Wu W

References (53)

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Mechanisms of biochar assisted di-2-ethylhexyl phthalate (DEHP) biodegradation in tomato rhizosphere by metabolic and metagenomic analysis - Lin_2024_Chemosphere__141520
Author(s) : Lin Z , Wu W , Yang C , Yang G , Wei T , Huang F , Li H , Ren L , Liang Y , Zhang D , Li Z , Zhen Z
Ref : Chemosphere , :141520 , 2024
Abstract : The intensive accumulation of di-2-ethylhexyl phthalate (DEHP) in agricultural soils has resulted in severe environmental pollution that endangers ecosystem and human health. Biochar is an eco-friendly material that can help in accelerating organic pollutant degradation; nevertheless, its roles in enhancing DEHP removal in rhizosphere remain unclear. This work investigated the impacts of biochar dosage (0%-2.0%) on DEHP degradation performance in tomato rhizosphere by comprehensively exploring the change in DEHP metabolites, bacterial communities and DEHP-degrading genes. Our results showed a significant increase of rhizosphere pH, organic matter and humus by biochar amendment, which achieved a satisfactorily higher DEHP removal efficiency, maximally 77.53% in treatments with 1.0% of biochar. Biochar addition also remarkably changed rhizosphere bacterial communities by enriching some potential DEHP degraders of Nocardioides, Sphingomonas, Bradyrhizobium and Rhodanobacter. The abundance of genes encoding key enzymes (hydrolase, esterase and cytochrome P450) and DEHP-degrading genes (pht3, pht4, pht5, benC-xylZ and benD-xylL) were increased after biochar amendment, leading to the change in DEHP degradation metabolism, primarily from benzoic acid pathway to protocatechuic acid pathway. Our findings evidenced that biochar amendment could accelerate DEHP degradation by altering rhizosphere soil physicochemical variables, bacterial community composition and metabolic genes, providing clues for the mechanisms of biochar-assisted DEHP degradation in organic contaminated farmland soils.
ESTHER : Lin_2024_Chemosphere__141520
PubMedSearch : Lin_2024_Chemosphere__141520
PubMedID: 38395368

Title : Pralidoxime-like reactivator with increased lipophilicity - Molecular modeling and in vitro study - Kuca_2023_Chem.Biol.Interact_14ChEPon_110734
Author(s) : Kuca K , Valle da Silva JA , Nepovimova E , Pham NL , Wu W , Valis M , Wu Q , Franca TCC
Ref : Chemico-Biological Interactions , :110734 , 2023
Abstract : Acetylcholinesterase (AChE, EC 3.1.1.7) reactivators (2-PAM, trimedoxime, obidoxime, asoxime) have become an integral part of antidotal treatment in cases of nerve agent and organophosphorus (OP) pesticide poisonings. They are often referred to as specific antidotes due to their ability to restore AChE function when it has been covalently inhibited by an OP compound. Currently available commercial reactivators exhibit limited ability to penetrate the blood-brain barrier, where reactivation of inhibited AChE is crucial. Consequently, there have been numerous efforts to discover more brain-penetrating AChE reactivators. In this study, we examined a derivative of 2-PAM designed to possess increased lipophilicity. This enhanced lipophilicity was achieved through the incorporation of a benzyl group into its molecular structure. Initially, a molecular modeling study was conducted, followed by a comparison of its reactivation efficacy with that of 2-PAM against 10 different AChE inhibitors in vitro. Unfortunately, this relatively significant structural modification of 2-PAM resulted in a decrease in its reactivation potency. Consequently, this derivative cannot be considered as a broad-spectrum AChE reactivator.
ESTHER : Kuca_2023_Chem.Biol.Interact_14ChEPon_110734
PubMedSearch : Kuca_2023_Chem.Biol.Interact_14ChEPon_110734
PubMedID: 37788753

Title : Computational Modeling Study of the Binding of Aging and Non-Aging Inhibitors with Neuropathy Target Esterase - Wu_2023_Molecules_28_
Author(s) : Wu W , Huang J , Han P , Zhang J , Wang Y , Jin F , Zhou Y , Wang P
Ref : Molecules , 28 : , 2023
Abstract : Neuropathy target esterase (NTE) is a serine hydrolase with phospholipase B activity, which is involved in maintaining the homeostasis of phospholipids. It can be inhibited by aging inhibitors such as some organophosphorus (OP) compounds, which leads to delayed neurotoxicity with distal degeneration of axons. However, the detailed binding conformation of aging and non-aging inhibitors with NTE is not known. In this study, new computational models were constructed by using MODELLER 10.3 and AlphaFold2 to further investigate the inhibition mechanism of aging and non-aging compounds using molecular docking. The results show that the non-aging compounds bind the hydrophobic pocket much deeper than aging compounds and form the hydrophobic interaction with Phe1066. Therefore, the unique binding conformation of non-aging compounds may prevent the aging reaction. These important differences of the binding conformations of aging and non-aging inhibitors with NTE may help explain their different inhibition mechanism and the protection of non-aging NTE inhibitors against delayed neuropathy.
ESTHER : Wu_2023_Molecules_28_
PubMedSearch : Wu_2023_Molecules_28_
PubMedID: 38005352 || 38067477

Title : Preclinical Development of PNT6555, a Boronic Acid-Based, Fibroblast Activation Protein-alpha (FAP)-Targeted Radiotheranostic for Imaging and Treatment of FAP-Positive Tumors - Poplawski_2023_J.Nucl.Med__
Author(s) : Poplawski SE , Hallett RM , Dornan MH , Novakowski KE , Pan S , Belanger AP , Nguyen QD , Wu W , Felten AE , Liu Y , Ahn SH , Hergott VS , Jones B , Lai JH , McCann JAB , Bachovchin WW
Ref : J Nucl Med , : , 2023
Abstract : The overexpression of fibroblast activation protein-alpha (FAP) in solid cancers relative to levels in normal tissues has led to its recognition as a target for delivering agents directly to tumors. Radiolabeled quinoline-based FAP ligands have established clinical feasibility for tumor imaging, but their therapeutic potential is limited due to suboptimal tumor retention, which has prompted the search for alternative pharmacophores. One such pharmacophore is the boronic acid derivative N-(pyridine-4-carbonyl)-d-Ala-boroPro, a potent and selective FAP inhibitor (FAPI). In this study, the diagnostic and therapeutic (theranostic) potential of N-(pyridine-4-carbonyl)-d-Ala-boroPro-based metal-chelating DOTA-FAPIs was evaluated. Methods: Three DOTA-FAPIs, PNT6555, PNT6952, and PNT6522, were synthesized and characterized with respect to potency and selectivity toward soluble and cell membrane FAP; cellular uptake of the Lu-chelated analogs; biodistribution and pharmacokinetics in mice xenografted with human embryonic kidney cell-derived tumors expressing mouse FAP; the diagnostic potential of (68)Ga-chelated DOTA-FAPIs by direct organ assay and small-animal PET; the antitumor activity of (177)Lu-, (225)Ac-, or (161)Tb-chelated analogs using human embryonic kidney cell-derived tumors expressing mouse FAP; and the tumor-selective delivery of (177)Lu-chelated DOTA-FAPIs via direct organ assay and SPECT. Results: DOTA-FAPIs and their (nat)Ga and (nat)Lu chelates exhibited potent inhibition of human and mouse sources of FAP and greatly reduced activity toward closely related prolyl endopeptidase and dipeptidyl peptidase 4. (68)Ga-PNT6555 and (68)Ga-PNT6952 showed rapid renal clearance and continuous accumulation in tumors, resulting in tumor-selective exposure at 60 min after administration. (177)Lu-PNT6555 was distinguished from (177)Lu-PNT6952 and (177)Lu-PNT6522 by significantly higher tumor accumulation over 168 h. In therapeutic studies, all 3 (177)Lu-DOTA-FAPIs exhibited significant antitumor activity at well-tolerated doses, with (177)Lu-PNT6555 producing the greatest tumor growth delay and animal survival. (225)Ac-PNT6555 and (161)Tb-PNT6555 were similarly efficacious, producing 80% and 100% survival at optimal doses, respectively. Conclusion: PNT6555 has potential for clinical translation as a theranostic agent in FAP-positive cancer.
ESTHER : Poplawski_2023_J.Nucl.Med__
PubMedSearch : Poplawski_2023_J.Nucl.Med__
PubMedID: 38050111

Title : Water in liquid crystal emulsion-based sensing platform for colorimetric detection of organophosphorus pesticide - Li_2023_Food.Chem_436_137732
Author(s) : Li B , Wu W , Lin JM , Wang T , Hu Conceptuation Q , Yu L
Ref : Food Chem , 436 :137732 , 2023
Abstract : Development of a simple and convenient method for the rapid detection of organophosphorus pesticides (OPs) is particular important for the safety of environmental water and agriculture products. In this work, the water/liquid crystal (W/LC) emulsion is obtained via dispersing an aqueous solution of sodium dodecyl sulfate (SDS) and peroxidase from horseradish (HRP) into a water-immiscible nematic LC and employed as a sensing platform for the detection of dichlorvos (2, 2-dichlorovinyl dimethyl phosphate, DDVP) that is a typical OP with acute toxicity. Remarkably, the stepwise release of the encapsulated cargo HRP from the W/LC emulsion can be triggered upon the addition of the cationic surfactant myristoylcholine chloride (Myr) due to the strong interfacial charge interactions with the anionic surfactant SDS. The released HRP induces an obvious color change of the overlaying bulk aqueous solution via the H(2)O(2)-HRP-TMB reaction system. As Myr can be enzymatically cleaved by AChE, the detection of AChE is fulfilled successfully. This approach is also employed to detect DDVP that can irreversibly inhibit the activity of AChE. This assay shows a linear response between the absorbance of the oxidized TMB solution and the DDVP concentration in the range of 0.001-10 microg/mL (R(2) = 0.99). The limit of detection (LOD) and the limit of quantity (LOQ) of DDVP are determined to be 1.9 ng/mL and 6.3 ng/mL, respectively. In addition, this strategy also demonstrates excellent performance for the DDVP detection in real samples, the detection recovery rate of DDVP in water samples (lake water and tap water) and vegetables (tomatoes and cole) by this method is 88.0 % -112.6 %, the relative standard deviation (RSD) >= 7.5 %. These results suggest the W/LC emulsion-based sensing platform shows great potential for visual detection of DDVP in real samples. In conclusion, the proposed approach is scalable for practical application in food safety as well as environmental monitoring fields, and will provide promising solutions for the assay of pesticide residues.
ESTHER : Li_2023_Food.Chem_436_137732
PubMedSearch : Li_2023_Food.Chem_436_137732
PubMedID: 37857198

