Zhang R

References (93)

Title : ABHD6 suppresses colorectal cancer progression via AKT signaling pathway - Xiong_2024_Mol.Carcinog__
Author(s) : Xiong X , Yang C , Jin Y , Zhang R , Wang S , Gan L , Hou S , Bao Y , Zeng Z , Ye Y , Gao Z
Ref : Mol Carcinog , : , 2024
Abstract : Colorectal cancer (CRC) continues to be a prevalent malignancy, posing a significant risk to human health. The involvement of alpha/beta hydrolase domain 6 (ABHD6), a serine hydrolase family member, in CRC development was suggested by our analysis of clinical data. However, the role of ABHD6 in CRC remains unclear. This study seeks to elucidate the clinical relevance, biological function, and potential molecular mechanisms of ABHD6 in CRC. We investigated the role of ABHD6 in clinical settings, conducting proliferation, migration, and cell cycle assays. To determine the influence of ABHD6 expression levels on Oxaliplatin sensitivity, we also performed apoptosis assays. RNA sequencing and KEGG analysis were utilized to uncover the potential molecular mechanisms of ABHD6. Furthermore, we validated its expression levels using Western blot and reactive oxygen species (ROS) detection assays. Our results demonstrated that ABHD6 expression in CRC tissues was notably lower compared to adjacent normal tissues. This low expression correlated with a poorer prognosis for CRC patients. Moreover, ABHD6 overexpression impeded CRC cell proliferation and migration while inducing G0/G1 cell cycle arrest. In vivo experiments revealed that downregulation of ABHD6 resulted in an increase in tumor weight and volume. Mechanistically, ABHD6 overexpression inhibited the activation of the AKT signaling pathway and decreased ROS levels in CRC cells, suggesting the role of ABHD6 in CRC progression via the AKT signaling pathway. Our findings demonstrate that ABHD6 functions as a tumor suppressor, primarily by inhibiting the AKT signaling pathway. This role establishes ABHD6 as a promising prognostic biomarker and a potential therapeutic target for CRC patients.
ESTHER : Xiong_2024_Mol.Carcinog__
PubMedSearch : Xiong_2024_Mol.Carcinog__
PubMedID: 38197491
Gene_locus related to this paper: human-ABHD6

Title : Neurotoxicity of tetramethylammonium ion on larval and juvenile zebrafish: Effects on neurobehaviors and multiple biomarkers - Zhang_2024_J.Environ.Sci.(China)_143_138
Author(s) : Zhang R , Wang R , Chang J , Sheng GD , Yin D
Ref : J Environ Sci (China) , 143 :138 , 2024
Abstract : Tetramethylammonium hydroxide (TMAH) is an important compound that utilized and released by the rapidly expanding semiconductor industry, which could hardly be removed by the conventional wastewater treatment techniques. As a cholinergic agonist, the tetramethylammonium ion (TMA(+)) has been reported to induce toxicity to muscular and respiratory systems of mammals and human, however the toxicity on aquatic biota remains poorly known. We investigated the neurotoxic effects of TMA(+) exposure on zebrafish, based on neurobehavior tests and a series of biomarkers. Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L, and significant alterations on swimming path angles (straight and deflective movements) occurred even at 10 mg/L. The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species (ROS) and malondialdehyde (MDA), significantly negatively related with the activities of antioxidant enzymes, but not significantly correlated with the level of acetylcholinesterase (AChE). Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress, rather than the alterations of neurotransmitter. At the highest exposure concentration (200 mg/L), TMA(+) evoked more severe toxicity on zebrafish juveniles, showing significantly stronger elevation on the MDA activity, and greater inhibitions on the activities of antioxidant enzymes and AChE, suggesting juveniles were more susceptible to TMA(+) exposure than larval zebrafish.
ESTHER : Zhang_2024_J.Environ.Sci.(China)_143_138
PubMedSearch : Zhang_2024_J.Environ.Sci.(China)_143_138
PubMedID: 38644012

Title : Corrigendum to Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease [Eur. J. Med. Chem. 265 (2024) 116071] -
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , :116169 , 2024
PubMedID: 38290915

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

Title : Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients - Zhang_2024_BMC.Cardiovasc.Disord_24_251
Author(s) : Zhang S , Wang J , Chen S , Zhang Y , He R , Wang X , Ding F , Hu W , Dai Y , Lu L , Zhang R , Ni J , Chen Q
Ref : BMC Cardiovasc Disord , 24 :251 , 2024
Abstract : BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.
ESTHER : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedSearch : Zhang_2024_BMC.Cardiovasc.Disord_24_251
PubMedID: 38745157

Title : A unified model for regulating lipoprotein lipase activity - Zhang_2024_Trends.Endocrinol.Metab__
Author(s) : Zhang R , Zhang K
Ref : Trends Endocrinol Metab , : , 2024
Abstract : The regulation of triglyceride (TG) tissue distribution, storage, and utilization, a fundamental process of energy homeostasis, critically depends on lipoprotein lipase (LPL). We review the intricate mechanisms by which LPL activity is regulated by angiopoietin-like proteins (ANGPTL3, 4, 8), apolipoproteins (APOA5, APOC3, APOC2), and the cAMP-responsive element-binding protein H (CREBH). ANGPTL8 functions as a molecular switch, through complex formation, activating ANGPTL3 while deactivating ANGPTL4 in their LPL inhibition. The ANGPTL3-4-8 model integrates the roles of the aforementioned proteins in TG partitioning between white adipose tissue (WAT) and oxidative tissues (heart and skeletal muscles) during the feed/fast cycle. This model offers a unified perspective on LPL regulation, providing insights into TG metabolism, metabolic diseases, and therapeutics.
ESTHER : Zhang_2024_Trends.Endocrinol.Metab__
PubMedSearch : Zhang_2024_Trends.Endocrinol.Metab__
PubMedID: 38521668

Title : A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity - Kim_2023_Sci.Signal_16_eadd6702
Author(s) : Kim H , Song Z , Zhang R , Davies BSJ , Zhang K
Ref : Sci Signal , 16 :eadd6702 , 2023
Abstract : The endoplasmic reticulum (ER)-tethered, liver-enriched stress sensor CREBH is processed in response to increased energy demands or hepatic stress to release an amino-terminal fragment that functions as a transcription factor for hepatic genes encoding lipid and glucose metabolic factors. Here, we discovered that the carboxyl-terminal fragment of CREBH (CREBH-C) derived from membrane-bound, full-length CREBH was secreted as a hepatokine in response to fasting or hepatic stress. Phosphorylation of CREBH-C mediated by the kinase CaMKII was required for efficient secretion of CREBH-C through exocytosis. Lipoprotein lipase (LPL) mediates the lipolysis of circulating triglycerides for tissue uptake and is inhibited by a complex consisting of angiopoietin-like (ANGPTL) 3 and ANGPTL8. Secreted CREBH-C blocked the formation of ANGPTL3-ANGPTL8 complexes, leading to increased LPL activity in plasma and metabolic tissues in mice. CREBH-C administration promoted plasma triglyceride clearance and partitioning into peripheral tissues and mitigated hypertriglyceridemia and hepatic steatosis in mice fed a high-fat diet. Individuals with obesity had higher circulating amounts of CREBH-C than control individuals, and human CREBH loss-of-function variants were associated with dysregulated plasma triglycerides. These results identify a stress-induced, secreted protein fragment derived from CREBH that functions as a hepatokine to stimulate LPL activity and triglyceride homeostasis.
ESTHER : Kim_2023_Sci.Signal_16_eadd6702
PubMedSearch : Kim_2023_Sci.Signal_16_eadd6702
PubMedID: 36649378

Title : Design, synthesis and biological evaluation of carbamate derivatives incorporating multifunctional carrier scaffolds as pseudo-irreversible cholinesterase inhibitors for the treatment of Alzheimer's disease - Liu_2023_Eur.J.Med.Chem_265_116071
Author(s) : Liu Y , Ma C , Li Y , Li M , Cui T , Zhao X , Li Z , Jia H , Wang H , Xiu X , Hu D , Zhang R , Wang N , Liu P , Yang H , Cheng M
Ref : Eur Journal of Medicinal Chemistry , 265 :116071 , 2023
Abstract : In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC(50) = 30.35 +/- 2.07 nM) and human butyrylcholinesterase (hBuChE, IC(50) = 48.03 +/- 6.41 nM) with minimal neurotoxicity. Further investigations have demonstrated that C7 exhibited a remarkable capacity to safeguard PC12 cells against H(2)O(2)-induced apoptosis and effectively suppressed the production of reactive oxygen species (ROS). Moreover, in an inflammation model of BV2 cells induced by lipopolysaccharide (LPS), C7 effectively attenuated the levels of pro-inflammatory cytokines. After 12 h of dialysis, C7 continued to exhibit an inhibitory effect on cholinesterase activity. An acute toxicity test in vivo demonstrated that C7 exhibited a superior safety profile and no hepatotoxicity compared to the parent nucleus tacrine. In the scopolamine-induced AD mouse model, C7 (20 mg/kg) significantly reduced cholinesterase activity in the brain of the mice. C7 was tested in a pharmacological AD mouse model induced by Abeta(1-42) and attenuated memory deficits at doses as low as 5 mg/kg. The pseudo-irreversible cholinesterase inhibitory properties and multifunctional therapeutic attributes of C7 render it a promising candidate for further investigation in the treatment of AD.
ESTHER : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedSearch : Liu_2023_Eur.J.Med.Chem_265_116071
PubMedID: 38157596

Title : Development of biodegradable nanogels for lipase accelerated drug release of 5-aminolevulinic acid - Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
Author(s) : Liu X , Zhang Y , Zhang P , Ge K , Zhang R , Sun Y , Sheng Y , Bradley M
Ref : Colloids Surf B Biointerfaces , 225 :113268 , 2023
Abstract : Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) is an important approach for the treatment of some skin diseases and cancers. A major defect of this approach is that it is difficult for 5-ALA to accumulate around lesions in deeper regions of tissue, resulting in poor conversion to the active fluorophore and photodynamic efficiencies. Because of their targeting and controlled release abilities, nanogel carriers could solve this problem. In this paper, nanogels were prepared by using micro-emulsion polymerization with various biodegradable polyester crosslinkers (L-lactide and sigma-caprolactone). The swelling and degradation properties and entrapment efficiency, drug loading and drug release ability of the nanogels were investigated. Nanogels co-cultured with skin cancer cells (A2058) allowed the efficiency of the PDT in vitro to be demonstrated. The results showed that the swelling rate of hydrogels reduced with increasing crosslinker levels, which caused a slow-down in the release of 5-ALA, but lipase accelerated degradation of nanogels increased 5-ALA concentrations in tumor cells and leading to higher PDT efficiency. It was proved by in vivo experiment indicating that the development of skin cancer tissues were efficiently inhibited by the 5-ALA loaded nanogels.
ESTHER : Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
PubMedSearch : Liu_2023_Colloids.Surf.B.Biointerfaces_225_113268
PubMedID: 36989818

Title : Elucidating the Impact of Bacterial Lipases, Human Serum Albumin, and FASII Inhibition on the Utilization of Exogenous Fatty Acids by Staphylococcus aureus - Pruitt_2023_bioRxiv__
Author(s) : Pruitt EL , Zhang R , Ross DH , Ashford NK , Chen X , Alonzo F , Bush MF , Werth BJ , Xu L
Ref : Biorxiv , : , 2023
Abstract : Staphylococcus aureus only synthesizes straight-chain or branched-chain saturated fatty acids (SCFAs or BCFAs) via the type II fatty acid synthesis (FASII) pathway, but as a highly adaptive pathogen, S. aureus can also utilize host-derived exogenous fatty acids (eFAs), including SCFAs and unsaturated fatty acids (UFAs). S. aureus secretes three lipases, Geh, sal1, and SAUSA300_0641, which could perform the function of releasing fatty acids from host lipids. Once released, the FAs are phosphorylated by the fatty acid kinase, FakA, and incorporated into the bacterial lipids. In this study, we determined the substrate specificity of S. aureus secreted lipases, the effect of human serum albumin (HSA) on eFA incorporation, and the effect of FASII inhibitor, AFN-1252, on eFA incorporation using comprehensive lipidomics. When grown with major donors of fatty acids, cholesteryl esters (CEs) and triglycerides (TGs), Geh was found to be the primary lipase responsible for hydrolyzing CEs, but other lipases could compensate for the function of Geh in hydrolyzing TGs. Lipidomics showed that eFAs were incorporated into all major S. aureus lipid classes and that fatty acid-containing HSA can serve as a source of eFAs. Furthermore, S. aureus grown with UFAs displayed decreased membrane fluidity and increased production of reactive oxygen species (ROS). Exposure to AFN-1252 enhanced UFAs in the bacterial membrane, even without a source of eFAs, indicating a FASII pathway modification. Thus, the incorporation of eFAs alters the S. aureus lipidome, membrane fluidity, and ROS formation, which could affect host-pathogen interactions and susceptibility to membrane-targeting antimicrobials. IMPORTANCE: Incorporation of host-derived exogenous fatty acids (eFAs), particularly unsaturated fatty acids (UFAs), by Staphylococcus aureus could affect the bacterial membrane fluidity and susceptibility to antimicrobials. In this work, we found that Geh is the primary lipase hydrolyzing cholesteryl esters and, to a less extent, triglycerides (TGs) and that human serum albumin (HSA) could serve as a buffer of eFAs, where low levels of HSA facilitate the utilization of eFAs, but high levels of HSA inhibit it. The fact that the FASII inhibitor, AFN-1252, leads to an increase in UFA content even in the absence of eFA suggests that membrane property modulation is part of its mechanism of action. Thus, Geh and/or the FASII system look to be promising targets to enhance S. aureus killing in a host environment by restricting eFA utilization or modulating membrane property, respectively.
ESTHER : Pruitt_2023_bioRxiv__
PubMedSearch : Pruitt_2023_bioRxiv__
PubMedID: 37425828

Title : Genome-wide identification and expression analysis of the cotton patatin-related phospholipase A genes and response to stress tolerance - Wei_2023_Planta_257_49
Author(s) : Wei Y , Chong Z , Lu C , Li K , Liang C , Meng Z , Wang Y , Guo S , He L , Zhang R
Ref : Planta , 257 :49 , 2023
Abstract : Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance.
ESTHER : Wei_2023_Planta_257_49
PubMedSearch : Wei_2023_Planta_257_49
PubMedID: 36752875

Title : Co-Immobilization of Lipases with Different Specificities for Efficient and Recyclable Biodiesel Production from Waste Oils: Optimization Using Response Surface Methodology - Wang_2023_Int.J.Mol.Sci_24_4726
Author(s) : Wang Q , Zhang R , Liu M , Ma L , Zhang W
Ref : Int J Mol Sci , 24 :4726 , 2023
Abstract : Lipase-catalyzed transesterification is a promising and sustainable approach to producing biodiesel. To achieve highly efficient conversion of heterogeneous oils, combining the specificities and advantages of different lipases is an attractive strategy. To this end, highly active Thermomyces lanuginosus lipase (1,3-specific) and stable Burkholderia cepacia lipase (non-specific) were covalently co-immobilized on 3-glycidyloxypropyltrimethoxysilane (3-GPTMS) modified Fe(3)O(4) magnetic nanoparticles (co-BCL-TLL@Fe(3)O(4)). The co-immobilization process was optimized using response surface methodology (RSM). The obtained co-BCL-TLL@Fe(3)O(4) exhibited a significant improvement in activity and reaction rate compared with mono and combined-use lipases, achieving 92.9% yield after 6 h under optimal conditions, while individually immobilized TLL, immobilized BCL and their combinations exhibited yields of 63.3%, 74.2% and 70.6%, respectively. Notably, co-BCL-TLL@Fe(3)O(4) achieved 90-98% biodiesel yields after 12 h using six different feedstocks, demonstrating the perfect synergistic effect of BCL and TLL remarkably motivated in co-immobilization. Furthermore, co-BCL-TLL@Fe(3)O(4) could maintain 77% of initial activity after nine cycles by removing methanol and glycerol from catalyst surface, accomplished by washing with t-butanol. The high catalytic efficiency, wide substrate adaptability and favorable reusability of co-BCL-TLL@Fe(3)O(4) suggest that it will be an economical and effective biocatalyst for further applications.
ESTHER : Wang_2023_Int.J.Mol.Sci_24_4726
PubMedSearch : Wang_2023_Int.J.Mol.Sci_24_4726
PubMedID: 36902155

Title : Clinical and genetic characteristics of CEL-MODY (MODY8): a literature review and screening in Chinese individuals diagnosed with early-onset type 2 diabetes - Sun_2023_Endocrine__
Author(s) : Sun S , Gong S , Li M , Wang X , Wang F , Cai X , Liu W , Luo Y , Zhang S , Zhang R , Zhou L , Zhu Y , Ma Y , Ren Q , Zhang X , Chen J , Chen L , Wu J , Gao L , Zhou X , Li Y , Zhong L , Han X , Ji L
Ref : Endocrine , : , 2023
Abstract : OBJECTIVE: CEL-related maturity-onset diabetes of the young (CEL-MODY, MODY8) is a special type of monogenetic diabetes caused by mutations in the carboxyl-ester lipase (CEL) gene. This study aimed to summarize the genetic and clinical characteristics of CEL-MODY patients and to determine the prevalence of the disease among Chinese patients with early-onset type 2 diabetes (EOD). METHODS: We systematically reviewed the literature associated with CEL-MODY in PubMed, Embase, Web of Science, China National Knowledge Infrastructure and Wanfang Data to analyze the features of patients with CEL-MODY. We screened and evaluated rare variants of the CEL gene in a cohort of 679 Chinese patients with EOD to estimate the prevalence of CEL-MODY in China. RESULTS: In total, 21 individuals reported in previous studies were diagnosed with CEL-MODY based on the combination of diabetes and pancreatic exocrine dysfunction as well as frameshift mutations in exon 11 of the CEL gene. CEL-MODY patients were nonobese and presented with exocrine pancreatic affection (e.g., chronic pancreatitis, low fecal elastase levels, pancreas atrophy and lipomatosis) followed by insulin-dependent diabetes. No carriers of CEL missense mutations were reported with exocrine pancreatic dysfunction. Sequencing of CEL in Chinese EOD patients led to the identification of the variant p.Val736Cysfs*22 in two patients. However, these patients could not be diagnosed with CEL-MODY because there were no signs that the exocrine pancreas was afflicted. CONCLUSION: CEL-MODY is a very rare disease caused by frameshift mutations affecting the proximal VNTR segments of the CEL gene. Signs of exocrine pancreatic dysfunction provide diagnostic clues for CEL-MODY, and genetic testing is vital for proper diagnosis. Further research in larger cohorts is needed to investigate the characteristics and prevalence of CEL-MODY in the Chinese population.
ESTHER : Sun_2023_Endocrine__
PubMedSearch : Sun_2023_Endocrine__
PubMedID: 37726640

