Jiang N

References (36)

Title : Soluble epoxide hydrolase inhibitor (TPPU) alleviates ferroptosis by regulating CCL5 after intracerebral hemorrhage in mice - Wu_2024_Biomed.Pharmacother_172_116301
Author(s) : Wu Q , Jiang N , Wang Y , Song G , Li P , Fang Y , Xu L , Wang W , Xie M
Ref : Biomed Pharmacother , 172 :116301 , 2024
Abstract : Soluble epoxide hydrolase (sEH) inhibition has been shown multiple beneficial effects against brain injuries of Intracerebral hemorrhage (ICH). However, the underlying mechanism of its neuroprotective effects after ICH has not been explained fully. Ferroptosis, a new form of iron-dependent programmed cell death, has been shown to be implicated in the secondary injuries after ICH. In this study, We examined whether sEH inhibition can alleviate brain injuries of ICH through inhibiting ferroptosis. Expression of several markers for ferroptosis was observed in the peri-hematomal brain tissues in mice after ICH. lip-1, a ferroptosis inhibitor, alleviated iron accumulation, lipid peroxidation and the secondary damages post-ICH in mice model. Intraperitoneal injection of 1-Trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl)urea (TPPU), a highly selective sEH inhibitor, could inhibit ferroptosis and alleviate brain damages in ICH mice. Furthermore, RNA-sequencing was applied to explore the potential regulatory mechanism underlying the effects of TPPU in ferroptosis after ICH. C-C chemokine ligand 5 (CCL5) may be the key factor by which TPPU regulated ferroptosis after ICH since CCL5 antagonist could mimic the effects of TPPU and CCL5 reversed the inhibitive effect of TPPU on ferroptosis and the neuroprotective effects of TPPU on secondary damage after ICH. Taken together, these data indicate that ferroptosis is a key pathological feature of ICH and Soluble epoxide hydrolase inhibitor can exert neuroprotective effect by preventing ferroptosis after ICH.
ESTHER : Wu_2024_Biomed.Pharmacother_172_116301
PubMedSearch : Wu_2024_Biomed.Pharmacother_172_116301
PubMedID: 38377737

Title : In vitro and in vivo Biological Evaluation of Newly Tacrine-Selegiline Hybrids as Multi-Target Inhibitors of Cholinesterases and Monoamine Oxidases for Alzheimer's Disease - Huang_2024_Drug.Des.Devel.Ther_18_133
Author(s) : Huang ST , Luo JC , Zhong GH , Teng LP , Yang CY , Tang CL , Jing L , Zhou ZB , Liu J , Jiang N
Ref : Drug Des Devel Ther , 18 :133 , 2024
Abstract : PURPOSE: Alzheimer's disease (AD) is the most common neurodegenerative disease, and its multifactorial nature increases the difficulty of medical research. To explore an effective treatment for AD, a series of novel tacrine-selegiline hybrids with ChEs and MAOs inhibitory activities were designed and synthesized as multifunctional drugs. METHODS: All designed compounds were evaluated in vitro for their inhibition of cholinesterases (AChE/BuChE) and monoamine oxidases (MAO-A/B) along with their blood-brain barrier permeability. Then, further biological activities of the optimizing compound 7d were determined, including molecular model analysis, in vitro cytotoxicity, acute toxicity studies in vivo, and pharmacokinetic and pharmacodynamic property studies in vivo. RESULTS: Most synthesized compounds demonstrated potent inhibitory activity against ChEs/MAOs. Particularly, compound 7d exhibited good and well-balanced activity against ChEs (hAChE: IC(50) = 1.57 microM, hBuChE: IC(50) = 0.43 microM) and MAOs (hMAO-A: IC(50) = 2.30 microM, hMAO-B: IC(50) = 4.75 microM). Molecular modeling analysis demonstrated that 7d could interact simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE in a mixed-type manner and also exhibits binding affinity towards BuChE and MAO-B. Additionally, 7d displayed excellent permeability of the blood-brain barrier, and under the experimental conditions, it elicited low or no toxicity toward PC12 and BV-2 cells. Furthermore, 7d was not acutely toxic in mice at doses up to 2500 mg/kg and could improve the cognitive function of mice with scopolamine-induced memory impairment. Lastly, 7d possessed well pharmacokinetic characteristics. CONCLUSION: In light of these results, it is clear that 7d could potentially serve as a promising multi-functional drug for the treatment of AD.
ESTHER : Huang_2024_Drug.Des.Devel.Ther_18_133
PubMedSearch : Huang_2024_Drug.Des.Devel.Ther_18_133
PubMedID: 38283137

Title : Biotoxicity responses of Zebrafish in environmentally relevant concentration of Di (2-ethylhexyl) phthalate - Li_2024_Environ.Toxicol.Pharmacol__104423
Author(s) : Li X , Hu S , Jiang N , Yao X , Wang C , Wang Q , Yang Z , Wang J
Ref : Environ Toxicol Pharmacol , :104423 , 2024
Abstract : As an emerging environmental contaminant, di (2-ethylhexyl) phthalate (DEHP) is widely present in the aquatic environment, however, the effects and underlying mechanisms of DEHP on the aquatic organisms are poorly understood. This study systematically investigated the ecotoxicity induced by chronic exposure to environmental relevant concentrations of DEHP (0.03mg/L, 0.1mg/L, and 0.3mg/L) on zebrafish brain. Results indicated that DEHP exposure significantly increased the levels of ROS and disturbance of the antioxidant enzymes activities in the brain, which may further enhance lipid peroxidation and DNA damage. Furthermore, acetylcholinesterase activity was first stimulated and inhibited by exposure to DEHP, and the antioxidant and apoptosis related genes were mainly upregulated. Risk assessment indicated that the ecotoxicity of DEHP on the zebrafish showed an "enhancement-reduction" trend as the exposure time was prolonged. Overall, these results provided new insights and useful information to ecological risk assessment and environmental management of DEHP pollution.
ESTHER : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedSearch : Li_2024_Environ.Toxicol.Pharmacol__104423
PubMedID: 38521434

Title : Design, synthesis, and biological evaluation of novel capsaicin-tacrine hybrids as multi-target agents for the treatment of Alzheimer's disease - Long_2023_Bioorg.Chem_143_107026
Author(s) : Long J , Qin F , Luo J , Zhong G , Huang S , Jing L , Yi T , Liu J , Jiang N
Ref : Bioorg Chem , 143 :107026 , 2023
Abstract : A series of novel hybrid compounds were designed, synthesized, and utilized as multi-target drugs to treat Alzheimer's disease (AD) by connecting capsaicin and tacrine moieties. The biological assays indicated that most of these compounds demonstrated strong inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities with IC(50) values in the nanomolar, as well as good blood-brain barrier permeability. Among the synthesized hybrids, compound 5s displayed the most balanced inhibitory effect on hAChE (IC(50) = 69.8 nM) and hBuChE (IC(50) = 68.0 nM), and exhibited promising inhibitory activity against beta-secretase-1 (BACE-1) (IC(50) = 3.6 microM). Combining inhibition kinetics and molecular model analysis, compound 5s was shown to be a mixed inhibitor affecting both the catalytic active site (CAS) and peripheral anionic site (PAS) of hAChE. Additionally, compound 5s showed low toxicity in PC12 and BV2 cell assays. Moreover, compound 5s demonstrated good tolerance at the dose of up to 2500 mg/kg and exhibited no hepatotoxicity at the dose of 3 mg/kg in mice, and it could effectively improve memory ability in mice. Taken together, these findings suggest that compound 5s is a promising and effective multi-target agent for the potential treatment of AD.
ESTHER : Long_2023_Bioorg.Chem_143_107026
PubMedSearch : Long_2023_Bioorg.Chem_143_107026
PubMedID: 38103330

Title : EETs alleviate alveolar epithelial cell senescence by inhibiting endoplasmic reticulum stress through the Trim25\/Keap1\/Nrf2 axis - Zhang_2023_Redox.Biol_63_102765
Author(s) : Zhang CY , Zhong WJ , Liu YB , Duan JX , Jiang N , Yang HH , Ma SC , Jin L , Hong JR , Zhou Y , Guan CX
Ref : Redox Biol , 63 :102765 , 2023
Abstract : Alveolar epithelial cell (AEC) senescence is a key driver of a variety of chronic lung diseases. It remains a challenge how to alleviate AEC senescence and mitigate disease progression. Our study identified a critical role of epoxyeicosatrienoic acids (EETs), downstream metabolites of arachidonic acid (ARA) by cytochrome p450 (CYP), in alleviating AEC senescence. In vitro, we found that 14,15-EET content was significantly decreased in senescent AECs. Exogenous EETs supplementation, overexpression of CYP2J2, or inhibition of EETs degrading enzyme soluble epoxide hydrolase (sEH) to increase EETs alleviated AECs' senescence. Mechanistically, 14,15-EET promoted the expression of Trim25 to ubiquitinate and degrade Keap1 and promoted Nrf2 to enter the nucleus to exert an anti-oxidant effect, thereby inhibiting endoplasmic reticulum stress (ERS) and alleviating AEC senescence. Furthermore, in D-galactose (D-gal)-induced premature aging mouse model, inhibiting the degradation of EETs by Trifluoromethoxyphenyl propionylpiperidin urea (TPPU, an inhibitor of sEH) significantly inhibited the protein expression of p16, p21, and gammaH2AX. Meanwhile, TPPU reduced the degree of age-related pulmonary fibrosis in mice. Our study has confirmed that EETs are novel anti-senescence substances for AECs, providing new targets for the treatment of chronic lung diseases.
ESTHER : Zhang_2023_Redox.Biol_63_102765
PubMedSearch : Zhang_2023_Redox.Biol_63_102765
PubMedID: 37269686

Title : Ecological risk assessment of environmentally relevant concentrations of propofol on zebrafish (Danio rerio) at early life stage: Insight into physiological, biochemical, and molecular aspects - Jiang_2023_Chemosphere__137846
Author(s) : Jiang N , Li X , Wang Q , Baihetiyaer B , Fan X , Li M , Sun H , Yin X , Wang J
Ref : Chemosphere , :137846 , 2023
Abstract : Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L(-1)) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC(50) = 4.260 mg L(-1)), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L(-1) propofol treatment group was activated in response to oxidative damage, while activities of superoxide dismutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L(-1) was significant inhibited compared with the control group (p0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment.
ESTHER : Jiang_2023_Chemosphere__137846
PubMedSearch : Jiang_2023_Chemosphere__137846
PubMedID: 36646180

Title : Novel AP2238-clorgiline hybrids as multi-target agents for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation - Zhong_2022_Bioorg.Chem_130_106224
Author(s) : Zhong G , Guo J , Pang C , Su D , Tang C , Jing L , Zhang F , He P , Yan Y , Chen Z , Liu J , Jiang N
Ref : Bioorg Chem , 130 :106224 , 2022
Abstract : Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC(50) = 4.03 +/- 0.03 microM, eqBuChE: IC(50) = 5.64 +/- 0.53 microM; hAChE: IC(50) = 8.30 +/- 0.04 microM, hBuChE: IC(50) = 1.91 +/- 0.06 microM) and hMAO-B (IC(50) = 3.29 +/- 0.09 microM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 microM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.
ESTHER : Zhong_2022_Bioorg.Chem_130_106224
PubMedSearch : Zhong_2022_Bioorg.Chem_130_106224
PubMedID: 36332315

Title : Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke - Zhang_2022_BMC.Neurol_22_482
Author(s) : Zhang X , Liu L , Jiang N , Liu Y , Wang Q , Tang X , Zhai Q , Zhao L
Ref : BMC Neurol , 22 :482 , 2022
Abstract : BACKGROUND AND AIMS: Cerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS). METHODS: From April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve. RESULTS: CMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79 ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR] = 1.460, 95% confidence interval [CI]: 1.188-1.795, P = 0.000). This correlation persisted after adjusting for relevant risk factors (OR = 1.370, 95% CI: 1.096-1.713, P = 0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36 ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%. CONCLUSIONS: Our data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs.
ESTHER : Zhang_2022_BMC.Neurol_22_482
PubMedSearch : Zhang_2022_BMC.Neurol_22_482
PubMedID: 36517761

Title : Identification and structure-activity relationship exploration of uracil-based benzoic acid and ester derivatives as novel dipeptidyl Peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus - Li_2021_Eur.J.Med.Chem_225_113765
Author(s) : Li Q , Deng X , Jiang N , Meng L , Xing J , Jiang W , Xu Y
Ref : Eur Journal of Medicinal Chemistry , 225 :113765 , 2021
Abstract : Our previously reported carboxyl-containing DPP-4 inhibitors were highly potent but were poorly bioavailable. Esters of the carboxyl analogs exhibited a significant DPP-4 potency loss albeit with enhanced oral absorption. Herein, we described identification and structure-activity relationship (SAR) exploration of a novel series of benzoic acid and ester derivatives as low single-digit nanomolar DPP-4 inhibitors. Importantly, the esters displayed comparable activities to the acids counterparts. Molecular simulation revealed that ester adopts a similar binding mode to acid. Moreover, the selected esters and acids demonstrated high selectivity and low cytotoxicity, as well as good metabolic stability. And more importantly, the esters possessed excellent pharmacokinetic profiles for oral administration. The best compound ester 19b demonstrated long DPP-4 inhibition in vivo, and robustly improved the glucose tolerance in normal and db/db mice while ensuring glucose-lowering potency in chronic treatment. Our results supported that the compound 19b can be served as a potential candidate for the treatment of type 2 diabetes.
ESTHER : Li_2021_Eur.J.Med.Chem_225_113765
PubMedSearch : Li_2021_Eur.J.Med.Chem_225_113765
PubMedID: 34399391

Title : Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease - Wang_2020_RSC.Med.Chem_11_225
Author(s) : Wang XB , Yin FC , Huang M , Jiang N , Lan JS , Kong LY
Ref : RSC Med Chem , 11 :225 , 2020
Abstract : A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC(50) = 5.24 microM; AChE: IC(50) = 0.37 microM) and hMAO-B selectivity (IC(50) = 0.272 microM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.
ESTHER : Wang_2020_RSC.Med.Chem_11_225
PubMedSearch : Wang_2020_RSC.Med.Chem_11_225
PubMedID: 33479629