Title : A molecular imaging tool for monitoring carboxylesterase 2 during early diagnosis of liver-related diseases - Li_2023_Sens.Actuators.B.Chem_377_133122
Author(s) : Li J , Cao J , Wu W , Xu L , Zhang S , Ma P , Wu Q , Song D
Ref : Sensors and Actuators B: Chemical , 377 :133122 , 2023
Abstract : Early disease diagnosis is crucial for human health and successful therapy. Carboxylesterase 2 (CES2), the main enzyme found in many tumor tissues, is closely associated with many malignant diseases. Therefore, the ability to detect endogenous CES2-associated diseases can be of therapeutic significance. In this study, we designed a novel mitochondria-targeting near-infrared (NIR) chemosensor (YDT) to visualize the endogenous CES2. This is the first study to track CES2 at the mitochondrial level and present the currently most sensitive CES2 detection sensor. With various features including large Stokes shift, quick response time, excellent selectivity, and ultrahigh sensitivity, the sensor can overcome numerous limitations faced by traditional CES2 probes. YDT is an "off-on" chemosensor that releases fluorophore YD-1 upon interacting with CES2, emits strong fluorescence at 660 nm. Importantly, YDT can dynamically monitor immediate changes in CES2 level under external stimuli. Moreover, we used YDT to systematically study the CES2 expression in drug-induced liver injury and its remediation model, as well as in an inflammation model. With these outstanding characteristics, YDT is a considerably promising tool for further research on biological processes and for examining the physiological roles of CES2 in living systems
ESTHER : Li_2023_Sens.Actuators.B.Chem_377_133122
PubMedSearch : Li_2023_Sens.Actuators.B.Chem_377_133122
PubMedID:
Gene_locus related to this paper: human-CES2

Title : Paper-Based Distance Sensor for the Detection of Lipase via a Phase Separation-Induced Viscosity Change - Xia_2022_Anal.Chem__
Author(s) : Xia S , Yin F , Xu L , Zhao B , Wu W , Ma Y , Lin JM , Liu Y , Zhao M , Hu Q
Ref : Analytical Chemistry , : , 2022
Abstract : Human pancreatic lipase is a symbolic biomarker for the diagnosis of acute pancreatitis, which has profound significance for clinical detection and disease treatment. Herein, we first demonstrate a paper-based lipase sensor via a phase separation-induced viscosity change. Lipase catalyzes triolein to produce oleic acid and glycerol. Adding an excess of Ca(2+) produces calcium oleate. The remaining Ca(2+) binds with sodium alginate, triggering hydrogelation with an "egg-box" structure. The viscosity change of the aqueous solution induced by the phase separation process can be quantified by measuring the solution flow distance on a pH test paper. The paper-based lipase sensor has high sensitivity with a detection limit of 0.052 U/mL and also shows excellent specificity. Additionally, it is also utilized for quantitative lipase analysis in human serum samples to exhibit its potency in acute pancreatitis detection. This method overcomes the drawbacks of low sensitivity, slow response, and poor reproducibility caused by the nonuniform distribution of the highly viscous hydrogel on the sensing interface in existing approaches. In conclusion, thanks to the prominent characteristics of high portability, low cost, and easy operation, it is prospective for simple quantitative detection of lipase and has great potential for commercialization.
ESTHER : Xia_2022_Anal.Chem__
PubMedSearch : Xia_2022_Anal.Chem__
PubMedID: 36455011

Title : Electrochemical (Bio)Sensors for the Detection of Organophosphorus Pesticides Based on Nanomaterial-Modified Electrodes: A Review - Ding_2022_Crit.Rev.Anal.Chem__1
Author(s) : Ding R , Li Z , Xiong Y , Wu W , Yang Q , Hou X
Ref : Crit Rev Analytical Chemistry , :1 , 2022
Abstract : Organophosphorus pesticides were easily remained in fruits and vegetables which would be harm to the environmental safety and human health. In recent years, due to the simple preparation process, fast response and high sensitivity, the electrochemical (bio)sensors have received increasing attention, which were extensively used as the sensing platform for the detection of OPPs. The mechanisms for the determination of OPPs mainly included redox of nitrophenyl OPPs, enzyme hydrolysis and inhibition, immunosensor, aptasensor. Nowadays, the mainly explored electrode material has focused on metal-organic frameworks, metal and metal derivatives, carbon materials (carbon nanotube, graphene, g-C(3)N(4)), MXene, etc. These nanomaterials played important roles in the electrochemical (bio)sensors, which included: (a) as an electrocatalyst to promote the redox reaction, (b) as a carrier to load the enzyme or aptamer, (c) as a recognizer to identify the targets. The nanomaterials-based electrochemical (bio)sensor was a rapid, cost-effective methods to detect OPPs with high sensitivity. Besides, this review compared the analytical performance of different nanomaterials-based electrochemical (bio)sensors, and also identified the key challenges in the future. It would provide new ideas and insights to the further development and application of electrochemical (bio)sensors and the detection of pesticides in real samples.
ESTHER : Ding_2022_Crit.Rev.Anal.Chem__1
PubMedSearch : Ding_2022_Crit.Rev.Anal.Chem__1
PubMedID: 35235478

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 : Design, Synthesis, and Study of the Insecticidal Activity of Novel Steroidal 1,3,4-Oxadiazoles - Ma_2021_J.Agric.Food.Chem__
Author(s) : Ma S , Jiang W , Li Q , Li T , Wu W , Bai H , Shi B
Ref : Journal of Agricultural and Food Chemistry , : , 2021
Abstract : A series of novel steroidal derivatives with a substituted 1,3,4-oxadiazole structure was designed and synthesized, and the target compounds were evaluated for their insecticidal activity against five aphid species. Most of the tested compounds exhibited potent insecticidal activity against Eriosoma lanigerum (Hausmann), Myzus persicae, and Aphis citricola. Compounds 20g and 24g displayed the highest activity against E. lanigerum, showing LC(50) values of 27.6 and 30.4 microg/mL, respectively. Ultrastructural changes in the midgut cells of E. lanigerum were detected by transmission electron microscopy, indicating that these steroidal oxazole derivatives might exert their insecticidal activity by destroying the mitochondria and nuclear membranes in insect midgut cells. Furthermore, a field trial showed that compound 20g exhibited effects similar to those of the positive controls chlorpyrifos and thiamethoxam against E. lanigerum, reaching a control rate of 89.5% at a dose of 200 microg/mL after 21 days. We also investigated the hydrolysis and metabolism of the target compounds in E. lanigerum by assaying the activities of three insecticide-detoxifying enzymes. Compound 20g at 50 microg/mL exhibited inhibitory action on carboxylesterase similar to the known inhibitor triphenyl phosphate. The above results demonstrate the potential of these steroidal oxazole derivatives to be developed as novel pesticides.
ESTHER : Ma_2021_J.Agric.Food.Chem__
PubMedSearch : Ma_2021_J.Agric.Food.Chem__
PubMedID: 34554742

Title : Rapid screening of lipase inhibitors in licorice extract by using porcine pancreatic lipase immobilized on Fe(3)O(4) magnetic nanoparticles - Zeng_2021_Food.Funct__
Author(s) : Zeng F , Wu W , Zhang Y , Pan X , Duan J
Ref : Food Funct , : , 2021
Abstract : Chalcones, a class of natural lipase inhibitors, have received substantial attention from researchers in recent years. Although many kinds of chalcones are typically distributed in G. inflata, there is little literature about the anti-lipase activity of G. inflata extracts (GIEs). In the present study, a ligand fishing strategy for fast screening of lipase inhibitors from GIEs was thus proposed. Porcine pancreatic lipase (PPL) was firstly immobilized on carboxyl modified Fe3O4 magnetic nanoparticles (MNPs) to obtain PPL functionalized MNPs (PPL@MNPs), and then the PPL@MNPs were incubated with a bioactive fraction to fish out the ligands. Eight ligands were obtained and identified as one flavone together with seven chalcones. Licochalcone A, licochalcone D and licochalcone E inhibited pancreatic lipase (PL) with IC50 of 4.9, 3.2 and 5.8 microM, respectively. Meanwhile, investigation of the structure-activity relationship also revealed that isopentenyl and hydroxyl substituents at ring A were essential for the noncovalent inhibitory potency of the chalcones.
ESTHER : Zeng_2021_Food.Funct__
PubMedSearch : Zeng_2021_Food.Funct__
PubMedID: 34018495

Title : miR-4454 up-regulated by HPV16 E6\/E7 promotes invasion and migration by targeting ABHD2\/NUDT21 in cervical cancer - Wang_2020_Biosci.Rep_40_
Author(s) : Wang H , Hu H , Luo Z , Liu S , Wu W , Zhu M , Wang J , Liu Y , Lu Z
Ref : Bioscience Reports , 40 : , 2020
Abstract : The abnormal expression of HPV16 E6/E7 activates oncogenes and/or inactivates tumor suppressor genes, resulting in the selective growth and malignant transformation of cancer cells. miR-4454 was selected by sequencing due to its abnormal high expression in HPV16 E6/E7 positive CaSki cell compared with HPV16 E6/E7 negative C33A cell. Overexpression of miR-4454 enhances cervical cancer cell invasion and migration. ABHD2 and NUDT21 are identified as a target gene of miR-4454.The effects of ABHD2 and NUDT21 on migration and invasion of CaSki and C33A cells were determined. The dual luciferase and RT-qPCR assays confirmed that miR-4454 might regulate its targets ABHD2 and NUDT21 to promote the proliferation, invasion and migration, whereas, inhibit the apoptosis in CaSki and C33A cells.
ESTHER : Wang_2020_Biosci.Rep_40_
PubMedSearch : Wang_2020_Biosci.Rep_40_
PubMedID: 32816024

Title : An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment - Wu_2020_Arch.Toxicol_94_3645
Author(s) : Wu Q , Qin Z , Kuca K , You L , Zhao Y , Liu A , Musilek K , Chrienova Z , Nepovimova E , Oleksak P , Wu W , Wang X
Ref : Archives of Toxicology , 94 :3645 , 2020
Abstract : T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms.
ESTHER : Wu_2020_Arch.Toxicol_94_3645
PubMedSearch : Wu_2020_Arch.Toxicol_94_3645
PubMedID: 32910237

