Zhu J

References (95)

Title : Presence of Multiple Genetic Mutations Related to Insecticide Resistance in Chinese Field Samples of Two Phthorimaea Pest Species - Zhu_2024_Insects_15_
Author(s) : Zhu J , Chen R , Liu J , Lin W , Liang J , Nauen R , Li S , Gao Y
Ref : Insects , 15 : , 2024
Abstract : Potatoes hold the distinction of being the largest non-cereal food crop globally. The application of insecticides has been the most common technology for pest control. The repeated use of synthetic insecticides of the same chemical class and frequent applications have resulted in the emergence of insecticide resistance. Two closely related pests that feed on potato crops are the potato tuber moth, Phthorimaea operculella, and the tomato leafminer, Phthorimaea absoluta (syn. Tuta absoluta). Previous studies indicated the existence of insecticide resistance to various classes of insecticides including organophosphates, carbamates, and pyrethroids in field populations of P. operculella and P. absoluta. However, the exact mechanisms of insecticide resistance in P. operculella and to a lesser extent P. absoluta remain still poorly understood. Detecting resistance genotypes is crucial for the prediction and management of insecticide resistance. In this study, we identified multiple genetic mutations related to insecticide resistance in two species of Phthorimaea. An unexpected genetic divergence on target-site mutations was observed between P. operculella and P. absoluta. Three mutations (A201S, L231V, and F290V) in Ace1 (acetylcholinesterase), four mutations (M918T, L925M, T928I, and L1014F) in VGSC (voltage-gated sodium channel), and one mutation (A301S) in RDL (GABA-gated chloride channel) have been detected with varying frequencies in Chinese P. absoluta field populations. In contrast, P. operculella field populations showed three mutations (F158Y, A201S, and L231V) in Ace1, one mutation (L1014F) in VGSC at a lower frequency, and no mutation in RDL. These findings suggest that pyrethroids, organophosphates, and carbamates are likely to be ineffective in controlling P. absoluta, but not P. operculella. These findings contributed to a deeper understanding of the presence of target-site mutations conferring resistance to commonly used (and cheap) classes of insecticides in two closely related potato pests. It is recommended to consider the resistance status of both pests for the implementation of resistance management strategies in potatoes.
ESTHER : Zhu_2024_Insects_15_
PubMedSearch : Zhu_2024_Insects_15_
PubMedID: 38535389

Title : DPPX antibody-mediated autoimmune encephalitisthe first case with breast cancer and review of the literature - Dai_2024_Heliyon_10_e27413
Author(s) : Dai Y , Zheng Y , Zhu J , Ding J , Qiu K , Tang B
Ref : Heliyon , 10 :e27413 , 2024
Abstract : Dipeptidyl-peptidase-like protein 6 (DPPX) antibody-mediated encephalitis is a rare type of autoimmune encephalitis (AE), which mainly manifests as diarrhea accompanied by weight loss, cognitive decline, epileptic seizures, and even psychiatric symptoms. Remarkably, it is also reported to be associated with tumors, predominantly B-cell lymphoma. Overall, the AE remains uncharacterized clinically and its long-term prognosis remains elusive. Herein, we report the first case of DPPX antibody-mediated AE secondary to breast cancer. Importantly, it substantially improves after aggressive immunotherapy. Our case highlights DPPX antibody-mediated AE as a paraneoplastic syndrome and discusses the pearls in its diagnosis and management.
ESTHER : Dai_2024_Heliyon_10_e27413
PubMedSearch : Dai_2024_Heliyon_10_e27413
PubMedID: 38449607

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 : MAGL protects against renal fibrosis through inhibiting tubular cell lipotoxicity - Zhou_2024_Theranostics_14_1583
Author(s) : Zhou S , Ling X , Zhu J , Liang Y , Feng Q , Xie C , Li J , Chen Q , Chen S , Miao J , Zhang M , Li Z , Shen W , Li X , Wu Q , Wang X , Liu R , Wang C , Hou FF , Kong Y , Liu Y , Zhou L
Ref : Theranostics , 14 :1583 , 2024
Abstract : Rationale: Renal fibrosis, with no therapeutic approaches, is a common pathological feature in various chronic kidney diseases (CKD). Tubular cell injury plays a pivotal role in renal fibrosis. Commonly, injured tubular cells exhibit significant lipid accumulation. However, the underlying mechanisms remain poorly understood. Methods: 2-arachidonoylglycerol (2-AG) levels in CKD patients and CKD model specimens were measured using mass spectrometry. 2-AG-loaded nanoparticles were infused into unilateral ureteral obstruction (UUO) mice. Lipid accumulation and renal fibrosis were tested. Furthermore, monoacylglycerol lipase (MAGL), the hydrolyzing enzyme of 2-AG, was assessed in CKD patients and models. Tubular cell-specific MAGL knock-in mice were generated. Moreover, MAGL recombination protein was also administered to unilateral ischemia reperfusion injury (UIRI) mice. Besides, a series of methods including RNA sequencing, metabolomics, primary cell culture, lipid staining, etc. were used. Results: 2-AG was increased in the serum or kidneys from CKD patients and models. Supplement of 2-AG further induced lipid accumulation and fibrogenesis through cannabinoid receptor type 2 (CB2)/beta-catenin signaling. beta-catenin knockout blocked 2-AG/CB2-induced fatty acid beta-oxidation (FAO) deficiency and lipid accumulation. Remarkably, MAGL significantly decreased in CKD, aligning with lipid accumulation and fibrosis. Specific transgene of MAGL in tubular cells significantly preserved FAO, inhibited lipid-mediated toxicity in tubular cells, and finally retarded fibrogenesis. Additionally, supplementation of MAGL in UIRI mice also preserved FAO function, inhibited lipid accumulation, and protected against renal fibrosis. Conclusion: MAGL is a potential diagnostic marker for kidney function decline, and also serves as a new therapeutic target for renal fibrosis through ameliorating lipotoxicity.
ESTHER : Zhou_2024_Theranostics_14_1583
PubMedSearch : Zhou_2024_Theranostics_14_1583
PubMedID: 38389852
Gene_locus related to this paper: human-MGLL , mouse-MGLL

Title : Myclobutanil induces neurotoxicity by activating autophagy and apoptosis in zebrafish larvae (Danio rerio) - Zhu_2024_Chemosphere__142027
Author(s) : Zhu J , Huang M , Jiang P , Wang J , Zhu R , Liu C
Ref : Chemosphere , :142027 , 2024
Abstract : Myclobutanil (MYC), a typical broad-spectrum triazole fungicide, is often detected in surface water. This study aimed to explore the neurotoxicity of MYC and the underlying mechanisms in zebrafish and in PC12 cells. In this study, zebrafish embryos were exposed to 0, 0.5 and 1 mg/L of MYC from 4 to 96 hours post fertilization (hpf) and neurobehavior was evaluated. Our data showed that MYC decreased the survival rate, hatching rate and heart rate, but increased the malformation rate and spontaneous movement. MYC caused abnormal neurobehaviors characterized by decreased swimming distance and movement time. MYC impaired cerebral histopathological morphology and inhibited neurogenesis in HuC:egfp transgenic zebrafish. MYC also reduced the activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and downregulated neurodevelopment related genes (gfap, syn2a, gap43 and mbp) in zebrafish and PC12 cells. Besides, MYC activated autophagy through enhanced expression of the LC3-II protein and suppressed expression of the p62 protein and autophagosome formation, subsequently triggering apoptosis by upregulating apoptotic genes (p53, bax, bcl-2 and caspase 3) and the cleaved caspase-3 protein in zebrafish and PC12 cells. These processes were restored by the autophagy inhibitor 3-methyladenine (3-MA) both in vivo and in vitro, indicating that MYC induces neurotoxicity by activating autophagy and apoptosis. Overall, this study revealed the potential autophagy and apoptosis mechanisms of MYC-induced neurotoxicity and provided novel strategies to counteract its toxicity.
ESTHER : Zhu_2024_Chemosphere__142027
PubMedSearch : Zhu_2024_Chemosphere__142027
PubMedID: 38621487

Title : Rhizoma Atractylodis Macrocephalae-Assessing the influence of herbal processing methods and improved effects on functional dyspepsia - Yang_2023_Front.Pharmacol_14_1236656
Author(s) : Yang SH , Zhu J , Wu WT , Li JM , Tong HL , Huang Y , Gong QF , Gong FP , Zhong LY
Ref : Front Pharmacol , 14 :1236656 , 2023
Abstract : Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD). Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug-metabolite-target-disease (BMTD) network and a protein-protein interaction (PPI) network, and the predictions were validated using an FD rat model. Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE). Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings.
ESTHER : Yang_2023_Front.Pharmacol_14_1236656
PubMedSearch : Yang_2023_Front.Pharmacol_14_1236656
PubMedID: 37601055

Title : Curcumin protects against fenvalerate-induced neurotoxicity in zebrafish (Danio rerio) larvae through inhibition of oxidative stress - Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
Author(s) : Zhu J , Huang M , Liu C , Wang J , Zou L , Yang F , Zhu R
Ref : Ecotoxicology & Environmental Safety , 264 :115484 , 2023
Abstract : Fenvalerate (FEN), a typical type II pyrethroid pesticide, is widely used in agriculture. FEN has been detected in the environment and human body. However, the neurotoxicity of FEN has not been well elucidated. This study aimed to explore the mechanisms underlying FEN-induced neurotoxicity using the zebrafish (Danio rerio) model. We also investigated whether curcumin (CUR), a polyphenol antioxidant that exhibits neuroprotective properties, can prevent FEN-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 3.5, 7 and 14 microg/L of FEN from 4 to 96 h post fertilization (hpf) and neurotoxicity was assessed. Our results showed that FEN decreased the survival rate, heart rate, body length and spontaneous movement, and increased malformation rate. FEN caused neurobehavioral alterations, including decreased swimming distance and velocity, movement time and clockwise rotation times. FEN also suppressed neurogenesis in transgenic HuC:egfp zebrafish, reduced cholinesterase activity and downregulated the expression of neurodevelopment related genes (elavl3, gfap, gap43 and mbp). In addition, FEN enhanced oxidative stress via excessive reactive oxygen species and antioxidant enzyme inhibition, then triggered apoptosis by upregulation of apoptotic genes (p53, bcl-2, bax and caspase 3). These adverse outcomes were alleviated by CUR, indicating that CUR mitigated FEN-induced neurotoxicity by inhibiting oxidative stress. Overall, this study revealed that CUR ameliorated FEN-induced neurotoxicity via its antioxidant, indicating a promising protection of CUR against environmental pollutant-induced developmental anomalies.
ESTHER : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedSearch : Zhu_2023_Ecotoxicol.Environ.Saf_264_115484
PubMedID: 37716069

Title : Metabolism-guided development of Ko143 analogs as ABCG2 inhibitors - Zhu_2023_Eur.J.Med.Chem_259_115666
Author(s) : Zhu J , Lei S , Lu J , Hao Y , Qian Q , Devanathan AS , Feng Z , Xie XQ , Wipf P , Ma X
Ref : Eur Journal of Medicinal Chemistry , 259 :115666 , 2023
Abstract : ATP-binding cassette subfamily G member 2 (ABCG2), an efflux transporter, is involved in multiple pathological processes. Ko143 is a potent ABCG2 inhibitor; however, it is quickly metabolized through carboxylesterase 1-mediated hydrolysis of its t-butyl ester moiety. The current work aimed to develop more metabolically stable ABCG2 inhibitors. Novel Ko143 analogs were designed and synthesized by replacing the unstable t-butyl ester moiety in Ko143 with an amide group. The synthesized Ko143 analogs were evaluated for their ABCG2 inhibitory activity, binding mode with ABCG2, cytotoxicity, and metabolic stability. We found that the amide modification of Ko143 led to metabolically stable ABCG2 inhibitors. Among these Ko143 analogs, K2 and K34 are promising candidates with favorable oral pharmacokinetic profiles in mice. In summary, we synthesized novel Ko143 analogs with improved metabolic stability, which can potentially be used as lead compounds for the future development of ABCG2 inhibitors.
ESTHER : Zhu_2023_Eur.J.Med.Chem_259_115666
PubMedSearch : Zhu_2023_Eur.J.Med.Chem_259_115666
PubMedID: 37482017

Title : Ovalbumin-coated gold nanoparticles with interesting colloidal stability for colorimetric detection of carbaryl in complex media - Hao_2023_Food.Chem_403_134485
Author(s) : Hao H , Zhu J , Yang B , Peng L , Lou S
Ref : Food Chem , 403 :134485 , 2023
Abstract : Pesticide carbaryl can cause serious environmental pollution and its sensitive detection is of increasing interest. Gold nanoparticles (AuNPs) are classically colorimetric probes for detection of many analytes, but the instability in complex media limits their application. Here, Au@Ova NPs have been developed as a stable, effective, sensitive, and selective sensing system for colorimetric detection of carbaryl. Au@Ova NPs present unique and proper colloidal stability in various medias containing salt, small molecules, organic solvent (DMSO), and seawater, which are distinct from previous ones including citrate (or rhodamine B) capped AuNPs. Compared with Au@BSA NPs, Au@Ova NPs showed efficient responses to carbaryl by inhibiting acetylcholinesterase, with a linear concentration range between 0 and 25 g/L and a detection limit of 0.25 g/L. In addition, this nanoprobe also has good selectivity and can be applied in different real samples analysis, including fruit juice (tomato and apple) and real water samples (artificial urine and seawater).
ESTHER : Hao_2023_Food.Chem_403_134485
PubMedSearch : Hao_2023_Food.Chem_403_134485
PubMedID: 36358087

Title : Strigolactones positively regulate Verticillium wilt resistance in cotton via crosstalk with other hormones - Yi_2023_Plant.Physiol__
Author(s) : Yi F , An G , Song A , Cheng K , Liu J , Wang C , Wu S , Wang P , Zhu J , Liang Z , Chang Y , Chu Z , Cai C , Zhang X , Chen A , Xu J , Burritt DJ , Herrera-Estrella L , Tran LP , Li W , Cai Y
Ref : Plant Physiol , : , 2023
Abstract : Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation.
ESTHER : Yi_2023_Plant.Physiol__
PubMedSearch : Yi_2023_Plant.Physiol__
PubMedID: 36718522

Title : Comprehensive multi-omics analysis reveals the core role of glycerophospholipid metabolism in rheumatoid arthritis development - Jian_2023_Arthritis.Res.Ther_25_246
Author(s) : Jian C , Wei L , Wu T , Li S , Wang T , Chen J , Chang S , Zhang J , He B , Wu J , Su J , Zhu J , Wu M , Zhang Y , Zeng F
Ref : Arthritis Res Ther , 25 :246 , 2023
Abstract : OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis and eventually lead to joint deformity. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis. METHODS: A total of 113 RA patients and 75 controls were included in our study. Plasma and stool samples were obtained for 16S rRNA sequencing, internally transcribed spacer (ITS) sequencing and metabolomics analysis. And PBMCs were obtained for RNA sequencing. We used three models, logistic regression, least absolute shrinkage and selection operator (LASSO), and random forest, respectively, to distinguish NORA from CRA, and finally we validated model performance using an external cohort of 26 subjects. RESULTS: Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance of Escherichia-Shigella and Proteobacteria in NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 29 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics. Additionally, we applied three approaches to develop disease classifier models that were based on plasma metabolites and gut microbiota, which effectively distinguished between new-onset and chronic RA patients in both discovery cohort and external validation cohort. CONCLUSIONS: These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
ESTHER : Jian_2023_Arthritis.Res.Ther_25_246
PubMedSearch : Jian_2023_Arthritis.Res.Ther_25_246
PubMedID: 38102690

Title : Lonicera japonica polysaccharides alleviate D-galactose-induced oxidative stress and restore gut microbiota in ICR mice - Sun_2023_Int.J.Biol.Macromol__125517
Author(s) : Sun W , Zhu J , Qin G , Huang Y , Cheng S , Chen Z , Zhang Y , Shu Y , Zeng X , Guo R
Ref : Int J Biol Macromol , :125517 , 2023
Abstract : Lonicera japonica polysaccharides (LJPs) exhibit anti-aging effect in nematodes. Here, we further studied the function of LJPs on aging-related disorders in D-galactose (D-gal)-induced ICR mice. Four groups of mice including the control group, the D-gal-treated group, the intervening groups with low and high dose of LJPs (50 and 100 mg/kg/day) were raised for 8 weeks. The results showed that intragastric administration with LJPs improved the organ indexes of D-gal-treated mice. Moreover, LJPs improved the activity of superoxide dismutase (SOD), catalase (CAT) as well as glutathione peroxidase (GSH-Px) and decreasing the malondialdehyde (MDA) level in serum, liver and brain. Meanwhile, LJPs restored the content of acetylcholinesterase (AChE) in the brain. Further, LJPs reversed the liver tissue damages in aging mice. Mechanistically, LJPs alleviate oxidative stress at least partially through regulating Nrf2 signaling. Additionally, LJPs restored the gut microbiota composition of D-gal-treated mice by adjusting the Firmicutes/Bacteroidetes ratio at the phylum level and upregulating the relative abundances of Lactobacillaceae and Bifidobacteriacesa. Notably, the KEGG pathways involved in hazardous substances degradation and flavone and flavonol biosynthesis were significantly enhanced by LJPs treatment. Overall, our study uncovers the role of LJPs in modulating oxidative stress and gut microbiota in the D-gal-induced aging mice.
ESTHER : Sun_2023_Int.J.Biol.Macromol__125517
PubMedSearch : Sun_2023_Int.J.Biol.Macromol__125517
PubMedID: 37353132

Title : Design of 2,5-furandicarboxylic based polyesters degraded in different environmental conditions: Comprehensive experimental and theoretical study - Hu_2022_J.Hazard.Mater_425_127752
Author(s) : Hu H , Li J , Luo S , Tian Y , Wang J , Zhao YL , Zhang R , Zhu J
Ref : J Hazard Mater , 425 :127752 , 2022
Abstract : Nowadays, the promotion and application of aliphatic-aromatic copolyesters, such as poly (butylene adipate-co-terephthalate) (PBAT), are growing into a general trend. Although the structures of diacids exerted substantial impacts on degradation behavior, the underlying mechanisms have rarely been studied. In this work, 2,5-Furandicarboxylic acid was combined with succinic acid (PBSF), adipic acid (PBAF) and diglycolic acid (PBDF) to prepare three kinds of copolyesters. They showed unique degradation behaviors in buffer, enzyme environment and artificial seawater. These characteristics are closely related to the structural compositions of diacids. PBAFs displayed impressive biodegradability when catalyzed by Candida antarctica lipase B (CALB), while the more hydrophilic PBDFs exhibited faster hydrolysis in both buffer and artificial seawater. PBSFs, with hydrophobic and short segments, obtained a relatively slower rate of hydrolysis and enzymatic degradation. The reactivity sites and hydrolytic pathway were revealed by the combination of DFT calculation and Fukui function analysis. MD simulations, QM/MM optimizations and theozyme calculations showed that PBAF-CALB was prone to form a pre-reaction state, leading to the reduced energy barrier in the acylation process. This work revealed the effects of different structural features of diacids on polymer degradation and paved a way to design target biodegradable polymers in different degradation conditions.
ESTHER : Hu_2022_J.Hazard.Mater_425_127752
PubMedSearch : Hu_2022_J.Hazard.Mater_425_127752
PubMedID: 34906869
Gene_locus related to this paper: canar-LipB

Title : The adverse effects of fluxapyroxad on the neurodevelopment of zebrafish embryos - Yu_2022_Chemosphere_307_135751
Author(s) : Yu H , Zhang J , Chen Y , Chen J , Qiu Y , Zhao Y , Li H , Xia S , Chen S , Zhu J
Ref : Chemosphere , 307 :135751 , 2022
Abstract : Fluxapyroxad (Flu), one of the succinate dehydrogenase-inhibited (SDHI) fungicides, has been extensively used in crop fungal disease control. Despite its increasing use in modern agriculture and long-term retention in the environment, the potentially toxic effects of Flu in vivo, especially on neurodevelopment, remain under-evaluated. In this study, zebrafish embryos were exposed to Flu at concentrations of 0.5, 0.75, and 1 mg/L for 96 h to evaluate the neurotoxicity of Flu. The results showed that Flu caused concentration-dependent malformations, including shorter body length, smaller head and eyes, and yolk sac edema. After exposure to Flu, larval zebrafish exhibited severe motor aberrations. Flu at a concentration of 1 mg/L significantly decreased dopamine level and notably altered acetylcholinesterase (AChE) activity and acetylcholine (ACh) content. Abnormal central nervous system (CNS) neurogenesis and disordered motor neuron development were observed in Tg (HUC-GFP) and Tg (hb9-GFP) zebrafish in Flu-treated groups. The expression of key genes involved in neurotransmission and neurodevelopment further proved that Flu impaired the zebrafish nervous system. This work contributes to our understanding of the neurotoxic effects and mechanisms induced by Flu in zebrafish and may help us take precautions against the neurotoxicity of Flu.
ESTHER : Yu_2022_Chemosphere_307_135751
PubMedSearch : Yu_2022_Chemosphere_307_135751
PubMedID: 35863420

