Wang D

References (142)

Title : StructuralDPPIV: a novel deep learning model based on atom-structure for predicting dipeptidyl peptidase-IV inhibitory peptides - Wang_2024_Bioinformatics__
Author(s) : Wang D , Jin J , Li Z , Wang Y , Fan M , Liang S , Su R , Wei L
Ref : Bioinformatics , : , 2024
Abstract : MOTIVATION: Diabetes is a chronic metabolic disorder that has been a major cause of blindness, kidney failure, heart attacks, stroke, and lower limb amputation across the world. To alleviate the impact of diabetes, researchers have developed the next generation of anti-diabetic drugs, known as dipeptidyl peptidase IV inhibitory peptides (DPP-IV-IPs). However, the discovery of these promising drugs has been restricted due to the lack of effective peptide-mining tools. RESULTS: Here, we presented StructuralDPPIV, a deep learning model designed for DPP-IV-IP identification, which takes advantage of both molecular graph features in amino acid and sequence information. Experimental results on the independent test dataset and two wet experiment datasets show that our model outperforms the other state-of-art methods. Moreover, to better study what StructuralDPPIV learns, we used CAM technology and perturbation experiment to analyze our model, which yielded interpretable insights into the reasoning behind prediction results. AVAILABILITY: The project code is available at https://github.com/WeiLab-BioChem/Structural-DPP-IV. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
ESTHER : Wang_2024_Bioinformatics__
PubMedSearch : Wang_2024_Bioinformatics__
PubMedID: 38305458

Title : Role of soluble epoxide hydrolase in pain and depression comorbidity - Bu_2024_Neurobiol.Dis_193_106443
Author(s) : Bu Y , Yang S , Wang D , Hu S , Zhang Q , Wu Z , Yang C
Ref : Neurobiol Dis , 193 :106443 , 2024
Abstract : The coexistence of chronic pain and depression in clinical practice places a substantial social burden and profoundly impacts in patients. Although a clear correlation exists, the underlying mechanism of comorbidity between chronic pain and depression remains elusive. Research conducted in recent decades has uncovered that soluble epoxide hydrolase, a pivotal enzyme in the metabolism of polyunsaturated fatty acids, plays a crucial role in inflammation. Interestingly, this enzyme is intricately linked to the development of both pain and depression. With this understanding, this review aims to summarize the roles of soluble epoxide hydrolase in pain, depression, and their comorbidity. Simultaneously, we will also explore the underlying mechanisms, providing guidance for future research and drug development.
ESTHER : Bu_2024_Neurobiol.Dis_193_106443
PubMedSearch : Bu_2024_Neurobiol.Dis_193_106443
PubMedID: 38395315

Title : ANGPTL3 is a novel HDL component that regulates HDL function - Yang_2024_J.Transl.Med_22_263
Author(s) : Yang L , Wang Y , Xu Y , Li K , Yin R , Zhang L , Wang D , Wei L , Lang J , Cheng Y , Wang L , Ke J , Zhao D
Ref : J Transl Med , 22 :263 , 2024
Abstract : BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) is secreted by hepatocytes and inhibits lipoprotein lipase and endothelial lipase activity. Previous studies reported the correlation between plasma ANGPTL3 levels and high-density lipoprotein (HDL). Recently ANGPTL3 was found to preferentially bind to HDL in healthy human circulation. Here, we examined whether ANGPTL3, as a component of HDL, modulates HDL function and affects HDL other components in human and mice with non-diabetes or type 2 diabetes mellitus. METHODS: HDL was isolated from the plasma of female non-diabetic subjects and type-2 diabetic mellitus (T2DM) patients. Immunoprecipitation, western blot, and ELISA assays were used to examine ANGPTL3 levels in HDL. Db/m and db/db mice, AAV virus mediated ANGPTL3 overexpression and knockdown models and ANGPTL3 knockout mice were used. The cholesterol efflux capacity induced by HDL was analyzed in macrophages preloaded with fluorescent cholesterol. The anti-inflammation capacity of HDL was assessed using flow cytometry to measure VCAM-1 and ICAM-1 expression levels in TNF-alpha-stimulated endothelial cells pretreated with HDL. RESULTS: ANGPTL3 was found to bind to HDL and be a component of HDL in both non-diabetic subjects and T2DM patients. Flag-ANGPTL3 was found in the HDL of transgenic mice overexpressing Flag-ANGPTL3. ANGPLT3 of HDL was positively associated with cholesterol efflux in female non-diabetic controls (r = 0.4102, p = 0.0117) but not in female T2DM patients (r = - 0.1725, p = 0.3224). Lower ANGPTL3 levels of HDL were found in diabetic (db/db) mice compared to control (db/m) mice and were associated with reduced cholesterol efflux and inhibition of VCAM-1 and ICAM-1 expression in endothelial cells (p < 0.05 for all). Following AAV-mediated ANGPTL3 cDNA transfer in db/db mice, ANGPTL3 levels were found to be increased in HDL, and corresponded to increased cholesterol efflux and decreased ICAM-1 expression. In contrast, knockdown of ANGPTL3 levels in HDL by AAV-mediated shRNA transfer led to a reduction in HDL function (p < 0.05 for both). Plasma total cholesterol, total triglycerides, HDL-c, protein components of HDL and the cholesterol efflux function of HDL were lower in ANGPTL3-/- mice than ANGPTL3+/+ mice, suggesting that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. CONCLUSION: ANGPTL3 was identified as a component of HDL in humans and mice. ANGPTL3 of HDL regulated cholesterol efflux and the anti-inflammatory functions of HDL in T2DM mice. Both the protein components of HDL and cholesterol efflux capacity of HDL were decreased in ANGPTL3-/- mice. Our findings suggest that ANGPTL3 in HDL may regulate HDL function by disrupting the balance of protein components in HDL. Our study contributes to a more comprehensive understanding of the role of ANGPTL3 in lipid metabolism.
ESTHER : Yang_2024_J.Transl.Med_22_263
PubMedSearch : Yang_2024_J.Transl.Med_22_263
PubMedID: 38462608

Title : Synthesis and evaluation of a highly selective cannabidiol amide cholinesterase inhibitor - Zhang_2024_Results.Chem_7_101492
Author(s) : Zhang R , Zhao M , Wang D , Zhao Y , Li J , Zhang S , Zhang W , Shi Z
Ref : Results in Chemistry , 7 :101492 , 2024
Abstract : The therapeutic mechanism for the treatment of Alzheimer's disease (AD) is mainly by inhibiting the activity of cholinesterase (ChE) and increasing the transmission of choline and the function of neurons. In this study, two series of ChE inhibitors (CA1CA8 and CB1CB7) were designed and synthesized by the acylation of a cannabinoid (CBD) with bromoacetyl bromide, or the esterification of a CBD with an amino acid. All the synthesized compounds were tested for in vitro activity to evaluate the compounds as AD therapies. Compound CB7 was identified as a potential butyrylcholinesterase (BuChE) inhibitor (IC50=0.310.09microM), which did not display toxicity against HepG2 or PC12 cells at 6.25microM. Compound CB7 showed good antioxidant behavior, effective anti-tyrosinase activity (IC50=0.0370.003microM), and anti-acetylcholinesterase (AChE) activity (IC50=19.730.79microM). Kinetic studies also showed that CB7 can act as a dual inhibitor. These results provide a theoretical basis for the use of the natural product CBD in the design and development of anti-AD drugs.
ESTHER : Zhang_2024_Results.Chem_7_101492
PubMedSearch : Zhang_2024_Results.Chem_7_101492
PubMedID:

Title : Biochemical and molecular-level effects of co-exposure to chlorpyrifos and lambda-cyhalothrin on the earthworm (Eisenia fetida) - Wang_2024_Ecotoxicol.Environ.Saf_277_116374
Author(s) : Wang D , Chen L , Yang G , Xu Z , Lv L , Tang T , Wang Y
Ref : Ecotoxicology & Environmental Safety , 277 :116374 , 2024
Abstract : Farmland soil organisms frequently encounter pesticide mixtures presented in their living environment. However, the underlying toxic mechanisms employed by soil animals to cope with such combined pollution have yet to be explored. This investigation aimed to reveal the changes in cellular and mRNA levels under chlorpyrifos (CPF) and lambda-cyhalothrin (LCT) co-exposures in earthworms (Eisenia fetida). Results exhibited that the combination of CPF and LCT triggered an acute synergistic influence on the animals. Most exposures resulted in significant alterations in the activities of total superoxide dismutase (T-SOD), copper/zinc superoxide dismutase (Cu/Zn-SOD), caspase 3, and carboxylesterase (CarE) compared to the basal level. Moreover, when exposed to chemical mixtures, the transcription levels of four genes [heat shock protein 70 (hsp70), gst, sod, and calreticulin (crt)] also displayed more pronounced changes compared with their individual exposures. These changes in determined parameters indicated the occurrence of oxidative stress, cell death, detoxification dysfunction, and endoplasmic reticulum damage after co-exposure to CPF and LCT in E. fetida. The comprehensive examination of mixture toxicities of CPF and LCT at different endpoints would help to understand the overall toxicity they cause to soil invertebrates. The augmented deleterious effect of these pesticides in a mixture suggested that mixture toxicity assessment was necessary for the safety evaluation and application of pesticide mixtures.
ESTHER : Wang_2024_Ecotoxicol.Environ.Saf_277_116374
PubMedSearch : Wang_2024_Ecotoxicol.Environ.Saf_277_116374
PubMedID: 38677072

Title : Kinetic and thermodynamic-based studies on the interaction mechanism of novel R. roxburghii seed peptides against pancreatic lipase and cholesterol esterase - Yin_2024_Food.Chem_447_139006
Author(s) : Yin H , Zhu J , Zhong Y , Wang D , Deng Y
Ref : Food Chem , 447 :139006 , 2024
Abstract : Pancreatic lipase (PL) and cholesterol esterase (CE) are vital digestive enzymes that regulate lipid digestion. Three bioactive peptides (LFCMH, RIPAGSPF, YFRPR), possessing enzyme inhibitory activities, were identified in the seed proteins of R. roxburghii. It is hypothesized that these peptides could inhibit the activities of these enzymes by binding to their active sites or altering their conformation. The results showed that LFCMH exhibited superior inhibitory activity against these enzymes compared to the other peptides. The inhibition mechanisms of the three peptides were identified as either competitive or mixed, according to inhibition models. Further studies have shown that peptides could bind to the active sites of enzymes, thus affecting their spatial conformation and restricting substrate entry into the active site. Molecular simulation further proved that hydrogen bonds and hydrophobic interactions played a vital role in the binding of peptides to enzymes. This study enriches our understanding of interaction mechanisms of peptides on PL and CE.
ESTHER : Yin_2024_Food.Chem_447_139006
PubMedSearch : Yin_2024_Food.Chem_447_139006
PubMedID: 38492305

Title : Identification and biochemical characterization of a carboxylesterase gene associated with beta-cypermethrin resistance in Dermanyssus gallinae - Zhang_2024_Poult.Sci_103_103612
Author(s) : Zhang X , Zhang Y , Xu K , Qin J , Wang D , Xu L , Wang C
Ref : Poult Sci , 103 :103612 , 2024
Abstract : Dermanyssus gallinae is a major hematophagous ectoparasite in layer hens. Although the acaricide beta-cypermethrin has been used to control mites worldwide, D. gallinae has developed resistance to this compound. Carboxylesterases (CarEs) are important detoxification enzymes that confer resistance to beta-cypermethrin in arthropods. However, CarEs associated with beta-cypermethrin resistance in D. gallinae have not yet been functionally characterized. Here, we isolated a CarE gene (Deg-CarE) from D. gallinae and assayed its activity. The results revealed significantly higher expression of Deg-CarE in the beta-cypermethrin-resistant strain (RS) than in the susceptible strain (SS) toward alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA). These findings suggest that enhanced esterase activities might have contributed to beta-cypermethrin resistance in D. gallinae. Quantitative real-time PCR analysis revealed that Deg-CarE expression levels were significantly higher in adults than in other life stages. Although Deg-CarE was upregulated in the RS, significant differences in gene copy numbers were not observed. Additionally, Deg-CarE expression was significantly induced by beta-cypermethrin in both the SS and RS. Moreover, silencing Deg-CarE via RNA interference decreased the enzyme activity and increased the susceptibility of the RS to beta-cypermethrin, confirming that Deg-CarE is crucial for beta-cypermethrin detoxification. Finally, recombinant Deg-CarE (rDeg-CarE) expressed in Escherichia coli displayed high enzymatic activity toward alpha/beta-NA. However, metabolic analysis indicated that rDeg-CarE did not directly metabolize beta-cypermethrin. The collective findings indicate that D. gallinae resistance to beta-cypermethrin is associated with elevated CarEs protein activity and increased Deg-CarE expression levels. These findings provide insights into the metabolic resistance of D. gallinae and offer scientific guidance for the management and control of D. gallinae.
ESTHER : Zhang_2024_Poult.Sci_103_103612
PubMedSearch : Zhang_2024_Poult.Sci_103_103612
PubMedID: 38492248

Title : Biomimetic Metal-Pyrimidine Nanoflowers: Enzyme Immobilization Platforms with Boosted Activity - Gong_2023_Small__e2304077
Author(s) : Gong C , Wang D , Zhao H
Ref : Small , :e2304077 , 2023
Abstract : For the enzyme immobilization platform, enhancing enzyme activity retention while improving enzyme stability remains a challenge for sensitive sensing analysis. Herein, an in situ biomimetic immobilized enzyme carrier (metal-pyrimidine nanoflowers, MPNFs) synthesized by the coordination of DNA base derivative (2-aminopyrimidine) with Zn(2+) in the aqueous phase at room temperature is developed. The biocompatibility of 2-aminopyrimidine and the hydrophilicity and green synthetic conditions of MPNFs allows the immobilized enzymes to retain above 91.2% catalytic activity. On this basis, a cascade catalytic platform is constructed by simultaneously immobilizing acetylcholinesterase (AChE), choline oxidase (CHO), and horseradish peroxidase (HRP) in MPNFs (AChE/CHO/HRP@MPNFs) for organophosphorus pesticides (OPs) colorimetric biosensing detection. The assay could specifically detect parathion-methyl within 13 min with a wider linear range (0.1-1000.0 nm) and a lower limit of detection (LOD) (0.032 nm). The remarkable stability of the immobilized enzymes is also achieved under harsh environments, room temperature storage, and recycling. Furthermore, a portable and cost-effective biosensing platform is developed by integrating AChE/CHO/HRP@MPNFs with a smartphone-assisted paper device for the on-site detection of OPs. Overall, the high catalytic activity retention and the enhanced detection performance demonstrate that MPNF is a robust carrier in enzyme immobilization and holds great promise in biosensing and other field applications.
ESTHER : Gong_2023_Small__e2304077
PubMedSearch : Gong_2023_Small__e2304077
PubMedID: 37612822

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

Title : Strigolactone and gibberellin signalling coordinately regulates metabolic adaptations to changes in nitrogen availability in rice - Sun_2023_Mol.Plant__
Author(s) : Sun H , Guo X , Zhu X , Gu P , Zhang W , Tao W , Wang D , Wu Y , Zhao Q , Xu G , Fu X , Zhang Y
Ref : Mol Plant , : , 2023
Abstract : Modern semi-dwarf rice varieties of the 'Green Revolution' require a high nitrogen (N) fertilizer supply to obtain a high yield. A better understanding of the interplay between N metabolic and developmental processes is required for improved N use efficiency (NUE) and agricultural sustainability. Here, we show that strigolactones (SLs) modulate root metabolic and developmental adaptations to low N availability, which ensure efficient uptake and translocation of available N. The key repressor DWARF 53 (D53) of the SL signalling interacts with the transcription factor GROWTH-REGULATING FACTOR 4 (GRF4) and prevents GRF4 from binding to its target gene promoters. N limitation induces the accumulation of SLs, which in turn promotes SL-mediated degradation of D53, leading to the release of GRF4 and thus promoting the genes expression associated with N metabolism. N limitation also induces degradation of the rice DELLA protein SLENDER RICE 1 (SLR1) in the D14- and D53-dependent manners, and that is effective for the release of GRF4 from the competitive inhibition caused by SLR1. Our findings reveal a previously unknown mechanism underlying SL and gibberellin crosstalk in response to N availability, which advances our understanding of plant growth-metabolic coordination that can be useful to improve NUE in high-yield crops.
ESTHER : Sun_2023_Mol.Plant__
PubMedSearch : Sun_2023_Mol.Plant__
PubMedID: 36683328

Title : Genome-wide identification and analysis of the SUPPRESSOR of MAX2 1-LIKE gene family and its interaction with DWARF14 in poplar - Sun_2023_BMC.Plant.Biol_23_105
Author(s) : Sun M , Wang D , Liu C , Liu Y , Niu M , Wang J , Li J
Ref : BMC Plant Biol , 23 :105 , 2023
Abstract : BACKGROUND: Strigolactones (SLs) are important phytohormones that can regulate branch development in plants. Although SUPPRESSOR of MAX2 1-LIKE proteins (SMXLs) play a crucial role in SL signaling transduction, the SMXL gene family has not been well characterized in poplar. RESULTS: In this study, 12 members of the poplar SMXL gene family were identified and phylogenetically classified into four clades. Motif and 3D structural analyses revealed that PtSMXL proteins are structurally very conserved; however, the P-loop NTPase domain at the C-terminal was found to vary substantially among clades. A genomic collinearity analysis indicated that PtSMXL gene family members have expanded during recent genome doubling events in poplar, with all gene pairs subsequently undergoing purifying selection. According to a Cis-element analysis, PtSMXL promoters contain many light-responsive elements. In an expression pattern analysis, all 12 PtSMXL genes displayed tissue-specific expression, especially PtSMXL8a. PtSMXL7b expression was significantly downregulated after axillary bud growth begins. In addition, the expressions of PtSMXL7b and PtSMXL8a were highly induced by 2 microM GR24, a synthetic SL analog, thus suggesting that these genes are involved in SL-regulated axillary bud growth. In a yeast two-hybrid assay, only PtSMXL7b in clade II was able to interact with the SL receptor PtD14a in an SL dependent manner, which indicates that PtSMXL7b may be the functional homolog of D53/SMXL6/7/8 in poplar. Finally, we established its ability to affect axillary bud growth by constructing poplar overexpressing the PtSMXL7b gene. CONCLUSIONS: Our findings may inform future research on the functions of SMXLs in poplar, especially with respect to branch development.
ESTHER : Sun_2023_BMC.Plant.Biol_23_105
PubMedSearch : Sun_2023_BMC.Plant.Biol_23_105
PubMedID: 36814183

Title : Polyethylene Degradation by a Rhodococcous Strain Isolated from Naturally Weathered Plastic Waste Enrichment - Tao_2023_Environ.Sci.Technol__
Author(s) : Tao X , Ouyang H , Zhou A , Wang D , Matlock H , Morgan JS , Ren AT , Mu D , Pan C , Zhu X , Han A , Zhou J
Ref : Environ Sci Technol , : , 2023
Abstract : Polyethylene (PE) is the most widely produced synthetic polymer and the most abundant plastic waste worldwide due to its recalcitrance to biodegradation and low recycle rate. Microbial degradation of PE has been reported, but the underlying mechanisms are poorly understood. Here, we isolated a Rhodococcus strain A34 from 609 day enriched cultures derived from naturally weathered plastic waste and identified the potential key PE degradation enzymes. After 30 days incubation with A34, 1% weight loss was achieved. Decreased PE molecular weight, appearance of C-O and C=O on PE, palmitic acid in the culture supernatant, and pits on the PE surface were observed. Proteomics analysis identified multiple key PE oxidation and depolymerization enzymes including one multicopper oxidase, one lipase, six esterase, and a few lipid transporters. Network analysis of proteomics data demonstrated the close relationships between PE degradation and metabolisms of phenylacetate, amino acids, secondary metabolites, and tricarboxylic acid cycles. The metabolic roadmap generated here provides critical insights for optimization of plastic degradation condition and assembly of artificial microbial communities for efficient plastic degradation.
ESTHER : Tao_2023_Environ.Sci.Technol__
PubMedSearch : Tao_2023_Environ.Sci.Technol__
PubMedID: 37682848

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

Title : Deacylated Derivative of Hericenone C Treated by Lipase Shows Enhanced Neuroprotective Properties Compared to Its Parent Compound - Tamrakar_2023_Molecules_28_
Author(s) : Tamrakar S , Wang D , Hiraki E , Han C , Ruan Y , Allam AE , Amen Y , Katakura Y , Shimizu K
Ref : Molecules , 28 : , 2023
Abstract : Hericium erinaceus, a mushroom species commonly known as Yamabushitake in Japan, is known to have a stimulatory effect on neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Hericenone C, a meroterpenoid with palmitic acid as the fatty acid side chain, is reported to be one such stimulant. However, according to the structure of the compound, the fatty acid side chain seems highly susceptible to lipase decomposition, under in vivo metabolic conditions. To study this phenomenon, hericenone C from the ethanol extract of the fruiting body was subjected to lipase enzyme treatment and observed for changes in the chemical structure. The compound formed after the lipase enzyme digestion was isolated and identified using LC-QTOF-MS combined with (1)H-NMR analysis. It was found to be a derivative of hericenone C without its fatty acid side chain and was named deacylhericenone. Interestingly, a comparative investigation of the neuroprotective properties of hericenone C and deacylhericenone showed that the BDNF mRNA expression in human astrocytoma cells (1321N1) and the protection against H(2)O(2-)induced oxidative stress was considerably higher in the case of deacylhericenone. These findings suggest that the stronger bioactive form of the hericenone C compound is in fact deacylhericenone.
ESTHER : Tamrakar_2023_Molecules_28_
PubMedSearch : Tamrakar_2023_Molecules_28_
PubMedID: 37299024

Title : Insecticide resistance of Anopheles sinensis after elimination of malaria in Henan Province, China - He_2023_Parasit.Vectors_16_180
Author(s) : He ZQ , Hu YB , Wang D , Liu YT , Yang CY , Qian D , Zhou RM , Lu DL , Li SH , Liu Y , Zhang HW
Ref : Parasit Vectors , 16 :180 , 2023
Abstract : BACKGROUND: Historically, malaria due to Plasmodium vivax has been epidemic in Henan Province, China, with Anopheles sinensis as the main vector. The most effective measures to prevent malaria transmission are based on vector control through the use of insecticides. However, insecticides exert a strong selective pressure on mosquito populations for insecticide resistance. The aim of this study was to investigate the susceptibility profile and population genetic characteristics of An. sinensis to provide basic data and scientific guidance for the study of resistance mechanisms and the control of An. sinensis in Henan Province. METHODS: Adult Anopheles mosquitoes were collected at sites near local farmers' sheepfolds, pigsties and/or cowsheds located in Pingqiao, Xiangfu, Xiangcheng and Tanghe counties/districts of Henan Province during July-September 2021 for insecticide susceptibility testing. Molecular identification of collected mosquitoes as belonging to genus Anopheles was by PCR, and the frequencies of mutations in the knockdown resistance gene (kdr) and acetylcholinesterase-1 gene (ace-1) were detected using gene amplification. The mitochondrial DNA cytochrome oxidase subunit I (COI) gene was amplified in deltamethrin-resistant and deltamethrin-sensitive mosquitoes to analyze the genetic evolutionary relationship. RESULTS: A total of 1409 Anopheles mosquitoes were identified by molecular identification, of which 1334 (94.68%) were An. sinensis, 28 (1.99%) were An. yatsushiroensis, 43 (3.05%) were An. anthropophagus and four (0.28%) were An. belenrae. The 24-h mortality rates of An. sinensis in Pingqiao, Tanghe, Xiangcheng and Xiangfu counties/districts exposed to deltamethrin were 85.85%, 25.38%, 29.73% and 7.66%, respectively; to beta-cyfluthrin, 36.24%, 70.91%, 34.33% and 3.28%, respectively; to propoxur, 68.39%, 80.60%, 37.62% and 9.29%, respectively; and to malathion, 97.43%, 97.67%, 99.21% and 64.23%, respectively. One mutation, G119S, was detected in the ace-1 gene. The frequencies of the main genotypes were 84.21% of specimens collected in Xiangfu (G/S), 90.63% of speciments collected in Xiangcheng (G/G) and 2.44% of speciments collected in Tanghe (S/S). Significantly higher G119S allele frequencies were observed in both propoxur- and malathion-resistant mosquitoes than in their sensitive counterparts in the Tanghe population (P < 0.05). Three mutations, L1014F (41.38%), L1014C (9.15%) and L1014W (0.12%), were detected in the kdr gene. The genotypes with the highest frequency in the populations of An. sinensis in Xiangfu and Tanghe were the mutant TTT (F/F) and wild-type TTG (L/L), at 67.86% (57/84) and 74.29% (52/70), respectively. In Pingqiao and Xiangfu, higher frequencies of the L1014F allele and lower frequencies of the L1014C allele were observed in mosquitoes resistant for beta-cyfluthrin than in those which were sensitive for this insecticide (P < 0.05). The results of Tajima's D and of Fu and Li's D and F were not significantly negative (P > 0.10), and each haplotype was interlaced and did not form two distinct branches. CONCLUSIONS: High resistance to pyrethroids and propoxur was observed at four sites, but the resistance to malathion varied according to the location. Anopheles belenrae and the L1014W (TGG) mutation in An. sinensis were first discovered in Henan Province. The deltamethrin-resistant and deltamethrin-sensitive mosquito populations showed no genetic differentiation. The generation of resistance might be the result of the combination of multiple factors.
ESTHER : He_2023_Parasit.Vectors_16_180
PubMedSearch : He_2023_Parasit.Vectors_16_180
PubMedID: 37268968

Title : Mixture toxic effects of thiacloprid and cyproconazole on honey bees (Apis mellifera L.) - Lv_2023_Sci.Total.Environ__161700
Author(s) : Lv L , Li W , Li X , Wang D , Weng H , Zhu YC , Wang Y
Ref : Sci Total Environ , :161700 , 2023
Abstract : Pesticide exposure to pesticides remains one of the main factors in the population decline of insect pollinators. It is urgently necessary to assess the effects of mixtures on pollinator risk assessments because they are often exposed to numerous agrochemicals. In the present study, we explored the mixture toxic effects of thiacloprid (THI) and cyproconazole (CYP) on honey bees (Apis mellifera L.). Our findings revealed that THI possessed higher acute toxicity to A. mellifera (96-h LC(50) value of 216.3 mg a.i. L(-1)) than CYP (96-h LC(50) value of 601.4 mg a.i. L(-1)). It's worth noting that the mixture of THI and CYP exerted an acute synergistic effect on honey bees. At the same time, the activities of detoxification enzyme cytochrome P450s (CYP450s) and neuro target enzyme Acetylcholinesterase (AChE), as well as the expressions of seven genes (CRBXase, CYP306A1, CYP6AS14, apidaecin, defensing-2, vtg, and gp-93) associated with detoxification metabolism, immune response, development, and endoplasmic reticulum stress, were significantly altered in the combined exposure compared with the corresponding individual exposures of THI or CYP. These data indicated that a mixture of THI and CYP could disturb the physiological homeostasis of honey bees. Our study provides a theoretical basis for in-depth studies on the impacts of pesticide mixtures on the health of honey bees. Our study also provides important guidance for the rational application of pesticide mixtures to protect pollinators in agricultural production effectively.
ESTHER : Lv_2023_Sci.Total.Environ__161700
PubMedSearch : Lv_2023_Sci.Total.Environ__161700
PubMedID: 36690094

Title : A promising tool for clinical diagnostics: Dual-emissive carbonized polymer dots based cross-linking enhanced emission for sensitive detection of alkaline phosphatase and butyrylcholinesterase - Li_2023_Biosens.Bioelectron_238_115576
Author(s) : Li T , Wang D , Hu J , Fu X , Ji Y , Li R
Ref : Biosensors & Bioelectronics , 238 :115576 , 2023
Abstract : Compared with single signal readout, dual-signal readout commendably corrects the impact of systematic or background error, achieving more accurate results for the diagnosis of many diseases. This work aimed to design and prepare dual-emissive fluorescent probes for the construction of ratiometric fluorescence biosensors to detect liver disease biomarkers. Sodium alginate (SA) with numerous potential sub-fluorophores and active sites and 4,4',4'',4'''-(porphine-5,10,15,20-tetrayl) tetrakis (benzoic acid) (TCPP) with macrocyclic conjugated structures were introduced to prepare the carbonized polymer dots (CPDs) with red/blue dual emission based on the cross-linking enhanced emission (CEE) effect and the luminescence of macrocyclic conjugated structures. The ratiometric fluorescence sensing systems were constructed by integrating the specific response of CPDs to Cu(2+) and the affinity difference of Cu(2+) to substrates or products of enzymes. The sensing systems, CPDs/Cu(2+)/PPi and CPDs/Cu(2+)/BTCh, were designed to detect liver disease biomarkers, alkaline phosphatase (ALP) and butyrylcholinesterase (BChE), respectively. The limit of detection for ALP and BChE was 0.35 U/L and 0.19 U/L, respectively. The proposed sensors were successfully applied to human serum samples from different health stages with satisfactory recoveries. These results demonstrate the successful design of a novel dual-emissive fluorescent probe and provide a feasible strategy for clinical detection.
ESTHER : Li_2023_Biosens.Bioelectron_238_115576
PubMedSearch : Li_2023_Biosens.Bioelectron_238_115576
PubMedID: 37557027

