Huang W

References (65)

Title : Antisolvent precipitation for the synergistic preparation of ultrafine particles of nobiletin under ultrasonication-homogenization and evaluation of the inhibitory effects of alpha-glucosidase and porcine pancreatic lipase in vitro - Zhang_2024_Ultrason.Sonochem_105_106865
Author(s) : Zhang X , Huang Y , Huang S , Xie W , Huang W , Chen Y , Li Q , Zeng F , Liu X
Ref : Ultrason Sonochem , 105 :106865 , 2024
Abstract : To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.
ESTHER : Zhang_2024_Ultrason.Sonochem_105_106865
PubMedSearch : Zhang_2024_Ultrason.Sonochem_105_106865
PubMedID: 38564909

Title : Improvement of plant resistance to geminiviruses via protein de-S-acylation - Zhao_2024_Stress.Biol_4_23
Author(s) : Zhao Y , Li Z , Wang Z , Huang L , Li G , Liu X , Yuan M , Huang W , Ling L , Yang C , He Z , Lai J
Ref : Stress Biol , 4 :23 , 2024
Abstract : Geminiviruses are an important group of viruses that infect a variety of plants and result in heavy agricultural losses worldwide. The homologs of C4 (or L4) in monopartite geminiviruses and AC4 (or AL4) in bipartite geminiviruses are critical viral proteins. The C4 proteins from several geminiviruses are the substrates of S-acylation, a dynamic post-translational modification, for the maintenance of their membrane localization and function in virus infection. Here we initiated a screening and identified a plant protein ABAPT3 (Alpha/Beta Hydrolase Domain-containing Protein 17-like Acyl Protein Thioesterase 3) as the de-S-acylation enzyme of C4 encoded by BSCTV (Beet severe curly top virus). Overexpression of ABAPT3 reduced the S-acylation of BSCTV C4, disrupted its plasma membrane localization, inhibited its function in pathogenesis, and suppressed BSCTV infection. Because the S-acylation motifs are conserved among C4 from different geminiviruses, we tested the effect of ABAPT3 on the C4 protein of ToLCGdV (Tomato leaf curl Guangdong virus) from another geminivirus genus. Consistently, ABAPT3 overexpression also disrupted the S-acylation, subcellular localization, and function of ToLCGdV C4, and inhibited ToLCGdV infection. In summary, we provided a new approach to globally improve the resistance to different types of geminiviruses in plants via de-S-acylation of the viral C4 proteins and it can be extendedly used for suppression of geminivirus infection in crops.
ESTHER : Zhao_2024_Stress.Biol_4_23
PubMedSearch : Zhao_2024_Stress.Biol_4_23
PubMedID: 38662136
Gene_locus related to this paper: arath-At5g14390

Title : Depletion of ApoA5 aggravates spontaneous and diet-induced nonalcoholic fatty liver disease by reducing hepatic NR1D1 in hamsters - Guo_2024_Theranostics_14_2036
Author(s) : Guo J , Miao G , Zhang W , Shi H , Lai P , Xu Y , Zhang L , Chen G , Han Y , Zhao Y , Liu G , Wang Y , Huang W , Xian X
Ref : Theranostics , 14 :2036 , 2024
Abstract : Background: ApoA5 mainly synthesized and secreted by liver is a key modulator of lipoprotein lipase (LPL) activity and triglyceride-rich lipoproteins (TRLs). Although the role of ApoA5 in extrahepatic triglyceride (TG) metabolism in circulation has been well documented, the relationship between ApoA5 and nonalcoholic fatty liver disease (NAFLD) remains incompletely understood and the underlying molecular mechanism still needs to be elucidated. Methods: We used CRISPR/Cas9 gene editing to delete Apoa5 gene from Syrian golden hamster, a small rodent model replicating human metabolic features. Then, the ApoA5-deficient (ApoA5(-/-)) hamsters were used to investigate NAFLD with or without challenging a high fat diet (HFD). Results: ApoA5(-/-) hamsters exhibited hypertriglyceridemia (HTG) with markedly elevated TG levels at 2300 mg/dL and hepatic steatosis on a regular chow diet, accompanied with an increase in the expression levels of genes regulating lipolysis and small adipocytes in the adipose tissue. An HFD challenge predisposed ApoA5(-/-) hamsters to severe HTG (sHTG) and nonalcoholic steatohepatitis (NASH). Mechanistic studies in vitro and in vivo revealed that targeting ApoA5 disrupted NR1D1 mRNA stability in the HepG2 cells and the liver to reduce both mRNA and protein levels of NR1D1, respectively. Overexpression of human NR1D1 by adeno-associated virus 8 (AAV8) in the livers of ApoA5(-/-) hamsters significantly ameliorated fatty liver without affecting plasma lipid levels. Moreover, restoration of hepatic ApoA5 or activation of UCP1 in brown adipose tissue (BAT) by cold exposure or CL316243 administration could significantly correct sHTG and hepatic steatosis in ApoA5(-/-) hamsters. Conclusions: Our data demonstrate that HTG caused by ApoA5 deficiency in hamsters is sufficient to elicit hepatic steatosis and HFD aggravates NAFLD by reducing hepatic NR1D1 mRNA and protein levels, which provides a mechanistic link between ApoA5 and NAFLD and suggests the new insights into the potential therapeutic approaches for the treatment of HTG and the related disorders due to ApoA5 deficiency in the clinical trials in future.
ESTHER : Guo_2024_Theranostics_14_2036
PubMedSearch : Guo_2024_Theranostics_14_2036
PubMedID: 38505614

Title : Astaxanthin activates the Nrf2\/Keap1\/HO-1 pathway to inhibit oxidative stress and ferroptosis, reducing triphenyl phosphate (TPhP)-induced neurodevelopmental toxicity - Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
Author(s) : Zhang Q , Luo C , Li Z , Huang W , Zheng S , Liu C , Shi X , Ma Y , Ni Q , Tan W , Peng J , Chen Y , Wu W , Li J , Wu K
Ref : Ecotoxicology & Environmental Safety , 271 :115960 , 2024
Abstract : Triphenyl phosphate (TPhP) serves as a major organophosphorus flame retardant, and its induced neurodevelopmental toxicity has attracted widespread attention, but the mechanism remains unclear. In this study, we involved zebrafish to explore the new mechanism of TPhP inducing oxidative stress and ferroptosis to promote neurodevelopmental toxicity. The results suggested that TPhP affected the embryonic development, reduced the number of new neurons, and led to abnormal neural behavior in zebrafish larvae. TPhP also induced ROS accumulation, activated the antioxidant defense signal Nrf2 and Keap1, and significantly changed the activities of Acetylcholinesterase (AChE), Adenosine triphosphatase (ATPase) and glutathione S-transferase (GST). In addition, TPhP induced ferroptosis in zebrafish, which was reflected in the increase of Fe(2+) content, the abnormal expression of GPX4 protein and genes related to iron metabolism (gpx4a, slc7a11, acsl4b, tfa, slc40a1, fth1b, tfr2, tfr1a, tfr1b and ncoa4). Astaxanthin intervention specifically inhibited ROS levels, and reversed SLC7A11 and GPX4 expression levels and Fe(2+) metabolism thus alleviating ferroptosis induced by TPhP. Astaxanthin also partially reversed the activity of AChE, GST and the expression of neurodevelopmental-related genes (gap43, gfap, neurog1 and syn2a), so as to partially rescue the embryonic developmental abnormalities and motor behavior disorders induced by TPhP. More interestingly, the expression of mitochondrial apoptosis-related protein BAX, anti-apoptotic protein BCL-2, Caspase3 and Caspase9 was significantly altered in the TPhP exposed group, which could be also reversed by Astaxanthin intervention. In summary, our results suggested that TPhP exposure can induce oxidative stress and ferroptosis, thereby causing neurodevelopment toxicity to zebrafish, while Astaxanthin can partially reverse oxidative stress and reduce the neurodevelopmental toxicity of zebrafish larvae by activating Nrf2/Keap1/HO-1 signaling pathway.
ESTHER : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedSearch : Zhang_2024_Ecotoxicol.Environ.Saf_271_115960
PubMedID: 38219622

Title : Effects of inoculating feruloyl esterase-producing Lactiplantibacillus plantarum A1 on ensiling characteristics, in vitro ruminal fermentation and microbiota of alfalfa silage - Li_2023_J.Anim.Sci.Biotechnol_14_43
Author(s) : Li F , Usman S , Huang W , Jia M , Kharazian ZA , Ran T , Ding Z , Guo X
Ref : J Anim Sci Biotechnol , 14 :43 , 2023
Abstract : BACKGROUND: Ferulic acid esterase (FAE)-secreting Lactiplantibacillus plantarum A1 (Lp A1) is a promising silage inoculant due to the FAE's ability to alter the plant cell wall structure during ensiling, an action that is expected to improve forage digestibility. However, little is known regarding the impacts of Lp A1 on rumen microbiota. Our research assessed the influences of Lp A1 in comparison to a widely adopted commercial inoculant Lp MTD/1 on alfalfa's ensilage, in vitro rumen incubation and microbiota. RESULTS: Samples of fresh and ensiled alfalfa treated with (either Lp A1 or Lp MTD/1) or without additives (as control; CON) and ensiled for 30, 60 and 90 d were used for fermentation quality, in vitro digestibility and batch culture study. Inoculants treated silage had lower (P < 0.001) pH, acetic acid concentration and dry matter (DM) loss, but higher (P = 0.001) lactic acid concentration than the CON during ensiling. Compared to the CON and Lp MTD/1, silage treated with Lp A1 had lower (P < 0.001) aNDF, ADF, ADL, hemicellulose, and cellulose contents and higher (P < 0.001) free ferulic acid concentration. Compared silage treated with Lp MTD/1, silage treated with Lp A1 had significantly (P < 0.01) improved ruminal gas production and digestibility, which were equivalent to those of fresh alfalfa. Real-time PCR analysis indicated that Lp A1 inoculation improved the relative abundances of rumen's total bacteria, fungi, Ruminococcus albus and Ruminococcus flavefaciens, while the relative abundance of methanogens was reduced by Lp MTD/1 compared with CON. Principal component analysis of rumen bacterial 16S rRNA gene amplicons showed a clear distinction between CON and inoculated treatments without noticeable distinction between Lp A1 and Lp MTD/1 treatments. Comparison analysis revealed differences in the relative abundance of some bacteria in different taxa between Lp A1 and Lp MTD/1 treatments. Silage treated with Lp A1 exhibited improved rumen fermentation characteristics due to the inoculant effects on the rumen microbial populations and bacterial community. CONCLUSIONS: Our findings suggest that silage inoculation of the FAE-producing Lp A1 could be effective in improving silage quality and digestibility, and modulating the rumen fermentation to improve feed utilization.
ESTHER : Li_2023_J.Anim.Sci.Biotechnol_14_43
PubMedSearch : Li_2023_J.Anim.Sci.Biotechnol_14_43
PubMedID: 36915166

Title : Identification of Potent and Selective Acetylcholinesterase\/Butyrylcholinesterase Inhibitors by Virtual Screening - Xu_2023_J.Chem.Inf.Model__
Author(s) : Xu T , Li S , Li AJ , Zhao J , Sakamuru S , Huang W , Xia M , Huang R
Ref : J Chem Inf Model , : , 2023
Abstract : Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) play important roles in human neurodegenerative disorders such as Alzheimer's disease. In this study, machine learning methods were applied to develop quantitative structure-activity relationship models for the prediction of novel AChE and BChE inhibitors based on data from quantitative high-throughput screening assays. The models were used to virtually screen an in-house collection of -360K compounds. The optimal models achieved good performance with area under the receiver operating characteristic curve values ranging from 0.83 +/- 0.03 to 0.87 +/- 0.01 for the prediction of AChE/BChE inhibition activity and selectivity. Experimental validation showed that the best-performing models increased the assay hit rate by several folds. We identified 88 novel AChE and 126 novel BChE inhibitors, 25% (AChE) and 53% (BChE) of which showed potent inhibitory effects (IC(50) < 5 microM). In addition, structure-activity relationship analysis of the BChE inhibitors revealed scaffolds for chemistry design and optimization. In conclusion, machine learning models were shown to efficiently identify potent and selective inhibitors against AChE and BChE and novel structural series for further design and development of potential therapeutics against neurodegenerative disorders.
ESTHER : Xu_2023_J.Chem.Inf.Model__
PubMedSearch : Xu_2023_J.Chem.Inf.Model__
PubMedID: 37011147

Title : Design, synthesis, and biological evaluation studies of novel carboxylesterase 2 inhibitors for the treatment of irinotecan-induced delayed diarrhea - Yang_2023_Bioorg.Chem_138_106625
Author(s) : Yang Z , Cao Z , Wang W , Chen Y , Huang W , Jiao S , Chen S , Chen L , Liu Y , Mao J , Zhang L , Li Z
Ref : Bioorg Chem , 138 :106625 , 2023
Abstract : Human carboxylesterase 2 (hCES2A), one of the most important serine hydrolases distributed in the small intestine and colon, plays a crucial role in the hydrolysis of various prodrugs and esters. Accumulating evidence has demonstrated that the inhibition of hCES2A effectively alleviate the side effects induced by some hCES2A-substrate drugs, including delayed diarrhea caused by the anticancer drug irinotecan. Nonetheless, there is a scarcity of selective and effective inhibitors that are suitable for irinotecan-induced delayed diarrhea. Following screening of the in-house library, the lead compound 01 was identified with potent inhibition on hCES2A, which was further optimized to obtain LK-44 with potent inhibitory activity (IC(50) = 5.02 +/- 0.67 microM) and high selectivity on hCES2A. Molecular docking and molecular dynamics simulations indicated that LK-44 can formed stable hydrogen bonds with amino acids surrounding the active cavity of hCES2A. The results of inhibition kinetics studies unveiled that LK-44 inhibited hCES2A-mediated FD hydrolysis in a mixed inhibition manner, with a K(i) value of 5.28 microM. Notably, LK-44 exhibited low toxicity towards HepG2 cells according to the MTT assay. Importantly, in vivo studies showed that LK-44 significantly reduced the side effects of irinotecan-induced diarrhea. These findings suggested that LK-44 is a potent inhibitor of hCES2A with high selectivity against hCES1A, which has potential as a lead compound for the development of more effective hCES2A inhibitors to mitigate irinotecan-induced delayed diarrhea.
ESTHER : Yang_2023_Bioorg.Chem_138_106625
PubMedSearch : Yang_2023_Bioorg.Chem_138_106625
PubMedID: 37300962
Gene_locus related to this paper: human-CES2

