Liu M

References (82)

Title : Improved lipase performance by covalent immobilization of Candida antarctica lipase B on amino acid modified microcrystalline cellulose as green renewable support - Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
Author(s) : Li J , Shi X , Qin X , Liu M , Wang Q , Zhong J
Ref : Colloids Surf B Biointerfaces , 235 :113764 , 2024
Abstract : Development of immobilized lipase with excellent catalytic performance and low cost is the major challenge for large-scale industrial applications. In this study, green renewable microcrystalline cellulose (MCC) that was hydrophobically modified with D-alanine (Ala) or L-lysine (Lys) was used for immobilizing Candida antarctica lipase B (CALB). The improved catalytic properties were investigated by experimental and computational methods. CALB immobilized on MCC-Ala with higher hydrophobicity showed better catalytic activity than CALB@MCC-Lys because the increased flexibility of the lid region of CALB@MCC-Ala favored the formation of open conformation. Additionally, the low root mean square deviation and the high beta-sheet and alpha-helix contents of CALB@MCC-Ala indicated that the structure became more stable, leading to a significantly enhanced stability (54.80% and 90.90% relative activity at 70 degreesC and pH 9.0, respectively) and good reusability (48.92% activity after 5 cycles). This study provides a promising avenue to develop immobilized lipase with high catalytic properties for industry applications.
ESTHER : Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
PubMedSearch : Li_2024_Colloids.Surf.B.Biointerfaces_235_113764
PubMedID: 38301428

Title : Bifunctional enzyme-mimicking metal-organic frameworks for sensitive acetylcholine analysis - Wen_2024_Talanta_275_126112
Author(s) : Wen Y , Xu W , Wu Y , Tang Y , Liu M , Sha M , Li J , Xiao R , Hu L , Lin Y , Zhu C , Gu W
Ref : Talanta , 275 :126112 , 2024
Abstract : The development of nanomaterials with multi-enzyme-like activity is crucial for addressing challenges in multi-enzyme-based biosensing systems, including cross-talk between different enzymes and the complexities and costs associated with detection. In this study, Pt nanoparticles (Pt NPs) were successfully supported on a Zr-based metal-organic framework (MOF-808) to create a composite catalyst named MOF-808/Pt NPs. This composite catalyst effectively mimics the functions of acetylcholinesterase (AChE) and peroxidase (POD). Leveraging this capability, we replaced AChE and POD with MOF-808/Pt NPs and constructed a biosensor for sensitive detection of acetylcholine (ACh). The MOF-808/Pt NPs catalyze the hydrolysis of ACh, resulting in the production of acetic acid. The subsequent reduction in pH value further enhances the POD-like activity of the MOFs, enabling signal amplification through the oxidation of a colorimetric substrate. This biosensor capitalizes on pH variations during the reaction to modulate the different enzyme-like activities of the MOFs, simplifying the detection process and eliminating cross-talk between different enzymes. The developed biosensor holds great promise for clinical diagnostic analysis and offers significant application value in the field.
ESTHER : Wen_2024_Talanta_275_126112
PubMedSearch : Wen_2024_Talanta_275_126112
PubMedID: 38677169

Title : Design, synthesis, and evaluation of a carboxylesterase detection probe with therapeutic effects - Lin_2024_Talanta_274_126060
Author(s) : Lin X , Liu M , Yi Q , Zhou Y , Su J , Qing B , Lu Y , Pu C , Lan W , Zou L , Wang J
Ref : Talanta , 274 :126060 , 2024
Abstract : In this study, a lysosomal targeting fluorescent probe recognition on CEs was designed and synthesized. The obtained probe BF(2)-cur-Mor demonstrated excellent selectivity, sensitivity, pH-independence, and enzyme affinity towards CEs within 5 min. BF(2)-cur-Mor could enable recognition of intracellular CEs and elucidate that the CEs content of different cancer cells follows the rule of HepG2 > HCT-116 > A549 > HeLa, and the CEs expression level of hepatoma cancer cells far exceeds that of normal hepatic cells, being in good agreement with the previous reports. The ability of BF(2)-cur-Mor to monitor CEs in vivo was confirmed by zebrafish experiment. BF(2)-cur-Mor exhibits some pharmacological activity in that it can induce apoptosis in hepatocellular carcinoma cells but is weaker in normal hepatocyte cells, being expected to be a potential "diagnostic and therapeutic integration" tool for the clinical diagnosis of CEs-related diseases.
ESTHER : Lin_2024_Talanta_274_126060
PubMedSearch : Lin_2024_Talanta_274_126060
PubMedID: 38604044

Title : The Role of PNPLA3_rs738409 Gene Variant, Lifestyle Factors, and Bioactive Compounds in Nonalcoholic Fatty Liver Disease: A Population-Based and Molecular Approach towards Healthy Nutrition - Liu_2024_Nutrients_16_
Author(s) : Liu M , Park S
Ref : Nutrients , 16 : , 2024
Abstract : This study aimed to investigate the impact of a common non-synonymous gene variant (C>G, rs738409) in patatin-like phospholipase domain-containing 3 (PNPLA3), leading to the substitution of isoleucine with methionine at position 148 (PNPLA3-I148M), on susceptibility to nonalcoholic fatty liver disease (NAFLD) and explore potential therapeutic nutritional strategies targeting PNPLA3. It contributed to understanding sustainable dietary practices for managing NAFLD, recently referred to as metabolic-dysfunction-associated fatty liver. NAFLD had been diagnosed by ultrasound in a metropolitan hospital-based cohort comprising 58,701 middle-aged and older Korean individuals, identifying 2089 NAFLD patients. The interaction between PNPLA3 and lifestyle factors was investigated. In silico analyses, including virtual screening, molecular docking, and molecular dynamics simulations, were conducted to identify bioactive compounds from foods targeting PNPLA3(I148M). Subsequent cellular experiments involved treating oleic acid (OA)-exposed HepG2 cells with selected bioactive compounds, both in the absence and presence of compound C (AMPK inhibitor), targeting PNPLA3 expression. Carriers of the risk allele PNPLA3_rs738409G showed an increased association with NAFLD risk, particularly with adherence to a plant-based diet, avoidance of a Western-style diet, and smoking. Delphinidin 3-caffeoyl-glucoside, pyranocyanin A, delta-viniferin, kaempferol-7-glucoside, and petunidin 3-rutinoside emerged as potential binders to the active site residues of PNPLA3, exhibiting a reduction in binding energy. These compounds demonstrated a dose-dependent reduction in intracellular triglyceride and lipid peroxide levels in HepG2 cells, while pretreatment with compound C showed the opposite trend. Kaempferol-7-glucoside and petunidin-3-rutinoside showed potential as inhibitors of PNPLA3 expression by enhancing AMPK activity, ultimately reducing intrahepatic lipogenesis. In conclusion, there is potential for plant-based diets and specific bioactive compounds to promote sustainable dietary practices to mitigate NAFLD risk, especially in individuals with genetic predispositions.
ESTHER : Liu_2024_Nutrients_16_
PubMedSearch : Liu_2024_Nutrients_16_
PubMedID: 38674929

Title : Dextran-assisted ultrasonic exfoliation of two-dimensional metal-organic frameworks to evaluate acetylcholinesterase activity and inhibitor screening - Wang_2023_Anal.Chim.Acta_1243_340815
Author(s) : Wang F , Liu M , Niu X , Xia L , Qu F
Ref : Anal Chim Acta , 1243 :340815 , 2023
Abstract : Acetylcholinesterase (AChE) is regarded as a biomarker of Alzheimer's disease (AD), and its inhibitors show great potential in AD therapy as AChE can increase the neurotoxicity of the amyloid component that induces AD. Because of this, it is crucial and significant to develop a simple and highly sensitive strategy to monitor AChE levels and screen highly efficient AChE inhibitors. Herein, we synthesize an ultrathin two-dimensional (2D) metal-organic framework (MOF) based on copper-catecholate (Cu-CAT) via dextran assisted ultrasound exfoliation, followed by construction of a sensitive sensor for the monitoring AChE and screening of its inhibitors. By adding AChE, the acetylthiocholine (ATCh) substrate is hydrolyzed to be thiocholine (TCh), which decreases the peroxidase-like activity of Cu-CAT nanosheets (Cu-CAT NSs), impairing the signal reaction of 3,3',5,5'-tetramethylbenzidine (TMB) to oxidized-TMB (ox-TMB). In the presence of an AChE inhibitor, the signal can be gradually restored. The newly developed sensor shows high sensitivity and selectivity for AChE and huperzine A (HA, an effective drug for AD, an acetylcholine receptor antagonist), as well as for AD drug discovery from traditional Chinese herbs. The limit of detection of the sensor for AChE is 0.01 mU mL(-1) and the average IC(50) value of HA is 30.81 nM under the optimal of catalysis conditions. Compared with the 3D bulk Cu-CAT, the current 2D Cu-CAT NSs exhibit higher peroxidase activity due to more catalytic active site exposure. This study provides a strategy to prepare an ultrathin 2D MOF with high catalytic activity and new insights for the construction of a biosensor to monitor AChE and new AD drugs.
ESTHER : Wang_2023_Anal.Chim.Acta_1243_340815
PubMedSearch : Wang_2023_Anal.Chim.Acta_1243_340815
PubMedID: 36697184

Title : Co-Immobilization of Lipases with Different Specificities for Efficient and Recyclable Biodiesel Production from Waste Oils: Optimization Using Response Surface Methodology - Wang_2023_Int.J.Mol.Sci_24_4726
Author(s) : Wang Q , Zhang R , Liu M , Ma L , Zhang W
Ref : Int J Mol Sci , 24 :4726 , 2023
Abstract : Lipase-catalyzed transesterification is a promising and sustainable approach to producing biodiesel. To achieve highly efficient conversion of heterogeneous oils, combining the specificities and advantages of different lipases is an attractive strategy. To this end, highly active Thermomyces lanuginosus lipase (1,3-specific) and stable Burkholderia cepacia lipase (non-specific) were covalently co-immobilized on 3-glycidyloxypropyltrimethoxysilane (3-GPTMS) modified Fe(3)O(4) magnetic nanoparticles (co-BCL-TLL@Fe(3)O(4)). The co-immobilization process was optimized using response surface methodology (RSM). The obtained co-BCL-TLL@Fe(3)O(4) exhibited a significant improvement in activity and reaction rate compared with mono and combined-use lipases, achieving 92.9% yield after 6 h under optimal conditions, while individually immobilized TLL, immobilized BCL and their combinations exhibited yields of 63.3%, 74.2% and 70.6%, respectively. Notably, co-BCL-TLL@Fe(3)O(4) achieved 90-98% biodiesel yields after 12 h using six different feedstocks, demonstrating the perfect synergistic effect of BCL and TLL remarkably motivated in co-immobilization. Furthermore, co-BCL-TLL@Fe(3)O(4) could maintain 77% of initial activity after nine cycles by removing methanol and glycerol from catalyst surface, accomplished by washing with t-butanol. The high catalytic efficiency, wide substrate adaptability and favorable reusability of co-BCL-TLL@Fe(3)O(4) suggest that it will be an economical and effective biocatalyst for further applications.
ESTHER : Wang_2023_Int.J.Mol.Sci_24_4726
PubMedSearch : Wang_2023_Int.J.Mol.Sci_24_4726
PubMedID: 36902155

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 : Multi- and trans-generational effects of di-n-octyl phthalate on behavior, lifespan and reproduction of Caenorhabditis elegans through neural regulation and lipid metabolism - Zhang_2023_Sci.Total.Environ__165268
Author(s) : Zhang J , Wang L , Liu M , Yu Z
Ref : Sci Total Environ , :165268 , 2023
Abstract : Di-n-octyl phthalate (DOP) is one important phthalate analog whose toxicities need comprehensive investigation to fully demonstrate phthalates health risks. In the present study, apical effects of DOP on behavior, lifespan and reproduction and the underlying mechanisms were explored in Caenorhabditis elegans for four consecutive generations (F1 to F4) and the trans-generational effects were also measured in the great-grand-children (T4 and T4') of F1 and F4. Multi-generational results showed that DOP caused both stimulation and inhibition on head swing, body bending, reverse, Omega steering, pharyngeal pump and satiety quiescence. The stimulation and inhibition altered over concentrations and across generations, and the alteration was the greatest in reverse locomotion which showed both concentration-dependent hormesis and trans-hormesis. DOP stimulated lifespan and inhibited reproduction, showing trade-off relationships. Significant trans-generational residual effects were found in T4 and T4' where the exposure was completed eliminated. Moreover, both similar and different effects were found in comparisons between F1 and F4, between F1 and T4, between F4 and T4' and also between T4 and T4'. Further analysis showed close connections between effects of DOP on neurotransmitters (including dopamine, acetylcholine, gamma-aminobutyric acid and serotonin) and enzymes in lipid metabolism (including lipase, acetyl CoA carboxylase, fatty acid synthetase, carnitine palmitoyl-transferase, glycerol phosphate acyltransferase and acetyl CoA synthetase). Moreover, the close connections were also found between biochemical and apical effects. Notably, the connections were different in multi- and trans-generational effects, which urged further studies to reveal the response strategies underlying the exposure scenarios.
ESTHER : Zhang_2023_Sci.Total.Environ__165268
PubMedSearch : Zhang_2023_Sci.Total.Environ__165268
PubMedID: 37406686

Title : The phospholipase effector Tle1(Vc) promotes Vibrio cholerae virulence by killing competitors and impacting gene expression - Liu_2023_Gut.Microbes_15_2241204
Author(s) : Liu M , Wang H , Liu Y , Tian M , Wang Z , Shu RD , Zhao MY , Chen WD , Fu Y
Ref : Gut Microbes , 15 :2241204 , 2023
Abstract : Vibrio cholerae utilizes the Type VI secretion system (T6SS) to gain an advantage in interbacterial competition by delivering anti-prokaryotic effectors in a contact-dependent manner. However, the impact of T6SS and its secreted effectors on physiological behavior remains poorly understood. In this study, we present Tle1(Vc), a phospholipase effector in atypical pathogenic V. cholerae E1 that is secreted by T6SS via its interaction with VgrG1(E1). Tle1(Vc) contains a DUF2235 domain and belongs to the Tle1 (type VI lipase effector) family. Bacterial toxicity assays, lipase activity assays and site-directed mutagenesis revealed that Tle1(Vc) possessed phospholipase A(1) activity and phospholipase A(2) activity, and that Tle1(Vc)-induced toxicity required a serine residue (S356) and two aspartic acid residues (D417 and D496). Cells intoxication with Tle1(Vc) lead to membrane depolarization and alter membrane permeability. Tli1(tox-), a cognate immunity protein, directly interacts with Tle1(Vc) to neutralize its toxicity. Moreover, Tle1(Vc) can kill multiple microorganisms by T6SS and promote in vivo fitness of V. cholerae through mediating antibacterial activity. Tle1(Vc) induces bacterial motility by increasing the expression of flagellar-related genes independently of functional T6SS and the tit-for-tat (TFT) response, where Pseudomonas aeruginosa uses its T6SS-H1 cluster to counterattack other offensive attackers. Our study also demonstrated that the physical puncture of E1 T6SS can induce a moderate TFT response, which is essential to the Tle1(Vc)-mediated strong TFT response, maximizing effector functions. Overall, our study characterized the antibacterial mechanism of phospholipase effector Tle1(Vc) and its multiple physiological significance.
ESTHER : Liu_2023_Gut.Microbes_15_2241204
PubMedSearch : Liu_2023_Gut.Microbes_15_2241204
PubMedID: 37526354