Title : Modelling enzyme inhibition toxicity of ionic liquid from molecular structure via convolutional neural network model - Zhang_2023_SAR.QSAR.Environ.Res__1
Author(s) : Zhang R , Chen Y , Fan D , Liu T , Ma Z , Dai Y , Wang Y , Zhu Z
Ref : SAR QSAR Environ Research , :1 , 2023
Abstract : Deep learning (DL) methods further promote the development of quantitative structure-activity/property relationship (QSAR/QSPR) models by dealing with complex relationships between data. An acetylcholinesterase inhibitory toxicity model of ionic liquids (ILs) was established using a convolution neural network (CNN) combined with support vector machine (SVM), random forest (RF) and multilayer perceptron (MLP). A CNN model was proposed for feature self-learning and extraction of ILs. By comparing with the model results through feature engineering (FE), the model regression results based on the CNN model for feature extraction have been substantially improved. The results showed that all six models (FE-SVM, FE-RF, FE-MLP, CNN-SVM, CNN-RF, and CNN-MLP) had good prediction accuracy, but the results based on the CNN model were better. The hyperparameters of six models were optimized by grid search and the 10-fold cross validation. Compared with the existing models in the literature, the model performance has been further improved. The model could be used as an intelligent tool to guide the design or screening of low-toxicity ILs.
ESTHER : Zhang_2023_SAR.QSAR.Environ.Res__1
PubMedSearch : Zhang_2023_SAR.QSAR.Environ.Res__1
PubMedID: 37722394

Title : Computational biology-based study of the molecular mechanism of spermidine amelioration of acute pancreatitis - Shen_2023_Mol.Divers__1
Author(s) : Shen Y , Duan H , Yuan L , Asikaer A , Liu Y , Zhang R , Wang Y , Lin Z
Ref : Mol Divers , : , 2023
Abstract : Acute pancreatitis (AP) is an acute inflammatory gastrointestinal disease, the mortality and morbility of which has been on the increase in the past years. Spermidine, a natural polyamine, has a wide range of pharmacological effects including anti-inflammation, antioxidation, anti-aging, and anti-tumorigenic. This study aimed to investigate the reliable targets and molecular mechanisms of spermidine in treating AP. By employing computational biology methods including network pharmacology, molecular docking, and molecular dynamics (MD) simulations, we explored the potential targets of spermidine in improving AP with dietary supplementation. The computational biology results revealed that spermidine had high degrees (degree: 18, betweenness: 38.91; degree: 18, betweenness: 206.41) and stable binding free energy (deltaG(bind): - 12.81 +/- 0.55 kcal/mol, - 15.00 +/- 1.00 kcal/mol) with acetylcholinesterase (AchE) and serotonin transporter (5-HTT). Experimental validation demonstrates that spermidine treatment could reduce the necrosis and AchE activity in pancreatic acinar cells. Cellular thermal shift assay (CETSA) results revealed that spermidine could bind to and stabilize the 5-HTT protein in acinar cells. Moreover, spermidine treatment impeded the rise of the expression of 5-HTT in pancreatic tissues of caerulein induced acute pancreatitis mice. In conclusion, serotonin transporter might be a reliable target of spermidine in treating AP. This study provides new idea for the exploration of potential targets of natural compounds.
ESTHER : Shen_2023_Mol.Divers__1
PubMedSearch : Shen_2023_Mol.Divers__1
PubMedID: 37523101

Title : Structure, function, and pathology of Neurexin-3 - Zhang_2023_Genes.Dis_10_1908
Author(s) : Zhang R , Jiang H , Liu Y , He G
Ref : Genes Dis , 10 :1908 , 2023
Abstract : Neurexin-3 is primarily localized in the presynaptic membrane and forms complexes with various ligands located in the postsynaptic membrane. Neurexin-3 has important roles in synapse development and synapse functions. Neurexin-3 mediates excitatory presynaptic differentiation by interacting with leucine-rich-repeat transmembrane neuronal proteins. Meanwhile, neurexin-3 modulates the expression of presynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors and gamma-aminobutyric acid A receptors by interacting with neuroligins at excitatory and inhibitory synapses. Numerous studies have documented the potential contribution of neurexin-3 to neurodegenerative and neuropsychiatric disorders, such as Alzheimer's disease, addiction behaviors, and other diseases, which raises hopes that understanding the mechanisms of neurexin-3 may hold the key to developing new strategies for related illnesses. This review comprehensively covers the literature to provide current knowledge of the structure, function, and clinical role of neurexin-3.
ESTHER : Zhang_2023_Genes.Dis_10_1908
PubMedSearch : Zhang_2023_Genes.Dis_10_1908
PubMedID: 37492720

Title : N-Doped Carbon Nanotubes Supported Fe-Mn Dual-Single-Atoms Nanozyme with Synergistically Enhanced Peroxidase Activity for Sensitive Colorimetric Detection of Acetylcholinesterase and Its Inhibitor - Mao_2023_Anal.Chem__
Author(s) : Mao YW , Zhang J , Zhang R , Li JQ , Wang AJ , Zhou XC , Feng JJ
Ref : Analytical Chemistry , : , 2023
Abstract : Monitoring acetylcholinesterase (AChE) and its inhibitors is of importance for early diagnosis and therapy of neurological diseases. Herein, N-doped carbon nanotubes supported Fe-Mn dual-single-atoms (FeMn DSAs/N-CNTs) were fabricated by a simple pyrolysis, as thoroughly figured out by a series of the characterization techniques. The peroxidase-like activity of FeMn DSAs/N-CNTs was investigated by catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to generate rich hydroxyl radicals (.OH) in the H(2)O(2) system, which effectively catalyzed colorless TMB oxidation to blue oxidized TMB (ox-TMB). Besides, the peroxidase-like activity was greatly weakened by thiocholine (derived from AChE), accompanied by making blue ox-TMB fade. Impressively, the highly improved peroxidase-like property is further evidenced by density functional theory (DFT) calculations, where the dual-single atoms show a lower energy barrier (0.079 eV) and their interactions with the N-CNTs played critical roles for producing the oxygen radicals. By virtue of the nanozyme, a low-cost, specific, and sensitive colorimetric sensor was built for detection of AChE with a broader linear range of 0.1-30 U L(-1) and a lower limit of detection (LOD, 0.066 U L(-1)), combined with its feasible analysis in human serum samples. Also, this platform was applied for measuring huperzine A inhibitor with a wide linear scope of 5-500 nM and a LOD down to 4.17 nM. This strategy provides a low-cost and convenient approach for early clinical diagnosis and drug development.
ESTHER : Mao_2023_Anal.Chem__
PubMedSearch : Mao_2023_Anal.Chem__
PubMedID: 37220384

Title : Mulberry (Morus alba L.) leaf water extract attenuates type 2 diabetes mellitus by regulating gut microbiota dysbiosis, lipopolysaccharide elevation and endocannabinoid system disorder - Du_2023_J.Ethnopharmacol__117681
Author(s) : Du Y , Zhang R , Zheng XX , Zhao YL , Chen YL , Ji S , Guo MZ , Tang DQ
Ref : J Ethnopharmacol , :117681 , 2023
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaf is a well-known herbal medicine and has been used to treat diabetes in China for thousands of years. Our previous studies have proven mulberry leaf water extract (MLWE) could improve type 2 diabetes mellitus (T2D). However, it is still unclear whether MLWE could mitigate T2D by regulating gut microbiota dysbiosis and thereof improve intestinal permeability and metabolic dysfunction through modulation of lipopolysaccharide (LPS) and endocannabinoid system (eCBs). AIM OF STUDY: This study aims to explore the potential mechanism of MLWE on the regulation of metabolic function disorder of T2D mice from the aspects of gut microbiota, LPS and eCBs. MATERIALS AND METHODS: Gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. LPS, N-arachidonoylethanolamine (AEA) and 2-ararchidonylglycerol (2-AG) contents in blood were determined by kits or liquid phase chromatography coupled with triple quadrupole tandem mass spectrometry, respectively. The receptors, enzymes or tight junction protein related to eCBs or gut barrier were detected by RT-PCR or Western blot, respectively. RESULTS: MLWE reduced the serum levels of AEA, 2-AG and LPS, decreased the expressions of N-acylphophatidylethanolamine phospholipase D, diacylglycerol lipase-alpha and cyclooxygenase 2, and increased the expressions of fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), alpha/beta hydrolases domain 6/12 in the liver and ileum and occludin, monoacylglycerol lipase and cannabinoid receptor 1 in the ileum of T2D mice. Furthermore, MLWE could change the abundances of the genera including Acetatifactor, Anaerovorax, Bilophila, Colidextribacter, Dubosiella, Gastranaerophilales, Lachnospiraceae_NK4A136_group, Oscillibacter and Rikenella related to LPS, AEA and/or 2-AG. Moreover, obvious improvement of MLWE treatment on serum AEA level, ileum occludin expression, and liver FAAH and NAAA expression could be observed in germ-free-mimic T2D mice. CONCLUSION: MLWE could ameliorate intestinal permeability, inflammation, and glucose and lipid metabolism imbalance of T2D by regulating gut microbiota, LPS and eCBs.
ESTHER : Du_2023_J.Ethnopharmacol__117681
PubMedSearch : Du_2023_J.Ethnopharmacol__117681
PubMedID: 38163557

Title : Aerobic Treadmill Exercise Upregulates Epidermal Growth Factor Levels and Improves Learning and Memory in d-galactose-Induced Aging in a Mouse Model - Guo_2023_Am.J.Alzheimers.Dis.Other.Demen_38_15333175231211082
Author(s) : Guo C , Kong X , Fan Y , Zhang R
Ref : Am J Alzheimers Dis Other Demen , 38 :15333175231211082 , 2023
Abstract : Previous studies have demonstrated that exercise improves cognitive function in Alzheimer's disease mice but the exact mechanism needs further studies. This research aimed to study the effects of aerobic treadmill exercise on epidermal growth factor (EGF) levels and learning and memory in d-galactose-induced aging in a mouse model. Forty male Kunming mice were analyzed in this study and randomly divided into 4 groups: control (C group), aerobic exercise (AE group), d-galactose (D-gal group), and d-galactose + aerobic exercise (D-gal + AE group). The C and AE groups received a daily mid-scapular subcutaneous injection of .9% saline for 40 days. Mice in the D-gal and D-gal + AE groups were subcutaneously injected with d-galactose (1.25 mg/kg) once daily for 40 days. The mice in the AE group and D-gal + AE group completed 40 days of aerobic treadmill exercise. Learning and memory were evaluated by step-down tests. Specifically, 24 h after the behavioral test, blood was collected and brain tissue was extracted, and superoxide dismutase (SOD) and acetylcholinesterase activities were detected. The neurons in the CA1 and CA3 regions of the hippocampus were counted by Nissl staining. The number of EGF-positive cells was observed by immunohistochemical methods. In the learning test, the reaction time in the D-gal group increased significantly (P < .05), while the error numbers in the D-gal group tended to decrease compared with AE, D-gal + AE, and C groups. In the memory test, the latency of mice in the D-gal group was lower, while the error in this group was higher than in the other groups (P < .05). The activities of SOD and acetylcholinesterase were lower in the D-gal group than in the other groups (P < .05). The number of EGF-positive cells and neurons in the hippocampal CA1 and CA3 regions in the D-gal + AE group was higher compared to those in the D-gal group (P < .05), and lower in groups with mice that were not injected with d-galactose. Aerobic treadmill exercise inhibited SOD activity, increased EGF-positive cells, and decreased neuronal death and apoptosis, thereby improving learning and memory in the mouse model of d-galactose-induced aging.
ESTHER : Guo_2023_Am.J.Alzheimers.Dis.Other.Demen_38_15333175231211082
PubMedSearch : Guo_2023_Am.J.Alzheimers.Dis.Other.Demen_38_15333175231211082
PubMedID: 37977137

Title : Emerging insights into the roles of ANGPTL8 beyond glucose and lipid metabolism - Ye_2023_Front.Physiol_14_1275485
Author(s) : Ye H , Zong Q , Zou H , Zhang R
Ref : Front Physiol , 14 :1275485 , 2023
Abstract : Angiopoietin-like protein 8 (ANGPTL8) is a secreted protein predominantly expressed in liver and adipose tissue. ANGPTL8 modulates the clearance of triglycerides (TGs) by suppressing the activity of lipoprotein lipase (LPL) within the plasma. Previous studies found that circulating ANGPTL8 levels were significantly increased in metabolic disorder-related diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Whether ANGPTL8 has a direct pathogenic role in these diseases remains to be determined. In this review, we summarize the emerging roles of ANGPTL8 in the regulation of inflammation, tumours, circulatory system-related diseases, and ectopic lipid deposition, which may provide new insights into the diverse functions of ANGPTL8 in various diseases beyond its well-established functions in glucose and lipid metabolism.
ESTHER : Ye_2023_Front.Physiol_14_1275485
PubMedSearch : Ye_2023_Front.Physiol_14_1275485
PubMedID: 38107478

Title : PGC 1alpha-Mediates Mitochondrial Damage in the Liver by Inhibiting the Mitochondrial Respiratory Chain as a Non-cholinergic Mechanism of Repeated Low-Level Soman Exposure - Jin_2023_Biol.Pharm.Bull_46_563
Author(s) : Jin Q , Zhang Y , Cui Y , Shi M , Shi J , Zhu S , Shi T , Zhang R , Chen X , Zong X , Wang C , Li L
Ref : Biol Pharm Bull , 46 :563 , 2023
Abstract : This work aimed to assess whether mitochondrial damage in the liver induced by subacute soman exposure is caused by peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and whether PGC-1alpha regulates mitochondrial respiratory chain damage. Toxicity mechanism research may provide theoretical support for developing anti-toxic drugs in the future. First, a soman animal model was established in male Sprague-Dawley (SD) rats by subcutaneous soman injection. Then, liver damage was biochemically evaluated, and acetylcholinesterase (AChE) activity was also determined. Transmission electron microscopy (TEM) was performed to examine liver mitochondrial damage, and high-resolution respirometry was carried out for assessing mitochondrial respiration function. In addition, complex I-IV levels were quantitatively evaluated in isolated liver mitochondria by enzyme-linked immunosorbent assay (ELISA). PGC-1alpha levels were detected with a Jess capillary-based immunoassay device. Finally, oxidative stress was analyzed by quantifying superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), and reactive oxygen species (ROS) levels. Repeated low-level soman exposure did not alter AChE activity, while increasing morphological damage of liver mitochondria and liver enzyme levels in rat homogenates. Complex I, II and I + II activities were 2.33, 4.95, and 5.22 times lower after treatment compared with the control group, respectively. Among complexes I-IV, I-III decreased significantly (p < 0.05), and PGC-1alpha levels were 1.82 times lower after soman exposure than in the control group. Subacute soman exposure significantly increased mitochondrial ROS production, which may cause oxidate stress. These findings indicated dysregulated mitochondrial energy metabolism involves PGC-1alpha protein expression imbalance, revealing non-cholinergic mechanisms for soman toxicity.
ESTHER : Jin_2023_Biol.Pharm.Bull_46_563
PubMedSearch : Jin_2023_Biol.Pharm.Bull_46_563
PubMedID: 37005300

Title : Study of Huperzine A derivatives with extended protection against soman intoxication - Cui_2023_Toxicol.Appl.Pharmacol__116646
Author(s) : Cui Y , Chen X , Shi J , Jin Q , Zhang R , Shi T , Wang C , Li L
Ref : Toxicol Appl Pharmacol , :116646 , 2023
Abstract : Pre-administration of huperzine A (Hup A) was validated to prevent poisoning from exposure to nerve agents (NAs) by reversibly inhibiting acetylcholinesterase (AChE). However, like the currently commonly used reversible inhibitors, Hup A has a short half-life and is unable to produce a long-term preventative effect. To extend the protective time of Hup A against NAs, 42 derivatives with a CN bond were designed based on the structure of Hup A in this study. All designed derivatives showed good binding capability with AChE via molecular docking. Six compounds (H3, H4, H11, H14, H16, and H25) with representative structures were selected for synthesis by Schiff base reaction, and their structures were stable. The modified Ellman's method showed the six compounds concentration-dependently inhibited AChE, and the half maximal inhibitory concentration (IC(50)) were higher than that of Hup A. Pretreatment of AChE with the derivatives significantly increased the IC(50) of soman. In vivo experiments demonstrated H3, H4, H14, H16, and H25 had longer protective capacities against 1 x LD(95) soman-induced death in mice than Hup A. The 12 h protective index showed that the protective ratios of H3, H4, H14 and H16 were 2.31, 1.85, 2.23 and 1.99 respectively, better than that of Hup A. The extended protection of the derivatives against soman may be explained by their transformation to Hup A in vivo. Furthermore, all six compounds showed lower acute oral toxicity than Hup A. Overall, our study provided an optional strategy to acquire pretreatment agents for NAs with extended action and low toxicity.
ESTHER : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedSearch : Cui_2023_Toxicol.Appl.Pharmacol__116646
PubMedID: 37517785