Title : Novel chromanone-dithiocarbamate hybrids as multifunctional AChE inhibitors with beta-amyloid anti-aggregation properties for the treatment of Alzheimer's disease - Jiang_2019_Bioorg.Chem_89_103027
Author(s) : Jiang N , Ding J , Liu J , Sun X , Zhang Z , Mo Z , Li X , Yin H , Tang W , Xie SS
Ref : Bioorg Chem , 89 :103027 , 2019
Abstract : By connecting chromanone with dithiocarbamate moieties through flexible linkers, a series of hybrids as novel multifunctional AChE inhibitors have been designed and synthesized. Most of these compounds displayed strong and excellently selective inhibition to eeAChE as well as potent inhibition to self- and AChE-induced Abeta aggregation. Among them, compound 6c showed the best activity to inhibit eeAChE (IC50=0.10muM) and AChE-induced Abeta aggregation (33.02% at 100muM), and could effectively inhibit self-induced Abeta aggregation (38.25% at 25muM). Kinetic analysis and docking study indicated that compound 6c could target both the CAS and PAS, suggesting that it was a dual binding site inhibitor for AChE. Besides, it exhibited good ability to penetrate the BBB and low neurotoxicity in SH-SY5Y cells. More importantly, compound 6c was well tolerated in mice (2500mg/kg, po) and could attenuate the memory impairment in a scopolamine-induced mouse model. Overall, these results highlight 6c as a promising multifunctional agent for treating AD and also demonstrate that the dithiocarbamate is a valid scaffold for design of multifunctional AChE inhibitors.
ESTHER : Jiang_2019_Bioorg.Chem_89_103027
PubMedSearch : Jiang_2019_Bioorg.Chem_89_103027
PubMedID: 31176237

Title : Neuroprotective effects of 20(S)-protopanaxatriol (PPT) on scopolamine-induced cognitive deficits in mice - Lu_2018_Phytother.Res_32_1056
Author(s) : Lu C , Lv J , Dong L , Jiang N , Wang Y , Wang Q , Li Y , Chen S , Fan B , Wang F , Liu X
Ref : Phytother Res , 32 :1056 , 2018
Abstract : 20(S)-protopanaxatriol (PPT), one of the ginsenosides from Panax ginseng, has been reported to have neuroprotective effects and to improve memory. The present study was designed to investigate the protective effect of PPT on scopolamine-induced cognitive deficits in mice. Male Institute of Cancer Research mice were pretreated with 2 different doses of PPT (20 and 40 mumol/kg) for 27 days by intraperitoneal injection, and scopolamine (0.75 mg/kg) was injected intraperitoneally for 9 days to induce memory impairment. Thirty minutes after the last pretreatment, the locomotor activity was firstly examined to evaluate the motor function of mice. Then, memory-related behaviors were evaluated, and the related mechanism was further researched. It was founded that PPT treatment significantly reversed scopolamine-induced cognitive impairment in the object location recognition experiment, the Morris water maze test, and the passive avoidance task, showing memory-improving effects. PPT also significantly improved cholinergic system reactivity and suppressed oxidative stress, indicated by inhibition of acetylcholinesterase activity, elevation of acetylcholine levels, increasing superoxide dismutase activity and lowering levels of malondialdehyde in the hippocampus. In addition, the expression levels of Egr-1, c-Jun, and cAMP responsive element binding in the hippocampus were significantly elevated by PPT administration. These results suggest that PPT may be a potential drug candidate for the treatment of cognitive deficit in Alzheimer's disease.
ESTHER : Lu_2018_Phytother.Res_32_1056
PubMedSearch : Lu_2018_Phytother.Res_32_1056
PubMedID: 29468740

Title : Effects of Late Evening Snack on Cirrhotic Patients: A Systematic Review and Meta-Analysis - Guo_2018_Gastroenterol.Res.Pract_2018_9189062
Author(s) : Guo YJ , Tian ZB , Jiang N , Ding XL , Mao T , Jing X
Ref : Gastroenterol Res Pract , 2018 :9189062 , 2018
Abstract : Background: Energetic effects of late evening snack (LES) on cirrhotic patients were reported recently, but there was no quantitative analysis. In this meta-analysis, we reviewed and quantified the effects of LES on energy metabolism and substrate oxidation in the patients with cirrhosis, which will be of benefit for liver cirrhosis nutritional therapy. Methods: A systematic search was conducted in PubMed, Embase, Web of Science, Elsevier, China National Knowledge Infrastructure, and Wanfang Database for relevant trials published until July 2017. These studies statistically were combined and analyzed by RevMan 5.3. Results: Fourteen trials comprising 478 cases were eligible for analysis. The results showed that the respiratory quotient value (MD = 11.09) and carbohydrate oxidation value (MD = 0.05) significantly elevated with one week or with up to three weeks of LES treatment in cirrhotic patients (P < 0.05). Meanwhile, the levels of serum albumin (MD = 2.98) and cholinesterase (SMD = 1.09) were increased with LES administration for three weeks or that lasting twelve weeks (P < 0.05). However, there was no significant improvement for the levels of alanine aminotransferase (ALT) (P = 0.53), aspartate aminotransferase (AST) (P = 0.96), and total bilirubin (TB) (P = 0.32). Conclusions: LES could improve the energy malnutrition state of cirrhotic patients. However, it may have little effect on reducing liver parenchymal injury indexes such as serum aminotransferase.
ESTHER : Guo_2018_Gastroenterol.Res.Pract_2018_9189062
PubMedSearch : Guo_2018_Gastroenterol.Res.Pract_2018_9189062
PubMedID: 29805447

Title : Design, synthesis and biological evaluation of new coumarin-dithiocarbamate hybrids as multifunctional agents for the treatment of Alzheimer's disease - Jiang_2018_Eur.J.Med.Chem_146_287
Author(s) : Jiang N , Huang Q , Liu J , Liang N , Li Q , Xie SS
Ref : Eur Journal of Medicinal Chemistry , 146 :287 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's Disease (AD). The biological assays indicated that most of them showed potent inhibition and excellent selectivity towards acetylcholinesterase (AChE), and could inhibit self-induced beta-amyloid (Abeta) aggregation. Especially, compound 4n presented the highest ability to inhibit AChE (IC50, 0.027muM for hAChE) and good inhibition of Abeta aggregation (40.19% at 25muM). Kinetic and molecular modeling studies revealed that 4n was a mixed-type inhibitor, which could interact simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, it also possessed specific metal-chelating ability, good BBB permeability and low toxicity on SH-SY5Y neuroblastoma cells. Moreover, compound 4n did not exhibit any acute toxicity in mice at doses up to 1000mg/kg, and could reverse the cognitive dysfunction of scopolamine-induced AD mice. As far as we know, 4n was the first reported dithiocarbamate derivative with multifunctional activity. Its excellent profiles in vitro and effectivity in vivo highlight this structurally distinct compound as a potential lead compound in the research of innovative multifunctional drugs for AD.
ESTHER : Jiang_2018_Eur.J.Med.Chem_146_287
PubMedSearch : Jiang_2018_Eur.J.Med.Chem_146_287
PubMedID: 29407958

Title : Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits - Zhang_2018_Cardiovasc.Diabetol_17_160
Author(s) : Zhang X , Zhang Z , Yang Y , Suo Y , Liu R , Qiu J , Zhao Y , Jiang N , Liu C , Tse G , Li G , Liu T
Ref : Cardiovasc Diabetol , 17 :160 , 2018
Abstract : BACKGROUND: There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. METHODS: A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-beta1, NF-kappaB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. RESULTS: DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1alpha/NRF1/Tfam signaling pathway. CONCLUSIONS: The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis.
ESTHER : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedSearch : Zhang_2018_Cardiovasc.Diabetol_17_160
PubMedID: 30591063

Title : Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation - He_2018_Bioorg.Chem_81_512
Author(s) : He Q , Liu J , Lan JS , Ding J , Sun Y , Fang Y , Jiang N , Yang Z , Sun L , Jin Y , Xie SS
Ref : Bioorg Chem , 81 :512 , 2018
Abstract : A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold.
ESTHER : He_2018_Bioorg.Chem_81_512
PubMedSearch : He_2018_Bioorg.Chem_81_512
PubMedID: 30245233

Title : Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer's disease - Xie_2016_Bioorg.Med.Chem_24_1528
Author(s) : Xie SS , Lan JS , Wang X , Wang ZM , Jiang N , Li F , Wu JJ , Wang J , Kong LY
Ref : Bioorganic & Medicinal Chemistry , 24 :1528 , 2016
Abstract : Combining N-benzylpiperidine moiety of donepezil and coumarin into in a single molecule, novel hybrids with ChE and MAO-B inhibitory activity were designed and synthesized. The biological screening results indicated that most of compounds displayed potent inhibitory activity for AChE and BuChE, and clearly selective inhibition to MAO-B. Of these compounds, 5m was the most potent inhibitor for eeAChE and eqBuChE (0.87muM and 0.93muM, respectively), and it was also a good and balanced inhibitor to hChEs and hMAO-B (1.37muM for hAChE; 1.98muM for hBuChE; 2.62muM for hMAO-B). Molecular modeling and kinetic studies revealed that 5m was a mixed-type inhibitor, which bond simultaneously to CAS, PAS and mid-gorge site of AChE, and it was also a competitive inhibitor, which occupied the active site of MAO-B. In addition, 5m showed good ability to cross the BBB and had no toxicity on SH-SY5Y neuroblastoma cells. Collectively, all these results suggested that 5m might be a promising multi-target lead candidate worthy of further pursuit.
ESTHER : Xie_2016_Bioorg.Med.Chem_24_1528
PubMedSearch : Xie_2016_Bioorg.Med.Chem_24_1528
PubMedID: 26917219

Title : Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer's disease - Xie_2015_Eur.J.Med.Chem_95_153
Author(s) : Xie SS , Wang X , Jiang N , Yu W , Wang KD , Lan JS , Li ZR , Kong LY
Ref : Eur Journal of Medicinal Chemistry , 95 :153 , 2015
Abstract : A series of novel tacrine-coumarin hybrids were designed, synthesized and evaluated as multi-target agents against Alzheimer's disease. The biological assays indicated that most of compounds displayed potent inhibitory activity toward AChE and BCHE, and clearly selective inhibition for MAO-B. Among these compounds, 14c exhibited strong inhibitory activity for AChE (IC50 values of 33.63 nM for eeAChE and 16.11 nM for hAChE) and BCHE (IC50 values of 80.72 nM for eqBCHE and 112.72 nM for hBCHE), and the highest inhibitory activity against hMAO-B (IC50 value of 0.24 muM). Kinetic and molecular modeling studies revealed that 14c was a mixed-type inhibitor, binding simultaneously to catalytic, peripheral and mid-gorge sites of AChE. It was also a competitive inhibitor, which covered the substrate and entrance cavities of MAO-B. Moreover, 14c could penetrate the CNS and show low cell toxicity. Overall, these results suggested that 14c might be an excellent multi-target agent for AD treatment.
ESTHER : Xie_2015_Eur.J.Med.Chem_95_153
PubMedSearch : Xie_2015_Eur.J.Med.Chem_95_153
PubMedID: 25812965

Title : Multifunctional tacrine-trolox hybrids for the treatment of Alzheimer's disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties - Xie_2015_Eur.J.Med.Chem_93C_42
Author(s) : Xie SS , Lan JS , Wang XB , Jiang N , Dong G , Li ZR , Wang KD , Guo PP , Kong LY
Ref : Eur Journal of Medicinal Chemistry , 93C :42 , 2015
Abstract : Combining tacrine with trolox in a single molecule, novel multifunctional hybrids have been designed and synthesized. All these hybrids showed ChE inhibitory activity in nanomolar range and strong antioxidant activity close to the parent compound trolox. Among them, compound 6d was the most potent inhibitor against AChE (IC50 value of 9.8 nM for eeAChE and 23.5 nM for hAChE), and it was also a strong inhibitor to BCHE (IC50 value of 22.2 nM for eqBCHE and 20.5 nM for hBCHE). Molecular modeling and kinetic studies suggested that 6d was a mixed-type inhibitor, binding simultaneously to CAS and PAS of AChE. In vivo hepatotoxicity assays indicated that 6d was much less toxic than tacrine. In addition, it showed neuroprotective effect and good ability to penetrate the BBB. Overall, all these results highlighted 6d a promising multifunctional agent for AD treatment.
ESTHER : Xie_2015_Eur.J.Med.Chem_93C_42
PubMedSearch : Xie_2015_Eur.J.Med.Chem_93C_42
PubMedID: 25656088

Title : Pictet-Spengler reaction-based biosynthetic machinery in fungi - Yan_2014_Proc.Natl.Acad.Sci.U.S.A_111_18138
Author(s) : Yan W , Ge HM , Wang G , Jiang N , Mei YN , Jiang R , Li SJ , Chen CJ , Jiao RH , Xu Q , Ng SW , Tan RX
Ref : Proc Natl Acad Sci U S A , 111 :18138 , 2014
Abstract : The Pictet-Spengler (PS) reaction constructs plant alkaloids such as morphine and camptothecin, but it has not yet been noticed in the fungal kingdom. Here, a silent fungal Pictet-Spenglerase (FPS) gene of Chaetomium globosum 1C51 residing in Epinephelus drummondhayi guts is described and ascertained to be activable by 1-methyl-L-tryptophan (1-MT). The activated FPS expression enables the PS reaction between 1-MT and flavipin (fungal aldehyde) to form "unnatural" natural products with unprecedented skeletons, of which chaetoglines B and F are potently antibacterial with the latter inhibiting acetylcholinesterase. A gene-implied enzyme inhibition (GIEI) strategy has been introduced to address the key steps for PS product diversifications. In aggregation, the work designs and validates an innovative approach that can activate the PS reaction-based fungal biosynthetic machinery to produce unpredictable compounds of unusual and novel structure valuable for new biology and biomedicine.
ESTHER : Yan_2014_Proc.Natl.Acad.Sci.U.S.A_111_18138
PubMedSearch : Yan_2014_Proc.Natl.Acad.Sci.U.S.A_111_18138
PubMedID: 25425666

Title : Persistent Na and K channel dysfunctions after chronic exposure to insecticides and pyridostigmine bromide - Nutter_2013_Neurotoxicol_39C_72
Author(s) : Nutter TJ , Jiang N , Cooper BY
Ref : Neurotoxicology , 39C :72 , 2013
Abstract : Many soldiers that served in the 1991 Gulf War developed widespread chronic pain. Exposure to insecticides and the nerve gas prophylactic pyridostigmine bromide (PB) was identified as risk factors by the Research Advisory Committee on Gulf War Veterans' Illnesses (GWI). We examined whether a 60 day exposure to neurotoxicants/PB (NTPB) produced behavioral, molecular and cellular indices of chronic pain in the rat. Male rats were exposed to chlorpyrifos (120mg/kg; SC), permethrin (2.6mg/kg; topical), and PB (13.0mg/kg; oral) or their respective vehicles (corn oil, ethanol, and water). Permethrin can exert profound influences on voltage activated Na+ channel proteins; while chlorpyrifos and PB can increase absorption and/or retard metabolism of permethrin as well as inhibit cholinesterases. During and after exposure to these agents, we assessed muscle pressure pain thresholds and activity (distance and rest time). Eight and 12 weeks after treatments ceased, we used whole cell patch electrophysiology to examine the physiology of tissue specific DRG nociceptor channel proteins expressed in muscle and putative vascular nociceptors (voltage dependent, activation, inactivation, and deactivation). Behavioral indices were unchanged after treatment with NTPB. Eight weeks after treatments ended, the peak and average conductance of Kv7 mediated K+ currents were significantly increased in vascular nociceptors. When a specific Kv7 inhibitor was applied (linopirdine, 10muM) NTPB treated vascular nociceptors emitted significantly more spontaneous APs than vehicle treated neurons. Changes to Kv7 channel physiology were resolved 12 weeks after treatment. The molecular alterations to Kv7 channel proteins and the specific susceptibility of the vascular nociceptor population could be important for the etiology of GWI pain.
ESTHER : Nutter_2013_Neurotoxicol_39C_72
PubMedSearch : Nutter_2013_Neurotoxicol_39C_72
PubMedID: 23994030

Title : Hopeahainol A attenuates memory deficits by targeting beta-amyloid in APP\/PS1 transgenic mice - Zhu_2013_Aging.Cell_12_85
Author(s) : Zhu X , Ye L , Ge H , Chen L , Jiang N , Qian L , Li L , Liu R , Ji S , Zhang S , Jin J , Guan D , Fang W , Tan R , Xu Y
Ref : Aging Cell , 12 :85 , 2013
Abstract : Increasing evidence demonstrates that amyloid beta (Abeta) elicits mitochondrial dysfunction and oxidative stress, which contributes to the pathogenesis of Alzheimer's disease (AD). Identification of the molecules targeting Abeta is thus of particular significance in the treatment of AD. Hopeahainol A (HopA), a polyphenol with a novel skeleton obtained from Hopea hainanensis, is potentially acetylcholinesterase-inhibitory and anti-oxidative in H(2) O(2) -treated PC12 cells. In this study, we reported that HopA might bind to Abeta(1-42) directly and inhibit the Abeta(1-42) aggregation using a combination of molecular dynamics simulation, binding assay, transmission electron microscopic analysis and staining technique. We also demonstrated that HopA decreased the interaction between Abeta(1-42) and Abeta-binding alcohol dehydrogenase, which in turn reduced mitochondrial dysfunction and oxidative stress in vivo and in vitro. In addition, HopA was able to rescue the long-term potentiation induction by protecting synaptic function and attenuate memory deficits in APP/PS1 mice. Our data suggest that HopA might be a promising drug for therapeutic intervention in AD.
ESTHER : Zhu_2013_Aging.Cell_12_85
PubMedSearch : Zhu_2013_Aging.Cell_12_85
PubMedID: 23107435

Title : Multifunctional tacrine-flavonoid hybrids with cholinergic, beta-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease - Li_2013_Eur.J.Med.Chem_69C_632
Author(s) : Li SY , Wang XB , Xie SS , Jiang N , Wang KD , Yao HQ , Sun HB , Kong LY
Ref : Eur Journal of Medicinal Chemistry , 69C :632 , 2013
Abstract : A new series of tacrine-flavonoid hybrids (13a-u) had been designed, synthesized, and evaluated as multifunctional cholinesterase (ChE) inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of the molecules exhibited a significant ability to inhibit ChE and self-induced amyloid-beta (Abeta1-42) aggregation. Kinetic and molecular modeling studies also indicated compounds were mixed-type inhibitors, binding simultaneously to active, peripheral and mid-gorge sites of AChE. Particularly, compound 13k was found to be highly potent and showed a balanced inhibitory profile against ChE and self-induced Abeta1-42 aggregation. Moreover, it also showed excellent metal chelating property and low cell toxicity. These results suggested that 13k might be an excellent multifunctional agent for AD treatment.
ESTHER : Li_2013_Eur.J.Med.Chem_69C_632
PubMedSearch : Li_2013_Eur.J.Med.Chem_69C_632
PubMedID: 24095756

Title : Genome of the long-living sacred lotus (Nelumbo nucifera Gaertn.) - Ming_2013_Genome.Biol_14_R41
Author(s) : Ming R , VanBuren R , Liu Y , Yang M , Han Y , Li LT , Zhang Q , Kim MJ , Schatz MC , Campbell M , Li J , Bowers JE , Tang H , Lyons E , Ferguson AA , Narzisi G , Nelson DR , Blaby-Haas CE , Gschwend AR , Jiao Y , Der JP , Zeng F , Han J , Min XJ , Hudson KA , Singh R , Grennan AK , Karpowicz SJ , Watling JR , Ito K , Robinson SA , Hudson ME , Yu Q , Mockler TC , Carroll A , Zheng Y , Sunkar R , Jia R , Chen N , Arro J , Wai CM , Wafula E , Spence A , Xu L , Zhang J , Peery R , Haus MJ , Xiong W , Walsh JA , Wu J , Wang ML , Zhu YJ , Paull RE , Britt AB , Du C , Downie SR , Schuler MA , Michael TP , Long SP , Ort DR , Schopf JW , Gang DR , Jiang N , Yandell M , dePamphilis CW , Merchant SS , Paterson AH , Buchanan BB , Li S , Shen-Miller J
Ref : Genome Biol , 14 :R41 , 2013
Abstract : BACKGROUND: Sacred lotus is a basal eudicot with agricultural, medicinal, cultural and religious importance. It was domesticated in Asia about 7,000 years ago, and cultivated for its rhizomes and seeds as a food crop. It is particularly noted for its 1,300-year seed longevity and exceptional water repellency, known as the lotus effect. The latter property is due to the nanoscopic closely packed protuberances of its self-cleaning leaf surface, which have been adapted for the manufacture of a self-cleaning industrial paint, Lotusan. RESULTS: The genome of the China Antique variety of the sacred lotus was sequenced with Illumina and 454 technologies, at respective depths of 101x and 5.2x. The final assembly has a contig N50 of 38.8 kbp and a scaffold N50 of 3.4 Mbp, and covers 86.5% of the estimated 929 Mbp total genome size. The genome notably lacks the paleo-triplication observed in other eudicots, but reveals a lineage-specific duplication. The genome has evidence of slow evolution, with a 30% slower nucleotide mutation rate than observed in grape. Comparisons of the available sequenced genomes suggest a minimum gene set for vascular plants of 4,223 genes. Strikingly, the sacred lotus has 16 COG2132 multi-copper oxidase family proteins with root-specific expression; these are involved in root meristem phosphate starvation, reflecting adaptation to limited nutrient availability in an aquatic environment. CONCLUSIONS: The slow nucleotide substitution rate makes the sacred lotus a better resource than the current standard, grape, for reconstructing the pan-eudicot genome, and should therefore accelerate comparative analysis between eudicots and monocots.
ESTHER : Ming_2013_Genome.Biol_14_R41
PubMedSearch : Ming_2013_Genome.Biol_14_R41
PubMedID: 23663246
Gene_locus related to this paper: nelnu-a0a1u8aj84 , nelnu-a0a1u8bpe4 , nelnu-a0a1u7z9m9 , nelnu-a0a1u7ywy5 , nelnu-a0a1u8aik2 , nelnu-a0a1u7zmb5 , nelnu-a0a1u8a7m7 , nelnu-a0a1u8b0n9 , nelnu-a0a1u8b461 , nelnu-a0a1u7zzj3 , nelnu-a0a1u8ave7 , nelnu-a0a1u7yn26

Title : Draft genome sequence of Alicyclobacillus hesperidum strain URH17-3-68 - Wang_2012_J.Bacteriol_194_6348
Author(s) : Wang P , Li L , Chen X , Jiang N , Liu G , Chen L , Xu J , Song H , Chen Z , Ma Y
Ref : Journal of Bacteriology , 194 :6348 , 2012
Abstract : Alicyclobacillus hesperidum is a thermoacidophilic bacterium. We isolated strain URH17-3-68 from hot spring sludge in Tengchong, Yunnan province, China. Its extracellular products include heat- and acid-stable enzymes which are important for industrial applications. Here we report the draft genome of this strain.
ESTHER : Wang_2012_J.Bacteriol_194_6348
PubMedSearch : Wang_2012_J.Bacteriol_194_6348
PubMedID: 23105079
Gene_locus related to this paper: 9bacl-h2esd6 , 9bacl-j9e7t9

Title : Sodium aescinate ameliorates liver injury induced by methyl parathion in rats - Du_2012_Exp.Ther.Med_3_818
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Li C , Li CK , Fu FH
Ref : Exp Ther Med , 3 :818 , 2012
Abstract : Methyl parathion, a highly cytotoxic insecticide, has been used in agricultural pest control for several years. The present study investigated the protective effect of sodium aescinate (SA, the sodium salt of aescin) against liver injury induced by methyl parathion. Forty male Sprague-Dawley rats were randomly divided into 5 groups of 8 animals: the control group; the methyl parathion (15 mg/kg) poisoning (MP) group; and the MP plus SA at doses of 0.45, 0.9 and 1.8 mg/kg groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and acetylcholinesterase (AChE) in the plasma were assayed. Nitric oxide (NO) and antioxidative parameters were measured. Histopathological examination of the liver was also performed. The results revealed that SA had no effect on AChE. Treatment with SA decreased the activities of ALT and AST, and the levels of malondialdehyde and NO. Treatment with SA also increased the level of glutathione and the activities of superoxide dismutase and glutathione peroxidase. SA administration also ameliorated liver injury induced by methyl parathion poisoning. The findings indicate that SA protects against liver injury induced by methyl parathion and that the mechanism of action is related to the antioxidative and anti-inflammatory effects of SA.
ESTHER : Du_2012_Exp.Ther.Med_3_818
PubMedSearch : Du_2012_Exp.Ther.Med_3_818
PubMedID: 22969975

Title : Polyphenolic acetylcholinesterase inhibitors from Hopea chinensis - Yan_2012_Planta.Med_78_1015
Author(s) : Yan T , Wang T , Wei W , Jiang N , Qin YH , Tan RX , Ge HM
Ref : Planta Med , 78 :1015 , 2012
Abstract : Bioassay-guided investigation of the stem bark of Hopea chinensis led to the isolation of two new polyphenols, hopeachinols C(1) and D(2), together with ten known compounds (3-12). Compounds 1 and 2 were determined by extensive analysis of spectroscopic data and computational methods. All of these phytochemicals were tested for acetylcholinesterase inhibitory activity, and five resveratrol-derived compounds (1 and 7-10) exhibited significant activity with their IC(5)(0) values ranging from 4.81 to 11.71 microM.
ESTHER : Yan_2012_Planta.Med_78_1015
PubMedSearch : Yan_2012_Planta.Med_78_1015
PubMedID: 22628156

Title : Steady and fluctuant methods of inhibition of acetylcholinesterase differentially regulate neurotrophic factors in the hippocampus of juvenile mice - Li_2012_Exp.Ther.Med_3_269
Author(s) : Li C , Wang T , Jiang N , Yu P , Du Y , Ren R , Fu F
Ref : Exp Ther Med , 3 :269 , 2012
Abstract : The present study was designed to evaluate the effects of steady and fluctuant inhibition of acetylcholinesterase (AChE) activity on neurotrophic factors in the hippocampus of juvenile mice. Steady inhibition of AChE activity was induced by an intramuscular injection of huperizine A (HupA) sustained-release microspheres. Fluctuant inhibition of AChE activity was induced by an intragastric administration of HupA tablets. Six days after cessation of steady AChE inhibition, there was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In contrast, fluctuant AChE inhibition had no effect on BDNF and NGF levels. Additionally, neither steady nor fluctuant inhibition of AChE activity altered the choline acetyltransferase activity or spatial learning in juvenile mice. These findings indicate that steady and fluctuant methods of inhibition of AChE have different effects on the levels of BDNF and NGF in the hippocampus. In addition, the effects of AChE inhibitors may not improve learning in normal juvenile animals.
ESTHER : Li_2012_Exp.Ther.Med_3_269
PubMedSearch : Li_2012_Exp.Ther.Med_3_269
PubMedID: 22969880