Title : Detection of organophosphorus pesticides with liquid crystals supported on the surface deposited with polyoxometalate-based acetylcholinesterase-responsive supramolecular spheres - Qi_2020_Food.Chem_320_126683
Author(s) : Qi L , Wu W , Kang Q , Hu Q , Yu L
Ref : Food Chem , 320 :126683 , 2020
Abstract : Here, we demonstrate use of acetylcholinesterase (AChE)-responsive polyoxometalate (POM)/surfactant supramolecular spheres to build a liquid crystal (LC)-based sensing platform for detection of organophosphorus pesticides. The self-assembled spheres are composed of hybrid materials of a POM, sodium dodecatungstophosphate (PW12), and a surfactant, myristoylcholine (Myr). It displays dark appearance when the aqueous solution is in contact with LCs supported on the octadecyltrichlorosilane-treated glass deposited with the supramolecular spheres, suggesting perpendicular orientation of LCs at the aqueous/LC interface. In contrast, LCs show bright appearance when the surface-deposited supramolecular spheres are enzymatically hydrolyzed by AChE, corresponding to planar orientation of LCs at the aqueous/LC interface. Detection of organophosphates are successfully achieved as they are potent inhibitors of AChE. The detection limit of the sensing platform reached 0.9 ng/mL for dimethoate. This method can avoid disturbance of external interference with excellent specificity and sensitivity, which makes it very promise in detection of organophosphorus pesticides.
ESTHER : Qi_2020_Food.Chem_320_126683
PubMedSearch : Qi_2020_Food.Chem_320_126683
PubMedID: 32229401

Title : A Network-Based Approach to Explore the Mechanisms of Uncaria Alkaloids in Treating Hypertension and Alleviating Alzheimer's Disease - Wu_2020_Int.J.Mol.Sci_21_
Author(s) : Wu W , Zhang Z , Li F , Deng Y , Lei M , Long H , Hou J
Ref : Int J Mol Sci , 21 : , 2020
Abstract : Uncaria alkaloids are the major bioactive chemicals found in the Uncaria genus, which have a long history of clinical application in treating cardiovascular and mental diseases in traditional Chinese medicine (TCM). However, there are gaps in understanding the multiple targets, pathways, and biological activities of Uncaria alkaloids. By constructing the interactions among drug-targets-diseases, network pharmacology provides a systemic methodology and a novel perspective to present the intricate connections among drugs, potential targets, and related pathways. It is a valuable tool for studying TCM drugs with multiple indications, and how these multi-indication drugs are affected by complex interactions in the biological system. To better understand the mechanisms and targets of Uncaria alkaloids, we built an integrated analytical platform based on network pharmacology, including target prediction, protein-protein interaction (PPI) network, topology analysis, gene enrichment analysis, and molecular docking. Using this platform, we revealed the underlying mechanisms of Uncaria alkaloids' anti-hypertensive effects and explored the possible application of Uncaria alkaloids in preventing Alzheimer's disease. These results were further evaluated and refined using biological experiments. Our study provides a novel strategy for understanding the holistic pharmacology of TCM, as well as for exploring the multi-indication properties of TCM beyond its traditional applications.
ESTHER : Wu_2020_Int.J.Mol.Sci_21_
PubMedSearch : Wu_2020_Int.J.Mol.Sci_21_
PubMedID: 32143538

Title : ABHD11 Is Critical for Embryonic Stem Cell Expansion, Differentiation and Lipid Metabolic Homeostasis - Liu_2020_Front.Cell.Dev.Biol_8_570
Author(s) : Liu G , Ruan Y , Zhang J , Wang X , Wu W , He P , Wang J , Xiong J , Cheng Y , Liu L , Yang Y , Tian Y , Jian R
Ref : Front Cell Developmental Biology , 8 :570 , 2020
Abstract : Growing evidence supports the notion that lipid metabolism is critical for embryonic stem cell (ESC) maintenance. Recently, alpha/beta-hydrolase domain-containing (ABHD) proteins have emerged as novel pivotal regulators in lipid synthesis or degradation while their functions in ESCs have not been investigated. In this study, we revealed the role of ABHD11 in ESC function using classical loss and gain of function experiments. Knockout of Abhd11 hampered ESC expansion and differentiation, triggering the autophagic flux and apoptosis. In contrast, Abhd11 overexpression exerted anti-apoptotic effects in ESCs. Moreover, Abhd11 knockout disturbed GSK3beta/beta-Catenin and ERK signaling transduction. Finally, Abhd11 knockout led to the misexpression of key metabolic enzymes related to lipid synthesis, glycolysis, and amino acid metabolism, and ABHD11 contributed to the homeostasis of lipid metabolism. These findings provide new insights into the broad role of ABHD proteins and highlight the significance of regulators of lipid metabolism in the control of stem cell function.
ESTHER : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedSearch : Liu_2020_Front.Cell.Dev.Biol_8_570
PubMedID: 32733886
Gene_locus related to this paper: human-ABHD11

Title : Sex Differences in the Prevalent Use of Oral Formulations of Cholinesterase Inhibitors in Older Adults with Dementia - Zhu_2019_Drugs.Aging_36_875
Author(s) : Zhu L , Rochon PA , Gruneir A , Wu W , Giannakeas V , Austin PC , Stall NM , McCarthy L , Alberga A , Herrmann N , Gill SS , Bronskill SE
Ref : Drugs & Aging , 36 :875 , 2019
Abstract : BACKGROUND: Cholinesterase inhibitors (ChEIs) are one of only two drug therapies available to manage cognitive decline in dementia. Given sex-specific differences in medication access and effects, it is important to understand how ChEIs are used by women and men. OBJECTIVE: The objective of this study was to provide contemporary sex-stratified evidence on patterns of ChEI use by community-dwelling older adults with dementia to inform opportunities to optimize drug prescribing. METHODS: We conducted a population-based cross-sectional study examining ChEI use in older adults with dementia in Ontario, Canada. We identified all community-dwelling individuals aged 66 years and older with a pre-existing diagnosis of dementia as of 1 April, 2016. We examined the prevalence of ChEI use among women and men separately, and explored the association between ChEI use and age, sex, income status, geographic location of residence, use of palliative care services, comorbidity, and polypharmacy. Concurrent use of drugs known to impair cognition (including antipsychotics, benzodiazepines, and medications with strong anticholinergic properties) was separately assessed among women and men using multivariable analyses and prevalence risk ratios. RESULTS: Of 74,799 women and 52,231 men living with dementia in the community, nearly 30% currently were using a ChEI (29.3% women, 28.6% men). Close to 70% of users were receiving the target therapeutic dose. Compared to men, women were less often taking the target therapeutic dose (67.8% women vs. 71.6% men, p < 0.001). Over 20% of users also were using drugs known to impair cognition, while being treated for cognitive decline using ChEIs. Compared to men, women were more often concurrently using drugs known to impair cognition (23.9% women vs. 21.8% men, p < 0.001). CONCLUSIONS: This is one of the first studies of ChEI use to account for important sex differences. The results remind clinicians and researchers that patterns of ChEI therapy use differ by sex, as women were less likely to receive target therapeutic doses and more vulnerable to potentially problematic polypharmacy than men.
ESTHER : Zhu_2019_Drugs.Aging_36_875
PubMedSearch : Zhu_2019_Drugs.Aging_36_875
PubMedID: 31309528

Title : Fibroblast activation protein is dispensable for control of glucose homeostasis and body weight in mice - Panaro_2019_Mol.Metab_19_65
Author(s) : Panaro BL , Coppage AL , Beaudry JL , Varin EM , Kaur K , Lai JH , Wu W , Liu Y , Bachovchin WW , Drucker DJ
Ref : Mol Metab , 19 :65 , 2019
Abstract : OBJECTIVE: Fibroblast Activation Protein (FAP), an enzyme structurally related to dipeptidyl peptidase-4 (DPP-4), has garnered interest as a potential metabolic drug target due to its ability to cleave and inactivate FGF-21 as well as other peptide substrates. Here we investigated the metabolic importance of FAP for control of body weight and glucose homeostasis in regular chow-fed and high fat diet-fed mice. METHODS: FAP enzyme activity was transiently attenuated using a highly-specific inhibitor CPD60 and permanently ablated by genetic inactivation of the mouse Fap gene. We also assessed the FAP-dependence of CPD60 and talabostat (Val-boroPro), a chemical inhibitor reportedly targeting both FAP and dipeptidyl peptidase-4 RESULTS: CPD60 robustly inhibited plasma FAP activity with no effect on DPP-4 activity. Fap gene disruption was confirmed by assessment of genomic DNA, and loss of FAP enzyme activity in plasma and tissues. CPD60 did not improve lipid tolerance but modestly improved acute oral and intraperitoneal glucose tolerance in a FAP-dependent manner. Genetic inactivation of Fap did not improve glucose or lipid tolerance nor confer resistance to weight gain in male or female Fap(-/-) mice fed regular chow or high-fat diets. Moreover, talabostat markedly improved glucose homeostasis in a FAP- and FGF-21-independent, DPP-4 dependent manner. CONCLUSION: Although pharmacological FAP inhibition improves glucose tolerance, the absence of a metabolic phenotype in Fap(-/-)mice suggest that endogenous FAP is dispensable for the regulation of murine glucose homeostasis and body weight. These findings highlight the importance of characterizing the specificity and actions of FAP inhibitors in different species and raise important questions about the feasibility of mouse models for targeting FAP as a treatment for diabetes and related metabolic disorders.
ESTHER : Panaro_2019_Mol.Metab_19_65
PubMedSearch : Panaro_2019_Mol.Metab_19_65
PubMedID: 30477988

Title : Enhancing thermostability of Yarrowia lipolytica lipase 2 through engineering multiple disulfide bonds and mitigating reduced lipase production associated with disulfide bonds - Li_2019_Enzyme.Microb.Technol_126_41
Author(s) : Li L , Zhang S , Wu W , Guan W , Deng Z , Qiao H
Ref : Enzyme Microb Technol , 126 :41 , 2019
Abstract : The limited thermostability of Yarrowia lipolytica lipase 2 (Lip2) hampers its industrial application. To improve its thermostability, we combined single disulfide bonds which our group identified previously. In this study, combining different regional disulfide bonds had greater effect than combining same regional disulfide bonds. Furthermore, mutants with 4, 5, and 6 disulfide bonds exhibited dramatically enhanced thermostability. Compared with the wild-type, sextuple mutant 6s displayed a 22.53 and 31.23 degC increase in the melting temperature (T(m)) and the half loss temperature at 15 min (T15 50), respectively, with greater pH stability and a wider reaction pH range. Molecular dynamics simulation revealed that multiple disulfide bonds resulted in more rigid structures of mutants 4s, 5s and 6s, and prolonged enzyme unfolding times. Moreover, secretions of mutants 5s and 6s were significantly increased by 60% and 80% by co-expressing with the chaperone protein disulfide isomerase (PDI), which mitigated the reduced production issue caused by multiple disulfide bonds. Results of this study indicated that enhanced heat endurance giving more potential for industrial application.
ESTHER : Li_2019_Enzyme.Microb.Technol_126_41
PubMedSearch : Li_2019_Enzyme.Microb.Technol_126_41
PubMedID: 31000163

