Shen L

References (24)

Title : A new terrein dimer and a new meroterpene from the mangrove endophytic fungus Lichtheimia sp - Ren_2023_J.Asian.Nat.Prod.Res__1
Author(s) : Ren JL , Li CM , Shen L , Wu J
Ref : J Asian Nat Prod Res , :1 , 2023
Abstract : A new terrein dimer named lichtheicol A (1) and a new meroterpene named lichtheiterpene A (2), were isolated from the mangrove endophytic fungus Lichtheimia sp. J2B1, together with 10 known compounds (3-12). The planar structures and absolute configurations of 1 and 2 were established by a combination of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 exhibited marked inhibitory effects against butyrylcholinesterase (BuChE) with IC(50) values of 0.71 and 0.53 microM, respectively.
ESTHER : Ren_2023_J.Asian.Nat.Prod.Res__1
PubMedSearch : Ren_2023_J.Asian.Nat.Prod.Res__1
PubMedID: 37042744

Title : Conjugation of haloalkane dehalogenase DhaA with arabinogalactan to increase its stability - Wang_2021_J.Biotechnol_335_47
Author(s) : Wang M , Yu W , Shen L , Zheng H , Guo X , Zhong J , Hu T
Ref : J Biotechnol , 335 :47 , 2021
Abstract : Haloalkane dehalogenase DhaA can catalyze the hydrolytic cleavage of carbonhalogen bonds, along with production of the corresponding alcohol, a proton and a halide. However, DhaA suffers from poor environmental tolerance, such as sensitivity to high temperature, low pH and hypersaline. Arabinogalactan (AG) is a hydrophilic polysaccharide with highly branched long chains. DhaA was conjugated with AG to improve the environmental stability of DhaA in the present study. Each DhaA was averagely conjugated with 4-5 AG molecules. Conjugation of AG essentially maintained the enzymatic activity of DhaA (91.4 %) without apparent structural alteration. The hydration layer formed by AG could reduce the solvent accessible area of DhaA and slow the protonation process, thereby improving the pH and high salt stability of DhaA. In particular, the remaining activities of the conjugate (AG-DhaA) were 35.3 % after treatment at pH4.0 for 1 h, and 80.8 % in 1 M NaCl after treatment for 16 h. As compared with DhaA, AG-DhaA showed slightly different kinetic parameters (K M of 1.90 micromol/L and k cat of 2.60 s -1).
ESTHER : Wang_2021_J.Biotechnol_335_47
PubMedSearch : Wang_2021_J.Biotechnol_335_47
PubMedID: 34118331

Title : Conjugation with inulin improves the environmental stability of haloalkane dehalogenase DhaA - Shan_2021_Enzyme.Microb.Technol_149_109832
Author(s) : Shan Y , Yu W , Shen L , Guo X , Zheng H , Zhong J , Hu T , Han Y
Ref : Enzyme Microb Technol , 149 :109832 , 2021
Abstract : Haloalkane dehalogenase DhaA catalyzes the hydrolytic cleavage of carbon-halogen bonds and produces alcohol, a proton and a halide. However, DhaA suffers from the poor environmental stability, such as sensitivity to high temperature, low pH, hypersaline and organic solvent. In order to improve the environmental stability of DhaA, DhaA was covalently conjugated with inulin, a hydrophilic polysaccharide in the present study. Each DhaA was averagely conjugated with 7-8 inulin molecules. The conjugated inulin could form a hydration layer around DhaA, which increased the conformational rigidity and decreased the entropy of the enzyme. Conjugation of inulin maintained 75.5 % of the enzymatic activity of DhaA and slightly altered the structure of DhaA. As compared with DhaA, the conjugate (inu-DhaA) showed slightly different kinetic parameters (K(m) of 2.9 micromol/L and K(cat) of 1.0 s(-1)). Inulin conjugation could delay the structural unfolding and/or slow the protonation process of DhaA under undesirable environment, including the long-term storage, low pH, hypersaline and organic solvent stability. As a result, the environmental stability of DhaA was markedly increased upon conjugation with inulin. Thus, inulin conjugation was an effective approach to enhance the environmental stability of DhaA.
ESTHER : Shan_2021_Enzyme.Microb.Technol_149_109832
PubMedSearch : Shan_2021_Enzyme.Microb.Technol_149_109832
PubMedID: 34311877

Title : Multiple transcriptomic profiling: potential novel metabolism-related genes predict prepubertal testis damage caused by DEHP exposure - Kang_2021_Environ.Sci.Pollut.Res.Int__
Author(s) : Kang L , Chen J , Wang J , Zhao T , Wei Y , Wu Y , Han L , Zheng X , Shen L , Long C , Wei G , Wu S
Ref : Environ Sci Pollut Res Int , : , 2021
Abstract : The toxic effect of di(2-ethylhexyl) phthalate (DEHP) on prepubertal testes was examined in this study. We treated 3-week-old male mice with 4.8 mg/kg/day (milligram/kilogram/day) (no observed adverse effect level), 30 mg/kg/day (high exposure dose relative to humans), 100 mg/kg/day (level causing a reproductive system disorder), and 500 mg/kg/day (dose causing a multigenerational reproductive system disorder) of DEHP via gavage. Obvious abnormalities in the testicular organ coefficient, spermatogenic epithelium, and testosterone levels occurred in the 500 mg/kg DEHP group. Ribonucleic acid sequencing (RNA-seq) showed that differentially expressed genes (DEGs) in each group could enrich reproduction and reproductive process terms according to the gene ontology (GO) results, and coenrichment of metabolism pathway was observed by the Reactome pathway analysis. Through the analysis of common genes in the metabolism pathway, we discovered that DEHP exposure at 4.8 to 500 mg/kg or 100 mg/kg caused the same damages to the prepubertal testis. In general, we identified two key transcriptional biomarkers (fatty acid binding protein 3 (Fabp3) and carboxylesterase (Ces) 1d), which provided new insight into the gene regulatory mechanism associated with DEHP exposure and will contribute to the prediction and diagnosis of prepuberty testis injury caused by DEHP.
ESTHER : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedSearch : Kang_2021_Environ.Sci.Pollut.Res.Int__
PubMedID: 34595713