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

Title : Recent Advances on the Role of ATGL in Cancer - Zhang_2022_Front.Oncol_12_944025
Author(s) : Zhang R , Meng J , Yang S , Liu W , Shi L , Zeng J , Chang J , Liang B , Liu N , Xing D
Ref : Front Oncol , 12 :944025 , 2022
Abstract : The hypoxic state of the tumor microenvironment leads to reprogramming lipid metabolism in tumor cells. Adipose triglyceride lipase, also known as patatin-like phospholipase= domain-containing protein 2 and Adipose triglyceride lipase (ATGL), as an essential lipid metabolism-regulating enzyme in cells, is regulated accordingly under hypoxia induction. However, studies revealed that ATGL exhibits both tumor-promoting and tumor-suppressing effects, which depend on the cancer cell type and the site of tumorigenesis. For example, elevated ATGL expression in breast cancer is accompanied by enhanced fatty acid oxidation (FAO), enhancing cancer cells' metastatic ability. In prostate cancer, on the other hand, tumor activity tends to be negatively correlated with ATGL expression. This review outlined the regulation of ATGL-mediated lipid metabolism pathways in tumor cells, emphasizing the Hypoxia-inducible factors 1 (HIF-1)/Hypoxia-inducible lipid droplet-associated (HIG-2)/ATGL axis, peroxisome proliferator-activated receptor (PPAR)/G0/G1 switch gene 2 (G0S2)/ATGL axis, and fat-specific protein 27 (FSP-27)/Early growth response protein 1 (EGR-1)/ATGL axis. In the light of recent research on different cancer types, the role of ATGL on tumorigenesis, tumor proliferation, and tumor metastasis was systemically reviewed.
ESTHER : Zhang_2022_Front.Oncol_12_944025
PubMedSearch : Zhang_2022_Front.Oncol_12_944025
PubMedID: 35912266

Title : Integrative assessment of biomarker responses in Mytilus galloprovincialis exposed to seawater acidification and copper ions - Qu_2022_Sci.Total.Environ_851_158146
Author(s) : Qu Y , Zhang T , Zhang R , Wang X , Zhang Q , Wang Q , Dong Z , Zhao J
Ref : Sci Total Environ , 851 :158146 , 2022
Abstract : The interactive effects of ocean acidification (OA) and copper (Cu) ions on the mussel Mytilus galloprovincialis are not well understood. The underlying mechanisms also remain obscure. In this study, individuals of M. galloprovincialis were exposed for 28 days to 25 microg/L and 50 microg/L Cu ions at two pH levels (ambient level - pH 8.1; acidified level - pH 7.6). The mussels were then monitored for 56 days to determine their recovery ability. Physiological parameters (clearance rate and respiration rate), oxidative stress and neurotoxicity biomarkers (activities of superoxide dismutase, lipid peroxidation, catalase, and acetylcholinesterase), as well as the recovery ability of these parameters, were investigated in two typical tissues (i.e., gills and digestive glands). Results showed that (1) OA affected the bioconcentration of Cu in the gills and digestive glands of the mussels; (2) both OA and Cu can lead to physiological disturbance, oxidative stress, cellular damage, energy metabolism disturbance, and neurotoxicity on M. galloprovincialis; (3) gill is more sensitive to OA and Cu than digestive gland; (4) Most of the biochemical and physiological alternations caused by Cu and OA exposures in M. galloprovincialis can be repaired by the recovery experiments; (5) integrated biomarker response (IBR) analysis demonstrated that both OA and Cu ions exposure caused survival stresses to the mussels, with the highest effect shown in the co-exposure treatment. This study highlights the necessity to include OA along with pollutants in future studies to better elucidate the risks of ecological perturbations. The work also sheds light on the recovery of marine animals after short-term environmental stresses when the natural environment has recovered.
ESTHER : Qu_2022_Sci.Total.Environ_851_158146
PubMedSearch : Qu_2022_Sci.Total.Environ_851_158146
PubMedID: 35987231

Title : Effect of dipeptidyl peptidase-4 inhibitors on postprandial glucagon level in patients with type 2 diabetes mellitus: A systemic review and meta-analysis - Chai_2022_Front.Endocrinol.(Lausanne)_13_994944
Author(s) : Chai S , Zhang R , Zhang Y , Carr RD , Zheng Y , Rajpathak S , Ji L
Ref : Front Endocrinol (Lausanne) , 13 :994944 , 2022
Abstract : AIMS: Hyperglucagonemia occurs in the pathogenesis of type 2 diabetes mellitus (T2DM). In this meta-analysis, we summarized the effects of DPP4 inhibitors on glucagon levels in patients with T2DM. MATERIALS AND METHODS: Randomized controlled trials (RCTs) comparing the influence of DPP4 inhibitors on circulating glucagon levels with placebo or other oral antidiabetic drugs (OADs) in patients with T2DM were identified by searches of Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library). Only studies reporting changes in glucagon level presented as total area under the curve (AUC(glucagon)) using a meal or oral glucose tolerance test were included. Results were combined using a random-effects model that incorporated potential heterogeneity among the included studies. RESULTS: A total of 36 RCTs with moderate to high quality were included. Overall, the numbers of T2DM patients included for the meta-analyses comparing DPP4 inhibitors with placebo and other OADs were 4266 and 1652, respectively. Compared to placebo, DPP4 inhibitors significantly reduced circulating glucagon levels (standard mean difference [SMD]: -0.32, 95% CI: -0.40 to -0.24, P<0.001; I(2 =) 28%). Analysis of subgroups revealed that study characteristics had no significant effect on results, such as study design (parallel group or crossover), number of patients, mean patient age, proportion of men, baseline HbA1c, duration of diabetes, background therapy, treatment duration, or methods for glucagon measurement (all P for subgroup differences >0.05). Moreover, DPP4 inhibitors significantly reduced glucagon levels compared to other OADs (SMD: -0.35, 95% CI: -0.53 to -0.16, P<0.001; I(2) = 66%), and the reduction in glucagon was greater in comparison with insulin secretagogues than in comparison with non-insulin secretagogues (P for subgroup difference =0.03). SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/, identifier INPLASY202280104. CONCLUSIONS: DPP4 inhibitors are effective at reducing the circulating postprandial glucagon level in T2DM patients.
ESTHER : Chai_2022_Front.Endocrinol.(Lausanne)_13_994944
PubMedSearch : Chai_2022_Front.Endocrinol.(Lausanne)_13_994944
PubMedID: 36313782

Title : Molecular and Biochemical Analyses of a Novel Trifunctional Endoxylanase\/Endoglucanase\/Feruloyl Esterase from the Human Colonic Bacterium Bacteroides intestinalis DSM 17393 - Zhang_2022_J.Agric.Food.Chem__
Author(s) : Zhang R , Lin D , Zhang L , Zhan R , Wang S , Wang K
Ref : Journal of Agricultural and Food Chemistry , : , 2022
Abstract : A novel enzyme Bi76 comprising GH10, E_set_Esterase_N, and CE1 modules was identified, with the highest homology (62.9%) with a bifunctional endoxylanase/feruloyl esterase among characterized enzymes. Interestingly, Bi76 hydrolyzed glucan substrates besides xylans and feruloylated substrates, suggesting that it is the first characterized trifunctional endoxylanase/endoglucanase/feruloyl esterase. Analyses of truncation variants revealed that GH10 and E_set_Esterase_N + CE1 modules encoded endoxylanase/endoglucanase and feruloyl esterase activities, respectively. Synergism analyses indicated that endoxylanase, alpha-l-arabinofuranosidase, and feruloyl esterase acted cooperatively in releasing ferulic acid (FA) and xylooligosaccharides from feruloylated arabinoxylan. The interdomain synergism of Bi76 overmatched the intermolecular synergism of TM1 and TM2. Importantly, Bi76 exhibited good capacity in producing FA, releasing 5.20, 4.38, 2.12, 1.35, 0.46, and 0.19 mg/g from corn bran, corn cob, wheat bran, corn stover, rice husk, and rice bran, respectively. This study expands the trifunctional endoxylanase/endoglucanase/feruloyl esterase repertoire and demonstrates the great potential of Bi76 in agricultural residue utilization.
ESTHER : Zhang_2022_J.Agric.Food.Chem__
PubMedSearch : Zhang_2022_J.Agric.Food.Chem__
PubMedID: 35316064
Gene_locus related to this paper: 9bace-b3c594

Title : Repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus - Shi_2021_Toxicol.Lett_338_32
Author(s) : Shi M , Deng S , Cui Y , Chen X , Shi T , Song L , Zhang R , Zhang Y , Xu J , Shi J , Wang C , Li L
Ref : Toxicol Lett , 338 :32 , 2021
Abstract : Repeated low-level exposure to sarin results to hippocampus dysfunction. Metabonomics involves a holistic analysis of a set of metabolites in an organism in the search for a relationship between these metabolites and physiological or pathological changes. The objective of the present study was to evaluate the effects of repeated exposure to low-level sarin on the metabonomics in hippocampus of a guinea pig model. Guinea pigs were divided randomly into control and sarin treated groups (n = 14). Guinea pigs in the control group received saline; while the sarin-treated group received 0.4xLD(50) (16.8 microg/kg) sarin. Daily injections (a total of 14 days) were administered sc between the shoulder blades in a volume of 1.0 ml/kg body weight. At the end of the final injection, 6 animals in each group were chosen for Morris water maze test. The rest guinea pigs (n = 8 for each group) were sacrificed by decapitation, and hippocampus were dissected for analysis. Compared with the control-group, the escape latency in sarin-group was significantly (p < 0.05) longer while the crossing times were significantly decreased in the Morris water task (p < 0.05). Sarin inhibited activities of acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in hippocampus. The AChE activity of hippocampus from sarin-treated groups is equivalent to 59.9 +/- 6.4 %, and the NTE activity of hippocampus from sarin-groups is equivalent to 78.1 +/- 8.3 % of that from control-group. Metabolites were identified and validated. A total of 14 variables were selected as potential biomarkers. Phospholipids [phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylinositol (PI), Lysophosphatidylethanolamine (LysoPE or LPE)] and sphingolipids (SPs) [sphinganine (SA), phytosphingosine (PSO) and sphinganine-1-phosphate (SA1P)] were clearly modified. In conclusion, repeated low-dose exposures to sarin disrupted the homeostasis of phospholipid and sphingolipid metabolism in guinea pig hippocampus and may lead to a neuronal-specific function disorders. Identified metabolites such as SA1P need to be studied more deeply on their biological function that against sarin lesions. In future research, we should pay more attention to characterize the physiological roles of lipid metabolism enzymes as well as their involvement in pathologies induced by repeated low-level sarin exposure.
ESTHER : Shi_2021_Toxicol.Lett_338_32
PubMedSearch : Shi_2021_Toxicol.Lett_338_32
PubMedID: 33253782

Title : One-Step Synthesis of 4-Octyl Itaconate through the Structure Control of Lipase - Liu_2021_J.Org.Chem__
Author(s) : Liu C , Wang Y , Liu J , Chen A , Xu J , Zhang R , Wang F , Nie K , Deng L
Ref : J Org Chem , : , 2021
Abstract : 4-Octyl itaconate is a novel antiviral and immunoregulatory small molecule showing great potential in the treatment of various autoimmune diseases and viral infections. It is difficult to selectively esterify the C4 carboxyl group of itaconate acid via one-step direct esterification using chemical catalysts, while the two-step route with itaconic anhydride as an intermediate is environmentally unfriendly and costly. This research investigated the one-step and green synthesis of 4-octyl itaconate through the structure control of lipase, obtaining 4-octyl itaconate with over 98% yield and over 99% selectivity. Multiscale molecular dynamics simulations were applied to investigate the reaction mechanism. The cavity pocket of lipases resulted in a 4-octyl itaconate selectivity by affecting distribution of substrates toward the catalytic site. Toluene could enhance monoesterification in the C4 carboxyl group and contribute to a nearly 100% conversion from itaconate acid into 4-octyl itaconate by adjusting the catalytic microenvironment around the lipase, producing a shrinkage effect on the channel.
ESTHER : Liu_2021_J.Org.Chem__
PubMedSearch : Liu_2021_J.Org.Chem__
PubMedID: 34085515

Title : Acer truncatum Bunge: A comprehensive review on ethnobotany, phytochemistry and pharmacology - Fan_2021_J.Ethnopharmacol__114572
Author(s) : Fan Y , Lin F , Zhang R , Wang M , Gu R , Long C
Ref : J Ethnopharmacol , :114572 , 2021
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Acer truncatum Bunge is a multifunctional plant in northern China. It has traditionally been used to prevent cardiovascular and cerebrovascular diseases and treat skin trauma by different linguistic groups including Mongolian, Tibetan, and Korean. Although research has verified that A. truncatum contains a variety of active ingredients, especially nervonic acid, an important component in delaying brain aging, to date no review has been made to compile its traditional use, phytochemistry, and pharmacology. AIMS OF THE REVIEW: This review aimed to update the traditional uses, phytochemistry, and pharmacology of A. truncatum, which expect to provide theoretical support for the future utilization as well as highlight the further investigation of this important plant. MATERIALS AND METHODS: The ethnobotanical, phytochemical, and pharmacological information related to A. truncatum from 1949 to March 2021 were collated by surveying the traditional medicinal books and ethnomedicinal publications and searching the online databases including Google Scholar, Sci Finder, Web of Science, Springer Link, PubMed, Wiley, China National Knowledge Infrastructure (CNKI), Baidu Scholar, and Wan Fang Database. RESULTS: A. truncatum has traditionally been used for medicinal, edible and ornamental purposes in northern China for many centuries. Different parts of the plant including leaves, fruits and bark, are mainly used as herbal medicine to treat hyperpiesia, hyperlipidemia, bruises, back pain, etc. A total of 288 compounds in A. truncatum, including polyphenols, organic acids or lipids, and biological volatile organic compounds were isolated or identified by phytochemical studies. Pharmacological research showed that A. truncatum has various bioactivities such as acetylcholinesterase inhibition, antibacterial, antioxidant, antitumor, and fatty acid synthase inhibition effects. CONCLUSION: A. truncatum has been used as a traditional herbal medicine for centuries in northern China. Polyphenols, organic acids, lipids and other compounds were isolated or identified from different parts of the plant. Most of the pharmacological activities of A. truncatum have been reported, which showed its potential in the development of new drugs or nutraceuticals. However, detailed information on the molecular mechanisms, metabolic activity, and toxicology of active components is limited. Further comprehensive research to evaluate the medicinal properties of A. truncatum will be necessary.
ESTHER : Fan_2021_J.Ethnopharmacol__114572
PubMedSearch : Fan_2021_J.Ethnopharmacol__114572
PubMedID: 34487848

Title : The N-terminus of Lactobacillus amylovorus feruloyl esterase plays an important role in its secretion by Lactobacillus plantarum and Escherichia coli - Xu_2021_Microb.Cell.Fact_20_152
Author(s) : Xu Z , Zhang R , Wang T , Kong J
Ref : Microb Cell Fact , 20 :152 , 2021
Abstract : BACKGROUND: Feruloyl esterase is a multifunctional esterase with potential industrial applications. In the present study, we found the Lactobacillus amylovorus feruloyl esterase (FaeLam) could be secreted by L. plantarum and Escherichia coli. However, no signal peptide was detected in this protein as predicted by SignalP-5.0. Therefore, experiments were carried out to propose an explanation for the extracellular release of FaeLam. RESULTS: Here, we identified that the FaeLam could be secreted to the culture medium of L. plantarum CGMCC6888 and E. coli DH5alpha, respectively. To exclude the possibility that FaeLam secretion was caused by its hydrolytic activity on the cell membrane, the inactive FaeLam(S106A) was constructed and it could still be secreted out of L. plantarum and E. coli cells. Furthermore, the truncated version of the FaeLam without the N-terminal residues was constructed and demonstrated the importance of the 20 amino acids of N-terminus (N20) on FaeLam secretion. In addition, fusion of heterologous proteins with N20 or FaeLam could carry the target protein out of the cells. These results indicated the N-terminus of FaeLam played the key role in the export process. CONCLUSIONS: We proved the N-terminus of L. amylovorus FaeLam plays an important role in its secretion by L. plantarum and E. coli. To our best knowledge, this is the first reported protein which can be secreted out of the cells of both Gram-positive and Gram-negative bacteria. Furthermore, the results of this study may provide a new method for protein secretion in L. plantarum and E. coli through fusion the target protein to N20 of FaeLam.
ESTHER : Xu_2021_Microb.Cell.Fact_20_152
PubMedSearch : Xu_2021_Microb.Cell.Fact_20_152
PubMedID: 34344368
Gene_locus related to this paper: lacam-a0a1c9u7k7

Title : The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels - Zhang_2021_Front.Cardiovasc.Med_8_795370
Author(s) : Zhang R
Ref : Front Cardiovasc Med , 8 :795370 , 2021
Abstract : Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.
ESTHER : Zhang_2021_Front.Cardiovasc.Med_8_795370
PubMedSearch : Zhang_2021_Front.Cardiovasc.Med_8_795370
PubMedID: 34869703

Title : Differential responses of larval zebrafish to the fungicide propamocarb: Endpoints at development, locomotor behavior and oxidative stress - Liu_2020_Sci.Total.Environ_731_139136
Author(s) : Liu X , Zhang R , Jin Y
Ref : Sci Total Environ , 731 :139136 , 2020
Abstract : The fungicide propamocarb (PM) is widely used to protect cucumbers, tomatoes and other plants from pathogens. According to previous studies, PM could be detected in the aquatic system in some area. However, the toxic effects of PM on zebrafish received very limited attention. In this study, we examined the toxic effects of various concentration of PM on the endpoints of development, locomotor behavior and oxidative stress in larval zebrafish. It was observed that PM exposure delayed embryonic development, inhibited hatchability at 60 and 72 h postfertilization and increased heart rate. After PM exposure, the larval zebrafish showed abnormal free swimming behavior and the swimming behavior in response to light-dark transition, indicating that PM had the potential to induce neurotoxicity. Moreover, PM exposure also affected the enzymatic activity of acetylcholinesterase and dopamine and the transcriptional level of genes related to neurotoxicity. In addition, PM exposure not only affects catalase (CAT), glutathione peroxidase (GPX), and glutathione S-transferase (GST) activity but also affects the transcription level of various genes. We believed that PM induced oxidative stress was also a possible reason to cause neurotoxicity in larval zebrafish. In summary, our results suggested that PM could disturb the endpoints at development, locomotor behavior and oxidative stress in larval zebrafish.
ESTHER : Liu_2020_Sci.Total.Environ_731_139136
PubMedSearch : Liu_2020_Sci.Total.Environ_731_139136
PubMedID: 32438087