Title : Initial Cholinesterase Inhibitor Therapy Dose and Serious Events in Older Women and Men - Rochon_2018_J.Am.Geriatr.Soc_66_1692
Author(s) : Rochon PA , Gruneir A , Gill SS , Wu W , Zhu L , Herrmann N , Bell CM , Austin PC , Stall NM , McCarthy L , Giannakeas V , Alberga A , Seitz DP , Normand SL , Gurwitz JH , Bronskill SE
Ref : J Am Geriatr Soc , 66 :1692 , 2018
Abstract : OBJECTIVES: To examine dose-related prescribing and short-term serious events associated with initiation of cholinesterase inhibitor (ChEI) therapy. DESIGN: Retrospective, population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women (n=47,829) and men (n=32,503) aged 66 and older who initiated a ChEI between April 1, 2010, and June 30, 2016. MEASUREMENTS: All-cause serious events (emergency department (ED) visits, inpatient hospitalizations, death) within 30 days of ChEI initiation. Multivariable Cox proportional hazards models were used to estimate adjusted rates of serious events. RESULTS: Overall, 4.8% of older adults were dispensed a lower-than-recommended ChEI starting dose, 87.9% a recommended dose, and 7.3% a higher-than-recommended starting dose. Eight thousand six hundred seventy-one (10.8%) individuals experienced a serious event within 30 days of initiating therapy, primarily ED visits (8,540, 10.6%). Relative to those initiated on a recommended starting dose, those initiated on a higher dose had a significantly increased rate of serious events (women adjusted hazard ratio (aHR) 1.50, 95% confidence interval (CI) =1.38-1.63; men aHR 1.31, 95% CI=1.19-1.45). Similar patterns were found for ED visits and inpatient hospitalizations but not death. The relative effect of higher-than-recommended starting dose dispensed vs. recommended starting dose dispensed was greater in women than it was in men: the number needed to harm was 22 (95% confidence interval (CI)=18-29) for women and 36 (95% CI= 26-61) for men. CONCLUSION: Serious events immediately after initiation of ChEIs were associated with starting ChEI dose. This association was stronger in women.
ESTHER : Rochon_2018_J.Am.Geriatr.Soc_66_1692
PubMedSearch : Rochon_2018_J.Am.Geriatr.Soc_66_1692
PubMedID: 30019755

Title : Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships - Zhang_2018_Cell_174_1450
Author(s) : Zhang P , Lu H , Peixoto RT , Pines MK , Ge Y , Oku S , Siddiqui TJ , Xie Y , Wu W , Archer-Hartmann S , Yoshida K , Tanaka KF , Aricescu AR , Azadi P , Gordon MD , Sabatini BL , Wong ROL , Craig AM
Ref : Cell , 174 :1450 , 2018
Abstract : Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin's role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced survival, as well as structural and functional deficits at central synapses. HS directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual binding mode involving intrinsic glycan and protein domains for canonical synapse-organizing complexes. Neurexin HS chains also bind novel ligands, potentially expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS structure is heterogeneous, our findings indicate an additional dimension to neurexin diversity, provide a molecular basis for fine-tuning synaptic function, and open therapeutic directions targeting glycan-binding motifs critical for brain development.
ESTHER : Zhang_2018_Cell_174_1450
PubMedSearch : Zhang_2018_Cell_174_1450
PubMedID: 30100184

Title : Synthesis and Evaluation of Novel Ligustrazine Derivatives as Multi-Targeted Inhibitors for the Treatment of Alzheimer's Disease - Wu_2018_Molecules_23_
Author(s) : Wu W , Liang X , Xie G , Chen L , Liu W , Luo G , Zhang P , Yu L , Zheng X , Ji H , Zhang C , Yi W
Ref : Molecules , 23 : , 2018
Abstract : A series of novel ligustrazine derivatives 8a(-)r were designed, synthesized, and evaluated as multi-targeted inhibitors for anti-Alzheimer's disease (AD) drug discovery. The results showed that most of them exhibited a potent ability to inhibit both ChEs, with a high selectivity towards AChE. In particular, compounds 8q and 8r had the greatest inhibitory abilities for AChE, with IC50 values of 1.39 and 0.25 nM, respectively, and the highest selectivity towards AChE (for 8q, IC50 BuChE/IC50 AChE = 2.91 x 10(6); for 8r, IC50 BuChE/IC50 AChE = 1.32 x 10(7)). Of note, 8q and 8r also presented potent inhibitory activities against Abeta aggregation, with IC50 values of 17.36 microM and 49.14 microM, respectively. Further cellular experiments demonstrated that the potent compounds 8q and 8r had no obvious cytotoxicity in either HepG2 cells or SH-SY5Y cells, even at a high concentration of 500 muM. Besides, a combined Lineweaver-Burk plot and molecular docking study revealed that these compounds might act as mixed-type inhibitors to exhibit such effects via selectively targeting both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChEs. Taken together, these results suggested that further development of these compounds should be of great interest.
ESTHER : Wu_2018_Molecules_23_
PubMedSearch : Wu_2018_Molecules_23_
PubMedID: 30301153

Title : Comparison of prescribing practices for older adults treated by female versus male physicians: A retrospective cohort study - Rochon_2018_PLoS.One_13_e0205524
Author(s) : Rochon PA , Gruneir A , Bell CM , Savage R , Gill SS , Wu W , Giannakeas V , Stall NM , Seitz DP , Normand SL , Zhu L , Herrmann N , McCarthy L , Faulkner C , Gurwitz JH , Austin PC , Bronskill SE
Ref : PLoS ONE , 13 :e0205524 , 2018
Abstract : IMPORTANCE: Subtle but important differences have been described in the way that male and female physicians care for their patients, with some evidence suggesting women are more likely to adhere to best practice recommendations. OBJECTIVE: To determine if male and female physicians differ in their prescribing practices as measured by the initiation of lower-than-recommended dose cholinesterase inhibitor (ChEI) drug therapy for dementia management. DESIGN, SETTING, AND PARTICIPANTS: All community-dwelling Ontario residents aged 66 years and older with dementia and newly dispensed an oral ChEI drug (donepezil, galantamine, or rivastigmine) between April 1, 2010 and June 30, 2016 were included. MAIN OUTCOME AND MEASURES: The association between physician sex and the initiation of a lower than recommended-dose ChEI was examined using generalized linear mixed regression models, adjusting for patient and physician characteristics. Data were stratified by specialty. Secondary analyses explored the association between physician sex and cardiac screening as well as shorter duration of the initial prescription. RESULTS: The analysis included 3,443 female and 5,811 male physicians and the majority (83%) were family physicians, Female physicians were more likely to initiate ChEI therapy at a lower-than-recommended dose (Adjusted odds ratio = 1.43,95% confidence interval = 1.17 to 1.74). Compared to their male counterparts, female physicians were also more likely to follow other conservative prescribing practices including cardiac screening (55.1% vs. 49.2%, P-value<0.001) around the time of ChEI initiation, and dispensing a shorter duration of initial prescription (41.8% vs 35.5% P-value<0.001). CONCLUSIONS: There is a statistically significant and important difference in ChEI prescribing patterns between female and male physicians, suggesting that female physicians may be more careful and conservative in their approaches. This will inform future research to determine if patients receiving lower-than-recommended initial doses also have better outcomes.
ESTHER : Rochon_2018_PLoS.One_13_e0205524
PubMedSearch : Rochon_2018_PLoS.One_13_e0205524
PubMedID: 30346974

Title : Targeting dipeptidyl peptidase 8 genes inhibits proliferation, migration and invasion by inhibition of cyclin D1 and MMP2MMP9 signal pathway in cervical cancer - Chen_2018_J.Gene.Med_20_e3056
Author(s) : Chen Y , Liu F , Wu K , Wu W , Wu H , Zhang W
Ref : J Gene Med , 20 :e3056 , 2018
Abstract : BACKGROUND: DPP8 is a member of the dipeptidyl peptidase IV family, which belongs to the S9b protease subfamily. It regulates cell proliferation, apoptosis, migration and invasion during cancer progression. METHODS: To investigate the role of DPP8 in cervical cancer, we examined DPP8 levels in cervical cancer tissues and cells. The localization of DPP8 was determined by immunofluorescence staining. Subsequently, SiHa and HeLa cells were treated with small interfering RNA (siRNA)-DPP8. We used cell cycle analysis, an 5-ethyl-2'-deoxyuridine assay proliferation assay and a cellular apoptosis assay to determine the effect of DPP8 on the proliferation and apoptosis of cervical cancer cells. We used a Transwell assay to assess the number of transfection cancer cells migrating through the matrix. A real-time polymerase chain reaction and western blot analysis were used to analyze the expression of related proteins and to determine the phenotype caused by the depletion or overexpression of DPP8 in cervical cancer cells. RESULTS: We observed that DPP8 was highly expressed in cervical cancer tissues and cells. DPP8 expression was observed in the cytosol and in the perinuclear area, as well as in the nuclei of cervical cancer cells. Notably, when cells were treated with siRNA-DPP8, the expression of BAX increased, and the expression of cyclin D1, Bcl-2, MMP2 and MMP9 was downregulated. In cervical cancer cell lines, silencing the expression of DPP8 not only suppressed the proliferation, migration and invasion of the cervical cancer cells, but also promoted cervical cancer cell apoptosis. CONCLUSIONS: The data obtained in the present study reveal that DPP8 promotes the progression of cervical cancer.
ESTHER : Chen_2018_J.Gene.Med_20_e3056
PubMedSearch : Chen_2018_J.Gene.Med_20_e3056
PubMedID: 30225951

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

Title : Study of acetylcholinesterase activity and apoptosis in SH-SY5Y cells and mice exposed to ethanol - Sun_2017_Toxicology_384_33
Author(s) : Sun W , Chen L , Zheng W , Wei X , Wu W , Duysen EG , Jiang W
Ref : Toxicology , 384 :33 , 2017
Abstract : Ethanol is one of the most commonly abused psychotropic substances with deleterious effects on the central nervous system. Ethanol exposure during development results in the loss of neurons in brain regions and when exposed to ethanol cultured cells undergo apoptosis. To date no information is available on whether abnormally high AChE activity is characteristic of apoptosis in animals exposed to ethanol. The aims of the present study were to determine whether induction of AChE activity is associated with ethanol-induced apoptosis and to explore the mechanism of enhanced AChE activity induced by ethanol. For this purpose, in vitro and in vivo experiments were performed. AChE activity was quantified by spectrophotometry and apoptosis by flow cytometer in SH-SY5Y cells exposed to ethanol. The results showed that cells treated with 500mM ethanol for 24h had a 9-fold increase in apoptotic cells and a 6-fold increase in AChE activity compared with controls. Mice exposed acutely to 200mul of 20% ethanol daily on days 1-4 had elevated AChE activity in plasma on days 3-7. On day 4, plasma AChE activity was 2.4-fold higher than pretreatment activity. More apoptotic cells were found in the brains of treated mice compared to controls. Cells in brain sections that were positive in the TUNEL assay stained for AChE activity. In conclusion, AChE activity and apoptosis were induced in SH-SY5Y cells and mice treated with ethanol, which may indicate that increased AChE may related to apoptosis induced by ethanol. Unusually high AChE activity may be an effect marker of exposure to ethanol. The relationship between AChE and apoptosis might represent a novel mechanism of ethanol-associated neuronal injury.
ESTHER : Sun_2017_Toxicology_384_33
PubMedSearch : Sun_2017_Toxicology_384_33
PubMedID: 28427893