Title : Nickel Single-Atom Catalyst-Mediated Efficient Redox Cycle Enables Self-Checking Photoelectrochemical Biosensing with Dual Photocurrent Readouts - Tan_2023_ACS.Sens__
Author(s) : Tan R , Qin Y , Liu M , Wang H , Li J , Luo Z , Hu L , Gu W , Zhu C
Ref : ACS Sens , : , 2023
Abstract : Developing a self-checking photoelectrochemical biosensor with dual photocurrent signals could efficiently eliminate false-positive or false-negative signals. Herein, a novel biosensor with dual photocurrent responses was established for the detection of acetylcholinesterase activity. To achieve photocurrent polarity-switchable behavior, the iodide/tri-iodide redox couple was innovatively introduced to simultaneously consume the photoexcited electrons and holes, which circumvents the inconvenience caused by the addition of different hole- and electron-trapping agents in the electrolyte. Importantly, benefiting from the high catalytic activity, the enhanced photoelectric responsivity can be realized after decorating the counter electrode with nickel single-atom catalysts, which promotes a more efficient iodide/tri-iodide redox reaction under low applied voltages. It is envisioned that the proposed photocurrent polarity switching system offers new routes to sensitive and reliable biosensing.
ESTHER : Tan_2023_ACS.Sens__
PubMedSearch : Tan_2023_ACS.Sens__
PubMedID: 36624088

Title : Novel MAGL Inhibitors Alleviate LPS-Induced Acute Kidney Injury by Inhibiting NLRP3 Inflammatory Vesicles, Modulating Intestinal Flora, Repairing the Intestinal Barrier, and Interfering with Serum Metabolism - Xiang_2023_Molecules_28_7245
Author(s) : Xiang H , Wang Y , Yang L , Liu M , Sun C , Gu Y , Yao J
Ref : Molecules , 28 : , 2023
Abstract : Acute kidney injury (AKI) is a complication of a wide range of serious illnesses for which there is still no better therapeutic agent. We demonstrated that M-18C has a favorable inhibitory effect on monoacylglycerol lipase (MAGL), and several studies have demonstrated that nerve inflammation could be effectively alleviated by inhibiting MAGL, suggesting that M-18C has good anti-inflammatory activity. In this study, we investigated the effect of M-18C on LPS-induced acute kidney injury (AKI), both in vivo and in vitro, by using liquid chromatography-mass spectrometry (LC-MS), 16S rRNA gene sequencing, Western blot, and immunohistochemistry. The results showed that both in vivo and in vitro M-18C reduced the release of TNF-alpha and IL-1beta by inhibiting the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) and apoptosis-associated speck-like protein containing a CARD (ASC) protein; in addition, M-18C was able to intervene in LPS-induced AKI by ameliorating renal pathological injury, repairing the intestinal barrier, and regulating gut bacterial flora and serum metabolism. In conclusion, this study suggests that M-18C has the potential to be a new drug for the treatment of AKI.
ESTHER : Xiang_2023_Molecules_28_7245
PubMedSearch : Xiang_2023_Molecules_28_7245
PubMedID: 37959665
Gene_locus related to this paper: human-MGLL

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 : Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals - Xu_2023_Mol.Nutr.Food.Res__e2200816
Author(s) : Xu X , Song Y , Jiang M , Liu M , Zhang X , Wang D , Pan Y , Ren S , Liu X
Ref : Mol Nutr Food Res , :e2200816 , 2023
Abstract : SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.
ESTHER : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedSearch : Xu_2023_Mol.Nutr.Food.Res__e2200816
PubMedID: 38018298

Title : Polysaccharide from Polygala tenuifolia alleviates cognitive decline in Alzheimer's disease mice by alleviating Abeta damage and targeting the ERK pathway - Li_2023_J.Ethnopharmacol__117564
Author(s) : Li Y , Wu H , Liu M , Zhang Z , Ji Y , Xu L , Liu Y
Ref : J Ethnopharmacol , :117564 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect beta-amyloid (Abeta) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Abeta deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Abeta damage and targeting the ERK pathway.
ESTHER : Li_2023_J.Ethnopharmacol__117564
PubMedSearch : Li_2023_J.Ethnopharmacol__117564
PubMedID: 38081400

Title : Bioactive Polyketides and Benzene Derivatives from Two Mangrove Sediment-Derived Fungi in the Beibu Gulf - Peng_2023_Mar.Drugs_21_
Author(s) : Peng B , Cai J , Xiao Z , Liu M , Li X , Yang B , Fang W , Huang YY , Chen C , Zhou X , Tao H
Ref : Mar Drugs , 21 : , 2023
Abstract : To discover bioactive natural products from mangrove sediment-derived microbes, a chemical investigation of the two Beibu Gulf-derived fungi strains, Talaromyces sp. SCSIO 41050 and Penicillium sp. SCSIO 41411, led to the isolation of 23 natural products. Five of them were identified as new ones, including two polyketide derivatives with unusual acid anhydride moieties named cordyanhydride A ethyl ester (1) and maleicanhydridane (4), and three hydroxyphenylacetic acid derivatives named stachylines H-J (10-12). Their structures were determined by detailed nuclear magnetic resonance (NMR) and mass spectroscopic (MS) analyses, while the absolute configurations were established by theoretical electronic circular dichroism (ECD) calculation. A variety of bioactive screens revealed three polyketide derivatives (1-3) with obvious antifungal activities, and 4 displayed moderate cytotoxicity against cell lines A549 and WPMY-1. Compounds 1 and 6 at 10 microM exhibited obvious inhibition against phosphodiesterase 4 (PDE4) with inhibitory ratios of 49.7% and 39.6%, respectively, while 5, 10, and 11 showed the potential of inhibiting acetylcholinesterase (AChE) by an enzyme activity test, as well as in silico docking analysis.
ESTHER : Peng_2023_Mar.Drugs_21_
PubMedSearch : Peng_2023_Mar.Drugs_21_
PubMedID: 37367652

Title : Aaptamine - a dual acetyl - and butyrylcholinesterase inhibitor as potential anti-Alzheimer's disease agent - Miao_2022_Pharm.Biol_60_1502
Author(s) : Miao S , He Q , Li C , Wu Y , Liu M , Chen Y , Qi S , Gong K
Ref : Pharm Biol , 60 :1502 , 2022
Abstract : CONTEXT: Alzheimer's disease (AD) is a neurodegenerative disorder that affects millions of people worldwide. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) are promising therapeutic targets for AD. OBJECTIVE: To evaluate the inhibitory effects of aaptamine on two cholinesterases and investigate the in vivo therapeutic effect on AD in a zebrafish model. MATERIALS AND METHODS: Aaptamine was isolated from the sponge Aaptos suberitoides Brondsted (Suberitidae). Enzyme inhibition, kinetic analysis, surface plasmon resonance (SPR) and molecular docking assays were used to determine its inhibitory effect on AChE and BuChE in vitro. Zebrafish were divided into six groups: control, model, 8 microM donepezil, 5 , 10 and 20 microM aaptamine. After three days of drug treatment, the behaviour assay was performed. RESULTS: The IC(50) values of aaptamine towards AChE and BuChE were 16.0 and 4.6 microM. And aaptamine directly inhibited the two cholinesterases in the mixed inhibition type, with K(i) values of 6.96 +/- 0.04 and 6.35 +/- 0.02 microM, with K(d) values of 87.6 and 10.7 microM. Besides, aaptamine interacts with the crucial anionic sites of AChE and BuChE. In vivo studies indicated that the dyskinesia recovery rates of 5 , 10 and 20 microM aaptamine group were 34.8, 58.8 and 60.0%, respectively, and that of donepezil was 63.7%. DISCUSSION AND CONCLUSIONS: Aaptamine showed great potential to exert its anti-AD effects by directly inhibiting the activities of AChE and BuChE. Therefore, this study identified a novel medicinal application of aaptamine and provided a new structural scaffold for the development of anti-AD drugs.
ESTHER : Miao_2022_Pharm.Biol_60_1502
PubMedSearch : Miao_2022_Pharm.Biol_60_1502
PubMedID: 35968601

Title : Iron Single-Atom Catalysts Boost Photoelectrochemical Detection by Integrating Interfacial Oxygen Reduction and Enzyme-Mimicking Activity - Qin_2022_ACS.Nano__
Author(s) : Qin Y , Wen J , Wang X , Jiao L , Wei X , Wang H , Li J , Liu M , Zheng L , Hu L , Gu W , Zhu C
Ref : ACS Nano , : , 2022
Abstract : The investigations on the generation, separation, and interfacial-redox-reaction processes of the photoinduced carriers are of paramount importance for realizing efficient photoelectrochemical (PEC) detection. However, the sluggish interfacial reactions of the photogenerated carriers, combined with the need for appropriate photoactive layers for sensing, remain challenges for the construction of advanced PEC platforms. Here, as a proof of concept, well-defined Fe single-atom catalysts (Fe SACs) were integrated on the surface of semiconductors, which amplified the PEC signals via boosting oxygen reduction reaction. Besides, Fe SACs were evidenced with efficient peroxidase-like activity, which depresses the PEC signals through the Fe SACs-mediated enzymatic precipitation reaction. Harnessing the oxygen reduction property and peroxidase-like activity of Fe SACs, a robust PEC sensing platform was successfully constructed for the sensitive detection of acetylcholinesterase activity and organophosphorus pesticides, providing guidelines for the employment of SACs for sensitive PEC analysis.
ESTHER : Qin_2022_ACS.Nano__
PubMedSearch : Qin_2022_ACS.Nano__
PubMedID: 35147022

Title : Characterization of the synergistic inhibitory effect of cyanidin-3-O-glucoside and catechin on pancreatic lipase - Wang_2022_Food.Chem_404_134672
Author(s) : Wang Y , Chen L , Liu H , Xie J , Yin W , Xu Z , Ma H , Wu W , Zheng M , Liu M , Liu J
Ref : Food Chem , 404 :134672 , 2022
Abstract : This study aimed to identify novel pancreatic lipase (PL) inhibitors using affinity ultrafiltration combined with spectroscopy and molecular docking. Cyanidin-3-O-glucoside (C3G; IC(50): 0.268 mg/mL) and catechin (IC(50): 0.280 mg/mL) were shown to be potent PL inhibitors extracted from black rice and adzuki bean coat extracts. Isobologram analysis revealed that the combined use of C3G and catechin at a ratio of 2:3 had a remarkable synergistic effect (IC(50) of the mixture: 0.201 mg/mL). The inhibitory mechanism of C3G-catechin mixture was of mixed type. The C3G-catechin mixture had a great impact on PL secondary structures. Molecular docking analysis further demonstrated that these polyphenols formed hydrophobic interactions and hydrogen bonds with amino acid residues in the binding pocket of PL. Collectively, C3G and catechin were shown to inhibit PL in a synergistic manner and can be potentially used for the development of food supplements for obesity prevention.
ESTHER : Wang_2022_Food.Chem_404_134672
PubMedSearch : Wang_2022_Food.Chem_404_134672
PubMedID: 36323025

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

Title : Maintaining the thyroid gland in mutant thyroglobulin-induced hypothyroidism requires thyroid cell proliferation that must continue in adulthood - Zhang_2022_J.Biol.Chem_298_102066
Author(s) : Zhang X , Malik B , Young C , Zhang H , Larkin D , Liao XH , Refetoff S , Liu M , Arvan P
Ref : Journal of Biological Chemistry , 298 :102066 , 2022
Abstract : Congenital hypothyroidism with biallelic thyroglobulin (Tg protein, encoded by the TG gene) mutation is an endoplasmic reticulum (ER) storage disease. Many patients (and animal models) grow an enlarged thyroid (goiter), yet some do not. In adulthood, hypothyroid TG(cog/cog) mice (bearing a Tg-L2263P mutation) exhibit a large goiter, whereas adult WIC rats bearing the TG(rdw/rdw) mutation (Tg-G2298R) exhibit a hypoplastic thyroid. Homozygous TG mutation has been linked to thyroid cell death, and cytotoxicity of the Tg-G2298R protein was previously thought to explain the lack of goiter in WIC-TG(rdw/rdw) rats. However, recent studies revealed that TG(cog/cog) mice also exhibit widespread ER stress-mediated thyrocyte death, yet under continuous feedback stimulation, thyroid cells proliferate in excess of their demise. Here, to examine the relative proteotoxicity of the Tg-G2298R protein, we have used CRISPR-CRISPR-associated protein 9 technology to generate homozygous TG(rdw/rdw) knock-in mice in a strain background identical to that of TG(cog/cog) mice. TG(rdw/rdw) mice exhibit similar phenotypes of defective Tg protein folding, thyroid histological abnormalities, hypothyroidism, and growth retardation. TG(rdw/rdw) mice do not show evidence of greater ER stress response or stress-mediated cell death than TG(cog/cog) mice, and both mouse models exhibit sustained thyrocyte proliferation, with comparable goiter growth. In contrast, in WIC-TG(rdw/rdw) rats, as a function of aging, the thyrocyte proliferation rate declines precipitously. We conclude that the mutant Tg-G2298R protein is not intrinsically more proteotoxic than Tg-L2263P; rather, aging-dependent difference in maintenance of cell proliferation is the limiting factor, which accounts for the absence of goiter in adult WIC-TG(rdw/rdw) rats.
ESTHER : Zhang_2022_J.Biol.Chem_298_102066
PubMedSearch : Zhang_2022_J.Biol.Chem_298_102066
PubMedID: 35618019

Title : Light-Addressable Paper-Based Photoelectrochemical Analytical Device with Tunable Detection Throughput for On-Site Biosensing - Liu_2022_Anal.Chem_94_583
Author(s) : Liu M , Yang J , Wang J , Liu Z , Hu C
Ref : Analytical Chemistry , 94 :583 , 2022
Abstract : Development of biosensing systems resembling optical 96-well plates using portable single-channel electrochemical analyzers is usually a great challenge. Herein, a light-addressable paper-based photoelectrochemical (PEC) analytical device suitable for on-site high-throughput biosensing is reported. This device consists of a solar cell-type single-channel PEC system with plenty of separated detection zones. Each zone contains a silver nanowires/fullerene-Congo red (AgNWs/C(60)-CR) disc working electrode and a AgNWs ring reference/counter electrode, which can be massively produced by a simple filtration and laser cutting method. Taking advantage of the sensitive photocurrent response of thiocholine (TCl) on AgNWs/C(60)-CR, an acetylcholinesterase (AChE)-based PEC biosensing system with tunable detection throughput for the on-site screening of ultratrace organophosphorus pesticides (OPs) was established.
ESTHER : Liu_2022_Anal.Chem_94_583
PubMedSearch : Liu_2022_Anal.Chem_94_583
PubMedID: 34978797

Title : Zeaxanthin remodels cytoplasmic lipid droplets via beta3-adrenergic receptor signaling and enhances perilipin 5-mediated lipid droplet-mitochondrion interactions in adipocytes - Xie_2022_Food.Funct__
Author(s) : Xie J , Liu H , Yin W , Ge S , Jin Z , Zheng M , Cai D , Liu M , Liu J
Ref : Food Funct , : , 2022
Abstract : Cytoplasmic lipid droplets (LDs), which are remarkably dynamic, neutral lipid storage organelles, play fundamental roles in lipid metabolism and energy homeostasis. Both the dynamic remodeling of LDs and LD-mitochondrion interactions in adipocytes are effective mechanisms to ameliorate obesity and related comorbidities. Zeaxanthin (ZEA) is a natural carotenoid and has beneficial effects on anti-obesity. However, the underlying mechanisms of ZEA on LD modulation are still unclear. In the present study, ZEA efficiently inhibited LD accumulation and attenuated adipocyte proliferation by arresting the cell cycle. ZEA drove transcriptional alterations to reprogram a lipid oxidative metabolism phenotype in mature 3T3-L1 adipocytes. ZEA significantly decreased the TAG and FA content and modulated the dynamic alterations of LDs by upregulating the expression of lipases and the LD-mitochondrion contact site protein, perilipin 5 (PLIN5), and downregulating the LD fusion protein, fat-specific protein 27 (FSP27). Mechanistically, ZEA stimulated LD remodeling and ameliorated mitochondrial defects caused by large and unilocular LD accumulation by activating beta3-adrenergic receptor (beta3-AR) signaling. Furthermore, the knockdown of PLIN5 impaired the LD-mitochondrion interactions, thereby disrupting the role of ZEA in promoting mitochondrial fatty acid oxidation and respiratory chain operation. Collectively, the present study demonstrates that ZEA induces LD structural and metabolic remodeling by activating beta3-AR signaling and enhances PLIN5-mediated LD-mitochondrion interactions in hypertrophic white adipocytes, thereby enhancing oxidative capacity, and has the potential as a nutritional intervention for the prevention and treatment of obesity and associated metabolic syndrome.
ESTHER : Xie_2022_Food.Funct__
PubMedSearch : Xie_2022_Food.Funct__
PubMedID: 35924967