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

Title : Identification of S419 on human serum albumin as a novel biomarker for sarin and cyclosarin exposure - Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
Author(s) : Fu F , Liu H , Lu X , Zhang R , Li L , Gao R , Xie J , Wang H , Pei C
Ref : Rapid Commun Mass Spectrom , :e8721 , 2020
Abstract : RATIONALE: Organophosphorus nerve agents are highly toxic because they inhibit acetylcholinesterase activity, thereby causing a series of symptomatic poisoning. Upon entering the body, nerve agents bind active amino acid residues to form phosphonylated adducts. A potentially beneficial method for specific verification of exposure of nerve agents is based on albumin adducts, which have a half-life of 18 days. This appears to be more effective than the fluoride reactivation method, based on acetylcholinesterase. METHODS: After the exposure of human serum albumin to nine nerve agents, human serum albumin was denatured, reduced, alkylated and digested with trypsin according to standard mass spectrometry-based proteomics procedures. The phosphonylated peptides of human serum albumin were identified using positive ion electrospray ionization with a quadrupole orbitrap mass spectrometer. RESULTS: The peptide KVPQVSTPTLVESR showed a good mass spectrometric response to the nine nerve agents. The tendency of sarin and cyclosarin was to bind to S419 on the peptide, while the other nerve agents (tabun, soman, and V-type nerve agents) were shown to bind more readily to K414 on the peptide. CONCLUSIONS: This research revealed the new site, S419, of the tryptic peptide KVPQVSTPTLVEVSR on human albumin to be a valuable biomarker for sarin/cyclosarin exposure, helping to further distinguish sarin and cyclosarin poisoning from nerve agents and providing an important tool for identification of sarin or cyclosarin in terrorist attacks.
ESTHER : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedSearch : Fu_2020_Rapid.Commun.Mass.Spectrom__e8721
PubMedID: 31899842

Title : Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation - Xu_2020_Bioorg.Chem_98_103721
Author(s) : Xu A , He F , Zhang X , Li X , Ran Y , Wei C , James Chou C , Zhang R , Wu J
Ref : Bioorg Chem , 98 :103721 , 2020
Abstract : In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Abeta1-42 self-aggregation as well as disaggregation activity on pre-formed Abeta fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics.
ESTHER : Xu_2020_Bioorg.Chem_98_103721
PubMedSearch : Xu_2020_Bioorg.Chem_98_103721
PubMedID: 32193030

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

Title : Transcription Factor CfSte12 of Colletotrichum fructicola Is a Key Regulator of Early Apple Glomerella Leaf Spot Pathogenesis - Liu_2020_Appl.Environ.Microbiol_87_
Author(s) : Liu W , Liang X , Gleason ML , Cao M , Zhang R , Sun G
Ref : Applied Environmental Microbiology , 87 : , 2020
Abstract : Glomerella leaf spot (GLS), caused by Colletotrichum fructicola, is a rapidly emerging disease leading to defoliation, fruit spot, and storage fruit rot on apple in China. Little is known about the mechanisms of GLS pathogenesis. Early transcriptome analysis revealed that expression of the zinc finger transcription factor Ste12 gene in C. fructicola (CfSte12) was upregulated in appressoria and leaf infection. To investigate functions of CfSte12 during pathogenesis, we constructed gene deletion mutants (deltaCfSte12) by homologous recombination. Phenotypic analysis revealed that CfSte12 was involved in pathogenesis of nonwounded apple fruit and leaf, as well as wounded apple fruit. Subsequent histological studies revealed that loss of pathogenicity by deltaCfSte12 on apple leaf was expressed as defects of conidium germination, appressorium development, and appressorium-mediated penetration. Further RNA sequencing-based transcriptome comparison revealed that CfSte12 modulates the expression of genes related to appressorium function (e.g., genes for the tetraspanin PLS1, Gas1-like proteins, cutinases, and melanin biosynthesis) and candidate effectors likely involved in plant interaction. In sum, our results demonstrated that CfSte12 is a key regulator of early apple GLS pathogenesis in C. fructicola In addition, CfSte12 is also needed for sexual development of perithecia and ascospores.IMPORTANCE Glomerella leaf spot (GLS) is an emerging fungal disease of apple that causes huge economic losses in Asia, North America, and South America. The damage inflicted by GLS manifests in rapid necrosis of leaves, severe defoliation, and necrotic spot on the fruit surface. However, few studies have addressed mechanisms of GLS pathogenesis. In this study, we identified and characterized a key pathogenicity-related transcription factor, CfSte12, of Colletotrichum fructicola that contributes to GLS pathogenesis. We provide evidence that the CfSte12 protein regulates many important pathogenic processes of GLS, including conidium germination, appressorium formation, appressorium-mediated penetration, and colonization. CfSte12 also impacts development of structures needed for sexual reproduction which are vital for the GLS disease cycle. These results reveal a key pathogenicity-related transcription factor, CfSte12, in C. fructicola that causes GLS.
ESTHER : Liu_2020_Appl.Environ.Microbiol_87_
PubMedSearch : Liu_2020_Appl.Environ.Microbiol_87_
PubMedID: 33067192

Title : Degradation mechanism for Zearalenone ring-cleavage by Zearalenone hydrolase RmZHD: A QM\/MM study - Zhou_2020_Sci.Total.Environ_709_135897
Author(s) : Zhou J , Zhu L , Chen J , Wang W , Zhang R , Li Y , Zhang Q
Ref : Sci Total Environ , 709 :135897 , 2020
Abstract : The danger of zearalenone (ZEN) as an endocrine disruptor to humans and the environment has aroused increasing attention. In this study, we implemented the quantum mechanics/molecular mechanics (QM/MM) method to investigate the degradation mechanism of ZEN hydrolase (RmZHD) toward ZEN at the atomic level. The degradation process involves two concerted reaction pathways, where the active site contains a Ser-His-Glu triplet as a proton donor. With the Boltzmann-weighted average potential barriers of 18.1 and 21.5 kcal/mol, the process undergoes proton transfer and nucleophilic-substituted ring opening to form a hydroxyl product. Non-covalent interaction analyses elucidated hydrogen bonding between key amino acids with ZEN. The electrostatic influence analysis of 16 amino acids proposes residues Asp34 and His128 as the possible mutation target for future mutation design of enzyme RmZHD. An in-depth investigation of the protein environment of RmZHD can improve the bioremediation efficiency of endocrine disrupting chemicals.
ESTHER : Zhou_2020_Sci.Total.Environ_709_135897
PubMedSearch : Zhou_2020_Sci.Total.Environ_709_135897
PubMedID: 31887512
Gene_locus related to this paper: 9euro-a0a0d2ilk1

Title : Separation of saturated fatty acids from docosahexaenoic acid-rich algal oil by enzymatic ethanolysis in tandem with molecular distillation - He_2020_Food.Sci.Nutr_8_2234
Author(s) : He J , Hong B , Lu R , Zhang R , Fang H , Huang W , Bai K , Sun J
Ref : Food Sci Nutr , 8 :2234 , 2020
Abstract : Algal oil, rich in docosahexaenoic acid (DHA) and an environmentally sustainable source of omega-3 fatty acids, is receiving increasing attention. In the present study, a novel approach combining ethanolysis with a 1,3-specific immobilized lipase (Lipozyme() TL IM) and molecular distillation was investigated to increase the DHA content of algal oil. Algal oil with a 45.94% DHA content was mixed with ethanol, pumped into a column filled with Lipozyme() TL IM, and then circulated for 4 hr at room temperature. The ethanol was then recycled by vacuum distillation. At an evaporator temperature of 150 degC, the residue was separated by molecular distillation into a heavy component enriched with DHA glycerides (in the form of triglyceride (TG), diglyceride (DG), and monoglyceride (MG)) and a light component enriched with palmitic acid (PA) and DHA ethyl ester (EE). As a result, 76.55% of the DHA from the algal oil was present in the heavy component, whose DHA content was 70.27%. DHA-MG was collected in the heavy component mostly in the form of 1-MG. Lipozyme() TL IM appeared to specifically target PA rather than DHA at the sn-1(3) position. The Lipozyme() TL IM allowed 90.03% of the initial DHA yield to be retained after seven reaction cycles. Therefore, an eco-friendly and simple method for increasing the DHA content in algal oil has been developed.
ESTHER : He_2020_Food.Sci.Nutr_8_2234
PubMedSearch : He_2020_Food.Sci.Nutr_8_2234
PubMedID: 32405380

Title : Amino acid, fatty acid, and carbohydrate metabolomic profiles with ginsenoside-induced insecticidal efficacy against Ostrinia furnacalis (Guenee) - Liu_2020_J.Ginseng.Res_44_544
Author(s) : Liu S , Wang X , Zhang R , Song M , Zhang N , Li W , Wang Y , Xu Y , Zhang L
Ref : J Ginseng Res , 44 :544 , 2020
Abstract : Background: Previous studies have shown the insecticidal efficacy of ginsenosides. In the present study, we aimed to investigate the metabolic mechanism related to the inhibitory effect of panaxadiol saponins (PDSs) against the Asian corn borer Ostrinia furnacalis (Guenee). Methods: Third instar larvae of O. furnacalis were fed normal diets with different concentrations of PDSs for 4 days. The consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food were recorded. A targeted gas chromatography-mass spectrometry assay was performed to detect the profiles of amino acids, fatty acids, and carbohydrates in larvae of O. furnacalis. In addition, the activity of detoxification-related enzymes was determined. Results and Conclusions: PDSs decreased the consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food in the 3rd instar larvae of O. furnacalis in a dose-dependent manner. PDSs decreased 15 free amino acids, 16 free fatty acids, and 5 carbohydrates and increased the levels of palmitoleic acid, palmitic acid, and 9-octadecenoic acid in the 3rd instar larvae. The activity of detoxification-related enzymes, such as acetylcholinesterase, glutathione S-transferase, cytochrome P450, carboxylesterase, trehalase, acid phosphatase, and alkaline phosphatase, was reduced in a dose-dependent manner in the 3rd instar larvae exposed to PDSs. These data confirmed the inhibitory effect of PDSs against growth, food utilization, and detoxification in the 3rd instar larvae of O. furnacalis and the potential for using PDSs as an efficient tool for insect pest management for O. furnacalis larvae.
ESTHER : Liu_2020_J.Ginseng.Res_44_544
PubMedSearch : Liu_2020_J.Ginseng.Res_44_544
PubMedID: 32617034

Title : Schizophreniaassociated microRNA148b3p regulates COMT and PRSS16 expression by targeting the ZNF804A gene in human neuroblastoma cells - Wu_2020_Mol.Med.Rep_22_1429
Author(s) : Wu S , Wang P , Tao R , Yang P , Yu X , Li Y , Shao Q , Nie F , Ha J , Zhang R , Tian Y , Ma J
Ref : Mol Med Rep , 22 :1429 , 2020
Abstract : Zinc finger protein 804A (ZNF804A) has been identified by genomewide association studies as a robust risk gene in schizophrenia, but how ZNF804A contributes to schizophrenia and its upstream regulation remains unknown. Previous studies have indicated that microRNAs (miRs) are key factors that regulate the expression levels of their target genes. The present study revealed significantly increased expression of miR148b3p in the peripheral blood of patients with firstonset schizophrenia compared with healthy controls, and bioinformatics analysis predicted that the ZNF804A gene is a target of miR148b3p. Therefore, the present study investigated the possible upstream regulation of ZNF804A by miR148b3p in the human neuroblastoma SHSY5Y cell line, and assessed the implications for schizophrenia. The results revealed significantly reversed expression levels of miR148b3p (P=0.0051) and ZNF804A (P=0.0218) in the peripheral blood of patients with firstonset schizophrenia compared with healthy individuals. Furthermore, it was demonstrated that miR148b3p directly targeted ZNF804A via binding to conserved target sites in the 3'untranslated region of ZNF804A mRNA, where it inhibited the endogenous expression of ZNF804A at both the mRNA (P=0.048) and protein levels (P=0.013) in SHSY5Y cells. Furthermore, miR148b3p was revealed to regulate the expression levels of catecholOmethyltransferase (COMT) and serine protease 16 (PRSS16) by targeting ZNF804A in SHSY5Y cells. Collectively, the present results indicated that there was a direct upstream regulation of the schizophrenia risk gene ZNF804A by miR148b3p, which contributed to the regulation of the downstream genes COMT and PRSS16. Thus, the miR148b3p/ZNF804A/COMT/PRSS16 pathway may play an important role in the pathophysiology of schizophrenia, and may serve as a potential target in drug discovery and gene therapy for this disorder.
ESTHER : Wu_2020_Mol.Med.Rep_22_1429
PubMedSearch : Wu_2020_Mol.Med.Rep_22_1429
PubMedID: 32626976
Gene_locus related to this paper: human-PRSS16

Title : Metabolism and pharmacological activities of the natural health-benefiting compound diosmin - Zheng_2020_Food.Funct_11_8472
Author(s) : Zheng Y , Zhang R , Shi W , Li L , Liu H , Chen Z , Wu L
Ref : Food Funct , 11 :8472 , 2020
Abstract : Diosmin is a famous natural flavonoid for treating chronic venous insufficiency and varicose veins. Recently, extensive study has indicated that diosmin possesses diverse pharmacological activities, including anti-inflammation, anti-oxidation, anti-diabetes, anti-cancer, anti-microorganism, liver protection, neuro-protection, cardiovascular protection, renoprotection, and retinal protection activities. Due to its low water solubility, diosmin is dramatically limited in clinical application. Expectedly, many potential strategies have been developed for improving its pharmacokinetic values and bioavailability. This health-benefiting compound has been explored as the major component of Daflon and micronized purified flavonoid fraction (MPFF), which have been used in clinics to improve micro-circulation. However, no specific drug targets for diosmin are reported, although some potential factors have been involved in screening, such as P-glycoprotein (P-gp), IKKbeta, acetylcholinesterase (AChE), and aldose reductase (AR). More investigations on the underlying mechanisms of diosmin in mediating cellular processes with high specificity is still needed.
ESTHER : Zheng_2020_Food.Funct_11_8472
PubMedSearch : Zheng_2020_Food.Funct_11_8472
PubMedID: 32966476

Title : Evaluation of toxicological responses and promising biomarkers of topmouth gudgeon (Pseudorasbora parva) exposed to fipronil at environmentally relevant levels - Li_2020_Environ.Sci.Pollut.Res.Int__
Author(s) : Li H , Zhang R , Sun F , Zhang Y
Ref : Environ Sci Pollut Res Int , : , 2020
Abstract : Fipronil is an insecticide commonly used in agriculture. We report here on the sublethal and sub-chronic effects of fipronil on non-target topmouth gudgeon (Pseudorasbora parva) at environmentally relevant levels. The results showed that fipronil did not cause significant changes in brain acetylcholinesterase activities, glutathione S-transferase (GST) activities in the intestine, and GST, glutamic pyruvic transaminase (GPT), and glutamic oxaloacetic transaminase (GOT) activities in the liver tissues at environmentally relevant levels for 96-h exposure. In the further test for a 12-day exposure, dose-dependent responses of the serum GPT and GOT activities were observed in all treated groups with sublethal concentrations of fipronil. Furthermore, fipronil could reduce the liver mitochondrial membrane fluidity of P. parva, especially with high concentration of fipronil at high temperature. The results suggest that serum GPT and GOT in P. parva might be useful biomarkers for effects of fipronil exposure at environmentally relevant level, and reducing fluidity of liver mitochondrial membrane may be one toxic mechanism of fipronil.
ESTHER : Li_2020_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Li_2020_Environ.Sci.Pollut.Res.Int__
PubMedID: 32304060

Title : Effects of BIS-MEP on Reversing Amyloid Plaque Deposition and Spatial Learning and Memory Impairments in a Mouse Model of beta-Amyloid Peptide- and Ibotenic Acid-Induced Alzheimer's Disease - Wang_2019_Front.Aging.Neurosci_11_3
Author(s) : Wang Y , Xia J , Shen M , Zhou Y , Wu Z , Shi Y , Xu J , Hou L , Zhang R , Qiu Z , Xie Q , Chen H , Zhang Y , Wang H
Ref : Front Aging Neurosci , 11 :3 , 2019
Abstract : Alzheimer's disease (AD) is the main type of dementia and is characterized by progressive memory loss and a notable decrease in cholinergic neuron activity. As classic drugs currently used in the clinic, acetylcholinesterase inhibitors (AChEIs) restore acetylcholine levels and relieve the symptoms of AD, but are insufficient at delaying the onset of AD. Based on the multi-target-directed ligand (MTDL) strategy, bis-(-)-nor-meptazinol (BIS-MEP) was developed as a multi-target AChEI that mainly targets AChE catalysis and the beta-amyloid (Abeta) aggregation process. In this study, we bilaterally injected Abeta oligomers and ibotenic acid (IBO) into the hippocampus of ICR mice and then subcutaneously injected mice with BIS-MEP to investigate its therapeutic effects and underlying mechanisms. According to the results from the Morris water maze test, BIS-MEP significantly improved the spatial learning and memory impairments in AD model mice. Compared with the vehicle control, the BIS-MEP treatment obviously inhibited the AChE activity in the mouse brain, consistent with the findings from the behavioral tests. The BIS-MEP treatment also significantly reduced the Abeta plaque area in both the hippocampus and cortex, suggesting that BIS-MEP represents a direct intervention for AD pathology. Additionally, the immunohistochemistry and ELISA results revealed that microglia (ionized calcium-binding adapter molecule 1, IBA1) and astrocyte (Glial fibrillary acidic protein, GFAP) activation and the secretion of relevant inflammatory factors (TNFalpha and IL-6) induced by Abeta were decreased by the BIS-MEP treatment. Furthermore, BIS-MEP showed more advantages than donepezil (an approved AChEI) as an Abeta intervention. Based on our findings, BIS-MEP improved spatial learning and memory deficits in AD mice by regulating acetylcholinesterase activity, Abeta deposition and the inflammatory response in the brain.
ESTHER : Wang_2019_Front.Aging.Neurosci_11_3
PubMedSearch : Wang_2019_Front.Aging.Neurosci_11_3
PubMedID: 30723404

