Lee B

References (21)

Title : Theoretical prediction on the hydrolysis rate of the new types of nerve agents: A density functional study - Rashid_2023_Toxicol.Rep_10_27
Author(s) : Rashid MAM , Lee B , Kim KH , Jeong K
Ref : Toxicol Rep , 10 :27 , 2023
Abstract : Although the hydrolysis mechanism of the nerve agents, which is the main decontamination pathway, has been studied experimentally and theoretically, the reliable theoretical prediction method for the hydrolysis rate is not studied yet. Furthermore, after the CWC (Chemical Warfare Agent) list is updated, Novichok candidate structures can be more than 10,000 structures, for which it is not possible to perform the experiment for all of them for synthesizing and getting the hydrolysis rate. Therefore, developing a reliable theoretical method for hydrolysis rate prediction is crucial to prepare for the forthcoming usage of new types of nerve agents. Herein, by using DFT (Density Functional Theory), we successfully developed a new method of predicting the hydrolysis rate on nerve agents by investigating the electrophilicity index (EI) of the various A-, V-, and G-series nerve agents and found a suitable correlation with the experimental hydrolysis rate. Among the several DFT methods, wb97xD predicts the EI with the lowest % deviation of the studied nerve agents. Our results show that EI can be a good indicator to predict the hydrolysis rate of the anticipated nerve agents. Based on the result, we predicted the hydrolysis rate on another type of Novichok candidates, which could be the firm basis for developing a decontaminant and antidote with much fewer experimental efforts on new types of nerve agents.
ESTHER : Rashid_2023_Toxicol.Rep_10_27
PubMedSearch : Rashid_2023_Toxicol.Rep_10_27
PubMedID: 36569478

Title : Mouse Pharmacokinetics and In Vitro Metabolism of SH-11037 and SH-11008, Synthetic Homoisoflavonoids for Retinal Neovascularization - Kim_2022_Pharmaceutics_14_
Author(s) : Kim EY , Lee B , Kwon S , Corson TW , Seo SY , Lee K
Ref : Pharmaceutics , 14 : , 2022
Abstract : Cremastranone is a member of the homoisoflavanone family with anti-angiogenic activity in the eyes. SH-11037, a potent and selective synthetic homoisoflavonoid derived from cremastranone, was studied here for pharmacokinetics and metabolism characterization with a special focus on esterase-mediated hydrolysis. SH-11037 was shown to be converted rapidly and nearly completely to SH-11008 following an intravenous dose in mice. SH-11008 showed a high systemic clearance well exceeding the hepatic blood flow in mice. Neither SH-11037 nor SH-11008 were detected in plasma following oral administration of SH-11037 and SH-11008 in mice. Carboxylesterase was shown to be responsible for the rapid and quantitative hydrolysis of SH-11037 to SH-11008 in mouse plasma; the hydrolytic bioconversion was much slower in dog and human plasma, with butyrylcholinesterase and paraoxonase 1 likely being responsible. In vitro metabolism studies with liver S9 fractions suggested that SH-11008 was likely to have a high hepatic metabolic clearance with a predicted hepatic extraction ratio close to 1 in both mouse and human. In conclusion, SH-11037 and SH-11008 both appear to possess pharmacokinetic profiles suboptimal as a systemic agent. SH-11008 is suggested to possess a low potential for systemic toxicity suitable as a topical ocular therapeutic agent.
ESTHER : Kim_2022_Pharmaceutics_14_
PubMedSearch : Kim_2022_Pharmaceutics_14_
PubMedID: 36365089

Title : Characterization of Oncolytic Vaccinia Virus Harboring the Human IFNB1 and CES2 Transgenes - Cho_2020_Cancer.Res.Treat_52_309
Author(s) : Cho E , Islam S , Jiang F , Park JE , Lee B , Kim ND , Hwang TH
Ref : Cancer Research Treat , 52 :309 , 2020
Abstract : PURPOSE: The purpose of this study was to assess characteristics of SJ-815, a novel oncolytic vaccinia virus lacking a functional thymidine kinase-encoding TK gene, and instead, having two human transgenes: the IFNB1 that encodes interferon beta1, and the CES2 that encodes carboxylesterase 2, which metabolizes the prodrug, irinotecan, into cytotoxic SN-38. Materials and Methods: Viral replication and dissemination of SJ-815 were measured by plaque assay and comet assay, respectively, and compared to the backbone of SJ-815, a modified Western Reserve virus named WI. Tumor cytotoxicity of SJ-815 (or mSJ-815, which has the murine IFNB1 transgene for mouse cancers) was evaluated using human and mouse cancer cells. Antitumor effects of SJ-815, with/without irinotecan, were evaluated using a human pancreatic cancer-bearing mouse model and a syngeneic melanoma-bearing mouse model. The SN-38/ irinotecan ratios in mouse melanoma tissue 4 days post irinotecan treatment were compared between groups with and without SJ-815 intravenous injection. RESULTS: SJ-815 demonstrated significantly lower viral replication and dissemination, but considerably stronger in vitro tumor cytotoxicity than WI. The combination use of SJ-815 plus irinotecan generated substantial tumor regression in the human pancreatic cancer model, and significantly prolonged survival in the melanoma model (hazard ratio, 0.11; 95% confidence interval, 0.02 to 0.50; p=0.013). The tumor SN-38/irinotecan ratios were over 3-fold higher in the group with SJ-815 than those without (p < 0.001). CONCLUSION: SJ-815 demonstrates distinct characteristics gained from the inserted IFNB1 and CES2 transgenes. The potent antitumor effects of SJ-815, particularly when combined with irinotecan, against multiple solid tumors make SJ-815 an attractive candidate for further preclinical and clinical studies.
ESTHER : Cho_2020_Cancer.Res.Treat_52_309
PubMedSearch : Cho_2020_Cancer.Res.Treat_52_309
PubMedID: 31401821

Title : Sexually Dimorphic Crosstalk at the Maternal-Fetal Interface - Sun_2020_J.Clin.Endocrinol.Metab_105_e4831
Author(s) : Sun T , Gonzalez TL , Deng N , DiPentino R , Clark EL , Lee B , Tang J , Wang Y , Stripp BR , Yao C , Tseng HR , Karumanchi SA , Koeppel AF , