Zhao X

References (150)

Title : A Long-Acting Lyotropic Liquid Crystalline Implant Promotes the Drainage of Macromolecules by Brain-Related Lymphatic System in Treating Aged Alzheimer's Disease - Shan_2024_ACS.Nano__
Author(s) : Shan X , Lu Y , Luo Z , Zhao X , Pang M , Yin H , Guo X , Zhou H , Zhang J , Huang J , Shi Y , Lou J , Luo L , You J
Ref : ACS Nano , : , 2024
Abstract : Numerous evidence has demonstrated that the brain is not an immune-privileged organ but possesses a whole set of lymphatic transport system, which facilitates the drainage of harmful waste from brains to maintain cerebral homeostasis. However, as individuals age, the shrinkage and dysfunction of meningeal and deep cervical lymphatic networks lead to reduced waste outflow and elevated neurotoxic molecules deposition, further inducing aging-associated cognitive decline, which act as one of the pathological mechanisms of Alzheimer's disease. Consequently, recovering the function of meningeal and deep cervical lymph node (dCLNs) networks (as an important part of the brain waste removal system (BWRS)) of aged brains might be a feasible strategy. Herein we showed that the drug brain-entering efficiency was highly related to administration routes (oral, subcutaneous, or dCLN delivery). Besides, by injecting a long-acting lyotropic liquid crystalline implant encapsulating cilostazol (an FDA-approved selective PDE-3 inhibitor) and donepezil hydrochloride (a commonly used symptomatic relief agent to inhibit acetylcholinesterase for Alzheimer's disease) near the deep cervical lymph nodes of aged mice (about 20 months), an increase of lymphatic vessel coverage in the nodes and meninges was observed, along with accelerated drainage of macromolecules from brains. Compared with daily oral delivery of cilostazol and donepezil hydrochloride, a single administered dual drugs-loaded long-acting implants releasing for more than one month not only elevated drug concentrations in brains, improved the clearing efficiency of brain macromolecules, reduced Abeta accumulation, enhanced cognitive functions of the aged mice, but improved patient compliance as well, which provided a clinically accessible therapeutic strategy toward aged Alzheimer's diseases.
ESTHER : Shan_2024_ACS.Nano__
PubMedSearch : Shan_2024_ACS.Nano__
PubMedID: 38517764

Title : Immobilization of Thermomyces lanuginosus lipase in a novel polysaccharide-based hydrogel by a two-step crosslinking method and its use in the lauroylation of alpha-arbutin - Chen_2024_Bioresour.Bioprocess_11_7
Author(s) : Chen M , She W , Zhao X , Chen C , Zhu B , Sun Y , Yao Z
Ref : Bioresour Bioprocess , 11 :7 , 2024
Abstract : The Thermomyces lanuginosus lipase (TLLs) was successfully immobilized within a novel hydrogel matrix through a two-step crosslinking method. TLLs were initially crosslinked through the Schiff base reaction by oxidized carboxymethyl cellulose (OCMC). The water-soluble OCMC@TLLs complex was subsequently crosslinked by carboxymethyl chitosan (CMCSH) in a microfluidic apparatus to form the CMCHS/OCMC@TLLs microspheres. The CD (Circular Dichroism, CD) and FT-IR (Fourier Transform infrared spectroscopy, FT-IR) spectra demonstrated that the crosslinking of TLLs with OCMC resulted in a less significant impact on their structure compared to that with glutaraldehyde. CMCHS/OCMC@TLLs showed decreased catalytic performance due to the mass transfer resistance, while its thermal stability was greatly improved. The CMCHS/OCMC@TLLs were used to catalyze the lauroylation of arbutin in tetrahydrofuran. After 12 h of reaction under optimal conditions, the yield of 6'-O-lauryl arbutin reached an impressive 92.12%. The prepared 6'-O-lauryl arbutin has high lipophilicity and exhibits similar tyrosinase inhibitory activity and higher antioxidant activity compared to its parent compound.
ESTHER : Chen_2024_Bioresour.Bioprocess_11_7
PubMedSearch : Chen_2024_Bioresour.Bioprocess_11_7
PubMedID: 38647918

Title : Upconversion-based hydrogel kit with Python-assisted analysis platform for sample-to-result detection of organophosphorus pesticide - Kong_2024_J.Colloid.Interface.Sci_670_626
Author(s) : Kong M , Lu Y , Ma Y , Zhao X , Wu J , Lu G , Yan X , Liu X
Ref : J Colloid Interface Sci , 670 :626 , 2024
Abstract : On-site quantitative analysis of pesticide residues is crucial for monitoring environmental quality and ensuring food safety. Herein, we have developed a reliable hydrogel portable kit using NaYbF(4)@NaYF(4): Yb, Tm upconversion nanoparticles (UCNPs) combined with MnO(2) nanoflakes. This portable kit is integrated with a smartphone reader and Python-assisted analysis platform to enable sample-to-result analysis for chlorpyrifos. The novel UCNPs maximizes energy donation to MnO(2) acceptor by employing 100 % of activator Yb(3+) in the nucleus for NIR excitation energy collection and confining emitter Tm(3+) to the surface layer to shorten energy transfer distance. Under NIR excitation, efficient quenching of upconversion blue-violet emission by MnO(2) nanoflakes occurs, and the quenched emission is recovered with acetylcholinesterase-mediated reactions. This process allows for the determination of chlorpyrifos by inhibiting enzymatic activity. The UCNPs/MnO(2) were embedded to fabricate a hydrogel portable kit, the blue-violet emission images captured by smartphone were converted into corresponding gray values by Python-assisted superiority chart algorithm which achieves a real-time rapid quantitative analysis of chlorpyrifos with a detection limit of 0.17 ng mL(-1). At the same time, pseudo-color images were also added by Python in "one run" to distinguish images clearly. This sensor detection with Python-assisted analysis platform provides a new perspective on pesticide monitoring and broadens the application prospects in bioanalysis.
ESTHER : Kong_2024_J.Colloid.Interface.Sci_670_626
PubMedSearch : Kong_2024_J.Colloid.Interface.Sci_670_626
PubMedID: 38781653

Title : Screening of Active Substances Regulating Alzheimer's Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets - Pan_2024_Foods_13_
Author(s) : Pan Y , Li Z , Zhao X , Du Y , Zhang L , Lu Y , Yang L , Cao Y , Qiu J , Qian Y
Ref : Foods , 13 : , 2024
Abstract : Ginger has been reported to potentially treat Alzheimer's disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In this study, a combination of network pharmacology, molecular docking, and dynamic simulation technology was used to screen active substances that regulate AD and explore their mechanisms. The TCMSP, GeneCards, OMIM, and DisGeNET databases were utilized to obtain 95 cross-targets related to ginger's active ingredients and AD as key targets. A functional enrichment analysis revealed that the pathways in which ginger's active substances may be involved in regulating AD include response to exogenous stimuli, response to oxidative stress, response to toxic substances, and lipid metabolism, among others. Furthermore, a drug-active ingredient-key target interaction network diagram was constructed, highlighting that 6-Gingerol is associated with 16 key targets. Additionally, a protein-protein interaction (PPI) network was mapped for the key targets, and HUB genes (ALB, ACTB, GAPDH, CASP3, and CAT) were identified. Based on the results of network pharmacology and cell experiments, 6-Gingerol was selected as the active ingredient for further investigation. Molecular docking was performed between 6-Gingerol and its 16 key targets, and the top three proteins with the strongest binding affinities (ACHE, MMP2, and PTGS2) were chosen for molecular dynamics analysis together with the CASP3 protein as the HUB gene. The findings indicate that 6-Gingerol exhibits strong binding ability to these disease targets, suggesting its potential role in regulating AD at the molecular level, as well as in abnormal cholinesterase metabolism and cell apoptosis, among other related regulatory pathways. These results provide a solid theoretical foundation for future in vitro experiments using actual cells and animal experiments to further investigate the application of 6-Gingerol.
ESTHER : Pan_2024_Foods_13_
PubMedSearch : Pan_2024_Foods_13_
PubMedID: 38397589

Title : Corrigendum to Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease [Eur. J. Med. Chem. 265 (2024) 116071] -
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , :116169 , 2024
PubMedID: 38290915

Title : The acute neurotoxicity of inorganic mercury in Mactra chinensis philippi - Ma_2024_Aquat.Toxicol_270_106896
Author(s) : Ma B , Zhao X , Zhang X , Yang B , Cai Z , Xing Z , Xu M , Mi L , Zhang J , Wang L , Zhao Y , Liu X
Ref : Aquat Toxicol , 270 :106896 , 2024
Abstract : Inorganic mercury (IHg) is hazardous to marine organisms especially resulting in neurotoxicity, bivalves are sensitive to pollutants as "ocean sentinel", but data on the neurotoxicity of IHg in bivalves are sparse. So we chosed M. chinensis philippi with typical neural structures in bivalves to investigate the neurotoxicity of IHg, which could be helpful to understand the specificity of neural regulation and the response characteristics of bivalves. After acute exposed to IHg (HgCl(2)) for 24 h, the metabolites of ganglion tissues in M. chinensis philippi were evaluated using (1)H-nuclear magnetic resonance based metabolomics; Ca(2+), neurotransmitters (nitric oxide, glutamate, acetylcholine) and related enzymes (calcineurin, nitric oxide synthase and acetylcholinesterase) were measured using biochemical detection. Compared to the control group, the levels of the nitric oxide (81.04 +/- 12.84 micromol/g prot) and acetylcholine (30.93 +/- 12.57 microg/mg prot) in M. chinensis philippi of IHg-treated were decreased, while glutamate (2.11 +/- 0.61 mmol/L) increased significantly; the activity of nitric oxide synthase (679.34 +/- 135.33 U/mg prot) was increased, while acetylcholinesterase (1.39 +/- 0.44 U/mg prot) decreased significantly, and the activity of calcineurin (0.52 +/- 0.02 U/mg prot) had a statistically insignificant increasing tendency. The concentration of Ca(2+) (0.92 +/- 0.46 mmol/g prot) in the IHg-treated group was significantly higher than that in the control group. OPLS-DA was performed to reveal the difference in metabolites between the control and IHg-challenged groups, the metabolites of glucose, glutamine, inosine, succinate, glutamate, homarine, and alanine were sensitive to IHg, subsequently metabolic pathways that were affected including glucose metabolism, glutamine metabolism, nucleotide metabolism, Krebs cycle, amino acid metabolism and osmotic regulation. In our study, IHg interfered with metabolites in M. chinensis philippi, thus the corresponding metabolic pathways were changed, which influenced the neurotransmitters subsequently. Furthermore, Ca(2+)overload affected the synthesis or degradation of the neurotransmitters, and then the altered neurotransmitters involved in changes in metabolic pathways again. Overall, we hypothesized that the neurotoxic effects of IHg on bivalve were in close contact with metabolism, neurotransmitters, related enzymes and Ca(2+), which could be effective neurotoxic biomarkers for marine environmental quality assessment, and also provide effective data for the study of the regulatory mechanism of the nervous system in response to IHg in bivalves.
ESTHER : Ma_2024_Aquat.Toxicol_270_106896
PubMedSearch : Ma_2024_Aquat.Toxicol_270_106896
PubMedID: 38490093

Title : Antennal transcriptomic analysis of carboxylesterases and glutathione S-transferases associated with odorant degradation in the tea gray geometrid, Ectropis grisescens (Lepidoptera, Geometridae) - Zhang_2023_Front.Physiol_14_1183610
Author(s) : Zhang F , Chen Y , Zhao X , Guo S , Hong F , Zhi Y , Zhang L , Zhou Z , Zhang Y , Zhou X , Li X
Ref : Front Physiol , 14 :1183610 , 2023
Abstract : Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown. Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively. Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae. Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens.
ESTHER : Zhang_2023_Front.Physiol_14_1183610
PubMedSearch : Zhang_2023_Front.Physiol_14_1183610
PubMedID: 37082242

Title : Comparison of the chronic and multigenerational toxicity of racemic glufosinate and l-glufosinate to Caenorhabditis elegans at environmental concentrations - Zhao_2023_Chemosphere_316_137863
Author(s) : Zhao X , Fu K , Xiang KP , Wang LY , Zhang YF , Luo YP
Ref : Chemosphere , 316 :137863 , 2023
Abstract : Glufosinate-ammonium, the second largest transgene crop resistant herbicide, is classified as a mobile persistent pollutant by the U.S. Environmental Protection Agencybecause of its slow decomposition and easy mobile transfer in a water environment. The chronic and multigeneration toxicity of this compound to environmental organisms are alarming. In this study, racemic glufosinate-ammonium and the effective isomer, l-glufosinate-ammonium, were used as the test agents. The developmental, neurotoxic and reproductive toxicities of Caenorhabditis elegans to their parents and progeny were studied by continuous exposure in water at concentrations of 0.1, 1, 10 and 100 microg/L. The causes of toxicity differences were analysed from oxidative stress and transcription levels. Through oxidative stress of C. elegans, racemic glufosinate-ammonium and l-glufosinate-ammonium both mediated the developmental toxicity (shortened developmental cycle, reduced body length and width, promoted ageingand decreased longevity), neurotoxicity (inhibited head swinging, body bending frequency and acetylcholinesterase [AchE] activity) and reproductive toxicity (significant reductions in the number of eggs and offspring in vivo and induced apoptosis of gonadal cells). These phenomena caused oxidative damage (protein and membrane lipid peroxidation) and further induced apoptosis. The changes in various indicators caused by racemic glufosinate-ammonium exposure were more significant than those caused by l-glufosinate-ammonium exposure, and the reproduction-related indicators were more significant than the developmental and neurological indicators. A continuous accumulation of toxicity was observed after multiple generations of continuous exposure. These research results provide a data reference for the ecotoxicological evaluation and risk assessment of glufosinate-ammonium and contribute to the revision and improvement of the related environmental policies of glufosinate-ammonium.
ESTHER : Zhao_2023_Chemosphere_316_137863
PubMedSearch : Zhao_2023_Chemosphere_316_137863
PubMedID: 36649895

Title : A near-infrared fluorescent probe based on a hemi-cyanine skeleton for detecting CES1 activity and evaluating pesticide toxicity - Zhao_2023_J.Mater.Chem.B__
Author(s) : Zhao X , Tian M , Wang Y , Yang F , Liang G , Tian X , Feng L , Cui J
Ref : J Mater Chem B , : , 2023
Abstract : A novel near-infrared (NIR) fluorescent probe CHC-CES1 based on a hemi-cyanine skeleton for detecting carboxylesterase 1 (CES1) activity was developed. Herein, CHC-CES1 could be specifically hydrolysed to CHC-COOH along with a significant NIR fluorescence signal enhancement at 670 nm. Systematic evaluation indicated that CHC-CES1 possessed an outstanding selectivity and sensitivity towards CES1, and possessed good chemical stability in complex biosamples. Finally, CHC-CES1 was successfully used for the real-time imaging of endogenous CES1 activity in living cells. Moreover, CHC-CES1 was applied to evaluate the inhibitory effects of various pesticides towards CES1, and visually revealed the inhibitory effect of combined residue pesticides.
ESTHER : Zhao_2023_J.Mater.Chem.B__
PubMedSearch : Zhao_2023_J.Mater.Chem.B__
PubMedID: 37071077

Title : Novel harmine derivatives as potent acetylcholinesterase and amyloid beta aggregation dual inhibitors for management of Alzheimer's disease - Du_2023_J.Enzyme.Inhib.Med.Chem_38_2281893
Author(s) : Du H , Song J , Ma F , Gao H , Zhao X , Mao R , He X , Yan Y
Ref : J Enzyme Inhib Med Chem , 38 :2281893 , 2023
Abstract : In this study, a series of potential ligands for the treatment of AD were synthesised and characterised as novel harmine derivatives modified at position 9 with benzyl piperazinyl. In vitro studies revealed that the majority of the derivatives exhibited moderate to potent inhibition against hAChE and Abeta(1-42) aggregation. Notably, compounds 13 and 17d displayed potent drug-likeness and ADMET properties, demonstrating remarkable inhibitory activities towards AChE (IC(50) = 58.76 nM and 89.38 nM, respectively) as well as Abeta aggregation (IC(50) = 9.31 microM and 13.82 microM, respectively). More importantly, compounds 13 and 17d showed exceptional neuroprotective effects against Abeta(1-42)-induced SH-SY5Y damage, while maintaining low toxicity in SH-SY5Y cells. Further exploration of the mechanism through kinetic studies and molecular modelling confirmed that compound 13 could interact with both the CAS and the PAS of AChE. These findings suggested that harmine derivatives hold great potential as dual-targeted candidates for treating AD.
ESTHER : Du_2023_J.Enzyme.Inhib.Med.Chem_38_2281893
PubMedSearch : Du_2023_J.Enzyme.Inhib.Med.Chem_38_2281893
PubMedID: 37965884

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

Title : Comparative metaproteomics reveal co-contribution of onion maggot and its gut microbiota to phoxim resistance - Zhou_2023_Ecotoxicol.Environ.Saf_267_115649
Author(s) : Zhou F , Liang Q , Zhao X , Wu X , Fan S , Zhang X
Ref : Ecotoxicology & Environmental Safety , 267 :115649 , 2023
Abstract : Pesticide resistance inflicts significant economic losses on a global scale each year. To address this pressing issue, substantial efforts have been dedicated to unraveling the resistance mechanisms, particularly the newly discovered microbiota-derived pesticide resistance in recent decades. Previous research has predominantly focused on investigating microbiota-derived pesticide resistance from the perspective of the pest host, associated microbes, and their interactions. However, a gap remains in the quantification of the contribution by the pest host and associated microbes to this resistance. In this study, we investigated the toxicity of phoxim by examining one resistant and one sensitive Delia antiqua strain. We also explored the critical role of associated microbiota and host in conferring phoxim resistance. In addition, we used metaproteomics to compare the proteomic profile of the two D. antiqua strains. Lastly, we investigated the activity of detoxification enzymes in D. antiqua larvae and phoxim-degrading gut microbes, and assessed their respective contributions to phoxim resistance in D. antiqua. The results revealed contributions by D. antiqua and its gut bacteria to phoxim resistance. Metaproteomics showed that the two D. antiqua strains expressed different protein profiles. Detoxifying enzymes including Glutathione S-transferases, carboxylesterases, Superoxide Dismutase, Glutathione Peroxidase, and esterase B1 were overexpressed in the resistant strain and dominated in differentially expressed insect proteins. In addition, organophosphorus hydrolases combined with a group of ABC type transporters were overexpressed in the gut microbiota of resistant D. antiqua compared to the sensitive strain. 85.2% variation of the larval mortality resulting from phoxim treatment could be attributed to the combined effects of proteins from both from gut bacteria and D. antiqua, while the individual contribution of proteins from gut bacteria or D. antiqua alone accounted for less than 10% of the variation in larval mortality caused by phoxim. The activity of the overexpressed insect enzymes and the phoxim-degrading activity of gut bacteria in resistant D. antiqua larvae were further confirmed. This work enhances our understanding of microbiota-derived pesticide resistance and illuminates new strategies for controlling pesticide resistance in the context of insect-microbe mutualism.
ESTHER : Zhou_2023_Ecotoxicol.Environ.Saf_267_115649
PubMedSearch : Zhou_2023_Ecotoxicol.Environ.Saf_267_115649
PubMedID: 37913580

Title : Ultrasensitivity Detecting AChE through "\;Covalent Assembly"\; and Signal Amplification Strategic Approaches and Applied to Screen Its Inhibitor - Zhao_2023_Anal.Chem__
Author(s) : Zhao Y , Shen A , Hao X , Li M , Hou L , Li Z , Duan R , Du M , Li X , Wang X , Zhao X , Yang Y
Ref : Analytical Chemistry , : , 2023
Abstract : An ultrasensitivity detecting assay for acetylcholinesterase (AChE) activity was developed based on "covalent assembly" and signal amplification strategic approaches. After hydrolyzing thioacetylcholine by AChE and participation of thiol in a self-inducing cascade accelerated by the Meldrum acid derivatives of 2-[bis(methylthio) methylene] malonitrile (CA-2), mercaptans triggered an intramolecular cyclization assembly by the probe of 2-(2,2-dicyanovinyl)-5-(diethylamino) phenyl 2,4-dinitrobenzenesulfonate (Sd-I) to produce strong fluorescence. The limit of detection for AChE activity was as low as 0.0048 mU/mL. The detection system also had a good detecting effect on AChE activity in human serum and could also be used to screen its inhibitors. By constructing a Sd-I@agarose hydrogel with a smartphone, a point-of-care detection of AChE activity was achieved again.
ESTHER : Zhao_2023_Anal.Chem__
PubMedSearch : Zhao_2023_Anal.Chem__
PubMedID: 36812425

Title : Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease - Liu_2023_Eur.J.Med.Chem_265_116071
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , 265 :116071 , 2023
Abstract : In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC(50) = 30.35 +/- 2.07 nM) and human butyrylcholinesterase (hBuChE, IC(50) = 48.03 +/- 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H(2)O(2)-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Abeta(1-42) and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.
ESTHER : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedSearch : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedID: 38157596

Title : Genome-wide identification and expression of monoacylglycerol lipase (MAGL) gene family in peanut (Arachis hypogaea L.) and functional analysis of AhMGATs in neutral lipid metabolism - Zhan_2023_Int.J.Biol.Macromol_243_125300
Author(s) : Zhan Y , Wu T , Zhao X , Wang J , Guo S , Chen S , Qu S , Zheng Z
Ref : Int J Biol Macromol , 243 :125300 , 2023
Abstract : Monoacylglycerol lipase (MAGL) involved in regulating plant growth and development and stress responses, hydrolyzes monoacylglycerol (MAG) into free fatty acid and glycerol, which is the last step of triacylglycerol (TAG) breakdown. Here, a genome-wide characterization of MAGL gene family from cultivated peanut (Arachis hypogaea L.) was performed. In total, 24 MAGL genes were identified and unevenly distributed on 14 chromosomes, encoding 229-414 amino acids with molecular weights ranging from 25.91 to 47.01 kDa. Spatiotemporal and stress-induced expression was analyzed by qRT-PCR. Multiple sequence alignment revealed that AhMAGL1a/b and AhMAGL3a/b were the only four bifunctional enzymes with conserved regions of hydrolase and acyltransferase, which could also be named as AhMGATs. GUS histochemical assay showed that AhMAGL1a and -1b were strongly expressed in all tissues of the plants; whereas both AhMAGL3a and -3b were weakly expressed in plants. Subcellular localization analysis indicated that AhMGATs were localized in the endoplasmic reticulum and/or Golgi complex. Seed-specific overexpression of AhMGATs in Arabidopsis decreased the oil content of the seeds and altered the fatty acid compositions, indicating that AhMGATs were involved in TAG breakdown but not TAG biosynthesis in plant seeds. This study lays the foundation for better understanding AhMAGL genes biological function in planta.
ESTHER : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedSearch : Zhan_2023_Int.J.Biol.Macromol_243_125300
PubMedID: 37315669
Gene_locus related to this paper: arahy-h9lbh7

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

Title : New advances in clinical application of neostigmine: no longer focusing solely on increasing skeletal muscle strength - Si_2023_Front.Pharmacol_14_1227496
Author(s) : Si S , Zhao X , Su F , Lu H , Zhang D , Sun L , Wang F , Xu L
Ref : Front Pharmacol , 14 :1227496 , 2023
Abstract : Neostigmine is a clinical cholinesterase inhibitor, that is, commonly used to enhance the function of the cholinergic neuromuscular junction. Recent studies have shown that neostigmine regulates the immune-inflammatory response through the cholinergic anti-inflammatory pathway, affecting perioperative neurocognitive function. This article reviews the relevant research evidence over the past 20 years, intending to provide new perspectives and strategies for the clinical application of neostigmine.
ESTHER : Si_2023_Front.Pharmacol_14_1227496
PubMedSearch : Si_2023_Front.Pharmacol_14_1227496
PubMedID: 37601044

Title : Effects and mechanism of extracts rich in phenylpropanoids-polyacetylenes and polysaccharides from Codonopsis Radix on improving scopolamine-induced memory impairment of mice - Xie_2023_J.Ethnopharmacol__117106
Author(s) : Xie Q , Hu X , Zhao X , Xiang Z , Chen Q , Xie Z , Wang H , Zhao Y , Cheng X , Wang C
Ref : J Ethnopharmacol , :117106 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a progressive developmental neurodegenerative disease that primarily develops in old age. Memory impairment is an important manifestation of AD. It has been demonstrated that inflammation and oxidative stress are important mediators in the development and progression of AD. Codonopsis Radix (CR) has a long history of consumption, exhibiting lots of beneficial health effects, including anti-ageing, antioxidant, and anti-inflammatory properties. However, studies on the effects of CR on scopolamine-induced amnesia have rarely been reported. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of macromolecular portion (polysaccharides, POL) and small molecule portion (fine extract rich in phenylpropanoids-polyacetylenes, EPP) from CR on improving scopolamine-induced memory impairment and to elucidate the potential mechanism of action. MATERIALS AND METHODS: C57BL/6 mice were pretreated with EPP (0.2, 0.4, and 0.6 g/kg), POL (0.3, 0.6, and 0.9 g/kg), and donepezil (5 mg/kg) by gavage for 7 days, followed by intraperitoneal injection of scopolamine (1 mg/kg) to induce memory impairment. The 16S rRNA gene sequencing, histopathological, western blotting, and biochemical analysis (various biochemical markers and protein expressions related to cholinergic system, oxidative stress, and neuroinflammation) were performed to further elucidate the mechanism of action. Moreover, the acetylcholinesterase (AChE) inhibitory activities of POL, EPP, and its main compounds tangshenoside I, lobetyol, lobetyolin, and lobetyolinin were evaluated. RESULTS: Experiments have confirmed that both POL and EPP from CR could improve scopolamine-induced spatial learning memory deficits. Both of them could regulate cholinergic function by inhibiting AChE and activating choline acetyltransferase (ChAT) activities. They also could enhance antioxidant defense via increasing the activities of superoxide dismutase and glutathione peroxidase, and anti-inflammatory function through suppressing inflammatory factors (nitric oxide, TNF-alpha, and IL-6) and regulating gut flora. Besides, in vitro experiments demonstrated that four monomeric compounds and EPP, except POL, exhibited inhibition of AChE activity. CONCLUSION: EPP and POL from CR exert a beneficial effect on learning and memory processes in mice with scopolamine-induced memory impairment. CR may be a promising medicine for preventing and improving learning memory.
ESTHER : Xie_2023_J.Ethnopharmacol__117106
PubMedSearch : Xie_2023_J.Ethnopharmacol__117106
PubMedID: 37652198

Title : Rational design of a NIR fluorescent probe for carboxylesterase 1 detection during endoplasmic reticulum stress and drug-induced acute liver injury - Han_2023_Chem.Commun.(Camb)__
Author(s) : Han C , Zhao X , Huo X , Yu Z , Wang C , Feng L , Cui J , Tian X , Ma X
Ref : Chem Commun (Camb) , : , 2023
Abstract : An endoplasmic reticulum targeting NIR fluorescent probe (ERBM) was developed for real-time monitoring of carboxylesterase 1 (CES1) and exhibited excellent ER location in living cell imaging. In addition, ERBM was applied to illustrate the regulation characteristics of CES1 under ER stress and acute liver injury models at the cell and animal level.
ESTHER : Han_2023_Chem.Commun.(Camb)__
PubMedSearch : Han_2023_Chem.Commun.(Camb)__
PubMedID: 36594784

Title : Self-ratiometric fluorescent platform based on upconversion nanoparticles for on-site detection of chlorpyrifos - Zhao_2023_Food.Chem_439_138100
Author(s) : Zhao X , Lu Y , Li B , Kong M , Sun Y , Li H , Liu X , Lu G
Ref : Food Chem , 439 :138100 , 2023
Abstract : Chromobacterium sp. USM2, a locally isolated bacterium was found to synthesize poly(3-hydroxybutyrate-co-3-hydroxyvalerate), P(3HB-co-3HV) copolymer with high 3HV monomer composition. The PHA synthase gene was cloned and expressed in Cupriavidus necator PHB4 to investigate the possibilities of incorporating other monomer. The recombinant successfully incorporated 3-hydroxyhexanoate (3HHx) monomer when fed with crude palm kernel oil (CPKO) as the sole carbon source. Approximately 63 2 wt% of P(3HB-co-3HHx) copolymer with 4 mol% of 3HHx was synthesized from 5 g/L of oil after 48 h of cultivation. In addition, P(3HB-co-3HV-co-3HHx) terpolymer with 9 mol% 3HV and 4 mol% 3HHx could be synthesized with a mixture of CPKO and sodium valerate. The presence of 3HV and 3HHx monomers in the copolymer and terpolymer was further confirmed with +H-NMR analysis. This locally isolated PHA synthase has demonstrated its ability to synthesize P(3HB-co-3HHx) copolymer from a readily available and renewable carbon source; CPKO, without the addition of 3HHx precursors.
ESTHER : Zhao_2023_Food.Chem_439_138100
PubMedSearch : Zhao_2023_Food.Chem_439_138100
PubMedID: 38041885

Title : Aporphines: A privileged scaffold in CNS drug discovery - Zhu_2023_Eur.J.Med.Chem_256_115414
Author(s) : Zhu R , Jiang G , Tang W , Zhao X , Chen F , Zhang X , Ye N
Ref : Eur Journal of Medicinal Chemistry , 256 :115414 , 2023
Abstract : Aporphine alkaloids embedded in 4H-dibenzo[de,g]quinoline four-ring structures belong to one of the largest subclasses of isoquinoline alkaloids. Aporphine is a privileged scaffold in the field of organic synthesis and medicinal chemistry for the discovery of new therapeutic agents for central nervous system (CNS) diseases, cancer, metabolic syndrome, and other diseases. In the past few decades, aporphine has attracted continuing interest to be widely used to develop selective or multitarget directed ligands (MTDLs) targeting the CNS (e.g., dopamine D(1/2/5), serotonin 5-HT(1A/2A/2C) and 5-HT(7), adrenergic alpha/beta receptors, and cholinesterase enzymes), thereby serving as valuable pharmacological probes for mechanism studies or as potential leads for CNS drug discovery. The aims of the present review are to highlight the diverse CNS activities of aporphines, discuss their SAR, and briefly summarize general synthetic routes, which will pave the way for the design and development of new aporphine derivatives as promising CNS active drugs in the future.
ESTHER : Zhu_2023_Eur.J.Med.Chem_256_115414
PubMedSearch : Zhu_2023_Eur.J.Med.Chem_256_115414
PubMedID: 37172474