Title : Discovery of novel tacrine derivatives as potent antiproliferative agents with CDKs inhibitory property - Liu_2022_Bioorg.Chem_126_105875
Author(s) : Liu W , Wu L , Li D , Huang Y , Liu M , Tian C , Liu X , Jiang X , Hu X , Gao X , Xu Z , Lu H , Zhao Q
Ref : Bioorg Chem , 126 :105875 , 2022
Abstract : Tacrine was the first approved drug by the FDA for the treatment of Alzheimer's disease (AD) but was withdrawn from the market due to its dose-dependent hepatotoxicity. Herein, we describe our efforts toward the discovery of a novel series of tacrine derivatives for cancer therapeutics. Intensive structural modifications of tacrine led to the identification of N-(4-{9-[(3S)-3-aminopyrrolidin-1-yl]-5,6,7,8-tetrahydroacridin-2-yl}pyridin-2-yl)cyclopropanecarboxamide hydrochloride ((S)-45, ZLWT-37) as a potent antiproliferative agent (GI(50) = 0.029 microM for HCT116). In addition, ZLWT-37 exhibited lower inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) compared to tacrine. The in vitro studies demonstrated that ZLWT-37 could significantly induce apoptosis and arrest the cell cycle in the G2/M phase in HCT116 cells. The in vivo studies revealed that compound ZLWT-37 showed excellent antitumor efficacy in HCT116 xenograft tumor model and favorable pharmacokinetics profiles (F% = 28.70%) as well as low toxicity in the acute toxicity test with a median lethal dose (LD(50)) of 380.3 mg/kg. Encouragingly, ZLWT-37 had no obvious hepatotoxicity, nephrotoxicity, and hematologic toxicity. Kinase assay suggested that ZLWT-37 possessed potent cyclin-dependent kinase 9 (CDK9) inhibitory activity (IC(50) = 0.002 microM) and good selectivity over CDK2 (IC(50) = 0.054 microM). Collectively, these findings indicate that compound ZLWT-37 is a promising anti-cancer agent that deserves further preclinical evaluation.
ESTHER : Liu_2022_Bioorg.Chem_126_105875
PubMedSearch : Liu_2022_Bioorg.Chem_126_105875
PubMedID: 35623141

Title : Development and structure-activity relationship of tacrine derivatives as highly potent CDK2\/9 inhibitors for the treatment of cancer - Wu_2022_Eur.J.Med.Chem_242_114701
Author(s) : Wu L , Liu W , Huang Y , Zhu C , Ma Q , Wu Q , Tian L , Feng X , Liu M , Wang N , Xu X , Liu X , Xu C , Qiu J , Xu Z , Zhao Q
Ref : Eur Journal of Medicinal Chemistry , 242 :114701 , 2022
Abstract : CDK2/9 are members of the CDKs family, which play key roles in the occurrence and development of many cancers by regulating cell cycle and transcriptional prolongation, respectively. To further optimize and discuss the structure-activity relationships (SARs), a series of tacrine-based compounds were designed and synthesized from the compound ZLWT-37, which was studied by our group previously but no detailed SARs study was conducted on CDK2/9. Among this series, compounds ZLMT-12 (35) exhibited the most potent antiproliferative activity (GI(50) = 0.006 microM for HCT116) and superior CDK2/9 inhibitory properties (CDK2: IC(50) = 0.011 microM, CDK9: IC(50) = 0.002 microM). Meanwhile, ZLMT-12 showed a weak inhibitory effect on acetylcholinesterase (AChE, IC(50) = 19.023 microM) and butyrylcholinesterase (BuChE, IC(50) = 2.768 microM). In addition, ZLMT-12 can suppress colony formation and migration in HCT116 cells, as well as induce the apoptosis and arrest the cell cycle in the S phase and G2/M phase. In vivo investigations revealed that ZLMT-12 inhibits tumor growth in the HCT116 xenograft tumor model at a low dose of 10 mg/kg without causing hepatotoxicity. The acute toxicity test showed low toxicity with a median lethal dosage (LD(50)) of 104.417 mg/kg. These findings showed that ZLMT-12 might be used as a drug candidate by targeting CDK2/9.
ESTHER : Wu_2022_Eur.J.Med.Chem_242_114701
PubMedSearch : Wu_2022_Eur.J.Med.Chem_242_114701
PubMedID: 36054949

Title : Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity - Huang_2021_J.Inflamm.Res_14_6735
Author(s) : Huang Y , Liu C , Song X , An M , Liu M , Yao L , Famurewa AC , Olatunji OJ
Ref : J Inflamm Res , 14 :6735 , 2021
Abstract : BACKGROUND: Cisplatin (CDDP) is an efficacious anticancer agent used widely in chemotherapy despite its severe side effect related to neurotoxicity. Redox imbalance and inflammatory mechanism have been implicated in the pathophysiology of CDDP-induced neurotoxicity. Herein, we investigated whether Tiliacora triandra (TT) extract could inhibit CDDP-induced redox-mediated neurotoxicity and behavioural deficit in rats. MATERIALS AND METHODS: CDDP-induced redox-mediated neurotoxicity and behavioral deficit in rats. Rats were administered TT for five consecutive weeks (250 and 500 mg/kg bw), while weekly i.p. injection of CDDP commenced on the second week (2.5 mg/kg bw) of the TT administration. RESULTS: CCDDP caused significant body weight reduction and cognitive diminution as revealed by Morris water maze and Y maze tests. In the CDDP-induced cognitive impairment (CICI) rats, there were remarkable increases in the brain levels of TNF-alpha, IL-6 and IL-1beta and malondialdehyde (MDA), whereas catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities considerably decreased compared to normal control. The brain acetylcholinesterase (AChE) activity in CDDP control rats was significantly increased compared to the normal control. The expression of caspase-3 and p53 proteins was upregulated by CDDP injection, whereas Bcl2 was downregulated coupled with histopathological alterations in the rat brain. Interestingly, treatment with TT significantly abated neurobehavioral deficits, MDA and cytokine levels and restored CAT, GPx, GSH, SOD, and AChE activities compared to the CDDP control rats. Caspase-3 level as well as Bcl2 and p53 expressions were modulated with alleviated changes in histopathology. CONCLUSION: The findings highlight neuroprotective and cognitive function improvement efficacy of TT against CICI via redox-inflammatory balance and antiapoptotic mechanism in rats.
ESTHER : Huang_2021_J.Inflamm.Res_14_6735
PubMedSearch : Huang_2021_J.Inflamm.Res_14_6735
PubMedID: 34916822

Title : Light-accelerating oxidase-mimicking activity of black phosphorus quantum dots for colorimetric detection of acetylcholinesterase activity and inhibitor screening - Ren_2021_Analyst_145_8022
Author(s) : Ren L , Li H , Liu M , Du J
Ref : Analyst , 145 :8022 , 2021
Abstract : A feasible and sensitive colorimetric platform was established for the assay of acetylcholinesterase (AChE) activity and evaluation of its inhibitor screening, based upon the light-accelerating oxidase-mimicking activity of black phosphorus quantum dots (BP QDs). The BP QDs were synthesized through a thermal exfoliation method and characterized using various techniques. The BP QDs exhibit oxidase-mimicking catalytic activity on dissolved oxygen-mediating oxidation of 3,3',5,5'-tetramethylbenzidine, a typical substrate of oxidase. This results in a transformation of 3,3',5,5'-tetramethylbenzidine into its blue oxidized product, which has a visible absorption peak at 652 nm. The exposure of 365 nm light irradiation significantly accelerates the oxidase-mimicking activity of the BP QDs and speeds up the reaction efficiency. AChE can specifically catalyze the decomposition of its substrate acetylthiocholine chloride to thiocholine. Thiocholine has reducing capacity and can thus reduce the oxidase-mimicking activity of the BP QDs. As a result, the oxidation of 3,3',5,5'-tetramethylbenzidine is hindered and the blue solution becomes paler. This gives a linear response for AChE ranging from 0.5 to 10.0 mU mL-1 and a detection limit of 0.17 mU mL-1. The assay was successfully applied to evaluate inhibitor screening with neostigmine as the model.
ESTHER : Ren_2021_Analyst_145_8022
PubMedSearch : Ren_2021_Analyst_145_8022
PubMedID: 33057486

Title : Dietary administration of probiotic Lactobacillus rhamnosus modulates the neurological toxicities of perfluorobutanesulfonate in zebrafish - Liu_2020_Environ.Pollut_265_114832
Author(s) : Liu M , Song S , Hu C , Tang L , Lam JCW , Lam PKS , Chen L
Ref : Environ Pollut , 265 :114832 , 2020
Abstract : Perfluorobutanesulfonate (PFBS), an aquatic pollutant of emerging concern, is found to disturb the neural signaling along gut-brain axis, whereas probiotic additives have been applied to improve neuroendocrine function of teleosts. Both PFBS and probiotics can commonly target nervous system. However, whether and how probiotic bacteria can modulate the neurotoxicities of PFBS remain not explored. It is thus necessary to elucidate the probiotic modulation of PFBS neurotoxicity, which can provide implications to the application of probiotic bacteria in aquaculture industry. In the present study, adult zebrafish were exposed to 0, 10 and 100 mug/L PFBS with or without dietary administration of probiotic Lactobacillus rhamnosus. Interaction between PFBS and probiotic along gut-brain axis was examined, covering three dominant pathways (i.e., neurotransmission, immune response and hypothalamic-pituitary-adrenal (HPA) axis). The results showed that, compared to the single effects, PFBS and probiotic coexposure significantly altered the acetylcholinesterase activity and neurotransmitter profiles in gut and brain of zebrafish, with mild effects on neuronal integrity. Neurotransmitters closely correlated reciprocally in intestines, which, however, was distinct from the correlation profile in brains. In addition, PFBS and probiotic were combined to impact brain health through absorption of bacterial lipopolysaccharides and production of inflammatory cytokines. Relative to neurotransmission and immune signaling, HPA axis was not involved in the neurotoxicological interaction between PFBS and probiotic. Furthermore, it needs to point out that interactive modes between PFBS and probiotic varied a lot, depending on exposure concentrations, sex and toxic indices. Overall, the present study provided the first evidence that probiotic supplement could dynamically modulate the neurotoxicities of PFBS in teleost.
ESTHER : Liu_2020_Environ.Pollut_265_114832
PubMedSearch : Liu_2020_Environ.Pollut_265_114832
PubMedID: 32454362

Title : Synthesis, Biological Activity, Molecular Docking Studies of a Novel Series of 3-Aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one Derivatives as the Acetylcholinesterase Inhibitors - Jin_2020_J.Biomol.Struct.Dyn__1
Author(s) : Jin Z , Zhang C , Liu M , Jiao S , Zhao J , Liu X , Lin H , Wan DC , Hu C
Ref : J Biomol Struct Dyn , :1 , 2020
Abstract : The acetylcholinesterase inhibitors play a critical role in the drug therapy for Alzheimer's disease. In this study, twenty-nine novel 3-aryl-7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives were synthesized and assayed for their human acetylcholinesterase (hAChE) inhibitory activities. Inhibitory ratio values of seventeen compounds were above 55% with 4c having the highest value as 77.19%. The compounds with the halogen atoms in the aromatic ring, and N,N-diethylamino or N,N-dimethylamino groups in the side chains at C-3 positions exhibited good inhibitory activity. SAR study was carried out by means of molecular docking technique. According to molecular docking results, the common interacting site for all compounds were found to be peripheral anionic site whereas highly active compounds were interacting with the catalytic active site too.
ESTHER : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedSearch : Jin_2020_J.Biomol.Struct.Dyn__1
PubMedID: 32266865

Title : Rhizoma Coptidis for Alzheimer's Disease and Vascular Dementia: A Literature Review - Wang_2020_Curr.Vasc.Pharmacol_18_358
Author(s) : Wang Z , Yang Y , Liu M , Wei Y , Liu J , Pei H , Li H
Ref : Curr Vasc Pharmacol , 18 :358 , 2020
Abstract : BACKGROUND: Alzheimer's disease (AD) and vascular dementia (VaD) are major types of dementia, both of which cause heavy economic burdens for families and society. However, no currently available medicines can control dementia progression. Rhizoma coptidis, a Chinese herbal medicine, has been used for >2000 years and is now gaining attention as a potential treatment for AD and VaD. METHODS: We reviewed the mechanisms of the active ingredients of Rhizoma coptidis and Rhizoma coptidis-containing Chinese herbal compounds in the treatment of AD and VaD. We focused on studies on ameliorating the risk factors and the pathological changes of these diseases. RESULTS: The Rhizoma coptidis active ingredients include berberine, palmatine, coptisine, epiberberine, jatrorrhizine and protopine. The most widely studied ingredient is berberine, which has extensive therapeutic effects on the risk factors and pathogenesis of dementia. It can control blood glucose and lipid levels, regulate blood pressure, ameliorate atherosclerosis, inhibit cholinesterase activity, Abeta generation, and tau hyperphosphorylation, decrease neuroinflammation and oxidative stress and alleviate cognitive impairment. Other ingredients (such as jatrorrhizine, coptisine, epiberberine and palmatine) also regulate blood lipids and blood pressure; however, there are relatively few studies on them. Rhizoma coptidis-containing Chinese herbal compounds like Huanglian-Jie-Du-Tang, Huanglian Wendan Decoction, Banxia Xiexin Decoction and Huannao Yicong Formula have anti-inflammatory and antioxidant stress activities, regulate insulin signaling, inhibit gamma-secretase activity, neuronal apoptosis, tau hyperphosphorylation, and Abeta deposition, and promote neural stem cell differentiation, thereby improving cognitive function. CONCLUSION: The "One-Molecule, One-Target" paradigm has suffered heavy setbacks, but a "multitarget- directed ligands" strategy may be viable. Rhizoma coptidis active ingredients and Rhizoma coptidiscontaining Chinese herbal compounds have multi-aspect therapeutic effects on AD and VaD.
ESTHER : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedSearch : Wang_2020_Curr.Vasc.Pharmacol_18_358
PubMedID: 31291876

Title : Evaluation of Cholinesterase Inhibitory Potential of Different Genotypes of Ziziphus nummularia, Their HPLC-UV, and Molecular Docking Analysis - Uddin_2020_Molecules_25_5011
Author(s) : Uddin N , Ali N , Uddin Z , Nazir N , Zahoor M , Rashid U , Ullah R , Alqahtani AS , Alqahtani AM , Nasr FA , Liu M , Nisar M
Ref : Molecules , 25 :5011 , 2020
Abstract : Ziziphus nummularia is an important source of valuable phytoconstituents, which are widely used in traditional medicine system of Indo-Pak sub-continent. In this study we investigated the distribution of phenolic compounds in the fruit pericarps of six different genotypes (ZNP01-06) of Z. nummularia growing in the unexplored hilly areas of Pakistan. The methanolic extracts of these genotypes were screened for total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and cholinesterase inhibitory potentials. The observed biological potentials were explained in terms of the outcome of molecular docking and HPLC analyses. Among them, genotype ZNP02 displayed high TPC (88.50 +/- 1.23 g/mL) and showed potent scavenging activity against DPPH (67.03 +/- 1.04 g/mL) and ABTS (65.3 +/- 1.74 g/mL) in comparison to ascorbic acid (68.7 +/- 0.47 g/mL). Moreover, genotypes ZNP01, ZNP02, and ZNP04 displayed potent inhibition against acetyl and butyryl cholinesterases (AChE and BChE) with IC(50) values of 21.2, 20.5, and 23.7 g/mL (AChE) and 22.7, 24.4, and 33.1 g/mL (BChE), respectively. Furthermore, the individual compounds in the most potent species ZNP01 responsible for potent enzyme inhibition (identified through HPLC-UV analysis), were computed via docking simulation software to the enzyme structures. Among these compounds rutin exhibited significant binding affinity with value of -9.20 kcal/mol. The differences amongst the phytochemical compositions of the selected genotypes highlighted the genotypic variations in them. Based on our results it was concluded that the selected plant can be used as remedy of oxidative stress and neurodegenerative diseases. However, further studies are needed to isolate responsible compounds and test the observed potential in vivo, along with toxicological evaluations in animal models.
ESTHER : Uddin_2020_Molecules_25_5011
PubMedSearch : Uddin_2020_Molecules_25_5011
PubMedID: 33137939

Title : Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats - Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
Author(s) : Wu Q , Cao Y , Liu M , Liu F , Brantner AH , Yang Y , Wei Y , Zhou Y , Wang Z , Ma L , Wang F , Pei H , Li H
Ref : Neuropsychiatr Dis Treat , 15 :3167 , 2019
Abstract : Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction.
ESTHER : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedSearch : Wu_2019_Neuropsychiatr.Dis.Treat_15_3167
PubMedID: 31814724

Title : Peach Carboxylesterase PpCXE1 Is Associated with Catabolism of Volatile Esters - Cao_2019_J.Agric.Food.Chem_67_5189
Author(s) : Cao X , Xie K , Duan W , Zhu Y , Liu M , Chen K , Klee H , Zhang B
Ref : Journal of Agricultural and Food Chemistry , 67 :5189 , 2019
Abstract : Peach fruit volatile acetate esters impact consumer sensory preference and contribute to defense against biotic stresses. Previous studies showed that alcohol acyltransferase (AAT) family PpAAT1 is correlated with volatile ester formation in peach fruits. However, fruits also contain carboxylesterase (CXE) enzymes that hydrolyze esters. The functions of this family with regard to volatile ester content has not been explored. Here, we observed that content of acetate ester was negatively correlated with expression of PpCXE1. Recombinant PpCXE1 protein exhibited hydrolytic activity toward acetate esters present in peach fruit. Kinetic analysis showed that PpCXE1 showed the highest catalytic activity toward E-2-hexenyl acetate. Subcellular localization demonstrated that PpCXE1 is present in the cytoplasm. Transient expression in peach fruit and stable overexpression in tomato fruit resulted in significant reduction of volatile esters in vivo. Taken together, the results indicate that PpCXE1 expression is associated with catabolism of volatile acetate esters in peach fruit.
ESTHER : Cao_2019_J.Agric.Food.Chem_67_5189
PubMedSearch : Cao_2019_J.Agric.Food.Chem_67_5189
PubMedID: 30997798
Gene_locus related to this paper: prupe-m5w2v0 , prupe-m5vkk2 , prupe-m5vq13

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

Title : Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Abeta1-42 Induced Cognitive Deficit Mice - Zhu_2019_Front.Pharmacol_10_258
Author(s) : Zhu Y , Shi Y , Cao C , Han Z , Liu M , Qi M , Huang R , Zhu Z , Qian D , Duan JA
Ref : Front Pharmacol , 10 :258 , 2019
Abstract : Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on beta amyloid protein 1-42 (Abeta1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Abeta1-42 injection mice. JWKXS granules significantly decreased Abeta level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Abeta production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Abeta and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Abeta levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.
ESTHER : Zhu_2019_Front.Pharmacol_10_258
PubMedSearch : Zhu_2019_Front.Pharmacol_10_258
PubMedID: 30941041

Title : ATGL promotes the proliferation of hepatocellular carcinoma cells via the p-AKT signaling pathway - Liu_2019_J.Biochem.Mol.Toxicol__e22391
Author(s) : Liu M , Yu X , Lin L , Deng J , Wang K , Xia Y , Tang X , Hong H
Ref : J Biochem Mol Toxicol , :e22391 , 2019
Abstract : Abnormal metabolism, including abnormal lipid metabolism, is a hallmark of cancer cells. Some studies have demonstrated that the lipogenic pathway might promote the development of hepatocellular carcinoma (HCC). However, the role of adipose triglyceride lipase (ATGL) in hepatocellular carcinoma cells has not been elucidated. We evaluated the function of ATGL in hepatocellular carcinoma using methyl azazolyl blue and migration assay through overexpression of ATGL in HepG2 cells. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses were used to assess the mechanisms of ATGL in hepatocellular carcinoma. In the current study, we first constructed and transiently transfected ATGL into hepatocellular carcinoma cells. Secondly, we found that ATGL promoted the proliferation of hepatoma cell lines via upregulating the phosphorylation of AKT, but did not affect the metastatic ability of HCC cells. Moreover, the p-AKT inhibitor significantly eliminated the effect of ATGL on the proliferation of hepatoma carcinoma cells. Taken together, our results indicated that ATGL promotes hepatocellular carcinoma cells proliferation through upregulation of the AKT signaling pathway.
ESTHER : Liu_2019_J.Biochem.Mol.Toxicol__e22391
PubMedSearch : Liu_2019_J.Biochem.Mol.Toxicol__e22391
PubMedID: 31476254

Title : Carbon dots co-doped with nitrogen and chlorine for off-on fluorometric determination of the activity of acetylcholinesterase and for quantification of organophosphate pesticides - Yang_2019_Mikrochim.Acta_186_585
Author(s) : Yang M , Liu M , Wu Z , He Y , Ge Y , Song G , Zhou J
Ref : Mikrochim Acta , 186 :585 , 2019
Abstract : Nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) were hydrothermally prepared starting from 4-chloro-1,2-diaminobenzene and dopamine. The N,Cl-CDs exhibit strong orange fluorescence, with excitation/emission maxima at 420/570 nm and a relative high quantum yield (15%). The N,Cl-CDs were employed to detect acetylcholinesterase (AChE) activity and organophosphate pesticides (OPs) which are enzyme inhibitors. Acetylthiocholine is enzymatically split by AChE to produce thiocholine which triggers the decomposition of Ellmans's reagent to form a yellow colored product (2-nitro-5-thiobenzoate anion). The product causes an inner filter effect (IEF) on the fluorescence of the N,Cl-CDs. Fluorescence decreases linearly in the 0.017 to 5.0 Unit.L(-1) AChE activity range, and the detection limit is 2 mUnit.L(-1). If organophosphates are present, the activity of AChE becomes increasingly blocked, and this leads to a less expressed IFE and an increasing recovery of fluorescence. This was used for the quantification of OPs. Response is linear in the 0.3-1000 mug.L(-1) OP concentration range with a 30 ng.L(-1) detection limit. Graphical abstractSchematic representation of the synthesis of nitrogen and chlorine dually-doped carbon dots (N,Cl-CDs) and the recognition of organophosphate pesticides by N,Cl-CDs.
ESTHER : Yang_2019_Mikrochim.Acta_186_585
PubMedSearch : Yang_2019_Mikrochim.Acta_186_585
PubMedID: 31363918

Title : Large-scale separation of acetylcholinesterase inhibitors from Zanthoxylum nitidum by pH-zone-refining counter-current chromatography target-guided by ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry screening - Liu_2019_J.Sep.Sci_42_1194
Author(s) : Liu M , Liu Q , Chen M , Huang X , Chen X
Ref : J Sep Sci , 42 :1194 , 2019
Abstract : A new strategy by converging ultrafiltration high-performance liquid chromatography with ultraviolet and mass spectrometry and pH-zone-refining counter-current chromatography was developed for the rapid screening and separation of potential acetylcholinesterase inhibitors from the crude alkaloidals extract of Zanthoxylum nitidum. An optimized two-phase solvent system composed of chloroform/methanol/water (4:3:3, v/v) was used in this study. And, in the optimal solvent system, 45 mM hydrochloric acid was added to the aqueous stationary phase as the retainer, while 5 mM triethylamine was added to the organic mobile phase as the eluter. As a result, with the purity of over 95%, five alkaloids including jatrorrhizine (1, 340 mg), columbamine (2, 112 mg), skimmianine (3, 154 mg), palmatine (4, 226 mg), and epiberberine (5, 132 mg) were successfully purified in one step from 3.0 g crude alkaloidals extract. And their structures were identified by ultraviolet, mass spectrometry, (1) H and (13) C NMR spectroscopy. Notably, compounds 2, 4 and 5 were firstly reported in Z. nitidum. In addition, acetylcholinesterase inhibitory activities of compounds 1-5 were evaluated, and compounds 3, 4 and 5 exhibited stronger acetylcholinesterase inhibitory activity (IC50 values at 8.52 +/- 0.64, 14.82 +/- 1.21 and 3.12 +/- 0.32 mug/mL, respectively) than berberine (IC50 value at 32.86 +/- 2.14 mug/mL, positive control). The results indicated that the proposed method is an efficient technique to rapidly screen acetylcholinesterase inhibitors from complex samples, and could be served as a large-scale preparative technique for separating ionizable active compounds.
ESTHER : Liu_2019_J.Sep.Sci_42_1194
PubMedSearch : Liu_2019_J.Sep.Sci_42_1194
PubMedID: 30638299

Title : Comparative transcriptome reveals the potential modulation mechanisms of estradiol affecting ovarian development of female Portunus trituberculatus - Liu_2019_PLoS.One_14_e0226698
Author(s) : Liu M , Pan J , Dong Z , Cheng Y , Gong J , Wu X
Ref : PLoS ONE , 14 :e0226698 , 2019
Abstract : Estradiol is an important sex steroid hormone that is involved in the regulation of crustacean ovarian development. However, the molecular regulatory mechanisms of estradiol on ovarian development are largely unknown. This study performed transcriptome sequencing of ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ of crabs after estradiol treatment (0.1mug g-1 crab weight). A total of 23, 806 genes were annotated, and 316, 1300, 669, 142, 383 genes were expressed differently in ovary, hepatopancreas, brain ganglion, eyestalk, and mandibular organ respectively. Differentially expressed gene enrichment analysis revealed several crucial pathways including protein digestion and absorption, pancreatic secretion, insect hormone biosynthesis, drug metabolism-cytochrome P450 and signal transduction pathway. Through this study, some key genes in correlation with the ovarian development and nutrition metabolism were significantly affected by estradiol, such as vitelline membrane outer layer 1-like protein, heat shock protein 70, Wnt5, JHE-like carboxylesterase 1, cytochrome P302a1, crustacean hyperglycemic hormone, neuropeptide F2, trypsin, carboxypeptidase B, pancreatic triacylglycerol lipase-like, and lipid storage droplet protein. Moreover, RT-qPCR validation demonstrated that expression of transcripts related to ovarian development (vitelline membrane outer layer 1-like protein and cytochrome P302a1) and nutrition metabolism (trypsin, glucose dehydrogenase and lipid storage droplet protein) were significantly affected by estradiol treatment. This study not only has identified relevant genes and several pathways that are involved in estradiol regulation on ovarian development of P. trituberculatus, but also provided new insight into the understanding of the molecular function mechanisms of estradiol in crustacean.
ESTHER : Liu_2019_PLoS.One_14_e0226698
PubMedSearch : Liu_2019_PLoS.One_14_e0226698
PubMedID: 31856263

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

Title : N-Carbamoylmaleimide-treated carbon dots: stabilizing the electrochemical intermediate and extending it for the ultrasensitive detection of organophosphate pesticides - Xu_2018_Nanoscale_10_19390
Author(s) : Xu J , Yu C , Feng T , Liu M , Li F , Wang Y
Ref : Nanoscale , 10 :19390 , 2018
Abstract : To date, numerous methods have been reported for the detection of organophosphorus pesticides (OP) due to their severe potential hazard to the environment, public health and national security. However, very few works have ever found that the signal loss of thiocholine (TCh) during electrochemical processing is a key factor leading to the low sensitivity of acetylcholinesterase (AChE)-based OP electrochemical sensing platforms. Herein, we propose an ultrasensitive detection method for multiple OPs including parathion-methyl, paraoxon, dimethoate and O,O-dimethyl-O-2,2-dichlorovinyl-phosphate using N-carbamoylmaleimide-functionalized carbon dots (N-MAL-CDs) as a nano-stabilizer. For the first time, Michael addition is introduced into an AChE-based OP electrochemical sensing platform to enrich the electrochemical intermediate TCh. The Michael addition between TCh and N-MAL-CDs is demonstrated via XRD, FTIR, SEM and EDS elemental mapping experiments. Due to the stabilization and enhancement of TCh with N-MAL-CDs, the as prepared OP sensing platform achieves ultrahigh sensitivity by detecting the initial electrochemical signals of TCh without signal loss, showing a wide linear range of 3.8 x 10(-15)-3.8 x 10(-10) M for parathion-methyl and 1.8 x 10(-14)-3.6 x 10(-10) M for paraoxon, with a limit of detection of 1.4 x 10(-15) M for parathion-methyl and 4.8 x 10(-15) M for paraoxon.
ESTHER : Xu_2018_Nanoscale_10_19390
PubMedSearch : Xu_2018_Nanoscale_10_19390
PubMedID: 30307023

Title : Biopanning of allergens from wasp sting patients - Chai_2018_Biosci.Rep_38_
Author(s) : Chai L , Yang X , Liu M , Liu C , Han L , Guo H , Li C , Sun Y , Li X , Xiao M , Fang Z
Ref : Bioscience Reports , 38 : , 2018
Abstract : OBJECTIVE: Wasp venom is a potentially important natural drug, but it can cause hypersensitivity reactions. The purpose of the present study was to systematically study the epitopes of wasp venom. METHODS: Using a random 12-peptide phage library, we performed antibody-binding epitope panning on ten serum samples from wasp sting victims at 3 h and 4 days after the sting. The panning epitopes were identified by high-throughput sequencing and matched with wasp venom proteins by BLAST. The panned antibody-binding epitopes were verified by ELISA. RESULTS: A total of 35 specific potential wasp venom epitopes in 4 days were identified. Amongst them, twelve peptide epitopes were matched with nine wasp venom proteins, namely, vitellogenin precursor, hexamerin 70b precursor, venom carboxylesterase-6 precursor, MRJP5, major royal jelly protein 8 precursor, venom acid phosphatase Acph-1 precursor, phospholipase A2, venom serine protease 34 precursor, and major royal jelly protein 9 precursor. The changes in serum IgM antibodies induced by wasp venom were confirmed by ELISA based on the 12 peptide epitopes. CONCLUSION: The nine wasp venom proteins are potential allergens, which should be excluded or modified in the potential biomedical applications of wasp venom.
ESTHER : Chai_2018_Biosci.Rep_38_
PubMedSearch : Chai_2018_Biosci.Rep_38_
PubMedID: 30249752

Title : New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus - Qi_2018_Org.Biomol.Chem_16_9046
Author(s) : Qi C , Qiao Y , Gao W , Liu M , Zhou Q , Chen C , Lai Y , Xue Y , Zhang J , Li D , Wang J , Zhu H , Hu Z , Zhou Y , Zhang Y
Ref : Org Biomol Chem , 16 :9046 , 2018
Abstract : Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A-D (1-4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1-4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran-H2O-MeOH solvent. All these compounds were evaluated for the beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC50 values of 5.98 and 11.42 muM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC50 values of 1.91 and 8.86 muM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.
ESTHER : Qi_2018_Org.Biomol.Chem_16_9046
PubMedSearch : Qi_2018_Org.Biomol.Chem_16_9046
PubMedID: 30430177

Title : Mechanism hypotheses for the electrophysiological manifestations of two cases of endplate acetylcholinesterase deficiency related congenital myasthenic syndrome - Ding_2018_J.Clin.Neurosci_48_229
Author(s) : Ding Q , Shen D , Dai Y , Hu Y , Guan Y , Liu M , Cui L
Ref : J Clin Neurosci , 48 :229 , 2018
Abstract : OBJECTIVE: To summarize the electrophysiological characteristics of two cases of endplate acetylcholinesterase deficiency (EAD) related congenital myasthenic syndrome (CMS) caused by COLQ mutation and to discuss the possible mechanism of these electrophysiological phenomena. METHODS: Electrophysiological examinations were conducted including nerve conduction studies, routine electromyography (EMG), repetitive nerve stimulation (RNS) and single fiber EMG (SFEMG). The ulnar nerve was also stimulated at 50Hz followed by 0.5Hz to record the recovery process of compound muscle action potential (CMAP). RESULTS: Repetitive CMAP (R-CMAP) was found in motor nerve conduction in both cases. Needle EMG showed myogenic damages and SFEMG showed remarkably increased jitter values. Of note, the amplitude of CMAP and R-CMAP showed regular changing trends, and so did their time intervals in RNS studies. CONCLUSIONS: The change patterns of CMAP and R-CMAP, in combination with other electrophysiological features are very useful for the diagnosis of EAD related CMS, especially in predicting the presence of correct gene mutations.
ESTHER : Ding_2018_J.Clin.Neurosci_48_229
PubMedSearch : Ding_2018_J.Clin.Neurosci_48_229
PubMedID: 29150079

Title : Controllable Growth of Core-Shell Nanogels via Esterase-Induced Self-Assembly of Peptides for Drug Delivery - Wu_2018_J.Biomed.Nanotechnol_14_354
Author(s) : Wu C , Hu W , Wei Q , Qiao L , Gao Y , Lv Y , Liu M , Li C , Wang X , Wang Q
Ref : J Biomed Nanotechnol , 14 :354 , 2018
Abstract : In this work, we developed an unexplored enzyme-responsive core-shell nanogel via the assembly of hydrogelators at the surface of silicon nanoparticles. The immobilized carboxylesterase at the surface of silicon nanoparticles can catalyse precursors into hydrogelators, self-assembling around the surface of silicon nanoparticles owing to its surface confinement effect. These novel phenomena can be confirmed by observation of their morphology and increased diameters through scanning electron microscopy, transmission electron microscopy and dynamic light scattering. Moreover, these resulting core-shell nanogels can achieve controlled growth of the gel layer by means of changing the concentrations of precursors. Because of their good biocompatibility, these nanogels can realize applications in enzyme-specific drug delivery as nanocarriers.
ESTHER : Wu_2018_J.Biomed.Nanotechnol_14_354
PubMedSearch : Wu_2018_J.Biomed.Nanotechnol_14_354
PubMedID: 31352931

Title : Effect of carboxylesterase 1 S75N on clopidogrel therapy among acute coronary syndrome patients - Xiao_2017_Sci.Rep_7_7244
Author(s) : Xiao FY , Luo JQ , Liu M , Chen BL , Cao S , Liu ZQ , Zhou HH , Zhou G , Zhang W
Ref : Sci Rep , 7 :7244 , 2017
Abstract : Carboxylesterase 1 (CES1) hydrolyzes the prodrug clopidogrel to an inactive carboxylic acid metabolite. The effects of CES1 S75N (rs2307240,C>T) on clopidogrel response among 851 acute coronary syndrome patients who came from the north, central and south of China were studied. The occurrence ratios of each endpoint in the CC group were significantly higher than in the CT + TT group for cerebrovascular events (14% vs 4.8%, p < 0.001, OR = 0.31), acute myocardial infarction (15.1% vs 6.1%, p < 0.001, OR = 0.37) and unstable angina (62.8% vs 37.7%, p < 0.001, OR = 0.36). The results showed that there was a significant association between CES1 S75N (rs2307240) and the outcome of clopidogrel therapy. Moreover, the frequency of the T allele of rs2307240 in acute coronary syndrome patients (MAF = 0.22) was more than four times higher than that in the general public (MAF = 0.05).
ESTHER : Xiao_2017_Sci.Rep_7_7244
PubMedSearch : Xiao_2017_Sci.Rep_7_7244
PubMedID: 28775293
Gene_locus related to this paper: human-CES1

Title : Effect of single-wall carbon nanotubes on bioconcentration and toxicity of perfluorooctane sulfonate in zebrafish (Danio rerio) - Li_2017_Sci.Total.Environ_607-608_509
Author(s) : Li Y , Men B , He Y , Xu H , Liu M , Wang D
Ref : Sci Total Environ , 607-608 :509 , 2017
Abstract : The wide application of nanoparticles will lead its release into the aquatic environment, which may alter the bioavailability and toxicity of other contaminants to aquatic organisms. This work aimed to study the effects of perfluorooctane sulfonate (PFOS), single-wall carbon nanotubes (SWCNT), and their mixture on PFOS accumulation, antioxidant defenses and acetylcholinesterase (AChE) activity in zebrafish. The fish was dissected after being exposed (24, 48, 72 and 96h) separately to PFOS, SWCNT and PFOS+SWCNT co-exposure. The bioaccumulation of PFOS in fish tissues (liver, intestines, gills and brain) decreased with increasing dosage of SWCNT, however, the opposite trend was observed in fish skin, which indicated that the bioavailability of PFOS changed by adsorption on SWCNT. Meanwhile, co-exposure induced more reactive oxygen species (ROS) than PFOS alone and enhanced the effect of PFOS on the superoxide dismutase (SOD), and catalase (CAT) and AChE activities. Furthermore, the integrated biomarker response (IBR) showed that co-exposure was the most stressful circumstance.
ESTHER : Li_2017_Sci.Total.Environ_607-608_509
PubMedSearch : Li_2017_Sci.Total.Environ_607-608_509
PubMedID: 28704675

Title : Genetic mutations in sodium channel domain II and carboxylesterase genes associated with phenotypic resistance against synthetic pyrethroids by Rhipicephalus (Boophilus) decoloratus ticks in Uganda - Vudriko_2017_Pestic.Biochem.Physiol_143_181
Author(s) : Vudriko P , Umemiya-Shirafuji R , Okwee-Acai J , Tayebwa DS , Byaruhanga J , Jirapattharasate C , Liu M , Adjou Moumouni PF , Fujisaki K , Xuan X , Suzuki H
Ref : Pestic Biochem Physiol , 143 :181 , 2017
Abstract : We previously reported emergence of super synthetic pyrethroid (SP) resistant Rhipicephalus (Boophilus) decoloratus ticks in Uganda. This study investigated the genetic basis of phenotypic resistance against SP in R. (B.) decoloratus and sought to identify novel diagnostic mutations for rapid detection of SP resistance in the above tick species. Genomic DNA was extracted from pooled larvae of 20 tick populations (19 of known SP susceptibility and 1 unknown susceptibility). The voltage sensitive sodium channel (VSSC) domain II S4-5 linker (SP target) and partial carboxylesterase (SP metabolizing enzyme) genes were amplified by PCR, cloned and sequenced. The resultant sequences were analyzed to determine single nucleotide polymorphisms (SNPs) associated with phenotypic resistance in the various tick populations investigated. Novel SNPs that introduced Eco RI and Eco RII restriction sites in carboxylesterase gene were identified in silco and validated with restriction fragment length polymorphism (RFLP) against 18 tick populations of known SP susceptibility. The study identified a super knock down resistance (kdr) mutation T58C in R. (B.) decoloratus VSSC associated with stable SP resistance. We further identified multiple nonsynonymous mutations in carboxylesterase of SP resistant ticks; one of which conferred novel EcoRII (G195C) restriction site for PCR-RFLP detection of SP resistance. In conclusion, this study is the first to report super kdr mutation in sodium channel domain II and multiple mutations in carboxylesterase genes that may concurrently mediate stable resistance against synthetic pyrethroids in R. (B.) decoloratus ticks from Uganda. The Eco RII based PCR-RFLP is a useful tool for rapid detection of stable SP resistant R. (B.) decoloratus ticks.
ESTHER : Vudriko_2017_Pestic.Biochem.Physiol_143_181
PubMedSearch : Vudriko_2017_Pestic.Biochem.Physiol_143_181
PubMedID: 29183590

Title : Point mutations in acetylcholinesterase 1 associated with chlorpyrifos resistance in the brown planthopper, Nilaparvata lugens Stal - Zhang_2017_Insect.Mol.Biol_26_453
Author(s) : Zhang Y , Yang B , Li J , Liu M , Liu Z
Ref : Insect Molecular Biology , 26 :453 , 2017
Abstract : Insecticide resistance frequently results from target-site insensitivity, such as point mutations in acetylcholinesterases (AChEs) for resistance to organophosphates and carbamates. From a field-originated population of Nilaparvata lugens, a major rice pest, a resistant population (R9) was obtained by nine-generation continuous selection with chlorpyrifos. From the same field population, a relatively susceptible population (S9) was also constructed through rearing without any insecticides. Compared to the susceptible strain, Sus [medium lethal dose (LC50 ) = 0.012 mg/l], R9 had a resistance ratio (RR) of 253.08-fold, whereas the RR of S9 was only 2.25-fold. Piperonyl butoxide and triphenyl phosphate synergized chlorpyrifos in R9 less than three-fold, indicating other important mechanisms for high resistance. The target-site insensitivity was supported by the key property differences of crude AChEs between R9 and S9. Compared to S9, three mutations (G119S, F331C and I332L) were detected in NlAChE1 from individuals of the R9 and field populations, but no mutation was detected in NlAChE2. G119S and F331C could decreased insecticide sensitivities in recombinant NlAChE1, whereas I332L took effect through increasing the influence of F331C on target insensitivity. F331C might be deleterious because of its influence on the catalytic efficiency of NlAChE1, whereas I332L would decrease these adverse effects and maintain the normal functions of AChEs.
ESTHER : Zhang_2017_Insect.Mol.Biol_26_453
PubMedSearch : Zhang_2017_Insect.Mol.Biol_26_453
PubMedID: 28407384

Title : Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice - Liu_2016_Brain.Res_1631_137
Author(s) : Liu C , Wu Y , Zha S , Liu M , Wang Y , Yang G , Ma K , Fei Y , Zhang Y , Hu X , Yang W , Qian Y
Ref : Brain Research , 1631 :137 , 2016
Abstract : Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by beta-amyloid protein (Abeta) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan IIA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus. Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD.
ESTHER : Liu_2016_Brain.Res_1631_137
PubMedSearch : Liu_2016_Brain.Res_1631_137
PubMedID: 26656068

Title : Cloning of two carboxylesterase cDNAs from the swimming crab Portunus trituberculatus: Molecular evidences for their putative roles in methyl farnesotae degradation - Tao_2016_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_203_100
Author(s) : Tao T , Xie X , Liu M , Jiang Q , Zhu D
Ref : Comparative Biochemistry & Physiology B Biochem Mol Biol , 203 :100 , 2016
Abstract : The sesquiterpenoid methyl farnesoate (MF) is the unepoxidized form of insect juvenile hormone (JH) III, and is considered an equivalent of JH in crustaceans. Degradation of MF is similar to that of JH which occurs through ester hydrolysis by specific carboxylesterases (CXEs). In this study, the full-length cDNAs of two JH esterase-like CXEs were cloned from the swimming crab, Portunus trituberculatus. The predicted amino acid sequences of the two PtCXEs contain the conserved motifs including catalytic triad and oxyanion hole, which are the hallmark of the CXE family proteins. The phylogenetic analysis showed that the two PtCXEs may belong to the hormone/semiochemical processing group of CXE family, indicating their possible roles on metabolism of hormones. Transcripts of both PtCXEs were most abundant in hepatopancreas and the PtCXE2 was also highly expressed in ovary. The mRNA levels of two PtCXEs in hepatopancreas were induced by in vivo MF treatment and eyestalk ablation, further indicating their potential in degrading MF. However, during the ovarian maturation, expression of the two PtCXEs increased significantly in the early-vitellogenic stage, prior to the remarkable rise in hemolymph MF titer reported by our previous studies. Taken together, our results suggest that the two PtCXEs can potentially serve as the MF esterases, but their catalytic activity may not be restricted to MF.
ESTHER : Tao_2016_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_203_100
PubMedSearch : Tao_2016_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_203_100
PubMedID: 27720728
Gene_locus related to this paper: portr-a0a1i9kj57 , portr-a0a1i9ky23

Title : Glutathione regulation-based dual-functional upconversion sensing-platform for acetylcholinesterase activity and cadmium ions - Fang_2016_Biosens.Bioelectron_87_545
Author(s) : Fang A , Chen H , Li H , Liu M , Zhang Y , Yao S
Ref : Biosensors & Bioelectronics , 87 :545 , 2016
Abstract : A dual-functional platform for the sensing of acetylcholinesterase (AChE) activity and cadmium ions (Cd2+) was developed based on the fluorescence resonance energy transfer (FRET) between NaYF4:Yb,Er upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) via glutathione regulation. The detection mechanism is based on the fact that AuNPs can quench the fluorescence of UCNPs. AChE catalyzes the hydrolysis of acetylthiocholine (ATC) into thiocholine which reacts with AuNPs by S-Au conjunction and results the aggregation of AuNPs and change in fluorescence of UCNPs. Therefore, the AChE activity can be detected through the changes of the color of solution and fluorescence recovery of UCNPs. However, the presence of glutathione (GSH) can protect AuNPs from aggregation and enlarge the inter-particle distance between AuNPs and UCNPs. When Cd2+ is added into the stable mixture of AuNPs, GSH and AChE/ATC, Cd2+ could interact with GSH to form a spherical shaped (GSH)4Cd complex, which decreases the free GSH on the surface of AuNPs to weaken the stability of AuNPs and lead to the easily aggregation of them in the system. The aggregated-AuNPs are released from the surface of UCNPs, which results in the fluorescence of UCNPs gradually recovered. Under the optimized conditions, the detection limits of AChE activity and Cd2+ are estimated to be 0.015mU/mL and 0.2microM, respectively. The small molecules regulated dual-functional platform based on UCNPs/AuNPs is a simple, label-free method and can be applied for the turn-on fluorescence detection of AChE activity in human serum and Cd2+ in real water samples. The present work demonstrates a general strategy for the design of small molecules regulated multifunctional platform and will be expanded for different areas in the future.
ESTHER : Fang_2016_Biosens.Bioelectron_87_545
PubMedSearch : Fang_2016_Biosens.Bioelectron_87_545
PubMedID: 27611473

Title : Serum vitamin D3 does not correlate with liver fibrosis in chronic hepatitis C - Ren_2015_World.J.Gastroenterol_21_11152
Author(s) : Ren Y , Liu M , Zhao J , Ren F , Chen Y , Li JF , Zhang JY , Qu F , Zhang JL , Duan ZP , Zheng SJ
Ref : World J Gastroenterol , 21 :11152 , 2015
Abstract : AIM: To investigate the relationship between serum vitamin D3 levels and liver fibrosis or inflammation in treatment-naive Chinese patients with chronic hepatitis C (CHC).
METHODS: From July 2010 to June 2011, we enrolled 122 CHC patients and 11 healthy controls from Dingxi city, Gansu Province, China. The patients were infected with Hepatitis C virus (HCV) during blood cell re-transfusion following plasma donation in 1992-1995, and had never received antiviral treatment. At present, all the patients except two underwent liver biopsy with ultrasound guidance. The Scheuer Scoring System was used to evaluate hepatic inflammation and the Metavir Scoring System was used to evaluate hepatic fibrosis. Twelve-hour overnight fasting blood samples were collected in the morning of the day of biopsy. Serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, cholinesterase, prothrombin activity, albumin, gamma-glutamyl transpeptidase, hemoglobin, calcium and phosphorus were determined. Serum HCV RNA levels were measured by real-time PCR. Serum levels of 25-hydroxyvitamin D3 [25(OH)D3] and 24,25-dihydroxyvitamin D3 [24,25(OH)2D3] were measured by high-performance liquid chromatography tandem mass spectrometry.
RESULTS: Serum levels of 25(OH)D3 but not 24,25(OH)2D3 were significantly lower in CHC patients than in control subjects. Serum 25(OH)D3 levels did not correlate with liver fibrosis, inflammation, patient age, or levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, prothrombin activity, cholinesterase or HCV RNA. However, serum 25(OH)D3 levels did correlate with serum 24,25(OH)2D3 levels. Serum 25(OH)D3 and 24,25(OH)2D3 levels, and the 25(OH)D3/24,25(OH)2D3 ratio, have no difference among the fibrosis stages or inflammation grades. CONCLUSION: We found that serum levels of 25(OH)D3 and its degradation metabolite 24,25(OH)2D3 did not correlate with liver fibrosis in treatment-naive Chinese patient with CHC.
ESTHER : Ren_2015_World.J.Gastroenterol_21_11152
PubMedSearch : Ren_2015_World.J.Gastroenterol_21_11152
PubMedID: 26494969

Title : New chemiluminescent substrates of paraoxonase 1 with improved specificity: synthesis and properties - Abulimite_2015_Appl.Biochem.Biotechnol_176_301
Author(s) : Abulimite Z , Mu X , Xiao S , Liu M , Li Q , Chen G
Ref : Appl Biochem Biotechnol , 176 :301 , 2015
Abstract : Paraoxonase 1 (PON1) is an important hydrolase, and the enzyme activity decreases in patients with liver disease, diabetes, coronary heart disease, etc. Phenyl acetate and organophosphates are usually employed as substrates for serum PON1 activity assay. However, phenyl acetate for arylesterase activity assay exhibits disadvantage of high background. According to properties of PON1, four new chemiluminescent acridinium esters were designed, prepared through three steps, and characterized with (1)H NMR and mass spectrometry (MS) data, and their properties as PON1 substrates were investigated. The hydrolyses of the four compounds catalyzed by recombinant human PON1 (rhPON1) (or serum) followed first-order kinetics within 22 min. The PON1 activator (NaCl, 0.10 mol L(-1)) could boost the rhPON1-mediated and serum-mediated hydrolyses of the acridinium esters to 2.01 ~ 2.26 folds, but 1.0 mol L(-1) NaCl decreased the serum arylesterase activity. RhPON1 showed selectivity over other serum esterases such as lipase, acetylcholinesterase, and esterase D more than 300 folds. By using ethylene diamine tetraacetic acid (EDTA) inhibitor, the specificities of the four substrates toward serum PON1 were determined as 78.3 ~ 92.9 %, which is improved than that of the model compound 9-(4-chloro-phenoxycarbonyl)-10-methylacridinium ester triflate. Due to low toxicity, high specificity, and sensitivity of the substrates, they are useful for serum PON1 activity assay.
ESTHER : Abulimite_2015_Appl.Biochem.Biotechnol_176_301
PubMedSearch : Abulimite_2015_Appl.Biochem.Biotechnol_176_301
PubMedID: 25809994

Title : MADD-4\/Punctin and Neurexin Organize C. elegans GABAergic Postsynapses through Neuroligin - Maro_2015_Neuron_86_1420
Author(s) : Maro GS , Gao S , Olechwier AM , Hung WL , Liu M , Ozkan E , Zhen M , Shen K
Ref : Neuron , 86 :1420 , 2015
Abstract : At synapses, the presynaptic release machinery is precisely juxtaposed to the postsynaptic neurotransmitter receptors. We studied the molecular mechanisms underlying this exquisite alignment at the C. elegans inhibitory synapses. We found that the sole C. elegans neuroligin homolog, NLG-1, localizes specifically at GABAergic postsynapses and is required for clustering the GABAA receptor UNC-49. Two presynaptic factors, Punctin/MADD-4, an ADAMTS-like extracellular protein, and neurexin/NRX-1, act partially redundantly to recruit NLG-1 to synapses. In the absence of both MADD-4 and NRX-1, NLG-1 and GABAA receptors fail to cluster, and GABAergic synaptic transmission is severely compromised. Biochemically, we detect an interaction between MADD-4 and NLG-1, as well as between MADD-4 and NRX-1. Interestingly, the presence of NRX-1 potentiates binding between Punctin/MADD-4 and NLG-1, suggestive of a tripartite receptor ligand complex. We propose that presynaptic terminals induce postsynaptic receptor clustering through the action of both secreted ECM proteins and trans-synaptic adhesion complexes.
ESTHER : Maro_2015_Neuron_86_1420
PubMedSearch : Maro_2015_Neuron_86_1420
PubMedID: 26028574
Gene_locus related to this paper: caeel-NLGN1

Title : Pullulan encapsulation of labile biomolecules to give stable bioassay tablets - Jahanshahi-Anbuhi_2014_Angew.Chem.Int.Ed.Engl_53_6155
Author(s) : Jahanshahi-Anbuhi S , Pennings K , Leung V , Liu M , Carrasquilla C , Kannan B , Li Y , Pelton R , Brennan JD , Filipe CD
Ref : Angew Chem Int Ed Engl , 53 :6155 , 2014
Abstract : A simple and inexpensive method is reported for the long-term stabilization of enzymes and other unstable reagents in premeasured quantities in water-soluble tablets (cast, not compressed) made with pullulan, a nonionic polysaccharide that forms an oxygen impermeable solid upon drying. The pullulan tablets dissolve in aqueous solutions in seconds, thereby facilitating the easy execution of bioassays at remote sites with no need for special reagent handling and liquid pipetting. This approach is modular in nature, thus allowing the creation of individual tablets for enzymes and their substrates. Proof-of-principle demonstrations include a Taq polymerase tablet for DNA amplification through PCR and a pesticide assay kit consisting of separate tablets for acetylcholinesterase and its chromogenic substrate, indoxyl acetate, both of which are highly unstable. The encapsulated reagents remain stable at room temperature for months, thus enabling the room-temperature shipping and storage of bioassay components.
ESTHER : Jahanshahi-Anbuhi_2014_Angew.Chem.Int.Ed.Engl_53_6155
PubMedSearch : Jahanshahi-Anbuhi_2014_Angew.Chem.Int.Ed.Engl_53_6155
PubMedID: 24764260

Title : Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs - Zhou_2014_Molecules_19_19718
Author(s) : Zhou M , Liu M , He X , Yu H , Wu D , Yao Y , Fan S , Zhang P , Shi W , Zhong B
Ref : Molecules , 19 :19718 , 2014
Abstract : In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC50 values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC50 values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo.
ESTHER : Zhou_2014_Molecules_19_19718
PubMedSearch : Zhou_2014_Molecules_19_19718
PubMedID: 25438082

Title : Sensitive detection of acetylcholine based on a novel boronate intramolecular charge transfer fluorescence probe - Liu_2014_Anal.Biochem_465C_172
Author(s) : Liu C , Shen Y , Yin P , Li L , Liu M , Zhang Y , Li H , Yao S
Ref : Analytical Biochemistry , 465C :172 , 2014
Abstract : A highly sensitive and selective fluorescence method for the detection of acetylcholine (ACh) based on enzyme-generated hydrogen peroxide (H2O2) and a new boronate intramolecular charge transfer (ICT) fluorescence probe, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-butyl-1,8-naphthalimide (BN), was developed. This strategy involves the reaction of ACh with acetylcholinesterase (AChE) to produce choline, which is further oxidized by choline oxidase (ChOx) to obtain betaine and H2O2. The enzyme-generated H2O2 reacts with BN and results in hydrolytic deprotection of BN to generate fluorescent product (4-hydroxyl-N-butyl-1,8-naphthalimide, ON). Two consecutive linear response ranges allow determining ACh in a wide concentration range with a low detection limit of 2.7nM (signal/noise=3). Compared with other fluorescent probes based on the mechanism of nonspecific oxidation, this reported boronate probe has the advantage of no interference from other biologically relevant reactive oxygen species (ROS) on the detection of ACh. This study provides a new method for the detection of ACh with high selectivity and sensitivity.
ESTHER : Liu_2014_Anal.Biochem_465C_172
PubMedSearch : Liu_2014_Anal.Biochem_465C_172
PubMedID: 25132563

Title : Establishment of a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins - Liu_2014_Acta.Pharm.Sin.B_4_135
Author(s) : Liu J , Huan Y , Li C , Liu M , Shen Z
Ref : Acta Pharm Sin B , 4 :135 , 2014
Abstract : Dipeptidyl peptidase 4 (DPP4) is recognised as an attractive anti-diabetic drug target, and several DPP4 inhibitors are already on the market. As members of the same gene family, dipeptidyl peptidase 8 (DPP8) and dipeptidyl peptidase 9 (DPP9) share high sequence and structural homology as well as functional activity with DPP4. However, the inhibition of their activities was reported to cause severe toxicities. Thus, the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy. To achieve this goal, we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells. In this method, we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system. The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL, respectively, and the corresponding concentrations of their substrates were both 0.2 mmol/L. This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates, which would provide valuable guidance in the development of safe DPP4 inhibitors.
ESTHER : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedSearch : Liu_2014_Acta.Pharm.Sin.B_4_135
PubMedID: 26579375

Title : Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats - Wang_2014_Toxicol.Appl.Pharmacol_280_169
Author(s) : Wang T , Zhao L , Liu M , Xie F , Ma X , Zhao P , Liu Y , Li J , Wang M , Yang Z , Zhang Y
Ref : Toxicol Appl Pharmacol , 280 :169 , 2014
Abstract : Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75mg/kg body weight (1/20 LD50) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity.
ESTHER : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedSearch : Wang_2014_Toxicol.Appl.Pharmacol_280_169
PubMedID: 24967689

Title : Ginsenoside Rg5 improves cognitive dysfunction and beta-amyloid deposition in STZ-induced memory impaired rats via attenuating neuroinflammatory responses - Chu_2014_Int.Immunopharmacol_19_317
Author(s) : Chu S , Gu J , Feng L , Liu J , Zhang M , Jia X , Liu M , Yao D
Ref : Int Immunopharmacol , 19 :317 , 2014
Abstract : Neuroinflammatory responses play a crucial role in the pathogenesis of Alzheimer's disease (AD). Ginsenoside Rg5 (Rg5), an abundant natural compound in Panax ginseng, has been found to be beneficial in treating AD. In the present study, we demonstrated that Rg5 improved cognitive dysfunction and attenuated neuroinflammatory responses in streptozotocin (STZ)-induced memory impaired rats. Cognitive deficits were ameliorated with Rg5 (5, 10 and 20mg/kg) treatment in a dose-dependent manner together with decreased levels of inflammatory cytokines TNF-alpha and IL-1beta (P<0.05) in brains of STZ rats. Acetylcholinesterase (AChE) activity was also significantly reduced by Rg5 whereas choline acetyltransferase (ChAT) activity was remarkably increased in the cortex and hippocampus of STZ-induced AD rats (P<0.05). In addition, Congo red and immunohistochemistry staining results showed that Rg5 alleviated Abeta deposition but enhanced the expressions of insulin-like growth factors 1 (IGF-1) and brain derived neurophic factor (BDNF) in the hippocampus and cerebral cortex (P<0.05). Western blot analysis also demonstrated that Rg5 increased remarkably BDNF and IGF-1 expressions whereas decreased significantly Abeta deposits (P<0.05). Furthermore, it was observed that the expressions of COX-2 and iNOS were significantly up-regulated in STZ-induced AD rats and down-regulated strongly (P<0.05) by Rg5 compared with control rats. These data demonstrated that STZ-induced learning and memory impairments in rats could be improved by Rg5, which was associated with attenuating neuroinflammatory responses. Our findings suggested that Rg5 could be a beneficial agent for the treatment of AD.
ESTHER : Chu_2014_Int.Immunopharmacol_19_317
PubMedSearch : Chu_2014_Int.Immunopharmacol_19_317
PubMedID: 24503167

Title : Strategies for prevention of postoperative delirium: a systematic review and meta-analysis of randomized trials - Zhang_2013_Crit.Care_17_R47
Author(s) : Zhang H , Lu Y , Liu M , Zou Z , Wang L , Xu FY , Shi XY
Ref : Crit Care , 17 :R47 , 2013
Abstract : INTRODUCTION: The ideal measures to prevent postoperative delirium remain unestablished. We conducted this systematic review and meta-analysis to clarify the significance of potential interventions.
METHODS: The PRISMA statement guidelines were followed. Two researchers searched MEDLINE, EMBASE, CINAHL and Cochrane Library for articles published in English before August 2012. Additional sources included reference lists from reviews and related articles from "Google Scholar". Randomized clinical trials (RCTs) on interventions seeking to prevent postoperative delirium in adult patients were included. Data extraction and methodological quality assessment were performed using predefined data fields and scoring system. Meta-analysis was accomplished for studies that used similar strategies. The primary outcome measure was the incidence of postoperative delirium. We further tested whether interventions effective in preventing postoperative delirium shortened the length of hospital stay.
RESULTS: We identified 38 RCTs with interventions ranging from perioperative managements to pharmacological, psychological or multicomponent interventions. Meta-analysis showed dexmedetomidine sedation was associated with less delirium compared to sedation produced by other drugs (2 RCTs with 415 patients, pooled risk ratio (RR) = 0.39; 95% confidence interval (CI) = 0.16-0.95). Both typical (3 RCTs with 965 patients, RR = 0.71; 95% CI = 0.54-0.93) and atypical antipsychotics (3 RCTs with 627 patients, RR = 0.36; 95% CI = 0.26-0.50) decreased delirium occurrence when compared to placebos. Multicomponent interventions (2 RCTs with 325 patients, RR = 0.71; 95% CI = 0.58-0.86) were effective in preventing delirium. No difference in the incidences of delirium was found between: neuraxial and general anesthesia (4 RCTs with 511 patients, RR = 0.99; 95% CI = 0.65-1.50); epidural and intravenous analgesia (3 RCTs with 167 patients, RR = 0.93; 95% CI = 0.61-1.43) or acetylcholinesterase inhibitors and placebo (4 RCTs with 242 patients, RR = 0.95; 95% CI = 0.63-1.44). Effective prevention of postoperative delirium did not shorten the length of hospital stay (10 RCTs with 1636 patients, pooled SMD (standard mean difference) = -0.06; 95% CI = -0.16-0.04).
CONCLUSIONS: The included studies showed great inconsistencies in denition, incidence, severity and duration of postoperative delirium. Meta-analysis supported dexmedetomidine sedation, multicomponent interventions and antipsychotics were useful in preventing postoperative delirium.
ESTHER : Zhang_2013_Crit.Care_17_R47
PubMedSearch : Zhang_2013_Crit.Care_17_R47
PubMedID: 23506796