Title : Characteristics of CXE family of Salvia miltiorrhiza and identification of interactions between SmGID1s and SmDELLAs - Li_2023_Plant.Physiol.Biochem_206_108140
Author(s) : Li Y , Pang Q , Li B , Fu Y , Guo M , Zhang C , Tian Q , Hu S , Niu J , Wang S , Wang D , Wang Z
Ref : Plant Physiol Biochem , 206 :108140 , 2023
Abstract : Carboxylesterase (CXE) is a class of hydrolases that contain an alpha/beta folding domain, which plays critical roles in plant growth, development, and stress responses. Based on the genomic and transcriptomic data of Salvia miltiorrhiza, the SmCXE family was systematically analyzed using bioinformatics. The results revealed 34 SmCXE family members in S. miltiorrhiza, and the SmCXE family could be divided into five groups (Group I, Group II, Group III, Group IV, and Group V). Cis-regulatory elements indicated that the SmCXE promoter region contained tissue-specific and development-related, hormone-related, stress-related, and photoresponsive elements. Transcriptome analysis revealed that the expression levels of SmCXE2 were highest in roots and flowers (SmCXE8 was highest in stems and SmCXE19 was highest in leaves). Further, two GA receptors SmCXE1 (SmGID1A) and SmCXE2 (SmGID1B) were isolated from the SmCXE family, which are homologous to other plants. SmGID1A and SmGID1B have conserved HGGSF motifs and active amino acid sites (Ser-Asp-Val/IIe), which are required to maintain their GA-binding activities. SmGID1A and SmGID1B were significantly responsive to gibberellic acid (GA(3)) and methyl jasmonate (MeJA) treatment. A subcellular assay revealed that SmCXE1 and SmCXE2 resided within the nucleus. SmGID1B can interact with SmDELLAs regardless of whether GA(3) exists, whereas SmGID1A can only interact with SmDELLAs in the presence of GA(3). A Further assay showed that the GRAS domain mediated the interactions between SmGID1s and SmDELLAs. This study lays a foundation for further elucidating the role of SmCXE in the growth and development of S. miltiorrhiza.
ESTHER : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedSearch : Li_2023_Plant.Physiol.Biochem_206_108140
PubMedID: 38134738
Gene_locus related to this paper: salmi-SmCXE1 , salmi-SmCXE2 , salmi-SmCXE3 , salmi-SmCXE4 , salmi-SmCXE5 , salmi-SmCXE6 , salmi-SmCXE7 , salmi-SmCXE8 , salmi-SmCXE9 , salmi-SmCXE10 , salmi-SmCXE11 , salmi-SmCXE12 , salmi-SmCXE13 , salmi-SmCXE14 , salmi-SmCXE15 , salmi-SmCXE16 , salmi-SmCXE17 , salmi-SmCXE18 , salmi-SmCXE19 , salmi-SmCXE20 , salmi-SmCXE21 , salmi-SmCXE22 , salmi-SmCXE23 , salmi-SmCXE24 , salmi-SmCXE25 , salmi-SmCXE26 , salmi-SmCXE27 , salmi-SmCXE28 , salmi-SmCXE29 , salmi-SmCXE30 , salmi-SmCXE31 , salmi-SmCXE32 , salmi-SmCXE33 , salmi-SmCXE34

Title : Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients - Liu_2023_Front.Med.(Lausanne)_10_1175089
Author(s) : Liu J , Shao T , Chen H , Ma C , Lu X , Yang X , Song K , Wang L , Lei S , Wang D
Ref : Front Med (Lausanne) , 10 :1175089 , 2023
Abstract : AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48 h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p < 0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p < 0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p = 0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p < 0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p < 0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients.
ESTHER : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedSearch : Liu_2023_Front.Med.(Lausanne)_10_1175089
PubMedID: 37502364

Title : Artificial Intelligence Aided Lipase Production and Engineering for Enzymatic Performance Improvement - Ge_2023_J.Agric.Food.Chem__
Author(s) : Ge F , Chen G , Qian M , Xu C , Liu J , Cao J , Li X , Hu D , Xu Y , Xin Y , Wang D , Zhou J , Shi H , Tan Z
Ref : Journal of Agricultural and Food Chemistry , : , 2023
Abstract : With the development of artificial intelligence (AI), tailoring methods for enzyme engineering have been widely expanded. Additional protocols based on optimized network models have been used to predict and optimize lipase production as well as properties, namely, catalytic activity, stability, and substrate specificity. Here, different network models and algorithms for the prediction and reforming of lipase, focusing on its modification methods and cases based on AI, are reviewed in terms of both their advantages and disadvantages. Different neural networks coupled with various algorithms are usually applied to predict the maximum yield of lipase by optimizing the external cultivations for lipase production, while one part is used to predict the molecule variations affecting the properties of lipase. However, few studies have directly utilized AI to engineer lipase by affecting the structure of the enzyme, and a set of research gaps needs to be explored. Additionally, future perspectives of AI application in enzymes, including lipase engineering, are deduced to help the redesign of enzymes and the reform of new functional biocatalysts. This review provides a new horizon for developing effective and innovative AI tools for lipase production and engineering and facilitating lipase applications in the food industry and biomass conversion.
ESTHER : Ge_2023_J.Agric.Food.Chem__
PubMedSearch : Ge_2023_J.Agric.Food.Chem__
PubMedID: 37800676

Title : Microplastics induce neurotoxicity in aquatic animals at environmentally realistic concentrations: A meta-analysis - Xiong_2022_Environ.Pollut_318_120939
Author(s) : Xiong F , Liu J , Xu K , Huang J , Wang D , Li F , Wang S , Zhang J , Pu Y , Sun R
Ref : Environ Pollut , 318 :120939 , 2022
Abstract : Microplastics (MPs) draw international attention owing to their widespread distribution in water ecosystems, but whether MPs cause neurotoxic effects in aquatic animals at environmentally realistic concentrations is still controversial. This meta-analysis recompiled 35 studies to determine whether MPs could change the levels of brain (in vivo) neurotransmitters in aquatic animals at environmentally realistic concentrations (>=1smg/L, median = 0.100 mg/L). Then, a group comparison was conducted to compare the effects of different factors on the effect size and to explore the significant factors affecting the neurotoxicity of MPs. The results demonstrated that MP exposure could considerably decrease the levels of acetylcholinesterase (AchE) in the brain of aquatic animals by 16.2%. However, the effects of MPs on cholinesterase (CHE), acetylcholine (ACh), dopamine (DA) and gamma-aminobutyric acid (GABA) were not statistically significant due to the small number of studies and samples. The neurotoxicity of MPs was closely linked with particle size and exposure time but independent of animal species, MP compositions, MP morphology and MP concentrations. Further literatures review indicated that MP-induced neurotoxicity and behavioral changes are related with multiple biological processes, including nerve damage, oxidative stress, intestinal flora disturbance and metabolic disorder. Furthermore, some factors influencing MP neurotoxicity in the real environment (e.g. the aging of MPs, the release of MP additives, and the co-exposure of MPs and pollutants) were discussed. Overall, this study preliminarily explored whether MPs induced changes in neurotoxicity-related indicators in aquatic animals through meta-analysis and provided scientific evidence for evaluating the health risks and neurotoxicity of MPs at the environmental level.
ESTHER : Xiong_2022_Environ.Pollut_318_120939
PubMedSearch : Xiong_2022_Environ.Pollut_318_120939
PubMedID: 36581239

Title : AADAC promotes therapeutic activity of cisplatin and imatinib against ovarian cancer cells - Wang_2022_Histol.Histopathol__18460
Author(s) : Wang H , Wang D , Gu T , Zhu M , Cheng L , Dai W
Ref : Histol Histopathol , :18460 , 2022
Abstract : OBJECTIVE: To explore how AADAC functions in the malignant progression of ovarian cancer, and the effect of AADAC on drug therapeutic activity against ovarian cancer cells. METHODS: AADAC level in tumor and normal samples from TCGA-OV dataset and its survival significance were analyzed by bioinformatics methods. Signaling pathway enrichment analysis for the high- and low-AADAC patients was achieved by using GSEA software. AADAC expression in the cell lines with different treatments was evaluated via qRT-PCR. Cell proliferative ability was assessed via MTT assay Cell migratory and invasive abilities were evaluated via transwell assay. Angiogenesis assay was performed to examine the angiogenetic ability. RESULTS: AADAC was upregulated in ovarian cancer tissues, and patients with high expression of AADAC had favorable survival conditions compared to the low AADAC expression ones. Overexpression of AADAC inhibited the malignant progression of ovarian cancer cells. Both cisplatin and imatinib suppressed cancer cell malignant progression, while overexpressed AADAC synergistically enhanced such inhibition. CONCLUSIONS: The study demonstrated that AADAC could somehow suppress the malignant progression of ovarian cancer, especially at the cellular level. In addition, synergic tumor-inhibitory effects between AADAC and the anti-cancer drugs were identified. All the above results proposed a novel idea and candidate biomarker for ovarian cancer therapy.
ESTHER : Wang_2022_Histol.Histopathol__18460
PubMedSearch : Wang_2022_Histol.Histopathol__18460
PubMedID: 35451495

Title : Design, synthesis, and biological evaluation of carbamate derivatives of N-salicyloyl tryptamine as multifunctional agents for the treatment of Alzheimer's disease - Liu_2022_Eur.J.Med.Chem_229_114044
Author(s) : Liu D , Zhang H , Wang Y , Liu W , Yin G , Wang D , Li J , Shi T , Wang Z
Ref : Eur Journal of Medicinal Chemistry , 229 :114044 , 2022
Abstract : In this study, we designed, synthesized, and evaluated a series of carbamate derivatives of N-salicyloyl tryptamine as multifunctional therapeutic agents for the treatment of Alzheimer's disease (AD). After screening the acetylcholinesterase (AChE)/butyrylcholinesterase (BChE) inhibitory activities, target compound 1g stood out as a mixed type reversible dual inhibitor of AChE and BChE. In addition, molecular docking studies were conducted to explore the actions on AChE and BChE. The results showed that 1g could decrease the level of pro-inflammatory cytokines NO, iNOS, IL-6, TNF-alpha, and ROS, increase the level of anti-inflammatory cytokines IL-4, and inhibit the aggregation of Abeta(1-42). Moreover, the administration of 1g suppressed the activity of AChE in the brain. In a word, the compound 1g is effective for improving learning and memory behavior, blood-brain barrier permeation, pharmacokinetics, ChE inhibition, and anti-neuroinflammation. It may be considered as a promising multi-functional therapeutic agent for further investigation for the treatment of AD.
ESTHER : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedSearch : Liu_2022_Eur.J.Med.Chem_229_114044
PubMedID: 34923430

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

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

Title : The dark side of synaptic proteins in tumours - Li_2022_Br.J.Cancer__
Author(s) : Li J , Xu Y , Zhu H , Wang Y , Li P , Wang D
Ref : Br J Cancer , : , 2022
Abstract : Research in the past decade has uncovered the essential role of the nervous system in the tumour microenvironment. The recent advances in cancer neuroscience, especially the discovery of neuron-tumour synaptic/perisynaptic structures, have revealed the dark side of synaptic proteins in the progression of brain tumours. Here, we provide an overview of the synaptic proteins expressed by tumour cells and analyse their molecular functions and organisation by comparing them with neuronal synaptic proteins. We focus on the studies of neuroligin-3, the glutamate receptors AMPAR and NMDAR and the synaptic scaffold protein DLGAP1, for their newly discovered regulatory role in the proliferation and progression of tumours. Progress in cancer neuroscience has brought novel insights into the treatment of cancers. In the last part of this review, we discuss the therapeutical strategies targeting synaptic proteins and the current challenges and possible toolkits regarding their clinical application in cancer treatment. Our understanding of cancer neuroscience is still in its infancy; deeper investigation of how tumour cells co-opt synaptic signaling will help fulfil the therapeutical potential of the synaptic proteins as promising anti-tumour targets.
ESTHER : Li_2022_Br.J.Cancer__
PubMedSearch : Li_2022_Br.J.Cancer__
PubMedID: 35624299

Title : Physiological Responses of the Firefly Pyrocoelia analis (Coleoptera: Lampyridae) to an Environmental Residue From Chemical Pesticide Imidacloprid - Wang_2022_Front.Physiol_13_879216
Author(s) : Wang YZ , Cao CQ , Wang D
Ref : Front Physiol , 13 :879216 , 2022
Abstract : Imidacloprid, a neonicotinoid insecticide, is widely applied to control insect pests across a broad spectrum. Though the impact of residues from this chemical pesticide on non-target organisms in the field has been reported, it was not well characterized across a wide range of ecosystems, especially for some species considered as environmental indicators that live in forests. The effects of sublethal dose of imidacloprid on firefly, Pyrocoelia analis, were analyzed physiologically and biochemically in this study to better understand the impact of chemical pesticide application on environmental indicators such as fireflies. After imidacloprid treatment, the midgut tissues of the larva presented an abnormal morphology featured as atrophy of fat body cells, shrinking cells, and the destruction of a midgut structure. The activities of antioxidant enzymes, superoxide dismutase, catalase, and peroxidase were noticeably increased during early exposure to sublethal imidacloprid and then decreased at later stages. The malondialdehyde content significantly increased after 12 h of exposure to imidacloprid compared with the control. Similarly, the enzyme activities of polyphenol oxidase and acetylcholinesterase were increased after the imidacloprid treatment and then decreased at the later stage. In summary, a sublethal dose of imidacloprid caused destructive change in the tissue structure, and this damage was followed by an excessive reactive oxygen species that could not be eliminated by antioxidant enzymes. Our results indicated that the residues of imidacloprid might cause severe toxicity to non-target insects in the environment even far away from the agro-ecosystem where the chemicals were applied.
ESTHER : Wang_2022_Front.Physiol_13_879216
PubMedSearch : Wang_2022_Front.Physiol_13_879216
PubMedID: 35784886

Title : Substrate-dependent inhibition of hypericin on human carboxylesterase 2: implications for herb-drug combination - Wang_2022_Curr.Drug.Metab__
Author(s) : Wang D , Zhao T , Zhao S , Chen J , Dou T , Ge G , Wang C , Sun H , Liu K , Meng Q , Wu J
Ref : Curr Drug Metab , : , 2022
Abstract : BACKGROUND: Hypericin is the main active ingredient of St. John's wort, a Chinese herb commonly used in treating depression. Previous studies have shown that hypericin can strongly inhibit human cytochrome P450 (CYP) enzyme activities; however, its potential interactions that inhibit human carboxylesterases 2 (hCE2) were unclear. PURPOSE: The study aimed to investigate the inhibition of hypericin on hCE2. METHODS: The inhibition of hypericin on hCE2 was studied by using N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN). The type of inhibition of hypericin on hCE2 and the corresponding inhibition constant (Ki) value were determined. The inhibition of hypericin on hCE2 in living cells was discussed. The herb-drug interactions (HDI) risk of hypericin and hCE2 in vivo was predicted by estimating the drug concentration-time curve (AUC) ratio of hypericin and hypericin free. To understand the inhibition mechanism of hypericin on the activity of hCE2 in-depth, molecular docking was performed. RESULTS: The half-maximal inhibitory concentration (IC50) values of hypericin against the hydrolysis of NCEN and irinotecan (CPT-11) were calculated to be 26.59 microM and 112.8 microM, respectively. Hypericin inhibited the hydrolysis of NCEN and CPT-11. Their Ki values were 10.53 microM and 81.77 microM, respectively. Moreover, hypericin distinctly suppressed hCE2 activity in living cells. In addition, the AUC of hCE2 metabolic drugs with metabolic sites similar to NCEN was estimated to increase by up to 5%, in the presence of hypericin. More importantly, the exposure of CPT-11 in the intestinal epithelium was predicted to increase by 2%-69% following the oral co-administration of hypericin. Further, molecular simulations indicated that hypericin could strongly interact with ASP98, PHE307, and ARG355 to form four hydrogen bonds within hCE2. CONCLUSION: These findings are of considerable clinical significance to the combination of hypericin-containing herbs and drugs metabolized by hCE2.
ESTHER : Wang_2022_Curr.Drug.Metab__
PubMedSearch : Wang_2022_Curr.Drug.Metab__
PubMedID: 35114918

Title : Expression and structural analysis of human neuroligin 2 and neuroligin 3 implicated in autism spectrum disorders - Zhang_2022_Front.Endocrinol.(Lausanne)_13_1067529
Author(s) : Zhang Z , Hou M , Ou H , Wang D , Li Z , Zhang H , Lu J
Ref : Front Endocrinol (Lausanne) , 13 :1067529 , 2022
Abstract : The development of autism spectrum disorders (ASDs) involves both environmental factors such as maternal diabetes and genetic factors such as neuroligins (NLGNs). NLGN2 and NLGN3 are two members of NLGNs with distinct distributions and functions in synapse development and plasticity. The relationship between maternal diabetes and NLGNs, and the distinct working mechanisms of different NLGNs currently remain unclear. Here, we first analyzed the expression levels of NLGN2 and NLGN3 in a streptozotocin-induced ASD mouse model and different brain regions to reveal their differences and similarities. Then, cryogenic electron microscopy (cryo-EM) structures of human NLGN2 and NLGN3 were determined. The overall structures are similar to their homologs in previous reports. However, structural comparisons revealed the relative rotations of two protomers in the homodimers of NLGN2 and NLGN3. Taken together with the previously reported NLGN2-MDGA1 complex, we speculate that the distinct assembly adopted by NLGN2 and NLGN3 may affect their interactions with MDGAs. Our results provide structural insights into the potential distinct mechanisms of NLGN2 and NLGN3 implicated in the development of ASD.
ESTHER : Zhang_2022_Front.Endocrinol.(Lausanne)_13_1067529
PubMedSearch : Zhang_2022_Front.Endocrinol.(Lausanne)_13_1067529
PubMedID: 36479216
Gene_locus related to this paper: human-NLGN2 , human-NLGN3

Title : Improved pea reference genome and pan-genome highlight genomic features and evolutionary characteristics - Yang_2022_Nat.Genet_54_1553
Author(s) : Yang T , Liu R , Luo Y , Hu S , Wang D , Wang C , Pandey MK , Ge S , Xu Q , Li N , Li G , Huang Y , Saxena RK , Ji Y , Li M , Yan X , He Y , Liu Y , Wang X , Xiang C , Varshney RK , Ding H , Gao S , Zong X
Ref : Nat Genet , 54 :1553 , 2022
Abstract : Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future.
ESTHER : Yang_2022_Nat.Genet_54_1553
PubMedSearch : Yang_2022_Nat.Genet_54_1553
PubMedID: 36138232
Gene_locus related to this paper: pea-a0a9d4zt76

Title : Probing strigolactone perception mechanisms with rationally designed small-molecule agonists stimulating germination of root parasitic weeds - Wang_2022_Nat.Commun_13_3987
Author(s) : Wang D , Pang Z , Yu H , Thiombiano B , Walmsley A , Yu S , Zhang Y , Wei T , Liang L , Wang J , Wen X , Bouwmeester HJ , Yao R , Xi Z
Ref : Nat Commun , 13 :3987 , 2022
Abstract : The development of potent strigolactone (SL) agonists as suicidal germination inducers could be a useful strategy for controlling root parasitic weeds, but uncertainty about the SL perception mechanism impedes real progress. Here we describe small-molecule agonists that efficiently stimulate Phelipanchce aegyptiaca, and Striga hermonthica, germination in concentrations as low as 10(-8) to 10(-17) M. We show that full efficiency of synthetic SL agonists in triggering signaling through the Striga SL receptor, ShHTL7, depends on the receptor-catalyzed hydrolytic reaction of the agonists. Additionally, we reveal that the stereochemistry of synthetic SL analogs affects the hydrolytic ability of ShHTL7 by influencing the probability of the privileged conformations of ShHTL7. Importantly, an alternative ShHTL7-mediated hydrolysis mechanism, proceeding via nucleophilic attack of the NE2 atom of H246 to the 2'C of the D-ring, is reported. Together, our findings provide insight into SL hydrolysis and structure-perception mechanisms, and potent suicide germination stimulants, which would contribute to the elimination of the noxious parasitic weeds.
ESTHER : Wang_2022_Nat.Commun_13_3987
PubMedSearch : Wang_2022_Nat.Commun_13_3987
PubMedID: 35810153

Title : Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation - Zhang_2022_Int.J.Mol.Sci_23_16182
Author(s) : Zhang H , Wang D , Sun J , Wang Y , Wu S , Wang J
Ref : Int J Mol Sci , 23 :16182 , 2022
Abstract : Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_16182
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_16182
PubMedID: 36555825

Title : Glutathione-modified graphene quantum dots as fluorescent probes for detecting organophosphorus pesticide residues in Radix Angelica Sinensis - Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
Author(s) : Mu XQ , Wang D , Meng LY , Wang YQ , Chen J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 286 :122021 , 2022
Abstract : A novel fluorescent sensor was developed in this study based on glutathione-functionalized graphene quantum dots (GQDs@GSH) to detect organophosphorus pesticide residues in Radix Angelica Sinensis. GQDs@GSH was synthesized by a one-step pyrolysis method with a fluorescence quantum yield as high as 33.9% and its structure was characterized by transmission electron microscopy and X-ray photoelectron spectroscopy. GQDs@GSH exhibited excellent fluorescence property showing strong blue fluorescence under UV irradiation. The fluorescence of GQDs@GSH could be quenched by Fe(3+) by electron transfer and the quenched fluorescence could be recovered due to the strong chelating and reducing ability of phytic acid (PA). Under the catalyzation of acetylcholinesterase (AChE) and choline oxidase (ChOx), acetylcholine (ACh) could be decomposed to H(2)O(2), which could further oxidize Fe(2+) to Fe(3+) thus quenching the fluorescence of GQDs@GSH once again. Coumaphos, a kind of organophosphorus pesticide, could inhibit AChE activity, thus making the quenched fluorescence turn on again. Several parameters influencing the fluorescence response such as Fe(3+), PA, ACh and coumaphos concentration, pH value and reaction time were optimized. Based on such a fluorescence "off-on-off-on" ngkmechanism, GQDs@GSH was successfully applied to the detection of coumaphos in Radix Angelica Sinensis. A good linear relationship between the fluorescence intensity and coumaphos concentration was obtained in the range of 0.1-10.0 micromol.L(-1). By a standard addition method, the recoveries were measured to be 101.44-117.90% with RSDs lower than 1.98%. The biosensor system is simple, sensitive and accurate. It has a good application prospect in the detection of organophosphorus pesticide residues in traditional Chinese medicine and agricultural products, and also expanded the application scope for glutathione as a highly selective biological molecule.
ESTHER : Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
PubMedSearch : Mu_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_286_122021
PubMedID: 36283209

Title : Comparison of the Inhibitory Effects of Clotrimazoleand Ketoconazole against Human Carboxylesterase 2 - Zhao_2021_Curr.Drug.Metab__
Author(s) : Zhao T , Wang D , Shan Z , Chen J , Dou T , Ge G , Wang C , Meng Q , Sun H , Liu K , Wu J
Ref : Curr Drug Metab , : , 2021
Abstract : BACKGROUND: Both clotrimazole and ketoconazole have been verified that they have an inhibitory effect on CYP3A4. hCE2 is an enzyme closely related to the side effects of several anti-cancer drugs. However, the interactions between hCE2 and clotrimazole and ketoconazole remain unclear. OBJECTIVE: The objective of this study was to investigate and compare the inhibition behaviors of these two antifungal agents, ketoconazole and clotrimazole, on the human liver microsome hCE2 and to explore the underlying mechanism. METHODS: The inhibitory effects were investigated in human liver microsomes (HLMs) using fluorescein diacetate (FD), N-(2-butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-chloroacetamide (NCEN) and irinotecan (CPT-11) as substrates of hCE2. RESULTS: Clotrimazole significantly inhibited the hCE2 activity, which was manifested by attenuated fluorescence when the substrates were FD and NCEN. The inhibitory effect of clotrimazole towards hCE2 was much stronger than that of ketoconazole, and the inhibitory behaviors displayed substrate-dependent inhibition. The IC50 value of clotrimazole with CPT-11 as the substate increased by 5 and 37 times than that with FD and NCEN respectively. Furthermore, the inhibitions of clotrimazole towards hCE2-mediated hydrolysis of FD, NCEN and CPT-11 were all in competitive mode with the Ki values of 0.483 microM, 8.63 microM and 29.0 microM, respectively. Molecular docking result of clotrimazole binding to hCE2 illustrated that clotrimazole could efficiently orient itself in the Z site cavity of hCE2. CONCLUSION: Clotrimazole displayed a strong inhibitory effect against hCE2, which might be used as a potential combined agent co-administrated with CPT-11 to alleviate the hCE2-mediated severe side effects.
ESTHER : Zhao_2021_Curr.Drug.Metab__
PubMedSearch : Zhao_2021_Curr.Drug.Metab__
PubMedID: 33568030

Title : The Roles of Dipeptidyl Peptidase 4 (DPP4) and DPP4 Inhibitors in Different Lung Diseases: New Evidence - Zhang_2021_Front.Pharmacol_12_731453
Author(s) : Zhang T , Tong X , Zhang S , Wang D , Wang L , Wang Q , Fan H
Ref : Front Pharmacol , 12 :731453 , 2021
Abstract : CD26/Dipeptidyl peptidase 4 (DPP4) is a type II transmembrane glycoprotein that is widely expressed in various organs and cells. It can also exist in body fluids in a soluble form. DPP4 participates in various physiological and pathological processes by regulating energy metabolism, inflammation, and immune function. DPP4 inhibitors have been approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes mellitus. More evidence has shown the role of DPP4 in the pathogenesis of lung diseases, since it is highly expressed in the lung parenchyma and the surface of the epithelium, vascular endothelium, and fibroblasts of human bronchi. It is a potential biomarker and therapeutic target for various lung diseases. During the coronavirus disease-19 (COVID-19) global pandemic, DPP4 was found to be an important marker that may play a significant role in disease progression. Some clinical trials on DPP4 inhibitors in COVID-19 are ongoing. DPP4 also affects other infectious respiratory diseases such as Middle East respiratory syndrome and non-infectious lung diseases such as pulmonary fibrosis, lung cancer, chronic obstructive pulmonary disease (COPD), and asthma. This review aims to summarize the roles of DPP4 and its inhibitors in infectious lung diseases and non-infectious diseases to provide new insights for clinical physicians.
ESTHER : Zhang_2021_Front.Pharmacol_12_731453
PubMedSearch : Zhang_2021_Front.Pharmacol_12_731453
PubMedID: 34955820

Title : Transcriptional regulation of carboxylesterase 1 (CES1) in human liver: role of the nuclear receptor NR1H3 (LXRalpha) and its splice isoforms - Collins_2021_Drug.Metab.Dispos__
Author(s) : Collins JM , Lu R , Wang X , Zhu HJ , Wang D
Ref : Drug Metabolism & Disposition: The Biological Fate of Chemicals , : , 2021
Abstract : Carboxylesterase 1 (CES1) is the predominant carboxylesterase in the human liver, involved in metabolism of both xenobiotics and endogenous substrates. Genetic or epigenetic factors that alter CES1 activity or expression are associated with changes in drug response, lipid, and glucose homeostasis. However, the transcriptional regulation of CES1 in the human liver remains uncertain. By applying both the random forest and Sobol's Sensitivity Indices (SSI) to analyze existing liver RNA expression microarray data (GSE9588), we identified NR1H3 (LXRalpha) as a key factor regulating constitutive CES1 expression. This model prediction was validated using siRNA knockdown and CRISPR-mediated transcriptional activation of NR1H3 in Huh7 and HepG2 cells. We found that NR1H3's activation of CES1 is splice isoform-specific, namely that increased expression of the NR1H3-211 isoform increased CES1 expression while NR1H3-201 did not. Also, in human liver samples, expression of NR1H3-211 and CES1 are correlated, while NR1H3-201 and CES1 are not. This trend also occurs during differentiation of induced pluripotent stem cells (iPSCs) to hepatocytes, where only expression of the NR1H3-211 isoform parallels expression of CES1 Moreover, we found that treatment with the NR1H3 agonist T0901317 in HepG2 cells had no effect on CES1 expression. Overall, our results demonstrate a key role of NR1H3 in maintaining the constitutive expression of CES1 in the human liver. Furthermore, our results support that the effect of NR1H3 is splice isoform-specific and appears to be ligand independent. Significance Statement Despite the central role of CES1 in metabolism of numerous medications, little is known about its transcriptional regulation. Here we identify NR1H3 as a key regulator of constitutive CES1 expression, and therefore is a potential target for future studies to understand inter-person variabilities in CES1 activity and drug metabolism.
ESTHER : Collins_2021_Drug.Metab.Dispos__
PubMedSearch : Collins_2021_Drug.Metab.Dispos__
PubMedID: 34697082
Gene_locus related to this paper: human-CES1