Title : High-resolution structural-omics of human liver enzymes - Su_2023_Cell.Rep_42_112609
Author(s) : Su CC , Lyu M , Zhang Z , Miyagi M , Huang W , Taylor DJ , Yu EW
Ref : Cell Rep , 42 :112609 , 2023
Abstract : We applied raw human liver microsome lysate to a holey carbon grid and used cryo-electron microscopy (cryo-EM) to define its composition. From this sample we identified and simultaneously determined high-resolution structural information for ten unique human liver enzymes involved in diverse cellular processes. Notably, we determined the structure of the endoplasmic bifunctional protein H6PD, where the N- and C-terminal domains independently possess glucose-6-phosphate dehydrogenase and 6-phosphogluconolactonase enzymatic activity, respectively. We also obtained the structure of heterodimeric human GANAB, an ER glycoprotein quality-control machinery that contains a catalytic alpha subunit and a noncatalytic beta subunit. In addition, we observed a decameric peroxidase, PRDX4, which directly contacts a disulfide isomerase-related protein, ERp46. Structural data suggest that several glycosylations, bound endogenous compounds, and ions associate with these human liver enzymes. These results highlight the importance of cryo-EM in facilitating the elucidation of human organ proteomics at the atomic level.
ESTHER : Su_2023_Cell.Rep_42_112609
PubMedSearch : Su_2023_Cell.Rep_42_112609
PubMedID: 37289586
Gene_locus related to this paper: human-CES1

Title : Discovery of novel carboxylesterase 2 inhibitors for the treatment of delayed diarrhea and ulcerative colitis - Cao_2023_Biochem.Pharmacol__115742
Author(s) : Cao Z , Liu Y , Chen S , Wang W , Yang Z , Chen Y , Jiao S , Huang W , Chen L , Sun L , Li Z , Zhang L
Ref : Biochemical Pharmacology , :115742 , 2023
Abstract : Human carboxylesterase 2 (hCES2) is an enzyme that metabolizes irinotecan to SN-38, a toxic metabolite considered a significant source of side effects (lethal delayed diarrhea). The hCES2 inhibitors could block the hydrolysis of irinotecan in the intestine and thus reduce the exposure of intestinal SN-38, which may alleviate irinotecan-associated diarrhea. However, existing hCES2 inhibitors (except loperamide) are not used in clinical applications due to lack of validity or acceptable safety. Therefore, developing more effective and safer drugs for treating delayed diarrhea is urgently needed. This study identified a lead compound 1 with a novel scaffold by high-throughput screening in our in-house library. After a comprehensive structure-activity relationship study, the optimal compound 24 was discovered as an efficient and highly selective hCES2 inhibitor (hCES2: IC(50) = 6.72 microM; hCES1: IC(50) > 100 microM). Further enzyme kinetics study indicated that compound 24 is a reversible inhibitor of hCES2 with competitive inhibition mode (Ki = 6.28 microM). The cell experiments showed that compound 24 could reduce the level of hCES2 in living cells (IC(50) = 6.54 microM). The modeling study suggested that compound 24 fitted very well with the binding pocket of hCES2 by forming multiple interactions. Notably, compound 24 can effectively treat irinotecan-induced delayed diarrhea and DSS-induced ulcerative colitis, and its safety has also been verified in subtoxic studies. Based on the overall pharmacological and preliminary safety profiles, compound 24 is worthy of further evaluation as a novel agent for irinotecan-induced delayed diarrhea.
ESTHER : Cao_2023_Biochem.Pharmacol__115742
PubMedSearch : Cao_2023_Biochem.Pharmacol__115742
PubMedID: 37567318

Title : Acalculous cholecystitis is a common extrahepatic manifestation of hepatitis E and suggests a more serious condition - Cao_2023_Virol.J_20_77
Author(s) : Cao X , Jiang W , Shi L , Wang Y , Chen J , Huang W , Zhang S
Ref : Virol J , 20 :77 , 2023
Abstract : BACKGROUND: This study aimed to understand the incidence and clinical significance of acalculous cholecystitis in patients with acute hepatitis E (HE). PATIENTS AND METHODS: A single center enrolled 114 patients with acute HE. All patients underwent imaging of the gallbladder, and patients with gallstones and cholecystectomy were excluded. RESULTS: Acalculous cholecystitis was found in 66 patients (57.89%) with acute HE. The incidence in males was 63.95%, which was significantly higher than in females (39.29%) (P = 0.022). The mean length of hospital stay and the incidence of spontaneous peritonitis in patients with cholecystitis (20.12 +/- 9.43 days and 9.09%, respectively) were significantly higher than those in patients without cholecystitis (12.98 +/- 7.26 days and 0%, respectively) (P < 0.001 and P = 0.032). Albumin, total bile acid, bilirubin, cholinesterase, and prothrombin activity in patients with cholecystitis were significantly inferior to those in patients without cholecystitis (P < 0.001, P < 0.001, P < 0.001, P < 0.001 and P = 0.003, respectively). After correction by multivariate analysis, albumin and total bile acid were found to be closely related to acalculous cholecystitis in HE. CONCLUSION: Acalculous cholecystitis is very common in patients with acute HE, and may serve as a predictor of increased peritonitis, synthetic decompensation, and longer hospital stay.
ESTHER : Cao_2023_Virol.J_20_77
PubMedSearch : Cao_2023_Virol.J_20_77
PubMedID: 37095526

Title : Organism-wide, cell-type-specific secretome mapping of exercise training in mice - Wei_2023_Cell.Metab__
Author(s) : Wei W , Riley NM , Lyu X , Shen X , Guo J , Raun SH , Zhao M , Moya-Garzon MD , Basu H , Sheng-Hwa Tung A , Li VL , Huang W , Wiggenhorn AL , Svensson KJ , Snyder MP , Bertozzi CR , Long JZ
Ref : Cell Metab , : , 2023
Abstract : There is a significant interest in identifying blood-borne factors that mediate tissue crosstalk and function as molecular effectors of physical activity. Although past studies have focused on an individual molecule or cell type, the organism-wide secretome response to physical activity has not been evaluated. Here, we use a cell-type-specific proteomic approach to generate a 21-cell-type, 10-tissue map of exercise training-regulated secretomes in mice. Our dataset identifies >200 exercise training-regulated cell-type-secreted protein pairs, the majority of which have not been previously reported. Pdgfra-cre-labeled secretomes were the most responsive to exercise training. Finally, we show anti-obesity, anti-diabetic, and exercise performance-enhancing activities for proteoforms of intracellular carboxylesterases whose secretion from the liver is induced by exercise training.
ESTHER : Wei_2023_Cell.Metab__
PubMedSearch : Wei_2023_Cell.Metab__
PubMedID: 37141889

Title : Comparative genomics of Sarcoptes scabiei provide new insights into adaptation to permanent parasitism and within-host species divergence - Xu_2022_Transbound.Emerg.Dis__
Author(s) : Xu J , Wang Q , Wang S , Huang W , Xie Y , Gu X , He R , Peng X , Wu S , Yang G
Ref : Transbound Emerg Dis , : , 2022
Abstract : Sarcoptic scabiei is the causative agent of a highly contagious skin disease in humans and more than 100 mammals. Here, we report the first chromosome-level reference genome of S. scabiei isolated from rabbits, with a contig N50 size of 5.92 Mb, a total assembled length of 57.30 Mb, -12.65% repetitive sequences, and 9,333 predicted protein-coding genes. The phylogenetic tree based on 1,338 shared high-confidence single-copy orthologous genes estimated that the mammalian ectoparasite S. scabiei and the plant-feeding mite Tetranychus urticae separated approximately 340 million years ago. Both neighbor-joining tree and principal component analysis of 20 mite populations isolated from four hosts (humans, pigs, dogs and rabbits) distributed in three countries (China, Australia and the US) consistently supported the genetic subdivisions according to host species rather than geographical location. The demographic history of S. scabiei reconstructed by multiple sequentially Markovian coalescent analysis suggested that S. scabiei isolated from rabbits, humans, dogs, and pigs diverged -5,000 years ago. Investigation of the homeobox (Hox) genes revealed that S. scabiei contains eight of 10 canonical Hox genes that are present in the arthropod ancestor, and the absence of the Abd-A gene may correlate with the long gap between their front and back legs. Comparative genomics demonstrated that genes specific to scabies mites were mainly enriched in nutrition digestive systems and genes in the families that involved detoxification (cytochrome P450, carboxyl/cholinesterases, and the ATP-binding cassette transporter C group) were extremely contracted compared with that of other mites analyzed in this study. Selective sweep analysis of mite populations from either two of the four host species revealed that the strongest selective sweep signals were mainly enriched in cysteine-type peptidase activity and apoptosis. The results provided clues for the mechanisms of S. scabiei adaptation to a permanent parasitic lifestyle and knowledge that would enable further control of this highly contagious skin disease. This article is protected by copyright. All rights reserved.
ESTHER : Xu_2022_Transbound.Emerg.Dis__
PubMedSearch : Xu_2022_Transbound.Emerg.Dis__
PubMedID: 36134513

Title : Structure-guided preparation of functional oil rich in 1,3-diacylglycerols and linoleic acid from Camellia oil by combi-lipase - Huang_2022_J.Sci.Food.Agric__
Author(s) : Huang C , Lin Z , Zhang Y , Liu Z , Tang X , Li C , Lin L , Huang W , Ye Y
Ref : J Sci Food Agric , : , 2022
Abstract : BACKGROUND: The diacylglycerols (DAG) enriched oil has been attracting attention on nutritional benefits and biological functions, but its various free fatty acids (FFA) composition and unclear relationship between substrate and yield make it difficult to be identified and qualified to produce. In this research, the linoleic acid-enriched diacylglycerols (LA-DAG) was synthesized and enriched from Camellia oil by the esterification process using the combi-lipase Lipozyme TL IM/RM IM systems. RESULTS: The relationship between the FFA compositions and the DAG species productivity was revealed. Results showed that heterogeneous FFA with a major constituent (more than 50%) exhibited higher DAG productivity and inhibited TAG productivity than homogeneous constituents. The joint characterization by HPLC-ELSD, GC-MS and UPLC-HESI-MS/MS identified that DAG components contained dilinoleic acid acyl glyceride, linoleyl-oleyl glyceride, and dioleic acid acyl glyceride in esterification products. Under the optimum conditions, 60.4% 1,3-DAG and 61.3% LA-DAG in the crude product at 1 h reaction were obtained, and further purified to 81.7% LA-DAG and 94.7% DAG by the silica column chromatography. CONCLUSION: This research provides a guideline for identification of DAG species, and a structure-guided preparing method of the DAG enriched oils by the cost-effective combi-lipase. This article is protected by copyright. All rights reserved.
ESTHER : Huang_2022_J.Sci.Food.Agric__
PubMedSearch : Huang_2022_J.Sci.Food.Agric__
PubMedID: 35810339

Title : SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate - Feng_2021_Mikrochim.Acta_188_280
Author(s) : Feng J , Lu H , Yang Y , Huang W , Cheng H , Kong H , Li L
Ref : Mikrochim Acta , 188 :280 , 2021
Abstract : By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 x 10(-13) mol.L(-1), and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determine hCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng.mL(-1), the SERS signal intensity of benzidine at 1609 cm(-1) gradually decreases with the increase of hCE 1 concentration (R(2) = 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.
ESTHER : Feng_2021_Mikrochim.Acta_188_280
PubMedSearch : Feng_2021_Mikrochim.Acta_188_280
PubMedID: 34331134

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

Title : Structure-guided engineering of a Thermobifida fusca cutinase for enhanced hydrolysis on natural polyester substrate - Dong_2020_Bioresour.Bioprocess_7_37
Author(s) : Dong Q , Yuan S , Wu L , Su L , Zhao Q , Wu J , Huang W , Zhou J
Ref : Bioresour. Bioprocess , 7 :37 , 2020
Abstract : Cutinases could degrade insoluble polyester, including natural cutin and synthetic plastic. However, their turnover efficiency for polyester remains too low for industrial application. Herein, we report the 1.54-A resolution X-ray crystal structure of a cutinase from Thermobifida fusca and modeling structure in complex with a cutin mimic oligo-polyester C24H42O8. These efforts subsequently guided our design of cutinase variants with less bulky residues in the vicinity of the substrate binding site. The L90A and I213A variants exhibit increased hydrolysis activity (5- and 2.4-fold, respectively) toward cutin and also showed enhanced cotton scouring efficiency compared with the wild-type enzyme.
ESTHER : Dong_2020_Bioresour.Bioprocess_7_37
PubMedSearch : Dong_2020_Bioresour.Bioprocess_7_37
PubMedID:
Gene_locus related to this paper: thefu-q6a0i4