Title : Cloning and Molecular Characterization of HSL and Its Expression Pattern in HPG Axis and Testis during Different Stages in Bactrian Camel - Nan_2022_Curr.Issues.Mol.Biol_44_3779
Author(s) : Nan J , Wang Q , Yan Q , Wang J , Zhang Y , Zhao X
Ref : Curr Issues Mol Biol , 44 :3779 , 2022
Abstract : Hormone-sensitive lipase (HSL) is a key enzyme in animal fat metabolism and is involved in the rate-limiting step of catalyzing the decomposition of fat and cholesterol. It also plays an important regulatory role in maintaining seminiferous epithelial structure, androgen synthesis and primordial germ cell differentiation. We previously reported that HSL is involved the synthesis of steroids in Bactrian camels, although it is unclear what role it plays in testicular development. The present study was conducted to characterize the biological function and expression pattern of the HSL gene in the hypothalamic pituitary gonadal (HPG) axis and the development of testis in Bactrian camels. We analyzed cloning of the cDNA sequence of the HSL gene of Bactrian camels by RT-PCR, as well as the structural features of HSL proteins, using bioinformatics software, such as ProtParam, TMHMM, Signal P 4.1, SOPMA and MEGA 7.0. We used qRT-PCR, Western blotting and immunofluorescence staining to clarify the expression pattern of HSL in the HPG axis and testis of two-week-old (2W), two-year-old (2Y), four-year-old (4Y) and six-year-old (6Y) Bactrian camels. According to sequence analysis, the coding sequence (CDS) region of the HSL gene is 648 bp in length and encodes 204 amino acids. According to bioinformatics analysis, the nucleotide and amino acid sequence of Bactrian camel HSL are most similar to those of Camelus pacos and Camelusdromedarius, with the lowest sequence similarity with Mus musculus. In adult Bactrian camel HPG axis tissues, both HSL mRNA and protein expression were significantly higher in the testis than in other tissues (hypothalamus, pituitary and pineal tissues) (p < 0.05). The expression of mRNA in the testis increased with age and was the highest in six-year-old testis (p < 0.01). The protein expression levels of HSL in 2Y and 6Y testis were clearly higher than in 2W and 4Y testis tissues (p < 0.01). Immunofluorescence results indicate that the HSL protein was mainly localized in the germ cells, Sertoli cells and Leydig cells from Bactrian camel testis, and strong positive signals were detected in epididymal epithelial cells, basal cells, spermatocytes and smooth muscle cells, with partially expression in hypothalamic glial cells, pituitary suspensory cells and pineal cells. According to the results of gene ontology (GO) analysis enrichment, HSL indirectly regulates the anabolism of steroid hormones through interactions with various targets. Therefore, we conclude that the HSL gene may be associated with the development and reproduction of Bactrian camels in different stages of maturity, and these results will contribute to further understanding of the regulatory mechanisms of HSL in Bactrian camel reproduction.
ESTHER : Nan_2022_Curr.Issues.Mol.Biol_44_3779
PubMedSearch : Nan_2022_Curr.Issues.Mol.Biol_44_3779
PubMedID: 36005155

Title : Preparation and characterization of immobilized 5-HT(1A) receptor stationary phase for high throughput screening of the receptor-binding ligands from complex systems like Curcuma wenyujin Y. H. Chen et C. Ling extract - Chen_2022_J.Pharm.Biomed.Anal_211_114632
Author(s) : Chen YY , Jin YH , Shayiranbieke A , Zhao X , Fan HS , Li Q , Zhao XF
Ref : J Pharm Biomed Anal , 211 :114632 , 2022
Abstract : The incidence of depression has increased significantly during the COVID-19 pandemic. This disease is closely associated with serotonin (1A) (5-HT(1A)) receptor and often treated by complex prescription containing Curcuma wenyujin Y. H. Chen et C. Ling. Therefore, we hypothesized that this herb contains bioactive compounds specially binding to the receptor. However, the rapid discovery of new ligands of 5-HT(1A) receptor is still challenging due to the lack of efficient screening methods. To address this problem, we developed and characterized a novel approach for the rapid screening of ligands by using immobilized 5-HT(1A) receptor as the chromatographic stationary phase. Briefly, haloalkane dehalogenase was fused at the C-terminal of 5-HT(1A) receptor, and the modified 5-HT(1A) receptor was immobilized on amino-microspheres by the reaction between haloalkane dehalogenase and 6-chlorohexanoic acid linker. Scanning electron microscope and X-ray photo-electron were used to characterize the morphology and element of the immobilized receptor. The binding of three specific ligands to 5-HT(1A) receptor was investigated by two different methods. Moreover, we examined the feasibility of 5-HT(1A) receptor colume in high throughput screening of new ligands from complex systems as exemplified by Curcuma wenyujin Y. H. Chen et C. Ling. Gweicurculactone, 2-hydroxy-1-(3,4-dihydroxybenzene)-7-(4'-hydroxybezene)-heptane and curcuminol F were identified as the ligands of 5-HT(1A) receptor with the binding energies of -7.06 kcal/mol, -7.77 kcal/mol and -5.26 kcal/mol, respectively. Collectively, these results indicated that the immobilized 5-HT(1A) receptor was capable of screening bioactive compound from complex system, providing an effective methodology for high throughput screening.
ESTHER : Chen_2022_J.Pharm.Biomed.Anal_211_114632
PubMedSearch : Chen_2022_J.Pharm.Biomed.Anal_211_114632
PubMedID: 35131672

Title : Differences in susceptibility to chlorantraniliprole between Chilo suppressalis (Lepidoptera: Crambidae) and two dominant parasitic wasps collected from Sichuan Province, China - Li_2022_Pestic.Biochem.Physiol_185_105150
Author(s) : Li MY , Gong CW , Zhang YZ , Zhao X , Jia Y , Pu J , Liu XM , Xu X , Wang XG
Ref : Pestic Biochem Physiol , 185 :105150 , 2022
Abstract : Chilo suppressalis Walker (Lepidoptera: Crambidae) is one of the most destructive pests occurring in the rice-growing regions of Asia. Parasitoids, mainly egg parasitoids, have been of interest for several years even with practical used cases. Therefore, the potential impact of insecticides on natural enemies needs great attention. In this study, chlorantraniliprole was evaluated for its impact on C. suppressalis and two dominant parasitic wasps. Bioassays showed that chlorantraniliprole had negligible toxicity to Eriborus terebrans but was significantly toxic to Chelonus munakatae; the mortality exceeded 50% when the concentration reached 46.83 ng/cm(2). Enzyme assays suggested that the significantly different carboxylesterase activity may be involved in the high-level detoxification metabolism of E. terebrans. According to the results of enzyme gene correlation analysis, P450s may be the dominant factor in the detoxification metabolism of C. munakatae. In addition, the ryanodine receptor C-terminus of C. suppressalis (CsRyR), C. munakatae (CmRyR) and E. terebrans (EtRyR) were successfully cloned. Different amino acids at resistance mutation I4758 M between susceptible C. suppressalis (I) and parasitic wasps (M) may be related to susceptibility differences. Simulated docking showed that CsRyR and CmRyR can interact with chlorantraniliprole but not EtRyR. More interaction forces were formed between CsRyR and chlorantraniliprole than CmRyR. Furthermore, a Pi-Pi T-shape formed between 73PHE in CsRyR and the benzene ring in chlorantraniliprole. These results indicated that both detoxification metabolism and the target site could mediate the susceptibility difference between C. suppressalis and its parasitic wasps.
ESTHER : Li_2022_Pestic.Biochem.Physiol_185_105150
PubMedSearch : Li_2022_Pestic.Biochem.Physiol_185_105150
PubMedID: 35772843

Title : Combined toxicity of chlorpyrifos, abamectin, imidacloprid, and acetamiprid on earthworms (Eisenia fetida) - Teng_2022_Environ.Sci.Pollut.Res.Int__
Author(s) : Teng M , Zhao X , Wang C , Zhou L , Wu X , Wu F
Ref : Environ Sci Pollut Res Int , : , 2022
Abstract : Mixed pesticides have been broadly used in agriculture. However, assessing the combined effects of pesticides in the environment is essential for potential risk assessment, though the task is far from complete. Median lethal concentrations of pesticides as well as acetylcholinesterase (AChE) levels and cellulose activities were measured in earthworms (Eisenia fetida) individually and jointly exposed to pesticides imidacloprid (IMI), acetamiprid (ACE), chlorpyrifos (CRF), and abamectin (ABM)). A 3:1 mixture of CRF and IMI had additive effects, while a 3:1 mixture of CRF and ACE had synergic effects. The joint effects of ABM with IMI or with ACE were synergistic. As CRF concentration increased, AChE activities were significantly decreased. For high concentrations of IMI, AChE activities under combined CRF and IMI applications were significantly inhibited following increased exposure time. Moreover, the cellulase activities under combined applications of CRF with IMI or with ACE had similar effects. This study provides basic data for scientifically evaluating the environmental risk and safety of combined uses of pesticides.
ESTHER : Teng_2022_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Teng_2022_Environ.Sci.Pollut.Res.Int__
PubMedID: 35297002

Title : Improved Aitongxiao prescription (I-ATXP) induces apoptosis, cell cycle arrest and blocks exosomes release in hepatocellular carcinoma (HCC) cells - Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
Author(s) : Huang MB , Gao Z , Xia M , Zhao X , Fan X , Lin S , Zhang L , Huang L , Wei A , Zhou H , Wu JY , Roth WW , Bond VC , Leng J
Ref : Int Journal de Physiologie Pathophysiol Pharmacol , 14 :90 , 2022
Abstract : BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy globally, after lung cancer, accounting for 85-90% of primary liver cancer. Hepatitis B virus (HBV) infection is considered the leading risk factor for HCC development in China. HCC is a highly malignant cancer whose metastasis is primarily influenced by the tumor microenvironment. The role of exosomes in cancer development has become the focus of much research due to the many newly described contents of exosomes, which may contribute to tumorigenesis. However, the possible role exosomes play in the interactions between HCC cells and their surrounding hepatic milieu is mainly unknown. We discovered an Improved Aitongxiao Prescription (I-ATXP): an 80% alcohol extract from a mix of 15 specific plant and animal compounds, which had been shown to have an anticancer effect through inducing apoptosis and cell cycle arrest and blocking exosomes release in HCC cells. However, the anticancer mechanism of I-ATXP on human liver carcinoma is still unclear. OBJECTIVE: Due to its inhibitory effects on chemical carcinogenesis and inflammation, I-ATXP has been proposed as an effective agent for preventing or treating human liver carcinoma. In this study, we aimed to explore the effect of I-ATXP on proliferation, apoptosis, and cell cycles of different HCC cell lines. We investigated the impact of I-ATXP on exosomes' secretion derived from these HCC cells. METHODS: The inhibitory effect of I-ATXP on proliferation and cytotoxicity of HepG2, SMMC7721, HKCL-C3 HCC cell lines, and MIHA immortalized hepatocyte cell line was assessed by CCK-8 assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry using Annexin V-FITC/PI staining. The expression of Alix and CD63 of exosome marker proteins was detected by western blotting. The exosome protein concentration was measured by a fluorescent plate reader. The exosome-specific enzyme activity was measured by acetylcholinesterase (AchE) assay, and exosome morphological characteristics were identified by transmission electron microscopy (TEM). RESULTS: I-ATXP inhibited the growth of HCC cells in a dose and time-dependent manner. Flow cytometry analysis showed that I-ATXP induced G0/G1 phase arrest and cell apoptosis. The I-ATX reduced HepG2, SMMC7721, and HKCI-C HCC cell lines exosomes release and low-dose I-ATXP significantly enhanced the growth inhibition induced by 5-Fu. Western blot analysis shows that after HCC cell lines were treated with various concentrations of I-ATXP (0.125-1 mg/ml) for 24 h, exosomes derived from three different HCC cells expressed exosome-specific proteins Alix and CD63. Compared with the untreated group, with the increment of the concentration of I-ATXP, the expression of exosome-specific proteins Alix and CD63 were reduced. These results suggest that I-ATXP can inhibit the release of exosomes with Alix and CD63 protein from HCC cells. CONCLUSIONS: I-ATXP is a traditional Chinese medicine that acts as an effective agent for preventing or treating human liver carcinoma. (i) I-ATXP can effectively inhibit cell proliferation of different HCC cells in a time and dose-dependent manner. Compared with 5-Fu, I-ATXP exhibited more selective proliferation inhibition in HCC cells, displaying traditional Chinese medicine advantages on tumor therapy and providing the experimental basis for I-ATXP clinical application. (ii) I-ATXP can induce apoptosis and cell cycle arrest in HCC cells. The CCK-8 assay results indicated that I-ATXP could inhibit HCC cell proliferation mediated by apoptosis and cell cycle arrest. (iii) I-ATXP can inhibit both the exosome releases and expression of CD63, and Alix derived from HCC cells, but the exosomes derived from liver cancer cells affect liver cancer cells' biological properties such as proliferation, invasion, and migration. These suggest that I-ATXP may affect HCC cells via regulation of exosomes of HCC cells, further indicating the potential clinical values of I-ATXP for the prevention or treatment of human liver carcinoma.
ESTHER : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedSearch : Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90
PubMedID: 35619665

Title : Interleukin-6 and YKL-40 predicted recurrent stroke after ischemic stroke or TIA: analysis of 6 inflammation biomarkers in a prospective cohort study - Li_2022_J.Neuroinflammation_19_131
Author(s) : Li J , Lin J , Pan Y , Wang M , Meng X , Li H , Wang Y , Zhao X , Qin H , Liu L
Ref : J Neuroinflammation , 19 :131 , 2022
Abstract : OBJECTIVE: Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. METHODS: In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A(2) mass (Lp-PLA(2)) and activity (Lp-PLA(2)-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2-6 within 1 year. RESULTS: There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13-1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17-1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06-1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64-2.27; P < 0.0001), IL-1Ra (adjusted OR 1.60; 95% CI 1.37-1.87; P < 0.0001), hsCRP (adjusted OR 1.60; 95% CI 1.37-1.86; P < 0.0001) and YKL-40 (adjusted OR 1.21; 95% CI 1.03-1.42; P = 0.02) were correlated with increased risk of poor functional outcome. In the multivariate stepwise regression analysis including all markers with backward selection, elevated levels of IL-6 or YKL-40 were associated with recurrent stroke (IL6: OR, 1.34; 95% CI 1.19-1.52; P < 0.0001; YKL-40: OR, 1.01; 95% CI 1.01-1.03; P = 0.004) and poor functional outcome (IL6: OR, 1.68; 95% CI 1.46-1.93; P < 0.0001; YKL-40: OR, 1.02; 95% CI 1.01-1.03; P = 0.0001). Adding IL-6 and YKL-40 significantly increased the area under the receiver operating characteristic curves for the prediction models of Essen Stroke Risk Score (0.03, P < 0.0001) and Totaled Health Risks in Vascular Events Score (0.07, P < 0.0001), and yielded continuous net reclassification improvement (19.0%, P < 0.0001; 33.0, P < 0.0001). CONCLUSIONS: In the patients with ischemic stroke or TIA, IL-6 and YKL-40 were independently associated with recurrent stroke and poor functional outcome, and improved risk classification of clinical risk algorithms.
ESTHER : Li_2022_J.Neuroinflammation_19_131
PubMedSearch : Li_2022_J.Neuroinflammation_19_131
PubMedID: 35761288

Title : Integrated Proteomic and Metabolomic Analyses of Chicken Ovary Revealed the Crucial Role of Lipoprotein Lipase on Lipid Metabolism and Steroidogenesis During Sexual Maturity - Cui_2022_Front.Physiol_13_885030
Author(s) : Cui Z , Ning Z , Deng X , Du X , Amevor FK , Liu L , Kang X , Tian Y , Wang Y , Li D , Zhao X
Ref : Front Physiol , 13 :885030 , 2022
Abstract : During sexual maturation and ovulatory cycle in chickens, ovaries undergo dynamic morphological and functional changes. The aim of this study was to evaluate the integrated proteome and metabolome analyses of chicken ovaries to characterize the changes in protein and metabolite profiles during sexual maturity. The ovary of Rohman layers before (125 days of age) and after (139 days of age) sexual maturation were collected for proteome and metabolome sequencing. The results showed that a total of 680 differentially expressed proteins (DEPs) and 1,046 differential metabolites (DMs) were identified in the chicken ovary during sexual maturity. Among the DEPs, 595 proteins were up-regulated and 85 were down-regulated, whereas 519 metabolites were up-regulated and 527 were down-regulated. KEGG pathway enrichment analysis showed that DEPs were significantly enriched in glycerolipid metabolism, calcium signaling pathway, folate biosynthesis, fat digestion and absorption, NF-kB signaling pathway, and PPAR signaling pathway. However, DMs were significantly enriched in the metabolism pathways, PPAR signalling pathway, glycerolipid metabolism, ferroptosis, biosynthesis of amino acids, and biosynthesis of unsaturated fatty acids. The results of the integrated analyses of DEPs and DMs revealed that the PPAR signaling pathway and glycerolipid metabolism were the most significantly enriched pathways. Among the identified DEPs, lipoprotein lipase (LPL) was upregulated in sexually mature chicken ovaries and was significantly enriched in the glycerolipid metabolism pathway, which may partially explain the possible reasons for steroidogenesis and lipid reserves responsible for oocyte maturation and ovarian follicle development during sexual maturity in chickens. The results further revealed that LPL silencing decreased the content of lipid droplets (LDs), as well as the mRNA expression of lipid metabolism-related genes including; sterol regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FASN); and steroidogenesis-related genes such as; cytochrome P450 11A1 (CYP11A1) and steroidogenic acute regulatory (StAR). The present study revealed that upregulation of LPL in the chicken ovary during sexual maturity promotes granulosa cell (GC) lipid metabolism and steroidogenesis. These findings provide a theoretical support for further studies to elucidate the mechanism of lipid metabolism to regulate the function of avian GCs during sexual maturity in chickens.
ESTHER : Cui_2022_Front.Physiol_13_885030
PubMedSearch : Cui_2022_Front.Physiol_13_885030
PubMedID: 35574488

Title : Site-selective covalently immobilized alpha 1A adrenergic receptor for thermodynamic and extra-thermodynamic study of four ligands binding to the receptor by chromatographic methods - Yuan_2022_J.Chromatogr.A_1665_462827
Author(s) : Yuan X , Shayiranbieke A , Xu R , Jiang H , Yang Y , Zhang Y , Yin G , Zhao X
Ref : Journal of Chromatography A , 1665 :462827 , 2022
Abstract : Immobilized G protein-coupled receptor is a versatile tool to study ligand-receptor interactions. In this work, we synthesized the immobilized alpha 1A adrenergic receptor (alpha(1A)-AR), a GPCR subtype mediating smooth muscle contraction, through a site-selective covalent method that relies on the reaction between haloalkane dehalogenase tagged alpha(1A)-AR and macroporous silica gel coated with 6-chlorohexanoic acid. To investigate thermodynamic and extra-thermodynamic parameters for ligand binding, we utilized the covalently immobilized receptor as stationary phase to perform frontal analysis and injection-amount dependent analysis as well as compared with the random immobilization method. Terazosin gave the association constant of 1.48 x 10(5) M(-1) to alpha(1A)-AR, indicating that the oriented immobilization of alpha(1A)-AR enhances the ligand-binding activity by one order of magnitude in comparison with the random immobilization method (7.9 x 10(4) M(-1)). The binding of phentolamine and tamsulosin to the receptor was accompanied by a large absolute heat capacity (deltaC(p)) of 1.28 +/- 0.23 kJ mol(-1), demonstrating that the binding enthalpy and entropy appear to compensate for one another. These results indicated that the covalent immobilization of the receptor onto solid support has a profound impact on the ligand-binding activity of the receptor and the determination of ligand-receptor binding parameters. The receptor immobilized through the site-selective method will act as a benchmark for chromatographic determination of binding parameters in ligand-receptor interactions and can be used as an effective approach for rapid analysis of drug-protein interactions with high accuracy.
ESTHER : Yuan_2022_J.Chromatogr.A_1665_462827
PubMedSearch : Yuan_2022_J.Chromatogr.A_1665_462827
PubMedID: 35078002

Title : An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase - Zhao_2022_EMBO.Rep__e52669
Author(s) : Zhao X , Wang W , Yao Y , Li X , Huang X , Wang Y , Ding M
Ref : EMBO Rep , :e52669 , 2022
Abstract : The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high-fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet-resident protein Plin2 and the RDH/CG2064-Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH-Plin2 axis modulates lipid droplet size.
ESTHER : Zhao_2022_EMBO.Rep__e52669
PubMedSearch : Zhao_2022_EMBO.Rep__e52669
PubMedID: 35132760

Title : Detecting the combined toxicity of 18 binary and 24 ternary pesticide combinations to carboxylesterase based on fluorescence probe technology - Zhu_2022_J.Environ.Sci.Health.B__1
Author(s) : Zhu X , Chen L , Liu T , He S , Zhao X , Tian Y , Fang Y , Cui J
Ref : J Environ Sci Health B , :1 , 2022
Abstract : A rapid test method for the determination of pesticide toxicity was established by using carboxylesterase (CES) and fluorescence probe ACE-NH based on the principle of enzyme inhibition, and this method was applied to detect the combined toxicity of 18 binary and 24 ternary pesticide combinations commonly used for fruits and vegetables to CES. The results show that chlorpyrifos + carbendazim, carbofuran + carbendazim, imidacloprid + carbendazim, imidacloprid + dimethomorph, dimethoate + dimethomorph, prochloraz + carbendazim and imidacloprid + acetamiprid + carbendazim had synergistic effects under three concentration gradients, it indicated that most binary combinations containing carbendazim or imidacloprid had synergistic effects. Based on structure-activity relationship between pesticides and CES, pesticides with phosphate ester bonds had great toxicity to CES, or though they have no toxicity to CES alone, they showed a strong synergistic effect when mixed with other pesticides. Pesticides with amide or ester bond had medium toxicity and little synergistic effect. Pesticides with urea, carbamate or nitrite nitrogen group had little or no toxicity, while there was a strong synergistic effect after mixing with other pesticides. The test method and results in this study can provide scientific basis for risk assessment of cumulative exposure to mixed pesticide residues.
ESTHER : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedSearch : Zhu_2022_J.Environ.Sci.Health.B__1
PubMedID: 35287560

Title : Hepatitis B virus genotype is an independent prognostic factor of telbivudine and tenofovir treatment in hepatitis B surface antigen-positive pregnant women - Zhang_2022_Food.Sci.Nutr_10_3
Author(s) : Zhang B , Yu L , Cheng M , Zhang Q , Wu J , Yang J , Liu Q , Lu S , Zhao X , Deng K , Liu Y , Wang J , Zhao P
Ref : Food Sci Nutr , 10 :3 , 2022
Abstract : To investigate whether HBV genotype influences the effect of tenofovir and telbivudine on HBV DNA and RNA levels in HBsAg-positive pregnant women. This was a retrospective study of 74 HBsAg-positive pregnant women in Guizhou of China. All patients were treated with telbivudine or tenofovir from 12 weeks of pregnancy and HBV infection to the date of delivery. Blood samples were collected at 12-24, 28-32, and 36-40 weeks of pregnancy for the measurement of genotype, HBsAg, hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA, and liver function, including alanine transaminase, aspartate transaminase, total bilirubin, total bile acids, cholinesterase, alkaline phosphatase (ALP), and gamma-glutamyl transferase. All women with HBsAg were followed up. The HBV genotype was B in 64.9% and C in 35.1%. There were 37 patients of telbivudine and tenofovir group respectively. The telbivudine and tenofovir groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA). Compared with baseline (12-24 weeks), telbivudine group showed a significant increase in ALP and significant reductions in HBsAg, HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks (p < .05). Tenofovir group exhibited a significant increase in ALP and significant reductions in HBeAg, log(10)(HBV DNA), and log(10)(HBV RNA) at 36-40 weeks, compared with baseline (p < .05). HBV genotype (B vs. C) was independently associated with HBV DNA change after therapy (p = .005). In telbivudine group, log(10) (HBV DNA) increased from 3.38 (2.00-7.30) to 7.43 (4.68-8.70). In tenofovir group, log(10) (HBV DNA) decreased from 7.52 (3.32-8.70) to 2.98 (2.00-5.01). HBV genotype was independently associated with HBV DNA change response to telbivudine or tenofovir in pregnant women with hepatitis B. These findings might be helpful for risk assessment regarding vertical transmission of HBV in HBeAg-positive mothers treated with nucleos(t)ide analogues.
ESTHER : Zhang_2022_Food.Sci.Nutr_10_3
PubMedSearch : Zhang_2022_Food.Sci.Nutr_10_3
PubMedID: 35035905

Title : Caulophyine A, a Rare Azapyrene Alkaloid from the Roots of Caulophyllum robustum - Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
Author(s) : Wei W , Yuan YH , Jiao FR , Zhao X , Xiao L , Hu JY , Ji P , Xiao J , Wang XL
Ref : Chem Pharm Bull (Tokyo) , 70 :283 , 2022
Abstract : A novel alkaloid caulophyine A (1) was isolated from the roots of Caulophyllum robustum Maxim., along with six known alkaloids 2-7. The structure of 1 was elucidated by extensive NMR and high resolution-time-of-flight (HR-TOF)-MS analyses, it is a rare nitrogen containing polycyclic aromatic hydrocarbon. The in vitro bioassays revealed that 2 presented remarkable cytotoxicity against A549 with an IC(50) value of 3.83 microM in comparison with the positive control etoposide (IC(50) = 11.63 microM). Compounds 1 and 2 also displayed weak Acetylcholinesterase (AChE) inhibitory activity with IC(50) values of 123.03 and 80.74 microM respectively.
ESTHER : Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
PubMedSearch : Wei_2022_Chem.Pharm.Bull.(Tokyo)_70_283
PubMedID: 35370205

Title : Preventive Effect of Limosilactobacillus fermentum SCHY34 on Lead Acetate-Induced Neurological Damage in SD Rats - Long_2022_Front.Nutr_9_852012
Author(s) : Long X , Wu H , Zhou Y , Wan Y , Kan X , Gong J , Zhao X
Ref : Front Nutr , 9 :852012 , 2022
Abstract : Lead poisoning caused by lead pollution seriously affects people's health. Lactic acid bacteria has been shown to be useful for biological scavenging of lead. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral Limosilactobacillus fermentum (L. fermentum) SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity. The L. fermentum SCHY34 showed competent results on in vitro survival rate and the lead ion adsorption rate. Animal experiments showed that L. fermentum SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue. Further, L. fermentum SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats, such as glutamate (Glu), monoamine oxidase (MAO), acetylcholinesterase (AchE), cyclic adenosine monophosphate (cAMP), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity, antioxidation, and anti-apoptotic in rat brain tissues were increased L. fermentum SCHY34 treatment, such as brain-derived neurotrophic factor (BDNF), c-fos, c-jun, superoxide dismutase (SOD)1/2, Nuclear factor erythroid 2-related factor 2 (Nrf2), and B-cell lymphoma 2 (Bcl-2), and so on. L. fermentum SCHY34 showed a great biological scavenging and potential effect on alleviating the toxicity of lead ions.
ESTHER : Long_2022_Front.Nutr_9_852012
PubMedSearch : Long_2022_Front.Nutr_9_852012
PubMedID: 35571929

Title : A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 \% Ho(3+)@NaYF(4) upconversion nano-probe - Zhao_2021_Talanta_235_122784
Author(s) : Zhao X , Zhang L , Yan X , Lu Y , Pan J , Zhang M , Wang C , Suo H , Jia X , Liu X , Lu G
Ref : Talanta , 235 :122784 , 2021
Abstract : Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.
ESTHER : Zhao_2021_Talanta_235_122784
PubMedSearch : Zhao_2021_Talanta_235_122784
PubMedID: 34517642

Title : Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6\/STAT3 pathway - Yang_2021_J.Obstet.Gynaecol.Res__
Author(s) : Yang X , Zhu Y , Shi Q , Zhao X , Huang Y , Yao F , Zhang Y , Wang Z
Ref : J Obstet Gynaecol Res , : , 2021
Abstract : AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling.
ESTHER : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedSearch : Yang_2021_J.Obstet.Gynaecol.Res__
PubMedID: 33969570

Title : Characteristics of a recombinant Fusarium verticillioides cutinase and its effects on enzymatic hydrolysis of rice straw - Gu_2021_Int.J.Biol.Macromol_171_382
Author(s) : Gu S , Liu C , Zhang W , Qu M , Li Y , Zang Y , Xiong X , Pan K , Zhao X
Ref : Int J Biol Macromol , 171 :382 , 2021
Abstract : The current study heterologously expressed a cutinase from Fusarium verticillioides by Pichia pastoris and investigated its properties and effects on the hydrolysis of rice straw. The optimal pH and temperature for F. verticillioides cutinase were 8.0 and 50 degreesC, respectively. F. verticillioides cutinase had poor thermal stability and could be inhibited by some metal ions, inhibitors, and detergents (5 mM), including Ni(2+), Zn(2+), Cu(2+), Ca(2+), Mn(2+), sodium dodecyl sulfate, EDTA, and Tween-20. F. verticillioides cutinase could tolerate 15% methanol and dimethyl sulfoxide but was significantly repressed by 15% ethanol and acetone with 48% and 63% residual activity, respectively. F. verticillioides cutinase could degrade the cuticle of rice straw with palmitic acid and stearic acid as the main products. However, the dissolving sugars released from the rice straw treated with F. verticillioides cutinase were significantly reduced by 29.2 microg/mL compared with the control (107.9 microg/mL). Similarly, the reducing sugars produced from the cellulase hydrolysis of rice straw pretreated with F. verticillioides cutinase were reduced by 63.5 microg/mL relative to the control (253.6 microg/mL). Scanning electron microscopy results showed that numerous tuberculate or warty protrusions were present nearly everywhere on the surface of rice straw treated with F. verticillioides cutinase, and some protrusions even covered and blocked the stomata of the rice straw surface. Current limited data indicate that F. verticillioides cutinase might not be an appropriate choice for improving the utilization of agricultural straws.
ESTHER : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedSearch : Gu_2021_Int.J.Biol.Macromol_171_382
PubMedID: 33434547
Gene_locus related to this paper: gibm7-w7lbp5

Title : Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes sinensis) hepatopancreas under ectoparasitic isopod (Tachaea chinensis) infection - Yu_2021_Fish.Shellfish.Immunol__
Author(s) : Yu C , Xu W , Li X , Jin J , Zhao X , Wang S , Zhang Z , Wei Y , Chen Q , Li Y
Ref : Fish Shellfish Immunol , : , 2021
Abstract : Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species. To better understand the interaction between shrimp immunity and isopod infection, we performed a transcriptome analysis of the hepatopancreas of Palaemonetes sinensis challenged with T. chinensis. After assembly and annotation, 75,980 high-quality unigenes were obtained using RNA-seq data. Dierential gene expression analysis revealed 896 signicantly dierently expressed genes (DEGs) after infection, with 452 and 444 upregulated and downregulated genes, respectively. Specifically, expression levels of genes involved in detoxification, such as the interferon regulatory factor, venom carboxylesterase-6, serine proteinase inhibitor, and cytochrome P450, were upregulated. Furthermore, expression levels of genes corresponding to retinol dehydrogenase, triosephosphate isomerase, variant ionotropic glutamate receptor, and phosphoenolpyruvate carboxykinase were significantly upregulated after isopod parasitization, indicating that the shrimp's visual system was influenced by isopod parasitization. Moreover, quantitative real-time PCR of 10 DEGs helped validate the RNA-seq findings. These results provide a valuable basis for future studies on the elucidation of immune responses of P. sinensis to T. chinensis infection.
ESTHER : Yu_2021_Fish.Shellfish.Immunol__
PubMedSearch : Yu_2021_Fish.Shellfish.Immunol__
PubMedID: 34303835