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

Title : Thifluzamide exposure induced neuro-endocrine disrupting effects in zebrafish (Danio rerio) - Yang_2021_Arch.Toxicol__
Author(s) : Yang Y , Chang J , Wang D , Ma H , Li Y , Zheng Y
Ref : Archives of Toxicology , : , 2021
Abstract : Thifluzamide is widely used fungicide and frequently detected in aquatic system. In this study, the toxicity of fungicide thifluzamide to non-targeted aquatic organisms was investigated for neuroendocrine disruption potentials. Here, zebrafish embryos were exposed to a series of concentrations of thifluzamide for 6 days. The results showed that both the development of embryos/larvae and the behavior of hatched larvae were significantly affected by thifluzamide. Importantly, the decreased activity of acetylcholinesterase (AchE) and the increased contents of neurotransmitters such as serotonin (5-HT) and norepinephrine (NE), along with transcriptional changes of nervous system related genes were observed following 4 days exposure to thifluzamide. Besides, the decreased contents of triiodothyronine (T3) and thyroxine (T4) in whole body, as well as significant expression alteration in hypothalamic-pituitary-thyroid (HPT) axis associated genes were discovered in zebrafish embryos after 4 days of exposure to thifluzamide. Our results clearly demonstrated that zebrafish embryos exposed to thifluzamide could disrupt neuroendocrine, compromise behavior and induce developmental abnormality, suggesting impact of this fungicide on developmental programming in zebrafish.
ESTHER : Yang_2021_Arch.Toxicol__
PubMedSearch : Yang_2021_Arch.Toxicol__
PubMedID: 34635929

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

Title : Berberine Ameliorates Glucose Metabolism in Diabetic Rats through the alpha7 Nicotinic Acetylcholine Receptor-Related Cholinergic Anti-Inflammatory Pathway - Wang_2021_Planta.Med__
Author(s) : Wang D , Ren Y , Sun W , Gong J , Zou X , Dong H , Xu L , Wang K , Lu F
Ref : Planta Med , : , 2021
Abstract : Berberine is an isoquinoline derivative alkaloid extracted from Chinese herbs. Recent studies have demonstrated the therapeutic effect of berberine on glucose metabolic disorders. However, its specific mechanism is still unclear. Our study aimed to research the glucose-lowering effect of berberine in diabetic rats and to reveal the possible role of the cholinergic anti-inflammatory pathway. Diabetic rats induced by administration of a high-calorie diet and streptozocin tail vein injection were assessed by the oral glucose tolerance test. Then, the diabetic rats were divided into two groups, those with or without the alpha7 nicotinic acetylcholine receptor gene downregulated, respectively, followed by treatment including berberine for 6 weeks. Results of this study show that the administration of berberine downregulated levels of fasting blood glucose and fasting insulin, and ameliorated insulin resistance in diabetic rats. Treatment with berberine inhibited acetylcholinesterase activity, and upregulated acetylcholine levels in the serum and alpha7 nicotinic acetylcholine receptor gene expression in the liver tissue. Meanwhile, berberine reversed elevated expression of cytokines interleukin-1beta and TNF-alpha in the serum and downregulated nuclear factor kappaB expression. However, berberine administration showed no glucose-lowering or anti-inflammatory effect in diabetic rats in which alpha7 nicotinic acetylcholine receptor gene expression was downregulated, and acetylcholinesterase activity was also significantly inhibited. In conclusion, berberine may ameliorate glucose metabolism by activating the alpha7 nicotinic acetylcholine receptor-mediated cholinergic anti-inflammatory pathway.
ESTHER : Wang_2021_Planta.Med__
PubMedSearch : Wang_2021_Planta.Med__
PubMedID: 33682914

Title : Catalytic Descriptors to Investigate Catalytic Power in the Reaction of Haloalkane Dehalogenase Enzyme with 1,2-Dichloroethane - Xin_2021_Int.J.Mol.Sci_22_
Author(s) : Xin X , Li C , Gao D , Wang D
Ref : Int J Mol Sci , 22 : , 2021
Abstract : Enzymes play a fundamental role in many biological processes. We present a theoretical approach to investigate the catalytic power of the haloalkane dehalogenase reaction with 1,2-dichloroethane. By removing the three main active-site residues one by one from haloalkane dehalogenase, we found two reactive descriptors: one descriptor is the distance difference between the breaking bond and the forming bond, and the other is the charge difference between the transition state and the reactant complex. Both descriptors scale linearly with the reactive barriers, with the three-residue case having the smallest barrier and the zero-residue case having the largest. The results demonstrate that, as the number of residues increases, the catalytic power increases. The predicted free energy barriers using the two descriptors of this reaction in water are 23.1 and 24.2 kcal/mol, both larger than the ones with any residues, indicating that the water solvent hinders the reactivity. Both predicted barrier heights agree well with the calculated one at 25.2 kcal/mol using a quantum mechanics and molecular dynamics approach, and also agree well with the experimental result at 26.0 kcal/mol. This study shows that reactive descriptors can also be used to describe and predict the catalytic performance for enzyme catalysis.
ESTHER : Xin_2021_Int.J.Mol.Sci_22_
PubMedSearch : Xin_2021_Int.J.Mol.Sci_22_
PubMedID: 34072602

Title : Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus - Liu_2021_Front.Neural.Circuits_15_638000
Author(s) : Liu X , Shi M , Ren H , Xie M , Zhang C , Wang D , Li J , Wang M
Ref : Front Neural Circuits , 15 :638000 , 2021
Abstract : Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme-DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, P < 0.05). Our findings demonstrated Vme-DMV circuit via which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level.
ESTHER : Liu_2021_Front.Neural.Circuits_15_638000
PubMedSearch : Liu_2021_Front.Neural.Circuits_15_638000
PubMedID: 33776655

Title : Toxicological and biochemical analyses demonstrate no toxic effect of Bt maize on the Folsomia candida - Jiang_2020_PLoS.One_15_e0232747
Author(s) : Jiang Z , Zhou L , Wang B , Wang D , Wu F , Yin J , Song X
Ref : PLoS ONE , 15 :e0232747 , 2020
Abstract : The potential effects of Bt (Bacillus thuringiensis) maize on non-target organisms must be conducted before the Bt maize is commercially planted. Folsomia candida is one of the non-target organisms of Bt maize, also as an important indicator of soil quality and environmental pollution. In this study, a 90-day F. candida feeding test were conducted to evaluate the potential effects of two Bt maize lines IE09S034 and BT799 and their non-Bt conventional isolines Zong 31 and Zheng 58. The results show that Bt maize lines had no significant effects on the survival rate, reproduction, adult body length, larval body length, and the activities of acetyl cholinesterase, catalase and superoxide dismutase on the F. candida. Namely, Bt maize had no toxic effects on the F. candida.
ESTHER : Jiang_2020_PLoS.One_15_e0232747
PubMedSearch : Jiang_2020_PLoS.One_15_e0232747
PubMedID: 32374765

Title : New Flavoalkaloids with Potent alpha-Glucosidase and Acetylcholinesterase Inhibitory Activities from Yunnan Black Tea 'Jin-Ya' - Li_2020_J.Agric.Food.Chem_68_7955
Author(s) : Li N , Zhu HT , Wang D , Zhang M , Yang CR , Zhang YJ
Ref : Journal of Agricultural and Food Chemistry , 68 :7955 , 2020
Abstract : As the subgroup of flavoalkaloids, N-ethyl-2-pyrrolidinone substituted flavan-3-ols are reported to possess various biological activities that may play important roles in the beneficial healthcare functions of tea. The HPLC and LC-MS analyses showed the existence of N-ethyl-2-pyrrolidinone substituted flavan-3-ols in 'Jin-Ya', which is a Yunnan black tea produced only from buds of tea plant, Camellia sinensis var. assamica. Further phytochemical study on this precious black tea led to the identification of eight flavoalkaloids, 1-8, along with 11 known flavan-3-ols (9-14) and flavonol glycosides (15-19). The new compounds, (-)-6-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin (1), (-)-8-(5''R)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2a) and (-)-8-(5''S)-N-ethyl-2-pyrrolidinone-epiafzelechin-3-O-gallate (2b), were identified based on extensive spectroscopic analysis. Flavoalkaloids 2-6 showed inhibitory activity on alpha-glucosidase with IC50 values ranging from 2.09 to 8.47 muM, comparing to those of quercetin and acarbose (IC50 = 6.87 and 228.9 muM, resp.). Moreover, compounds 2, 3 and 6 displayed inhibitory effect on acetyl-cholinesterase with IC50 values of 14.23, 33.79 and 34.82 muM, respectively, comparing to tacrine (IC50 = 0.223 muM).
ESTHER : Li_2020_J.Agric.Food.Chem_68_7955
PubMedSearch : Li_2020_J.Agric.Food.Chem_68_7955
PubMedID: 32628847

Title : Ecological risk assessment of heavy metals in fish from the Dianchi Lake, China using the integrated biomarker response approach - Gao_2020_Environ.Sci.Pollut.Res.Int_27_45712
Author(s) : Gao Y , Fang L , Xiang QQ , Wang D , Ding LY , Ding CZ , Chen LQ
Ref : Environ Sci Pollut Res Int , 27 :45712 , 2020
Abstract : This study used the integrated biomarker response (IBR) index approach to assess the ecological risks of heavy metals in different regions of Dianchi Lake, combined with active monitoring and passive monitoring. The contents of five heavy metals (Cu, As, Cd, Hg, and Pb) and six biomarkers (acetylcholinesterase, sodium-potassium ATPase, metallothionein, superoxide dismutase, glutathione peroxidase, and malondialdehyde) in the muscles of crucians (Carassius auratus) were measured to calculate the IBR value. The results indicate that the contents of heavy metal in the fish under active monitoring and passive monitoring were rather low and did not exceed the National Food Safety Standards of China. The IBR value of day 14 of active monitoring correlated with the heavy metal Cd content in the fish, suggesting a potential risk of Cd pollution in the aquatic environment of Dianchi Lake. The IBR values obtained for different regions of the lake on day 14 can be arranged in the following order: West S3 (9.24) > East S1 (3.97) > South S2 (2.39) > North S4 (0.36). These results suggest a potential risk of heavy metal contamination in the western part of Dianchi Lake.
ESTHER : Gao_2020_Environ.Sci.Pollut.Res.Int_27_45712
PubMedSearch : Gao_2020_Environ.Sci.Pollut.Res.Int_27_45712
PubMedID: 32803585

Title : Effects of ammonia exposure on antioxidant function, immune response and NF-kappaB pathway in Chinese Strip-necked Turtle (Mauremys sinensis) - Liang_2020_Aquat.Toxicol__105621
Author(s) : Liang L , Huang Z , Li N , Wang D , Ding L , Shi H , Hong M
Ref : Aquat Toxicol , :105621 , 2020
Abstract : As one of the main toxic substances in aquaculture water, ammonia causes seriously physiological harm to aquatic animals. In order to investigate the effects of ammonia exposure on the antioxidant defense, immune response, and NF-kappaB signaling pathway in Chinese Strip-necked Turtle (Mauremys sinensis), we designed two experimental groups (control and 6.45 mM ammonia), and sampled at 6 h, 24 h, 48 h, re 24 h (recover 24 h), and re 48 h. The results showed that the blood ammonia (BA) content was significantly increased when the turtles were subjected to ammonia, and the activities of cholinesterase (CHE) and aspartate aminotransferase (AST) in the serum also showed a significant upward trend. The malondialdehyde (MDA) content continuously increased during ammonia exposure, and more than doubled at 48 h compared with the control group. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) and their corresponding relative mRNA expression levels in the liver during ammonia exposure were obviously increased when compared to the control group, but most decreased to the normal levels at re 48 h. In addition, the relative mRNA and protein expression levels of NF-E2 related factor 2 (Nrf2) showed similar up-regulation patterns to antioxidase during ammonia exposed periods; whereas kelch-like ECH-binding protein 1 (Keap1), as Nrf2 negative regulator, showed opposite patterns. Moreover, the relative mRNA expression levels of heat shock proteins (HSP70, HSP90) significantly elevated upon the exposure of ammonia. Furthermore, ammonia increased the relative mRNA and protein expression levels of p50 and p65 at different exposed times. The reative mRNA expression levels of immune cytokines (BAFF and IL-6) were upregulated during ammonia exposured time, while there was a decline but did not return to normal levels, in the recovery periods. Taken together, these results indicated that antioxidation, immunity, and NF-kappaB signaling played a certain protective role for Mauremys sinensis under ammonia exposure. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in turtles.
ESTHER : Liang_2020_Aquat.Toxicol__105621
PubMedSearch : Liang_2020_Aquat.Toxicol__105621
PubMedID: 33129562

Title : Crystal structure and biochemical characterization of Striga hermonthica HYPO-SENSITIVE TO LIGHT 8 (ShHTL8) in strigolactone signaling pathway - Zhang_2020_Biochem.Biophys.Res.Commun_523_1040
Author(s) : Zhang Y , Wang D , Shen Y , Xi Z
Ref : Biochemical & Biophysical Research Communications , 523 :1040 , 2020
Abstract : Striga is a parasitic weed that disperses easily, and its seeds can persist in the soil for many years, presenting long-term threats to food security. If SLs stimulate the seed germination of root parasitic weeds before planting, weeds will wither due to no host. Therefore, it is necessary to determine the mechanism of strigolactone (SL) signaling in Striga to reduce the impacts of this parasitic weed. Striga has eleven different kinds of HYPO-SENSITIVE to LIGHT (ShHTL) hydrolases. Different ShHTL hydrolases exhibit distinct responses to SLs, despite these ShHTLs exhibiting more than 60% sequence identity. Currently, structural information is available for only five ShHTL proteins, and more structural information is needed to design Striga germination stimulants or inhibitors. In this paper, we report the crystal structure of ShHTL8, which is determined at a resolution of 1.4 A. Scanning fluorimetry and HPLC assays indicate that L125, M147, M154 and I194 are important binding sites, and of which L125 may act as a key holder involved in the catalytic reaction. Additionally, the corresponding residue, Y124 of ShHTL1 and F135 of ShHTL2 also play a significant role in the substrate recognition.
ESTHER : Zhang_2020_Biochem.Biophys.Res.Commun_523_1040
PubMedSearch : Zhang_2020_Biochem.Biophys.Res.Commun_523_1040
PubMedID: 31973817
Gene_locus related to this paper: strhe-ShHTL8

Title : Perinatal exposure to 2-Ethylhexyl Diphenyl Phosphate (EHDPHP) affected the metabolic homeostasis of male mouse offspring: Unexpected findings help to explain dose- and diet- specific phenomena - Yan_2020_J.Hazard.Mater_388_122034
Author(s) : Yan S , Wang D , Teng M , Meng Z , Yan J , Li R , Jia M , Tian S , Zhou Z , Zhu W
Ref : J Hazard Mater , 388 :122034 , 2020
Abstract : The environmental health risks of a new type of organophosphate flame retardant, 2-ethylhexyl diphenyl phosphate (EHDPHP), which is present in large quantities in various Nordic foods, have attracted the attention of scientists recently. In this study, the metabolic homeostasis of low-fat diet (LFD) and high-fat diet (HFD) fed male mice offspring was assessed after perinatal exposure to two doses (30 microg/kg bw/day and 300 microg/kg bw/day) of EHDPHP. Perinatal exposure to EHDPHP resulted in weight changes in male mice offspring, altered glucose tolerance and induced liver damage, and surprisingly these changes were dose- and diet- specific. Then the (1)H NMR-based metabolomics, 16S rRNA sequencing, and qRT-PCR techniques were used to explore the mechanisms of these specific changes. The results indicate that the increase in short-chain fatty acids and the increase in Clostridium in the high-dose group may be responsible for the dose-specificity, while the attenuation of the purine metabolic pathway and the decrease in glutamine levels in the HFD group are accountable for the diet-specificity. In addition, down-regulation of PPARG (peroxisome proliferator-activated receptor gamma) gene expression levels might have caused the decrease in body weight in the H + HFD (high dose exposure with HFD feeding) group. Over all, these results elucidated the effects of dosage and diet on the toxicology of EHDPHP.
ESTHER : Yan_2020_J.Hazard.Mater_388_122034
PubMedSearch : Yan_2020_J.Hazard.Mater_388_122034
PubMedID: 31951990

Title : The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea - Zou_2020_BMC.Complement.Med.Ther_20_236
Author(s) : Zou Y , Hu J , Huang W , Zhu L , Shao M , Dordoe C , Ahn YJ , Wang D , Zhao Y , Xiong Y , Wang X
Ref : BMC Complement Med Ther , 20 :236 , 2020
Abstract : BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human beta-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC(50) from 292.0 to 673.9 microg/mL. Fourteen samples presented potent inhibitory activity against human BACE1 with EC(50) from 236.0 to 881.1 microg/mL. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC(50) from 2.7 to 14.4mG/Ml, 0.9 to 12.7mG/Ml, 5.0 to > 25mG/Ml, 2.7 to 17.7mG/Ml, and 2.4 to 8.7mG/Ml, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.
ESTHER : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedSearch : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedID: 32711521

Title : Effect of a Novel Alpha\/Beta Hydrolase Domain Protein on Tolerance of K. marxianus to Lignocellulosic Biomass Derived Inhibitors - Wu_2020_Front.Bioeng.Biotechnol_8_844
Author(s) : Wu D , Wang D , Hong J
Ref : Front Bioeng Biotechnol , 8 :844 , 2020
Abstract : The multiple inhibitors tolerance of microorganism is important in bioconversion of lignocellulosic biomass which is a promising renewable and sustainable source for biofuels and other chemicals. The disruption of an unknown alpha/beta hydrolase, which was termed KmYME and located in mitochondria in this study, resulted in the yeast more susceptible to lignocellulose-derived inhibitors, particularly to acetic acid, furfural and 5-HMF. The KmYME disrupted strain lost more mitochondrial membrane potential, showed increased plasma membrane permeability, severer redox ratio imbalance, and increased ROS accumulation, compared with those of the non-disrupted strain in the presence of the same inhibitors. The intracellular concentration of ATP, NAD and NADP in the KmYME disrupted strain was decreased. However, disruption of KmYME did not result in a significant change of gene expression at the transcriptional level. The KmYME possessed esterase/thioesterase activity which was necessary for the resistance to inhibitors. In addition, KmYME was also required for the resistance to other stresses including ethanol, temperature, and osmotic pressure. Disruption of two possible homologous genes in S. cerevisiae also reduced its tolerance to inhibitors.
ESTHER : Wu_2020_Front.Bioeng.Biotechnol_8_844
PubMedSearch : Wu_2020_Front.Bioeng.Biotechnol_8_844
PubMedID: 32850717
Gene_locus related to this paper: kluma-w0t4a7

Title : Construction and application of a high-content analysis for identifying human carboxylesterase 2 inhibitors in living cell system - Xue_2020_Anal.Bioanal.Chem__
Author(s) : Xue L , Qian X , Jin Q , Zhu Y , Wang X , Wang D , Ge G , Yang L
Ref : Anal Bioanal Chem , : , 2020
Abstract : Human carboxylesterase 2 (hCE2), one of the most principal drug-metabolizing enzymes, catalyzes the hydrolysis of a variety of endogenous esters, anticancer agents, and environmental toxicants. The significant roles of hCE2 in both endobiotic and xenobiotic metabolism sparked great interest in the discovery and development of efficacious and selective inhibitors. However, the safe and effective inhibitors of hCE2 are scarce, due to the lack of efficient screening and evaluation systems for complex biological systems. To offer a solution to this problem, a high-content analysis (HCA)-based cell imaging and multiparametric assay method was constructed for evaluating the inhibitory effect and safety of hCE2 inhibitors in living cell system. In this study, we first established a cell imaging-based method for identifying hCE2 inhibitors at the living cell level with hCE2 fluorescent probe NCEN. Meanwhile, two nuclear probes, Hoechst 33342 and PI, were integrated to evaluate the potential cytotoxicity of compounds simultaneously. Then, the accuracy of the HCA-based method was verified by the LC-FD-based method with a positive inhibitor BNPP, and the results showed that the HCA-based method exhibited excellent precision, robustness, and reliability. Finally, the newly established HCA-based multiparametric assay panel was successfully applied to re-evaluate a series of reported hCE2 inhibitors in living cells. In summary, the HCA-based multiparametric method could serve as an efficient tool for the accuracy measurement inhibitory effect and cytotoxicity of compounds against hCE2 in living cell system. Graphical abstract.
ESTHER : Xue_2020_Anal.Bioanal.Chem__
PubMedSearch : Xue_2020_Anal.Bioanal.Chem__
PubMedID: 32123952

Title : 4-Benzyloxylonchocarpin and Muracatanes A-C from Ranunculus muricatus L. and Their Biological Effects - Hussain_2020_Biomolecules_10_
Author(s) : Hussain H , Ali I , Wang D , Mamadalieva NZ , Hussain W , Csuk R , Loesche A , Fischer L , Staerk D , Anam S , AlZain MN , Mushtaq M , Ul-Haq Z , Ullah R , Noman OM , Abbas G , Green IR
Ref : Biomolecules , 10 : , 2020
Abstract : Ranunculus muricatus L. is a spiny fruit buttercup that is used in various traditional medicinal systems. In the current investigation of R. muricatus, the new chalcone 4-benzyloxylonchocarpin (1), the new anthraquinone muracatanes A (2), the new-to-nature anthraquinone muracatanes B (3), and the new naphthalene analog muracatanes C (4) were isolated, in addition to the three previously reported compounds, 4-methoxylonchocarpin (5), beta-sitosterol (6), and beta-sitosterol beta-D-glucopyranoside (7). Their structures were elucidated using 1D ((1)H and (13)C) and 2D (COSY, HSQC, and HMBC) NMR spectroscopy and HR-ESI-MS. Chalcone 1 showed potent acetylcholinesterase inhibitory effects with K(i) of 5.39 microM and K(i') of 3.54 microM, but none of the isolated compounds showed inhibitory activity towards butyrylcholinesterase. Anthraquinone 3 illustrated alpha-glucosidase inhibitory effects with IC(50)-values of 164.46 +/- 83.04 microM. Compound 5 displayed moderate cytotoxic activity towards ovarian carcinoma (A2780, IC(50) = 25.4 microM), colorectal adenocarcinoma (HT29, IC(50) = 20.2 microM), breast cancer (MCF7, IC(50) = 23.7 microM), and thyroid carcinoma (SW1736, IC(50) = 26.2 microM) while it was inactive towards pharynx carcinoma (FaDu: IC(50) > 30 microM).
ESTHER : Hussain_2020_Biomolecules_10_
PubMedSearch : Hussain_2020_Biomolecules_10_
PubMedID: 33212893

Title : [Value of serum cholinesterase in the prognosis of septic shock] - Zhao_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_44
Author(s) : Zhao R , Zhang X , Wang H , Zhang R , Duan X , Liu S , Han B , Ding X , Wang D , Sun T
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 32 :44 , 2020
Abstract : OBJECTIVE: To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS). METHODS: A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation II (APACHE II) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels. RESULTS: A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHE II score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk (RR) = 1.444, 95% confidence interval (95%CI) was 1.090-1.914, P = 0.010], APACHE II score (RR = 2.249, 95%CI was 1.688-2.997, P = 0.000), SChE (RR = 1.469, 95%CI was 1.057-2.043, P = 0.022), and Lac (RR = 2.190, 95%CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHE II score and Lac was greater than APACHE II score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group (n = 88), the 28-day mortality of patients in the low SChE group (n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: chi(2) = 5.852, P = 0.016). CONCLUSIONS: Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS.
ESTHER : Zhao_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_44
PubMedSearch : Zhao_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_44
PubMedID: 32148230

Title : Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines - Zhang_2020_J.Pharm.Anal_10_253
Author(s) : Zhang J , Wang D , Zou L , Xiao M , Zhang Y , Li Z , Yang L , Ge G , Zuo Z
Ref : J Pharm Anal , 10 :253 , 2020
Abstract : In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 activities in human blood and kidney should be considered. In summary, a selective and sensitive bioluminescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.
ESTHER : Zhang_2020_J.Pharm.Anal_10_253
PubMedSearch : Zhang_2020_J.Pharm.Anal_10_253
PubMedID: 32612872

Title : Circulating lncRNA ABHD11-AS1 serves as a biomarker for early pancreatic cancer diagnosis - Liu_2019_J.Cancer_10_3746
Author(s) : Liu Y , Feng W , Liu W , Kong X , Li L , He J , Wang D , Zhang M , Zhou G , Xu W , Chen W , Gong A , Xu M
Ref : J Cancer , 10 :3746 , 2019
Abstract : Background: Recent studies have shown that circulating long noncoding RNAs (lncRNAs) could be stably detectable in the blood of cancer patients and play important roles in the diagnosis of many different cancers. However, the value of lncRNAs in the diagnosis of pancreatic cancer (PC) has not been fully explored. Methods: Eleven PC-related lncRNAs were selected by analyzing bioinformatics databases. The expression levels of the lncRNAs were further analyzed in a small set of plasma samples from a training group including 30 noncancer samples (15 healthy and 15 chronic pancreatitis (CP) subjects) and 15 PC samples. Then, the candidate lncRNAs were validated with data from 46 healthy controls, 97 CP patients and 114 PC patients. Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance of the identified lncRNAs. Results: After selection and validation, three characteristic plasma candidate lncRNAs, ABHD11-AS1, LINC00176 and SNHG11, were identified, and their levels were significantly higher in PC patients than in normal controls. We found that among the three candidate lncRNAs, ABHD11-AS1 showed the best diagnostic performance for the detection of PC. Furthermore, ABHD11-AS1 had a higher area under the ROC curve (AUC) than CEA, CA199 and CA125 for early PC diagnosis, while the combination of ABHD11-AS1 and CA199 was more effective than ABHD11-AS1 alone. Conclusions: Plasma ABHD11-AS1 could serve as a potential biomarker for detecting PC, and the combination of ABHD11-AS1 and CA199 was more efficient for the diagnosis of PC than ABHD11-AS1 alone, particularly for early tumor screening.
ESTHER : Liu_2019_J.Cancer_10_3746
PubMedSearch : Liu_2019_J.Cancer_10_3746
PubMedID: 31333792
Gene_locus related to this paper: human-ABHD11

Title : Investigation of the neuroprotective effects of crocin via antioxidant activities in HT22 cells and in mice with Alzheimer's disease - Wang_2019_Int.J.Mol.Med_43_956
Author(s) : Wang C , Cai X , Hu W , Li Z , Kong F , Chen X , Wang D
Ref : Int J Mol Med , 43 :956 , 2019
Abstract : Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including antiapoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In lglutamatedamaged HT22 cells, 3h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase3 and increased the expression levels of Bcell lymphomaextra large, phosphorylated (P) protein kinase B and Pmammalian target of rapamycin compared with untreated cells. In mice with AD induced by dgalactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Abeta142 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Abeta142 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stressassociated apoptosis signaling pathway.
ESTHER : Wang_2019_Int.J.Mol.Med_43_956
PubMedSearch : Wang_2019_Int.J.Mol.Med_43_956
PubMedID: 30569175

