotic factors, such as caspase-3, Fas cell surface death receptor, and Bax, and increases in the mRNA expression levels of Bcl2), DNA damage (reductions in tail length and tail DNA%), and nanomaterial-induced injuries of the liver (reduced alanine aminotransferase and aspartate aminotransferase activities), kidney (reduced urea, blood urea nitrogen, creatinine, and uric acid concentration), testis (increased testosterone, sperm motility, 17beta-hydroxysteroid dehydrogenase type, and reduced sperm abnormalities), and brain (enhanced acetylcholinesterase activities). Most of the results were not changed by subgroup analyses. CONCLUSION: Our findings suggest that appropriate supplementation of flavonoids may be effective to prevent the occupational detriments resulting from nanomaterial exposure.
ESTHER : Xie_2022_Front.Nutr_9_929343
PubMedSearch : Xie_2022_Front.Nutr_9_929343
PubMedID: 35774549

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

Title : Iridium Single-Atomic Site Catalysts with Superior Oxygen Reduction Reaction Activity for Sensitive Monitoring of Organophosphorus Pesticides - Luo_2021_Anal.Chem__
Author(s) : Luo X , Luo Z , Wei X , Jiao L , Fang Q , Wang H , Wang J , Gu W , Hu L , Zhu C
Ref : Analytical Chemistry , : , 2021
Abstract : Tremendous efforts have been made in developing single-atomic site catalysts (SASCs) for oxygen reduction reaction (ORR), which is regarded as a pivotal cornerstone in electrochemical energy conversion. However, SASCs for ORR have not been explored for electrochemical sensing. Herein, a template-sacrificed strategy is reported for the synthesis of atomically dispersed Ir SASCs, serving as a sensing platform to detect organophosphorus pesticides (OPs) with high sensitivity and selectivity. Owing to abundant Ir single-atom active sites, Ir SASCs show excellent ORR activity and stability in a neutral medium. It is found that the ORR activity of Ir SASCs can be inhibited by thiocholine, which is the hydrolysate of acetylthiocholine. After being integrated with acetylcholinesterase (AChE), the AChE-Ir SASC-based electrochemical sensor is established and shows a superior sensitivity, which shows a wide detection range of 0.5-500 ng mL(-1) with a low detection limit of 0.17 ng mL(-1) for OPs. This work exhibits a broad application prospect of ORR for sensitive detection of biomolecules.
ESTHER : Luo_2021_Anal.Chem__
PubMedSearch : Luo_2021_Anal.Chem__
PubMedID: 34969242

Title : Bioactive Polyketide and Diketopiperazine Derivatives from the Mangrove-Sediment-Derived Fungus Aspergillus sp. SCSIO41407 - Cai_2021_Molecules_26_
Author(s) : Cai J , Chen C , Tan Y , Chen W , Luo X , Luo L , Yang B , Liu Y , Zhou X
Ref : Molecules , 26 : , 2021
Abstract : Ten polyketide derivatives (1-10), including a new natural product named (E)-2,4-dihydroxy-3-methyl-6-(2-oxopent-3-en-1-yl) benzaldehyde (1), and five known diketopiperazines (11-15), were isolated from the mangrove-sediment-derived fungus Aspergillus sp. SCSIO41407. The structures of 1-15 were determined via NMR and MS spectroscopic analysis. In a variety of bioactivity screening, 3 showed weak cytotoxicity against the A549 cell line, and 2 exhibited weak antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Compounds 3, 5, and 6 showed inhibition against acetylcholinesterase (AChE) with IC(50) values of 23.9, 39.9, and 18.6 microM. Compounds 11, 12, and 14 exhibited obvious inhibitory activities of lipopolysaccharide (LPS)-induced nuclear factor-kappaB (NF-kappaB) with IC(50) values of 19.2, 20.9, and 8.7 microM, and they also suppressed RANKL-induced osteoclast differentiation in bone marrow macrophages cells (BMMCs), with the concentration of 5 microM. In silico molecular docking with AChE and NF-kappaB p65 protein were also performed to understand the inhibitory activities, and 1, 11-14 showed obvious protein/ligand-binding effects to the NF-kappaB p65 protein.
ESTHER : Cai_2021_Molecules_26_
PubMedSearch : Cai_2021_Molecules_26_
PubMedID: 34443439

Title : Biological detoxification of fumonisin by a novel carboxylesterase from Sphingomonadales bacterium and its biochemical characterization - Li_2021_Int.J.Biol.Macromol_169_18
Author(s) : Li Z , Wang Y , Liu Z , Jin S , Pan K , Liu H , Liu T , Li X , Zhang C , Luo X , Song Y , Zhao J , Zhang T
Ref : Int J Biol Macromol , 169 :18 , 2021
Abstract : Fumonisins have posed hazardous threat to human and animal health worldwide. Enzymatic degradation is a desirable detoxification approach but is severely hindered by serious shortage of detoxification enzymes. After mining enzymes by bioinformatics analysis, a novel carboxylesterase FumDSB from Sphingomonadales bacterium was expressed in Escherichia coli, and confirmed to catalyze fumonisin B1 to produce hydrolyzed fumonisin B1 by liquid chromatography mass spectrometry for the first time. FumDSB showed high sequence novelty, sharing only ~34% sequence identity with three reported fumonisin detoxification carboxylesterases. Besides, FumDSB displayed its high degrading activity at 30-40 degreesC within a broad pH range from 6.0 to 9.0, which is perfectly suitable to be used in animal physiological condition. It also exhibited excellent pH stability and moderate thermostability. This study provides a FB1 detoxification carboxylesterase which could be further used as a potential food and feed additive.
ESTHER : Li_2021_Int.J.Biol.Macromol_169_18
PubMedSearch : Li_2021_Int.J.Biol.Macromol_169_18
PubMedID: 33309671
Gene_locus related to this paper: 9sphn-a0a101vlk1

Title : Discovery of novel reversible monoacylglycerol lipase inhibitors via docking-based virtual screening - Xiong_2021_Bioorg.Med.Chem.Lett__127986
Author(s) : Xiong F , Ding X , Zhang H , Luo X , Chen K , Jiang H , Luo C , Xu H
Ref : Bioorganic & Medicinal Chemistry Lett , :127986 , 2021
Abstract : Monoacylglycerol lipase (MAGL) is the major enzyme that catalyzes the hydrolysis of monoacylglycerols (MAGs). MAGL is responsible for degrading 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain and specific tissues. The inhibition of MAGL could attenuate the inflammatory response. Here, we report a series of reversible non-covalent MAGL inhibitors via virtual screening combined with biochemical analysis. The hit, DC630-8 showed low-micromolar activity against MAGL in vitro, and exhibited significant anti-inflammatory effects.
ESTHER : Xiong_2021_Bioorg.Med.Chem.Lett__127986
PubMedSearch : Xiong_2021_Bioorg.Med.Chem.Lett__127986
PubMedID: 33766770
Gene_locus related to this paper: human-MGLL