Title : Soluble Epoxide Hydrolase Inhibitors Regulate Ischemic Arrhythmia by Targeting MicroRNA-1 - Chen_2021_Front.Physiol_12_717119
Author(s) : Chen Y , Liu Q , Yang T , Shen L , Xu D
Ref : Front Physiol , 12 :717119 , 2021
Abstract : Background: Soluble epoxide hydrolase inhibitors (sEHis) inhibit the degradation of epoxyeicosatrienoic acids (EETs) in cells, and EETs have antiarrhythmic effects. Our previous experiments confirmed that t-AUCB, a preparation of sEHis, inhibited ischemic arrhythmia by negatively regulating microRNA-1 (miR-1), but its specific mechanism remained unclear. Aim: This study aimed to examine the role of serum response factor (SRF) and the PI3K/Akt/GSK3beta pathway in t-AUCB-mediated regulation of miR-1 and the interaction between them. Methods/Results: We used SRF small interfering RNA (siSRF), SRF small hairpin (shSRF) RNA sequence adenovirus, PI3K/Akt/GSK3beta pathway inhibitors, t-AUCB, and 14,15-EEZE (a preparation of EETs antagonists) to treat mouse cardiomyocytes overexpressing miR-1 and mice with myocardial infarction (MI). We found that silencing SRF attenuated the effects on miR-1 and its target genes KCNJ2 and GJA1 in the presence of t-AUCB, and inhibition of the PI3K/Akt/GSK3beta pathway antagonized the effects of t-AUCB on miR-1, KCNJ2, and GJA1, which were associated with PI3Kalpha, Akt, and Gsk3beta but not PI3Kbeta or PI3Kgamma. Moreover, the PI3K/Akt/GSK3beta pathway was involved in the regulation of SRF by t-AUCB, and silencing SRF inhibited the t-AUCB-induced increases in Akt and Gsk3beta phosphorylation. Conclusions: Both the SRF and the PI3K/Akt/GSK3beta pathway are involved in the t-AUCB-mediated regulation of miR-1, and these factors interact with each other.
ESTHER : Chen_2021_Front.Physiol_12_717119
PubMedSearch : Chen_2021_Front.Physiol_12_717119
PubMedID: 34646152

Title : Brain-targeted delivery of obidoxime, using aptamer-modified liposomes, for detoxification of organophosphorus compounds - Zhang_2021_J.Control.Release_329_1117
Author(s) : Zhang Y , He J , Shen L , Wang T , Yang J , Li Y , Wang Y , Quan D
Ref : J Control Release , 329 :1117 , 2021
Abstract : Effective intracerebral delivery acetylcholinesterase (AChE) reactivator is key for the acute organophosphorus (OPs) poison treatment. However, the blood-brain barrier (BBB) restricts the transport of these drugs from blood into the brain. Herein, we developed transferrin receptor (TfR) aptamer-functionalized liposomes (Apt-LP) that could deliver AChE reactivator (obidoxime) across the BBB to act against paraoxon (POX) poisoning. The aptamer had strong affinity for TfR and was modified with 3'-inverted deoxythymidine (dT) to improve serum stability. The uptake of Apt-LP by bEnd.3 cells was significantly higher than that of non-targeting liposomes. The ability of Apt-LP to penetrate intact BBB was confirmed in in vitro BBB mice model and in vivo biodistribution studies. Treatment of POX-poisoned mice with Apt-LP-LuH-6 reactivated 18% of the brain AChE activity and prevented brain damage to some extent. Taken together, these results showed that Apt-LP may be used as a promising brain-targeted drug delivery system against OPs toxicity.
ESTHER : Zhang_2021_J.Control.Release_329_1117
PubMedSearch : Zhang_2021_J.Control.Release_329_1117
PubMedID: 33096123

Title : Discovery of Thai mangrove tetranortriterpenoids as agonists of human pregnane-X-receptor and inhibitors against human carboxylesterase 2 - Ren_2020_Bioorg.Chem_107_104599
Author(s) : Ren YX , Zou XP , Li WS , Wu J , Shen L
Ref : Bioorg Chem , 107 :104599 , 2020
Abstract : Human pregnane-X-receptor (hPXR) is considered to be the key target for the treatment of cholestasis and liver injury. Agonists of hPXR are potential drug leads. Potent and selective inhibitors of human carboxylesterase 2 (hCES2) could be utilized to alleviate the toxicity induced by ester drugs. In this work, fifteen new tetranortriterpenoids with structure diversity, named thaigranatins F-T (1-15), including four limonoids containing a C(1)-O-C(29) bridge (1-4), four mexicanolides (5-8), three phragmalins (9-11), two limonoids belonging to the small group of trichiliton A (12-13), and two apotirucallanes (14-15), were isolated from seeds of the Thai mangrove, Xylocarpus granatum. The structures of these compounds were established by high resolution-electrospray ionization mass spectroscopy, extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism spectra. Most notably, thaigranatins L (7) and P (11) exhibited agonistic effects on hPXR at the concentration of 10.0 microM and 10.0 nM, respectively, whereas thaigranatins J (5), M (8), and T (15) showed inhibitory activities against hCES2 with IC(50) values of 6.63, 11.35, and 5.05 microM, respectively. The 8alpha,30alpha-epoxy moiety of mexicanolide and the delta(8,14) double bond of phragmalin are pivotal for agonistic effects of these limonoids on hPXR, whereas the 6-OAc group of mexicanolide is crucial for its inhibitory activity against hCES2. Additionally, the flexible C-17-side-chain with appropriate hydroxy groups is considered to be important for the inhibitory activity of apotirucallane against hCES2.
ESTHER : Ren_2020_Bioorg.Chem_107_104599
PubMedSearch : Ren_2020_Bioorg.Chem_107_104599
PubMedID: 33421954

