Gao H

References (43)

Title : The transcription factor CREB3-2 regulated neutral lipase gene expression in ovary of Nilaparvata lugens - Lin_2023_Pestic.Biochem.Physiol_196_105632
Author(s) : Lin X , Zhang H , Gao H , Yuan X , Liu Z
Ref : Pestic Biochem Physiol , 196 :105632 , 2023
Abstract : The cyclic AMP-responsive element-binding protein 3 (CREB3) members have unique regulatory roles in cellular lipid metabolism as transcription factors. Two CREB3 proteins in Nilaparvata lugens were identified and analyzed. In ovary, when silencing NlCREB3-2, triacylglycerol (TAG) content dramatically increased but glycerol and free fatty acid (FFA) significantly decreased, which implicated that NlCREB3-2 was involved in the lipase-related TAG metabolism. In N. lugens, five neutral lipases with complete features for TAG hydrolytic activity and high expression in ovary were focused. Among them, the expression levels of three neutral lipase genes were significantly down-regulated by NlCREB3-2 RNAi. The direct regulation of NlCREB3-2 towards the three neutral lipase genes was evidenced by the dual-luciferase reporter assay. After jointly silencing three neutral lipase genes, TAG and glycerol contents displayed similar changes as NlCREB3-2 RNAi. The study proved that NlCREB3-2 participated in TAG metabolism in ovary via the direct activation towards the ovary-specific neutral lipase genes.
ESTHER : Lin_2023_Pestic.Biochem.Physiol_196_105632
PubMedSearch : Lin_2023_Pestic.Biochem.Physiol_196_105632
PubMedID: 37945264

Title : Changes in the VOC of Fruits at Different Refrigeration Stages of 'Ruixue' and the Participation of Carboxylesterase MdCXE20 in the Catabolism of Volatile Esters - Li_2023_Foods_12_1977
Author(s) : Li D , Guo J , Ma H , Pei L , Liu X , Wang H , Chen R , Zhao Z , Gao H
Ref : Foods , 12 :1977 , 2023
Abstract : Aroma is a crucial quality attribute of apple fruit, which significantly impacts its commercial value and consumer choice. Despite its importance the volatile aroma substances produced by the new variety 'Ruixue' after harvest remain unclear. In this study, we utilized headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) to investigate the changes in volatile substances, fruit hardness, crispness, and related aroma synthase activity of commercially mature 'Ruixue' apples during cold storage. Our findings revealed a gradual decline in fruit firmness and brittleness of 'Ruixue' apples during cold storage, with hexyl acetate, hexyl caproate, and hexyl thiocyanate being the main hexyl esters detected. To gain a better understanding of the metabolic pathway of esters, we identified 42 MdCXE gene members that are associated with ester degradation. Through RT-qPCR analysis, we discovered that carboxylesterase MdCXE20 exhibited higher expression levels compared to other MdCXE genes during cold storage. To confirm the role of MdCXE20, we conducted a transient injection of apple fruits and observed that overexpression of MdCXE20 led to the degradation of esters such as hexyl hexanoate, butyl hexanoate, butyl 2-methylbutyrate, hexyl butyrate, and hexyl 2-methylbutyrate. The results of the study showed that the virus-induced gene silencing of MdCXE20 found the opposite results. Additionally, the esters of OE-MdCXE20 callus showed a lower content of ester VOC than the control callus, according to the homologous stable transformation of 'Wanglin' callus. Overall, these findings suggest that the MdCXE20 gene plays a crucial role in the decrease of esters in 'Ruixue' apples, which ultimately affects their flavor.
ESTHER : Li_2023_Foods_12_1977
PubMedSearch : Li_2023_Foods_12_1977
PubMedID: 37238795

Title : The clinicopathological significance of thymic epithelial markers expression in thymoma and thymic carcinoma - Li_2023_BMC.Cancer_23_161
Author(s) : Li H , Ren B , Yu S , Gao H , Sun PL
Ref : BMC Cancer , 23 :161 , 2023
Abstract : BACKGROUND: The classification of thymomas is based on the morphology of epithelial tumor cells and the proportion of lymphocytes. Type A thymomas are composed of the spindle or oval tumor epithelial cells. Tumor cells of B thymomas are epithelioid-shaped with increasing atypia. Type AB thymomas have the features of epithelial tumor cells of A and B thymomas. The diagnosis can be difficult because of the complex morphology. Some novel thymic epithelial markers have been reported in several preclinical studies, but they have not been applied to clinical practice. Here, we investigated the expression of 3 cortical and 3 medullary markers, which are thymoproteasome-specific subunit beta5t (beta5t), thymus-specific serine protease 16 (PRSS16), cathepsin V, autoimmune regulator (AIRE), CD40 and claudin-4. METHODS: Immunohistochemistry was used to analyze 53 cases of thymomas and thymic squamous cell carcinomas (TSCC), aiming to explore the expression of cortical and medullary epithelial markers and their correlation with histological classification, Masaoka-Koga stage, and prognosis. RESULTS: Our results found that for cortical epithelial markers the expression of beta5t, PRSS16, and cathepsin V was higher in type AB and B thymomas than in micronodular thymoma with lymphoid stroma (MNT), and we observed a dramatic increase of beta5t and PRSS16 expression in type AB compared to type A thymomas. In medullary epithelial markers, the expression of AIRE was higher in type A than in B3 thymomas. CD40 and beta5t expression were associated with the Masaoka-Koga stage. High cathepsin V expression was related to a good prognosis and a longer progression-free survival. CONCLUSION: This is the first comprehensive analysis of the role of thymic cortical and medullary epithelial markers as biomarkers for differential diagnosis and prognosis in thymic tumors. Thymic medullary epithelial immunophenotype was found to exhibit in type A, MNT, and TSCC. Type B thymomas primarily exhibited a cortical epithelial immunophenotype. Type AB thymomas showed cortical, medullary, or mixed corticomedullary epithelial immunophenotype. Our results demonstrated that thymic cortical and medullary epithelial markers including beta5t, PRSS16, cathepsin V, and AIRE could be used as ancillary markers in the diagnosis and prognosis of thymic epithelial tumors.
ESTHER : Li_2023_BMC.Cancer_23_161
PubMedSearch : Li_2023_BMC.Cancer_23_161
PubMedID: 36797681

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

Title : Weighted gene coexpression network analysis reveals negative regulation of hypertrophic cardiomyopathy by carboxylesterase 1 and cathepsin C - Kuang_2023_Gen.Physiol.Biophys_42_361
Author(s) : Kuang Y , Wang J , Dong Y , Cheng Y , Li H , Ji Y , Gao H , Cao X
Ref : Gen Physiol Biophys , 42 :361 , 2023
Abstract : Hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy characterized by hypertrophic cardiomyocytes. It is one of the leading causes of sudden death in adolescents. However, the molecular mechanism of HCM is not clear. In our study, ribonucleic acid (RNA) sequence data of myocardial tissue in HCM patients were extracted from the Gene Expression Omnibus (GEO) database (GSE130036) and analyzed by weighted gene coexpression network analysis (WGCNA). A total of 31 coexpression modules were identified. The coexpression black module significantly correlated with maximum left ventricular wall thickness (Maxi LVWT). We screened the differentially expressed mRNAs between normal tissues and HCM tissues using the dplyr and tidyr packages in R3.6.2. The genes in the black module and differentially expressed genes were further intersected. We found that the expression of carboxylesterase 1 (CES1) and cathepsin C (CTSC) was downregulated in HCM tissues and negatively correlated with Maxi LVWT. We further verified the expression of CES1 and CTSC was downregulated in HCM clinical blood and negatively correlated with Maxi LVWT. Finally, we demonstrated that overexpression of CTSC and CES1 could alleviate HCM in an HCM cell model. In summary, the study suggests that CES1 and CTSC negatively regulate the development of HCM and have potential as therapeutic and diagnostic targets for HCM.
ESTHER : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedSearch : Kuang_2023_Gen.Physiol.Biophys_42_361
PubMedID: 37449320