Title : Non-neuronal Role of Acetylcholinesterase in Bone Development and Degeneration - Luo_2021_Front.Cell.Dev.Biol_8_620543
Author(s) : Luo X , Lauwers M , Layer PG , Wen C
Ref : Front Cell Developmental Biology , 8 :620543 , 2021
Abstract : Acetylcholinesterase (AChE), an enzyme catalyzing the degradation of acetylcholine, plays an important suppressive role in the cholinergic regulation by terminating the action of acetylcholine. The expression of acetylcholinesterase and other cholinergic components is not restricted to only brain and nerve tissues but can also be found in non-neuronal tissues like the immune system and bone tissue. Primary identification of these components has been achieved. However, the information about their specific functions and underlying molecular mechanisms in bone remains scattered. Here, the physiological process of bone development, homeostasis, and degeneration are introduced. Next, the cholinergic system and its expression in bone tissue is documented. Among them, special attention goes to AChE, as the structure of this enzyme suggests diverse binding affinities, enabled by a peripheral site and a catalytic site. The peripheral site supports the non-enzymatic function of AChE in non-neuronal systems. Based on recent studies, the non-neuronal roles of acetylcholinesterase, both enzymatically and non-enzymatically, in bone development, homeostasis and degeneration are summarized briefly together with potential mechanisms to support these functions. We conclude that AChE may be a potential therapeutic target for bone diseases like osteoporosis.
ESTHER : Luo_2021_Front.Cell.Dev.Biol_8_620543
PubMedSearch : Luo_2021_Front.Cell.Dev.Biol_8_620543
PubMedID: 33585459

Title : Visualization of carboxylesterase 2 with a near-infrared two-photon fluorescent probe and potential evaluation of its anticancer drug effects in an orthotopic colon carcinoma mice model - Wang_2020_Chem.Commun.(Camb)_56_4412
Author(s) : Wang Y , Yu F , Luo X , Li M , Zhao L
Ref : Chem Commun (Camb) , 56 :4412 , 2020
Abstract : We establish a near-infrared two-photon fluorescent probe for the detection of CE2 with high selectivity and sensitivity. This probe exhibits low cytotoxicity and superior tissue penetration ability for evaluating the real-time activity of CE2 in living cells, in cancer tissues, and in a colon carcinoma mice model.
ESTHER : Wang_2020_Chem.Commun.(Camb)_56_4412
PubMedSearch : Wang_2020_Chem.Commun.(Camb)_56_4412
PubMedID: 32186556

Title : ABHD5 blunts the sensitivity of colorectal cancer to fluorouracil via promoting autophagic uracil yield - Ou_2019_Nat.Commun_10_1078
Author(s) : Ou J , Peng Y , Yang W , Zhang Y , Hao J , Li F , Chen Y , Zhao Y , Xie X , Wu S , Zha L , Luo X , Xie G , Wang L , Sun W , Zhou Q , Li J , Liang H
Ref : Nat Commun , 10 :1078 , 2019
Abstract : The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy.
ESTHER : Ou_2019_Nat.Commun_10_1078
PubMedSearch : Ou_2019_Nat.Commun_10_1078
PubMedID: 30842415
Gene_locus related to this paper: human-ABHD5

Title : Oncogenic role of ABHD5 in endometrial cancer - Zhou_2019_Cancer.Manag.Res_11_2139
Author(s) : Zhou Q , Wang F , Zhou K , Huang K , Zhu Q , Luo X , Yu J , Shi Z
Ref : Cancer Manag Res , 11 :2139 , 2019
Abstract : Background: Abhydrolase domain containing 5 (ABHD5) functions as a tumor suppressor in colorectal and prostate cancers. The aim of this study was to investigate the roles of ABHD5 in endometrial cancer. Materials and methods: ABHD5 expression was detected in clinical samples by immunohistochemical staining. Cell proliferation and invasion were evaluated with the Cell Counting Kit-8 and Transwell assay, respectively. Western blotting was performed to analyze protein expression. Glucose uptake was assessed by 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose. Lactate production was detected by a lactate assay kit. Results: In the present study, ABHD5 was overexpressed in endometrial cancer tissues, and its expression was closely correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage and lymph node metastasis. In addition, we observed that the knockdown of ABHD5 inhibited cell proliferation, invasion, glucose uptake and lactate production in HEC-1A cells, which expressed high levels of ABHD5. Conversely, the opposite effects were observed when ABHD5 was ectopically expressed in Ishikawa cells, which had low levels of ABHD5. Furthermore, the changes in glycolysis regulators (enolase 1 [ENO1], glucose transporter 1 [GLUT1] and lactate dehydrogenase A [LDHA]) and epithelial-to-mesenchymal transition-related proteins (E-cadherin and Snail) in HEC-1A cells with ABHD5 knockdown were consistent with the effects of ABHD5 on glycolysis and cell invasion. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was increased, while the phosphorylated AKT (p-AKT) was decreased when ABHD5 was downregulated. Notably, treatment with the allosteric AKT inhibitor MK-2206 completely abolished the effects caused by ABHD5 overexpression in Ishikawa cells. Finally, ABHD5 knockdown potently suppressed tumor growth in vivo. Conclusion: Overall, these results suggest that ABHD5 may play an oncogenic role in endometrial cancer via the AKT pathway.
ESTHER : Zhou_2019_Cancer.Manag.Res_11_2139
PubMedSearch : Zhou_2019_Cancer.Manag.Res_11_2139
PubMedID: 30936746
Gene_locus related to this paper: human-ABHD5