Title : Lipase Elevation in Patients With COVID-19 - McNabb-Baltar_2020_Am.J.Gastroenterol__
Author(s) : McNabb-Baltar J , Jin DX , Grover AS , Redd WD , Zhou JC , Hathorn KE , McCarty TR , Bazarbashi AN , Shen L , Chan WW
Ref : Am J Gastroenterol , : , 2020
Abstract : INTRODUCTION: Although coronavirus disease (COVID-19) has been associated with gastrointestinal manifestations, its effect on the pancreas remains unclear. We aimed to assess the frequency and characteristics of hyperlipasemia in patients with COVID-19. METHODS: A retrospective cohort study of hospitalized patients across 6 US centers with COVID-19. RESULTS: Of 71 patients, 9 (12.1%) developed hyperlipasemia, with 2 (2.8%) greater than 3 times upper limit of normal. No patient developed acute pancreatitis. Hyperlipasemia was not associated with poor outcomes or symptoms. DISCUSSION: Although a mild elevation in serum lipase was observed in some patients with COVID-19, clinical acute pancreatitis was not seen.
ESTHER : McNabb-Baltar_2020_Am.J.Gastroenterol__
PubMedSearch : McNabb-Baltar_2020_Am.J.Gastroenterol__
PubMedID: 32496339

Title : Limonoids with diverse structures of rings-A,B from the Thai mangrove, Xylocarpus moluccensis - Shen_2020_Fitoterapia__104737
Author(s) : Shen L , Liao Q , Zhang M , Wu J
Ref : Fitoterapia , :104737 , 2020
Abstract : Nine new limonoids, named thaixylomolins S-Z (1-8) and 2-O-acetylthaixylomolin Z (9), were isolated from seeds of the mangrove, Xylocarpus moluccensis, collected in the mangrove swamp of Trang Province, Thailand. Thaixylomolin S (1) is the fourth member of the khayalactone class of limonoids containing a hexahydro-2H-2,5- propanocyclopenta[b]furan motif. Thaixylomolins T-Y (2-7) are structurally diverse mexicanolides; whereas thaixylomolin Z (8) and 2-O-acetylthaixylomolin Z (9) are phragmalin 8,9,30-orthoesters. The structures of these compounds were established by HRESIMS and extensive 1D and 2D NMR investigations. The absolute configurations of thaixylomolins S (1), U (3), and Z (8) were unambiguously established by single-crystal X-ray diffraction analyses, conducted with Cu Kalpha radiation; whereas that of 2-O-acetylthaixylomolin Z (9) was determined to be the same as that of thaixylomolin Z (8) by the accurate fit of their experimental electronic circular dichroism spectra. Thaixylomolin S (1), featuring the presence of a 30-(2'-methyl)butyryloxy group, is the first limonoid of the khayalactone class, whose constitution and absolute configuration are unequivocally determined by X-ray crystallography. The inhibitory activities of all the compounds, except for the epimers 4, were assayed against human carboxylesterase 2. All the tested compounds exhibited inhibition rates in the range of 16-65% at the concentration of 100.0muM.
ESTHER : Shen_2020_Fitoterapia__104737
PubMedSearch : Shen_2020_Fitoterapia__104737
PubMedID: 33022332

Title : Twenty-five limonoids from the Hainan mangrove, Xylocarpus granatum - Zhang_2020_Bioorg.Chem_100_103903
Author(s) : Zhang JC , Liao Q , Shen L , Wu J
Ref : Bioorg Chem , 100 :103903 , 2020
Abstract : Twenty-four new limonoids (1-24), named hainanxylogranins A-X, were isolated from leaves and barks of the Hainan mangrove, Xylocarpus granatum, together with a known compound, tabulvelutin B (25). The structures of these compounds were established by high resolution electrospray ionization mass spectroscopy (HRESIMS), extensive NMR spectroscopic investigations, single-crystal X-ray diffraction analyses, and the comparison of experimental electronic circular dichroism (ECD) spectra. Most notably, the absolute configurations of seven compounds, viz., 1, 2, 6, 16, 17, 22, and 25, were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kalpha radiation. Compounds 1-4 belong to a unique group of mexicanolides containing a C3-O-C8 bridge and a C-17 substituted gamma(21)-hydroxybutenolide moiety, whereas 5-9 are mexicanolides comprising a C1-O-C8 bridge. Compounds 10-16 are typical mexicanolides, among which 14 and 15 contain a C-17 substituted gamma(23)-hydroxybutenolide moiety. Compounds 17 and 18 are phragmalin 8,9,30-orthoesters, whereas 19 and 20 are phragmalin 1,8,9-orthoesters. Compound 21 consists of a C1-O-C29 bridge, while 22-24 are derivatives of azadirone. The inhibitory activities of 1, 5-8, 11, 17, 19, 21-23, and 25 against human carboxylesterase 2 (CES2) were assayed. All the tested compounds exhibited inhibition rates of 30-64% at the concentration of 100.0 microM.
ESTHER : Zhang_2020_Bioorg.Chem_100_103903
PubMedSearch : Zhang_2020_Bioorg.Chem_100_103903
PubMedID: 32413629

Title : Left Atrial Appendage Thrombus Formation in a Patient on Dabigatran Therapy Associated With ABCB1 and CES-1 Genetic Defect - Gu_2018_Front.Pharmacol_9_491
Author(s) : Gu ZC , Ma XW , Zheng XY , Shen L , Shi FH , Li H
Ref : Front Pharmacol , 9 :491 , 2018
Abstract : Dabigatran, directly targeting thrombin, is widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF). We reported a rare case of left atrial appendage thrombus formation in a persistent NVAF patient despite the 31 months uninterrupted treatment with dabigatran 110 mg twice daily. The patient is a carrier of ABCB1 variant alleles with 7 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167) as well as CES-1 variant alleles with 2 homozygote SNPs (rs2244613 and rs4122238) and 2 heterozygote SNPs (rs8192935 and rs4580160), which may contribute to the changes of dabigatran plasma concentration. In addition, Drug-drug interaction with atorvastatin may also play a role to decrease dabigatran plasma concentration. There are only four such cases till date, of which had thrombus in the left atrium, reported in the literature. We firstly reported the documented case in a Chinese patient carrying multiple alleles of ABCB1 and CES-1, who suffered from thrombus in the left atrial appendage despite long-term anticoagulation with dabigatran. More clinical data are required to elucidate the impact of CES-1 and ABCB1 polymorphism on dabigatran pharmacokinetics, especially for Asian.
ESTHER : Gu_2018_Front.Pharmacol_9_491
PubMedSearch : Gu_2018_Front.Pharmacol_9_491
PubMedID: 29867495

