Wu X

References (99)

Title : Simultaneous determination of HD56, a novel prodrug, and its active metabolite in cynomolgus monkey plasma using LC-MS\/MS for elucidating its pharmacokinetic profile - Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
Author(s) : Yao S , Zhang W , Xiao J , Zhang Z , Wang L , Ai H , Wu X , Chen A , Zhuang X
Ref : Journal of Chromatography B Analyt Technol Biomed Life Sciences , 1235 :124045 , 2024
Abstract : An LC-MS/MS method was developed and validated for the simultaneous determination of the carboxylic acid ester precursor HD56 and the active product HD561 in cynomolgus monkey plasma. Then, the pharmacokinetic characteristics of both compounds following single and multiple i.g. administrations in cynomolgus monkeys were elucidated. In the method, chromatographic separation was achieved with a C18 reversed-phase column and the target quantification was carried out by an electrospray ionization (ESI) source coupled with triple quadrupole mess detector in positive ionization mode with multiple reaction monitoring (MRM) approach. Using the quantification method, the in vitro stability of HD56 in plasma and HD56 pharmacokinetic behavior after i.g. administration in cynomolgus monkey were investigated. It was approved that HD56 did convert into HD561 post-administration. The overall systemic exposure of HD561 post-conversion from HD56 accounted for only about 17% of HD56. After repeated administration at the same dose, there was no significant difference in exposure levels of both HD56 and HD561. However, after multiple dosing, the exposure of HD56 tended to decrease while that of HD561 tended to increase, resulting in a 30% in the exposure ratio. Remarkably, with a carboxylesterase (CES) activity profile akin to humans, the observed in vivo pharmacokinetic profile in cynomolgus monkeys holds promise for predicting HD56/HD561 PK profiles in humans.
ESTHER : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedSearch : Yao_2024_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1235_124045
PubMedID: 38367406

Title : Design, Synthesis, and Biological Evaluation of Novel Tetrahydroacridin Hybrids with Sulfur-Inserted Linkers as Potential Multitarget Agents for Alzheimer's Disease - Wu_2024_Molecules_29_
Author(s) : Wu X , Ze X , Qin S , Zhang B , Li X , Gong Q , Zhang H , Zhu Z , Xu J
Ref : Molecules , 29 : , 2024
Abstract : Alzheimer's disease (AD) is a complex neurodegenerative disease that can lead to the loss of cognitive function. The progression of AD is regulated by multiple signaling pathways and their associated targets. Therefore, multitarget strategies theoretically have greater potential for treating AD. In this work, a series of new hybrids were designed and synthesized by the hybridization of tacrine (4, AChE: IC(50) = 0.223 microM) with pyrimidone compound 5 (GSK-3beta: IC(50) = 3 microM) using the cysteamine or cystamine group as the connector. The biological evaluation results demonstrated that most of the compounds exhibited moderate to good inhibitory activities against acetylcholinesterase (AChE) and glycogen synthase kinase 3beta (GSK-3beta). The optimal compound 18a possessed potent dual AChE/GSK-3beta inhibition (AChE: IC(50) = 0.047 +/- 0.002 microM, GSK-3beta: IC(50) = 0.930 +/- 0.080 microM). Further molecular docking and enzymatic kinetic studies revealed that this compound could occupy both the catalytic anionic site and the peripheral anionic site of AChE. The results also showed a lack of toxicity to SH-SY5Y neuroblastoma cells at concentrations of up to 25 microM. Collectively, this work explored the structure-activity relationships of novel tetrahydroacridin hybrids with sulfur-inserted linkers, providing a reference for the further research and development of new multitarget anti-AD drugs.
ESTHER : Wu_2024_Molecules_29_
PubMedSearch : Wu_2024_Molecules_29_
PubMedID: 38675602

Title : Inhibition of MAGL attenuates Intervertebral Disc Degeneration by Delaying nucleus pulposus senescence through STING - Fan_2024_Int.Immunopharmacol_131_111904
Author(s) : Fan C , Du J , Yu Z , Wang J , Yao L , Ji Z , He W , Deng Y , Geng D , Wu X , Mao H
Ref : Int Immunopharmacol , 131 :111904 , 2024
Abstract : Intervertebral disc degeneration (IVDD) stands as the primary cause of low back pain (LBP). A significant contributor to IVDD is nucleus pulposus cell (NPC) senescence. However, the precise mechanisms underlying NPC senescence remain unclear. Monoacylglycerol lipase (MAGL) serves as the primary enzyme responsible for the hydrolysis of 2-arachidonoylglycerol (2-AG), breaking down monoglycerides into glycerol and fatty acids. It plays a crucial role in various pathological processes, including pain, inflammation, and oxidative stress. In this study, we utilized a lipopolysaccharide (LPS)-induced NPC senescence model and a rat acupuncture-induced IVDD model to investigate the role of MAGL in IVDD both in vitro and in vivo. Initially, our results showed that MAGL expression was increased 2.41-fold and 1.52-fold within NP tissues from IVDD patients and rats induced with acupuncture, respectively. This increase in MAGL expression was accompanied by elevated expression of p16INK4alpha. Following this, it was noted that the suppression of MAGL resulted in a notable decrease in the quantity of SA-beta-gal-positive cells and hindered the manifestation of p16INK4alpha and the inflammatory factor IL-1beta in NPCs. MAGL inhibition promotes type II collagen (Col-2) expression and inhibits matrix metalloproteinase 13 (MMP13), thereby restoring the balance of extracellular matrix (ECM) metabolism both in vitro and in vivo. A significant role for STING has also been demonstrated in the regulation of NPC senescence by MAGL. The expression of the STING protein was reduced by 57% upon the inhibition of MAGL. STING activation can replicate the effects of MAGL and substantially increase LPS-induced inflammation while accelerating the senescence of NPCs. These results strongly indicate that the inhibition of MAGL can significantly suppress nucleus pulposus senescence via its interaction with STING, consequently restoring the balance of ECM metabolism. This insight provides new perspectives for potential treatments for IVDD.
ESTHER : Fan_2024_Int.Immunopharmacol_131_111904
PubMedSearch : Fan_2024_Int.Immunopharmacol_131_111904
PubMedID: 38518595

Title : A machine learning-based QSAR model reveals important molecular features for understanding the potential inhibition mechanism of ionic liquids to acetylcholinesterase - Wu_2024_Sci.Total.Environ__169974
Author(s) : Wu X , Gong J , Ren S , Tan F , Wang Y , Zhao H
Ref : Sci Total Environ , :169974 , 2024
Abstract : The broad application of ionic liquids (ILs) has been hindered by uncertainties surrounding their ecotoxicity. In this work, a Quantitative Structure-Activity Relationship (QSAR) model was devised to predict the inhibition of ILs towards the activity of AChE, employing both Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) machine learning approaches. Fourteen kings of essential molecular feature descriptors were screened from an initial roster of 244 descriptors through the application of a feature importance index and they showed a significant impact on the activity of AChE activity. The two models based solely on the 14 most critical molecular descriptors could maintain model's robustness and reliability. The correlation analysis between these 14 descriptors and the inhibition of AChE activity revealed the potential impact of the molecular characteristics on ILs toxicity. The results underscored the main influence of cations in ILs on the inhibitory activity towards the AChE enzyme. Specifically, cations exhibiting hydrophobicity properties were found to exert more potent inhibitory effects on the AChE enzyme. In addition, some other properties of the cations, such as the degree of branching, atomic weight and partial charge also modulated their inhibition potential. This study enhances the comprehension of the structure-activity relationship between ILs and AChE inhibition, providing a reference for designing safer and greener ILs.
ESTHER : Wu_2024_Sci.Total.Environ__169974
PubMedSearch : Wu_2024_Sci.Total.Environ__169974
PubMedID: 38199350

Title : AAV-mediated hepatic expression of LPL ameliorates severe hypertriglyceridemia and its related acute pancreatitis in Gpihbp1 deficient mice and rats - Yuan_2023_Mol.Ther__
Author(s) : Yuan C , Xu Y , Lu G , Hu Y , Mao W , Ke L , Tong Z , Xia Y , Ma S , Dong X , Xian X , Wu X , Liu G , Li B , Li W
Ref : Mol Ther , : , 2023
Abstract : GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPL). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1(-/-) mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1(-/-) rat pups, without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1(-/-) mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1(-/-) rat pups, and reduced the susceptibility and severity of both Gpihbp1(-/-) animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.
ESTHER : Yuan_2023_Mol.Ther__
PubMedSearch : Yuan_2023_Mol.Ther__
PubMedID: 37974401

Title : Efficient decolorization of melanoidin in raw molasses wastewater by thermophilic esterase in actual extreme conditions - Zhang_2023_Bioresour.Technol_382_129191
Author(s) : Zhang Z , Hu W , Xie Q , Shi Y , Zhao Y , Deng Y , He J , Wu X , Zhang Y , Zhang W , Liu P , Yang H , Wang W
Ref : Bioresour Technol , 382 :129191 , 2023
Abstract : This work was developed to explore the versatility of thermophilic esterase for decolorizing raw molasses wastewater at high temperature and acidic pH. Combining covalent crosslinking method with deep eutectic solvent, a thermophilic esterase from Pyrobaculum calidifontis was immobilized on chitosan/macroporous resin composite carrier. The application of this immobilized thermophilic esterase eliminated 92.35% of colorants in raw molasses wastewater, achieving maximal decolorization efficiency across all the enzymes tested. Strikingly, this immobilized thermophilic esterase was capable of engaging in continuous activity for a 5-day period while removing 76.23% of pigments from samples. It effectively and continuously eliminated BOD(5) and COD, effectively and directly facilitating raw molasses wastewater decolorization under extreme conditions more readily than control group. In addition, this thermophilic esterase was believed to achieve decolorization through an addition reaction that disrupted conjugated system of melanoidins. Together, these results highlight an efficient and practical means of achieving enzyme-based molasses wastewater decolorization.
ESTHER : Zhang_2023_Bioresour.Technol_382_129191
PubMedSearch : Zhang_2023_Bioresour.Technol_382_129191
PubMedID: 37196742

Title : Systematic assessment of cyflumetofen toxicity in soil-earthworm (Eisenia fetida) microcosms - Shi_2023_J.Hazard.Mater_452_131300
Author(s) : Shi L , Zhang P , Xu J , Wu X , Pan X , He L , Dong F , Zheng Y
Ref : J Hazard Mater , 452 :131300 , 2023
Abstract : Cyflumetofen was widely applied in agriculture with its excellent acaricidal effect. However, the impact of cyflumetofen on the soil non-target organism earthworm (Eisenia fetida) is unclear. This study aimed to elucidate the bioaccumulation of cyflumetofen in soil-earthworm systems and the ecotoxicity of earthworms. The highest concentration of cyflumetofen enriched by earthworms was found on the 7th day. Long-term exposure of earthworms to the cyflumetofen (10 mg/kg) could suppress protein content and increases Malondialdehyde content leading to severe peroxidation. Transcriptome sequencing analysis demonstrated that catalase and superoxide-dismutase activities were significantly activated while genes involved in related signaling pathways were significantly upregulated. In terms of detoxification metabolic pathways, high concentrations of cyflumetofen stimulated the number of Differentially-Expressed-Genes involved in the detoxification pathway of the metabolism of glutathione. Identification of three detoxification genes (LOC100376457, LOC114329378, and JGIBGZA-33J12) had synergistic detoxification. Additionally, cyflumetofen promoted disease-related signaling pathways leading to higher disease risk, affecting the transmembrane capacity and cell membrane composition, ultimately causing cytotoxicity. Superoxide-Dismutase in oxidative stress enzyme activity contributed more to detoxification. Carboxylesterase and glutathione-S-transferase activation play a major detoxification role in high-concentration treatment. Altogether, these results contribute to a better understanding of toxicity and defense mechanisms involved in long-term cyflumetofen exposure in earthworms.
ESTHER : Shi_2023_J.Hazard.Mater_452_131300
PubMedSearch : Shi_2023_J.Hazard.Mater_452_131300
PubMedID: 37002996

Title : The advantages of penehyclidine hydrochloride over atropine in acute organophosphorus pesticide poisoning: A meta-analysis - Zeng_2023_J.Intensive.Med_3_171
Author(s) : Zeng S , Ma L , Yang L , Hu X , Wang C , Guo X , Li Y , Gou Y , Zhang Y , Li S , Zhang S , Wu X , Li M , Lei J , Li B , Bi C , Luo Q
Ref : J Intensive Med , 3 :171 , 2023
Abstract : BACKGROUND: Penehyclidine hydrochloride (PHC) has been used for many years as an anticholinergic drug for the treatment of acute organophosphorus pesticide poisoning (AOPP). The purpose of this meta-analysis was to explore whether PHC has advantages over atropine in the use of anticholinergic drugs in AOPP. METHODS: We searched Scopus, Embase, Cochrane, PubMed, ProQuest, Ovid, Web of Science, China Science and Technology Journal Database (VIP), Duxiu, Chinese Biomedical literature (CBM), WanFang, and Chinese National Knowledge Infrastructure (CNKI), from inception to March 2022. After all qualified randomized controlled trials (RCTs) were included, we conducted quality evaluation, data extraction, and statistical analysis. Statistics using risk ratios (RR), weighted mean difference (WMD), and standard mean difference (SMD). RESULTS: Our meta-analysis included 20,797 subjects from 240 studies across 242 different hospitals in China. Compared with the atropine group, the PHC group showed decreased mortality rate (RR=0.20, 95% confidence intervals [CI]: 0.16-0.25, P <0.001), hospitalization time (WMD=-3.89, 95% CI: -4.37 to -3.41, P <0.001), overall incidence rate of complications (RR=0.35, 95% CI: 0.28-0.43, P <0.001), overall incidence of adverse reactions (RR=0.19, 95% CI: 0.17-0.22, P <0.001), total symptom disappearance time (SMD=-2.13, 95% CI: -2.35 to -1.90, P <0.001), time for cholinesterase activity to return to normal value 50-60% (SMD=-1.87, 95% CI: -2.03 to -1.70, P <0.001), coma time (WMD=-5.57, 95% CI: -7.20 to -3.95, P <0.001), and mechanical ventilation time (WMD=-2.16, 95% CI: -2.79 to -1.53, P <0.001). CONCLUSION: PHC has several advantages over atropine as an anticholinergic drug in AOPP.
ESTHER : Zeng_2023_J.Intensive.Med_3_171
PubMedSearch : Zeng_2023_J.Intensive.Med_3_171
PubMedID: 37188113

Title : Phytochemical analysis, antioxidant, antimicrobial, and anti-enzymatic properties of Alpinia coriandriodora (sweet ginger) rhizome - Wu_2023_Front.Plant.Sci_14_1284931
Author(s) : Wu X , Wei F , Ding F , Yang N , Niu J , Ran Y , Tian M
Ref : Front Plant Sci , 14 :1284931 , 2023
Abstract : Alpinia coriandriodora, also known as sweet ginger, is a medicinal and edible plant. A. coriandriodora rhizome is popularly utilized in traditional Chinese medicine and as flavouring spices, but there are few reports on its constituents and bioactivities. This study analyzed the phytochemical components of A. coriandriodora rhizome by GC-MS and UHPLC-Q-Orbitrap-MS and evaluated its antioxidant, antimicrobial, and anti-enzymatic properties. According to the GC-FID/MS data, its rhizome essential oil (EO) consisted mainly of (E)-2-decenal (53.8%), (E)-2-decenyl acetate (24.4%), (Z)-3-dodecenyl acetate (3.5%), and (E)-2-octenal (3.5%). Its water extract (WE) and 70% ethanol extract (EE) showed high total phenolic content (TPC, 52.99-60.49 mg GAEs/g extract) and total flavonoid content (TFC, 260.69-286.42 mg REs/g extract). In addition, the phytochemicals of WE and EE were further characterized using UHPLC-Q-Orbitrap-MS, and a total of sixty-three compounds were identified, including fourteen phenolic components and twenty-three flavonoid compounds. In the antioxidant assay, WE and EE revealed a potent scavenging effect on DPPH (IC(50): 6.59 +/- 0.88 mg/mL and 17.70 +/- 1.15 mg/mL, respectively), surpassing the BHT (IC(50): 21.83 +/- 0.89 mg/mL). For the antimicrobial activities, EO displayed excellent antibacterial capabilities against Proteus vulgaris, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus with DIZ (12.60-22.17 mm), MIC (0.78-1.56 mg/mL), and MBC (3.13 mg/mL) and significantly inhibited Aspergillus flavus growth (MIC = 0.313 mg/mL, MFC = 0.625 mg/mL, respectively). In addition to weak tyrosinase and cholinesterase inhibition, EE and WE had a prominent inhibitory effect against alpha-glucosidase (IC(50): 0.013 +/- 0.001 mg/mL and 0.017 +/- 0.002 mg/mL), which was significantly higher than acarbose (IC(50): 0.22 +/- 0.01 mg/mL). Hence, the rhizome of A. coriandriodora has excellent potential for utilization in the pharmaceutical and food fields as a source of bioactive substances.
ESTHER : Wu_2023_Front.Plant.Sci_14_1284931
PubMedSearch : Wu_2023_Front.Plant.Sci_14_1284931
PubMedID: 37936928

Title : Protective effects of fisetin in an Abeta1-42-induced rat model of Alzheimer's disease - Wang_2023_Folia.Neuropathol_61_196
Author(s) : Wang Y , Wu X , Ren W , Liu Y , Dai X , Wang S , Huo Q , Sun Y
Ref : Folia Neuropathol , 61 :196 , 2023
Abstract : Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer's disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.
ESTHER : Wang_2023_Folia.Neuropathol_61_196
PubMedSearch : Wang_2023_Folia.Neuropathol_61_196
PubMedID: 37587894

Title : Abamectin induced brain and liver toxicity in carp: The healing potential of silybin and potential molecular mechanisms - Wu_2023_Fish.Shellfish.Immunol__109152
Author(s) : Wu X , Xin Y , Ma Y , Ping K , Li Q , Sun Y , Hu Z , Dong J
Ref : Fish Shellfish Immunol , :109152 , 2023
Abstract : Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid, has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp. Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin, MMP2, MMP9, and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3beta/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-kappaB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.
ESTHER : Wu_2023_Fish.Shellfish.Immunol__109152
PubMedSearch : Wu_2023_Fish.Shellfish.Immunol__109152
PubMedID: 37821005

Title : Fotagliptin monotherapy with alogliptin as an active comparator in patients with uncontrolled type 2 diabetes mellitus: a randomized, multicenter, double-blind, placebo-controlled, phase 3 trial - Xu_2023_BMC.Med_21_388
Author(s) : Xu M , Sun K , Xu W , Wang C , Yan D , Li S , Cong L , Pi Y , Song W , Sun Q , Xiao R , Peng W , Wang J , Peng H , Zhang Y , Duan P , Zhang M , Liu J , Huang Q , Li X , Bao Y , Zeng T , Wang K , Qin L , Wu C , Deng C , Huang C , Yan S , Zhang W , Li M , Sun L , Wang Y , Li H , Wang G , Pang S , Zheng X , Wang H , Wang F , Su X , Ma Y , Li Z , Xie Z , Xu N , Ni L , Zhang L , Deng X , Pan T , Dong Q , Wu X , Shen X , Zhang X , Zou Q , Jiang C , Xi J , Ma J , Sun J , Yan L
Ref : BMC Med , 21 :388 , 2023
Abstract : BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) have become firmly established in treatment algorithms and national guidelines for improving glycemic control in type 2 diabetes mellitus (T2DM).To report the findings from a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial, which was designed to assess the efficacy and safety of a novel DPP-4 inhibitor fotagliptin in treatment-naive patients with T2DM. METHODS: Patients with T2DM were randomized to receive fotagliptin (n = 230), alogliptin (n = 113) or placebo (n = 115) at a 2:1:1 ratio for 24 weeks of double-blind treatment period, followed by an open-label treatment period, making up a total of 52 weeks. The primary efficacy endpoint was to determine the superiority of fotagliptin over placebo in the change of HbA1c from baseline to Week 24. All serious or significant adverse events were recorded. RESULTS: After 24 weeks, mean decreases in HbA1c from baseline were -0.70% for fotagliptin, -0.72% for alogliptin and -0.26% for placebo. Estimated mean treatment differences in HbA1c were -0.44% (95% confidence interval [CI]: -0.62% to -0.27%) for fotagliptin versus placebo, and -0.46% (95% CI: -0.67% to -0.26%) for alogliptin versus placebo, and 0.02% (95%CI: -0.16% to 0.19%; upper limit of 95%CI < margin of 0.4%) for fotagliptin versus alogliptin. So fotagliptin was non-inferior to alogliptin. Compared with subjects with placebo (15.5%), significantly more patients with fotagliptin (37.0%) and alogliptin (35.5%) achieved HbA1c < 7.0% after 24 weeks of treatment. During the whole 52 weeks of treatment, the overall incidence of hypoglycemia was low for both of the fotagliptin and alogliptin groups (1.0% each). No drug-related serious adverse events were observed in any treatment group. CONCLUSIONS: In summary, the study demonstrated improvement in glycemic control and a favorable safety profile for fotagliptin in treatment-naive patients with T2DM. TRIAL REGISTRATION: ClinicalTrail.gov NCT05782192.
ESTHER : Xu_2023_BMC.Med_21_388
PubMedSearch : Xu_2023_BMC.Med_21_388
PubMedID: 37814306

Title : 3-Monochloropropane-1,2-diol reduced bioaccessibility of sn-2 palmitate via bounding with pancreatic lipase in infant formula during gastrointestinal digestion - Jia_2023_J.Dairy.Sci__
Author(s) : Jia W , Wu X , Shu J , Shi L
Ref : J Dairy Sci , : , 2023
Abstract : Infant formula contains 3-monochloropropane-1,2-diol esters which are formed during the deodorization step of vegetable oils refining. European Food Safety Authority stated that 3-monochloropropane-1,2-diol esters can be hydrolyzed in the gastrointestinal tract to free-form 3-monochloropropane-1,2-diol, which has potential toxicity and can be rapidly absorbed. Evaluating the effect of 3-monochloropropane-1,2-diol on nutrition absorption is a prerequisite for establishing effective management strategies. A total of 66 crucial lipid molecules associated with 3-monochloropropane-1,2-diol were identified based on Debiased Sparse Partial Correlation analysis. 3-Monochloropropane-1,2-diol affected triglyceride hydrolyzation and increased the concentration of undigested sn-2 palmitate (9.57 to 17.06 mg kg(-1)). 3-Monochloropropane-1,2-diol reduced the bioaccessibility of fatty acids and more short- (31.42 to 58.02 mg kg(-1)) and medium-chain fatty acids (17.03 to 26.43 mg kg(-1)) remained unabsorbed. Lipidomics profiles of infant formula models spiked with different 3-MCPDE levels were investigated and the results were consistent with the experiments with the commercial formula indicating lipid alteration was mainly affected by the digestive 3-MCPD. The formation of 3-monochloropropane-1,2-diol ester-pancreatic lipase with the binding energy of -4.9 kcal mol(-1) was more stable than triglyceride-pancreatic lipase (-4.0 kcal mol(-1)), affecting triglyceride hydrolyzation. 3-Monochloropropane-1,2-diol was bound to Glu13 and Asp331 residues of the pancreatic lipase via hydrogen bonds, which resulted in a conformational change of pancreatic lipase and spatial shielding effect. The existence of the spatial shielding effect reduced the accessibility of pancreatic lipase and further affected triglyceride hydrolyzation. These findings indicated that 3-monochloropropane-1,2-diol obstructed nutrient acquisition and laid the foundation for the subsequent nutrition enhancement design.
ESTHER : Jia_2023_J.Dairy.Sci__
PubMedSearch : Jia_2023_J.Dairy.Sci__
PubMedID: 37690726

Title : Simple and novel icariin-loaded pro-glycymicelles as a functional food: physicochemical characteristics, in vitro biological activities, and in vivo experimental hyperlipidemia prevention evaluations - Cui_2023_Food.Funct__
Author(s) : Cui Q , Wang C , Zhou L , Wei Y , Liu Z , Wu X
Ref : Food Funct , : , 2023
Abstract : A novel functional food for hyperlipidemia named icariin (ICA) pro-glycymicelles (ICA-PGs) using glycyrrhizin as a phytonanomaterial was easily prepared with improved storage, pH, and salt stabilities. ICA-PGs can easily dissolve in water to self-assemble into a clear glycymicelle solution with high ICA encapsulation efficiency. The ICA in ICA-PGs exhibits significantly increased aqueous solubility, faster in vitro release, and higher bioaccessibility than bare ICA. The ICA-PGs exhibited improved in vitro activities including antioxidant, anti-alpha-glucosidase, anti-lipase, and anti-cholesterol esterase activities. The ICA-PG also demonstrated improved antioxidant activity in cells. In vivo evaluation confirmed that the ICA-PG demonstrated a significant protective effect against experimental hyperlipidemia in mice, exhibiting decreasing levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the serum, and restoring the hepatic morphology to the normal state. These results indicated that the ICA-PG could improve in vitro/in vivo profiles of ICA, providing a new concept and a promising functional food for hyperlipidemia.
ESTHER : Cui_2023_Food.Funct__
PubMedSearch : Cui_2023_Food.Funct__
PubMedID: 37853783

Title : Identification of genes related to glucose metabolism and analysis of the immune characteristics in Alzheimer's disease - Wang_2023_Brain.Res_1819_148545
Author(s) : Wang Y , Shen Z , Wu H , Yu Z , Wu X , Zhou L , Guo F
Ref : Brain Research , 1819 :148545 , 2023
Abstract : OBJECTIVE: Glucose metabolism plays a crucial role in the progression of Alzheimer's disease (AD). The purpose of this study is to identify genes related to glucose metabolism in AD by bioinformatics, construct an early AD prediction model from the perspective of glucose metabolism, and analyze the characteristics of immune cell infiltration. METHODS: AD-related modules and genes were screened by weighted gene co-expression network analysis (WGCNA). The GO and KEEG enrichment analysis were used to explore the potential biological functions of glucose metabolism related genes (GMRGs) in AD. The Least Absolute Shrinkage Selection Operator (LASSO) method was used to construct an early AD prediction model based on GMRGs. Then, the receiver operating characteristic curve (ROC) and nomogram were introduced to evaluate the effectiveness of this model. Finally, CIBERSORT and single-cell analysis were applied for illustrating the immune characteristics in AD patients. RESULTS: A total of 462 differential expressed genes (DEGs) were obtained between Non-Alzheimer's disease (ND,) and AD groups. The genes in the blue module had the highest correlation with AD by WGCNA analysis. We found 18 intersected genes among DEGs, blue model genes and GMRGs according to the Venn diagram. The GO and KEEG enrichment analysis showed that these 18 genes were mainly involved in the production of metabolites and energy, glycolysis, amino acid biosynthesis and so on. The early AD prediction model including ENO2, TPI1, AEBP1, HERC1, PCSK1, PREPL, SLC25A4, UQCRC2, CHST6, DDIT4, ACSS1 and SUCLA2 was constructed by LASSO analysis. The area under the curve (AUC) of this model in brain tissues was 0.942. Then, we draw the nomogram of this model and the C-index was 0.942. The model was further validated in blood samples and the AUC was 0.644. Immune cell infiltration analysis showed that the proportion of plasma cells, T cells follicular helper and activated NK cells in AD group were significantly lower than ND group, while the proportion of M1 macrophages, neutrophils, T cells CD4 naive and gamma-delta T cells was significantly increased when compared with the ND group. Additionally, the specific GMRGs such as ENO2, DDIT4, and SUCLA2 are significantly correlated with certain immune cells such as plasma cells, follicular helper T cells, and M1 macrophages. Single-cell analysis results suggested that the increased macrophages in AD was associated with the up-regulation of AEBP1, DDIT4 and ACSS1. CONCLUSIONS: The diagnosis model based on the twelve GMRGs has strong predictive ability and can be used as early diagnosis biomarkers for AD. In addition, these GMRGs closely associate with AD development by influencing the glucose metabolism of immune cells.
ESTHER : Wang_2023_Brain.Res_1819_148545
PubMedSearch : Wang_2023_Brain.Res_1819_148545
PubMedID: 37619853

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

Title : Effects of Methyl Jasmonate Fumigation on the Growth and Detoxification Ability of Spodoptera litura to Xanthotoxin - Chen_2023_Insects_14_
Author(s) : Chen L , Song J , Wang J , Ye M , Deng Q , Wu X , Ren B
Ref : Insects , 14 : , 2023
Abstract : Methyl jasmonate (MeJA) is a volatile substance derived from jasmonic acid (JA), and it responds to interbiotic and abiotic stresses by participating in interplant communication. Despite its function in interplant communication, the specific role of MeJA in insect defense responses is poorly understood. In this study, we found that carboxylesterase (CarE) activities, glutathione-S-transferase (GSTs) activities, and cytochrome mono-oxygenases (P450s) content increased more after the feeding of diets containing xanthotoxin, while larvae exposed to MeJA fumigation also showed higher enzyme activity in a dose-dependent manner: lower and medium concentrations of MeJA induced higher detoxification enzyme activities than higher concentrations of MeJA. Moreover, MeJA improved the growth of larvae fed on the control diet without toxins and diets with lower concentrations of xanthotoxin (0.05%); however, MeJA could not protect the larvae against higher concentrations of xanthotoxin (0.1%, 0.2%). In summary, we demonstrated that MeJA is effective at inducing S. litura defense response, but the enhanced detoxifying ability could not overcome the strong toxins.
ESTHER : Chen_2023_Insects_14_
PubMedSearch : Chen_2023_Insects_14_
PubMedID: 36835714

Title : Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population - Bai_2022_Microbiome_10_147
Author(s) : Bai X , Sun Y , Li Y , Li M , Cao Z , Huang Z , Zhang F , Yan P , Wang L , Luo J , Wu J , Fan D , Chen H , Zhi M , Lan P , Zeng Z , Wu X , Miao Y , Zuo T
Ref : Microbiome , 10 :147 , 2022
Abstract : BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract.
ESTHER : Bai_2022_Microbiome_10_147
PubMedSearch : Bai_2022_Microbiome_10_147
PubMedID: 36100953

Title : Exploring the Inhibition of Quercetin on Acetylcholinesterase by Multispectroscopic and In Silico Approaches and Evaluation of Its Neuroprotective Effects on PC12 Cells - Liao_2022_Molecules_27_
Author(s) : Liao Y , Mai X , Wu X , Hu X , Luo X , Zhang G
Ref : Molecules , 27 : , 2022
Abstract : This study investigated the inhibitory mechanism of quercetin in acetylcholinesterase (AChE) and its neuroprotective effects on beta-amyloid(25-35)-induced oxidative stress injury in PC12 cells. Quercetin inhibited AChE in a reversible mixed manner with an IC(50) of 4.59 +/- 0.27 microM. The binding constant of quercetin with AChE at 25 degreesC was (5.52 +/- 0.05) x 10(4) L mol(-1). Hydrogen bonding and van der Waals forces were the main interactions in forming the stable quercetin-AChE complex. Computational docking revealed that quercetin was dominant at the peripheral aromatic site in AChE and induced enzymatic allosterism; meanwhile, it extended deep into the active center of AChE and destabilized the hydrogen bond network, which caused the constriction of the gorge entrance and prevented the substrate from entering the enzyme, thus resulting in the inhibition of AChE. Molecular dynamics (MD) simulation emphasized the stability of the quercetin-AChE complex and corroborated the previous findings. Interestingly, a combination of galantamine hydrobromide and quercetin exhibited the synergistic inhibition effect by binding to different active sites of AChE. In a beta-amyloid(25-35)-induced oxidative stress injury model in PC12 cells, quercetin exerted neuroprotective effects by increasing the glutathione level and reducing the malondialdehyde content and reactive oxygen species levels. These findings may provide novel insights into the development and application of quercetin in the dietary treatment of Alzheimer's disease.
ESTHER : Liao_2022_Molecules_27_
PubMedSearch : Liao_2022_Molecules_27_
PubMedID: 36432070

Title : Activation of GPR55 attenuates cognitive impairment, oxidative stress, neuroinflammation, and synaptic dysfunction in a streptozotocin-induced Alzheimer's mouse model - Xiang_2022_Pharmacol.Biochem.Behav__173340
Author(s) : Xiang X , Wang X , Wu Y , Hu J , Li Y , Jin S , Wu X
Ref : Pharmacol Biochem Behav , :173340 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by cascading changes in cognition and behavior. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for the treatment of diabetes, but its function in AD is unclear. The objective of this study was to investigate the neuroprotective effects of O-1602, a GPR55 agonist, on the streptozotocin (STZ)-induced AD mouse model. A single intracerebroventricular (i.c.v.) injection of STZ into the brains of mice significantly induced cognitive impairment. In contrast, O-1602 (2.0 or 4.0 microg/mouse, i.c.v.) can improve the cognitive dysfunction caused by STZ in the Morris water maze (MWM) and novel object recognition (NOR) tests. Importantly, O-1602 treatment reversed STZ-induced GPR55 down-regulation, reduced the activity of beta-secretase 1 (BACE1) and the level of Abeta(1-42), and abolished the up-regulation of acetylcholinesterase (AChE) activity in the hippocampus and frontal cortex. Besides, O-1602 markedly suppressed STZ-induced oxidative stress, characterized by decreased malondialdehyde (MDA) level, and increased the levels of glutathione (GSH), superoxide dismutases (SOD), and catalase (CAT), as well as attenuated neuroinflammation as indicated by decreased series of pro-inflammatory cytokines and microglia activation. O-1602 treatment also ameliorated synaptic dysfunction by promoting the up-regulation of PSD-95 protein in the STZ-treated mice. Our results suggest that O-1602 has potent neuroprotective effects against STZ-induced neurotoxicity. Meanwhile, these findings suggest that GPR55 might be a novel and promising target for the treatment of AD.
ESTHER : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedSearch : Xiang_2022_Pharmacol.Biochem.Behav__173340
PubMedID: 35090841

Title : Mitigation of Memory Impairment with Fermented Fucoidan and lambda-Carrageenan Supplementation through Modulating the Gut Microbiota and Their Metagenome Function in Hippocampal Amyloid-beta Infused Rats - Zhang_2022_Cells_11_
Author(s) : Zhang T , Wu X , Yuan H , Huang S , Park S
Ref : Cells , 11 : , 2022
Abstract : Attenuating acetylcholinesterase and insulin/insulin-like growth factor-1 signaling in the hippocampus is associated with Alzheimer's disease (AD) development. Fucoidan and carrageenan are brown and red algae, respectively, with potent antibacterial, anti-inflammatory, antioxidant and antiviral activities. This study examined how low-molecular-weight (MW) and high-MW fucoidan and lambda-carrageenan would improve memory impairment in Alzheimer's disease-induced rats caused by an infusion of toxic amyloid-beta(Abeta). Fucoidan and lambda-carrageenan were dissected into low-MW by Luteolibacter&nbsp;algae and Pseudoalteromonas&nbsp;carrageenovora. Rats receiving an Abeta(25-35) infusion in the CA1 region of the hippocampus were fed dextrin (AD-Con), 1% high-MW fucoidan (AD-F-H), 1% low-MW fucoidan (AD-F-L), 1% high-MW lambda-carrageenan (AD-C-H), and 1% low-MW lambda-carrageenan (AD-C-L) for six weeks. Rats to receive saline infusion (Normal-Con) had an AD-Con diet. The AD-F-L group showed an improved memory function, which manifested as an enhanced Y-maze spontaneous alternation test, water maze, and passive avoidance tests, similar to the Normal-Con group. AD-F-L also potentiated hippocampal insulin signaling and increased the expression of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) in the hippocampus. AD-C-L improved the memory function mainly by increasing the BDNF content. AD-F-H and AD-C-H did not improve the memory function. Compared to AD-Con, the ascending order of AD-C-H, AD-F-H, AD-C-L, and AD-F-L increased insulin signaling by enhancing the pSTAT3(a)pAkt(a)pGSK-3beta pathway. AD-F-L improved glucose tolerance the most. Compared to AD-CON, the AD-F-L treatment increased the serum acetate concentrations and compensated for the defect of cerebral glucose metabolism. AD-Con increased Clostridium, Terrisporobacter and Sporofaciens compared to Normal-Con, and AD-F-L and AD-C-L increased Akkermentia. In conclusion, AD-F-L and AD-C-L alleviated the memory function in the rats with induced AD symptoms by modulating.
ESTHER : Zhang_2022_Cells_11_
PubMedSearch : Zhang_2022_Cells_11_
PubMedID: 35892598

Title : Production of Red Pigments by a Newly Isolated Talaromyces aurantiacus Strain with LED Stimulation for Screen Printing - Gong_2022_Indian.J.Microbiol_62_280
Author(s) : Gong X , Luo H , Wu X , Liu H , Sun C , Chen S
Ref : Indian J Microbiol , 62 :280 , 2022
Abstract : Microbial pigments have been widely applied to printing in food, textile, and paper industries as a sustainable alternative to synthetic dyes. Herein, we isolated a novel Talaromyces aurantiacus strain with a strong ability to produce red pigments. We further studied pigment production conditions, stability, screen printing application, and bioactivities. Our results showed that sucrose was a favourable carbon source and the addition of l-histidine significantly enhanced the production of red pigments. Pigment production was strictly photo-regulated with effective wavelengths around 450 nm (blue light). We mixed the red pigments with cellulosic materials and explored their application potentials for screen printing on paper, cotton fabrics, and polymeric carriers. The printing density was significantly improved from 0.3 to 0.7 by overlay printing. T. aurantiacus pigments could be stably stored at pH 5-11, temperature - 10 to 70 degreesC, and redox potential - 200 to 300 mV. Moreover, the stable ranges were extended to pH 1-11 and temperature over 100 degreesC after screen-printed on paper. The red pigments exhibited antioxidant activity towards 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (IC(50) 10.4 mg L(-1) in solution). Our results further indicated the red pigments by T. aurantiacus was environmentally friendly based on acetylcholinesterase activity assay. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12088-022-01008-x.
ESTHER : Gong_2022_Indian.J.Microbiol_62_280
PubMedSearch : Gong_2022_Indian.J.Microbiol_62_280
PubMedID: 35462713

Title : Long-Term Effect of Porcine Brain Enzyme Hydrolysate Intake on Scopolamine-Induced Memory Impairment in Rats - Zhang_2022_Int.J.Mol.Sci_23_3361
Author(s) : Zhang T , Kim MJ , Wu X , Yang HJ , Yuan H , Huang S , Yoon SM , Kim KN , Park S
Ref : Int J Mol Sci , 23 :3361 , 2022
Abstract : No study has revealed the effect of porcine brain enzyme hydrolysate (PBEH) on memory impairment. We aimed to examine the hypothesis that PBEH intake modulates memory deficits and cognitive behavior in scopolamine (SC)-induced amnesia rats, and its mechanism, including gut microbiota changes, was determined. Sprague-Dawley male rats had intraperitoneal injections of SC (2 mg/kg body weight/day) at 30 min after daily feeding of casein (MD-control), PBEH (7 mg total nitrogen/mL) at 0.053 mL (Low-PBEH), 0.159 mL (Medium-PBEH), 0.478 mL (High-PBEH), or 10 mg donepezil (Positive-control) per kilogram body weight per day through a feeding needle for six weeks. The Normal-control rats had casein feeding without SC injection. PBEH dose-dependently protected against memory deficits determined by passive avoidance test, Y-maze, water-maze, and novel object recognition test in SC-induced rats compared to the MD-control. The High-PBEH group had a similar memory function to the Positive-control group. Systemic insulin resistance determined by HOMA-IR was lower in the PBEH groups than in the Normal-control but not the Positive-control. In parallel with systemic insulin resistance, decreased cholesterol and increased glycogen contents in the hippocampus in the Medium-PBEH and High-PBEH represented reduced brain insulin resistance. PBEH intake prevented the increment of serum TNF-alpha and IL-1beta concentrations in the SC-injected rats. Hippocampal lipid peroxide and TNF-alpha contents and mRNA TNF-alpha and IL-1beta expression were dose-dependently reduced in PBEH and Positive-control. PBEH decreased the hippocampal acetylcholinesterase activity compared to the MD-control, but not as much as the Positive-control. PBEH intake increased the alpha-diversity of the gut microbiota compared to the MD-control, and the gut microbiota community was separated from MD-control. In metagenome function analysis, PBEH increased the energy metabolism-related pathways of the gut microbiota, including citric acid cycle, oxidative phosphorylation, glycolysis, and amino acid metabolism, which were lower in the MD-control than the Normal-control. In conclusion, alleviated memory deficit by PBEH was associated potentially with not only reducing acetylcholinesterase activity but also improving brain insulin resistance and neuroinflammation potentially through modulating gut microbiota. PBEH intake (1.5-4.5 mL of 7 mg total nitrogen/mL for human equivalent) can be a potential therapeutic agent for improving memory impairment.
ESTHER : Zhang_2022_Int.J.Mol.Sci_23_3361
PubMedSearch : Zhang_2022_Int.J.Mol.Sci_23_3361
PubMedID: 35328781