Title : A magnetic SERS immunosensor for highly sensitive and selective detection of human carboxylesterase 1 in human serum samples - Feng_2020_Anal.Chim.Acta_1097_176
Author(s) : Feng J , Xu Y , Huang W , Kong H , Li Y , Cheng H , Li L
Ref : Anal Chim Acta , 1097 :176 , 2020
Abstract : Hepatocellular carcinoma (HCC) is a common and lethal cancer. New serum markers for detecting HCC are urgently needed. Human carboxylesterase 1 (hCE1) is an important member of the serine hydrolase superfamily and is closely related to the occurrence of HCC. It can be used as a good serum marker for early diagnosis of HCC. Here, we developed a surface enhanced Raman scattering (SERS)- based magnetic immunosensor that specifically recognizes and detects trace amounts of hCE1 in human serum via a sandwich structure consisting of a SERS tags, magnetic supporting substrates, and target antigen (hCE1). The SERS tags are 4-mercaptobenzoic acid (4-MBA)-labeled AgNPs, and the SERS supporting substrates are composed of a raspberry-like morphology of Fe3O4@SiO2@AgNPs magnetic nanocomposites surface-functionalized with a hCE1 antibody. The prepared SERS magnetic immunosensor exhibits excellent selectivity and extremely high sensitivity for hCE1 detection. The SERS signal and logarithm of hCE1 concentration presented a wide linear response range of 0.1ngmL(-1) to 1.0mgmL(-1), and the detection limit of hCE1 was 0.1ngmL(-1). The results indicate that the immunosensor can be used for the rapid determination of hCE1 in human serum without a complicated sample pre-treatment. Furthermore, the immunosensor has good reproducibility and stability, and has a promising prospect for the quantitative detection of other tumor markers in early clinical diagnosis.
ESTHER : Feng_2020_Anal.Chim.Acta_1097_176
PubMedSearch : Feng_2020_Anal.Chim.Acta_1097_176
PubMedID: 31910958

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 : Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea - Wang_2020_Environ.Pollut_267_115397
Author(s) : Wang X , Hu M , Gu H , Zhang L , Shang Y , Wang T , Zeng J , Ma L , Huang W , Wang Y
Ref : Environ Pollut , 267 :115397 , 2020
Abstract : In recent years, antibiotics have been widely detected in coastal waters of China, which raising concerns for coastal biodiversity and aquaculture. This study evaluated the effects of short-term exposure of norfloxacin (NOR) on oxidative stress and intestinal health of the large yellow croaker Pseudosciaena crocea. Juvenile fish were exposed to four concentrations of NOR (0.1, 10, 100 and 1000 g/L) for 14 days. The results showed that NOR inhibited growth and threatened the survival of juveniles. According to the changes of intestinal microbiota, we found that NOR led to a significant decrease in intestinal microbiota diversity, with the decreased relative abundance of Proteobacteria, but the increased Tenericutes. From the perspective of microbial function, NOR inhibited metabolism, cellular defence mechanism and information transduction process. In terms of biochemical indicators, NOR caused an increase in malondialdehyde (MDA) level and inhibited superoxide dismutase (SOD) and acetyl cholinesterase (AChE) activities. Catalase (CAT) activity was activated at low concentration but significantly inhibited at high concentration of NOR. Moreover, there was a high correlation between change in biochemical indicators and change in the microbial community. Overall, environmentally relevant concentrations (0.1 g/L) and high concentrations (10, 100 and 1000 g/L) of NOR have negative effects on the defence function and intestinal health of large yellow croaker juveniles.
ESTHER : Wang_2020_Environ.Pollut_267_115397
PubMedSearch : Wang_2020_Environ.Pollut_267_115397
PubMedID: 33254654

Title : The botanical origin and antioxidant, anti-BACE1 and antiproliferative properties of bee pollen from different regions of South Korea - Zou_2020_BMC.Complement.Med.Ther_20_236
Author(s) : Zou Y , Hu J , Huang W , Zhu L , Shao M , Dordoe C , Ahn YJ , Wang D , Zhao Y , Xiong Y , Wang X
Ref : BMC Complement Med Ther , 20 :236 , 2020
Abstract : BACKGROUND: Bee pollen (BP) has been used as a traditional medicine and food diet additive due to its nutritional and biological properties. The potential biological properties of bee pollen vary greatly with the botanical and geographical origin of the pollen grains. This study was conducted to characterize the botanical origin and assess the antioxidant effects of ethanol extracts of 18 different bee pollen (EBP) samples from 16 locations in South Korea and their inhibitory activities on human beta-amyloid precursor cleavage enzyme (BACE1), acetylcholinesterase (AChE), human intestinal bacteria, and 5 cancer cell lines. METHODS: The botanical origin and classification of each BP sample was evaluated using palynological analysis by observing microscope slides. We measured the biological properties, including antioxidant capacity, inhibitory activities against human BACE1, and AChE, and antiproliferative activities toward five cancer cell lines, of the 18 EBPs. In addition, the growth inhibitory activities on four harmful intestinal bacteria, six lactic acid-producing bacteria, two nonpathogenic bacteria, and an acidulating bacterium were also assessed. RESULTS: Four samples (BP3, BP4, BP13 and BP15) were found to be monofloral and presented four dominant pollen types: Quercus palustris, Actinidia arguta, Robinia pseudoacacia, and Amygdalus persica. One sample (BP12) was found to be bifloral, and the remaining samples were considered to be heterofloral. Sixteen samples showed potent antioxidant activities with EC(50) from 292.0 to 673.9 microg/mL. Fourteen samples presented potent inhibitory activity against human BACE1 with EC(50) from 236.0 to 881.1 microg/mL. All samples showed antiproliferative activity toward the cancer cell lines PC-3, MCF-7, A549, NCI-H727 and AGS with IC(50) from 2.7 to 14.4mG/Ml, 0.9 to 12.7mG/Ml, 5.0 to > 25mG/Ml, 2.7 to 17.7mG/Ml, and 2.4 to 8.7mG/Ml, respectively. In addition, total phenol and flavonoid contents had no direct correlation with antioxidant, anti-human BACE1, or antiproliferative activities. CONCLUSION: Fundamentally, Korean bee pollen-derived preparations could be considered a nutritional addition to food to prevent various diseases related to free radicals, neurodegenerative problems, and cancers. The botanical and geographical origins of pollen grains could help to establish quality control standards for bee pollen consumption and industrial production.
ESTHER : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedSearch : Zou_2020_BMC.Complement.Med.Ther_20_236
PubMedID: 32711521

Title : Structure and characterization of Aspergillus fumigatus lipase B with a unique, oversized regulatory subdomain - Huang_2019_FEBS.J_286_2366
Author(s) : Huang W , Lan D , Popowicz GM , Zak KM , Zhao Z , Yuan H , Yang B , Wang Y
Ref : Febs J , 286 :2366 , 2019
Abstract : Fungal lipases are efficient and environment-friendly biocatalysts for many industrially relevant processes. One of the most widely applied lipases in the manufacturing industry is Candida antarctica lipase B (CALB). Here, we report the biochemical and structural characterization of a novel CALB-like lipase from an important human pathogen-Aspergillus fumigatus (AFLB), which has high sn-1,3-specificity toward triolein. AFLB crystal structure displays a CALB-like catalytic domain and hosts a unique tightly closed 'lid' domain that contains a disulfide bridge, as well as an extra N-terminal subdomain composed of residues 1-128 (including the helix alpha1-alpha5 located above the active site). To gain insight into the function of this novel lid and N-terminal subdomain, we constructed and characterized a series of mutants in these two domains. Deleting the protruding bulk lid's residues, replacing the bulk and tight lid with a small and loose lid from CALB, or breaking the disulfide bridge increased the affinity of CALB for glyceride substrates and improved its catalytic activity, along with the loss of enzyme fold stability and thermostability. N-terminal truncation mutants revealed that the N-terminal peptide (residues 1-59) is a strong inhibitor of AFLB binding to lipid films. This peptide thus limits AFLB's penetration power and specific activity, revealing a unique enzyme activity regulatory mechanism. Our findings on the functional and structural properties of AFLB provide a better understanding of the functions of the CALB-like lipases and pave the way for its future protein engineering. DATABASE: Structural data are available in the Protein Data Bank under the accession numbers 6IDY.
ESTHER : Huang_2019_FEBS.J_286_2366
PubMedSearch : Huang_2019_FEBS.J_286_2366
PubMedID: 30908847
Gene_locus related to this paper: aspfu-q4wg73

Title : First Genome-wide Association Analysis for Growth Traits in the Largest Coral Reef-Dwelling Bony Fishes, the Giant Grouper (Epinephelus lanceolatus) - Wu_2019_Mar.Biotechnol.(NY)_21_707
Author(s) : Wu L , Yang Y , Li B , Huang W , Wang X , Liu X , Meng Z , Xia J
Ref : Mar Biotechnol (NY) , 21 :707 , 2019
Abstract : The giant grouper, Epinephelus lanceolatus, is the largest coral reef-dwelling bony fish species. However, despite extremely fast growth performance and the considerable economic importance in this species, its genetic regulation of growth remains unknown. Here, we performed the first genome-wide association study (GWAS) for five growth traits in 289 giant groupers using 42,323 single nucleotide polymorphisms (SNPs) obtained by genotyping-by-sequencing (GBS). We identified a total of 36 growth-related SNPs, of which 11 SNPs reached a genome-wide significance level. The phenotypic variance explained by these SNPs varied from 7.09% for body height to 18.42% for body length. Moreover, 22 quantitative trait loci (QTLs) for growth traits, including nine significant QTLs and 13 suggestive QTLs, were found on multiple chromosomes. Interestingly, the QTL (LG17: 6934451) was shared between body weight and body height, while two significant QTLs (LG7: 22596399 and LG15: 11877836) for body length were consistent with the associated regions of total length at the genome-wide suggestive level. Eight potential candidate genes close to the associated SNPs were selected for expression analysis, of which four genes (phosphatidylinositol transfer protein cytoplasmic 1, protein tyrosine phosphatase receptor type E, alpha/beta hydrolase domain-containing protein 17C, and vascular endothelial growth factor A-A) were differentially expressed and involved in metabolism, development, response stress, etc. This study improves our understanding of the complex genetic architecture of growth in the giant grouper. The results contribute to the selective breeding of grouper species and the conservation of coral reef fishes.
ESTHER : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedSearch : Wu_2019_Mar.Biotechnol.(NY)_21_707
PubMedID: 31392592

Title : Development of the hidden multifunctional agents for Alzheimer's disease - Huang_2019_Eur.J.Med.Chem_177_247
Author(s) : Huang W , Liang M , Li Q , Zheng X , Zhang C , Wang Q , Tang L , Zhang Z , Wang B , Shen Z
Ref : Eur Journal of Medicinal Chemistry , 177 :247 , 2019
Abstract : Alzheimer's disease (AD) is a chronic, fatal and complex neurodegenerative disorder, which is characterized by cholinergic system dysregulation, metal dyshomeostasis, amyloid-beta (Abeta) aggregation, etc. Therefore in most cases, single-target or single-functional agents are insufficient to achieve the desirable effect against AD. Multi-Target-Directed Ligand (MTDL), which is rationally designed to simultaneously hit multiple targets to improve the pharmacological profiles, has been developed as a promising approach for drug discovery against AD. To identify the multifunctional agents for AD, we developed an innovative method to successfully conceal the metal chelator into acetylcholinesterase (AChE) inhibitor. Briefly, the "hidden" agents first cross the Blood Brain Barrier (BBB) to inhibit the function of AChE, and the metal chelator will then be released via the enzymatic hydrolysis by AChE. Therefore, the AChE inhibitor, in this case, is not only a single-target agent against AD, but also a carrier of the metal chelator. In this study a total of 14 quinoline derivatives were synthesized and biologically evaluated. Both in vitro and in vivo results demonstrated that compound 9b could cross the BBB efficiently, then release 8a, the metabolite of 9b, into brain. In vitro, 9b had a potent AChE inhibitory activity, while 8a displayed a significant metal ion chelating function, therefore in combination, both 9b and 8a exhibited a considerable inhibition of Abeta aggregation, one of the observations that plays important roles in the pathogenesis of AD. The efficacy of 9b against AD was further investigated in both a zebrafish model and two different mice models.
ESTHER : Huang_2019_Eur.J.Med.Chem_177_247
PubMedSearch : Huang_2019_Eur.J.Med.Chem_177_247
PubMedID: 31158742

Title : Lipoprotein-Associated Phospholipase A2 Activity and Mass as Independent Risk Factor of Stroke: A Meta-Analysis - Hu_2019_Biomed.Res.Int_2019_8642784
Author(s) : Hu G , Liu D , Tong H , Huang W , Hu Y , Huang Y
Ref : Biomed Res Int , 2019 :8642784 , 2019
Abstract : BACKGROUND: The association between lipoprotein-associated phospholipase A2 (Lp-PLA2) and stroke risk is inconsistent. We conducted a meta-analysis to determine whether elevated Lp-PLA2 is a risk factor for stroke. METHODS: Studies were included if they reported Lp-PLA2 mass and/or activity levels and adjusted risk estimates of stroke. The primary outcome was overall stroke incidence. The combined results were shown as relative risks (RRs) with 95% confidence intervals (CI) for per 1 standard deviation (SD) higher value of Lp-PLA2 and the highest versus lowest Lp-PLA2 category. RESULTS: Twenty-two studies involving 157,693 participants were included for analysis. After adjusting for conventional risk factors, the RRs for overall stroke with 1 SD higher Lp-PLA2 activity and mass were 1.07 (95% CI 1.02-1.13) and 1.11 (95% CI 1.04-1.19), respectively. The RRs of ischemic stroke with 1 SD higher Lp-PLA2 activity and mass were 1.08 (95% CI 1.01-1.15) and 1.11 (95% CI 1.02-1.22), respectively. When comparing the highest and lowest levels of Lp-PLA2, the RRs of stroke for Lp-PLA2 activity and mass were 1.26 (95% CI 1.03-1.54) and 1.56 (95% CI 1.21-2.00), respectively. Finally, when comparing the highest and lowest levels of Lp-PLA2, the pooled RRs of ischemic stroke for Lp-PLA2 activity and mass were 1.29 (95% CI 1.07-1.56) and 1.68 (95% CI 1.12-2.53), respectively. CONCLUSIONS: Elevated baseline Lp-PLA2 levels, detected either by activity or mass, are associated with increased stroke risk.
ESTHER : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedSearch : Hu_2019_Biomed.Res.Int_2019_8642784
PubMedID: 31236414
Gene_locus related to this paper: human-PLA2G7