Title : New Hydrolase from Aeromicrobium sp. HA for the Biodegradation of Zearalenone: Identification, Mechanism, and Application - Hu_2023_J.Agric.Food.Chem_71_2411
Author(s) : Hu J , Wang G , Hou M , Du S , Han J , Yu Y , Gao H , He D , Shi J , Lee YW , Mohamed SR , Dawood DH , Hong Q , Liu X , Xu J
Ref : Journal of Agricultural and Food Chemistry , 71 :2411 , 2023
Abstract : Zearalenone (ZEN) is an estrogenic mycotoxin most frequently found in cereals that can cause reproductive disorders in livestock and pose a severe threat to animal husbandry. In this study, we isolated a ZEN-degrading Aeromicrobium strain from soil and found that ZenH, a hydrolase, is responsible for the hydrolysis of ZEN through comparative proteomics and biochemical studies. ZenH exhibited the highest similarity with lactone hydrolase ZHD607 from Phialophora americana at 21.52%. ZenH displayed maximal enzymatic activity at pH 7.0 and 55 degreesC with a Michaelis constant of 12.64 microM. The catalytic triad of ZenH was identified as S117-D142-H292 by molecular docking and site-directed mutagenesis. ZenH catalyzed the hydrolysis of ZEN to a novel metabolite, (S,E)-4-hydroxy-2-(10-hydroxy-6-oxoundec-1-en-1-yl)-7-oxabicyclo[4.2.0]octa-1,3,5-trien-8-one, which exhibited significantly lower estrogenic toxicity than ZEN. This study illustrates a novel ZEN-degrading enzyme and reveals a new degradation product. Furthermore, the enzyme showed good potential for detoxifying ZEN during food processing.
ESTHER : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedSearch : Hu_2023_J.Agric.Food.Chem_71_2411
PubMedID: 36701132

Title : Identification of differentially expressed genes based on antennae RNA-seq analyses in Culex quinquefasciatus and Culex pipiens molestus - Gao_2022_Parasit.Vectors_15_353
Author(s) : Gao H , Gu Z , Xing D , Yang Q , Li J , Zhou X , Zhao T , Li C
Ref : Parasit Vectors , 15 :353 , 2022
Abstract : BACKGROUND: Both Culex quinquefasciatus and Cx. pipiens molestus are sibling species within Cx. pipiens complex. Even though they are hard to distinguish morphologically, they have different physiological behaviors. However, the molecular mechanisms underlying these differences remain poorly understood. METHODS: Transcriptome sequencing was conducted on antennae of two sibling species. The identification of the differentially expressed genes (DEGs) was performed by the software DESeq2. Database for Annotation, Visualization and Integrated Discovery was used to perform GO pathway enrichment analysis. The protein-protein interaction (PPI) network was constructed with Cytoscape software. The hub genes were screened by the CytoHubba plugin and Degree algorithms. The identified genes were verified by quantitative real-time PCR. RESULTS: Most annotated transcripts (14,687/16,005) were expressed in both sibling species. Among 15 identified odorant-related DEGs, OBP10 was expressed 17.17 fold higher in Cx. pipiens molestus than Cx. quinquefasciatus. Eighteen resistance-related DEGs were identified, including 15 from CYP gene family and three from acetylcholinesterase, in which CYP4d1 was 86.59 fold more highly expressed in C. quinquefasciatus. Three reproductive DEGs were indentified with the expression from 5.01 to 6.55 fold. Among eight vision-related DEGs, retinoic acid receptor RXR-gamma in Cx. pipiens molestus group was more expressed with 214.08 fold. Among the 30 hub genes, there are 10 olfactory-related DEGs, 16 resistance-related DEGs, and four vision-related DEGs, with the highest score hub genes being OBP lush (6041148), CYP4C21 (6044704), and Rdh12 (6043932). The RT-qPCR results were consistent with the transcriptomic data with the correlation coefficient R = 0.78. CONCLUSION: The study provided clues that antennae might play special roles in reproduction, drug resistance, and vision, not only the traditional olfactory function. OBP lush, CYP4C21, and Rdh12 may be key hints to the potential molecular mechanisms behind the two sibling species' biological differences.
ESTHER : Gao_2022_Parasit.Vectors_15_353
PubMedSearch : Gao_2022_Parasit.Vectors_15_353
PubMedID: 36182902

Title : Resistance to Beta-cypermethrin, Azadirachtin, and Matrine, and Biochemical Characterization of Field Populations of Oedaleus asiaticus (Bey-Bienko) in Inner Mongolia, Northern China - Gao_2022_J.Insect.Sci_22_
Author(s) : Gao S , Tan Y , Han H , Guo N , Gao H , Xu L , Lin K
Ref : J Insect Sci , 22 : , 2022
Abstract : Oedaleus asiaticus (Bey-Bienko) is an economically devastating locust species found in grassland and pastoral areas of the Inner Mongolia region of northern China. In this study, resistance to three frequently used insecticides (beta-cypermethrin, matrine, and azadirachtin) was investigated in six field populations of O. asiaticus using the leaf-dip bioassay method. The inhibitory effects of synergists and the activities of detoxification enzyme activities in the different populations were determined to explore potential biochemical resistance mechanisms. The results showed that the field populations SB (resistance ratio [RR]=7.85), ZB (RR=5.64), and DB (RR=6.75) had developed low levels of resistance to beta-cypermethrin compared with a susceptible control strain. Both the SB (RR=5.92) and XC (RR=6.38) populations had also developed low levels of resistance against matrine, with the other populations remaining susceptible to both beta-cypermethrin and matrine. All field populations were susceptible to azadirachtin. Synergism analysis showed that triphenyl phosphate (TPP) and diethyl-maleate (DEM) increased the toxicity of beta-cypermethrin significantly in the SB population, while the synergistic effects of TPP, piperonyl butoxide (PBO), and DEM on the toxicity of matrine were higher in SB (SR 3.86, 4.18, and 3.07, respectively) than in SS (SR 2.24, 2.86, and 2.29, respectively), but no synergistic effects of TPP, PBO, and DEM on azadirachtin were found. Biochemical assays showed that the activities of carboxylesterases (CarEs) and glutathione-S-transferases (GSTs) were significantly raised in all field populations of O. asiaticus, with a significant positive correlation observed between beta-cypermethrin resistance and CarE activity. The activities of cytochrome P450 monooxygenases (P450) and multi-function oxidases (MFO) were elevated in all six field populations, and P450 activity displayed strong positive correlations with the three insecticides. Our findings suggest that resistance to beta-cypermethrin in O. asiaticus may be mainly attributed to elevated CarE and GST activities, while P450 plays an important role in metabolizing matrine and azadirachtin. Our study provides insights that will help improve insecticide resistance management strategies.
ESTHER : Gao_2022_J.Insect.Sci_22_
PubMedSearch : Gao_2022_J.Insect.Sci_22_
PubMedID: 36374481

Title : Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects - Wang_2022_Front.Neurol_13_933217
Author(s) : Wang R , Gao H , Xie H , Jia Z , Chen Q
Ref : Front Neurol , 13 :933217 , 2022
Abstract : Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with (18)F-flortaucipir and (11)C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the (11)C-DOPA and (11)C-CFT in PET and the (123)I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the (11)C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the (11)C-DAA1106 and (11)C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. (18)F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.
ESTHER : Wang_2022_Front.Neurol_13_933217
PubMedSearch : Wang_2022_Front.Neurol_13_933217
PubMedID: 36051222

Title : Excavation, expression, and functional analysis of a novel zearalenone-degrading enzyme - Gao_2022_Folia.Microbiol.(Praha)_67_633
Author(s) : Gao H , Lu D , Xing M , Xu Q , Xue F
Ref : Folia Microbiol (Praha) , 67 :633 , 2022
Abstract : Zearalenone (ZEN) is a toxic secondary metabolite of Fusarium sp. commonly found in wheat, corn, and other crops. In addition to economic losses, ZEN can seriously endanger the health of both humans and livestock, thus presenting an urgent need for ZEN-detoxifying enzymes that function in the extreme heat or pH conditions of industrial fermenters. Here, we identify and characterize the activity of the ZEN-degrading enzyme from Exophiala spinifera, ZHD_LD, which shares 60.15% amino acid identity and a conserved catalytic triad with the well-characterized ZEN-detoxifying protein ZHD101 from Clonostachys rosea. Biochemical activity and stability assays indicated that purified recombinant ZHD_LD exhibited high activity against ZEN with optimal reaction conditions of 50 degC and pH 7.0-10.0. Structural modeling of the ZHD_LD active site and comparison with ZHD101 revealed its likely mechanism of ZEN degradation. This research provides an industrially valuable candidate enzyme for ZEN detoxification in food and livestock feed.
ESTHER : Gao_2022_Folia.Microbiol.(Praha)_67_633
PubMedSearch : Gao_2022_Folia.Microbiol.(Praha)_67_633
PubMedID: 35349103
Gene_locus related to this paper: 9euro-a0a0d2b6n4