Title : Effects of larval exposure to the insecticide flumethrin on the development of honeybee (Apis mellifera) workers - Liu_2022_Front.Physiol_13_1054769
Author(s) : Liu C , Wu X , Yang H , Yu L , Zhang Y
Ref : Front Physiol , 13 :1054769 , 2022
Abstract : Flumethrin is a widely used acaricide, but its improper use often leads to residue accumulation in honeybee colonies, thus threatening the health of honeybees, especially at the larval stage. Therefore, this study aimed to describe the direct toxicity of flumethrin on honeybee (Apis mellifera) larvae by conducting bioassays for immune and detoxification-related enzymes and transcriptome sequencing to determine the potential effects on newly emerged adults who were exposed to flumethrin during the larval stage. Results showed that the higher the concentration of flumethrin the honeybee larvae were exposed to, the greater the damage to the physiology of honeybee larvae and the newly emerged worker bees. When honeybee larvae were exposed to flumethrin concentrations higher than 0.01smg/L, the activities of glutathione sulfur transferase and carboxylesterase were affected, and the metabolism-related genes in the head of newly emerged honeybees exposed to flumethrin during the larval stage were down-regulated. Flumethrin concentration higher than 0.1smg/L significantly increased mixed-functional oxidase content in honeybee larvae, reduced the larval survival rate, and down-regulated the expression levels of olfactory-related and antioxidant-related genes in newly emerged honeybees. Furthermore, a flumethrin concentration of 1smg/L significantly down-regulated the expression levels of immune and detoxification-related genes in newly emerged honeybees. These findings provide a comprehensive understanding of the response of honeybee larvae to sublethal flumethrin toxicity and could be used to further investigate the complex molecular mechanisms in honeybees under pesticide stress.
ESTHER : Liu_2022_Front.Physiol_13_1054769
PubMedSearch : Liu_2022_Front.Physiol_13_1054769
PubMedID: 36589443

Title : Strigolactone is involved in nitric oxide-enhanced the salt resistance in tomato seedlings - Liu_2022_J.Plant.Res__
Author(s) : Liu H , Li C , Yan M , Zhao Z , Huang P , Wei L , Wu X , Wang C , Liao W
Ref : J Plant Res , : , 2022
Abstract : Both strigolactones (SLs) and nitric oxide (NO) are regulatory signals with diverse roles during stress responses. At present, the interaction and mechanism of SLs and NO in tomato salt tolerance remain unclear. In the current study, tomato 'Micro-Tom' was used to study the roles and interactions of SLs and NO in salinity stress tolerance. The results show that 15 microM SLs synthetic analogs GR24 and 10 microM NO donor S-nitrosoglutathione (GSNO) promoted seedling growth under salt stress. TIS108 (an inhibitor of strigolactone synthesis) suppressed the positive roles of NO in tomato growth under salt stress, indicating that endogenous SLs might be involved in NO-induced salt response in tomato seedlings. Meanwhile, under salt stress, GSNO or GR24 treatment induced the increase of endogenous SLs content in tomato seedlings. Moreover, GR24 or GSNO treatment effectively increased the content of chlorophyll, carotenoids and ascorbic acid (ASA), and enhanced the activities of antioxidant enzymes (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), glutathione reductase (GR) and cleavage dioxygenase (CCD) enzyme. Additionally, GSNO or GR24 treatment also up-regulated the expression of SLs synthesis genes (SlCCD7, SlCCD8, SlD27 and SlMAX1) and its signal transduction genes (SlD14 and SlMAX2) in tomato seedlings under salt stress. While, a strigolactone synthesis inhibitor TIS108 blocked the increase of endogenous SLs, chlorophyll, carotenoids and ASA content, and antioxidant enzyme, GR, CCD enzyme activity and SLs-related gene expression levels induced by GSNO. Thus, SLs may play an important role in NO-enhanced salinity tolerance in tomato seedlings by increasing photosynthetic pigment content, enhancing antioxidant capacity and improving endogenous SLs synthesis.
ESTHER : Liu_2022_J.Plant.Res__
PubMedSearch : Liu_2022_J.Plant.Res__
PubMedID: 35106650

Title : An esterase-activatable prodrug formulated liposome strategy: potentiating the anticancer therapeutic efficacy and drug safety - Shi_2022_Nanoscale.Adv_4_952
Author(s) : Shi L , Wu X , Li T , Wu Y , Song L , Zhang W , Yin L , Han W , Yang Y
Ref : Nanoscale Adv , 4 :952 , 2022
Abstract : Liposomal nanomedicine represents a common and versatile carrier for the delivery of both lipophilic and hydrophilic drugs. However, the direct formulation of many chemotherapeutics into a liposomal system remains an enormous challenge. Using the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN38) as a model drug, we combined lipophilic prodrug construction with subsequent integration into an exogenous liposomal scaffold to assemble a prodrug-formulated liposome for systemic administration. Reconstructing SN38 with lipid cholesterol via the esterase-activatable bond endows the resulting prodrug with elevated miscibility with liposomal compositions and esterase-responsive drug release in cancerous cells. The systemic administration of the prodrug-based nanoassemblies (Chol-SN38@LP) exhibited preferential accumulation of therapeutic payloads in tumor lesions. Compared to the SN38 clinical counterpart irinotecan, our prodrug-based nanoassemblies with adaptive features showed elevated therapeutic efficacy (-1.5 times increase of tumor inhibition) in a preclinical A549 lung carcinoma cell-derived mouse model and improved drug tolerability (i.e., alleviated bloody diarrhea and liver damage) in multiple mice models. These results may be ascribed to extended systemic circulation and preferential tumor accumulation of our nanodrugs. Hence, our findings demonstrate that rational engineering of therapeutic nanomedicine is a promising approach for effective and safe delivery of antitumor chemotherapeutics, especially to rescue drug candidates that have failed in clinical trials owing to poor PK properties or severe toxicity in patients.
ESTHER : Shi_2022_Nanoscale.Adv_4_952
PubMedSearch : Shi_2022_Nanoscale.Adv_4_952
PubMedID: 36131817

Title : Protective effects of isofraxidin against scopolamine-induced cognitive and memory impairments in mice involve modulation of the BDNF-CREB-ERK signaling pathway - Lian_2022_Metab.Brain.Dis__
Author(s) : Lian B , Gu J , Zhang C , Zou Z , Yu M , Li F , Wu X , Zhao AZ
Ref : Metabolic Brain Disease , : , 2022
Abstract : BACKGROUND: Isofraxidin is a coumarin compound mainly isolated from several traditional and functional edible plants beneficial for neurodegenerative diseases, including Sarcandra glabra and Apium graveolens, and Siberian Ginseng. OBJECTIVE: This study aimed to assess effects of isofraxidin against memory impairments and cognition deficits in a scopolamine-induced mouse model. MATERIALS & METHODS: Animals were randomly divided into 6 groups, control, vehicle, donepezil (10 mg/kg, p.o.), and isofraxidin (3, 10, and 30 mg/kg, p.o.). Isofraxidin or donepezil was administered for 44 days, once per day. The scopolamine insults (1 mg/kg, i.p.) was given from the 21st day, once per day. Morris water maze test and Y-maze test were used for the behavioral test. After that, brain samples were collected for analysis. RESULTS: Firstly, isofraxidin significantly improved scopolamine-induced behavioral impairments and cognition deficits in Morris water maze and Y-maze test. Then, isofraxidin facilitated cholinergic activity via inhibiting acetylcholinesterase (AChE) activity. Besides, isofraxidin decreased lipid peroxidation level but enhanced levels of glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, isofraxidin suppressed the expression of inflammatory mediators and cytokines. Further investigations showed that isofraxidin up-regulated expression of brain-derived neurotrophic factor (BDNF), and promoted phosphorylation of tropomyosin-related kinase B (TrkB), cyclic AMP-response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK). DISCUSSION & CONCLUSIONS: These results suggested that isofraxidin ameliorated scopolamine-induced cognitive and memory impairments, possibly through regulating AChE activity, suppressing oxidative stress and inflammatory response, and modulating BDNF-CREB-ERK pathways.
ESTHER : Lian_2022_Metab.Brain.Dis__
PubMedSearch : Lian_2022_Metab.Brain.Dis__
PubMedID: 35921056

Title : Diverse myopathological features in the congenital myasthenia syndrome with GFPT1 mutation - Jiang_2022_Brain.Behav__e2469
Author(s) : Jiang K , Zheng Y , Lin J , Wu X , Yu Y , Zhu M , Fang X , Zhou M , Li X , Hong D
Ref : Brain Behav , :e2469 , 2022
Abstract : INTRODUCTION: Mutations in the GFPT1 gene are associated with a particular subtype of congenital myasthenia syndrome (CMS) called limb-girdle myasthenia with tubular aggregates. However, not all patients show tubular aggregates in muscle biopsy, suggesting the diversity of myopathology should be further investigated. METHODS: In this study, we reported two unrelated patients clinically characterized by easy fatigability, limb-girdle muscle weakness, positive decrements of repetitive stimulation, and response to pyridostigmine. The routine examinations of myopathology were conducted. The causative gene was explored by whole-exome screening. In addition, we summarized all GFPT1-related CMS patients with muscle biopsy in the literature. RESULTS: Pathogenic biallelic GFPT1 mutations were identified in the two patients. In patient one, muscle biopsy indicated vacuolar myopathic changes and atypical pathological changes of myofibrillar myopathy characterized by desmin deposits, Z-disc disorganization, and electronic dense granulofilamentous aggregation. In patient two, muscle biopsy showed typical myopathy with tubular aggregates. Among the 51 reported GFPT1-related CMS patients with muscle biopsy, most of them showed tubular aggregates myopathy, while rimmed vacuolar myopathy, autophagic vacuolar myopathy, mitochondria-like myopathy, neurogenic myopathy, and unspecific myopathic changes were also observed in some patients. These extra-synaptic pathological changes might be associated with GFPT1-deficiency hypoglycosylation and altered function of muscle-specific glycoproteins, as well as partly responsible for the permanent muscle weakness and resistance to acetylcholinesterase inhibitor therapy. CONCLUSIONS: Most patients with GFPT1-related CMS had tubular aggregates in the muscle biopsy, but some patients could show great diversities of the pathological change. The myopathological findings might be a biomarker to predict the prognosis of the disease.
ESTHER : Jiang_2022_Brain.Behav__e2469
PubMedSearch : Jiang_2022_Brain.Behav__e2469
PubMedID: 34978387

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

Title : Integrating network pharmacology analysis and pharmacodynamic evaluation for exploring the active components and molecular mechanism of moutan seed coat extract to improve cognitive impairment - Wang_2022_Front.Pharmacol_13_952876
Author(s) : Wang Y , Wu X , Yang K , Liu Q , Jiang B , Yang R , Xiao P , He C
Ref : Front Pharmacol , 13 :952876 , 2022
Abstract : Paeonia suffruticosa (Moutan) is a traditional medicinal plant in China. Its seed coat is rich in resveratrol oligomer, especially suffruticosol B (SB). Previous studies had shown that the seed coat extracts of Paeonia suffruticosa (PSCE) had good cholinesterase inhibitory activity and neuroprotective effect, but the effective dose range was unknown, and the pharmacodynamic components and molecular mechanism of PSCE had not been discussed. The current study aimed to screen the pharmacodynamic components in PSCE and investigate the improvement effect of PSCE and the selected SB on scopolamine-induced cognitive dysfunction in mice and its mechanism. The results of high-throughput sequencing and bioinformatics analysis showed that suffruticosol B (SB) and trans-gnetin H (GH) might be the main active components of PSCE; PSCE might improve cognitive dysfunction through p53, HIF-1, MAPK, and PI3K-Akt signaling pathways, while SB and GH might improve cognitive dysfunction through HIF-1 signaling pathway. SB and GH had good molecular docking activity with the target of HIF-1 signaling pathway. The pharmacodynamic activities of PSCE and SB were further verified by behavioral experiments. PSCE and SB could improve the recognition ability of familiar and new objects and shorten the escape latency in the Morris Water Maze test (PSCE 120 mgkg-1, p < 0.05; SB 60 mgkg-1, p < 0.01); PSCE and SB could increase Ach and GSH levels, enhance the activities of ChAT, SOD and CAT, decrease the levels of IL-1beta, IL-6, and TNF-alpha, and decrease the activity of AChE. In conclusion, the results indicated that PSCE might exert pharmacodynamic activity through multiple components, targets, and pathways, and SB and GH might be the main active components of PSCE. PSCE and SB might improve cognitive dysfunction by regulating cholinergic, antioxidant, and anti-inflammatory effects. These results indicated that PSCE and SB might be potential anti-AD drug candidates, providing a scientific basis for the development and utilization of Moutan bark.
ESTHER : Wang_2022_Front.Pharmacol_13_952876
PubMedSearch : Wang_2022_Front.Pharmacol_13_952876
PubMedID: 36034803

Title : Improved liver lipid catabolism and utilization in growth hormone transgenic common carp (Cyprinus carpio L.) through enhanced lipolytic and fatty acid beta-oxidation pathways - Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
Author(s) : Wu Y , Li R , Wu X , Guo W , Li Y , Song Y , Tao B , Chen J , Han D , Xie S , Wang Y , Zhu Z , Hu W
Ref : Front Endocrinol (Lausanne) , 13 :982488 , 2022
Abstract : Growth hormone (GH) transgenic common carp (Cyprinus carpio L.) show desirable aquaculture traits. Their specific growth rate (SGR) and feed efficiency (FE) are approximately 12% and 17% higher than the wild-type (WT) common carp, respectively. However, the mechanisms of lipid catabolism (lipolysis and fatty acid beta-oxidation) and utilization in GH transgenic common carp are still unclear. In this study, we firstly compared the lipid metabolism of GH transgenic (initial weight 3.72 +/- 0.32 g) and WT (initial weight 3.30 +/- 0.28 g) common carp fed with a normal fat level diet (6% lipid, 33% protein) for two months, then compared the growth performance of GH transgenic (initial weight 3.65 +/- 0.33 g) and WT (initial weight 3.27 +/- 0.26 g) common carp fed with different fat levels diets (6% lipid and 12% lipid, 33% protein) for two months. We found that the lipid content in serum, liver and whole body was significantly reduced in GH transgenic common carp, the hepatic activities of the lipolytic enzymes hormone-sensitive lipase and adipose triglyceride lipase were enhanced, and the hepatic expression level of hormone-sensitive lipase was upregulated. In addition, the mitochondrion numbers were increased, and the expression level of carnitine palmitoyltransferase-1a and carnitine palmitoyltransferase-1b was upregulated in the liver of GH transgenic common carp. GH transgenic common carp showed higher weight gain and SGR than that in WT carp when fed with a normal-fat diet as they did when fed with a high-fat diet, and GH transgenic common carp showed higher FE than that in WT carp when fed with a high-fat diet. These results suggested that the lipid catabolism and utilization was improved in the GH transgenic common carp liver through enhanced lipolytic and fatty acid beta-oxidation pathways. Our study provides new insights into improving lipid utilization in some aquaculture fish species.
ESTHER : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedSearch : Wu_2022_Front.Endocrinol.(Lausanne)_13_982488
PubMedID: 36171901

Title : Exposure of Helicoverpa armigera Larvae to Plant Volatile Organic Compounds Induces Cytochrome P450 Monooxygenases and Enhances Larval Tolerance to the Insecticide Methomyl - Wu_2021_Insects_12_
Author(s) : Wu C , Ding C , Chen S , Wu X , Zhang L , Song Y , Li W , Zeng R
Ref : Insects , 12 : , 2021
Abstract : Plants release an array of volatile chemicals into the air to communicate with other organisms in the environment. Insect attack triggers emission of herbivore-induced plant volatiles (HIPVs). How insect herbivores use these odors to plan their detoxification systems is vital for insect adaptation to environmental xenobiotics. Here we show that the larvae of Helicoverpa armigera (Hubner), a broadly polyphagous lepidopteran herbivore, have the capacity to use plant volatiles as cues to upregulate multiple detoxification systems, including cytochrome P450 monooxygenases (P450s), for detoxification of insecticides. Olfactory exposure of the fifth instars to two terpene volatiles limonene and nerolidol, and two green-leaf volatiles 2-heptanone and cis-3-hexenyl acetate significantly reduced larval susceptibility to the insecticide methomyl. However, larval pretreatment with piperonyl butoxide (PBO), a known P450 inhibitor, neutralized the effects of volatile exposure. Furthermore, larval exposure to the four plant volatiles enhanced activities of P450 enzymes in midguts and fatbodies, and upregulated expression of CYP6B2, CYP6B6 and CYP6B7, P450s involved in detoxification of the insecticide. Larval exposure to 2-heptanone and limonene volatiles also enhanced activities of glutathione-s-transferase and carboxylesterase. Our findings suggest that olfactory exposure to HIPVs enhances larval insecticide tolerance via induction of detoxification P450s.
ESTHER : Wu_2021_Insects_12_
PubMedSearch : Wu_2021_Insects_12_
PubMedID: 33808968

Title : Biological responses of Eisenia fetida towards the exposure and metabolism of tris (2-butoxyethyl) phosphate - Wu_2021_Sci.Total.Environ__152285
Author(s) : Wu X , Zhu Y , Yang M , Zhang J , Lin D
Ref : Sci Total Environ , :152285 , 2021
Abstract : The toxicity of various organophosphorus flame retardants (OPFRs) is of increasing concern. However, there is still a lack of research on the toxicity of OPFRs to terrestrial invertebrates and its metabolism in vivo. Herein, earthworms (Eisenia fetida) were exposed to soil spiked with 0, 0.05, 0.5, and 5 mg/kg tris(2-butoxyethyl) phosphate (TBOEP, a typical alkyl OPFRs) for 28 d to study the biological responses to the exposure and metabolism of TBOEP. TBOEP exposure inhibited the activity of acetyl-cholinesterase (64.4-68.6% of that in the control group), increased the energy consumption level, and affected calcium-dependent pathways of E. fetida, which caused a 3.6-12.4% reduction in the weight gain rate (developmental toxicity), a 10.6-69.4% reduction in the number of juveniles (reproduction toxicity), and neurotoxicity to E. fetida. The 5 mg/kg TBOEP exposure caused a significant accumulation of malondialdehyde (1.68 times higher than that in the control group) in E. fetida, which indicated that the balance of oxidation and anti-oxidation of E. fetida was broken. Meanwhile, E. fetida maintained the absorption and metabolic abilities to TBOEP under the environmental condition. The removal rate of soil TBOEP was increased by 25.1-35.5% by the presence of E. fetida. Importantly, TBOEP could accumulate in E. fetida (0.09-76.0 microg/kg) and the activation of cytochrome P450 and glutathione detoxification pathway promoted the metabolism of TBOEP in E. fetida. These findings link the biological responses and metabolic behavior of earthworms under pollution stress and provide fundamental data for the environmental risk assessment and pollution removal of OPFRs in soil.
ESTHER : Wu_2021_Sci.Total.Environ__152285
PubMedSearch : Wu_2021_Sci.Total.Environ__152285
PubMedID: 34933047

Title : A highly contiguous genome assembly of a polyphagous predatory mite Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae) - Yan_2021_Genome.Biol.Evol__
Author(s) : Yan Y , Zhang N , Liu C , Wu X , Liu K , Yin Z , Zhou X , Xie L
Ref : Genome Biol Evol , : , 2021
Abstract : As a polyphagous soil-dwelling predatory mite, Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae), formerly known as Stratiolaelaps miles (Berlese), is native to the Northern hemisphere and preys on soil invertebrates, including fungus gnats, springtails, thrips nymphs, nematodes, and other species of mites. Already mass-produced and commercialized in North America and Europe, S. scimitus is now introduced in China as a biocontrol agent for field crop. The introduction, however, can lead to unexpected genetic changes within populations of biological control agents, which might decrease the efficacy of pest management or increase the risks to local environments. To better understand the genetic basis of its biology and behavior, we sequenced and assembled the draft genome of S. scimitus using the PacBio Sequel platform II. We generated -150 x (64.81 Gb) PacBio long reads with an average read length of 12.60 kb. Reads longer than 5 kb were assembled into contigs, resulting in the final assembly of 158 contigs with a N50 length of 7.66 Mb, and captured 93.1% of the BUSCO gene set (n = 1,066). We identified 16.39% (69.91 Mb) repetitive elements, 1,686 non-coding RNAs, and 13,305 protein-coding genes, which represented 95.8% BUSCO completeness. Combining analyses of genome family evolution and function enrichment of gene ontology and pathway, a total of 135 families experienced significant expansions, which were mainly involved in digestion, detoxification, immunity and venom. Major expansions of the detoxification enzymes, i.e., P450s and carboxylesterases, suggest a possible genetic mechanism underlying polyphagy and ecological adaptions. Our high-quality genome assembly and annotation provide new insights on the evolutionary biology, soil ecology and biological control for predaceous mites.
ESTHER : Yan_2021_Genome.Biol.Evol__
PubMedSearch : Yan_2021_Genome.Biol.Evol__
PubMedID: 33528489