Title : Design, synthesis, and evaluation of genipin derivatives for the treatment of Alzheimer's Disease - Huang_2019_Chem.Biol.Drug.Des_93_110
Author(s) : Huang W , Wang Y , Li J , Zhang Y , Ma X , Zhu P
Ref : Chemical Biology Drug Des , 93 :110 , 2019
Abstract : Twenty-two novel genipin derivatives have been designed, synthesized, and evaluated for their inhibitory activity against acetylcholinesterase (AChE). As a result, compound 13a bearing ligustrazine moiety displayed the most potent AChE inhibitory activity in this series with IC50 value of 218 nm. Besides, MTT assay was performed to investigate the neuroprotection of these compounds against PC12 cells injured by Amyloid beta-protein 1-42 (Abeta1-42 ). Among them, 8a showed higher inhibition rate (%Inhibition = 22.29) than the positive reference Donepezil (%Inhibition = 17.65).
ESTHER : Huang_2019_Chem.Biol.Drug.Des_93_110
PubMedSearch : Huang_2019_Chem.Biol.Drug.Des_93_110
PubMedID: 29543387

Title : Genome-wide association studies reveal genetic loci associated with plasma cholinesterase activity in ducks - Xu_2019_Anim.Genet_50_287
Author(s) : Xu Y , Liu H , Jiang Y , Fan W , Hu J , Zhang Y , Guo Z , Xie M , Huang W , Liu X , Zhou Z , Hou S
Ref : Anim Genet , 50 :287 , 2019
Abstract : Plasma cholinesterase (PCHE) activity is an important auxiliary test in human clinical medicine. It can distinguish liver diseases from non-liver diseases and help detect organophosphorus poisoning. Animal experiments have confirmed that PCHE activity is associated with obesity and hypertension and changes with physiological changes in an animal's body. The objective of this study was to locate the genetic loci responsible for PCHE activity variation in ducks. PCHE activity of Pekin duck x mallard F2 ducks at 3 and 8 weeks of age were analyzed, and genome-wide association studies were conducted. A region of about 1.5 Mb (21.8-23.3 Mb) on duck chromosome 9 was found to be associated with PCHE activity at both 3 and 8 weeks of age. The top SNP, g.22643979C>T in the butyrylcholinesterase (BCHE) gene, was most highly associated with PCHE activity at 3 weeks (-logP = 21.45) and 8 weeks (-logP = 27.60) of age. For the top SNP, the strong associations of CC and CT genotypes with low PCHE activity and the TT genotype with high PCHE activity indicates the dominant inheritance of low PCHE activity. Problems with block inheritance or linkage exist in this region. This study supports that BCHE is a functional gene for determining PCHE levels in ducks and that the genetic variations around this gene can cause phenotypic variations of PCHE activity.
ESTHER : Xu_2019_Anim.Genet_50_287
PubMedSearch : Xu_2019_Anim.Genet_50_287
PubMedID: 30994195
Gene_locus related to this paper: anapl-BCHE

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 : Responses of Antioxidant Defense and Immune Gene Expression in Early Life Stages of Large Yellow Croaker (Pseudosciaena crocea) Under Methyl Mercury Exposure - Wu_2018_Front.Physiol_9_1436
Author(s) : Wu F , Huang W , Liu Q , Xu X , Zeng J , Cao L , Hu J , Gao Y , Jia S
Ref : Front Physiol , 9 :1436 , 2018
Abstract : Early life stages of marine organisms are the most sensitive stages to environment stressors including pollutants. In order to understand the toxicological effects induced by MeHg exposure on juveniles of large yellow croaker (Pseudosciaena crocea), a toxicity test was performed wherein fish were exposed to sub-lethal concentrations of MeHg under laboratory conditions (18 +/- 1 degrees C; 26 +/- 1 in salinity). After 30 days of 0-4.0 mug L(-1) MeHg exposure, SOD activity was significantly decreased in the 0.25, 1.0, and 4.0 mug L(-1) treatments; while CAT activity was significantly increased in the 4.0 mug L(-1) treatments; GSH level, GPx activity were significantly elevated in the 4.0 mug L(-1) treatments, respectively. Meanwhile, malondialdehyde content was also significantly increased in the 1.0 and 4.0 mug L(-1) treatments with respect to the control. Acetylcholinesterase activity was significantly decreased by 18.3, 25.2, and 21.7% in the 0.25, 1.0, and 4.0 mug L(-1) treatments, respectively. The expression of TCTP, GST3, Hsp70, Hsp27 mRNA were all up-regulated in juveniles with a dose-dependent manner exposed to MeHg. These results suggest that large yellow croaker juveniles have the potential to regulate the levels of antioxidant enzymes and initiate immune response in order to protect fish to some extent from oxidative stress induced by MeHg.
ESTHER : Wu_2018_Front.Physiol_9_1436
PubMedSearch : Wu_2018_Front.Physiol_9_1436
PubMedID: 30364149

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

Title : LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer - Lo_2018_Elife_7_e31334
Author(s) : Lo PK , Yao Y , Lee JS , Zhang Y , Huang W , Kane MA , Zhou Q
Ref : Elife , 7 : , 2018
Abstract : Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG executes its oncogenic function through its involvement in interferon-related DTX3L-ISG15 signaling, which regulates protein function and stability by ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15 signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling is essential for malignancies of TNBC cells. Targeting this pathway provides a novel strategy for basal-like TNBC therapy.
ESTHER : Lo_2018_Elife_7_e31334
PubMedSearch : Lo_2018_Elife_7_e31334
PubMedID: 29350614
Gene_locus related to this paper: human-LIPG

Title : Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation - Yang_2018_Proc.Natl.Acad.Sci.U.S.A_115_613
Author(s) : Yang YM , Sun D , Kandhi S , Froogh G , Zhuge J , Huang W , Hammock BD , Huang A
Ref : Proc Natl Acad Sci U S A , 115 :613 , 2018
Abstract : To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice. The same increase in CG methylation was also observed in male vessels incubated with a physiological concentration of 17beta-estradiol (17beta-E2) for 48 hours. All vessels that displayed increases in CG methylation were concomitantly associated with decreases in their Ephx2 mRNA and protein, suggesting a methylation-induced gene silencing. Transient transfection assays indicate that the activity of Ephx2 promoter-coding luciferase was significantly attenuated in HEK293T cells treated with 17beta-E2, which was prevented by additional treatment with an estrogen receptor antagonist (ICI). ChIP analysis indicates significantly reduced binding activities of transcription factors (including SP1, AP-1, and NF-kappaB with their binding elements located in the Ephx2 promoter) in vessels of female mice and human cells treated with 17beta-E2, responses that were prevented by ICI and Decitabine (DNA methyltransferase inhibitor), respectively. In conclusion, estrogen/estrogen receptor-dependent methylation of the promoter of Ephx2 gene silences sEH expression, which is involved in specific transcription factor-directed regulatory pathways.
ESTHER : Yang_2018_Proc.Natl.Acad.Sci.U.S.A_115_613
PubMedSearch : Yang_2018_Proc.Natl.Acad.Sci.U.S.A_115_613
PubMedID: 29295935

Title : IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata - Wingfield_2018_IMA.Fungus_9_199
Author(s) : Wingfield BD , Bills GF , Dong Y , Huang W , Nel WJ , Swalarsk-Parry BS , Vaghefi N , Wilken PM , An Z , de Beer ZW , De Vos L , Chen L , Duong TA , Gao Y , Hammerbacher A , Kikkert JR , Li Y , Li H , Li K , Li Q , Liu X , Ma X , Naidoo K , Pethybridge SJ , Sun J , Steenkamp ET , van der Nest MA , van Wyk S , Wingfield MJ , Xiong C , Yue Q , Zhang X
Ref : IMA Fungus , 9 :199 , 2018
Abstract : Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi.
ESTHER : Wingfield_2018_IMA.Fungus_9_199
PubMedSearch : Wingfield_2018_IMA.Fungus_9_199
PubMedID: 30018880
Gene_locus related to this paper: 9helo-a0a370tge3 , 9helo-a0a3d8spg6 , 9euro-a0a3d8t2t6 , 9euro-a0a3d8t644 , 9helo-a0a370te58 , 9helo-a0a370tt42 , 9helo-a0a370u2s4 , 9helo-a0a3d8s0y2 , 9helo-a0a3d8stp9 , 9helo-a0a370u370 , 9euro-a0a3d8rk78 , 9helo-a0a370tat5 , 9helo-a0a3d8qpi0

Title : Fatal poisoning by terbufos following occupational exposure - Liang_2017_Clin.Toxicol.(Phila)__1
Author(s) : Liang Y , Tong F , Zhang L , Li W , Huang W , Zhou Y
Ref : Clinical Toxicology (Phila) , :1 , 2017
Abstract : CONTEXT: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. CASE: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 x 10-2 mug/ml in the heart blood and 0.17 mug/g in the liver. DISCUSSIONS: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors.
CONCLUSIONS: TBF is a highly toxic OP. Inadequate regulatory control, improper environmental application, and ineffective PPE resulted in a fatal human exposure.
ESTHER : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedSearch : Liang_2017_Clin.Toxicol.(Phila)__1
PubMedID: 28681657

Title : Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita - Cui_2017_Exp.Parasitol_176_75
Author(s) : Cui R , Zhang L , Chen Y , Huang W , Fan C , Wu Q , Peng D , da Silva W , Sun X
Ref : Experimental Parasitology , 176 :75 , 2017
Abstract : The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant.
ESTHER : Cui_2017_Exp.Parasitol_176_75
PubMedSearch : Cui_2017_Exp.Parasitol_176_75
PubMedID: 28238686
Gene_locus related to this paper: melin-ACHE1 , melin-ACHE2 , melic-a0a0m5m7r8

Title : A comprehensive draft genome sequence for lupin (Lupinus angustifolius), an emerging health food: insights into plant-microbe interactions and legume evolution - Hane_2017_Plant.Biotechnol.J_15_318
Author(s) : Hane JK , Ming Y , Kamphuis LG , Nelson MN , Garg G , Atkins CA , Bayer PE , Bravo A , Bringans S , Cannon S , Edwards D , Foley R , Gao LL , Harrison MJ , Huang W , Hurgobin B , Li S , Liu CW , McGrath A , Morahan G , Murray J , Weller J , Jian J , Singh KB
Ref : Plant Biotechnol J , 15 :318 , 2017
Abstract : Lupins are important grain legume crops that form a critical part of sustainable farming systems, reducing fertilizer use and providing disease breaks. It has a basal phylogenetic position relative to other crop and model legumes and a high speciation rate. Narrow-leafed lupin (NLL; Lupinus angustifolius L.) is gaining popularity as a health food, which is high in protein and dietary fibre but low in starch and gluten-free. We report the draft genome assembly (609 Mb) of NLL cultivar Tanjil, which has captured >98% of the gene content, sequences of additional lines and a dense genetic map. Lupins are unique among legumes and differ from most other land plants in that they do not form mycorrhizal associations. Remarkably, we find that NLL has lost all mycorrhiza-specific genes, but has retained genes commonly required for mycorrhization and nodulation. In addition, the genome also provided candidate genes for key disease resistance and domestication traits. We also find evidence of a whole-genome triplication at around 25 million years ago in the genistoid lineage leading to Lupinus. Our results will support detailed studies of legume evolution and accelerate lupin breeding programmes.
ESTHER : Hane_2017_Plant.Biotechnol.J_15_318
PubMedSearch : Hane_2017_Plant.Biotechnol.J_15_318
PubMedID: 27557478
Gene_locus related to this paper: lupan-a0a1j7h2u5 , lupan-a0a4p1r201 , lupan-a0a4p1rve4 , lupan-a0a1j7inr2 , lupan-a0a4p1rbl4 , lupan-a0a1j7ifk4 , lupan-a0a4p1rs77 , lupan-a0a1j7h5s4

Title : The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut - Bertioli_2016_Nat.Genet_48_438
Author(s) : Bertioli DJ , Cannon SB , Froenicke L , Huang G , Farmer AD , Cannon EK , Liu X , Gao D , Clevenger J , Dash S , Ren L , Moretzsohn MC , Shirasawa K , Huang W , Vidigal B , Abernathy B , Chu Y , Niederhuth CE , Umale P , Araujo AC , Kozik A , Kim KD , Burow MD , Varshney RK , Wang X , Zhang X , Barkley N , Guimaraes PM , Isobe S , Guo B , Liao B , Stalker HT , Schmitz RJ , Scheffler BE , Leal-Bertioli SC , Xun X , Jackson SA , Michelmore R , Ozias-Akins P
Ref : Nat Genet , 48 :438 , 2016
Abstract : Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of -2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut.
ESTHER : Bertioli_2016_Nat.Genet_48_438
PubMedSearch : Bertioli_2016_Nat.Genet_48_438
PubMedID: 26901068
Gene_locus related to this paper: aradu-a0a6p4dix2 , aradu-a0a6p4dpj0 , aradu-a0a6p4dix7

Title : Novel inhibitor against Malassezia globosa LIP1 (SMG1), a potential anti-dandruff target - Guo_2015_Bioorg.Med.Chem.Lett_25_3464
Author(s) : Guo S , Huang W , Zhang J , Wang Y
Ref : Bioorganic & Medicinal Chemistry Lett , 25 :3464 , 2015
Abstract : Compelling evidence have demonstrated the role of lipase activity in the pathogenicity of Malassezia globosa toward dandruff and seborrheic dermatitis (D/SD). As a representative secreted lipase from M. globosa CBS 7966, Malassezia globosa LIP1 (SMG1) is considered a potential anti-dandruff target. In this study, homology modeling, docking-based virtual screening and in vitro lipase-based assay were integrated to identify the first hit compound against SMG1, with an IC50 of 20 microM against synthetic lipase substrate, and of 0.19 microM when using natural lipase substrate. Evaluation of similar compounds, along with docking, offered information on the binding patterns of the hit compound. This work is expected to serve as a starting point for the rational design of more potent inhibitors against SMG1.
ESTHER : Guo_2015_Bioorg.Med.Chem.Lett_25_3464
PubMedSearch : Guo_2015_Bioorg.Med.Chem.Lett_25_3464
PubMedID: 26199121
Gene_locus related to this paper: malgo-a8puy1