Title : Surface charge engineering of Thermomyces lanuginosus lipase improves enzymatic activity and biodiesel synthesis - Han_2021_Biotechnol.Lett__
Author(s) : Han N , Tang M , Wan S , Jiang Z , Yue Y , Zhao X , Yang J , Huang Z
Ref : Biotechnol Lett , : , 2021
Abstract : OBJECTIVES: This study was aimed at engineering charged residues on the surface of Thermomyces lanuginosus lipase (TLL) to obtain TLL variant with elevated performance for industrial applications. RESULTS: Site-directed mutagenesis of eight charged amino acids on the TLL surface were conducted and substitutions on the negatively charged residues D111, D158, D165, and E239 were identified with elevated specific activities and biodiesel yields. Synergistic effect was not discovered in the double mutants, D111E/D165E and D165E/E239R, when compared with the corresponding single mutants. One TLL mutant, D165E, was identified with increased specific activity (456.60 U/mg), catalytic efficiency (k(cat)/K(m): 44.14 s(-1) mM(-1)), the highest biodiesel conversion yield (93.56%), and comparable thermostability with that of the TLL. CONCLUSIONS: Our study highlighted the importance of surface charge engineering in improving TLL activity and biodiesel production, and the resulting TLL mutant, D165E, is a promising candidate for biodiesel industry.
ESTHER : Han_2021_Biotechnol.Lett__
PubMedSearch : Han_2021_Biotechnol.Lett__
PubMedID: 33834350

Title : Cloning, characterization of a novel acetyl xylan esterase, and its potential application on wheat straw utilization - Xu_2021_All.Life_14_622
Author(s) : Xu J , Zhao X , Yao Q , Zong W , Dai S , Deng Z , Liu S , Yun J , Yang X , Li H
Ref : All life , 14 :622 , 2021
Abstract : Acetyl xylan esterases are among the key enzymes in the xylan degradation enzyme system. However, acetyl xylan esterases from natural microorganisms have low expression and low enzyme activity and are impure. In this study, a new xylanase gene, est1051, from the metagenomic library, was expressed in the prokaryotic system. Its enzymatic properties were explored, including optimum temperature and pH, thermal and pH stability, and tolerance against organic solvents, metal ions and salt solutions. Then the fermentation conditions of EST1051 were optimized by the response surface method, and the maximum enzyme yield reached 1909.32 U/L. Finally, the synergism with cellulase on straw degradation was evaluated. EST1051 displays high homology with acetylxylan esterases in terms of amino acid sequences and conserved active sites. EST1051 shows high stability across a broad temperature range, and retains more than 60% of its enzymatic activity between 4 and 60C after 24 h of incubation. Single-factor analysis and orthogonal design were conducted to determine the optimal conditions for the maximizing the saccharification rate of wheat straws. Interestingly, the synergism of EST1051 with cellulase contributes to the efficient transformation of wheat straws. These findings may open the door to significant industrial applications of this novel acetylxylan esterase.
ESTHER : Xu_2021_All.Life_14_622
PubMedSearch : Xu_2021_All.Life_14_622
Gene_locus related to this paper: 9bact-est1051

Title : Antibodies to Full-Length Agrin Protein in Chinese Patients With Myasthenia Gravis - Wang_2021_Front.Immunol_12_753247
Author(s) : Wang S , Yang H , Guo R , Wang L , Zhang Y , Lv J , Zhao X , Zhang J , Fang H , Zhang Q , Yang J , Cui X , Gao P , Chang T , Gao F
Ref : Front Immunol , 12 :753247 , 2021
Abstract : This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.
ESTHER : Wang_2021_Front.Immunol_12_753247
PubMedSearch : Wang_2021_Front.Immunol_12_753247
PubMedID: 34956185

Title : Inhibitory Effect of Lactococcus lactis subsp. lactis HFY14 on Diphenoxylate-Induced Constipation in Mice by Regulating the VIP-cAMP-PKA-AQP3 Signaling Pathway - Tan_2021_Drug.Des.Devel.Ther_15_1971
Author(s) : Tan Q , Hu J , Zhou Y , Wan Y , Zhang C , Liu X , Long X , Tan F , Zhao X
Ref : Drug Des Devel Ther , 15 :1971 , 2021
Abstract : AIM: The naturally fermented yak yogurt of pastoralists in the Tibetan Plateau, China, because of its unique geographical environment and the unique lifestyle of Tibetan pastoralists, is very different from other kinds of sour milk, and the microorganisms it contains are special. Lactococcus lactis subsp. lactis HFY14 (LLSL-HFY14) is a new lactic acid bacterium isolated from naturally fermented yak yogurt. The purpose of this study was to study the inhibitory effect of the bacterium on constipation. METHODS: Constipation was induced in ICR mice with diphenoxylate, and the constipated mice were treated with LLSL-HFY14. The weight and feces of the mice were visually detected. Colonic tissues were observed on hematoxylin and eosin-stained sections. Serum indices were detected with kits. mRNA expression in the colon was determined by quantitative polymerase chain reaction assay. RESULTS: Constipation caused weight loss, the number of defecation granules, defecation weight, fecal water content decreased, and the first black stool excretion time increased. LLSL-HFY14 alleviated these symptoms, and the effects were similar to those of lactulose (drug). The pathological examination revealed that constipation caused pathological changes in the colon, and LLSL-HFY14 effectively alleviated the disease. LLSL-HFY14 increased serum levels of motilin, gastrin, endothelin, substance P, acetylcholinesterase, and vasoactive intestinal peptide (VIP) and decreased serum levels of somatostatin in constipated mice. In addition, LLSL-HFY14 upregulated VIP, cAMP, protein kinase A, and aquaporin 3 expression in colonic tissues of constipated mice in a dose-dependent manner. CONCLUSION: LLSL-HFY14 inhibited constipation, similar to lactulose, and has the potential to become a biological agent.
ESTHER : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedSearch : Tan_2021_Drug.Des.Devel.Ther_15_1971
PubMedID: 34007157

Title : Development and characterization of a selective chromatographic approach to the rapid discovery of ligands binding to muscarinic-3 acetylcholine receptor - Zhao_2021_J.Chromatogr.A_1653_462443
Author(s) : Zhao X , Fu X , Yuan X , Shayiranbieke A , Xu R , Cao F , Ren J , Liang Q
Ref : Journal of Chromatography A , 1653 :462443 , 2021
Abstract : The pursuit of new ligands binding to muscarinic-3 acetylcholine receptor (M(3)R) is viewed as challenging due to the lack of screening methods with high efficiency. To address such challenges, this work developed and characterized an approach to the rapid discovery of M(3)R ligands using the immobilized receptor as the chromatographic stationary phase. We fused haloalkane dehalogenase (Halo) as a tag at the C-terminus of M(3)R. The fusion M(3)R was immobilized on 6-chlorocaproic acid-activated ammino-microspheres by the specific covalent reaction between the Halo-tag and the linker. Comprehensive characterizations of the immobilized M(3)R were performed by scanning electron microscope, X-ray photoelectron spectroscopy, and the investigation on the binding of three specific ligands to the receptor. The feasibility of the immobilized M(3)R in complex matrices was tested by screening the bioactive compounds in Zhisou oral liquid, assessing the interaction between the screened compounds and the receptor using zonal elution, and evaluating the in vivo activity of the targeted compounds. The results evidenced that the immobilized M(3)R has high specificity, good stability, and the capacity to separate M(3)R ligands from complex matrices. These allowed us to identify naringin, hesperidin, liquiritigenin, platycodin D, and glycyrrhizic acid as the potential ligands of M(3)R. The association constants of the five compounds to M(3)R were 4.44 x 10(4), 1.11 x 10(4), 7.20 x 10(4), 4.15 x 10(4), and 3.36 x 10(4) M(-1). The synergistic application of the five compounds exhibited an equivalent expectorant activity to the original formula. We reasoned that the current method is possible to provide a highly efficient strategy for the discovery of receptor ligands.
ESTHER : Zhao_2021_J.Chromatogr.A_1653_462443
PubMedSearch : Zhao_2021_J.Chromatogr.A_1653_462443
PubMedID: 34365202

Title : Key Metabolic Enzymes Involved in Remdesivir Activation in Human Lung Cells - Li_2021_Antimicrob.Agents.Chemother__AAC0060221
Author(s) : Li R , Liclican A , Xu Y , Pitts J , Niu C , Zhang J , Kim C , Zhao X , Soohoo D , Babusis D , Yue Q , Ma B , Murray BP , Subramanian R , Xie X , Zou J , Bilello JP , Li L , Schultz BE , Sakowicz R , Smith BJ , Shi PY , Murakami E , Feng JY
Ref : Antimicrobial Agents & Chemotherapy , :AAC0060221 , 2021
Abstract : Remdesivir (RDV; GS-5734; Veklury(a)), the first FDA-approved antiviral to treat COVID-19, is a single diastereomer monophosphoramidate prodrug of an adenosine analogue. RDV is taken up in the target cells and metabolized in multiple steps to form the active nucleoside triphosphate (TP) (GS-443902), which in turn acts as a potent and selective inhibitor of multiple viral RNA polymerases. In this report, we profiled the key enzymes involved in the RDV metabolic pathway with multiple parallel approaches: (1) bioinformatic analysis of nucleoside/tide metabolic enzyme mRNA expression using public human tissue and lung single-cell RNAseq datasets; (2) protein and mRNA quantification of enzymes in human lung tissue and primary lung cells; (3) biochemical studies on the catalytic rate of key enzymes; (4) effects of specific enzyme inhibitors on the GS-443902 formation; and (5) the effects of these inhibitors on RDV antiviral activity against SARS-CoV-2 in cell culture. Our data collectively demonstrated that carboxylesterase 1 (CES1) and cathepsin A (CatA) are enzymes involved in hydrolyzing RDV to its alanine intermediate Met X, which is further hydrolyzed to the monophosphate form by histidine triad nucleotide-binding protein 1 (HINT1). The monophosphate is then consecutively phosphorylated to diphosphate and triphosphate by cellular phosphotransferases. Our data support the hypothesis that the unique properties of RDV prodrug not only allow lung-specific accumulation critical for the treatment of respiratory viral infection such as COVID-19, they also enable efficient intracellular metabolism of RDV and its Met X to monophosphate and successive phosphorylation to form the active TP in disease-relevant cells.
ESTHER : Li_2021_Antimicrob.Agents.Chemother__AAC0060221
PubMedSearch : Li_2021_Antimicrob.Agents.Chemother__AAC0060221
PubMedID: 34125594

Title : Degradation and toxicity of the antidepressant fluoxetine in an aqueous system by UV irradiation - Pan_2021_Chemosphere__132434
Author(s) : Pan C , Zhu F , Wu M , Jiang L , Zhao X , Yang M
Ref : Chemosphere , :132434 , 2021
Abstract : Fluoxetine (FLU), a selective serotonin reuptake inhibitor, is commonly found in aquatic environments. Ultraviolet (UV) photolysis is widely used to remove certain pharmaceuticals from water and wastewater. The present study aimed to investigate the toxicity of FLU and its transformed products formed during UV photolysis by using zebrafish embryos (Danio rerio) as a model. The degradation rates of FLU for five days were approximately 63.6% +/- 2.14%, 84.6% +/- 0.99%, and 97.5% +/- 0.25% after 15, 30, and 60 min of UV irradiation, respectively. Furthermore, the degradation mechanism was explored using LC-MS measurements and density flooding theory (DFT) theoretical calculations. Comprehensive toxicity preassessment of FLU and its degradation products was carried out using the T.E.S.T. software. The effects of physiological and biochemical parameters and neuron- and apoptosis-related gene expression were examined in zebrafish embryos exposed to non-irradiated (0-min) and irradiated (15, 30- and 60-min) solutions from 4 h post-fertilization (hpf) to 120 hpf. The hatching time of zebrafish embryos exposed to the non-irradiated solution (0-min) and irradiated solution (60-min) was delayed, their heart rate at 48 and 72 hpf increased, and their body length at 120 hpf decreased. Significant differences were found between the non-irradiated (0-min) and UV-irradiated (15- or 30-min) groups. A dynamic response involving acetylcholinesterase (AChE) and superoxide dismutase (SOD) activity was also observed in the non-irradiated and UV-irradiated groups. During the UV treatment experiments, the expression levels of neuron-related and apoptosis-related genes were significantly reduced over time alongside the formation of FLU degradation products. Overall, this study provides new concepts to remove and assess the toxicity of emerging contaminants in aquatic environments and highlights the need to consider the formation and persistence of toxic transformation products.
ESTHER : Pan_2021_Chemosphere__132434
PubMedSearch : Pan_2021_Chemosphere__132434
PubMedID: 34606890

Title : Background-free sensing platform for on-site detection of carbamate pesticide through upconversion nanoparticles-based hydrogel suit - Su_2021_Biosens.Bioelectron_194_113598
Author(s) : Su D , Zhao X , Yan X , Han X , Zhu Z , Wang C , Jia X , Liu F , Sun P , Liu X , Lu G
Ref : Biosensors & Bioelectronics , 194 :113598 , 2021
Abstract : On-site monitoring of carbamate pesticide in complex matrix remians as a challenge in terms of the real-time control of food safety and supervision of environmental quality. Herein, we fabricated robust upconversion nanoparticles (UCNPS)/polydopamine (PDA)-based hydrogel portable suit that precisely quantified carbaryl in complex tea samples with smartphone detector. UCNPS/PDA nanoprobe was developed by polymerization of dopamine monomers on the surface of NaErF(4): 0.5% Tm(3+)@NaYF(4) through electrostatic interaction, leading to efficient red luminescence quenching of UCNPS under near-infrared excitation, which circumvented autofluorescence and background interference in complicated environment. Such a luminescence quenching could be suppressed by thiocholine that was produced by acetylcholinesterase-mediated catalytic reaction, thus enabling carbaryl bioassay by inhibiting the activity of enzyme. Bestowed with the feasibility analysis of fluorescent output, portable platform was designed by integrating UCNPS-embedded sodium alginate hydrogel with 3D-printed smartphone device for quantitatively on-site monitoring of carbaryl in the range of 0.5-200 ng mL(-1) in tea sample, accompanied by a detection limit of 0.5 ng mL(-1). Owing to specific UCNPS signatures and hydrogel immobilization, this modular platform displayed sensitive response, portability and anti-interference capability in complex matrix analysis, thus holding great potential in point-of-care application.
ESTHER : Su_2021_Biosens.Bioelectron_194_113598
PubMedSearch : Su_2021_Biosens.Bioelectron_194_113598
PubMedID: 34507097

Title : LIPG: an inflammation and cancer modulator - Hong_2021_Cancer.Gene.Ther_28_27
Author(s) : Hong C , Deng R , Wang P , Lu X , Zhao X , Wang X , Cai R , Lin J
Ref : Cancer Gene Therapy , 28 :27 , 2021
Abstract : Endothelial lipase (LIPG/EL) performs fundamental and vital roles in the human body, including cell composition, cytokine expression, and energy provision. Since LIPG predominantly functions as a phospholipase as well as presents low levels of triglyceride lipase activity, it plays an essential role in lipoprotein metabolism, and involves in the metabolic syndromes such as inflammatory response and atherosclerosis. Cytokines significantly affect LIPG expression in endothelial cells in many diseases. Recently, it is suggested that LIPG contributes to cancer initiation and progression, and LIPG attached increasing importance to its potential for future targeted therapy.
ESTHER : Hong_2021_Cancer.Gene.Ther_28_27
PubMedSearch : Hong_2021_Cancer.Gene.Ther_28_27
PubMedID: 32572177
Gene_locus related to this paper: human-LIPG

Title : Chemical Composition, Antibacterial, Anti-Inflammatory, and Enzyme Inhibitory Activities of Essential Oil from Rhynchanthus beesianus Rhizome - Zhao_2020_Molecules_26_
Author(s) : Zhao X , Chen Q , Lu T , Wei F , Yang Y , Xie D , Wang H , Tian M
Ref : Molecules , 26 : , 2020
Abstract : Rhynchanthus beesianus W. W. Smith, an edible, medicinal, and ornamental plant, is mainly cultivated in China and Myanmar. The essential oil (EO) from R. beesianus rhizome has been used as an aromatic stomachic in China. The chemical composition and biological activities of EO from R. beesianus rhizome were reported for the first time. Based on gas chromatography with flame ionization or mass selective detection (GC-FID/MS) results, the major constituents of EO were 1,8-cineole (47.6%), borneol (15.0%), methyleugenol (11.2%), and bornyl formate (7.6%). For bioactivities, EO showed a significant antibacterial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Proteus vulgaris with the diameter of the inhibition zone (DIZ) (8.66-10.56 mm), minimal inhibitory concentration (MIC) (3.13-6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25-12.5 mg/mL). Moreover, EO (128 microg/mL) significantly inhibited the production of proinflammatory mediators nitric oxide (NO) (92.73 +/- 1.50%) and cytokines tumor necrosis factor-alpha (TNF-alpha) (20.29 +/- 0.17%) and interleukin-6 (IL-6) (61.08 +/- 0.13%) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages without any cytotoxic effect. Moreover, EO exhibited significant acetylcholinesterase (AChE) inhibitory activity (the concentration of the sample that affords a 50% inhibition in the assay (IC(50)) = 1.03 +/- 0.18 mg/mL) and moderate alpha-glucosidase inhibition effect (IC(50) = 11.60 +/- 0.25 mg/mL). Thus, the EO could be regarded as a bioactive natural product and has a high exploitation potential in the cosmetics and pharmaceutical industries.
ESTHER : Zhao_2020_Molecules_26_
PubMedSearch : Zhao_2020_Molecules_26_
PubMedID: 33396533

Title : Effect of Solvent on Acyl Migration of 2-Monoacylglycerols in Enzymatic Ethanolysis - Wang_2020_J.Agric.Food.Chem_68_12358
Author(s) : Wang X , Zhao X , Yang Z , Wang T
Ref : Journal of Agricultural and Food Chemistry , 68 :12358 , 2020
Abstract : Acyl migration occurs in many reactions and is the main obstacle for structured lipid synthesis. In this study, 2-monoacylglycerol (2-MAG) was prepared by enzymatic ethanolysis in three different media to evaluate the effect of environment on product composition. The contents of 2-MAG obtained in ethanol, hexane + ethanol, and t-butanol + ethanol systems were 30.6, 15.7, and 32.4%, respectively, after 3 h reaction. Afterward, the acyl migration kinetics of 2-MAG were studied in solvent and solventless systems without the use of lipase. Results indicate that 2-MAG in the solventless system had the highest acyl migration rate. The isomerization was efficiently prevented by the use of polar solvents, especially t-butanol. The rate constants were shown to be the highest and activation energy values were the lowest in solventless systems. The novel finding in this study was that solvent had inhibitory effect on 2-MAG isomerization, but the nonpolar hexane had the lowest inhibition of acyl migration compared to other solvents.
ESTHER : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedSearch : Wang_2020_J.Agric.Food.Chem_68_12358
PubMedID: 33084305

Title : Post-exercise Effects and Long-Term Training Adaptations of Hormone Sensitive Lipase Lipolysis Induced by High-Intensity Interval Training in Adipose Tissue of Mice - Liu_2020_Front.Physiol_11_535722
Author(s) : Liu Y , Dong G , Zhao X , Huang Z , Li P , Zhang H
Ref : Front Physiol , 11 :535722 , 2020
Abstract : Although studies have proven that high-intensity interval training (HIIT) shows a comparable effect to moderate-intensity continuous training (MICT) on reducing body fat, especially visceral fat, the mechanism is still unclear. Since MICT consumes more fat during exercise, the mechanism of HIIT weight loss may be related to post-exercise effects, long-term adaptive changes, and hormone sensitive lipase (HSL). The objective of this study was to compare the post-effects of acute exercise, long-term adaptive changes on HSL activity, and catecholamine-induced lipolysis between HIIT and MICT. Following a 14-week high-fat diet (HFD), obese female C57Bl/6 mice were divided into acute exercise groups (one time training, sacrificed at rest and 0, 1, and 12 h after exercise, n = 49), -L groups (12-week long-term training, 12-h fasting, n = 21), and -C groups (12-week training, primary adipocytes were isolated and stimulated by catecholamine in vitro, n = 18). MICT or HIIT treadmill protocols (running distance matched) were carried out during training. Comparison of acute exercise effects by two-way ANOVA showed no time x group interaction effect, however, a significant increase in HSL-Ser563 (at 0 and 1 h) and Ser660 phosphorylation (at 0, 1, and 12 h) in inguinal (subcutaneous) fat was only observed in HIIT mice (p < 0.05 vs. rest), but not in MICT mice. The periuterine (visceral) fat HSL expression and phosphorylation of HIIT mice was similar to or lower than MICT mice. After long-term training, 12-h fasting significantly increased periuterine fat Ser563 phosphorylation in HIIT mice (p < 0.05), but there was no change in MICT mice. Under stimulation of catecholamine in vitro, isolated primary adipocytes from periuterine fat of long-term HIIT mice showed a higher Ser563 increase than that found in MICT mice (p < 0.05). The quantity of triglyceride (TG) lipid bonds (representing lipolysis level) was significantly lower after HIIT than MICT (p < 0.05). The results indicate that (1) acute HIIT can induce an increase of HSL phosphorylation in subcutaneous fat lasting at least 12 h, implying longer post-exercise lipolysis than MICT and (2) long-time HIIT has a better effect on improving catecholamine resistance of visceral adipocytes caused by a HFD, which allows fat to be mobilized more easily when stimulated.
ESTHER : Liu_2020_Front.Physiol_11_535722
PubMedSearch : Liu_2020_Front.Physiol_11_535722
PubMedID: 33324231

Title : Triphenyl phosphate permeates the blood brain barrier and induces neurotoxicity in mouse brain - Liu_2020_Chemosphere_252_126470
Author(s) : Liu X , Zhao X , Wang Y , Hong J , Shi M , Pfaff D , Guo L , Tang H
Ref : Chemosphere , 252 :126470 , 2020
Abstract : Concerns have been raised over the neurotoxicity of triphenyl phosphate (TPP), but there have been few studies of the neurotoxic effects of TPP on mammals and the underlying mechanisms. In this study, weaned male mice (C57/BL6) were used and exposed to 0, 50, or 150 mg/kg TPP daily by oral gavage for 30 days. The blood brain barrier (BBB) permeability of TPP and its metabolite diphenyl phosphate (DPP) in the brain, and TPP induced metabolomic and transcriptomic changes of the brain were investigated. The results showed that TPP and DPP can cross the BBB of mice. Histopathological examination of the brain revealed abnormalities in the hippocampus, cortex and thalamus, and mice treated with high doses showed a potential inflammation in the thalamus and hippocampus. Untargeted metabolomic results revealed that the changed level of glutamic acid, N-acetyl CoA metabolites, and organic acid in the brain of treated mice, suggest that amino acid and lipid metabolism was interfered. RNA-seq data indicated that neuronal transcription processes and cell apoptosis pathway (forkhead box (FOXO), and mitogen-activated protein kinase (MAPK) signaling pathways) were significantly affected by TPP exposure. RT-PCR showed proinflammation cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6)) levels were increased, while antioxidant genes including nuclear factor-E2-related factor 2 (Nrf2), heme oxygenase1 (HO-1) and superoxide dismutase (SOD1) decreased. These results suggest that TPP could cause a degree of neurotoxicity by inducing neuroinflammation and neuronal apoptosis, which are related to oxidative stress. The potential implications for neurophysiology and behavioral regulation cannot be ignored.
ESTHER : Liu_2020_Chemosphere_252_126470
PubMedSearch : Liu_2020_Chemosphere_252_126470
PubMedID: 32443258

Title : Impact of deprescribing AChEIs on aggressive behaviors and antipsychotic prescribing - Niznik_2020_Alzheimers.Dement__
Author(s) : Niznik JD , Zhao X , He M , Aspinall SL , Hanlon JT , Nace D , Thorpe JM , Thorpe CT
Ref : Alzheimers Dement , : , 2020
Abstract : INTRODUCTION: We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. METHODS: We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using the aggressive behavior scale (ABS; n = 30,788). Incident antipsychotic prescriptions were evaluated among antipsychotic non-users (n = 25,188). Marginal structural models and inverse probability of treatment weights were used to evaluate associations of AChEI deprescribing and outcomes. RESULTS: The severity of aggressive behaviors was low at baseline (mean ABS = 0.5) and was not associated with deprescribing AChEIs (0.002 increase in ABS, P = .90). Incident antipsychotic prescribing occurred in 5.1% of residents and was less likely with AChEI deprescribing (adjusted odds ratio = 0.52 [0.40-0.68], P <.001]). DISCUSSION: Deprescribing AChEIs was not associated with a worsening of aggressive behaviors or incident antipsychotic prescriptions.
ESTHER : Niznik_2020_Alzheimers.Dement__
PubMedSearch : Niznik_2020_Alzheimers.Dement__
PubMedID: 32052930

Title : Reply to: Acetylcholinesterase Inhibitors and Dementia: Over Both Sides of the Atlantic Ocean -
Author(s) : Niznik JD , Zhao X , Aspinall SL , Hanlon JT , Hanson LC , Nace D , Thorpe JM , Thorpe CT
Ref : J Am Geriatr Soc , 68 :2412 , 2020
PubMedID: 32776517

Title : Phytochemical Analysis, Antioxidant, Antibacterial, Cytotoxic, and Enzyme Inhibitory Activities of Hedychium flavum Rhizome - Tian_2020_Front.Pharmacol_11_572659
Author(s) : Tian M , Wu X , Lu T , Zhao X , Wei F , Deng G , Zhou Y
Ref : Front Pharmacol , 11 :572659 , 2020
Abstract : Hedychium flavum Roxb., a medicinal, edible, and ornamental plant, is widely cultivated throughout China, India, and Southeast Asia. The rhizome from this plant has been used for food flavoring and in traditional Chinese medicine to treat diverse diseases, but the detailed constituents and bioactivities are still limited known. Therefore, phytochemical analysis by GC-MS and UHPLC-Q-Orbitrap-MS, and antioxidant, antibacterial, cytotoxic, and enzyme inhibitory activities tests have been conducted in the current study. Based on the GC-MS results, the essential oil (EO) of rhizome was mainly composed of coronarin E (20.3%), beta-pinene (16.8%), E-nerolidol (11.8%), and linalool (8.5%). Among them, coronarin E was reported in H. flavum EO firstly. Furthermore, the spectrophotometric indicated rhizome had high total phenolic content (TPC, 50.08-57.42 mg GAEs/g extract) and total flavonoid content (TFC, 12.45-21.83 mg REs/g extract), no matter in water extract (WE) or in 70% ethanol extract (EE). UHPLC-Q-Orbitrap-MS was applied to further characterize composition, and 86 compounds were putatively identified from WE and EE, including 13 phenolic components. For the bioactivities, both WE and EE showed remarkable antioxidant activity by DPPH and ABTS tests, being superior to the positive control (butylated hydroxytoluene, BTH). EO revealed significant antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris with DIZ (10.34-24.43 mm), MIC (78.13-312.50 mug/mL), and MBC (156.25-625.00 mug/mL). Moreover, EO exhibited a considerable selectivity to human tumor cell K562 (IC(50) = 27.16 mug/mL), and its toxicity was more than 3.5-fold different from that of non-cancerous MRC-5 cell (IC(50) = 95.96 mug/mL) and L929 cell (IC(50) = 129.91 mug/mL). A series of apoptosis analysis demonstrated that EO induced apoptosis against K562 cells in a dose-dependent manner. In enzyme inhibitory effect assays, WE and EE showed strong alpha-glucosidase inhibition activity, being superior to the positive control (acarbose). Besides, the EO, WE, and EE didn't show a promising inhibition on tyrosinase (19.30-32.51 mg KAEs/g sample) and exhibited a weak inhibitory effect on cholinesterase. Based on the current results, H. flavum could be considered as a source of bioactive compounds and has high exploitation potential in the cosmetics, food, and pharmaceutical industries.
ESTHER : Tian_2020_Front.Pharmacol_11_572659
PubMedSearch : Tian_2020_Front.Pharmacol_11_572659
PubMedID: 33041813

Title : Risk for Health Events After Deprescribing Acetylcholinesterase Inhibitors in Nursing Home Residents With Severe Dementia - Niznik_2020_J.Am.Geriatr.Soc_68_699
Author(s) : Niznik JD , Zhao X , He M , Aspinall SL , Hanlon JT , Hanson LC , Nace D , Thorpe JM , Thorpe CT
Ref : J Am Geriatr Soc , 68 :699 , 2020
Abstract : BACKGROUND/OBJECTIVE: Reevaluation of the appropriateness of acetylcholinesterase inhibitors (AChEIs) is recommended in older adults with severe dementia, given the lack of strong evidence to support their continued effectiveness and risk for medication-induced adverse events. We sought to evaluate the impact of deprescribing AChEIs on risk of all-cause events (hospitalizations, emergency department visits, and mortality) and serious falls or fractures in older nursing home (NH) residents with severe dementia. DESIGN: Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS) version 3.0, Area Health Resource File, and Nursing Home Compare. Marginal structural models with inverse probability of treatment weights were used to evaluate the association of deprescribing AChEIs and all-cause negative events as well as serious falls or fractures. SETTING: US Medicare-certified NHs. PARTICIPANTS: Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). RESULTS: The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). Deprescribing AChEIs was associated with an increased likelihood of all-cause negative events in unadjusted models (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.11-1.23; P < .01), but not in fully adjusted models (adjusted OR [aOR] = 1.00; 95% CI = 0.94-1.06; P = .94). By contrast, deprescribing was associated with a reduced likelihood of serious falls or fractures in unadjusted models (OR = 0.59; 95% CI = 0.52-0.66; P < .001) and remained significant in adjusted models (aOR = 0.64; 95% CI = 0.56-0.73; P < .001). CONCLUSION: Deprescribing AChEIs was not associated with a significant increase in the likelihood for all-cause negative events and was associated with a reduced likelihood of falls and fractures in older NH residents with dementia. Our findings suggest that deprescribing AChEIs is a reasonable approach to reduce the risk of serious falls or fractures without increasing the risk for all-cause events. J Am Geriatr Soc 68:699-707, 2020.
ESTHER : Niznik_2020_J.Am.Geriatr.Soc_68_699
PubMedSearch : Niznik_2020_J.Am.Geriatr.Soc_68_699
PubMedID: 31769507