Title : Rational Design of Highly Selective Near-Infrared Two-Photon Fluorogenic Probe for Imaging Orthotopic Hepatocellular Carcinoma Chemotherapy - Wu_2021_Angew.Chem.Int.Ed.Engl__
Author(s) : Wu X , Wang R , Qi S , Kwon N , Han J , Kim H , Li H , Yu F , Yoon J
Ref : Angew Chem Int Ed Engl , : , 2021
Abstract : Selective fluorescence imaging of biomarker in vivo and in situ for evaluating orthotopic hepatocellular carcinoma (HCC) chemotherapy remains a great challenge due to current imaging agents suffering from the potential interferences of other hydrolases. Herein, we observed that carbamate unit showed a high selectivity toward HCC-related biomarker (carboxylesterase, CE) for evaluation of treatment. A near-infrared two-photon fluorescent probe was developed to not only specially image CE activity in vivo and in situ but also target orthotopic liver tumor after systemic administration. In vivo signals of probe correlating well with tumor apoptosis make it possible to evaluate the status of treatment. Excellent property of probe enables the first imaging of CE activity in situ with high resolution three-dimensional view. This study may promote advancements in optical imaging approach for precise imaging-guided diagnosis of HCC in situ and its evaluation of treatment.
ESTHER : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedSearch : Wu_2021_Angew.Chem.Int.Ed.Engl__
PubMedID: 33942436

Title : Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets - Zhang_2021_Talanta_228_122268
Author(s) : Zhang L , Zhang Q , Liu Q , Wu X , Dong Y , Wang GL
Ref : Talanta , 228 :122268 , 2021
Abstract : Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity.
ESTHER : Zhang_2021_Talanta_228_122268
PubMedSearch : Zhang_2021_Talanta_228_122268
PubMedID: 33773716

Title : Reducing alcohol and\/or cocaine-induced reward and toxicity via an epidermal stem cell-based gene delivery platform - Kong_2021_Mol.Psychiatry__
Author(s) : Kong Q , Li Y , Yue J , Wu X , Xu M
Ref : Mol Psychiatry , : , 2021
Abstract : Alcohol use disorder (AUD) is one of the foremost public health problems. Alcohol is also frequently co-abused with cocaine. There is a huge unmet need for the treatment of AUD and/or cocaine co-abuse. We recently demonstrated that skin grafts generated from mouse epidermal stem cells that had been engineered by CRISPR-mediated genome editing could be transplanted onto mice as a gene delivery platform. Here, we show that expression of the glucagon-like peptide-1 (GLP1) gene delivered by epidermal stem cells attenuated development and reinstatement of alcohol-induced drug-taking and seeking as well as voluntary oral alcohol consumption. GLP1 derived from the skin grafts decreased alcohol-induced increase in dopamine levels in the nucleus accumbens. In exploring the potential of this platform in reducing concurrent use of drugs, we developed a novel co-grafting procedure for both modified human butyrylcholinesterase (hBChE)- and GLP1-expressing cells. Epidermal stem cell-derived hBChE and GLP1 reduced acquisition of drug-taking and toxicity induced by alcohol and cocaine co-administration. These results imply that cutaneous gene delivery through skin transplants may add a new option to treat drug abuse and co-abuse.
ESTHER : Kong_2021_Mol.Psychiatry__
PubMedSearch : Kong_2021_Mol.Psychiatry__
PubMedID: 33619338

Title : High specific immobilization of His-tagged recombinant Microbacterium esterase by Ni-NTA magnetic chitosan microspheres for efficient synthesis of key chiral intermediate of d-biotin - He_2021_Bioprocess.Biosyst.Eng__
Author(s) : He S , Wu X , Ma B , Xu Y
Ref : Bioprocess Biosyst Eng , : , 2021
Abstract : The novel Ni-NTA-functionalized magnetic chitosan microspheres (MCS-NTA-Ni) were prepared via amino functionalization of MCS with epichlorohydrin and ethylenediamine, followed by the introduction of the aldehyde groups and NTA in turn, and nickel (II) ions were chelated in the end. MCS-NTA-Ni contained numerous long-armed NTA-Ni surface groups, ensuring high enzyme loading and providing more space and flexibility to attach enzymes and maintain their activity. This microsphere can have highly selective adsorption of his-tagged recombinant protein. The his-tagged recombinant Microbacterium esterase of E. coli BL21 (DE3)/pET21a-EstSIT01 was first immobilized on MCS-NTA-Ni by affinity fixation, giving high immobilization yield (90.1%) and enzyme loading (120 mg/g). Compared with free esterase, the immobilized esterase was found to exhibit higher pH stability and thermal stability. In addition, the immobilized esterase had excellent reusability for the synthesis of key chiral intermediate of d-biotin and the substrate conversion could still keep 100% after 8 cycles continuously.
ESTHER : He_2021_Bioprocess.Biosyst.Eng__
PubMedSearch : He_2021_Bioprocess.Biosyst.Eng__
PubMedID: 34089090

Title : Impacts of chronic exposure to sublethal diazepam on behavioral traits of female and male zebrafish (Danio rerio) - Chen_2021_Ecotoxicol.Environ.Saf_208_111747
Author(s) : Chen K , Wu M , Chen C , Xu H , Wu X , Qiu X
Ref : Ecotoxicology & Environmental Safety , 208 :111747 , 2021
Abstract : Residues of the psychoactive drug diazepam (DZP) may pose potential risks to fish in aquatic environments, especially by disrupting their behavioral traits. In this study, female and male zebrafish were subjected to chronic exposure (21 days) to sublethal doses (120 and 12 microg/L) of DZP, aimed to compare the characteristics of their behavioral responses to DZP exposure, and to investigate the possible links between those behavioral responses and variations in their brain gamma-aminobutyric acid (GABA) and acetylcholinesterase (AChE) levels. Chronic exposure to DZP significantly decreased the swimming velocity and locomotor activity of both genders, indicating a typical sedative effect. Compared with males, whose locomotor activity was only significantly decreased by exposure to DZP for 21 days, females became hypoactive on day 14 (i.e., more sensitive), and they developed tolerance to the hypoactive effect induced by 120 microg/L DZP by day 21. Exposure to DZP significantly disturbed the behavioral traits related to social interactions in females but not in males. Those results indicate that DZP exhibits sex-dependent effects on the behaviors of fish. Moreover, exposure to DZP for 21 days significantly disturbed almost all of the tested behavioral traits associated with courtship when both genders were put together. Sex-dependent responses in brain GABA and AChE levels due to DZP exposure were also identified. Significant relationships between the brain GABA/AChE levels and some behavioral parameters related to locomotor activity were detected in females, but not in males.
ESTHER : Chen_2021_Ecotoxicol.Environ.Saf_208_111747
PubMedSearch : Chen_2021_Ecotoxicol.Environ.Saf_208_111747
PubMedID: 33396073

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

Title : A molecular approach to rationally constructing specific fluorogenic substrates for the detection of acetylcholinesterase activity in live cells, mice brains and tissues - Wu_2020_Chem.Sci_11_11285
Author(s) : Wu X , An JM , Shang J , Huh E , Qi S , Lee E , Li H , Kim G , Ma H , Oh MS , Kim D , Yoon J
Ref : Chem Sci , 11 :11285 , 2020
Abstract : Acetylcholinesterase (AChE) is an extremely critical hydrolase tightly associated with neurological diseases. Currently, developing specific substrates for imaging AChE activity still remains a great challenge due to the interference from butyrylcholinesterase (BChE) and carboxylesterase (CE). Herein, we propose an approach to designing specific substrates for AChE detection by combining dimethylcarbamate choline with a self-immolative scaffold. The representative P10 can effectively eliminate the interference from CE and BChE. The high specificity of P10 has been proved via imaging AChE activity in cells. Moreover, P10 can also be used to successfully map AChE activity in different regions of a normal mouse brain, which may provide important data for AChE evaluation in clinical studies. Such a rational and effective approach can also provide a solid basis for designing probes with different properties to study AChE in biosystems and another way to design specific substrates for other enzymes.
ESTHER : Wu_2020_Chem.Sci_11_11285
PubMedSearch : Wu_2020_Chem.Sci_11_11285
PubMedID: 34094370

Title : Edaravone at high concentrations attenuates cognitive dysfunctions induced by abdominal surgery under general anesthesia in aged mice - Zhou_2020_Metab.Brain.Dis__
Author(s) : Zhou Y , Wu X , Ye L , Bai Y , Zhang H , Xuan Z , Feng Y , Zhang P , Chen Y , Yan Y , Zhu B , Cui W
Ref : Metabolic Brain Disease , : , 2020
Abstract : Postoperative cognitive dysfunction (POCD) is a common neurological disease affecting the elderly patients after surgery. Unfortunately, no effective treatment for this disease has been discovered. Edaravone, a clinical-used free radical scavenger, at 3 mg/kg has been reported to prevent neuroinflammation induced by the combination of surgery and lipopolysaccharide in adult rodents. However, we found that edaravone at such low concentration could not inhibit POCD in aged mice. Instead, edaravone at 33.2 mg/kg significantly prevented recognition and spatial cognitive dysfunctions in 14 month aged mice after abdominal surgery under general anesthesia with isoflurane. Furthermore, edaravone significantly prevented the increase of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) induced by abdominal surgery in aged mice. Edaravone could also decrease glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule-1 (Iba-1) positive areas in the hippocampal regions of surgery mice, suggesting that edaravone might inhibit surgery-induced over-activation of microglia and astrocytes. Moreover, edaravone substantially increased the expression of PSD-95 and pSer9-glycogen synthase kinase-3beta (pSer9-GSK3beta) as demonstrated by Western blotting assay. Furthermore, the activity of acetylcholinesterase (AChE) is decreased in the mice in edaravone group. All these results suggested that edaravone at high concentrations could inhibit surgery-induced cognitive impairments in aged animals, possibly via the attenuation of neuroinflammation, the increase of synaptic proteins, and the elevation of cholinergic transmission, providing a further support that edaravone might be developed as a treatment of POCD.
ESTHER : Zhou_2020_Metab.Brain.Dis__
PubMedSearch : Zhou_2020_Metab.Brain.Dis__
PubMedID: 31916204

Title : Inhibition of acetylcholinesterase activity and beta-amyloid oligomer formation by 6-bromotryptamine A, a multi-target anti-Alzheimer's molecule - Jin_2020_Oncol.Lett_19_1593
Author(s) : Jin X , Wang M , Shentu J , Huang C , Bai Y , Pan H , Zhang D , Yuan Z , Zhang H , Xiao X , Wu X , Ding L , Wang Q , He S , Cui W
Ref : Oncol Lett , 19 :1593 , 2020
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and beta-amyloid (Abeta) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Abeta oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Abeta oligomer formation.
ESTHER : Jin_2020_Oncol.Lett_19_1593
PubMedSearch : Jin_2020_Oncol.Lett_19_1593
PubMedID: 31966085

Title : Acupuncture of the Beishu acupoint participates in regulatory effects of ginsenoside Rg1 on T cell subsets of rats with chronic fatigue syndrome - He_2020_Ann.Palliat.Med_9_3436
Author(s) : He J , Yu Q , Wu C , Sun Z , Wu X , Liu R , Zhang H
Ref : Ann Palliat Med , 9 :3436 , 2020
Abstract : BACKGROUND: There are close relationships between the spleen and limb muscles and thoughts. The study aims to test the effects of ginsenoside Rg1 in combination with acupuncture of the Beishu acupoint on T cell subsets of rats with chronic fatigue syndrome (CFS). METHODS: The model was set up by combining forced cold-water swimming with chronic restraint. The rats were randomly divided into blank control, model, ginsenoside, acupuncture, and ginsenoside plus acupuncture groups (n=10). For the acupuncture group, the Beishu acupoint was acupunctured on the 2nd day after modeling. For the ginsenoside group, the ginsenoside Rg1 solution was injected into the tail vein on the 2nd day after modeling. For the combination group, both processes were conducted. These groups were compared regarding exhausted swimming time, number of struggles, resting time, serum levels of IgA, IgG, IgM, IFN-alpha, IFN-beta, and IFN-gamma, lymphocyte transformation rate, T cell subsets, and skeletal muscle activities of malondialdehyde (MDA), total antioxidative capacity (T-AOC) and acetylcholinesterase (Ache). RESULTS: The exhausted swimming time, number of struggles, and resting time of combination group surpassed those in the ginsenoside and acupuncture groups significantly (P<0.05). The serum levels of IgA, IgG, IgM, IFN-beta, IFN-gamma, T-AOC, and Ache, together with CD3+ and CD8+ T cell percentages of combination groups, were significantly higher than those of ginsenoside and acupuncture groups. However, the IFN-alpha level, MDA activity, and CD4+ T cell percentage were significantly lower (P<0.05). Compared with the model group, the CD4+/CD8+ T cell ratios of acupuncture, ginsenoside, and combination groups decreased significantly (P<0.05). Compared with the combination group, the ratio of the ginsenoside group increased significantly (P<0.05). CONCLUSIONS: Both acupuncture of the Beishu acupoint and intravenous injection of ginsenoside Rg1 have anti-fatigue effects, and their combination works synergistically. This study supplies an experimental basis for joint therapy using acupuncture and drugs to combat fatigue synergistically.
ESTHER : He_2020_Ann.Palliat.Med_9_3436
PubMedSearch : He_2020_Ann.Palliat.Med_9_3436
PubMedID: 33065794

Title : Protective effects of chondroitin sulphate nano-selenium on a mouse model of Alzheimer's disease - Ji_2020_Int.J.Biol.Macromol__
Author(s) : Ji D , Wu X , Li D , Liu P , Zhang S , Gao D , Gao F , Zhang M , Xiao Y
Ref : Int J Biol Macromol , : , 2020
Abstract : In this study, the effect of chondroitin sulphate nano-selenium (CS@Se) on Alzheimer's disease (AD) in mice was investigated. CS@Se alleviated anxiety and improved the spatial learning and memory impairment in AD mice. CS@Se significantly reduced cell oedema and pyknosis, protected the mitochondria, and improved abnormal changes in the ultrastructure of hippocampal neuron synapses of AD mice. Moreover, CS@Se significantly increased the levels of superoxide dismutase(SOD), glutathione peroxidase (GSH-Px), Na(+)/K(+)-ATPase assay (Na(+)/K(+)-ATPase) and acetyltransferase (ChAT), and decreased the levels of malondialdehyde (MDA) and acetylcholinesterase (ChAE) in AD mice. Western blot results showed that CS@Se can attenuate excessive phosphorylation of tau (Ser396/Ser404) by regulating the expression of glycogen synthase kinase-3 beta (GSK-3beta). In addition, CS@Se can activate the extracellular signal-regulated kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (p38 MAPK) signalling pathways to inhibit nuclear transcription factor kappa B (NF-kappaB) nuclear translocation, thereby regulating the expression of pro-inflammatory cytokines. In summary, CS@Se can reduce oxidative stress damage, inhibit excessive tau phosphorylation, reduce inflammation to delay AD development, and increase the learning and memory capacities of AD mice.
ESTHER : Ji_2020_Int.J.Biol.Macromol__
PubMedSearch : Ji_2020_Int.J.Biol.Macromol__
PubMedID: 32171837

Title : Exposure to acetamiprid influences the development and survival ability of worker bees (Apis mellifera L.) from larvae to adults - Shi_2020_Environ.Pollut_266_115345
Author(s) : Shi J , Zhang R , Pei Y , Liao C , Wu X
Ref : Environ Pollut , 266 :115345 , 2020
Abstract : In most cases, honey bees experience pesticide pollution in a long-term period through direct or indirect exposure, such as the development process from larvae to the pre-harvest stage. At present, little is known about how honey bees respond to pesticide stresses during the continuous development period. This study aims to examine effects of long-term acetamiprid exposure on the development and survival of honey bees, and further present the expression profile in larvae, 1-day-old, and 7-day-old adult worker bees that related to immune, detoxification, acetylcholinesterase (AChE) and memory. Honey bees from 2-day-old larvae to 14-day-old adults except the pupal stage were continuously fed with different acetamiprid solutions (0, 5, and 25 mg/L). We found that acetamiprid over 5 mg/L disturbed the development involving birth weight and emergence rate of newly emerged bees, and reduced the proportion of capped cells of larvae at 25 mg/L; gene expression related to immune and detoxification of worker bees exposed to acetamiprid was roughly activated, returned and then inhibited from larval to emerged and to the late adult stage, respectively. Moreover, lifespans of bees treated with acetamiprid at 25 mg/L were significantly reduced. The present study reflects the potential risk for honey bees continuously exposed to acetamiprid in the development stage.
ESTHER : Shi_2020_Environ.Pollut_266_115345
PubMedSearch : Shi_2020_Environ.Pollut_266_115345
PubMedID: 32814180

Title : Cell Wall Polysaccharide-Mediated Cadmium Tolerance Between Two Arabidopsis thaliana Ecotypes - Xiao_2020_Front.Plant.Sci_11_473
Author(s) : Xiao Y , Wu X , Liu D , Yao J , Liang G , Song H , Ismail AM , Luo JS , Zhang Z
Ref : Front Plant Sci , 11 :473 , 2020
Abstract : Cadmium (Cd) is a toxic metal element and the mechanism(s) underlying Cd tolerance in plants are still unclear. Increasingly more studies have been conducted on Cd binding to plant cell walls (CW) but most of them have focused on Cd fixation by CW pectin, and few studies have examined Cd binding to cellulose and hemicellulose. Here we found that Cd binding to CW pectin, cellulose, and hemicellulose was significantly higher in Tor-1, a Cd tolerant A. thaliana ecotype, than in Ph2-23, a sensitive ecotype, as were the concentrations of pectin, cellulose, and hemicellulose. Transcriptome analysis revealed that the genes regulating CW pectin, cellulose, and hemicellulose polysaccharide concentrations in Tor-1 differed significantly from those in Ph2-23. The expressions of most genes such as pectin methyl esterase inhibitors (PMEIs), pectin lyases, xyloglucan endotransglucosylase/hydrolase, expansins (EXPAs), and cellulose hydrolase were higher in Ph2-23, while the expressions of cellulose synthase-like glycosyltransferase 3 (CSLG3) and pectin ethyl esterase 4 (PAE4) were higher in Tor-1. The candidate genes identified here seem to regulate CW Cd fixation by polysaccharides. In conclusion, an increase in pectin demethylation activity, the higher concentration of cellulose and hemicellulose, regulated by related genes, in Tor-1 than in Ph2-23 are likely involved in enhanced Cd CW retention and reduce Cd toxicity.
ESTHER : Xiao_2020_Front.Plant.Sci_11_473
PubMedSearch : Xiao_2020_Front.Plant.Sci_11_473
PubMedID: 32477379

Title : Neurological effects of subchronic exposure to dioctyl phthalate (DOP), lead, and arsenic, individual and mixtures, in immature mice - Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
Author(s) : Feng W , Wu X , Mao G , Zhao T , Wang W , Chen Y , Zhang M , Yang L
Ref : Environ Sci Pollut Res Int , 27 :9247 , 2020
Abstract : Dioctyl phthalate (DOP) (200, 500, and 1000 mg kg(-1) bw, i.g.), Pb (Ac)(2) (50 mg L(-1), p.o.), and NaAsO(2) (10 mg L(-1), p.o.) were administered individually and as mixtures to weanling male mice for 8 weeks. It was observed that Pb, As, and DOP exposure could significantly inhibit the growth and development of mice. Compared with the Pb, As, and Pb + As groups, the activities of iNOS and TNOS were significantly increased, the levels of AChE and SOD were significantly decreased, and the level of MDA was significantly increased in the Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups. The factorial analysis shows that the iNOS, TNOS, and AChE present synergistic effects on Pb, As, and DOP. A significant increase of escape latency and a significant decrease of original platform quadrant stops were observed between Pb + As + DOP-H and Pb + As groups. The factorial analysis shows that there was a synergistic effect on Pb, As, and DOP. Compared with that of the control group, the expression levels of caspase-3 and Bax expression in Pb + As, DOP-H, Pb + DOP-H, As + DOP-H, and Pb + As + DOP-H groups were significantly increased in the hippocampus. The expression levels of Bcl-2 expression decreased significantly and the Bax/Bcl-2 ratio increased significantly. Pathological alterations on the hippocampus were found in exposed groups. This result shows that combined exposure of Pb, As, and DOP could induce neurotoxicity, of which possible mechanism is hippocampal neuronal apoptosis. Graphical abstract This study shows that there were three components with eigenvalues greater than 1, which together explained 89.40% of total variance. The first component (PC1) showed high loadings on B-SOD, L-SOD, B-MDA, L-MDA, K-MDA, iNOS, tNOS, and AChE and accounted for 46.55% of the total variance after Varimax rotation. PC2 accounted for 23.81% of the total variance with high loadings on B-As, L-As, K-As, and K-SOD, whereas PC3 showed high loadings on B-Pb, L-Pb, and K-Pb and accounted for 19.04% of the total variance.
ESTHER : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedSearch : Feng_2020_Environ.Sci.Pollut.Res.Int_27_9247
PubMedID: 31916164