Title : Two Triacylglycerol Lipases Are Negative Regulators of Chilling Stress Tolerance in Arabidopsis - Wang_2022_Int.J.Mol.Sci_23_
Author(s) : Wang L , Qian B , Zhao L , Liang MH , Zhan X , Zhu J
Ref : Int J Mol Sci , 23 : , 2022
Abstract : Cold stress is one of the abiotic stress conditions that severely limit plant growth and development and productivity. Triacylglycerol lipases are important metabolic enzymes for the catabolism of triacylglycerols and, therefore, play important roles in cellular activities including seed germination and early seedling establishment. However, whether they play a role in cold stress responses remains unknown. In this study, we characterized two Arabidopsis triacylglycerol lipases, MPL1 and LIP1 and defined their role in cold stress. The expression of MPL1 and LIP1 is reduced by cold stress, suggesting that they may be negative factors related to cold stress. Indeed, we found that loss-of-function of MPL1 and LIP1 resulted in increased cold tolerance and that the mpl1lip1 double mutant displayed an additive effect on cold tolerance. We performed RNA-seq analysis to reveal the global effect of the mpl1 and lip1 mutations on gene expression under cold stress. The mpl1 mutation had a small effect on gene expression under both under control and cold stress conditions whereas the lip1 mutation caused a much stronger effect on gene expression under control and cold stress conditions. The mpl1lip1 double mutant had a moderate effect on gene expression under control and cold stress conditions. Together, our results indicate that MPL1 and LIP1 triacylglycerol lipases are negative regulators of cold tolerance without any side effects on growth in Arabidopsis and that they might be ideal candidates for breeding cold-tolerant crops through genome editing technology.
ESTHER : Wang_2022_Int.J.Mol.Sci_23_
PubMedSearch : Wang_2022_Int.J.Mol.Sci_23_
PubMedID: 35328798

Title : Identification of novel immune-related targets mediating disease progression in acute pancreatitis - Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
Author(s) : Liu Q , Li L , Xu D , Zhu J , Huang Z , Yang J , Cheng S , Gu Y , Zheng L , Zhang X , Shen H
Ref : Front Cell Infect Microbiol , 12 :1052466 , 2022
Abstract : INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear. METHODS: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo. RESULTS: The numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 x 10(-3)), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 x 10(-8)), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation. DISCUSSION: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression.
ESTHER : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedSearch : Liu_2022_Front.Cell.Infect.Microbiol_12_1052466
PubMedID: 36590588

Title : A green photocatalytic-biosensor for colorimetric detection of pesticide (carbaryl) based on inhibition of acetylcholinesterase - Peng_2022_Talanta_246_123525
Author(s) : Peng L , Zhu J , Yang B , Hao H , Lou S
Ref : Talanta , 246 :123525 , 2022
Abstract : Carbaryl is a widely-used carbamate pesticide and the detection of its residues in environmental, food and clinical samples is of great importance. In this sturdy, we developed a green photocatalytic-biosensor based on double strand DNA-SYBR green I complex for sensitively colorimetric detection of carbaryl. This green photocatalytic-biosensor can oxidize 3,3',5,5'-tetramethylbenzidine (TMB) into blue ox-TMB. Meanwhile thiocholine is catalytically produced by acetylcholinesterase (AChE) to directly reduce blue ox-TMB into colorless TMB. But the activity of AChE will be suppressed by carbaryl, thus generating less thiocholine and resulting in more ox-TMB for colorimetric analysis. After the careful optimization of sensing conditions (2 microM for DNA concentration, 50 x concentration for SYBR Green I, 10 min for illumination time), the lowest detectable concentration for carbaryl is 0.008 ng/mL with a linear response in the range of 0.01-0.25 ng/mL. In addition, this photocatalytic-biosensor has good selectivity over non-target chemicals (acetamiprid, atrazine, carbendazim, melamine, bisphenol A, estradiol). It also allows detection of pesticides in real samples verified by a standard HPLC method.
ESTHER : Peng_2022_Talanta_246_123525
PubMedSearch : Peng_2022_Talanta_246_123525
PubMedID: 35533565

Title : Phytochemical profiling and antioxidant, enzyme-inhibitory, and toxic activities of extracts from Adonis ramosa Franch - Guo_2022_Nat.Prod.Res__1
Author(s) : Guo X , Chen M , He X , Zhao Y , Yu J , Zhu J , Li L , Xia G , Zang H
Ref : Nat Prod Res , :1 , 2022
Abstract : This study investigated the content and biological activity of three solvent extracts of Adonis ramosa Franch (AR), which contains 12 types of phytochemicals. The overall yield and total protein content of the aqueous extract were the highest, and it exhibited the highest hydroxyl and superoxide radical-scavenging abilities, copper chelating abilities, and cupric reducing antioxidant capacity. Ethanol extract had the highest total phenolic, flavonoid, and carbohydrate contents, and it showed the highest iron chelating activity, and HClO- and nitrite-scavenging abilities. Methanol AR extract contained the highest total steroid and tannin contents; it also demonstrated high radical- and reactive oxygen species-scavenging abilities and had the best ferric reducing antioxidant power, which allowed it to effectively prevent beta-carotene bleaching. Methanol extract also showed good stability and low toxicity. All tested solvent extracts of AR exhibited weak enzyme-inhibitory activities for four enzymes (alpha-glucosidase, alpha-amylase, acetylcholinesterase and butyrylcholinesterase). Overall, AR can serve as a natural antioxidant.
ESTHER : Guo_2022_Nat.Prod.Res__1
PubMedSearch : Guo_2022_Nat.Prod.Res__1
PubMedID: 35045779

Title : The inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit on acetylcholinesterase: A interaction, kinetic, spectroscopic, and molecular simulation study - Wu_2022_Food.Res.Int_158_111497
Author(s) : Wu M , Liu M , Wang F , Cai J , Luo Q , Li S , Zhu J , Tang Z , Fang Z , Wang C , Chen H
Ref : Food Res Int , 158 :111497 , 2022
Abstract : The present study aimed to investigate the inhibition mechanism of polyphenols from Phyllanthus emblica Linn. fruit (PEF, family Euphorbiaceous) on acetylcholinesterase (AChE). Interaction assay, enzyme kinetics, spectroscopic methods, and molecular simulations were performed. Results showed that myricetin, quercetin, fisetin, and gallic acid were the most active components in PEF, because of their low docking scores and strong inhibition ability on AChE with IC(50) values of 0.1974 +/- 0.0047, 0.2589 +/- 0.0131, 1.0905 +/- 0.0598 and 1.503 +/- 0.0728 mM, respectively. Among them, the results of kinetic study showed that myricetin, quercetin, and fisetin reversibly inhibited AChE in a competitive manner, while gallic acid inhibited it through a noncompetition type. The interaction assay implied that a combination of the four polyphenols at the selected concentrations manifested a synergistic inhibition effect on AChE in a mixed inhibition type. Fluorescence and UV-vis spectrophotometry revealed that the active PEF polyphenols could strongly quench the intrinsic fluorescence of AChE via a static quenching mechanism. Circular dichroism spectroscopy analysis indicated that the active PEF polyphenols gave rise to the secondary structure changes of AChE by increasing the content of alpha-helix and reducing beta-sheet and random coil conformation. The molecular dynamics simulation results validated that all the four docked polyphenol-AChE complexes were relatively stable according to their root-mean-square distance, root-mean-square fluctuations, solvent accessible surface area, radius of gyration values and hydrogen bonds evaluations during the whole simulation process. Overall, our study provides a creative insight into the further utilization of PEF polyphenols as functional components in exploring natural AChE inhibitors.
ESTHER : Wu_2022_Food.Res.Int_158_111497
PubMedSearch : Wu_2022_Food.Res.Int_158_111497
PubMedID: 35840206

Title : Functional characterization of CYP6G4 from the house fly in propoxur metabolism and resistance - Zhu_2022_Pestic.Biochem.Physiol_187_105186
Author(s) : Zhu J , Feng J , Tian K , Li C , Li M , Qiu X
Ref : Pestic Biochem Physiol , 187 :105186 , 2022
Abstract : The house fly (Musca domestica L.) (Diptera: Muscidae) is a global vector that can transmit >250 human and animal diseases. The control of house flies has heavily relied on the application of various chemical insecticides. The carbamate insecticide propoxur has been widely used for the control of house flies, and resistance to propoxur has been documented in many house fly populations worldwide. Previous studies have identified several propoxur resistance-conferring mutations in the target protein acetylcholinesterase; however, the molecular basis for metabolic resistance to propoxur remains unknown. In this study, we investigated the involvement of CYP6G4, a cytochrome P450 overexpressed in many insecticide resistant populations of Musca domestica, in propoxur metabolism and resistance by using combined approaches of recombinant protein-based insecticide metabolism and the Drosophila GAL4/UAS transgenic system. The recombinant CYP6G4 and its redox partners (NADPH-dependent cytochrome P450 reductase and cytochrome b5) were functionally expressed in Escherichia coli. Metabolism experiments showed that CYP6G4 was able to transform propoxur with a turnover rate of around 0.79 min(-1). Six metabolites were putatively identified, suggesting that CYP6G4 could metabolize propoxur via hydroxylation, O-depropylation and N-demethylation. Moreover, bioassay results showed that ectopic overexpression of CYP6G4 in fruit flies significantly increased their tolerance to propoxur. Our in vivo and in vitro data convincingly demonstrate that CYP6G4 contributes to propoxur metabolism and resistance.
ESTHER : Zhu_2022_Pestic.Biochem.Physiol_187_105186
PubMedSearch : Zhu_2022_Pestic.Biochem.Physiol_187_105186
PubMedID: 36127048

Title : Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster - Zhu_2022_Theor.Appl.Genet__
Author(s) : Zhu K , Li M , Wu H , Zhang D , Dong L , Wu Q , Chen Y , Xie J , Lu P , Guo G , Zhang H , Zhang P , Li B , Li W , Wang Q , Zhu J , Hu W , Guo L , Wang R , Yuan C , Li H , Liu Z , Hua W
Ref : Theor Appl Genet , : , 2022
Abstract : Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars.
ESTHER : Zhu_2022_Theor.Appl.Genet__
PubMedSearch : Zhu_2022_Theor.Appl.Genet__
PubMedID: 35006335

Title : Ferulic acid regulates miR-17\/PTEN axis to inhibit LPS-induced pulmonary microvascular endothelial cells apoptosis through activation of PI3K\/Akt pathway - Zhang_2022_J.Toxicol.Sci_47_61
Author(s) : Zhang Q , Wang Z , Zhu J , Peng Z , Tang C
Ref : Journal of Toxicological Sciences , 47 :61 , 2022
Abstract : Acute lung injury (ALI) is mainly mediated by the damage of pulmonary microvascular endothelial cells (PMVECs). LPS is one of the pathogenic factors leading to microcirculatory abnormalities of ALI. Ferulic acid (FA) exhibits therapeutic eects against various diseases. During lipopolysaccharide-induced acute respiratory distress syndrome, FA, when given beforehand, could depress inflammation and oxidative stress. However, the concrete role and underlying mechanism of FA in ALI have not been well characterized. Ten microg/mL Lipopolysaccharide (LPS) was used to treat rat PMVECs for 24 hr. qRT-PCR was used to detect the level of miR-17 and phosphatase and tensin homolog deleted on chromosome ten (PTEN). Western blot was used to analyze the associated proteins in the PI3K/Akt pathway, and the apoptosis-related proteins. Flow cytometric analysis was performed to detect the apoptosis of PMVECs. MTT assay was constructed to detect the cell viability. Luciferase assay was conducted to detect the target gene of miR-17 and PTEN. A cell model for in vitro studying the role of FA in ALI was established using PMVECs. Our data demonstrate that FA up-regulates miR-17 and declines apoptosis induced by LPS. FA inhibits apoptosis mediated by up-regulating miR-17. Furthermore, we found miR-17 targeted PTEN negatively. FA inhibits cleaved caspase-3 and Bax expression through the PI3K/Akt pathway mediated by up-regulating miR-17. Over-expression of PTEN could contribute to the similar expression trend of the PI3K/Akt signal pathway protein compared to miR-17 inhibitor transfected cells. FA inhibits PMVECs apoptosis induced by LPS via miR-17/PTEN to further regulate the activation of the PI3K/Akt pathway in ALI. We anticipate that our data will provoke additional studies for ALI clinical therapy.
ESTHER : Zhang_2022_J.Toxicol.Sci_47_61
PubMedSearch : Zhang_2022_J.Toxicol.Sci_47_61
PubMedID: 35110471

Title : The novel therapeutic strategy of vilazodone-donepezil chimeras as potent triple-target ligands for the potential treatment of Alzheimer's disease with comorbid depression - Li_2021_Eur.J.Med.Chem_229_114045
Author(s) : Li X , Li J , Huang Y , Gong Q , Fu Y , Xu Y , Huang J , You H , Zhang D , Mao F , Zhu J , Wang H , Zhang H
Ref : Eur Journal of Medicinal Chemistry , 229 :114045 , 2021
Abstract : Depression is one of the most frequent comorbid psychiatric symptoms of Alzheimer's disease (AD), and no efficacious drugs have been approved specifically for this purpose thus far. Herein, we proposed a novel therapeutic strategy that merged the key pharmacophores of the antidepressant vilazodone (5-HT(1A) receptor partial agonist and serotonin transporter inhibitor) and the anti-AD drug donepezil (acetylcholinesterase inhibitor) together to develop a series of multi-target-directed ligands for potential therapy of the comorbidity of AD and depression. Accordingly, 55 vilazodone-donepezil chimeric derivatives were designed and synthesized, and their triple-target activities against acetylcholinesterase, 5-HT(1A) receptor, and serotonin transporter were systematically evaluated. Among them, compound 5 displayed strong triple-target bioactivities in vitro, low hERG potassium channel inhibition and acceptable brain distribution. Importantly, oral intake of 5 mg/kg of the compound 5 dihydrochloride significantly alleviated the depressive symptoms and ameliorated cognitive dysfunction in mouse models. In brief, these results highlight vilazodone-donepezil chimeras as a prospective therapeutic approach for the treatment of the comorbidity of AD and depression.
ESTHER : Li_2021_Eur.J.Med.Chem_229_114045
PubMedSearch : Li_2021_Eur.J.Med.Chem_229_114045
PubMedID: 34922191

Title : Identification, Classification, and Expression Analysis of the Triacylglycerol Lipase (TGL) Gene Family Related to Abiotic Stresses in Tomato - Wang_2021_Int.J.Mol.Sci_22_1387
Author(s) : Wang Q , Xu X , Cao X , Hu T , Xia D , Zhu J , Zhan X
Ref : Int J Mol Sci , 22 :1387 , 2021
Abstract : Triacylglycerol Lipases (TGLs) are the major enzymes involved in triacylglycerol catabolism. TGLs hydrolyze long-chain fatty acid triglycerides, which are involved in plant development and abiotic stress responses. Whereas most studies of TGLs have focused on seed oil metabolism and biofuel in plants, limited information is available regarding the genome-wide identification and characterization of the TGL gene family in tomato (Solanum lycopersicum L.). Based on the latest published tomato genome annotation ITAG4.0, 129 SlTGL genes were identified and classified into 5 categories according to their structural characteristics. Most SlTGL genes were distributed on 3 of 12 chromosomes. Segment duplication appeared to be the driving force underlying expansion of the TGL gene family in tomato. The promoter analysis revealed that the promoters of SlTGLs contained many stress responsiveness cis-elements, such as ARE, LTR, MBS, WRE3, and WUN-motifs. Expression of the majority of SlTGL genes was suppressed following exposure to chilling and heat, while it was induced under drought stress, such as SlTGLa9, SlTGLa6, SlTGLa25, SlTGLa26, and SlTGLa13. These results provide valuable insights into the roles of the SlTGL genes family and lay a foundation for further functional studies on the linkage between triacylglycerol catabolism and abiotic stress responses in tomato.
ESTHER : Wang_2021_Int.J.Mol.Sci_22_1387
PubMedSearch : Wang_2021_Int.J.Mol.Sci_22_1387
PubMedID: 33573234

Title : Multiple Genetic Mutations Related to Insecticide Resistance are Detected in Field Kazakhstani House Flies (Muscidae: Diptera) - Qu_2021_J.Med.Entomol__
Author(s) : Qu R , Zhu J , Li M , Jashenko R , Qiu X
Ref : Journal of Medical Entomology , : , 2021
Abstract : The house fly (Musca domestica Linnaeus) is an important disease vector. Insecticide resistance is an obstacle to effective house fly control. Previous studies have demonstrated that point mutations in acetylcholinesterase (Ace), carboxylesterase (MdalphaE7) and voltage-sensitive sodium channel (Vssc), and over-expression of CYP6D1v1 confer insecticide resistance in the house fly. However, information about the status and underlying mechanisms of insecticide resistance in Kazakhstani house flies is lacking. In this study, we investigated the occurrence of genetic mutations associated with insecticide resistance in field house flies collected at six different locations in southern Kazakhstan. Four mutations (V260L, G342A/V, and F407Y) in Ace and three mutations (G137D and W251L/S) in MdalphaE7 were detected with appreciable frequencies. Notably, haplotypes carrying triple-loci mutations in Ace and double mutations in MdalphaE7 were found in Kazakhstan. The L1014H and L1014F mutations in Vssc, and CYP6D1v1 resistance allele were detected at a low frequency in some of the six investigated house fly populations. Phylogenetic analyses of haplotypes supported multiple origins of resistance mutations in Ace and MdalphaE7. These observations suggest that house flies in southern Kazakhstan may exhibit significant resistance to organophosphates and carbamates. Regular monitoring of insecticide resistance is recommended to achieve effective house fly control by chemical agents in southern Kazakhstan.
ESTHER : Qu_2021_J.Med.Entomol__
PubMedSearch : Qu_2021_J.Med.Entomol__
PubMedID: 34197608

Title : Preparation of MED1(transcription mediator subunit) gene nanocarrier and its mechanism of action on liver cell regeneration in chronic acute liver failure - Guo_2021_Bioengineered_12_7600
Author(s) : Guo J , Zhang Z , Zhu J
Ref : Bioengineered , 12 :7600 , 2021
Abstract : Liver failure has attracted attention in clinical work due to its high mortality, and the development of liver transplantation is restricted by various factors. Therefore, it is very important to carry out research on the mechanism of liver cell regeneration. This article has studied in depth the preparation of MED1 gene nanocarriers, collected human plasmids and cells through experimental materials and experimental instruments, and conducted comparative research on conventional culture. This question conducts a regeneration experiment on liver cells in chronic-onset acute liver failure, divides patients into an experimental group and a control group, and understands the recovery of liver function according to the screening of their plasma samples and separation of plasma. This article selects the commonly used clinical biological markers, such as Na+, AFP, Alb, CHE (serum cholinesterase) and other indicators to reflect the regeneration ability of liver function. The incidence of surgical complications in the control group, such as ascites, infection, bleeding, HE, hepatorenal syndrome, and hyponatremia were 71.3%, 87.4%, 16.1%, 41.4%, 19.5%, and 33.3%, respectively. Significantly higher than the experimental group, the difference was statistically significant (P < 0.05); while gender, age, PLT level and whether to use hormones, artificial liver or not there was no significant difference between the two groups (P > 0.05).
ESTHER : Guo_2021_Bioengineered_12_7600
PubMedSearch : Guo_2021_Bioengineered_12_7600
PubMedID: 34612778