Title : Nox4 and soluble epoxide hydrolase synergistically mediate homocysteine-induced inflammation in vascular smooth muscle cells - Liu_2019_Vascul.Pharmacol_120_106544
Author(s) : Liu X , Qin Z , Liu C , Song M , Luo X , Zhao H , Qian D , Chen J , Huang L
Ref : Vascul Pharmacol , 120 :106544 , 2019
Abstract : BACKGROUND: Hyperhomocysteinemia leads to a vascular smooth muscle cell (VSMC) inflammatory response. Meanwhile, Nox4 dependent reactive oxygen species (ROS) signaling and soluble epoxide hydrolase (sEH)/epoxyeicosatrienoic acids (EETs) are both involved in vascular inflammation. Herein, we hypothesized that Nox4 and soluble epoxide hydrolase cross regulated during homocysteine-induced VSMC inflammation. METHODS AND RESULTS: In cultured VSMCs, the expression of the inflammatory factors VCAM1 and ICAM1 was measured by real-time PCR and Western blotting, while supernatant MCP1 was measured by ELISA. Upon VSMC stimulation with 50 muMu homocysteine, we observed the VCAM1 and ICAM1 mRNA levels were increased by 1.15 and 1.0 folds, respectively. The MCP1 levels in the supernatant of cultured VSMCs treated with 100 muMu increased to 1.76 folds. As expected, homocysteine induced Nox4 expression and Nox4-dependent ROS generation. The sEH expression was also upregulated in the presence of homocysteine in a dose-dependent manner. Furthermore, we knocked down Nox4 with siRNA. Knockdown of Nox4 decreased ROS generation and homocysteine-induced sEH expression. Overexpression of Nox4 with an adenovirus stimulated sEH expression. Similarly, knockdown or chemical inhibition of sEH blunted the upregulation of Nox4 by homocysteine. In vivo, in homocysteine-fed mice, concomitant upregulation of Nox4 and sEH was associated with increased VCAM1 and ICAM1 expression in the aortic wall. CONCLUSIONS: The inflammatory response induced by homocysteine in VSMCs was accompanied by Nox4 and sEH upregulation. Nox4 and soluble epoxide hydrolase synergistically contribute to homocysteine-induced inflammation.
ESTHER : Liu_2019_Vascul.Pharmacol_120_106544
PubMedSearch : Liu_2019_Vascul.Pharmacol_120_106544
PubMedID: 30610956

Title : Impact of the Chinese herbal medicines on dual antiplatelet therapy with clopidogrel and aspirin: Pharmacokinetics and pharmacodynamics outcomes and related mechanisms in rats - Xiao_2019_J.Ethnopharmacol_235_100
Author(s) : Xiao M , Qian C , Luo X , Yang M , Zhang Y , Wu C , Mok C , Lee P , Zuo Z
Ref : J Ethnopharmacol , 235 :100 , 2019
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dual antiplatelet therapy (DAPT) with aspirin (ASA) and clopidogrel (CLP) has been consistently shown clinical effectiveness in patients with coronary artery disease. According to the literature, four traditional Chinese medicine (TCM) herbs effective for prevention cardiovascular diseases, namely Radix Salvia Miltiorrhiza (Red sage root, Danshen), Radix Pueraria Lobata (Kudzu root, Gegen), Radix Angelica Sinensis (Angelica root, Danggui), and Rhizoma Ligusticum chuanxiong (Szehuan lovage rhizome, Chuanxiong), are of high potential to be co-administered during DAPT. Since all these herbs are blood vitalizing medicines and can promote blood circulation and eliminate blood stasis, it was hypothesized that they may potentially alter the clinical outcomes of DAPT with clopidogrel and aspirin. AIM OF STUDY: The current study is proposed aiming to preliminarily evaluate the impact of these four commonly used Chinese medicinal herbs on the pharmacokinetics and pharmacodynamics of the combination therapy with clopidogrel and aspirin and its relevant outcomes and mechanisms. MATERIALS AND METHODS: In order to mimic the standard dosing regimen for DAPT in human, various Sprague-Dawley rats treatment groups were received a bolus oral dose of DAPT on day 1 followed by DAPT for consecutive 13 days in absence and presence of orally co-administered four TCM herbs (Danshen, Gegen, Danggui and Chuanxiong) at their low and high doses. On day 14, serial blood samples were collected after dosing to obtain the plasma concentrations of ASA, CLP and their corresponding metabolites by LC/MS/MS. At the end of last blood sampling point of each rat, about 4.5ml of whole blood were collected to estimate the prothrombin time from each treatment groups. After all the blood sampling, the rats were sacrificed followed by collecting their livers for evaluations of enzyme activities and expressions in the related liver microsome preparations and stomach tissues for evaluations of their potential ulcer index. In addition, gene expression and protein levels of related biomarkers (COX-1, COX-2, P2Y12) in rat livers were measured by RT-PCR and Western blot, respectively, and compared among different treatment groups. RESULTS: Co-administration of Gegen and Danggui significantly altered the pharmacokinetics of ASA and CLP in DAPT with increased systemic exposure of ASA and CLP respectively. Although minimal impact on aspirin esterase activity for all co-administered herbs, significant inhibition on rCyp2c11 and carboxylesterase activities were observed for DAPT with Danshen, Gegen and Danggui co-treatment. In addition, significantly longer PT were found in all DAPT treatment groups. However, a trend of decrease in PT of DAPT in presence of Gegen, Danggui and Chuanxiong was noticed. Nevertheless, all the treatments did not cause detectable changes in COX and P2Y12 mRNA and protein expressions. CONCLUSION: Among the four studied TCMs, it was demonstrated that co-administration of Gegen and Danggui could lead to altered pharmacokinetics of DAPT with significant inhibition on rCyp2c11 and carboxylesterase activities. Although Gegen, Danggui and Chuanxiong might potentially offset the anticoagulant activity of DAPT, the overall pharmacodynamics outcome was not considered to be harmful due to lack of risk in bleeding, which warrant further verification for its clinical impact.
ESTHER : Xiao_2019_J.Ethnopharmacol_235_100
PubMedSearch : Xiao_2019_J.Ethnopharmacol_235_100
PubMedID: 30710735

Title : Oxidase-Like Fe-N-C Single-Atom Nanozymes for the Detection of Acetylcholinesterase Activity - Wu_2019_Small__e1903108
Author(s) : Wu Y , Jiao L , Luo X , Xu W , Wei X , Wang H , Yan H , Gu W , Xu BZ , Du D , Lin Y , Zhu C
Ref : Small , :e1903108 , 2019
Abstract : Single-atom catalysts (SACs) have attracted extensive attention in the catalysis field because of their remarkable catalytic activity, gratifying stability, excellent selectivity, and 100% atom utilization. With atomically dispersed metal active sites, Fe-N-C SACs can mimic oxidase by activating O2 into reactive oxygen species, O2 (-) * radicals. Taking advantages of this property, single-atom nanozymes (SAzymes) can become a great impetus to develop novel biosensors. Herein, the performance of Fe-N-C SACs as oxidase-like nanozymes is explored. Besides, the Fe-N-C SAzymes are applied in biosensor areas to evaluate the activity of acetylcholinesterase based on the inhibition toward nanozyme activity by thiols. Moreover, this SAzymes-based biosensor is further used for monitoring the amounts of organophosphorus compounds.
ESTHER : Wu_2019_Small__e1903108
PubMedSearch : Wu_2019_Small__e1903108
PubMedID: 31482681