Title : Astrocyte-specific NDRG2 gene: functions in the brain and neurological diseases - Li_2020_Cell.Mol.Life.Sci_77_2461
Author(s) : Li X , Wu X , Luo P , Xiong L
Ref : Cell Mol Life Sciences , 77 :2461 , 2020
Abstract : In recent years, the roles of astrocytes of the central nervous system in brain function and neurological disease have drawn increasing attention. As a member of the N-myc downstream-regulated gene (NDRG) family, NDRG2 is principally expressed in astrocytes of the central nervous system. NDRG2, which is involved in cell proliferation and differentiation, is commonly regarded as a tumor suppressor. In astrocytes, NDRG2 affects the regulation of apoptosis, astrogliosis, blood-brain barrier integrity, and glutamate clearance. Several preclinical studies have revealed that NDRG2 is implicated in the pathogenesis of many neurological diseases not limited to tumors (mostly glioma in the nervous system), such as stroke, neurodegeneration (Alzheimer's disease and Parkinson's disease), and psychiatric disorders (depression and attention deficit hyperactivity disorder). This review summarizes the biological functions of NDRG2 under physiological and pathological conditions, and further discusses the roles of NDRG2 during the occurrence and development of neurological diseases.
ESTHER : Li_2020_Cell.Mol.Life.Sci_77_2461
PubMedSearch : Li_2020_Cell.Mol.Life.Sci_77_2461
PubMedID: 31834421
Gene_locus related to this paper: human-NDRG2

Title : Enzyme-responsive sulfatocyclodextrin\/prodrug supramolecular assembly for controlled release of anti-cancer drug chlorambucil - Guan_2019_Chem.Commun.(Camb)_55_953
Author(s) : Guan X , Chen Y , Wu X , Li P , Liu Y
Ref : Chem Commun (Camb) , 55 :953 , 2019
Abstract : Supramolecular drug delivery systems are becoming an increasingly important part in controlled drug release. In this work, we report a novel enzyme-responsive supramolecular assembly directly constructed using biocompatible sulfato-beta-cyclodextrin (SCD) and an anti-cancer prodrug, i.e. choline modified anti-cancer drug chlorambucil (QA-Cbl). The supramolecular assembly acts as an effective drug delivery system via the controlled drug loading and enzyme-responsive drug release, because the butyrylcholinesterase (BChE) can cleave the ester bond of QA-Cbl prodrug, resulting in the release of anti-cancer drug chlorambucil (Cbl). Compared to other sophisticated drug delivery systems, the present system provides a feasible and functional approach for achievement of controlled drug release.
ESTHER : Guan_2019_Chem.Commun.(Camb)_55_953
PubMedSearch : Guan_2019_Chem.Commun.(Camb)_55_953
PubMedID: 30604783

Title : Noninvasive Evaluation of Liver Fibrosis Reverse Using Artificial Neural Network Model for Chronic Hepatitis B Patients - Wei_2019_Comput.Math.Methods.Med_2019_7239780
Author(s) : Wei W , Wu X , Zhou J , Sun Y , Kong Y , Yang X
Ref : Comput Math Methods Med , 2019 :7239780 , 2019
Abstract : The diagnostic performance of an artificial neural network model for chronic HBV-induced liver fibrosis reverse is not well established. Our research aims to construct an ANN model for estimating noninvasive predictors of fibrosis reverse in chronic HBV patients after regular antiviral therapy. In our study, 141 consecutive patients requiring liver biopsy at baseline and 1.5 years were enrolled. Several serum biomarkers and liver stiffness were measured during antiviral therapy in both reverse and nonreverse groups. Statistically significant variables between two groups were selected to form an input layer of the ANN model. The ROC (receiver-operating characteristic) curve and AUC (area under the curve) were calculated for comparison of effectiveness of the ANN model and logistic regression model in predicting HBV-induced liver fibrosis reverse. The prevalence of fibrosis reverse of HBV patients was about 39% (55/141) after 78-week antiviral therapy. The Ishak scoring system was used to assess fibrosis reverse. Our study manifested that AST (aspartate aminotransferase; importance coefficient = 0.296), PLT (platelet count; IC = 0.159), WBC (white blood cell; IC = 0.142), CHE (cholinesterase; IC = 0.128), LSM (liver stiffness measurement; IC = 0.125), ALT (alanine aminotransferase; IC = 0.110), and gender (IC = 0.041) were the most crucial predictors of reverse. The AUC of the ANN model and logistic model was 0.809 +/- 0.062 and 0.756 +/- 0.059, respectively. In our study, we concluded that the ANN model with variables consisting of AST, PLT, WBC, CHE, LSM, ALT, and gender may be useful in diagnosing liver fibrosis reverse for chronic HBV-induced liver fibrosis patients.
ESTHER : Wei_2019_Comput.Math.Methods.Med_2019_7239780
PubMedSearch : Wei_2019_Comput.Math.Methods.Med_2019_7239780
PubMedID: 31428186

Title : Small Molecule Natural Products and Alzheimer's Disease - Wu_2019_Curr.Top.Med.Chem_19_187
Author(s) : Wu X , Cai H , Pan L , Cui G , Qin F , Li Y , Cai Z
Ref : Curr Top Med Chem , 19 :187 , 2019
Abstract : Alzheimer's disease (AD) is a progressive and deadly neurodegenerative disease that is characterized by memory loss, cognitive impairment and dementia. Several hypotheses have been proposed for the pathogenesis based on the pathological changes in the brain of AD patients during the last few decades. Unfortunately, there is no effective agents/therapies to prevent or control AD at present. Currently, only a few drugs, which function as acetylcholinesterase (AChE) inhibitors or N-methyl-Daspartate (NMDA) receptor antagonists, are available to alleviate symptoms. Since many small molecule natural products have shown their functions as agonists or antagonists of receptors, as well as inhibitors of enzymes and proteins in the brain during the development of central nervous system (CNS) drugs, it is likely that natural products will play an important role in anti-AD drug development. We review recent papers on using small molecule natural products as drug candidates for the treatment of AD. These natural products possess antioxidant, anti-inflammatory, anticholinesterase, anti-amyloidogenic and neuroprotective activities. Moreover, bioactive natural products intended to be used for preventing AD, reducing the symptoms of AD and the new targets for treatment of AD are summarized.
ESTHER : Wu_2019_Curr.Top.Med.Chem_19_187
PubMedSearch : Wu_2019_Curr.Top.Med.Chem_19_187
PubMedID: 30714527

Title : Neuroligin-1 Signaling Controls LTP and NMDA Receptors by Distinct Molecular Pathways - Wu_2019_Neuron_102_621
Author(s) : Wu X , Morishita WK , Riley AM , Hale WD , Sudhof TC , Malenka RC
Ref : Neuron , 102 :621 , 2019
Abstract : Neuroligins, postsynaptic cell adhesion molecules that are linked to neuropsychiatric disorders, are extensively studied, but fundamental questions about their functions remain. Using in vivo replacement strategies in quadruple conditional knockout mice of all neuroligins to avoid heterodimerization artifacts, we show, in hippocampal CA1 pyramidal neurons, that neuroligin-1 performs two key functions in excitatory synapses by distinct molecular mechanisms. N-methyl-D-aspartate (NMDA) receptor-dependent LTP requires trans-synaptic binding of postsynaptic neuroligin-1 to presynaptic beta-neurexins but not the cytoplasmic sequences of neuroligins. In contrast, postsynaptic NMDA receptor (NMDAR)-mediated responses involve a neurexin-independent mechanism that requires the neuroligin-1 cytoplasmic sequences. Strikingly, deletion of neuroligins blocked the spine expansion associated with LTP, as monitored by two-photon imaging; this block involved a mechanism identical to that of the role of neuroligin-1 in NMDAR-dependent LTP. Our data suggest that neuroligin-1 performs two mechanistically distinct signaling functions and that neurolign-1-mediated trans-synaptic cell adhesion signaling critically regulates LTP.
ESTHER : Wu_2019_Neuron_102_621
PubMedSearch : Wu_2019_Neuron_102_621
PubMedID: 30871858

Title : Fluorescence sensor for facile and visual detection of organophosphorus pesticides using AIE fluorogens-SiO2-MnO2 sandwich nanocomposites - Wu_2019_Talanta_198_8
Author(s) : Wu X , Wang P , Hou S , Wu P , Xue J
Ref : Talanta , 198 :8 , 2019
Abstract : Organophosphorus pesticides (OPs) are frequently for pest control in the agriculture industry. Accumulation of OPs is harmful to the environment and human health. Thus, facile and portable detection of organophosphorus pesticides is of great importance. Among these methods, the fluorescence assay holds the advantages of high sensitivity, simplicity, nondestructive properties. Conventional fluorophores have the drawbacks of poor photostability and low signal-to-noise ratio due to their aggregation-caused quenching drawbacks at high concentration or in the aggregate state. Aggregation-induced emission fluorogens (AIEgens) are one key to develop next-generation fluorescence sensor due to their high emission efficiency in the aggregated state. 1,2-bis[4-(3-sulfonatopropoxyl) phenyl]-1,2-diphenylethene (BSPOTPE) is a typical AIE molecule containing two hydroxyl group. In this study, a fluorescence sensor based on BSPOTPE-SiO2-MnO2 sandwich nanocomposites was fabricated. Thiocholine (TCh), which produced from acetylthiocholine(ATCh) by the hydrolysis of acetylcholinesterase (AChE), can "turn on" the fluorescence sensor. Based on the inhibition effect of OPs on AChE activity and the corresponding "turn off" effect on the fluorescence sensor, an AIE-based assay for OPs determination was developed. The fabricated sensor for paraoxon determination has a good linear relationship in the range of 1-100mug/L and the LOD of 1mug/L. Moreover, a simple, convenient fluorescence strip for visual semi-quantitative of OPs was fabricated, indicating this "on-off" fluorescent sensor is promising for on-site and infield detection.
ESTHER : Wu_2019_Talanta_198_8
PubMedSearch : Wu_2019_Talanta_198_8
PubMedID: 30876606

Title : Genome-edited skin epidermal stem cells protect mice from cocaine-seeking behaviour and cocaine overdose - Li_2019_Nat.Biomed.Eng_3_105
Author(s) : Li Y , Kong Q , Yue J , Gou X , Xu M , Wu X
Ref : Nat Biomed Eng , 3 :105 , 2019
Abstract : Cocaine addiction is associated with compulsive drug-seeking, and exposure to the drug or to drug-associated cues leads to relapse, even after long periods of abstention. A variety of pharmacological targets and behavioral interventions have been explored to counteract cocaine addiction, but to date no market-approved medications for treating cocaine addiction or relapse exist, and effective interventions for acute emergencies resulting from cocaine overdose are lacking. We recently demonstrated that skin epidermal stem cells can be readily edited by using CRISPR (clustered regularly interspaced short palindromic repeats) and then transplanted back into the donor mice. Here, we show that the transplantation, into mice, of skin cells modified to express an enhanced form of butyrylcholinesterase, an enzyme that hydrolyzes cocaine, enables the long-term release of the enzyme and efficiently protects the mice from cocaine-seeking behavior and cocaine overdose. Cutaneous gene therapy through skin transplants that elicit drug elimination may offer a therapeutic option to address drug abuse.
ESTHER : Li_2019_Nat.Biomed.Eng_3_105
PubMedSearch : Li_2019_Nat.Biomed.Eng_3_105
PubMedID: 30899600

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

Title : Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice - Chen_2018_Front.Cell.Neurosci_12_396
Author(s) : Chen H , Wu X , Gu X , Zhou Y , Ye L , Zhang K , Pan H , Wang J , Wei H , Zhu B , Naman CB , Mak SH , Carlier PR , Cui W , Han YF
Ref : Front Cell Neurosci , 12 :396 , 2018
Abstract : Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD.
ESTHER : Chen_2018_Front.Cell.Neurosci_12_396
PubMedSearch : Chen_2018_Front.Cell.Neurosci_12_396
PubMedID: 30483056

Title : Insecticidal Mechanism of Wintergreen Oil Against the Health Pest Paederus fuscipes (Coleoptera: Staphylinidae) - Liu_2018_J.Med.Entomol_55_155
Author(s) : Liu Z , Zhang Q , Wu X , Yu W , Guo S
Ref : Journal of Medical Entomology , 55 :155 , 2018
Abstract : Paederus fuscipes, a health pest, causes dermatitis linearis in humans. Wintergreen oil exhibits optimal insecticidal activity against P. fuscipes. However, the insecticidal mechanism remains unclear not only in P. fuscipes but also in other pests. In this study, we explored the insecticidal mechanism of wintergreen oil in terms of its effect on the activity of acetylcholinesterase (AChE) enzyme and detoxifying enzymes (carboxylesterase, glutathione-S-transferase, and mixed function oxidase); such effect was studied by fumigation both in vivo and in vitro in P. fuscipes male and female adults. In the in vivo and in vitro experiments on male and female adults, wintergreen oil did not significantly affect the activities of the three detoxifying enzymes. Hence, the mode of action of wintergreen oil may be unrelated to the three detoxifying enzymes. Wintergreen oil significantly inhibited AChE activity. When wintergreen oil was tested at different times in vivo, the highest inhibition rates were 41.99% (male) and 40.91% (female). When different doses of wintergreen oil were used for in vivo treatment, the highest inhibition rates were 33.78% (male) and 43.33% (female). When wintergreen oil was tested in vitro, the highest inhibition rates were 31.06% (male) and 35.57% (female). In vitro with chlorpyrifos as a positive control, the AChE activity of 3-mul wintergreen oil treatment was significantly lower than that of 10 mg/liter chlorpyrifos in both P. fuscipes male and female adults. The results demonstrated that AChE is a potential key factor, maybe a target enzyme, in the mechanism of wintergreen oil against P. fuscipes.
ESTHER : Liu_2018_J.Med.Entomol_55_155
PubMedSearch : Liu_2018_J.Med.Entomol_55_155
PubMedID: 29029320

Title : A Human DPP4-Knockin Mouse's Susceptibility to Infection by Authentic and Pseudotyped MERS-CoV - Fan_2018_Viruses_10_
Author(s) : Fan C , Wu X , Liu Q , Li Q , Liu S , Lu J , Yang Y , Cao Y , Huang W , Liang C , Ying T , Jiang S , Wang Y
Ref : Viruses , 10 : , 2018
Abstract : Infection by the Middle East respiratory syndrome coronavirus (MERS-CoV) causes respiratory illness and has a high mortality rate (~35%). The requirement for the virus to be manipulated in a biosafety level three (BSL-3) facility has impeded development of urgently-needed antiviral agents. Here, we established anovel mouse model by inserting human dipeptidyl peptidase 4 (hDPP4) into the Rosa26 locus using CRISPR/Cas9, resulting in global expression of the transgene in a genetically stable mouse line. The mice were highly susceptible to infection by MERS-CoV clinical strain hCoV-EMC, which induced severe diffuse pulmonary disease in the animals, and could also be infected by an optimized pseudotyped MERS-CoV. Administration of the neutralizing monoclonal antibodies, H111-1 and m336, as well as a fusion inhibitor peptide, HR2P-M2, protected mice from challenge with authentic and pseudotyped MERS-CoV. These results confirmed that the hDPP4-knockin mouse is a novel model for studies of MERS-CoV pathogenesis and anti-MERS-CoV antiviral agents in BSL-3 and BSL-2facilities, respectively.
ESTHER : Fan_2018_Viruses_10_
PubMedSearch : Fan_2018_Viruses_10_
PubMedID: 30142928

Title : Endothelial Nox4-based NADPH oxidase regulates atherosclerosis via soluble epoxide hydrolase - Hu_2017_Biochim.Biophys.Acta_1863_1382
Author(s) : Hu P , Wu X , Khandelwal AR , Yu W , Xu Z , Chen L , Yang J , Weisbrod RM , Lee KSS , Seta F , Hammock BD , Cohen RA , Zeng C , Tong X
Ref : Biochimica & Biophysica Acta , 1863 :1382 , 2017
Abstract : Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial. OBJECTIVE: Our goal was to investigate the mechanisms of endothelial Nox4 in regulating atherosclerosis. APPROACH AND
RESULTS: Atherosclerosis-prone conditions (disturbed blood flow, type I diabetes, and Western diet) downregulated endothelial Nox4 mRNA in arteries. To address whether the downregulated endothelial Nox4 was directly involved in the development of atherosclerosis, we generated mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), driven by the endothelial specific promoter Tie-2, on atherosclerosis-prone genetic background (ApoE deficient mice) to mimic the effect of decreased endothelial Nox4. Nox4DN significantly increased type I diabetes-induced aortic stiffness and atherosclerotic lesions. Gene analysis indicated that soluble epoxide hydrolase 2 (sEH) was significantly upregulated in Nox4DN endothelial cells (EC). Inhibition of sEH activity in Nox4DN EC suppressed inflammation and macrophage adhesion to EC. On the contrary, overexpression of endothelial wild type Nox4 suppressed sEH, ameliorated Western diet-induced atherosclerosis and decreased aortic stiffness.
CONCLUSIONS: Atherosclerosis-prone conditions downregulated endothelial Nox4 to accelerate the progress of atherosclerosis, at least in part, by upregulating sEH to enhance inflammation.
ESTHER : Hu_2017_Biochim.Biophys.Acta_1863_1382
PubMedSearch : Hu_2017_Biochim.Biophys.Acta_1863_1382
PubMedID: 28185955

Title : Screening and characterization of a novel thermostable lipase with detergent-additive potential from the metagenomic library of a mangrove soil - Tang_2017_Gene_625_64
Author(s) : Tang L , Xia Y , Wu X , Chen X , Zhang X , Li H
Ref : Gene , 625 :64 , 2017
Abstract : One clone (Lip906) exhibiting lipase activity was screened from a metagenomic library by using a medium containing tricaprylin. A novel lipase gene from the inserted fragment of Lip906 was obtained by sequencing. The phylogenetic analysis of Lip906 lipase exhibited 34% and 32% homologue to lipases from Streptomyces sp. MspMP-M5 and Rhodopirellula europaea. This gene was expressed in Escherichia coli (E. coli) BL21 (DE3), and the recombinant protein was purified and characterized. The best substrate of the recombinant Lip906 lipase was p-nitrophenyl myristate (C14). The lipase expressed maximum activity at 74 degrees C and pH7.8, and it was found to be stable at pH values and temperatures ranging from 6.0-8.0 and 4-78 degrees C, respectively. Furthermore, the lipase was found to be highly resistant to commercial detergent, DMSO, and EDTA, whereas its activity was stimulated in the presence of methanol and ethanol at low concentrations. The lipase showed enhanced activity in the presence of Hg2+, whereas the presence of the metal ions Fe2+, Ca2+, Co2+, and Mg2+ inhibited the activity. These beneficial characteristics of Lip906 lipase provide some advantages for its potential application in industry.
ESTHER : Tang_2017_Gene_625_64
PubMedSearch : Tang_2017_Gene_625_64
PubMedID: 28457984

Title : Oxidase-mimicking activity of ultrathin MnO2 nanosheets in colorimetric assay of acetylcholinesterase activity - Yan_2017_Nanoscale_9_2317
Author(s) : Yan X , Song Y , Wu X , Zhu C , Su X , Du D , Lin Y
Ref : Nanoscale , 9 :2317 , 2017
Abstract : In the present study, a novel colorimetric sensing platform was constructed for quantitative detection of acetylcholinesterase (AChE) activity and its inhibitor. Manganese dioxide (MnO2) nanosheets as an oxidase-mimicking nanomaterial could directly oxidize 3,3',5,5'-tetramethylbenzidine (TMB) into oxTMB without the need for horseradish peroxidase and H2O2. When AChE was introduced, acetylthiocholine could be catalytically hydrolyzed to produce thiocholine, which easily triggers the decomposition of MnO2 nanosheets, causing the decrease of solution absorbance. Owing to the inhibition effect of organophosphorus pesticides, the enzymatic activity was suppressed, preventing the decomposition of MnO2 and resulting in the increase of absorbance. Under optimal conditions, the colorimetric platform shows sensitive responses to AChE and paraoxon in the range of 0.1-15 mU mL-1 and 0.001-0.1 mug mL-1, respectively. The detection limits of AChE and paraoxon reached 35 muU mL-1 and 1.0 ng mL-1, respectively. Furthermore, the MnO2-TMB platform has been used to fabricate test strips for rapid and convenient visual detection of AChE and its inhibitor with highly promising performance.
ESTHER : Yan_2017_Nanoscale_9_2317
PubMedSearch : Yan_2017_Nanoscale_9_2317
PubMedID: 28134376