Title : Neuroprotective effects of maize tetrapeptide-anchored gold nanoparticles in Alzheimer's disease - Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
Author(s) : Zhang J , Liu R , Zhang D , Zhang Z , Zhu J , Xu L , Guo Y
Ref : Colloids Surf B Biointerfaces , 200 :111584 , 2021
Abstract : Nanopeptide assembled from peptide-anchored nanoparticles possess an enormous research potential in the field of cellular medicine and disease treatment. The aim of this study was to explore the neuroprotective effects of maize tetrapeptide anchored gold nanoparticles against l-glutamic acid-induced PC12 cell apoptosis and a murine Alzheimer's disease model induced by aluminum chloride and d-galactose. The results revealed that the nanopeptide antioxidant inhibited intracellular ROS accumulation and promoted cell differentiation than that of maize bioactive tetrapeptide. Compared with untreated Alzheimer's disease model mice, nanopeptide administration shortened the escape latency time in a water maze test and improved the movements in the autonomic activity test. After 16 days of nanopeptide administration, the central cholinergic system function of acetylcholine and cholineacetyltransferase were enhanced, and the level of acetylcholinesterase was reduced. It also increased superoxide dismutase and glutathione peroxidase activity in sera and hypothalami. Moreover, nanopeptide treatment upregulated cerebral nuclear factor erythroid 2-related factor 2 and heme-oxygenase-1 and downregulated kelch-like ECH-associated protein 1 relative to untreated Alzheimer's disease model mice. Thus, the novel nanopeptide is expected to be used as the neuroprotective agent to prevent Alzheimer's disease.
ESTHER : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedSearch : Zhang_2021_Colloids.Surf.B.Biointerfaces_200_111584
PubMedID: 33508658

Title : Molecular Dynamic Simulation of the Porcine Pancreatic Lipase in Non-aqueous Organic Solvents - Chen_2020_Front.Bioeng.Biotechnol_8_676
Author(s) : Chen ZS , Wu YD , Hao JH , Liu YJ , He KP , Jiang WH , Xiong MJ , Lv YS , Cao SL , Zhu J
Ref : Front Bioeng Biotechnol , 8 :676 , 2020
Abstract : This paper investigates the conformational stability of porcine pancreatic lipase (PPL) in three non-aqueous organic solvents, including dimethyl sulfoxide (DMSO), propylene glycol (PRG), and ethanol (EtOH) through molecular dynamic (MD) simulation. The root mean square deviations (RMSDs), radius of gyration (Rg), solution accessible surface area (SASA), radial distribution function (RDF), hydrogen bond (H-bond), Ramachandran plot analysis, secondary structure, and enzyme substrate affinity of the PPL in the various organic solvents were comparatively investigated. The results showed that the backbone and active pocket RMSD, and hydrophilic ASA of PPL in three solvents increase with the increase in the solvent LogP, while the Rg, hydrophobic ASA, and H-bond between the solvent and PPL decrease. Among the three organic solvents, DMSO acts as a better solvent, in which the PPL can be loose and extended, and retains its native backbone in DMSO compared to PRG and EtOH. Moreover, Ramachandran plot analysis indicated that the PPL structure quality in DMSO was higher than that in PRG and EtOH. Also, the molecular docking results showed that PPL in DMSO exhibited the highest enzyme-substrate affinity.
ESTHER : Chen_2020_Front.Bioeng.Biotechnol_8_676
PubMedSearch : Chen_2020_Front.Bioeng.Biotechnol_8_676
PubMedID: 32766212

Title : [Effects of Moringa flavone on cognitive function and neuropathological indexes in diabetic encephalopathy rats] - Zhu_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_1491
Author(s) : Zhu J , Zhao C , Qiao Y , Liu Y , Sui Y
Ref : Zhonghua Wei Zhong Bing Ji Jiu Yi Xue , 32 :1491 , 2020
Abstract : OBJECTIVE: To investigate the effect of Moringa flavone on cognitive impairment and neuropathological indexes in diabetic encephalopathy (DE) rats. METHODS: Sixty male Sprague-Dawley (SD) rats were divided into control group, model group, positive drug group, Moringa low-dose and high-dose groups according to the random number table method, with 10 rats in each group. Diabetic rat model was established by intraperitoneal injection of 25 mg/kg streptozotocin (STZ) after continuous feeding of high fat and high sugar diet for one week. Blood was collected from the tail vein after 72 hours, the mean value of twice random blood glucose was <= 16.67 mmol/L, and the continuous positive urine glucose showed that the diabetes model was successfully prepared. The control group was fed with conventional feed. After successful model establishment, the rats in the Moringa low and high dose groups were given 4.0 g/kg and 8.0 g/kg Moringa extract (Moringa flavone) by gavage everyday, the rats in the positive drug group were given piracetam 0.48 g/kg, and the rats in the model group and control group were given the same amount of normal saline once a day for 30 days. Morris water maze was used to evaluate the cognitive impairment of the rats. The hippocampus of the rats was harvested 12 hours after the last administration, and the advanced glycation end product receptor (RAGE) and nuclear factor-kappaB (NF-kappaB) were detected by immunohistochemistry. The contents of acetylcholinesterase (AChE), advanced glycation end product (AGE) and choline acetyl transferase (ChAT) were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the control group, the escape latency and the exploration distance in model group were extended, target quadrant stay time was shortened, the levels of AChE and AGE in brain tissue were significantly increased, and ChAT level was significantly decreased. Morris water maze experiment showed that compared with the model group, in the Moringa low and high dose groups from the 3rd day, the escape latency (s: 35.07+/-7.21, 33.14+/-5.35 vs. 43.09+/-9.83, both P < 0.05) and the exploration distance (m: 8.32+/-4.23, 8.10+/-4.97 vs. 13.02+/-3.67) were significantly shortened (both P < 0.05). The target qauadrant stay time was extended (s: 35.12+/-3.12, 41.53+/-8.37 vs. 23.15+/-4.89, both P < 0.01). The results of ELISA showed that compared with the model group, the levels of AChE and AGE in brain tissue of the Moringa low and high dose groups were significantly decreased [AChE (U/L): 180.22+/-12.03, 142.67+/-20.56 vs. 205.27+/-25.14, AGE (microg/L): 439.10+/-25.19, 428.27+/-19.14 vs. 501.28+/-21.53, all P < 0.05], and the levels of ChAT were significantly increased (U/L: 51.95+/-5.27, 53.13+/-5.04 vs. 37.91+/-5.10, both P < 0.01). There were no significant differences in AChE, AGE or ChAT between the Moringa low and high dose groups. The results of immunohistochemistry showed that the number of RAGE and NF-kappaB positive cells in DG area of hippocampus increased significantly, and the average gray values of RAGE and NF-kappaB decreased significantly. Compared with the model group, the RAGE and NF-kappaB positive cells in the Moringa low and high dose groups were significantly reduced, and the average gray values of RAGE and NF-kappaB in hippocampus were significantly increased [RAGE (gray value): 110.46+/-10.04, 117.76+/-8.64 vs. 92.19+/-8.76, NF-kappaB (gray value): 109.40+/-8.93, 116.59+/-7.26 vs. 90.74+/-13.27, all P < 0.05]. There were no significant differences in the expressions of RAGE or NF-kappaB between the Moringa low and high dose groups. CONCLUSIONS: Moringa flavonoids could obviously improve the cognitive dysfunction and memory ability of DE model rats, improve the pathological changes of hippocampus, and have a certain protective effect on brain.
ESTHER : Zhu_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_1491
PubMedSearch : Zhu_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_1491
PubMedID: 33541503

Title : Discovery of nitazoxanide-based derivatives as autophagy activators for the treatment of Alzheimer's disease - Li_2020_Acta.Pharm.Sin.B_10_646
Author(s) : Li X , Lu J , Xu Y , Wang J , Qiu X , Fan L , Li B , Liu W , Mao F , Zhu J , Shen X , Li J
Ref : Acta Pharm Sin B , 10 :646 , 2020
Abstract : Drug repurposing is an efficient strategy for new drug discovery. Our latest study found that nitazoxanide (NTZ), an approved anti-parasite drug, was an autophagy activator and could alleviate the symptom of Alzheimer's disease (AD). In order to further improve the efficacy and discover new chemical entities, a series of NTZ-based derivatives were designed, synthesized, and evaluated as autophagy activator against AD. All compounds were screened by the inhibition of phosphorylation of p70S6K, which was the direct substrate of mammalian target of rapamycin (mTOR) and its phosphorylation level could reflect the mTOR-dependent autophagy level. Among these analogs, compound 22 exhibited excellent potency in promoting beta-amyloid (Abeta) clearance, inhibiting tau phosphorylation, as well as stimulating autophagy both in vitro and in vivo. What's more, 22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice. These results demonstrated that 22 was a potential candidate for the treatment of AD.
ESTHER : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedSearch : Li_2020_Acta.Pharm.Sin.B_10_646
PubMedID: 32322468

Title : MS1, a direct target of MS188, regulates the expression of key sporophytic pollen coat protein genes in Arabidopsis - Lu_2020_J.Exp.Bot__
Author(s) : Lu JY , Xiong SX , Yin W , Teng XD , Lou Y , Zhu J , Zhang C , Gu JN , Wilson ZA , Yang ZN
Ref : J Exp Bot , : , 2020
Abstract : Sporophytic pollen coat proteins (sPCPs) derived from the anther tapetum are deposited into pollen wall cavities and function in pollen-stigma interactions, pollen hydration and environmental protection. In Arabidopsis, 13 highly-abundant proteins have been identified in pollen coat, including 7 major Glycine-Rich Proteins GRP14, 16, 17, 18, 19, 20 and GRP-Oleosin; two Caleosin-related family proteins (AT1G23240, AT1G23250); three lipase proteins EXL4, EXL5, EXL6 and ATA27/BGLU20. Here, we show that GRP14, 17, 18, 19, and EXL4 and EXL6 fused with GFP are translated in the tapetum and then accumulate in the anther locule following tapetum degeneration. The expression of these sPCPs is dependent on two essential tapetum transcription factors, MALE STERILE188 (MS188) and MALE STERILITY 1 (MS1). The majority of sPCP genes are up-regulated within 30h after MS1 induction and could be restored by MS1 expression driven by the MS188 promoter in ms188, indicating that MS1 is sufficient to activate their expression, however additional MS1-downstream factors appear to be required for high-level sPCP expression. Our ChIP, in vivo transactivation assays and EMSA data indicate that MS188 directly activates MS1. Together, these results reveal a regulatory cascade that outer pollen wall formation is regulated by MS188 followed by sPCPs synthesis controlled by MS1.
ESTHER : Lu_2020_J.Exp.Bot__
PubMedSearch : Lu_2020_J.Exp.Bot__
PubMedID: 32374882

Title : Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation - Huang_2020_Int.J.Biol.Macromol_164_1927
Author(s) : Huang X , Zhu J , Wang L , Jing H , Ma C , Kou X , Wang H
Ref : Int J Biol Macromol , 164 :1927 , 2020
Abstract : This study aimed to reveal the interaction and inhibitory mechanisms of tangeretin (TAN), nobiletin (NBT), and their acidic hydroxylated forms, 5-demethyltangeretin (5-DT) and 5-demethylnobiletin (5-DN) on porcine pancreatic lipase (PPL) using spectroscopic techniques and molecular dynamics (MD) simulation. PPL inhibition assay showed that the inhibitory activity of NBT (IC(50) value of 3.60 +/- 0.19 microM) was superior to those of three polymethoxylated flavones (PMFs), indicating it may be related to the methoxy groups at the 3'-position in its molecular structure. Inhibition kinetic analyses demonstrated that the inhibition types of the 4 PMFs were consistent with the mixed inhibition model, which agreed well with the results from the ultraviolet-visible (UV-Vis) spectroscopy, Circular dichroism (CD), fluorescence spectroscopy, molecular docking, and MD simulation that PMFs could bind to the PPL catalytic site and non-catalytic site, affecting the normal spatial conformation of PPL and weakening its ability to decompose the substrate. All these findings suggest that PMFs are a kind of natural lipase inhibitors, and NBT has the potential as a lipase inhibition precursor because of its unique flavone skeleton structure.
ESTHER : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedSearch : Huang_2020_Int.J.Biol.Macromol_164_1927
PubMedID: 32795575

Title : The effect on congenital heart diseases of maternal EPHX1 polymorphisms modified by polycyclic aromatic hydrocarbons exposure - Tao_2019_Medicine.(Baltimore)_98_e16556
Author(s) : Tao J , Li N , Liu Z , Deng Y , Li X , Chen M , Yu J , Zhu J , Yu P , Wang Y
Ref : Medicine (Baltimore) , 98 :e16556 , 2019
Abstract : Polycyclic aromatic hydrocarbons (PAHs) may be 1 of etiologic factors responsible for congenital heart diseases (CHDs). Variations of the microsomal epoxide hydrolase (EPHX1) gene, as well as their possible interactions with PAHs exposure, may increase susceptibility to CHDs.This case-control study investigated the risk of CHDs in relation to the EPHX1 polymorphisms and assessed the interactions between these polymorphisms and PAHs exposure in 357 mothers of CHDs fetuses and 270 control mothers. Logistic regression models for the risk of CHDs were applied to determine the effect of genetic polymorphisms using additive, recessive, and dominant genetic models, as well as gene-exposure interactions. Multiple testing was adjusted by applying the false discovery rate (FDR).None of the maternal genetic polymorphisms of EPHX1 was associated with CHDs occurrence. Only the single nucleotide polymorphism rs1051740 was associated with an increased risk of right-sided obstructive malformations under the recessive model (adjusted odds ratio [aOR] = 1.852, 95% confidence interval [CI]: 1.065, 3.22) before FDR correction. A possible modifying effect of PAHs exposure on genetic polymorphisms of EPHX1 was found in susceptibility to CHDs, though no multiplicative-scale interactions between maternal exposure to PAHs and polymorphisms of EPHX1 gene were seento affect the risk of CHDs.The role of EPHX1 gene polymorphisms for CHDs need to be further evaluated, in particularly by interacting with PAHs exposure.
ESTHER : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedSearch : Tao_2019_Medicine.(Baltimore)_98_e16556
PubMedID: 31348278

Title : Chemical composition and biological activities of an essential oil from the aerial parts of Artemisia Gmelinii weber ex Stechm - Xu_2019_Nat.Prod.Res__1
Author(s) : Xu Q , Zhang L , Yu S , Xia G , Zhu J , Zang H
Ref : Nat Prod Res , :1 , 2019
Abstract : The aerial parts of Artemisia gmelinii Weber ex Stechm were collected from the northeast of China. The essential oil was obtained by hydrodistillation and analysed by GC-MS. A set of 66 compounds were identified representing 99.1% of the oil composition. The major compounds in the oil were cyclobutaneethanol, endo-borneol, germacrene D, eucalyptol, selin-6-en-4alpha-ol, bisabolone oxide A, caryophyllene and terpinen-4-ol. Moreover, the essential oil was evaluated for its antioxidant, antidiabetic, and anticholinesterase activities in vitro. Additionally, the antioxidant potential of the oil was evaluated using DPPH and ABTS assays. The oil showed good antidiabetic activity with an IC50 of 63.2 microg/mL, which was similar to that of the positive control acarbose, and weak anticholinesterase activities. These findings demonstrated that the essential oil of Artemisia gmelinii may be a good natural antidiabetic.
ESTHER : Xu_2019_Nat.Prod.Res__1
PubMedSearch : Xu_2019_Nat.Prod.Res__1
PubMedID: 31177847

Title : Preparation, characterization and application of rod-like chitin nanocrystal by using p-toluenesulfonic acid\/choline chloride deep eutectic solvent as a hydrolytic media - Cao_2019_Carbohydr.Polym_213_304
Author(s) : Cao SL , Gu WM , Ou-Yang WD , Chen DC , Yang BY , Lai LH , Wu YD , Liu YJ , Zhu J , Chen WJ , Gai ZQ , Hou XD , Ma YZ , An YX
Ref : Carbohydr Polym , 213 :304 , 2019
Abstract : Chitin nanocrystal (ChiNC) was fabricated based on p-toluenesulfonic acid -choline chloride deep eutectic solvent treatment. The obtained ChiNC was about 12-44 nm in width and 206-399 nm in length. The crystalline structure and the functional groups of ChiNC were maintained during the preparation process. Moreover, porcine pancreas lipase (PPL) was successfully immobilized onto the ChiNC to form the immobilized PPL (PPL@ChiNC). The resulting PPL@ChiNC has enzyme loading and activity recovery of 35.6 mg/g and 82.5%, respectively. The thermal stability, pH and temperature adaptabilities of PPL@ChiNC was improved, comparing with free PPL. The demonstrated DES treatment process was efficient for ChiNC preparation and the as-prepared ChiNC exhibited great potentials in biocatalysis and biomedical field.
ESTHER : Cao_2019_Carbohydr.Polym_213_304
PubMedSearch : Cao_2019_Carbohydr.Polym_213_304
PubMedID: 30879673

Title : Design, synthesis, evaluation and molecular modeling study of 4-N-phenylaminoquinolines for Alzheimer disease treatment - Zhu_2019_Bioorg.Med.Chem.Lett_29_1325
Author(s) : Zhu J , Wang LN , Cai R , Geng SQ , Dong YF , Liu YM
Ref : Bioorganic & Medicinal Chemistry Lett , 29 :1325 , 2019
Abstract : Dual binding site acetylcholinesterase (AChE) inhibitors and butyrylcholinesterase (BChE) inhibitors have recently emerged as two classes of new anti-Alzheimer agents to positively modify the disease's course. In this work, a new series of 4-N-phenylaminoquinolines was synthesized and evaluated for their abilities to inhibit AChE and BChE. Compound 11b showed significant inhibitory activities on AChE and BChE with IC50 values of 0.86 and 2.65muM, respectively, a lot better than that of reference drug galanthamine. Furthermore, docking study showed that compound 11b interacted simultaneously not only with active and peripheral sites of AChE, but also with all five regions of BChE active site. These findings suggest that these derivatives could be regarded as promising starting points for further drug discovery developments.
ESTHER : Zhu_2019_Bioorg.Med.Chem.Lett_29_1325
PubMedSearch : Zhu_2019_Bioorg.Med.Chem.Lett_29_1325
PubMedID: 30956012

Title : Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents - Xu_2019_ACS.Chem.Neurosci_10_482
Author(s) : Xu Y , Zhang J , Wang H , Mao F , Bao K , Liu W , Zhu J , Li X , Zhang H , Li J
Ref : ACS Chem Neurosci , 10 :482 , 2019
Abstract : Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases (MAOs) are promising therapy for Alzheimer's disease (AD). Herein, a series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed and synthesized as dual inhibitors of ChEs and MAOs with other functions against AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of targeting the AChE (IC50 = 0.032 +/- 0.007 muM) and MAO-B (IC50 = 2.117 +/- 0.061 muM), along with the improved blood-brain barrier (BBB) permeability, antioxidant ability, and good copper chelating property in vitro. Animal studies showed that compound 1c.HCl could inhibit the cerebral AChE/MAO-B activities and alleviate scopolamine-induced cognitive impairment in mice. Combined with good oral bioavailability ( F = 45.55%), these findings demonstrated that compound 1c may be a potent brain permeable multifunctional candidate for the treatment of AD.
ESTHER : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedSearch : Xu_2019_ACS.Chem.Neurosci_10_482
PubMedID: 30110536

Title : De novo transcriptomic analysis of the alimentary tract of the tephritid gall fly, Procecidochares utilis - Li_2018_PLoS.One_13_e0201679
Author(s) : Li L , Lan M , Lu W , Li Z , Xia T , Zhu J , Ye M , Gao X , Wu G
Ref : PLoS ONE , 13 :e0201679 , 2018
Abstract : The tephritid gall fly, Procecidochares utilis, is an important obligate parasitic insect of the malignant weed Eupatorium adenophorum which biosynthesizes toxic secondary metabolites. Insect alimentary tracts secrete several enzymes that are used for detoxification, including cytochrome P450s, glutathione S-transferases, and carboxylesterases. To explore the adaptation of P. utilis to its toxic host plant, E. adenophorum at molecular level, we sequenced the transcriptome of the alimentary tract of P. utilis using Illumina sequencing. Sequencing and de novo assembly yielded 62,443 high-quality contigs with an average length of 604 bp that were further assembled into 45,985 unigenes with an average length of 674 bp and an N50 of 983 bp. Among the unigenes, 30,430 (66.17%) were annotated by alignment against the NCBI non-redundant protein (Nr) database, while 16,700 (36.32%), 16,267 (35.37%), and 11,530 (25.07%) were assigned functions using the Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) databases, respectively. Using the comprehensive transcriptome data set, we manually identified several important gene families likely to be involved in the detoxification of toxic compounds including 21 unigenes within the glutathione S-transferase (GST) family, 22 unigenes within the cytochrome P450 (P450) family, and 16 unigenes within the carboxylesterase (CarE) family. Quantitative PCR was used to verify eight, six, and two genes of GSTs, P450s, and CarEs, respectively, in different P. utilis tissues and at different developmental stages. The detoxification enzyme genes were mainly expressed in the foregut and midgut. Moreover, the unigenes were higher expressed in the larvae, pupae, and 3-day adults, while they were expressed at lower levels in eggs. These transcriptomic data provide a valuable molecular resource for better understanding the function of the P. utilis alimentary canal. These identified genes could be pinpoints to address the molecular mechanisms of P. utilis interacting with toxic plant host.
ESTHER : Li_2018_PLoS.One_13_e0201679
PubMedSearch : Li_2018_PLoS.One_13_e0201679
PubMedID: 30138350