Title : DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis - Okondo_2017_Nat.Chem.Biol_13_46
Author(s) : Okondo MC , Johnson DC , Sridharan R , Go EB , Chui AJ , Wang MS , Poplawski SE , Wu W , Liu Y , Lai JH , Sanford DG , Arciprete MO , Golub TR , Bachovchin WW , Bachovchin DA
Ref : Nat Chemical Biology , 13 :46 , 2017
Abstract : Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC. Activated pro-caspase-1 does not efficiently process itself or IL-1beta but does cleave and activate gasdermin D to induce pyroptosis. Mice lacking caspase-1 do not show immune stimulation after treatment with Val-boroPro. Our data identify what is to our knowledge the first small molecule that induces pyroptosis and reveals a new checkpoint that controls the activation of the innate immune system.
ESTHER : Okondo_2017_Nat.Chem.Biol_13_46
PubMedSearch : Okondo_2017_Nat.Chem.Biol_13_46
PubMedID: 27820798
Gene_locus related to this paper: human-DPP8 , human-DPP9

Title : Systematic Review of Sex-Specific Reporting of Data: Cholinesterase Inhibitor Example - Mehta_2017_J.Am.Geriatr.Soc_65_2213
Author(s) : Mehta N , Rodrigues C , Lamba M , Wu W , Bronskill SE , Herrmann N , Gill SS , Chan AW , Mason R , Day S , Gurwitz JH , Rochon PA
Ref : J Am Geriatr Soc , 65 :2213 , 2017
Abstract : OBJECTIVES: To improve the value of research for older adults, we examine sex-specific reporting of data from drug trials for the management of dementia. These data are important because they may influence considerations ranging from the health of populations to shared decision-making by individual patient and caregiver about the risk and benefit of a drug therapy. METHODS: Randomized controlled trials of cholinesterase inhibitors (i.e., donepezil, rivastigmine, or galantamine) with clinical outcomes were identified from searches of MEDLINE, EMBASE, and the Cochrane Library. Sex-specific data were extracted from nine sections (title, abstract, introduction, methods, outcomes, results, discussion, limitations, and conclusion). Among the donepezil trials only, more detailed harms data were obtained. FINDINGS: Thirty-three randomized controlled trials were identified evaluating 15,971 participants (9,103 (57%) female). Trials were highly cited (median citations 158, interquartile range 62-441) and published in high impact journals (median impact factor 7.4, interquartile range 3.4-8.2). Sex was not mentioned in the title, introduction, limitations, or conclusion section of any trial. Only three trials (9%) mentioned sex in the abstract (all as a demographic characteristic), and 8 (24%) in the methods. Almost all (32 (97%)) trials mentioned sex in the results as a demographic variable. One trial reported a sex difference for a secondary outcome. Among the 16 trials studying donepezil, adverse events were frequently reported and often dose-related. No trial provided sex-specific reporting of adverse events. CONCLUSIONS: There is an almost complete lack of sex-specific reporting of data in clinical trials for dementia drug therapies, and no sex-specific reporting of adverse events. Sex-specific reporting of data should be required in drug trials to increase research value and ultimately inform more tailored prescribing for older adults.
ESTHER : Mehta_2017_J.Am.Geriatr.Soc_65_2213
PubMedSearch : Mehta_2017_J.Am.Geriatr.Soc_65_2213
PubMedID: 28832937

Title : Characterization of four endophytic fungi as potential consolidated bioprocessing hosts for conversion of lignocellulose into advanced biofuels - Wu_2017_Appl.Microbiol.Biotechnol_101_2603
Author(s) : Wu W , Davis RW , Tran-Gyamfi MB , Kuo A , LaButti K , Mihaltcheva S , Hundley H , Chovatia M , Lindquist E , Barry K , Grigoriev IV , Henrissat B , Gladden JM
Ref : Applied Microbiology & Biotechnology , 101 :2603 , 2017
Abstract : Recently, several endophytic fungi have been demonstrated to produce volatile organic compounds (VOCs) with properties similar to fossil fuels, called "mycodiesel," while growing on lignocellulosic plant and agricultural residues. The fact that endophytes are plant symbionts suggests that some may be able to produce lignocellulolytic enzymes, making them capable of both deconstructing lignocellulose and converting it into mycodiesel, two properties that indicate that these strains may be useful consolidated bioprocessing (CBP) hosts for the biofuel production. In this study, four endophytes Hypoxylon sp. CI4A, Hypoxylon sp. EC38, Hypoxylon sp. CO27, and Daldinia eschscholzii EC12 were selected and evaluated for their CBP potential. Analysis of their genomes indicates that these endophytes have a rich reservoir of biomass-deconstructing carbohydrate-active enzymes (CAZys), which includes enzymes active on both polysaccharides and lignin, as well as terpene synthases (TPSs), enzymes that may produce fuel-like molecules, suggesting that they do indeed have CBP potential. GC-MS analyses of their VOCs when grown on four representative lignocellulosic feedstocks revealed that these endophytes produce a wide spectrum of hydrocarbons, the majority of which are monoterpenes and sesquiterpenes, including some known biofuel candidates. Analysis of their cellulase activity when grown under the same conditions revealed that these endophytes actively produce endoglucanases, exoglucanases, and beta-glucosidases. The richness of CAZymes as well as terpene synthases identified in these four endophytic fungi suggests that they are great candidates to pursue for development into platform CBP organisms.
ESTHER : Wu_2017_Appl.Microbiol.Biotechnol_101_2603
PubMedSearch : Wu_2017_Appl.Microbiol.Biotechnol_101_2603
PubMedID: 28078400
Gene_locus related to this paper: 9pezi-a0a1y2u1s8 , 9pezi-a0a1y2x077 , 9pezi-a0a1y2vv92 , 9pezi-a0a1y2txs8 , 9pezi-a0a1y2wzb7 , 9pezi-a0a1y2ufj7 , 9pezi-a0a1y2vvc9 , 9pezi-a0a1y2w3w4

Title : Efficient immobilization of acetylcholinesterase onto amino functionalized carbon nanotubes for the fabrication of high sensitive organophosphorus pesticides biosensors - Yu_2015_Biosens.Bioelectron_68C_288
Author(s) : Yu G , Wu W , Zhao Q , Wei X , Lu Q
Ref : Biosensors & Bioelectronics , 68C :288 , 2015
Abstract : This work introduced an efficient immobilization of acetylcholinesterase (AChE) onto amino functionalized carbon nanotubes (CNT-NH2), in order to fabricate high sensitive and practical organophosphorus pesticide (OPs) biosensors. Compared with the pristine, -COOH and -OH decorated CNTs, there were larger amount of enzymes adsorbed on the surface of CNT-NH2 with a favorable orientation and the best amperometric response was obtained on the AChE/CNT-NH2/GC electrode. Furthermore, the biosensor modified with CNT-NH2 showed a high affinity to acetylthiocholine chloride (ATCh) and could catalyze the hydrolysis of ATCh with an apparent Michaelis-Menten constant (Km) value of 67.4microM. Using paraoxon as a model compound, wide linear ranges from 0.2nM to 1nM and 1nM to 30nM, and a low detection limit of 0.08nM were obtained with satisfactory reproducibility and stability. Moreover, the biosensor had also been successfully employed for the determination of low concentrations of pesticides in real vegetable samples. This method could be extended to other functionalized nano-materials for their application in constructing biosensors.
ESTHER : Yu_2015_Biosens.Bioelectron_68C_288
PubMedSearch : Yu_2015_Biosens.Bioelectron_68C_288
PubMedID: 25594160

Title : Characterization of an Enterobacter cloacae Strain Producing both KPC and NDM Carbapenemases by Whole-Genome Sequencing - Wu_2015_Antimicrob.Agents.Chemother_59_6625
Author(s) : Wu W , Feng Y , Carattoli A , Zong Z
Ref : Antimicrobial Agents & Chemotherapy , 59 :6625 , 2015
Abstract : A carbapenem-resistant Enterobacter cloacae strain, WCHECl-14653, causing a fatal bloodstream infection, was characterized by genome sequencing and conjugation experiments. The strain carried two carbapenemase genes, blaNDM-1 and blaKPC-2, on separate IncF plasmids. The coexistence of blaNDM-1 and blaKPC-2 conferred slightly higher-level carbapenem resistance compared with that of blaNDM-1 or blaKPC-2 alone, and the coexistence of two IncF plasmids may generate new platforms for spreading carbapenemase genes.
ESTHER : Wu_2015_Antimicrob.Agents.Chemother_59_6625
PubMedSearch : Wu_2015_Antimicrob.Agents.Chemother_59_6625
PubMedID: 26248381
Gene_locus related to this paper: entcl-a0a0k0npw0

Title : (-)-phenserine attenuates soman-induced neuropathology - Chen_2014_PLoS.One_9_e99818
Author(s) : Chen J , Pan H , Chen C , Wu W , Iskandar K , He J , Piermartiri T , Jacobowitz DM , Yu QS , McDonough JH , Greig NH , Marini AM
Ref : PLoS ONE , 9 :e99818 , 2014
Abstract : Organophosphorus (OP) nerve agents are deadly chemical weapons that pose an alarming threat to military and civilian populations. The irreversible inhibition of the critical cholinergic degradative enzyme acetylcholinesterase (AChE) by OP nerve agents leads to cholinergic crisis. Resulting excessive synaptic acetylcholine levels leads to status epilepticus that, in turn, results in brain damage. Current countermeasures are only modestly effective in protecting against OP-induced brain damage, supporting interest for evaluation of new ones. (-)-Phenserine is a reversible AChE inhibitor possessing neuroprotective and amyloid precursor protein lowering actions that reached Phase III clinical trials for Alzheimer's Disease where it exhibited a wide safety margin. This compound preferentially enters the CNS and has potential to impede soman binding to the active site of AChE to, thereby, serve in a protective capacity. Herein, we demonstrate that (-)-phenserine protects neurons against soman-induced neuronal cell death in rats when administered either as a pretreatment or post-treatment paradigm, improves motoric movement in soman-exposed animals and reduces mortality when given as a pretreatment. Gene expression analysis, undertaken to elucidate mechanism, showed that (-)-phenserine pretreatment increased select neuroprotective genes and reversed a Homer1expression elevation induced by soman exposure. These studies suggest that (-)-phenserine warrants further evaluation as an OP nerve agent protective strategy.
ESTHER : Chen_2014_PLoS.One_9_e99818
PubMedSearch : Chen_2014_PLoS.One_9_e99818
PubMedID: 24955574