Title : Anti-Alzheimer's disease potential of traditional chinese medicinal herbs as inhibitors of BACE1 and AChE enzymes - Dai_2022_Biomed.Pharmacother_154_113576
Author(s) : Dai R , Sun Y , Su R , Gao H
Ref : Biomed Pharmacother , 154 :113576 , 2022
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease that often occurs in the elderly population. At present, most drugs for AD on the market are single-target drugs, which have achieved certain success in the treatment of AD. However, the efficacy and safety of single-target drugs have not achieved the expected results because AD is a multifactorial disease. Multi-targeted drugs act on multiple factors of the disease network to improve efficacy and reduce adverse reactions. Therefore, the search for effective dual-target or even multi-target drugs has become a new research trend. Many of results found that the dual-target inhibitors of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) found from traditional Chinese medicine have a good inhibitory effect on AD with fewer side effects. This article reviews sixty-six compounds extracted from Chinese medicinal herbs, which have inhibitory activity on BACE1 and AChE. This provides a theoretical basis for the further development of these compounds as dual-target inhibitors for the treatment of AD.
ESTHER : Dai_2022_Biomed.Pharmacother_154_113576
PubMedSearch : Dai_2022_Biomed.Pharmacother_154_113576
PubMedID: 36007279

Title : Improving the catalytic efficiency and substrate affinity of a novel esterase from marine Klebsiella aerogenes by random and site-directed mutation - Gao_2021_World.J.Microbiol.Biotechnol_37_106
Author(s) : Gao H , Zhu R , Li Z , Wang W , Liu Z , Hu N
Ref : World J Microbiol Biotechnol , 37 :106 , 2021
Abstract : A novel esterase (EstKa) from marine Klebsiella aerogenes was characterized with hydrolytic activity against p-nitrophenyl caprylate (pNPC, C(8)) under optimum conditions (50 degreesC and pH 8.5). After two rounds of mutagenesis, two highly potential mutants (I6E9 and L7B11) were obtained with prominent activity, substrate affinity and thermostability. I6E9 (L90Q/P96T) and L7B11 (A37S/Q100L/S133G/R138C/Q156R) were 1.56- and 1.65-fold higher than EstKa in relative catalytic efficiency. The influence of each amino acid on enzyme activity was explored by site-directed mutation. The mutants Pro96Thr and Gln156Arg showed 1.29- and 1.48-fold increase in catalytic efficiency (Kcat/Km) and 54.4 and 36.2% decrease in substrate affinity (Km), respectively. The compound mutant Pro96Thr/Gln156Arg exhibited 68.9% decrease in Km and 1.41-fold increase in Kcat/Km relative to EstKa. Homology model structure analysis revealed that the replacement of Gln by hydrophilic Arg on the esterase surface improved the microenvironment stability and the activity. The replacement of Pro by Thr enabled the esterase enzyme to retain 90% relative activity after 3 h incubation at 45 degreesC. Structural analysis confirmed that the formation of a hydrogen bond leads to a notable increase of catalytic efficiency under high temperature conditions.
ESTHER : Gao_2021_World.J.Microbiol.Biotechnol_37_106
PubMedSearch : Gao_2021_World.J.Microbiol.Biotechnol_37_106
PubMedID: 34037848

Title : Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents - Gao_2021_Bioorg.Chem_114_105149
Author(s) : Gao H , Jiang Y , Zhan J , Sun Y
Ref : Bioorg Chem , 114 :105149 , 2021
Abstract : For the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in the future. The best 3D-QSAR acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors pharmacophore hypotheses Hypo1 A and Hypo1 B were generated and validated by HypoGen program in Discovery Studio 2016 based on the training set of flavonoids, and then they were used as 3D query for screening the ZINC database. Next, the hit molecules were then subjected to the ADMET and molecular docking study to prioritize the compounds. Finally, 6 compounds showed good estimated activities and promising ADMET properties. The result of best compound ZINC08751495 with AChE estimate activity (0.028), BChE estimate activity (1.55), AChE fit value (9.369), BChE fit value (8.415), AChE -CDOCKER ENERGY (30.22), BChE -CDOCKER ENERGY (33.13) has the potential for further development as a supplement to treat Alzheimer's disease.
ESTHER : Gao_2021_Bioorg.Chem_114_105149
PubMedSearch : Gao_2021_Bioorg.Chem_114_105149
PubMedID: 34252860

Title : The Role of Cholinesterase in Differential Diagnosis between Gastric Cancer and Benign Gastric Diseases - Gao_2021_Clin.Lab_67_
Author(s) : Gao H , Wan Y , Fan X , Dong Y , Ji X , Song W
Ref : Clin Lab , 67 : , 2021
Abstract : BACKGROUND: Gastric cancer is the fifth most common malignancy worldwide. In early stages, no obvious symptoms are usually observed in gastric cancer patients, and it is especially hard to distinguish gastric cancer from benign gastric diseases, resulting in delayed diagnosis and poor prognosis. Common biomarkers of gastric cancer, such as CEA and CA19-9, are also elevated in benign diseases. There is an urgent need to develop a convenient and reliable biomarker for differentiating between gastric cancer and benign gastric diseases. METHODS: This study retrospectively analyzed the data of 126 patients, including 73 gastric cancer patients and 53 benign gastric disease patients. Patient characteristics collected for analysis included age, gender, laboratory data, and clinical staging. Unpaired t-test was used to check the difference of cholinesterase level between the gastric cancer group and the benign gastric disease group. Kruskal Wallis H test and Mann-Whitney U test were used to check the difference of cholinesterase level among different stage groups. Receiver operating characteristic (ROC) curve was used to assess whether cholinesterase level can be used as a biomarker for differentiating between gastric cancer and benign gastric diseases. RESULTS: Serum cholinesterase level was decreased significantly in the gastric cancer group in comparison to that of the benign gastric disease group (p < 0.001). In addition, cholinesterase level of stage IV patients was significantly lower than stage I patients. ROC curve analysis revealed that with a cutoff of 5,969.00 U/L, cholinesterase level showed an area under the curve of 0.819 (95% CI 0.732 - 0.905, p < 0.001) in differentiating between gastric cancer and benign gastric diseases. No significant difference in the levels of CEA and CA19-9 was observed between gastric cancer patients and benign gastric disease patients. CONCLUSIONS: This study indicated that serum cholinesterase level could be considered as a potential biomarker for differentiating between gastric cancer and benign gastric diseases.
ESTHER : Gao_2021_Clin.Lab_67_
PubMedSearch : Gao_2021_Clin.Lab_67_
PubMedID: 33616318

Title : Expression Levels of Detoxification Enzyme Genes from Dendroctonus armandi (Coleoptera: Curculionidae) Fed on a Solid Diet Containing Pine Phloem and Terpenoids - Dai_2021_Insects_12_
Author(s) : Dai L , Gao H , Chen H
Ref : Insects , 12 : , 2021
Abstract : Bark beetles overcome the toxic terpenoids produced by pine trees by both detoxifying and converting them into a pheromone system. Detoxification enzymes such as cytochrome P450s, glutathione S-transferases, and carboxylesterases are involved in the ability of Dendroctonus armandi to adapt to its chemical environment. Ten genes from these three major classes of detoxification enzymes were selected to study how these enzymes help D. armandi to respond to the host defenses. The expression profile of these detoxification enzyme genes was observed in adult beetles after feeding on different types of diet. Significant differences were observed between two types of seminatural diet containing the phloem of pines, and a purely artificial diet containing five monoterpenes ((-)-alpha-pinene, (-)-beta-pinene, (+)-3-carene, (+/-)-limonene, and turpentine oil) also caused differential transcript levels in the detoxification enzyme genes. The results suggest that monoterpenes enter the beetles through different routes (i.e., respiratory and digestive systems) and cause the expression of different genes in response, which might be involved in pheromone metabolism. In addition, the xenobiotic metabolism in bark beetles should be considered as a system comprising multiple detoxifying enzymes.
ESTHER : Dai_2021_Insects_12_
PubMedSearch : Dai_2021_Insects_12_
PubMedID: 34680695