Title : Carbon quantum dots as fluorescence resonance energy transfer sensors for organophosphate pesticides determination - Wu_2017_Biosens.Bioelectron_94_292
Author(s) : Wu X , Song Y , Yan X , Zhu C , Ma Y , Du D , Lin Y
Ref : Biosensors & Bioelectronics , 94 :292 , 2017
Abstract : Carbon quantum dots (CQDs) obtained from natural organics attract significant attention due to the abundance of carbon sources, varieties of heteroatom doping (such as N, S, P) and good biocompatibility of precursor. In this study, tunable fluorescence emission CQDs originated from chlorophyll were synthesized and characterized. The fluorescence emission can be effectively quenched by gold nanoparticles (Au NPs) via fluorescence resonance energy transfer (FRET). Thiocholine, which was produced from acetylthiocholine (ATC) by the hydrolysis of butyrylcholinesterase (BChE), could cause the aggregation of Au NPs and the corresponding recovery of FRET-quenched fluorescence emission. The catalytic activity of BChE could be irreversibly inhibited by organophosphorus pesticides (OPs), thus, the recovery effect was reduced. By evaluating the fluorescence emission intensity of CQDs, a FRET-based sensing platform for OPs determination was established. Paraoxon was studied as an example of OPs. The sensing platform displayed a linear relationship with the logarithm of the paraoxon concentrations in the range of 0.05-50mugL-1 and the limit of detection (LOD) was 0.05mugL-1. Real sample study in tap and river water revealed that this sensing platform was repeatable and accurate. The results indicate that the OP sensor is promising for applications in food safety and environmental monitoring.
ESTHER : Wu_2017_Biosens.Bioelectron_94_292
PubMedSearch : Wu_2017_Biosens.Bioelectron_94_292
PubMedID: 28315592

Title : Organophosphate esters in sediment cores from coastal Laizhou Bay of the Bohai Sea, China - Wang_2017_Sci.Total.Environ_607-608_103
Author(s) : Wang Y , Wu X , Zhang Q , Hou M , Zhao H , Xie Q , Du J , Chen J
Ref : Sci Total Environ , 607-608 :103 , 2017
Abstract : Concentrations and vertical distributions of organophosphate esters (OPEs) were investigated in the sediment cores collected from the Laizhou Bay, Bohai Sea of China. The total concentrations of OPEs in the sediment core (CA) collected near the Yellow River Estuary were in the range of 11.8-102ng/g, while the total concentrations in the sediment core (CB) near a mariculture area were 6.65-41.5ng/g. Significantly high concentrations of OPEs were found in the sediments near the Yellow River Estuary than those in the mariculture area. Vertical distributions in the sediment cores demonstrated a recent increase of OPE emissions, especially for tri-n-butyl phosphate (TnBP), tris (2-chloroethyl) phosphate (TCEP), and tris (2-chloroisopropyl) phosphate (TCPP). Generally, TCEP and TCPP were the dominant congeners in the sediment cores, while the profiles of TnBP were increase in the surface 0-20cm layers of the CA core. OPEs in the CA core may be remarkably influenced by the discharge of Yellow River, whereas OPEs in the CB core may originate from the transport through seawater. The remarkable increase of OPE flame retardants in the surface sediments raises the concern about their emissions and risks to the environment and indicates the need for further monitoring.
ESTHER : Wang_2017_Sci.Total.Environ_607-608_103
PubMedSearch : Wang_2017_Sci.Total.Environ_607-608_103
PubMedID: 28688252

Title : Association between L55M polymorphism in Paraoxonase 1 and cancer risk: a meta-analysis based on 21 studies - Chen_2016_Onco.Targets.Ther_9_1151
Author(s) : Chen L , Lu W , Fang L , Xiong H , Wu X , Zhang M , Wu S , Yu D
Ref : Onco Targets Ther , 9 :1151 , 2016
Abstract : L55M polymorphism in Paraoxonase 1 (PON1) has been regarded as a risk factor for many cancer types. Nevertheless, the results remain controversial and inconclusive. We therefore performed a meta-analysis of all eligible case-control studies to evaluate the association between L55M polymorphism and cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the associations. Finally, a total of 5,627 cases and 6,390 controls, arising from 21 case-control studies, were enrolled in our study. Significant associations between PON1-L55M polymorphism and overall cancer risk were identified in all genetic models. In the stratified analyses by cancer type, PON1-L55M polymorphism was a risk factor for breast cancer in all genetic models, prostate cancer in the heterozygote model (ML vs LL: OR =1.304, 95% CI =1.049-1.620, P heterogeneity=0.067), and ovarian cancer in the recessive model (MM vs ML/LL: OR =1.526, 95% CI =1.110-2.097, P heterogeneity=0.464). Similarly, an increased risk was also identified for the Caucasian population in the heterozygote comparison and homozygote models, and hospital-based controls in all genetic models. To sum up, our study suggests that the PON1-L55M allele increased the risk of cancer. Future well-designed studies with larger sample sizes are warranted to further verify these findings.
ESTHER : Chen_2016_Onco.Targets.Ther_9_1151
PubMedSearch : Chen_2016_Onco.Targets.Ther_9_1151
PubMedID: 27019599

Title : Chemical Probes to Directly Profile Palmitoleoylation of Proteins - Zheng_2016_Chembiochem_17_2022
Author(s) : Zheng B , Jarugumilli GK , Chen B , Wu X
Ref : Chembiochem , 17 :2022 , 2016
Abstract : Palmitoleoylation is a unique fatty acylation of proteins in which a monounsaturated fatty acid, palmitoleic acid (C16:1), is covalently attached to a protein. Wnt proteins are known to be palmitoleoylated by cis-delta9 palmitoleate at conserved serine residues. O-palmitoleoylation plays a critical role in regulating Wnt secretion, binding to the receptors, and in the dynamics of Wnt signaling. Therefore, protein palmitoleoylation is important in tissue homeostasis and tumorigenesis. Chemical probes based on saturated fatty acids, such as omega-alkynyl palmitic acid (Alk-14 or Alk-C(16) ), have been used to study Wnt palmitoleoylation. However, such probes require prior conversion to the unsaturated fatty acid by stearoyl-CoA desaturase (SCD) in cells, significantly decreasing their selectivity and efficiency for studying protein palmitoleoylation. We synthesized and characterized omega-alkynyl cis- and trans-palmitoleic acids (cis- and trans-Alk-14:1) as chemical probes to directly study protein palmitoleoylation. We found that cis-Alk-14:1 could more efficiently label Wnt proteins in cells. Interestingly, the DHHC family of palmitoyl acyltransferases can charge both saturated and unsaturated fatty acids, potentially using both as acyl donors in protein palmitoylation and palmitoleoylation. Furthermore, proteomic analysis of targets labeled by these probes revealed new cis- and trans-palmitoleoylated proteins. Our studies provided new chemical tools and revealed new insights into palmitoleoylation in cell signaling.
ESTHER : Zheng_2016_Chembiochem_17_2022
PubMedSearch : Zheng_2016_Chembiochem_17_2022
PubMedID: 27558878

Title : Inhibition behavior of fructus psoraleae's ingredients towards human carboxylesterase 1 (hCES1) - Sun_2016_Xenobiotica_46_503
Author(s) : Sun DX , Ge GB , Dong PP , Cao YF , Fu ZW , Ran RX , Wu X , Zhang YY , Hua HM , Zhao Z , Fang ZZ
Ref : Xenobiotica , 46 :503 , 2016
Abstract : 1. Fructus psoraleae (FP) is the dried ripe seeds of Psoralea corylifolia L. (Fabaceae) widely used in Asia, and has been reported to exert important biochemical and pharmacological activities. The adverse effects of FP remain unclear. The present study aims to determine the inhibition of human carboxylesterase 1 (CES1) by FP's major ingredients, including neobavaisoflavone, corylifolinin, coryfolin, psoralidin, corylin and bavachinin. 2. The probe substrate of CES1 2-(2-benzoyl-3-methoxyphenyl) benzothiazole (BMBT) was derived from 2-(2-hydroxy-3-methoxyphenyl) benzothiazole (HMBT), and human liver microsomes (HLMs)-catalyzed BMBT metabolism was used to phenotype the activity of CES1. In silico docking method was employed to explain the inhibition mechanism. 3. All the tested compounds exerted strong inhibition towards the activity of CES1 in a concentration-dependent behavior. Furthermore, the inhibition kinetics was determined for the inhibition of neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin towards CES1. Both Dixon and Lineweaver-Burk plots showed that neobavaisoflavone, corylifolinin, coryfolin and corylin noncompetitively inhibited the activity of CES1, and bavachinin competitively inhibited the activity of CES1. The inhibition kinetic parameters (Ki) were calculated to be 5.3, 9.4, 1.9, 0.7 and 0.5 muM for neobavaisoflavone, corylifolinin, coryfolin, corylin and bavachinin, respectively. In conclusion, the inhibition behavior of CES1 by the FP's constituents was given in this article, indicating the possible adverse effects of FP through the disrupting CES1-catalyzed metabolism of endogenous substances and xenobiotics.
ESTHER : Sun_2016_Xenobiotica_46_503
PubMedSearch : Sun_2016_Xenobiotica_46_503
PubMedID: 26560012

Title : Severity and prognosis of acute organophosphorus pesticide poisoning are indicated by C-reactive protein and copeptin levels and APACHE II score - Wu_2016_Exp.Ther.Med_11_806
Author(s) : Wu X , Xie W , Cheng Y , Guan Q
Ref : Exp Ther Med , 11 :806 , 2016
Abstract : The aim of the present study was to investigate the plasma levels of C-reactive protein (CRP) and copeptin, in addition to the acute physiology and chronic health evaluation II (APACHE II) scores, in patients with acute organophosphorus pesticide poisoning (AOPP). A total of 100 patients with AOPP were included and divided into mild, moderate and severe groups according to AOPP diagnosis and classification standards. Blood samples were collected from all patients on days 1, 3 and 7 following AOPP. The concentrations of CRP and copeptin in the plasma were determined using enzyme-linked immunosorbent assay. All AOPP patients underwent APACHE II scoring and the diagnostic value of these scores was analyzed using receiver operating characteristic curves (ROCs). On days 1, 3 and 7 after AOPP, the levels of CRP and copeptin were increased in correlation with the increase in AOPP severity, and were significantly higher compared with the control groups. Furthermore, elevated CRP and copeptin plasma levels were detected in patients with severe AOPP on day 7, whereas these levels were reduced in patients with mild or moderate AOPP. APACHE II scores, blood lactate level, acetylcholine esterase level, twitch disappearance time, reactivating agent dose and inability to raise the head were the high-risk factors that affected the prognosis of AOPP. Patients with plasma CRP and copeptin levels higher than median values had worse prognoses. The areas under curve for ROCs were 0.89, 0.75 and 0.72 for CRP levels, copeptin levels and APACHE II scores, respectively. In addition, the plasma contents of CRP and copeptin are increased according to the severity of AOPP. Therefore, the results of the present study suggest that CRP and copeptin levels and APACHE II scores may be used for the determination of AOPP severity and the prediction of AOPP prognosis.
ESTHER : Wu_2016_Exp.Ther.Med_11_806
PubMedSearch : Wu_2016_Exp.Ther.Med_11_806
PubMedID: 26997996

Title : Ultrasensitive Fluorescent Probes Reveal an Adverse Action of Dipeptide Peptidase IV and Fibroblast Activation Protein during Proliferation of Cancer Cells - Gong_2016_Anal.Chem_88_8309
Author(s) : Gong Q , Shi W , Li L , Wu X , Ma H
Ref : Analytical Chemistry , 88 :8309 , 2016
Abstract : Dipeptide peptidase IV (DPPIV) and fibroblast activation protein (FAP) are isoenzymes. Evidence shows that DPPIV is related to antitumor immunity, and FAP may be a drug target in cancer therapy, making it seem that the two enzymes might have a synergistic role during the proliferation of cancer cells. Surprisingly, herein, we find an adverse action of DPPIV and FAP in the proliferation process by analyzing their changes with two tailor-made ultrasensitive fluorescent probes. First, the up-regulation of DPPIV and down-regulation of FAP in cancer cells under the stimulation of genistein are detected. Then, we find that MGC803 cells with a higher FAP but lower DPPIV level than SGC7901 cells exhibit a faster proliferation rate. Importantly, inhibiting the DPPIV expression with siRNA increases the proliferation rate of MGC803 cells, whereas the FAP inhibition decreases the rate. These findings suggest that the two enzymes play an adverse role during the proliferation of cancer cells, which provides us a new viewpoint for cancer studies.
ESTHER : Gong_2016_Anal.Chem_88_8309
PubMedSearch : Gong_2016_Anal.Chem_88_8309
PubMedID: 27444320

Title : Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP\/PS1 transgenic mice and scopolamine-induced memory impairment mice - He_2015_Eur.J.Pharmacol_768_96
Author(s) : He D , Wu H , Wei Y , Liu W , Huang F , Shi H , Zhang B , Wu X , Wang C
Ref : European Journal of Pharmacology , 768 :96 , 2015
Abstract : Harmine, a beta-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency.
ESTHER : He_2015_Eur.J.Pharmacol_768_96
PubMedSearch : He_2015_Eur.J.Pharmacol_768_96
PubMedID: 26526348

Title : Characterization of large structural genetic mosaicism in human autosomes - Machiela_2015_Am.J.Hum.Genet_96_487
Author(s) : Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD, 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF, Jr. , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , Lacroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ
Ref : American Journal of Human Genetics , 96 :487 , 2015
Abstract : Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.
ESTHER : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedSearch : Machiela_2015_Am.J.Hum.Genet_96_487
PubMedID: 25748358

Title : Repositioning proton pump inhibitors as anticancer drugs by targeting the thioesterase domain of human fatty acid synthase - Fako_2015_J.Med.Chem_58_778
Author(s) : Fako VE , Wu X , Pflug B , Liu JY , Zhang JT
Ref : Journal of Medicinal Chemistry , 58 :778 , 2015
Abstract : Fatty acid synthase (FASN), the enzyme responsible for de novo synthesis of free fatty acids, is up-regulated in many cancers. FASN is essential for cancer cell survival and contributes to drug resistance and poor prognosis. However, it is not expressed in most nonlipogenic normal tissues. Thus, FASN is a desirable target for drug discovery. Although different FASN inhibitors have been identified, none has successfully moved into clinical use. In this study, using in silico screening of an FDA-approved drug database, we identified proton pump inhibitors (PPIs) as effective inhibitors of the thioesterase activity of human FASN. Further investigation showed that PPIs inhibited proliferation and induced apoptosis of cancer cells. Supplementation of palmitate, the end product of FASN catalysis, rescued cancer cells from PPI-induced cell death. These findings provide new evidence for the mechanism by which this FDA-approved class of compounds may be acting on cancer cells.
ESTHER : Fako_2015_J.Med.Chem_58_778
PubMedSearch : Fako_2015_J.Med.Chem_58_778
PubMedID: 25513712

Title : CHRNA5 risk variant predicts delayed smoking cessation and earlier lung cancer diagnosis--a meta-analysis - Chen_2015_J.Natl.Cancer.Inst_107_
Author(s) : Chen LS , Hung RJ , Baker T , Horton A , Culverhouse R , Saccone N , Cheng I , Deng B , Han Y , Hansen HM , Horsman J , Kim C , Lutz S , Rosenberger A , Aben KK , Andrew AS , Breslau N , Chang SC , Dieffenbach AK , Dienemann H , Frederiksen B , Han J , Hatsukami DK , Johnson EO , Pande M , Wrensch MR , McLaughlin J , Skaug V , van der Heijden HF , Wampfler J , Wenzlaff A , Woll P , Zienolddiny S , Bickeboller H , Brenner H , Duell EJ , Haugen A , Heinrich J , Hokanson JE , Hunter DJ , Kiemeney LA , Lazarus P , Le Marchand L , Liu G , Mayordomo J , Risch A , Schwartz AG , Teare D , Wu X , Wiencke JK , Yang P , Zhang ZF , Spitz MR , Kraft P , Amos CI , Bierut LJ
Ref : J Natl Cancer Inst , 107 : , 2015
Abstract : BACKGROUND: Recent meta-analyses show strong evidence of associations among genetic variants in CHRNA5 on chromosome 15q25, smoking quantity, and lung cancer. This meta-analysis tests whether the CHRNA5 variant rs16969968 predicts age of smoking cessation and age of lung cancer diagnosis.
METHODS: Meta-analyses examined associations between rs16969968, age of quitting smoking, and age of lung cancer diagnosis in 24 studies of European ancestry (n = 29 072). In each dataset, we used Cox regression models to evaluate the association between rs16969968 and the two primary phenotypes (age of smoking cessation among ever smokers and age of lung cancer diagnosis among lung cancer case patients) and the secondary phenotype of smoking duration. Heterogeneity across studies was assessed with the Cochran Q test. All statistical tests were two-sided.
RESULTS: The rs16969968 allele (A) was associated with a lower likelihood of smoking cessation (hazard ratio [HR] = 0.95, 95% confidence interval [CI] = 0.91 to 0.98, P = .0042), and the AA genotype was associated with a four-year delay in median age of quitting compared with the GG genotype. Among smokers with lung cancer diagnoses, the rs16969968 genotype (AA) was associated with a four-year earlier median age of diagnosis compared with the low-risk genotype (GG) (HR = 1.08, 95% CI = 1.04 to 1.12, P = 1.1*10(-5)). CONCLUSION: These data support the clinical significance of the CHRNA5 variant rs16969968. It predicts delayed smoking cessation and an earlier age of lung cancer diagnosis in this meta-analysis. Given the existing evidence that this CHRNA5 variant predicts favorable response to cessation pharmacotherapy, these findings underscore the potential clinical and public health importance of rs16969968 in CHRNA5 in relation to smoking cessation success and lung cancer risk.
ESTHER : Chen_2015_J.Natl.Cancer.Inst_107_
PubMedSearch : Chen_2015_J.Natl.Cancer.Inst_107_
PubMedID: 25873736

Title : Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors - Wang_2015_Bioorg.Med.Chem.Lett_25_5212
Author(s) : Wang C , Wu Z , Cai H , Xu S , Liu J , Jiang J , Yao H , Wu X , Xu J
Ref : Bioorganic & Medicinal Chemistry Lett , 25 :5212 , 2015
Abstract : A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.9nM and high AChE/BuChE selectivity (SI>230). Kinetic and molecular modeling studies suggested that compound 9d was mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. Besides, the preliminary structure-activity relationships were discussed.
ESTHER : Wang_2015_Bioorg.Med.Chem.Lett_25_5212
PubMedSearch : Wang_2015_Bioorg.Med.Chem.Lett_25_5212
PubMedID: 26454504

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

Title : N-myc downstream regulated gene 1 acts as a tumor suppressor in ovarian cancer - Wang_2014_Oncol.Rep_31_2279
Author(s) : Wang B , Li J , Ye Z , Li Z , Wu X
Ref : Oncol Rep , 31 :2279 , 2014
Abstract : Although implicated in a number of tumor types, the role of N-myc downstream regulated gene 1 (NDRG1) in ovarian cancer (OC) is unclear. In the present study, we used short hairpin RNA (shRNA) to silence NDRG1 in the OC cell line OVCAR3 and assessed the effect of its knockdown on cell morphology, proliferation, colony formation, migration and invasion. To complement these knockdown studies, we overexpressed NDRG1 in the same cell line. We found that NDRG1 knockdown significantly enhanced OVCAR3 proliferation, migration and invasion; however, there were no apparent changes in cell morphology. We also examined the effect in vivo and found that NDRG1 depletion promoted OVCAR3 xenograft growth in nude mice. In accordance with these data, we found that NDRG1 overexpression decreased proliferation, adhesion and apoptosis, and induced G0/G1 cell cycle arrest in OVCAR3 cells; expression of p21 and p53 was also increased. In conclusion, we demonstrated that NDRG1 acts as a tumor suppressor in ovarian carcinogenesis and may be a potential therapeutic target in this disease.
ESTHER : Wang_2014_Oncol.Rep_31_2279
PubMedSearch : Wang_2014_Oncol.Rep_31_2279
PubMedID: 24626771