Title : Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer's disease - Wang_2019_Eur.J.Med.Chem_168_207
Author(s) : Wang D , Hu M , Li X , Zhang D , Chen C , Fu J , Shao S , Shi G , Zhou Y , Wu S , Zhang T
Ref : Eur Journal of Medicinal Chemistry , 168 :207 , 2019
Abstract : A series of novel isoflavone analogs were designed, synthesized, and evaluated as multitarget-directed ligands for the treatment of Alzheimer's disease. In vitro evaluations revealed that some ligands had multifunctional profiles, including potent blockage of histamine 3 receptor (H3R), excellent inhibition of acetylcholinesterase (AChE), neuroprotective effects and anti-neuroinflammatory properties. Among these derivatives, compound 9b exhibited the highest ability to block H3R (IC50=0.27muM) and good inhibitory activity against AChE (IC50=0.08muM). Additionally, compound 9b showed obvious neuroprotective effect on SH-SY5Y by preventing copper-induced neuronal damage and potent anti-neuroinflammatory activity by inhibiting the production of inflammatory factors on BV-2cells. A molecular modeling study revealed that 9b acts as a mixed-type inhibitor that interacts simultaneously with H3R and AChE. Moreover, in vivo data revealed that compound 9b did not cause acute toxicity in mice at doses up to 1000mg/kg, and had desirable pharmacokinetic properties, as well as a good blood-brain barrier (BBB) permeability (log BB=1.24+/-0.07). Further studies demonstrated that chronic oral treatment with 9b significantly improved cognitive dysfunction in scopolamine-induced AD mice in the step-down passive avoidance test. Taken together, the present study showed that compound 9b is a promising multifunctional drug candidate for the treatment of Alzheimer's disease.
ESTHER : Wang_2019_Eur.J.Med.Chem_168_207
PubMedSearch : Wang_2019_Eur.J.Med.Chem_168_207
PubMedID: 30822710

Title : Graphene oxide disrupts the protein-protein interaction between Neuroligin\/NLG-1 and DLG-1 or MAGI-1 in nematode Caenorhabditis elegans - Zhao_2019_Sci.Total.Environ_700_134492
Author(s) : Zhao Y , Chen H , Yang Y , Wu Q , Wang D
Ref : Sci Total Environ , 700 :134492 , 2019
Abstract : Graphene oxide (GO) is a carbon-based engineered nanomaterial (ENM). Using Caenorhabditis elegans as an animal model, we investigated the effect of GO exposure on protein-protein interactions. In nematodes, NLG-1/Neuroligin, a postsynaptic protein, acted only in the neurons to regulate the GO toxicity. In the neurons, DLG-1, a PSD-95 protein, and MAGI-1, a S-SCAM protein, were identified as the downstream targets of NLG-1 in the regulation of GO toxicity. PKC-1, a serine/threonine protein kinase C, further acted downstream of neuronal DLG-1 and MAGI-1 to regulate the GO toxicity. Co-immunoprecipitation analysis demonstrated the protein-protein interaction between NLG-1 and DLG-1 or MAGI-1. After GO expression, this protein-protein interaction between NLG-1 and DLG-1 or MAGI-1 was significantly inhibited. Therefore, our data raised the evidence to suggest the potential of GO exposure in disrupting protein-protein interactions in organisms.
ESTHER : Zhao_2019_Sci.Total.Environ_700_134492
PubMedSearch : Zhao_2019_Sci.Total.Environ_700_134492
PubMedID: 31627046
Gene_locus related to this paper: caeel-NLGN1 , human-NLGN1

Title : Identification of interneurons required for the aversive response of Caenorhabditis elegans to graphene oxide - Xiao_2018_J.Nanobiotechnology_16_45
Author(s) : Xiao G , Chen H , Krasteva N , Liu Q , Wang D
Ref : J Nanobiotechnology , 16 :45 , 2018
Abstract : BACKGROUND: So far, how the animals evade the environmental nanomaterials is still largely unclear. In this study, we employed in vivo assay system of Caenorhabditis elegans to investigate the aversive behavior of nematodes to graphene oxide (GO) and the underlying neuronal basis. RESULTS: In this assay model, we detected the significant aversive behavior of nematodes to GO at concentrations more than 50 mg/L. Loss-of-function mutation of nlg-1 encoding a neuroligin with the function in connecting pre- and post-synaptic neurons suppressed the aversive behavior of nematodes to GO. Moreover, based on the neuron-specific activity assay, we found that the NLG-1 activity in AIY or AIB interneurons was required for the regulation of aversive behavior to GO. The neuron-specific activities of NLG-1 in AIY or AIB interneurons were also required for the regulation of GO toxicity. CONCLUSIONS: Using nlg-1 mutant as a genetic tool, we identified the AIY and AIB interneurons required for the regulation of aversive behavior to GO. Our results provide an important neuronal basis for the aversive response of animals to environmental nanomaterials.
ESTHER : Xiao_2018_J.Nanobiotechnology_16_45
PubMedSearch : Xiao_2018_J.Nanobiotechnology_16_45
PubMedID: 29703212

Title : Effects of a novel neonicotinoid insecticide cycloxaprid on earthworm, Eisenia fetida - Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
Author(s) : Qi S , Wang D , Zhu L , Teng M , Wang C , Xue X , Wu L
Ref : Environ Sci Pollut Res Int , 25 :14138 , 2018
Abstract : Cycloxaprid (CYC) is a novel neonicotinoid insecticide with high activity against resistant pests but is safe for mammals. The toxic effects of CYC on earthworms (Eisenia fetida) were studied in this paper. The 14-day exposure results showed that CYC is potentially toxic to earthworms, with a 14d-LC50 of 10.21 mg/kg dry soil, and that it induced tissue damage to the epidermis, gut, and neurochord at sublethal doses. During a 21-day exposure, CYC induced oxidative stress in earthworms, and both enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were impacted. In addition, expression of the genes Cat and Sod were down- and upregulated, respectively. The activity of the enzyme acetylcholinesterase (AChE) was increased at day 7 but decreased at day 21 after CYC exposure, while expression of the signal transduction-related genes was significantly regulated. Our study shows for the first time that negative impacts could be induced by CYC on earthworms under both acute and chronic exposure through oxidative stress and gene regulation. The present study provides a database for assessing the environmental risk to non-target organisms resulting from the use of CYC.
ESTHER : Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
PubMedSearch : Qi_2018_Environ.Sci.Pollut.Res.Int_25_14138
PubMedID: 29520554

Title : Epidemiology of Dementia in Elderly Chronic Obstructive Pulmonary Disease Patients Living in China's Northwestern High-Elevation Area - Mei_2018_Med.Sci.Monit_24_7742
Author(s) : Mei L , Wu S , Wang D , Li H , Zhang H , Wang M
Ref : Med Sci Monit , 24 :7742 , 2018
Abstract : BACKGROUND The aim of this study was to investigate the effects of oxygen and cholinesterase inhibitor (donepezil) therapy on dementia in patients with age-exacerbated chronic obstructive pulmonary disease (COPD) in China's northwestern high-altitude area. MATERIAL AND METHODS A total of 145 patients with acute exacerbation of COPD admitted to the Gerontology Department of the First People's Hospital of Xining City were initially retrospectively screened. From among these 145 patients, we selected 33 cases with dementia and 33 patients without dementia through use of the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and Activities of Daily Living (ADL) Scale evaluated before, 7 days after, and at the end of the treatment after 3 months. Both patient groups received oxygen therapy for 7 days, but patients with dementia in the intervention group were medicated additionally with donepezil (5 mg/day for 1 week, followed by 10 mg/day for another 12 weeks). RESULTS Mild dementia was found in 35 of the 145 COPD patients. ADL, MMSE, and ADAS-Cog scores were all significantly lower in the intervention group before treatment, improved after the first 7 days, and continued to improve significantly until week 12 in the intervention group, but were still significantly lower than in the control group. CONCLUSIONS Dementia in elderly COPD patients was mainly manifested as decreased executive function, attention, language, and delayed recall, while oxygen and donepezil therapy had beneficial effects on the symptoms.
ESTHER : Mei_2018_Med.Sci.Monit_24_7742
PubMedSearch : Mei_2018_Med.Sci.Monit_24_7742
PubMedID: 30372705

Title : C-8 N-Ethyl-2-pyrrolidinone-Substituted Flavan-3-ols from the Leaves of Camellia sinensis var. pubilimba - Meng_2018_J.Agric.Food.Chem_66_7150
Author(s) : Meng XH , Zhu HT , Yan H , Wang D , Yang CR , Zhang YJ
Ref : Journal of Agricultural and Food Chemistry , 66 :7150 , 2018
Abstract : Camellia sinensis var. pubilimba, one variety of the genus Camellia sect. Thea (Theaceae), has been used for producing green tea mainly by the local people of its growing areas of Guangxi province, China. Forty compounds, including eight C-8 N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (1-8) and their substituted unit N-ethyl-5-hydroxy-2-pyrrolidinone (9), four flavan-3-ol monomers (10-13) and one dimer (14), nine flavonoids (15-23), three hydrolyzable tannins (24-26), two lignans (27-28), 11 simple phenolics (29-39), and caffeine (40), were first isolated and identified from the leaves. Their structures were determined by detailed spectroscopic analysis and comparison with the literature data and authentic samples. Both 1 and 4 were obtained as a mixture of the N-ethyl-2-pyrrolidinone C-5 enantiomers (1a and 1b and 4a and 4b), respectively, while the resolution of another three pairs of enantiomers (2 and 3, 5 and 6, and 7 and 8) was achieved. Among them, 1b is a new compound whose NMR data together with its enantiomer (1a) were reported for the first time, while 2 and 3 are two new natural products. Most of the isolates exhibited significant antioxidant activities, stronger than ascorbic acid and trolox, while parts of the isolates, particularly C-8 N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, showed obvious inhibitory effects on acetylcholinesterase (AChE). The results indicated that C. sinensis var. pubilimba is a valuable plant resource for tea production.
ESTHER : Meng_2018_J.Agric.Food.Chem_66_7150
PubMedSearch : Meng_2018_J.Agric.Food.Chem_66_7150
PubMedID: 29889511

Title : Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein - Zhang_2018_Cell.Rep_24_441
Author(s) : Zhang S , Zhou P , Wang P , Li Y , Jiang L , Jia W , Wang H , Fan A , Wang D , Shi X , Fang X , Hammel M , Wang S , Wang X , Zhang L
Ref : Cell Rep , 24 :441 , 2018
Abstract : The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the beta5-beta6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection.
ESTHER : Zhang_2018_Cell.Rep_24_441
PubMedSearch : Zhang_2018_Cell.Rep_24_441
PubMedID: 29996104

Title : Naringenin induces laxative effects by upregulating the expression levels of c-Kit and SCF, as well as those of aquaporin 3 in mice with loperamide-induced constipation - Yin_2018_Int.J.Mol.Med_41_649
Author(s) : Yin J , Liang Y , Wang D , Yan Z , Yin H , Wu D , Su Q
Ref : Int J Mol Med , 41 :649 , 2018
Abstract : Constipation is a common affliction which causes discomfort and affects the quality of life of affected individuals. Naringenin (NAR), a natural flavonoid widely found in citrus fruits and tomatoes, has been reported to exhibit various pharmacological effects, such as anti-inflammatory, anti-atherogenic, anti-mutagenic, hepatoprotective and anticancer effects. Increasing evidence has indicated that NAR has potential for use in the treatment of constipation. Thus, the aim of this study was to evaluate the laxative effects of NAR in mice with loperamide-induced (Lop-induced) constipation. The data indicated that NAR relieved Lop-induced constipation in mice based on the changes of fecal parameters (numbers, weight and water content), the intestinal charcoal transit ratio and the histological alteration. ELISA revealed that NAR regulated the production levels of gastrointestinal metabolic components, such as motilin (MTL), gastrin (Gas), endothelin (ET), substance P (SP), acetylcholinesterase (AChE) and vasoactive intestinal peptide (VIP) in serum. The expression levels of enteric nerve-related factors, glial cell line-derived neurotrophic factor (GDNF), transient receptor potential vanilloid 1 (TRPV1), nitric oxide synthase (NOS), c-Kit, stem cell factor (SCF) and aquaporin 3 (AQP3) were examined by western blot analysis and RT-PCR analysis. The results of this study suggest that NAR relieves Lop-induced constipation by increasing the levels of interstitial cells of Cajal markers (c-Kit and SCF), as well as AQP3. Thus, NAR may be effective as a candidate in patients suffering from lifestyle-induced constipation.
ESTHER : Yin_2018_Int.J.Mol.Med_41_649
PubMedSearch : Yin_2018_Int.J.Mol.Med_41_649
PubMedID: 29207043

Title : Chronic brain toxicity response of juvenile Chinese rare minnows (Gobiocypris rarus) to the neonicotinoid insecticides imidacloprid and nitenpyram - Tian_2018_Chemosphere_210_1006
Author(s) : Tian X , Yang W , Wang D , Zhao Y , Yao R , Ma L , Ge C , Li X , Huang Z , He L , Jiao W , Lin A
Ref : Chemosphere , 210 :1006 , 2018
Abstract : Imidacloprid and nitenpyram are widely used neonicotinoid pesticides worldwide and were observed to adversely affect non-target aquatic organisms. In this study, the toxic effect of imidacloprid and nitenpyram on the brain of juvenile Chinese rare minnows (Gobiocypris rarus) was investigated by determining the oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG) content and acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities did not significantly change after long-term exposure to imidacloprid and nitenpyram. A noticeable increase of catalase (CAT) activities was observed on the brain tissues under 0.1mg/L imidacloprid and under all nitenpyram treatments (p<0.05). The malondialdehyde (MDA) content increased markedly under 2.0mg/L imidacloprid and 0.1mg/L nitenpyram treatments (p<0.05). The glutathione (GSH) content in the brain significantly increased under 0.5 and 2.0mg/L imidacloprid (p<0.05). A significant decrease was observed in the mRNA levels of Cu/Zn-sod under 2.0mg/L imidacloprid and those of cat under 0.1 and 0.5mg/L nitenpyram (p<0.05). The mRNA levels of gpx1 clearly decreased under 2.0mg/L imidacloprid and under 0.1mg/L nitenpyram (p<0.05). The treatments of 0.1 and 0.5mg/L nitenpyram decreased cat expression levels markedly (p<0.05). 2.0mg/L imidacloprid raised the 8-OHdG content. The AChE activities increased markedly under 0.5 and 2.0mg/L imidacloprid while clearly decreasing under 2.0mg/L nitenpyram (p<0.05). Therefore, our results indicate that imidacloprid and nitenpyram might cause adverse effects on juvenile Chinese rare minnows brain. Notably, imidacloprid had greater impacts on juvenile rare minnows compared to nitenpyram.
ESTHER : Tian_2018_Chemosphere_210_1006
PubMedSearch : Tian_2018_Chemosphere_210_1006
PubMedID: 30208524

Title : Electrocardiogram Changes of Donepezil Administration in Elderly Patients with Ischemic Heart Disease - Wang_2018_Cardiol.Res.Pract_2018_9141320
Author(s) : Wang D , Wu Y , Wang A , Chen Y , Zhang T , Hu N
Ref : Cardiol Res Pract , 2018 :9141320 , 2018
Abstract : Objective: Donepezil, a widely used cholinesterase inhibitor for treating Alzheimer's disease, has been reported to induce bradyarrhythmias and torsade de pointes. In this study, we aimed at determining electrocardiogram changes of donepezil administration in elderly patients with ischemic heart disease, who tend to suffer from cognitive disorders. Methods: Sixty patients with ischemic heart disease and mild cognitive impairment were treated with donepezil (5 mg/day) and followed up for at least four weeks. A twenty-four-hour ambulatory electrocardiogram was performed for the analysis of heart rate variability. The ECG parameters including heart rate (HR), PR and RR intervals, QT interval, and QRS duration were recorded at the baseline and after donepezil administration. Results: Donepezil administration resulted in significant reduction in mean HR and the lowest HR and prolongation of PR and RR intervals, whereas it had no significant effects on QRS duration and QT parameters including QT, corrected QT interval, QT dispersion, and Tpeak-end interval. HRV analysis showed that donepezil administration significantly improved parasympathetic function, indicated by decreased low/high frequency (LF/HF) ratio and high frequency (HF) components and oscillation of RR intervals. Conclusions: These data demonstrated that donepezil administration decreased HR, prolonged PR interval, and increased parasympathetic function without affecting QRS duration and QT intervals, suggesting that it can be used safely in elderly patients with ischemic heart disease.
ESTHER : Wang_2018_Cardiol.Res.Pract_2018_9141320
PubMedSearch : Wang_2018_Cardiol.Res.Pract_2018_9141320
PubMedID: 29850230

Title : Human carboxylesterases: a comprehensive review - Wang_2018_Acta.Pharm.Sin.B_8_699
Author(s) : Wang D , Zou L , Jin Q , Hou J , Ge G , Yang L
Ref : Acta Pharm Sin B , 8 :699 , 2018
Abstract : Mammalian carboxylesterases (CEs) are key enzymes from the serine hydrolase superfamily. In the human body, two predominant carboxylesterases (CES1 and CES2) have been identified and extensively studied over the past decade. These two enzymes play crucial roles in the metabolism of a wide variety of endogenous esters, ester-containing drugs and environmental toxicants. The key roles of CES in both human health and xenobiotic metabolism arouse great interest in the discovery of potent CES modulators to regulate endobiotic metabolism or to improve the efficacy of ester drugs. This review covers the structural and catalytic features of CES, tissue distributions, biological functions, genetic polymorphisms, substrate specificities and inhibitor properties of CES1 and CES2, as well as the significance and recent progress on the discovery of CES modulators. The information presented here will help pharmacologists explore the relevance of CES to human diseases or to assign the contribution of certain CES in xenobiotic metabolism. It will also facilitate medicinal chemistry efforts to design prodrugs activated by a given CES isoform, or to develop potent and selective modulators of CES for potential biomedical applications.
ESTHER : Wang_2018_Acta.Pharm.Sin.B_8_699
PubMedSearch : Wang_2018_Acta.Pharm.Sin.B_8_699
PubMedID: 30245959

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

Title : Pharmacological Basis for the Use of Evodiamine in Alzheimer's Disease: Antioxidation and Antiapoptosis - Zhang_2018_Int.J.Mol.Sci_19_
Author(s) : Zhang Y , Wang J , Wang C , Li Z , Liu X , Zhang J , Lu J , Wang D
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Evodiamine (Evo), a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus, has a wide range of pharmacological activities. The present study sought to explore the neuroprotective effects of Evo in l-glutamate (l-Glu)-induced apoptosis of HT22 cells, and in a d-galactose and aluminum trichloride-developed Alzheimer’s disease (AD) mouse model. Evo significantly enhanced cell viability, inhibited the accumulation of reactive oxygen species, ameliorated mitochondrial function, increased the B-cell lymphoma-2 protein content, and inhibited the high expression levels of Bax, Bad, and cleaved-caspase-3 and -8 in l-Glu-induced HT22 cells. Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the l-Glu-induced HT22 cells. In the AD mouse model, Evo reduced the aimless and chaotic movements, reduced the time spent in the central area in the open field test, and decreased the escape latency time in the Morris water maze test. Evo reduced the deposition of amyloid beta 42 (Aβ42) in the brain, and increased the serum level of Aβ42, but showed no significant effects on Aβ40. In addition, six weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels. In the central cholinergic system of AD mice, Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum, hypothalamus, and brain. Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases.
ESTHER : Zhang_2018_Int.J.Mol.Sci_19_
PubMedSearch : Zhang_2018_Int.J.Mol.Sci_19_
PubMedID: 29883380

Title : Improved genomic resources and new bioinformatic workflow for the carcinogenic parasite Clonorchis sinensis: Biotechnological implications - Wang_2018_Biotechnol.Adv_36_894
Author(s) : Wang D , Korhonen PK , Gasser RB , Young ND
Ref : Biotechnol Adv , 36 :894 , 2018
Abstract : Clonorchis sinensis (family Opisthorchiidae) is an important foodborne parasite that has a major socioeconomic impact on ~35 million people predominantly in China, Vietnam, Korea and the Russian Far East. In humans, infection with C. sinensis causes clonorchiasis, a complex hepatobiliary disease that can induce cholangiocarcinoma (CCA), a malignant cancer of the bile ducts. Central to understanding the epidemiology of this disease is knowledge of genetic variation within and among populations of this parasite. Although most published molecular studies seem to suggest that C. sinensis represents a single species, evidence of karyotypic variation within C. sinensis and cryptic species within a related opisthorchiid fluke (Opisthorchis viverrini) emphasise the importance of studying and comparing the genes and genomes of geographically distinct isolates of C. sinensis. Recently, we sequenced, assembled and characterised a draft nuclear genome of a C. sinensis isolate from Korea and compared it with a published draft genome of a Chinese isolate of this species using a bioinformatic workflow established for comparing draft genome assemblies and their gene annotations. We identified that 50.6% and 51.3% of the Korean and Chinese C. sinensis genomic scaffolds were syntenic, respectively. Within aligned syntenic blocks, the genomes had a high level of nucleotide identity (99.1%) and encoded 15 variable proteins likely to be involved in diverse biological processes. Here, we review current technical challenges of using draft genome assemblies to undertake comparative genomic analyses to quantify genetic variation between isolates of the same species. Using a workflow that overcomes these challenges, we report on a high-quality draft genome for C. sinensis from Korea and comparative genomic analyses, as a basis for future investigations of the genetic structures of C. sinensis populations, and discuss the biotechnological implications of these explorations.
ESTHER : Wang_2018_Biotechnol.Adv_36_894
PubMedSearch : Wang_2018_Biotechnol.Adv_36_894
PubMedID: 29454982
Gene_locus related to this paper: closi-h2krw6

Title : A Verticillium dahliae Extracellular Cutinase Modulates Plant Immune Responses - Gui_2018_Mol.Plant.Microbe.Interact_31_260
Author(s) : Gui YJ , Zhang WQ , Zhang DD , Zhou L , Short DPG , Wang J , Ma XF , Li TG , Kong ZQ , Wang BL , Wang D , Li NY , Subbarao KV , Chen JY , Dai XF
Ref : Mol Plant Microbe Interact , 31 :260 , 2018
Abstract : Cutinases have been implicated as important enzymes during the process of fungal infection of aerial plant organs. The function of cutinases in the disease cycle of fungal pathogens that invade plants through the roots has been less studied. Here, functional analysis of 13 cutinase (carbohydrate esterase family 5 domain-containing) genes (VdCUTs) in the highly virulent vascular wilt pathogen Verticillium dahliae Vd991 was performed. Significant sequence divergence in cutinase family members was observed in the genome of V. dahliae Vd991. Functional analyses demonstrated that only VdCUT11, as purified protein, induced cell death and triggered defense responses in Nicotiana benthamiana, cotton, and tomato plants. Virus-induced gene silencing showed that VdCUT11 induces plant defense responses in Nicotiana benthamania in a BAK1 and SOBIR-dependent manner. Furthermore, coinfiltration assays revealed that the carbohydrate-binding module family 1 protein (VdCBM1) suppressed VdCUT11-induced cell death and other defense responses in N. benthamiana. Targeted deletion of VdCUT11 in V. dahliae significantly compromised virulence on cotton plants. The cutinase VdCUT11 is an important secreted enzyme and virulence factor that elicits plant defense responses in the absence of VdCBM1.
ESTHER : Gui_2018_Mol.Plant.Microbe.Interact_31_260
PubMedSearch : Gui_2018_Mol.Plant.Microbe.Interact_31_260
PubMedID: 29068240

Title : Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins - Wang_2018_Genetica_146_179
Author(s) : Wang D , Zhang L , Hu J , Gao D , Liu X , Sha Y
Ref : Genetica , 146 :179 , 2018
Abstract : Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of alpha/beta hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors.
ESTHER : Wang_2018_Genetica_146_179
PubMedSearch : Wang_2018_Genetica_146_179
PubMedID: 29468429

Title : Chemo-Enzymatic Synthesis of Poly(4-piperidine lactone- b-w-pentadecalactone) Block Copolymers as Biomaterials with Antibacterial Properties - Xiao_2018_Biomacromolecules_19_2673
Author(s) : Xiao Y , Pan J , Wang D , Heise A , Lang M
Ref : Biomacromolecules , 19 :2673 , 2018
Abstract : With increasing troubles in bacterial contamination and antibiotic-resistance, new materials possessing both biocompatibility and antimicrobial efficacy are supposed to be developed for future biomedical application. Herein, we demonstrated a chemo-enzymatic ring opening polymerization (ROP) approach for block copolyester, that is, poly(4-benzyl formate piperidine lactone- b-omega-pentadecalactone) (PNPIL- b-PPDL), in a one-pot two-step process. Afterward, cationic poly(4-piperidine lactone- b-omega-pentadecalactone) (PPIL- b-PPDL) with pendent secondary amino groups was obtained via acidic hydrolysis of PNPIL- b-PPDL. The resulting cationic block copolyester exhibited high antibacterial activity against Gram negative E. coli and Gram positive S. aureus, while showed low toxicity toward NIH-3T3 cells. Moreover, the antibacterial property, cytotoxicity and degradation behavior could be tuned simply by variation of PPIL content. Therefore, we anticipate that such cationic block copolymers could potentially be applied as biomaterials for medicine or implants.
ESTHER : Xiao_2018_Biomacromolecules_19_2673
PubMedSearch : Xiao_2018_Biomacromolecules_19_2673
PubMedID: 29698599

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 : Down-regulation of fibronectin and the correlated expression of neuroligin in hirschsprung disease - Zheng_2017_Neurogastroenterol.Motil_29_
Author(s) : Zheng Y , Lv X , Wang D , Gao N , Zhang Q , Li A
Ref : Neurogastroenterol Motil , 29 : , 2017
Abstract : AIM: The goal of this study was to investigate the expression of fibronectin (FN) and the correlated abundance of neuroligins (NLs) in the enteric nervous system (ENS) and to find a novel diagnostic marker in the serum of Hirschsprung disease (HSCR) patients. METHODS: The expression levels of FN, neuroligin-1 and neuroligin-2 were detected in 114 children with or without HSCR. The expression and localization of the NLs and FN were assessed morphologically by immunohistochemical staining. Western blot analysis and real-time fluorescence quantitative PCR (qPCR) were performed to examine the correlated expression of the NLs and FN in aganglionic, transitional, and normal ganglionic colon tissues. An enzyme-linked immunosorbent assay (ELISA) was performed to evaluate and compare serum FN levels between HSCR and non-HSCRand between long-type HSCR and short-type HSCR. RESULTS: These studies showed that both neuroligin-1 and neuroligin-2 were expressed at low levels in aganglionic segments and at intermediate levels in transitional segments compared to their high level of expression in normal tissue. In contrast, FN expression was negatively correlated, with expression in these three samples transitioning from highest to lowest. The serum FN level was higher in HSCR than in non-HSCR, but no significant difference between short-type HSCR and long-type HSCR was observed. CONCLUSION: FN affects the expression of both neuroligin-1 and neuroligin-2 in HSCR, which may lead to the hypoplasia of ganglion cells in the ENS. This correlation may play a key role in the pathogenesis, diagnosis, or classification of HSCR.
ESTHER : Zheng_2017_Neurogastroenterol.Motil_29_
PubMedSearch : Zheng_2017_Neurogastroenterol.Motil_29_
PubMedID: 28656720

Title : Proprioceptive mechanisms in occlusion-stimulated masseter hypercontraction - Liu_2017_Eur.J.Oral.Sci_125_127
Author(s) : Liu X , Zhang C , Wang D , Zhang H , Li J , Wang M
Ref : Eur J Oral Sci , 125 :127 , 2017
Abstract : Neurons in the trigeminal mesencephalic nucleus (Vme) have an axon that branches peripherally to innervate the orofacial region and projects centrally to the trigeminal motor nucleus (Vmo). They function as the primary neurons conveying proprioceptive messages. The present study aimed to demonstrate the presence of a periodontal-Vme-Vmo circuit and to provide evidence for its involvement in an experimental unilateral anterior crossbite (UAC) model, which can induce osteoarthritis in the temporomandibular joint. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons in the Vmo. The levels of vesicular glutamate transporter 1 (VGLUT1) expressed in the periodontal region, Vme, Vmo, and masseter, and the level of acetylcholinesterase (AChE) expressed in the masseter, were assessed in UAC rats and controls. In CTb-treated rats, many CTb-labeled cell bodies and endings were identified in the Vme and in the Vmo, respectively. In UAC rats, VGLUT1 was expressed at a statistically significantly higher level in the periodontal ligament, Vme, Vmo, and masseter than it was in control rats. The level of AChE protein was 1.97 times higher in UAC rat masseter compared with control rat masseter. These findings reveal a trigeminal mechanism underlying masseter hyperactivity induced by an altered occlusion.
ESTHER : Liu_2017_Eur.J.Oral.Sci_125_127
PubMedSearch : Liu_2017_Eur.J.Oral.Sci_125_127
PubMedID: 28145597