Title : miR-1b overexpression suppressed proliferation and migration of RSC96 and increased cell apoptosis - Liu_2018_Neurosci.Lett_687_137
Author(s) : Liu YP , Xu P , Guo CX , Luo ZR , Zhu J , Mou FF , Cai H , Wang C , Ye XC , Shao SJ , Guo HD
Ref : Neuroscience Letters , 687 :137 , 2018
Abstract : Peripheral nerve injury (PNI) is a global problem that leads to severe disability and high healthcare expenditure. Accumulating evidence suggested that the phenotypes of Schwann cells (SCs) could be regulated by microRNAs (miRNAs) and expressions of various miRNAs are altered after PNI. In this study, the expression of miR-1b in the injured nerve and hypoxia-treated SCs was detected through qRT-PCR. The target genes of miR-1b were predicted by bioinformatics prediction and dual-luciferase reporter assay and verified through qRT-PCR and western blot. The effects of miR-1b and its specific target gene on the proliferation, migration and apoptosis of SCs were determined and the regulation of miR-1b on peripheral nerve regeneration after PNI was further investigated in vivo. We found that miR-1b was obviously downregulated in the injured nerve in a rat sciatic nerve transection model and directly targeted N-myc downstream-regulated gene 3 (NDRG3) by binding to its 3'-UTR and caused both mRNA degradation and translation suppression of NDRG3. Overexpression of miR-1b or knockdown of NDRG3 decreased the proliferation and migration as well as increased the apoptosis of SCs. NDRG3 reversed the effects of miR-1b overexpression on proliferation/migration/apoptosis of RSC96. In addition, injection of miR-1b antagomir promoted the expression of NDRG3 in the injured nerve following sciatic nerve injury. Compared to the model group, the rats treated with miR-1b agomir had lower functional recovery rate, and downregulation of miR-1b through injection of specific antagomir improved the functional recovery rate according to the results of sciatic functional index and nerve conduction velocity. Overall, our results will contribute to the development of novel targets for promoting nerve regeneration after PNI.
ESTHER : Liu_2018_Neurosci.Lett_687_137
PubMedSearch : Liu_2018_Neurosci.Lett_687_137
PubMedID: 30261232

Title : Synthesis, pharmacology and molecular docking on multifunctional tacrine-ferulic acid hybrids as cholinesterase inhibitors against Alzheimer's disease - Zhu_2018_J.Enzyme.Inhib.Med.Chem_33_496
Author(s) : Zhu J , Yang H , Chen Y , Lin H , Li Q , Mo J , Bian Y , Pei Y , Sun H
Ref : J Enzyme Inhib Med Chem , 33 :496 , 2018
Abstract : The cholinergic hypothesis has long been a "polar star" in drug discovery for Alzheimer's disease (AD), resulting in many small molecules and biological drug candidates. Most of the drugs marketed for AD are cholinergic. Herein, we report our efforts in the discovery of cholinesterases inhibitors (ChEIs) as multi-target-directed ligands. A series of tacrine-ferulic acid hybrids have been designed and synthesised. All these compounds showed potent acetyl-(AChE) and butyryl cholinesterase(BuChE) inhibition. Among them, the optimal compound 10g, was the most potent inhibitor against AChE (electrophorus electricus (eeAChE) half maximal inhibitory concentration (IC50) = 37.02 nM), it was also a strong inhibitor against BuChE (equine serum (eqBuChE) IC50 = 101.40 nM). Besides, it inhibited amyloid beta-protein self-aggregation by 65.49% at 25 muM. In subsequent in vivo scopolamine-induced AD models, compound 10g obviously ameliorated the cognition impairment and showed preliminary safety in hepatotoxicity evaluation. These data suggest compound 10g as a promising multifunctional agent in the drug discovery process against AD.
ESTHER : Zhu_2018_J.Enzyme.Inhib.Med.Chem_33_496
PubMedSearch : Zhu_2018_J.Enzyme.Inhib.Med.Chem_33_496
PubMedID: 29405075

Title : Synthesis and bioevaluation of new tacrine-cinnamic acid hybrids as cholinesterase inhibitors against Alzheimer's disease - Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
Author(s) : Chen Y , Zhu J , Mo J , Yang H , Jiang X , Lin H , Gu K , Pei Y , Wu L , Tan R , Hou J , Chen J , Lv Y , Bian Y , Sun H
Ref : J Enzyme Inhib Med Chem , 33 :290 , 2018
Abstract : Small molecule cholinesterases inhibitor (ChEI) provides an effective therapeutic strategy to treat Alzheimer's disease (AD). Currently, the discovery of new ChEI with multi-target effect is still of great importance. Herein, we report the synthesis, structure-activity relationship study and biological evaluation of a series of tacrine-cinnamic acid hybrids as new ChEIs. All target compounds are evaluated for their in vitro cholinesterase inhibitory activities. The representatives which show potent activity on cholinesterase, are evaluated for the amyloid beta-protein self-aggregation inhibition and in vivo assays. The optimal compound 19, 27, and 30 (human AChE IC50 = 10.2 +/- 1.2, 16.5 +/- 1.7, and 15.3 +/- 1.8 nM, respectively) show good performance in ameliorating the scopolamine-induced cognition impairment and preliminary safety in hepatotoxicity evaluation. These compounds deserve further evaluation for the development of new therapeutic agents against AD.
ESTHER : Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
PubMedSearch : Chen_2018_J.Enzyme.Inhib.Med.Chem_33_290
PubMedID: 29278947

Title : Theoretical Study on Zearalenol Compounds Binding with Wild Type Zearalenone Hydrolase and V153H Mutant - Liu_2018_Int.J.Mol.Sci_19_
Author(s) : Liu Y , Wan Y , Zhu J , Yu Z , Tian X , Han J , Zhang Z , Han W
Ref : Int J Mol Sci , 19 : , 2018
Abstract : Zearalenone hydrolase (ZHD) is the only reported alpha/beta-hydrolase that can detoxify zearalenone (ZEN). ZHD has demonstrated its potential as a treatment for ZEN contamination that will not result in damage to cereal crops. Recent researches have shown that the V153H mutant ZHD increased the specific activity against alpha-ZOL, but decreased its specific activity to beta-ZOL. To understand whyV153H mutation showed catalytic specificity for alpha-ZOL, four molecular dynamics simulations combining with protein network analysis for wild type ZHD alpha-ZOL, ZHD beta-ZOL, V153H alpha-ZOL, and V153H beta-ZOL complexes were performed using Gromacs software. Our theoretical results indicated that the V153H mutant could cause a conformational switch at the cap domain (residues Gly161(-)Thr190) to affect the relative position catalytic residue (H242). Protein network analysis illustrated that the V153H mutation enhanced the communication with the whole protein and residues with high betweenness in the four complexes, which were primarily assembled in the cap domain and residues Met241 to Tyr245 regions. In addition, the existence of alpha-ZOL binding to V153H mutation enlarged the distance from the OAE atom in alpha-ZOL to the NE2 atom in His242, which prompted the side chain of H242 to the position with catalytic activity, thereby increasing the activity of V153H on the alpha-ZOL. Furthermore, alpha-ZOL could easily form a right attack angle and attack distance in the ZHD and alpha-ZOL complex to guarantee catalytic reaction. The alanine scanning results indicated that modifications of the residues in the cap domain produced significant changes in the binding affinity for alpha-ZOL and beta-ZOL. Our results may provide useful theoretical evidence for the mechanism underlying the catalytic specificity of ZHD.
ESTHER : Liu_2018_Int.J.Mol.Sci_19_
PubMedSearch : Liu_2018_Int.J.Mol.Sci_19_
PubMedID: 30231501
Gene_locus related to this paper: biooc-ZHD101

Title : Understanding the interactions of different substrates with wild-type and mutant acylaminoacyl peptidase using molecular dynamics simulations - Zhu_2017_J.Biomol.Struct.Dyn__1
Author(s) : Zhu J , Wang Y , Li X , Han W , Zhao L
Ref : J Biomol Struct Dyn , :1 , 2017
Abstract : Acylaminoacylpeptidase (AAP) belongs to peptidase protein family (POP), which can degrade amyloid beta-peptide forms in the brains of patients and hence leads to Alzheimer's disease. And so, AAP is considered to be a novel target in the design of drugs against Alzheimer's disease. In this investigation, six molecular dynamics simulations were used to find that the interaction between the wild-type and R526V AAP with two different substrates (p-nitrophenylcaprylate and Ac-Leu-p-nitroanilide). Our results were as follows: firstly, Ac-Leu-p-nitroanilide bound to R526V AAP to form a more disordered loop (residues 552-562) in the alpha/beta-hydrolase fold like of AAP, which caused an open and inactive AAP domain form, secondly, binding p-nitrophenylcaprylate and Ac-Leu-p-nitroanilide to AAP can decrease the flexibility of residues 225-250, 260-270 and 425-450, in which the ordered secondary structures may contain the suitable geometrical structure and so it is useful to serine attack. Our theoretical results showed that the binding of the two substrates can induce specific conformational changes responsible for the diverse AAP catalytic specificity. These theoretical substrate-induced structural diversities can help explain the abilities of AAPs to recognize and hydrolyze extremely different substrates.
ESTHER : Zhu_2017_J.Biomol.Struct.Dyn__1
PubMedSearch : Zhu_2017_J.Biomol.Struct.Dyn__1
PubMedID: 29235404
Gene_locus related to this paper: aerpe-APE1547

Title : Novel Vilazodone-Tacrine Hybrids as Potential Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease Accompanied with Depression: Design, Synthesis, and Biological Evaluation - Li_2017_ACS.Chem.Neurosci_8_2708
Author(s) : Li X , Wang H , Xu Y , Liu W , Gong Q , Wang W , Qiu X , Zhu J , Mao F , Zhang H , Li J
Ref : ACS Chem Neurosci , 8 :2708 , 2017
Abstract : Depression is one of the most frequent psychiatric complications of Alzheimer's disease (AD), affecting up to 50% of the patients. A novel series of hybrid molecules were designed and synthesized by combining the pharmacophoric features of vilazodone and tacrine as potential multitarget-directed ligands for the treatment of AD with depression. In vitro biological assays were conducted to evaluate the compounds; among the 30 hybrids, compound 1e showed relatively balanced profiles between acetylcholinesterase inhibition (IC50 = 3.319 +/- 0.708 muM), 5-HT1A agonist (EC50 = 107 +/- 37 nM), and 5-HT reuptake inhibition (IC50 = 76.3 +/- 33 nM). Compound 1e displayed tolerable hepatotoxicity and moderate hERG inhibition activity, and could penetrate the blood-brain barrier in vivo. Furthermore, an oral intake of 30 mg/kg 1e.HCl could significantly improve the cognitive function of scopolamine-induced amnesia mice and alleviate the depressive symptom in tail suspension test. The effectivity of 1e validates the rationality of our design strategy.
ESTHER : Li_2017_ACS.Chem.Neurosci_8_2708
PubMedSearch : Li_2017_ACS.Chem.Neurosci_8_2708
PubMedID: 28872831

Title : Therapeutic Agents in Alzheimer's Disease Through a Multi-targetdirected Ligands Strategy: Recent Progress Based on Tacrine Core - Lin_2017_Curr.Top.Med.Chem_17_3000
Author(s) : Lin H , Li Q , Gu K , Zhu J , Jiang X , Chen Y , Sun H
Ref : Curr Top Med Chem , 17 :3000 , 2017
Abstract : Alzheimer's Disease (AD) is one of the most common forms of dementia in elderly people. To date, efficacious therapeutic agent for the treatment of AD is still very limited, so it has long been a challenging and attractive task to discover new anti-AD drugs. Considering the multifactorial nature of AD, recently, the concept of Multi-Target-Directed Ligands (MTDLs) has emerged as a new strategy for designing therapeutic agents on AD. MTDLs are believed to exert their effects through simultaneously affecting multiple targets which contribute to etiology of AD. Therefore, MTDLs are considered to be more efficacious than mono-target agents. Tacrine is the first drug approved by Food and Drug Administration (FDA). Although the clinical use of tacrine is restricted because of its hepatotoxicity, the high Ligand Efficiency (LE) of this compound makes it an ideal component for designing MTDLs. This article provides an update review of the advances on the development of MTDLs based on tacrine. Case studies are carefully selected to show the detailed strategy on medicinal modification of Tacrine-Based MTDLs. Finally, several concerns and opinions on designing new MTDLs are discussed as well.
ESTHER : Lin_2017_Curr.Top.Med.Chem_17_3000
PubMedSearch : Lin_2017_Curr.Top.Med.Chem_17_3000
PubMedID: 28714419

Title : Metabolism of KO143, an ABCG2 inhibitor - Liu_2017_Drug.Metab.Pharmacokinet_32_193
Author(s) : Liu K , Zhu J , Huang Y , Li C , Lu J , Sachar M , Li S , Ma X
Ref : Drug Metab Pharmacokinet , 32 :193 , 2017
Abstract : The ATP-binding cassette sub-family G member 2 (ABCG2) plays an important role in modulating drug disposition and endobiotic homeostasis. KO143 is a potent and relatively selective ABCG2 inhibitor. We found that the metabolic stability of KO143 was very poor in human liver microsomes (HLM). Our further studies illustrated that the tert-butyl ester group in KO143 can be rapidly hydrolyzed and removed by carboxylesterase 1. This metabolic pathway was confirmed as a major pathway of KO143 metabolism in both HLM and mice. K1 is an analog of KO143 without the ester group. We found that the metabolic stability of K1 was significantly improved in HLM when compared to KO143. These data suggest that the ester group in KO143 is the major cause of the poor metabolic stability of KO143. The data from this study can be used to guide the development of KO143 analogs with better metabolic properties.
ESTHER : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedSearch : Liu_2017_Drug.Metab.Pharmacokinet_32_193
PubMedID: 28619281

Title : The Role of AChE in Swimming Behavior of Daphnia magna: Correlation Analysis of Both Parameters Affected by Deltamethrin and Methomyl Exposure - Ren_2017_J.Toxicol_2017_3265727
Author(s) : Ren Q , Zhao R , Wang C , Li S , Zhang T , Ren Z , Yang M , Pan H , Xu S , Zhu J , Wang X
Ref : J Toxicol , 2017 :3265727 , 2017
Abstract : The unpredictable toxicity of insecticides may cause behavior disorder of biological organisms. In order to assess the role of acetylcholinesterase (AChE) in swimming behavior of Daphnia magna, a correlation analysis of both parameters in 24 h exposure of deltamethrin (DM) and methomyl (MT) was investigated. The behavior responses of D. magna in DM (13.36 mug/L and 33.40 mug/L) and MT (19.66 mug/L and 49.15 mug/L) suggested that recovery behavior in the adjustment phase was crucial, and behavior homeostasis provided them with an optimal way to achieve a wider tolerance against environmental stress. During the experiment, positive effects on AChE activity occurred in the beginning of the exposure. Even though the de novo synthesis of AChE in D. magna might help it recover, the AChE inhibition in different treatments could be observed. Some induction effects on AChE activity at the beginning of exposure occurred, and a 50% decrease may cause toxic effects on behavior. In most treatments, the results showed that both behavior strength and AChE activity stayed in the same field within a correlation circle. These results illustrated that the environmental stress caused by both DM and MT could inhibit AChE activity and subsequently induce a stepwise behavior response, though both pesticides affect it as direct and indirect inhibitors, respectively.
ESTHER : Ren_2017_J.Toxicol_2017_3265727
PubMedSearch : Ren_2017_J.Toxicol_2017_3265727
PubMedID: 29201050
Gene_locus related to this paper: dapul-ACHE1

Title : Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting - Ma_2016_Atherosclerosis_251_305
Author(s) : Ma W , Liang Y , Zhu J , Chen T , Feng G , Yang Y , Liu X , Wang X
Ref : Atherosclerosis , 251 :305 , 2016
Abstract : BACKGROUND AND AIMS: Asians have very different genotype distributions of cytochrome P450 2C19 (CYP2C19), ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase-1 (PON1), in whom relevant studies based on large samples are scarce. The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in Chinese patients after coronary stenting.
METHODS: A total of 2569 acute coronary syndrome (ACS) patients were enrolled in a gene database study. Among the 1674 patients receiving coronary stenting, 504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort.
RESULTS: The prevalence of the CYP2C19 loss-of-function carriers (had at least 1 allele of *2, *3 and *4) was considerable high (52.2%). During re-angiography, in-stent restenosis occurred in 106 (21.0%) out of the 504 patients; the mean restenosis degree was 71.3% and 152 (30.2%) patients received re-stenting treatment. In multivariate regression, only age and left ventricular ejection fraction (LVEF) were significantly associated with in-stent restenosis. As for predictors of re-stenting, multivariate regression identified variables of LVEF, coronary artery lesions, and PON1 Q192R genotype. Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR (OR 1.95, 95% CI 1.30-2.93, p = 0.001). The genotypes of CYP2C19, ABCB1 C3435T, and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting.
CONCLUSIONS: Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.
ESTHER : Ma_2016_Atherosclerosis_251_305
PubMedSearch : Ma_2016_Atherosclerosis_251_305
PubMedID: 27450784

Title : Development of Multifunctional Pyrimidinylthiourea Derivatives as Potential Anti-Alzheimer Agents - Li_2016_J.Med.Chem_59_8326
Author(s) : Li X , Wang H , Lu Z , Zheng X , Ni W , Zhu J , Fu Y , Lian F , Zhang N , Li J , Zhang H , Mao F
Ref : Journal of Medicinal Chemistry , 59 :8326 , 2016
Abstract : Starting from a screening-hit compound, via structure modifications and optimizations, a series of nonfused and nonassembly pyrimidinylthiourea derivatives (2-5) was designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer's disease. Biological activity results demonstrated that compounds 5r and 5t exhibited potent inhibition and excellent selectivity toward acetylcholinesterase (AChE, 5r, IC50 = 0.204 muM, SI > 196; 5t, IC50 = 0.067 muM, SI > 597), specific metal-chelating ability, significant antioxidant effects, modulation of metal-induced Abeta aggregation, inhibition of ROS production by copper redox cycle, low cytotoxicity, and moderate neuroprotection to human neuroblastoma SH-SY5Y cells. Moreover, compound 5r displayed appropriate blood-brain barrier (BBB) permeability both in vitro and in vivo and could improve memory and cognitive function of scopolamine-induced amnesia mice. The multifunctional profiles of 5r and its effectivity in AD mice highlight these structurally distinct pyrimidinylthiourea derivatives as prospective prototypes in the research of innovative multifunctional drugs for Alzheimer's disease.
ESTHER : Li_2016_J.Med.Chem_59_8326
PubMedSearch : Li_2016_J.Med.Chem_59_8326
PubMedID: 27552582

Title : Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel - Yan_2016_Appl.Environ.Microbiol_82_6748
Author(s) : Yan X , Wang J , Sun Y , Zhu J , Wu S
Ref : Applied Environmental Microbiology , 82 :6748 , 2016
Abstract : Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both gamma-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any gamma-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies.
ESTHER : Yan_2016_Appl.Environ.Microbiol_82_6748
PubMedSearch : Yan_2016_Appl.Environ.Microbiol_82_6748
PubMedID: 27613682
Gene_locus related to this paper: 9mico-e3svs0