Title : High expression of NDRG3 associates with unfavorable overall survival in non-small cell lung cancer - Luo_2018_Cancer.Biomark_21_461
Author(s) : Luo X , Hou N , Chen X , Xu Z , Xu J , Wang L , Yang S , Liu S , Xu L , Chen Y , Xiong L , Wang J , Fan W
Ref : Cancer Biomark , 21 :461 , 2018
Abstract : BACKGROUND AND OBJECTIVE: N-myc downstream-regulated gene 3 (NDRG3) is one of the important members of the NDRG family which crucially take part in cell proliferation, differentiation and other biological processes. METHODS: In this present study, western-blotting analysis was performed to evaluate NDRG3 expression in NSCLC cell lines. One-step quantitative reverse transcription-polymerase chain reaction (qPCR) with 16 fresh-frozen NSCLC samples and immunohistochemistry (IHC) analysis in 100 NSCLC cases were conducted to explore the relationship between NDRG3 expression and the clinicopathological characteristics of NSCLC. RESULTS: NDRG3 expression levels were statistically higher in NSCLC cell lines and tissue samples, compared with that of in non-cancerous cell line and tissue samples (p< 0.05). The IHC data demonstrated that the NDRG3 expression was significantly correlated with pathological grade (p= 0.038), N (p= 0.020) and TNM stage (p= 0.002). Survival analysis and Kaplan-Meier curve indicated that NDRG3 expression (p= 0.002) and T (p= 0.047) were independently associated with the unfavorable overall survival of patients with NSCLC. CONCLUSIONS: The data implied that NDRG3 expression may be identified as a new predictor in NSCLC prognosis.
ESTHER : Luo_2018_Cancer.Biomark_21_461
PubMedSearch : Luo_2018_Cancer.Biomark_21_461
PubMedID: 29171988

Title : Resting-State Functional Connectivity of the Basal Nucleus of Meynert in Cigarette Smokers: Dependence Level and Gender Differences - Zhang_2017_Nicotine.Tob.Res_19_452
Author(s) : Zhang S , Hu S , Fucito LM , Luo X , Mazure CM , Zaborszky L , Li CR
Ref : Nicotine Tob Res , 19 :452 , 2017
Abstract : Introduction: Numerous studies have characterized impaired cerebral functioning in nicotine-addicted individuals. Whereas nicotine interacts with multiple neurotransmitters in cortical and subcortical circuits, it directly targets the cholinergic system, sourced primarily from the basal nucleus of Meynert (BNM). However, no studies have examined how this cholinergic system is influenced by cigarette smoking. Here, we addressed this gap of research. Methods: Using a dataset from the Functional Connectome Projects, we investigated this issue by contrasting seed-based BNM connectivity of 40 current smokers and 170 age- and gender-matched nonsmokers. We followed our data analytic routines in recent work and examined differences between smokers and nonsmokers in men and women combined as well as separately. Results: Compared to nonsmokers, female but not male smokers demonstrated greater positive BNM connectivity to the supplementary motor area, bilateral anterior insula, and right superior temporal/supramarginal gyri as well as greater negative connectivity to the posterior cingulate cortex and precuneus. Further, BNM connectivity to the supplementary motor area is negatively correlated to the Fagerstrom Test for Nicotine Dependence score in male but not female smokers. Conclusions: Along with a previous report of upregulated nicotinic acetylcholine receptor in male but not female smokers, these new findings highlight functional changes of the cholinergic systems in cigarette smokers. The results suggest sex-specific differences in cholinergic dysregulation and a need for multiple imaging modalities to capture the neural markers of nicotine addiction. Implications: Nicotine influences cognition via cholinergic projections of the basal forebrain to the cerebral cortex. This study examined changes in resting-state whole-brain functional connectivity of the BNM in cigarette smokers. The new findings elucidate for the first time sex differences in BNM-cerebral connectivity in cigarette smoking.
ESTHER : Zhang_2017_Nicotine.Tob.Res_19_452
PubMedSearch : Zhang_2017_Nicotine.Tob.Res_19_452
PubMedID: 27613921

Title : DNA methylation-associated repression of MEST\/PEG1 expression contributes to the invasion of extravillous trophoblast cells - Peng_2016_Placenta_46_92
Author(s) : Peng W , Chen Y , Luo X , Shan N , Lan X , Olson D , Zhang H , Ding YB , Qi HB
Ref : Placenta , 46 :92 , 2016
Abstract : INTRODUCTION: The invasion of extravillous cytotrophoblasts (EVTs) into the maternal uterine decidua and vasculature is critical for human placenta development and pregnancy maintenance. The imprinted gene MEST/PEG1 has been implicated in trophoblast development; however, the role of MEST in EVT invasion and the accompanying early pregnancy complications are not fully understood. METHODS: Western blot, immunofluorescence and immunohistochemistry were used to detect MEST protein expression and localization by using antibodies recognize 2 reported isoforms. Specific small interference RNA (siRNA) targeting both of the MEST isoforms was applied to silence MEST expression in extravillous explants and HTR8/SVneo cells. Cell invasion and migration were assessed using the Matrigel invasion, Transwell migration assay and the xCELLigence system. Promoter DNA methylation was examined using bisulfite-sequencing polymerase chain reaction (BSP). RESULTS: MEST protein was highly expressed in EVTs in the first trimester placenta and in the invasive EVT cell lines HTR-8/Svneo and HPT-8. Weak MEST expression was found in cytotrophoblasts (CTBs) and the choriocarcinoma-derived CTB cell line JEG-3. The specific siRNA knockdown of MEST expression significantly reduced HTR-8/Svneo cell invasion and migration as well as extravillous explant outgrowth, which were associated with the downregulation of Twist, N-cadherin and Vimentin. Decreased MEST protein expression with isoform 2 promoter hypermethylation was observed in the placentas of missed abortions, suggesting a possible pathological mechanism of missed abortion. CONCLUSIONS: Suppressed expression of MEST was associated with its isoform 2 promoter hypermethylation ex vivo placenta tissues and in vitro cultured EVT cell lines. The present results provide a possible pathological mechanism of missed abortion.
ESTHER : Peng_2016_Placenta_46_92
PubMedSearch : Peng_2016_Placenta_46_92
PubMedID: 27697227

Title : Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models - Wu_2015_Sci.Rep_5_15032
Author(s) : Wu Y , Luo X , Liu X , Liu D , Wang X , Guo Z , Zhu L , Tian Q , Yang X , Wang JZ
Ref : Sci Rep , 5 :15032 , 2015
Abstract : Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models.
ESTHER : Wu_2015_Sci.Rep_5_15032
PubMedSearch : Wu_2015_Sci.Rep_5_15032
PubMedID: 26463268

Title : Plant Esterase-Chitosan\/Gold Nanoparticles-Graphene Nanosheet Composite-Based Biosensor for the Ultrasensitive Detection of Organophosphate Pesticides - Bao_2015_J.Agric.Food.Chem_63_10319
Author(s) : Bao J , Hou C , Chen M , Li J , Huo D , Yang M , Luo X , Lei Y
Ref : Journal of Agricultural and Food Chemistry , 63 :10319 , 2015
Abstract : As broad-spectrum pesticides, organophosphates (OPs) are widely used in agriculture all over the world. However, due to their neurotoxicity in humans and their increasing occurrence in the environment, there is growing interest in their sensitive and selective detection. This paper reports a new cost-effective plant esterase-chitosan/gold nanoparticles-graphene nanosheet (PLaE-CS/AuNPs-GNs) biosensor for the sensitive detection of methyl parathion and malathion. Highly pure plant esterase is produced from plants at low cost and shares the same inhibition mechanism with OPs as acetylcholinesterase, and then it was used to prepare PLaE-CS/AuNPs-GNs nanocomposites, which were systematically characterized using SEM, TEM, and UV-vis. The PLaE-CS/AuNPs-GNs composite-based biosensor measured as low as 50 ppt (0.19 nM) of methyl parathion and 0.5 ppb (1.51 nM) of malathion (S/N = 3) with a calibration curve up to 200 ppb (760 nM) and 500 ppb (1513.5 nM) for methyl parathion and malathion, respectively. There is also no interference observed from most of common species such as metal ions, inorganic ions, glucose, and citric acid. In addition, its applicability to OPs-contaminated real samples (carrot and apple) was also demonstrated with excellent response recovery. The developed simple, sensitive, and reliable PLaE-CS/AuNPs-GNs composite-based biosensor holds great potential in OPs detection for food and environmental safety.
ESTHER : Bao_2015_J.Agric.Food.Chem_63_10319
PubMedSearch : Bao_2015_J.Agric.Food.Chem_63_10319
PubMedID: 26554573

Title : Exosomes are unlikely involved in intercellular nef transfer - Luo_2015_PLoS.One_10_e0124436
Author(s) : Luo X , Fan Y , Park IW , He JJ
Ref : PLoS ONE , 10 :e0124436 , 2015
Abstract : HIV-1 Nef is an important pathogenic factor for HIV/AIDS pathogenesis. Several recent studies including ours have demonstrated that Nef can be transferred to neighboring cells and alters the function of these cells. However, how the intercellular Nef transfer occurs is in dispute. In the current study, we attempted to address this important issue using several complementary strategies, a panel of exosomal markers, and human CD4+ T lymphocyte cell line Jurkat and a commonly used cell line 293T. First, we showed that Nef was transferred from Nef-expressing or HIV-infected Jurkat to naive Jurkat and other non-Jurkat cells and that the transfer required the membrane targeting function of Nef and was cell density-dependent. Then, we showed that Nef transfer was cell-cell contact-dependent, as exposure to culture supernatants or exosomes from HIV-infected Jurkat or Nef-expressing Jurkat and 293T led to little Nef detection in the target cells Jurkat. Thirdly, we demonstrated that Nef was only detected to be associated with HIV virions but not with acetylcholinesterase (AChE+) exosomes from HIV-infected Jurkat and not in the exosomes from Nef-expressing Jurkat. In comparison, when it was over-expressed in 293T, Nef was detected in detergent-insoluble AChE+/CD81low/TSG101low exosomes, but not in detergent-soluble AChE-/CD81high/TSG101high exosomes. Lastly, microscopic imaging showed no significant Nef detection in exosomal vesicle-like structures in and out 293T. Taken together, these results show that exosomes are unlikely involved in intercellular Nef transfer. In addition, this study reveals existence of two types of exosomes: AChE+/CD81low/TSG101low exosomes and AChE-/CD81high/TSG101high exosomes.
ESTHER : Luo_2015_PLoS.One_10_e0124436
PubMedSearch : Luo_2015_PLoS.One_10_e0124436
PubMedID: 25919665

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 : The genomes of four tapeworm species reveal adaptations to parasitism - Tsai_2013_Nature_496_57
Author(s) : Tsai IJ , Zarowiecki M , Holroyd N , Garciarrubio A , Sanchez-Flores A , Brooks KL , Tracey A , Bobes RJ , Fragoso G , Sciutto E , Aslett M , Beasley H , Bennett HM , Cai J , Camicia F , Clark R , Cucher M , De Silva N , Day TA , Deplazes P , Estrada K , Fernandez C , Holland PW , Hou J , Hu S , Huckvale T , Hung SS , Kamenetzky L , Keane JA , Kiss F , Koziol U , Lambert O , Liu K , Luo X , Luo Y , Macchiaroli N , Nichol S , Paps J , Parkinson J , Pouchkina-Stantcheva N , Riddiford N , Rosenzvit M , Salinas G , Wasmuth JD , Zamanian M , Zheng Y , Cai X , Soberon X , Olson PD , Laclette JP , Brehm K , Berriman M
Ref : Nature , 496 :57 , 2013
Abstract : Tapeworms (Cestoda) cause neglected diseases that can be fatal and are difficult to treat, owing to inefficient drugs. Here we present an analysis of tapeworm genome sequences using the human-infective species Echinococcus multilocularis, E. granulosus, Taenia solium and the laboratory model Hymenolepis microstoma as examples. The 115- to 141-megabase genomes offer insights into the evolution of parasitism. Synteny is maintained with distantly related blood flukes but we find extreme losses of genes and pathways that are ubiquitous in other animals, including 34 homeobox families and several determinants of stem cell fate. Tapeworms have specialized detoxification pathways, metabolism that is finely tuned to rely on nutrients scavenged from their hosts, and species-specific expansions of non-canonical heat shock proteins and families of known antigens. We identify new potential drug targets, including some on which existing pharmaceuticals may act. The genomes provide a rich resource to underpin the development of urgently needed treatments and control.
ESTHER : Tsai_2013_Nature_496_57
PubMedSearch : Tsai_2013_Nature_496_57
PubMedID: 23485966
Gene_locus related to this paper: echgr-k4epc5 , hymmi-a0a068x9f5 , echmu-u6hbw4 , echgr-w6ugl0 , echmu-u6hr32 , echmu-a0a068y5f4 , hymmi-a0a068xag4 , hymmi-a0a068x810 , hymmi-a0a068xcc1 , echmu-a0a068yf54 , echgr-a0a068wxj3 , echgr-a0a068wgw1 , hymmi-a0a068xge7 , hymmi-a0a068x8h9 , echmu-a0a068y747 , hymmi-a0a068xgj7 , echgr-a0a068wl60

Title : Potential tumor-suppressive role of monoglyceride lipase in human colorectal cancer - Sun_2013_Oncogene_32_234
Author(s) : Sun H , Jiang L , Luo X , Jin W , He Q , An J , Lui K , Shi J , Rong R , Su W , Lucchesi C , Liu Y , Sheikh MS , Huang Y
Ref : Oncogene , 32 :234 , 2013
Abstract : Human monoglyceride lipase (MGL) is a recently identified lipase and very little is known about its regulation and function in cellular regulatory processes, particularly in context to human malignancy. In this study, we investigated the regulation and function of MGL in human cancer(s) and report that MGL expression was either absent or reduced in the majority of primary colorectal cancers. Immunohistochemical studies showed that reduction of MGL expression in the colorectal tumor tissues predominantly occurred in the cancerous epithelial cells. MGL was found to reside in the core surface of a cellular organelle named 'lipid body'. Furthermore, it was found to interact selectively with a number of phospholipids, including phosphatidic acid and phosphoinositol(3,4,5)P3, phosphoinositol(3,5)P2, phosphoinositol(3,4)P2 and several other phosphoinositides, and among all phosphoinositides analyzed, its interaction with PI(3,4,5)P3 was found to be the strongest. In addition, overexpression of MGL suppressed colony formation in tumor cell lines and knockdown of MGL resulted in increased Akt phosphorylation. Taken together, our results suggest that MGL plays a negative regulatory role in phosphatidylinositol-3 kinase/Akt signaling and tumor cell growth.
ESTHER : Sun_2013_Oncogene_32_234
PubMedSearch : Sun_2013_Oncogene_32_234
PubMedID: 22349814

Title : A novel Escherichia coli O157:H7 clone causing a major hemolytic uremic syndrome outbreak in China - Xiong_2012_PLoS.One_7_e36144
Author(s) : Xiong Y , Wang P , Lan R , Ye C , Wang H , Ren J , Jing H , Wang Y , Zhou Z , Bai X , Cui Z , Luo X , Zhao A , Zhang S , Sun H , Wang L , Xu J
Ref : PLoS ONE , 7 :e36144 , 2012
Abstract : An Escherichia coli O157:H7 outbreak in China in 1999 caused 177 deaths due to hemolytic uremic syndrome. Sixteen outbreak associated isolates were found to belong to a new clone, sequence type 96 (ST96), based on multilocus sequence typing of 15 housekeeping genes. Whole genome sequencing of an outbreak isolate, Xuzhou21, showed that the isolate is phylogenetically closely related to the Japan 1996 outbreak isolate Sakai, both of which share the most recent common ancestor with the US outbreak isolate EDL933. The levels of IL-6 and IL-8 of peripheral blood mononuclear cells induced by Xuzhou21 and Sakai were significantly higher than that induced by EDL933. Xuzhou21 also induced a significantly higher level of IL-8 than Sakai while both induced similar levels of IL-6. The expression level of Shiga toxin 2 in Xuzhou21 induced by mitomycin C was 68.6 times of that under non-inducing conditions, twice of that induced in Sakai (32.7 times) and 15 times higher than that induced in EDL933 (4.5 times). Our study shows that ST96 is a novel clone and provided significant new insights into the evolution of virulence of E. coli O157:H7.
ESTHER : Xiong_2012_PLoS.One_7_e36144
PubMedSearch : Xiong_2012_PLoS.One_7_e36144
PubMedID: 22558360
Gene_locus related to this paper: ecoli-ycfp , ecoli-YFBB , ecoli-yqia , ecoli-Z1341

Title : Emergence of a new multidrug-resistant serotype X variant in an epidemic clone of Shigella flexneri - Ye_2010_J.Clin.Microbiol_48_419
Author(s) : Ye C , Lan R , Xia S , Zhang J , Sun Q , Zhang S , Jing H , Wang L , Li Z , Zhou Z , Zhao A , Cui Z , Cao J , Jin D , Huang L , Wang Y , Luo X , Bai X , Wang P , Xu Q , Xu J
Ref : J Clin Microbiol , 48 :419 , 2010
Abstract : Shigella spp. are the causative agent of shigellosis with Shigella flexneri serotype 2a being the most prevalent in developing countries. Epidemiological surveillance in China found that a new serotype of S. flexneri appeared in 2001 and replaced serotype 2a in 2003 as the most prevalent serotype in Henan Province. The new serotype also became the dominant serotype in 7 of the 10 other provinces under surveillance in China by 2007. The serotype was identified as a variant of serotype X. It differs from serotype X by agglutination to the monovalent anti-IV type antiserum and the group antigen-specific monoclonal antibody MASF IV-I. Genome sequencing of a serotype X variant isolate, 2002017, showed that it acquired a Shigella serotype conversion island, also as an SfX bacteriophage, containing gtr genes for type X-specific glucosylation. Multilocus sequence typing of 15 genes from 37 serotype X variant isolates and 69 isolates of eight other serotypes, 1a, 2a, 2b, 3a, 4a, 5b, X, and Y, found that all belong to a new sequence type (ST), ST91. Pulsed-field gel electrophoresis revealed 154 pulse types with 655 S. flexneri isolates analyzed and identified 57 serotype switching events. The data suggest that S. flexneri epidemics in China have been caused by a single epidemic clone, ST91, with frequent serotype switching to evade infection-induced immunity to serotypes to which the population was exposed previously. The clone has also acquired resistance to multiple antibiotics. These findings underscore the challenges to the current vaccine development and control strategies for shigellosis.
ESTHER : Ye_2010_J.Clin.Microbiol_48_419
PubMedSearch : Ye_2010_J.Clin.Microbiol_48_419
PubMedID: 19955273
Gene_locus related to this paper: shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-S2753 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-ycfp , shifl-YFBB , shifl-YHET , shifl-YJFP , shifl-YPFH , shiss-yqia