Title : Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats - Wang_2017_Biomed.Res.Int_2017_1209360
Author(s) : Wang D , Pan J , Song G , Gao N , Zheng Y , Zhang Q , Li A
Ref : Biomed Res Int , 2017 :1209360 , 2017
Abstract : Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance. Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue. Finally, the histological appearance of neuroligin-1 and neurexin IIalpha was elucidated using immunohistochemical staining. Results. qRT-PCR showed that the neuroligin-1 and neurexin II mRNA expressions of groups E16, E18, E20, and Ep0 increased gradually with the growth of embryonic rats (P < 0.05). Western blotting confirmed the increasing tendency. In immunohistochemical staining, proteins neuroligin-1 and neurexin IIalpha positive cells concentrated mostly in the myenteric nerve plexus of the colon and their expressions depend on the embryonic time. Conclusion. Neuroligin-1 and neurexin II were both expressed in the ENS and have temporal correlation with the development of ENS, during which neuronal intestinal malformations (NIM) may occur due to their disruptions and consequent abnormal ENS development.
ESTHER : Wang_2017_Biomed.Res.Int_2017_1209360
PubMedSearch : Wang_2017_Biomed.Res.Int_2017_1209360
PubMedID: 28194405

Title : Scallop genome provides insights into evolution of bilaterian karyotype and development - Wang_2017_Nat.Ecol.Evol_1_120
Author(s) : Wang S , Zhang J , Jiao W , Li J , Xun X , Sun Y , Guo X , Huan P , Dong B , Zhang L , Hu X , Sun X , Wang J , Zhao C , Wang Y , Wang D , Huang X , Wang R , Lv J , Li Y , Zhang Z , Liu B , Lu W , Hui Y , Liang J , Zhou Z , Hou R , Li X , Liu Y , Li H , Ning X , Lin Y , Zhao L , Xing Q , Dou J , Mao J , Guo H , Dou H , Li T , Mu C , Jiang W , Fu Q , Fu X , Miao Y , Liu J , Yu Q , Li R , Liao H , Kong Y , Jiang Z , Chourrout D , Bao Z
Ref : Nat Ecol Evol , 1 :120 , 2017
Abstract : Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology.
ESTHER : Wang_2017_Nat.Ecol.Evol_1_120
PubMedSearch : Wang_2017_Nat.Ecol.Evol_1_120
PubMedID: 28812685
Gene_locus related to this paper: mizye-a0a210qls6 , mizye-a0a210qis3 , mizye-a0a210qg00 , mizye-a0a210ped6 , mizye-a0a210q4h5 , mizye-a0a210q4h9 , mizye-a0a210q4j1 , mizye-a0a210qf86 , mizye-a0a210q332 , mizye-a0a210pqn0 , mizye-a0a210q7t5 , mizye-a0a210pij5 , mizye-a0a210qyk8 , mizye-a0a210pwl7 , mizye-a0a210q8u5 , mizye-a0a210r5n9 , mizye-a0a210qbv2 , mizye-a0a210pu25 , mizye-a0a210pek1 , mizye-a0a210pul3 , mizye-a0a210pum3 , mizye-a0a210ptr6 , mizye-a0a210ptq5 , mizye-a0a210ptc4.1 , mizye-a0a210ptc4.2 , mizye-a0a210ptv1 , mizye-a0a210ptv7 , mizye-a0a210qgl6 , mizye-a0a210qg90 , mizye-a0a210ptq0 , mizye-a0a210qg72 , mizye-a0a210ptb1 , mizye-a0a210pjd3 , mizye-a0a210qg92 , mizye-a0a210q8v2 , mizye-a0a210qg93 , mizye-a0a210q160.1 , mizye-a0a210q160.2 , mizye-a0a210qes4 , mizye-a0a210pk25 , mizye-a0a210q1b8 , mizye-a0a210q110 , mizye-a0a210r503 , mizye-P021348901.1 , mizye-P021348901.2

Title : Neonicotinoid insecticides imidacloprid, guadipyr, and cycloxaprid induce acute oxidative stress in Daphnia magna - Qi_2017_Ecotoxicol.Environ.Saf_148_352
Author(s) : Qi S , Wang D , Zhu L , Teng M , Wang C , Xue X , Wu L
Ref : Ecotoxicology & Environmental Safety , 148 :352 , 2017
Abstract : Cycloxaprid (CYC) and guadipyr (GUA) are two new and promising neonicotinoid insecticides whose effects on Daphnia magna are as yet unknown. In this study, the acute toxicities of CYC and GUA to D. magna, including immobilization and embryo-hatching inhibition, and their effects on antioxidant enzymes and related gene expression were determined after a 48-h exposure. Imidacloprid (IMI) was evaluated at the same time as a reference agent. The 48-h EC50 values of IMI, GUA, and CYC for neonate immobilization were 13.0-16.5mg/L and for embryo hatching were 11.3-16.2mg/L. The specific activity of the enzymes superoxide dismutase (SOD) and catalase (CAT) were interfered by IMI, but not by GUA and CYC, while the activity of acetylcholinesterase (AChE) was significantly increased by IMI, but inhibited by GUA and CYC. The relative expressions of the Sod-Cu/Zn, Sod-Mn, Cat, and Ache genes were usually inhibited by IMI, GUA, and CYC, except for Cat by CYC, Ache by GUA, and Sods by IMI. For vitellogenin genes with a SOD-like domain (Vtg1/2-sod), relative expression was increased by IMI and inhibited by GUA and CYC, indicating that IMI, GUA, and CYC have potential toxicity toward reproduction. CYC and GUA are highly active against IMI-resistant pests, and considering the similar toxicity of IMI to D. magna, CYC and GUA are suitable for use in future integrated pest management systems.
ESTHER : Qi_2017_Ecotoxicol.Environ.Saf_148_352
PubMedSearch : Qi_2017_Ecotoxicol.Environ.Saf_148_352
PubMedID: 29096261

Title : Graphene Oxide Dysregulates Neuroligin\/NLG-1-Mediated Molecular Signaling in Interneurons in Caenorhabditis elegans - Chen_2017_Sci.Rep_7_41655
Author(s) : Chen H , Li H , Wang D
Ref : Sci Rep , 7 :41655 , 2017
Abstract : Graphene oxide (GO) can be potentially used in many medical and industrial fields. Using assay system of Caenorhabditis elegans, we identified the NLG-1/Neuroligin-mediated neuronal signaling dysregulated by GO exposure. In nematodes, GO exposure significantly decreased the expression of NLG-1, a postsynaptic cell adhesion protein. Loss-of-function mutation of nlg-1 gene resulted in a susceptible property of nematodes to GO toxicity. Rescue experiments suggested that NLG-1 could act in AIY interneurons to regulate the response to GO exposure. In the AIY interneurons, PKC-1, a serine/threonine protein kinase C (PKC) protein, was identified as the downstream target for NLG-1 in the regulation of response to GO exposure. LIN-45, a Raf protein in ERK signaling pathway, was further identified as the downstream target for PKC-1 in the regulation of response to GO exposure. Therefore, GO may dysregulate NLG-1-mediated molecular signaling in the interneurons, and a neuronal signaling cascade of NLG-1-PKC-1-LIN-45 was raised to be required for the control of response to GO exposure. More importantly, intestinal RNAi knockdown of daf-16 gene encoding a FOXO transcriptional factor in insulin signaling pathway suppressed the resistant property of nematodes overexpressing NLG-1 to GO toxicity, suggesting the possible link between neuronal NLG-1 signaling and intestinal insulin signaling in the regulation of response to GO exposure.
ESTHER : Chen_2017_Sci.Rep_7_41655
PubMedSearch : Chen_2017_Sci.Rep_7_41655
PubMedID: 28128356

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

Title : Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways - Chu_2016_J.Infect.Dis_213_904
Author(s) : Chu H , Zhou J , Wong BH , Li C , Chan JF , Cheng ZS , Yang D , Wang D , Lee AC , Yeung ML , Cai JP , Chan IH , Ho WK , To KK , Zheng BJ , Yao Y , Qin C , Yuen KY
Ref : J Infect Dis , 213 :904 , 2016
Abstract : Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.
ESTHER : Chu_2016_J.Infect.Dis_213_904
PubMedSearch : Chu_2016_J.Infect.Dis_213_904
PubMedID: 26203058

Title : Exploration of the chlorpyrifos escape pathway from acylpeptide hydrolases using steered molecular dynamics simulations - Wang_2016_J.Biomol.Struct.Dyn_34_749
Author(s) : Wang D , Jin H , Wang J , Guan S , Zhang Z , Han W
Ref : J Biomol Struct Dyn , 34 :749 , 2016
Abstract : Acylpeptide hydrolases (APH) catalyze the removal of an N-acylated amino acid from blocked peptides. APH is significantly more sensitive than acetylcholinesterase, a target of Alzheimer's disease, to inhibition by organophosphorus (OP) compounds. Thus, OP compounds can be used as a tool to probe the physiological functions of APH. Here, we report the results of a computational study of molecular dynamics simulations of APH bound to the OP compounds and an exploration of the chlorpyrifos escape pathway using steered molecular dynamics (SMD) simulations. In addition, we apply SMD simulations to identify potential escape routes of chlorpyrifos from hydrolase hydrophobic cavities in the APH-inhibitor complex. Two previously proposed APH pathways were reliably identified by CAVER 3.0, with the estimated relative importance of P1 > P2 for its size. We identify the major pathway, P2, using SMD simulations, and Arg526, Glu88, Gly86, and Asn65 are identified as important residues for the ligand leaving via P2. These results may help in the design of APH-targeting drugs with improved efficacy, as well as in understanding APH selectivity of the inhibitor binding in the prolyl oligopeptidase family.
ESTHER : Wang_2016_J.Biomol.Struct.Dyn_34_749
PubMedSearch : Wang_2016_J.Biomol.Struct.Dyn_34_749
PubMedID: 26155973
Gene_locus related to this paper: aerpe-APE1547

Title : Two new isoxazolines from the husks of Xanthoceras sorbifolia Bunge - Ge_2016_J.Asian.Nat.Prod.Res__1
Author(s) : Ge HQ , Wan GS , Wang D , Wu JM , Sun BH , Wu LJ , Gao HY
Ref : J Asian Nat Prod Res , :1 , 2016
Abstract : Two new isoxazoline compounds, 1-oxa-2-azaspiro[4.5]dec-2-ene-8beta-ol (1) and 1-oxa-2-azaspiro[4.5]dec-2-ene-8alpha-ol (2), were isolated from the husks of fruits of Xanthoceras sorbifolia Bunge and their structures were determined by spectroscopic analyses, including X-ray crystallography, HRESI-MS, UV, IR, and 1D and 2D NMR (HSQC, HMBC, NOESY) methods. Neither compound showed significant inhibitory effects on butyrylcholinesterase (BuchE) and acetylcholinesterase (AChE), nor the selected tumor cells growth. Based on an online activity prediction program (PASS ONLINE), the structures with isoxazoline skeletons were found to show potential anti-asthmatic (AM) and anti-anaphylaxis (AP) activities; moreover, compounds 1 and 2 were predicted to possess high affinities for many enzymes involved in AM and AP according to the RCSB Protein Data Bank. High-affinity binding to phosphodiesterase IV (PDE-4), an important inflammatory modulator in asthma, was demonstrated experimentally, beside that, the predicted structures based on compounds 1 and 2 were analyzed for PDE-4 interactions using the molecular docking methodology of Discovery Studio 3.0 (DS 3.0). The predicted structure 2A-6 exhibited much higher affinity and stability of PDE-4 binding than the clinical PDE-4 inhibitor rolipram.
ESTHER : Ge_2016_J.Asian.Nat.Prod.Res__1
PubMedSearch : Ge_2016_J.Asian.Nat.Prod.Res__1
PubMedID: 27053149

Title : Regulatory effects of genomic translocations at the human carboxylesterase-1 (CES1) gene locus - Sanford_2016_Pharmacogenet.Genomics_26_197
Author(s) : Sanford JC , Wang X , Shi J , Barrie ES , Wang D , Zhu HJ , Sadee W
Ref : Pharmacogenet Genomics , 26 :197 , 2016
Abstract : OBJECTIVE: CES1 encodes carboxylesterase-1, an important drug-metabolizing enzyme with high expression in the liver. Previous studies have reported a genomic translocation of the 5' region from the poorly expressed pseudogene CES1P1, to CES1, yielding the structural variant CES1VAR. The aim of this study was to characterize this translocation and its effect on CES1 expression in the human liver. MATERIALS AND
METHODS: Experiments were conducted in human liver tissues and cell culture (HepG2). The promoter and exon 1 of CES1 were sequenced by Sanger and Ion Torrent sequencing to identify gene translocations. The effects of CES1 5'UTRs on mRNA and protein expression were assessed by quantitative real-time PCR, allelic ratio mRNA analysis by primer extension (SNaPshot), quantitative targeted proteomics, and luciferase reporter gene assays.
RESULTS: Sequencing of CES1 identified two translocations: first, CES1VAR (17% minor allele frequency) comprising the 5'UTR, exon 1, and part of intron 1. A second shorter translocation, CES1SVAR, was observed excluding exon 1 and intron 1 regions (<0.01% minor allele frequency). CES1VAR is associated with 2.6-fold decreased CES1 mRNA and approximately 1.35-fold lower allelic mRNA. Luciferase reporter constructs showed that CES1VAR decreases luciferase activity 1.5-fold, whereas CES1SVAR slightly increases activity. CES1VAR was not associated with CES1 protein expression or metabolism of the CES1 substrates enalapril, clopidogrel, or methylphenidate in the liver. CONCLUSION: The frequent translocation variant CES1VAR reduces mRNA expression of CES1 in the liver by approximately 30%, but protein expression and metabolizing activity in the liver were not detectably altered - possibly because of variable CES1 expression masking small allelic effects. Whether drug therapies are affected by CES1VAR will require further in-vivo studies.
ESTHER : Sanford_2016_Pharmacogenet.Genomics_26_197
PubMedSearch : Sanford_2016_Pharmacogenet.Genomics_26_197
PubMedID: 26871237
Gene_locus related to this paper: human-CES1

Title : An in vitro AChE inhibition assay combined with UF-HPLC-ESI-Q-TOF\/MS approach for screening and characterizing of AChE inhibitors from roots of Coptis chinensis Franch - Zhao_2015_J.Pharm.Biomed.Anal_120_235
Author(s) : Zhao H , Zhou S , Zhang M , Feng J , Wang S , Wang D , Geng Y , Wang X
Ref : J Pharm Biomed Anal , 120 :235 , 2015
Abstract : In this study, an in vitro acetylcholinesterase (AChE) inhibition assay based on microplate reader combined with ultrafiltration high performance liquid chromatography-electrospray quadrupole time of flight mass (UF-HPLC-ESI-Q-TOF/MS) was developed for the rapid screening and identification of acetylcholinesterase inhibitors (AChEI) from roots of Coptis chinensis Franch. Incubation conditions such as enzyme concentration, incubation time, incubation temperature and co-solvent was optimized so as to get better screening results. Five alkaloids including columbamine, jatrorrhizine, coptisine, palmatine and berberine were found with AChE inhibition activity in the 80% ethanol extract of C. chinensis Franch. The screened compounds were identified by HPLC-DAD-ESI-Q-TOF/MS compared with the reference stands and literatures. The screened results were verified by in vitro AChE inhibition assays, palmatine showed the best AChE inhibitory activities with IC50 values of 36.6muM among the five compounds. Results of the present study indicated that the combinative method using in vitro AChE inhibition assay and UF-HPLC-ESI-Q-TOF/MS could be widely applied for rapid screening and identification of AChEI from complex TCM extract.
ESTHER : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedSearch : Zhao_2015_J.Pharm.Biomed.Anal_120_235
PubMedID: 26760241

Title : Molecular dynamics simulations of acylpeptide hydrolase bound to chlorpyrifosmethyl oxon and dichlorvos - Jin_2015_Int.J.Mol.Sci_16_6217
Author(s) : Jin H , Zhou Z , Wang D , Guan S , Han W
Ref : Int J Mol Sci , 16 :6217 , 2015
Abstract : Acylpeptide hydrolases (APHs) catalyze the removal of N-acylated amino acids from blocked peptides. Like other prolyloligopeptidase (POP) family members, APHs are believed to be important targets for drug design. To date, the binding pose of organophosphorus (OP) compounds of APH, as well as the different OP compounds binding and inducing conformational changes in two domains, namely, alpha/beta hydrolase and beta-propeller, remain poorly understood. We report a computational study of APH bound to chlorpyrifosmethyl oxon and dichlorvos. In our docking study, Val471 and Gly368 are important residues for chlorpyrifosmethyl oxon and dichlorvos binding. Molecular dynamics simulations were also performed to explore the conformational changes between the chlorpyrifosmethyl oxon and dichlorvos bound to APH, which indicated that the structural feature of chlorpyrifosmethyl oxon binding in APH permitted partial opening of the beta-propeller fold and allowed the chlorpyrifosmethyl oxon to easily enter the catalytic site. These results may facilitate the design of APH-targeting drugs with improved efficacy.
ESTHER : Jin_2015_Int.J.Mol.Sci_16_6217
PubMedSearch : Jin_2015_Int.J.Mol.Sci_16_6217
PubMedID: 25794283
Gene_locus related to this paper: aerpe-APE1547

Title : Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida - Wang_2015_Bull.Environ.Contam.Toxicol_95_475
Author(s) : Wang K , Qi S , Mu X , Chai T , Yang Y , Wang D , Li D , Che W , Wang C
Ref : Bulletin of Environmental Contamination & Toxicology , 95 :475 , 2015
Abstract : Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.
ESTHER : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedSearch : Wang_2015_Bull.Environ.Contam.Toxicol_95_475
PubMedID: 26293707

Title : Pioglitazone reduces lipid droplets in cholesterolosis of the gallbladder by increasing ABCA1 and NCEH1 expression - Wang_2015_Mol.Cell.Biochem_399_7
Author(s) : Wang JM , Wang D , Tan YY , Zhao G , Ji ZL
Ref : Molecular & Cellular Biochemistry , 399 :7 , 2015
Abstract : As a cholesterol-induced metabolic disease, cholesterolosis of the gallbladder is often resected clinically, which could lead to many complications. The histopathology of cholesterolosis is due to excessive lipid droplet accumulation in epithelial and subcutaneous tissues. The main components of lipid droplets are cholesterol esters (CEs). Removal of CEs from gallbladder epithelial cells (GBECs) is very important for maintaining intracellular cholesterol homeostasis and for treating cholesterol-related diseases. In this study, pioglitazone was used to reduce intracellular CEs. To further elucidate the mechanism, cholesterolosis GBECs were treated with pioglitazone, 22-(R)-hydroxycholesterol (a liver X receptor alpha (LXRalpha) agonist), or peroxisome proliferator-activated receptor gamma (PPARgamma) siRNA. Western blotting for PPARgamma, LXRalpha, ATP-binding cassette transporter A1 (ABCA1), and neutral cholesteryl ester hydrolase 1 (NCEH1) was performed. At length, cholesterol efflux to apoA-I was measured, and oil red O staining was used to visualize lipid droplet variations in cells. In conclusion, we observed that pioglitazone increased ABCA1 expression in an LXR-dependent manner and NCEH1 expression in an LXRalpha-independent manner, which mobilized CE hydrolysis and cholesterol efflux to reduce lipid droplet content in cholesterolosis GBECs. Our data provide a plausible alternative to human gallbladder cholesterolosis.
ESTHER : Wang_2015_Mol.Cell.Biochem_399_7
PubMedSearch : Wang_2015_Mol.Cell.Biochem_399_7
PubMedID: 25280398

Title : The Toxicity and Detoxifying Mechanism of Cycloxaprid and Buprofezin in Controlling Sogatella furcifera (Homoptera: Delphacidae) - Chang_2015_J.Insect.Sci_15_
Author(s) : Chang X , Yuan Y , Zhang T , Wang D , Du X , Wu X , Chen H , Chen Y , Jiao Y , Teng H
Ref : J Insect Sci , 15 : , 2015
Abstract : The effects of cycloxaprid (a modified neonicotinoid insecticide) and buprofezin (a thiadiazine insecticide) on mortality of the white-backed planthopper (WBPH), Sogatella furcifera, were determined in laboratory assays. Cycloxaprid killed WBPH nymphs and adults but buprofezin killed only nymphs, and cycloxaprid acted faster than buprofezin. One day after infestation, mortality of third-instar nymphs was >65% with cycloxaprid at 125 mg liter(-1) but was <38% with buprofezin at 148 mg liter(-1). By the 4th day after infestation, however, control of nymphs by the two insecticides was similar, and cycloxaprid at 125 mg liter(-1) caused >/=80% mortality of adults but buprofezin at 148 mg liter(-1) (the highest rate tested) caused almost no adult mortality. LC50 values for cycloxaprid were lowest with nymphs, intermediate with adult males, and highest with adult females. Although buprofezin was slower acting than cycloxaprid, its LC50 for nymphs 5 d after infestation was 3.79-fold lower than that of cycloxaprid. Mean carboxylesterase (CarE) specific activity of nymphal WBPH treated with cycloxaprid and buprofezin was higher than that of control, but there was no significant difference between cycloxaprid and control (no insecticide), and it was significantly higher for buprofezin than those of cycloxaprid and control. For glutathione S-transferase and mixed function oxygenase, the specific activity of nymphal WBPH treated with buprofezin was significantly higher than those of cycloxaprid and control, too.
ESTHER : Chang_2015_J.Insect.Sci_15_
PubMedSearch : Chang_2015_J.Insect.Sci_15_
PubMedID: 26175461

Title : Draft Genome Sequence of Enterobacter cloacae Strain S611 - Wang_2014_Genome.Announc_2_
Author(s) : Wang D , Han CS , Dichosa AE , Gleasner CD , Johnson SL , Daligault HE , Davenport KW , Li PE , Pierson EA , Pierson LS, 3rd
Ref : Genome Announc , 2 : , 2014
Abstract : We report draft genomes of Enterobacter cloacae strain S611, an endophytic bacterium isolated from surface-sterilized germinating wheat seeds. We present the assembly and annotation of its genome, which may provide insights into the metabolic pathways involved in adaptation.
ESTHER : Wang_2014_Genome.Announc_2_
PubMedSearch : Wang_2014_Genome.Announc_2_
PubMedID: 25502660
Gene_locus related to this paper: entcl-v5ata3

Title : Changes in monoclonal HLA-DR antigen expression in acute organophosphorus pesticide-poisoned patients - Xia_2014_Exp.Ther.Med_7_137
Author(s) : Xia C , Wang M , Liang Q , Yun L , Kang H , Fan L , Wang D , Zhang G
Ref : Exp Ther Med , 7 :137 , 2014
Abstract : The aim of this study was to investigate changes in human leukocyte antigen (HLA)-DR expression of peripheral blood mononuclear cells (MNCs) in patients with acute organophosphorus pesticide poisoning (AOPP). HLA-DR antigen expression of peripheral blood MNCs was examined in 75 patients with AOPP, including 36 patients without multiple organ dysfunction syndrome (non-MODS) and 39 patients with multiple organ dysfunction syndrome (MODS), as well as in 30 healthy individuals using flow cytometry assay. The associations between HLA-DR antigen expression and certain parameters were analyzed, including acute physiology and chronic health evaluation II (APACHE II) score, serum cholinesterase (ChE) activity, cardiac troponin I (cTnI), cardiac enzymes, and liver and kidney function. The mean fluorescence intensity (MCF) of HLA-DR expression in the AOPP group (21.59+/-5.36) was significantly lower than that in the control group (27.85+/-4.86) (P<0.001). The MCF in the MODS group (18.17+/-4.23) was lower than that in the non-MODS group (25.15+/-6.15). In addition, the MCF of the deceased patients (15.29+/-3.97) was lower than that of the surviving patients (22.34+/-2.76) (P<0.001). The MCF of patients with AOPP and MODS was positively correlated with serum ChE (P<0.01) and negatively correlated with the APACHE II score, creatine kinase isoenzyme, cTnI, lactate dehydrogenase, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and serum creatinine (P<0.05). In conclusion, HLA-DR expression in patients with AOPP was significantly decreased compared with that in healthy individuals; HLA-DR expression may therefore be a good indicator for evaluating AOPP, MODS disease severity, immune function, efficacy of prognosis and prognosis. Examination of HLA-DR antigen expression may be of crucial clinical value.
ESTHER : Xia_2014_Exp.Ther.Med_7_137
PubMedSearch : Xia_2014_Exp.Ther.Med_7_137
PubMedID: 24348778

Title : Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history - Zhou_2014_Nat.Genet_46_1303
Author(s) : Zhou X , Wang B , Pan Q , Zhang J , Kumar S , Sun X , Liu Z , Pan H , Lin Y , Liu G , Zhan W , Li M , Ren B , Ma X , Ruan H , Cheng C , Wang D , Shi F , Hui Y , Tao Y , Zhang C , Zhu P , Xiang Z , Jiang W , Chang J , Wang H , Cao Z , Jiang Z , Li B , Yang G , Roos C , Garber PA , Bruford MW , Li R
Ref : Nat Genet , 46 :1303 , 2014
Abstract : Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates.
ESTHER : Zhou_2014_Nat.Genet_46_1303
PubMedSearch : Zhou_2014_Nat.Genet_46_1303
PubMedID: 25362486
Gene_locus related to this paper: rhibe-a0a2k6jtl7 , rhibe-ACHE , rhibe-a0a2k6k3y7 , rhibe-a0a2k6k493 , rhibe-a0a2k6lev4 , rhibe-a0a2k6lfa5 , rhibe-a0a2k6m6k8 , rhiro-a0a2k6p1u8 , rhiro-a0a2k6q1t8 , rhiro-a0a2k6q1w3 , rhibe-a0a2k6n5t9 , rhibe-a0a2k6ju46 , rhibe-a0a2k6kt48 , rhibe-a0a2k6llm5 , rhibe-a0a2k6lnt5 , rhiro-a0a2k6qzp6 , rhiro-a0a2k6q4a6 , rhibe-a0a2k6kn93 , rhibe-a0a2k6lm22 , rhibe-a0a2k6jwp8 , rhiro-a0a2k6qun2 , rhiro-a0a2k6nj56 , rhiro-a0a2k6n885 , rhiro-a0a2k6nnj4 , rhiro-a0a2k6n7n5 , rhibe-a0a2k6jvz4 , rhiro-a0a2k6nfk9 , rhiro-a0a2k6qjv0 , rhibe-a0a2k6jn19 , rhibe-a0a2k6k333 , rhibe-a0a2k6mff5

Title : The Report of Sustained Low-Efficiency Dialysis (SLED) Treatment in Fifteen Patients of Severe Snakebite - Cheng_2014_Cell.Biochem.Biophys_69_71
Author(s) : Cheng J , Wang D , Hu S , Jiang H , Lu H , Lei Q , Liu J , Yuan F , Chen R
Ref : Cell Biochem Biophys , 69 :71 , 2014
Abstract : To investigate the therapeutic efficacy of sustained low-efficiency dialysis (SLED) in severe snakebite patients. Fifteen patients of severe snakebite was treated with SLED from July 2005 to August 2009 were included in the study. Central venous access was established in all patients. SLED was administered using Dialog(+) dialyzer (B. Braun, Germany). SLED sessions were 6-12 h in duration at a blood flow rate of 200 ml/min and a dialysate flow rate of 300 ml/min. Heparin or low molecular weight heparin was used as anticoagulant. Biochemical indicators, APACHE II scores before and after SLED, and clinical outcomes were evaluated. The levels of serum creatinine, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, creatine kinase isozyme MB, and creatine kinase were significantly lower than the level before SLED (P < 0.05); the level of cholinesterase was significantly higher after SLED (P < 0.01); the APACHE II score before SLED was 14.1 +/- 3.8, but decreased significantly to 7.9 +/- 1.4, 6.2 +/- 1.1, and 4.2 +/- 0.8 on days 1, 2, and 7 after SLED, respectively (P < 0.01). Three patients died on days 1, 3, and 4 after SLED, respectively. The remaining twelve patients were either cured or showed improvement at the time of discharge. The survival rate was 80 % where as mortality was 20 %. SLED may be an effective treatment option in severe snakebite patients. It can reduce mortality, thereby, resulting in increased survival rates.
ESTHER : Cheng_2014_Cell.Biochem.Biophys_69_71
PubMedSearch : Cheng_2014_Cell.Biochem.Biophys_69_71
PubMedID: 24068524