Title : Constructing Bayesian networks by integrating gene expression and copy number data identifies NLGN4Y as a novel regulator of prostate cancer progression - Gong_2016_Oncotarget_7_68688
Author(s) : Gong Y , Wang L , Chippada-Venkata U , Dai X , Oh WK , Zhu J
Ref : Oncotarget , 7 :68688 , 2016
Abstract : To understand the heterogeneity of prostate cancer (PCa) and identify novel underlying drivers, we constructed integrative molecular Bayesian networks (IMBNs) for PCa by integrating gene expression and copy number alteration data from published datasets. After demonstrating such IMBNs with superior network accuracy, we identified multiple sub-networks within IMBNs related to biochemical recurrence (BCR) of PCa and inferred the corresponding key drivers. The key drivers regulated a set of common effectors including genes preferentially expressed in neuronal cells. NLGN4Y-a protein involved in synaptic adhesion in neurons-was ranked as the top gene closely linked to key drivers of myogenesis subnetworks. Lower expression of NLGN4Y was associated with higher grade PCa and an increased risk of BCR. We show that restoration of the protein expression of NLGN4Y in PC-3 cells leads to decreased cell proliferation, migration and inflammatory cytokine expression. Our results suggest that NLGN4Y is an important negative regulator in prostate cancer progression. More importantly, it highlights the value of IMBNs in generating biologically and clinically relevant hypotheses about prostate cancer that can be validated by independent studies.
ESTHER : Gong_2016_Oncotarget_7_68688
PubMedSearch : Gong_2016_Oncotarget_7_68688
PubMedID: 27626693
Gene_locus related to this paper: human-NLGN4Y

Title : Prefrontal microRNA-221 Mediates Environmental Enrichment-Induced Increase of Locomotor Sensitivity to Nicotine - Gomez_2015_Int.J.Neuropsychopharmacol_19_
Author(s) : Gomez AM , Altomare D , Sun WL , Midde NM , Ji H , Shtutman M , Turner JR , Creek KE , Zhu J
Ref : Int J Neuropsychopharmacol , 19 : , 2015
Abstract : BACKGROUND: Environmental enrichment alters susceptibility in developing drug addiction. We have demonstrated that rats raised in an enriched condition are more sensitive than rats raised in an impoverished condition to nicotine-induced locomotor activity, and this is associated with alterations of phosphorylated extracellular signal-regulated kinase 1/2 within the prefrontal cortex. This study determined the impact of microRNA-221 in the prefrontal cortex on phosphorylated extracellular signal-regulated kinase 1/2 and the enriched environment-dependent behavioral changes in response to nicotine.
METHODS: A microRNA array was conducted to profile microRNA expression in the prefrontal cortex of enriched condition and impoverished condition rats in response to repeated nicotine (0.35mg/kg, s.c.) administration. microRNA-221 in the prefrontal cortex, nucleus accumbens, and striatum was further verified by quantitative real-time PCR. Lentiviral-mediated overexpression of microRNA-221 in PC12 cells and the medial prefrontal cortex was performed to determine the effects of microRNA-221 on nicotine-mediated phosphorylated extracellular signal-regulated kinase 1/2, phosphorylated cAMP-response element-binding protein, and locomotor activity.
RESULTS: microRNA-221 was profoundly upregulated in the prefrontal cortex but not in nucleus accumbens and striatum of enriched condition rats relative to impoverished condition rats following repeated administration of nicotine. Overexpression of lentiviral-microRNA-221 attenuated nicotine-induced increase in phosphorylated extracellular signal-regulated kinase 1/2 in PC12 cells. Lentiviral-microRNA-221 overexpression in the medial prefrontal cortex further increased locomotor activity in impoverished condition but not in enriched condition rats in response to repeated nicotine administration. Accordingly, lentiviral-microRNA-221 attenuated nicotine-induced increases in phosphorylated extracellular signal-regulated kinase 1/2 and phosphorylated cAMP-response element-binding protein in the medial prefrontal cortex of impoverished condition but not enriched condition rats. CONCLUSION: These findings suggest that environmental enrichment, via upregulation of prefrontal microRNA-221 expression, suppresses the nicotine-induced activation of extracellular signal-regulated kinase and cAMP-response element-binding protein, which provides a potential mechanism underlying enhanced locomotor sensitivity to nicotine.
ESTHER : Gomez_2015_Int.J.Neuropsychopharmacol_19_
PubMedSearch : Gomez_2015_Int.J.Neuropsychopharmacol_19_
PubMedID: 26232787

Title : Serum Total Cholinesterase Activity on Admission Is Associated with Disease Severity and Outcome in Patients with Traumatic Brain Injury - Zhang_2015_PLoS.One_10_e0129082
Author(s) : Zhang QH , Li AM , He SL , Yao XD , Zhu J , Zhang ZW , Sheng ZY , Yao YM
Ref : PLoS ONE , 10 :e0129082 , 2015
Abstract : BACKGROUND: Traumatic brain injury (TBI) is one of the leading causes of neurological disability. In this retrospective study, serum total cholinesterase (ChE) activities were analyzed in 188 patients for diagnostic as well as predictive values for mortality. METHODS AND FINDINGS: Within 72 hours after injury, serum ChE activities including both acetylcholinesterase and butyrylcholinesterase were measured. Disease severity was evaluated with Acute Physiology and Chronic Health Evaluation (APACHE) II score, Glasgow Coma Score, length of coma, post-traumatic amnesia and injury feature. Neurocognitive and functional scores were assessed using clinical records. Of 188 patients, 146 (77.7%) survived and 42 (22.3%) died within 90 days. Lower ChE activities were noted in the non-survivors vs. survivors (5.94+/-2.19 vs. 7.04+/-2.16 kU/L, p=0.023), in septic vs. non-infected patients (5.93+/-1.89 vs. 7.31+/-2.45 kU/L, p=0.0005) and in patients with extremely severe injury vs. mild injury (6.3+/-1.98 vs. 7.57+/-2.48 kU/L, p=0.049). The trajectories of serum ChE levels were also different between non-survivors and survivors, septic and non-infected patients, mild and severely injured patients, respectively. Admission ChE activities were closely correlated with blood cell counts, neurocognitive and functional scores both on admission and at discharge. Receiver operating characteristic analysis showed that the area under the curve for ChE was inferior to that for either APACHE II or white blood cell (WBC) count. However, at the optimal cutoff value of 5 kU/L, the sensitivity of ChE for correct prediction of 90-day mortality was 65.5% and the specificity was 86.4%. Kaplan-Meier analysis showed that lower ChE activity (<5 kU/L) was more closely correlated with poor survival than higher ChE activity (>5 kU/L) (p=0.04). After adjusting for other variables, ChE was identified as a borderline independent predictor for mortality as analyzed by Binary logistic regression (P=0.078).
CONCLUSIONS: Lowered ChE activity measured on admission appears to be associated with disease severity and outcome for TBI patients.
ESTHER : Zhang_2015_PLoS.One_10_e0129082
PubMedSearch : Zhang_2015_PLoS.One_10_e0129082
PubMedID: 26107885

Title : Effects of environmental enrichment on ERK1\/2 phosphorylation in the rat prefrontal cortex following nicotine-induced sensitization or nicotine self-administration - Gomez_2015_Eur.J.Neurosci_41_109
Author(s) : Gomez AM , Sun WL , Midde NM , Harrod SB , Zhu J
Ref : European Journal of Neuroscience , 41 :109 , 2015
Abstract : Rats raised in an enriched condition (EC) exhibit alterations in the neurobiological and behavioral response to nicotine compared with rats reared in an impoverished condition (IC) or a standard condition (SC). The current study determined whether environmental enrichment differentially regulates extracellular signal-regulated kinase1/2 (ERK1/2) activity in the prefrontal cortex in rats following nicotine sensitization or nicotine self-administration. Under the saline control condition, EC rats displayed diminished baseline activity and greater sensitization to repeated administration of nicotine compared with IC and SC rats. After repeated saline injections, the basal levels of phosphorylated ERK1/2 (pERK1/2) were higher in EC compared with IC and SC rats, which was negatively correlated with their respective baseline activities. Repeated nicotine (0.35 mg/kg) injections induced pERK1/2 to similar levels in SC and IC rats; however, the induction of pERK1/2 in EC rats by nicotine was not significantly different from saline controls, owing to their high baseline. In the self-administration paradigm, EC rats self-administered less nicotine (0.03 mg/kg/infusion) relative to IC or SC rats on a fixed ratio-1 schedule of reinforcement. Accordingly, no differences in pERK1/2 were found between EC and IC rats self-administering saline, whereas nicotine self-administration resulted in an increase in pERK1/2 in IC rats but not in EC rats. Furthermore, the levels of pERK1/2 in EC and IC rats were positively correlated with their respective total number of nicotine infusions. Thus, these findings suggest that environmental enrichment alters the basal and nicotine-mediated pERK1/2, which may contribute to enrichment-induced behavioral alterations in response to nicotine.
ESTHER : Gomez_2015_Eur.J.Neurosci_41_109
PubMedSearch : Gomez_2015_Eur.J.Neurosci_41_109
PubMedID: 25328101

Title : The acetylcholinesterase (AChE) inhibition analysis of medaka (Oryzias latipes) in the exposure of three insecticides - Zhu_2015_Pak.J.Pharm.Sci_28_671
Author(s) : Zhu J , Huan C , Si G , Yang H , Yin L , Ren Q , Ren B , Fu R , Miao M , Ren Z
Ref : Pak J Pharm Sci , 28 :671 , 2015
Abstract : The continuous effects on Acetylcholinesterase (AChE) activity of medaka (Oryzias latipes) caused by dichlorvos, methomyl and deltamethrin in vivo were investigated, and the trends of AChE activity inhibition due to the influence of these insecticides were discussed. The LC50-24h of dichlorvos, methomyl and deltamethrin on medaka were 2.3 mg/L, 0.2 mg/L, and 2.9x10(-3) mg/L respectively. The result suggested that at the beginning of the exposure, the AChE activity might increase, and the AChE activity in dead individuals was obviously lower than the live individuals. Though the de novo synthesis of AChE in medaka might help the AChE activity recover, the trends during the exposure in different treatments were downward, and it showed both exposure time and concentration dependent. Meanwhile, higher temperature might cause the AChE inhibition earlier due to the higher metabolic rate. Therefore, as a specific biomarker for organophosphate, carbamate pesticides and pyrethroids, the degree of the AChE inhibition with in vivo conditions is a good tool in continuous monitoring of insecticides, which may induce the nerve conduction disorders.
ESTHER : Zhu_2015_Pak.J.Pharm.Sci_28_671
PubMedSearch : Zhu_2015_Pak.J.Pharm.Sci_28_671
PubMedID: 25796143

Title : [Effects of lingonberry extraction on the mice cognitive function damaged by chronic stress] - Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
Author(s) : Zuo C , Li W , Wang L , Zhu J , Wang Z
Ref : Wei Sheng Yan Jiu , 44 :943 , 2015
Abstract : OBJECTIVE: To study the effects of lingonberry extraction on mice cognitive impairment caused by chronic stress.
METHODS: Kunming mice were randomly divided into six groups, which were control group, stress model group, the fluoxetine group (dose of 4.4 mg . kg(-1) . d(-1)), lingonberry extraction low, medium and high dose group (respectively 50, 100 and 200 mg . kg(-1) . d(-1)). All groups were given chronic uncertainty stress but the control group, and were intragastric administration for 18 days. Then the cognition of the mice was tested by using water maze, the contents of the SOD, GSH-Px, MDA and the activity of the neurotransmitters such as noradreline (NE), serotonin (5-HT), glucocorticoids (GC), acetylcholinesterase (AchE) were measured by using kit.
RESULTS: Lingonberry extraction improved the cognition and memory of the mice induced by chronic uncertainty stress, increased the content of the SOD and GSH-Px in mice brain, and decreased the content of oxidative damage markers MDA. Lingonberry extraction could also inhibit the increase of GC, inhibit the activity of AchE in blood serum, elevated the content of 5-HT and NE in mice blood serum and brain. CONCLUSION: Lingonberry extraction improved the cognition and memory of the mice induced by chronic uncertainty stress. The possible mechanism was that lingonberry enhanced the antioxidative ability of tissue and improved the disorder of neurotransmitter levels caused by chronic stress.
ESTHER : Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
PubMedSearch : Zuo_2015_Wei.Sheng.Yan.Jiu_44_943
PubMedID: 26738388

Title : Intra-ventral tegmental area HIV-1 Tat1-86 attenuates nicotine-mediated locomotor sensitization and alters mesocorticolimbic ERK and CREB signaling in rats - Zhu_2015_Front.Microbiol_6_540
Author(s) : Zhu J , Midde NM , Gomez AM , Sun WL , Harrod SB
Ref : Front Microbiol , 6 :540 , 2015
Abstract : Cigarette smoking prevalence in the HIV-positive individuals is profoundly higher than that in the HIV-negative individuals. We have demonstrated that HIV-1 transgenic rats exhibit attenuated nicotine-mediated locomotor activity, altered cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the mesocorticolimbic regions. This study investigated the role of HIV-1 transactivator of transcription (Tat) protein in the alterations of nicotine-mediated behavior and the signaling pathway observed in the HIV-1 transgenic rats. Rats received bilateral microinjection of recombinant Tat1-86 (25 mug/side) or vehicle directed at ventral tegmental area (VTA) followed by locomotor testing in response to 13 daily intravenous injections of nicotine (0.05 mg/kg, freebase, once/day) or saline. Further, we examined the phosphorylated levels of CREB (pCREB) and ERK1/2 (pERK1/2) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and VTA. Tat diminished baseline activity in saline control rats, and attenuated nicotine-induced behavioral sensitization. Following repeated saline injection, the basal levels of pERK1 in the NAc and VTA and pERK2 in VTA were lower in the vehicle control group, relative to the Tat group. After repeated nicotine injection, pERK1 in NAc and VTA and pERK2 in VTA were increased in the vehicle group, but not in the Tat group. Moreover, repeated nicotine injections decreased pCREB in the PFC and VTA in the Tat group but not in the vehicle group. Thus, these findings indicate that the direct injection of Tat at the VTA may mediate CREB and ERK activity in response to nicotine-induced locomotor activity.
ESTHER : Zhu_2015_Front.Microbiol_6_540
PubMedSearch : Zhu_2015_Front.Microbiol_6_540
PubMedID: 26150803

Title : Effects of ultrasound-combined microbubbles on hippocampal AchE fibers in rats - Gong_2014_Asian.Pac.J.Trop.Med_7_352
Author(s) : Gong ZL , Luo CM , Wu SZ , Ran H , Zhu J , Zheng J
Ref : Asian Pac J Trop Med , 7 :352 , 2014
Abstract : OBJECTIVE: To investigate the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholinesterase (AchE) fibers in rats.
METHODS: According to random digits table, 60 SD rats were divided into two groups, marrow stromal cells (MSCs) intracranial transplantation group and MSCs intracranial transplantation + ultrasonic microbubbles group. Marrow stromal cells were cultivated and isolated in vitro; 12 weeks after transplantation, spatial learning and memorizing abilities of rats were assessed by Morris water maze; AchE staining method was used to observe changes in density and appearance of AchE staining positive fibers in hippocampal CA1 region.
RESULTS: There was asignificant increase in spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group. Hippocampal AchE staining suggested an increase in the density of AchE staining positive fibers in MSCs intracranial transplantation group; the fibers were regular, intact and dense. Density of hippocampal AchE positive fibers was negatively correlated with the escape latent period and was positively correlated with percentage of the time needed to cross each platform quadrant.
CONCLUSIONS: Better promotion of spatial learning and memorizing abilities of rats in MSCs intracranial transplantation + ultrasonic microbubbles group may be related with the protective effect of ultrasound-combined microbubbles on hippocampal acetylcholine fibers.
ESTHER : Gong_2014_Asian.Pac.J.Trop.Med_7_352
PubMedSearch : Gong_2014_Asian.Pac.J.Trop.Med_7_352
PubMedID: 25063059

Title : Homozygous missense mutation in the LIPH gene causing autosomal recessive hypotrichosis simplex in a Chinese patient -
Author(s) : Liu LH , Wang JW , Chen G , Chang RX , Zhou Y , Tang HY , Zhu J , Wang PG , Yang S , Zhang XJ
Ref : J Dermatol , 41 :105 , 2014
PubMedID: 24354445

Title : Host species restriction of Middle East respiratory syndrome coronavirus through its receptor, dipeptidyl peptidase 4 - van Doremalen_2014_J.Virol_88_9220
Author(s) : van Doremalen N , Miazgowicz KL , Milne-Price S , Bushmaker T , Robertson S , Scott D , Kinne J , McLellan JS , Zhu J , Munster VJ
Ref : J Virol , 88 :9220 , 2014
Abstract : UNLABELLED: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and ferret cells enabled MERS-CoV replication, whereas expression of hamster or ferret DPP4 did not. Modeling the binding energies of MERS-CoV spike protein RBD to DPP4 of human (susceptible) or hamster (nonsusceptible) identified five amino acid residues involved in the DPP4-RBD interaction. Expression of hamster DPP4 containing the five human DPP4 amino acids rendered BHK cells susceptible to MERS-CoV, whereas expression of human DPP4 containing the five hamster DPP4 amino acids did not. Using the same approach, the potential of MERS-CoV to utilize the DPP4s of common Middle Eastern livestock was investigated. Modeling of the DPP4 and MERS-CoV RBD interaction predicted the ability of MERS-CoV to bind the DPP4s of camel, goat, cow, and sheep. Expression of the DPP4s of these species on BHK cells supported MERS-CoV replication. This suggests, together with the abundant DPP4 presence in the respiratory tract, that these species might be able to function as a MERS-CoV intermediate reservoir. IMPORTANCE: The ongoing outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) has caused 701 laboratory-confirmed cases to date, with 249 fatalities. Although bats and dromedary camels have been identified as potential MERS-CoV hosts, the virus has so far not been isolated from any species other than humans. The inability of MERS-CoV to infect commonly used animal models, such as hamster, mice, and ferrets, indicates the presence of a species barrier. We show that the MERS-CoV receptor DPP4 plays a pivotal role in the observed species tropism of MERS-CoV and subsequently identified the amino acids in DPP4 responsible for this restriction. Using a combined modeling and experimental approach, we predict that, based on the ability of MERS-CoV to utilize the DPP4 of common Middle East livestock species, such as camels, goats, sheep, and cows, these form a potential MERS-CoV intermediate host reservoir species.
ESTHER : van Doremalen_2014_J.Virol_88_9220
PubMedSearch : van Doremalen_2014_J.Virol_88_9220
PubMedID: 24899185

Title : Molecular traces of alternative social organization in a termite genome - Terrapon_2014_Nat.Commun_5_3636
Author(s) : Terrapon N , Li C , Robertson HM , Ji L , Meng X , Booth W , Chen Z , Childers CP , Glastad KM , Gokhale K , Gowin J , Gronenberg W , Hermansen RA , Hu H , Hunt BG , Huylmans AK , Khalil SM , Mitchell RD , Munoz-Torres MC , Mustard JA , Pan H , Reese JT , Scharf ME , Sun F , Vogel H , Xiao J , Yang W , Yang Z , Zhou J , Zhu J , Brent CS , Elsik CG , Goodisman MA , Liberles DA , Roe RM , Vargo EL , Vilcinskas A , Wang J , Bornberg-Bauer E , Korb J , Zhang G , Liebig J
Ref : Nat Commun , 5 :3636 , 2014
Abstract : Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.
ESTHER : Terrapon_2014_Nat.Commun_5_3636
PubMedSearch : Terrapon_2014_Nat.Commun_5_3636
PubMedID: 24845553
Gene_locus related to this paper: zoone-a0a067r283 , zoone-a0a067qst6 , zoone-a0a067rbc7 , zoone-a0a067qz43 , zoone-a0a067qn94 , zoone-a0a067rbw9 , zoone-a0a067qx93 , zoone-a0a067rcf4 , zoone-a0a067r8q8 , zoone-a0a067rh81 , zoone-a0a067r506 , zoone-a0a067qxd4 , zoone-a0a067qy86 , zoone-a0a067qsw2 , zoone-a0a067qfp9 , zoone-a0a067ru91 , zoone-a0a067rwu7 , zoone-a0a067rmu8 , zoone-a0a067r773 , zoone-a0a067qlt8 , zoone-a0a067qhm6 , zoone-a0a067qjz2 , zoone-a0a067qs20 , zoone-a0a067rmu4 , zoone-a0a067qty7 , zoone-a0a067rk35 , zoone-a0a067rk64 , zoone-a0a067rj74 , zoone-a0a067rp97 , zoone-a0a067rjm1