Title : Bioactive phenylpropanoid derivatives from the fruits of Lycium ruthenicum Murr - Zhao_2021_Bioorg.Chem_116_105307
Author(s) : Zhao SS , Li S , Luo ZH , Zhou ZQ , Li N , Wang Y , Yao XS , Gao H
Ref : Bioorg Chem , 116 :105307 , 2021
Abstract : Eight new (1-7 and 15) and 18 known (8-14 and 16-26) phenylpropanoid derivatives were isolated from the fruits of Lycium ruthenicum Murr. (black wolfberry). Their structures were determined by comprehensive spectroscopic analyses, chemical methods, and comparisons of spectroscopic data. Four known compounds (16, 17, 24, and 26) were firstly isolated from the genus Lycium. Interestingly, compounds 1/2 and 4/5 were isolated as two pairs of inseparable anomers owing to the tautomerism of the free hemiacetal at C-1'' in solution. The antioxidant, alpha-glucosidase inhibitory, and acetylcholinesterase (AChE) inhibitory activities of compounds 1-26 were evaluated. Some compounds possessed DPPH radical scavenging activity, and all compounds (1-26) exhibited different levels of oxygen radical absorbance capacity (ORAC). One compound displayed alpha-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).
ESTHER : Zhao_2021_Bioorg.Chem_116_105307
PubMedSearch : Zhao_2021_Bioorg.Chem_116_105307
PubMedID: 34482167

Title : Explainable machine learning model for predicting spontaneous bacterial peritonitis in cirrhotic patients with ascites - Hu_2021_Sci.Rep_11_21639
Author(s) : Hu Y , Chen R , Gao H , Lin H , Wang J , Wang X , Liu J , Zeng Y
Ref : Sci Rep , 11 :21639 , 2021
Abstract : Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with cirrhosis. We aimed to develop an explainable machine learning model to achieve the early prediction and outcome interpretation of SBP. We used CatBoost algorithm to construct MODEL-1 with 46 variables. After dimensionality reduction, we constructed MODEL-2. We calculated and compared the sensitivity and negative predictive value (NPV) of MODEL-1 and MODEL-2. Finally, we used the SHAP (SHapley Additive exPlanations) method to provide insights into the model's outcome or prediction. MODEL-2 (AUROC: 0.822; 95% confidence interval [CI] 0.783-0.856), liked MODEL-1 (AUROC: 0.822; 95% CI 0.784-0.856), could well predict the risk of SBP in cirrhotic ascites patients. The 6 most influential predictive variables were total protein, C-reactive protein, prothrombin activity, cholinesterase, lymphocyte ratio and apolipoprotein A1. For binary classifier, the sensitivity and NPV of MODEL-1 were 0.894 and 0.885, respectively, while for MODEL-2 they were 0.927 and 0.904, respectively. We applied CatBoost algorithm to establish a practical and explainable prediction model for risk of SBP in cirrhotic patients with ascites. We also identified 6 important variables closely related to the occurrence of SBP.
ESTHER : Hu_2021_Sci.Rep_11_21639
PubMedSearch : Hu_2021_Sci.Rep_11_21639
PubMedID: 34737270

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

Title : Effect of Harmine and Its Derivatives Against Echinococcus granulosus and Comparison of DNA Damage Targets - Gong_2020_J.Biomed.Nanotechnol_16_827
Author(s) : Gong Y , Lv S , Tian C , Gao Y , Chen B , Wen L , Gao H , Aimaiti W , Ma R , Zhao J , Wang J
Ref : J Biomed Nanotechnol , 16 :827 , 2020
Abstract : Cystic echinococcosis (CE) is a worldwide zoonotic disease. At present, the treatment options of CE are limited. The main drugs used in clinical chemotherapy of echinococcosis are albendazole and mebendazole, but they mainly exert longterm antiparasitic effects based on high doses. Therefore, there is an urgent need for effective and safe anti-CE drugs. Previous studies have identified harmine (HM) as a new anti-CE drug. In this study, the efficacy of harmine derivatives was evaluated in vitro and in vivo. The harmine derivatives were tested against E. granulosus protoscoleces (PSC) in vitro. The effect of harmine derivatives was time and concentration dependent at different concentrations, and the anti-CE effect was better than that of harmine. The mortality rate of PSC reached 100% on the 5th day after exposure to harmine derivatives at a concentration of 100 mol . L (-1). Compared with the untreated model control mice, the weight of the cyst was significantly reduced in infected mice treated with harmine derivatives. The effect of harmine derivatives was better than that of harmine, and there was significant difference between harmine derivatives and albendazole (P <0.001). Histopathological examination of experimental mice organs (liver, spleen, lung, brain and small intestine) showed that there was no change in the tissues except for mild inflammation in the liver. The neurotoxicity test in Caenorhabditis elegans showed that the derivative inhibited the movement, feeding, perceptual behavior and acetylcholinesterase activity of C. elegans , and its effect was lower than that of harmine. In addition, intervention with HM derivatives was preliminarily proved to cause DNA damage. This study reveals the potential of HM derivatives as a new class of anti-CE agents and indicates that Topo2a may be a promising target for the development of anti-CE drugs.
ESTHER : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedSearch : Gong_2020_J.Biomed.Nanotechnol_16_827
PubMedID: 33187579

Title : Design of Red Emissive Carbon Dots: Robust Performance for Analytical Applications in Pesticide Monitoring - Li_2020_Anal.Chem_92_3198
Author(s) : Li H , Su D , Gao H , Yan X , Kong D , Jin R , Liu X , Wang C , Lu G
Ref : Analytical Chemistry , 92 :3198 , 2020
Abstract : Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.0%) based on solvothermal treatment of citric acid and thiourea using dimethylformamide as solvent. Further investigations reveal that the conjugating sp(2)-domain controlling the incorporation of nitrogen and surface engineering are mainly responsible for the obtained red emission of CDs. Taking advantage of optical properties and abundant surface functional groups, CDs were considered to facilely construct a ratiometric fluorescent platform for quantifying trace levels of organophosphorus pesticides (OPs). Combining the acetylcholinesterase-mediated polymerization of dopamine and the inhibition of pesticide toward the enzyme, the degree of polymerization of dopamine rationally depends on the concentration of OPs. By measuring the fluorescence intensity ratio, the proposed platform exhibited highly selective and robust performance toward OPs, displaying ultrasensitive recognition in the pg L(-1) level. The multiexcitation format could efficiently shield background interference from complex samples by introducing a self-calibrated reference signal, which affords accurate and reliable quantitative information, endowing CDs as a universal candidate for a biosensing application by combining target-specific recognition elements.
ESTHER : Li_2020_Anal.Chem_92_3198
PubMedSearch : Li_2020_Anal.Chem_92_3198
PubMedID: 32008315

Title : Neuronal Lipoprotein Lipase Deficiency Alters Neuronal Function and Hepatic Metabolism - Bruce_2020_Metabolites_10_
Author(s) : Bruce KD , Dobrinskikh E , Wang H , Rudenko I , Gao H , Libby AE , Gorkhali S , Yu T , Zsombok A , Eckel RH
Ref : Metabolites , 10 : , 2020
Abstract : The autonomic regulation of hepatic metabolism offers a novel target for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the molecular characteristics of neurons that regulate the brain-liver axis remain unclear. Since mice lacking neuronal lipoprotein lipase (LPL) develop perturbations in neuronal lipid-sensing and systemic energy balance, we reasoned that LPL might be a component of pre-autonomic neurons involved in the regulation of hepatic metabolism. Here, we show that, despite obesity, mice with reduced neuronal LPL (NEXCreLPL(flox) (LPL KD)) show improved glucose tolerance and reduced hepatic lipid accumulation with aging compared to wilt type (WT) controls (LPL(flox)). To determine the effect of LPL deficiency on neuronal physiology, liver-related neurons were identified in the paraventricular nucleus (PVN) of the hypothalamus using the transsynaptic retrograde tracer PRV-152. Patch-clamp studies revealed reduced inhibitory post-synaptic currents in liver-related neurons of LPL KD mice. Fluorescence lifetime imaging microscopy (FLIM) was used to visualize metabolic changes in LPL-depleted neurons. Quantification of free vs. bound nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) revealed increased glucose utilization and TCA cycle flux in LPL-depleted neurons compared to controls. Global metabolomics from hypothalamic cell lines either deficient in or over-expressing LPL recapitulated these findings. Our data suggest that LPL is a novel feature of liver-related preautonomic neurons in the PVN. Moreover, LPL loss is sufficient to cause changes in neuronal substrate utilization and function, which may precede changes in hepatic metabolism.
ESTHER : Bruce_2020_Metabolites_10_
PubMedSearch : Bruce_2020_Metabolites_10_
PubMedID: 32998280