Title : Clinical, experimental, and genomic differences between intermediately pathogenic, highly pathogenic, and epidemic Streptococcus suis - Ye_2009_J.Infect.Dis_199_97
Author(s) : Ye C , Zheng H , Zhang J , Jing H , Wang L , Xiong Y , Wang W , Zhou Z , Sun Q , Luo X , Du H , Gottschalk M , Xu J
Ref : J Infect Dis , 199 :97 , 2009
Abstract : BACKGROUND: Streptococcus suis emerged to cause an unusual outbreak of streptococcal toxic-shock-like syndrome (STSLS) in 2005. The mechanisms involved are unknown. METHODS: Clinical, laboratory, and epidemiologic data on patients infected with culture-confirmed S. suis were analyzed. The strain involved in the outbreak, "epidemic" strain ST7, was compared with both a classical highly pathogenic strain, ST1, and an intermediately pathogenic strain, ST25, to determine both its capacity to induce cytokines in experimentally infected mice and its genomic difference. RESULTS: Of 38 patients infected with culture-confirmed S. suis, 14 presented with STSLS. During the early phase of the disease, serum levels of interleukin (IL)-1beta, IL-6, IL-8, IL-12p70, interferon-gamma, and tumor necrosis factor-alpha were more elevated in patients with STSLS than in those with meningitis only. Serum levels of proinflammatory cytokines were significantly higher in mice infected with ST7 than in those infected with either ST1 or ST25. Genomic comparisons with ST25 showed that ST1 had acquired 132 genomic islands, including 5 pathogenicity islands, and that ST7, the epidemic strain, had acquired an additional 5 genomic islands. CONCLUSION: Intermediately pathogenic strain ST25 has evolved to become highly pathogenic strain ST1, which, in turn, has more recently evolved to become epidemic strain ST7. ST7 has the ability to stimulate the production of massive amounts of proinflammatory cytokines, leading to STSLS.
ESTHER : Ye_2009_J.Infect.Dis_199_97
PubMedSearch : Ye_2009_J.Infect.Dis_199_97
PubMedID: 19016627
Gene_locus related to this paper: strsu-a4vws4 , strsu-q673u2 , strsy-a4vus4

Title : Sequence variation and molecular evolution of hormone-sensitive lipase genes in species of bovidae - Ma_2007_J.Genet.Genomics_34_26
Author(s) : Ma Z , Zhong J , Cheng Z , Liu L , Chang H , Luo X
Ref : J Genet Genomics , 34 :26 , 2007
Abstract : The partial sequences of exon I of hormone-sensitive lipase (HSL) genes in yak (Bos grunniens), cattle (Bos taurus), zebu (Bos indicus), and buffalo (Bubalus bubalis) were analyzed. Comparisons of these sequences and the deduced amino acid sequences with the homologous HSL gene and protein sequences in other mammalian species including pig (Sus scrofa), human (Homo sapiens), mouse (Mus musculus), and rat (Rattus sp.) retrieved from the GenBank were carried out and finally a phylogenetic tree was constructed using the partial DNA sequences of the HSL genes in all species. The results showed that the homologies of the partial exon I sequences of the HSL genes between yak and cattle, zebu, buffalo, pig, human, mouse, and rat were as high as 99.8%, 99.6%, 97.4%, 90.6%, 88.4%, 83.5%, and 82.3%, respectively. This was accompanied by highly homologous amino acid sequences of the HSLs: 100%, 100%, 98.2%, 94.0%, 92.2%, 89.8%, and 89.8% identity, respectively. There are more transitions, less transversions, and no insertion or deletion in variable nucleotides of the HSL genes between the yak and other species. The majority of the variable mutations was synonymous and was found most frequently at the third codon, followed by the first and second codons, a finding that was in accordance with the neutralism hypothesis for molecular evolution. In the phylogenetic tree, the cattle and zebu were clustered together first, followed by the yak, buffalo, pig, human, mouse, and rat. This was in agreement with taxonomy suggesting that the partial sequences of exon I of the HSL genes were useful in constructing the phylogenetic tree of mammalian species. Among the four species of Bovidae, genetic differentiation in the HSL genes between yak and buffalo is equivalent to that between buffalo and cattle and between buffalo and zebu. Furthermore, the genetic distances in the HSL genes are much smaller between yak, cattle, and zebu than those between each of the three species and the buffalo. Therefore, it is reasonable to consider yak as an independent species of the genus Bos.
ESTHER : Ma_2007_J.Genet.Genomics_34_26
PubMedSearch : Ma_2007_J.Genet.Genomics_34_26
PubMedID: 17469775

Title : Dynamic mechanism of E2020 binding to acetylcholinesterase: a steered molecular dynamics simulation - Niu_2005_J.Phys.Chem.B_109_23730
Author(s) : Niu C , Xu Y , Luo X , Duan W , Silman I , Sussman JL , Zhu W , Chen K , Shen J , Jiang H
Ref : J Phys Chem B , 109 :23730 , 2005
Abstract : The unbinding process of E2020 ((R,S)-1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methylpiperidine) leaving from the long active site gorge of Torpedo californica acetylcholinesterase (TcAChE) was studied by using steered molecular dynamics (SMD) simulations on a nanosecond scale with different velocities, and unbinding force profiles were obtained. Different from the unbinding of other AChE inhibitors, such as Huperzine A that undergoes the greatest barrier located at the bottleneck of the gorge, the major resistance preventing E2020 from leaving the gorge is from the peripheral anionic site where E2020 interacts intensively with several aromatic residues (e.g., Tyr70, Tyr121, and Trp279) through its benzene ring and forms a strong direct hydrogen bond and a water bridge with Ser286 via its O24. These interactions cause the largest rupture force, approximately 550 pN. It was found that the rotatable bonds of the piperidine ring to the benzene ring and dimethoxyindanone facilitate E2020 to pass the bottleneck through continuous conformation change by rotating those bonds to avoid serious conflict with Tyr121 and Phe330. The aromatic residues lining the gorge wall are the major components contributing to hydrophobic interactions between E2020 and TcAChE. Remarkably, these aromatic residues, acting in three groups as "sender" and "receiver", compose a "conveyer belt" for E2020 entering and leaving the TcAChE gorge.
ESTHER : Niu_2005_J.Phys.Chem.B_109_23730
PubMedSearch : Niu_2005_J.Phys.Chem.B_109_23730
PubMedID: 16375354