Title : Plant-symbiotic fungi as chemical engineers: multi-genome analysis of the clavicipitaceae reveals dynamics of alkaloid loci - Schardl_2013_PLoS.Genet_9_e1003323
Author(s) : Schardl CL , Young CA , Hesse U , Amyotte SG , Andreeva K , Calie PJ , Fleetwood DJ , Haws DC , Moore N , Oeser B , Panaccione DG , Schweri KK , Voisey CR , Farman ML , Jaromczyk JW , Roe BA , O'Sullivan DM , Scott B , Tudzynski P , An Z , Arnaoudova EG , Bullock CT , Charlton ND , Chen L , Cox M , Dinkins RD , Florea S , Glenn AE , Gordon A , Guldener U , Harris DR , Hollin W , Jaromczyk J , Johnson RD , Khan AK , Leistner E , Leuchtmann A , Li C , Liu J , Liu M , Mace W , Machado C , Nagabhyru P , Pan J , Schmid J , Sugawara K , Steiner U , Takach JE , Tanaka E , Webb JS , Wilson EV , Wiseman JL , Yoshida R , Zeng Z
Ref : PLoS Genet , 9 :e1003323 , 2013
Abstract : The fungal family Clavicipitaceae includes plant symbionts and parasites that produce several psychoactive and bioprotective alkaloids. The family includes grass symbionts in the epichloae clade (Epichloe and Neotyphodium species), which are extraordinarily diverse both in their host interactions and in their alkaloid profiles. Epichloae produce alkaloids of four distinct classes, all of which deter insects, and some-including the infamous ergot alkaloids-have potent effects on mammals. The exceptional chemotypic diversity of the epichloae may relate to their broad range of host interactions, whereby some are pathogenic and contagious, others are mutualistic and vertically transmitted (seed-borne), and still others vary in pathogenic or mutualistic behavior. We profiled the alkaloids and sequenced the genomes of 10 epichloae, three ergot fungi (Claviceps species), a morning-glory symbiont (Periglandula ipomoeae), and a bamboo pathogen (Aciculosporium take), and compared the gene clusters for four classes of alkaloids. Results indicated a strong tendency for alkaloid loci to have conserved cores that specify the skeleton structures and peripheral genes that determine chemical variations that are known to affect their pharmacological specificities. Generally, gene locations in cluster peripheries positioned them near to transposon-derived, AT-rich repeat blocks, which were probably involved in gene losses, duplications, and neofunctionalizations. The alkaloid loci in the epichloae had unusual structures riddled with large, complex, and dynamic repeat blocks. This feature was not reflective of overall differences in repeat contents in the genomes, nor was it characteristic of most other specialized metabolism loci. The organization and dynamics of alkaloid loci and abundant repeat blocks in the epichloae suggested that these fungi are under selection for alkaloid diversification. We suggest that such selection is related to the variable life histories of the epichloae, their protective roles as symbionts, and their associations with the highly speciose and ecologically diverse cool-season grasses.
ESTHER : Schardl_2013_PLoS.Genet_9_e1003323
PubMedSearch : Schardl_2013_PLoS.Genet_9_e1003323
PubMedID: 23468653
Gene_locus related to this paper: clap2-m1w2a8 , clap2-m1w555 , clap2-m1wa31 , clap2-m1whd2 , clap2-m1weh2 , clap2-m1w5y7 , clap2-m1wh11 , clap2-m1vyn7 , clap2-m1w670

Title : Dominant protein interactions that influence the pathogenesis of conformational diseases - Wright_2013_J.Clin.Invest_123_3124
Author(s) : Wright J , Wang X , Haataja L , Kellogg AP , Lee J , Liu M , Arvan P
Ref : J Clinical Investigation , 123 :3124 , 2013
Abstract : Misfolding of exportable proteins can trigger endocrinopathies. For example, misfolding of insulin can result in autosomal dominant mutant INS gene-induced diabetes of youth, and misfolding of thyroglobulin can result in autosomal recessive congenital hypothyroidism with deficient thyroglobulin. Both proinsulin and thyroglobulin normally form homodimers; the mutant versions of both proteins misfold in the ER, triggering ER stress, and, in both cases, heterozygosity creates potential for cross-dimerization between mutant and WT gene products. Here, we investigated these two ER-retained mutant secretory proteins and the selectivity of their interactions with their respective WT counterparts. In both cases and in animal models of these diseases, we found that conditions favoring an increased stoichiometry of mutant gene product dominantly inhibited export of the WT partner, while increased relative level of the WT gene product helped to rescue secretion of the mutant partner. Surprisingly, the bidirectional consequences of secretory blockade and rescue occur simultaneously in the same cells. Thus, in the context of heterozygosity, expression level and stability of WT subunits may be a critical factor influencing the effect of protein misfolding on clinical phenotype. These results offer new insight into dominant as well as recessive inheritance of conformational diseases and offer opportunities for the development of new therapies.
ESTHER : Wright_2013_J.Clin.Invest_123_3124
PubMedSearch : Wright_2013_J.Clin.Invest_123_3124
PubMedID: 23722904

Title : The anti-inflammatory effect of donepezil on experimental autoimmune encephalomyelitis in C57 BL\/6 mice - Jiang_2013_Neuropharmacol_73C_415
Author(s) : Jiang Y , Zou Y , Chen S , Zhu C , Wu A , Liu Y , Ma L , Zhu D , Ma X , Liu M , Kang Z , Pi R , Peng F , Wang Q , Chen X
Ref : Neuropharmacology , 73C :415 , 2013
Abstract : Donepezil is a potent and selective acetylcholinesterase inhibitor. It has been reported to restore cognitive performance in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) mice, an established model of MS. However, there are no reports about the anti-inflammatory effects of donepezil on EAE. In this study, the donepezil treatments on EAE mice were initiated at day 7 post immunization (7 p.i., subclinical periods, early donepezil treatment) and day 13 p.i. (clinical periods, late donepezil treatment) with the dosage of 1, 2 and 4 mg/kg/d respectively and the treatments persisted throughout the experiments. Blood-brain barrier (BBB) permeability was detected by Evan's blue content, the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9, Akt and phosphorylated Akt (p-Akt) as well as nerve growth factor (NGF) and its precursor form (proNGF) in the brains of EAE mice were detected by Western blot, and the levels of interferon-gamma and interleukin-4 in the splenocytes culture supernatants and brains of EAE mice were evaluated by ELISA. The results showed that the 2 mg/kg/d late donepezil treatment was the optimal dosage and could ameliorate clinical and pathological parameters, improve magnetic resonance imaging outcomes, reduce the permeability of BBB, inhibit the production of MMP-2 and MMP-9, modulate the expression of NGF and proNGF, increase Th2 bias and the phosphorylation of Akt in the brains of EAE mice. Our data suggested that the anti-inflammatory effects of donepezil may be a novel mechanism on treating EAE and provided further insights to understand the donepezil's neuroprotective activities in MS.
ESTHER : Jiang_2013_Neuropharmacol_73C_415
PubMedSearch : Jiang_2013_Neuropharmacol_73C_415
PubMedID: 23831366

Title : Propionibacterium acnes strain populations in the human skin microbiome associated with acne - Fitz-Gibbon_2013_J.Invest.Dermatol_133_2152
Author(s) : Fitz-Gibbon S , Tomida S , Chiu BH , Nguyen L , Du C , Liu M , Elashoff D , Erfe MC , Loncaric A , Kim J , Modlin RL , Miller JF , Sodergren E , Craft N , Weinstock GM , Li H
Ref : Journal of Investigative Dermatology , 133 :2152 , 2013
Abstract : The human skin microbiome has important roles in skin health and disease. However, bacterial population structure and diversity at the strain level is poorly understood. We compared the skin microbiome at the strain level and genome level of Propionibacterium acnes, a dominant skin commensal, between 49 acne patients and 52 healthy individuals by sampling the pilosebaceous units on their noses. Metagenomic analysis demonstrated that although the relative abundances of P. acnes were similar, the strain population structures were significantly different in the two cohorts. Certain strains were highly associated with acne, and other strains were enriched in healthy skin. By sequencing 66 previously unreported P. acnes strains and comparing 71 P. acnes genomes, we identified potential genetic determinants of various P. acnes strains in association with acne or health. Our analysis suggests that acquired DNA sequences and bacterial immune elements may have roles in determining virulence properties of P. acnes strains, and some could be future targets for therapeutic interventions. This study demonstrates a previously unreported paradigm of commensal strain populations that could explain the pathogenesis of human diseases. It underscores the importance of strain-level analysis of the human microbiome to define the role of commensals in health and disease.
ESTHER : Fitz-Gibbon_2013_J.Invest.Dermatol_133_2152
PubMedSearch : Fitz-Gibbon_2013_J.Invest.Dermatol_133_2152
PubMedID: 23337890
Gene_locus related to this paper: proac-q6a5t3 , proac-q6a981

Title : Harnessing single cell sorting to identify cell division genes and regulators in bacteria - Burke_2013_PLoS.One_8_e60964
Author(s) : Burke C , Liu M , Britton W , Triccas JA , Thomas T , Smith AL , Allen S , Salomon R , Harry E
Ref : PLoS ONE , 8 :e60964 , 2013
Abstract : Cell division is an essential cellular process that requires an array of known and unknown proteins for its spatial and temporal regulation. Here we develop a novel, high-throughput screening method for the identification of bacterial cell division genes and regulators. The method combines the over-expression of a shotgun genomic expression library to perturb the cell division process with high-throughput flow cytometry sorting to screen many thousands of clones. Using this approach, we recovered clones with a filamentous morphology for the model bacterium, Escherichia coli. Genetic analysis revealed that our screen identified both known cell division genes, and genes that have not previously been identified to be involved in cell division. This novel screening strategy is applicable to a wide range of organisms, including pathogenic bacteria, where cell division genes and regulators are attractive drug targets for antibiotic development.
ESTHER : Burke_2013_PLoS.One_8_e60964
PubMedSearch : Burke_2013_PLoS.One_8_e60964
PubMedID: 23565292
Gene_locus related to this paper: ecoli-ycjy

Title : An oligopeptide ligand-mediated therapeutic gene nanocomplex for liver cancer-targeted therapy - Liu_2012_Biomaterials_33_2240
Author(s) : Liu M , Li ZH , Xu FJ , Lai LH , Wang QQ , Tang GP , Yang WT
Ref : Biomaterials , 33 :2240 , 2012
Abstract : The epidermal growth factor receptor (EGFR) is over-expressed in a wide variety of epithelial-derived cancer cells. In this study, EGFR-targeted gene carriers were designed to complex the therapeutic acetylcholinesterase gene (AChE gene), which suppresses cell proliferation via inactivating mitogen-activated protein kinase and PI3K/Akt pathways in cells, for treatment of EGFR-positive liver cancers. Different amounts of target ligand YC21 (an oligopeptide composed of 21 amino acid units) were coupled with the PEI(600)-CD (PC) vectors composed of beta-cyclodextrin (beta-CD) and low-molecular-weight polyethylenimine (PEI, Mw 600) to form the EGFR-targeted gene vectors (termed as YPCs). The YPC vectors possessed the highly efficient gene delivery ability to the EGFR-positive liver cancer cells. YPCs could effectively promote AChE gene expression. The YPC/AChE complexes produced excellent gene transfection abilities in EGFR-positive liver cancer cells in vitro and in vivo.
ESTHER : Liu_2012_Biomaterials_33_2240
PubMedSearch : Liu_2012_Biomaterials_33_2240
PubMedID: 22177837

Title : [Effect of Kaixin San on learning and memory in chronic stress depression model rats] - Liu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2439
Author(s) : Liu M , Yan J , Zhou X , Hu Y , Liu P
Ref : Zhongguo Zhong Yao Za Zhi , 37 :2439 , 2012
Abstract : OBJECTIVE: To study the effect of classic ancient prescription Kaixin San (KXS) on learning and memory abilities in chronic stress depression model rats and its possible mechanisms. METHOD: Rats were randomly assigned to six groups: the control group, the model group, the positive drug group (fluoxetine 10 mg x kg(-1)) and KXS groups (1000, 500, 250, 125 mg x kg(-1)). KXS were orally administrated to CMS rats for 21 days. The anti-depression activity of KXS was assessed using the sucrose consumption and the open-field test. The protecting effect for learning and memory abilities was assessed using the Morris water maze (MWM) test. Furthermore, the levels of monoamine neurotransmitters, acetylcholine (Ach) and acetyl cholinesterase (AchE) in the total brain and brain-derived neurotrophic factor (BDNF) protein in the hippocampus were determined. RESULT: The behavior test showed that KXS significantly increased the sucrose consumption and total distance in the open-field test and notably reduce the incubation period of location and navigation in the MWM test. It could also help increase the number of times passing through the platform, the swimming distance and time in quadrant of original platform, the levels of serotonin (5-HT) and dopamine (DA) , noradrenergic (NE), Ach, BDNF protein and reduce the level of AchE in the CMS-induced rats. CONCLUSION: KXS can ameliorate the CMS-induced depression behavior in rats and improved their learning and memory abilities, which may be related to the increase in monoamine neurotransmitters, Ach and BDNF levels.
ESTHER : Liu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2439
PubMedSearch : Liu_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2439
PubMedID: 23234145

Title : CGI-58\/ABHD5-derived signaling lipids regulate systemic inflammation and insulin action - Lord_2012_Diabetes_61_355
Author(s) : Lord CC , Betters JL , Ivanova PT , Milne SB , Myers DS , Madenspacher J , Thomas G , Chung S , Liu M , Davis MA , Lee RG , Crooke RM , Graham MJ , Parks JS , Brasaemle DL , Fessler MB , Brown HA , Brown JM
Ref : Diabetes , 61 :355 , 2012
Abstract : Mutations of comparative gene identification 58 (CGI-58) in humans cause Chanarin-Dorfman syndrome, a rare autosomal recessive disease in which excess triacylglycerol (TAG) accumulates in multiple tissues. CGI-58 recently has been ascribed two distinct biochemical activities, including coactivation of adipose triglyceride lipase and acylation of lysophosphatidic acid (LPA). It is noteworthy that both the substrate (LPA) and the product (phosphatidic acid) of the LPA acyltransferase reaction are well-known signaling lipids. Therefore, we hypothesized that CGI-58 is involved in generating lipid mediators that regulate TAG metabolism and insulin sensitivity. Here, we show that CGI-58 is required for the generation of signaling lipids in response to inflammatory stimuli and that lipid second messengers generated by CGI-58 play a critical role in maintaining the balance between inflammation and insulin action. Furthermore, we show that CGI-58 is necessary for maximal TH1 cytokine signaling in the liver. This novel role for CGI-58 in cytokine signaling may explain why diminished CGI-58 expression causes severe hepatic lipid accumulation yet paradoxically improves hepatic insulin action. Collectively, these findings establish that CGI-58 provides a novel source of signaling lipids. These findings contribute insight into the basic mechanisms linking TH1 cytokine signaling to nutrient metabolism.
ESTHER : Lord_2012_Diabetes_61_355
PubMedSearch : Lord_2012_Diabetes_61_355
PubMedID: 22228714
Gene_locus related to this paper: human-ABHD5

Title : Tacrine-ferulic acid-nitric oxide (NO) donor trihybrids as potent, multifunctional acetyl- and butyrylcholinesterase inhibitors - Chen_2012_J.Med.Chem_55_4309
Author(s) : Chen Y , Sun J , Fang L , Liu M , Peng S , Liao H , Lehmann J , Zhang Y
Ref : Journal of Medicinal Chemistry , 55 :4309 , 2012
Abstract : In search of multifunctional cholinesterase inhibitors as potential anti-Alzheimer drug candidates, tacrine-ferulic acid-NO donor trihybrids were synthesized and tested for their cholinesterase inhibitory activities, release of nitric oxide, vasodilator properties, cognition improving potency, and hepatotoxicity. All of the novel target compounds show higher in vitro cholinesterase inhibitory activity than tacrine. Three selected compounds (3a, 3f, and 3k) produce moderate vasorelaxation in vitro, which correlates with the release of nitric oxide. Compared to its non-nitrate dihybrid analogue (3u), the trihybrid 3f exhibits better performance in improving the scopolamine-induced cognition impairment (mice) and, furthermore, less hepatotoxicity than tacrine.
ESTHER : Chen_2012_J.Med.Chem_55_4309
PubMedSearch : Chen_2012_J.Med.Chem_55_4309
PubMedID: 22512543