Title : Association of serum adipose triglyceride lipase levels with obesity and diabetes - Yang_2014_Genet.Mol.Res_13_6746
Author(s) : Yang L , Chen SJ , Yuan GY , Zhou LB , Wang D , Wang XZ , Chen JJ
Ref : Genet Mol Res , 13 :6746 , 2014
Abstract : The aim of this study was to detect the serum adipose triglyceride lipase (ATGL) levels in obesity and newly diagnosed type 2 diabetes patients, and to explore the association between ATGL with glucose and lipid metabolism. We enrolled 66 patients with type 2 diabetes and 48 patients with normal glucose regulation, who were divided into an overweight or obese subgroup and a normal weight subgroup according to body mass index (BMI) >/= 25 kg/m(2). The enzyme-linked immunosorbent assay was used to detect fasting blood glucose, blood lipids, fasting insulin, and ATGL levels. The serum ATGL level in the overweight or obese group was lower than that in the non-obese group including patients with type 2 diabetes and normal glucose regulation: 239 +/- 61 vs 355 +/- 54 mg/L and 242 +/- 60 vs 383 +/- 58 mg/L, respectively (t = 22.53, t = 8.23, P < 0.05). The Pearson correlation analysis showed that fasting serum ATGL was negatively correlated with body fat content, BMI, waist-to-hip ratio, triglycerides, and the homeostatic model assessment-insulin resistance level (r = -0.271, r = -0.238, r = -0.375, r = -0.313, and r = -0.164, respectively, P < 0.05). The stepwise regression analysis showed that the waist-to-hip ratio and body fat content were independently associated with the serum ATGL level. Our results indicated that the ATGL level may be closely related to obesity.
ESTHER : Yang_2014_Genet.Mol.Res_13_6746
PubMedSearch : Yang_2014_Genet.Mol.Res_13_6746
PubMedID: 25177954

Title : Identification of residues on human receptor DPP4 critical for MERS-CoV binding and entry - Song_2014_Virology_471-473C_49
Author(s) : Song W , Wang Y , Wang N , Wang D , Guo J , Fu L , Shi X
Ref : Virology , 471-473C :49 , 2014
Abstract : Middle East respiratory syndrome coronavirus (MERS-CoV) infects host cells through binding the receptor binding domain (RBD) on its spike glycoprotein to human receptor dipeptidyl peptidase 4 (hDPP4). Here, we report identification of critical residues on hDPP4 for RBD binding and virus entry through analysis of a panel of hDPP4 mutants. Based on the RBD-hDPP4 crystal structure we reported, the mutated residues were located at the interface between RBD and hDPP4, which potentially changed the polarity, hydrophobic or hydrophilic properties of hDPP4, thereby interfering or disrupting their interaction with RBD. Using surface plasmon resonance (SPR) binding analysis and pseudovirus infection assay, we showed that several residues in hDPP4-RBD binding interface were important on hDPP4-RBD binding and viral entry. These results provide atomic insights into the features of interactions between hDPP4 and MERS-CoV RBD, and also provide potential explanation for cellular and species tropism of MERS-CoV infection.
ESTHER : Song_2014_Virology_471-473C_49
PubMedSearch : Song_2014_Virology_471-473C_49
PubMedID: 25461530
Gene_locus related to this paper: human-DPP4

Title : Therapeutic effectiveness of sustained low-efficiency hemodialysis plus hemoperfusion and continuous hemofiltration plus hemoperfusion for acute severe organophosphate poisoning - Hu_2014_Artif.Organs_38_121
Author(s) : Hu SL , Wang D , Jiang H , Lei QF , Zhu XH , Cheng JZ
Ref : Artif Organs , 38 :121 , 2014
Abstract : There is no report on the effects of sustained low-efficiency dialysis (SLED) plus hemoperfusion (HP) (SLED + HP) in patients with acute severe organophosphate (OP) poisoning (ASOPP). This study was designed to compare the therapeutic effectiveness between SLED + HP and continuous hemofiltration (CHF) plus HP (CHF + HP) in patients with ASOPP. In order to assess the two treatment methods, 56 patients with ASOPP were divided into CHF + HP group and SLED + HP group. The biochemical indicators, in-hospital duration, hemodynamic parameters, Acute Physiology, and Chronic Health Evaluation (APACHE II) score, and survival and mortality rates were compared. In both groups after treatment, the levels of serum creatine kinase isozyme MB, creatine kinase, creatinine, glutamic-oxalacetic transaminease, and glutamate-pyruvate transaminase, and the APACHE II scores on the first, second, and seventh day decreased (P < 0.05), whereas the levels of serum acetylcholinesterase increased. The two groups showed no statistical differences in in-hospital duration, biochemical indicators, APACHE II score, hemodynamic parameters, survival rate, or the mortality rate (P > 0.05). In conclusion, SLED has similar hemodynamic stability to CHF and the two treatment methods have similar effects on ASOPP patients. More importantly, SLED plus HP is relatively economical and convenient for patients with ASOPP in clinical practice.
ESTHER : Hu_2014_Artif.Organs_38_121
PubMedSearch : Hu_2014_Artif.Organs_38_121
PubMedID: 23957329

Title : Inhibition of acetylcholinesterase by two genistein derivatives: kinetic analysis, molecular docking and molecular dynamics simulation - Fang_2014_Acta.Pharm.Sin.B_4_430
Author(s) : Fang J , Wu P , Yang R , Gao L , Li C , Wang D , Wu S , Liu AL , Du GH
Ref : Acta Pharm Sin B , 4 :430 , 2014
Abstract : In this study two genistein derivatives (G1 and G2) are reported as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and differences in the inhibition of AChE are described. Although they differ in structure by a single methyl group, the inhibitory effect of G1 (IC50=264 nmol/L) on AChE was 80 times stronger than that of G2 (IC50=21,210 nmol/L). Enzyme-kinetic analysis, molecular docking and molecular dynamics (MD) simulations were conducted to better understand the molecular basis for this difference. The results obtained by kinetic analysis demonstrated that G1 can interact with both the catalytic active site and peripheral anionic site of AChE. The predicted binding free energies of two complexes calculated by the molecular mechanics/generalized born surface area (MM/GBSA) method were consistent with the experimental data. The analysis of the individual energy terms suggested that a difference between the net electrostatic contributions (DeltaE ele+DeltaG GB) was responsible for the binding affinities of these two inhibitors. Additionally, analysis of the molecular mechanics and MM/GBSA free energy decomposition revealed that the difference between G1 and G2 originated from interactions with Tyr124, Glu292, Val294 and Phe338 of AChE. In conclusion, the results reveal significant differences at the molecular level in the mechanism of inhibition of AChE by these structurally related compounds.
ESTHER : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedSearch : Fang_2014_Acta.Pharm.Sin.B_4_430
PubMedID: 26579414

Title : Structure of the type VI secretion phospholipase effector Tle1 provides insight into its hydrolysis and membrane targeting - Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
Author(s) : Hu H , Zhang H , Gao Z , Wang D , Liu G , Xu J , Lan K , Dong Y
Ref : Acta Crystallographica D Biol Crystallogr , 70 :2175 , 2014
Abstract : A diverse superfamily of phospholipases consisting of the type VI lipase effectors Tle1-Tle5 secreted by the bacterial type VI secretion system (T6SS) have recently been identified as antibacterial effectors that hydrolyze membrane phospholipids. These effectors show no significant homology to known lipases, and their mechanism of membrane targeting and hydrolysis of phospholipids remains unknown. Here, the crystal structure of Tle1 ( approximately 96.5 kDa) from Pseudomonas aeruginosa refined to 2.0 A resolution is reported, representing the first structure of this superfamily. Its overall structure can be divided into two distinct parts, the phospholipase catalytic module and the putative membrane-anchoring module; this arrangement has not previously been observed in known lipase structures. The phospholipase catalytic module has a canonical alpha/beta-hydrolase fold and mutation of any residue in the Ser-Asp-His catalytic triad abolishes its toxicity. The putative membrane-anchoring module adopts an open conformation composed of three amphipathic domains, and its partial folds are similar to those of several periplasmic or membrane proteins. A cell-toxicity assay revealed that the putative membrane-anchoring module is critical to Tle1 antibacterial activity. A molecular-dynamics (MD) simulation system in which the putative membrane-anchoring module embedded into a bilayer was stable over 50 ns. These structure-function studies provide insight into the hydrolysis and membrane-targeting process of the unique phospholipase Tle1.
ESTHER : Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
PubMedSearch : Hu_2014_Acta.Crystallogr.D.Biol.Crystallogr_70_2175
PubMedID: 25084336
Gene_locus related to this paper: pseae-q9hyv3

Title : D14-SCFD3-dependent degradation of D53 regulates strigolactone signalling - Zhou_2013_Nature_504_406
Author(s) : Zhou F , Lin Q , Zhu L , Ren Y , Zhou K , Shabek N , Wu F , Mao H , Dong W , Gan L , Ma W , Gao H , Chen J , Yang C , Wang D , Tan J , Zhang X , Guo X , Wang J , Jiang L , Liu X , Chen W , Chu J , Yan C , Ueno K , Ito S , Asami T , Cheng Z , Lei C , Zhai H , Wu C , Wang H , Zheng N , Wan J
Ref : Nature , 504 :406 , 2013
Abstract : Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses.
ESTHER : Zhou_2013_Nature_504_406
PubMedSearch : Zhou_2013_Nature_504_406
PubMedID: 24336215

Title : Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 - Wang_2013_Cell.Res_23_986
Author(s) : Wang N , Shi X , Jiang L , Zhang S , Wang D , Tong P , Guo D , Fu L , Cui Y , Liu X , Arledge KC , Chen YH , Zhang L , Wang X
Ref : Cell Res , 23 :986 , 2013
Abstract : The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 A-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 beta-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection.
ESTHER : Wang_2013_Cell.Res_23_986
PubMedSearch : Wang_2013_Cell.Res_23_986
PubMedID: 23835475
Gene_locus related to this paper: human-DPP4

Title : Draft genome of the wheat A-genome progenitor Triticum urartu - Ling_2013_Nature_496_87
Author(s) : Ling HQ , Zhao S , Liu D , Wang J , Sun H , Zhang C , Fan H , Li D , Dong L , Tao Y , Gao C , Wu H , Li Y , Cui Y , Guo X , Zheng S , Wang B , Yu K , Liang Q , Yang W , Lou X , Chen J , Feng M , Jian J , Zhang X , Luo G , Jiang Y , Liu J , Wang Z , Sha Y , Zhang B , Tang D , Shen Q , Xue P , Zou S , Wang X , Liu X , Wang F , Yang Y , An X , Dong Z , Zhang K , Luo MC , Dvorak J , Tong Y , Yang H , Li Z , Wang D , Zhang A
Ref : Nature , 496 :87 , 2013
Abstract : Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat.
ESTHER : Ling_2013_Nature_496_87
PubMedSearch : Ling_2013_Nature_496_87
PubMedID: 23535596
Gene_locus related to this paper: triua-m8a764 , triua-m8ag96 , triua-m7zp69 , wheat-w5d1z6 , wheat-w5d232 , wheat-w5bnf5 , triua-t1nm05 , wheat-w5cae4 , triua-m7ytf7 , wheat-w5f1j8 , triua-m8ad49 , wheat-a0a077s1q2 , wheat-a0a3b6c2m6 , triua-m7zi26 , wheat-a0a3b6at77 , wheat-a0a3b6atp7

Title : Draft Genome Sequence of Pseudomonas putida Strain S610, a Seed-Borne Bacterium of Wheat - Wang_2013_Genome.Announc_1_e01048
Author(s) : Wang D , Han CS , Dichosa AE , Gleasner CD , Johnson SL , Daligault HE , Davenport KW , Li PE , Pierson EA , Pierson LS, 3rd
Ref : Genome Announc , 1 : , 2013
Abstract : We report the genome sequence of a seed-borne bacterium, Pseudomonas putida strain S610. The size of the draft genome sequence is approximately 4.6 Mb, which is the smallest among all P. putida strains sequenced to date.
ESTHER : Wang_2013_Genome.Announc_1_e01048
PubMedSearch : Wang_2013_Genome.Announc_1_e01048
PubMedID: 24371199
Gene_locus related to this paper: psepu-PIP , psepu-v6jk66 , psepu-v6j3y1

Title : Effects of puerarin on cholinergic enzymes in the brain of ovariectomized guinea pigs - Zhang_2013_Int.J.Neurosci_123_783
Author(s) : Zhang Y , Chen Y , Shan Y , Wang D , Zhu C , Xu Y
Ref : International Journal of Neuroscience , 123 :783 , 2013
Abstract : Estrogen has beneficial effects on neurodegenerative disorders and cognitive function of postmenopausal women. Puerarin, isolated from Pueraria lobota, has been classified as a phytoestrogen, which can be highly effective against cerebrovascular diseases. In this study, the effects of puerarin on neural cholinergic system in the brain of ovariectomized guinea pigs were studied. The puerarin at the doses used (15 mg/kg body weight (bw)/day and 30 mg/kg bw/day) for 10 days had the estrogenic activity indicated by the attenuation of the reduction of uterine weight induced by ovariectomy. In brain, puerarin treatment increased choline acetyltransferase (ChAT) activity and expression in hippocampus, and increased ChAT immnuopositive signals in septal diagonal region. Puerarin treatment could suppress the increase of acetylcholinesterase expression and activity to the levels of the intact group, although they were not significantly different from those of the ovariectomized animals. Moreover, puerarin decreased the beta-amyloid immunopositive staining in hippocampus. In brief, the present study suggests that puerarin prevents the dysfunction of the neuronal cholinergic system and ameliorates the increase of beta-amyloid caused by estrogen deficiency.
ESTHER : Zhang_2013_Int.J.Neurosci_123_783
PubMedSearch : Zhang_2013_Int.J.Neurosci_123_783
PubMedID: 23668913

Title : Chemistry and behavioral studies identify chiral cyclopropanes as selective alpha4beta2-nicotinic acetylcholine receptor partial agonists exhibiting an antidepressant profile - Zhang_2012_J.Med.Chem_55_717
Author(s) : Zhang H , Tuckmantel W , Eaton JB , Yuen PW , Yu LF , Bajjuri KM , Fedolak A , Wang D , Ghavami A , Caldarone B , Paterson NE , Lowe DA , Brunner D , Lukas RJ , Kozikowski AP
Ref : Journal of Medicinal Chemistry , 55 :717 , 2012
Abstract : Despite their discovery in the early 20th century and intensive study over the last 20 years, nicotinic acetylcholine receptors (nAChRs) are still far from being well understood. Only a few chemical entities targeting nAChRs are currently undergoing clinical trials, and even fewer have reached the marketplace. In our efforts to discover novel and truly selective nAChR ligands, we designed and synthesized a series of chiral cyclopropane-containing alpha4beta2-specific ligands that display low nanomolar binding affinities and excellent subtype selectivity while acting as partial agonists at alpha4beta2-nAChRs. Their favorable antidepressant-like properties were demonstrated in the classical mouse forced swim test. Preliminary ADMET studies and broad screening toward other common neurotransmitter receptors were also carried out to further evaluate their safety profile and eliminate their potential off-target activity. These highly potent cyclopropane ligands possess superior subtype selectivity compared to other alpha4beta2-nAChR agonists reported to date, including the marketed drug varenicline, and therefore may fully satisfy the crucial prerequisite for avoiding adverse side effects. These novel chemical entities could potentially be advanced to the clinic as new drug candidates for treating depression.
ESTHER : Zhang_2012_J.Med.Chem_55_717
PubMedSearch : Zhang_2012_J.Med.Chem_55_717
PubMedID: 22171543

Title : Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease - Chen_2012_Cell.Rep_2_1329
Author(s) : Chen R , Zhang J , Wu Y , Wang D , Feng G , Tang YP , Teng Z , Chen C
Ref : Cell Rep , 2 :1329 , 2012
Abstract : Alzheimer's disease (AD) is the most common cause of dementia among older people. There are no effective medications currently available to prevent and treat AD and halt disease progression. Monoacylglycerol lipase (MAGL) is the primary enzyme metabolizing the endocannabinoid 2-arachidonoylglycerol in the brain. We show here that inactivation of MAGL robustly suppressed production and accumulation of beta-amyloid (Abeta) associated with reduced expression of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in a mouse model of AD. MAGL inhibition also prevented neuroinflammation, decreased neurodegeneration, maintained integrity of hippocampal synaptic structure and function, and improved long-term synaptic plasticity, spatial learning, and memory in AD animals. Although the molecular mechanisms underlying the beneficial effects produced by MAGL inhibition remain to be determined, our results suggest that MAGL, which regulates endocannabinoid and prostaglandin signaling, contributes to pathogenesis and neuropathology of AD, and thus is a promising therapeutic target for the prevention and treatment of AD.
ESTHER : Chen_2012_Cell.Rep_2_1329
PubMedSearch : Chen_2012_Cell.Rep_2_1329
PubMedID: 23122958

Title : Enhanced activity of Rhizomucor miehei lipase by directed evolution with simultaneous evolution of the propeptide - Wang_2012_Appl.Microbiol.Biotechnol_96_443
Author(s) : Wang J , Wang D , Wang B , Mei ZH , Liu J , Yu HW
Ref : Applied Microbiology & Biotechnology , 96 :443 , 2012
Abstract : Propeptides are short sequences that facilitate the folding of their associated proteins. The present study found that the propeptide of Rhizomucor miehei lipase (RML) was not proteolytically removed in Escherichia coli. Moreover, RML was not expressed if the propeptide was removed artificially during the cloning process in E. coli. This behavior in E. coli permitted the application of directed evolution to full-length RML, which included both propeptide and catalytic domain, to explore the role played by the propeptide in governing enzyme activity. The catalytic rate constant, k (cat), of the most active mutant RML protein (Q5) was increased from 10.63 +/- 0.80 to 71.44 +/- 3.20 min(-1) after four rounds of screening. Sequence analysis of the mutant displayed three mutations in the propeptide (L57V, S65A, and V67A) and two mutations in the functional region (I111T and S168P). This result showed that improved activity was obtained with essential involvement by mutations in the propeptide, meaning that the majority of mutants with enhanced activity had simultaneous mutations in propeptide and catalytic domains. This observation leads to the hypothesis that directed evolution has simultaneous and synergistic effects on both functional and propeptide domains that arise from the role played by the propeptide in the folding and maturation of the enzyme. We suggest that directed evolution of full-length proteins including their propeptides is a strategy with general validity for extending the range of conformations available to proteins, leading to the enhancement of the catalytic rates of the enzymes.
ESTHER : Wang_2012_Appl.Microbiol.Biotechnol_96_443
PubMedSearch : Wang_2012_Appl.Microbiol.Biotechnol_96_443
PubMedID: 22584429
Gene_locus related to this paper: rhimi-lipas

Title : Evidence for diazinon-mediated inhibition of cis-permethrin metabolism and its effects on reproductive toxicity in adult male mice - Wang_2012_Reprod.Toxicol_34_489
Author(s) : Wang D , Kamijima M , Okamura A , Ito Y , Yanagiba Y , Jia XF , Naito H , Ueyama J , Nakajima T
Ref : Reprod Toxicol , 34 :489 , 2012
Abstract : The potential toxicity resulting from combinatorial effects of organophosphorus and pyrethroid insecticides are not completely known. We evaluated male reproductive toxicity in mice co-exposed to diazinon and cis-permethrin. Nine-week-old male Sv/129 mice were exposed to diazinon (10 mumol/kg/day) or cis-permethrin (90 mumol/kg/day) alone or in combination (100 mumol/kg/day), or vehicle (corn oil), for 6 weeks. Diazinon and the diazinon-permethrin mixture inhibited plasma and liver carboxylesterase activities. In the mixture group, urinary excretion of cis-permethrin metabolite 3-phenoxybenzoic acid decreased along with increased plasma and testicular concentrations of cis-permethrin, while excretion of diazinon metabolites, diethylphosphate and diethylthiophosphate, did not change, versus mice exposed to each chemical alone, which suggested that inhibition of carboxylesterase decreased the metabolic capacity to cis-permethrin. Though the co-exposure decreased testosterone biosynthesis, increased degenerate germ cells in seminiferous tubule and sperm morphological abnormalities versus controls more clearly than exposure to cis-permethrin alone, the expected potentiation of toxicity was not evident.
ESTHER : Wang_2012_Reprod.Toxicol_34_489
PubMedSearch : Wang_2012_Reprod.Toxicol_34_489
PubMedID: 22944209

Title : Discovery of isoxazole analogues of sazetidine-A as selective alpha4beta2-nicotinic acetylcholine receptor partial agonists for the treatment of depression - Liu_2011_J.Med.Chem_54_7280
Author(s) : Liu J , Yu LF , Eaton JB , Caldarone B , Cavino K , Ruiz C , Terry M , Fedolak A , Wang D , Ghavami A , Lowe DA , Brunner D , Lukas RJ , Kozikowski AP
Ref : Journal of Medicinal Chemistry , 54 :7280 , 2011
Abstract : Depression, a common neurological condition, is one of the leading causes of disability and suicide worldwide. Standard treatment, targeting monoamine transporters selective for the neurotransmitters serotonin and noradrenaline, is not able to help many patients that are poor responders. This study advances the development of sazetidine-A analogues that interact with alpha4beta2 nicotinic acetylcholine receptors (nAChRs) as partial agonists and that possess favorable antidepressant profiles. The resulting compounds that are highly selective for the alpha4beta2 subtype of nAChR over alpha3beta4-nAChRs are partial agonists at the alpha4beta2 subtype and have excellent antidepressant behavioral profiles as measured by the mouse forced swim test. Preliminary absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies for one promising ligand revealed an excellent plasma protein binding (PPB) profile, low CYP450-related metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as well as a drug candidate to be advanced through the drug discovery pipeline.
ESTHER : Liu_2011_J.Med.Chem_54_7280
PubMedSearch : Liu_2011_J.Med.Chem_54_7280
PubMedID: 21905669

Title : Integrated transcriptional and proteomic analysis with in vitro biochemical assay reveal the important role of CYP3A46 in T-2 toxin hydroxylation in porcine primary hepatocytes - Wang_2011_Mol.Cell.Proteomics_10_M111 008748
Author(s) : Wang J , Jiang J , Zhang H , Cai H , Li C , Li K , Liu J , Guo X , Zou G , Wang D , Deng Y , Dai J
Ref : Mol Cell Proteomics , 10 :M111 008748 , 2011
Abstract : Both T-2 toxin and its metabolites are highly potent mycotoxins that can cause severe human and animal diseases upon exposure. Understanding the toxic mechanism and biotransformation process of T-2 toxin at a cellular level is essential for the development of counter-measures. We investigated the effect of T-2 toxin in porcine primary hepatocytes using porcine genome array and two-dimensional difference gel electrophoresis with matrix-assisted laser desorption/ionization tandem time of flight mass spectrometry. Integrated transcriptional and proteomic analysis demonstrated that T-2 toxin adversely affected porcine hepatocytes by initiating lipid metabolism disorder, oxidative stress response, and apoptosis. In addition, xenobiotic metabolism genes, including cytochrome P450 3As (CYP3A46 and CYP3A39), carboxylesterase 1Cs (CES1C4 and CES1C5), and epoxide hydrolase (EPHX1), increased in T-2 toxin treatment cells. Using HepG2 cells to over-express the recombinant xenobiotic metabolism genes above and rapid resolution liquid chromatography/tandem mass spectrometry to detect metabolites of T-2 toxin, we determined that porcine CYP3A46 mainly catalyzed T-2 to form 3'-hydroxy-T-2, which was further confirmed by purified CYP3A46 protein. However, recombinant porcine CES1C5 and EPHX1 did not enhance hydrolysis and de-epoxidation of T-2 implying that other esterases and epoxide hydrolases may play dominant roles in those reactions.
ESTHER : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedSearch : Wang_2011_Mol.Cell.Proteomics_10_M111 008748
PubMedID: 21685020

Title : Genome sequencing reveals unique mutations in characteristic metabolic pathways and the transfer of virulence genes between V. mimicus and V. cholerae - Wang_2011_PLoS.One_6_e21299
Author(s) : Wang D , Wang H , Zhou Y , Zhang Q , Zhang F , Du P , Wang S , Chen C , Kan B
Ref : PLoS ONE , 6 :e21299 , 2011
Abstract : Vibrio mimicus, the species most similar to V. cholerae, is a microbe present in the natural environmental and sometimes causes diarrhea and internal infections in humans. It shows similar phenotypes to V. cholerae but differs in some biochemical characteristics. The molecular mechanisms underlying the differences in biochemical metabolism between V. mimicus and V. cholerae are currently unclear. Several V. mimicus isolates have been found that carry cholera toxin genes (ctxAB) and cause cholera-like diarrhea in humans. Here, the genome of the V. mimicus isolate SX-4, which carries an intact CTX element, was sequenced and annotated. Analysis of its genome, together with those of other Vibrio species, revealed extensive differences within the Vibrionaceae. Common mutations in gene clusters involved in three biochemical metabolism pathways that are used for discrimination between V. mimicus and V. cholerae were found in V. mimicus strains. We also constructed detailed genomic structures and evolution maps for the general types of genomic drift associated with pathogenic characters in polysaccharides, CTX elements and toxin co-regulated pilus (TCP) gene clusters. Overall, the whole-genome sequencing of the V. mimicus strain carrying the cholera toxin gene provides detailed information for understanding genomic differences among Vibrio spp. V. mimicus has a large number of diverse gene and nucleotide differences from its nearest neighbor, V. cholerae. The observed mutations in the characteristic metabolism pathways may indicate different adaptations to different niches for these species and may be caused by ancient events in evolution before the divergence of V. cholerae and V. mimicus. Horizontal transfers of virulence-related genes from an uncommon clone of V. cholerae, rather than the seventh pandemic strains, have generated the pathogenic V. mimicus strain carrying cholera toxin genes.
ESTHER : Wang_2011_PLoS.One_6_e21299
PubMedSearch : Wang_2011_PLoS.One_6_e21299
PubMedID: 21731695
Gene_locus related to this paper: vibmi-d0gt41 , vibmi-u4zh77 , vibmi-g0sil5

Title : Dissociation between duration of action in the forced swim test in mice and nicotinic acetylcholine receptor occupancy with sazetidine, varenicline, and 5-I-A85380 - Caldarone_2011_Psychopharmacology.(Berl)_217_199
Author(s) : Caldarone BJ , Wang D , Paterson NE , Manzano M , Fedolak A , Cavino K , Kwan M , Hanania T , Chellappan SK , Kozikowski AP , Olivier B , Picciotto MR , Ghavami A
Ref : Psychopharmacology (Berl) , 217 :199 , 2011
Abstract : RATIONALE: Nicotinic acetylcholine receptor (nAChR) agonists, partial agonists, and antagonists have antidepressant-like effects in rodents and reduce symptoms of depression in humans. OBJECTIVES: The study determined whether the antidepressant-like effect of the nAChR beta2* partial agonist sazetidine-A (sazetidine) in the forced swim test was due to activation or desensitization of beta2* nAChRs. The study also determined if sazetidine's behavioral responses in the forced swim test corresponded to beta2* nAChRs receptor occupancy and drug bioavailability.
RESULTS: Acute antidepressant-like effects in the forced swim test were seen with sazetidine and the full beta2* agonist 5-I-A8350 (BALB/cJ mice) and the less selective beta2* partial agonist varenicline in C57BL/6J but not BALB/cJ mice. The role of beta2* nAChRs was confirmed by results showing: (1) reversal of sazetidine's antidepressant-like effects in the forced swim test by nAChR antagonists mecamylamine and dihydro-beta-erythroidine; (2) absence of sazetidine's effect in mice lacking the beta2 subunit of the nAChR; and (3) a high correspondence between behaviorally active doses of sazetidine and beta2* receptor occupancy. beta2* receptor occupancy following acute sazetidine, varenicline, and 5-I-A8350 lasted beyond the duration of action in the forced swim test. Sazetidine's long lasting receptor occupancy did not diminish behavioral efficacy in the forced swim test following repeated dosing.
CONCLUSIONS: Results demonstrate that activation of a small population of beta2* nAChRs (10-40%) is sufficient to elicit sazetidine's antidepressant-like actions without producing tolerance and suggest that ligands that activate beta2* nAChRs would be promising targets for the development of a new class of antidepressant.
ESTHER : Caldarone_2011_Psychopharmacology.(Berl)_217_199
PubMedSearch : Caldarone_2011_Psychopharmacology.(Berl)_217_199
PubMedID: 21487659

Title : Genome sequence analyses of Pseudomonas savastanoi pv. glycinea and subtractive hybridization-based comparative genomics with nine pseudomonads - Qi_2011_PLoS.One_6_e16451
Author(s) : Qi M , Wang D , Bradley CA , Zhao Y
Ref : PLoS ONE , 6 :e16451 , 2011
Abstract : Bacterial blight, caused by Pseudomonas savastanoi pv. glycinea (Psg), is a common disease of soybean. In an effort to compare a current field isolate with one isolated in the early 1960s, the genomes of two Psg strains, race 4 and B076, were sequenced using 454 pyrosequencing. The genomes of both Psg strains share more than 4,900 highly conserved genes, indicating very low genetic diversity between Psg genomes. Though conserved, genome rearrangements and recombination events occur commonly within the two Psg genomes. When compared to each other, 437 and 163 specific genes were identified in B076 and race 4, respectively. Most specific genes are plasmid-borne, indicating that acquisition and maintenance of plasmids may represent a major mechanism to change the genetic composition of the genome and even acquire new virulence factors. Type three secretion gene clusters of Psg strains are near identical with that of P. savastanoi pv. phaseolicola (Pph) strain 1448A and they shared 20 common effector genes. Furthermore, the coronatine biosynthetic cluster is present on a large plasmid in strain B076, but not in race 4. In silico subtractive hybridization-based comparative genomic analyses with nine sequenced phytopathogenic pseudomonads identified dozens of specific islands (SIs), and revealed that the genomes of Psg strains are more similar to those belonging to the same genomospecies such as Pph 1448A than to other phytopathogenic pseudomonads. The number of highly conserved genes (core genome) among them decreased dramatically when more genomes were included in the subtraction, suggesting the diversification of pseudomonads, and further indicating the genome heterogeneity among pseudomonads. However, the number of specific genes did not change significantly, suggesting these genes are indeed specific in Psg genomes. These results reinforce the idea of a species complex of P. syringae and support the reclassification of P. syringae into different species.
ESTHER : Qi_2011_PLoS.One_6_e16451
PubMedSearch : Qi_2011_PLoS.One_6_e16451
PubMedID: 21304594
Gene_locus related to this paper: pse14-q48cb3 , pse14-q48ck7 , pse14-q48e33 , pse14-q48ji2 , pse14-q48nt0 , pse14-q48pq2 , psesy-PIP , psesy-PSPTO3135 , pseu2-q4zwv7 , psesg-e7p3i0

Title : Phenolic compounds from the whole plants of Gentiana rhodantha (Gentianaceae) - Xu_2011_Chem.Biodivers_8_1891
Author(s) : Xu M , Zhang M , Wang D , Yang CR , Zhang YJ
Ref : Chem Biodivers , 8 :1891 , 2011
Abstract : Gentiana rhodantha Franch. ex Hemsl. (Gentianaceae), an annual herb widely distributed in the southwest of China, has been medicinally used for the treatment of inflammation, cholecystitis, and tuberculosis by the local people of its growing areas. Chemical investigation on the whole plants led to the identification of eight new phenolic compounds, rhodanthenones A-D (1-4, resp.), apigenin 7-O-glucopyranosyl-(1-->3)-glucopyranosyl-(1-->3)-glucopyranoside (5), 1,2-dihydroxy-4-methoxybenzene 1-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (6), 1,2-dihydroxy-4,6-dimethoxybenzene 1-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (7), and methyl 2-O-beta-D-glucopyranosyl-2,4,6-trihydroxybenzoate (8), together with eleven known compounds, 9-19. Their structures were determined on the basis of detailed spectroscopic analyses and chemical methods. Acetylcholinesterase (AChE) inhibition and cytotoxicity tests against five human cancer cell lines showed that only rhodanthenone D (4) and mangiferin (12) exhibited 18.4 and 13.4% of AChE inhibitory effects at a concentration of 10(-4) M, respectively, while compounds 1-5 and the known xanthones lancerin (11), mangiferin (12), and neomangiferin (13) displayed no cytotoxicity at a concentration of 40 muM.
ESTHER : Xu_2011_Chem.Biodivers_8_1891
PubMedSearch : Xu_2011_Chem.Biodivers_8_1891
PubMedID: 22006717

Title : [Selective isolation and diversity of cold-adapted lipase-producing strains from permafrost soil at the terminus of a glacier in the Tianshan Mountains] - Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
Author(s) : Xu Y , Wang D , Shi X , Zheng X , Zhou H , Liu Y , Ni Y
Ref : Wei Sheng Wu Xue Bao , 51 :233 , 2011
Abstract : OBJECTIVE: The diversity of culturable lipase-producing bacterial strains from permafrost soils at the terminus of a glacier in the Tianshan Mountains was investigated. Isolation and molecular phylogenetic analysis were performed to expand our knowledge on diversity of psychrotrophic and psychrophilic bacteria. In addition, efforts were made focusing on screening for cold active lipases. METHODS: Lipase-producing bacterial strains were detected on tween 80 and olive oil plates, respectively. Identity and genetic diversity of strains isolated were determined by spatial 16S rRNA gene sequences and rep-PCR fingerprint. The physiological tests were carried out to determine the phonotypic differences between strains showing high similarity of 16S rRNA gene sequences. RESULTS: Of the total 17 bacterial stains exhibiting cold-adapted lipase activity, we found that only 8 stains were able to hydrolyze olive oil. Based on 16S rRNA gene sequences, the lipase-producing bacterial isolates fell in five phylogenetic groups: subclasses (, ( and ( of Proteobacteria, Actinobacteria, and the Cytophaga-Flexibacter-Bacteroides (CFB) phylum. Nearly 59% of the isolates were affiliated with the genus Pseudomonas. CONCLUSION: The results enrich our knowledge on the psychrotrophic bacterial diversity and biogeographic distribution of cold active lipases-producing bacteria in cold environments.
ESTHER : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedSearch : Xu_2011_Wei.Sheng.Wu.Xue.Bao_51_233
PubMedID: 21574385

Title : An Enterotoxin-Bearing Pathogenicity Island in Staphylococcus epidermidis - Madhusoodanan_2011_J.Bacteriol_193_1854
Author(s) : Madhusoodanan J , Seo KS , Remortel B , Park JY , Hwang SY , Fox LK , Park YH , Deobald CF , Wang D , Liu S , Daugherty SC , Gill AL , Bohach GA , Gill SR
Ref : Journal of Bacteriology , 193 :1854 , 2011
Abstract : Cocolonization of human mucosal surfaces causes frequent encounters between various staphylococcal species, creating opportunities for the horizontal acquisition of mobile genetic elements. The majority of Staphylococcus aureus toxins and virulence factors are encoded on S. aureus pathogenicity islands (SaPIs). Horizontal movement of SaPIs between S. aureus strains plays a role in the evolution of virulent clinical isolates. Although there have been reports of the production of toxic shock syndrome toxin 1 (TSST-1), enterotoxin, and other superantigens by coagulase-negative staphylococci, no associated pathogenicity islands have been found in the genome of Staphylococcus epidermidis, a generally less virulent relative of S. aureus. We show here the first evidence of a composite S. epidermidis pathogenicity island (SePI), the product of multiple insertions in the genome of a clinical isolate. The taxonomic placement of S. epidermidis strain FRI909 was confirmed by a number of biochemical tests and multilocus sequence typing. The genome sequence of this strain was analyzed for other unique gene clusters and their locations. This pathogenicity island encodes and expresses staphylococcal enterotoxin C3 (SEC3) and staphylococcal enterotoxin-like toxin L (SElL), as confirmed by quantitative reverse transcription-PCR (qRT-PCR) and immunoblotting. We present here an initial characterization of this novel pathogenicity island, and we establish that it is stable, expresses enterotoxins, and is not obviously transmissible by phage transduction. We also describe the genome sequence, excision, replication, and packaging of a novel bacteriophage in S. epidermidis FRI909, as well as attempts to mobilize the SePI element by this phage.
ESTHER : Madhusoodanan_2011_J.Bacteriol_193_1854
PubMedSearch : Madhusoodanan_2011_J.Bacteriol_193_1854
PubMedID: 21317317
Gene_locus related to this paper: staep-SE0386 , staep-SE0389 , staep-SE0424 , staep-SE0564 , staep-SE0980 , staep-SE1436 , staep-SE1460 , staep-SE1510 , staep-SE1929 , staep-SERP2035 , staep-SE2328

Title : Galantamine ameliorates the impairment of recognition memory in mice repeatedly treated with methamphetamine: involvement of allosteric potentiation of nicotinic acetylcholine receptors and dopaminergic-ERK1\/2 systems - Noda_2010_Int.J.Neuropsychopharmacol_13_1343
Author(s) : Noda Y , Mouri A , Ando Y , Waki Y , Yamada SN , Yoshimi A , Yamada K , Ozaki N , Wang D , Nabeshima T
Ref : Int J Neuropsychopharmacol , 13 :1343 , 2010
Abstract : Galantamine, a drug used to treat Alzheimer's disease, inhibits acetylcholinesterase (AChE) and allosterically modulates nicotinic acetylcholine receptors (nAChRs) resulting in stimulation of catecholamine neurotransmission. In this study, we investigated whether galantamine exerts cognitive-improving effects through the allosteric modulation of nAChRs in an animal model of methamphetamine (Meth) psychosis. The mice treated with Meth (1 mg/kg.d) for 7 d showed memory impairment in a novel object recognition test. Galantamine (3 mg/kg) ameliorated the memory impairment, and it increased the extracellular dopamine release in the prefrontal cortex (PFC) of Meth-treated mice. Donepezil, an AChE inhibitor (1 mg/kg) increased the extracellular ACh release in the PFC, whereas it had no effect on the memory impairment in Meth-treated mice. The nAChR antagonist, mecamylamine, and dopamine D1 receptor antagonist, SCH 23390, blocked the ameliorating effect of galantamine on Meth-induced memory impairment, whereas the muscarinic AChR antagonist, scopolamine, had no effect. The effects of galantamine on extracellular dopamine release were also antagonized by mecamylamine. Galantamine attenuated the defect of the novelty-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). The ameliorating effect of galantamine on recognition memory in Meth-treated mice was negated by microinjection of an ERK inhibitor, PD98059, into the PFC. These results suggest that the ameliorating effect of galantamine on Meth-induced memory impairment is associated with indirect activation of dopamine D1 receptor-ERK1/2 following augmentation with dopaminergic neurotransmission in the PFC through the allosteric activation of nAChRs. Galantamine could be a useful therapeutic agent for treating cognitive deficits in schizophrenia/Meth psychosis, as well as Alzheimer's disease.
ESTHER : Noda_2010_Int.J.Neuropsychopharmacol_13_1343
PubMedSearch : Noda_2010_Int.J.Neuropsychopharmacol_13_1343
PubMedID: 20219155

Title : A nodule-specific protein secretory pathway required for nitrogen-fixing symbiosis - Wang_2010_Science_327_1126
Author(s) : Wang D , Griffitts J , Starker C , Fedorova E , Limpens E , Ivanov S , Bisseling T , Long S
Ref : Science , 327 :1126 , 2010
Abstract : The nitrogen-fixing symbiosis between Sinorhizobium meliloti and its leguminous host plant Medicago truncatula occurs in a specialized root organ called the nodule. Bacteria that are released into plant cells are surrounded by a unique plant membrane compartment termed a symbiosome. We found that in the symbiosis-defective dnf1 mutant of M. truncatula, bacteroid and symbiosome development are blocked. We identified the DNF1 gene as encoding a subunit of a signal peptidase complex that is highly expressed in nodules. By analyzing data from whole-genome expression analysis, we propose that correct symbiosome development in M. truncatula requires the orderly secretion of protein constituents through coordinated up-regulation of a nodule-specific pathway exemplified by DNF1.
ESTHER : Wang_2010_Science_327_1126
PubMedSearch : Wang_2010_Science_327_1126
PubMedID: 20185723

Title : Changes in morphology of Rhizopus chinensis in submerged fermentation and their effect on production of mycelium-bound lipase - Teng_2009_Bioprocess.Biosyst.Eng_32_397
Author(s) : Teng Y , Xu Y , Wang D
Ref : Bioprocess Biosyst Eng , 32 :397 , 2009
Abstract : In order to control suitable mycelium morphology to obtain high lipase productivity by Rhizopus chinensis in submerged fermentation, the effects of fungal morphology on the lipase production by this strain both in shake flask and fermentor were investigated. Different inoculum level and shear stress were used to develop distinctive morphologies. Analyses and investigations both on micromorphology and macromorphology were performed. Study of micromorphology reveals that micromorphologies for dispersed mycelia and aggregated mycelia are different in cell shape, biosynthetic activity. Macromorphology and broth rheology study in fermentor indicate that pellet formation results in low broth viscosity. Under this condition, the oil can disperse sufficiently in broth which is very important for lipase production. These results indicate that morphology changes affected the lipase production significantly for R. chinensis and the aggregated mycelia were suggested to achieve high lipase production.
ESTHER : Teng_2009_Bioprocess.Biosyst.Eng_32_397
PubMedSearch : Teng_2009_Bioprocess.Biosyst.Eng_32_397
PubMedID: 18779980

Title : Resistance selection and biochemical characterization of spinosad resistance in Helicoverpa armigera (Hubner) (Lepidoptera: Noctuidae) - Wang_2009_Pestic.Biochem.Physiol_95_90
Author(s) : Wang D , Qiu X , Ren X , Niu F , Wang K
Ref : Pesticide Biochemistry and Physiology , 95 :90 , 2009
Abstract : A Helicoverpa armigera population was collected from Shandong province, China. After 15 generations of selection in the laboratory, the H. armigera strain developed more than 20-fold resistance to spinosad. At LD50 level, no significant cross-resistance was found between spinosad and chlorpyrifos, methomyl, avermectin and chlorfenapyr except for fenvalerate with a low cross-resistance of 2.4-fold. However, LD99 values of fenvalerate against the parental and resistant strains were not different significantly. After inhibitors were used, spinosad resistance could be partially suppressed by piperonylbutoxide (PBO) and triphenylphosphate (TPP), but not by diethylmaleate (DEM). Activities of p-nitroanisole O-demethylase (ODM) developed to 8.26-fold compared with the parental strain, but no obvious changes were found in activities of carboxyl esterase (CarE) and glutathione-S-transferase (GST). The results indicated that resistance to spinosad in the cotton bollworm might be associated with an increase in cytochrome P450 monooxygenase.
ESTHER : Wang_2009_Pestic.Biochem.Physiol_95_90
PubMedSearch : Wang_2009_Pestic.Biochem.Physiol_95_90
PubMedID:

Title : Effects of spinosad on Helicoverpa armigera (Lepidoptera: Noctuidae) from China: tolerance status, synergism and enzymatic responses - Wang_2009_Pest.Manag.Sci_65_1040
Author(s) : Wang D , Qiu X , Ren X , Zhang W , Wang K
Ref : Pest Manag Sci , 65 :1040 , 2009
Abstract : BACKGROUND: Spinosad is increasingly used in pest management programmes, and resistance to it has been detected in recent years. However, there is no report on the susceptibilities of field populations of Helicoverpa armigera (Hbner) from China. Furthermore, the impact of spinosad on metabolic enzymes in this pest remains unknown. RESULTS: Four populations of H. armigera from different locations in China displayed less than 6.5-fold difference in LC(50) to spinosad, the highest being in the Xinjiang population, followed by Xiajin, Taian and Hubei populations, while there was no significant difference at LC(99) level among the four populations. The toxicity of spinosad could be synergised by piperonyl butoxide (PBO) and triphenylphosphate (TPP), but not by diethyl maleate (DEM). Spinosad exposure for 48 h significantly increased the activities of p-nitroanisole O-demethylase (ODM), while no significant changes in glutathione-S-transferase (GST) and carboxyl esterase (CarE) were observed. CONCLUSION: Field populations of H. armigera from China displayed marginally different susceptibilities to spinosad and had a relatively low LC(50). Cytochrome P450 monooxygenase might be involved in the metabolism of, and hence resistance to, spinosad in this pest in China.
ESTHER : Wang_2009_Pest.Manag.Sci_65_1040
PubMedSearch : Wang_2009_Pest.Manag.Sci_65_1040
PubMedID: 19533589

Title : Novel minor lipase from Rhizopus chinensis during solid-state fermentation: biochemical characterization and its esterification potential for ester synthesis - Sun_2009_Bioresour.Technol_100_2607
Author(s) : Sun SY , Xu Y , Wang D
Ref : Bioresour Technol , 100 :2607 , 2009
Abstract : Rhizopus chinensis produces two lipases that catalyze ester synthesis when cultured under solid-state fermentation. The Lip2 was purified to homogeneity by ammonium sulphate precipitation, hydrophobic interaction chromatography and gel filtration chromatography. It has an apparent molecular weight of 33 kDa estimated from SDS-PAGE and 32 kDa calculated from analytical gel permeation, with synthetic activity and purification fold of 96.8 U/mg and 138.3, respectively. Maximum hydrolytic activity was obtained at pH 8.0-8.5 and 40 degrees C using pNPP as substrate. Slight activation of the enzyme was observed when Mn(2+) is present. The enzyme was most active on p-nitrophenyl laurate (C12). The purified lipase exhibited maximum synthetic activity at pH memory of 6.0 and 30 degrees C. Most of ethyl esters synthesized by lyophilized enzyme achieved good yields (>90%), and caprylic acid served as the best acyl donor. The enzyme presented a particular affinity for ethanol, n-propanol and n-hexanol, with conversion of 92%, 93% and 92%, respectively, after 20 h incubation.
ESTHER : Sun_2009_Bioresour.Technol_100_2607
PubMedSearch : Sun_2009_Bioresour.Technol_100_2607
PubMedID: 19157870

Title : Mapping and expression analysis of chicken NDRG1 and NDRG3 genes - Tian_2008_Biochem.Genet_46_677
Author(s) : Tian Y , Xu M , Fu Y , Yuan A , Wang D , Li G , Liu G , Lu L
Ref : Biochemical Genetics , 46 :677 , 2008
Abstract : N-myc downstream-regulated genes 1 and 3 (NDRG1 and NDRG3) are members of the alpha/beta hydrolase superfamily. Phylogenetic analysis of the family demonstrated that human NDRG1 and 3 belong to a subfamily. The mapping and gene expression patterns of these genes represent one step toward further investigation into their possible roles in the chicken (Gallus gallus). To map these genes in the chicken chromosome, a 6000 rads chicken-hamster radiation hybrid panel (ChickRH6) was used. Primers were designed according to the published human sequences for amplification of those two genes. We compared the corresponding human mRNA sequences with the predicted coding sequences of the chicken NDRG1 and 3 genes and found that the assembled contigs shared a high percentage of similarity with the human genes. PCR of samples from ChickRH6 revealed that the locations of NDRG1 and 3 are linked to the markers MYC (58 cRs away, LOD score 4.52) and SEQ0265 (10 cRs away, LOD score 17.81), respectively. This result adds two new markers to the chicken RH map, and it reinforces that the RH technique is indeed a powerful tool for mapping genes due to its rapidity, precision, convenience, and reproducibility. In addition, we detected the gene expression and distribution of chicken NDRG1 and 3 in seven tissues, including heart, liver, spleen, lung, muscle, brain, and thymus, by RT-PCR, and found that NDRG1 is relatively ubiquitously expressed in all the tested tissues and highly expressed in heart and liver, whereas NDRG3 is high in heart, muscle, and brain.
ESTHER : Tian_2008_Biochem.Genet_46_677
PubMedSearch : Tian_2008_Biochem.Genet_46_677
PubMedID: 18751885

Title : Effect of the organophosphorus pesticide diazinon on glucose tolerance in type 2 diabetic rats - Ueyama_2008_Toxicol.Lett_182_42
Author(s) : Ueyama J , Kamijima M , Asai K , Mochizuki A , Wang D , Kondo T , Suzuki T , Takagi K , Kanazawa H , Miyamoto K , Wakusawa S , Hasegawa T
Ref : Toxicol Lett , 182 :42 , 2008
Abstract : We have reported that the toxicity of the organophosphorus pesticide diazinon (DZN) and its metabolites is increased in streptozotocin-induced diabetic rats (type 1 diabetic rats). In the present study, we have investigated the effect of DZN on glucose tolerance in genetic type 2 diabetic rats, Goto-Kakizaki (GK) rats. Oral glucose tolerance test (OGTT) (2g/(5 ml kg)) was assessed before, and 1 and 2 weeks after intraperitoneal injection of DZN (6.5 mg/kg) in Wistar and GK rats. DZN significantly increased the levels of glucose in plasma at designated blood sampling points in GK rats. The activity of hepatic drug-metabolizing enzymes and expression of hepatic cytochrome P450 (CYP) 1A2, CYP3A2 and CYP2D1, which oxidize DZN to DZN-oxon, a potent ChE inhibitor, were measured before DZN injection. There were no significant differences in the activity and expression of CYPs between both rat groups, indicating that the ability of metabolic activation might be almost the same in Wistar and GK rats. DZN dramatically decreased the activity of cholinesterase (ChE) in plasma by approximately 40% in both Wistar and GK rats. However, no significant differences in the activity of ChE in plasma were observed between Wistar and GK rats for 5 days after DZN injection. No massive necrotic and apoptotic areas, leukocyte infiltration and immunoreactive insulin-positive cells (beta-cells) were observed in pancreas 2 weeks after DZN injection. Moreover, DZN might not affect plasma insulin levels in Wistar and GK rats. These results suggest that DZN deteriorates the glucose tolerance in GK rats. It is unlikely that this phenomenon is due to differences in ChE activity and/or DZN-oxon production levels between Wistar and GK rats.
ESTHER : Ueyama_2008_Toxicol.Lett_182_42
PubMedSearch : Ueyama_2008_Toxicol.Lett_182_42
PubMedID: 18789379

Title : Effect of (R)-salsolinol and N-methyl-(R)-salsolinol on the balance impairment between dopamine and acetylcholine in rat brain: involvement in pathogenesis of Parkinson disease - Zhu_2008_Clin.Chem_54_705
Author(s) : Zhu W , Wang D , Zheng J , An Y , Wang Q , Zhang W , Jin L , Gao H , Lin L
Ref : Clinical Chemistry , 54 :705 , 2008
Abstract : BACKGROUND: Parkinson disease (PD), a progressive neurodegenerative disease, affects at least 1% of population above the age of 65. Although the specific etiology of PD remains unclear, recently the endogenous neurotoxins such as (R)-salsolinol [(R)-Sal] and N-methyl-(R)-salsolinol [(R)-NMSal] have been thought to play a major role in PD. Much interest is focused on the degeneration of dopamine neurons induced by these neurotoxins. However, little literature is available on the impact of endogenous neurotoxins on the balance between dopamine (DA) and acetylcholine (ACh). METHODS: After injection of (R)-Sal or (R)-NMSal into the rat brain striatum, the concentrations of DA and its metabolites were detected by HPLC with electrochemical detection. We assessed the influence of neurotoxins on acetylcholinesterase (AChE) activity and developed a microdialysis-electrochemical device to measure ACh concentrations with enzyme-modified electrodes. RESULTS: (R)-Sal and (R)-NMSal led to concentration-dependent decreases in the activity of AChE. ACh concentrations in striatum treated with (R)-Sal or (R)-NMSal were increased to 131.7% and 239.8% of control, respectively. As to the dopaminergic system, (R)-NMSal caused a significant decrease in DA concentrations and (R)-Sal reduced the concentrations of DA metabolites in the striatum. CONCLUSIONS: (R)-Sal and (R)-NMSal exerted a considerable effect on the balance between DA and ACh by impairing the cholinergic system as well as the dopaminergic system. It is likely that the disruption of balance between DA and ACh plays a critical role in the pathogenesis of neurotoxin-induced PD.
ESTHER : Zhu_2008_Clin.Chem_54_705
PubMedSearch : Zhu_2008_Clin.Chem_54_705
PubMedID: 18238832

Title : The allosteric potentiation of nicotinic acetylcholine receptors by galantamine ameliorates the cognitive dysfunction in beta amyloid25-35 i.c.v.-injected mice: involvement of dopaminergic systems - Wang_2007_Neuropsychopharmacology_32_1261
Author(s) : Wang D , Noda Y , Zhou Y , Mouri A , Mizoguchi H , Nitta A , Chen W , Nabeshima T
Ref : Neuropsychopharmacology , 32 :1261 , 2007
Abstract : Galantamine, a drug for Alzheimer's disease, is a novel cholinergic agent with a dual mode of action, which inhibits acetylcholinesterase and allosterically modulates nicotinic acetylcholine receptors (nAChRs), as a result stimulates catecholamine neurotransmission. In the present study, we investigated whether galantamine exerts cognitive improving effects through the allosteric modulation of nAChR in the intracerebroventricular beta amyloid (Abeta)(25-35)-injected animal model of Alzheimer's disease. Galantamine (3 mg/kg p.o.) significantly increased the extracellular dopamine release in the hippocampus of saline- and Abeta(25-35)-injected mice. The effects of nicotine on the extracellular dopamine release were potentiated by galantamine, but antagonized by mecamylamine, a nAChR antagonist. Abeta(25-35)-injected mice, compared with saline-injected mice, could not discriminate between new and familiar objects in the novel object recognition test and exhibited less freezing response in the fear-conditioning tasks, suggesting Abeta(25-35) induced cognitive impairment. Galantamine improved the Abeta(25-35)-induced cognitive impairment in the novel object recognition and fear-conditioning tasks. These improving effects of galantamine were blocked by the treatment with mecamylamine, SCH-23390, a dopamine-D1 receptor antagonist, and sulpiride, a dopamine-D2 receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist. This study provides the first in vivo evidence that galantamine augments dopaminergic neurotransmission within the hippocampus through the allosteric potentiation of nAChRs. The improving-effects of galantamine on the Abeta(25-35)-induced cognitive impairment may be mediated through the activation of, at least in part, dopaminergic systems, and the enhancement of dopamine release may be one of multiple mechanisms underlying the therapeutic benefit of galantamine.
ESTHER : Wang_2007_Neuropsychopharmacology_32_1261
PubMedSearch : Wang_2007_Neuropsychopharmacology_32_1261
PubMedID: 17133263

Title : Synergistic effect of galantamine with risperidone on impairment of social interaction in phencyclidine-treated mice as a schizophrenic animal model - Wang_2007_Neuropharmacol_52_1179
Author(s) : Wang D , Noda Y , Zhou Y , Nitta A , Furukawa H , Nabeshima T
Ref : Neuropharmacology , 52 :1179 , 2007
Abstract : Social withdrawal is the first sign and key component of the negative symptoms of schizophrenia. The efficacy of risperidone, an atypical antipsychotic, on the symptom is practically limited by dose-dependent side effects in clinical trials, therefore there is the need for adjuvant treatments. In the present study, we aimed to investigate the synergistic effect and mechanism of risperidone and galantamine, which is a nicotinic acetylcholine receptor (nAChR)-allosteric modulator and a modest cholinesterase inhibitor, on phencyclidine (PCP)-treated mouse model of social withdrawal. At non-effective doses by themselves, co-administration of galantamine (0.05mg/kg) and risperidone (0.05mg/kg) showed synergistic effects on PCP-induced impairments of social interaction and dopamine release in the medial prefrontal cortex (mPFC). The behavioral synergistic effect was abolished by the administration of a dopamine-D(1) receptor antagonist, SCH 23390 (0.02mg/kg, systemic; or 0.02microg/0.5microL/mouse, intra-mPFC), and a nAChR antagonist, mecamylamine (3mg/kg), but not a muscarinic receptor antagonist, scopolamine (0.1mg/kg). Mecamylamine (3mg/kg) also abolished the synergistic effect on dopamine release in the mPFC. We conclude that galantamine may have synergistic effect with risperidone on the negative symptom of social withdrawal in schizophrenia, which is mediated by dopamine-D(1) receptors in the mPFC through nAChR activation-increased dopamine release.
ESTHER : Wang_2007_Neuropharmacol_52_1179
PubMedSearch : Wang_2007_Neuropharmacol_52_1179
PubMedID: 17313962