Title : Acetylcholinesterase overexpression mediated by oncolytic adenovirus exhibited potent anti-tumor effect - Xu_2014_BMC.Cancer_14_668
Author(s) : Xu H , Shen Z , Xiao J , Yang Y , Huang W , Zhou Z , Shen J , Zhu Y , Liu XY , Chu L
Ref : BMC Cancer , 14 :668 , 2014
Abstract : BACKGROUND: Acetylcholinesterase (AChE) mainly functions as an efficient terminator for acetylcholine signaling transmission. Here, we reported the effect of AChE on gastric cancer therapy.
METHODS: The expression of AChE in gastric cancerous tissues and adjacent non-cancerous tissues was examined by immunohistochemistry. Gastric cancer cells were treated with AChE delivered by replication-deficient adenoviral vector (Ad.AChE) or oncolytic adenoviral vector (ZD55-AChE), respectively, followed by measurement of cell viability and apoptosis by MTT assay and apoptosis detection assays. In vivo, the tumor growth of gastric cancer xenografts in mice treated with Ad.AChE or ZD55-AChE (1 x 109 PFU) were measured. In addition, the cell viability of gastric cancer stem cells treated with Ad.AChE or ZD55-AChE were evaluated by MTT assay.
RESULTS: A positive correlation was found between higher level of AChE expression in gastric cancer patient samples and longer survival time of the patients. Ad.AChE and ZD55-AChE inhibited gastric cancer cell growth, and low dose of ZD55-AChE induced mitochondrial pathway of apoptosis in cells. ZD55-AChE repressed tumor growth in vivo, and the anti-tumor efficacy is greater than Ad.AChE. Moreover, ZD55-AChE suppressed the growth of gastric cancer stem cells. CONCLUSION: ZD55-AChE represented potential therapeutic effect for human gastric cancer.
ESTHER : Xu_2014_BMC.Cancer_14_668
PubMedSearch : Xu_2014_BMC.Cancer_14_668
PubMedID: 25220382

Title : Elevated 14,15- epoxyeicosatrienoic acid by increasing of cytochrome P450 2C8, 2C9 and 2J2 and decreasing of soluble epoxide hydrolase associated with aggressiveness of human breast cancer - Wei_2014_BMC.Cancer_14_841
Author(s) : Wei X , Zhang D , Dou X , Niu N , Huang W , Bai J , Zhang G
Ref : BMC Cancer , 14 :841 , 2014
Abstract : BACKGROUND: Epoxyeicosatrienoic acids (EETs) are derived from arachidonic acid by cytochrome P450 (CYP) and metabolized by soluble epoxide hydrolase (sEH). EETs have been associated with cardiovascular disease, diabetes and several cancer diseases. However, the distribution in tissue and role of CYP2C8, 2C9, 2J2 and sEH in human breast carcinogenesis remains uncertain. METHODS: Breast cancer (BC) and adjacent noncancerous tissue was obtained from 40 breast cancer patients in the Chaoshan region in China from 2010 to 2012. The level of 14,15-EET/14,15-DHET in BC patients was detected by ELISA; the expression and distribution of CYP2C8, 2C9, 2J2 and sEH was determined by quantitative RT-PCR and immunohistochemical staining; and cell proliferation and migration was analyzed by MTT and transwell assays, respectively. RESULTS: The median 14,15-EET and 14,15-EET/DHET level was 2.5-fold higher in BC than noncancerous tissue. The mRNA and protein levels of CYP2C8, 2C9 and 2J2 were higher, and sEH was lower in BC than noncancerous tissue. Furthermore, CYP2C8 and 2C9 protein levels positively correlated with Ki67 status, and CYP2J2 levels positively correlated with histological grade and tumor size. The sEH protein level negatively correlated with tumor size, estrogen receptors and Ki67. In MDA-MB-231 cells, siRNA knockdown of CYP2C8, 2C9 or 2J2 reduced cell proliferation, by 24.5%, 29.13%, or 22.7% and decreased cell migration by 49.1%, 44.9%, and 50.9%, respectively. Similarly, with adenovirus overexpression of sEH, both cell proliferation and migration rates were reduced by 31.4% and 45.8%, respectively. CONCLUSIONS: The present study shows that elevated EET levels in BC tissues are associated with upregulation of CYP2C8, 2C9, and 2J2, and downregulation of sEH, and are also associated with aggressive cell behavior in BC patients.
ESTHER : Wei_2014_BMC.Cancer_14_841
PubMedSearch : Wei_2014_BMC.Cancer_14_841
PubMedID: 25406731

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

Title : mTORC2 controls actin polymerization required for consolidation of long-term memory - Huang_2013_Nat.Neurosci_16_441
Author(s) : Huang W , Zhu PJ , Zhang S , Zhou H , Stoica L , Galiano M , Krnjevic K , Roman G , Costa-Mattioli M
Ref : Nat Neurosci , 16 :441 , 2013
Abstract : A major goal of biomedical research is the identification of molecular and cellular mechanisms that underlie memory storage. Here we report a previously unknown signaling pathway that is necessary for the conversion from short- to long-term memory. The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), was discovered only recently and little is known about its function. We found that conditional deletion of Rictor in the postnatal murine forebrain greatly reduced mTORC2 activity and selectively impaired both long-term memory (LTM) and the late phase of hippocampal long-term potentiation (L-LTP). We also found a comparable impairment of LTM in dTORC2-deficient flies, highlighting the evolutionary conservation of this pathway. Actin polymerization was reduced in the hippocampus of mTORC2-deficient mice and its restoration rescued both L-LTP and LTM. Moreover, a compound that promoted mTORC2 activity converted early LTP into late LTP and enhanced LTM. Thus, mTORC2 could be a therapeutic target for the treatment of cognitive dysfunction.
ESTHER : Huang_2013_Nat.Neurosci_16_441
PubMedSearch : Huang_2013_Nat.Neurosci_16_441
PubMedID: 23455608

Title : Synthesis, biological evaluation and molecular modeling of aloe-emodin derivatives as new acetylcholinesterase inhibitors - Shi_2013_Bioorg.Med.Chem_21_1064
Author(s) : Shi DH , Huang W , Li C , Wang LT , Wang SF
Ref : Bioorganic & Medicinal Chemistry , 21 :1064 , 2013
Abstract : A series of aloe-emodin derivatives were designed, synthesized and evaluated as acetylcholinesterase inhibitors. Most of the new prepared compounds showed remarkable acetylcholinesterase inhibitory activities. Among them, the compound 1-((4,5-dihydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl) methyl) pyridin-1-ium chloride (C3) which has a pyridinium substituent possessed the best inhibitory activity of acetylcholinesterase (IC(50)=0.09 muM). The docking study performed with AUTODOCK demonstrated that C3 could interact with the catalytic active site (CAS) and the peripheral anionic site (PAS) of acetylcholinesterase.
ESTHER : Shi_2013_Bioorg.Med.Chem_21_1064
PubMedSearch : Shi_2013_Bioorg.Med.Chem_21_1064
PubMedID: 23380475

Title : The oyster genome reveals stress adaptation and complexity of shell formation - Zhang_2012_Nature_490_49
Author(s) : Zhang G , Fang X , Guo X , Li L , Luo R , Xu F , Yang P , Zhang L , Wang X , Qi H , Xiong Z , Que H , Xie Y , Holland PW , Paps J , Zhu Y , Wu F , Chen Y , Wang J , Peng C , Meng J , Yang L , Liu J , Wen B , Zhang N , Huang Z , Zhu Q , Feng Y , Mount A , Hedgecock D , Xu Z , Liu Y , Domazet-Loso T , Du Y , Sun X , Zhang S , Liu B , Cheng P , Jiang X , Li J , Fan D , Wang W , Fu W , Wang T , Wang B , Zhang J , Peng Z , Li Y , Li N , Chen M , He Y , Tan F , Song X , Zheng Q , Huang R , Yang H , Du X , Chen L , Yang M , Gaffney PM , Wang S , Luo L , She Z , Ming Y , Huang W , Huang B , Zhang Y , Qu T , Ni P , Miao G , Wang Q , Steinberg CE , Wang H , Qian L , Liu X , Yin Y
Ref : Nature , 490 :49 , 2012
Abstract : The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa.
ESTHER : Zhang_2012_Nature_490_49
PubMedSearch : Zhang_2012_Nature_490_49
PubMedID: 22992520
Gene_locus related to this paper: cragi-k1qzk7 , cragi-k1rad0 , cragi-k1p6v9 , cragi-k1pa46 , cragi-k1pga2 , cragi-k1pp63 , cragi-k1pwa8 , cragi-k1q0b1.1 , cragi-k1q0b1.2 , cragi-k1q1h2 , cragi-k1q2z6 , cragi-k1qaj8 , cragi-k1qaw5 , cragi-k1qhl5 , cragi-k1qly1 , cragi-k1qqb1.1 , cragi-k1qqb1.2 , cragi-k1qs61 , cragi-k1qs99 , cragi-k1qwl6 , cragi-k1r068 , cragi-k1r0n3.1 , cragi-k1r0n3.2 , cragi-k1r0r4 , cragi-k1r1i9 , cragi-k1r8q9 , cragi-k1rgi1 , cragi-k1rig4 , cragi-k1s0a7.1 , cragi-k1s0a7.2 , cragi-k1s0a7.3 , cragi-k1q6q0 , cragi-k1rru1 , cragi-k1qfi4 , cragi-k1qvm5 , cragi-k1qq58 , cragi-k1qdc0 , cragi-k1r754 , cragi-k1pje5 , cragi-k1qca6 , cragi-k1qdt5 , cragi-k1qkz7 , cragi-k1rgd2 , cragi-k1puh6 , cragi-k1raz4 , cragi-k1qqj4 , cragi-k1rbs1

Title : Er Zhi Wan, an ancient herbal decoction for woman menopausal syndrome, activates the estrogenic response in cultured MCF-7 cells: an evaluation of compatibility in defining the optimized preparation method - Xu_2012_J.Ethnopharmacol_143_109
Author(s) : Xu H , Su ZR , Huang W , Choi RC , Zheng YZ , Lau DT , Dong TTX , Wang ZT , Tsim KWK
Ref : J Ethnopharmacol , 143 :109 , 2012
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Er Zhi Wan (EZW), a Chinese medicinal preparation, has been used clinically for treating menopausal syndrome for its kidney-invigorating function, which contains simply two herbs, Ecliptae Herba (EH) and Ligustri Lucidi Fructus (LLF). Although this herbal extract has been used for many years, there is no scientific basis about its effectiveness on menopausal symptom. Here, we aimed to evaluate the estrogenic activities of EZW and to study the compatibilities of two herbs including different processed-LLF in single and mixed preparation of EZW. Moreover, the weight ratio of EH to LLF in EZW was determined according to their estrogenic activities. MATERIALS AND
METHODS: The extractions of LLF, processed-LLF and EH were prepared separately by extracting the powders with water, 50% alcohol or 95% alcohol. Steamed-LLF and EH were extracted separately, or together, in preparing EZW extracts. A promoter-reporter construct (pERE-Luc) containing three repeats of estrogen responsive elements (ERE) was stably transfected into MCF-7 cells, and this stable breast cancer cell line was used to determine the estrogenic property. The cell proliferation was measured by MTT assay.
RESULTS: The results showed that EZW could significantly induce the expression of luciferase driven by an estrogen responsive element in a pERE-Luc vector. The proliferation of MCF-7 cells was not altered by this herbal treatment. The best preparation of EZW was from: (i) LLF was firstly steamed over water and then dried to make steamed-LLF; and (ii) steamed-LLF and EH were extracted separately by 95% alcohol and then mixed together according to a weight ratio of 1:1.
CONCLUSIONS: Under the optimized extracting method, EZW possessed robust effect in activating the estrogenic activity, but which did not alter the proliferation of cultured MCF-7 cells. Thus, EZW is an effective and safe estrogenic herbal extract.
ESTHER : Xu_2012_J.Ethnopharmacol_143_109
PubMedSearch : Xu_2012_J.Ethnopharmacol_143_109
PubMedID: 22710293

Title : Searching for the Multi-Target-Directed Ligands against Alzheimer's disease: discovery of quinoxaline-based hybrid compounds with AChE, H(3)R and BACE 1 inhibitory activities - Huang_2011_Bioorg.Med.Chem_19_7158
Author(s) : Huang W , Tang L , Shi Y , Huang S , Xu L , Sheng R , Wu P , Li J , Zhou N , Hu Y
Ref : Bioorganic & Medicinal Chemistry , 19 :7158 , 2011
Abstract : A novel series of quinoxaline derivatives, as Multi-Target-Directed Ligands (MTDLs) for AD treatment, were designed by lending the core structural elements required for H(3)R antagonists and hybridizing BACE 1 inhibitor 1 with AChE inhibitor BYYT-25. A virtual database consisting of quinoxaline derivatives was first screened on a pharmacophore model of BACE 1 inhibitors, and then filtered by a molecular docking model of AChE. Seventeen quinoxaline derivatives with high score values were picked out, synthesized and evaluated for their biological activities. Compound 11a, the most effective MTDL, showed the potent activity to H(3)R/AChE/BACE 1 (H(3)R antagonism, IC(50)=280.0 +/- 98.0 nM; H(3)R inverse agonism, IC(50)=189.3 +/- 95.7 nM; AChE, IC(50)=483 +/- 5 nM; BACE 1, 46.64+/-2.55% inhibitory rate at 20 muM) and high selectivity over H(1)R/H(2)R/H(4)R. Furthermore, the protein binding patterns between 11a and AChE/BACE 1 showed that it makes several essential interactions with the enzymes.
ESTHER : Huang_2011_Bioorg.Med.Chem_19_7158
PubMedSearch : Huang_2011_Bioorg.Med.Chem_19_7158
PubMedID: 22019465