Title : Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats - Wang_2019_Front.Pharmacol_10_1003
Author(s) : Wang K , Chen Q , Wu N , Li Y , Zhang R , Wang J , Gong D , Zou X , Liu C , Chen J
Ref : Front Pharmacol , 10 :1003 , 2019
Abstract : Background: Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairment via the cholinergic anti-inflammatory and insulin signaling pathways. Methods: Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit and beta-Amyloid (Abeta) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression. Results: We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Abeta formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine. Discussion: In conclusion, berberine clears Abeta deposit and consequently ameliorates spatial learning memory impairment via the activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.
ESTHER : Wang_2019_Front.Pharmacol_10_1003
PubMedSearch : Wang_2019_Front.Pharmacol_10_1003
PubMedID: 31551793

Title : Serum Triglyceride Lipase Concentrations are Independent Risk Factors for Coronary Artery Disease and In-Stent Restenosis - Yu_2019_J.Atheroscler.Thromb_26_762
Author(s) : Yu X , Lu J , Li J , Guan W , Deng S , Deng Q , Ye H , Han W , Yu Y , Zhang R
Ref : J Atheroscler Thromb , 26 :762 , 2019
Abstract : AIM: Endothelial lipase (EL), hepatic lipase (HL), and lipoprotein lipase (LPL) are all triglyceride lipases and are associated with coronary artery disease (CAD). However, whether they can be simultaneous independent risk factors for CAD is unknown. In the present study, we investigated whether the three lipases can be independent risk factors simultaneously for CAD and whether combining these lipases could provide greater predictive power than high-density lipoprotein cholesterol (HDL-c) for the development of CAD. METHODS: Eighty-six patients with CAD and 65 healthy controls were enrolled in the study. Additionally, 38 patients who underwent one-year follow-up angiography after percutaneous coronary intervention with stent implantation were collected to investigate in-stent restenosis. Serum EL, HL, and LPL concentrations were measured and compared with other coronary risk factors. RESULTS: Serum EL and HL concentrations were both significantly increased in patients with CAD or in-stent restenosis, whereas serum LPL concentration was reduced significantly in patients with CAD. Multivariate logistic regression analysis indicated that the three lipases were simultaneous independent risk factors for CAD. However, only serum EL concentration was considered an independent risk factor for in-stent restenosis. Importantly, the receiver operating characteristic curve showed that the combined measurement of the three lipases displayed better predictive power than HDL-c or any one of the three lipases for CAD. CONCLUSIONS: Serum EL concentration was an independent risk factor for both CAD and in-stent restenosis. Moreover, the combined assessment of serum EL, HL, and LPL concentrations as multiple risk factors provided potent predictive power for CAD.
ESTHER : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedSearch : Yu_2019_J.Atheroscler.Thromb_26_762
PubMedID: 30651409

Title : De novo genome assembly of the endangered Acer yangbiense, a plant species with extremely small populations endemic to Yunnan Province, China - Yang_2019_Gigascience_8_giz085
Author(s) : Yang J , Wariss HM , Tao L , Zhang R , Yun Q , Hollingsworth P , Dao Z , Luo G , Guo H , Ma Y , Sun W
Ref : Gigascience , 8 : , 2019
Abstract : BACKGROUND: Acer yangbiense is a newly described critically endangered endemic maple tree confined to Yangbi County in Yunnan Province in Southwest China. It was included in a programme for rescuing the most threatened species in China, focusing on "plant species with extremely small populations (PSESP)". FINDINGS: We generated 64, 94, and 110 Gb of raw DNA sequences and obtained a chromosome-level genome assembly of A. yangbiense through a combination of Pacific Biosciences Single-molecule Real-time, Illumina HiSeq X, and Hi-C mapping, respectively. The final genome assembly is -666 Mb, with 13 chromosomes covering -97% of the genome and scaffold N50 sizes of 45 Mb. Further, BUSCO analysis recovered 95.5% complete BUSCO genes. The total number of repetitive elements account for 68.0% of the A. yangbiense genome. Genome annotation generated 28,320 protein-coding genes, assisted by a combination of prediction and transcriptome sequencing. In addition, a nearly 1:1 orthology ratio of dot plots of longer syntenic blocks revealed a similar evolutionary history between A. yangbiense and grape, indicating that the genome has not undergone a whole-genome duplication event after the core eudicot common hexaploidization. CONCLUSION: Here, we report a high-quality de novo genome assembly of A. yangbiense, the first genome for the genus Acer and the family Aceraceae. This will provide fundamental conservation genomics resources, as well as representing a new high-quality reference genome for the economically important Acer lineage and the wider order of Sapindales.
ESTHER : Yang_2019_Gigascience_8_giz085
PubMedSearch : Yang_2019_Gigascience_8_giz085
PubMedID: 31307060
Gene_locus related to this paper: 9rosi-a0a5c7hxy4 , 9rosi-a0a5c7h0k5 , 9rosi-a0a5n5kbl1

Title : Donepezil, a drug for Alzheimer's disease, promotes oligodendrocyte generation and remyelination - Cui_2019_Acta.Pharmacol.Sin_40_1386
Author(s) : Cui X , Guo YE , Fang JH , Shi CJ , Suo N , Zhang R , Xie X
Ref : Acta Pharmacol Sin , 40 :1386 , 2019
Abstract : Myelin sheaths play important roles in neuronal functions. In the central nervous system (CNS), the myelin is formed by oligodendrocytes (OLs), which are differentiated from oligodendrocyte precursor cells (OPCs). In CNS demyelinating disorders such as multiple sclerosis (MS), the myelin sheaths are damaged and the remyelination process is hindered. Small molecule drugs that promote OPC to OL differentiation and remyelination may provide a new way to treat these demyelinating diseases. Here we report that donepezil, an acetylcholinesterase inhibitor (AChEI) developed for the treatment of Alzheimer's disease (AD), significantly promotes OPC to OL differentiation. Interestingly, other AChEIs, including huperzine A, rivastigmine, and tacrine, have no such effect, indicating that donepezil's effect in promoting OPC differentiation is not dependent on the inhibition of AChE. Donepezil also facilitates the formation of myelin sheaths in OPC-DRG neuron co-culture. More interestingly, donepezil also promotes the repair of the myelin sheaths in vivo and provides significant therapeutic effect in a cuprizone-mediated demyelination animal model. Donepezil is a drug that has been used to treat AD safely for many years; our findings suggest that it might be repurposed to treat CNS demyelinating diseases such as MS by promoting OPC to OL differentiation and remyelination.
ESTHER : Cui_2019_Acta.Pharmacol.Sin_40_1386
PubMedSearch : Cui_2019_Acta.Pharmacol.Sin_40_1386
PubMedID: 30918344

Title : Bis(9)-(-)-Meptazinol, a novel dual-binding AChE inhibitor, rescues cognitive deficits and pathological changes in APP\/PS1 transgenic mice - Shi_2018_Transl.Neurodegener_7_21
Author(s) : Shi Y , Huang W , Wang Y , Zhang R , Hou L , Xu J , Qiu Z , Xie Q , Chen H , Zhang Y , Wang H
Ref : Transl Neurodegener , 7 :21 , 2018
Abstract : Background: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative brain disorder, which is the most common form of dementia. Intensive efforts have been made to find effective and safe treatment against AD. Acetylcholinesterase inhibitors (AChEIs) have been widely used for the treatment of mild to moderate AD. In this study, we investigated the effect of Bis(9)-(-)-Meptazinol (B9M), a novel potential dual-binding acetylcholinesterase (AChE) inhibitor, on learning and memory abilities, as well as the underlying mechanism in the APP/PS1 mouse model of AD. Methods: B9M (0.1 mug/kg, 0.3 mug/kg, and 1 mug/kg) was administered by subcutaneous injection into eight-month-old APP/PS1 transgenic mice for four weeks. Morris water maze, nest-building and novel object recognition were used to examine learning and memory ability. Abeta levels and Abeta plaque were evaluated by ELISA and immunochemistry. Results: Our results showed that chronic treatment with B9M significantly improved the cognitive function of APP/PS1 transgenic mice in the Morris water maze test, nest-building test and novel object recognition test. Moreover, B9M improved cognitive deficits in APP/PS1 mice by a mechanism that may be associated with its inhibition of the AChE activity, Abeta plaque burden, levels of Abeta and the consequent activation of astrocytes and microglia in the brain of APP/PS1 transgenic mice. Most of important, the most effective dose of B9M in the present study is 1 mug/kg, which is one thousand of the dosage of Donepezil acted as the control treatment. Furthermore, B9M reduced Abeta plaque burden better than Donepezil. Conclusion: These results indicate that B9M appears to have potential as an effective AChE inhibitor for the treatment of AD with symptom-relieving and disease-modifying properties.
ESTHER : Shi_2018_Transl.Neurodegener_7_21
PubMedSearch : Shi_2018_Transl.Neurodegener_7_21
PubMedID: 30237878

Title : A novel non-enzymatic hydrolytic probe for dipeptidyl peptidase IV specific recognition and imaging - Xing_2018_Chem.Commun.(Camb)_54_8773
Author(s) : Xing J , Gong Q , Zhang R , Sun S , Zou R , Wu A
Ref : Chem Commun (Camb) , 54 :8773 , 2018
Abstract : A novel non-enzymatic hydrolytic probe for DPP IV is obtained. And this new probe can be used for special DPP IV recognition and imaging in living cells. Importantly, one general strategy for the construction of new non-enzymatic fluorescent probes for many important proteases can be proposed based on the present study.
ESTHER : Xing_2018_Chem.Commun.(Camb)_54_8773
PubMedSearch : Xing_2018_Chem.Commun.(Camb)_54_8773
PubMedID: 30035284

Title : Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane - Wang_2018_Phys.Chem.Chem.Phys_20_20540
Author(s) : Wang J , Tang X , Li Y , Zhang R , Zhu L , Chen J , Sun Y , Zhang Q , Wang W
Ref : Phys Chem Chem Phys , 20 :20540 , 2018
Abstract : The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts.
ESTHER : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedSearch : Wang_2018_Phys.Chem.Chem.Phys_20_20540
PubMedID: 30051124

Title : Enantioselectivity of haloalkane dehalogenase LinB on the degradation of 1,2-dichloropropane: A QM\/MM study - Tang_2017_Bioorg.Chem_73_16
Author(s) : Tang X , Zhang R , Li Y , Zhang Q , Wang W
Ref : Bioorg Chem , 73 :16 , 2017
Abstract : The hydrolysis dechlorination mechanism of a chiral organochlorinepollutant, 1,2-dichloropropane (DCP), catalyzed by haloalkane dehalogenase LinB has been investigated by using a combined quantum mechanics/molecular mechanics method. LinB was confirmed to be enantioselective towards the catabolism of the racemic mixture. Based on the SN2 nucleophilic substitution mechanism, the dechlorination process was identified as the rate-determining step in LinB-catalyzed degradation of 1,2-dichloropropane, the Boltzmann-weighted average potential barrier of which is 18.8kcal/mol for the (R)-isomer and 24.0kcal/mol for the (S)-isomer. A particular water molecule near (S)-DCP in the reaction system can strongly disturb the dechlorination process, which can account for the enantioselectivity of LinB. Further electrostatic influence analysis indicates that proper mutation of Gly37 may improve the catalytic efficiency of LinB towards DCP.
ESTHER : Tang_2017_Bioorg.Chem_73_16
PubMedSearch : Tang_2017_Bioorg.Chem_73_16
PubMedID: 28527381

Title : Efficient Generation of Functionally Active Spinal Cord Neurons from Spermatogonial Stem Cells - Yang_2017_Mol.Neurobiol_54_788
Author(s) : Yang H , Liu C , Chen B , An J , Zhang R , Zhang Q , Zhao J , He B , Hao DJ
Ref : Molecular Neurobiology , 54 :788 , 2017
Abstract : Neural stem cells (NSCs) are hitherto regarded as perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and function restoration. However, the extreme drawbacks of NSCs available for injury transplantation still represent a significant bottleneck in neural regeneration medicine. Therefore, it is essential to establish a suitable cell reservoir as an issue-free alternative. Here, we demonstrate that spermatogonial stem cells (SSCs) derived from rat testis robustly give rise to terminally differentiated, functionally mature spinal cord neurons by using an optimized differentiation protocol. After performing a 3-week in vitro differentiation procedure, most cells exhibited neural morphological features and were Tuj-1 positive. Of note, approximately 60 % of the obtained cells coexpressed choline acetyltransferase (CHAT), acetylcholinesterase (AchE), and calcitonin gene-related peptide (CGRP). More importantly, apart from acquisition of neural antigenic and biochemical properties, nearly all neurons efficiently exhibited in vitro functionality similar to wild-type neurons, such as synapse formation, increased neuronal calcium influx, and electrophysiology. This is the first report revealing consistent and reproducible generation of large amounts of functional neurons from SSCs. Collectively, this system is suitable for studies of SSC transdifferentiation into neuronal cells and can provide sufficient neurons for the treatment of spinal cord injury as well as for genetic and small molecule screenings.
ESTHER : Yang_2017_Mol.Neurobiol_54_788
PubMedSearch : Yang_2017_Mol.Neurobiol_54_788
PubMedID: 27566610

Title : Genome sequence of the ectophytic fungus Ramichloridium luteum reveals unique evolutionary adaptations to plant surface niche - Wang_2017_BMC.Genomics_18_729
Author(s) : Wang B , Liang X , Gleason ML , Zhang R , Sun G
Ref : BMC Genomics , 18 :729 , 2017
Abstract : BACKGROUND: Ectophytic fungi occupy the waxy plant surface, an extreme environment characterized by prolonged desiccation, nutrient limitation, and exposure to solar radiation. The nature of mechanisms that facilitate adaptation to this environment remains unclear. In this study, we sequenced the complete genome of an ectophytic fungus, Ramichloridium luteum, which colonizes the surface of apple fruit, and carried out comparative genomic and transcriptome analysis.
RESULTS: The R. luteum genome was 28.18 Mb and encoded 9466 genes containing 1.85% repetitive elements. Compared with cell-penetrating pathogens, genes encoding plant cell wall degrading enzymes (PCWDEs), PTH11-like G protein-coupled receptors (GPCRs) and effectors were drastically reduced. In contrast, genes encoding cutinases and secretory lipases were strikingly expanded, and four of nine secretory lipases were probably acquired by horizontal gene transfer from Basidiomycota. Transcriptomic analysis revealed elevated expression of genes involved in cuticle degradation (cutinase, secretory lipase) and stress responses (melanin biosynthesis, aquaporins, lysozymes and HOG pathway).
CONCLUSIONS: Taken together, our results highlight genomic features associated with evolution of surface niche adaptation by the ectophytic fungus R. luteum, namely the contraction of PCWDEs, PTH11-like GPCRs and effectors, and the expansion of cuticle degradation and stress tolerance.
ESTHER : Wang_2017_BMC.Genomics_18_729
PubMedSearch : Wang_2017_BMC.Genomics_18_729
PubMedID: 28915794

Title : Interaction of a digestive protease, Candida rugosa lipase, with three surfactants investigated by spectroscopy, molecular docking and enzyme activity assay - Zhang_2017_Sci.Total.Environ_622-623_306
Author(s) : Zhang R , Liu Y , Huang X , Xu M , Liu R , Zong W
Ref : Sci Total Environ , 622-623 :306 , 2017
Abstract : The extensive use of surfactants in food, laundry products and agriculture has caused concern about their biosafety. However, few studies have been done on their potential effect on the lipase which has always been used with surfactants in food and laundry industry. Herein, we investigated the interaction of three surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), sodium lauryl sulfonate (SLS)) with Candida rugosa lipase (CRL), which is a popular biocatalyst used regularly with surfactants. The effect of the three surfactants on the conformation and activity of CRL was evaluated by using multiple spectral methods, enzyme activity assay and molecular docking modeling. The results demonstrated that CRL interacted with SDS, SDBS and SLS primarily through hydrophobic forces, H-bonding and electrostatic forces, respectively. The binding constants (KA) of SDBS with CRL varied with temperature: 1.99x10(3)mol/L at 298K and 4.13x10(3)mol/L at 318K. SDS and SDBS affected the secondary structure and skeleton of CRL, which changed the polarity of CRL and enhanced its activity. SLS also changed the secondary structure and activity of CRL moderately, but had little effect on its polarity and chromophore microenvironment. Accordingly, all three surfactants exhibited effect to CRL on the molecular level calling for more attention to pay on their biosafety. The work demonstrates that SDS, SDBS and SLS could cause negative effects to CRL from different angles and therefore are not bio-friendly detergents.
ESTHER : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedSearch : Zhang_2017_Sci.Total.Environ_622-623_306
PubMedID: 29220758