Title : Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-beta-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo - Pi_2012_PLoS.One_7_e31921
Author(s) : Pi R , Mao X , Chao X , Cheng Z , Liu M , Duan X , Ye M , Chen X , Mei Z , Liu P , Li W , Han Y
Ref : PLoS ONE , 7 :e31921 , 2012
Abstract : We have previously synthesized a series of hybrid compounds by linking ferulic acid to tacrine as multifunctional agents based on the hypotheses that Alzheimer's disease (AD) generates cholinergic deficiency and oxidative stress. Interestingly, we found that they may have potential pharmacological activities for treating AD. Here we report for the first time that tacrine-6-ferulic acid (T6FA), one of these compounds, can prevent amyloid-beta peptide (Abeta)-induced AD-associated pathological changes in vitro and in vivo. Our results showed that T6FA significantly inhibited auto- and acetylcholinesterase (AChE)-induced aggregation of Abeta(1-40)in vitro and blocked the cell death induced by Abeta(1-40) in PC12 cells. In an AD mouse model by the intracerebroventricular injection of Abeta(1-40), T6FA significantly improved the cognitive ability along with increasing choline acetyltransferase and superoxide dismutase activity, decreasing AChE activity and malondialdehyde level. Based on our findings, we conclude that T6FA may be a promising multifunctional drug candidate for AD.
ESTHER : Pi_2012_PLoS.One_7_e31921
PubMedSearch : Pi_2012_PLoS.One_7_e31921
PubMedID: 22384101

Title : Genome sequence of Mycoplasma iowae strain 695, an unusual pathogen causing deaths in turkeys - Wei_2012_J.Bacteriol_194_547
Author(s) : Wei S , Guo Z , Li T , Zhang T , Li X , Zhou Z , Li Z , Liu M , Luo R , Bi D , Chen H , Zhou R , Jin H
Ref : Journal of Bacteriology , 194 :547 , 2012
Abstract : Mycoplasma iowae is associated mainly with reduced hatchability in turkeys and is well known for the unusual ability of phenotypic variation in the Mycoplasma surface components as well as a relative resistance to heat, bile salts, and many antimicrobials. A subset of unique genes and a gene cluster responsible for these characteristics could be identified from the genome. Here, we report the first genome sequence of this species.
ESTHER : Wei_2012_J.Bacteriol_194_547
PubMedSearch : Wei_2012_J.Bacteriol_194_547
PubMedID: 22207750

Title : Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens - Park_2012_BMC.Genomics_13_545
Author(s) : Park J , Zhang Y , Buboltz AM , Zhang X , Schuster SC , Ahuja U , Liu M , Miller JF , Sebaihia M , Bentley SD , Parkhill J , Harvill ET
Ref : BMC Genomics , 13 :545 , 2012
Abstract : BACKGROUND: The classical Bordetella subspecies are phylogenetically closely related, yet differ in some of the most interesting and important characteristics of pathogens, such as host range, virulence and persistence. The compelling picture from previous comparisons of the three sequenced genomes was of genome degradation, with substantial loss of genome content (up to 24%) associated with adaptation to humans.
RESULTS: For a more comprehensive picture of lineage evolution, we employed comparative genomic and phylogenomic analyses using seven additional diverse, newly sequenced Bordetella isolates. Genome-wide single nucleotide polymorphism (SNP) analysis supports a reevaluation of the phylogenetic relationships between the classical Bordetella subspecies, and suggests a closer link between ovine and human B. parapertussis lineages than has been previously proposed. Comparative analyses of genome content revealed that only 50% of the pan-genome is conserved in all strains, reflecting substantial diversity of genome content in these closely related pathogens that may relate to their different host ranges, virulence and persistence characteristics. Strikingly, these analyses suggest possible horizontal gene transfer (HGT) events in multiple loci encoding virulence factors, including O-antigen and pertussis toxin (Ptx). Segments of the pertussis toxin locus (ptx) and its secretion system locus (ptl) appear to have been acquired by the classical Bordetella subspecies and are divergent in different lineages, suggesting functional divergence in the classical Bordetellae.
CONCLUSIONS: Together, these observations, especially in key virulence factors, reveal that multiple mechanisms, such as point mutations, gain or loss of genes, as well as HGTs, contribute to the substantial phenotypic diversity of these versatile subspecies in various hosts.
ESTHER : Park_2012_BMC.Genomics_13_545
PubMedSearch : Park_2012_BMC.Genomics_13_545
PubMedID: 23051057
Gene_locus related to this paper: borbr-BB0273

Title : Genome sequence of duck pathogen Mycoplasma anatis strain 1340 - Guo_2011_J.Bacteriol_193_5883
Author(s) : Guo Z , Chen P , Ren P , Kuang S , Zhou Z , Li Z , Liu M , Shi D , Xiao Y , Wang X , Zhou R , Jin H , Bi D
Ref : Journal of Bacteriology , 193 :5883 , 2011
Abstract : Mycoplasma anatis, a member of the class Mollicutes, is the causative agent of a contagious infectious disease of domestic ducklings, wild birds, and eggs. Increasing reports show that coinfection of M. anatis with Escherichia coli results in substantial economic impacts on the duck farms in China. Here, we announce the first genome sequence of M. anatis.
ESTHER : Guo_2011_J.Bacteriol_193_5883
PubMedSearch : Guo_2011_J.Bacteriol_193_5883
PubMedID: 21952548

Title : Genome sequence of poultry pathogen Riemerella anatipestifer strain RA-YM - Zhou_2011_J.Bacteriol_193_1284
Author(s) : Zhou Z , Peng X , Xiao Y , Wang X , Guo Z , Zhu L , Liu M , Jin H , Bi D , Li Z , Sun M
Ref : Journal of Bacteriology , 193 :1284 , 2011
Abstract : Riemerella anatipestifer is a Gram-negative, rod-shaped bacterium associated with epizootic infections in poultry. R. anatipestifer strain RA-YM, belonging to the serotype 1 prevalent in China, is a clinically isolated strain with high-level virulence. Here, we report the first genome sequence of this species.
ESTHER : Zhou_2011_J.Bacteriol_193_1284
PubMedSearch : Zhou_2011_J.Bacteriol_193_1284
PubMedID: 21183670
Gene_locus related to this paper: riean-e6jgw6 , riean-e6jh69 , riean-e6jim0

Title : Genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiPoco6, ReqiPine5, and ReqiDocB7 - Summer_2011_Appl.Environ.Microbiol_77_669
Author(s) : Summer EJ , Liu M , Gill JJ , Grant M , Chan-Cortes TN , Ferguson L , Janes C , Lange K , Bertoli M , Moore C , Orchard RC , Cohen ND , Young R
Ref : Applied Environmental Microbiology , 77 :669 , 2011
Abstract : The isolation and results of genomic and functional analyses of Rhodococcus equi phages ReqiPepy6, ReqiDocB7, ReqiPine5, and ReqiPoco6 (hereafter referred to as Pepy6, DocB7, Pine5, and Poco6, respectively) are reported. Two phages, Pepy6 and Poco6, more than 75% identical, exhibited genome organization and protein sequence likeness to Lactococcus lactis phage 1706 and clostridial prophage elements. An unusually high fraction, 27%, of Pepy6 and Poco6 proteins were predicted to possess at least one transmembrane domain, a value much higher than the average of 8.5% transmembrane domain-containing proteins determined from a data set of 36,324 phage protein entries. Genome organization and protein sequence comparisons place phage Pine5 as the first nonmycobacteriophage member of the large Rosebush cluster. DocB7, which had the broadest host range among the four isolates, was not closely related to any phage or prophage in the database, and only 23 of 105 predicted encoded proteins could be assigned a functional annotation. Because of the relationship of Rhodococcus to Mycobacterium, it was anticipated that these phages should exhibit some of the features characteristic of mycobacteriophages. Traits that were identified as shared by the Rhodococcus phages and mycobacteriophages include the prevalent long-tailed morphology and the presence of genes encoding LysB-like mycolate-hydrolyzing lysis proteins. Application of DocB7 lysates to soils amended with a host strain of R. equi reduced recoverable bacterial CFU, suggesting that phage may be useful in limiting R. equi load in the environment while foals are susceptible to infection.
ESTHER : Summer_2011_Appl.Environ.Microbiol_77_669
PubMedSearch : Summer_2011_Appl.Environ.Microbiol_77_669
PubMedID: 21097585
Gene_locus related to this paper: 9caud-d4p744

Title : Microsomal epoxide hydrolase deletion enhances tyrosine hydroxylase phosphorylation in mice after MPTP treatment - Liu_2008_J.Neurosci.Res_86_2792
Author(s) : Liu M , Hunter R , Nguyen XV , Kim HC , Bing G
Ref : Journal of Neuroscience Research , 86 :2792 , 2008
Abstract : Parkinson's disease (PD) is the most prevalent neurodegenerative movement disorder. Epidemiological studies have suggested most cases of PD are linked to environmental risk factors. Microsomal epoxide hydrolase (mEH) is a conserved enzyme that catalyzes hydrolysis of a large number of epoxide intermediates such as drugs and epoxides of environmental toxins. We hypothesize that changes in mEH are involved in the pathogenesis of PD by modulating the vulnerability of dopaminergic neurons to environmental stress. Herein we reported that acute treatment with the neurotoxin MPTP (1-methyl-4-phemyl-1,2,3,6-tetrahydropyridine) markedly increased the mEH immunoreactivity in the nigrostriatal system of C57BL/6 mice. Next, mEH knockout (KO) mice were used, and we found that tyrosine hydroxylase (TH)-positive cell loss was significantly lower in the substantia nigra of mEH KO mice compared with wild-type (WT) mice after MPTP treatment. The mean dopamine turnover ratios were significantly increased in MPTP-treated mEH KO mice compared with WT. In addition, TH is the rate-limiting enzyme for dopamine biosynthesis, and its activity is mainly regulated by TH phosphorylation at Ser-31 (pSer31) and Ser-40 (pSer40). Double immunofluorescence showed that both pSer31 and pSer40 are completely colocalized in total TH-positive cells. However, immunoblotting confirmed that there was a significantly higher level of pSer31 in mEH-KO mice when compared with WT mice after MPTP, and no marked differences among TH and its phosphorylation levels occurred after saline injection. These data suggested that mEH deficiency facilitates TH phosphorylation in the nigrostriatal dopamine system, which may be associated with an increased resistance of dopaminergic neurons to environmental toxins.
ESTHER : Liu_2008_J.Neurosci.Res_86_2792
PubMedSearch : Liu_2008_J.Neurosci.Res_86_2792
PubMedID: 18500758

Title : Esterase SeE of Streptococcus equi ssp. equi is a novel nonspecific carboxylic ester hydrolase - Xie_2008_FEMS.Microbiol.Lett_289_181
Author(s) : Xie G , Liu M , Zhu H , Lei B
Ref : FEMS Microbiology Letters , 289 :181 , 2008
Abstract : Extracellular carboxylic ester hydrolases are produced by many bacterial pathogens and have been shown recently to be important for virulence of some pathogens. However, these hydrolases are poorly characterized in enzymatic activity. This study prepared and characterized the secreted ester hydrolase of Streptococcus equi ssp. equi (designated SeE for S. equi esterase). SeE hydrolyzes ethyl acetate, acetylsalicylic acid, and tributyrin but not ethyl butyrate. This substrate specificity pattern does not match those of the three conventional types of nonspecific carboxylic ester hydrolases (carboxylesterases, arylesterases, and acetylesterases). To determine whether SeE has lipase activity, a number of triglycerides and vinyl esters were tested in SeE-catalyzed hydrolysis. SeE does not hydrolyze triglycerides and vinyl esters of long-chain carboxylic acids nor display interfacial activation, indicating that SeE is not a lipase. Like the conventional carboxylesterases, SeE is inhibited by di-isopropylfluorophosphate. These findings indicate that SeE is a novel carboxylesterase with optimal activity for acetyl esters.
ESTHER : Xie_2008_FEMS.Microbiol.Lett_289_181
PubMedSearch : Xie_2008_FEMS.Microbiol.Lett_289_181
PubMedID: 19054107

Title : Investigation of differentially expressed proteins in rat gastrocnemius muscle during denervation-reinnervation - Sun_2006_J.Muscle.Res.Cell.Motil_27_241
Author(s) : Sun H , Liu J , Ding F , Wang X , Liu M , Gu X
Ref : J Muscle Res Cell Motil , 27 :241 , 2006
Abstract : To have a better insight into the molecular events involved in denervation-induced atrophy and reinnervation-induced regeneration of skeletal muscles, it is important to investigate the changes in expression levels of a great multitude of muscle proteins during the process of denervation-reinnervation. In this study, we employed an experimental model of rat sciatic nerve crush to examine the differentially expressed proteins in the rat gastrocnemius muscle at different time points (0, 1, 2, 3, 4 weeks) after sciatic nerve crush by using two-dimensional gel electrophoresis (2-DE) followed by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS), collectively referred to as the modern proteomic analysis. The results showed that 16 proteins in the rat gastrocnemius muscle exhibited two distinct types of change pattern in their relative abundance: (1) The relative expression levels of 11 proteins (including alpha actin, myosin heavy chain, etc.) were decreased either within 1 or 2 weeks post-sciatic nerve injury, followed by restoration during the ensuing days until 4 weeks. (2) The other 5 proteins (including alpha enolase, beta enolase, signal peptide peptidase-like 3, etc.) displayed an up-regulation in their relative expression levels within 1 week following sciatic nerve injury, and a subsequent gradual decrease in their relative expression levels until 4 weeks. Moreover, the significance of the changes in expression levels of the 16 proteins during denervation-reinnervation has been selectively discussed.
ESTHER : Sun_2006_J.Muscle.Res.Cell.Motil_27_241
PubMedSearch : Sun_2006_J.Muscle.Res.Cell.Motil_27_241
PubMedID: 16752196

Title : Inhibitory effect of tellimagrandin I on chemically induced differentiation of human leukemia K562 cells - Yi_2004_Toxicol.Lett_147_109
Author(s) : Yi Z , Wang Z , Li H , Liu M
Ref : Toxicol Lett , 147 :109 , 2004
Abstract : Tellimagrandin I is a hydrolysable tannin compound widely present in plants. In this study, the effect of tellimagrandin I on chemically induced erythroid and megakaryocytic differentiation was investigated using K562 cells as differentiation model. It was found that tellimagrandin I not only inhibited the hemoglobin synthesis in butyric acid (BA)- and hemin-induced K562 cells with IC50 of 3 and 40microM, respectively, but also inhibited other erythroid differentiation marker including acetylcholinesterase (AChE) and glycophorin A (GPA) in BA-induced K562 cells. Tellimagrandin I also inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced expression of CD61 protein, a megakaryocytic marker. RT-PCR analysis showed that tellimagrandin I decreased the expression of erythroid genes (gamma-globin and porphobilinogen deaminase (PBGD)) and related transcription factors (GATA-1 and NF-E2) in BA-induced K562 cells, whereas tellimagrandin I induced the overexpresison of GATA-2 transcription factor that played negative regulation on erythroid differentiation. These results indicated that tellimagrandin I had inhibitory effects on erythroid and megakaryocytic differentiation, which suggested that tannins like tellimagrandin I might influence the anti-tumor efficiency of some drugs and the hematopoiesis processes.
ESTHER : Yi_2004_Toxicol.Lett_147_109
PubMedSearch : Yi_2004_Toxicol.Lett_147_109
PubMedID: 14757314

Title : Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation - Goyal_1997_J.Biol.Chem_272_16231
Author(s) : Goyal J , Wang K , Liu M , Subbaiah PV
Ref : Journal of Biological Chemistry , 272 :16231 , 1997
Abstract : Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.
ESTHER : Goyal_1997_J.Biol.Chem_272_16231
PubMedSearch : Goyal_1997_J.Biol.Chem_272_16231
PubMedID: 9195924