Title : A pan inhibitor of DASH family enzymes induces immunogenic modulation and sensitizes murine and human carcinoma cells to antigen-specific cytotoxic T lymphocyte killing: implications for combination therapy with cancer vaccines - Donahue_2014_Vaccine_32_3223
Author(s) : Donahue RN , Duncan BB , Fry TJ , Jones B , Bachovchin WW , Kiritsy CP , Lai JH , Wu W , Zhao P , Liu Y , Tsang KY , Hodge JW
Ref : Vaccine , :3223 , 2014
Abstract : Recent studies have suggested that pan inhibitors of dipeptidyl peptidase-4 activity and/or structure homologs (DASH), including ARI-4175, can mediate tumor regression by immune-mediated mechanisms. This study assessed the potential of combining ARI-4175 with cancer vaccines. We evaluated ARI-4175's effect on immunogenic modulation, ability to sensitize tumor cells to antigen-specific CTL killing, effect on immune-cell subsets and function, and antitumor activity in 2 tumor models, both as a monotherapy and in combination with a recombinant viral or dendritic cell (DC)-based tumor-cell vaccine. ARI-4175's effects on the growth, surface phenotype, and antigen-specific CTL-mediated lysis of murine and human carcinoma cell lines were assessed in vitro. In vivo, C57BL-6 mice were treated orally with ARI-4175, after which splenocytes were assessed by flow cytometry and functional assays. Antitumor studies were performed in murine models of colon carcinoma (MC38-CEA+ in CEA-transgenic C57BL-6 mice) and rhabdomyosarcoma (M3-9-M in C57BL-6 mice). Mice received oral ARI-4175 alone or in combination with a vaccine consisting of recombinant vaccinia/fowlpox CEA-TRICOM (colon model) or a DC-based tumor-cell vaccine (rhabdomyosarcoma model). Exposure to ARI-4175 had no effect on the proliferation or viability of carcinoma cells in vitro; however, it did alter tumor phenotype, making murine and human tumor cells more sensitive to antigen-specific CTL killing. Assessment of immune-cell subsets and function indicated that ARI-4175 increased levels of natural killer cells and DCs. Detrimental immune effects, including reduced T effector cells and increased immunosuppressive cells (Tregs, MDSCs), were normalized when treatment stopped, suggesting that scheduling is critical when combining this agent with vaccine. As a monotherapy, ARI-4175 had potent antitumor activity in both tumor models, and had even greater effects when combined with a vaccine (either DC-based or poxviral vector based). These findings provide the rationale for the combined use of cancer immunotherapy with DASH enzyme inhibitors such as ARI-4175.
ESTHER : Donahue_2014_Vaccine_32_3223
PubMedSearch : Donahue_2014_Vaccine_32_3223
PubMedID: 24731809

Title : Effects of Fraxinellone on the Midgut Enzyme Activities of the 5th Instar Larvae of Oriental Armyworm, Mythimna separata Walker - Lv_2014_Toxins.(Basel)_6_2708
Author(s) : Lv M , Wu W , Liu H
Ref : Toxins (Basel) , 6 :2708 , 2014
Abstract : Isolated from Dictamnus dasycarpus Turcz., fraxinellone exhibited multiple bioactivities against insects. In the present paper, the changes of digestive enzymes and detoxification enzymes of Mythimna separata Walker (5th instar larvae), treated with fraxinellone, were investigated. Compared with those of the control, the alpha-amylase activity of the fraxinellone-treated 5th instar larvae was inhibited, whereas the level of their protease activity was increased. Based upon further studies on the specific proteases, the levels of the active alkaline trypsin-like enzyme (BApNA as the substrate) and the chymotrypsin-like enzyme (BTEE as the substrate) activities of the treated larvae were declined; however, the level of activity of the weak alkaline trypsin-like enzyme (TAME as the substrate) of the treated ones was increased. Meanwhile, the activities of two detoxification enzymes, such as carboxylesterase (CarE) and glutathione S-transferase (GST), of the treated larvae were increased to some extent, but the activities of NADPH-P450 reductase and O-demethylase of the treated ones declined. Therefore, protease (especially the weak alkaline trypsin-like enzyme), CarE and GST played important roles in the metabolism of fraxinellone in the midgut of Mythimna separata (M. separata).
ESTHER : Lv_2014_Toxins.(Basel)_6_2708
PubMedSearch : Lv_2014_Toxins.(Basel)_6_2708
PubMedID: 25216084

Title : A high-throughput, multiplexed assay for superfamily-wide profiling of enzyme activity - Bachovchin_2014_Nat.Chem.Biol_10_656
Author(s) : Bachovchin DA , Koblan LW , Wu W , Liu Y , Li Y , Zhao P , Woznica I , Shu Y , Lai JH , Poplawski SE , Kiritsy CP , Healey SE , DiMare M , Sanford DG , Munford RS , Bachovchin WW , Golub TR
Ref : Nat Chemical Biology , 10 :656 , 2014
Abstract : The selectivity of an enzyme inhibitor is a key determinant of its usefulness as a tool compound or its safety as a drug. Yet selectivity is never assessed comprehensively in the early stages of the drug discovery process, and only rarely in the later stages, because technical limitations prohibit doing otherwise. Here, we report EnPlex, an efficient, high-throughput method for simultaneously assessing inhibitor potency and specificity, and pilot its application to 96 serine hydrolases. EnPlex analysis of widely used serine hydrolase inhibitors revealed numerous previously unrecognized off-target interactions, some of which may help to explain previously confounding adverse effects. In addition, EnPlex screening of a hydrolase-directed library of boronic acid- and nitrile-containing compounds provided structure-activity relationships in both potency and selectivity dimensions from which lead candidates could be more effectively prioritized. Follow-up of a series of dipeptidyl peptidase 4 inhibitors showed that EnPlex indeed predicted efficacy and safety in animal models. These results demonstrate the feasibility and value of high-throughput, superfamily-wide selectivity profiling and suggest that such profiling can be incorporated into the earliest stages of drug discovery.
ESTHER : Bachovchin_2014_Nat.Chem.Biol_10_656
PubMedSearch : Bachovchin_2014_Nat.Chem.Biol_10_656
PubMedID: 24997602
Gene_locus related to this paper: human-PPME1

Title : Identification of selective and potent inhibitors of fibroblast activation protein and prolyl oligopeptidase - Poplawski_2013_J.Med.Chem_56_3467
Author(s) : Poplawski SE , Lai JH , Li Y , Jin Z , Liu Y , Wu W , Wu Y , Zhou Y , Sudmeier JL , Sanford DG , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 56 :3467 , 2013
Abstract : Fibroblast activation protein (FAP) is a serine protease selectively expressed on reactive stromal fibroblasts of epithelial carcinomas. It is widely believed to play a role in tumor invasion and metastasis and therefore to represent a potential new drug target for cancer. Investigation into its biological function, however, has been hampered by the current unavailability of selective inhibitors. The challenge has been in identifying inhibitors that are selective for FAP over both the dipeptidyl peptidases (DPPs), with which it shares exopeptidase specificity, and prolyl oligopeptidase (PREP), with which it shares endopeptidase specificity. Here, we report the first potent FAP inhibitor with selectivity over both the DPPs and PREP, N-(pyridine-4-carbonyl)-d-Ala-boroPro (ARI-3099, 6). We also report a similarly potent and selective PREP inhibitor, N-(pyridine-3-carbonyl)-Val-boroPro (ARI-3531, 22). Both are boronic acid based inhibitors, demonstrating that high selectivity can be achieved using this electrophile. The inhibitors are stable, easy to synthesize, and should prove to be useful in helping to elucidate the biological functions of these two unique and interesting enzymes, as well as their potential as drug targets.
ESTHER : Poplawski_2013_J.Med.Chem_56_3467
PubMedSearch : Poplawski_2013_J.Med.Chem_56_3467
PubMedID: 23594271

Title : Quantitation of fibroblast activation protein (FAP)-specific protease activity in mouse, baboon and human fluids and organs - Keane_2013_FEBS.Open.Bio_4_43
Author(s) : Keane FM , Yao TW , Seelk S , Gall MG , Chowdhury S , Poplawski SE , Lai JH , Li Y , Wu W , Farrell P , Vieira de Ribeiro AJ , Osborne B , Yu DM , Seth D , Rahman K , Haber P , Topaloglu AK , Wang C , Thomson S , Hennessy A , Prins J , Twigg SM , McLennan SV , McCaughan GW , Bachovchin WW , Gorrell MD
Ref : FEBS Open Bio , 4 :43 , 2013
Abstract : The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was approximately 20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.
ESTHER : Keane_2013_FEBS.Open.Bio_4_43
PubMedSearch : Keane_2013_FEBS.Open.Bio_4_43
PubMedID: 24371721

Title : Whole-Genome Shotgun Assembly and Analysis of the Genome of Streptomyces mobaraensis DSM 40847, a Strain for Industrial Production of Microbial Transglutaminase - Yang_2013_Genome.Announc_1_e0014313
Author(s) : Yang H , He T , Wu W , Zhu W , Lu B , Sun W
Ref : Genome Announc , 1 :e0014313 , 2013
Abstract : Here, we report the draft annotated genome sequence of Streptomyces mobaraensis strain DSM 40847, which is used in industry to produce microbial transglutaminase. The genome sequence will allow for the characterization of the molecular mechanisms underlying the beneficial properties of this organism.
ESTHER : Yang_2013_Genome.Announc_1_e0014313
PubMedSearch : Yang_2013_Genome.Announc_1_e0014313
PubMedID: 23558536
Gene_locus related to this paper: strmb-m3c6n2 , strmb-m3c3t3 , strmb-m3a818 , strmb-m3ceh8 , strmb-m3cfp8 , strmb-m3bfl5 , strmb-m3c970 , 9actn-q9fb38 , strmb-m2zv71