Title : Synthesis and characterization of biodegradable poly(ether-ester) urethane acrylates for controlled drug release - Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
Author(s) : Feng X , Wang G , Neumann K , Yao W , Ding L , Li S , Sheng Y , Jiang Y , Bradley M , Zhang R
Ref : Mater Sci Eng C Mater Biol Appl , 74 :270 , 2017
Abstract : Three polyether-ester triblock diols, with various molecular weights, were synthesized from sigma-caprolactone and polyethylene glycol and used, with diisocyanates, as soft segments for the preparation of polyurethane acrylate oligomers. The polyurethane acrylates were used to generate cross-linked polyurethane films via UV initiated polymerization with and without cargo incorporation. Degradation experiment indicated that in PBS/H(2)O(2)/CoCl(2) the films degraded rapidly compared to PBS alone or with lipase. The polyurethane membrane loaded with the antibiotic tetracycline, demonstrated prolonged release over 200h, suggesting that the polymers could be used as an implant coating for controlled drug release.
ESTHER : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedSearch : Feng_2017_Mater.Sci.Eng.C.Mater.Biol.Appl_74_270
PubMedID: 28254295

Title : Rational Design of a Red-Emissive Fluorophore with AIE and ESIPT Characteristics and Its Application in Light-Up Sensing of Esterase - Peng_2017_Anal.Chem_89_3162
Author(s) : Peng L , Xu S , Zheng X , Cheng X , Zhang R , Liu J , Liu B , Tong A
Ref : Analytical Chemistry , 89 :3162 , 2017
Abstract : The development of red fluorophores with efficient solid-state emission is still challenging. Herein, a red fluorophore 1 with aggregation-induced emission (AIE) and excited-state intramolecular proton transfer (ESIPT) characteristics is rationally designed and facilely synthesized by attaching an electron-donor diethylamine and an electron-acceptor maleonitrile group to salicyladazine. In contrast to many red fluorophores which undergo serious aggregation-caused quenching (ACQ), compound 1 emits bright red fluorescence (lambdaem = 650 nm, PhiF = 24.3%) in the solid state with a large Stokes shift of 174 nm. Interestingly, control compounds 2 and 3, which have similar structures as 1, exhibit obvious aggregation-caused quenching (ACQ) characteristics. The difference in the crystal structures of 1, 2, and 3 reveals that the interplanar spacing among molecules plays a decisive role in realizing the AIE characteristics of 1. Moreover, when the hydroxyl group of 1 was substituted by an esterase reactive acetoxyl, a fluorescence light-up probe 4 was developed for sensing of esterase based on the selective reaction between 4 and esterase to generate the AIE and ESIPT active molecule 1. The linear range for in vitro quantification of esterase is 0.01-0.15 U/mL with a detection limit of 0.005 U/mL. Probe 4 was also successfully applied to image esterase in mitochondria of living cells.
ESTHER : Peng_2017_Anal.Chem_89_3162
PubMedSearch : Peng_2017_Anal.Chem_89_3162
PubMedID: 28192960

Title : Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome - Zhang_2017_Lipids.Health.Dis_16_57
Author(s) : Zhang R , Song Q , Liu H , Bai H , Zhang Y , Liu Q , Guan L , Fan P
Ref : Lipids Health Dis , 16 :57 , 2017
Abstract : BACKGROUND: The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women.
METHODS: A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed.
RESULTS: No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women.
CONCLUSIONS: There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 --> H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.
ESTHER : Zhang_2017_Lipids.Health.Dis_16_57
PubMedSearch : Zhang_2017_Lipids.Health.Dis_16_57
PubMedID: 28320416

Title : Ultrahigh pressure-assisted enzymatic extraction maximizes the yield of longan pulp polysaccharides and their acetylcholinesterase inhibitory activity in vitro - Bai_2016_Int.J.Biol.Macromol_96_214
Author(s) : Bai Y , Liu L , Zhang R , Huang F , Deng Y , Zhang M
Ref : Int J Biol Macromol , 96 :214 , 2016
Abstract : An extraction method employing ultrahigh pressure-assisted enzymatic treatment was developed and optimized by response surface methodology to increase the yield of longan pulp polysaccharides (LP-UE). A maximum polysaccharides yield of 8.55% was obtained under the optimal conditions of 407MPa ultrahigh pressure maintained for 6min with an enzyme to pretreated material ratio of 1:100, an enzymolysis time of 1.7h and a water to pretreated material ratio of 42ml/g. Subsequently, the physicochemical properties and acetylcholinesterase (AChE) inhibitory activity of LP-UE were compared to those of longan pulp polysaccharides (LP) extracted by hot water (LP-H), ultrahigh pressure (LP-U) or enzymatic treatment (LP-E). Results demonstrated that the extraction yield, hexuronic acid content and AChE inhibitory activity of LP-UE was the highest among the four LP samples. LP-UE was primarily made up of arabinose, glucose, and galactose and was linked mainly by beta-type glycosidic linkage. The FTIR spectrum of LP-UE was very similar to those of LP-H, LP-U, and LP-E. In summary, ultrahigh pressure-assisted enzymatic treatment is a more efficient technique for extracting LP with considerable improvement of both yield and memory enhancement function.
ESTHER : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedSearch : Bai_2016_Int.J.Biol.Macromol_96_214
PubMedID: 27908719

Title : Differentially expressed lncRNAs and mRNAs identified by microarray analysis in GBS patients vs healthy controls - Xu_2016_Sci.Rep_6_21819
Author(s) : Xu J , Gao C , Zhang F , Ma X , Peng X , Zhang R , Kong D , Simard AR , Hao J
Ref : Sci Rep , 6 :21819 , 2016
Abstract : The aim of our present study was to determine whether message RNAs (mRNAs) and long noncoding RNAs (lncRNAs) are expressed differentially in patients with Guillain-Barre syndrome (GBS) compared with healthy controls. The mRNA and lncRNA profiles of GBS patients and healthy controls were generated by using microarray analysis. From microarray analysis, we listed 310 mRNAs and 114 lncRNAs with the mRMR software classed into two sample groups, GBS patients and healthy controls. KEGG mapping demonstrated that the top seven signal pathways may play important roles in GBS development. Several GO terms, such as cytosol, cellular macromolecular complex assembly, cell cycle, ligase activity, protein catabolic process, etc., were enriched in gene lists, suggesting a potential correlation with GBS development. Co-expression network analysis indicated that 113 lncRNAs and 303 mRNAs were included in the co-expression network. Our present study showed that these differentially expressed mRNAs and lncRNAs may play important roles in GBS development, which provides basic information for defining the mechanism(s) that promote GBS.
ESTHER : Xu_2016_Sci.Rep_6_21819
PubMedSearch : Xu_2016_Sci.Rep_6_21819
PubMedID: 26898505

Title : Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population - Wang_2016_Sci.Rep_6_20691
Author(s) : Wang T , Ma X , Peng D , Zhang R , Sun X , Chen M , Yan J , Wang S , Yan D , He Z , Jiang F , Bao Y , Hu C , Jia W
Ref : Sci Rep , 6 :20691 , 2016
Abstract : Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 x 10(-5) and 6.54 x 10(-4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 x 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 x 10(-8) and 4.43 x 10(-8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 x 10(-4) and 4.65 x 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population.
ESTHER : Wang_2016_Sci.Rep_6_20691
PubMedSearch : Wang_2016_Sci.Rep_6_20691
PubMedID: 26848030

Title : Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism - Gunawardane_2016_J.Biol.Chem_291_2799
Author(s) : Gunawardane RN , Fordstrom P , Piper DE , Masterman S , Siu S , Liu D , Brown M , Lu M , Tang J , Zhang R , Cheng J , Gates A , Meininger D , Chan J , Carlson T , Walker N , Schwarz M , Delaney J , Zhou M
Ref : Journal of Biological Chemistry , 291 :2799 , 2016
Abstract : Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouse(TM) platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 A LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease.
ESTHER : Gunawardane_2016_J.Biol.Chem_291_2799
PubMedSearch : Gunawardane_2016_J.Biol.Chem_291_2799
PubMedID: 26644477
Gene_locus related to this paper: human-LCAT

Title : FAM172A protein promotes the proliferation of human papillary thyroid carcinoma cells via the p38 mitogen-activated protein kinase pathway - Li_2016_Mol.Med.Rep_13_353
Author(s) : Li MF , Zhang R , Guo MG , Li LX , Lu HK , Lu JX , Jia WP
Ref : Mol Med Rep , 13 :353 , 2016
Abstract : Family with sequence similarity 172, member A (FAM172A), was cloned from human aortic tissues and confirmed in our previous study in 2009, however, its functions remain to be fully elucidated. In our previous studies, the protein expression of FAM172A in human aortic smooth muscle cells was found to be upregulated by high glucose in a concentration and timedependent manner. Several reports have shown that insulin resistance is associated with papillary thyroid carcinoma (PTC). Thus, in the present study, the protein expression levels of FAM172A in human papillary thyroid carcinoma were investigated, and the effect of the FAM172A protein on the proliferation of IHH4 human papillary thyroid carcinoma cells, and its potential molecular underlying mechanisms were examined. Immunohistochemistry and western blotting demonstrated that the protein expression of FAM172A in papillary thyroid carcinoma tissues was not only significantly higher than that in noncancerous tissues adjacent to the carcinoma tissues, but it was also markedly higher than that in normal thyroid and thyroid adenoma tissues. Overexpression of the FAM172A protein activated the p38 MAPK pathway, but not the PI3K and AMPK pathways, in the IHH4 cells. In addition, overexpression of the FAM172A protein accelerated IHH4 cell proliferation, compared with the control group, and the proproliferative effect of FAM172A protein on IHH4 cells was markedly attenuated by SB202190, an inhibitor of p38 MAPK. Taken together, these results suggest that the FAM172A protein is expressed at high levels in human PTC, which may promote cell proliferation via activation of the p38 MAPK signaling pathway, and be involved in the pathogenesis of PTC.
ESTHER : Li_2016_Mol.Med.Rep_13_353
PubMedSearch : Li_2016_Mol.Med.Rep_13_353
PubMedID: 26573560
Gene_locus related to this paper: human-f172a

Title : The high-resolution crystal structure of human LCAT - Piper_2015_J.Lipid.Res_56_1711
Author(s) : Piper DE , Romanow WG , Gunawardane RN , Fordstrom P , Masterman S , Pan O , Thibault ST , Zhang R , Meininger D , Schwarz M , Wang Z , King C , Zhou M , Walker NP
Ref : J Lipid Res , 56 :1711 , 2015
Abstract : LCAT is intimately involved in HDL maturation and is a key component of the reverse cholesterol transport (RCT) pathway which removes excess cholesterol molecules from the peripheral tissues to the liver for excretion. Patients with loss-of-function LCAT mutations exhibit low levels of HDL cholesterol and corneal opacity. Here we report the 2.65 A crystal structure of the human LCAT protein. Crystallization required enzymatic removal of N-linked glycans and complex formation with a Fab fragment from a tool antibody. The crystal structure reveals that LCAT has an alpha/beta hydrolase core with two additional subdomains that play important roles in LCAT function. Subdomain 1 contains the region of LCAT shown to be required for interfacial activation, while subdomain 2 contains the lid and amino acids that shape the substrate binding pocket. Mapping the naturally occurring mutations onto the structure provides insight into how they may affect LCAT enzymatic activity.
ESTHER : Piper_2015_J.Lipid.Res_56_1711
PubMedSearch : Piper_2015_J.Lipid.Res_56_1711
PubMedID: 26195816
Gene_locus related to this paper: human-LCAT

Title : Genome Sequence and Annotation of Trichoderma parareesei, the Ancestor of the Cellulase Producer Trichoderma reesei - Yang_2015_Genome.Announc_3_e00885
Author(s) : Yang D , Pomraning K , Kopchinskiy A , Karimi Aghcheh R , Atanasova L , Chenthamara K , Baker SE , Zhang R , Shen Q , Freitag M , Kubicek CP , Druzhinina IS
Ref : Genome Announc , 3 :e00885 , 2015
Abstract : The filamentous fungus Trichoderma parareesei is the asexually reproducing ancestor of Trichoderma reesei, the holomorphic industrial producer of cellulase and hemicellulase. Here, we present the genome sequence of the T. parareesei type strain CBS 125925, which contains genes for 9,318 proteins.
ESTHER : Yang_2015_Genome.Announc_3_e00885
PubMedSearch : Yang_2015_Genome.Announc_3_e00885
PubMedID: 26272569
Gene_locus related to this paper: hypjr-a0a024s1s9

Title : Genome-wide transcriptomic analysis of a superior biomass-degrading strain of A. fumigatus revealed active lignocellulose-degrading genes - Miao_2015_BMC.Genomics_16_459
Author(s) : Miao Y , Liu D , Li G , Li P , Xu Y , Shen Q , Zhang R
Ref : BMC Genomics , 16 :459 , 2015
Abstract : BACKGROUND: Various saprotrophic microorganisms, especially filamentous fungi, can efficiently degrade lignocellulose that is one of the most abundant natural materials on earth. It consists of complex carbohydrates and aromatic polymers found in the plant cell wall and thus in plant debris. Aspergillus fumigatus Z5 was isolated from compost heaps and showed highly efficient plant biomass-degradation capability. RESULTS: The 29-million base-pair genome of Z5 was sequenced and 9540 protein-coding genes were predicted and annotated. Genome analysis revealed an impressive array of genes encoding cellulases, hemicellulases and pectinases involved in lignocellulosic biomass degradation. Transcriptional responses of A. fumigatus Z5 induced by sucrose, oat spelt xylan, Avicel PH-101 and rice straw were compared. There were 444, 1711 and 1386 significantly differently expressed genes in xylan, cellulose and rice straw, respectively, when compared to sucrose as a control condition. CONCLUSIONS: Combined analysis of the genomic and transcriptomic data provides a comprehensive understanding of the responding mechanisms to the most abundant natural polysaccharides in A. fumigatus. This study provides a basis for further analysis of genes shown to be highly induced in the presence of polysaccharide substrates and also the information which could prove useful for biomass degradation and heterologous protein expression.
ESTHER : Miao_2015_BMC.Genomics_16_459
PubMedSearch : Miao_2015_BMC.Genomics_16_459
PubMedID: 26076650
Gene_locus related to this paper: neofi-a1d0b8

Title : A QM\/MM study of the reaction mechanism of (R)-hydroxynitrile lyases from Arabidopsis thaliana (AtHNL) - Zhu_2015_Proteins_83_66
Author(s) : Zhu W , Liu Y , Zhang R
Ref : Proteins , 83 :66 , 2015
Abstract : Hydroxynitrile lyases (HNLs) catalyze the conversion of chiral cyanohydrins to hydrocyanic acid (HCN) and aldehyde or ketone. Hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) is the first R-selective HNL enzyme containing an alpha/beta-hydrolases fold. In this article, the catalytic mechanism of AtHNL was theoretically studied by using QM/MM approach based on the recently obtained crystal structure in 2012. Two computational models were constructed, and two possible reaction pathways were considered. In Path A, the calculation results indicate that the proton transfer from the hydroxyl group of cyanohydrin occurs firstly, and then the cleavage of C1-C2 bond and the rotation of the generated cyanide ion (CN(-)) follow, afterwards, CN(-) abstracts a proton from His236 via Ser81. The C1-C2 bond cleavage and the protonation of CN(-) correspond to comparable free energy barriers (12.1 vs. 12.2 kcal mol(-1)), suggesting that both of the two processes contribute a lot to rate-limiting. In Path B, the deprotonation of the hydroxyl group of cyanohydrin and the cleavage of C1-C2 bond take place in a concerted manner, which corresponds to the highest free energy barrier of 13.2 kcal mol(-1). The free energy barriers of Path A and B are very similar and basically agree well with the experimental value of HbHNL, a similar enzyme of AtHNL. Therefore, both of the two pathways are possible. In the reaction, the catalytic triad (His236, Ser81, and Asp208) acts as the general acid/base, and the generated CN(-) is stabilized by the hydroxyl group of Ser81 and the main-chain NH-groups of Ala13 and Phe82.
ESTHER : Zhu_2015_Proteins_83_66
PubMedSearch : Zhu_2015_Proteins_83_66
PubMedID: 25052541
Gene_locus related to this paper: arath-HNL

Title : Colorimetric and Phosphorimetric Dual-Signaling Strategy Mediated by Inner Filter Effect for Highly Sensitive Assay of Organophosphorus Pesticides - Zhang_2015_J.Agric.Food.Chem_63_8947
Author(s) : Zhang R , Li N , Sun J , Gao F
Ref : Journal of Agricultural and Food Chemistry , 63 :8947 , 2015
Abstract : We describe here a colorimetric and phosphorimetric dual-signaling strategy for sensitive assay of organophosphorus pesticides (OPPs). The principle for assay depends on the phenomenon that the phosphorescence of Mn-ZnS quantum dots (QDs) can be dramatically quenched by Au nanoparticles (AuNPs) through the inner filter effect (IFE) and the activity of acetylcholinesterase (AChE), an enzyme that catalytically hydrolyzes acetylthiocholine to thiocholine that can be inhibited by OPPs. By virtue of the variations of absorbance and phosphorescence of the analytical system, a dual-readout assay for OPPs has been proposed. The limits of detection for different OPPs including paraoxon, parathion, omethoate, and dimethyl dichlorovinyl phosphate (DDVP) are found to be 0.29, 0.59, 0.67, and 0.44 ng/L, respectively. The proposed assay was allowed to detect pesticides in real spiked samples and authentic contaminated apples with satisfactory results, suggesting its potential applications to detect pesticides in complicated samples.
ESTHER : Zhang_2015_J.Agric.Food.Chem_63_8947
PubMedSearch : Zhang_2015_J.Agric.Food.Chem_63_8947
PubMedID: 26411607