Title : Protective effect of sodium aescinate on lung injury induced by methyl parathion - Du_2011_Hum.Exp.Toxicol_30_1584
Author(s) : Du Y , Wang T , Jiang N , Ren RT , Zhao DL , Li C , Fu FH
Ref : Hum Exp Toxicol , 30 :1584 , 2011
Abstract : Methyl parathion (MP) is a high venenosus insecticide. It has been used in pest control of agriculture for several years. The present study is performed to investigate the protective effect of sodium aescinate (SA) on lung injury induced by MP. Forty male Sprague-Dawley rats are randomly divided into five groups, with 8 animals in each group: control group, MP administration group, MP plus SA at doses of 0.45 mg/kg, 0.9 mg/kg and 1.8 mg/kg groups. Acetylcholinesterase (AChE) activity and nitric oxide (NO) level in plasma, myeloperoxidase (MPO) activity, NO level, and antioxidative parameters in lung tissue are assayed. Histopathological examination of lung is also performed. The results show that SA has no effect on AChE. Treatment with SA decreases the activity of MPO in lung and the level of NO in plasma and lung. The level of malondialdehyde in lung is decreased after SA treatments. SA increases the activities of superoxide dismutase, glutathione peroxidase and the content of glutathione in lung. SA administration also ameliorates lung injury induced by MP. The findings indicate that SA could protect lung injury induced by MP and the mechanism of action is related to the anti-inflammatory and anti-oxidative effect of SA.
ESTHER : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedSearch : Du_2011_Hum.Exp.Toxicol_30_1584
PubMedID: 21177729

Title : Reduced glutathione attenuates liver injury induced by methyl parathion in rats - Jiang_2010_Toxicol.Mech.Methods_20_69
Author(s) : Jiang N , Lu L , Wang T , Zhang L , Xin W , Fu F
Ref : Toxicol Mech Methods , 20 :69 , 2010
Abstract : The aim of this study was to investigate whether exogenous reduced glutathione (GSH) could protect liver injury induced by methyl parathion. Rats were allocated into four groups named as control, MP (methyl parathion poisoning), MP+GSH1 (methyl parathion poisoning treated with GSH 600 mg/kg), and MP+GSH2 (methyl parathion poisoning treated with GSH 1200 mg/kg). Each one of the last three groups was assigned into 6 h, 24 h, and 72 h sub-groups. The activities of acetylcholinesterase (AChE), glutamate pyruvate transaminase (GPT), and glutamic oxalacetic transaminase (GOT) in plasma, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver were assayed. The malondialdehyde (MDA) in liver was also determined. Histopathological changes in liver were observed. Results showed that AChE activity was significantly inhibited by methyl parathion and attenuated after GSH administered. GSH could relieve hepatocellular edema and fatty degeneration, and attenuate the increased activities of GPT and GOT. GSH treatment increased the SOD and GPx activities, but had no effect on the MDA level. These results indicated that GSH could attenuate liver injury induced by methyl parathion.
ESTHER : Jiang_2010_Toxicol.Mech.Methods_20_69
PubMedSearch : Jiang_2010_Toxicol.Mech.Methods_20_69
PubMedID: 20100039

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

Title : The B73 maize genome: complexity, diversity, and dynamics - Schnable_2009_Science_326_1112
Author(s) : Schnable PS , Ware D , Fulton RS , Stein JC , Wei F , Pasternak S , Liang C , Zhang J , Fulton L , Graves TA , Minx P , Reily AD , Courtney L , Kruchowski SS , Tomlinson C , Strong C , Delehaunty K , Fronick C , Courtney B , Rock SM , Belter E , Du F , Kim K , Abbott RM , Cotton M , Levy A , Marchetto P , Ochoa K , Jackson SM , Gillam B , Chen W , Yan L , Higginbotham J , Cardenas M , Waligorski J , Applebaum E , Phelps L , Falcone J , Kanchi K , Thane T , Scimone A , Thane N , Henke J , Wang T , Ruppert J , Shah N , Rotter K , Hodges J , Ingenthron E , Cordes M , Kohlberg S , Sgro J , Delgado B , Mead K , Chinwalla A , Leonard S , Crouse K , Collura K , Kudrna D , Currie J , He R , Angelova A , Rajasekar S , Mueller T , Lomeli R , Scara G , Ko A , Delaney K , Wissotski M , Lopez G , Campos D , Braidotti M , Ashley E , Golser W , Kim H , Lee S , Lin J , Dujmic Z , Kim W , Talag J , Zuccolo A , Fan C , Sebastian A , Kramer M , Spiegel L , Nascimento L , Zutavern T , Miller B , Ambroise C , Muller S , Spooner W , Narechania A , Ren L , Wei S , Kumari S , Faga B , Levy MJ , McMahan L , Van Buren P , Vaughn MW , Ying K , Yeh CT , Emrich SJ , Jia Y , Kalyanaraman A , Hsia AP , Barbazuk WB , Baucom RS , Brutnell TP , Carpita NC , Chaparro C , Chia JM , Deragon JM , Estill JC , Fu Y , Jeddeloh JA , Han Y , Lee H , Li P , Lisch DR , Liu S , Liu Z , Nagel DH , McCann MC , SanMiguel P , Myers AM , Nettleton D , Nguyen J , Penning BW , Ponnala L , Schneider KL , Schwartz DC , Sharma A , Soderlund C , Springer NM , Sun Q , Wang H , Waterman M , Westerman R , Wolfgruber TK , Yang L , Yu Y , Zhang L , Zhou S , Zhu Q , Bennetzen JL , Dawe RK , Jiang J , Jiang N , Presting GG , Wessler SR , Aluru S , Martienssen RA , Clifton SW , McCombie WR , Wing RA , Wilson RK
Ref : Science , 326 :1112 , 2009
Abstract : We report an improved draft nucleotide sequence of the 2.3-gigabase genome of maize, an important crop plant and model for biological research. Over 32,000 genes were predicted, of which 99.8% were placed on reference chromosomes. Nearly 85% of the genome is composed of hundreds of families of transposable elements, dispersed nonuniformly across the genome. These were responsible for the capture and amplification of numerous gene fragments and affect the composition, sizes, and positions of centromeres. We also report on the correlation of methylation-poor regions with Mu transposon insertions and recombination, and copy number variants with insertions and/or deletions, as well as how uneven gene losses between duplicated regions were involved in returning an ancient allotetraploid to a genetically diploid state. These analyses inform and set the stage for further investigations to improve our understanding of the domestication and agricultural improvements of maize.
ESTHER : Schnable_2009_Science_326_1112
PubMedSearch : Schnable_2009_Science_326_1112
PubMedID: 19965430
Gene_locus related to this paper: maize-b4ffc7 , maize-b6u7e1 , maize-c0pcy5 , maize-c0pgf7 , maize-c0pgw1 , maize-c0pfl3 , maize-b4fpr7 , maize-k7vy73 , maize-a0a096swr3 , maize-k7v3i9 , maize-b6u9v9 , maize-a0a3l6e780 , maize-b4fv80 , maize-a0a1d6nse2 , maize-c4j9a1 , maize-k7uba1