Title : Brain explorer for connectomic analysis - Li_2017_Brain.Inform_4_253
Author(s) : Li H , Fang S , Contreras JA , West JD , Risacher SL , Wang Y , Sporns O , Saykin AJ , Goni J , Shen L
Ref : Brain Inform , 4 :253 , 2017
Abstract : Visualization plays a vital role in the analysis of multimodal neuroimaging data. A major challenge in neuroimaging visualization is how to integrate structural, functional, and connectivity data to form a comprehensive visual context for data exploration, quality control, and hypothesis discovery. We develop a new integrated visualization solution for brain imaging data by combining scientific and information visualization techniques within the context of the same anatomical structure. In this paper, new surface texture techniques are developed to map non-spatial attributes onto both 3D brain surfaces and a planar volume map which is generated by the proposed volume rendering technique, spherical volume rendering. Two types of non-spatial information are represented: (1) time series data from resting-state functional MRI measuring brain activation; (2) network properties derived from structural connectivity data for different groups of subjects, which may help guide the detection of differentiation features. Through visual exploration, this integrated solution can help identify brain regions with highly correlated functional activations as well as their activation patterns. Visual detection of differentiation features can also potentially discover image-based phenotypic biomarkers for brain diseases.
ESTHER : Li_2017_Brain.Inform_4_253
PubMedSearch : Li_2017_Brain.Inform_4_253
PubMedID: 28836134

Title : Suppressive subtractive hybridization reveals different gene expression between high and low virulence strains of Cladosporium cladosporioides - Gu_2016_Microb.Pathog_100_276
Author(s) : Gu Y , Liu Y , Cao S , Huang X , Zuo Z , Yu S , Deng J , Ding C , Yuan M , Shen L , Wu R , Wen Y , Ren Z , Zhao Q , Peng G , Zhong Z , Wang C , Ma X
Ref : Microb Pathog , 100 :276 , 2016
Abstract : Cladosporium cladosporioides is a ubiquitous fungus, causing infections in plants, humans, and animals. Suppression subtractive hybridization (SSH) and quantitative real-time PCR (qRT-PCR) were used in this study to identify differences in gene expression between two C. cladosporioides strains, the highly virulent Z20 strain and the lowly virulent Zt strain. A total of 61 unigenes from the forward library and 42 from the reverse library were identified. Gene ontology (GO) analysis showed that these genes were involved in various biological processes, cellular components and molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the unigenes in the forward library corresponded to 5 different pathways and the reverse library unigenes were involved in 3 different pathways. The qRT-PCR results indicated that expressions of APL1, GUD1, CSE1, SPBC3E7.04c and MFS were significantly different between Z20 and Zt strains, while genes encoding the senescence-associated proteins, pse1, nup107, mip1, pex2, icl1 and alpha/beta hydrolase exhibited no significant differences between the two strains. In addition, we found that 5 unigenes encoding mip1, chk1, icl1, alpha/beta hydrolase and beta-glucosidase may be associated with pathogenicity. One unigene (MFS) may be related to the resistance to 14 alpha-demethylase inhibitor fungicides, and 5 unigenes (PEX2, NUP107, PSE1, APL1, and SPBC3E7.04c) may be related to either low spore yield or earlier aging of the Zt strain. Our study may help better understand the molecular mechanism of C. cladosporioides infection, and therefore improve the treatment and prevention of C. cladosporioides induced diseases.
ESTHER : Gu_2016_Microb.Pathog_100_276
PubMedSearch : Gu_2016_Microb.Pathog_100_276
PubMedID: 27744104

Title : Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis - Shen_2015_Atherosclerosis_239_557
Author(s) : Shen L , Peng H , Peng R , Fan Q , Zhao S , Xu D , Morisseau C , Chiamvimonvat N , Hammock BD
Ref : Atherosclerosis , 239 :557 , 2015
Abstract : Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease. The sEH is highly expressed in adipocytes, and it converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids. We previously showed that increasing EETs levels with a sEH inhibitor (sEHI) (t-AUCB) resulted in elevated ABCA1 expression and promoted ABCA1-mediated cholesterol efflux from 3T3-L1 adipocytes. The present study investigates the impacts of t-AUCB in mice deficient for the low density lipoprotein (LDL) receptor (Ldlr(-/-) mice) with established atherosclerotic plaques. The sEH inhibitor delivered in vivo for 4 weeks decreased the activity of sEH in adipose tissue, enhanced ABCA1 expression and cholesterol efflux from adipose depots, and consequently increased HDL levels. Furthermore, t-AUCB enhanced RCT to the plasma, liver, bile and feces. It also showed the reduction of plasma LDL-C levels. Consistently, t-AUCB-treated mice showed reductions in the size of atherosclerotic plaques. These studies establish that raising adipose ABCA1 expression, cholesterol efflux, and plasma HDL levels with t-AUCB treatment promotes RCT, decreasing LDL-C and atherosclerosis regression, suggesting that sEH inhibition may be a promising strategy to treat atherosclerotic vascular disease.
ESTHER : Shen_2015_Atherosclerosis_239_557
PubMedSearch : Shen_2015_Atherosclerosis_239_557
PubMedID: 25733327