Title : Protein-Coated Microcrystals from Candida rugosa Lipase: Its Immobilization, Characterization, and Application in Resolution of Racemic Ibuprofen - Huang_2015_Appl.Biochem.Biotechnol_177_36
Author(s) : Huang S , Li X , Xu L , Ke C , Zhang R , Yan Y
Ref : Appl Biochem Biotechnol , 177 :36 , 2015
Abstract : In this study, an economical heterogeneous biocatalyst, protein-coated microcrystals (PCMCs), was prepared from a commercial Candida rugosa lipase (CRL) and used for catalyzing esterification of (R, S)-ibuprofen enantiomers with isooctanol in isooctane. The main variables controlling the process (precipitating solvents, pH, saturated K2SO4 solution, and water content) were optimized via single-factorial experiments. Under optimum conditions, the enantiomeric excess of active S(+)-ibuprofen and total conversion rate were 97.34 and 49.83 %, respectively, and the corresponding enzyme (PCMC-CRL) activity attained 387.29 mumol/min/g protein, a 5.78-fold enhancement over the free lipase powder. Additionally, the thermostability, organic-solvent tolerance, and operational stability of PCMC-CRL were greatly improved as compared to the free enzyme. Fourier transform infrared (FTIR) spectroscopy was employed to reveal the correlation between conformation and enzyme activity enhancement. Moreover, the PCMC-CRL retained most of its original activity following use in more than 15 successive batches, suggesting that it exhibits adequate operational stability. These results indicate that PCMC-CRL is of great potential use in industrial applications.
ESTHER : Huang_2015_Appl.Biochem.Biotechnol_177_36
PubMedSearch : Huang_2015_Appl.Biochem.Biotechnol_177_36
PubMedID: 26137875

Title : Chrysin attenuates experimental autoimmune neuritis by suppressing immuno-inflammatory responses - Xiao_2014_Neurosci_262_156
Author(s) : Xiao J , Zhai H , Yao Y , Wang C , Jiang W , Zhang C , Simard AR , Zhang R , Hao J
Ref : Neuroscience , 262 :156 , 2014
Abstract : Guillain-Barre syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. This study was designed to investigate the anti-inflammatory and neuroprotective properties of preventative and therapeutic chrysin treatment in EAN rats. For preventative treatment, chrysin was administered orally from day 1 to day 16 (50mg/kg once daily) while, for therapeutic treatment, rats received chrysin from day 7 to day 16 at the same dose once daily. Control animals received the same volume of the vehicle (phosphate-buffered saline/2% dimethylsulfoxide). Regardless of the treatment regimen, chrysin attenuated the severity and duration of the clinical course of EAN and reduced inflammatory cell infiltration and demyelination of sciatic nerves. In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1beta, interleukin-2, interleukin-6, inteleukin-12, interferon gamma and tumor necrosis factor alpha, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.
ESTHER : Xiao_2014_Neurosci_262_156
PubMedSearch : Xiao_2014_Neurosci_262_156
PubMedID: 24412705

Title : Complete Genome Sequence of Paenibacillus polymyxa SQR-21, a Plant Growth-Promoting Rhizobacterium with Antifungal Activity and Rhizosphere Colonization Ability - Li_2014_Genome.Announc_2_e00281
Author(s) : Li S , Yang D , Qiu M , Shao J , Guo R , Shen B , Yin X , Zhang R , Zhang N , Shen Q
Ref : Genome Announc , 2 : , 2014
Abstract : Here we report the complete genome sequence of a plant growth-promoting rhizobacterium (PGPR), Paenibacillus polymyxa SQR-21, which consists of one circular chromosome of 5,828,438 bp with 5,024 coding sequences (CDS). The data presented highlight multiple sets of functional genes associated with its plant-beneficial characteristics.
ESTHER : Li_2014_Genome.Announc_2_e00281
PubMedSearch : Li_2014_Genome.Announc_2_e00281
PubMedID: 24723719
Gene_locus related to this paper: paep6-e0rmc7

Title : Physiological effects of Paichongding applied to rice on the Nilaparvata lugens (Sta L), the brown planthopper - Qin_2014_Arch.Insect.Biochem.Physiol_87_72
Author(s) : Qin X , Zhang R , Zhang J , Shi Y
Ref : Archives of Insect Biochemistry & Physiology , 87 :72 , 2014
Abstract : Nilaparvata lugens (Stal) is a major rice pest in Asia. Paichongding is a novel neonicotinoid insecticide developed in 2008. The effects of this insecticide on the activity of detoxification enzymes of N. lugens and on rice resistance to the pest were examined in the laboratory. The results showed that paichongding could significantly decrease the acetylcholinesterase and GSHs transferase activities of N. lugens. The variation tendency of mixed function oxidase (MFO) activity was similar with that of the esterase. After 12 h treatment, there was no significance between the treatment and control. However, the activities of MFO and esterase increased after 24 and 48 h treatment, which suggested that MFO and esterase may play an important role in the detoxification of paichongding for N. lugens. Our results also demonstrated that treated with paichongding, damage levels of rice plants were significantly lower than those of control plants except 15 days after treatment. Compared with the control, injury indices decreased 70.22, 49.12, 34.44, and 23.23% at 3 , 6 , 9, and 12 days after paichongding treatment, respectively. The laboratory results suggested that paichongding may be effective for the control of brown planthopper.
ESTHER : Qin_2014_Arch.Insect.Biochem.Physiol_87_72
PubMedSearch : Qin_2014_Arch.Insect.Biochem.Physiol_87_72
PubMedID: 25042427

Title : Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer's disease-like lesions - Zhang_2014_Int.J.Mol.Sci_15_14396
Author(s) : Zhang R , Zhang J , Fang L , Li X , Zhao Y , Shi W , An L
Ref : Int J Mol Sci , 15 :14396 , 2014
Abstract : Alzheimer's disease (AD) is a common neurodegenerative disease in elderly individuals, and effective therapies are unavailable. This study was designed to investigate the neuroprotective effects of sulforaphane (an activator of NF-E2-related factor 2) on mice with AD-like lesions induced by combined administration of aluminum and d-galactose. Step-down-type passive avoidance tests showed sulforaphane ameliorated cognitive impairment in AD-like mice. Immunohistochemistry results indicated sulforaphane attenuated cholinergic neuron loss in the medial septal and hippocampal CA1 regions in AD-like mice. However, spectrophotometry revealed no significant difference in acetylcholine level or the activity of choline acetyltransferase or acetylcholinesterase in the cerebral cortex among groups of control and AD-like mice with and without sulforaphane treatment. Sulforaphane significantly increased the numbers of 5-bromo-2'-deoxyuridine-positive neurons in the subventricular and subgranular zones in AD-like mice which were significantly augmented compared with controls. Atomic absorption spectrometry revealed significantly lower aluminum levels in the brains of sulforaphane-treated AD-like mice than in those that did not receive sulforaphane treatment. In conclusion, sulforaphane ameliorates neurobehavioral deficits by reducing cholinergic neuron loss in the brains of AD-like mice, and the mechanism may be associated with neurogenesis and aluminum load reduction. These findings suggest that phytochemical sulforaphane has potential application in AD therapeutics.
ESTHER : Zhang_2014_Int.J.Mol.Sci_15_14396
PubMedSearch : Zhang_2014_Int.J.Mol.Sci_15_14396
PubMedID: 25196440

Title : Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex - Huang_2013_J.Clin.Invest_123_3815
Author(s) : Huang Y , Wu Z , Riwanto M , Gao S , Levison BS , Gu X , Fu X , Wagner MA , Besler C , Gerstenecker G , Zhang R , Li XM , Didonato AJ , Gogonea V , Tang WH , Smith JD , Plow EF , Fox PL , Shih DM , Lusis AJ , Fisher EA , Didonato JA , Landmesser U , Hazen SL
Ref : J Clinical Investigation , 123 :3815 , 2013
Abstract : Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
ESTHER : Huang_2013_J.Clin.Invest_123_3815
PubMedSearch : Huang_2013_J.Clin.Invest_123_3815
PubMedID: 23908111

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

Title : Draft Genome Sequence of Ochrobactrum pseudogrignonense Strain CDB2, a Highly Efficient Arsenate-Resistant Soil Bacterium from Arsenic-Contaminated Cattle Dip Sites - Yang_2013_Genome.Announc_1_e0017313
Author(s) : Yang Y , Yu X , Zhang R
Ref : Genome Announc , 1 :e0017313 , 2013
Abstract : We report the 4.97-Mb draft genome sequence of a highly efficient arsenate-resistant bacterium, Ochrobactrum sp. strain CDB2. It contains a novel arsenic resistance (ars) operon (arsR-arsC1-ACR3-arsC2-arsH-mfs) and two non-operon-associated ars genes, arsC3 and arsB. The genome information will aid in the understanding of the arsenic resistance mechanism of this and other bacterial species.
ESTHER : Yang_2013_Genome.Announc_1_e0017313
PubMedSearch : Yang_2013_Genome.Announc_1_e0017313
PubMedID: 23599296

Title : Smilagenin attenuates beta amyloid (25-35)-induced degeneration of neuronal cells via stimulating the gene expression of brain-derived neurotrophic factor - Zhang_2012_Neurosci_210_275
Author(s) : Zhang R , Wang Z , Howson PA , Xia Z , Zhou S , Wu E , Hu Y
Ref : Neuroscience , 210 :275 , 2012
Abstract : The development of drugs that attenuate neurodegeneration is important for the treatment of Alzheimer's disease (AD). We previously found that smilagenin (SMI), a steroidal sapogenin from traditional Chinese medicinal herbs improves memory in animal models, is neither a cholinesterase inhibitor nor a glutamate receptor antagonist, but can significantly elevate the declined muscarinic receptor (M receptor) density. In this article, to clarify whether SMI represents a new approach for treating neurodegeneration disease, we first demonstrate that SMI pretreatment significantly attenuates the neurodegenerative changes induced by beta amyloid 25-35 (Abeta(25-35)) in cultured rat cortical neurons, including decreased cholinergic neuron number, shortened neurite outgrowth length, and declined M receptor density. Brain-derived neurotrophic factor (BDNF) protein levels in the culture medium were also decreased by Abeta(25-35) and significantly elevated by SMI. Parallel experiments revealed that when the trk receptors were inhibited by K252a or the action of BDNF was inhibited by a neutralizing anti-BDNF antibody, the effects of SMI on the Abeta(25-35)-induced neurodegeneration in rat cortical neurons were almost completely abolished. In the all-trans retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cells, the BDNF transcription rate measured by a nuclear run-on assay was significantly suppressed by Abeta(25-35) and elevated by SMI, but the BDNF degradation rate measured by half-life determination was unchanged by Abeta(25-35) and SMI. Transcript analysis of the SH-SY5Y cells using quantitative RT-PCR (qRT-PCR) showed that the IV and VI transcripts of BDNF mRNA were significantly decreased by Abeta(25-35) and elevated by SMI. Taken together, we conclude that SMI attenuates Abeta(25-35)-induced neurodegeneration in cultured rat cortical neurons and SH-SY5Y cells mainly through stimulating BDNF mRNA transcription implicating that SMI may represent a novel therapeutic strategy for AD.
ESTHER : Zhang_2012_Neurosci_210_275
PubMedSearch : Zhang_2012_Neurosci_210_275
PubMedID: 22441042

Title : Characterization of a thermostable beta-glucosidase from Aspergillus fumigatus Z5, and its functional expression in Pichia pastoris X33 - Liu_2012_Microb.Cell.Fact_11_25
Author(s) : Liu D , Zhang R , Yang X , Zhang Z , Song S , Miao Y , Shen Q
Ref : Microb Cell Fact , 11 :25 , 2012
Abstract : BACKGROUND: Recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and beta-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful beta-glucosides. Although the beta-glucosidases of different sources have been investigated, the amount of beta-glucosidases are insufficient for effective conversion of cellulose. The goal of this work was to search for new resources of beta-glucosidases, which was thermostable and with high catalytic efficiency.
RESULTS: In this study, a thermostable native beta-glucosidase (nBgl3), which is secreted by the lignocellulose-decomposing fungus Aspergillus fumigatus Z5, was purified to electrophoretic homogeneity. Internal sequences of nBgl3 were obtained by LC-MS/MS, and its encoding gene, bgl3, was cloned based on the peptide sequences obtained from the LC-MS/MS results. bgl3 contains an open reading frame (ORF) of 2622 bp and encodes a protein with a predicted molecular weight of 91.47 kDa; amino acid sequence analysis of the deduced protein indicated that nBgl3 is a member of the glycoside hydrolase family 3. A recombinant beta-glucosidase (rBgl3) was obtained by the functional expression of bgl3 in Pichia pastoris X33. Several biochemical properties of purified nBgl3 and rBgl3 were determined - both enzymes showed optimal activity at pH 6.0 and 60 degrees C, and they were stable for a pH range of 4-7 and a temperature range of 50 to 70 degrees C. Of the substrates tested, nBgl3 and rBgl3 displayed the highest activity toward 4-Nitrophenyl-beta-D-glucopyranoside (pNPG), with specific activities of 103.5 +/- 7.1 and 101.7 +/- 5.2 U mg-1, respectively. However, these enzymes were inactive toward carboxymethyl cellulose, lactose and xylan.
CONCLUSIONS: An native beta-glucosidase nBgl3 was purified to electrophoretic homogeneity from the crude extract of A. fumigatus Z5. The gene bgl3 was cloned based on the internal sequences of nBgl3 obtained from the LC-MS/MS results, and the gene bgl3 was expressed in Pichia pastoris X33. The results of various biochemical properties of two enzymes including specific activity, pH stability, thermostability, and kinetic properties (Km and Vmax) indicated that they had no significant differences.
ESTHER : Liu_2012_Microb.Cell.Fact_11_25
PubMedSearch : Liu_2012_Microb.Cell.Fact_11_25
PubMedID: 22340848

Title : Memory defect induced by beta-amyloid plus glutamate receptor agonist is alleviated by catalpol and donepezil through different mechanisms - Xia_2012_Brain.Res_1441_27
Author(s) : Xia Z , Zhang R , Wu P , Hu Y
Ref : Brain Research , 1441 :27 , 2012
Abstract : Our previous studies demonstrate that a non-cholinesterase inhibitor (AChEI) compound catalpol, purified from a traditional Chinese medicinal herb Rehmannia glutinosa, could improve the symptoms and pathological changes in animal and cellular models of memory related neurodegenerative diseases. In this study, we compared catalpol with the most commonly used AChEI donepezil in respect to their mechanism of action on the neurodegenerative changes in an animal model induced by beta-amyloid (Abeta) plus glutamate receptor agonist. It was found that the model mice showed significant deficit in the learning ability and memory in Y maze avoidance test, and meanwhile both donepezil and catalpol greatly improve the learning ability and memory after 2 to 3 months' administration. At the selected doses, donepezil only partially raised the declined brain muscarinic acetylcholine receptor (M receptor) density and choline acetyltransferase (ChAT) activity resulting in these levels still lower than normal control, while catalpol completely retrieved these two parameters. ELISA revealed that catalpol, instead of donepezil, possessed the capability of elevating the declined brain BDNF level of the animal model. The ELISA results on the BDNF protein level was confirmed by quantitative RT-PCR measurement of BDNF mRNA in Abeta(2)(5)(-)(3)(5)-treated primary culture of forebrain neurons. In combination with our previous work, we think the neuroprotective effects of donepezil and catalpol are mediated through different mechanisms. Since BDNF has been proved to be an important intrinsic factor in protecting neurodegenerative diseases, catalpol may be a hopefully effective compound against neurodegenerative changes induced by Abeta and glutamate receptor agonist.
ESTHER : Xia_2012_Brain.Res_1441_27
PubMedSearch : Xia_2012_Brain.Res_1441_27
PubMedID: 22305339

Title : Biochemical effects of acute phoxim administration on antioxidant system and acetylcholinesterase in Oxya chinensis (Thunberg) (Orthoptera: Acrididae) - Wu_2011_Pestic.Biochem.Physiol_100_23
Author(s) : Wu H , Liu J , Zhang R , Zhang J , Guo Y , Ma E
Ref : Pesticide Biochemistry and Physiology , 100 :23 , 2011
Abstract : The study was undertaken to evaluate the effects of different concentrations of phoxim on acetylcholinesterase (AChE) and esterase (EST) activities, and antioxidant system after topical application to Oxya chinensis. The results showed that phoxim inhibited AChE activity, and did not cause significant changes in the EST activity and the levels of malondialdehyde (MDA) and reduced glutathione (GSH). After phoxim administration, superoxide (SOD) and catalase (CAT) activities showed a biphasic response with an initial increase followed by a decline in their activities. Glutathione reductase (GR) and glutathione peroxidase (GPx) activities were inhibited in comparison with the control. Glutathione S-transferase (GST) activity showed irregular changes. Its activity increased significantly at the concentrations of 0.06 and 0.12 ug/uL and decreased at the concentrations of 0.09 and 0.24 ug/uL compared with the control. Changes in SOD, CAT, GST, GPx, and GR activities indicated that phoxim caused oxidative damage in O. chinensis. However, no significant changes in MDA content suggested that these enzymes played important roles in scavenging the oxidative free radicals induced by phoxim in O. chinensis. The formation of oxygen free radicals might be a factor in the toxicity of phoxim.
ESTHER : Wu_2011_Pestic.Biochem.Physiol_100_23
PubMedSearch : Wu_2011_Pestic.Biochem.Physiol_100_23

Title : Over-expression of human lipoprotein lipase in mouse mammary glands leads to reduction of milk triglyceride and delayed growth of suckling pups - Wang_2011_PLoS.One_6_e20895
Author(s) : Wang Y , Tong J , Li S , Zhang R , Chen L , Zheng M , Wang M , Liu G , Dai Y , Zhao Y , Li N
Ref : PLoS ONE , 6 :e20895 , 2011
Abstract : BACKGROUND: The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. PRINCIPAL FINDINGS: Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. CONCLUSION: Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology.
ESTHER : Wang_2011_PLoS.One_6_e20895
PubMedSearch : Wang_2011_PLoS.One_6_e20895
PubMedID: 21698114