Title : Escherichia coli isolate for studying colonization of the mouse intestine and its application to two-component signaling knockouts - Lasaro_2014_J.Bacteriol_196_1723
Author(s) : Lasaro M , Liu Z , Bishar R , Kelly K , Chattopadhyay S , Paul S , Sokurenko E , Zhu J , Goulian M
Ref : Journal of Bacteriology , 196 :1723 , 2014
Abstract : The biology of Escherichia coli in its primary niche, the animal intestinal tract, is remarkably unexplored. Studies with the streptomycin-treated mouse model have produced important insights into the metabolic requirements for Escherichia coli to colonize mice. However, we still know relatively little about the physiology of this bacterium growing in the complex environment of an intestine that is permissive for the growth of competing flora. We have developed a system for studying colonization using an E. coli strain, MP1, isolated from a mouse. MP1 is genetically tractable and does not require continuous antibiotic treatment for stable colonization. As an application of this system, we separately knocked out each two-component system response regulator in MP1 and performed competitions against the wild-type strain. We found that only three response regulators, ArcA, CpxR, and RcsB, produce strong colonization defects, suggesting that in addition to anaerobiosis, adaptation to cell envelope stress is a critical requirement for E. coli colonization of the mouse intestine. We also show that the response regulator OmpR, which had previously been hypothesized to be important for adaptation between in vivo and ex vivo environments, is not required for MP1 colonization due to the presence of a third major porin.
ESTHER : Lasaro_2014_J.Bacteriol_196_1723
PubMedSearch : Lasaro_2014_J.Bacteriol_196_1723
PubMedID: 24563035
Gene_locus related to this paper: ecoli-yaim , ecoli-ybff , ecoli-ycfp , ecoli-yqia , ecoli-YfhR

Title : Age-dependent loss of cholinergic neurons in learning and memory-related brain regions and impaired learning in SAMP8 mice with trigeminal nerve damage - He_2014_Neural.Regen.Res_9_1985
Author(s) : He Y , Zhu J , Huang F , Qin L , Fan W , He H
Ref : Neural Regen Res , 9 :1985 , 2014
Abstract : The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory behaviors and structural changes in related brain regions, in a mouse model of Alzheimer's disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learning and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltransferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic fibers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no significant differences in histology or behavior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present findings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer's disease, and indicate that tooth extraction should be avoided in these populations.
ESTHER : He_2014_Neural.Regen.Res_9_1985
PubMedSearch : He_2014_Neural.Regen.Res_9_1985
PubMedID: 25598781

Title : Association between microsomal epoxide hydrolase 1 T113C polymorphism and susceptibility to lung cancer - Wang_2013_Tumour.Biol_34_1045
Author(s) : Wang S , Zhu J , Zhang R , Gu Z
Ref : Tumour Biol , 34 :1045 , 2013
Abstract : Previous case-control studies assessing the association between microsomal epoxide hydrolase 1 (EPHX1) T113C and susceptibility to lung cancer reported conflicting results. Thus, a systemic review and meta-analysis of published studies were performed to assess the possible association. PubMed and Embase databases were searched for all eligible studies. The strength of the association between EPHX1 T113C polymorphism and lung cancer risk was estimated by the pooled odds ratios (ORs) with its 95 % confidence interval. Twenty-four individual case-control studies involving a total of 4,970 lung cancer cases and 8,917 controls were finally included into the meta-analysis. When all 24 studies were included into the meta-analysis, the pooled results suggested that there was no association between EPHX1 T113C polymorphism and lung cancer risk under all four comparison models, and all P values for the pooled ORs were more than 0.05. In the subgroup analysis of Caucasians, the pooled results suggested that EPHX1 T113C polymorphism was associated with decreased risk of lung cancer under all four comparison models, and all P values for the pooled ORs were less than 0.05. However, in the subgroup analysis of Asians, the pooled results suggested that EPHX1 T113C polymorphism was associated with increased risk of lung cancer under three comparison models, and all P values for the pooled ORs were less than 0.05. There was no risk of publication bias. This current meta-analysis suggests that EPHX1 T113C polymorphism is associated with lung cancer risk, and there is an obvious race-specific effect in the association.
ESTHER : Wang_2013_Tumour.Biol_34_1045
PubMedSearch : Wang_2013_Tumour.Biol_34_1045
PubMedID: 23378225

Title : Tumebacillus flagellatus sp. nov., an alpha-amylase\/pullulanase-producing bacterium isolated from cassava wastewater - Wang_2013_Int.J.Syst.Evol.Microbiol_63_3138
Author(s) : Wang Q , Xie N , Qin Y , Shen N , Zhu J , Mi H , Huang R
Ref : Int J Syst Evol Microbiol , 63 :3138 , 2013
Abstract : A novel alpha-amylase/pullulanase-producing bacterium, designated strain GST4(T), was isolated from samples collected from the wastewater of a cassava starch factory in Nanning, Guangxi Autonomous Region, southern China. Cells of strain GST4(T) were rod-shaped bacilli containing ellipsoidal terminal spores and found to be Gram-reaction-positive, aerobic, motile, oxidase-positive, catalase-negative and formed light yellow colonies on agar plates. Strain GST4(T) was able to grow at pH 4.5-8.5 (optimum at pH 5.5), temperatures ranging from 20 to 42 degrees C (optimum at 37 degrees C) and salt concentrations of 0-1% (w/v) NaCl (optimum at 0.5%, w/v) on R2A medium. Strain GST4(T) grew heterotrophically on complex carbon substrates and chemolithoautotrophically on inorganic sulfur compounds, as demonstrated by growth on sodium thiosulfate and sulfite as sole electron donors. It can reduce nitrate and nitrite. Strain GST4(T) contained iso-C(15:0) and anteiso-C(15:0) as the major cellular fatty acids and menaquinone 7 (MK-7) as the major respiratory quinone. The cell-wall peptidoglycan was of type A1gamma. The genomic DNA G+C content of strain GST4(T) was 53.7 mol%. Physiological and chemotaxonomic characteristics combined with phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GST4(T) was a member of the genus Tumebacillus and most closely related to Tumebacillus permanentifrigoris DSM 18773(T) and Tumebacillus ginsengisoli DSM 18389(T) with 97.3 and 94.5% sequence similarity, respectively. The DNA-DNA relatedness values between strain GST4(T) and T. permanentifrigoris DSM 18773(T), and strain GST4(T) and T. ginsengisoli DSM 18389(T) were 44.0 and 60.4%, respectively. The new isolate differed from those species of the genus Tumebacillus in that it has peritrichous flagella for motility. Based on the evidence obtained from this study, strain GST4(T) represents a novel species of the genus Tumebacillus, for which the name Tumebacillus flagellatus sp. nov. is proposed. The type strain is GST4(T) ( =CGMCC 1.12170(T) =DSM 25748(T)).
ESTHER : Wang_2013_Int.J.Syst.Evol.Microbiol_63_3138
PubMedSearch : Wang_2013_Int.J.Syst.Evol.Microbiol_63_3138
PubMedID: 23435245
Gene_locus related to this paper: 9bacl-a0a074lri5 , 9bacl-a0a074ltm6

Title : Association of LIPC and advanced age-related macular degeneration - Lee_2013_Eye.(Lond)_27_265
Author(s) : Lee J , Zeng J , Hughes G , Chen Y , Grob S , Zhao L , Lee C , Krupa M , Quach J , Luo J , Wei X , Zhang X , Zhu J , Duan Y , Ferreyra H , Goldbaum M , Haw W , Shaw PX , Tang L , Zhang K
Ref : Eye (Lond) , 27 :265 , 2013
Abstract : PURPOSE: To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts.
METHODS: A discovery cohort of 1626 patients with advanced AMD and 859 normal controls and a replication cohort of 2159 cases and 1150 controls were genotyped for two single-nucleotide polymorphisms (SNPs) in the promoter region of LIPC. The associations between the SNPs and AMD were examined by chi(2) tests.
RESULTS: In the discovery cohort, rs493258 and rs10468017 were both associated with advanced AMD (P=9.63E-3 and P=0.048, respectively). The association was corroborated in the replication cohort (P=4.48E-03 for rs493258 and P=0.015 for rs10468017). Combined analysis resulted in even more significant associations (P=1.21E-04 for rs493258 and P=1.67E-03 for rs10468017). CONCLUSION: The LIPC promoter variants rs493258 and rs10468017 were associated with advanced AMD in two independent Caucasian populations, confirming that LIPC polymorphisms may be a genetic risk factor for AMD in the Caucasian population.
ESTHER : Lee_2013_Eye.(Lond)_27_265
PubMedSearch : Lee_2013_Eye.(Lond)_27_265
PubMedID: 23348725

Title : The evolution and pathogenic mechanisms of the rice sheath blight pathogen - Zheng_2013_Nat.Commun_4_1424
Author(s) : Zheng A , Lin R , Zhang D , Qin P , Xu L , Ai P , Ding L , Wang Y , Chen Y , Liu Y , Sun Z , Feng H , Liang X , Fu R , Tang C , Li Q , Zhang J , Xie Z , Deng Q , Li S , Wang S , Zhu J , Wang L , Liu H , Li P
Ref : Nat Commun , 4 :1424 , 2013
Abstract : Rhizoctonia solani is a major fungal pathogen of rice (Oryza sativa L.) that causes great yield losses in all rice-growing regions of the world. Here we report the draft genome sequence of the rice sheath blight disease pathogen, R. solani AG1 IA, assembled using next-generation Illumina Genome Analyser sequencing technologies. The genome encodes a large and diverse set of secreted proteins, enzymes of primary and secondary metabolism, carbohydrate-active enzymes, and transporters, which probably reflect an exclusive necrotrophic lifestyle. We find few repetitive elements, a closer relationship to Agaricomycotina among Basidiomycetes, and expand protein domains and families. Among the 25 candidate pathogen effectors identified according to their functionality and evolution, we validate 3 that trigger crop defence responses; hence we reveal the exclusive expression patterns of the pathogenic determinants during host infection.
ESTHER : Zheng_2013_Nat.Commun_4_1424
PubMedSearch : Zheng_2013_Nat.Commun_4_1424
PubMedID: 23361014
Gene_locus related to this paper: thaca-l8wvp3 , thaca-l8wv47 , thaca-l8wp17 , thaca-l8x532

Title : First report of a sequence type 239 vancomycin-intermediate Staphylococcus aureus isolate in Mainland China - Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
Author(s) : Zhang X , Hu Q , Yuan W , Shang W , Cheng H , Yuan J , Zhu J , Hu Z , Li S , Chen W , Hu X , Rao X
Ref : Diagn Microbiol Infect Dis , 77 :64 , 2013
Abstract : Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that causes a wide range of both hospital- and community-acquired infections. The high prevalence of MRSA and the extensive use of vancomycin in Mainland China may lead to the emergence of vancomycin-intermediate S. aureus (VISA) isolates. In this case, we report a VISA isolate from a 34-year-old male patient with steam burn. The isolate was determined to be sequence type 239 staphylococcal cassette chromosome mec type III, the most prevalent MRSA clone in Mainland China.
ESTHER : Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
PubMedSearch : Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64
PubMedID: 23876353

Title : Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase - Zhu_2013_Bioorg.Med.Chem_21_4218
Author(s) : Zhu J , Wu CF , Li X , Wu GS , Xie S , Hu QN , Deng Z , Zhu MX , Luo HR , Hong X
Ref : Bioorganic & Medicinal Chemistry , 21 :4218 , 2013
Abstract : A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BCHE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BCHE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BCHE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100muM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face pi-pi stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09A) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BCHE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BCHE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BCHE, potentially useful to treat neurodegenerative diseases.
ESTHER : Zhu_2013_Bioorg.Med.Chem_21_4218
PubMedSearch : Zhu_2013_Bioorg.Med.Chem_21_4218
PubMedID: 23719283

Title : Synthesis, structure-activity relationship, and pharmacophore modeling studies of pyrazole-3-carbohydrazone derivatives as dipeptidyl peptidase IV inhibitors - Wu_2012_Chem.Biol.Drug.Des_79_897
Author(s) : Wu D , Jin F , Lu W , Zhu J , Li C , Wang W , Tang Y , Jiang H , Huang J , Liu G , Li J
Ref : Chemical Biology Drug Des , 79 :897 , 2012
Abstract : Type 2 diabetes mellitus (T2DM) is a metabolic disease and a major challenge to healthcare systems around the world. Dipeptidyl peptidase IV (DPP-4), a serine protease, has been rapidly emerging as an effective therapeutic target for the treatment for T2DM. In this study, a series of novel DPP-4 inhibitors, featuring the pyrazole-3-carbohydrazone scaffold, have been discovered using an integrated approach of structure-based virtual screening, chemical synthesis, and bioassay. Virtual screening of SPECS Database, followed by enzymatic activity assay, resulted in five micromolar or low-to-mid-micromolar inhibitory level compounds (1-5) with different scaffold. Compound 1 was selected for the further structure modifications in considering inhibitory activity, structural variability, and synthetic accessibility. Seventeen new compounds were synthesized and tested with biological assays. Nine compounds (6e, 6g, 6k-l, and 7a-e) were found to show inhibitory effects against DPP-4. Molecular docking models give rational explanation about structure-activity relationships. Based on eight DPP-4 inhibitors (1-5, 6e, 6k, and 7d), the best pharmacophore model hypo1 was obtained, consisting of one hydrogen bond donor (HBD), one hydrogen bond acceptor (HBA), and two hydrophobic (HY) features. Both docking models and pharmacophore mapping results are in agreement with pharmacological results. The present studies give some guiding information for further structural optimization and are helpful for future DPP-4 inhibitors design.
ESTHER : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedSearch : Wu_2012_Chem.Biol.Drug.Des_79_897
PubMedID: 22381062

Title : Complete genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28 - Guan_2012_J.Bacteriol_194_6975
Author(s) : Guan P , Ai P , Dai X , Zhang J , Xu L , Zhu J , Li Q , Deng Q , Li S , Wang S , Liu H , Wang L , Li P , Zheng A
Ref : Journal of Bacteriology , 194 :6975 , 2012
Abstract : Bacillus thuringiensis is an important microbial insecticide used in the control of agricultural pests. Here we report the finished, annotated genome sequence of Bacillus thuringiensis serovar Sichuansis strain MC28, which can form parasporal crystals consisting of Cry4Cc1, Cry30Fa1, Cry53Ab1, Cry54Aa1, Cry54Ab1, Cry68Aa1, Cry69Aa1, Cry69Aa2, Cry70Ba1, Cyt1Da1, and Cyt2Aa3. It is also highly toxic to lepidopterous and dipterous insects.
ESTHER : Guan_2012_J.Bacteriol_194_6975
PubMedSearch : Guan_2012_J.Bacteriol_194_6975
PubMedID: 23209229

Title : [Elementary research of constructive feature and three-dimensional reconstruction of nerve bundles of C7 anterior and posterior division end] - Qin_2012_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_26_97
Author(s) : Qin B , Gu L , Xiang J , Fu G , Qi J , Wang H , Zhang D , Zheng J , Liu X , Zhu J
Ref : Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi , 26 :97 , 2012
Abstract : OBJECTIVE: To observe the distribution feature of nerve bundles in C7 nerve anterior and posterior division end. METHODS: The brachial plexus specimen was harvested from 1 fresh adult cadaver. After C7 nerve was confirmed, the distal end of anterior and posterior division was dissected and embedded by OCT. Then the samples were serially horizontally sliced with each 10 microm deep. After acetylcholinesterase (AChE) histochemical staining, the stain characteristics of different nerve fiber bundles were observed and amount of the nerve fiber bundles were counted under optic-microscope. At last, the imaging which were collected were three-dimensional (3-D) reconstructed by using Amira 4.1 software. RESULTS: There was no obvious difference in the stain between the anterior and posterior divisions. The running of the nerve fiber bundles were dispersive from proximal end of nerve to distal end of nerve. Nerve fiber bundles of anterior division were mainly sensor nerve fiber bundles, which located in medial side. Nerve fiber bundles of posterior division were mainly moter nerve fiber bundles, having no regularity in the distribution of nerve fiber bundles. The total number of nerve fiber bundles in distal end of anterior division was 7.85 +/- 1.04, the number of motor nerve fiber bundles was 2.85 +/- 0.36, and the number of sensor nerve fiber bundles was 5.13 +/- 1.01. The total number of nerve fiber bundles in distal end of posterior division was 9.79 +/- 1.53, the number of motor nerve fiber bundles was 6.00 +/- 0.69, and the number of sensor nerve fiber bundles was 3.78 +/- 0.94. There were significant differences in the numbers of motor and sensor nerve fiber bundles between anterior and posterior divisions (P < 0.05). The microstructure 3-D model was reconstructed based on serial slice through Amira 4.1. The intercross and recombination process of nerves bundles could be observed obviously. The nerve bundle distribution showed cross and combination. CONCLUSION: Nerve fiber bundles of anterior division are mainly sensor nerve fiber bundles and locate in medial side. Nerve fiber bundles of posterior division are mainly motor nerve fiber bundles, which has no regularity in the distribution of nerve fiber bundles. The 3-D reconstruction can display the internal structure feature of the C7 division end.
ESTHER : Qin_2012_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_26_97
PubMedSearch : Qin_2012_Zhongguo.Xiu.Fu.Chong.Jian.Wai.Ke.Za.Zhi_26_97
PubMedID: 22332529

Title : Activation of transcription factor MEF2D by bis(3)-cognitin protects dopaminergic neurons and ameliorates Parkinsonian motor defects - Yao_2012_J.Biol.Chem_287_34246
Author(s) : Yao L , Li W , She H , Dou J , Jia L , He Y , Yang Q , Zhu J , Capiro NL , Walker DI , Pennell KD , Pang Y , Liu Y , Han Y , Mao Z
Ref : Journal of Biological Chemistry , 287 :34246 , 2012
Abstract : Parkinson disease (PD) is characterized by the selective demise of dopaminergic (DA) neurons in the substantial nigra pars compacta. Dysregulation of transcriptional factor myocyte enhancer factor 2D (MEF2D) has been implicated in the pathogenic process in in vivo and in vitro models of PD. Here, we identified a small molecule bis(3)-cognitin (B3C) as a potent activator of MEF2D. We showed that B3C attenuated the toxic effects of neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) by activating MEF2D via multiple mechanisms. B3C significantly reduced MPP(+)-induced oxidative stress and potentiated Akt to down-regulate the activity of MEF2 inhibitor glycogen synthase kinase 3beta (GSK3beta) in a DA neuronal cell line SN4741. Furthermore, B3C effectively rescued MEF2D from MPP(+)-induced decline in both nucleic and mitochondrial compartments. B3C offered SN4741 cells potent protection against MPP(+)-induced apoptosis via MEF2D. Interestingly, B3C also protected SN4741 cells from wild type or mutant A53T alpha-synuclein-induced cytotoxicity. Using the in vivo PD model of C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), we showed that B3C maintained redox homeostasis, promoted Akt function activity, and restored MEF2D level in midbrain neurons. Moreover, B3C greatly prevented the loss of tyrosine hydroxylase signal in substantial nigra pars compacta DA neurons and ameliorated behavioral impairments in mice treated with MPTP. Collectedly, our studies identified B3C as a potent neuroprotective agent whose effectiveness relies on its ability to effectively up-regulate MEF2D in DA neurons against toxic stress in models of PD in vitro and in vivo.
ESTHER : Yao_2012_J.Biol.Chem_287_34246
PubMedSearch : Yao_2012_J.Biol.Chem_287_34246
PubMedID: 22891246