Title : Synthetic activity enhancement of membrane-bound lipase from Rhizopus chinensis by pretreatment with isooctane - Wang_2007_Bioprocess.Biosyst.Eng_30_147
Author(s) : Wang D , Xu Y , Teng Y
Ref : Bioprocess Biosyst Eng , 30 :147 , 2007
Abstract : The cell-bound lipase from Rhizopus chinensis CCTCC M201021 with high catalysis ability for ester synthesis was located as a membrane-bound lipase by the treatments of Yatalase firstly. In order to improve its synthetic activity in non-aqueous phase, the pretreatments of this enzyme with various organic solvents were investigated. The pretreatment with isooctane improved evidently the lipase synthetic activity, resulting in about 139% in relative synthetic activity and 115% in activity recovery. The morphological changes of mycelia caused by organic solvent pretreatments could influence the exposure of the membrane-bound enzyme from mycelia and the exhibition of the lipase activity. The pretreatment conditions with isooctane and acetone were further investigated, and the optimum effect was obtained by the isooctane pretreatment at 4 degrees C for 1 h, resulting in 156% in relative synthetic activity and 126% in activity recovery. When the pretreated lipases were employed as catalysts for the esterification production of ethyl hexanoate in heptane, higher initial reaction rate and higher final molar conversion were obtained using the lipase pretreated with isooctane, compared with the untreated lyophilized one. This result suggested that the pretreatment of the membrane-bound lipase with isooctane could be an effective method to substitute the lyophilization for preparing biocatalysts used in non-aqueous phase reactions.
ESTHER : Wang_2007_Bioprocess.Biosyst.Eng_30_147
PubMedSearch : Wang_2007_Bioprocess.Biosyst.Eng_30_147
PubMedID: 17252187

Title : Synergistic effect of combined treatment with risperidone and galantamine on phencyclidine-induced impairment of latent visuospatial learning and memory: Role of nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission - Wang_2007_Neuropharmacol_53_379
Author(s) : Wang D , Noda Y , Zhou Y , Nitta A , Furukawa H , Nabeshima T
Ref : Neuropharmacology , 53 :379 , 2007
Abstract : The clinically achievable efficacy of the atypical antipsychotics on cognitive symptoms of schizophrenia is practically limited by their dose-dependent side effects. Thus, there is the need for adjuvant treatments or strategies for the cognitive impairments. Further, human autopsy and genetic data in schizophrenia have indicated the existence of the abnormality of nicotinic acetylcholine receptors (nAChR). In the present study, we aimed to investigate the synergistic effect and mechanisms of a combined treatment with an atypical antipsychotic risperidone and galantamine, which is a nAChR-allosteric modulator and a modest cholinesterase inhibitor, on the impairment of latent visuospatial learning and memory in mice resembling the cognitive impairment of schizophrenia. Repeated treatment with phencyclidine (PCP, 10 mg/kg, 14 days)-induced cognitive impairment in mice in a one trial water-finding test was used as a model of the cognitive impairment of schizophrenia. In vivo microdialysis was used to investigate the extracellular concentration of dopamine in the medial prefrontal cortex (mPFC). Combined treatment with galantamine and risperidone, at low, ineffective doses (both at 0.05 mg/kg) showed a synergistic effect to reverse cognitive impairment and increase extracellular concentration of dopamine in the mPFC. The synergistic behavioral effect was abolished by a dopamine-D1 receptor antagonist, SCH 23390, and a nAChR antagonist, mecamylamine, but not a muscarinic AChR (mAChR) antagonist, scopolamine. Mecamylamine also blocked the synergistic effect on dopamine release in the mPFC of PCP-treated mice. The study indicates that galantamine and risperidone may have synergistic effect on the cognitive impairments in schizophrenia patients by synergistically promoting the nAChR activation-dependent increase of dopamine D1 receptor-mediated neurotransmission.
ESTHER : Wang_2007_Neuropharmacol_53_379
PubMedSearch : Wang_2007_Neuropharmacol_53_379
PubMedID: 17632185

Title : Stability in plasmas of various species of HPMA copolymer-PGE1 conjugates - Pan_2007_Pharm.Res_24_2270
Author(s) : Pan H , Kopeckova P , Liu J , Wang D , Miller SC , Kopecek J
Ref : Pharm Res , 24 :2270 , 2007
Abstract : PURPOSE: To determine the stability of HPMA copolymer-prostaglandin E(1) (PGE(1)) conjugates in plasmas of different species and to identify the enzymes responsible for the cleavage of the ester bond.
METHODS: The conjugates were incubated in human, rat, and mouse plasma at 37 degrees C in the presence and absence of specific esterase inhibitors. The released PGE(1) was analyzed using an HPLC assay. To evaluate the effect of the conformation of the conjugate on the rate of PGE(1) release, its structure was modified by the attachment of hydrophobic side chains.
RESULTS: The rate of PGE(1) release was strongly species dependent. Whereas the conjugate was stable in human plasma, the PGE(1) release in rat or mouse plasma was substantial. In rat plasma, the ester bond cleavage was mainly catalyzed by butyrylcholinesterase; in mouse plasma, in addition to butyrylcholinesterase, carboxylesterase also contributed to the cleavage. The formation of compact polymer coils stabilized the ester bond.
CONCLUSIONS: HPMA copolymer-PGE(1) conjugates are strong candidates as novel therapeutics for the treatment of osteoporosis. The observed species differences in plasma stability of ester bonds are of importance, because the ovariectomized rat model is recommended by the FDA for pre-clinical evaluation.
ESTHER : Pan_2007_Pharm.Res_24_2270
PubMedSearch : Pan_2007_Pharm.Res_24_2270
PubMedID: 17899324

Title : Toxicity of diazinon and its metabolites increases in diabetic rats - Ueyama_2007_Toxicol.Lett_170_229
Author(s) : Ueyama J , Wang D , Kondo T , Saito I , Takagi K , Kamijima M , Nakajima T , Miyamoto K , Wakusawa S , Hasegawa T
Ref : Toxicol Lett , 170 :229 , 2007
Abstract : The effect of diazinon (DZN) on the activities of cholinesterase (ChE) in plasma and acetylcholinesterase (AChE) in erythrocyte and brain was investigated in normal and streptozotocin-induced diabetic rats. Hepatic drug-metabolizing enzyme activity was also estimated by measuring the systemic clearance of antipyrine, and the expression of hepatic cytochrome P450 (CYP) 3A2 and CYP1A2, which is closely related to the metabolism from DZN to DZN-oxon, a strong inhibitor of both ChE and AChE. No significant differences in the activities of ChE in plasma and AChE in erythrocyte were observed between normal and diabetic rats. Treatment with DZN significantly decreased these activities in diabetic rats more than in normal rats 6h after injection (6.5 mg/kg). Treatment with DZN significantly decreased the activity of AChE in brain of diabetic rats than normal rats 3h after injection (65 mg/kg), although no significant difference in the activity was found between normal and diabetic rats. The urinary recovery of diethylphosphate (DEP), a metabolite of DZN-oxon, was significantly increased in diabetic rats, but that of diethylthiophosphate (DETP), a metabolite of DZN, was unchanged. Significant increases in the systemic clearance of antipyrine and protein levels of hepatic CYP1A2, not CYP3A2, were observed in diabetic rats. These results suggest the possibility that a metabolite of DZN, DZN-oxon, causes higher toxicity in diabetic rats due to the enhancement of hepatic CYP1A2-mediated metabolism of DZN.
ESTHER : Ueyama_2007_Toxicol.Lett_170_229
PubMedSearch : Ueyama_2007_Toxicol.Lett_170_229
PubMedID: 17442507

Title : Calmodulin binding to peptides derived from the i3 loop of muscarinic receptors - Lucas_2006_Pharm.Res_23_647
Author(s) : Lucas JL , Wang D , Sadee W
Ref : Pharm Res , 23 :647 , 2006
Abstract : PURPOSE: This study was conducted to identify and characterize the structural requirements of a calmodulin-binding motif identified in the third intracellular (i3) loop of muscarinic acetylcholine receptors (M1-M5), a region important for G protein coupling.
METHODS: GST fusion proteins and synthetic peptides derived from the hM1 i3 loop were tested for binding to CaM using a cross-linking gel shift assay and a dansyl-CaM fluorescence assay. Mutagenesis studies further characterized the structural requirements for the interaction and identified critical residues.
RESULTS: 28-Mer peptides from the C terminus of i3, representing the putative calmodulin domains of M1, M2, and M3, were found capable of interacting with CaM. In addition, smaller peptides defined a 5-amino-acid sequence essential for calmodulin binding. Studies performed with M1 peptides derived from GST fusion proteins, representing larger portions of the i3 C terminus, suggested the presence of a second adjacent CaM binding site. Mutagenesis studies identified two mutants that are unable to bind CaM: a point mutation, E360A, and a deletion mutant, delta232-358. CONCLUSION: Calmodulin can bind to an M1 region implicated in G protein coupling. This indicates an important role for CaM in the regulation of muscarinic signal transduction.
ESTHER : Lucas_2006_Pharm.Res_23_647
PubMedSearch : Lucas_2006_Pharm.Res_23_647
PubMedID: 16552497

Title : The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse - McLeod_2006_Proc.Natl.Acad.Sci.U.S.A_103_15582
Author(s) : McLeod MP , Warren RL , Hsiao WW , Araki N , Myhre M , Fernandes C , Miyazawa D , Wong W , Lillquist AL , Wang D , Dosanjh M , Hara H , Petrescu A , Morin RD , Yang G , Stott JM , Schein JE , Shin H , Smailus D , Siddiqui AS , Marra MA , Jones SJ , Holt R , Brinkman FS , Miyauchi K , Fukuda M , Davies JE , Mohn WW , Eltis LD
Ref : Proc Natl Acad Sci U S A , 103 :15582 , 2006
Abstract : Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids. A targeted insertion methodology was developed to determine the telomeric sequences. RHA1's 9,145 predicted protein-encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many of the oxygenases occur in the numerous pathways predicted to degrade aromatic compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes, providing evidence that rhodococci harbor an extensive secondary metabolism. Among sequenced genomes, RHA1 is most similar to those of nocardial and mycobacterial strains. The genome contains few recent gene duplications. Moreover, three different analyses indicate that RHA1 has acquired fewer genes by recent horizontal transfer than most bacteria characterized to date and far fewer than Burkholderia xenovorans LB400, whose genome size and catabolic versatility rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically similar bacteria can evolve large genomes by different means. Overall, RHA1 appears to have evolved to simultaneously catabolize a diverse range of plant-derived compounds in an O(2)-rich environment. In addition to establishing RHA1 as an important model for studying actinomycete physiology, this study provides critical insights that facilitate the exploitation of these industrially important microorganisms.
ESTHER : McLeod_2006_Proc.Natl.Acad.Sci.U.S.A_103_15582
PubMedSearch : McLeod_2006_Proc.Natl.Acad.Sci.U.S.A_103_15582
PubMedID: 17030794
Gene_locus related to this paper: rhoob-c1ar27 , rhoob-c1arb5 , rhoob-c1asz4 , rhoob-c1at13 , rhoob-c1ata3 , rhoob-c1atk8 , rhoob-c1atq0 , rhoob-c1ats8 , rhoob-c1att5 , rhoob-c1au11 , rhoob-c1auh5 , rhoob-c1aux1 , rhoob-c1av24 , rhoob-c1awr1 , rhoob-c1axf2 , rhoob-c1ayb0 , rhoob-c1b0a8 , rhoob-c1b0g7 , rhoob-c1b0w8 , rhoob-c1b1i6 , rhoob-c1b7t4 , rhoob-c1b8z9 , rhoob-c1b9l2 , rhoob-c1b9v1 , rhoob-c1b9y1 , rhoob-c1b930 , rhoob-c1b931 , rhoob-c1b932 , rhoob-c1b996 , rhoob-c1bbl3 , rhoob-c1bbq4 , rhoop-pcaL , rhosp-bphD2 , rhosp-EtbD1 , rhosr-q0rwt2 , rhosr-q0rwv3 , rhosr-q0rxc8 , rhosr-q0ryc0 , rhosr-q0ryn3 , rhosr-q0rz46 , rhosr-q0rz78 , rhosr-q0s0s0 , rhosr-q0s1l0 , rhosr-q0s1m1 , rhosr-q0s1n4 , rhosr-q0s1x5 , rhosr-q0s1x6 , rhosr-q0s2i6 , rhosr-q0s2n9 , rhosr-q0s2t5 , rhosr-q0s3c8 , rhosr-q0s3s6 , rhosr-q0s4f1 , rhosr-q0s5h5 , rhosr-q0s5m7 , rhosr-q0s6a9 , rhosr-q0s6b3 , rhosr-q0s6b5 , rhosr-q0s7i7 , rhosr-q0s7r1 , rhosr-q0s008 , rhosr-q0s8b3 , rhosr-q0s8f4 , rhosr-q0s8p7 , rhosr-q0s8z9 , rhosr-q0s9l3 , rhosr-q0s9m1 , rhosr-q0s101 , rhosr-q0s125 , rhosr-q0s230 , rhosr-q0s252 , rhosr-q0s393 , rhosr-q0s477 , rhosr-q0s545 , rhojr-q0s546 , rhosr-q0s837 , rhosr-q0s849 , rhosr-q0sa25 , rhosr-q0sa26 , rhosr-q0sa61 , rhosr-q0saa5 , rhosr-q0san0 , rhosr-q0saw3 , rhosr-q0sbd3 , rhosr-q0sc04 , rhosr-q0scq2 , rhosr-q0sd10 , rhosr-q0sdb8 , rhosr-q0sdh6 , rhosr-q0sdr2 , rhosr-q0sdr5 , rhosr-q0sdt1 , rhosr-q0sdu5 , rhosr-q0sej4 , rhosr-q0ses6 , rhosr-q0set7 , rhosr-q0sex8 , rhosr-q0sf05 , rhosr-q0sfh8 , rhosr-q0sfl2 , rhosr-q0sfz6 , rhosr-q0sgc8 , rhosr-q0sgj4 , rhosr-q0sgv4 , rhosr-q0sgw4 , rhosr-q0sh74 , rhosr-q0shd6 , rhosr-q0shi2 , rhosr-q0sjy0 , rhosr-q0skn1 , rhoob-c1b934 , rhosr-q0sab7 , rhosr-q0rwx4 , rhoob-c1asm3 , rhosr-q0ruu2 , rhosr-q0s747 , rhosr-q0ry47 , rhosr-q0rwa1 , rhosr-q0sj22 , 9noca-j2j8s8 , rhojr-q0sd80 , rhojr-q0sf05

Title : Opioid receptor homo- and heterodimerization in living cells by quantitative bioluminescence resonance energy transfer - Wang_2005_Mol.Pharmacol_67_2173
Author(s) : Wang D , Sun X , Bohn LM , Sadee W
Ref : Molecular Pharmacology , 67 :2173 , 2005
Abstract : Opioid receptors have been shown to dimerize or oligomerize among themselves and each other, affecting their functional properties. This study used bioluminescence resonance energy transfer (BRET) between the mu, delta, and kappa opioid receptors to study opioid receptor aggregation in transfected human embryonic kidney 293 cells. Titration of receptor levels indicated that all three opioid receptors have a similar affinity to form homo- or hetero-oligomers in combination with any other opioid receptor type. In contrast, none of the opioid receptors formed detectable oligomers with the muscarinic M2 receptor, indicating that interactions among opioid receptors are selective. The formation of opioid receptor dimers, rather than higher order oligomers, is supported by binding kinetics in competition experiments between labeled and unlabeled receptors. Opioid receptor dimerization occurred at physiological temperatures upon receptor biosynthesis, before trafficking to the plasma membrane. Moreover, using BRET, coimmunoprecipitation, receptor binding, and G protein coupling, we demonstrate for the first time functional mu opioid receptor-kappa opioid receptor heterodimerization. These combined results demonstrate that opioid receptors can undergo homo- and heterodimerization, a process with potential implications for opioid physiology and pharmacology.
ESTHER : Wang_2005_Mol.Pharmacol_67_2173
PubMedSearch : Wang_2005_Mol.Pharmacol_67_2173
PubMedID: 15778451

Title : Calmodulin interaction with peptides from G-protein coupled receptors measured with S-Tag labeling - Zhang_2005_Biochem.Biophys.Res.Commun_333_390
Author(s) : Zhang Y , Wang D , Sadee W
Ref : Biochemical & Biophysical Research Communications , 333 :390 , 2005
Abstract : We have developed a quantitative assay of calmodulin (CaM) binding to S-Tag labeled peptides derived from G-protein coupled receptor (GPCR) sequences. CaM binding of peptides derived from the third intracellular loop (i3) of mu opioid receptor (MOR) was confirmed and the CaM-binding motif refined. A MORi3 peptide with a Lys > Ala substitution--shown to reduce CaM-binding of intact MOR--bound fivefold less avidly than the wild-type peptide. Screening peptides derived from i3 loops of other GPCR families confirmed 5HT1A, and identified muscarinic receptor 3, and melanocortin receptor 1, as proteins carrying CaM-binding domains. The use of S-Tag labeling can serve for rapid screening of putative CaM-binding domains in GPCRs.
ESTHER : Zhang_2005_Biochem.Biophys.Res.Commun_333_390
PubMedSearch : Zhang_2005_Biochem.Biophys.Res.Commun_333_390
PubMedID: 15950946

Title : Rhesus monkey alpha7 nicotinic acetylcholine receptors: comparisons to human alpha7 receptors expressed in Xenopus oocytes - Papke_2005_Eur.J.Pharmacol_524_11
Author(s) : Papke RL , McCormack TJ , Jack BA , Wang D , Bugaj-Gaweda B , Schiff HC , Buhr JD , Waber AJ , Stokes C
Ref : European Journal of Pharmacology , 524 :11 , 2005
Abstract : An alpha7 nicotinic acetylcholine receptor sequence was cloned from Rhesus monkey (Macaca mulatta). This clone differs from the mature human alpha7 nicotinic acetylcholine receptor in only four amino acids, two of which are in the extracellular domain. The monkey alpha7 nicotinic receptor was characterized in regard to its functional responses to acetylcholine, choline, cytisine, and the experimental alpha7-selective agonists 4OH-GTS-21, TC-1698, and AR-R17779. For all of these agonists, the EC(50) for activation of monkey receptors was uniformly higher than for human receptors. In contrast, the potencies of mecamylamine and MLA for inhibiting monkey and human alpha7 were comparable. Acetylcholine and 4OH-GTS-21 were used to probe the significance of the single point differences in the extracellular domain. Mutants with the two different amino acids in the extracellular domain of the monkey receptor changed to the corresponding sequence of the human receptor had responses to these agonists that were not significantly different in EC(50) from wild-type human alpha7 nicotinic receptors. Monkey alpha7 nicotinic receptors have a serine at residue 171, while the human receptors have an asparagine at this site. Monkey S171N mutants were more like human alpha7 nicotinic receptors, while mutations at the other site (K186R) had relatively little effect. These experiments point toward the basic utility of the monkey receptor as a model for the human alpha7 nicotinic receptor, albeit with the caveat that these receptors will vary in their agonist concentration dependency. They also point to the potential importance of a newly identified sequence element for modeling the specific amino acids involved with receptor activation.
ESTHER : Papke_2005_Eur.J.Pharmacol_524_11
PubMedSearch : Papke_2005_Eur.J.Pharmacol_524_11
PubMedID: 16266703

Title : Serum response factor activation by muscarinic receptors via RhoA. Novel pathway specific to M1 subtype involving calmodulin, calcineurin, and Pyk2 - Lin_2002_J.Biol.Chem_277_40789
Author(s) : Lin K , Wang D , Sadee W
Ref : Journal of Biological Chemistry , 277 :40789 , 2002
Abstract : The muscarinic cholinergic receptor (mAChR) subtypes share high sequence similarity except in their third intracellular loop and COOH terminus, domains thought to be involved in signal transduction. Subtypes M1, M3, and M5 couple mainly through Galpha(q/11), and M2 and M4 couple mainly through Galpha(i/o). Whether subtypes within each of these two groups differ in their signaling pathways remains to be resolved. This study focused on nuclear signaling pathways leading to activation of the transcription factor, serum response factor (SRF). Genes encoding M1, M2, and M3 were co-expressed in Jurkat T lymphocytes with a reporter gene driven by a mutant serum response element, SRE.L, which responds to SRF activation. We show that only M1 mAChR activated SRF through a pathway involving the small GTPase RhoA, with no response observed for M2 and M3. Transfection of GTPase-deficient Galpha subunits (GalphaQL; constitutively active form) demonstrated that SRF was activated by Galpha(13)QL but only marginally by Galpha(q)QL and Galpha(12)QL in Jurkat cells. Yet transfection of regulator of G protein-signaling protein, RGS2 and RGS4, which inhibit Galpha(q/11) activity, indicated that Galpha(q/11) and Ca(2+) mobilization were required for SRF activation by M1. Calmodulin inhibitors suppressed the M1 and the Galpha(13)QL pathways, acting both upstream and downstream of RhoA. However, calcineurin inhibitors and the tyrosine kinase inhibitor genistein selectively suppressed SRF activation by M1, but not by Galpha(13)QL, indicating the presence of separate pathways. The calmodulin-dependent tyrosine kinase Pyk2 was also activated by M1 but not M3, and Pyk2 appears also to play a role in M1-SRF activation, as judged by experiments with two dominant-negative Pyk2 mutants. These results reveal a novel calmodulin-dependent RhoA-SRF signaling pathway unique to the M1 mAChR subtype.
ESTHER : Lin_2002_J.Biol.Chem_277_40789
PubMedSearch : Lin_2002_J.Biol.Chem_277_40789
PubMedID: 12200418

Title : Association between low-density lipoprotein receptor-related protein gene, butyrylcholinesterase gene and Alzheimer' s disease in Chinese - Bi_2001_Chin.Med.Sci.J_16_71
Author(s) : Bi S , Zhang Y , Wu J , Wang D , Zhao Q
Ref : Chin Med Sci J , 16 :71 , 2001
Abstract : OBJECTIVE: To research the relations between low-density lipoprotein receptor-related protein gene (LRP) polymorphism, butyrylcholinesterase gene (BchE) polymorphism and Alzheimer's disease (AD) in Chinese.
METHODS: The gene polymorphisms of LRP and BchE were genotyped in 38 AD cases and 40 controls with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. AD groups were classified according to the LRP C/C genotype and compared with matched controls.
RESULTS: AD group had higher frequencies of C/C homozygote (81.69% vs 60.0%, P < 0.05) and of C allele (89.5% vs 76.3%, P < 0.05), with no significant difference between any of these LRP genotypes classified AD groups and their respective control groups.
CONCLUSIONS: A positive correlation was found between LRP gene polymorphism and AD, but not between BchE gene polymorphism and AD in Chinese AD cases.
ESTHER : Bi_2001_Chin.Med.Sci.J_16_71
PubMedSearch : Bi_2001_Chin.Med.Sci.J_16_71
PubMedID: 12901493

Title : mu-Opioid receptor-mediated ERK activation involves calmodulin-dependent epidermal growth factor receptor transactivation - Belcheva_2001_J.Biol.Chem_276_33847
Author(s) : Belcheva MM , Szucs M , Wang D , Sadee W , Coscia CJ
Ref : Journal of Biological Chemistry , 276 :33847 , 2001
Abstract : Phosphorylation of the MAPK isoform ERK by G protein-coupled receptors involves multiple signaling pathways. One of these pathways entails growth factor receptor transactivation followed by ERK activation. This study demonstrates that a similar signaling pathway is used by the mu-opioid receptor (MOR) expressed in HEK293 cells and involves calmodulin (CaM). Stimulation of MOR resulted in both epidermal growth factor receptor (EGFR) and ERK phosphorylation. Data obtained with inhibitors of EGFR Tyr kinase and membrane metalloproteases support an intermediate role of EGFR activation, involving release of endogenous membrane-bound epidermal growth factor. Previous studies had demonstrated a role for CaM in opioid signaling based on direct CaM binding to MOR. To test whether CaM contributes to EGFR transactivation and ERK phosphorylation by MOR, we compared wild-type MOR with mutant K273A MOR, which binds CaM poorly, but couples normally to G proteins. Stimulation of K273A MOR with [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin (10-100 nm) resulted in significantly reduced ERK phosphorylation. Furthermore, wild-type MOR stimulated EGFR Tyr phosphorylation 3-fold more than K273A MOR, indicating that direct CaM-MOR interaction plays a key role in the transactivation process. Inhibitors of CaM and protein kinase C also attenuated [D-Ala(2),MePhe(4),Gly-ol(5)]enkephalin-induced EGFR transactivation in wild-type (but not mutant) MOR-expressing cells. This novel pathway of EGFR transactivation may be shared by other G protein-coupled receptors shown to interact with CaM.
ESTHER : Belcheva_2001_J.Biol.Chem_276_33847
PubMedSearch : Belcheva_2001_J.Biol.Chem_276_33847
PubMedID: 11457825

Title : Grafting of genetically modified human fetal fibroblasts to produce human butyrylcholinesterase in mice - Shao_1999_Chem.Biol.Interact_119-120_361
Author(s) : Shao H , Huang YZ , Wang D , Zhang H , Sun MJ
Ref : Chemico-Biological Interactions , 119-120 :361 , 1999
Abstract : Human diploid fibroblast cultures were established from fetal skin tissue. Enzymic dissociation yielded cultures of higher growth capacity of fibroblasts than those prepared by mechanical dissociation followed by spontaneous outgrowth of cells. Transfer of recombinant human butyrylcholinesterase (BChE, EC 3.1.1.8) gene into primary human fibroblasts was achieved successfully using lipofection and retrovirus-mediated transfection. The analysis of drug-resistant colonies suggested the presence of the transcripted BChE mRNA in the cytoplasm of transfected cells. The secreted BChE protein in culture medium was assayed for enzyme activity using butyrylthiocholine as substrate. The genetically modified fibroblasts were mixed with rat tail collagen and transplanted subcutaneously and intraperitoneally to mice. Immunoreactive human BChE appeared in the plasma from the transplanted mice. reaching the top level at day 13. It was not present any longer in most of the mice 20 days later.
ESTHER : Shao_1999_Chem.Biol.Interact_119-120_361
PubMedSearch : Shao_1999_Chem.Biol.Interact_119-120_361
PubMedID: 10421472

Title : C-Fos immunohistochemical localization of neurons in the mesencephalic locomotor region in the rat brain - Brudzynski_1996_Neurosci_75_793
Author(s) : Brudzynski SM , Wang D
Ref : Neuroscience , 75 :793 , 1996
Abstract : The projection from the limbic system via the subpallidal region to the mesencephalic locomotor region is implicated in limbic-motor integration. The goal of this study was to visualize neurons of the mesencephalic locomotor region which are active during locomotor activity induced by the disinhibition of the subpallidal region. The subpallidal region was disinhibited by picrotoxin, which antagonizes the effects of GABA. The unilateral injection of picrotoxin into the subpallidal region caused a significant increase in locomotor activity. Active tegmental neurons were subsequently visualized by immunocytochemical staining of c-Fos protein. There were significantly more immunostained neurons in the picrotoxin-injected animals than in the saline-treated rats. Heavily stained neuronal nuclei, prevailing on the brain side ipsilateral to the injection of picrotoxin, were localized within a narrow strip of tissue which stretched from the ventrolateral periaqueductal gray (including the dorsal raphe), the cuneiform nucleus, through the region of the dorsal tegmental bundle to the pedunculopontine nucleus. There were 3.5 times more immunostained neurons in the cuneiform/pedunculopontine region and 2.5 times more stained neurons in the periaqueductal region of the picrotoxin-injected rats, as compared to the saline group. This strip of immunostained cells represents neurons which are involved in the initiation and maintenance of locomotor activity due to subpallidal activation (predominantly pedunculopontine and cuneiform nuclei), as well as neurons possibly involved in the inhibition of locomotor activity (ventrolateral periaqueductal gray) and other feedback regulations. This study will help identify the neuronal pool involved in coupling the motivational commands with the locomotor system for execution of behaviour.
ESTHER : Brudzynski_1996_Neurosci_75_793
PubMedSearch : Brudzynski_1996_Neurosci_75_793
PubMedID: 8951873

Title : [Observations on damage and regeneration of corneal nerves of rabbit eyes with herpes simplex keratitis]. [Chinese] - Wang_1995_Chung.Hua.Yen.Ko.Tsa.Chih_31_52
Author(s) : Wang D , Wang C , Yang X
Ref : Chinese Journal of Ophthalmology , 31 :52 , 1995
Abstract : An experimental study on the damage and regeneration of the corneal sensory nerves in rabbit eyes with herpes simplex keratitis (HSK) was carried out by means of acetylcholine esterase staining and transmission electron microscopy. The results indicate that the diminution of the corneal sensitivity detected clinically in HSK is caused by the damage of the terminals of the sensory nerve plexus in the epithelial and subepithelial layers of the cornea and in the later stage of HSK, the corneal sensory nerves begin to regenerate, that is the basis of the restoration of corneal sensitivity.
ESTHER : Wang_1995_Chung.Hua.Yen.Ko.Tsa.Chih_31_52
PubMedSearch : Wang_1995_Chung.Hua.Yen.Ko.Tsa.Chih_31_52
PubMedID: 7781429