Title : N-methoxy-beta-carboline alkaloids with inhibitory activities against Abeta42 aggregation and acetylcholinesterase from the stems of Picrasma quassioides - Zhang_2020_Bioorg.Chem_101_104043
Author(s) : Zhang J , Zhao SS , Xie J , Yang J , Chen GD , Hu D , Zhang WG , Wang CX , Yao XS , Gao H
Ref : Bioorg Chem , 101 :104043 , 2020
Abstract : Nine new N-methoxy-beta-carboline alkaloids (NMCAs) (1a/1b-3a/3b and 4-6) and two known NMCAs (7 and 8) were isolated from the stems of Picrasma quassioides. Their structures were elucidated by spectroscopic data analyses, quantum chemical calculations, and single-crystal X-ray crystallographic data. An analysis of the (13)C NMR chemical shifts of the N-methoxy groups in these NMCAs and 41 gathered known compounds reveals the phenomenon that the chemical shifts of all these N-methoxy groups are greater than deltaC 62, which can be used to recognize the N-methoxy group rapidly. In addition, the acetylcholinesterase (AChE) and Abeta42 aggregation inhibitory activities of 1-8 were evaluated. Compounds 1, 2, 7, and 8 displayed AChE inhibitory activity with IC50 values of 14.9, 13.2, 17.6, and 43.9 muM, respectively. Compound 2 showed inhibition activity against Abeta42 aggregation with an IC50 value of 10.1 muM.
ESTHER : Zhang_2020_Bioorg.Chem_101_104043
PubMedSearch : Zhang_2020_Bioorg.Chem_101_104043
PubMedID: 32629286

Title : Dp44mT, an iron chelator, suppresses growth and induces apoptosis via RORA-mediated NDRG2-IL6\/JAK2\/STAT3 signaling in glioma - Zhou_2020_Cell.Oncol.(Dordr)_43_461
Author(s) : Zhou J , Jiang Y , Zhao J , Zhang H , Fu J , Luo P , Ma Y , Zou D , Gao H , Hu J , Zhang Y , Jing Z
Ref : Cell Oncol (Dordr) , 43 :461 , 2020
Abstract : PURPOSE: The iron-chelating agent di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has been found to inhibit cell growth and to induce apoptosis in several human cancers. However, its effects and mechanism of action in glioma are unknown. METHODS: Human glioma cell line LN229 and patient-derived glioma stem cells GSC-42 were applied for both in vitro and in vivo xenograft nude mouse experiments. The anti-tumor effects of Dp44mT were assessed using MTS, EdU, TUNEL, Western blotting, qRT-PCR, luciferase reporter, chromatin immunoprecipitation and immunohistochemical assays. RESULTS: We found that Dp44mT can upregulate the expression of the anti-oncogene N-myc downstream-regulated gene (NDRG)2 by directly binding to and activating the RAR-related orphan receptor (ROR)A. In addition, we found that NDRG2 overexpression suppressed inflammation via activation of interleukin (IL)-6/Janus kinase (JAK)2/signal transducer and activator of transcription (STAT)3 signaling. CONCLUSIONS: Our data indicate that Dp44mT may serve as an effective drug for the treatment of glioma by targeting RORA and enhancing NDRG2-mediated IL-6/JAK2/STAT3 signaling.
ESTHER : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedSearch : Zhou_2020_Cell.Oncol.(Dordr)_43_461
PubMedID: 32207044
Gene_locus related to this paper: human-NDRG2

Title : Discovery of Novel DPP-IV Inhibitors as Potential Candidates for the Treatment of Type 2 Diabetes mellitus Predicted by 3D QSAR Pharmacophore Models, Molecular Docking and de novo Evolution - Musoev_2019_Molecules_24_
Author(s) : Musoev A , Numonov S , You Z , Gao H
Ref : Molecules , 24 : , 2019
Abstract : Dipeptidyl peptidase-IV (DPP-IV) rapidly breaks down the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Thus, the use of DPP-IV inhibitors to retard the degradation of endogenous GLP-1 is a possible mode of therapy correcting the defect in incretin-related physiology. The aim of this study is to find a new small molecule and explore the inhibition activity to the DPP-IV enzyme using a computer aided simulation. In this study, the predicted compounds were suggested as potent anti-diabetic candidates. Chosen structures were applied following computational strategies: The generation of the three-dimensional quantitative structure-activity relationship (3D QSAR) pharmacophore models, virtual screening, molecular docking, and de novo Evolution. The method also validated by performing re-docking and cross-docking studies of seven protein systems for which crystal structures were available for all bound ligands. The molecular docking experiments of predicted compounds within the binding pocket of DPP-IV were conducted. By using 25 training set inhibitors, ten pharmacophore models were generated, among which hypo1 was the best pharmacophore model with the best predictive power on account of the highest cost difference (352.03), the lowest root mean squared deviation (RMSD) (2.234), and the best correlation coefficient (0.925). Hypo1 pharmacophore model was used for virtual screening. A total of 161 compounds including 120 from the databases, 25 from the training set, 16 from the test set were selected for molecular docking. Analyzing the amino acid residues of the ligand-receptor interaction, it can be concluded that Arg125, Glu205, Glu206, Tyr547, Tyr662, and Tyr666 are the main amino acid residues. The last step in this study was de novo Evolution that generated 11 novel compounds. The derivative dpp4_45_Evo_1 by all scores CDOCKER_ENERGY (CDOCKER, -41.79), LigScore1 (LScore1, 5.86), LigScore2 (LScore2, 7.07), PLP1 (-112.01), PLP2 (-105.77), PMF (-162.5)-have exceeded the control compound. Thus the most active compound among 11 derivative compounds is dpp4_45_Evo_1. Additionally, for derivatives dpp4_42_Evo_1, dpp4_43_Evo2, dpp4_46_Evo_4, and dpp4_47_Evo_2, significant upward shifts were recorded. The consensus score for the derivatives of dpp4_45_Evo_1 from 1 to 6, dpp4_43_Evo2 from 4 to 6, dpp4_46_Evo_4 from 1 to 6, and dpp4_47_Evo_2 from 0 to 6 were increased. Generally, predicted candidates can act as potent occurring DPP-IV inhibitors given their ability to bind directly to the active sites of DPP-IV. Our result described that the 6 re-docked and 27 cross-docked protein-ligand complexes showed RMSD values of less than 2 A. Further investigation will result in the development of novel and potential antidiabetic drugs.
ESTHER : Musoev_2019_Molecules_24_
PubMedSearch : Musoev_2019_Molecules_24_
PubMedID: 31394858

Title : New phthalide derivatives from the Biscogniauxia sp. and their activities - Liu_2019_Fitoterapia__104184
Author(s) : Liu YY , Zhao H , Xie J , Zou J , Hu D , Guo LD , Chen GD , Yao XS , Gao H
Ref : Fitoterapia , :104184 , 2019
Abstract : Five new phthalide derivatives, biscogniphthalides A-D (1, 2, 3a/3b, and 4), were isolated from Biscogniauxia sp. (No. 69-8-7-1), along with one related known phthalide (5). Their structures were determined by comprehensive spectroscopic analyses, chemical derivatization, and quantum chemical ECD calculations. In addition, the anti-acetyl cholinesterase, antimicrobial, and anti-alpha-glucosidase activities of 1-5 were evaluated.
ESTHER : Liu_2019_Fitoterapia__104184
PubMedSearch : Liu_2019_Fitoterapia__104184
PubMedID: 31145983

Title : Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B - Wu_2018_Liver.Int_38_1930
Author(s) : Wu D , Rao Q , Chen W , Ji F , Xie Z , Huang K , Chen E , Zhao Y , Ouyang X , Zhang S , Jiang Z , Zhang L , Xu L , Gao H , Li L
Ref : Liver Int , 38 :1930 , 2018
Abstract : BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis.
ESTHER : Wu_2018_Liver.Int_38_1930
PubMedSearch : Wu_2018_Liver.Int_38_1930
PubMedID: 29654711