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

Title : 4-Substituted boro-proline dipeptides: synthesis, characterization, and dipeptidyl peptidase IV, 8, and 9 activities - Wu_2012_Bioorg.Med.Chem.Lett_22_5536
Author(s) : Wu W , Liu Y , Milo LJ, Jr. , Shu Y , Zhao P , Li Y , Woznica I , Yu G , Sanford DG , Zhou Y , Poplawski SE , Connolly BA , Sudmeier JL , Bachovchin WW , Lai JH
Ref : Bioorganic & Medicinal Chemistry Lett , 22 :5536 , 2012
Abstract : The boroProline-based dipeptidyl boronic acids were among the first DPP-IV inhibitors identified, and remain the most potent known. We introduced various substitutions at the 4-position of the boroProline ring regioselectively and stereoselectively, and incorporated these aminoboronic acids into a series of 4-substituted boroPro-based dipeptides. Among these dipeptidyl boronic acids, Arg-(4S)-boroHyp (4q) was the most potent inhibitor of DPP-IV, DPP8 and DPP9, while (4S)-Hyp-(4R)-boroHyp (4o) exhibited the most selectivity for DPP-IV over DPP8 and DPP9.
ESTHER : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedSearch : Wu_2012_Bioorg.Med.Chem.Lett_22_5536
PubMedID: 22853995

Title : Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers - Varshney_2011_Nat.Biotechnol_30_83
Author(s) : Varshney RK , Chen W , Li Y , Bharti AK , Saxena RK , Schlueter JA , Donoghue MT , Azam S , Fan G , Whaley AM , Farmer AD , Sheridan J , Iwata A , Tuteja R , Penmetsa RV , Wu W , Upadhyaya HD , Yang SP , Shah T , Saxena KB , Michael T , McCombie WR , Yang B , Zhang G , Yang H , Wang J , Spillane C , Cook DR , May GD , Xu X , Jackson SA
Ref : Nat Biotechnol , 30 :83 , 2011
Abstract : Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries.
ESTHER : Varshney_2011_Nat.Biotechnol_30_83
PubMedSearch : Varshney_2011_Nat.Biotechnol_30_83
PubMedID: 22057054
Gene_locus related to this paper: cajca-a0a151r9d2 , cajca-a0a151u2m0 , cajca-a0a151tes0 , cajca-a0a151u784 , cajca-a0a151sf79 , cajca-a0a151qu18 , cajca-a0a151sz37 , cajca-a0a151ss18 , cajca-a0a151rb44 , cajca-a0a151ryr0 , cajca-a0a151qzm6 , cajca-a0a151rsm6 , cajca-a0a151rsn1 , cajca-a0a151tig2 , cajca-a0a151rwt3 , cajca-a0a151rx08 , cajca-a0a151rws4 , cajca-a0a151r0b7

Title : Pro-soft Val-boroPro: a strategy for enhancing in vivo performance of boronic acid inhibitors of serine proteases - Poplawski_2011_J.Med.Chem_54_2022
Author(s) : Poplawski SE , Lai JH , Sanford DG , Sudmeier JL , Wu W , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 54 :2022 , 2011
Abstract : Val-boroPro, 1, is a potent, but relatively nonspecific inhibitor of the prolyl peptidases. It has antihyperglycemic activity from inhibition of DPPIV but also striking anticancer activity and a toxicity for which the mechanisms are unknown. 1 cyclizes at physiological pH, which attenuates its inhibitory potency >100-fold, which is a "soft drug" effect. Here we show that this phenomenon can be exploited to create prodrugs with unique properties and potential for selective in vivo targeting. Enzyme-mediated release delivers 1 to the target in the active form at physiological pH; cyclization attenuates systemic pharmacological effects from subsequent diffusion. This "pro-soft" design is demonstrated with a construct activated by and targeted to DPPIV, including in vivo results showing improved antihyperglycemic activity and reduced toxicity relative to 1. Pro-soft derivatives of 1 can help to illuminate the mechanisms underlying the three biological activities, or to help localize 1 at a tumor and thereby lead to improved anticancer agents with reduced toxicity. The design concept can also be applied to a variety of other boronic acid inhibitors.
ESTHER : Poplawski_2011_J.Med.Chem_54_2022
PubMedSearch : Poplawski_2011_J.Med.Chem_54_2022
PubMedID: 21388136

Title : Crystal structure of a secreted lipase from Gibberella zeae reveals a novel double-lock mechanism - Lou_2010_Protein.Cell_1_760
Author(s) : Lou Z , Li M , Sun Y , Liu Y , Liu Z , Wu W , Rao Z
Ref : Protein Cell , 1 :760 , 2010
Abstract : Fusarium graminearum (sexual stage: Gibberella zeae) is the causative agent of Fusarium Head Blight (FHB), which is one of the most destructive plant disease of cereals, accounting for high grain yield losses, especially for wheat and maize. Like other fungal pathogens, several extracellular enzymes secreted by G. zeae are known to be involved in host infection. Among these secreted lipases, G. zeae lipase (GZEL), which is encoded by the FGL1 gene, was demonstrated to be crucial to G. zeae pathogenicity. However, the precise mechanism of GZEL remains unclear due to a lack of detailed structural information. In this study, we report the crystal structure of GZEL at the atomic level. The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique "double lock" enzymatic mechanism. To gain insight into substrate/inhibitor recognition, we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B (based on the reported structures of GZEL homologues), which defines possible substrate binding sites within the catalytic cleft and suggests an "anti sn-l" binding mode. These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors.
ESTHER : Lou_2010_Protein.Cell_1_760
PubMedSearch : Lou_2010_Protein.Cell_1_760
PubMedID: 21203917
Gene_locus related to this paper: gibze-q6wer3

Title : Genome sequencing and analysis of the model grass Brachypodium distachyon. -
Author(s) : Vogel JP , Garvin DF , Mockler TC , Schmutz J , Rokhsar D , Bevan MW , Barry K , Lucas S , Harmon-Smith M , Lail K , Tice H , Grimwood J , McKenzie N , Huo N , Gu YQ , Lazo GR , Anderson OD , You FM , Luo MC , Dvorak J , Wright J , Febrer M , Idziak D , Hasterok R , Lindquist E , Wang M , Fox SE , Priest HD , Filichkin SA , Givan SA , Bryant DW , Chang JH , Wu H , Wu W , Hsia AP , Schnable PS , Kalyanaraman A , Barbazuk B , Michael TP , Hazen SP , Bragg JN , Laudencia-Chingcuanco D , Weng Y , Haberer G , Spannagl M , Mayer K , Rattei T , Mitros T , Lee SJ , Rose JK , Mueller LA , York TL , Wicker T , Buchmann JP , Tanskanen J , Schulman AH , Gundlach H , Bevan M , de Oliveira AC , Maia Lda C , Belknap W , Jiang N , Lai J , Zhu L , Ma J , Sun C , Pritham E , Salse J , Murat F , Abrouk M , Bruggmann R , Messing J , Fahlgren N , Sullivan CM , Carrington JC , Chapman EJ , May GD , Zhai J , Ganssmann M , Gurazada SG , German M , Meyers BC , Green PJ , Tyler L , Wu J , Thomson J , Chen S , Scheller HV , Harholt J , Ulvskov P , Kimbrel JA , Bartley LE , Cao P , Jung KH , Sharma MK , Vega-Sanchez M , Ronald P , Dardick CD , De Bodt S , Verelst W , Inz D , Heese M , Schnittger A , Yang X , Kalluri UC , Tuskan GA , Hua Z , Vierstra RD , Cui Y , Ouyang S , Sun Q , Liu Z , Yilmaz A , Grotewold E , Sibout R , Hematy K , Mouille G , Hofte H , Michael T , Pelloux J , O'Connor D , Schnable J , Rowe S , Harmon F , Cass CL , Sedbrook JC , Byrne ME , Walsh S , Higgins J , Li P , Brutnell T , Unver T , Budak H , Belcram H , Charles M , Chalhoub B , Baxter I
Ref : Nature , 463 :763 , 2010
PubMedID: 20148030
Gene_locus related to this paper: bradi-i1grm0 , bradi-i1gx82 , bradi-i1hb80 , bradi-i1hkv6 , bradi-i1hpu6 , bradi-i1i3e4 , bradi-i1i9i0 , bradi-i1i435 , bradi-i1ix93 , bradi-i1gsk6 , bradi-i1hk44 , bradi-i1hk45 , bradi-i1hnk7 , bradi-i1hsd5 , bradi-i1huy4 , bradi-i1huy9 , bradi-i1huz0 , bradi-i1gxx9 , bradi-i1hl25 , bradi-i1hcw7 , bradi-i1hyv6 , bradi-i1hyb5 , bradi-i1hvr8 , bradi-i1hmu2 , bradi-i1hf05 , bradi-i1gry7 , bradi-i1hf06 , bradi-i1i5z8 , bradi-i1icy3 , bradi-i1j1h3 , bradi-i1h1e3 , bradi-i1hvr9 , bradi-a0a0q3r7i7 , bradi-i1i377 , bradi-i1hjg5 , bradi-i1h3i9 , bradi-i1gsg5 , bradi-a0a0q3mph9 , bradi-i1h682 , bradi-a0a0q3lc91 , bradi-i1gx49 , bradi-i1i839 , bradi-a0a2k2dsp5 , bradi-i1gsb5

Title : Morphing activity between structurally similar enzymes: from heme-free bromoperoxidase to lipase - Chen_2009_Biochemistry_48_11496
Author(s) : Chen B , Cai Z , Wu W , Huang Y , Pleiss J , Lin Z
Ref : Biochemistry , 48 :11496 , 2009
Abstract : In this study, to explore the plasticity of the alpha/beta-hydrolase fold family, we converted bromoperoxidase A2 (BPO-A2) from Streptomyces aureofaciens to a lipase by structure comparison with lipase A (LipA) from Bacillus subtilis. These two enzymes have similar structures (2.1 A rmsd) and a very low level of sequence identity ( approximately 18%). A variant BL1 was constructed by deleting the caplike domain of BPO-A2 and further fine-tuning the newly formed substrate binding site. The lipase activity was successfully transplanted on BL1, while the halogenation activity was totally lost. BL1 also showed higher hydrolytic activities toward long chain p-nitrophenyl esters, such as p-nitrophenyl caprylate (3.7-fold) and p-nitrophenyl palmitate (7.0-fold), while its activity toward a short chain ester (p-nitrophenyl acetate) decreased dramatically, to only 1.2% of that of BPO-A2. After two rounds of directed evolution and site-directed mutagenesis on selected residues, several mutants with both improved hydrolytic activities and substrate preferences toward long chain substrates were obtained. The highest hydrolytic activity toward p-nitrophenyl palmitate of the best mutant BL1-2-E8-plusI was improved by 40-fold compared with that of BL1. These results demonstrate the possibility of manipulating the caplike domain of alpha/beta-hydrolase fold enzymes and provide further understanding of the structure-function relationship of the alpha/beta-hydrolase fold enzymes. The design strategy used in this study could serve as a useful approach for constructing variants with targeted catalytic properties using the alpha/beta-hydrolase fold.
ESTHER : Chen_2009_Biochemistry_48_11496
PubMedSearch : Chen_2009_Biochemistry_48_11496
PubMedID: 19883129