Title : Importing, caring, breeding, genotyping, and phenotyping a genetic mouse in a chinese university - Kuo_2014_J.Mol.Neurosci_53_487
Author(s) : Kuo ST , Wu QH , Liu B , Xie ZL , Wu X , Shang SJ , Zhang XY , Kang XJ , Liu LN , Zhu FP , Wang YS , Hu MQ , Xu HD , Zhou L , Chai ZY , Zhang QF , Liu W , Teng SS , Wang CH , Guo N , Dou HQ , Zuo PL , Zheng LH , Zhang CX , Zhu DS , Wang L , Wang SR , Zhou Z
Ref : Journal of Molecular Neuroscience , 53 :487 , 2014
Abstract : The genetic manipulation of the laboratory mouse has been well developed and generated more and more mouse lines for biomedical research. To advance our science exploration, it is necessary to share genetically modified mouse lines with collaborators between institutions, even in different countries. The transfer process is complicated. Significant paperwork and coordination are required, concerning animal welfare, intellectual property rights, colony health status, and biohazard. Here, we provide a practical example of importing a transgenic mice line, Dynamin 1 knockout mice, from Yale University in the USA to Perking University in China for studying cell secretion. This example including the length of time that required for paper work, mice quarantine at the receiving institution, and expansion of the mouse line for experiments. The procedure described in this paper for delivery live transgenic mice from USA to China may serve a simple reference for transferring mouse lines between other countries too.
ESTHER : Kuo_2014_J.Mol.Neurosci_53_487
PubMedSearch : Kuo_2014_J.Mol.Neurosci_53_487
PubMedID: 24385195

Title : Evidences for B6C3-Tg (APPswe\/PSEN1dE9) Double-Transgenic Mice Between 3 and 10 Months as an Age-Related Alzheimer's Disease Model - Zhong_2014_J.Mol.Neurosci_53_370
Author(s) : Zhong Z , Yang L , Wu X , Huang W , Yan J , Liu S , Sun X , Liu K , Lin H , Kuang S , Tang X
Ref : Journal of Molecular Neuroscience , 53 :370 , 2014
Abstract : Transgenic mouse has shown great advantages in the study of Alzheimer's disease (AD) and drug screening as AD develops rapidly resent years, while more detail information of these transgenic mice and experience of application are needed. To obtain the basic background information of the B6C3-Tg (APPswe/PSEN1dE9) double-transgenic mouse, which was reported with early onset AD, three- to ten-month-old B6C3-Tg AD mice and normal C57BL/6 mice were selected randomly to test the ability of learning memory by Morris water maze, the brain acetylcholinesterase (AChE) activity by AChE kit, and beta amyloid protein level by immunohistochemistry staining. Compared with the control group, the escape latency time of B6C3-Tg AD mice at 9 and 10 months of age is significantly longer (P < 0.05) in Morris maze test, and the activity of brain AChE is higher. beta-Amyloid plaques were observed at 3 months of age and developed rapidly. Statistical analysis showed a positive correlation between the area of these plaques and the ages of B6C3-Tg AD mouse (y = 0.0355e(0.5557x), R = 0.9557). The model's behavior is conformed to simulate behaviors of human Alzheimer's disease at the early stage and may provide detail background information a new choice when transgenic mice are needed in the research of AD.
ESTHER : Zhong_2014_J.Mol.Neurosci_53_370
PubMedSearch : Zhong_2014_J.Mol.Neurosci_53_370
PubMedID: 24362678

Title : Effects of Di-n-butyl Phthalate and Diethyl Phthalate on Acetylcholinesterase Activity and Neurotoxicity Related Gene Expression in Embryonic Zebrafish - Xu_2013_Bull.Environ.Contam.Toxicol_91_635
Author(s) : Xu H , Shao X , Zhang Z , Zou Y , Chen Y , Han S , Wang S , Wu X , Yang L , Chen Z
Ref : Bulletin of Environmental Contamination & Toxicology , 91 :635 , 2013
Abstract : In the present study, zebrafish embryos were used to assess the neurotoxicity of di-n-butyl phthalate (DBP), diethyl phthalate (DEP) and their mixture. Four-hour post-fertilization (hpf) zebrafish embryos were exposed to various concentrations of DBP, DEP and their mixture (DBP-DEP) until 96 hpf. The transcriptions levels of selected neuron-related genes reported as neurotoxicity biomarkers were analyzed. The results showed that transcripts of growth associated protein 43 (gap43), embryonic lethal abnormal vision-like 3 (elavl3), glial fibrillary acidic protein (gfap), myelin basic protein (mbp), alpha1-tubulin and neurogenin1 (ngn1) were significantly up-regulated after DBP, DEP and DBP-DEP mixture exposure. In addition, acetylcholinesterase activity was significantly inhibited in the embryos. These results indicate that DBP and DEP have the potential neurotoxicity in zebrafish embryos.
ESTHER : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedSearch : Xu_2013_Bull.Environ.Contam.Toxicol_91_635
PubMedID: 24042840
Gene_locus related to this paper: danre-ACHE

Title : Genome Sequence of Streptomyces violaceusniger Strain SPC6, a Halotolerant Streptomycete That Exhibits Rapid Growth and Development - Chen_2013_Genome.Announc_1_e00494
Author(s) : Chen X , Zhang B , Zhang W , Wu X , Zhang M , Chen T , Liu G , Dyson P
Ref : Genome Announc , 1 : , 2013
Abstract : Streptomyces violaceusniger strain SPC6 is a halotolerant streptomycete isolated from the Linze desert in China. The strain has a very high growth rate and a short life cycle for a streptomycete. For surface-grown cultures, the period from spore germination to formation of colonies with mature spore chains is only 2 days at 37 degrees C. Additionally, the strain is remarkably resistant to osmotic, heat, and UV stress compared with other streptomycetes. Analysis of the draft genome sequence indicates that the strain has the smallest reported genome (6.4 Mb) of any streptomycete. The availability of this genome sequence allows us to investigate the genetic basis of adaptation for growth in an extremely arid environment.
ESTHER : Chen_2013_Genome.Announc_1_e00494
PubMedSearch : Chen_2013_Genome.Announc_1_e00494
PubMedID: 23868127
Gene_locus related to this paper: 9actn-a0a1d3dv58

Title : Reference genome sequence of the model plant Setaria - Bennetzen_2012_Nat.Biotechnol_30_555
Author(s) : Bennetzen JL , Schmutz J , Wang H , Percifield R , Hawkins J , Pontaroli AC , Estep M , Feng L , Vaughn JN , Grimwood J , Jenkins J , Barry K , Lindquist E , Hellsten U , Deshpande S , Wang X , Wu X , Mitros T , Triplett J , Yang X , Ye CY , Mauro-Herrera M , Wang L , Li P , Sharma M , Sharma R , Ronald PC , Panaud O , Kellogg EA , Brutnell TP , Doust AN , Tuskan GA , Rokhsar D , Devos KM
Ref : Nat Biotechnol , 30 :555 , 2012
Abstract : We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The approximately 400-Mb assembly covers approximately 80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum).
ESTHER : Bennetzen_2012_Nat.Biotechnol_30_555
PubMedSearch : Bennetzen_2012_Nat.Biotechnol_30_555
PubMedID: 22580951
Gene_locus related to this paper: setit-k3xwe0 , setit-k3xfs7 , setit-k3yh36 , setit-k3zes3 , setit-k3zlj8 , setvi-a0a4u6wd58 , setit-a0a368qif6 , setit-a0a368sru6 , setit-a0a368q9x4 , setit-k3zri0 , setit-k3ysv0 , setit-k3xj49 , setit-k4ac30

Title : Whole-genome sequence of Schistosoma haematobium - Young_2012_Nat.Genet_44_221
Author(s) : Young ND , Jex AR , Li B , Liu S , Yang L , Xiong Z , Li Y , Cantacessi C , Hall RS , Xu X , Chen F , Wu X , Zerlotini A , Oliveira G , Hofmann A , Zhang G , Fang X , Kang Y , Campbell BE , Loukas A , Ranganathan S , Rollinson D , Rinaldi G , Brindley PJ , Yang H , Wang J , Gasser RB
Ref : Nat Genet , 44 :221 , 2012
Abstract : Schistosomiasis is a neglected tropical disease caused by blood flukes (genus Schistosoma; schistosomes) and affecting 200 million people worldwide. No vaccines are available, and treatment relies on one drug, praziquantel. Schistosoma haematobium has come into the spotlight as a major cause of urogenital disease, as an agent linked to bladder cancer and as a predisposing factor for HIV/AIDS. The parasite is transmitted to humans from freshwater snails. Worms dwell in blood vessels and release eggs that become embedded in the bladder wall to elicit chronic immune-mediated disease and induce squamous cell carcinoma. Here we sequenced the 385-Mb genome of S. haematobium using Illumina-based technology at 74-fold coverage and compared it to sequences from related parasites. We included genome annotation based on function, gene ontology, networking and pathway mapping. This genome now provides an unprecedented resource for many fundamental research areas and shows great promise for the design of new disease interventions.
ESTHER : Young_2012_Nat.Genet_44_221
PubMedSearch : Young_2012_Nat.Genet_44_221
PubMedID: 22246508
Gene_locus related to this paper: schha-ACHE , schha-a0a094zs51 , schha-a0a095agr4 , schha-a0a095ai61 , schha-a0a095ayl3 , schha-a0a095c2i3 , schha-a0a095ce64

Title : In vivo functional expression of a screened P. aeruginosa chaperone-dependent lipase in E. coli - Wu_2012_BMC.Biotechnol_12_58
Author(s) : Wu X , You P , Su E , Xu J , Gao B , Wei D
Ref : BMC Biotechnol , 12 :58 , 2012
Abstract : BACKGROUND: Microbial lipases particularly Pseudomonas lipases are widely used for biotechnological applications. It is a meaningful work to design experiments to obtain high-level active lipase. There is a limiting factor for functional overexpression of the Pseudomonas lipase that a chaperone is necessary for effective folding. As previously reported, several methods had been used to resolve the problem. In this work, the lipase (LipA) and its chaperone (LipB) from a screened strain named AB which belongs to Pseudomonas aeruginosa were overexpressed in E. coli with two dual expression plasmid systems to enhance the production of the active lipase LipA without in vitro refolding process. RESULTS: In this work, we screened a lipase-produced strain named AB through the screening procedure, which was identified as P. aeruginosa on the basis of 16S rDNA. Genomic DNA obtained from the strain was used to isolate the gene lipA (936 bp) and lipase specific foldase gene lipB (1023 bp). One single expression plasmid system E. coli BL21/pET28a-lipAB and two dual expression plasmid systems E. coli BL21/pETDuet-lipA-lipB and E. coli BL21/pACYCDuet-lipA-lipB were successfully constructed. The lipase activities of the three expression systems were compared to choose the optimal expression method. Under the same cultured condition, the activities of the lipases expressed by E. coli BL21/pET28a-lipAB and E. coli BL21/pETDuet-lipA-lipB were 1300 U/L and 3200 U/L, respectively, while the activity of the lipase expressed by E. coli BL21/pACYCDuet-lipA-lipB was up to 8500 U/L. The lipase LipA had an optimal temperature of 30 degreesC and an optimal pH of 9 with a strong pH tolerance. The active LipA could catalyze the reaction between fatty alcohols and fatty acids to generate fatty acid alkyl esters, which meant that LipA was able to catalyze esterification reaction. The most suitable fatty acid and alcohol substrates for esterification were octylic acid and hexanol, respectively. CONCLUSIONS: The effect of different plasmid system on the active LipA expression was significantly different. pACYCDuet-lipA-lipB was more suitable for the expression of active LipA than pET28a-lipAB and pETDuet-lipA-lipB. The LipA showed obvious esterification activity and thus had potential biocatalytic applications. The expression method reported here can give reference for the expression of those enzymes that require chaperones.
ESTHER : Wu_2012_BMC.Biotechnol_12_58
PubMedSearch : Wu_2012_BMC.Biotechnol_12_58
PubMedID: 22950599
Gene_locus related to this paper: pseae-llipa

Title : Increased genetic vulnerability to smoking at CHRNA5 in early-onset smokers - Hartz_2012_Arch.Gen.Psychiatry_69_854
Author(s) : Hartz SM , Short SE , Saccone NL , Culverhouse R , Chen L , Schwantes-An TH , Coon H , Han Y , Stephens SH , Sun J , Chen X , Ducci F , Dueker N , Franceschini N , Frank J , Geller F , Gubjartsson D , Hansel NN , Jiang C , Keskitalo-Vuokko K , Liu Z , Lyytikainen LP , Michel M , Rawal R , Rosenberger A , Scheet P , Shaffer JR , Teumer A , Thompson JR , Vink JM , Vogelzangs N , Wenzlaff AS , Wheeler W , Xiao X , Yang BZ , Aggen SH , Balmforth AJ , Baumeister SE , Beaty T , Bennett S , Bergen AW , Boyd HA , Broms U , Campbell H , Chatterjee N , Chen J , Cheng YC , Cichon S , Couper D , Cucca F , Dick DM , Foroud T , Furberg H , Giegling I , Gu F , Hall AS , Hallfors J , Han S , Hartmann AM , Hayward C , Heikkila K , Hewitt JK , Hottenga JJ , Jensen MK , Jousilahti P , Kaakinen M , Kittner SJ , Konte B , Korhonen T , Landi MT , Laatikainen T , Leppert M , Levy SM , Mathias RA , McNeil DW , Medland SE , Montgomery GW , Muley T , Murray T , Nauck M , North K , Pergadia M , Polasek O , Ramos EM , Ripatti S , Risch A , Ruczinski I , Rudan I , Salomaa V , Schlessinger D , Styrkarsdottir U , Terracciano A , Uda M , Willemsen G , Wu X , Abecasis G , Barnes K , Bickeboller H , Boerwinkle E , Boomsma DI , Caporaso N , Duan J , Edenberg HJ , Francks C , Gejman PV , Gelernter J , Grabe HJ , Hops H , Jarvelin MR , Viikari J , Kahonen M , Kendler KS , Lehtimaki T , Levinson DF , Marazita ML , Marchini J , Melbye M , Mitchell BD , Murray JC , Nothen MM , Penninx BW , Raitakari O , Rietschel M , Rujescu D , Samani NJ , Sanders AR , Schwartz AG , Shete S , Shi J , Spitz M , Stefansson K , Swan GE , Thorgeirsson T , Volzke H , Wei Q , Wichmann HE , Amos CI , Breslau N , Cannon DS , Ehringer M , Grucza R , Hatsukami D , Heath A , Johnson EO , Kaprio J , Madden P , Martin NG , Stevens VL , Stitzel JA , Weiss RB , Kraft P , Bierut LJ
Ref : Arch Gen Psychiatry , 69 :854 , 2012
Abstract : CONTEXT: Recent studies have shown an association between cigarettes per day (CPD) and a nonsynonymous single-nucleotide polymorphism in CHRNA5, rs16969968. OBJECTIVE: To determine whether the association between rs16969968 and smoking is modified by age at onset of regular smoking. DATA SOURCES: Primary data. STUDY SELECTION: Available genetic studies containing measures of CPD and the genotype of rs16969968 or its proxy. DATA EXTRACTION: Uniform statistical analysis scripts were run locally. Starting with 94,050 ever-smokers from 43 studies, we extracted the heavy smokers (CPD >20) and light smokers (CPD </=10) with age-at-onset information, reducing the sample size to 33,348. Each study was stratified into early-onset smokers (age at onset </=16 years) and late-onset smokers (age at onset >16 years), and a logistic regression of heavy vs light smoking with the rs16969968 genotype was computed for each stratum. Meta-analysis was performed within each age-at-onset stratum. DATA SYNTHESIS: Individuals with 1 risk allele at rs16969968 who were early-onset smokers were significantly more likely to be heavy smokers in adulthood (odds ratio [OR] = 1.45; 95% CI, 1.36-1.55; n = 13,843) than were carriers of the risk allele who were late-onset smokers (OR = 1.27; 95% CI, 1.21-1.33, n = 19,505) (P = .01). CONCLUSION: These results highlight an increased genetic vulnerability to smoking in early-onset smokers.
ESTHER : Hartz_2012_Arch.Gen.Psychiatry_69_854
PubMedSearch : Hartz_2012_Arch.Gen.Psychiatry_69_854
PubMedID: 22868939

Title : Complete genome of the plant growth-promoting rhizobacterium Pseudomonas putida BIRD-1 - Matilla_2011_J.Bacteriol_193_1290
Author(s) : Matilla MA , Pizarro-Tobias P , Roca A , Fernandez M , Duque E , Molina L , Wu X , van der Lelie D , Gomez MJ , Segura A , Ramos JL
Ref : Journal of Bacteriology , 193 :1290 , 2011
Abstract : We report the complete sequence of the 5.7-Mbp genome of Pseudomonas putida BIRD-1, a metabolically versatile plant growth-promoting rhizobacterium that is highly tolerant to desiccation and capable of solubilizing inorganic phosphate and iron and of synthesizing phytohormones that stimulate seed germination and plant growth.
ESTHER : Matilla_2011_J.Bacteriol_193_1290
PubMedSearch : Matilla_2011_J.Bacteriol_193_1290
PubMedID: 21183676
Gene_locus related to this paper: psepk-q88nk6 , psepk-q88qt0 , psepu-ESTB , psepu-PHAC1 , psepu-PHAZ , psepu-PIP , psepu-PP1184 , psepu-PP1500 , psepu-PP3807 , psepu-PP3812 , psepu-PP4178 , psepu-PP4249 , psepu-PP4551 , psepu-PP4583 , psepu-PP4634 , psepu-PP4916 , psepu-PP5117 , psepu-PP5161 , psepu-PP5167 , psepu-PPSD , psepu-q9wwz4

Title : Enhanced pesticide sensitivity of novel housefly acetylcholinesterases: a new tool for the detection of residual pesticide contamination - Tan_2011_Bioprocess.Biosyst.Eng_34_305
Author(s) : Tan F , Wang L , Wang J , Wu X , Zhu H , Jiang L , Tao S , Zhao K , Yang Y , Tang X
Ref : Bioprocess Biosyst Eng , 34 :305 , 2011
Abstract : The full-length cDNA encoding an acetylcholinesterase (AChE) was cloned and sequenced from the housefly, Musca domestica, by reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence analysis revealed that this 2,076 bp sequence encodes a mature protein of 612 amino acids (67 kDa) and a 79 residue signal peptide. The amino acid sequence shared 52.8-81.4% identity with the AChE proteins of other insects. The cDNA sequence, which lacked the signal peptide was inserted into the vector pPIC9K and then introduced into strain GS115 of the yeast Pichia pastoris. The recombinant AChE protein was then expressed in P. pastoris strain GS115 by methanol induction. Site-directed mutagenesis of the A262G, Y327F, Y327D and I374D residues, either singly or in combination, was performed by reverse PCR. These mutants improved the catalytic activity and sensitivity to the organophosphate and carbamate insecticides. Although the sensitivity of other mutants was slightly increased, the results still showed that the sensitivity of triple mutant, GDD (A262G/Y327D/I374D), enhanced remarkably as much as 16 times for methomyl, 14 times for both carbofuran and chlorpyrifos, and ten times for parathion-methyl, compared to that of the wild-type. The results strongly suggested that these residues are the key structural elements controlling AChE enzyme catalytic activity and sensitivity to inhibition by insecticides. The AChE enzyme obtained by this method could be used to detect the organophosphate and carbamate insecticide residues in fruits and vegetables, a characteristic of great potential research and industrial application.
ESTHER : Tan_2011_Bioprocess.Biosyst.Eng_34_305
PubMedSearch : Tan_2011_Bioprocess.Biosyst.Eng_34_305
PubMedID: 20963445

Title : A highly sensitive and rapid organophosphate biosensor based on enhancement of CdS-decorated graphene nanocomposite - Wang_2011_Anal.Chim.Acta_695_84
Author(s) : Wang K , Liu Q , Dai L , Yan J , Ju C , Qiu B , Wu X
Ref : Anal Chim Acta , 695 :84 , 2011
Abstract : This work reports a rapid and sensitive organophosphates (OPs) amperometric biosensor based on acetylcholinesterase (AChE) immobilized on CdS-decorated graphene (CdS-G) nanocomposite. The as-prepared biosensor shows high affinity to acetylthiocholine (ATCl) with a Michaelis-Menten constant (K(m)) value of 0.24 mM. A rapid inhibition time (2 min) is obtained due to the integration of the CdS-G nanocomposite. Based on the inhibition of OPs on the enzymatic activity of the immobilized AChE, and used carbaryl as the model compound, the resulting biosensor exhibits excellent performance for OPs detection including good reproducibility, acceptable stability, and a reliable linear relationship between the inhibition and log[carbaryl] from 2 ng mL(-)(1) up to 2 mug mL(-)(1) with a detection limit of 0.7 ng mL(-)(1),which provides a new promising tool for analysis of enzyme inhibitors.
ESTHER : Wang_2011_Anal.Chim.Acta_695_84
PubMedSearch : Wang_2011_Anal.Chim.Acta_695_84
PubMedID: 21601034