Title : Immobilized angiotensin II type I receptor: A powerful method of high throughput screening for antihypertensive compound identification through binding interaction analysis - Liang_2020_J.Chromatogr.A__461003
Author(s) : Liang Q , Fu X , Zhang J , Hao J , Feng G , Wang J , Li Q , Ahmad F , Zhao X
Ref : Journal of Chromatography A , :461003 , 2020
Abstract : The enormous growth in drug discovery paradigm has necessitated continuous exploration of new methods for drug-protein interaction analysis. To enhance the role of these methodologies in designing rational drugs, this work extended an immobilized angiotensin II type I receptor (AT1R) based affinity chromatography in antihypertensive compound identification. We fused haloalkane dehalogenase at C-terminus of AT1R and expressed the fusion receptor in E. coli. The expressed receptor was covalently immobilized onto 8.0mum microspheres by mixing the cell lysate with 6-chlorocaproic acid-modified amino polystyrene microspheres. The immobilized AT1R was utilized for thermodynamic and kinetic interaction analysis between the receptor and four specific ligands. Following confirmation of these interactions by molecular docking, we identified puerarin and rosmarinic acid by determining their binding to the receptor. Azilsartan, candesartan, valsartan and olmesartan displayed two kinds of binding sites to AT1R by injection amount-dependent method. By molecular docking, we recognize the driving forces of the interaction as electrostatic interaction, hydrogen bonds and van der Waals force. The dissociation rate constants (kd) of azilsartan, candesartan, valsartan and olmesartan to AT1R were 0.01138 +/- 0.003, 0.05142 +/- 0.003, 0.07547 +/- 0.004 and 0.01310 +/- 0.005 min(-1) by peak profiling assay. Comparing with these parameters, puerarin and rosmarinic acid presented lower affinity (KA: 0.12x10(4) and 1.5x10(4)/M) and slower kinetics (kd: 0.6864 +/- 0.03 and 0.3005 +/- 0.01 min(-1)) to the receptor. These results, taking together, indicated that the immobilized AT1R has the capacity to probe antihypertensive compounds.
ESTHER : Liang_2020_J.Chromatogr.A__461003
PubMedSearch : Liang_2020_J.Chromatogr.A__461003
PubMedID: 32156458

Title : Lactobacillus plantarum KSFY06 and geniposide counteract montmorillonite-induced constipation in Kunming mice - Gan_2020_Food.Sci.Nutr_8_5128
Author(s) : Gan Y , Liang J , Diao W , Zhou X , Mu J , Pang L , Tan F , Zhao X
Ref : Food Sci Nutr , 8 :5128 , 2020
Abstract : Constipation is a common clinical manifestation of digestive system disorders and occurs worldwide. This study investigated the ability of Lactobacillus plantarum KSFY06 (LP-KSFY06) to promote the action of geniposide in preventing montmorillonite-induced constipation in Kunming mice, with the aim of providing a successful solution. The effects of LP-KSFY06 and geniposide on constipation were measured, and the results showed that the protective effect of geniposide on constipation was enhanced by LP-KSFY06 and that the combination resulted in increased weight, moisture content, and particle number of feces. The first black stool defecation time was decreased from 182 min to 87 min, which clearly indicates that defecating difficulty was alleviated in constipated mice. The synergic intervention of LP-KSFY06 and geniposide (LP + G) assisted in maintaining the body weight of constipated mice. The LP + G intervention significantly increased serum levels of motilin (MTL, 167.8 pg/ml), acetylcholinesterase (AChE, 45.3 pg/ml), substance P (SP, 61.0 pg/ml), vasoactive intestinal peptide (VIP, 70.5 pg/ml), endothelin-1 (ET-1, 16.1 pg/ml), and gastrin (73.0 pg/ml) and remarkably decreased somatostatin (SS, 35.2 pg/ml) when compared to those indexes in the LP-KSFY06 group and geniposide group. The LP + G treatment also significantly increased the mRNA expression of cluster of differentiation 117 (c-Kit), stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), and remarkably downregulated the expression of inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid-1 (TRPV1), and cyclooxygenase-2 (COX-2). The experimental results showed that the combination treatment has the strongest prevention effect against constipation, and LP-KSFY06 promotes the ability of geniposide to prevent constipation. Therefore, LP-KSFY06 is a potential probiotic strain with the capacity to prevent montmorillonite-induced constipation.
ESTHER : Gan_2020_Food.Sci.Nutr_8_5128
PubMedSearch : Gan_2020_Food.Sci.Nutr_8_5128
PubMedID: 32994973

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

Title : Biodegradation of mycotoxin fumonisin B1 by a novel bacterial consortium SAAS79 - Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
Author(s) : Zhao Z , Zhang Y , Gong A , Liu N , Chen S , Zhao X , Li X , Chen L , Zhou C , Wang J
Ref : Applied Microbiology & Biotechnology , 103 :7129 , 2019
Abstract : Fumonisin B1 (FB1) contamination in cereals and cereal products remains an important aspect of food safety because of its wide distribution and the potential health hazard. However, only a few microorganisms have been reported to effectively degrade FB1. In this present study, a bacterial consortium SAAS79 with highly FB1-degrading activity was isolated from the spent mushroom compost. The combination of antibiotic-driven selection and 16S rDNA sequencing identified the Pseudomonas genus as the key FB1-degrading member. The microbial consortium could degrade more than 90% of 10 microg/mL FB1 after incubation for 24 h at pH of 5-7 and temperature of 28-35 degreesC. The enzymes from the intracellular space were proved to be responsible for FB1 degradation, which eliminated about 90% of 10 microg/mL FB1 in 3 h. Besides, liquid chromatography time-of-flight mass spectrometry (LC-TOF/MS) analysis identified two degradation products of FB1, and their toxicity on the monkey kidney cells (MARC-145) was significantly lower (p < 0.05) compared with the parent FB1. Overall, the consortium SAAS79 and its crude enzymes may be a potential choice for the decontamination of FB1 in the feed and food industry. Also, the bacterial consortium provides a new source of genes for the development of enzymatic detoxification agent.
ESTHER : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedSearch : Zhao_2019_Appl.Microbiol.Biotechnol_103_7129
PubMedID: 31230101

Title : Design, synthesis and biological Evaluation of Dual acetyl cholinesterase and beta-secretase inhibitors in treatment for alzheimer's Disease - Deng_2019_Pak.J.Pharm.Sci_32_2091
Author(s) : Deng Y , Jiang Y , Zhao X , Wang J
Ref : Pak J Pharm Sci , 32 :2091 , 2019
Abstract : With the recent research advances in molecular biology and technology multiple credible hypotheses about the progress of Alzheimer's disease (AD) have been proposed, among which the amyloid and cholinergic hypotheses are commonly used to develop reliable therapeutic agents. The multitarget-directed ligand (MTDL) approach was taken in this work to develop muilti-functional agents, which can mainly serve as dual beta-secretase (BACE 1) and Acetylcholinesterase (AChE) inhibitors. Series of new compounds were designed, synthesized and evaluated in this work, from which we identified 2-((4-(1,3-dioxoisoindolin-2-yl)benzyl)amino)-2-oxoethyl-2-(4-methoxyphenyl)aceta te (1h) as a new dual cholinesterase and beta-secretase inhibitor without toxicity.
ESTHER : Deng_2019_Pak.J.Pharm.Sci_32_2091
PubMedSearch : Deng_2019_Pak.J.Pharm.Sci_32_2091
PubMedID: 31813875

Title : Integrating Target-Responsive Hydrogels with Smartphone for On-Site ppb-Level Quantitation of Organophosphate Pesticides - Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
Author(s) : Jin R , Kong D , Yan X , Zhao X , Li H , Liu F , Sun P , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :27605 , 2019
Abstract : Precise on-site profiling of organophosphate pesticides (OPs) is of significant importance for monitoring pollution and estimating poisoning. Herein, we designed a simple and convenient portable kit based on Ag(+)-responsive hydrogels for accurate detection of OPs. The newly developed hydrogels employed o-phenylenediamine (OPD) and silicon quantum dots (SiQDs) as indicator, which possessed ratiometric response. In this sensor, OPs as inhibitor of acetylcholinesterase prevented the generation of thiocholine, which blocked the formation of metal-polymer with Ag(+), further triggered the oxidation of OPD to yield yellow 2,3-diaminophenazine (DAP) with fluorescence emission at 557 nm. The fluorescence intensity of SiQDs (444 nm) was quenched by DAP through inner filter effect (IFE) process, emerging a typical ratiometric response. Interestingly, the ratiometric signal of kit, which was recorded by smartphone's camera, can be transduced by ImageJ software into the hue parameter that was linearly proportional to the concentration of OPs. The simplicity of portable kit combined with smartphone operation, which possessed high sensitivity (detection limit <10 ng mL(-1)) and rapid sample-to-answer detection time (45 min) in agricultural sample, indicating that the methodology offered a new sight for portable monitoring of food safety and human health.
ESTHER : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedSearch : Jin_2019_ACS.Appl.Mater.Interfaces_11_27605
PubMedID: 31291083

Title : Factors Associated With Deprescribing Acetylcholinesterase Inhibitors in Older Nursing Home Residents With Severe Dementia - Niznik_2019_J.Am.Geriatr.Soc_67_1871
Author(s) : Niznik JD , Zhao X , He M , Aspinall SL , Hanlon JT , Nace D , Thorpe JM , Thorpe CT
Ref : J Am Geriatr Soc , 67 :1871 , 2019
Abstract : BACKGROUND/OBJECTIVE: Uncertainty regarding benefits and risks associated with acetylcholinesterase inhibitors (AChEIs) in severe dementia means providers do not know if and when to deprescribe. We sought to identify which patient-, provider-, and system-level characteristics are associated with AChEI discontinuation. DESIGN: Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS), version 3.0, Area Health Resource File, and Nursing Home Compare. Cox-proportional hazards models with time-varying covariates were used to identify patient-, provider-, and system-level factors associated with AChEI discontinuation (30-day or more gap in supply). SETTING: US Medicare-certified nursing homes (NHs). PARTICIPANTS: Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). RESULTS: The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). The most commonly prescribed AChEIs were donepezil (77.8%), followed by transdermal rivastigmine (14.6%). The cumulative incidence of AChEI discontinuation was 29.7% at the end of follow-up (330 days), with mean follow-up times of 194 days for continuous users of AChEIs and 105 days for those who discontinued. Factors associated with increased likelihood of discontinuation were new admission, older age, difficulty being understood, aggressive behavior, poor appetite, weight loss, mechanically altered diet, limited prognosis designation, hospitalization in 90 days prior, and northeastern region. Factors associated with decreased likelihood of discontinuation included memantine use, use of strong anticholinergics, polypharmacy, rurality, and primary care prescriber vs geriatric specialist. CONCLUSION: Among NH residents with severe dementia being treated with AChEIs, the cumulative incidence of AChEI discontinuation was just under 30% at 1 year of follow-up. Our findings provide insight into potential drivers of deprescribing AChEIs, identify system-level barriers to deprescribing, and help to inform covariates that are needed to address potential confounding in studies evaluating the potential risks and benefits associated with deprescribing. J Am Geriatr Soc 67:1871-1879, 2019.
ESTHER : Niznik_2019_J.Am.Geriatr.Soc_67_1871
PubMedSearch : Niznik_2019_J.Am.Geriatr.Soc_67_1871
PubMedID: 31162642

Title : Protein-Inorganic Hybrid Nanoflower-Rooted Agarose Hydrogel Platform for Point-of-Care Detection of Acetylcholine - Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
Author(s) : Kong D , Jin R , Zhao X , Li H , Yan X , Liu F , Sun P , Gao Y , Liang X , Lin Y , Lu G
Ref : ACS Appl Mater Interfaces , 11 :11857 , 2019
Abstract : Rapid and precise profiling of acetylcholine (ACh) has become important for diagnosing diseases and safeguarding health care because of its pivotal role in the central nervous system. Herein, we developed a new colorimetric sensor based on protein-inorganic hybrid nanoflowers as artificial peroxidase, comprising a test kit and a smartphone reader, which sensitively quantifies ACh in human serum. In this sensor, ACh indirectly triggered the substrate reaction with the help of a multienzyme system including acetylcholinesterase, choline oxidase, and mimic peroxidase (nanoflowers), accompanying the enhancement of absorbance intensity at 652 nm. Therefore, the multienzyme platform can be used to detect ACh via monitoring the change of the absorbance in a range from 0.0005 to 6.0 mmol L(-1). It is worth mentioning that the platform was used to prepare a portable agarose gel-based kit for rapid qualitative monitoring of ACh. Coupling with ImageJ program, the image information of test kits can be transduced into the hue parameter, which provides a directly quantitative tool to identify ACh. Based on the advantages of simple operation, good selectivity, and low cost, the availability of a portable kit for point-of-care testing will achieve the needs of frequent screening and diagnostic tracking.
ESTHER : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedSearch : Kong_2019_ACS.Appl.Mater.Interfaces_11_11857
PubMedID: 30830739

Title : HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure - Wu_2019_J.Viral.Hepat_26_1334
Author(s) : Wu J , Guo N , Zhang X , Xiong C , Liu J , Xu Y , Fan J , Yu J , Zhao X , Liu B , Wang W , Zhang J , Cao H , Li L
Ref : J Viral Hepat , 26 :1334 , 2019
Abstract : A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages.
ESTHER : Wu_2019_J.Viral.Hepat_26_1334
PubMedSearch : Wu_2019_J.Viral.Hepat_26_1334
PubMedID: 31294523

Title : Preventive Effects of Different Fermentation Times of Shuidouchi on Diphenoxylate-Induced Constipation in Mice - Chen_2019_Foods_8_
Author(s) : Chen L , Zhang J , Suo H , Wang W , Wang H , Zhang Y , Hu Q , Zhao X , Li J
Ref : Foods , 8 : , 2019
Abstract : This study compares the prevention effects of Shuidouchi with different fermentation times on constipation in mice. Shuidouchi is a short-time fermented soybean product. By improving its processing technology, it can incur better biological activity and become a health food. The Shuidouchi-treated mice were evaluated using constipation-related kits, quantitative polymerase chain reaction (qPCR), and Western blot assays. After the mice were fed 72-h-fermented Shuidouchi (72-SDC) for 9 d, the defecation time to excrete the first black stool was lower than that of the control and 24-SDC and 48-SDC groups, but was much higher than that of the normal group. The gastrointestinal (GI) transit of the small intestine of the 72-SDC group was higher than that of the control and the 24-SDC and 48-SDC groups, but lower that of the normal group. Meanwhile, 72-SDC could significantly increase the levels of ghrelin, endothelin-1 (ET-1), vasoactive intestinal peptide (VIP), and acetylcholinesterase (AchE) in the serum of constipated mice compared to the levels in mice in the control group. Moreover, 72-SDC could raise c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GNDF), neuronal nitric oxide synthase (nNOS), and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) and protein expression levels, and reduce transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels in small-intestinal tissue compared to the levels in the control group. Meanwhile, 72-SDC also raised ghrelin mRNA expression in gastric tissue and transient receptor potential ankyrin 1 (TRPA1) mRNA expression in colon tissue compared to the control group mice; these effects were stronger than those of 24-SDC and 48-SDC. Shuidouchi has good preventative effects on constipation and performs best when fermented for at least 72 h.
ESTHER : Chen_2019_Foods_8_
PubMedSearch : Chen_2019_Foods_8_
PubMedID: 30832248

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

Title : Lactobacillus plantarum CQPC02-Fermented Soybean Milk Improves Loperamide-Induced Constipation in Mice - Yi_2019_J.Med.Food_22_1208
Author(s) : Yi R , Peng P , Zhang J , Du M , Lan L , Qian Y , Zhou J , Zhao X
Ref : J Med Food , 22 :1208 , 2019
Abstract : This study determined the ameliorative effects of the novel microorganism, Lactobacillus plantarum CQPC02 (LP-CQPC02), fermented in soybean milk, on loperamide-induced constipation in Kunming mice. High-performance liquid chromatography revealed that LP-CQPC02-fermented soybean milk (LP-CQPC02-FSM) had six types of soybean isoflavones, whereas Lactobacillus bulgaricus-fermented soybean milk (LB-FSM) and unfermented soybean milk (U-FSM) only had five types of soybean isoflavones. LP-CQPC02-FSM also contained more total and active soybean isoflavones than LB-FSM and U-FSM. Results from mouse experiments showed that the defecation factors (quantity, fecal weight and water content, gastrointestinal transit ability, and time to first black stool) in the LP-CQPC02-FSM-treated mice were better than those in the LB-FSM- and U-FSM-treated mice. The serum and small intestinal tissue experiments showed that soybean milk increased the motilin, gastrin, endothelin, acetylcholinesterase, substance P, vasoactive intestinal peptide, and glutathione levels and decreased the somatostatin, myeloperoxidase, nitric oxide, and malondialdehyde levels compared with the constipated mice in the control group. The LP-CQPC02-FSM also showed better effects than those of LB-FSM and U-FSM. Further results showed that LP-CQPC02-FSM upregulated cuprozinc-superoxide dismutase (Cu/Zn-SOD), manganese superoxide dismutase (Mn-SOD), catalase (CAT), c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF), neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), and aquaporin-9 (AQP9) and downregulated the expression levels of transient receptor potential cation channel subfamily V member 1 (TRPV1), inducible nitric oxide synthase (iNOS), and aquaporin-3 (AQP3) in the constipated mice. LP-CQPC02-FSM increased the Bacteroides and Akkermansia abundances and decreased the Firmicutes abundance in the feces of the constipated mice and decreased the Firmicutes/Bacteroides ratio. This study confirmed that LP-CQPC02-FSM partially reversed constipation in mice.
ESTHER : Yi_2019_J.Med.Food_22_1208
PubMedSearch : Yi_2019_J.Med.Food_22_1208
PubMedID: 31621475

Title : Sevoflurane-induced inflammation development: involvement of cholinergic anti-inflammatory pathway - Yin_2019_Behav.Pharmacol_30_730
Author(s) : Yin J , Zhao X , Wang L , Xie X , Geng H , Zhan X , Teng J
Ref : Behav Pharmacol , 30 :730 , 2019
Abstract : Chronic inflammation plays an important role in the mechanisms underpinning the development of anesthesia-induced cognitive dysfunction. However, less is known about how anesthesia causes inflammation. One possibility is that the inflammation is related to alteration of the activity of the alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway. This study analyzed the effect of sevoflurane administration on the cognitive function by using a novel object recognition test and Y-maze test, and on acetylcholinesterase activity and expression in hippocampal tissue by using an acetylcholinesterase assay kit and quantitative real-time PCR. This study also evaluated the effect of alpha 7 nicotinic acetylcholine receptor agonist PNU-282987 and antagonist methyllycaconitine on cognitive function and the level of hippocampal tumor necrosis factor-alpha in aged rats exposed to sevoflurane anesthesia. We found that 3% sevoflurane significantly impaired cognitive function and increased acetylcholinesterase activity by upregulating its expression in hippocampal tissue. Sevoflurane-induced impairment of cognitive function was significantly rescued by PNU-282987 but aggravated by methyllycaconitine. In addition to impairment of cognitive function, sevoflurane also significantly increased tumor necrosis factor-alpha level in plasma and hippocampal tissue. Similarly, this sevoflurane-induced change of tumor necrosis factor-alpha level in rats was antagonized by PNU-282987 but amplified by methyllycaconitine. In conclusion, our data show that the development of inflammation in sevoflurane-induced cognitive decline is associated with the downregulation of alpha 7 nicotinic acetylcholine receptor cholinergic anti-inflammatory pathway in aged rats.
ESTHER : Yin_2019_Behav.Pharmacol_30_730
PubMedSearch : Yin_2019_Behav.Pharmacol_30_730
PubMedID: 31625977

Title : Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis - Li_2019_Eur.J.Neurol_26_1296
Author(s) : Li M , Han J , Zhang Y , Lv J , Zhang J , Zhao X , Ren L , Fang H , Yang J , Cui X , Zhang Q , Li Q , Du Y , Gao F
Ref : Eur Journal of Neurology , 26 :1296 , 2019
Abstract : BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved.
ESTHER : Li_2019_Eur.J.Neurol_26_1296
PubMedSearch : Li_2019_Eur.J.Neurol_26_1296
PubMedID: 31050101

Title : Treatment Effects of Jinlingzi Powder and Its Extractive Components on Gastric Ulcer Induced by Acetic Acid in Rats - Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
Author(s) : Zhao X , Li J , Meng Y , Cao M , Wang J
Ref : Evid Based Complement Alternat Med , 2019 :7365841 , 2019
Abstract : Jinlingzi powder comprises Melia toosendan Sieb. et Zucc. and Corydalis yanhusuo (Y.H. Chou & Chun C.Hsu) W.T. Wang ex Z.Y. Su & C.Y. Wu and is usually applied in clinic as traditional Chinese medicine for pain. The present study aims to investigate the therapeutic actions of Jinlingzi powder and its extracted components and theirs treatment mechanism on the acetic acid induced-gastric ulcer in rats. The gastric ulcer model was induced by the administration of acetic acid in rats (84 male). Jinlingzi powder water decoction, its polysaccharide, and nonalkaloid and alkaloid components were used to investigate the therapeutic actions on the acetic acid induced-gastric ulcer by measuring the related pharmacy and pharmacodynamic factors, including ulcer index, ulcer area, ulcer healing rate, interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), neurotensin (NT), platelet activating factor (PAF), thromboxane B2 (TXB2), and vascular endothelial growth factor (VEGF) in rat serum, acetylcholinesterase (AChE) in brain tissue, prostaglandin E2 (PGE2), and basic fibroblast growth factor (bFGF) in gastric tissue. Among the various groups, Jinlingzi powder and the nonalkaloid components caused significant changes in IL-8, TNF-alpha, NT, PAF TXB2, and VEGF values in the serum. The AChE content in the rats' brain tissue was also reduced after using Jinlingzi powder and the nonalkaloid components. Additionally, Jinlingzi powder and the nonalkaloid components considerably affect the amount of PGE2 and bFGF in a rat's stomach tissue. Therefore, Jinlingzi powder and the nonalkaloid components can effectively inhibit neutral neutrophil activation, prevent capillaries thrombosis, and protect gastric mucosa. Thus, the nonalkaloid components of the Jinlingzi powder play a key role in the treatment of gastric ulcer.
ESTHER : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedSearch : Zhao_2019_Evid.Based.Complement.Alternat.Med_2019_7365841
PubMedID: 30719066

Title : Two new phenylpropanoids and a new dihydrostilbenoid from the flower buds of Magnolia biondii pamp and their acetylcholinesterase inhibitory activities - Cao_2019_Nat.Prod.Res__1
Author(s) : Cao YG , Li HW , Cao B , Wang JC , Zhang YL , Zhao X , Zheng XK , Feng WS
Ref : Nat Prod Res , :1 , 2019
Abstract : Two new phenylpropanoids, named (2'R*,3'R*)-2',3'-dihydroxy-4'-methoxy-caffeoyl butyrate (1), 9-acetoxy syringin (2), and a new dihydrostilbene, named (8'R)-4',5-dihydroxy-4,8'-dimethoxy-2-hydroxyethyl diphenylethane (3), together with five analogues (4-8), were isolated from the flower buds of Magnolia biondii Pamp. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The absolute configurations were deduced by comparison of experimental and calculated gauge-independent atomic orbital (GIAO) 1 D NMR data. Moreover, the isolated compounds (1-8) were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities.
ESTHER : Cao_2019_Nat.Prod.Res__1
PubMedSearch : Cao_2019_Nat.Prod.Res__1
PubMedID: 31746227

Title : One-step methodology for the direct covalent capture of GPCRs from complex matrices onto solid surfaces based on the bioorthogonal reaction between haloalkane dehalogenase and chloroalkanes - Zeng_2018_Chem.Sci_9_446
Author(s) : Zeng K , Li Q , Wang J , Yin G , Zhang Y , Xiao C , Fan T , Zhao X , Zheng X
Ref : Chem Sci , 9 :446 , 2018
Abstract : Protein immobilization techniques play an important role in the development of assays for disease diagnosis and drug discovery. However, many of these approaches are not applicable to transmembrane proteins. G protein-coupled receptors (GPCRs) are the largest protein superfamily encoded by the human genome and are targeted by a quarter of all prescription drugs. GPCRs are highly dynamic and sensitive to changes in the ambient environment, and current immobilization methodologies are not suitable for GPCRs. We used haloalkane dehalogenase (Halo) as an immobilization tag fused to the beta2-adrenoceptor (beta2-AR), angiotensin II type 1 (AT1) and angiotensin II type 2 (AT2) receptors. The engineered Halo-tag covalently binds to a specific substrate chloroalkane through Asp 106 in the catalytic pocket. The Halo-tagged GPCRs were expressed in Escherichia coli at a suitable yield. Accordingly, we loaded cell lysate containing Halo-tagged GPCRs onto a macroporous silica gel coated with chloroalkane. Morphological characterization indicated a homogeneous monolayer of immobilized Halo-tagged GPCRs on the silica gel surface. The immobilized receptors proved to be surrounded by specific bound phospholipids including PG C18:1/C18:1. We observed a radio-ligand binding ability and ligand-induced conformational changes in the immobilized GPCRs, suggesting the preservation of bioactivity. This method is a one-step approach for the specific immobilization of GPCRs from cell lysates and validates that immobilized receptors retain canonical ligand binding capacity. Our immobilization strategy circumvents labor-intensive purification procedures and minimizes loss of activity. The immobilized receptors can be applied to high-throughput drug and interaction partner screening for GPCRs.
ESTHER : Zeng_2018_Chem.Sci_9_446
PubMedSearch : Zeng_2018_Chem.Sci_9_446
PubMedID: 29629116

Title : Preventive Effect of Lactobacillus fermentum CQPC03 on Activated Carbon-Induced Constipation in ICR Mice - Zhang_2018_Medicina.(Kaunas)_54_
Author(s) : Zhang J , Chen B , Liu B , Zhou X , Mu J , Wang Q , Zhao X , Yang Z
Ref : Medicina (Kaunas) , 54 : , 2018
Abstract : Background and objectives: Paocai (pickled cabbage), which is fermented by lactic acid bacteria, is a traditional Chinese food. The microorganisms of Paocai were isolated and identified, and the constipation inhibition effect of one of the isolated Lactobacillus was investigated. Materials and Methods: The 16S rDNA technology was used for microbial identification. A mouse constipation model was established using activated carbon. After intragastric administration of Lactobacillus (10(8) CFU/mL), the mice were dissected to prepare pathological sections of the small intestine. Serum indicators were detected using kits, and the expression of small intestine-related mRNAs was detected by qPCR assay. Results: One strain of Lactobacillus was identified and named Lactobacillus fermentum CQPC03 (LF-CQPC03). Body weight and activated carbon propulsion rate were all higher in mice intragastrically administered with LF-CQPC03 compared with the control group, while the time to the first black stool in treated mice was lower than that in the control group. Serum assays showed that gastrin (Gas), endothelin (ET), and acetylcholinesterase (AchE) levels were significantly higher in the LF-CQPC03-treated mice than in the control group, while somatostatin (SS) levels were significantly lower than in the control mice. Mouse small intestine tissue showed that c-Kit, stem cell factor (SCF), and glial cell-derived neurotrophic factor (GDNF) mRNA expression levels were significantly higher in the LF-CQPC03 treated mice than in control mice, while transient receptor potential cation channel subfamily V member 1 (TRPV1) and inducible nitric oxide synthase (iNOS) expression levels were significantly lower in the LF-CQPC03 treated mice than in control mice. Conclusions: There is a better effect with high-dose LF-CQPC03, compared to the lower dose (LF-CQPC03-L), showing good probiotic potential, as well as development and application value.
ESTHER : Zhang_2018_Medicina.(Kaunas)_54_
PubMedSearch : Zhang_2018_Medicina.(Kaunas)_54_
PubMedID: 30463207

Title : Expression of soluble epoxide hydrolase in renal tubular epithelial cells regulates macrophage infiltration and polarization in IgA nephropathy - Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
Author(s) : Wang Q , Liang Y , Qiao Y , Zhao X , Yang Y , Yang S , Li B , Zhao Q , Dong L , Quan S , Tian R , Liu Z
Ref : American Journal of Physiology Renal Physiol , 315 :F915 , 2018
Abstract : Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in the kidney remains unknown. In this study, we investigated the relationships between the level of sEH and clinical and pathological parameters in IgA nephropathy. The level of sEH expression positively correlated with proteinuria and infiltration of macrophages. sEH-positive tubules were found to be surrounded by macrophages. Furthermore, we found that incubation of immortalized human proximal tubular HK-2 cells with total urinary protein and overexpression of sEH promoted inflammatory factor production, which was associated with M1 polarization. We also exposed RAW264.7 mouse leukemic monocytes/macrophages to different HK-2 cell culture media conditioned by incubation with various substances affecting sEH amount or activity. We found that the upregulation of sEH promoted M1 polarization. However, pharmacological inhibition of sEH and supplementation with EETs reversed the conditioning effects of urinary proteins by inhibiting M1 polarization through the NF-kappaB pathway and stimulating M2 polarization through the phosphatidylinositol 3-kinase pathway. These data suggest that inhibition of sEH could be a new strategy to prevent the progression of inflammation and to attenuate renal tubulointerstitial fibrosis.
ESTHER : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedSearch : Wang_2018_Am.J.Physiol.Renal.Physiol_315_F915
PubMedID: 29717935

Title : Evaluation of joint effects of cyprodinil and kresoxim-methyl on zebrafish, Danio rerio - Wang_2018_J.Hazard.Mater_352_80
Author(s) : Wang Y , Dai D , Yu Y , Yang G , Shen W , Wang Q , Weng H , Zhao X
Ref : J Hazard Mater , 352 :80 , 2018
Abstract : Aquatic organisms are usually exposed to a mixture of pesticides instead of individual chemicals. However, risk assessment of pesticides is traditionally based on toxicity data of individual compounds. In this study, we aimed to examine the joint toxicity of two fungicides cyprodinil (CYP) and kresoxim-methyl (KRM) to zebrafish (Danio rerio) using a systematic experimental approach. Results from 96-h semi-static test indicated that the LC50 values of KRM to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.034 (0.015-0.073) to 0.61 (0.39-0.83) mg a.i. L(-1), which were higher than those of CYP ranging from 1.05 (0.88-1.52) to 4.42 (3.24-6.02) mg a.i. L(-1). Pesticide mixtures of CYP and KRM exhibited synergistic effect on embryonic zebrafish. The activities of carboxylesterase (CarE) and cytochrome P450 (Cyp450) were significantly altered in most of the individual and combined exposures compared with the control group. The expressions of seven genes (Mnsod, cyp17, crhr 2, crh, gnrhr 4, gnrhr 1 and hmgrb) were significantly altered upon exposure to combined pesticides compared with their individual pesticides. Collectively, these findings suggested joint effects should be considered in the risk assessment of pesticides and development of water quality criteria for the protection of aquatic environment.
ESTHER : Wang_2018_J.Hazard.Mater_352_80
PubMedSearch : Wang_2018_J.Hazard.Mater_352_80
PubMedID: 29574263

Title : Lactobacillus plantarum YS-3 Prevents Activated Carbon-Induced Constipation in Mice - Zhao_2018_J.Med.Food_21_575
Author(s) : Zhao X , Yi R , Qian Y , Park KY
Ref : J Med Food , 21 :575 , 2018
Abstract : The aim of this study was to determine the effects of Lactobacillus plantarum YS-3 (LP-YS3) on activated carbon-induced constipation in Kunming mice. The results of the experiment show that the antigastric acid activity and bile salt tolerance of LP-YS3 were stronger than those of Lactobacillus bulgaricus (LB). LP-YS3 inhibited loss of body weight caused by constipation and further reductions in fecal weight, particle number, and water content in mice. Moreover, LP-YS3 elevated the gastrointestinal transit rate and reduced the time required for initial black stool defecation. LP-YS3 also elevated motilin (MTL), endothelin (ET), acetylcholinesterase (AChE), substance P (SP), and VIP serum levels and reduced somatostatin (SS) levels in constipated mice. Hematoxylin-eosin (H&E) staining revealed that high concentration of LP-YS3 reduced the incidence of injuries to small intestine villi and the intestinal wall compared to carbon-induced constipation groups. Reverse transcription-polymerase chain reaction and western blot experiments demonstrated that LP-YS3 upregulated c-Kit, stem cell factor, and glial cell line-derived neurotrophic factor mRNA and protein expression and downregulated transient receptor potential vanilloid 1 and nitric oxide synthase expression in small intestine tissue from constipated mice. In conclusion, high concentrations of LP-YS3 had stronger and more beneficial effects than LB. Based on these results, we conclude that LP-YS3 can effectively inhibit constipation.
ESTHER : Zhao_2018_J.Med.Food_21_575
PubMedSearch : Zhao_2018_J.Med.Food_21_575
PubMedID: 29757072

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

Title : Ultrasonic pretreatment promotes diacylglycerol production from lard by lipase-catalysed glycerolysis and its physicochemical properties - Zhao_2018_Ultrason.Sonochem_48_11
Author(s) : Zhao X , Sun Q , Qin Z , Liu Q , Kong B
Ref : Ultrason Sonochem , 48 :11 , 2018
Abstract : The objective of this study was to evaluate the effect of ultrasonic pretreatment on diacylglycerol (DAG) synthesis by lipase-catalysed glycerolysis of lard and to analyse the physicochemical properties of lard-based DAG. The optimal ultrasonic pretreatment conditions were: Rhizomucor miehei (Lipozyme(R) RMIM)-to-lard ratio 4:100 (W/W), 45 degrees C for 5min, and power 250W. The lard-based DAG samples for 4h of glycerolysis reactions with ultrasonic pretreatment (named DAG-U) and 11h of glycerolysis reactions without ultrasonic pretreatment (named DAG-N) had similar DAG contents and were used for further analysis. The major FA compositions and iodine value of lard, DAG-U and DAG-N were similar. Fourier transform infrared spectroscopy analysis proved that enzymatic glycerolysis with and without ultrasonic pretreatment did not change the structure of the lard. Differential scanning calorimetry analysis showed that the crystallization onset of DAG-U and DAG-N shifted to higher temperatures than that of lard, which indicated that DAG oils accelerated nucleation and crystal growth. X-ray diffraction analysis revealed that both DAG-U and DAG-N contained beta' crystal and a substantially lower amount of beta crystal. Overall, ultrasonic pretreatment promotes diacylglycerol production from lard through lipase-catalysed glycerolysis, and DAG-U and DAG-N have similar physicochemical properties.
ESTHER : Zhao_2018_Ultrason.Sonochem_48_11
PubMedSearch : Zhao_2018_Ultrason.Sonochem_48_11
PubMedID: 30080532

Title : Preparation of Diacylglycerol from Lard by Enzymatic Glycerolysis and Its Compositional Characteristics - Diao_2017_Korean.J.Food.Sci.Anim.Resour_37_813
Author(s) : Diao X , Guan H , Kong B , Zhao X
Ref : Korean J Food Sci Anim Resour , 37 :813 , 2017
Abstract : The aim of this study was to prepare diacylglycerol (DAG) by enzymatic glycerolysis of lard. The effects of reaction parameters such as lipase type, reaction temperature, enzyme amount, substrate molar ratio (lard/glycerol), reaction time, and magnetic stirring speed were investigated. Lipozyme RMIM was found to be a more active biocatalyst than Novozym 435, and the optimal reaction conditions were 14:100 (W/W) of enzyme to lard substrate ratio, 1:1 of lard to glycerol molar ratio, and 500 rpm magnetic stirring speed. The reaction mixture was first incubated at 65 for 2 h and then transferred to 45 for 8 h. At the optimum reaction conditions, the conversion rate of triacylglycerol (TAG) and the content of DAG in the reaction mixture reached 76.26% and 61.76%, respectively, and the DAG content in purified glycerolized lard was 82.03% by molecular distillation. The distribution of fatty acids and Fourier transform infrared spectra in glycerolized lard samples were similar to those in lard samples. The results revealed that enzymatic glycerolysis and molecular distillation can be used to prepare more highly purified DAG from lard.
ESTHER : Diao_2017_Korean.J.Food.Sci.Anim.Resour_37_813
PubMedSearch : Diao_2017_Korean.J.Food.Sci.Anim.Resour_37_813
PubMedID: 29725202

Title : Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus - Zhou_2017_Sci.Adv_3_eaao4966
Author(s) : Zhou J , Li C , Zhao G , Chu H , Wang D , Yan HH , Poon VK , Wen L , Wong BH , Zhao X , Chiu MC , Yang D , Wang Y , Au-Yeung RKH , Chan IH , Sun S , Chan JF , To KK , Memish ZA , Corman VM , Drosten C , Hung IF , Zhou Y , Leung SY , Yuen KY
Ref : Sci Adv , 3 :eaao4966 , 2017
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication. We also identified the evidence of enteric MERS-CoV infection in the stool specimen of a clinical patient. MERS-CoV was considerably resistant to fed-state gastrointestinal fluids but less tolerant to highly acidic fasted-state gastric fluid. In polarized Caco-2 cells cultured in Transwell inserts, apical MERS-CoV inoculation was more effective in establishing infection than basolateral inoculation. Notably, direct intragastric inoculation of MERS-CoV caused a lethal infection in human DPP4 transgenic mice. Histological examination revealed MERS-CoV enteric infection in all inoculated mice, as shown by the presence of virus-positive cells, progressive inflammation, and epithelial degeneration in small intestines, which were exaggerated in the mice pretreated with the proton pump inhibitor pantoprazole. With the progression of the enteric infection, inflammation, virus-positive cells, and live viruses emerged in the lung tissues, indicating the development of sequential respiratory infection. Taken together, these data suggest that the human intestinal tract may serve as an alternative infection route for MERS-CoV.
ESTHER : Zhou_2017_Sci.Adv_3_eaao4966
PubMedSearch : Zhou_2017_Sci.Adv_3_eaao4966
PubMedID: 29152574

Title : Multifunctional Compound AD-35 Improves Cognitive Impairment and Attenuates the Production of TNF-alpha and IL-1beta in an Abeta25-35-induced Rat Model of Alzheimer's Disease - Li_2017_J.Alzheimers.Dis_56_1403
Author(s) : Li L , Xu S , Liu L , Feng R , Gong Y , Zhao X , Li J , Cai J , Feng N , Wang L , Wang X , Peng Y
Ref : J Alzheimers Dis , 56 :1403 , 2017
Abstract : The dyshomeostasis of transition metal ions, accumulation of amyloid-beta (Abeta) senile plaques and neuroinflammatory response found in the brain of patients with Alzheimer's disease (AD) have been suggested to be involved in AD pathogenesis. Novel compounds capable of targeting metal-Abeta species and neuroinflammation would be valuable. AD-35 is such a patented small-molecule compound derived from innovative modification of the chemical structure of donepezil. This compound could moderately inhibit acetylcholinesterase and metal-induced Abeta aggregation in vitro and showed disassembly of Abeta aggregates. The effects of AD-35 on cognitive impairments and neuroinflammatory changes caused by intracerebroventricular injection of Abeta25-35 were studied in rats. Compared to sham group, Abeta25-35 injection significantly led to learning and memory deficits, astrocyte activation, and pro-inflammatory cytokines releases (TNF-alpha and IL-1beta). Further studies indicated that the phosphorylation of extracellular signal-regulated kinase was involved in astrocyte activation and pro-inflammatory cytokines production. Oral administration of AD-35 could markedly attenuate Abeta25-35 injection-induced astrocyte activation, pro-inflammatory cytokines TNF-alpha and IL-1beta release, and memory deficits. On the contrary, donepezil only showed inhibition of IL-1beta production, but failed to block astrocyte activation and TNF-alpha production. These results showed that AD-35 would be a novel multi-mechanism drug for the prevention and/or treatment of AD.
ESTHER : Li_2017_J.Alzheimers.Dis_56_1403
PubMedSearch : Li_2017_J.Alzheimers.Dis_56_1403
PubMedID: 28157092

Title : Soluble epoxide hydrolase inhibitors might prevent ischemic arrhythmias via microRNA-1 repression in primary neonatal mouse ventricular myocytes - Liu_2017_Mol.Biosyst_13_556
Author(s) : Liu Q , Zhao X , Peng R , Wang M , Zhao W , Gui YJ , Liao CX , Xu DY
Ref : Mol Biosyst , 13 :556 , 2017
Abstract : Ischemic arrhythmias are the main causes of sudden cardiac death. It has been reported that soluble epoxide hydrolase inhibitors (sEHis) could prevent arrhythmias; however, the underlying molecular mechanisms remain unclear. In recent years, the proarrhythmic role of microRNA-1 (miR-1) has been investigated. This study aimed to elucidate whether sEHis prevented ischemic arrhythmias by suppressing miR-1. The primary neonatal mouse ventricular myocyte model of miR-1 overexpression was established by incubating with agonist microONTM mmu-miR-1a-3p agomir (DAEDstainTM Dye) (agomiR-1). The sEHi, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), was administered following miR-1 overexpression. Quantitative real-time PCR (qPCR) and western blotting were used to test alterations in the expression of miR-1 and its target mRNAs GJA1 and KCNJ2 and their respective encoded proteins connexin 43 (Cx43) and the K+ channel subunit (Kir2.1). The whole-cell patch-clamp technique was used to record the alterations of the inward rectifying K+ current (IK1). Compared with the control group, miR-1 levels were significantly increased in the agomiR-1 group (p < 0.05), which suggested the successful construction of the miR-1 overexpression model. Compared with the control group, the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins in the agomiR-1 group were significantly decreased, and IK1 was significantly impaired (all p < 0.05). The miR-1 levels were dose-dependently decreased by t-AUCB, whereas t-AUCB dose-dependently increased the levels of GJA1 and KCNJ2 mRNAs and Cx43 and Kir2.1 proteins. Furthermore, t-AUCB restored the impaired IK1 (all p < 0.05). In conclusion, the sEHi t-AUCB has the ability to down-regulate proarrhythmic miR-1 and up-regulate its target genes and proteins, eventually restoring IK1.
ESTHER : Liu_2017_Mol.Biosyst_13_556
PubMedSearch : Liu_2017_Mol.Biosyst_13_556
PubMedID: 28112313

Title : Differential physiological effects of neonicotinoid insecticides on honey bees: A comparison between Apis mellifera and Apis cerana - Li_2017_Pestic.Biochem.Physiol_140_1
Author(s) : Li Z , Li M , He J , Zhao X , Chaimanee V , Huang WF , Nie H , Zhao Y , Su S
Ref : Pestic Biochem Physiol , 140 :1 , 2017
Abstract : Acute toxicities (LD50s) of imidacloprid and clothianidin to Apis mellifera and A. cerana were investigated. Changing patterns of immune-related gene expressions and the activities of four enzymes between the two bee species were compared and analyzed after exposure to sublethal doses of insecticides. Results indicated that A. cerana was more sensitive to imidacloprid and clothianidin than A. mellifera. The acute oral LD50 values of imidacloprid and clothianidin for A. mellifera were 8.6 and 2.0ng/bee, respectively, whereas the corresponding values for A. cerana were 2.7 and 0.5ng/bee. The two bee species possessed distinct abilities to mount innate immune response against neonicotinoids. After 48h of imidacloprid treatment, carboxylesterase (CCE), prophenol oxidase (PPO), and acetylcholinesterase (AChE) activities were significantly downregulated in A. mellifera but were upregulated in A. cerana. Glutathione-S-transferase (GST) activity was significantly elevated in A. mellifera at 48h after exposure to imidacloprid, but no significant change was observed in A. cerana. AChE was downregulated in both bee species at three different time points during clothianidin exposure, and GST activities were upregulated in both species exposed to clothianidin. Different patterns of immune-related gene expression and enzymatic activities implied distinct detoxification and immune responses of A. cerana and A. mellifera to imidacloprid and clothianidin.
ESTHER : Li_2017_Pestic.Biochem.Physiol_140_1
PubMedSearch : Li_2017_Pestic.Biochem.Physiol_140_1
PubMedID: 28755688

Title : Preventative effects of fermented Chimonobambusa quadrangularis shoot on activated carbon-induced constipation - Li_2017_Exp.Ther.Med_13_1093
Author(s) : Li G , Zou X , Kuang G , Ren Y , Deng C , Lin Q , Zhao X , Xu S , Song JL
Ref : Exp Ther Med , 13 :1093 , 2017
Abstract : The present study aimed to determine the preventative effects of fermented Chimonobambusa quadrangularis shoot (FCQS) on activated carbon constipation in Kun Ming mice. FCQS has a more loose fiber tissue structure than unfermented fresh C. quadrangularis shoot (CQS), which is preferable for relieving constipation. In mice fed with FCQS for 9 days the time from consumption to their first black stool defecation (117 min) was shorter than the control group (192 min) and the CQS group (148 min); however, it was longer than the normal (85 min) and bisacodyl treatment (99 min) groups. The gastrointestinal transit of the FCQS group (73.8%) was increased, as compared with the control (37.9%) and CQS (61.7%) groups; however, it was decreased as compared with the normal (100%) and bisacodyl (88.3%) groups. By observing the hemotoxylin and eosin-stained section of mice intestine, it was demonstrated that FCQS reduced injury to the intestinal tract resulting from constipation and alleviated the damage caused to the intestinal villi over the effects observed in the CQS group. Furthermore, FCQS was also able to increase the serum levels of motilin, endothelin-1, vasoactive intestinal peptide and acetylcholinesterase compared with the control group. c-Kit, stem cell factor (SCF), glial cell-derived neurotrophic factor (GDNF) mRNA and protein expression levels in the small intestinal cells of FCQS-fed mice were increased, as compared with CQS-fed mice. Transient receptor potential cation channel subfamily V member 1 (TRPV1) and nitric oxide synthase (NOS) expression levels of small intestinal cells of FCQS-fed mice were reduced, as compared with CQS-fed mice. These findings demonstrated that FCQS may induce improved preventative effects on constipation, compared with CQS.
ESTHER : Li_2017_Exp.Ther.Med_13_1093
PubMedSearch : Li_2017_Exp.Ther.Med_13_1093
PubMedID: 28450948

Title : Ultrasound enhances lipase-catalyzed synthesis of poly (ethylene glutarate) - Zhao_2016_Ultrason.Sonochem_31_506
Author(s) : Zhao X , Bansode SR , Ribeiro A , Abreu AS , Oliveira C , Parpot P , Gogate PR , Rathod VK , Cavaco-Paulo A
Ref : Ultrason Sonochem , 31 :506 , 2016
Abstract : The present work explores the best conditions for the enzymatic synthesis of poly (ethylene glutarate) for the first time. The start-up materials are the liquids; diethyl glutarate and ethylene glycol diacetate, without the need of addition of extra solvent. The reactions are catalyzed by lipase B from Candida antarctica immobilized on glycidyl methacrylate-ter-divinylbenzene-ter-ethylene glycol dimethacrylate at 40 degrees C during 18h in water bath with mechanical stirring or 1h in ultrasonic bath followed by 6h in vacuum in both the cases for evaporation of ethyl acetate. The application of ultrasound significantly intensified the polyesterification reaction with reduction of the processing time from 24h to 7h. The same degree of polymerization was obtained for the same enzyme loading in less time of reaction when using the ultrasound treatment. The degree of polymerization for long-term polyesterification was improved approximately 8-fold due to the presence of sonication during the reaction. The highest degree of polymerization achieved was 31, with a monomer conversion of 96.77%. The ultrasound treatment demonstrated to be an effective green approach to intensify the polyesterification reaction with enhanced initial kinetics and high degree of polymerization.
ESTHER : Zhao_2016_Ultrason.Sonochem_31_506
PubMedSearch : Zhao_2016_Ultrason.Sonochem_31_506
PubMedID: 26964978

Title : The Dendrobium catenatum Lindl. genome sequence provides insights into polysaccharide synthase, floral development and adaptive evolution - Zhang_2016_Sci.Rep_6_19029
Author(s) : Zhang GQ , Xu Q , Bian C , Tsai WC , Yeh CM , Liu KW , Yoshida K , Zhang LS , Chang SB , Chen F , Shi Y , Su YY , Zhang YQ , Chen LJ , Yin Y , Lin M , Huang H , Deng H , Wang ZW , Zhu SL , Zhao X , Deng C , Niu SC , Huang J , Wang M , Liu GH , Yang HJ , Xiao XJ , Hsiao YY , Wu WL , Chen YY , Mitsuda N , Ohme-Takagi M , Luo YB , Van de Peer Y , Liu ZJ
Ref : Sci Rep , 6 :19029 , 2016
Abstract : Orchids make up about 10% of all seed plant species, have great economical value, and are of specific scientific interest because of their renowned flowers and ecological adaptations. Here, we report the first draft genome sequence of a lithophytic orchid, Dendrobium catenatum. We predict 28,910 protein-coding genes, and find evidence of a whole genome duplication shared with Phalaenopsis. We observed the expansion of many resistance-related genes, suggesting a powerful immune system responsible for adaptation to a wide range of ecological niches. We also discovered extensive duplication of genes involved in glucomannan synthase activities, likely related to the synthesis of medicinal polysaccharides. Expansion of MADS-box gene clades ANR1, StMADS11, and MIKC(*), involved in the regulation of development and growth, suggests that these expansions are associated with the astonishing diversity of plant architecture in the genus Dendrobium. On the contrary, members of the type I MADS box gene family are missing, which might explain the loss of the endospermous seed. The findings reported here will be important for future studies into polysaccharide synthesis, adaptations to diverse environments and flower architecture of Orchidaceae.
ESTHER : Zhang_2016_Sci.Rep_6_19029
PubMedSearch : Zhang_2016_Sci.Rep_6_19029
PubMedID: 26754549
Gene_locus related to this paper: 9aspa-a0a2i0w093 , 9aspa-a0a2i0vyy1 , 9aspa-a0a2i0x5j6 , 9aspa-a0a2i0win6 , 9aspa-a0a2i0vg82

Title : Timosaponin B-II ameliorates scopolamine-induced cognition deficits by attenuating acetylcholinesterase activity and brain oxidative damage in mice - Zhao_2016_Metab.Brain.Dis_31_1455
Author(s) : Zhao X , Liu C , Qi Y , Fang L , Luo J , Bi K , Jia Y
Ref : Metabolic Brain Disease , 31 :1455 , 2016
Abstract : Timosaponin B-II (TB-II) is a main active saponin isolated from the rhizome of Anemarrhena asphodeloides Bge., which is widely used in traditional Chinese medicine. In this study, the effect of TB-II on learning and memory was investigated in a scopolamine-induced mouse model of Alzheimer's disease. The results of behavioral tests indicated that TB-II significantly increased the spontaneous alternation in the Y-maze test, and reversed the shortening of step-through latency induced by scopolamine in the passive avoidance test, showing protective effects on short-term and working memory. In the Morris water maze test, TB-II reduced the escape latency time in the training trial, and increased the swimming time in the target quadrant in the probe trial. Biochemical data demonstrated that TB-II significantly inhibited acetylcholinesterase (AChE) activity in the cerebral cortex and hippocampus of mice. Moreover, TB-II markably attenuated the reduction in glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and decreased malondialdehyde (MDA) levels, which are key biomarkers of brain oxidative stress. These results indicated that TB-II offers protection against scopolamine-induced deficits in learning and memory, possibly by inhibiting AChE and preventing oxidative stress damage. The findings suggested that TB-II has a potential therapeutic effect on cognitive and behavioral impairment.
ESTHER : Zhao_2016_Metab.Brain.Dis_31_1455
PubMedSearch : Zhao_2016_Metab.Brain.Dis_31_1455
PubMedID: 27444169

Title : Racial and Ethnic Differences in Initiation and Discontinuation of Antidementia Drugs by Medicare Beneficiaries - Thorpe_2016_J.Am.Geriatr.Soc_64_1806
Author(s) : Thorpe CT , Fowler NR , Harrigan K , Zhao X , Kang Y , Hanlon JT , Gellad WF , Schleiden LJ , Thorpe JM
Ref : J Am Geriatr Soc , 64 :1806 , 2016
Abstract : OBJECTIVES: To examine racial and ethnic differences in initiation and time to discontinuation of antidementia medication in Medicare beneficiaries. DESIGN: Retrospective cohort study. SETTING: Secondary analysis of 2009-10 enrollment, claims, and Part D prescription data for a 10% national sample of U.S. Medicare fee-for-service beneficiaries. PARTICIPANTS: Beneficiaries aged 65 and older with Alzheimer's disease or related dementia (ADRD) before 2009 and no fills for antidementia medications in the first half of 2009 (N = 84,043). MEASUREMENTS: Initiation was defined as having one or more fills for antidementia medication in the second half of 2009 and discontinuation as a gap in coverage of 30 days or more during the year after initiation. The Andersen Behavioral Model was used to guide covariate selection.
RESULTS: Overall, 3,481 (4.1%) of previous nonusers initiated antidementia medication in the second half of 2009. Of those initiating one drug class (acetylcholinesterase inhibitors (AChEIs) or memantine), 9% later added the other class, and 2% switched classes. Of initiators, 23% discontinued within 1 month, and 62% discontinued within 1 year. Hispanic beneficiaries were more likely than white beneficiaries to initiate (adjusted odds ratio = 1.25, 95% confidence interval (CI) = 1.10-1.41). Black and white beneficiaries did not differ in likelihood of initiation. Hispanic (adjusted hazard ratio (aHR) = 1.56, 95% CI = 1.34-1.82) and black (aHR = 1.25, 95% CI = 1.08-1.44) beneficiaries discontinued at a faster rate than white beneficiaries. CONCLUSION: Initiation of antidementia medications was no different in black and white beneficiaries and more likely in Hispanic beneficiaries; black and Hispanic beneficiaries discontinued at a faster rate. More research into reasons explaining these differences is needed.
ESTHER : Thorpe_2016_J.Am.Geriatr.Soc_64_1806
PubMedSearch : Thorpe_2016_J.Am.Geriatr.Soc_64_1806
PubMedID: 27549029

Title : NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway - Ai_2016_Cancer.Biol.Ther_17_943
Author(s) : Ai R , Sun Y , Guo Z , Wei W , Zhou L , Liu F , Hendricks DT , Xu Y , Zhao X
Ref : Cancer Biol Ther , 17 :943 , 2016
Abstract : N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however beta-catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and beta-catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and beta-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression.
ESTHER : Ai_2016_Cancer.Biol.Ther_17_943
PubMedSearch : Ai_2016_Cancer.Biol.Ther_17_943
PubMedID: 27414086

Title : Expression and characterization of a lipase-related protein in the malpighian tubules of the Chinese oak silkworm, Antheraea pernyi - Wang_2016_Bull.Entomol.Res_106_615
Author(s) : Wang L , Li J , Zhao X , Qian C , Wei G , Zhu B , Liu C
Ref : Bull Entomol Res , 106 :615 , 2016
Abstract : Lipases are ubiquitous enzymes in nature, which play a crucial role in fat metabolism by catalyzing the hydrolysis of triacylglycerol to free fatty acids and glycerol. However, reports concerning insect lipase are rare. In this study, we studied the expression and activity of a lipase-related protein from Antheraea pernyi (ApLRP). Recombinant ApLRP was expressed in Escherichia coli cells and used to raise rabbit anti-ApLRP polyclonal antibodies. ApLRP mRNA and protein expression were abundant in the midgut and malpighian tubules, respectively. After challenge with four different microorganisms (E. coli, Beauveria bassiana, Micrococcus luteus and nuclear polyhedrosis virus), the expression levels of ApLRP mRNA in midgut were inducted significantly compared with the control. The different pathogens induced different ApLRP gene expression patterns. The optimum temperature and pH for the enzyme's activity were 35 degrees C and 7.0, respectively. ApLRP activity was stimulated in the presence of Mg2+, Na+, Ca2+ and b-mercaptoethanol; while Zn2+, Cu2+ and Fe3+ inhibited its activity. Detergents such as SDS, glycerol and Tween-20 increased the lipase activity by 20-30%. Our results indicated that ApLRP might play an important role in the innate immunity of insects.
ESTHER : Wang_2016_Bull.Entomol.Res_106_615
PubMedSearch : Wang_2016_Bull.Entomol.Res_106_615
PubMedID: 27297450
Gene_locus related to this paper: antpe-a0a191xqw7

Title : Effects of electroacupuncture on recovery of the electrophysiological properties of the rabbit gastrocnemius after contusion: an in vivo animal study - Liu_2015_BMC.Complement.Altern.Med_15_69
Author(s) : Liu S , Wang R , Luo D , Xu Q , Xiao C , Lin P , Yu Z , Zhao X , Cai R , Ma J , Zhang Q , Wang Y
Ref : BMC Complement Altern Med , 15 :69 , 2015
Abstract : BACKGROUND: Our preliminary studies indicated that electroacupuncture (EA) at the ST36 and Ashi acupoints could promote regeneration of the rabbit gastrocnemius (GM) by improving microcirculation perfusion, promoting the recovery of myofiber structures, and inhibiting excessive fibrosis. However, the effects of EA on recovery of the electrophysiological properties of the GM after contusion are not yet clear. Thus, the purpose of this study was to investigate the effects of EA at the Zusanli (ST36) and Ashi acupoints with regard to recovery of the electrophysiological properties of the rabbit GM after contusion.
METHODS: Forty-five rabbits were randomly divided into three groups: normal, contusion, and EA. After an acute GM contusion was produced (in rabbits in the contusion and EA groups), rabbits in the EA group were treated with electrostimulation at the ST36 and Ashi acupoints with 0.4 mA (2 Hz) for 15 min. The contusion group received no EA treatment. At different time points (7, 14, and 28 days) after contusion, we performed surface electromyography (EMG) and measured the nerve conduction velocity (NCV) of the GM and the GM branch of the tibial nerve. We also examined acetylcholinesterase (AchE) and Agrin expression in the neuromuscular junction (NMJ) via immunohistochemistry.
RESULTS: Compared with the contusion group, the EMG amplitude and NCV in rabbits in the EA group were significantly higher at all time points after contusion. AchE and Agrin expression in the EA group were significantly higher than those in the contusion group.
CONCLUSIONS: Our results showed that EA at the ST36 and Ashi acupoints effectively promoted recovery of the electrophysiological properties of the rabbit GM after contusion. The effects of EA were realized by promotion of the regeneration of myofibers and nerve fibers, as well as acceleration of NMJ reconstruction by upregulation of AchE and Agrin expression in the motor endplate area.
ESTHER : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedSearch : Liu_2015_BMC.Complement.Altern.Med_15_69
PubMedID: 25887510

Title : Engineering surface hydrophobicity improves activity of Bacillus thermocatenulatus lipase 2 enzyme - Tang_2015_Biotechnol.J_10_1762
Author(s) : Tang T , Yuan C , Hwang HT , Zhao X , Ramkrishna D , Liu D , Varma A
Ref : Biotechnol J , 10 :1762 , 2015
Abstract : Bacillus thermocatenulatus lipase 2 (BTL2) is a promising industrial enzyme used in biodiesel production. Although BTL2 has high thermostability and good resistance to organic solvents, the activity of BTL2 is suboptimal for industrial processes. To improve BTL2 activity, we engineered BTL2 lipase by modulating hydrophobicity of its lid domain. Through site-directed mutagenesis, we constructed three mutants, namely Y225F+S232A, S232A+T236V and Q185L, to cover all uncharged hydrophilic amino acids within the lid domain. Activities of these mutants were characterized. Our findings suggest that one mutant (Y225F+S232A) showed approximately 35% activity increase in catalyzing heterogeneous hydrolytic reactions relevant for industrial applications. A mathematical framework was established to account for different molecular events that contribute to the observed apparent catalytic activities. Increases in hydrophobicity of lid domains were associated with increased interfacial adsorption of lipases and lower molecular enzymatic activities. The measured apparent activities of lipases include contributions from both events. Lid hydrophobicity can thus result in different changes in lipase activities depending on the mutation site. Our work demonstrates the feasibility of increasing BTL2 activity by modulating the hydrophobicity of lid domains and provides some guidelines for further improving BTL2 activity.
ESTHER : Tang_2015_Biotechnol.J_10_1762
PubMedSearch : Tang_2015_Biotechnol.J_10_1762
PubMedID: 26097135
Gene_locus related to this paper: bactc-lipas

Title : Preventive Effect of Lactobacillus fermentum Zhao on Activated Carbon-Induced Constipation in Mice - Zhao_2015_J.Nutr.Sci.Vitaminol.(Tokyo)_61_131
Author(s) : Zhao X , Qian Y , Suo H , Du M , Li G , Liu Z , Li J
Ref : J Nutr Sci Vitaminol (Tokyo) , 61 :131 , 2015
Abstract : The aim of this study was to investigate the effects of Lactobacillus fermentum Zhao (LF-Zhao) on activated carbon-induced constipation in ICR mice. ICR mice were administered lactic acid bacteria by gavage for 9 d. Body weight, diet intake, drinking amount, stool status, gastrointestinal transit distance and stool time, in addition to motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were monitored to evaluate the preventive effects of LF-Zhao on constipation. Bisacodyl, a laxative drug, was used as a positive control. Times to the first black stool for normal (untreated), control (no lactic acid bacteria treatment but activated carbon treated), bisacodyl-treated and L. delbrueckii subsp. bulgaricus (LB), LF-Zhao (L) (low concentration of 1x10(8) CFU/mL)- and LF-Zhao (H) (high concentration of 1x10(9) CFU/mL)-treated mice induced by activated carbon were 90, 218, 117, 180, 169 and 156 min, respectively. Following the consumption of LB, LF-Zhao (L) and LF-Zhao (H) or the oral administration of bisacodyl, the gastrointestinal transit distances were reduced by 55.2%, 61.3%, 70.6% and 94.6%, respectively. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Zhao compared with those in the control mice (p<0.05). These results demonstrated that lactic acid bacteria demonstrate preventive effects on mouse constipation and that LF-Zhao alleviated constipation symptoms better than LB.
ESTHER : Zhao_2015_J.Nutr.Sci.Vitaminol.(Tokyo)_61_131
PubMedSearch : Zhao_2015_J.Nutr.Sci.Vitaminol.(Tokyo)_61_131
PubMedID: 26052143

Title : Schisandrin C Ameliorates Learning and Memory Deficits by Abeta(1-42) -induced Oxidative Stress and Neurotoxicity in Mice - Mao_2015_Phytother.Res_29_1373
Author(s) : Mao X , Liao Z , Guo L , Xu X , Wu B , Xu M , Zhao X , Bi K , Jia Y
Ref : Phytother Res , 29 :1373 , 2015
Abstract : Schisandrin C (SCH-C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH-C on memory impairment and further research on pathological changes in Abeta(1-42) -induced Alzheimer's disease mice. Mice were administration with SCH-C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y-maze test, active avoidance test and Morris water maze test in all groups, and the level of Abeta(1-42) and neuronal injury induced by Abeta(1-42) were reversed remarkably following SCH-C treatment compared with sham group; meanwhile the impairment of short-term or working memory was dramatically improved. In addition, SCH-C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH-C offers protection against Abeta(1-42) -induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright 2015 John Wiley & Sons, Ltd.
ESTHER : Mao_2015_Phytother.Res_29_1373
PubMedSearch : Mao_2015_Phytother.Res_29_1373
PubMedID: 26074330

Title : Assessing joint toxicity of four organophosphate and carbamate insecticides in common carp (Cyprinus carpio) using acetylcholinesterase activity as an endpoint - Wang_2015_Pestic.Biochem.Physiol_122_81
Author(s) : Wang Y , Chen C , Zhao X , Wang Q , Qian Y
Ref : Pestic Biochem Physiol , 122 :81 , 2015
Abstract : Mixtures of organophosphate (OP) and carbamate (CB) pesticides are commonly detected in freshwater ecosystems. These pesticides inhibit the activity of acetylcholinesterase (AChE) and have potential to interfere with behaviors that may be essential for the survival of species. Although the effects of individual anticholinesterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood. In the present study, brain AChE inhibition in carp (Cyprinus carpio) exposed to a series of concentrations of the organophosphates (malathion and triazophos) as well as the carbamates (fenobucarb and carbosulfan) was measured. In equitoxic mixtures, the observed AChE activity inhibition of the malathion plus triazophos, and triazophos plus carbosulfan mixtures, was synergism. In equivalent concentration mixtures, the combination of malathion plus fenobucarb mixture conformed to synergism, while the observed AChE activity inhibition of the remaining pairings was less than additive. Single pesticide risk assessments are likely to underestimate the impacts of these insecticides on carps in aquatic environment where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in aquatic ecosystems may pose a more important challenge than previously anticipated.
ESTHER : Wang_2015_Pestic.Biochem.Physiol_122_81
PubMedSearch : Wang_2015_Pestic.Biochem.Physiol_122_81
PubMedID: 26071811

Title : Preventive effect of Wall. ex Lindl. on activated carbon-induced constipation in mice - Wang_2015_Exp.Ther.Med_9_563
Author(s) : Wang R , Sun P , Zhou Y , Zhao X
Ref : Exp Ther Med , 9 :563 , 2015
Abstract : The aim of this study was to investigate the effects of Dendrobium candidum Wall. ex Lindl. (D. candidum) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered D. candidum for 9 days. Body weight, defecation status, gastrointestinal (GI) transit and defecation times, in addition to the levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were used to evaluate the preventive effects of D. candidum on constipation. The laxative drug bisacodyl acted as a positive control. The time to the first defecation of a black stool for the normal, control, bisacodyl-treated (100 mg/kg), 200 and 400 mg/kg D. candidum-treated mice was 84, 202, 126, 161 and 142 min, respectively. Following the consumption of 200 and 400 mg/kg D. candidum or bisacodyl (100 mg/kg), the GI transit was reduced to 57.7, 74.6 and 90.2%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with D. candidum compared with those in the untreated control mice (P<0.05). These results demonstrate that D. candidum has preventive effects on constipation in mice, and a greater functional activity was observed when a higher concentration was administered.
ESTHER : Wang_2015_Exp.Ther.Med_9_563
PubMedSearch : Wang_2015_Exp.Ther.Med_9_563
PubMedID: 25574235

Title : Preventive effect of Lee on activated carbon-induced constipation in mice - Qian_2015_Exp.Ther.Med_9_272
Author(s) : Qian Y , Suo H , Du M , Zhao X , Li J , Li GJ , Song JL , Liu Z
Ref : Exp Ther Med , 9 :272 , 2015
Abstract : The aim of this study was to investigate the effects of Lactobacillus fermentum Lee (LF-Lee) on activated carbon-induced constipation in ICR mice. ICR mice were orally administered lactic acid bacteria for nine days. Body weight, dietary and water intake, defecation status, gastrointestinal (GI) transit and defecation time, as well as levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) in serum were measured to evaluate the preventive effects of LF-Lee on constipation. Bisacodyl, a laxative drug, was administered as a positive control. The time taken until the first defecation of a black stool for normal, control, bisacodyl- (100 mg/kg, oral administration), Lactobacillus bulgaricus (LB)-, LF-Lee low dose (L)- and LF-Lee high dose (H)-treated mice was 90, 218, 117, 180, 161 and 151 min, respectively. Following the consumption of LB, LF-Lee (L) or LF-Lee (H), or the oral administration of bisacodyl, the GI transit was reduced to 55.2, 65.8, 73.1 and 94.6%, respectively, of the transit in normal mice. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and those of SS were reduced in the mice treated with LF-Lee compared with those in the untreated control mice (P<0.05). These results demonstrate that lactic acid bacteria have preventive effects on constipation in mice and that LF-Lee has superior functional activity.
ESTHER : Qian_2015_Exp.Ther.Med_9_272
PubMedSearch : Qian_2015_Exp.Ther.Med_9_272
PubMedID: 25452815

Title : Enzymatic synthesis and characterization of galactosyl monoesters - An_2015_Carbohydr.Res_414_32
Author(s) : An D , Zhao X , Ye Z
Ref : Carbohydr Res , 414 :32 , 2015
Abstract : Enzyme-catalyzed synthesis of several fatty acyl-amino acid esters based on D-galactose, as well as their chemical evaluation, was performed. These novel galactosyl fatty acyl-amino acid monoesters were synthesized by utilizing lipase from lipozyme TL IM in tert-butanol with D-galactose and fatty acyl-amino acids as starting materials. The products were characterized by (1)H NMR, (13)C NMR and MS analysis. In addition, their primary physical properties, such as hydrophilic-lipophilic balance (HLB), critical micellar concentration (CMC), solubility in water, maximum surface excess (gamma max), and minimal surface tension (Amin) were measured. The experimental results showed that their CMC values are between 5 and 0.4 mM. The HLB values of galactosyl esters 15-17 indicate that they are useful as oil-in-water emulsions or detergents, whereas 18-22 can be employed as water-in-oil emulsifiers or wetting agents.
ESTHER : An_2015_Carbohydr.Res_414_32
PubMedSearch : An_2015_Carbohydr.Res_414_32
PubMedID: 26172090

Title : APA-style human milk fat analogue from silkworm pupae oil: Enzymatic production and improving storage stability using alkyl caffeates - Liu_2015_Sci.Rep_5_17909
Author(s) : Liu X , Wang X , Pang N , Zhu W , Zhao X , Wang F , Wu F , Wang J
Ref : Sci Rep , 5 :17909 , 2015
Abstract : Silkworm pupae oil derived from reeling waste is a rich source of alpha-linolenic acid (ALA), which has multipal applications. ALAs were added in sn-1, 3 positions in a triacylglycerol (TAG) to produce an APA-human milk fat analogues (APA-HMFAs, A: alpha-linolenic acid, P: palmitic acid). The optimum condition is that tripalmitin to free fatty acids of 1:12 (mole ratio) at 65 degreeC for 48 h using lipase Lipozyme RM IM. Results show that, the major TAG species that comprised APA-HMFAs were rich in ALA and palmitic acid, which contained 64.52% total unsaturated fatty acids (UFAs) and 97.05% PA at the sn-2 position. The melting point of APA was -27.5 degreeC which is much lower than tripalmitin (40.5 degreeC) indicating more plastic character. In addition, the practical application of alkyl caffeates as liposoluble antioxidants in APA was developed. Alkyl caffeate showed a superior IC50 (1.25-1.66 g/mL) compared to butyl hydroxy anisd (1.67 g/mL) and L-ascorbic acid-6-palmitate (L-AP) (1.87 g/mL) in DPPH analysis. The addition of ethyl caffeate to oil achieved a higher UFAs content (73.58%) at high temperatures. Overall, APA was obtained from silkworm pupae oil successfully, and the addition of caffeates extended storage ranges for APA-HMFAs.
ESTHER : Liu_2015_Sci.Rep_5_17909
PubMedSearch : Liu_2015_Sci.Rep_5_17909
PubMedID: 26643045

Title : Evaluating early administration of the hydroxymethylglutaryl-CoA reductase inhibitor simvastatin in the prevention and treatment of delirium in critically ill ventilated patients (MoDUS trial): study protocol for a randomized controlled trial - Casarin_2015_Trials_16_218
Author(s) : Casarin A , McAuley DF , Alce TM , Zhao X , Ely EW , Jackson JC , McDowell C , Agus A , Murphy L , Page VJ
Ref : Trials , 16 :218 , 2015
Abstract : BACKGROUND: The incidence of delirium in ventilated patients is estimated at up to 82%, and it is associated with longer intensive care and hospital stays, and long-term cognitive impairment and mortality. The pathophysiology of delirium has been linked with inflammation and neuronal apoptosis. Simvastatin has pleiotropic properties; it penetrates the brain and, as well as reducing cholesterol, reduces inflammation when used at clinically relevant doses over the short term. This is a single centre randomised, controlled trial which aims to test the hypothesis that treatment with simvastatin will modify delirium incidence and outcomes. METHODS/DESIGN: The ongoing study will include 142 adults admitted to the Watford General Hospital Intensive Care Unit who require mechanical ventilation in the first 72 hours of admission. The primary outcome is the number of delirium- and coma-free days in the first 14 days. Secondary outcomes include incidence of delirium, delirium- and coma-free days in the first 28 days, days in delirium and in coma at 14 and 28 days, number of ventilator-free days at 28 days, length of critical care and hospital stay, mortality, cognitive decline and healthcare resource use. Informed consent will be taken from patient's consultee before randomisation to receive either simvastatin (80 mg) or placebo once daily. Daily data will be recorded until day 28 after randomisation or until discharge from the ICU if sooner. Surviving patients will be followed up on at six months from discharge. Plasma and urine samples will be taken to investigate the biological effect of simvastatin on systemic markers of inflammation, as related to the number of delirium- and coma-free days, and the potential of cholinesterase activity and beta-amyloid as predictors of the risk of delirium and long-term cognitive impairment. DISCUSSION: This trial will test the efficacy of simvastatin on reducing delirium in the critically ill. If patients receiving the statin show a reduced number of days in delirium compared with the placebo group, the inflammatory theory implicated in the pathogenesis of delirium will be strengthened. TRIAL REGISTRATION: The trial was registered with the International Standard Randomised Controlled Trial Registry ( ISRCTN89079989 ) on 26 March 2013.
ESTHER : Casarin_2015_Trials_16_218
PubMedSearch : Casarin_2015_Trials_16_218
PubMedID: 25982544

Title : Therapeutic effects of Lactobacillus casei Qian treatment in activated carbon induced constipated mice - Zhao_2015_Mol.Med.Rep_12_3191
Author(s) : Zhao X , Suo HY , Qian Y , Li GJ , Liu ZH , Li J
Ref : Mol Med Rep , 12 :3191 , 2015
Abstract : In the present study, the therapeutic effects of Lactobacillus casei Qian (LCQian), the key microorganism in Tibetan yak yoghurt, on activated carboninduced constipation were determined in vivo. ICR mice were treated with LCQian for nine days by oral administration. The body weight, defecation status, gastrointestinal transit and defecation time of mice were assessed, and the serum levels of motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) were further evaluated. Bisacodyl was used as the positive control. The time until the first black stool defecation following carbon intake of the normal, control, 100 mg/kg bisacodyltreated, Lactobacillus bulgaricus (LB)treated, LCQian (L) and LCQian (H)treated mice was 93, 231, 121, 194, 172 and 157 min, respectively. Following treatment with LCQian, the gastrointestinal transit was increased to 52.4% [LCQian (L)] and 65.8% [LCQian (H)], while that in the group treated with the common lactic acid bacteria of LB was 40.3%. The MTL, Gas, ET, AChE, SP and VIP serum levels were significantly increased and levels of SS were reduced in mice following LCQian treatment compared with those in the control mice (P<0.05). Reverse transcription quantitative polymerase chain reaction indicated that LCQian raised the cKit, GDNF as well as SCF mRNA expression levels and reduced the TRPV1 and NOS expression levels in tissue of the small intestine in mice. These results suggested that lactic acid bacteria prevent constipation in mice, among which LCQian was the most effective.
ESTHER : Zhao_2015_Mol.Med.Rep_12_3191
PubMedSearch : Zhao_2015_Mol.Med.Rep_12_3191
PubMedID: 25955533

Title : Association of Lp-PLA2-A and early recurrence of vascular events after TIA and minor stroke - Lin_2015_Neurology_85_1585
Author(s) : Lin J , Zheng H , Cucchiara BL , Li J , Zhao X , Liang X , Wang C , Li H , Mullen MT , Johnston SC , Wang Y
Ref : Neurology , 85 :1585 , 2015
Abstract : OBJECTIVE: To determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) measured in the acute period and the short-term risk of recurrent vascular events in patients with TIA or minor stroke.
METHODS: We measured Lp-PLA2 activity (Lp-PLA2-A) in a subset of 3,201 participants enrolled in the CHANCE (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) trial. Participants with TIA or minor stroke were enrolled within 24 hours of symptom onset and randomized to single or dual antiplatelet therapy. In the current analysis, the primary outcome was defined as the composite of ischemic stroke, myocardial infarction, or death within 90 days.
RESULTS: The composite endpoint occurred in 299 of 3,021 participants (9.9%). The population average Lp-PLA2-A level was 209 +/- 59 nmol/min/mL (95% confidence interval [CI] 207-211). Older age, male sex, and current smoking were associated with higher Lp-PLA2-A levels. Lp-PLA2-A was significantly associated with the primary endpoint (adjusted hazard ratio 1.07, 95% CI 1.01-1.13 for every 30 nmol/min/mL increase). Similar results were seen for ischemic stroke alone. Adjustment for low-density lipoprotein cholesterol attenuated the association between Lp-PLA2-A and the primary endpoint (adjusted hazard ratio 1.04, 95% CI 0.97-1.11 for every 30 nmol/min/mL increase).
CONCLUSIONS: Higher levels of Lp-PLA2-A in the acute period are associated with increased short-term risk of recurrent vascular events.
ESTHER : Lin_2015_Neurology_85_1585
PubMedSearch : Lin_2015_Neurology_85_1585
PubMedID: 26311748

Title : The Effects of Sesquiterpenes-Rich Extract of Miq. on Amyloid- -Induced Cognitive Impairment and Neuronal Abnormalities in the Cortex and Hippocampus of Mice - Shi_2014_Oxid.Med.Cell.Longev_2014_451802
Author(s) : Shi SH , Zhao X , Liu B , Li H , Liu AJ , Wu B , Bi KS , Jia Y
Ref : Oxid Med Cell Longev , 2014 :451802 , 2014
Abstract : As a kind of medicine which can also be used as food, Alpinia oxyphylla Miq. has a long clinical history in China. A variety of studies demonstrated the significant neuroprotective activity effects of chloroform (CF) extract from the fruits of Alpinia oxyphylla. In order to further elucidate the possible mechanisms of CF extract which mainly contains sesquiterpenes with neuroprotection on the cognitive ability, mice were injected with Abeta 1-42 and later with CF in this study. The results showed that the long-term treatment of CF enhanced the cognitive performances in behavior tests, increased activities of glutathione peroxidase (GSH-px) and decreased the level of malondialdehyde (MDA), acetylcholinesterase (AChE), and amyloid-beta (Abeta), and reversed the activation of microglia, degeneration of neuronal acidophilia, and nuclear condensation in the cortex and hippocampus. These results demonstrate that CF ameliorates learning and memory deficits by attenuating oxidative stress and regulating the activation of microglia and degeneration of neuronal acidophilia to reinforce cholinergic functions.
ESTHER : Shi_2014_Oxid.Med.Cell.Longev_2014_451802
PubMedSearch : Shi_2014_Oxid.Med.Cell.Longev_2014_451802
PubMedID: 25180067

Title : Jujuboside A, a neuroprotective agent from semen Ziziphi Spinosae ameliorates behavioral disorders of the dementia mouse model induced by Abeta - Liu_2014_Eur.J.Pharmacol_738C_206
Author(s) : Liu Z , Zhao X , Liu B , Liu AJ , Li H , Mao X , Wu B , Bi KS , Jia Y
Ref : European Journal of Pharmacology , 738C :206 , 2014
Abstract : Semen Ziziphi Spinosae (SZS) has been used as a hypnotic-sedative medicine for thousands of years. Recently, SZS has also shown notable neuroprotective activities via anti-oxidative and anti-inflammatory effects in dementia animals. Jujuboside A (JuA), isolated from SZS, has been proved to be a major hypnotic-sedative component of SZS. In the present study, we firstly evaluated the effects of intracerebroventricular (ICV) injection of JuA (0.02 and 0.2mg/kg) for five consecutive days on cognitive impairment induced by ICV injection of Abeta1-42. The results showed that ICV treatment with JuA significantly mitigated learning and memory impairment in mice induced by Abeta1-42 as measured by the Y-maze, active avoidance and Morris water maze. Furthermore, ICV treatment with JuA reduced the level of Abeta1-42 in hippocampus, significantly inhibited the activities of acetylcholinesterase (AChE) and NO, and decreased the amount of the increased malondialdehyde (MDA) in the hippocampus and cerebral cortex of mice treated with ICV injection of Abeta1-42. Shrinkage of nuclei, swollen and eccentrically dispersed neuronal bodies were observed in hippocampus of AD mice induced by Abeta1-42, however, JuA noticeably improved the histopathological damage. Cumulatively, the present study indicates that JuA may serve as a potential therapeutic agent for the treatment of Alzheimers disease.
ESTHER : Liu_2014_Eur.J.Pharmacol_738C_206
PubMedSearch : Liu_2014_Eur.J.Pharmacol_738C_206
PubMedID: 24886882

Title : Gene expression profile in chronic mouse liver injury caused by long-term exposure to CeCl3 - Cheng_2014_Environ.Toxicol_29_837
Author(s) : Cheng J , Fei M , Sang X , Cheng Z , Gui S , Zhao X , Sheng L , Sun Q , Hu R , Wang L , Hong F
Ref : Environ Toxicol , 29 :837 , 2014
Abstract : Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and the corresponding damage; however, very little work has been done to evaluate the relationship between Ln-induced liver injury and its gene expression profile in mice. In this study, liver injury and gene-expressed profiles in male mice induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive days were investigated. The results showed that cerium accumulation, liver inflammation, and hepatocyte necrosis were observed. CeCl3 exposure significantly decreased the counts of white blood cells, lymphocyte, and platelet, the reticulocyte count (Ret) and neutrophilic granulocyte percentages as well as A/G ratio, whereas markedly increased the activities of alkaline phosphatase, lactate dehydrogenase, and cholinesterase, and the concentrations of triglycerides and total cholesterol. Furthermore, microarray results of liver showed that the differential expression of 675 known function genes involved in immune/inflammation response, apoptosis, metabolic process, cell cycle, cell proliferation, cytoskeleton, oxidative stress, signal transduction, transcription, translation, and transportation in CeCl3 exposed livers, respectively. Specifically, the significant downregulation of Nt5e led to inflammation, overexpressed Cyp4a12a and great suppression of Cdkn1a resulted in hepatocyte apoptosis, marked elevation of Cel, and Cyp7b1 expression caused the metabolic disorders in mouse liver after long-term CeCl3 exposure. Therefore, these genes may be in great relation to liver damages induced by exposure to CeCl3 .
ESTHER : Cheng_2014_Environ.Toxicol_29_837
PubMedSearch : Cheng_2014_Environ.Toxicol_29_837
PubMedID: 23139204

Title : Whole-genome sequencing of Mesorhizobium huakuii 7653R provides molecular insights into host specificity and symbiosis island dynamics - Wang_2014_BMC.Genomics_15_440
Author(s) : Wang S , Hao B , Li J , Gu H , Peng J , Xie F , Zhao X , Frech C , Chen N , Ma B , Li Y
Ref : BMC Genomics , 15 :440 , 2014
Abstract : BACKGROUND: Evidence based on genomic sequences is urgently needed to confirm the phylogenetic relationship between Mesorhizobium strain MAFF303099 and M. huakuii. To define underlying causes for the rather striking difference in host specificity between M. huakuii strain 7653R and MAFF303099, several probable determinants also require comparison at the genomic level. An improved understanding of mobile genetic elements that can be integrated into the main chromosomes of Mesorhizobium to form genomic islands would enrich our knowledge of how genome dynamics may contribute to Mesorhizobium evolution in general.
RESULTS: In this study, we sequenced the complete genome of 7653R and compared it with five other Mesorhizobium genomes. Genomes of 7653R and MAFF303099 were found to share a large set of orthologs and, most importantly, a conserved chromosomal backbone and even larger perfectly conserved synteny blocks. We also identified candidate molecular differences responsible for the different host specificities of these two strains. Finally, we reconstructed an ancestral Mesorhizobium genomic island that has evolved into diverse forms in different Mesorhizobium species.
CONCLUSIONS: Our ortholog and synteny analyses firmly establish MAFF303099 as a strain of M. huakuii. Differences in nodulation factors and secretion systems T3SS, T4SS, and T6SS may be responsible for the unique host specificities of 7653R and MAFF303099 strains. The plasmids of 7653R may have arisen by excision of the original genomic island from the 7653R chromosome.
ESTHER : Wang_2014_BMC.Genomics_15_440
PubMedSearch : Wang_2014_BMC.Genomics_15_440
PubMedID: 24906389
Gene_locus related to this paper: meslo-mlr7206

Title : The combined toxicity assessment of carp (Cyprinus carpio) acetylcholinesterase activity by binary mixtures of chlorpyrifos and four other insecticides - Chen_2014_Ecotoxicology_23_221
Author(s) : Chen C , Wang Y , Zhao X , Wang Q , Qian Y
Ref : Ecotoxicology , 23 :221 , 2014
Abstract : Mixtures of organophosphate (OP) and carbamate (CB) insecticides are commonly detected in freshwater habitats. These insecticides inhibit the activity of acetylcholinesterase (AChE) and have potential to interfere with behaviors that may be essential for survival of species. Although the effects of individual anticholinesterase insecticides on aquatic species have been studied for decades, the combined toxicity of mixtures is still poorly understood. In the present study, we assessed whether pesticides in a mixture act in isolation (resulting in additive AChE inhibition) or whether components interact to produce either antagonistic or synergistic toxicity. Brain AChE inhibition in carp (Cyprinus carpio L.) exposed to a series of concentrations of the OP (chlorpyrifos, malathion and triazophos) as well as the CB (fenobucarb and carbosulfan) were measured. The concentration addition (CA) model and the isobole method were used to determine whether toxicological responses to binary mixtures of pesticides. In 50:50 % effect mixtures, the observed combined toxicity of chlorpyrifos and malathion was significantly higher than observed and was considered as synergistic. For equivalent dose mixtures, when chlorpyrifos mixed with fenobucarb or malathion, the observed toxicities were significantly higher than predicted, suggesting synergistic joint actions. The rest five binary combinations exhibited concentration additive or slight antagonistic joint actions. The CA model and the isobole method provided estimates of mixture toxicity that did not markedly underestimate the measured toxicity, therefore these methods are suitable to use in ecological risk assessments of pesticide mixtures.
ESTHER : Chen_2014_Ecotoxicology_23_221
PubMedSearch : Chen_2014_Ecotoxicology_23_221
PubMedID: 24363216

Title : Single molecule sequencing and genome assembly of a clinical specimen of Loa loa, the causative agent of loiasis - Tallon_2014_BMC.Genomics_15_788
Author(s) : Tallon LJ , Liu X , Bennuru S , Chibucos MC , Godinez A , Ott S , Zhao X , Sadzewicz L , Fraser CM , Nutman TB , Dunning Hotopp JC
Ref : BMC Genomics , 15 :788 , 2014
Abstract : BACKGROUND: More than 20% of the world's population is at risk for infection by filarial nematodes and >180 million people worldwide are already infected. Along with infection comes significant morbidity that has a socioeconomic impact. The eight filarial nematodes that infect humans are Wuchereria bancrofti, Brugia malayi, Brugia timori, Onchocerca volvulus, Loa loa, Mansonella perstans, Mansonella streptocerca, and Mansonella ozzardi, of which three have published draft genome sequences. Since all have humans as the definitive host, standard avenues of research that rely on culturing and genetics have often not been possible. Therefore, genome sequencing provides an important window into understanding the biology of these parasites. The need for large amounts of high quality genomic DNA from homozygous, inbred lines; the availability of only short sequence reads from next-generation sequencing platforms at a reasonable expense; and the lack of random large insert libraries has limited our ability to generate high quality genome sequences for these parasites. However, the Pacific Biosciences single molecule, real-time sequencing platform holds great promise in reducing input amounts and generating sufficiently long sequences that bypass the need for large insert paired libraries.
RESULTS: Here, we report on efforts to generate a more complete genome assembly for L. loa using genetically heterogeneous DNA isolated from a single clinical sample and sequenced on the Pacific Biosciences platform. To obtain the best assembly, numerous assemblers and sequencing datasets were analyzed, combined, and compared. Quiver-informed trimming of an assembly of only Pacific Biosciences reads by HGAP2 was selected as the final assembly of 96.4 Mbp in 2,250 contigs. This results in ~9% more of the genome in ~85% fewer contigs from ~80% less starting material at a fraction of the cost of previous Roche 454-based sequencing efforts.
CONCLUSIONS: The result is the most complete filarial nematode assembly produced thus far and demonstrates the utility of single molecule sequencing on the Pacific Biosciences platform for genetically heterogeneous metazoan genomes.
ESTHER : Tallon_2014_BMC.Genomics_15_788
PubMedSearch : Tallon_2014_BMC.Genomics_15_788
PubMedID: 25217238
Gene_locus related to this paper: loalo-a0a1i7vgt8

Title : Therapeutic Effect of Activated Carbon-Induced Constipation Mice with Lactobacillus fermentum Suo on Treatment - Suo_2014_Int.J.Mol.Sci_15_21875
Author(s) : Suo H , Zhao X , Qian Y , Li G , Liu Z , Xie J , Li J
Ref : Int J Mol Sci , 15 :21875 , 2014
Abstract : The aim of this study was to investigate the effects of Lactobacillus fermentum Suo (LF-Suo) on activated carbon-induced constipation in ICR (Institute of Cancer Research) mice. ICR mice were orally administered with lactic acid bacteria for 9 days. Body weight, diet intake, drinking amount, defecation status, gastrointestinal transit and defecation time, and the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), SS (somatostatin), AChE (acetylcholinesterase), SP (substance P), VIP (vasoactive intestinal peptide) were used to evaluate the preventive effects of LF-Suo on constipation. Bisacodyl, a laxative drug, was used as a positive control. The normal, control, 100 mg/kg bisacodyl treatment, LB (Lactobacillus bulgaricus)-, LF-Suo (L)- and LF-Suo (H)-treated mice showed the time to the first black stool defecation at 90, 218, 117, 180, 155 and 137 min, respectively. By the oral administration of LB-, LF-Suo (L), LF-Suo (H) or bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 55.2%, 72.3%, 85.5% and 94.6%, respectively, of the transit in normal mice, respectively. In contrast to the control mice, the serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with LF-Suo (p < 0.05). By the RT-PCR (reverse transcription-polymerase chain reaction) and western blot assays, LF-Suo increased the c-Kit, SCF (stem cell factor), GDNF (glial cell line-derived neurotrophic factor) and decreased TRPV1 (transient receptor potential vanilloid 1), NOS (nitric oxide synthase) expressions of small intestine tissue in mice. These results demonstrate that lactic acid bacteria has preventive effects on mouse constipation and LF-Suo demonstrated the best functional activity.
ESTHER : Suo_2014_Int.J.Mol.Sci_15_21875
PubMedSearch : Suo_2014_Int.J.Mol.Sci_15_21875
PubMedID: 25464378

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

Title : Lipase-catalyzed process for biodiesel production: Protein engineering and lipase production - Hwang_2014_Biotechnol.Bioeng_111_639
Author(s) : Hwang HT , Qi F , Yuan C , Zhao X , Ramkrishna D , Liu D , Varma A
Ref : Biotechnol Bioeng , 111 :639 , 2014
Abstract : Biodiesel is an environment-friendly and renewable fuel produced by transesterification of various feedstocks. Although the lipase-catalyzed biodiesel production has many advantages over the conventional alkali catalyzed process, its industrial applications have been limited by high-cost and low-stability of lipase enzymes. This review provides a general overview of the recent advances in lipase engineering, including both protein modification and production. Recent advances in biotechnology such as in protein engineering, recombinant methods and metabolic engineering have been employed but are yet to impact lipase engineering for cost-effective production of biodiesel. A summary of the current challenges and perspectives for potential solutions are also provided. Biotechnol. Bioeng. 2014;111: 639-653. (c) 2013 Wiley Periodicals, Inc.
ESTHER : Hwang_2014_Biotechnol.Bioeng_111_639
PubMedSearch : Hwang_2014_Biotechnol.Bioeng_111_639
PubMedID: 24284881

Title : Isolation and identification of antifungal peptides from Bacillus BH072, a novel bacterium isolated from honey - Zhao_2013_Microbiol.Res_168_598
Author(s) : Zhao X , Zhou ZJ , Han Y , Wang ZZ , Fan J , Xiao HZ
Ref : Microbiol Res , 168 :598 , 2013
Abstract : A bacterial strain BH072 isolated from a honey sample showed antifungal activity against mold. Based on morphological, biochemical, physiological tests, and analysis of 16S rDNA sequence, the strain was identified to be a new subspecies of Bacillus sp. It had a broad spectrum of antifungal activity against various mold, such as Aspergillus niger, Pythium, and Botrytis cinerea. Six pairs of antifungal genes primers were designed and synthesized, and ituA, hag, tasA genes were detected by PCR analysis. The remarkable antifungal activity could be associated with the co-production of these three peptides. One of them was purified by 30-40% ammonium sulfate precipitation, Sephadex G-75 gel filtration and anion exchange chromatography on D201 resin. The purified peptide was estimated to be 35.615 kDa and identified to be flagellin by micrOTOF-Q II. By using methanol extraction, another substance was isolated from fermentation liquor, and determined to be iturin with liquid chromatography-mass spectrometry (LC-MS) method. The third possible peptide encoded by tasA was not isolated in this study. The culture liquor displayed antifungal activity in a wide pH range (5.0-9.0) and at 40-100 degrees C. The result of the present work suggested that Bacillus BH072 might be a bio-control bacterium of research value.
ESTHER : Zhao_2013_Microbiol.Res_168_598
PubMedSearch : Zhao_2013_Microbiol.Res_168_598
PubMedID: 23545354
Gene_locus related to this paper: bacsu-YVAK

Title : Preventive effect of resistant starch on activated carbon-induced constipation in mice - Qian_2013_Exp.Ther.Med_6_228
Author(s) : Qian Y , Zhao X , Kan J
Ref : Exp Ther Med , 6 :228 , 2013
Abstract : The aim of this study was to investigate the effects of resistant starch (RS) on activated carbon-induced constipation in ICR mice. ICR mice were fed on diet containing 15% RS of type RS2, RS3 or RS4 for 9 days. Gastrointestinal transit, defecation time and intestinal tissue histopathological sections, as well as motilin (MTL), gastrin (Gas), endothelin (ET), somatostatin (SS), acetylcholinesterase (AChE), substance P (SP) and vasoactive intestinal peptide (VIP) levels in serum were used to evaluate the preventive effects of RS on constipation. Bisacodyl, a laxative drug, was used as a positive control. The time to the first black stool defecation for normal, control, bisacodyl-treated (100 mg/kg, oral administration) and RS2-, RS3- and RS4-treated mice was 78, 208, 109, 181, 144 and 173 min, respectively. Following the consumption of RS2, RS3 and RS4 or the oral administration of bisacodyl (100 mg/kg), the gastrointestinal transit was reduced to 37.7, 52.1, 39.3 and 87.3%, respectively, of the transit in normal mice, respectively. Histopathological sections of intestinal tissue also underscored the protective effect of RS3. The serum levels of MTL, Gas, ET, AChE, SP and VIP were significantly increased and the serum levels of SS were reduced in the mice treated with RS compared with those in the untreated control mice (P<0.05). These results demonstrate that RS has preventive effects on mouse constipation and RS3 demonstrated the best functional activity.
ESTHER : Qian_2013_Exp.Ther.Med_6_228
PubMedSearch : Qian_2013_Exp.Ther.Med_6_228
PubMedID: 23935751

Title : Effects of soluble epoxide hydrolase inhibitor on the expression of fatty acid synthase in peripheral blood mononuclear cell in patients with acute coronary syndrome - Zhao_2013_Lipids.Health.Dis_12_3
Author(s) : Zhao X , Du JQ , Xu DY , Zhao SP
Ref : Lipids Health Dis , 12 :3 , 2013
Abstract : BACKGROUND: Researches have shown that soluble epoxide hydrolase inhibitors (sEHi) can protect against the development of atherosclerosis. Simultaneously, emerging evidences have implicated the association between fatty acid synthase (FAS) and acute coronary syndrome (ACS). We tested the hypothesis that sEHi could reduce the occurrence of ACS by regulating FAS.
METHODS: Hospitalized ACS patients were selected as the ACS group (n = 65) while healthy normal subjects as the control group (n = 65). The blood levels of lipoproteins, fasting glucose, myocardial enzyme and high-sensitivity C-reactive protein (hs-CRP) were measured within 24 hours after admission. The peripheral blood mononuclear cells (PBMCs) were isolated and cultured. Trans-4-[4-(3-Adamantan-1-ylureido)cyclohexyloxy] benzoic acid (t-AUCB), a kind of sEHi, was then added to cells in various concentrations (0, 10, 50, 100 mumol/L). The expression of FAS, interleukin-6 (IL-6) mRNA and protein was detected by real-time PCR or Western blot, respectively.
RESULTS: (1) Compared with the control group, the serum concentration of hs-CRP in the ACS group was increased (P<0.05). The expression of FAS, IL-6 mRNA and protein were significantly increased in PBMCs from the ACS group (all P<0.05). Moreover, the levels of FAS and IL-6 mRNA were positively correlated with the serum concentration of hs-CRP (r = 0.685, P<0.01; r = 0.715, P<0.01) respectively. (2) The expression of FAS, IL-6 mRNA and protein in PBMCs from the ACS group were dose-dependently inhibited by sEHi (all P<0.05).
CONCLUSIONS: sEH inhibition regulated FAS and inhibited inflammation in cultured PBMCs from ACS patients, a mechanism that might prevent rupture of atherosclerotic lesions and protect against development of ACS.
ESTHER : Zhao_2013_Lipids.Health.Dis_12_3
PubMedSearch : Zhao_2013_Lipids.Health.Dis_12_3
PubMedID: 23305094

Title : Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization - Xie_2012_Eur.J.Med.Chem_52_205
Author(s) : Xie H , Zeng L , Zeng S , Lu X , Zhang G , Zhao X , Cheng N , Tu Z , Li Z , Xu H , Yang L , Zhang X , Huang M , Zhao J , Hu W
Ref : Eur Journal of Medicinal Chemistry , 52 :205 , 2012
Abstract : We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development.
ESTHER : Xie_2012_Eur.J.Med.Chem_52_205
PubMedSearch : Xie_2012_Eur.J.Med.Chem_52_205
PubMedID: 22475866

Title : Cocaine esterase-cocaine binding process and the free energy profiles by molecular dynamics and potential of mean force simulations - Huang_2012_J.Phys.Chem.B_116_3361
Author(s) : Huang X , Zhao X , Zheng F , Zhan CG
Ref : J Phys Chem B , 116 :3361 , 2012
Abstract : The combined molecular dynamics (MD) and potential of mean force (PMF) simulations have been performed to determine the free energy profiles for the binding process of (-)-cocaine interacting with wild-type cocaine esterase (CocE) and its mutants (T172R/G173Q and L119A/L169K/G173Q). According to the MD simulations, the general protein-(-)-cocaine binding mode is not affected by the mutations; e.g.. the benzoyl group of (-)-cocaine is always bound in a subsite composed of aromatic residues W151, W166, F261, and F408 and hydrophobic residue L407, while the carbonyl oxygen on the benzoyl group of (-)-cocaine is hydrogen-bonded with the oxyanion-hole residues Y44 and Y118. According to the PMF-calculated free energy profiles for the binding process, the binding free energies for (-)-cocaine with the wild-type, T172R/G173Q, and L119A/L169K/G173Q CocEs are predicted to be -6.4, -6.2, and -5.0 kcal/mol, respectively. The computational predictions are supported by experimental kinetic data, as the calculated binding free energies are in good agreement with the experimentally derived binding free energies, i.e., -7.2, -6.7, and -4.8 kcal/mol for the wild-type, T172R/G173Q, and L119A/L169K/G173Q, respectively. The reasonable agreement between the computational and experimental data suggests that the PMF simulations may be used as a valuable tool in new CocE mutant design that aims to decrease the Michaelis-Menten constant of the enzyme for (-)-cocaine.
ESTHER : Huang_2012_J.Phys.Chem.B_116_3361
PubMedSearch : Huang_2012_J.Phys.Chem.B_116_3361
PubMedID: 22385120

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

Title : BmNPV Resistance of Silkworm Larvae Resulting from the Ingestion of TiO(2) Nanoparticles - Li_2012_Biol.Trace.Elem.Res_150_221
Author(s) : Li B , Xie Y , Cheng Z , Cheng J , Hu R , Gui S , Sang X , Sun Q , Zhao X , Sheng L , Shen W , Hong F
Ref : Biol Trace Elem Res , 150 :221 , 2012
Abstract : Bombyx mori nucleopolyhedrovirus (BmNPV) causes infection in the silkworm that is often lethal. The infection is hard to prevent, partly because of the nature of the virus particles and partly because of the different strains of B. mori. Titanium dioxide nanoparticles (TiO(2) NPs) have been demonstrated to have antimicrobial properties. The present study investigated whether TiO(2) NPs added to an artificial diet can increase the resistance of B. mori larvae to BmNPV and examined the molecular mechanism behind any resistance shown. The results indicated that ingested TiO(2) NPs decreased reactive oxygen species and NO accumulation in B. mori larvae under BmNPV infection, which in turn led to a decrease in their growth inhibition and mortality. In addition, the TiO(2) NPs significantly promoted the expression of resistance-related genes, including those encoding superoxide dismutase, catalase, glutathione peroxidase, acetylcholine esterase, carboxylesterase, heat shock protein 21, glutathione S transferase o1, P53, and transferring and of genes encoding cytochrome p302 and nitric oxide synthase. These findings are a useful addition to the understanding of the mechanism of BmNPV resistance of B. mori larvae in response to TiO(2) NPs addition. Such information also provides a theoretical basis for the use of TiO(2) NPs in sericulture.
ESTHER : Li_2012_Biol.Trace.Elem.Res_150_221
PubMedSearch : Li_2012_Biol.Trace.Elem.Res_150_221
PubMedID: 23054861

Title : [Soluble epoxide hydrolase inhibitor t-AUCB ameliorates ox-LDL induced conversion of macrophages into foam cells through activating the PPARgamma-ABCA1 pathway] - Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
Author(s) : Zhao TT , Peng R , Shen L , Zhao X , Xu DY , Zhao SP
Ref : Zhonghua Xin Xue Guan Bing Za Zhi , 40 :248 , 2012
Abstract : OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitor t-AUCB on foam cell formation and cholesterol efflux in macrophage.
METHODS: Mouse macrophages RAW264.7 were cultured and stimulated with ox-LDL (80 micromol/L) in the absence (group A) or presence of t-AUCB (1, 10, 50, 100 micromol/L, group B) or t-AUCB (100 micromol/L) pretreated with PPARgamma antagonist GW9662 (5 micromol/L, group C). The foam cell was identified by oil red O staining. The cholesterol efflux rates of (3)H-cholesterol in cells were measured by liquid scintillation counter. mRNA and protein expressions of ABCA1 were detected by real-time PCR or Western blot, respectively.
RESULTS: Oil red O staining showed that t-AUCB (100 micromol/L) significantly inhibited foam cell formation which could be significantly reversed by GW9662 (all P < 0.05). t-AUCB dose-dependently increased cholesterol efflux rates in mouse macrophage [(5.91 +/- 0.18)% in group A, (7.03 +/- 0.33)%, (8.05 +/- 0.32)%, (9.04 +/- 0.14)%, (10.06 +/- 0.85)% in 1, 10, 50, 100 micromol/L t-AUCB groups, all P < 0.05 vs. group A], which could be reversed by pretreatment with GW9662 [(6.33 +/- 0.15)% in 100 micromol/L t-AUCB + GW9662 group].t-AUCB also upregulated ABCA1 mRNA and protein expressions in a dose-dependent manner which could be significantly attenuated by pretreatment with GW9662. CONCLUSION: t-AUCB could inhibit foam cell formation by improving cholesterol efflux through activating PPARgamma-ABCA1 pathway in macrophage.
ESTHER : Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
PubMedSearch : Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
PubMedID: 22801272

Title : Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma - Wei_2012_Cancer.Biol.Ther_14_
Author(s) : Wei W , Bracher-Manecke JC , Zhao X , Davies NH , Zhou L , Ai R , Oliver L , Vallette FM , Hendricks DT
Ref : Cancer Biol Ther , 14 : , 2012
Abstract : N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction. Although no measurable effects on in vitro cell proliferation were observed with altered NDRG1 expression, the ectopic overexpression of NDRG1 was positively linked to recognized markers of metastasis, angiogenesis and apoptotic evasion. Accordingly, in the nude mouse xenograft model system, NDRG1 overexpression promoted the in vivo growth of KYSE30 derived xenografts, which could be attributed to the reduced apoptotic and enhanced angiogenic activities associated with this gene. These processes were mediated in part by increased NFkappaB activity in NDRG1 overexpressing cells. Nevertheless, no significant phenotypic changes were observed in response to NDRG1 knock-down, suggesting that this gene might not be essential for the neoplastic progression of ESCC. Taken together, our results suggest that NDRG1 may play positive but dispensable roles in the progression of esophageal squamous cell carcinoma.
ESTHER : Wei_2012_Cancer.Biol.Ther_14_
PubMedSearch : Wei_2012_Cancer.Biol.Ther_14_
PubMedID: 23192272

Title : Design, synthesis and structure-activity relationship (SAR) studies of 2,4-disubstituted pyrimidine derivatives: dual activity as cholinesterase and Abeta-aggregation inhibitors - Mohamed_2011_Bioorg.Med.Chem_19_2269
Author(s) : Mohamed T , Zhao X , Habib LK , Yang J , Rao PP
Ref : Bioorganic & Medicinal Chemistry , 19 :2269 , 2011
Abstract : A novel class of 2,4-disubstituted pyrimidines (7a-u, 8a-f, 9a-e) that possess substituents with varying steric and electronic properties at the C-2 and C-4 positions, were designed, synthesized and evaluated as dual cholinesterase and amyloid-beta (Abeta)-aggregation inhibitors. In vitro screening identified N-(naphth-1-ylmethyl)-2-(pyrrolidin-1-yl)pyrimidin-4-amine (9a) as the most potent AChE inhibitor (IC(50)=5.5 muM). Among this class of compounds, 2-(4-methylpiperidin-1-yl)-N-(naphth-1-ylmethyl)pyrimidin-4-amine (9e) was identified as the most potent and selective BuChE inhibitor (IC(50)=2.2 muM, selectivity index=11.7) and was about 5.7-fold more potent compared to the commercial, approved reference drug galanthamine (BuChE IC(50)=12.6 muM). In addition, the selective AChE inhibitor N-benzyl-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine (7d), exhibited good inhibition of hAChE-induced aggregation of Abeta(1-40) fibrils (59% inhibition). Furthermore, molecular modeling studies indicate that a central pyrimidine ring serves as a suitable template to develop dual inhibitors of cholinesterase and AChE-induced Abeta aggregation thereby targeting multiple pathological routes in AD.
ESTHER : Mohamed_2011_Bioorg.Med.Chem_19_2269
PubMedSearch : Mohamed_2011_Bioorg.Med.Chem_19_2269
PubMedID: 21429752

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

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

Title : Complete genome sequences of Mycobacterium tuberculosis strains CCDC5079 and CCDC5080, which belong to the Beijing family - Zhang_2011_J.Bacteriol_193_5591
Author(s) : Zhang Y , Chen C , Liu J , Deng H , Pan A , Zhang L , Zhao X , Huang M , Lu B , Dong H , Du P , Chen W , Wan K
Ref : Journal of Bacteriology , 193 :5591 , 2011
Abstract : Mycobacterium tuberculosis is one of most prevalent pathogens in the world. Drug-resistant strains of this pathogen caused by the excessive use of antibiotics have long posed serious threats to public health worldwide. A broader picture of drug resistance mechanisms at the genomic level can be obtained only with large-scale comparative genomic methodology. Two closely related Beijing family isolates, one resistant to four first-line drugs (CCDC5180) and one sensitive to them (CCDC5079), were completely sequenced. These sequences will serve as valuable references for further drug resistance site identification studies and could be of great importance for developing drugs targeting these sites.
ESTHER : Zhang_2011_J.Bacteriol_193_5591
PubMedSearch : Zhang_2011_J.Bacteriol_193_5591
PubMedID: 21914894
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv0160c , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c , myctu-RV3452 , myctu-RV3724 , myctu-Rv3802c , myctu-y0571

Title : The genome of the mesopolyploid crop species Brassica rapa - Wang_2011_Nat.Genet_43_1035
Author(s) : Wang X , Wang H , Wang J , Sun R , Wu J , Liu S , Bai Y , Mun JH , Bancroft I , Cheng F , Huang S , Li X , Hua W , Freeling M , Pires JC , Paterson AH , Chalhoub B , Wang B , Hayward A , Sharpe AG , Park BS , Weisshaar B , Liu B , Li B , Tong C , Song C , Duran C , Peng C , Geng C , Koh C , Lin C , Edwards D , Mu D , Shen D , Soumpourou E , Li F , Fraser F , Conant G , Lassalle G , King GJ , Bonnema G , Tang H , Belcram H , Zhou H , Hirakawa H , Abe H , Guo H , Jin H , Parkin IA , Batley J , Kim JS , Just J , Li J , Xu J , Deng J , Kim JA , Yu J , Meng J , Min J , Poulain J , Hatakeyama K , Wu K , Wang L , Fang L , Trick M , Links MG , Zhao M , Jin M , Ramchiary N , Drou N , Berkman PJ , Cai Q , Huang Q , Li R , Tabata S , Cheng S , Zhang S , Sato S , Sun S , Kwon SJ , Choi SR , Lee TH , Fan W , Zhao X , Tan X , Xu X , Wang Y , Qiu Y , Yin Y , Li Y , Du Y , Liao Y , Lim Y , Narusaka Y , Wang Z , Li Z , Xiong Z , Zhang Z
Ref : Nat Genet , 43 :1035 , 2011
Abstract : We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.
ESTHER : Wang_2011_Nat.Genet_43_1035
PubMedSearch : Wang_2011_Nat.Genet_43_1035
PubMedID: 21873998
Gene_locus related to this paper: braol-Q8GTM3 , braol-Q8GTM4 , brarp-m4ei94 , brarp-m4c988 , brana-a0a078j4a9 , brana-a0a078e1m0 , brana-a0a078cd75 , brarp-m4dwa6 , brana-a0a078j4f0 , brana-a0a078cus4 , brana-a0a078f8c2 , brana-a0a078jql1 , brana-a0a078dgj3 , brana-a0a078hw50 , brana-a0a078cuu0 , brana-a0a078dfa9 , brana-a0a078ic91 , brarp-m4ctw3 , brana-a0a078ca65 , brana-a0a078ctc8 , brana-a0a078h021 , brana-a0a078jx23 , brarp-m4da84 , brarp-m4dwr7 , brana-a0a078dh94 , brana-a0a078h612 , brana-a0a078j2t3 , braol-a0a0d3dpb2 , braol-a0a0d3dx76 , brana-a0a078jxa8 , brana-a0a078i2k3 , brarp-m4cwq4 , brarp-m4dcj8 , brarp-m4eh17 , brarp-m4eey4 , brarp-m4dnj8 , brarp-m4ey83 , brarp-m4ey84

Title : Reaction mechanism for cocaine esterase-catalyzed hydrolyses of (+)- and (-)-cocaine: unexpected common rate-determining step - Liu_2011_J.Phys.Chem.B_115_5017
Author(s) : Liu J , Zhao X , Yang W , Zhan CG
Ref : J Phys Chem B , 115 :5017 , 2011
Abstract : First-principles quantum mechanical/molecular mechanical free energy calculations have been performed to examine the catalytic mechanism for cocaine esterase (CocE)-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. It has been shown that the acylation of (+)-cocaine consists of nucleophilic attack of the hydroxyl group of Ser117 on the carbonyl carbon of (+)-cocaine benzoyl ester and the dissociation of (+)-cocaine benzoyl ester. The first reaction step of deacylation of (+)-cocaine, which is identical to that of (-)-cocaine, is rate-determining, indicating that CocE-catalyzed hydrolyses of (+)- and (-)-cocaine have a common rate-determining step. The computational results predict that the catalytic rate constant of CocE against (+)-cocaine should be the same as that of CocE against (-)-cocaine, in contrast with the remarkable difference between human butyrylcholinesterase-catalyzed hydrolyses of (+)- and (-)-cocaine. The prediction has been confirmed by experimental kinetic analysis on CocE-catalyzed hydrolysis of (+)-cocaine in comparison with CocE-catalyzed hydrolysis of (-)-cocaine. The determined common rate-determining step indicates that rational design of a high-activity mutant of CocE should be focused on the first reaction step of the deacylation. Furthermore, the obtained mechanistic insights into the detailed differences in the acylation between the (+)- and (-)-cocaine hydrolyses provide indirect clues for rational design of amino acid mutations that could more favorably stabilize the rate-determining transition state in the deacylation and, thus, improve the catalytic activity of CocE. This study provides a valuable mechanistic base for rational design of an improved esterase for therapeutic treatment of cocaine abuse.
ESTHER : Liu_2011_J.Phys.Chem.B_115_5017
PubMedSearch : Liu_2011_J.Phys.Chem.B_115_5017
PubMedID: 21486046

Title : Gene cloning and characterization of a novel thermophilic esterase from Fervidobacterium nodosum Rt17-B1 - Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
Author(s) : Yu S , Zheng B , Zhao X , Feng Y
Ref : Acta Biochim Biophys Sin (Shanghai) , 42 :288 , 2010
Abstract : A bioinformatic screening of the genome of the thermophilic bacterium Fervidobacterium nodosum Rt17-B1 for esterhydrolyzing enzymes revealed a putative bacterial esterase (FNE) encoded by Fond_1301 with typical GDSL family motifs. To confirm its putative esterase function, the FNE gene was cloned, functionally expressed in Escherichia coli, and purified to homogeneity. Recombinant FNE exhibited the highest esterase activity of 14,000 U/mg with p-nitrophenyl acetate (pNPC(2)) as substrate. The catalytic efficiency (k(cat)/K(m)) toward p-nitrophenyl acetate (C(2)) was approximately 120-fold higher than toward p-nitrophenyl butyrate (C(4)). No significant esterase activity was observed for the substrates with a chain length > or =C(8). The monomeric enzyme has a molecular mass of 27.5 kDa and exhibits optimal activity around 75 degrees C, at pH 8.5. Its thermostability is relatively high with a half-life of 80 min at 70 degrees C, but less stable compared with some other hyperthermophilic esterases. A structural model was constructed using acetylesterase from Aspergillus aculeatus as a template. The structure showed an alpha/beta-hydrolase fold and indicated the presence of a typical catalytic triad consisting of a serine, aspartate, and histidine, which was verified by site-directed mutagenesis. Sequence analysis showed that FNE was only distantly related to other esterases. A comparison of the conserved motifs shared with GDSL proteins revealed that FNE could be grouped into GDSL family and was further classified as SGNH hydrolase.
ESTHER : Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
PubMedSearch : Yu_2010_Acta.Biochim.Biophys.Sin.(Shanghai)_42_288
PubMedID: 20383468

Title : Peptidomic profiling of human cerebrospinal fluid identifies YPRPIHPA as a novel substrate for prolylcarboxypeptidase - Zhao_2010_Proteomics_10_2882
Author(s) : Zhao X , Southwick K , Cardasis HL , Du Y , Lassman ME , Xie D , El-Sherbeini M , Geissler WM , Pryor KD , Verras A , Garcia-Calvo M , Shen DM , Yates NA , Pinto S , Hendrickon RC
Ref : Proteomics , 10 :2882 , 2010
Abstract : Prolylcarboxypeptidase (PRCP) is a serine protease that catalyzes the cleavage of C-terminal amino acids linked to proline in peptides. It is ubiquitously expressed and is involved in regulating blood pressure, proliferation, inflammation, angiogenesis, and weight maintenance. To identify the candidate proximal target engagement markers for PRCP inhibition in the central nervous system, we profiled the peptidome of human cerebrospinal fluid to look for PRCP substrates using a MS-based in vitro substrate profiling assay. These experiments identified a single peptide, with the sequence YPRPIHPA, as a novel substrate for PRCP in human cerebrospinal fluid. The peptide YPRPIHPA is from the extracellular portion of human endothelin B receptor-like protein 2.
ESTHER : Zhao_2010_Proteomics_10_2882
PubMedSearch : Zhao_2010_Proteomics_10_2882
PubMedID: 20517885
Gene_locus related to this paper: human-PRCP

Title : Toxicological characteristics of nanoparticulate anatase titanium dioxide in mice - Duan_2010_Biomaterials_31_894
Author(s) : Duan Y , Liu J , Ma L , Li N , Liu H , Wang J , Zheng L , Liu C , Wang X , Zhao X , Yan J , Wang S , Wang H , Zhang X , Hong F
Ref : Biomaterials , 31 :894 , 2010
Abstract : In an effort to examine liver injury, immune response, and other physiological effects in mice caused by intragastric administration of nanoparticulate anatase titanium dioxide (5nm), we assessed T lymphocytes, B lymphocyte and NK lymphocyte counts, hematological indices, biochemical parameters of liver functions, and histopathological changes in nanoparticulate titanium dioxide -treated mice. Indeed, mice treated with higher dose nanoparticulate titanium dioxide displayed a reduction in body weight, an increase in coefficients of the liver and histopathological changes in the liver. Specifically, in these nanoparticulate titanium dioxide -treated mice, interleukin-2 activity, white blood cells, red blood cells, haemoglobin, mean corpuscular haemoglobin concentration, thrombocytes, reticulocytes, T lymphocytes (CD3(+), CD4(+), CD8(+)), NK lymphocytes, B lymphocytes, and the ratio of CD4 to CD8 of mice were decreased, whereas NO level, mean corpuscular volume, mean corpuscular haemoglobin, red (cell) distribution width, platelets, hematocrit, mean platelet volume of mice were increased. Furthermore, liver functions were also disrupted, as evidenced by the enhanced activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase and cholinesterase, an increase of the total protein, and the reduction of ratio of albumin to globulin, the total bilirubin, triglycerides, and the total cholesterol levels. These results suggested that the liver function damage observed in mice treated with higher dose nanoparticulate titanium dioxide is likely associated with the damage of haemostasis blood system and immune response. However, low dose nanoparticulate anatase TiO(2) has little influences on haemostasis blood system and immune response in mice.
ESTHER : Duan_2010_Biomaterials_31_894
PubMedSearch : Duan_2010_Biomaterials_31_894
PubMedID: 19857890

Title : Enzymatic synthesis of resorcylic acid lactones by cooperation of fungal iterative polyketide synthases involved in hypothemycin biosynthesis - Zhou_2010_J.Am.Chem.Soc_132_4530
Author(s) : Zhou H , Qiao K , Gao Z , Meehan MJ , Li JW , Zhao X , Dorrestein PC , Vederas JC , Tang Y
Ref : Journal of the American Chemical Society , 132 :4530 , 2010
Abstract : Hypothemycin is a macrolide protein kinase inhibitor from the fungus Hypomyces subiculosus. During biosynthesis, its carbon framework is assembled by two iterative polyketide synthases (PKSs), Hpm8 (highly reducing) and Hpm3 (nonreducing). These were heterologously expressed in Saccharomyces cerevisiae BJ5464-NpgA, purified to near homogeneity, and reconstituted in vitro to produce (6'S,10'S)-trans-7',8'-dehydrozearalenol (1) from malonyl-CoA and NADPH. The structure of 1 was determined by X-ray crystallographic analysis. In the absence of functional Hpm3, the reducing PKS Hpm8 produces and offloads truncated pyrone products instead of the expected hexaketide. The nonreducing Hpm3 is able to accept an N-acetylcysteamine thioester of a correctly functionalized hexaketide to form 1, but it is unable to initiate polyketide formation from malonyl-CoA. We show that the starter-unit:ACP transacylase (SAT) of Hpm3 is critical for crosstalk between the two enzymes and that the rate of biosynthesis of 1 is determined by the rate of hexaketide formation by Hpm8.
ESTHER : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedSearch : Zhou_2010_J.Am.Chem.Soc_132_4530
PubMedID: 20222707
Gene_locus related to this paper: hypsb-hpm3

Title : Purification and properties of digestive lipases from Chinook salmon (Oncorhynchus tshawytscha) and New Zealand hoki (Macruronus novaezelandiae) - Kurtovic_2010_Fish.Physiol.Biochem_36_1041
Author(s) : Kurtovic I , Marshall SN , Zhao X , Simpson BK
Ref : Fish Physiol Biochem , 36 :1041 , 2010
Abstract : Lipases were purified from delipidated pyloric ceca powder of two New Zealand-sourced fish, Chinook salmon (Oncorhynchus tshawytscha) and hoki (Macruronus novaezelandiae), by fractional precipitation with polyethylene glycol 1000, followed by affinity chromatography using cholate-Affi-Gel 102, and gel filtration on Sephacryl S-300 HR. For the first time, in-polyacrylamide gel activity of purified fish lipases against 4-methylumbelliferyl butyrate has been demonstrated. Calcium ions and sodium cholate were absolutely necessary both for lipase stability in the gel and for optimum activity against caprate and palmitate esters of p-nitrophenol. A single protein band was present in native polyacrylamide gels for both salmon and hoki final enzyme preparations. Under denaturing conditions, electrophoretic analysis revealed two bands of 79.6 and 54.9 kDa for salmon lipase. It is proposed that these bands correspond to an uncleaved and a final form of the enzyme. One band of 44.6 kDa was seen for hoki lipase. pI values of 5.8+/-0.1 and 5.7+/-0.1 were obtained for the two salmon lipase forms. The hoki lipase had a pI of 5.8+/-0.1. Both lipases had the highest activity at 35 degrees C, were thermally labile, had a pH optimum of 8-8.5, and were more acid stable compared to other fish lipases studied to date. Both enzymes were inhibited by the organophosphate paraoxon. Chinook salmon and hoki lipases showed good stability in several water-immiscible solvents. The enzymes had very similar amino acid composition to mammalian carboxyl ester lipases and one other fish digestive lipase. The salmon enzyme was an overall better catalyst based on its higher turnover number (3.7+/-0.3 vs. 0.71+/-0.05 s(-1) for the hoki enzyme) and lower activation energy (2.0+/-0.4 vs. 7.6+/-0.8 kcal/mol for the hoki enzyme) for the hydrolysis of p-nitrophenyl caprate. The salmon and hoki enzymes are homologous with mammalian carboxyl ester lipases.
ESTHER : Kurtovic_2010_Fish.Physiol.Biochem_36_1041
PubMedSearch : Kurtovic_2010_Fish.Physiol.Biochem_36_1041
PubMedID: 20143156

Title : AChE deficiency or inhibition decreases apoptosis and p53 expression and protects renal function after ischemia\/reperfusion - Ye_2010_Apoptosis_15_474
Author(s) : Ye W , Gong X , Xie J , Wu J , Zhang X , Ouyang Q , Zhao X , Shi Y
Ref : Apoptosis , 15 :474 , 2010
Abstract : We recently reported that the expression of the synaptic form of acetylcholinesterase (AChE) is induced during apoptosis in various cell types in vitro. Here, we provide evidence to confirm that AChE is expressed during ischemia-reperfusion (I/R)-induced apoptosis in vivo. Renal I/R is a major cause of acute renal failure (ARF), resulting in injury and the eventual death of renal cells due to a combination of apoptosis and necrosis. Using AChE-deficient mice and AChE inhibitors, we investigated whether AChE deficiency or inhibition can protect against apoptosis caused by I/R in a murine kidney model. Unilateral clamping of renal pedicles for 90 min followed by reperfusion for 24 h caused significant renal dysfunction and injury. Both genetic AChE deficiency and chemical inhibition of AChE (provided by huperzine A, tacrine and donepezil) significantly reduced the biochemical and histological evidence of renal dysfunction following I/R. Activation of caspases-8, -9, -12, and -3 in vivo were prevented and associated with reduced levels of cell apoptosis and cell death. A further investigation also confirmed that AChE deficiency down-regulated p53 induction and phosphorylation at serine-15, and decreased the Bax/Bcl-2 ratio during I/R. In conclusion, our study demonstrates that AChE may be a pro-apoptotic factor and the inhibition of AChE reduces renal I/R injury. These findings suggest that AChE inhibitors may represent a therapeutic strategy for protection against ischemic acute renal failure.
ESTHER : Ye_2010_Apoptosis_15_474
PubMedSearch : Ye_2010_Apoptosis_15_474
PubMedID: 20054652

Title : RanBPM is an acetylcholinesterase-interacting protein that translocates into the nucleus during apoptosis - Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
Author(s) : Gong X , Ye W , Zhou H , Ren X , Li Z , Zhou W , Wu J , Gong Y , Ouyang Q , Zhao X , Zhang X
Ref : Acta Biochim Biophys Sin (Shanghai) , 41 :883 , 2009
Abstract : Acetylcholinesterase (AChE) expression may be induced during apoptosis in various cell types. Here, we used the C-terminal of AChE to screen the human fetal brain library and found that it interacted with Ran-binding protein in the microtubule-organizing center (RanBPM). This interaction was further confirmed by coimmunoprecipitation analysis. In HEK293T cells, RanBPM and AChE were heterogeneously expressed in the cisplatin-untreated cytoplasmic extracts and in the cisplatin-treated cytoplasmic or nuclear extracts. Our previous studies performed using morphologic methods have shown that AChE translocates from the cytoplasm to the nucleus during apoptosis. Taken together, these results suggest that RanBPM is an AChE-interacting protein that is translocated from the cytoplasm into the nucleus during apoptosis, similar to the translocation observed in case of AChE.
ESTHER : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedSearch : Gong_2009_Acta.Biochim.Biophys.Sin.(Shanghai)_41_883
PubMedID: 19902122