Title : Putative EPHX1 enzyme activity is related with risk of lung and upper aerodigestive tract cancers: a comprehensive meta-analysis - Li_2011_PLoS.One_6_e14749
Author(s) : Li X , Hu Z , Qu X , Zhu J , Li L , Ring BZ , Su L
Ref : PLoS ONE , 6 :e14749 , 2011
Abstract : BACKGROUND: EPHX1 is a key enzyme in metabolizing some exogenous carcinogens such as products of cigarette-smoking. Two functional polymorphisms in the EPHX1 gene, Tyr113His and His139Arg can alter the enzyme activity, suggesting their possible association with carcinogenesis risk, particularly of some tobacco-related cancers. METHODOLOGY/PRINCIPAL FINDINGS: A comprehensive systematic review and meta-analysis was performed of available studies on these two polymorphisms and cancer risk published up to November 2010, consisting of 84 studies (31144 cases and 42439 controls) for Tyr113His and 77 studies (28496 cases and 38506 controls) for His139Arg primarily focused on lung cancer, upper aerodigestive tract (UADT) cancers (including oral, pharynx, larynx and esophagus cancers), colorectal cancer or adenoma, bladder cancer and breast cancer. Results showed that Y113H low activity allele (H) was significantly associated with decreased risk of lung cancer (OR = 0.88, 95%CI = 0.80-0.96) and UADT cancers (OR = 0.86, 95%CI = 0.77-0.97) and H139R high activity allele (R) with increased risk of lung cancer (OR = 1.18, 95%CI = 1.04-1.33) but not of UADT cancers (OR = 1.05, 95%CI = 0.93-1.17). Pooled analysis of lung and UADT cancers revealed that low EPHX1 enzyme activity, predicted by the combination of Y113H and H139R showed decreased risk of these cancers (OR = 0.83, 95%CI = 0.75-0.93) whereas high EPHX1 activity increased risk of the cancers (OR = 1.20, 95%CI = 0.98-1.46). Furthermore, modest difference for the risk of lung and UADT cancers was found between cigarette smokers and nonsmokers both in single SNP analyses (low activity allele H: OR = 0.77/0.85 for smokers/nonsmokers; high activity allele R: OR = 1.20/1.09 for smokers/nonsmokers) and in combined double SNP analyses (putative low activity: OR = 0.73/0.88 for smokers/nonsmokers; putative high activity: OR = 1.02/0.93 for smokers/ nonsmokers). CONCLUSIONS/SIGNIFICANCE: Putative low EPHX1 enzyme activity may have a potential protective effect on tobacco-related carcinogenesis of lung and UADT cancers, whereas putative high EPHX1 activity may have a harmful effect. Moreover, cigarette-smoking status may influence the association of EPHX1 enzyme activity and the related cancer risk.
ESTHER : Li_2011_PLoS.One_6_e14749
PubMedSearch : Li_2011_PLoS.One_6_e14749
PubMedID: 21445251

Title : The plant cuticle is required for osmotic stress regulation of abscisic acid biosynthesis and osmotic stress tolerance in Arabidopsis - Wang_2011_Plant.Cell_23_1971
Author(s) : Wang ZY , Xiong L , Li W , Zhu JK , Zhu J
Ref : Plant Cell , 23 :1971 , 2011
Abstract : Osmotic stress activates the biosynthesis of abscisic acid (ABA). One major step in ABA biosynthesis is the carotenoid cleavage catalyzed by a 9-cis epoxycarotenoid dioxygenase (NCED). To understand the mechanism for osmotic stress activation of ABA biosynthesis, we screened for Arabidopsis thaliana mutants that failed to induce the NCED3 gene expression in response to osmotic stress treatments. The ced1 (for 9-cis epoxycarotenoid dioxygenase defective 1) mutant isolated in this study showed markedly reduced expression of NCED3 in response to osmotic stress (polyethylene glycol) treatments compared with the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress. ced1 mutant plants are very sensitive to even mild osmotic stress. Map-based cloning revealed unexpectedly that CED1 encodes a putative alpha/beta hydrolase domain-containing protein and is allelic to the BODYGUARD gene that was recently shown to be essential for cuticle biogenesis. Further studies discovered that other cutin biosynthesis mutants are also impaired in osmotic stress induction of ABA biosynthesis genes and are sensitive to osmotic stress. Our work demonstrates that the cuticle functions not merely as a physical barrier to minimize water loss but also mediates osmotic stress signaling and tolerance by regulating ABA biosynthesis and signaling.
ESTHER : Wang_2011_Plant.Cell_23_1971
PubMedSearch : Wang_2011_Plant.Cell_23_1971
PubMedID: 21610183

Title : Synganglion transcriptome and developmental global gene expression in adult females of the American dog tick, Dermacentor variabilis (Acari: Ixodidae) - Bissinger_2011_Insect.Mol.Biol_20_465
Author(s) : Bissinger BW , Donohue KV , Khalil SM , Grozinger CM , Sonenshine DE , Zhu J , Roe RM
Ref : Insect Molecular Biology , 20 :465 , 2011
Abstract : 454 Pyrosequencing was used to characterize the expressed genes from the synganglion and associated neurosecretory organs of unfed and partially fed virgin and mated replete females of the American dog tick, Dermacentor variabilis. A total of 14,881 contiguous sequences (contigs) was assembled, with an average size of 229 bp. Gene ontology terms for Level 2 biological processes were assigned to 4366 contigs. Seven acetylcholinesterases, a muscarinic acetylcholine (ACh) receptor, two nicotinic ACh receptor beta-subunits, two ACh unc-18 regulators, two dopamine receptors, two gamma aminobutyric acid (GABA) receptors, two GABA transporters, two norepinephrine transporters and an octopamine receptor are described. Microarrays were conducted to examine global gene expression and quantitative real-time polymerase chain reaction was used to verify expression of selected neuropeptides. Hierarchical clustering of all differentially expressed transcripts grouped part-fed and replete ticks as being more similar in terms of differentially expressed genes with unfed ticks as the outgroup. Nine putative neuropeptides (allatostatin, bursicon-beta, preprocorazonin, glycoprotein hormone alpha, insulin-like peptide, three orcokinins, preprosulphakinin) and a gonadotropin releasing hormone receptor were differentially expressed, and their developmental expression and role in reproduction was investigated. The presence of eclosion hormone, corazonin and bursicon in the synganglion, which in insects regulate behaviour and cuticle development associated with moulting, suggest that this system may be used in ticks to regulate blood feeding, cuticle expansion and development related to female reproduction; adult ticks do not moult.
ESTHER : Bissinger_2011_Insect.Mol.Biol_20_465
PubMedSearch : Bissinger_2011_Insect.Mol.Biol_20_465
PubMedID: 21689185

Title : Comparative evaluation of the protective potentials of human paraoxonase 1 and 3 against CCl4-induced liver injury - Peng_2010_Toxicol.Lett_193_159
Author(s) : Peng W , Zhang C , Lv H , Zhu J , Zang Y , Pang X , Zhang J , Qin J
Ref : Toxicol Lett , 193 :159 , 2010
Abstract : We previously reported that electroporation mediated hPON1 or hPON3 gene delivery could protect against CCl(4)-induced liver injury. However, substantial evidence supported that the in vivo physiological functions of hPON1 and hPON3 were distinct. To compare the protective efficacies of hPON1 and hPON3 against liver injury, recombinant adenovirus AdPON1 and AdPON3, which were capable of expressing hPON1 and hPON3 respectively, were intravenously injected into mice before they were given CCl(4). Adenovirus mediated expression of hPON1 and hPON3 were demonstrated by elevated serum esterase activity, hepatic lactonase activity, and hPON1/hPON3 mRNA expression in liver. Serum transaminase assay, histological observation and TUNEL analysis revealed that the extent of liver injury and hepatocyte apoptosis in AdPON1 or AdPON3 treated mice was significantly ameliorated in comparison with control. Meanwhile, overexpression of hPON1 and hPON3 reduced the hepatic oxidative stress and strengthen the total antioxidant capabilities in liver through affecting the hepatic malondialdehyde (MDA), glutathione (GSH) and total antioxidant capability (T-AOC) levels, regardless of the exposure to CCl(4) or corn oil. Administration of AdPON1 or AdPON3 also suppressed inflammatory response by decreasing TNF-alpha and IL-1beta levels in CCl(4) mice. In this study, hPON1 exhibited a slightly higher efficacy than hPON3 in alleviating liver injury, but the difference between them were not significant.
ESTHER : Peng_2010_Toxicol.Lett_193_159
PubMedSearch : Peng_2010_Toxicol.Lett_193_159
PubMedID: 20079818

Title : Studies on protective effects of human paraoxonases 1 and 3 on atherosclerosis in apolipoprotein E knockout mice - Zhang_2010_Gene.Ther_17_626
Author(s) : Zhang C , Peng W , Wang M , Zhu J , Zang Y , Shi W , Zhang J , Qin J
Ref : Gene Therapy , 17 :626 , 2010
Abstract : Paraoxonase (PON) possesses antiatherogenic potentials, but the distinct functions of PON members in alleviating atherosclerosis are not yet clear. This study aimed to evaluate the protective effects of hPON1 and hPON3 against atherosclerosis, and thereby exploring their synergistic mechanism in atherosclerosis development. We generated the recombinant adenovirus AdPON1 and AdPON3, which were capable of expressing hPON1 and hPON3. After AdPON1 and AdPON3 were injected intravenously into 5-week-old apolipoprotein E knockout mice, abundant hPON1 and hPON3 mRNA expression levels were detected. However, increase in serum lactonase activity was detected only in AdPON1-treated mice. Serum antioxidation and anti-inflammation capabilities in AdPON1-treated mice, reflected by malondialdehyde, total antioxidant capability and tumor necrosis factor-alpha levels, were greatly enhanced, whereas those in AdPON3-treated mice were not significantly affected. Nevertheless, histological analysis revealed that adenovirus-mediated expression of hPON1, hPON3 or both of them reduced atherosclerotic plaque area to a similar extent. Although no synergistic mechanism was detected in reducing arterial lesion size, hPON1 and hPON3 showed synergistic effects on promoting macrophage cholesterol efflux. In conclusion, hPON1 and hPON3 exhibited similar potentials in reducing arterial lesion size, but they exerted antiatherogenic effects in distinct ways.
ESTHER : Zhang_2010_Gene.Ther_17_626
PubMedSearch : Zhang_2010_Gene.Ther_17_626
PubMedID: 20182519

Title : Isolation of an isocarbophos-degrading strain of Arthrobacter sp. scl-2 and identification of the degradation pathway - Rong_2009_J.Microbiol.Biotechnol_19_1439
Author(s) : Rong L , Guo X , Chen K , Zhu J , Li S , Jiang J
Ref : J Microbiol Biotechnol , 19 :1439 , 2009
Abstract : Isocarbophos is a widely used organophosphorus insecticide that has caused environmental pollution in many areas. However, degradation of isocarbophos by pure cultures has not been extensively studied, and the degradation pathway has not been determined. In this paper, a highly effective isocarbophos-degrading strain, scl-2, was isolated from isocarbophos-polluted soil. Strain scl-2 was preliminarily identified as Arthrobacter sp. based on its morphological, physiological, and biochemical properties, as well as 16S rDNA analysis. Strain scl-2 could utilize isocarbophos as its sole source of carbon and phosphorus for growth. One hundred mg/l isocarbophos could be degraded to a nondetectable level in 18 h by scl-2 in cell culture, and isofenphos-methyl, profenofos, and phosmet could also be degraded. During the degradation of isocarbophos, the metabolites isopropyl salicylate, salicylate, and gentisate were detected and identified based on MS/MS analysis and their retention times in HPLC. Transformation of gentisate to pyruvate and fumarate via maleylpyruvate and fumarylpyruvate was detected by assaying for the activities of gentisate 1,2- dioxygenase (GDO) and maleylpyruvate isomerase. Therefore, we have identified the degradation pathway of isocarbophos in Arthrobacter sp. scl-2 for the first time. This study highlights an important potential use of the strain scl-2 for the cleanup of environmental contamination by isocarbophos and presents a mechanism of isocarbophos metabolism.
ESTHER : Rong_2009_J.Microbiol.Biotechnol_19_1439
PubMedSearch : Rong_2009_J.Microbiol.Biotechnol_19_1439
PubMedID: 19996699

Title : Nicotinic receptor activation increases [3H]dopamine uptake and cell surface expression of dopamine transporters in rat prefrontal cortex - Zhu_2009_J.Pharmacol.Exp.Ther_328_931
Author(s) : Zhu J , Apparsundaram S , Dwoskin LP
Ref : Journal of Pharmacology & Experimental Therapeutics , 328 :931 , 2009
Abstract : Previous research shows that nicotine increases dopamine (DA) clearance in rat prefrontal cortex (PFC) and striatum via a nicotinic receptor (nAChR)-mediated mechanism. The present study investigated whether activation of nAChRs regulates DA transporter (DAT) function through a trafficking-dependent mechanism. After nicotine administration (0, 0.3, and 0.8 mg/kg s.c., 15-1440 min after injection), DAT function and trafficking in synaptosomes of PFC and striatum were determined. nAChR mediation of the effect of nicotine on DAT function and trafficking in PFC was determined by pretreatment with mecamylamine, dihydro-beta-erythroidine, or methyllycaconitine. Nicotine (0.8 mg/kg, 15 and 30 min after injection) increased the maximal velocity (V(max)) of [3H]DA uptake in PFC with no change in K(m), compared with control. Biotinylation and Western blot assays showed that nicotine (0.8 mg/kg; 30 min) increased DAT cell surface expression in PFC. In contrast, a lower dose of nicotine (0.3 mg/kg; 30 min) did not alter DAT function and trafficking in PFC. Pretreatment with mecamylamine, dihydro-beta-erythroidine, or methyllycaconitine (1.5, 8.0, and 10.0 mg/kg s.c., respectively) completely blocked the nicotine-induced increase in V(max) in PFC. In addition, mecamylamine completely blocked the nicotine-induced increase in DAT cell surface expression in PFC. Nicotine did not increase DAT function and cell surface expression in striatum, indicating that nicotine modulates DAT function in a brain region-specific manner. Thus, results from the present study suggest that the nicotine-induced increases in DAT function and cell surface expression in PFC may mediate some of the behavioral effects of nicotine.
ESTHER : Zhu_2009_J.Pharmacol.Exp.Ther_328_931
PubMedSearch : Zhu_2009_J.Pharmacol.Exp.Ther_328_931
PubMedID: 19088301

Title : HaloTag: a novel protein labeling technology for cell imaging and protein analysis - Los_2008_ACS.Chem.Biol_3_373
Author(s) : Los GV , Encell LP , McDougall MG , Hartzell DD , Karassina N , Zimprich C , Wood MG , Learish R , Ohana RF , Urh M , Simpson D , Mendez J , Zimmerman K , Otto P , Vidugiris G , Zhu J , Darzins A , Klaubert DH , Bulleit RF , Wood KV
Ref : ACS Chemical Biology , 3 :373 , 2008
Abstract : We have designed a modular protein tagging system that allows different functionalities to be linked onto a single genetic fusion, either in solution, in living cells, or in chemically fixed cells. The protein tag (HaloTag) is a modified haloalkane dehalogenase designed to covalently bind to synthetic ligands (HaloTag ligands). The synthetic ligands comprise a chloroalkane linker attached to a variety of useful molecules, such as fluorescent dyes, affinity handles, or solid surfaces. Covalent bond formation between the protein tag and the chloroalkane linker is highly specific, occurs rapidly under physiological conditions, and is essentially irreversible. We demonstrate the utility of this system for cellular imaging and protein immobilization by analyzing multiple molecular processes associated with NF-kappaB-mediated cellular physiology, including imaging of subcellular protein translocation and capture of protein--protein and protein--DNA complexes.
ESTHER : Los_2008_ACS.Chem.Biol_3_373
PubMedSearch : Los_2008_ACS.Chem.Biol_3_373
PubMedID: 18533659

Title : Variations in DNA elucidate molecular networks that cause disease - Chen_2008_Nature_452_429
Author(s) : Chen Y , Zhu J , Lum PY , Yang X , Pinto S , MacNeil DJ , Zhang C , Lamb J , Edwards S , Sieberts SK , Leonardson A , Castellini LW , Wang S , Champy MF , Zhang B , Emilsson V , Doss S , Ghazalpour A , Horvath S , Drake TA , Lusis AJ , Schadt EE
Ref : Nature , 452 :429 , 2008
Abstract : Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors.
ESTHER : Chen_2008_Nature_452_429
PubMedSearch : Chen_2008_Nature_452_429
PubMedID: 18344982

Title : Palladium-catalyzed enantioselective domino heck-cyanation sequence: development and application to the total synthesis of esermethole and physostigmine - Pinto_2007_Chemistry_13_961
Author(s) : Pinto A , Jia Y , Neuville L , Zhu J
Ref : Chemistry , 13 :961 , 2007
Abstract : An efficient synthesis of functionalized 3-alkyl-3-cyanomethyl-2-oxindole 1 by a palladium-catalyzed domino Heck-cyanation reaction has been developed. Reaction of ortho-iodoanilide 5 with potassium ferro(II)cyanide, K(4)[Fe(CN)(6)], dissolved in DMF in the presence of palladium acetate and sodium carbonate afforded oxindole 1 in good to excellent yields. An enantioselective domino Heck-cyanation process has been developed for the first time using (S)-DIFLUORPHOS as a chiral supporting ligand, and an enantioselectivity of up to 79 % ee in the enantiomerically enriched oxindole was obtained under optimized conditions. A concise total synthesis of esermethole and physostigmine, powerful inhibitors of acetyl- and butyryl-cholinesterase, is documented.
ESTHER : Pinto_2007_Chemistry_13_961
PubMedSearch : Pinto_2007_Chemistry_13_961
PubMedID: 17009368

Title : Individual differences in response to novelty predict prefrontal cortex dopamine transporter function and cell surface expression - Zhu_2007_Eur.J.Neurosci_26_717
Author(s) : Zhu J , Bardo MT , Bruntz RC , Stairs DJ , Dwoskin LP
Ref : European Journal of Neuroscience , 26 :717 , 2007
Abstract : Previous research has shown that individual differences in response to novelty predict self-administration and the locomotor response to psychostimulant drugs of abuse. The aim of the present study was to determine if individual differences in response to novelty based on inescapable or free-choice novelty tests predict dopamine transporter (DAT) function and trafficking as well as nicotine-induced modulation of DAT. Results show that the maximal velocity (Vmax) of [3H]dopamine uptake into prefrontal cortex (PFC) synaptosomes correlated negatively with the locomotor response to inescapable novelty. In contrast, Vmax correlated positively with novelty place preference in the free-choice novelty test. The divergent correlations between DAT and the two behavioral phenotypes suggest a differential contribution of DAT in these phenotypes, which are known not to be isomorphic. Furthermore, rats categorized as high responders to inescapable novelty had lower Vmax values, which were accompanied by less DAT expression at the cell surface in PFC compared with low responders, suggesting that inherent individual differences in DAT cellular localization may underlie the differential response to novelty. Compared with the saline control, nicotine increased Vmax and cell surface DAT immunoreactivity in PFC from high responders but not from low responders. Similarly, nicotine increased Vmax and cell surface DAT in PFC in rats classified as low in novelty place preference but not in rats classified as high in novelty place preference. Thus, despite the different behavioral phenotypes, the pharmacological effect of nicotine to increase DAT function and cell surface expression was apparent, such that rats with inherently lower DAT function show a greater sensitivity to the neurochemical effect of nicotine.
ESTHER : Zhu_2007_Eur.J.Neurosci_26_717
PubMedSearch : Zhu_2007_Eur.J.Neurosci_26_717
PubMedID: 17651428

Title : Nicotine increases dopamine clearance in medial prefrontal cortex in rats raised in an enriched environment - Zhu_2007_J.Neurochem_103_2575
Author(s) : Zhu J , Bardo MT , Green TA , Wedlund PJ , Dwoskin LP
Ref : Journal of Neurochemistry , 103 :2575 , 2007
Abstract : Environmental enrichment results in differential behavioral and neurochemical responsiveness to nicotine. The present study investigates dopamine clearance (CL(DA) ) in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in rats raised in enriched (EC) or impoverished conditions (IC) and administered nicotine (0.4 mg/kg) or saline. Baseline CL(DA) in striatum or mPFC was not different between EC and IC. Across repeated DA application, striatal CL(DA) increased in saline-control EC and IC. CL(DA) increased in mPFC in saline-control IC; CL(DA) did not change in saline-control EC. Thus, enrichment differentially alters dynamic responses of the dopamine transporter (DAT) to repeated DA application in mPFC, but not in striatum. In EC, nicotine increased mPFC CL(DA) compared to saline-control, but had no effect on CL(DA) in IC; nicotine had no effect in striatum in EC or IC. Compared to respective saline-controls, nicotine increased dihydroxyphenylacetic acid content in striatum and mPFC in EC, but not in IC. Nicotine also had no effect on DA content in striatum or mPFC in EC or IC. Results indicate that enrichment eliminated the dynamic response of mPFC DAT to repeated DA application in saline-control and augmented the nicotine-induced increase in DAT function in mPFC, but not in striatum.
ESTHER : Zhu_2007_J.Neurochem_103_2575
PubMedSearch : Zhu_2007_J.Neurochem_103_2575
PubMedID: 17953677