Title : Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of alpha7 nicotinic receptors and internalization of NMDA receptors - Shen_2010_Br.J.Pharmacol_161_127
Author(s) : Shen H , Kihara T , Hongo H , Wu X , Kem WR , Shimohama S , Akaike A , Niidome T , Sugimoto H
Ref : British Journal of Pharmacology , 161 :127 , 2010
Abstract : BACKGROUND AND PURPOSE: Glutamate excitotoxicity may be involved in ischaemic injury to the CNS and some neurodegenerative diseases, such as Alzheimer's disease. Donepezil, an acetylcholinesterase (AChE) inhibitor, exerts neuroprotective effects. Here we demonstrated a novel mechanism underlying the neuroprotection induced by donepezil. EXPERIMENTAL APPROACH: Cell damage in primary rat neuron cultures was quantified by lactate dehydrogenase release. Morphological changes associated with neuroprotective effects of nicotine and AChE inhibitors were assessed by immunostaining. Cell surface levels of the glutamate receptor sub-units, NR1 and NR2A, were analyzed using biotinylation. Immunoblot was used to measure protein levels of cleaved caspase-3, total NR1, total NR2A and phosphorylated NR1. Immunoprecipitation was used to measure association of NR1 with the post-synaptic protein, PSD-95. Intracellular Ca(2+) concentrations were measured with fura 2-acetoxymethylester. Caspase 3-like activity was measured using enzyme substrate, 7-amino-4-methylcoumarin (AMC)-DEVD. KEY RESULTS: Levels of NR1, a core subunit of the NMDA receptor, on the cell surface were significantly reduced by donepezil. In addition, glutamate-mediated Ca(2+) entry was significantly attenuated by donepezil. Methyllycaconitine, an inhibitor of alpha7 nicotinic acetylcholine receptors (nAChR), inhibited the donepezil-induced attenuation of glutamate-mediated Ca(2+) entry. LY294002, a phosphatidyl inositol 3-kinase (PI3K) inhibitor, had no effect on attenuation of glutamate-mediated Ca(2+) entry induced by donepezil. CONCLUSIONS AND IMPLICATIONS: Decreased glutamate toxicity through down-regulation of NMDA receptors, following stimulation of alpha7 nAChRs, could be another mechanism underlying neuroprotection by donepezil, in addition to up-regulating the PI3K-Akt cascade or defensive system.
ESTHER : Shen_2010_Br.J.Pharmacol_161_127
PubMedSearch : Shen_2010_Br.J.Pharmacol_161_127
PubMedID: 20718745

Title : Chylomicronemia elicits atherosclerosis in mice--brief report - Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
Author(s) : Weinstein MM , Yin L , Tu Y , Wang X , Wu X , Castellani LW , Walzem RL , Lusis AJ , Fong LG , Beigneux AP , Young SG
Ref : Arterioscler Thromb Vasc Biol , 30 :20 , 2010
Abstract : OBJECTIVE: The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in Gpihbp1-deficient mice (Gpihbp1(-/-)), which manifest severe chylomicronemia as a result of defective lipolysis. METHODS AND RESULTS: Gpihbp1(-/-) mice on a chow diet have plasma triglyceride and cholesterol levels of 2812+/-209 and 319+/-27 mg/dL, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50 to 135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both Gpihbp1-deficient "apo-B48-only" mice and Gpihbp1-deficient "apo-B100-only" mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48- and apo-B100-containing lipoproteins. CONCLUSIONS: Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48- and apo-B100-containing lipoproteins.
ESTHER : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
PubMedSearch : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
PubMedID: 19815815

Title : Localized vessel expression of lipoprotein lipase in rabbits leads to rapid lipid deposition in the balloon-injured arterial wall - Wu_2006_Atherosclerosis_187_65
Author(s) : Wu X , Wang J , Fan J , Chen M , Chen L , Huang W , Liu G
Ref : Atherosclerosis , 187 :65 , 2006
Abstract : Recent studies on mice demonstrated that lipoprotein lipase (LPL) located in the arterial wall might play a pro-atherogenic role. There are major differences between humans and mice in lipoprotein metabolism and in susceptibility to atherosclerosis. We have therefore used rabbits fed normal chow diet as a model to assess such localized effects by adenovirus-mediated gene transfer of human catalytically active wild type LPL (hLPLwt) and an inactive mutant (hLPL194) to balloon-injured carotid arteries. By morphometric analysis on cryosections stained with Oil Red O (ORO) we found 7- and 4-fold increases, respectively, of lipid deposition in the arterial walls 7 days after infection with adenovirus expressing hLPLwt or hLPL194, when compared with a virus expressing human alkaline phosphatase (hAP) as control. Macrophages were detected in the arteries expressing both forms of LPL, but apoB was only found in arteries expressing hLPLwt. Expression of the LPL gene products was transient and was gone after 2 weeks, but the accumulated lipid deposits remained between the neointimal and the media layers even after 8 weeks. Our data demonstrate that expression of LPL in the arterial wall (with or without lipase activity) leads to lipid accumulation in balloon-injured rabbit arteries, and could result in enhanced formation of atherosclerotic lesions.
ESTHER : Wu_2006_Atherosclerosis_187_65
PubMedSearch : Wu_2006_Atherosclerosis_187_65
PubMedID: 16191430

Title : Species-dependent smooth muscle contraction to Neuromedin U and determination of the receptor subtypes mediating contraction using NMU1 receptor knockout mice - Prendergast_2006_Br.J.Pharmacol_147_886
Author(s) : Prendergast CE , Morton MF , Figueroa KW , Wu X , Shankley NP
Ref : British Journal of Pharmacology , 147 :886 , 2006
Abstract : The peptide ligand neuromedin U (NMU) has been implicated in an array of biological activities, including contraction of uterine, intestinal and urinary bladder smooth muscle. However, many of these responses appear to be species-specific. This study was undertaken to fully elucidate the range of smooth muscle-stimulating effects of NMU in rats, mice and guinea-pigs, and to examine the extent of the species differences. In addition, the NMU1 receptor knockout mouse was used to determine which receptor subtype mediates the contractile responses generated by NMU in the mouse. A range of isolated organ in vitro bioassays were carried out, which were chosen to re-confirm previous literature reports (uterine and stomach fundus contraction) and also to explore potentially novel smooth muscle responses to NMU. This investigation uncovered a number of previously unidentified NMU-mediated responses: contraction of rat lower esophageal sphinster (LES), rat ileum, mouse gallbladder, enhancement of electrically evoked contractions in rat and mouse vas deferens, and a considerable degree of cross-species differences. Studies using the NMU1 receptor knockout mice revealed that in the mouse fundus and gallbladder assays the NMU contractile response was mediated entirely through the NMU1 receptor subtype, whereas, in assays of mouse uterus and vas deferens, the response to NMU was unchanged in the NMU1 receptor knockout mouse, suggesting that the NMU response may be mediated through the NMU2 receptor subtype. NMU receptor subtype-selective antagonists are required to further elucidate the role of the individual receptor subtypes.
ESTHER : Prendergast_2006_Br.J.Pharmacol_147_886
PubMedSearch : Prendergast_2006_Br.J.Pharmacol_147_886
PubMedID: 16474416

Title : Design, synthesis, and biological evaluation of new territrem B analogues - Jiang_2005_Chem.Biodivers_2_557
Author(s) : Jiang X , Ao L , Zhou C , Yang L , Zhang Q , Li H , Sun L , Wu X , Bai H , Zhao Y
Ref : Chem Biodivers , 2 :557 , 2005
Abstract : Some 23 analogues of the potent acetylcholinesterase (AChE) inhibitor territrem B (1) were designed, synthesized, and tested for their biological activities. Some of the new synthetic derivatives exhibited IC50 values for AChE inhibition in the upper micromolar range. Molecular-modeling studies indicated that a planar conformation seems to be crucial for AChE inhibition. The two N-atoms of the piperazine moieties in 5o, 5p, and 5r might further enhance the inhibitory effects. The cytotoxicities of selected compounds against six human tumor cell lines were also determined.
ESTHER : Jiang_2005_Chem.Biodivers_2_557
PubMedSearch : Jiang_2005_Chem.Biodivers_2_557
PubMedID: 17192004

Title : Determination and analysis of single nucleotide polymorphisms and haplotype structure of the human carboxylesterase 2 gene - Wu_2004_Pharmacogenet_14_595
Author(s) : Wu MH , Chen P , Wu X , Liu W , Strom S , Das S , Cook EH, Jr. , Rosner GL , Dolan ME
Ref : Pharmacogenetics , 14 :595 , 2004
Abstract : Carboxylesterases are members of the serine esterase super family important in the metabolism of a wide variety of substrates, including xenobiotics and prodrugs. There are two known carboxylesterases expressed in human liver, small intestine and other tissues, carboxylesterase 1 (CES1) and carboxylesterase 2 (CES2). The aim of this study was to identify polymorphisms in the CES2 gene and determine whether these polymorphisms affect expression levels of CES2 or rate of metabolism of irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin). Microsome samples prepared from liver tissues of 78 normal individuals were used to determine the rate of hydrolysis of irinotecan and procaine (an anaesthetic hydrolysed by CES2 but not CES1). The rate of hydrolysis of irinotecan is highly variable among individuals, ranging from 2.7-138 pmol/mg protein/h (mean +/- SD 26.0 +/- 22.9). Fifteen single nucleotide polymorphisms (SNPs) were identified, one is in an exon, 9 are in introns, three are in the 3'-untranslated region (UTR), and two are in the 5'-flanking region. Eight of the 15 SNP loci have rare allele frequencies greater than 5%, of which three were greater than 20%. Genotyping of samples from the SNP Consortium demonstrated different distributions among African-Americans, Asian-Americans and European-Americans. We also analysed the haplotype structure and estimated linkage disequilibrium (LD). A SNP located in the 5'-UTR (5'-UTR-363) was found in LD with loci in intron 1 (Intron1 + 947, Intron1 + 1361, Intron1 + 1643). Haplotypes with homozygous rare alleles on these loci exhibit lower mRNA levels as determined by real time polymerase chain reaction (P < 0.01) and the incorporation of rare alleles in haplotypes correlate with reduced mRNA (P = 0.03). The 5'-UTR-363 SNP is located in one of the three promoters of CES2. However, we did not observe significant differences in CES2 activities (irinotecan and procaine hydrolysis) among individuals with different haplotypes.
ESTHER : Wu_2004_Pharmacogenet_14_595
PubMedSearch : Wu_2004_Pharmacogenet_14_595
PubMedID: 15475733
Gene_locus related to this paper: human-CES2

Title : Gene expression profiling of androgen deficiency predicts a pathway of prostate apoptosis that involves genes related to oxidative stress - Pang_2002_Endocrinology_143_4897
Author(s) : Pang ST , Dillner K , Wu X , Pousette A , Norstedt G , Flores-Morales A
Ref : Endocrinology , 143 :4897 , 2002
Abstract : Androgens are critical for prostate development, growth, and functions. In general, they support proliferation and prevent cell death of prostatic epithelial cells. Here, we studied changes of gene expression after castration and testosterone replacement therapy in the rat ventral prostate using cDNA microarrays analysis. We could identify 230 genes that were regulated in either experimental condition. Using hierarchical clustering analysis, different groups of genes could be detected according to their expression pattern. This enabled us to distinguish the putative androgen-responsive genes from the secondary-responsive ones. Among genes that altered during castration and testosterone replacement, a set of oxidative stress-related genes, including thioredoxin, peroxiredoxin 5, superoxide dismutase 2, glutathione peroxidase 1, selenoprotein 15 kDa, microsomal glutathione-S-transferase, glutathione reductase, and epoxide hydrolase, were changed by castration. We hypothesize that modulation of redox status can be a factor of relevance in androgen withdrawal-induced prostate apoptosis. In selective cases, quantitative RT-PCR was used to confirm changes in gene expression. Immunohistochemistry was performed to detect thioredoxin and ezrin. Both of these were detected in the prostate and seem to be regulated in a similar manner as shown by gene expression analysis. In conclusion, gene expression profiling provides a unique opportunity for understanding the molecular mechanisms of androgen actions in prostate gland.
ESTHER : Pang_2002_Endocrinology_143_4897
PubMedSearch : Pang_2002_Endocrinology_143_4897
PubMedID: 12446617

Title : Microsomal epoxide hydrolase polymorphisms and lung cancer risk in non-Hispanic whites - Zhao_2002_Mol.Carcinog_33_99
Author(s) : Zhao H , Spitz MR , Gwyn KM , Wu X
Ref : Mol Carcinog , 33 :99 , 2002
Abstract : Microsomal epoxide hydrolase (mEPHX) is a critical metabolic enzyme involved in the activation and subsequent detoxification of specific tobacco carcinogens. mEPHX harbors polymorphisms in exon 3 and exon 4 that modulate enzymatic activity. The exon 3 polymorphism decreases mEPHX metabolic activity, whereas the exon 4 polymorphism increases activity. We hypothesized that the mEPHX polymorphisms modulate lung cancer risk. Using a case-control study design and restriction fragment length polymorphism polymerase chain reaction assay, we determined the mEPHX polymorphic genotypes of 181 lung cancer cases among non-Hispanic whites and 163 controls (matched for age, sex, ethnicity, and smoking history). Our results showed that the variant allele of mEPHX exon 4 increased the overall lung cancer risk by 56% (odds ratio [OR]=1.56, 95% confidence interval [CI]=0.99-2.46). Additionally, the risk estimates were elevated significantly for younger people (<64 yr) (OR=2.27, 95% CI=1.15-4.50) and current smokers (OR=2.22, 95% CI=1.06-4.65). The variant allele of mEPHX exon 3 had no effect overall (OR=0.88, 95% CI=0.56-1.38), but there was a 53% protective effect (OR=0.47, 95% CI=0.22-0.99) in younger people. When we analyzed the exon 3 and exon 4 polymorphisms together, those people with the high enzymatic activity genotype had an elevated lung cancer risk of 1.72 (95% CI=0.90-3.29). This elevated risk was also evident only in younger people. These findings suggest that these variant alleles of exon 3 and exon 4 of mEPHX modulates lung cancer risk.
ESTHER : Zhao_2002_Mol.Carcinog_33_99
PubMedSearch : Zhao_2002_Mol.Carcinog_33_99
PubMedID: 11813302

Title : The association of microsomal epoxide hydrolase polymorphisms and lung cancer risk in African-Americans and Mexican-Americans - Wu_2001_Carcinogenesis_22_923
Author(s) : Wu X , Gwyn K , Amos CI , Makan N , Hong WK , Spitz MR
Ref : Carcinogenesis , 22 :923 , 2001
Abstract : This study evaluated the influence of genetic polymorphisms in the microsomal epoxide hydrolase (mEPHX) gene on lung cancer risk in a case-control study of two different ethnic groups, Mexican-Americans and African-Americans. There were 138 lung cancer cases (60 Mexican-American and 78 African-American) and 148 controls (76 Mexican-American and 72 African-American). There was a significant difference in the distribution of the mEPHX exon 4 polymorphism between the two ethnic groups with African-Americans more likely to be heterozygous and Mexican-Americans to be wild-type. There was no significant difference between the ethnic groups for the allelic distribution of the mEPHX exon 3 polymorphism. When the exon 4 and exon 3 polymorphism distributions in cases and controls were examined by ethnicity, only the Mexican-American cases showed a substantial proportion with the exon 4 polymorphism. The exon 4 polymorphism was associated with a significantly increased risk of lung cancer only among the Mexican-American cases (adjusted OR 3.6, 95% CI 1.26, 10.42). Younger Mexican-Americans with the exon 4 polymorphism had a greater risk of lung cancer than older members of their groups (adjusted OR 7.4, 95% CI 1.36, 40.23; 1.6, 95% CI 0.33, 7.80, respectively). The exon 3 polymorphism did not appear to significantly increase the risk of lung cancer in all but one study group examined. Mexican-Americans younger than 65 years did demonstrate an elevated risk of lung cancer (adjusted OR 4.6, 95% CI 1.19, 17.56). However, no statistically significant risk was observed in the African-American study groups for both exon 3 and exon 4 polymorphisms. These findings suggest that the presence of the exon 4 and exon 3 polymorphisms of mEPHX may be associated with an increased risk of lung cancer particularly among younger Mexican-Americans in this study.
ESTHER : Wu_2001_Carcinogenesis_22_923
PubMedSearch : Wu_2001_Carcinogenesis_22_923
PubMedID: 11375900

Title : The highly reduced genome of an enslaved algal nucleus - Douglas_2001_Nature_410_1091
Author(s) : Douglas S , Zauner S , Fraunholz M , Beaton M , Penny S , Deng LT , Wu X , Reith M , Cavalier-Smith T , Maier UG
Ref : Nature , 410 :1091 , 2001
Abstract : Chromophyte algae differ fundamentally from plants in possessing chloroplasts that contain chlorophyll c and that have a more complex bounding-membrane topology. Although chromophytes are known to be evolutionary chimaeras of a red alga and a non-photosynthetic host, which gave rise to their exceptional membrane complexity, their cell biology is poorly understood. Cryptomonads are the only chromophytes that still retain the enslaved red algal nucleus as a minute nucleomorph. Here we report complete sequences for all three nucleomorph chromosomes from the cryptomonad Guillardia theta. This tiny 551-kilobase eukaryotic genome is the most gene-dense known, with only 17 diminutive spliceosomal introns and 44 overlapping genes. Marked evolutionary compaction hundreds of millions of years ago eliminated nearly all the nucleomorph genes for metabolic functions, but left 30 for chloroplast-located proteins. To allow expression of these proteins, nucleomorphs retain hundreds of genetic-housekeeping genes. Nucleomorph DNA replication and periplastid protein synthesis require the import of many nuclear gene products across endoplasmic reticulum and periplastid membranes. The chromosomes have centromeres, but possibly only one loop domain, offering a means for studying eukaryotic chromosome replication, segregation and evolution.
ESTHER : Douglas_2001_Nature_410_1091
PubMedSearch : Douglas_2001_Nature_410_1091
PubMedID: 11323671

Title : Five unique compounds: xyloketals from mangrove fungus Xylaria sp. from the South China Sea coast - Lin_2001_J.Org.Chem_66_6252
Author(s) : Lin Y , Wu X , Feng S , Jiang G , Luo J , Zhou S , Vrijmoed LL , Jones EB , Krohn K , Steingrover K , Zsila F
Ref : J Org Chem , 66 :6252 , 2001
Abstract : Five unique metabolites, xyloketals A (1), B (2), C (3), D (4), and E (5), and the known 6 were isolated from mangrove fungus Xylaria sp. (no. 2508), obtained from the South China Sea. The structures of these compounds were elucidated by spectroscopic and X-ray diffraction experiments. Xyloketal A is a ketal compound with a C(3) symmetry and xyloketals B-E are its analogues. It was found that xytoketal C slowly rearranged to xytoketal B in DMSO-d(6)() solution at room temperature. Xyloketal A exhibited the activity of inhibiting acetylcholine esterase.
ESTHER : Lin_2001_J.Org.Chem_66_6252
PubMedSearch : Lin_2001_J.Org.Chem_66_6252
PubMedID: 11559170

Title : Epitope mapping of polyclonal and monoclonal antibodies against two alpha-bungarotoxin-binding alpha subunits from neuronal nicotinic receptors - McLane_1992_J.Neuroimmunol_38_115
Author(s) : McLane KE , Wu X , Lindstrom JM , Conti-Tronconi BM
Ref : Journal of Neuroimmunology , 38 :115 , 1992
Abstract : Recently, cDNAs for alpha subunits of two different neuronal alpha-bungarotoxin-binding proteins (alpha BgtBP) were isolated from chick brain, designated alpha BgtBP alpha 1 and alpha BgtBP alpha 2. These are now also referred to as subunits alpha 7 and alpha 8, respectively. Expression studies in Xenopus oocytes have indicated that alpha 7 subunits are able to form cation channels that are sensitive to nicotinic ligands, and therefore represent bona fide nicotinic acetylcholine receptor subunits. Polyclonal and monoclonal antibodies (mAbs) have been produced against: (i) affinity-purified chick brain alpha BgtBP; and (ii) fusion proteins containing the unique cytoplasmic sequences alpha 7(327-412) and alpha 8(293-435). Here, synthetic overlapping peptides corresponding to their deduced amino acid sequences are used to map the epitopes recognized by the different antibodies. The polyclonal response to affinity-purified alpha BgtBPs and the fusion proteins indicates that sequence segments 290-420 of both subunits contain several major and minor epitopes. mAbs selected for their ability to bind both native and denatured alpha BgtBPs isolated from chick brain also recognize subunit-specific sequential epitopes within the sequence segment 290-420. The epitopes recognized by the mAbs correspond to the minor epitopes defined using antisera. The mAbs characterized in these studies will provide useful probes for further studies of alpha BgtBP structure and histological localization.
ESTHER : McLane_1992_J.Neuroimmunol_38_115
PubMedSearch : McLane_1992_J.Neuroimmunol_38_115
PubMedID: 1374423