Title : Detoxification of gramine by the cereal aphid Sitobion avenae - Cai_2009_J.Chem.Ecol_35_320
Author(s) : Cai QN , Han Y , Cao YZ , Hu Y , Zhao X , Bi JL
Ref : J Chem Ecol , 35 :320 , 2009
Abstract : Secondary metabolites play an important role in host plant resistance to insects, and insects, in turn, may develop mechanisms to counter plant resistance mechanisms. In this study, we investigated the toxicity of gramine to the cereal aphid Sitobion avenae and some enzymatic responses of S. avenae to this alkaloid. When S. avenae fed on an artificial diet containing gramine, mortality occurred in a dose-dependent manner. The LC(50) of gramine was determined to be 1.248 mM. In response to gramine, S. avenae developed increased activities of carboxylesterase and glutathione S-transferase, two important detoxification enzymes. The activities of both enzymes were positively correlated with the concentration of dietary gramine. In addition, the activities of peroxidase and polypheolic oxidase, two important oxidoreductase enzymes in S. avenae, increased in response to gramine; however, catalase activity decreased when insects were exposed to higher levels of dietary gramine. The potential role of gramine in host plant resistance and S. avenae counter-resistance is discussed.
ESTHER : Cai_2009_J.Chem.Ecol_35_320
PubMedSearch : Cai_2009_J.Chem.Ecol_35_320
PubMedID: 19224277

Title : Milk composition studies in transgenic goats expressing recombinant human butyrylcholinesterase in the mammary gland - Baldassarre_2008_Transgenic.Res_17_863
Author(s) : Baldassarre H , Hockley DK , Olaniyan B , Brochu E , Zhao X , Mustafa A , Bordignon V
Ref : Transgenic Res , 17 :863 , 2008
Abstract : The use of the mammary gland of transgenic goats as a bioreactor is a well established platform for the efficient production of recombinant proteins, especially for molecules that cannot be adequately produced in traditional systems using genetically engineered microorganisms and cells. However, the extraordinary demand placed on the secretory epithelium by the expression of large amounts of the recombinant protein, may result in a compromised mammary physiology. In this study, milk composition was compared between control and transgenic goats expressing high levels (1-5 g/l) of recombinant human butyrylcholinesterase in the milk. Casein concentration, as evaluated by acid precipitation, was significantly reduced in the transgenic compared with the control goats throughout lactation (P < 0.01). Milk fatty acid composition for transgenic goats, as determined by gas chromatography, was found to have significantly fewer short chain fatty acids (P < 0.01) and more saturated fatty acids (P < 0.05) compared to controls, suggesting an overall metabolic stress and/or decreased expression of key enzymes (e.g. fatty acid synthase, stearoyl-CoA desaturase). The concentration of Na(+), K(+), assessed by atomic absorption spectrophotometry, and serum albumin, determined by bromocresol green dye and scanning densitometry, were similar in transgenic and control goats during the first several weeks of lactation. However, as lactation progressed, a significant increase in Na and serum albumin concentrations and a decrease in K(+) concentration were found in the milk of transgenic goats, while control animals remained unchanged (P < 0.01). These findings suggest that: (a) high expression of recombinant proteins may be associated with a slow-down in other synthetic activities at the mammary epithelium, as evidenced by a reduced casein expression and a decreased de-novo synthesis of fatty acids; (b) the development of permeable tight junctions may be the main mechanism involved in the premature cessation of milk secretion observed in these transgenic goats.
ESTHER : Baldassarre_2008_Transgenic.Res_17_863
PubMedSearch : Baldassarre_2008_Transgenic.Res_17_863
PubMedID: 18483775

Title : Lactation performance of transgenic goats expressing recombinant human butyryl-cholinesterase in the milk - Baldassarre_2008_Transgenic.Res_17_73
Author(s) : Baldassarre H , Hockley DK , Dore M , Brochu E , Hakier B , Zhao X , Bordignon V
Ref : Transgenic Res , 17 :73 , 2008
Abstract : The production of recombinant proteins in the milk of transgenic animals has attracted significant interest in the last decade, as a valuable alternative for the production of recombinant proteins that cannot be or are inefficiently produced using conventional systems based on microorganisms or animal cells. Several recombinant proteins of pharmaceutical and biomedical interest have been successfully expressed in high quantities (g/l) in the milk of transgenic animals. However, this productivity may be associated with a compromised mammary physiology resulting, among other things, from the extraordinary demand placed on the mammary secretory cells. In this study we evaluated the lactation performance of a herd of 50 transgenic goats expressing recombinant human butyryl-cholinesterase (rBChE) in the milk. Our findings indicate that high expression levels of rBChE (range 1-5 g/l) are produced in these animals at the expense of an impaired lactation performance. The key features characterizing these transgenic performances were the decreased milk production, the reduced milk fat content which was associated with an apparent disruption in the lipid secretory mechanism at the mammary epithelium level, and a highly increased presence of leukocytes in milk which is not associated with mammary infection. Despite of having a compromised lactation performance, the amount of rBChE produced per transgenic goat represents several orders of magnitude more than the amount of rBChE present in the blood of hundreds of human donors, the only other available source of rBChE for pharmaceutical and biodefense applications. As a result, this development constitutes another successful example in the application of transgenic animal technology.
ESTHER : Baldassarre_2008_Transgenic.Res_17_73
PubMedSearch : Baldassarre_2008_Transgenic.Res_17_73
PubMedID: 17851771

Title : An organic soluble lipase for water-free synthesis of biodiesel - Zhao_2007_Appl.Biochem.Biotechnol_143_236
Author(s) : Zhao X , El-Zahab B , Brosnahan R , Perry J , Wang P
Ref : Appl Biochem Biotechnol , 143 :236 , 2007
Abstract : Lipase AK was modified with short alkyl chains to form a highly organic soluble enzyme and was used to catalyze the synthesis of biodiesel from soybean oil in organic media. The effects of several key factors including water content, temperature, and solvent were examined for the solubilized enzyme in comparison with several other commercially available lipases. Whereas native lipases showed no activity in the absence of water, the organic soluble lipase demonstrated reaction rates of up to 33 g-product/g-enzyme h. The biocatalyst remains soluble in the biodiesel product, and therefore, there is no need to be removed because it is expected to be burned along with the diesel in combustion engines. This provides a promising one-pot mix-and-use strategy for biodiesel production.
ESTHER : Zhao_2007_Appl.Biochem.Biotechnol_143_236
PubMedSearch : Zhao_2007_Appl.Biochem.Biotechnol_143_236
PubMedID: 18057451

Title : In vitro galantamine-memantine co-application: mechanism of beneficial action - Zhao_2006_Neuropharmacol_51_1181
Author(s) : Zhao X , Marszalec W , Toth PT , Huang J , Yeh JZ , Narahashi T
Ref : Neuropharmacology , 51 :1181 , 2006
Abstract : Several drugs are in clinical use for symptomatic treatment of Alzheimer's disease patients. Since Alzheimer's disease is known to be associated with down-regulation of the cholinergic and N-methyl-D-aspartate (NMDA) systems, most of these drugs inhibit acetylcholinesterase, potentiate the activity of nicotinic acetylcholine receptors (nAChRs), or modulate NMDA receptors. Galantamine is an anticholinesterase and allosterically potentiates the activity of the nicotinic receptors. We have recently found that galantamine potentiates the activity of NMDA receptors as well. Memantine is unique in that it inhibits the NMDA receptors. We have developed a hypothesis that combining galantamine and memantine will be more effective for improving the patient's conditions than monotherapy with either drug. Patch clamp and intracellular Ca(2+) imaging experiments using rat cortical and hippocampal neurons clearly provided the in vitro bases for our hypothesis. Memantine blocked the extrasynaptic NMDA receptor 100 times more potently than the synaptic NMDA receptor at negative membrane potentials and the block of both types of NMDA receptors was attenuated with depolarization. However, galantamine potentiation of the NMDA receptors was not voltage dependent. Thus, co-application of memantine with galantamine prevented the galantamine potentiation and the activation of extrasynaptic NMDA receptors, but membrane depolarization revealed the galantamine potentiation. Therefore, cell death is expected to be prevented by memantine near the resting potential while the NMDA-mediated synaptic transmission, which is down-regulated in the patients, is maintained and potentiated by galantamine. These results provide in vitro bases for the beneficial actions of galantamine and memantine combinations.
ESTHER : Zhao_2006_Neuropharmacol_51_1181
PubMedSearch : Zhao_2006_Neuropharmacol_51_1181
PubMedID: 17011596

Title : Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetes - Hui_2005_Diabetes.Metab.Res.Rev_21_313
Author(s) : Hui H , Zhao X , Perfetti R
Ref : Diabetes Metab Res Rev , 21 :313 , 2005
Abstract : Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide secreted from gut endocrine cells in response to nutrient ingestion. The multifaceted actions of GLP-1 include the following: (1) the stimulation of insulin secretion and of its gene expression, (2) the inhibition of glucagon secretion, (3) the inhibition of food intake, (4) the proliferation and differentiation of beta cells, and (5) the protection of beta-cells from apoptosis. The therapeutic utility of the native GLP-1 molecule is limited by its rapid enzymatic degradation by a serine protease termed dipeptidyl peptidase-IV (DPP-IV). The present article reviews the research studies aimed at elucidating the biosynthesis, metabolism, and molecular characteristics of GLP-1 since it is from these studies that the development of a GLP-1-like pharmacological agent may be derived.
ESTHER : Hui_2005_Diabetes.Metab.Res.Rev_21_313
PubMedSearch : Hui_2005_Diabetes.Metab.Res.Rev_21_313
PubMedID: 15852457

Title : Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats - Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
Author(s) : Zhao X , Dey A , Romanko OP , Stepp DW , Wang MH , Zhou Y , Jin L , Pollock JS , Webb RC , Imig JD
Ref : American Journal of Physiology Regul Integr Comp Physiol , 288 :R188 , 2005
Abstract : Previous studies suggest that epoxyeicosatrienoic acids (EETs) are vasodilators of the mesenteric artery; however, the production and regulation of EETs in the mesenteric artery remain unclear. The present study was designed 1) to determine which epoxygenase isoform may contribute to formation of EETs in mesenteric arteries and 2) to determine the regulation of mesenteric artery cytochrome P-450 (CYP) enzymes in obese Zucker rats. Microvessels were incubated with arachidonic acid, and CYP enzyme activity was determined. Mesenteric arteries demonstrate detectable epoxygenase and hydroxylase activities. Next, protein and mRNA expressions were determined in microvessels. Although renal microvessels express CYP2C23 mRNA and protein, mesenteric arteries lacked CYP2C23 expression. CYP2C11 and CYP2J mRNA and protein were expressed in mesenteric arteries and renal microvessels. In addition, mesenteric artery protein expression was evaluated in lean and obese Zucker rats. Compared with lean Zucker rats, mesenteric arterial CYP2C11 and CYP2J proteins were decreased by 38 and 43%, respectively, in obese Zucker rats. In contrast, soluble epoxide hydrolase mRNA and protein expressions were significantly increased in obese Zucker rat mesenteric arteries. In addition, nitric oxide-independent dilation evoked by acetylcholine was significantly attenuated in mesenteric arteries of obese Zucker rats. These data suggest that the main epoxygenase isoforms expressed in mesenteric arteries are different from those expressed in renal microvessels and that decreased epoxygenases and increased soluble epoxide hydrolase are associated with impaired mesenteric artery dilator function in obese Zucker rats.
ESTHER : Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
PubMedSearch : Zhao_2005_Am.J.Physiol.Regul.Integr.Comp.Physiol_288_R188
PubMedID: 15345471

Title : Modulation of N-methyl-D-aspartate receptors by donepezil in rat cortical neurons - Moriguchi_2005_J.Pharmacol.Exp.Ther_315_125
Author(s) : Moriguchi S , Zhao X , Marszalec W , Yeh JZ , Narahashi T
Ref : Journal of Pharmacology & Experimental Therapeutics , 315 :125 , 2005
Abstract : Nicotinic acetylcholine receptors and N-methyl-D-aspartate (NMDA) receptors are known to be down-regulated in the brain of patients with Alzheimer's disease. It was previously shown that the nootropic drugs nefiracetam and galantamine potentiate the activity of both nicotinic and NMDA receptors. We hypothesized that donepezil, a nootropic with a potent anticholinesterase activity, might also affect the NMDA system. NMDA-induced currents were recorded from rat cortical neurons in primary culture using the whole-cell patch-clamp technique at a holding potential of -70 mV in Mg2+-free solutions. In multipolar neurons, NMDA currents were decreased by bath and U-tube applications of 1 to 10 microM donepezil but were increased by 30 to 100 microM donepezil. Donepezil suppression occurred in a manner independent of NMDA concentrations ranging from 3 to 1000 microM. The donepezil suppression of NMDA currents was prevented by inhibition of protein kinase C (PKC) but unaffected by protein kinase A (PKA) and G proteins. In bipolar neurons, however, NMDA currents were potently augmented by bath and U-tube applications of 0.01 to 100 microM donepezil. Donepezil potentiation occurred at high NMDA concentrations that evoked the saturating responses and in a manner independent of NMDA concentrations ranging from 3 to 1000 microM. The potentiation of NMDA currents by donepezil was decreased by inhibition of PKC and abolished by modulation of G proteins but not by PKA inhibition. It was concluded that donepezil at low therapeutic concentrations (0.01-1 microM) potentiated the activity of the NMDA system and that this action together with cholinesterase inhibition would contribute to the improvement of learning, memory, and cognition in patients with Alzheimer's disease.
ESTHER : Moriguchi_2005_J.Pharmacol.Exp.Ther_315_125
PubMedSearch : Moriguchi_2005_J.Pharmacol.Exp.Ther_315_125
PubMedID: 15951396

Title : Mechanisms of action of cognitive enhancers on neuroreceptors - Narahashi_2004_Biol.Pharm.Bull_27_1701
Author(s) : Narahashi T , Moriguchi S , Zhao X , Marszalec W , Yeh JZ
Ref : Biol Pharm Bull , 27 :1701 , 2004
Abstract : No strategies for curing Alzheimer's disease have been developed yet as we do not know the exact cause of the disease. The only therapy that is available for patients is symptomatic treatment. Since Alzheimer's disease is associated with downregulation of the cholinergic system in the brain, its stimulation is expected to improve the patients' cognition, learning, and memory. Four anticholinesterases have been approved in the U.S.A. for the treatment of Alzheimer's disease patients. However, because of the inhibition of cholinesterases, these drugs have side effects and their effectiveness does not last long. Thus new approaches are needed. One approach is to stimulate directly nicotinic acetylcholine (nACh) receptors in the brain, and another is to stimulate NMDA receptors which are also known to be downregulated in Alzheimer's patients. Nefiracetam has been shown to potentiate ACh currents in the alpha4beta2 receptor of rat cortical neurons with a bell-shaped dose-response relationship and the maximum effect at 1 nM. This effect was exerted via G(s) proteins. The alpha7 receptor was almost unaffected by nefiracetam. Nefiracetam also potentiated NMDA currents with the maximum effect at 10 nM via interaction with the glycine-binding site of the receptor. Galantamine had a moderate potentiating effect on the alpha4beta2 receptor and potentiated NMDA currents with the maximum effect at 1 microM. However, galantamine did not interact with the glycine-binding site. Donepezil, a potent anticholinesterase, also potentiated NMDA currents at 1-10000 nM. In conclusion, these three drugs potentiate the activity not only of the cholinergic system but also of the NMDA system, thereby stimulating the downregulated nACh receptors and NMDA receptors to improve patients' learning, cognition, and memory.
ESTHER : Narahashi_2004_Biol.Pharm.Bull_27_1701
PubMedSearch : Narahashi_2004_Biol.Pharm.Bull_27_1701
PubMedID: 15516710

Title : Soluble epoxide hydrolase inhibition protects the kidney from hypertension-induced damage - Zhao_2004_J.Am.Soc.Nephrol_15_1244
Author(s) : Zhao X , Yamamoto T , Newman JW , Kim IH , Watanabe T , Hammock BD , Stewart J , Pollock JS , Pollock DM , Imig JD
Ref : J Am Soc Nephrol , 15 :1244 , 2004
Abstract : Epoxyeicosatrienoic acids (EET) have antihypertensive and anti-inflammatory properties and play a role in the maintenance of renal vascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EET to dihydroxyeicosatrienoic acids (DHET). We hypothesized that soluble epoxide hydrolase (SEH) inhibition would improve renal vascular function and ameliorate hypertension induced renal damage. Chronic administration of the specific SEH inhibitor 1-cyclohexyl-3-dodecylurea (CDU, 3 mg/d) for 10 d lowered BP in angiotensin hypertensive rats. The contribution of renal vascular SEH to afferent arteriolar function in angiotensin hypertension was also assessed. SEH protein expression was increased in renal microvessels from hypertensive rats. Although CDU did not change afferent arteriolar responsiveness to angiotensin in normotensive animals, CDU treatment significantly attenuated afferent arteriolar diameter responses to angiotensin in hypertensive kidneys from 51% +/- 8% to 28% +/- 7%. Protection of the renal vasculature and glomerulus during chronic CDU administration was demonstrated by histology. Urinary albumin excretion, an index of renal damage, was also lower in CDU-treated hypertensive rats. These data demonstrate that SEH inhibition has antihypertensive and renal vascular protective effects in angiotensin hypertension and suggests that SEH inhibitors may be a useful therapeutic intervention for cardiovascular diseases.
ESTHER : Zhao_2004_J.Am.Soc.Nephrol_15_1244
PubMedSearch : Zhao_2004_J.Am.Soc.Nephrol_15_1244
PubMedID: 15100364

Title : Crystal Structure of an Acylpeptide Hydrolase\/Esterase from Aeropyrum pernix K1. - Bartlam_2004_Structure.(Camb)_12_1481
Author(s) : Bartlam M , Wang G , Yang H , Gao R , Zhao X , Xie G , Cao S , Feng Y , Rao Z
Ref : Structure(Camb) , 12 :1481 , 2004
Abstract : Acylpeptide hydrolases (APH; also known as acylamino acid releasing enzyme) catalyze the removal of an N-acylated amino acid from blocked peptides. The crystal structure of an APH from the thermophilic archaeon Aeropyrum pernix K1 to 2.1 A resolution confirms it to be a member of the prolyl oligopeptidase family of serine proteases. The structure of apAPH is a symmetric homodimer with each subunit comprised of two domains. The N-terminal domain is a regular seven-bladed beta-propeller, while the C-terminal domain has a canonical alpha/beta hydrolase fold and includes the active site and a conserved Ser445-Asp524-His556 catalytic triad. The complex structure of apAPH with an organophosphorus substrate, p-nitrophenyl phosphate, has also been determined. The complex structure unambiguously maps out the substrate binding pocket and provides a basis for substrate recognition by apAPH. A conserved mechanism for protein degradation from archaea to mammals is suggested by the structural features of apAPH.
ESTHER : Bartlam_2004_Structure.(Camb)_12_1481
PubMedSearch : Bartlam_2004_Structure.(Camb)_12_1481
PubMedID: 15296741
Gene_locus related to this paper: aerpe-APE1547

Title : Mechanism of action of galantamine on N-methyl-D-aspartate receptors in rat cortical neurons - Moriguchi_2004_J.Pharmacol.Exp.Ther_310_933
Author(s) : Moriguchi S , Marszalec W , Zhao X , Yeh JZ , Narahashi T
Ref : Journal of Pharmacology & Experimental Therapeutics , 310 :933 , 2004
Abstract : Galantamine, a new Alzheimer's drug approved in the United States, is known to inhibit acetylcholinesterase and potentiate acetylcholine-induced currents in brain neurons. However, because both cholinergic and N-methyl-D-aspartate (NMDA) systems are down-regulated in the brain of Alzheimer's patients, we studied the effects of galantamine on NMDA receptors. NMDA-induced whole-cell currents were recorded from the rat multipolar cortical neurons in primary culture. NMDA currents recorded in Mg2+-free media without addition of glycine were reversibly potentiated by bath and U-tube applications of galantamine at 10 to 10,000 nM, showing a bell-shaped dose-response relationship. However, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate currents were not affected by galantamine. The maximum potentiation of NMDA currents to approximately 130% of the control was obtained at 1 microM galantamine. The potentiation was due to a shift of the NMDA dose-response curve in the direction of lower NMDA concentrations. Glycine at 1 to 3000 nM enhanced NMDA currents, and potentiation by 1 microM galantamine and 1 to 300 nM glycine was additive. The glycine site antagonist 7-chlorokynurenic acid did not prevent the galantamine action. These results suggested that galantamine did not interact with the glycine binding site. Experiments with various concentrations of Mg2+ indicated that galantamine did not affect the Mg2+ blocking site of the NMDA receptor. PKC was involved in galantamine potentiation of NMDA currents, but protein kinase A, Gi/Go proteins, and Gs proteins were not involved. Potentiation of the activity of NMDA receptors is deemed partially responsible for the improvement of cognition, learning, and memory in Alzheimer's patients.
ESTHER : Moriguchi_2004_J.Pharmacol.Exp.Ther_310_933
PubMedSearch : Moriguchi_2004_J.Pharmacol.Exp.Ther_310_933
PubMedID: 15121761

Title : Soluble epoxide hydrolase inhibition lowers arterial blood pressure in angiotensin II hypertension - Imig_2002_Hypertension_39_690
Author(s) : Imig JD , Zhao X , Capdevila JH , Morisseau C , Hammock BD
Ref : Hypertension , 39 :690 , 2002
Abstract : Epoxyeicosatrienoic acids (EETs) have antihypertensive properties and play a part in the maintenance of renal microvascular function. A novel approach to increase EET levels is to inhibit epoxide hydrolase enzymes that are responsible for conversion of biologically active EETs to dihydroxyeicosatrienoic acids (DHETs) that are void of effects on the preglomerular vasculature. We hypothesized that inhibition of soluble epoxide hydrolase (sEH) would lower blood pressure in angiotensin II (Ang II) hypertension. Rat renal cortical tissue was harvested and urine collected 2 weeks following implantation of an osmotic minipump containing Ang II (60 ng/min). Renal cortical sEH protein expression was significantly higher in Ang II hypertension compared with normotensive animals. Likewise, urinary 14,15-DHET levels were significantly increased in hypertensive compared with normotensive animals and averaged 8.1 +/- 1.3 and 2.7 +/- 1.1 ng/d; respectively. In additional experiments, the sEH inhibitor N-cyclohexyl-N-dodecyl urea (NCND; 3 mg/d) or vehicle (corn oil, 0.5 mL) was administered daily by intraperitoneal injection starting on day 10. Administration of NCND for 4 days lowered systolic blood pressure by 30 mm Hg in Ang II hypertensive animals, whereas the corn oil vehicle had no effect on blood pressure in normotensive or Ang II hypertensive animals. Measurement of blood pressure by indwelling arterial catheters in conscious animals with free movement in their cages confirmed that NCND had antihypertensive properties. Arterial blood pressure averaged 119 +/- 5 mm Hg in normotensive, 170 +/- 3 mm Hg in hypertensive and 149 +/- 10 mm Hg in NCND-treated, Ang II-infused animals. Administration of the potential metabolite of NCND, N-cyclohexylformamide to Ang II hypertensive rats did not lower the systolic blood pressure. These studies demonstrate that increased sEH expression in the Ang II hypertensive kidney leads to increased EET hydration. Moreover, sEH plays a role in the regulation of blood pressure, and inhibition of sEH during Ang II hypertension is antihypertensive.
ESTHER : Imig_2002_Hypertension_39_690
PubMedSearch : Imig_2002_Hypertension_39_690
PubMedID: 11882632

Title : Mannosylerythritol lipid induces characteristics of neuronal differentiation in PC12 cells through an ERK-related signal cascade - Wakamatsu_2001_Eur.J.Biochem_268_374
Author(s) : Wakamatsu Y , Zhao X , Jin C , Day N , Shibahara M , Nomura N , Nakahara T , Murata T , Yokoyama KK
Ref : European Journal of Biochemistry , 268 :374 , 2001
Abstract : Rat pheochromocytoma PC12 cells undergo neuronal differentiation in response to nerve growth factor (NGF). The differentiation involves protein kinase cascades that include the kinases MEK and ERK, as well as activation of the transcription factors c-Jun and c-Fos. We show here, that exposure of PC12 cells to mannosylerythritol lipid (MEL), a yeast extracellular glycolipid, enhances the activity of acetylcholinesterase and interrupts the cell cycle at the G1 phase, with resulting outgrowth of neurites and partial cellular differentiation. Treatment with MEL stimulates the phosphorylation of ERK to a similar extent as treatment with NGF, although, the appearance of phosphorylated ERK is somewhat delayed. Both the MEL-induced outgrowth of neurites and the increase in the activity of acetylcholinesterase are prevented by PD98059, a specific inhibitor of MEK. Northern blotting analysis of c-jun transcripts and analysis of transcription in PC12 cells of a c-jun/CAT reporter construct demonstrated a significant increase in the rate of transcription of the c-jun gene upon treatment with MEL. The sequence elements required for the MEL-mediated activation of transcription of the c-jun gene are located between nucleotides -126 and -79 in the 5' flanking region. Our results suggest that MEL induces characteristics of neuronal differentiation in PC12 cells, with transactivation of the c-jun gene, via an ERK-related signal cascade that is partially overlapping the pathways activated in response to NGF. These results might provide the groundwork for the use of microbial extracellular glycolipids as novel reagents for the treatment of cancer cells.
ESTHER : Wakamatsu_2001_Eur.J.Biochem_268_374
PubMedSearch : Wakamatsu_2001_Eur.J.Biochem_268_374
PubMedID: 11168372

Title : Nootropic drug modulation of neuronal nicotinic acetylcholine receptors in rat cortical neurons - Zhao_2001_Mol.Pharmacol_59_674
Author(s) : Zhao X , Kuryatov A , Lindstrom JM , Yeh JZ , Narahashi T
Ref : Molecular Pharmacology , 59 :674 , 2001
Abstract : Nefiracetam (DM-9384) is a new pyrrolidone nootropic drug being developed for the treatment of Alzheimer's type and poststroke vascular-type dementia. Because the cholinergic system plays an important role in cognitive functions and Alzheimer's disease dementia, the present study was conducted to elucidate the mechanism of action of nefiracetam and aniracetam on neuronal nicotinic acetylcholine receptors (nnAChRs). Currents were recorded from rat cortical neurons in long-term primary culture using the whole-cell, patch-clamp technique. Two types of currents were evoked by acetylcholine (ACh): alpha-bungarotoxin-sensitive, alpha 7-type currents and alpha-bungarotoxin-insensitive, alpha 4 beta 2-type currents. Although nefiracetam and aniracetam inhibited alpha 7-type currents only weakly, these nootropic agents potentiated alpha 4 beta 2-type currents in a very potent and efficacious manner. Nefiracetam at 1 nM and aniracetam at 0.1 nM reversibly potentiated alpha 4 beta 2-type currents to 200 to 300% of control. Nefiracetam at very high concentrations (approximately 10 microM) also potentiated alpha 4 beta 2-type currents but to a lesser extent, indicative of a bell-shaped dose-response relationship. Nefiracetam markedly increased the saturating responses induced by high concentrations of ACh. However, human alpha 4 beta 2 subunits expressed in human embryonic kidney cells were inhibited rather than potentiated by nefiracetam. The specific protein kinase A inhibitors (H-89, KT5720, and peptide 5-24) and protein kinase C inhibitors (chelerythrine, calphostin C, and peptide 19--63) did not prevent nefiracetam from potentiating alpha 4 beta 2-type currents, indicating that these protein kinases are not involved in nefiracetam action. The nefiracetam potentiating action was not affected by 24-h pretreatment of neurons with pertussis toxin, but was abolished by cholera toxin. Therefore, G(s) proteins, but not G(i)/G(o) proteins, are involved in nefiracetam potentiation. These results indicate that nnAChRs are an important site of action of nefiracetam and G(s) proteins may be its crucial target.
ESTHER : Zhao_2001_Mol.Pharmacol_59_674
PubMedSearch : Zhao_2001_Mol.Pharmacol_59_674
PubMedID: 11259610

Title : [Expression of the Cholinesterase-Related Cell Division Controller Gene in Peripheral Blood Cell from Patients with Myelodysplastic Syndrome] - Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
Author(s) : Liao J , Li Y , Cheng S , Ma X , Yang L , Zhao X
Ref : Zhongguo Shi Yan Xue Ye Xue Za Zhi , 8 :192 , 2000
Abstract : To investigate the expression of the cholinesterase-related cell division controller (CHED) gene in the patients with myelodysplastic syndrome (MDS), CHED gene expression was assayed by RT-PCR and its relative expression rate (RER) was determined by the semi-quantitative RT-PCR analysis in peripheral blood mononuclear cells from 21 patients with MDS, 12 normal individuals served as controls. Results showed that RER of CHED in the patients (2.69 +/- 0.76) was significantly higher than that in controls (1.12 +/- 0.51, P < 0.01), the RER out of 85.7% of the patients was higher than the mean value of the controls, in which three patients developed into acute leukemia; the RER out of 61.9% of the patients was higher than the upper limit of the mean value of the controls; three patients whose RER was lower than the mean value of the controls did not developed into leukemia. These findings suggested that the expression of CHED gene in patients with MDS was significantly higher than in controls.
ESTHER : Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
PubMedSearch : Liao_2000_Zhongguo.Shi.Yan.Xue.Ye.Xue.Za.Zhi_8_192
PubMedID: 12578681

Title : Mannosylerythritol lipid increases levels of galactoceramide in and neurite outgrowth from PC12 pheochromocytoma cells - Shibahara_2000_Cytotech_33_247
Author(s) : Shibahara M , Zhao X , Wakamatsu Y , Nomura N , Nakahara T , Jin C , Nagaso H , Murata T , Yokoyama KK
Ref : Cytotechnology , 33 :247 , 2000
Abstract : We report here that a microbial extracellular glycolipid,mannosylerythritol lipid (MEL), induces the outgrowth ofneurites from and enhances the activity of acetylcholinesterase(AChE) in PC12 pheochromocytoma cells. Furthermore, treatment ofPC12 cells with MEL increased levels of galactosylceramide(Galbeta1-1'Cer; GalCer). Exposure of PC12 cells to exogenous GalCer caused the dose-dependent outgrowth ofneurites. By contrast, treatment of PC12 cells with nerve growthfactor (NGF) did not increase the level of GalCer in the cells. The neurite-related morphological changes induced by GalCerdifferend from those induced by NGF, indicating differencesbetween the signal transduction pathways triggered by NGF and by GalCer.
ESTHER : Shibahara_2000_Cytotech_33_247
PubMedSearch : Shibahara_2000_Cytotech_33_247
PubMedID: 19002832