Title : APOE and BCHE as modulators of cerebral amyloid deposition: a florbetapir PET genome-wide association study - Ramanan_2014_Mol.Psychiatry_19_351
Author(s) : Ramanan VK , Risacher SL , Nho K , Kim S , Swaminathan S , Shen L , Foroud TM , Hakonarson H , Huentelman MJ , Aisen PS , Petersen RC , Green RC , Jack CR , Koeppe RA , Jagust WJ , Weiner MW , Saykin AJ
Ref : Mol Psychiatry , 19 :351 , 2014
Abstract : Deposition of amyloid-beta (Abeta) in the cerebral cortex is thought to be a pivotal event in Alzheimer's disease (AD) pathogenesis with a significant genetic contribution. Molecular imaging can provide an early noninvasive phenotype, but small samples have prohibited genome-wide association studies (GWAS) of cortical Abeta load until now. We employed florbetapir ((18)F) positron emission tomography (PET) imaging to assess brain Abeta levels in vivo for 555 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). More than six million common genetic variants were tested for association to quantitative global cortical Abeta load controlling for age, gender and diagnosis. Independent genome-wide significant associations were identified on chromosome 19 within APOE (apolipoprotein E) (rs429358, P=5.5 x 10(-14)) and on chromosome 3 upstream of BCHE (butyrylcholinesterase) (rs509208, P=2.7 x 10(-8)) in a region previously associated with serum BCHE activity. Together, these loci explained 15% of the variance in cortical Abeta levels in this sample (APOE 10.7%, BCHE 4.3%). Suggestive associations were identified within ITGA6, near EFNA5, EDIL3, ITGA1, PIK3R1, NFIB and ARID1B, and between NUAK1 and C12orf75. These results confirm the association of APOE with Abeta deposition and represent the largest known effect of BCHE on an AD-related phenotype. BCHE has been found in senile plaques and this new association of genetic variation at the BCHE locus with Abeta burden in humans may have implications for potential disease-modifying effects of BCHE-modulating agents in the AD spectrum.
ESTHER : Ramanan_2014_Mol.Psychiatry_19_351
PubMedSearch : Ramanan_2014_Mol.Psychiatry_19_351
PubMedID: 23419831

Title : Soluble epoxide hydrolase and ischemic cardiomyopathy - Zhao_2012_Int.J.Cardiol_155_181
Author(s) : Zhao TT , Wasti B , Xu DY , Shen L , Du JQ , Zhao SP
Ref : Int J Cardiol , 155 :181 , 2012
Abstract : BACKGROUND: The development of cardiovascular disease has been linked to lowered levels of epoxyeicosatrienoic acids (EETs) in the cardiovascular system. Ischemic cardiomyopathy is caused by atherosclerotic lesions in multi-coronary arteries especially diffusive lesions, which can lead to severe myocardial dysfunction, heart enlargement, heart failure, or arrhythmia, and so on. The EETs are metabolized by the soluble epoxide hydrolase (sEH) encoded by the EPHX2 gene that has several known polymorphisms. CONTENT: The EPHX2 gene polymorphism is associated with sEH catalytic activity and various cardiovascular diseases. sEH is distributed in a variety of organs and tissues and regulated by multiple factors. Research in the area has led to the presence of multiple powerful soluble epoxide hydrolase inhibitors (sEHIs), whose molecular structure and function has been optimized gradually. sEHIs increase EETs' concentration by inhibiting hydration of EETs into their corresponding vicinal diols. EETs are important signaling molecules and known as endothelium-derived hyperpolarizing factors (EDHF). sEHIs have been developed for their ability to prevent atherosclerosis, dilate the coronary artery, promote angiogenesis, ameliorate postischemic recovery of heart contractile function, decrease ischemia/reperfusion injury, modulate postischemic arrhythmia, and prevent heart failure. SUMMARY: sEH is one of the etiological factors of cardiovascular diseases, and plays an important role in the progression of myocardium ischemia. This indicates that sEHIs provide a new method for the prevention and treatment of ischemic cardiomyopathy.
ESTHER : Zhao_2012_Int.J.Cardiol_155_181
PubMedSearch : Zhao_2012_Int.J.Cardiol_155_181
PubMedID: 21704394

Title : [Soluble epoxide hydrolase inhibitor t-AUCB ameliorates ox-LDL induced conversion of macrophages into foam cells through activating the PPARgamma-ABCA1 pathway] - Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
Author(s) : Zhao TT , Peng R , Shen L , Zhao X , Xu DY , Zhao SP
Ref : Zhonghua Xin Xue Guan Bing Za Zhi , 40 :248 , 2012
Abstract : OBJECTIVE: To observe the effects of soluble epoxide hydrolase inhibitor t-AUCB on foam cell formation and cholesterol efflux in macrophage.
METHODS: Mouse macrophages RAW264.7 were cultured and stimulated with ox-LDL (80 micromol/L) in the absence (group A) or presence of t-AUCB (1, 10, 50, 100 micromol/L, group B) or t-AUCB (100 micromol/L) pretreated with PPARgamma antagonist GW9662 (5 micromol/L, group C). The foam cell was identified by oil red O staining. The cholesterol efflux rates of (3)H-cholesterol in cells were measured by liquid scintillation counter. mRNA and protein expressions of ABCA1 were detected by real-time PCR or Western blot, respectively.
RESULTS: Oil red O staining showed that t-AUCB (100 micromol/L) significantly inhibited foam cell formation which could be significantly reversed by GW9662 (all P < 0.05). t-AUCB dose-dependently increased cholesterol efflux rates in mouse macrophage [(5.91 +/- 0.18)% in group A, (7.03 +/- 0.33)%, (8.05 +/- 0.32)%, (9.04 +/- 0.14)%, (10.06 +/- 0.85)% in 1, 10, 50, 100 micromol/L t-AUCB groups, all P < 0.05 vs. group A], which could be reversed by pretreatment with GW9662 [(6.33 +/- 0.15)% in 100 micromol/L t-AUCB + GW9662 group].t-AUCB also upregulated ABCA1 mRNA and protein expressions in a dose-dependent manner which could be significantly attenuated by pretreatment with GW9662. CONCLUSION: t-AUCB could inhibit foam cell formation by improving cholesterol efflux through activating PPARgamma-ABCA1 pathway in macrophage.
ESTHER : Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
PubMedSearch : Zhao_2012_Zhonghua.Xin.Xue.Guan.Bing.Za.Zhi_40_248
PubMedID: 22801272