Title : Genome sequence of Aedes aegypti, a major arbovirus vector - Nene_2007_Science_316_1718
Author(s) : Nene V , Wortman JR , Lawson D , Haas B , Kodira C , Tu ZJ , Loftus B , Xi Z , Megy K , Grabherr M , Ren Q , Zdobnov EM , Lobo NF , Campbell KS , Brown SE , Bonaldo MF , Zhu J , Sinkins SP , Hogenkamp DG , Amedeo P , Arensburger P , Atkinson PW , Bidwell S , Biedler J , Birney E , Bruggner RV , Costas J , Coy MR , Crabtree J , Crawford M , Debruyn B , Decaprio D , Eiglmeier K , Eisenstadt E , El-Dorry H , Gelbart WM , Gomes SL , Hammond M , Hannick LI , Hogan JR , Holmes MH , Jaffe D , Johnston JS , Kennedy RC , Koo H , Kravitz S , Kriventseva EV , Kulp D , LaButti K , Lee E , Li S , Lovin DD , Mao C , Mauceli E , Menck CF , Miller JR , Montgomery P , Mori A , Nascimento AL , Naveira HF , Nusbaum C , O'Leary S , Orvis J , Pertea M , Quesneville H , Reidenbach KR , Rogers YH , Roth CW , Schneider JR , Schatz M , Shumway M , Stanke M , Stinson EO , Tubio JM , Vanzee JP , Verjovski-Almeida S , Werner D , White O , Wyder S , Zeng Q , Zhao Q , Zhao Y , Hill CA , Raikhel AS , Soares MB , Knudson DL , Lee NH , Galagan J , Salzberg SL , Paulsen IT , Dimopoulos G , Collins FH , Birren B , Fraser-Liggett CM , Severson DW
Ref : Science , 316 :1718 , 2007
Abstract : We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
ESTHER : Nene_2007_Science_316_1718
PubMedSearch : Nene_2007_Science_316_1718
PubMedID: 17510324
Gene_locus related to this paper: aedae-ACHE , aedae-ACHE1 , aedae-glita , aedae-q0iea6 , aedae-q0iev6 , aedae-q0ifn6 , aedae-q0ifn8 , aedae-q0ifn9 , aedae-q0ifp0 , aedae-q0ig41 , aedae-q1dgl0 , aedae-q1dh03 , aedae-q1dh19 , aedae-q1hqe6 , aedae-Q8ITU8 , aedae-Q8MMJ6 , aedae-Q8T9V6 , aedae-q16e91 , aedae-q16f04 , aedae-q16f25 , aedae-q16f26 , aedae-q16f28 , aedae-q16f29 , aedae-q16f30 , aedae-q16gq5 , aedae-q16iq5 , aedae-q16je0 , aedae-q16je1 , aedae-q16je2 , aedae-q16ks8 , aedae-q16lf2 , aedae-q16lv6 , aedae-q16m61 , aedae-q16mc1 , aedae-q16mc6 , aedae-q16mc7 , aedae-q16md1 , aedae-q16ms7 , aedae-q16nk5 , aedae-q16rl5 , aedae-q16rz9 , aedae-q16si8 , aedae-q16t49 , aedae-q16wf1 , aedae-q16x18 , aedae-q16xp8 , aedae-q16xu6 , aedae-q16xw5 , aedae-q16xw6 , aedae-q16y04 , aedae-q16y05 , aedae-q16y06 , aedae-q16y07 , aedae-q16y39 , aedae-q16y40 , aedae-q16yg4 , aedae-q16z03 , aedae-q17aa7 , aedae-q17av1 , aedae-q17av2 , aedae-q17av3 , aedae-q17av4 , aedae-q17b28 , aedae-q17b29 , aedae-q17b30 , aedae-q17b31 , aedae-q17b32 , aedae-q17bm3 , aedae-q17bm4 , aedae-q17bv7 , aedae-q17c44 , aedae-q17cz1 , aedae-q17d32 , aedae-q17g39 , aedae-q17g40 , aedae-q17g41 , aedae-q17g42 , aedae-q17g43 , aedae-q17g44 , aedae-q17gb8 , aedae-q17gr3 , aedae-q17if7 , aedae-q17if9 , aedae-q17ig1 , aedae-q17ig2 , aedae-q17is4 , aedae-q17l09 , aedae-q17m26 , aedae-q17mg9 , aedae-q17mv4 , aedae-q17mv5 , aedae-q17mv6 , aedae-q17mv7 , aedae-q17mw8 , aedae-q17mw9 , aedae-q17nw5 , aedae-q17nx5 , aedae-q17pa4 , aedae-q17q69 , aedae-q170k7 , aedae-q171y4 , aedae-q172e0 , aedae-q176i8 , aedae-q176j0 , aedae-q177k1 , aedae-q177k2 , aedae-q177l9 , aedae-j9hic3 , aedae-q179r9 , aedae-u483 , aedae-j9hj23 , aedae-q17d68 , aedae-q177c7 , aedae-q0ifp1 , aedae-a0a1s4fx83 , aedae-a0a1s4g2m0 , aedae-q1hr49

Title : Introduction of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: effect on affinity and selectivity - Sumithran_2005_AAPS.J_7_E201
Author(s) : Sumithran SP , Crooks PA , Xu R , Zhu J , Deaciuc AG , Wilkins LH , Dwoskin LP
Ref : AAPS J , 7 :E201 , 2005
Abstract : N-n-octylnicotinium iodide (NONI) and N-n-decylnicotinium iodide (NDNI) are selective nicotinic receptor (nAChR) antagonists mediating nicotine-evoked striatal dopamine (DA) release, and inhibiting [3H]nicotine binding, respectively. This study evaluated effects of introducing unsaturation into the N-n-alkyl chains of NONI and NDNI on inhibition of [3H]nicotine and [3H]methyllycaconitine binding (alpha4beta2* and alpha7* nAChRs, respectively), (86)Rb+ efflux and [3H]DA release (agonist or antagonist effects at alpha4beta2* and alpha6beta2*-containing nAChRs, respectively). In the NONI series, introduction of a C3-cis- (NONB3c), C3-trans- (NONB3t), C7-double-bond (NONB7e), or C3-triple-bond (NONB3y) afforded a 4-fold to 250-fold increased affinity for [3H]nicotine binding sites compared with NONI. NONB7e and NONB3y inhibited nicotine-evoked 86Rb+ efflux, indicating alpha4beta2* antagonism. NONI analogs exhibited a 3-fold to 8-fold greater potency inhibiting nicotine-evoked [3H]DA overflow compared with NONI (IC50 = 0.62 microM; Imax = 89%), with no change in Imax, except for NONB3y (Imax = 50%). In the NDNI series, introduction of a C4-cis- (NDNB4c), C4-trans-double-bond (NDNB4t), or C3-triple-bond (NDNB3y) afforded a 4-fold to 80-fold decreased affinity for [3H]nicotine binding sites compared with NDNI, whereas introduction of a C9 double-bond (NDNB9e) did not alter affinity. NDNB3y and NDNB4t inhibited nicotine-evoked 86Rb+ efflux, indicating antagonism at alpha4beta2* nAChRs. Although NDNI had no effect, NDNB4t and NDNB9e potently inhibited nicotine-evoked [3H]DA overflow (IC50 = 0.02-0.14 microM, Imax = 90%), as did NDNB4c (IC50 = 0.08 microM; Imax = 50%), whereas NDNB3y showed no inhibition. None of the analogs had significant affinity for alpha7* nAChRs. Thus, unsaturated NONI analogs had enhanced affinity at alpha4beta2*- and alpha6beta2*-containing nAChRs, however a general reduction of affinity at alpha4beta2* and an uncovering of antagonist effects at alpha6beta2*-containing nAChRs were observed with unsaturated NDNI analogs.
ESTHER : Sumithran_2005_AAPS.J_7_E201
PubMedSearch : Sumithran_2005_AAPS.J_7_E201
PubMedID: 16146341

Title : Specific inhibition of hormone-sensitive lipase improves lipid profile while reducing plasma glucose - Claus_2005_J.Pharmacol.Exp.Ther_315_1396
Author(s) : Claus TH , Lowe DB , Liang Y , Salhanick AI , Lubeski CK , Yang L , Lemoine L , Zhu J , Clairmont KB
Ref : Journal of Pharmacology & Experimental Therapeutics , 315 :1396 , 2005
Abstract : Elevation of plasma free fatty acids has been linked with insulin resistance and diabetes. Inhibition of lipolysis may provide a mechanism to decrease plasma fatty acids, thereby improving insulin sensitivity. Hormone-sensitive lipase (HSL) is a critical enzyme involved in the hormonally regulated release of fatty acids and glycerol from adipocyte lipid stores, and its inhibition may thus improve insulin sensitivity and blood glucose handling in type 2 diabetes. In rat adipocytes, forskolin-activated lipolysis was blocked by in vitro addition of a potent and selective HSL inhibitor or by prior treatment of the animals themselves. Antilipolytic effects also were demonstrated in overnight-fasted mice, rats, and dogs with species-dependent effects on plasma free fatty acid levels but with similar reductions in plasma glycerol being observed in all species. Inhibition of HSL also reduced hyperglycemia in streptozotocin-induced diabetic rats. The data support a connection between adipose tissue lipolysis and plasma glucose levels.
ESTHER : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedSearch : Claus_2005_J.Pharmacol.Exp.Ther_315_1396
PubMedID: 16162821

Title : Lobelane analogues as novel ligands for the vesicular monoamine transporter-2 - Zheng_2005_Bioorg.Med.Chem_13_3899
Author(s) : Zheng G , Dwoskin LP , Deaciuc AG , Zhu J , Jones MD , Crooks PA
Ref : Bioorganic & Medicinal Chemistry , 13 :3899 , 2005
Abstract : A series of lobelane analogues has been synthesized and their structure-activity relationships at the vesicular monoamine transporter-2 (VMAT2) have been evaluated. The most potent analogues in this series were the cis-2,6-piperidino analogues, 25b, 27b, 28b, and 30b, with K(i) values ranging from 430 to 580 nM.
ESTHER : Zheng_2005_Bioorg.Med.Chem_13_3899
PubMedSearch : Zheng_2005_Bioorg.Med.Chem_13_3899
PubMedID: 15911306

Title : Subtype-selective nicotinic receptor antagonists: potential as tobacco use cessation agents - Dwoskin_2004_Bioorg.Med.Chem.Lett_14_1863
Author(s) : Dwoskin LP , Sumithran SP , Zhu J , Deaciuc AG , Ayers JT , Crooks PA
Ref : Bioorganic & Medicinal Chemistry Lett , 14 :1863 , 2004
Abstract : N-n-Alkylpicolinium and N,N'-alkyl-bis-picolinium analogues were assessed in nicotinic receptor (nAChR) assays. The most potent and subtype-selective analogue, N,N'-dodecyl-bis-picolinium bromide (bPiDDB), inhibited nAChRs mediating nicotine-evoked [(3)H]dopamine release (IC(50)=5 nM; I(max) of 60%), and did not interact with alpha4beta2* or alpha7* nAChRs. bPiDDB represents the current lead compound for development as a tobacco use cessation agent.
ESTHER : Dwoskin_2004_Bioorg.Med.Chem.Lett_14_1863
PubMedSearch : Dwoskin_2004_Bioorg.Med.Chem.Lett_14_1863
PubMedID: 15050617

Title : Effects of environmental enrichment on behavior and dopamine transporter function in medial prefrontal cortex in adult rats prenatally treated with cocaine - Neugebauer_2004_Brain.Res.Dev.Brain.Res_153_213
Author(s) : Neugebauer NM , Cunningham ST , Zhu J , Bryant RI , Middleton LS , Dwoskin LP
Ref : Brain Research Developmental Brain Research , 153 :213 , 2004
Abstract : The present study determined if environmental enrichment modifies the effects of prenatal cocaine on open field activity, social interaction and dopamine transporter (DAT) function in the medial prefrontal cortex (mPFC) in rats. Cocaine (40 mg/kg) or saline was administered (s.c.) to pregnant dams from gestation days 8 to 20 (PCOC and PSAL, respectively). At postnatal day 25 (PND 25), female offspring from PCOC and PSAL groups were assigned to the enriched condition (EC; PCOC/EC and PSAL/EC) or impoverished condition (IC; PCOC/IC and PSAL/IC). On PND 60, 90 and 120, locomotor activity, rearing behavior and social interactions were assessed in the open field. On PND 345, rats were anesthetized, challenged with nicotine (0.4 mg/kg), and DAT function in medial prefrontal cortex (mPFC) was assessed using in vivo voltammetry. EC groups displayed decreased locomotor activity across test days, while activity in IC groups did not habituate across days. Generally, PCOC groups displayed more rearing behavior than PSAL groups. During social interaction assessment, IC groups followed their social partner more frequently than EC groups. Moreover, the PCOC/IC group initiated more play solicitations and was engaged in mutual rearing less frequently than PCOC/EC, PSAL/IC and PSAL/EC groups, indicating that epigenetic environmental factors decreased the divergent social behaviors displayed by the PCOC/IC group. Results from in vivo voltammetry experiments demonstrated differences in baseline DAT function in response to environmental enrichment in the prenatal saline groups; however, no effect of prenatal cocaine was observed under baseline conditions. Nicotine challenge unmasked an effect of prenatal cocaine on DA clearance rate in mPFC in the IC groups, which was attenuated by environmental enrichment. Taken together, PCOC/IC rats displayed divergent social interaction and altered DAT function in mPFC, whereas the PCOC/EC group generally was not different from PSAL groups, suggesting that environmental enrichment attenuates the behavioral and neurochemical effects of prenatal cocaine.
ESTHER : Neugebauer_2004_Brain.Res.Dev.Brain.Res_153_213
PubMedSearch : Neugebauer_2004_Brain.Res.Dev.Brain.Res_153_213
PubMedID: 15527889

Title : Genome sequence of Shigella flexneri 2a: insights into pathogenicity through comparison with genomes of Escherichia coli K12 and O157 - Jin_2002_Nucleic.Acids.Res_30_4432
Author(s) : Jin Q , Yuan Z , Xu J , Wang Y , Shen Y , Lu W , Wang J , Liu H , Yang J , Yang F , Zhang X , Zhang J , Yang G , Wu H , Qu D , Dong J , Sun L , Xue Y , Zhao A , Gao Y , Zhu J , Kan B , Ding K , Chen S , Cheng H , Yao Z , He B , Chen R , Ma D , Qiang B , Wen Y , Hou Y , Yu J
Ref : Nucleic Acids Research , 30 :4432 , 2002
Abstract : We have sequenced the genome of Shigella flexneri serotype 2a, the most prevalent species and serotype that causes bacillary dysentery or shigellosis in man. The whole genome is composed of a 4 607 203 bp chromosome and a 221 618 bp virulence plasmid, designated pCP301. While the plasmid shows minor divergence from that sequenced in serotype 5a, striking characteristics of the chromosome have been revealed. The S.flexneri chromosome has, astonishingly, 314 IS elements, more than 7-fold over those possessed by its close relatives, the non-pathogenic K12 strain and enterohemorrhagic O157:H7 strain of Escherichia coli. There are 13 translocations and inversions compared with the E.coli sequences, all involve a segment larger than 5 kb, and most are associated with deletions or acquired DNA sequences, of which several are likely to be bacteriophage-transmitted pathogenicity islands. Furthermore, S.flexneri, resembling another human-restricted enteric pathogen, Salmonella typhi, also has hundreds of pseudogenes compared with the E.coli strains. All of these could be subjected to investigations towards novel preventative and treatment strategies against shigellosis.
ESTHER : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedSearch : Jin_2002_Nucleic.Acids.Res_30_4432
PubMedID: 12384590
Gene_locus related to this paper: ecoli-Aes , ecoli-yafa , ecoli-ycfp , ecoli-yqia , ecoli-YfhR , shifl-AES , shifl-BIOH , shifl-entf , shifl-FES , shifl-PLDB , shifl-PTRB , shifl-SF1334 , shifl-SF1808 , shifl-SF3046 , shifl-SF3908 , shifl-yafa , shifl-YBFF , shifl-YCDJ , shifl-YCJY , shifl-YFBB , shifl-YHET , shifl-YIEL , shifl-YJFP , shifl-YPFH

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1

Title : bis-Azaaromatic quaternary ammonium analogues: ligands for alpha4beta2* and alpha7* subtypes of neuronal nicotinic receptors - Ayers_2002_Bioorg.Med.Chem.Lett_12_3067
Author(s) : Ayers JT , Dwoskin LP , Deaciuc AG , Grinevich VP , Zhu J , Crooks PA
Ref : Bioorganic & Medicinal Chemistry Lett , 12 :3067 , 2002
Abstract : A series of bis-nicotinium, bis-pyridinium, bis-picolinium, bis-quinolinium and bis-isoquinolinium compounds was evaluated for their binding affinity at nicotinic acetylcholine receptors (nAChRs) using rat brain membranes. N,N'-Decane-1,12-diyl-bis-nicotinium diiodide (bNDI) exhibited the highest affinity for [(3)H]nicotine binding sites (K(i)=330 nM), but did not inhibit [(3)H]methyllycaconitine binding (K(i) >100 microM), indicative of an interaction with alpha4beta2*, but not alpha7* receptor subtypes, respectively. Also, bNDI inhibited (IC(50)=3.76 microM) nicotine-evoked (86)Rb(+) efflux from rat thalamic synaptosomes, indicating antagonist activity at alpha4beta2* nAChRs. N,N'-Dodecane-1,12-diyl-bis-quinolinium dibromide (bQDDB) exhibited highest affinity for [(3)H]methyllycaconitine binding sites (K(i)=1.61 microM), but did not inhibit [(3)H]nicotine binding (K(i)>100 microM), demonstrating an interaction with alpha7*, but not alpha4beta2* nAChRs. Thus, variation of N-n-alkyl chain length together with structural modification of the azaaromatic quaternary ammonium moiety afforded selective antagonists for the alpha4beta2* nAChR subtype, as well as ligands with selectivity at alpha7* nAChRs.
ESTHER : Ayers_2002_Bioorg.Med.Chem.Lett_12_3067
PubMedSearch : Ayers_2002_Bioorg.Med.Chem.Lett_12_3067
PubMedID: 12372503

Title : Postinjury administration of L-deprenyl improves cognitive function and enhances neuroplasticity after traumatic brain injury - Zhu_2000_Exp.Neurol_166_136
Author(s) : Zhu J , Hamm RJ , Reeves TM , Povlishock JT , Phillips LL
Ref : Experimental Neurology , 166 :136 , 2000
Abstract : The rat model of combined central fluid percussion traumatic brain injury (TBI) and bilateral entorhinal cortical lesion (BEC) produces profound, persistent cognitive deficits, sequelae associated with human TBI. In contrast to percussive TBI alone, this combined injury induces maladaptive hippocampal plasticity. Recent reports suggest a potential role for dopamine in CNS plasticity after trauma. We have examined the effect of the dopamine enhancer l-deprenyl on cognitive function and neuroplasticity following TBI. Rats received fluid percussion TBI, BEC alone, or combined TBI + BEC lesion and were treated once daily for 7 days with l-deprenyl, beginning 24 h after TBI alone and 15 min after BEC or TBI + BEC. Postinjury motor assessment showed no effect of l-deprenyl treatment. Cognitive performance was assessed on days 11-15 postinjury and brains from the same cases examined for dopamine beta-hydroxylase immunoreactivity (DBH-IR) and acetylcholinesterase (AChE) histochemistry. Significant cognitive improvement relative to untreated injured cases was observed in both TBI groups following l-deprenyl treatment; however, no drug effects were seen with BEC alone. l-Deprenyl attenuated injury-induced loss in DBH-IR over CA1 and CA3 after TBI alone. However, after combined TBI + BEC, l-deprenyl was only effective in protecting CA1 DBH-IR. AChE histostaining in CA3 was significantly elevated with l-deprenyl in both injury models. After TBI + BEC, l-deprenyl also increased AChE in the dentate molecular layer relative to untreated injured cases. These results suggest that dopaminergic/noradrenergic enhancement facilitates cognitive recovery after brain injury and that noradrenergic fiber integrity is correlated with enhanced synaptic plasticity in the injured hippocampus.
ESTHER : Zhu_2000_Exp.Neurol_166_136
PubMedSearch : Zhu_2000_Exp.Neurol_166_136
PubMedID: 11031090