Title : Pharmacophore-based drug design for the identification of novel butyrylcholinesterase inhibitors against Alzheimer's disease - Jiang_2018_Phytomedicine_54_278
Author(s) : Jiang Y , Gao H
Ref : Phytomedicine , 54 :278 , 2018
Abstract : BACKGROUND: Alzheimer's disease is a severe neurodegenerative disease of the central nervous system in the elderly. HYPOTHESIS/PURPOSE: In our study, we aimed to find the best potential small molecule for AD treatment. STUDY DESIGN: We used many models in Discovery Studio 2016 to find new potential inhibitors of butyrylcholinesterase (BChE), including pharmacophore model, virtual screening model, molecular docking model, de novo evolution model. METHODS: Ligand-based pharmacophore models were used to identify the critical chemical features of BChE inhibitors using the module of 3D QSAR Pharmacophore Generation in Discovery Studio 2016. The best pharmacophore model was then validated by cost analysis, Fischer's randomization method, 3D-QSAR Method of the training set and test set. The compounds that match the best pharmacophore model with the predicted activity <1muM filtered by Lipinski's rule of five were subjected to molecular docking. RESULT: After virtual screening, 35 compounds filtered by Lipinski's rule of five and ADMET analysis were subjected to molecular docking and then the number were narrowed down on 10 compounds based on -CDOCKER_ENERGY. Finally, we obtained and modified the best potential candidate ENA739155. CONCLUSION: Ultimately, ENA739155_Evo with -CDOCKER_ENERGY of 47.12, estimate activity of 0.012, fit value of 10.02 could be further subjected to drug development and forwarded as better alternatives to the current batch of medicines used for the treatment of AD.
ESTHER : Jiang_2018_Phytomedicine_54_278
PubMedSearch : Jiang_2018_Phytomedicine_54_278
PubMedID: 30668379

Title : Polyphenols from wolfberry and their bioactivities - Zhou_2017_Food.Chem_214_644
Author(s) : Zhou ZQ , Xiao J , Fan HX , Yu Y , He RR , Feng XL , Kurihara H , So KF , Yao XS , Gao H
Ref : Food Chem , 214 :644 , 2017
Abstract : Nine new phenylpropanoids, one new coumarin, and 43 known polyphenols were isolated from wolfberry. Their structures were determined by spectroscopic analyses, chemical methods, and comparison of NMR data. Polyphenols, an important type of natural products, are notable constituents in wolfberry. 53 polyphenols, including 28 phenylpropanoids, four coumarins, eight lignans, five flavonoids, three isoflavonoids, two chlorogenic acid derivatives, and three other constituents, were identified from wolfberry. Lignans and isoflavonoids were firstly reported from wolfberry. 22 known polyphenols were the first isolates from the genus Lycium. This research presents a systematic study on wolfberry polyphenols, including their bioactivities. All these compounds exhibited oxygen radical absorbance capacity (ORAC), and some compounds displayed DPPH radical scavenging activity. One compound had acetylcholinesterase inhibitory activity. The discovery of new polyphenols and their bioactivities is beneficial for understanding the scientific basis of the effects of wolfberry.
ESTHER : Zhou_2017_Food.Chem_214_644
PubMedSearch : Zhou_2017_Food.Chem_214_644
PubMedID: 27507521

Title : Pharmacophore-based drug design for potential AChE inhibitors from Traditional Chinese Medicine Database - Jiang_2017_Bioorg.Chem_76_400
Author(s) : Jiang Y , Gao H
Ref : Bioorg Chem , 76 :400 , 2017
Abstract : Alzheimer's disease (AD) is a neurodegenerative disorder. Substrate-specific Acetylcholinesterase (AChE) plays a vital role in the AD treatment. Flavonoids with AChE inhibitory activities and low toxicity are used to developing new anti-AD agents. In this study, the best 3D QSAR pharmacophore model Hypo1 was generated by HypoGen program in Discovery Studio2016 based on the training set of flavonoids. We performed a virtual screening from Traditional Chinese Medicine (TCM), Druglike and MiniMaybridge databases using Hypo1. From docking analyses, we got the top 10 AChE inhibitors which were further evaluated by 8 different scoring functions. De Novo Evolution designed the top 10 derivatives, and three potential AChE inhibitor candidates were obtained eventually.
ESTHER : Jiang_2017_Bioorg.Chem_76_400
PubMedSearch : Jiang_2017_Bioorg.Chem_76_400
PubMedID: 29258018

Title : Traditional Chinese medicinal herbs as potential AChE inhibitors for anti-Alzheimer's disease: A review - Jiang_2017_Bioorg.Chem_75_50
Author(s) : Jiang Y , Gao H , Turdu G
Ref : Bioorg Chem , 75 :50 , 2017
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting 25 million people worldwide, and cholinergic hypothesis is considered as an important hypotheses in the processes of improving cognitive function and recognition skills in recent years. For the long-term treatment of AD, traditional Chinese medicine are particularly suitable for drug discovery. In this review, we sum up six traditional Chinese medicinal herbs concerned with development of AChEIs, including Herba Epimedii, Coptis Chinensis Franch, Rhizoma Curcumae Longae, Green tea, Ganoderma, Panax Ginseng. The listed compounds based on these herbs are belonging to six classes Flavonoids, Alkaloids, Ketones, Polyphenols, Terpenoid and Saponins, respectively. These compounds could be very promising agents in the search for potent anti-Alzheimer's drugs.
ESTHER : Jiang_2017_Bioorg.Chem_75_50
PubMedSearch : Jiang_2017_Bioorg.Chem_75_50
PubMedID: 28915465

Title : Chiral resolution, absolute configuration, and bioactivity of a new racemic asarone derivative from the rhizome of Acorus tatarinowii - Gao_2017_Fitoterapia_122_7
Author(s) : Gao E , Ren FF , Zou J , Yu Y , Fan HX , Zhou ZQ , Chen GD , He RR , Yao XS , Gao H
Ref : Fitoterapia , 122 :7 , 2017
Abstract : A new asarone-derived racemate (1) was isolated from the rhizome of Acorus tatarinowii. The structure of 1 was established by comprehensive spectroscopic analyses, and it was successfully resolved by chiral HPLC, demonstrating that it is racemic. The absolute configurations of 1a [(-)-acortatarone A] and 1b [(+)-acortatarone A] were determined using quantum chemical calculations. Compounds 1a and 1b were the first cases of asarone derivatives with the 5,7-dialkyl-6-aryl-8-oxabicyclo[3.2.1]oct-3-en-2-one core. The alpha-glucosidase inhibitory and acetylcholinesterase (AChE) inhibitory activities of 1 were evaluated, and it exhibited alpha-glucosidase inhibitory activity with potency close to that of the positive control (acarbose).
ESTHER : Gao_2017_Fitoterapia_122_7
PubMedSearch : Gao_2017_Fitoterapia_122_7
PubMedID: 28811187

Title : Prediction and evaluation of the lipase inhibitory activities of tea polyphenols with 3D-QSAR models - Li_2016_Sci.Rep_6_34387
Author(s) : Li YF , Chang YQ , Deng J , Li WX , Jian J , Gao JS , Wan X , Gao H , Kurihara H , Sun PH , He RR
Ref : Sci Rep , 6 :34387 , 2016
Abstract : The extraordinary hypolipidemic effects of polyphenolic compounds from tea have been confirmed in our previous study. To gain compounds with more potent activities, using the conformations of the most active compound revealed by molecular docking, a 3D-QSAR pancreatic lipase inhibitor model with good predictive ability was established and validated by CoMFA and CoMISA methods. With good statistical significance in CoMFA (r2cv = 0.622, r2 = 0.956, F = 261.463, SEE = 0.096) and CoMISA (r2cv = 0.631, r2 = 0.932, F = 75.408, SEE = 0.212) model, we summarized the structure-activity relationship between polyphenolic compounds and pancreatic lipase inhibitory activities and find the bulky substituents in R2, R4 and R5, hydrophilic substituents in R1 and electron withdrawing groups in R2 are the key factors to enhance the lipase inhibitory activities. Under the guidance of the 3D-QSAR results, (2R,3R,2'R,3'R)-desgalloyloolongtheanin-3,3'-O-digallate (DOTD), a potent lipase inhibitor with an IC50 of 0.08 mug/ml, was obtained from EGCG oxidative polymerization catalyzed by crude polyphenol oxidase. Furthermore, DOTD was found to inhibit lipid absorption in olive oil-loaded rats, which was related with inhibiting the activities of lipase in the intestinal mucosa and contents.
ESTHER : Li_2016_Sci.Rep_6_34387
PubMedSearch : Li_2016_Sci.Rep_6_34387
PubMedID: 27694956