Title : Molecular basis of inhibitory activities of berberine against pathogenic enzymes in Alzheimer's disease - Ji_2012_ScientificWorldJournal_2012_823201
Author(s) : Ji HF , Shen L
Ref : ScientificWorldJournal , 2012 :823201 , 2012
Abstract : The natural isoquinoline alkaloid berberine possesses potential to treat Alzheimer's disease (AD) by targeting multiple pathogenic factors. In the present study, docking simulations were performed to gain deeper insights into the molecular basis of berberine's inhibitory effects against the important pathogenic enzymes of AD, that is, acetylcholinesterase, butyrylcholinesterase, and two isoforms of monoamine oxidase. It was found that the theoretical binding affinities of berberine to the four enzymes are very close to the experimental values, which verify the methodology. Further inspection to the binding modes found that hydrophobic interactions between the hydrophobic surface of berberine and neighboring hydrophobic residues are the principal forces contributing to the ligand-receptor interactions. Although berberine cation also has potential to form electrostatic interaction with neighboring residues, it is interesting to find that electrostatic force is excluded in the four cases unexpectedly. These results have important implications for the berberine-based anti-AD drug design.
ESTHER : Ji_2012_ScientificWorldJournal_2012_823201
PubMedSearch : Ji_2012_ScientificWorldJournal_2012_823201
PubMedID: 22262957

Title : [Effects of soluble epoxide hydrolase inhibitors on the expression of fatty acid synthase in peripheral blood mononuclear cell of patients and inflammatory response with acute coronary syndrome] - Du_2012_Zhonghua.Yi.Xue.Za.Zhi_92_86
Author(s) : Du JQ , Peng R , Xu DY , Zhao TT , Shen L , Zhao SP
Ref : Zhonghua Yi Xue Za Zhi , 92 :86 , 2012
Abstract : OBJECTIVE: To explore the effects of soluble epoxide hydrolase inhibitor (sEHi) on the expressions of fatty acid synthase (FASN) mRNA and protein in peripheral blood mononuclear cell (PBMCs) of patients with acute coronary syndrome (ACS) and to discuss the influences of sEHi in the regulated expression of FASN and inflammatory reaction.
METHODS: The hospitalized ACS patients were selected as the ACS group (n = 35) while the healthy normal subjects as the control group (n = 30). The levels of lipoproteins, fasting blood glucose, myocardial enzyme and hs-CRP (high-sensitive C-reactive protein) were measured within 24 hours after admission. Meanwhile the PBMCs were separated and cultured and then t-AUCB was added in various concentrations (0, 1, 10, 50, 100 micromol/L). The cellular expressions of FASN, IL-6 mRNA and protein were detected by real-time PCR (polymerase chain reaction) and Western blot respectively.
RESULTS: (1) The serum concentration of hs-CRP reached (5.6 +/- 4.1) mg/L in the ACS group. And it was obviously higher than (1.3 +/- 0.9) mg/L in the control group (P < 0.05). Compared with the control group, the expression levels of FASN, IL-6 mRNA and protein significantly increased in the ACS group (the relative expression amount of FASN mRNA: 1 vs 1.709 +/- 0.272, FASN protein: 0.407 +/- 0.065 vs 1.298 +/- 0.087; relative expression amount of IL-6 mRNA: 1 vs 2.302 +/- 0.200, IL-6 protein: 0.715 +/- 0.058 vs 1.146 +/- 0.083, P < 0.05). Moreover, the levels of FASN and IL-6 mRNA had positive correlations with the serum concentration of hs-CRP (r = 0.714, P < 0.01; r = 0.685, P < 0.01). (2) Compared with the control group (t-AUCB 0 micromol/L), 10, 50, 100 micromol/L t-AUCB had inhibited the expressions quantity of FASN, IL-6 mRNA and protein in PBMCs from the ACS group (P < 0.05). The relative expressions of FASN mRNA in t-AUCB 0, 10, 50, 100 micromol/L group were 1, 0.813 +/- 0.038, 0.564 +/- 0.100, 0.293 +/- 0.043 respectively. The relative expressions of FASN protein in t-AUCB 0, 10, 50 and 100 micromol/L group were 0.957 +/- 0.280, 0.935 +/- 0.275, 0.855 +/- 0.253, 0.685 +/- 0.206 respectively. CONCLUSION: The inflammatory level increases obviously in the ACS group. And the expression level of FASN in PBMCs is closely correlated with the inflammatory level in the ACS patients; t-AUCB may prevent the ruptures of atherosclerotic lesions by regulating FASN and inhibiting inflammatory reactions in ACS patients.
ESTHER : Du_2012_Zhonghua.Yi.Xue.Za.Zhi_92_86
PubMedSearch : Du_2012_Zhonghua.Yi.Xue.Za.Zhi_92_86
PubMedID: 22490687