Title : Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional chinese medicine origin for the treatment of Alzheimer's disease - Jiang_2003_Curr.Med.Chem_10_2231
Author(s) : Jiang H , Luo X , Bai D
Ref : Curr Med Chem , 10 :2231 , 2003
Abstract : HupA is a potent, reversible AChEI, which crosses the blood-brain barrier smoothly, and shows high specificity for AChE with a prolonged biological half-life. It has been approved as the drug for the treatment of AD in China, and marketed in USA as a dietary supplement. HupA has been the subject of investigations by an ever-increasing number of researchers since 1980's. In the last four years, HupA has been further studied in many aspects such as the chemical synthesis, structural modification, structure-activity relationship, various biological effects, and mechanisms of action. A number of papers dealing with the computational modeling and X-ray crystallographic studies of HupA-AChE complex have also been published. This review represents a comprehensive documentation of the progress in the studies on HupA during the period of 1999-2002.
ESTHER : Jiang_2003_Curr.Med.Chem_10_2231
PubMedSearch : Jiang_2003_Curr.Med.Chem_10_2231
PubMedID: 14529340

Title : How does huperzine A enter and leave the binding gorge of acetylcholinesterase? Steered molecular dynamics simulations - Xu_2003_J.Am.Chem.Soc_125_11340
Author(s) : Xu Y , Shen J , Luo X , Silman I , Sussman JL , Chen K , Jiang H
Ref : Journal of the American Chemical Society , 125 :11340 , 2003
Abstract : The entering and leaving processes of Huperzine A (HupA) binding with the long active-site gorge of Torpedo californica acetylcholinesterase (TcAChE) have been investigated by using steered molecular dynamics simulations. The analysis of the force required along the pathway shows that it is easier for HupA to bind to the active site of AChE than to disassociate from it, which for the first time interprets at the atomic level the previous experimental result that unbinding process of HupA is much slower than its binding process to AChE. The direct hydrogen bonds, water bridges, and hydrophobic interactions were analyzed during two steered molecular dynamics (SMD) simulations. Break of the direct hydrogen bond needs a great pulling force. The steric hindrance of bottleneck might be the most important factor to produce the maximal rupture force for HupA to leave the binding site but it has a little effect on the binding process of HupA with AChE. Residue Asp72 forms a lot of water bridges with HupA leaving and entering the AChE binding gorge, acting as a clamp to take out HupA from or put HupA into the active site. The flip of the peptide bond between Gly117 and Gly118 has been detected during both the conventional MD and SMD simulations. The simulation results indicate that this flip phenomenon could be an intrinsic property of AChE and the Gly117-Gly118 peptide bond in both HupA bound and unbound AChE structures tends to adopt the native enzyme structure. At last, in a vacuum the rupture force is increased up to 1500 pN while in water solution the greatest rupture force is about 800 pN, which means water molecules in the binding gorge act as lubricant to facilitate HupA entering or leaving the binding gorge.
ESTHER : Xu_2003_J.Am.Chem.Soc_125_11340
PubMedSearch : Xu_2003_J.Am.Chem.Soc_125_11340
PubMedID: 16220957

Title : Synthesis and docking studies of alkylene-linked dimers of (-)-huperzine A - Jin_2003_Arzneimittelforschung_53_753
Author(s) : Jin G , Luo X , He X , Jiang H , Zhang H , Bai D
Ref : Arzneimittelforschung , 53 :753 , 2003
Abstract : (-)-Huperzine A (5, HupA), an alkaloid isolated from the herb Huperzia serrata, is a potent, selective and reversible acetylcholinesterase (AchE) inhibitor. Based on the hypothesis with respect to two binding sites in the active gorge of AChE and the good example of bis-tacrine, it was predicted from the docking studies of alkylene-linked dimers of HupA that dimers 6 (n = 5, 7, 9) might have good AChE inhibitory activity. Therefore, six dimers with 7-12 methylene units as tethers were thus prepared. It was found that these dimers were less potent than HupA in inhibition of AChE. The difference of the inhibitory potency between these dimers is coincident with the results of the docking studies.
ESTHER : Jin_2003_Arzneimittelforschung_53_753
PubMedSearch : Jin_2003_Arzneimittelforschung_53_753
PubMedID: 14677369

Title : The actin-driven movement and formation of acetylcholine receptor clusters - Dai_2000_J.Cell.Biol_150_1321
Author(s) : Dai Z , Luo X , Xie H , Peng HB
Ref : Journal of Cell Biology , 150 :1321 , 2000
Abstract : A new method was devised to visualize actin polymerization induced by postsynaptic differentiation signals in cultured muscle cells. This entails masking myofibrillar filamentous (F)-actin with jasplakinolide, a cell-permeant F-actin-binding toxin, before synaptogenic stimulation, and then probing new actin assembly with fluorescent phalloidin. With this procedure, actin polymerization associated with newly induced acetylcholine receptor (AChR) clustering by heparin-binding growth-associated molecule-coated beads and by agrin was observed. The beads induced local F-actin assembly that colocalized with AChR clusters at bead-muscle contacts, whereas both the actin cytoskeleton and AChR clusters induced by bath agrin application were diffuse. By expressing a green fluorescent protein-coupled version of cortactin, a protein that binds to active F-actin, the dynamic nature of the actin cytoskeleton associated with new AChR clusters was revealed. In fact, the motive force generated by actin polymerization propelled the entire bead-induced AChR cluster with its attached bead to move in the plane of the membrane. In addition, actin polymerization is also necessary for the formation of both bead and agrin-induced AChR clusters as well as phosphotyrosine accumulation, as shown by their blockage by latrunculin A, a toxin that sequesters globular (G)-actin and prevents F-actin assembly. These results show that actin polymerization induced by synaptogenic signals is necessary for the movement and formation of AChR clusters and implicate a role of F-actin as a postsynaptic scaffold for the assembly of structural and signaling molecules in neuromuscular junction formation.
ESTHER : Dai_2000_J.Cell.Biol_150_1321
PubMedSearch : Dai_2000_J.Cell.Biol_150_1321
PubMedID: 10995438