Title : Immobilization of a novel cold active esterase onto FeO approximately cellulose nano-composite enhances catalytic properties - Rahman_2016_Int.J.Biol.Macromol_87_488
Author(s) : Rahman MA , Culsum U , Kumar A , Gao H , Hu N
Ref : Int J Biol Macromol , 87 :488 , 2016
Abstract : A novel esterase, EstH was cloned, purified and characterized from the marine bacterium Zunongwangia sp. The purified EstH showed optimum activity at 30 degrees C and pH 8.5 with approximately 50% of original activity at 0 degrees C. EstH was stable in high salt conditions (0-4.5M NaCl). To improve the characteristics and explore the possibilities for application, a new immobilization matrix, Fe3O4 approximately cellulose nano-composite, was prepared and was characterized by Fourier Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscope (SEM). Interestingly the optimal temperature of immobilized EstH elevated to 35 degrees C. Compared to its free form, immobilized EstH showed better temperature stability (48.5% compared to 22.40% at 50 degrees C after 30min), prolonged half-life (32h compared to 18h), higher storage stability ( approximately 71% activity compared to approximately 40% after 50days of storage), improved pH tolerance ( approximately 73% activity at pH 4 and 10), and, more importantly, reusability ( approximately 50% activity after 8 repetitive cycles of usage). Enzyme kinetics showed an increase in the Vmax (from 35.76 to 51.14muM/min) and Kcat (from 365s-1 to 520s-1) after immobilization. The superior catalytic properties of immobilized EstH suggest its great potential in biotechnology and industrial processes.
ESTHER : Rahman_2016_Int.J.Biol.Macromol_87_488
PubMedSearch : Rahman_2016_Int.J.Biol.Macromol_87_488
PubMedID: 26976070

Title : Biosynthesis of LL-Z1272beta: Discovery of a New Member of NRPS-like Enzymes for Aryl-Aldehyde Formation - Li_2016_Chembiochem_17_904
Author(s) : Li C , Matsuda Y , Gao H , Hu D , Yao XS , Abe I
Ref : Chembiochem , 17 :904 , 2016
Abstract : LL-Z1272beta (1) is a prenylated aryl-aldehyde produced by several fungi; it also serves as a key pathway intermediate for many fungal meroterpenoids. Despite its importance in the biosynthesis of natural products, the molecular basis for the biosynthesis of 1 has yet to be elucidated. Here we identified the biosynthetic gene cluster for 1 from Stachybotrys bisbyi PYH05-7, and elucidated the biosynthetic route to 1. The biosynthesis involves a polyketide synthase, a prenyltransferase, and a nonribosomal peptide synthetase (NRPS)-like enzyme, which is responsible for the generation of the aldehyde functionality. Interestingly, the NRPS-like enzyme only accepts the farnesylated substrate to catalyze the carboxylate reduction; this represents a new example of a substrate for adenylation domains.
ESTHER : Li_2016_Chembiochem_17_904
PubMedSearch : Li_2016_Chembiochem_17_904
PubMedID: 26972702
Gene_locus related to this paper: stabi-stba

Title : Reduced vagal control of the heart in high-fat diet mice: a potential role of increased butyrylcholinesterase - Hartnett_2015_Physiol.Rep_3_
Author(s) : Hartnett S , Gao H , Schnack S , Li Y
Ref : Physiol Rep , 3 : , 2015
Abstract : Suppressed parasympathetic function is commonly present in cardiovascular diseases, aging, obesity, and various other health conditions. Impaired parasympathetic action is known as a detrimental factor and contributes to the adverse outcomes in these conditions. However, the underlying mechanisms remain to be fully addressed. In this study, using high-fat diet (HFD)-induced obese mice as a model, the potential peripheral mechanisms underlying the impaired parasympathetic vagal control of the heart was examined. The HFD induced obesity and metabolic disorder in mice. These obese mice exhibited an attenuated response in heart rate to vagal stimulation, indicating impairment of peripheral parasympathetic activity in the heart. In cholinergic function-related proteins in the atria, protein levels of choline transporter and vesicular acetylcholine transporter were not decreased but increased, and type 2 muscarinic receptors showed a trend toward a reduction in HFD mice atria as compared with regular diet (RD) mice controls. While the protein level of acetylcholinesterase was not different, butyrylcholinesterase (BChE) protein level showed a twofold increase in HFD mice atria as compared with RD mice. Functionally, inhibition of BChE activity partially and significantly improved the attenuated response in heart rate to vagal stimulation in HFD mice. Collectively, these data suggest that increased BChE activity in the atria may contribute to the decreased parasympathetic function in HFD-induced obese mice.
ESTHER : Hartnett_2015_Physiol.Rep_3_
PubMedSearch : Hartnett_2015_Physiol.Rep_3_
PubMedID: 26537347

Title : Simvastatin reverses the downregulation of M1\/4 receptor binding in 6-hydroxydopamine-induced parkinsonian rats: The association with improvements in long-term memory - Wang_2014_Neurosci_267_57
Author(s) : Wang Q , Wei X , Gao H , Li J , Liao J , Liu X , Qin B , Yu Y , Deng C , Tang B , Huang XF
Ref : Neuroscience , 267 :57 , 2014
Abstract : BACKGROUND: It is believed that muscarinic M1/4 receptors are closely correlated to the dopaminergic system and are strongly involved in the pathogenesis of Parkinson's disease (PD). In addition to regulating lipid metabolism and protection from stroke, statins have been used to regulate the declined cognition. We aimed to explore the regional changes in M1/4 receptors in the 6-hydroxydopamine (6-OHDA)-lesioned rat brain.
METHODS: PD rat model was set up by injecting 6-OHDA into the unilateral medial forebrain bundle; while simvastatin (10mg/kg/day) or saline was orally administrated for 3weeks, respectively. Long-term memory was measured using the Morris water maze. [(3)H]pirenzepine binding autoradiography was applied to investigate the alterations of M1/4 receptors in the PD rat brains.
RESULTS: 6-OHDA induced long-term memory deficits along with downregulation of M1/4 receptors in the hippocampus, the medial amygdala, the posteromedial cortical and the piriform cortex; simvastatin administration significantly ameliorated the impaired memory and reversed the downregulation of M1/4 receptors in the examined brain regions. Profound positive correlations were verified between the decline in long-term memory activity and the restoration of M1/4 receptors in different brain regions after simvastatin treatment. CONCLUSIONS/SIGNIFICANCE: Our results provide strong evidence that M1/4 receptor modulation after simvastatin administration did, at least partially, contribute to the improvement in the long-term memory in 6-OHDA-induced PD rats. These results provide a possible mechanism for simvastatin treatment in psycho-neurological diseases such as PD via M1/4 receptors.
ESTHER : Wang_2014_Neurosci_267_57
PubMedSearch : Wang_2014_Neurosci_267_57
PubMedID: 24613723