Title : Dynamic evolution of oryza genomes is revealed by comparative genomic analysis of a genus-wide vertical data set - Ammiraju_2008_Plant.Cell_20_3191
Author(s) : Ammiraju JS , Lu F , Sanyal A , Yu Y , Song X , Jiang N , Pontaroli AC , Rambo T , Currie J , Collura K , Talag J , Fan C , Goicoechea JL , Zuccolo A , Chen J , Bennetzen JL , Chen M , Jackson S , Wing RA
Ref : Plant Cell , 20 :3191 , 2008
Abstract : Oryza (23 species; 10 genome types) contains the world's most important food crop - rice. Although the rice genome serves as an essential tool for biological research, little is known about the evolution of the other Oryza genome types. They contain a historical record of genomic changes that led to diversification of this genus around the world as well as an untapped reservoir of agriculturally important traits. To investigate the evolution of the collective Oryza genome, we sequenced and compared nine orthologous genomic regions encompassing the Adh1-Adh2 genes (from six diploid genome types) with the rice reference sequence. Our analysis revealed the architectural complexities and dynamic evolution of this region that have occurred over the past approximately 15 million years. Of the 46 intact genes and four pseudogenes in the japonica genome, 38 (76%) fell into eight multigene families. Analysis of the evolutionary history of each family revealed independent and lineage-specific gain and loss of gene family members as frequent causes of synteny disruption. Transposable elements were shown to mediate massive replacement of intergenic space (>95%), gene disruption, and gene/gene fragment movement. Three cases of long-range structural variation (inversions/deletions) spanning several hundred kilobases were identified that contributed significantly to genome diversification.
ESTHER : Ammiraju_2008_Plant.Cell_20_3191
PubMedSearch : Ammiraju_2008_Plant.Cell_20_3191
PubMedID: 19098269

Title : Apolipoprotein E genotype as a determinant of survival in chronic lymphocytic leukemia - Weinberg_2008_Leukemia_22_2184
Author(s) : Weinberg JB , Volkheimer AD , Mihovilovic M , Jiang N , Chen Y , Bond K , Moore JO , Gockerman JP , Diehl LF , de Castro CM , Rizzieri DA , Levesque MC , Dekroon R , Strittmatter WJ
Ref : Leukemia , 22 :2184 , 2008
Abstract : Survival of chronic lymphocytic leukemia (CLL) cells requires sustained activation of the antiapoptotic PI-3-K/Akt pathway, and many therapies for CLL cause leukemia cell death by triggering apoptosis. Blood lipoprotein particles are either pro- or antiapoptotic. High-density lipoprotein particles are antiapoptotic through sphingosine-1-phosphate receptor 3-mediated activation of the PI-3-K/Akt pathway. Apolipoprotein E4 (apoE4)-very low density lipoproteins (VLDL) increase apoptosis, but the apoE2-VLDL and apoE3-VLDL isoforms do not. As increased B-cell apoptosis favors longer survival of CLL patients, we hypothesized that APOE4 genotype would beneficially influence the clinical course of CLL. We report here that women (but not men) with an APOE4 genotype had markedly longer survival than non-APOE4 patients. VLDL is metabolized to low-density lipoprotein through lipoprotein lipase. Higher levels of lipoprotein lipase mRNA in these CLL patients correlated with shorter survival. The beneficial effect of APOE4 in CLL survival is likely mediated through APOE4 allele-specific regulation of leukemia cell apoptosis. The APOE allele and genotype distribution in these CLL patients is the same as in unaffected control populations, suggesting that although APOE genotype influences CLL outcome and response to therapy, it does not alter susceptibility to developing this disease.
ESTHER : Weinberg_2008_Leukemia_22_2184
PubMedSearch : Weinberg_2008_Leukemia_22_2184
PubMedID: 18784741

Title : [Effects of 90-day oral dimethoate exposure on glutamatergic system and neurobehavioral performance in rats] - Wu_2007_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_25_513
Author(s) : Wu QE , Yao XM , Ban TT , Jiang N , Shao CF , Chang XL , Zhou ZJ
Ref : Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi , 25 :513 , 2007
Abstract : OBJECTIVE: To investigate the spatial learning and exploration along with the CNS excitatory amino acid neurotransmitters profiles in adult rats subchronically exposed to the anticholinesterase organophosphorus insecticide dimethoate.
METHODS: Rats were gavaged daily with dimethoate (0, 5, 10 or 20 mg/kg via oral) in NS. for 90 days. Morris water maze tasks were used to test the spatial learning and memory in the rats after the dimethoate exposure. Simultaneously, rats were decapitated for the determination of brain cholinesterase AChE activities, glutamate concentrations, and the NMDA receptor NMDA-R densities and affinities in hippocampus.
RESULTS: Latencies to find a hidden escape platform were significantly longer in dimethoate dosed groups than that of the control group in the place navigation tests. Subsequently, the times of crossing the location of platform which had been removed obviously decreased in the highest dose group compared with that of the control in the spatial probe tests (P < 0.05). AChE activity was significantly reduced 42% approximately 78% by all three doses of dimethoate (P < 0.05). Glutamate concentrations were increased significantly 132.9% approximately 134.5% by the two highest doses of dimethoate (P < 0.05). In addition, the NMDA receptor bindings were reduced 21.2% approximately 23.2% with the statistical significance at the same two highest doses (P < 0.05). Furthermore, the receptor affinities was reduced 33.1% by the highest dose group (P < 0.05). The lesions of spatial memory were statistically corrected with the decrease of the NMDA-R affinities (P < 0.05). CONCLUSION: The cholinergic lesion as well as the excitatory amino acid system alteration might attribute to the inferior ability in spatial learning and memory in dimethoate subchronically exposed rats.
ESTHER : Wu_2007_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_25_513
PubMedSearch : Wu_2007_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_25_513
PubMedID: 17997881

Title : Tobacco smoke dysregulates endothelial vasoregulatory transcripts in vivo - Maresh_2005_Physiol.Genomics_21_308
Author(s) : Maresh JG , Xu H , Jiang N , Gairola CG , Shohet RV
Ref : Physiol Genomics , 21 :308 , 2005
Abstract : We hypothesized that human smoking and its deleterious effects on endothelial function can be modeled by exposure of mice to tobacco smoke, and further that these changes would be reflected in gene regulation in vascular endothelium. We used for these studies a mouse strain that expresses green fluorescent protein under the control of an endothelial-specific promoter, Tie-2. Mice were exposed to sidestream smoke from reference cigarettes at 34 mg total suspended particulates/m3. After exposure for 5 days/wk for 1 and 6 wk, aortas were pooled from treatment and control groups. Endothelial cells were rapidly isolated by collagenase treatment followed by fluorescent activated cell sorting to yield populations of >95% purity. RNA isolated from >500 endothelial cells was amplified and analyzed on deeply representative long oligo microarrays. Transcripts dysregulated by >2.5-fold were confirmed by real-time PCR and selected proteins by immunofluorescent localization. In the endothelial cells, the observed more than threefold upregulation of complement factor H (Cfh), calcitonin receptor-like (Calcr1), and soluble epoxide hydrolase (Epxh2) may play a role in hypertensive responses of the vasculature to smoking. We have identified gene regulation in vivo in vascular endothelium that potentially underlies hypertensive responses to tobacco smoke.
ESTHER : Maresh_2005_Physiol.Genomics_21_308
PubMedSearch : Maresh_2005_Physiol.Genomics_21_308
PubMedID: 15728332