Title : Suppression of PKR promotes network excitability and enhanced cognition by interferon-gamma-mediated disinhibition - Zhu_2011_Cell_147_1384
Author(s) : Zhu PJ , Huang W , Kalikulov D , Yoo JW , Placzek AN , Stoica L , Zhou H , Bell JC , Friedlander MJ , Krnjevic K , Noebels JL , Costa-Mattioli M
Ref : Cell , 147 :1384 , 2011
Abstract : The double-stranded RNA-activated protein kinase (PKR) was originally identified as a sensor of virus infection, but its function in the brain remains unknown. Here, we report that the lack of PKR enhances learning and memory in several behavioral tasks while increasing network excitability. In addition, loss of PKR increases the late phase of long-lasting synaptic potentiation (L-LTP) in hippocampal slices. These effects are caused by an interferon-gamma (IFN-gamma)-mediated selective reduction in GABAergic synaptic action. Together, our results reveal that PKR finely tunes the network activity that must be maintained while storing a given episode during learning. Because PKR activity is altered in several neurological disorders, this kinase presents a promising new target for the treatment of cognitive dysfunction. As a first step in this direction, we show that a selective PKR inhibitor replicates the Pkr(-/-) phenotype in WT mice, enhancing long-term memory storage and L-LTP.
ESTHER : Zhu_2011_Cell_147_1384
PubMedSearch : Zhu_2011_Cell_147_1384
PubMedID: 22153080

Title : Genome sequencing and comparative transcriptomics of the model entomopathogenic fungi Metarhizium anisopliae and M. acridum - Gao_2011_PLoS.Genet_7_e1001264
Author(s) : Gao Q , Jin K , Ying SH , Zhang Y , Xiao G , Shang Y , Duan Z , Hu X , Xie XQ , Zhou G , Peng G , Luo Z , Huang W , Wang B , Fang W , Wang S , Zhong Y , Ma LJ , St Leger RJ , Zhao GP , Pei Y , Feng MG , Xia Y , Wang C
Ref : PLoS Genet , 7 :e1001264 , 2011
Abstract : Metarhizium spp. are being used as environmentally friendly alternatives to chemical insecticides, as model systems for studying insect-fungus interactions, and as a resource of genes for biotechnology. We present a comparative analysis of the genome sequences of the broad-spectrum insect pathogen Metarhizium anisopliae and the acridid-specific M. acridum. Whole-genome analyses indicate that the genome structures of these two species are highly syntenic and suggest that the genus Metarhizium evolved from plant endophytes or pathogens. Both M. anisopliae and M. acridum have a strikingly larger proportion of genes encoding secreted proteins than other fungi, while ~30% of these have no functionally characterized homologs, suggesting hitherto unsuspected interactions between fungal pathogens and insects. The analysis of transposase genes provided evidence of repeat-induced point mutations occurring in M. acridum but not in M. anisopliae. With the help of pathogen-host interaction gene database, ~16% of Metarhizium genes were identified that are similar to experimentally verified genes involved in pathogenicity in other fungi, particularly plant pathogens. However, relative to M. acridum, M. anisopliae has evolved with many expanded gene families of proteases, chitinases, cytochrome P450s, polyketide synthases, and nonribosomal peptide synthetases for cuticle-degradation, detoxification, and toxin biosynthesis that may facilitate its ability to adapt to heterogeneous environments. Transcriptional analysis of both fungi during early infection processes provided further insights into the genes and pathways involved in infectivity and specificity. Of particular note, M. acridum transcribed distinct G-protein coupled receptors on cuticles from locusts (the natural hosts) and cockroaches, whereas M. anisopliae transcribed the same receptor on both hosts. This study will facilitate the identification of virulence genes and the development of improved biocontrol strains with customized properties.
ESTHER : Gao_2011_PLoS.Genet_7_e1001264
PubMedSearch : Gao_2011_PLoS.Genet_7_e1001264
PubMedID: 21253567
Gene_locus related to this paper: metaq-dapb , metaq-e9dr02 , metaq-e9dr46 , metaq-e9dx32 , metaq-e9dy00 , metaq-e9e6i5 , metaq-e9e332 , metaq-e9e873 , metaq-e9eaq4 , metaq-e9ebs3 , metaq-e9ebt3 , metaq-e9edi2 , metaq-e9edr0 , metaq-e9ee29 , metaq-e9eej3 , metaq-e9ef60 , metaq-e9ef98 , metaq-e9efc1 , metaq-e9eg97 , metaq-e9egz7 , metaq-kex1 , metar-dapb , metar-e9ej81 , metar-e9ejw6 , metar-e9ek06 , metar-e9eka7 , metar-e9eku9 , metar-e9em68 , metar-e9emd0 , metar-e9enf9 , metar-e9eny8 , metar-e9ep20 , metar-e9ep60 , metar-e9eqh0 , metar-e9etb2 , metar-e9etp6 , metar-e9euh9 , metar-e9ey62 , metar-e9eyx6 , metar-e9ezk2 , metar-e9f3f2 , metar-e9f3j3 , metar-e9f3l3 , metar-e9f3z5 , metar-e9f6q5 , metar-e9f6t6 , metar-e9f7y7 , metar-e9f9h2 , metar-e9f029 , metar-e9f205 , metar-e9f721 , metar-e9fa63 , metar-e9fab1 , metar-e9fas3 , metar-e9fbn5 , metar-e9fbt1 , metar-e9fd34 , metaq-e9eej8 , metaq-e9dx35 , metar-e9f3e9 , metar-e9f0w8 , metan-a0a086npb7 , 9hypo-a0a014p983 , metan-a0a086nhe0 , 9hypo-a0a0a1v7e9 , metaq-e9e0y0 , metan-a0a0d9pev7 , metaq-e9edt7 , metra-e9ewg3 , metra-pks2 , metaf-pks1 , metaq-pks2 , metaq-e9e9z0

Title : Synthesis and bioactivity evaluation of dipeptidyl peptidase IV resistant glucagon-like peptide-1 analogues - Zhou_2010_Protein.Pept.Lett_17_1290
Author(s) : Zhou J , Ni S , Zhang H , Qian H , Chi Y , Huang W , Yu L , Hu X , Chen W
Ref : Protein Pept Lett , 17 :1290 , 2010
Abstract : Glucagon-like peptide -1 (GLP-1) is an incretin hormone displaying glucose-dependent stimulation of insulin secretion and trophic effects on the pancreatic beta-cells. However, GLP-1 is rapidly degraded to GLP-1(9-36) by dipeptidyl peptidase-IV (DPP-IV), which removes the N-terminal dipeptide His(7)-Ala(8). The rapid inactivation of GLP-1 in the blood circulation limits its clinical application. Hence, we replaced the enzymatic hydrolyzation position Ala(8) with other natural amino acids. The GLP-1 analogues were synthesized rapidly and efficiently under microwave irradiation, using Fmoc/tBu orthogonal protection strategy. Studies on blood-glucose-lowering effect of GLP-1 analogues in vivo were undertaken using 10-week-old male Kunming mice. The metabolic stability was tested by incubation with dipeptidyl peptidase-IV (DPP-IV). Generally, Xaa(8)-GLP-1 analogues exhibit resistance to DPP-IV degradation in vitro and stronger hypoglycemic effect than GLP-1. This may help to understand the structure-activity relationship of GLP-1 analogues.
ESTHER : Zhou_2010_Protein.Pept.Lett_17_1290
PubMedSearch : Zhou_2010_Protein.Pept.Lett_17_1290
PubMedID: 20594158

Title : Ontogenetic development of digestive enzymes and effect of starvation in miiuy croaker Miichthys miiuy larvae - Shan_2009_Fish.Physiol.Biochem_35_385
Author(s) : Shan XJ , Huang W , Cao L , Xiao ZZ , Dou SZ
Ref : Fish Physiol Biochem , 35 :385 , 2009
Abstract : The ontogenetic development of the digestive enzymes amylase, lipase, trypsin, and alkaline phosphatase and the effect of starvation in miiuy croaker Miichthys miiuy larvae were studied. The activities of these enzymes were detected prior to exogenous feeding, but their developmental patterns differed remarkably. Trypsin activity continuously increased from 2 days after hatching (dah), peaked on 20 dah, and decreased to 25 dah at weaning. Alkaline phosphatase activity oscillated at low levels within a small range after the first feeding on 3 dah. In contrast, amylase and lipase activities followed the general developmental pattern that has been characterized in fish larvae, with a succession of increases or decreases. Amylase, lipase, and trypsin activities generally started to increase or decrease at transitions from endogenous to exogenous feeding or diet changes, suggesting that these enzymatic activities can be modulated by feeding modes. The activities of all the enzymes remained stable from 25 dah onwards, coinciding with the formation of gastric glands and pyloric caecum. These results imply that specific activities of these enzymes underwent changes due to morphological and physiological modifications or diet shift during larval development but that they became stable after the development of the digestive organs and associated glands was fully completed and the organs/glands functioned. Trypsin and alkaline phosphatase were more sensitive to starvation than amylase and lipase because delayed feeding up to 2 days after mouth opening was able to adversely affect their activities. Enzyme activities did not significantly differ among feeding groups during endogenous feeding; however, all activities were remarkably reduced when delayed feeding was within 3 days after mouth opening. Initiation of larvae feeding should occur within 2 days after mouth opening so that good growth and survival can be obtained in the culture.
ESTHER : Shan_2009_Fish.Physiol.Biochem_35_385
PubMedSearch : Shan_2009_Fish.Physiol.Biochem_35_385
PubMedID: 18821026

Title : Quality evaluation of Rhizoma Belamcandae (Belamcanda chinensis (L.) DC.) by using high-performance liquid chromatography coupled with diode array detector and mass spectrometry - Li_2009_J.Chromatogr.A_1216_2071
Author(s) : Li J , Li WZ , Huang W , Cheung AW , Bi CWC , Duan R , Guo AJ , Dong TTX , Tsim KWK
Ref : Journal of Chromatography A , 1216 :2071 , 2009
Abstract : A high-performance liquid chromatography coupled with diode array detector and mass spectrometry (HPLC-DAD-MS) method was developed to evaluate the quality of Rhizoma Belamcandae (Belamcanda chinensis (L.) DC.) through establishing chromatographic fingerprint and simultaneous determination of seven phenolic compounds. The analysis was achieved on an Alltima C(18) analytical column (250 mm x 4.6 mm i.d. 5 microm) using linear gradient elution of acetonitrile-0.1% trifluoroacetic acid. The correlation coefficients of similarity were determined from the HPLC fingerprints, and they shared a close similarity. By using an online APCI-MS/MS, twenty phenols were identified. In addition, seven of these phenols including mangiferin, 7-O-methylmangiferin, tectoridin, resveratrol, tectorigenin, irigenin and irisflorentin were quantified by the validated HPLC-DAD method. These phenols are considered to be major constituents in Rhizoma Belamcandae, and are generally regarded as the index for quality assessment of this herb. This developed method by having a combination of chromatographic fingerprint and quantification analysis could be applied to the quality control of Rhizoma Belamcandae.
ESTHER : Li_2009_J.Chromatogr.A_1216_2071
PubMedSearch : Li_2009_J.Chromatogr.A_1216_2071
PubMedID: 18550076

Title : Can rhizoma chuanxiong replace radix Angelica sinensis in the traditional Chinese herbal decoction danggui buxue tang? - Li_2009_Planta.Med_75_602
Author(s) : Li WZ , Li J , Bi CWC , Cheung AW , Huang W , Duan R , Choi RC , Chen IS , Zhao KJ , Dong TTX , Duan JA , Tsim KWK
Ref : Planta Med , 75 :602 , 2009
Abstract : Herein, we test the hypothesis that a member of a formulated Chinese herbal decoction cannot be replaced by another herb. Danggui Buxue Tang (DBT) is being used as an example for illustration: this is a traditional decoction containing Radix Astragali (RA) and Radix Angelicae Sinensis (RAS) in a weight ratio of 5 to 1. Rhizoma Chuanxiong (RC) and RAS are two chemically very similar herbs but with a distinct function. Following the preparation method of DBT, a herbal decoction, namely Chuanxiong Buxue Tang (CBT), was created, which contained RA and RC in a weight ratio of 5 to 1. The two decoctions, DBT and CBT, were compared in parallel regarding their chemical and biological properties. In all the tested parameters, DBT showed superior properties, both chemically and biologically, to that of CBT. The current results reveal the uniqueness of Chinese herbal decoctions that require a well-defined formulation, which is indispensable for its specific composition.
ESTHER : Li_2009_Planta.Med_75_602
PubMedSearch : Li_2009_Planta.Med_75_602
PubMedID: 19204892

Title : [Molecular cloning and characterization of an acetylcholinesterase gene Dd-ace-2 from sweet potato stem nematode Ditylenchus destructor] - Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
Author(s) : Ding Z , Peng D , Huang W , He W , Gao B
Ref : Sheng Wu Gong Cheng Xue Bao , 24 :239 , 2008
Abstract : A cDNA, named Dd-ace-2, encoding an acetylcholinesterase (AChE, EC3.1.1.7), was isolated from sweet-potato-stem nematode, Ditylenchus destructor. The nucleotide and amino acid sequences among different nematode species were compared and analyzed with DNAMAN5.0, MEGA3.0 softwares. The results showed that the complete nucleotide sequence of Dd-ace-2 gene of Ditylenchus destructor contains 2425 base pairs from which deduced 734 amino acids (GenBank accession No. EF583058). The homology rates of amino acid sequences of Dd-ace-2 gene between Ditylenchus destructor and Meloidogyne incognita, Caenorhabditis elegans, Dictyocaulus viviparous were 48.0%, 42.7%, 42.1% respectively. The mature acetylcholinesterase sequences of Ditylenchus destructor may encode by the first 701 residues of deduced 734 amino acids.The conserved motifs involved in the catalytic triad, the choline binding site and 10 aromatic residues lining the catalytic gorge were present in the Dd-ace-2 deduced protein. Phylogenetic analysis based on AChEs of other nematodes and species showed that the deduced AChE formed the same cluster with ACE-2s.
ESTHER : Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
PubMedSearch : Ding_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_239
PubMedID: 18464607