Title : Design, synthesis, and biological evaluation of callophycin A and analogues as potential chemopreventive and anticancer agents - Shen_2011_Bioorg.Med.Chem_19_6182
Author(s) : Shen L , Park EJ , Kondratyuk TP , Guendisch D , Marler L , Pezzuto JM , Wright AD , Sun D
Ref : Bioorganic & Medicinal Chemistry , 19 :6182 , 2011
Abstract : Callophycin A was originally isolated from the red algae Callophycus oppositifolius and shown to mediate anticancer and cytotoxic effects. In our collaborative effort to identify potential chemopreventive and anticancer agents with enhanced potency and selectivity, we employed a tetrahydro-beta-carboline-based template inspired by callophycin A for production of a chemical library. Utilizing a parallel synthetic approach, 50 various functionalized tetrahydro-beta-carboline derivatives were prepared and assessed for activities related to cancer chemoprevention and cancer treatment: induction of quinone reductase 1 (QR1) and inhibition of aromatase, nitric oxide (NO) production, tumor necrosis factor (TNF)-alpha-induced NFkappaB activity, and MCF7 breast cancer cell proliferation. Biological results showed that the n-pentyl urea S-isomer 6a was the strongest inducer of QR1 with an induction ratio (IR) value of 4.9 at 50 muM [the concentration to double the activity (CD)=3.8 muM] and its corresponding R-isomer 6f had an IR value of 4.3 (CD=0.2 muM). The isobutyl carbamate derivative 3d with R stereochemistry demonstrated the most potent inhibitory activity of NFkappaB, with the half maximal inhibitory concentration (IC(50)) value of 4.8 muM, and also showed over 60% inhibition at 50 muM of NO production (IC(50)=2.8 muM). The R-isomer urea derivative 6j, having an appended adamantyl group, exhibited the most potent MCF7 cell proliferation inhibitory activity (IC(50)=14.7 muM). The S-isomer 12a of callophycin A showed the most potent activity in aromatase inhibition (IC(50)=10.5 muM).
ESTHER : Shen_2011_Bioorg.Med.Chem_19_6182
PubMedSearch : Shen_2011_Bioorg.Med.Chem_19_6182
PubMedID: 21978950

Title : Cardiac abnormalities in severe acute dichlorvos poisoning - He_2011_Crit.Care.Med_39_1906
Author(s) : He X , Li C , Wei D , Wu J , Shen L , Wang T
Ref : Critical Care Medicine , 39 :1906 , 2011
Abstract : OBJECTIVE: Patients with organophosphorus poisoning sometimes die suddenly during rigorous treatment, possibly from myocardial injury. This study sought to elucidate the mechanisms underlying organophosphorus poisoning-induced cardiotoxicity. DESIGN: Prospective observational study. SETTING: Urban, tertiary teaching hospital emergency intensive care unit with 10 beds. PATIENTS: Forty-one patients with severe acute dichlorvos poisoning were consecutively enrolled (n = 92) at emergency intensive care unit and followed for 3 months. MEASUREMENTS AND MAIN RESULTS: Levels of serum creatine kinase isoenzyme myocardium, cardiac troponin I, acetylcholinesterase, acetylcholine, epinephrine, and norepinephrine were tested on hospital days 1, 3, and 5 and on discharge day. Electrocardiography was recorded on admission and then every other day. Transthoracic echocardiography was performed at admission, in the acute phase, before discharge, and during follow-up. Technetium 99m-sestamibi myocardial single photon emission computed tomography was conducted in four patients. Thirty-seven (90.2%) patients survived and four (9.8%) patients died during treatment. We observed sinus tachycardia in 37 (90.2%) patients and ST-T changes in 33 (80.4%) patients. Creatine kinase isoenzyme myocardium and cardiac troponin I levels peaked at day 3 postadmission and then decreased to normal levels. Serum acetylcholine, epinephrine, and norepinephrine peaked at day 1 after admission and then decreased. Echocardiography revealed marked decreases in wall motion of the interventricular septum and left ventricle in the acute phase but returned to normal in the recovery phase. The left ventricular ejection fraction improved significantly from 42 +/- 5% to 59 +/- 4% (p = .001). Single photon emission computed tomography showed abnormal left ventricle perfusion. CONCLUSION: Severe acute dichlorvos poisoning is associated with reversible myocardial dysfunction, possibly through an increase in catecholamine levels.
ESTHER : He_2011_Crit.Care.Med_39_1906
PubMedSearch : He_2011_Crit.Care.Med_39_1906
PubMedID: 21516037