Title : The genome of the blood fluke Schistosoma mansoni - Berriman_2009_Nature_460_352
Author(s) : Berriman M , Haas BJ , LoVerde PT , Wilson RA , Dillon GP , Cerqueira GC , Mashiyama ST , Al-Lazikani B , Andrade LF , Ashton PD , Aslett MA , Bartholomeu DC , Blandin G , Caffrey CR , Coghlan A , Coulson R , Day TA , Delcher A , DeMarco R , Djikeng A , Eyre T , Gamble JA , Ghedin E , Gu Y , Hertz-Fowler C , Hirai H , Hirai Y , Houston R , Ivens A , Johnston DA , Lacerda D , Macedo CD , McVeigh P , Ning Z , Oliveira G , Overington JP , Parkhill J , Pertea M , Pierce RJ , Protasio AV , Quail MA , Rajandream MA , Rogers J , Sajid M , Salzberg SL , Stanke M , Tivey AR , White O , Williams DL , Wortman J , Wu W , Zamanian M , Zerlotini A , Fraser-Liggett CM , Barrell BG , El-Sayed NM
Ref : Nature , 460 :352 , 2009
Abstract : Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.
ESTHER : Berriman_2009_Nature_460_352
PubMedSearch : Berriman_2009_Nature_460_352
PubMedID: 19606141
Gene_locus related to this paper: schma-ACHE1 , schma-ACHE2 , schma-c4qb79 , schma-c4qmk4 , schma-g4v9h7 , schma-BCHE , schma-g4vmf3

Title : Dipeptide boronic acid inhibitors of dipeptidyl peptidase IV: determinants of potency and in vivo efficacy and safety - Connolly_2008_J.Med.Chem_51_6005
Author(s) : Connolly BA , Sanford DG , Chiluwal AK , Healey SE , Peters DE , Dimare MT , Wu W , Liu Y , Maw H , Zhou Y , Li Y , Jin Z , Sudmeier JL , Lai JH , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 51 :6005 , 2008
Abstract : Dipeptidyl peptidase IV (DPP-IV; E.C. 3.4.14.5), a serine protease that degrades the incretin hormones GLP-1 and GIP, is now a validated target for the treatment of type 2 diabetes. Dipeptide boronic acids, among the first, and still among the most potent DPP-IV inhibitors known, suffer from a concern over their safety. Here we evaluate the potency, in vivo efficacy, and safety of a selected set of these inhibitors. The adverse effects induced by boronic acid-based DPP-IV inhibitors are essentially limited to what has been observed previously for non-boronic acid inhibitors and attributed to cross-reactivity with DPP8/9. While consistent with the DPP8/9 hypothesis, they are also consistent with cross-reactivity with some other intracellular target. The results further show that the potency of simple dipeptide boronic acid-based inhibitors can be combined with selectivity against DPP8/9 in vivo to produce agents with a relatively wide therapeutic index (>500) in rodents.
ESTHER : Connolly_2008_J.Med.Chem_51_6005
PubMedSearch : Connolly_2008_J.Med.Chem_51_6005
PubMedID: 18783201

Title : Synthesis and characterization of constrained peptidomimetic dipeptidyl peptidase IV inhibitors: amino-lactam boroalanines - Lai_2007_J.Med.Chem_50_2391
Author(s) : Lai JH , Wu W , Zhou Y , Maw HH , Liu Y , Milo LJ, Jr. , Poplawski SE , Henry GD , Sudmeier JL , Sanford DG , Bachovchin WW
Ref : Journal of Medicinal Chemistry , 50 :2391 , 2007
Abstract : We describe here the epimerization-free synthesis and characterization of a new class of conformationally constrained lactam aminoboronic acid inhibitors of dipeptidyl peptidase IV (DPP IV; E.C. 3.4.14.5). These compounds have the advantage that they cannot undergo the pH-dependent cyclization prevalent in most dipeptidyl boronic acids that attenuates their potency at physiological pH. For example, D-3-amino-1-[L-1-boronic-ethyl]-pyrrolidine-2-one (amino-D-lactam-L-boroAla), one of the best lactam inhibitors of DPP IV, is several orders of magnitude less potent than L-Ala-L-boroPro, as measured by Ki values (2.3 nM vs 30 pM, respectively). At physiological pH, however, it is actually more potent than L-Ala-L-boroPro, as measured by IC50 values (4.2 nM vs 1400 nM), owing to the absence of the potency-attenuating cyclization. In an interesting and at first sight surprising reversal of the relationship between stereochemistry and potency observed with the conformationally unrestrained Xaa-boroPro class of inhibitors, the L-L diastereomers of the lactams are orders of magnitude less effective than the D-L lactams. However, this interesting reversal and the unexpected potency of the D-L lactams as DPP IV inhibitors can be understood in structural terms, which is explained and discussed here.
ESTHER : Lai_2007_J.Med.Chem_50_2391
PubMedSearch : Lai_2007_J.Med.Chem_50_2391
PubMedID: 17458948

Title : Comparative and functional genomic analyses of the pathogenicity of phytopathogen Xanthomonas campestris pv. campestris - Qian_2005_Genome.Res_15_757
Author(s) : Qian W , Jia Y , Ren SX , He YQ , Feng JX , Lu LF , Sun Q , Ying G , Tang DJ , Tang H , Wu W , Hao P , Wang L , Jiang BL , Zeng S , Gu WY , Lu G , Rong L , Tian Y , Yao Z , Fu G , Chen B , Fang R , Qiang B , Chen Z , Zhao GP , Tang JL , He C
Ref : Genome Res , 15 :757 , 2005
Abstract : Xanthomonas campestris pathovar campestris (Xcc) is the causative agent of crucifer black rot disease, which causes severe losses in agricultural yield world-wide. This bacterium is a model organism for studying plant-bacteria interactions. We sequenced the complete genome of Xcc 8004 (5,148,708 bp), which is highly conserved relative to that of Xcc ATCC 33913. Comparative genomics analysis indicated that, in addition to a significant genomic-scale rearrangement cross the replication axis between two IS1478 elements, loss and acquisition of blocks of genes, rather than point mutations, constitute the main genetic variation between the two Xcc strains. Screening of a high-density transposon insertional mutant library (16,512 clones) of Xcc 8004 against a host plant (Brassica oleraceae) identified 75 nonredundant, single-copy insertions in protein-coding sequences (CDSs) and intergenic regions. In addition to known virulence factors, full virulence was found to require several additional metabolic pathways and regulatory systems, such as fatty acid degradation, type IV secretion system, cell signaling, and amino acids and nucleotide metabolism. Among the identified pathogenicity-related genes, three of unknown function were found in Xcc 8004-specific chromosomal segments, revealing a direct correlation between genomic dynamics and Xcc virulence. The present combination of comparative and functional genomic analyses provides valuable information about the genetic basis of Xcc pathogenicity, which may offer novel insight toward the development of efficient methods for prevention of this important plant disease.
ESTHER : Qian_2005_Genome.Res_15_757
PubMedSearch : Qian_2005_Genome.Res_15_757
PubMedID: 15899963
Gene_locus related to this paper: xanax-DHAA , xanax-ENTF2 , xanax-GAA , xanax-PTRB , xanax-XAC0515 , xanax-XAC0628 , xanax-XAC0736 , xanax-XAC0753 , xanax-XAC1713 , xanca-acvB , xanca-BIOH , xanca-CATD , xanca-CPO , xanca-estA1 , xanca-impep , xanca-META , xanca-METX , xanca-PCAD , xanca-PHBC , xanca-Q8PB04 , xanca-W78 , xanca-XCC0080 , xanca-XCC0180 , xanca-XCC0243 , xanca-XCC0266 , xanca-XCC0372 , xanca-XCC0375 , xanca-XCC0753 , xanca-XCC0800 , xanca-XCC0843 , xanca-XCC1105 , xanca-XCC1734 , xanca-XCC2285 , xanca-XCC2374 , xanca-XCC2397 , xanca-XCC2405 , xanca-XCC2566 , xanca-XCC2722 , xanca-XCC2737 , xanca-XCC2811 , xanca-XCC2817 , xanca-XCC2854 , xanca-XCC2869 , xanca-XCC3028 , xanca-XCC3164 , xanca-XCC3219 , xanca-XCC3296 , xanca-XCC3320 , xanca-XCC3514 , xanca-XCC3548 , xanca-XCC3555 , xanca-XCC3623 , xanca-XCC3915 , xanca-XCC3961 , xanca-XCC3970 , xanca-XCC4016 , xanca-XCC4096 , xanca-XCC4180 , xanca-XYNB , xanca-XYNB2 , xancb-b0rq23 , xancp-q8pax3 , xancp-y2094

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

Title : Purification of Torpedo californica post-synaptic membranes and fractionation of their constituent proteins - Elliott_1980_Biochem.J_185_667
Author(s) : Elliott J , Blanchard SG , Wu W , Miller J , Strader CD , Hartig P , Moore HP , Racs J , Raftery MA
Ref : Biochemical Journal , 185 :667 , 1980
Abstract : A rapid methof for preparation of membrane fractions highly enriched in nicotinic acetylcholine receptor from Torpedo californica electroplax is described. The major step in this purification involves sucrose-density-gradient centrifugation in a reorienting rotor. Further purification of these membranes can be achieved by selective extraction of proteins by use of alkaline pH or by treatment with solutions of lithium di-idosalicylate. The alkali-treated membranes retain functional characteristics of the untreated membranes and in addition contain essentially only the four polypeptides (mol.wts. 40000, 50000, 60000 and 65000) characteristic of the receptor purified by affinity chromatography. Dissolution of the purified membranes or of the alkali-treated purified membranes in sodium cholate solution followed by sucrose-density-gradient centrifugation in the same detergent solution yields solubilized receptor preparations comparable with the most highly purified protein obtained by affinity-chromatographic procedures.
ESTHER : Elliott_1980_Biochem.J_185_667
PubMedSearch : Elliott_1980_Biochem.J_185_667
PubMedID: 7387629

Title : Properties of Torpedo californica acetylcholine receptor -
Author(s) : Raftery M , Blanchard S , Elliott J , Hartig P , Moore HP , Quast U , Schimerlik M , Witzemann V , Wu W
Ref : Advances in Cytopharmacology , 3 :159 , 1979
PubMedID: 382781