Title : Expression of LPL in endothelial-intact artery results in lipid deposition and vascular cell adhesion molecule-1 upregulation in both LPL and ApoE-deficient mice - Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
Author(s) : Wang J , Xian X , Huang W , Chen L , Wu L , Zhu Y , Fan J , Ross C , Hayden MR , Liu G
Ref : Arterioscler Thromb Vasc Biol , 27 :197 , 2007
Abstract : OBJECTIVE: Overexpression of lipoprotein lipase (LPL) in deendothelialized artery led to profound localized lipid deposition. In this study the role of LPL in atherogenesis in endothelial-intact carotid arteries was assessed in genetically hyperlipidemic LPL- and ApoE-deficient mice. METHODS AND RESULTS: Human wild-type LPL (hLPLwt), catalytically inactive LPL (hLPL194), or control alkaline phosphatase (hAP) were expressed in endothelial-intact carotid arteries via adenoviral vectors. Compared with Ad-hAP, lipid deposition in the arterial wall increased 10.0- and 5.1-fold for Ad-hLPLwt and Ad-hLPL194 in LPL-deficient mice, and 10.6- and 6.2-fold in ApoE-deficient mice, respectively. Vascular cell adhesion molecule-1 (VCAM-1) was upregulated in Ad-hLPLwt and Ad-hLPL194 transferred arteries. CONCLUSIONS: Endothelial cell associated LPL, either active or inactive, in the arterial wall is a strong proatherosclerotic factor in both LPL- and ApoE-deficient mice.
ESTHER : Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
PubMedSearch : Wang_2007_Arterioscler.Thromb.Vasc.Biol_27_197
PubMedID: 17038632

Title : The genome of black cottonwood, Populus trichocarpa (Torr. &\; Gray) - Tuskan_2006_Science_313_1596
Author(s) : Tuskan GA , Difazio S , Jansson S , Bohlmann J , Grigoriev I , Hellsten U , Putnam N , Ralph S , Rombauts S , Salamov A , Schein J , Sterck L , Aerts A , Bhalerao RR , Bhalerao RP , Blaudez D , Boerjan W , Brun A , Brunner A , Busov V , Campbell M , Carlson J , Chalot M , Chapman J , Chen GL , Cooper D , Coutinho PM , Couturier J , Covert S , Cronk Q , Cunningham R , Davis J , Degroeve S , Dejardin A , dePamphilis C , Detter J , Dirks B , Dubchak I , Duplessis S , Ehlting J , Ellis B , Gendler K , Goodstein D , Gribskov M , Grimwood J , Groover A , Gunter L , Hamberger B , Heinze B , Helariutta Y , Henrissat B , Holligan D , Holt R , Huang W , Islam-Faridi N , Jones S , Jones-Rhoades M , Jorgensen R , Joshi C , Kangasjarvi J , Karlsson J , Kelleher C , Kirkpatrick R , Kirst M , Kohler A , Kalluri U , Larimer F , Leebens-Mack J , Leple JC , Locascio P , Lou Y , Lucas S , Martin F , Montanini B , Napoli C , Nelson DR , Nelson C , Nieminen K , Nilsson O , Pereda V , Peter G , Philippe R , Pilate G , Poliakov A , Razumovskaya J , Richardson P , Rinaldi C , Ritland K , Rouze P , Ryaboy D , Schmutz J , Schrader J , Segerman B , Shin H , Siddiqui A , Sterky F , Terry A , Tsai CJ , Uberbacher E , Unneberg P , Vahala J , Wall K , Wessler S , Yang G , Yin T , Douglas C , Marra M , Sandberg G , Van de Peer Y , Rokhsar D
Ref : Science , 313 :1596 , 2006
Abstract : We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport.
ESTHER : Tuskan_2006_Science_313_1596
PubMedSearch : Tuskan_2006_Science_313_1596
PubMedID: 16973872
Gene_locus related to this paper: burvg-a4jw31 , delas-a9c1v9 , poptr-a9pfp5 , poptr-a9ph43 , poptr-a9ph71 , poptr-a9pha7 , poptr-b9giq0 , poptr-b9gjs0 , poptr-b9gl72 , poptr-b9gmx8 , poptr-b9gnp9 , poptr-b9gny4 , poptr-b9grg2 , poptr-b9gsc2 , poptr-b9gvp3 , poptr-b9gvs3 , poptr-b9gwn9 , poptr-b9gy32 , poptr-b9gyq1 , poptr-b9gys8 , poptr-b9h0h0 , poptr-b9h4j2 , poptr-b9h6c2 , poptr-b9h6c5 , poptr-b9h6l8 , poptr-b9h8c9 , poptr-b9h301 , poptr-b9h579 , poptr-b9hbl2 , poptr-b9hbw5 , poptr-b9hcn9 , poptr-b9hee0 , poptr-b9hee2 , poptr-b9hee5 , poptr-b9hee6 , poptr-b9hef3 , poptr-b9hfa7 , poptr-b9hfd3 , poptr-b9hfi6 , poptr-b9hft8 , poptr-b9hg83 , poptr-b9hif5 , poptr-b9hll5 , poptr-b9hmd0 , poptr-b9hnv3 , poptr-b9hqr6 , poptr-b9hqr7 , poptr-b9hrv7 , poptr-b9hs66 , poptr-b9huf0 , poptr-b9hur3 , poptr-b9hux1 , poptr-b9hwp2 , poptr-b9hxr7 , poptr-b9hyk8 , poptr-b9hyx2 , poptr-b9i2q8 , poptr-b9i5b8 , poptr-b9i5j8 , poptr-b9i5j9 , poptr-b9i5k0 , poptr-b9i6b6 , poptr-b9i7b7 , poptr-b9i9p8 , poptr-b9i484 , poptr-b9i994 , poptr-b9ial3 , poptr-b9ial4 , poptr-b9ib28 , poptr-b9ibr8 , poptr-b9id97 , poptr-b9idr4 , poptr-b9iid9 , poptr-b9iip0 , poptr-b9ik80 , poptr-b9ik90 , poptr-b9il63 , poptr-b9ink7 , poptr-b9iqa0 , poptr-b9iqd5 , poptr-b9mwf1 , poptr-b9mwi8 , poptr-b9n0c6 , poptr-b9n0n1 , poptr-b9n0n4 , poptr-b9n0z5 , poptr-b9n1t8 , poptr-b9n1z3 , poptr-b9n3m7 , poptr-b9n233 , poptr-b9n236 , poptr-b9n395 , poptr-b9nd33 , poptr-b9nd34 , poptr-b9ndi6 , poptr-b9ndj5 , poptr-b9p9i8 , poptr-a9pfa7 , poptr-b9hdp2 , poptr-b9inj0 , poptr-b9n5g7 , poptr-b9i8q4 , poptr-u5g0r4 , poptr-u5gf59 , poptr-u7e1l9 , poptr-b9hj61 , poptr-b9hwd0 , poptr-u5fz17 , poptr-a0a2k2brq1 , poptr-a0a2k2b9i6 , poptr-a0a2k1x9y8 , poptr-a9pch4 , poptr-a0a2k1wwt1 , poptr-a0a2k1wv10 , poptr-a0a2k2a850 , poptr-a0a2k2asj6 , poptr-a0a2k1x6k1 , poptr-u5fv96 , poptr-a0a2k2blg2 , poptr-a0a2k1xpi3 , poptr-a0a2k1xpj0 , poptr-a0a2k2b331 , poptr-a0a2k2byl7 , poptr-b9iek5 , poptr-a9pfg4 , poptr-a0a2k1xzs5 , poptr-b9gga9 , poptr-b9guw6 , poptr-b9hff2

Title : The DNA sequence, annotation and analysis of human chromosome 3 - Muzny_2006_Nature_440_1194
Author(s) : Muzny DM , Scherer SE , Kaul R , Wang J , Yu J , Sudbrak R , Buhay CJ , Chen R , Cree A , Ding Y , Dugan-Rocha S , Gill R , Gunaratne P , Harris RA , Hawes AC , Hernandez J , Hodgson AV , Hume J , Jackson A , Khan ZM , Kovar-Smith C , Lewis LR , Lozado RJ , Metzker ML , Milosavljevic A , Miner GR , Morgan MB , Nazareth LV , Scott G , Sodergren E , Song XZ , Steffen D , Wei S , Wheeler DA , Wright MW , Worley KC , Yuan Y , Zhang Z , Adams CQ , Ansari-Lari MA , Ayele M , Brown MJ , Chen G , Chen Z , Clendenning J , Clerc-Blankenburg KP , Davis C , Delgado O , Dinh HH , Dong W , Draper H , Ernst S , Fu G , Gonzalez-Garay ML , Garcia DK , Gillett W , Gu J , Hao B , Haugen E , Havlak P , He X , Hennig S , Hu S , Huang W , Jackson LR , Jacob LS , Kelly SH , Kube M , Levy R , Li Z , Liu B , Liu J , Liu W , Lu J , Maheshwari M , Nguyen BV , Okwuonu GO , Palmeiri A , Pasternak S , Perez LM , Phelps KA , Plopper FJ , Qiang B , Raymond C , Rodriguez R , Saenphimmachak C , Santibanez J , Shen H , Shen Y , Subramanian S , Tabor PE , Verduzco D , Waldron L , Wang Q , Williams GA , Wong GK , Yao Z , Zhang J , Zhang X , Zhao G , Zhou J , Zhou Y , Nelson D , Lehrach H , Reinhardt R , Naylor SL , Yang H , Olson M , Weinstock G , Gibbs RA
Ref : Nature , 440 :1194 , 2006
Abstract : After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.
ESTHER : Muzny_2006_Nature_440_1194
PubMedSearch : Muzny_2006_Nature_440_1194
PubMedID: 16641997
Gene_locus related to this paper: human-AADAC , human-AADACL2 , human-ABHD5 , human-ABHD6 , human-ABHD10 , human-ABHD14A , human-APEH , human-BCHE , human-CIB , human-LIPH , human-MGLL , human-NLGN1 , human-PLA1A

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

Title : Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia - Zhao_2006_Biochem.Biophys.Res.Commun_341_1066
Author(s) : Zhao T , Guo J , Li H , Huang W , Xian X , Ross CJ , Hayden MR , Wen Z , Liu G
Ref : Biochemical & Biophysical Research Communications , 341 :1066 , 2006
Abstract : Severe hypertriglyceridemia (HTG) is a metabolic disturbance often seen in clinical practice. It is known to induce life-threatening acute pancreatitis, but its role in atherogenesis remains elusive. Hemorheological abnormality was thought to play an important role in pathogenesis of both pancreatitis and atherosclerosis. However, hemorheology in severe HTG was not well investigated. Recently, we established a severe HTG mouse model deficient in lipoprotein lipase (LPL) in which severe HTG was observed to cause a significant increase in plasma viscosity. Disturbances of erythrocytes were also documented, including decreased deformability, electrophoresis rate, and membrane fluidity, and increased osmotic fragility. Scanning electron microscopy demonstrated that most erythrocytes of LPL deficient mice deformed with protrusions, irregular appearances or indistinct concaves. Analysis of erythrocyte membrane lipids showed decreased cholesterol (Ch) and phospholipid (PL) contents but unaltered Ch/PL ratio. The changes of membrane lipids may be partially responsible for the hemorheological and morphologic abnormalities of erythrocytes. This study indicated that severe HTG could lead to significant impairment of hemorheology and this model may be useful in delineating the role of severe HTG in the pathogenesis of hyperlipidemic pancreatitis and atherosclerosis.
ESTHER : Zhao_2006_Biochem.Biophys.Res.Commun_341_1066
PubMedSearch : Zhao_2006_Biochem.Biophys.Res.Commun_341_1066
PubMedID: 16460682

Title : Acetylcholinesterase expression mediated by c-Jun-NH2-terminal kinase pathway during anticancer drug-induced apoptosis - Deng_2006_Oncogene_25_7070
Author(s) : Deng R , Li W , Guan Z , Zhou JM , Wang Y , Mei YP , Li MT , Feng GK , Huang W , Liu ZC , Han Y , Zeng YX , Zhu XF
Ref : Oncogene , 25 :7070 , 2006
Abstract : It has been shown that acetylcholinesterase (AChE) expression was induced during apoptosis and the anti-sense oligonucleotides and siRNA of AChE may prevent apoptosis in various cell types. However, the mechanisms underlying AChE upregulation remain elusive. We demonstrated here that c-Jun NH2-terminal kinase (JNK) could mediate AChE expression. In this study, both etoposide and excisanin A, two anticancer agents, induced apoptosis in colon cancer cell line SW620 as determined by Annexin V staining, the cleavage of caspase-3 and the proteolytic degradation of poly (ADP-ribose) polymerase (PARP). The results showed that both the agents upregulated AChE in SW620 cells. In the meantime, JNK was also activated and the expression and phosphorylation of c-Jun increased in SW620 cells exposed to the two agents. The induced AChE mRNA and protein expression could be blocked by SP600125, a specific inhibitor of SAPK/JNK, and small interfering RNA directed against JNK1/2. Transfection with adenovirus-mediated dominant negative c-Jun also blocked the upregulation of AChE expression. Together, these results suggest that AChE expression may be mediated by the activation of JNK pathway during apoptosis through a c-Jun-dependent mechanism.
ESTHER : Deng_2006_Oncogene_25_7070
PubMedSearch : Deng_2006_Oncogene_25_7070
PubMedID: 16715131