Title : The genome sequence of taurine cattle: a window to ruminant biology and evolution - Elsik_2009_Science_324_522
Author(s) : Elsik CG , Tellam RL , Worley KC , Gibbs RA , Muzny DM , Weinstock GM , Adelson DL , Eichler EE , Elnitski L , Guigo R , Hamernik DL , Kappes SM , Lewin HA , Lynn DJ , Nicholas FW , Reymond A , Rijnkels M , Skow LC , Zdobnov EM , Schook L , Womack J , Alioto T , Antonarakis SE , Astashyn A , Chapple CE , Chen HC , Chrast J , Camara F , Ermolaeva O , Henrichsen CN , Hlavina W , Kapustin Y , Kiryutin B , Kitts P , Kokocinski F , Landrum M , Maglott D , Pruitt K , Sapojnikov V , Searle SM , Solovyev V , Souvorov A , Ucla C , Wyss C , Anzola JM , Gerlach D , Elhaik E , Graur D , Reese JT , Edgar RC , McEwan JC , Payne GM , Raison JM , Junier T , Kriventseva EV , Eyras E , Plass M , Donthu R , Larkin DM , Reecy J , Yang MQ , Chen L , Cheng Z , Chitko-McKown CG , Liu GE , Matukumalli LK , Song J , Zhu B , Bradley DG , Brinkman FS , Lau LP , Whiteside MD , Walker A , Wheeler TT , Casey T , German JB , Lemay DG , Maqbool NJ , Molenaar AJ , Seo S , Stothard P , Baldwin CL , Baxter R , Brinkmeyer-Langford CL , Brown WC , Childers CP , Connelley T , Ellis SA , Fritz K , Glass EJ , Herzig CT , Iivanainen A , Lahmers KK , Bennett AK , Dickens CM , Gilbert JG , Hagen DE , Salih H , Aerts J , Caetano AR , Dalrymple B , Garcia JF , Gill CA , Hiendleder SG , Memili E , Spurlock D , Williams JL , Alexander L , Brownstein MJ , Guan L , Holt RA , Jones SJ , Marra MA , Moore R , Moore SS , Roberts A , Taniguchi M , Waterman RC , Chacko J , Chandrabose MM , Cree A , Dao MD , Dinh HH , Gabisi RA , Hines S , Hume J , Jhangiani SN , Joshi V , Kovar CL , Lewis LR , Liu YS , Lopez J , Morgan MB , Nguyen NB , Okwuonu GO , Ruiz SJ , Santibanez J , Wright RA , Buhay C , Ding Y , Dugan-Rocha S , Herdandez J , Holder M , Sabo A , Egan A , Goodell J , Wilczek-Boney K , Fowler GR , Hitchens ME , Lozado RJ , Moen C , Steffen D , Warren JT , Zhang J , Chiu R , Schein JE , Durbin KJ , Havlak P , Jiang H , Liu Y , Qin X , Ren Y , Shen Y , Song H , Bell SN , Davis C , Johnson AJ , Lee S , Nazareth LV , Patel BM , Pu LL , Vattathil S , Williams RL, Jr. , Curry S , Hamilton C , Sodergren E , Wheeler DA , Barris W , Bennett GL , Eggen A , Green RD , Harhay GP , Hobbs M , Jann O , Keele JW , Kent MP , Lien S , McKay SD , McWilliam S , Ratnakumar A , Schnabel RD , Smith T , Snelling WM , Sonstegard TS , Stone RT , Sugimoto Y , Takasuga A , Taylor JF , Van Tassell CP , Macneil MD , Abatepaulo AR , Abbey CA , Ahola V , Almeida IG , Amadio AF , Anatriello E , Bahadue SM , Biase FH , Boldt CR , Carroll JA , Carvalho WA , Cervelatti EP , Chacko E , Chapin JE , Cheng Y , Choi J , Colley AJ , de Campos TA , De Donato M , Santos IK , de Oliveira CJ , Deobald H , Devinoy E , Donohue KE , Dovc P , Eberlein A , Fitzsimmons CJ , Franzin AM , Garcia GR , Genini S , Gladney CJ , Grant JR , Greaser ML , Green JA , Hadsell DL , Hakimov HA , Halgren R , Harrow JL , Hart EA , Hastings N , Hernandez M , Hu ZL , Ingham A , Iso-Touru T , Jamis C , Jensen K , Kapetis D , Kerr T , Khalil SS , Khatib H , Kolbehdari D , Kumar CG , Kumar D , Leach R , Lee JC , Li C , Logan KM , Malinverni R , Marques E , Martin WF , Martins NF , Maruyama SR , Mazza R , McLean KL , Medrano JF , Moreno BT , More DD , Muntean CT , Nandakumar HP , Nogueira MF , Olsaker I , Pant SD , Panzitta F , Pastor RC , Poli MA , Poslusny N , Rachagani S , Ranganathan S , Razpet A , Riggs PK , Rincon G , Rodriguez-Osorio N , Rodriguez-Zas SL , Romero NE , Rosenwald A , Sando L , Schmutz SM , Shen L , Sherman L , Southey BR , Lutzow YS , Sweedler JV , Tammen I , Telugu BP , Urbanski JM , Utsunomiya YT , Verschoor CP , Waardenberg AJ , Wang Z , Ward R , Weikard R , Welsh TH, Jr. , White SN , Wilming LG , Wunderlich KR , Yang J , Zhao FQ
Ref : Science , 324 :522 , 2009
Abstract : To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
ESTHER : Elsik_2009_Science_324_522
PubMedSearch : Elsik_2009_Science_324_522
PubMedID: 19390049
Gene_locus related to this paper: bovin-2neur , bovin-a0jnh8 , bovin-a5d7b7 , bovin-ACHE , bovin-balip , bovin-dpp4 , bovin-dpp6 , bovin-e1bi31 , bovin-e1bn79 , bovin-est8 , bovin-f1mbd6 , bovin-f1mi11 , bovin-f1mr65 , bovin-f1n1l4 , bovin-g3mxp5 , bovin-q0vcc8 , bovin-q2kj30 , bovin-q3t0r6 , bovin-thyro

Title : Immunohistochemical detection of Ndrg2 in the mouse nervous system - Shen_2008_Neuroreport_19_927
Author(s) : Shen L , Zhao ZY , Wang YZ , Ji SP , Liu XP , Liu XW , Che HL , Lin W , Li X , Zhang J , Yao LB
Ref : Neuroreport , 19 :927 , 2008
Abstract : NDRG2, a member of the N-myc downstream-regulated gene (NDRG) family, is involved in cell differentiation and development. However, the distribution and function of Ndrg2 in the central nervous system remains unclear. Here, we analyzed the expression and distribution of Ndrg2 in the mouse brain and explored the potential physiological functions of Ndrg2. Ndrg2 was expressed in different regions of the brain, including the cerebral cortex, olfactory bulb, midbrain, hippocampus, and thalamus, with high levels in the midbrain and thalamus. Immunohistochemistry assay revealed that Ndrg2-positive cells distributed widely in the adult mouse brain and some of them showed nuclear staining. Indirect immunofluorescence and confocal microscopy studies showed that Ndrg2 protein colocalized with glial fibrillary acidic protein, indicating that Ndrg2 is expressed in astrocytes. Furthermore, Ndrg2 expression increased in glioma cells that were differentiating into astrocytes. Taken together, these findings suggest that Ndrg2 is possibly associated with glial cell proliferation and differentiation based on its immunolocalization in this study.
ESTHER : Shen_2008_Neuroreport_19_927
PubMedSearch : Shen_2008_Neuroreport_19_927
PubMedID: 18520995

Title : The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter - Zhang_2006_J.Biol.Chem_281_39159
Author(s) : Zhang J , Li F , Liu X , Shen L , Liu J , Su J , Zhang W , Deng Y , Wang L , Liu N , Han W , Ji S , Yang A , Han H , Yao L
Ref : Journal of Biological Chemistry , 281 :39159 , 2006
Abstract : The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.
ESTHER : Zhang_2006_J.Biol.Chem_281_39159
PubMedSearch : Zhang_2006_J.Biol.Chem_281_39159
PubMedID: 17050536