Title : ContigScape: a Cytoscape plugin facilitating microbial genome gap closing - Tang_2013_BMC.Genomics_14_289
Author(s) : Tang B , Wang Q , Yang M , Xie F , Zhu Y , Zhuo Y , Wang S , Gao H , Ding X , Zhang L , Zhao G , Zheng H
Ref : BMC Genomics , 14 :289 , 2013
Abstract : BACKGROUND: With the emergence of next-generation sequencing, the availability of prokaryotic genome sequences is expanding rapidly. A total of 5,276 genomes have been released since 2008, yet only 1,692 genomes were complete. The final phase of microbial genome sequencing, particularly gap closing, is frequently the rate-limiting step either because of complex genomic structures that cause sequence bias even with high genomic coverage, or the presence of repeat sequences that may cause gaps in assembly.
RESULTS: We have developed a Cytoscape plugin to facilitate gap closing for high-throughput sequencing data from microbial genomes. This plugin is capable of interactively displaying the relationships among genomic contigs derived from various sequencing formats. The sequence contigs of plasmids and special repeats (IS elements, ribosomal RNAs, terminal repeats, etc.) can be displayed as well.
CONCLUSIONS: Displaying relationships between contigs using graphs in Cytoscape rather than tables provides a more straightforward visual representation. This will facilitate a faster and more precise determination of the linkages among contigs and greatly improve the efficiency of gap closing.
ESTHER : Tang_2013_BMC.Genomics_14_289
PubMedSearch : Tang_2013_BMC.Genomics_14_289
PubMedID: 23627759
Gene_locus related to this paper: myctu-cut3 , myctu-cutas1 , myctu-cutas2 , myctu-Rv0160c , myctu-Rv1069c , myctu-RV1215C , myctu-Rv2045c , myctu-RV3452 , myctu-Rv3802c , amyor-r4tdn6 , amyor-r4sys4 , amyor-r4svp2 , amyor-r4t193 , amyor-r4t8c7 , amyor-r4t8w6 , amyor-r4t1x8 , amyor-r4stv4 , amyor-r4t7z6 , 9pseu-r4sx12

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

Title : Improved thermal stability of lipase in W\/O microemulsion by temperature-sensitive polymers - Tao_2013_Colloids.Surf.B.Biointerfaces_111C_587
Author(s) : Tao Q , Li A , Liu X , Gao H , Zhang Z , Ma R , An Y , Shi L
Ref : Colloids Surf B Biointerfaces , 111C :587 , 2013
Abstract : Lipase is active at the water-oil interface and thus very useful for many applications in non-aqueous media. However, the use of lipase is often limited due to the heat inactivation which is mainly caused by the irreversible aggregation among lipase molecules. The temperature-sensitive polymers can spontaneously form complexes with lipases at higher temperature in the confined spaces of the water in oil microemulsion. With cooling, lipases are released from the complexes and refold into the native state. In this way, the thermal stability of lipase in a microemulsion is effectively improved, and so is the stability of lipase at ambient temperature. Apart from proving the effectiveness and generality of this method, the temperature-sensitive polymers/lipase microemulsion represents a simple and efficient system which could be used in practical applications, since lipase retains the interfacial activity in this system. Moreover, the influences of some factors on the improvement are discussed and the mechanism of this method is suggested after exploring the process by dynamic light scattering and fluorescence measurements.
ESTHER : Tao_2013_Colloids.Surf.B.Biointerfaces_111C_587
PubMedSearch : Tao_2013_Colloids.Surf.B.Biointerfaces_111C_587
PubMedID: 23907047

Title : Genome sequences of wild and domestic bactrian camels - Jirimutu_2012_Nat.Commun_3_1202
Author(s) : Jirimutu , Wang Z , Ding G , Chen G , Sun Y , Sun Z , Zhang H , Wang L , Hasi S , Zhang Y , Li J , Shi Y , Xu Z , He C , Yu S , Li S , Zhang W , Batmunkh M , Ts B , Narenbatu , Unierhu , Bat-Ireedui S , Gao H , Baysgalan B , Li Q , Jia Z , Turigenbayila , Subudenggerile , Narenmanduhu , Wang J , Pan L , Chen Y , Ganerdene Y , Dabxilt , Erdemt , Altansha , Altansukh , Liu T , Cao M , Aruuntsever , Bayart , Hosblig , He F , Zha-ti A , Zheng G , Qiu F , Zhao L , Zhao W , Liu B , Li C , Tang X , Guo C , Liu W , Ming L , Temuulen , Cui A , Li Y , Gao J , Wurentaodi , Niu S , Sun T , Zhai Z , Zhang M , Chen C , Baldan T , Bayaer T , Meng H
Ref : Nat Commun , 3 :1202 , 2012
Abstract : Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system.
ESTHER : Jirimutu_2012_Nat.Commun_3_1202
PubMedSearch : Jirimutu_2012_Nat.Commun_3_1202
PubMedID: 23149746
Gene_locus related to this paper: 9ceta-s9yik4 , 9ceta-s9yb99 , 9ceta-s9x0n3 , 9ceta-s9xqa3 , 9ceta-s9xi02 , camfr-s9wiw9 , camfr-s9x3r3 , camfr-s9xce1 , camfr-s9xcr2 , camfr-s9yuz0 , camfr-s9xlc8 , camfr-s9w5f6 , camfr-s9xmm4

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

Title : Transport of acyclovir ester prodrugs through rabbit cornea and SIRC-rabbit corneal epithelial cell line - Tak_2001_J.Pharm.Sci_90_1505
Author(s) : Tak RV , Pal D , Gao H , Dey S , Mitra AK
Ref : J Pharm Sci , 90 :1505 , 2001
Abstract : The purpose of this study is to assess the permeability of acyclovir (ACV) prodrugs through the rabbit corneal cell line (SIRC) as well as the cornea, and characterize the SIRC cell line for transport and metabolism studies of ester prodrugs. Prodrug derivatization of an acycloguanosine antiviral agent, acyclovir, was employed to improve its permeability across the cornea. New Zealand albino rabbits were used as an animal model for corneal studies. The SIRC cell line grown on polyester membranes was used for transport of these prodrugs. SIRC cells grown on the membrane support for 10 days developed four to six layers of epithelial cells, and this is comparable to the normal rabbit corneal epithelial layer. Transport experiments were conducted across the rabbit cornea and confluent SIRC cells using side-by-side diffusion-cell apparatus. Enzymatic hydrolysis of these compounds was evaluated in SIRC cell lysates. Appropriate reversed phase HPLC method(s) were employed for quantitation of both the prodrug and ACV simultaneously. Corneal permeabilities of some of these prodrugs (Malonyl ACV and Acetyl ACV) were higher relative to ACV. The SIRC cell line permeability values of all the prodrugs were higher compared to that of the intact cornea. The total amount of ACV-prodrugs transported, i.e., unhydrolyzed prodrugs and regenerated ACV, across the SIRC cell line was more relative to ACV. Hydrolytic studies in the SIRC cell line homogenate demonstrated the bioreversion potential of the prodrugs and the presence of enzymes, particularly the cholinesterase in the SIRC cell line. It may be concluded that the SIRC cell line is leakier compared to the cornea. Keeping in mind the limitations, the SIRC cell line after further characterization may be used for transport and metabolism studies of ester prodrugs.
ESTHER : Tak_2001_J.Pharm.Sci_90_1505
PubMedSearch : Tak_2001_J.Pharm.Sci_90_1505
PubMedID: 11745709

Title : Neurotrophins and Alzheimer's disease: beyond the cholinergic neurons - Knusel_1996_Life.Sci_58(22)_2019
Author(s) : Knusel B , Gao H
Ref : Life Sciences , 58 :2019 , 1996
Abstract : Improvement of the cholinergic deficit in Alzheimer's disease (AD) by intracerebral application of nerve growth factor (NGF) serves as a paradigmatic example for a novel approach to the treatment of neurodegeneration. The first part of this paper presents and discusses experiments which were performed in our laboratory to study the NGF receptor response after intracerebral NGF treatment in vivo. We found that intraparenchymal NGF elicits prolonged tyrosine phosphorylation of Trk type NGF receptors. Our results indicate that intraparenchymal injections are preferable to intraventricular application for targeting specific neuronal populations with minimal side effects. Besides the cholinergic deficit, severely disturbed brain energy metabolism, particularly in cortical association areas, is another consistent feature of AD. Metabolic hypofunction is observed early in the disease progression and correlates with the cognitive impairment. Cell culture findings are presented which indicate that brain-derived neurotrophic factor (BDNF), and other neurotrophins with activity on the TrkB tyrosine kinase receptor, increase mRNA levels and biochemical activity of enzymes of the glycolytic pathway in brain cells. Treatment with these factors was also found to stimulate glucose utilization in rat embryonic cortex cells in primary cultures. Our observations suggest that selected neurotrophins should become useful not only for the treatment of the cholinergic deficit in AD, but also of the cortical metabolic hypofunction associated with this disease.
ESTHER : Knusel_1996_Life.Sci_58(22)_2019
PubMedSearch : Knusel_1996_Life.Sci_58(22)_2019
PubMedID: 8637432