Title : Cross-resistance of bisultap resistant strain of Nilaparvata lugens and its biochemical mechanism - Ling_2011_J.Econ.Entomol_104_243
Author(s) : Ling S , Zhang R
Ref : J Econ Entomol , 104 :243 , 2011
Abstract : The resistant (R) strain of the planthopper Nilaparvata lugens (Stal) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.
ESTHER : Ling_2011_J.Econ.Entomol_104_243
PubMedSearch : Ling_2011_J.Econ.Entomol_104_243
PubMedID: 21404864

Title : Regulation of M1-receptor mRNA stability by smilagenin and its significance in improving memory of aged rats - Hu_2010_Neurobiol.Aging_31_1010
Author(s) : Hu Y , Wang Z , Zhang R , Wu P , Xia Z , Orsi A , Rees D
Ref : Neurobiology of Aging , 31 :1010 , 2010
Abstract : The purpose of this work is to study the effect of smilagenin on the mRNA stability of muscarinic receptor subtype 1 (M(1); m1 mRNA) in aged rat brains and its significance in improving memory. The Y-maze avoidance task showed that oral administration of smilagenin significantly improved spatial memory performance in aged rats. Mechanistic studies showed that smilagenin was neither a ligand of the M receptors nor a cholinesterase inhibitor, while radioligand binding assays revealed that smilagenin significantly increased the M(1)-receptor density. The increase of M(1)-receptor density correlated with memory improvement. Real-time polymerase chain reaction (RT-PCR) revealed that the m1 mRNA in m1 gene-transfected CHO cells increased significantly, and the average half-life of m1 mRNA was approximately doubled by smilagenin treatment. These results suggest that smilagenin improves memory of aged rats at least partially by increasing the stability of m1 mRNA. However since the ChAT activity in the cortex of aged rats was also elevated by smilagenin, it cannot be excluded that the increase of intrinsic acetylcholine excretion also plays a role in the memory-improvement effect of smilagenin.
ESTHER : Hu_2010_Neurobiol.Aging_31_1010
PubMedSearch : Hu_2010_Neurobiol.Aging_31_1010
PubMedID: 18676061

Title : Relationship between plasma HDL subclasses distribution and lipoprotein lipase gene HindIII polymorphism in hyperlipidemia - Long_2006_Clin.Chim.Acta_366_316
Author(s) : Long S , Tian Y , Zhang R , Yang L , Xu Y , Jia L , Fu M
Ref : Clinica Chimica Acta , 366 :316 , 2006
Abstract : BACKGROUND: Different high-density lipoprotein (HDL) subclasses have distinct but interrelated metabolic functions. HDL directly influences the atherogenic process, and changes in HDL subclasses distribution may be related to the incidence and prevalence of atherosclerosis. Lipoprotein lipase (LPL) is an important enzyme for hydrolysis of triglyceride-rich lipoproteins, and its activity is positively correlated with the plasma HDL cholesterol level. LPL gene HindIII polymorphism has been found associated with variations in lipid levels, but the impact on HDL subclasses distribution is less clearly established.
METHODS: The relative apolipoprotein (apo) A-I contents (% apoA-I) of plasma HDL subclasses were determined by two-dimensional gel electrophoresis coupled with immunodetection and LPL gene HindIII polymorphism was assayed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 173 hyperlipidemic and 155 normolipidemic subjects.
RESULTS: The frequencies of 495TT genotype and allele T were the highest both in the hyperlipidemic and control groups. Compared with the control group, the frequency of 495TT genotype was higher, while the frequencies of 495TG and 495GG genotypes were significantly lower (P<0.05) in the hyperlipidemic group. Two-dimensional gel electrophoresis and immunodetection showed that HDL subclasses distribution was altered in hyperlipidemia, and had a general shift toward smaller size. Compared with the control group, the hyperlipidemic group had significantly higher relative apoA-I contents of prebeta1-HDL, prebeta2-HDL, HDL3b and HDL3a (P<0.05) and lower HDL2a and HDL2b levels (P<0.001). In the hyperlipidemic group, allele T carriers' frequency was higher than that in the control group (P<0.05), and the genotype of 495TT showed higher levels of plasma TG, apoB100, TG/HDL-C ratio, relative apoA-I contents of prebeta1-HDL, HDL3b and lower HDL2a, HDL2b compared with that of the 495GG genotype subgroup (P<0.05). In the control group, the genotype of 495TT had higher plasma TG, HDL3c and lower HDL2a compared with that of 495GG subgroup (P<0.05).
CONCLUSIONS: The 495TT genotype of LPL gene HindIII polymorphism was associated with changes of HDL subclasses distribution in Chinese population with hyperlipidemia. The particle size of HDL shifted toward smaller, which, in turn, indicated that RCT might be weakened and HDL maturation might be abnormal in hyperlipidemic subjects with 495TT genotype.
ESTHER : Long_2006_Clin.Chim.Acta_366_316
PubMedSearch : Long_2006_Clin.Chim.Acta_366_316
PubMedID: 16364275

Title : Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders - Cummings_2006_Am.J.Geriatr.Psychiatry_14_605
Author(s) : Cummings JL , McRae T , Zhang R
Ref : American Journal of Geriatry & Psychiatry , 14 :605 , 2006
Abstract : OBJECTIVE: The objective of this study was to conduct exploratory analyses of data pertaining to the efficacy of donepezil treatment of patients with severe behavioral disturbances. Preliminary studies suggest that cholinesterase inhibitors, including donepezil, may reduce behavioral disturbances in patients with Alzheimer disease (AD). Most patients included in clinical trials have had low levels of psychopathology at baseline, and the effect of cholinesterase inhibitors on patients with more severe behavioral disturbances is unknown. The authors report the effects of donepezil on behavioral disturbances in patients with relatively severe psychopathology at baseline. METHODS: This is a hypothesis-driven secondary analysis of a three-phase study involving donepezil and sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3, patients on donepezil were randomized to receive placebo or sertraline for an additional 12 weeks. The data set analyzed is comprised of the patient population treated with donepezil (without sertraline) for 20 weeks. One hundred twenty patients were included in the analyses. Mean age was 76 years, average Mini-Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI) total score was 30. Primary efficacy assessments were the NPI, the Clinical Global Impression-Improvement, and the Clinical Global Impression-Severity scales. Secondary measures included the Behavioral Pathology in Alzheimer's Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's Disease Functional Assessment and Change Scale. RESULTS: Excellent concurrent validity was noted between the NPI and the Behavioral Pathology in Alzheimer's Disease Rating Scale. The total score of the NPI was significantly reduced over the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at least a 30% reduction in the total NPI score (significantly greater than the number with no meaningful response). Likewise, more patients had total or partial resolution of depression and delusions than those who had no meaningful change. Factor analysis of baseline NPI data revealed five factors, including a psychosis factor, an agitation factor, mood factor, frontal lobe function factor, and appetite and eating disorders factor. Clinically meaningful treatment effect sizes were notable for the delusion factor (0.340) and the mood factor (0.39). There were significant correlations between the Clinical Global Impression-Improvement and reductions in mood and agitation scores. CONCLUSION: The results of these analyses suggest that donepezil reduces behavioral symptoms, particularly mood disturbances and delusions, in patients with AD with relatively severe psychopathology.
ESTHER : Cummings_2006_Am.J.Geriatr.Psychiatry_14_605
PubMedSearch : Cummings_2006_Am.J.Geriatr.Psychiatry_14_605
PubMedID: 16816014

Title : Evaluation of alpha-cyanoesters as fluorescent substrates for examining interindividual variation in general and pyrethroid-selective esterases in human liver microsomes - Wheelock_2003_Anal.Biochem_315_208
Author(s) : Wheelock CE , Wheelock AM , Zhang R , Stok JE , Morisseau C , Le Valley SE , Green CE , Hammock BD
Ref : Analytical Biochemistry , 315 :208 , 2003
Abstract : Carboxylesterases hydrolyze many pharmaceuticals and agrochemicals and have broad substrate selectivity, requiring a suite of substrates to measure hydrolytic profiles. To develop new esterase substrates, a series of alpha-cyanoesters that yield fluorescent products upon hydrolysis was evaluated for use in carboxylesterase assays. The use of these substrates as surrogates for Type II pyrethroid hydrolysis was tested. The results suggest that these novel analogs are appropriate for the development of high-throughput assays for pyrethroid hydrolase activity. A set of human liver microsomes was then used to determine the ability of these substrates to report esterase activity across a small population. Results were compared against standard esterase substrates. A number of the esterase substrates showed correlations, demonstrating the broad substrate selectivity of these enzymes. However, for several of the substrates, no correlations in hydrolysis rates were observed, suggesting that multiple carboxylesterase isozymes are responsible for the array of substrate hydrolytic activity. These new substrates were then compared against alpha-naphthyl acetate and 4-methylumbelliferyl acetate for their ability to detect hydrolytic activity in both one- and two-dimensional native electrophoresis gels. Cyano-2-naphthylmethyl butanoate was found to visualize more activity than either commercial substrate. These applications demonstrate the utility of these new substrates as both general and pyrethroid-selective reporters of esterase activity.
ESTHER : Wheelock_2003_Anal.Biochem_315_208
PubMedSearch : Wheelock_2003_Anal.Biochem_315_208
PubMedID: 12689831
Gene_locus related to this paper: mouse-Ces2e

Title : An economic evaluation of donepezil in mild to moderate Alzheimer's disease: results of a 1-year, double-blind, randomized trial - Wimo_2003_Dement.Geriatr.Cogn.Disord_15_44
Author(s) : Wimo A , Winblad B , Engedal K , Soininen H , Verhey F , Waldemar G , Wetterholm AL , Mastey V , Haglund A , Zhang R , Miceli R , Chin W , Subbiah P
Ref : Dementia & Geriatric Cognitive Disorders , 15 :44 , 2003
Abstract : The costs and consequences of donepezil versus placebo treatment in patients with mild to moderate Alzheimer's disease (AD) were evaluated as part of a 1-year prospective, double-blind, randomized, multinational clinical trial. Patients received either donepezil (n = 142; 5 mg/day for 28 days followed by 10 mg/day according to the clinician's judgement) or placebo (n = 144). Unit costs were assessed in 1999 Swedish kronas (SEK) and converted to US dollars (USD). Donepezil-treated patients gained functional benefits relative to placebo on the Progressive Deterioration Scale (p = 0.042) and Instrumental Activities of Daily Living scale (p = 0.025) at week 52. Caregivers of donepezil-treated patients spent an average of 400 h less annually providing care than caregivers of placebo-treated patients. Mean annual healthcare costs were SEK 137,752 (USD 16,438) per patient for the donepezil group and SEK 135,314 (USD 16,147) in the placebo group. With the average annual cost of donepezil at SEK 10,723 (USD 1,280) per patient, the SEK 2,438 (USD 291) cost difference represented a 77% cost offset. When caregiver time and healthcare costs were included, mean annual costs were SEK 209,244 (USD 24,969) per patient in the donepezil group and SEK 218,434 (USD 26,066) in the placebo group, a total saving associated with donepezil treatment of SEK 9,190 (USD 1,097) per patient [95% CI of SEK -43,959 (USD -5,246), SEK 25,581 (USD 3,053); p = 0.6]. The positive effects on the efficacy outcome measures combined with no additional costs from a societal perspective indicate that donepezil is a cost-effective treatment, representing an improved strategy for the management of patients with AD.
ESTHER : Wimo_2003_Dement.Geriatr.Cogn.Disord_15_44
PubMedSearch : Wimo_2003_Dement.Geriatr.Cogn.Disord_15_44
PubMedID: 12457078

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

Title : [Microsomal epoxide hydrolase gene polymorphism and susceptibility to chronic obstructive pulmonary disease in Han nationality of North China] - Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
Author(s) : Zhang R , Zhang A , He Q , Lu B
Ref : Zhonghua Nei Ke Za Zhi , 41 :11 , 2002
Abstract : OBJECTIVE We investigated whether polymorphism in gene for microsomal epoxide hydrolase (mEH) has any bearing on individual susceptibility to the development of chronic obstructive pulmonary disease. METHOD: The genotypes of 55 patients with COPD and 52 healthy smoking control subjects were tested with polymerase chain reaction followed by restriction fragment length polymorphism for mEH gene. RESULT: The frequency of polymorphic genotypes of mEH showed no difference between the COPD group and the control group. In COPD group mEH exon 3 homozygous wild-type, heterozygote and homozygous mutant was 27.3%, 27.3% and 45.5% respectively and exon 4 homozygous wild-type, heterozygote and homozygous mutant was 72.7%, 18.2% and 9.1% respectively. CONCLUSION: Genetic polymorphism in mEH is not associated with development of COPD in Han nationality of North China.
ESTHER : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
PubMedSearch : Zhang_2002_Zhonghua.Nei.Ke.Za.Zhi_41_11
PubMedID: 11940289

Title : A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD - Winblad_2001_Neurology_57_489
Author(s) : Winblad B , Engedal K , Soininen H , Verhey F , Waldemar G , Wimo A , Wetterholm AL , Zhang R , Haglund A , Subbiah P
Ref : Neurology , 57 :489 , 2001
Abstract : OBJECTIVE: To evaluate the long-term clinical efficacy and safety of donepezil versus placebo over 1 year in patients with mild to moderate AD. METHODS: Patients (n = 286; mean age, 72.5 years) with possible or probable AD from five Northern European countries were randomized to receive either donepezil (n = 142; 5 mg/day for 28 days, followed by 10 mg/day) or placebo (n = 144) for 1 year. RESULTS: The study was completed by 66.9% of the donepezil- and 67.4% of the placebo-treated patients. The benefit of donepezil over placebo was demonstrated by the Gottfries-Brane-Steen (a global assessment for rating dementia symptoms) total score at weeks 24, 36, and 52 (p < 0.05) and at the study end point (week 52, last observation carried forward; p = 0.054). Advantages of donepezil over placebo were also observed in cognition and activities of daily living (ADL) assessed by the Mini-Mental State Examination at weeks 24, 36, and 52, and the end point (p < 0.02) and by the Progressive Deterioration Scale at week 52 and the end point (p < 0.05). Adverse events (AE) were recorded for 81.7% of donepezil- and 75.7% of placebo-treated patients, with 7% of donepezil- and 6.3% of placebo-treated patients discontinuing because of AE. Treatment response to donepezil was not predicted by APOE genotype or sex in this population. CONCLUSION: As the first 1-year, multinational, double-blinded, placebo-controlled study of a cholinesterase inhibitor in AD, these data support donepezil as a well tolerated and effective long-term treatment for patients with AD, with benefits over placebo on global assessment, cognition, and ADL.
ESTHER : Winblad_2001_Neurology_57_489
PubMedSearch : Winblad_2001_Neurology_57_489
PubMedID: 11502918

Title : [The colorimetric method for measuring activities of lipoprotein lipase and hepatic lipase in plasma] - Zhang_1996_Hua.Xi.Yi.Ke.Da.Xue.Xue.Bao_27_106
Author(s) : Zhang R , Liu Y , Liu B
Ref : Hua Xi Yi Ke Da Xue Xue Bao , 27 :106 , 1996
Abstract : To study the pathogenesis of hyperlipoidemia and atheromatosis and the metabolism of lipoprotein, we have developed a colorimetric method for simultaneously determining the activities of post-heparinplasma lipoprotein lipase (LPL) and hepatic lipase (HL). The intralipid was kept for LPL and HL at 37 degrees C, pH8.3 for 30 min, with 100 microliters post-heparin plasma. The LPL and HL in the post-heparin plasma could hydrolyse the triglyceride in intralipid into glycerine and free fatty acid (FFA). Determining the amount of FFA by copper-reagent method, we could measure the activities of LPL and HL. The kinetics of LPL and HL in post-heparin plasma was observed. K(m) values for LPL and HL were 0.9 mumol/L and 2.4 mumol/L respectively. The C. V. for LPL and HL were 4.5% (n = 4), 2.9% (n = 6) and 6.4% (n = 6), 4.8% (n = 6) respectively.
ESTHER : Zhang_1996_Hua.Xi.Yi.Ke.Da.Xue.Xue.Bao_27_106
PubMedSearch : Zhang_1996_Hua.Xi.Yi.Ke.Da.Xue.Xue.Bao_27_106
PubMedID: 9208634

Title : Evidence of paired M2 muscarinic receptors - Potter_1991_Mol.Pharmacol_39_211
Author(s) : Potter LT , Ballesteros LA , Bichajian LH , Ferrendelli CA , Fisher A , Hanchett HE , Zhang R
Ref : Molecular Pharmacology , 39 :211 , 1991
Abstract : Binding assays involving various antagonists, including N-[3H] methylscopolamine, [3H]quinuclidinyl benzilate, AFDX-116, pirenzepine, and propylbenzilylcholine mustard, disclosed only a single population of M2 muscarinic receptors in membranes from the rat "brainstem" (medulla, pons, and colliculi). However, competition curves between N-[3H]methylscopolamine and various agonists, including oxotremorine, cis-dioxolane, and acetylethylcholine mustard, showed approximately equal numbers of guanine nucleotide-sensitive high affinity (H) sites and guanine nucleotide-insensitive low affinity (L) sites. This 50% H phenomenon persisted in different buffers, at different temperatures, after the number of receptors was halved (and, thus, the remaining receptor to guanine nucleotide-binding protein ratio was doubled), after membrane solubilization with digitonin, and when rabbit cardiac membranes were used instead of rat brainstem membranes. Preferential occupation of H sites with acetylethylcholine mustard, and of L sites with quinuclidinyl benzilate or either mustard, yielded residual free receptor populations showing predominantly L and H sites, respectively. Low concentrations of [3H]-oxotremorine-M labeled only H sites, and the Bmax for these sites was 49% of the Bmax found with [3H]quinuclidinyl benzilate plus guanine nucleotide. These and other results are most consistent with the idea that H and L receptor sites exist on separate but dimeric receptor molecules and with the hypothesis that only the H receptors cycle between high and low affinity, depending upon interactions between this receptor molecule and a guanine nucleotide-binding protein.
ESTHER : Potter_1991_Mol.Pharmacol_39_211
PubMedSearch : Potter_1991_Mol.Pharmacol_39_211
PubMedID: 1899905