Title : Phytophthora genome sequences uncover evolutionary origins and mechanisms of pathogenesis - Tyler_2006_Science_313_1261
Author(s) : Tyler BM , Tripathy S , Zhang X , Dehal P , Jiang RH , Aerts A , Arredondo FD , Baxter L , Bensasson D , Beynon JL , Chapman J , Damasceno CM , Dorrance AE , Dou D , Dickerman AW , Dubchak IL , Garbelotto M , Gijzen M , Gordon SG , Govers F , Grunwald NJ , Huang W , Ivors KL , Jones RW , Kamoun S , Krampis K , Lamour KH , Lee MK , McDonald WH , Medina M , Meijer HJ , Nordberg EK , Maclean DJ , Ospina-Giraldo MD , Morris PF , Phuntumart V , Putnam NH , Rash S , Rose JK , Sakihama Y , Salamov AA , Savidor A , Scheuring CF , Smith BM , Sobral BW , Terry A , Torto-Alalibo TA , Win J , Xu Z , Zhang H , Grigoriev IV , Rokhsar DS , Boore JL
Ref : Science , 313 :1261 , 2006
Abstract : Draft genome sequences have been determined for the soybean pathogen Phytophthora sojae and the sudden oak death pathogen Phytophthora ramorum. Oomycetes such as these Phytophthora species share the kingdom Stramenopila with photosynthetic algae such as diatoms, and the presence of many Phytophthora genes of probable phototroph origin supports a photosynthetic ancestry for the stramenopiles. Comparison of the two species' genomes reveals a rapid expansion and diversification of many protein families associated with plant infection such as hydrolases, ABC transporters, protein toxins, proteinase inhibitors, and, in particular, a superfamily of 700 proteins with similarity to known oomycete avirulence genes.
ESTHER : Tyler_2006_Science_313_1261
PubMedSearch : Tyler_2006_Science_313_1261
PubMedID: 16946064
Gene_locus related to this paper: phyrm-h3ga89 , phyrm-h3gbl6.1 , phyrm-h3gbl6.2 , phyrm-h3gbl7 , phyrm-h3gdd4 , phyrm-h3gl36 , phyrm-h3gq42 , phyrm-h3gx86 , phyrm-h3gyi2 , phyrm-h3gyi3 , phyrm-h3gyi4 , phyrm-h3h292 , phyrm-h3h293 , phyrm-h3h967 , phyrm-h3hcf9 , physp-g4ynp3 , physp-g4yut6 , physp-g4yut8 , physp-g4yw23 , physp-g4zis3 , physp-g4zqe3 , physp-g4zqe4 , physp-g4zqf0 , physp-g4zqn9 , physp-g4zwy9 , physp-g5a582 , physp-g5a583 , physp-g5aav9 , phyrm-h3g9e7 , physp-g4zwu9 , phyrm-h3ggp1 , physp-g4ztq5 , physp-g4zwu8 , physp-g4zwv7 , physp-g4zwv6 , physp-g4zwv0 , physp-g4zwv8 , phyrm-h3gp95 , phyrm-h3g6r5 , physp-g4zwv9 , physp-g5a510 , phyrm-h3glu3 , physp-g5aci1 , phyrm-h3h2d0 , physp-g4ztb2 , physp-g4yg47 , phyrm-h3h2c9 , physp-g4ztb3 , phyrm-h3gvj3 , phyrm-h3gy62 , physp-g4yg46 , physp-g4zdt9 , phyrm-h3gdh5 , physp-g4zm41 , physp-g5abj7 , phyrm-h3gz76 , physp-g5a425 , phyrm-h3h080 , physp-g4ytv0 , phyrm-h3gcw7

Title : The DNA sequence and biology of human chromosome 19 - Grimwood_2004_Nature_428_529
Author(s) : Grimwood J , Gordon LA , Olsen A , Terry A , Schmutz J , Lamerdin J , Hellsten U , Goodstein D , Couronne O , Tran-Gyamfi M , Aerts A , Altherr M , Ashworth L , Bajorek E , Black S , Branscomb E , Caenepeel S , Carrano A , Caoile C , Chan YM , Christensen M , Cleland CA , Copeland A , Dalin E , Dehal P , Denys M , Detter JC , Escobar J , Flowers D , Fotopulos D , Garcia C , Georgescu AM , Glavina T , Gomez M , Gonzales E , Groza M , Hammon N , Hawkins T , Haydu L , Ho I , Huang W , Israni S , Jett J , Kadner K , Kimball H , Kobayashi A , Larionov V , Leem SH , Lopez F , Lou Y , Lowry S , Malfatti S , Martinez D , McCready P , Medina C , Morgan J , Nelson K , Nolan M , Ovcharenko I , Pitluck S , Pollard M , Popkie AP , Predki P , Quan G , Ramirez L , Rash S , Retterer J , Rodriguez A , Rogers S , Salamov A , Salazar A , She X , Smith D , Slezak T , Solovyev V , Thayer N , Tice H , Tsai M , Ustaszewska A , Vo N , Wagner M , Wheeler J , Wu K , Xie G , Yang J , Dubchak I , Furey TS , DeJong P , Dickson M , Gordon D , Eichler EE , Pennacchio LA , Richardson P , Stubbs L , Rokhsar DS , Myers RM , Rubin EM , Lucas SM
Ref : Nature , 428 :529 , 2004
Abstract : Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.
ESTHER : Grimwood_2004_Nature_428_529
PubMedSearch : Grimwood_2004_Nature_428_529
PubMedID: 15057824

Title : The sequence and analysis of duplication-rich human chromosome 16 - Martin_2004_Nature_432_988
Author(s) : Martin J , Han C , Gordon LA , Terry A , Prabhakar S , She X , Xie G , Hellsten U , Chan YM , Altherr M , Couronne O , Aerts A , Bajorek E , Black S , Blumer H , Branscomb E , Brown NC , Bruno WJ , Buckingham JM , Callen DF , Campbell CS , Campbell ML , Campbell EW , Caoile C , Challacombe JF , Chasteen LA , Chertkov O , Chi HC , Christensen M , Clark LM , Cohn JD , Denys M , Detter JC , Dickson M , Dimitrijevic-Bussod M , Escobar J , Fawcett JJ , Flowers D , Fotopulos D , Glavina T , Gomez M , Gonzales E , Goodstein D , Goodwin LA , Grady DL , Grigoriev I , Groza M , Hammon N , Hawkins T , Haydu L , Hildebrand CE , Huang W , Israni S , Jett J , Jewett PB , Kadner K , Kimball H , Kobayashi A , Krawczyk MC , Leyba T , Longmire JL , Lopez F , Lou Y , Lowry S , Ludeman T , Manohar CF , Mark GA , McMurray KL , Meincke LJ , Morgan J , Moyzis RK , Mundt MO , Munk AC , Nandkeshwar RD , Pitluck S , Pollard M , Predki P , Parson-Quintana B , Ramirez L , Rash S , Retterer J , Ricke DO , Robinson DL , Rodriguez A , Salamov A , Saunders EH , Scott D , Shough T , Stallings RL , Stalvey M , Sutherland RD , Tapia R , Tesmer JG , Thayer N , Thompson LS , Tice H , Torney DC , Tran-Gyamfi M , Tsai M , Ulanovsky LE , Ustaszewska A , Vo N , White PS , Williams AL , Wills PL , Wu JR , Wu K , Yang J , DeJong P , Bruce D , Doggett NA , Deaven L , Schmutz J , Grimwood J , Richardson P , Rokhsar DS , Eichler EE , Gilna P , Lucas SM , Myers RM , Rubin EM , Pennacchio LA
Ref : Nature , 432 :988 , 2004
Abstract : Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.
ESTHER : Martin_2004_Nature_432_988
PubMedSearch : Martin_2004_Nature_432_988
PubMedID: 15616553
Gene_locus related to this paper: human-CES1 , human-CES2 , human-CES3 , human-CES4A , human-CES5A

Title : Cloning of an alkaline lipase gene from Penicillium cyclopium and its expression in Escherichia coli - Wu_2003_Lipids_38_191
Author(s) : Wu M , Qian Z , Jiang P , Min T , Sun C , Huang W
Ref : Lipids , 38 :191 , 2003
Abstract : The gene encoding an alkaline lipase of Penicillium cyclopium PG37 was cloned with four steps of PCR amplification based on different principles. The cloned gene was 1,480 nucleotides in length, consisted of 94 bp of promoter region, and had 6 exons and 5 short introns ranging from 50 to 70 nucleotides. The open reading frame encoded a protein of 285 amino acid residues consisting of a 27-AA signal peptide and a 258-AA mature peptide, with a conserved motif of Gly-X-Ser-X-Gly shared by all types of alkaline lipases. However, this protein had a low homology with lipases of P. camembertii (22.9%), Humicola lanuginosa (25.6%), and Rhizomucor miehei (22.3%) at the amino acid level. The mature peptide-encoding cDNA was cloned and expressed in Escherichia coli on pET-30a for confirmation. A distinct band with a M.W. of 33 kDa was detected on SDS-PAGE. Results of a Western blot analysis and an enzyme activity assay verified the recombinant 33-kDa protein as an alkaline lipase. Its catalytic properties were not changed when compared with its natural counterpart.
ESTHER : Wu_2003_Lipids_38_191
PubMedSearch : Wu_2003_Lipids_38_191
PubMedID: 12784858
Gene_locus related to this paper: penex-Q9HFW6

Title : Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients - Christodoulou_2003_Neurology_60_1793
Author(s) : Christodoulou C , Krupp LB , Liang Z , Huang W , Melville P , Roque C , Scherl WF , Morgan T , MacAllister WS , Li L , Tudorica LA , Li X , Roche P , Peyster R
Ref : Neurology , 60 :1793 , 2003
Abstract : OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment.
METHODS: Participants were 37 individuals with relapsing-remitting (59.5%) and secondary progressive (40.5%) MS. They were tested at baseline as part of a clinical trial to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria included at least mild cognitive impairment on a verbal learning and memory task. A modified Brief Repeatable Battery of Neuropsychological Tests formed the core of the behavioral protocol. Neuroimaging measures were central (ventricular) cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both creatine and choline.
RESULTS: A clear, consistent relation was found between cognitive and MR measures. Among neuroimaging measures, central atrophy displayed the highest correlations with cognition, accounting for approximately half the variance in overall cognitive performance. NAA ratios in right hemisphere sites displayed larger correlations than those on the left. Multiple regression models combining the MR measures accounted for well over half the variance in overall cognitive performance. The Symbol Digit Modalities Test was the neuropsychological task most strongly associated with the neuroimaging variables.
CONCLUSIONS: If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease.
ESTHER : Christodoulou_2003_Neurology_60_1793
PubMedSearch : Christodoulou_2003_Neurology_60_1793
PubMedID: 12796533

Title : The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins - Dehal_2002_Science_298_2157
Author(s) : Dehal P , Satou Y , Campbell RK , Chapman J , Degnan B , De Tomaso A , Davidson B , Di Gregorio A , Gelpke M , Goodstein DM , Harafuji N , Hastings KE , Ho I , Hotta K , Huang W , Kawashima T , Lemaire P , Martinez D , Meinertzhagen IA , Necula S , Nonaka M , Putnam N , Rash S , Saiga H , Satake M , Terry A , Yamada L , Wang HG , Awazu S , Azumi K , Boore J , Branno M , Chin-Bow S , DeSantis R , Doyle S , Francino P , Keys DN , Haga S , Hayashi H , Hino K , Imai KS , Inaba K , Kano S , Kobayashi K , Kobayashi M , Lee BI , Makabe KW , Manohar C , Matassi G , Medina M , Mochizuki Y , Mount S , Morishita T , Miura S , Nakayama A , Nishizaka S , Nomoto H , Ohta F , Oishi K , Rigoutsos I , Sano M , Sasaki A , Sasakura Y , Shoguchi E , Shin-I T , Spagnuolo A , Stainier D , Suzuki MM , Tassy O , Takatori N , Tokuoka M , Yagi K , Yoshizaki F , Wada S , Zhang C , Hyatt PD , Larimer F , Detter C , Doggett N , Glavina T , Hawkins T , Richardson P , Lucas S , Kohara Y , Levine M , Satoh N , Rokhsar DS
Ref : Science , 298 :2157 , 2002
Abstract : The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.
ESTHER : Dehal_2002_Science_298_2157
PubMedSearch : Dehal_2002_Science_298_2157
PubMedID: 12481130
Gene_locus related to this paper: cioin-141645 , cioin-147959 , cioin-150181 , cioin-154370 , cioin-ACHE1 , cioin-ACHE2 , cioin-cxest , cioin-f6qcp0 , cioin-f6r8z1 , cioin-f6u176 , cioin-f6vac9 , cioin-f6x584 , cioin-f6xa69 , cioin-f6y403 , cioin-h2xqb4 , cioin-H2XTI0 , cioin-F6T1M3 , cioin-H2XUP7 , cioin-CIN.7233 , cioin-F6V269 , cioin-Cin16330 , cioin-h2xua2 , cioin-f6vaa5 , cioin-f6v9x6 , cioin-f6swc9 , cioin-f7amz2 , cioin-f6s021 , cioin-h2xxq9 , cioin-h2xne6 , cioin-f6ynr2

Title : Crystal structure of a catalytic antibody with a serine protease active site - Zhou_1994_Science_265_1059
Author(s) : Zhou GW , Guo J , Huang W , Fletterick RJ , Scanlan TS
Ref : Science , 265 :1059 , 1994
Abstract : The three-dimensional structure of an unusually active hydrolytic antibody with a phosphonate transition state analog (hapten) bound to the active site has been solved to 2.5 A resolution. The antibody (17E8) catalyzes the hydrolysis of norleucine and methionine phenyl esters and is selective for amino acid esters that have the natural alpha-carbon L configuration. A plot of the pH-dependence of the antibody-catalyzed reaction is bell-shaped with an activity maximum at pH 9.5; experiments on mechanism lend support to the formation of a covalent acyl-antibody intermediate. The structural and kinetic data are complementary and support a hydrolytic mechanism for the antibody that is remarkably similar to that of the serine proteases. The antibody active site contains a Ser-His dyad structure proximal to the phosphorous atom of the bound hapten that resembles two of the three components of the Ser-His-Asp catalytic triad of serine proteases. The antibody active site also contains a Lys residue to stabilize oxyanion formation, and a hydrophobic binding pocket for specific substrate recognition of norleucine and methionine side chains. The structure identifies active site residues that mediate catalysis and suggests specific mutations that may improve the catalytic efficiency of the antibody. This high resolution structure of a catalytic antibody-hapten complex shows that antibodies can converge on active site structures that have arisen through natural enzyme evolution.
ESTHER : Zhou_1994_Science_265_1059
PubMedSearch : Zhou_1994_Science_265_1059
PubMedID: 8066444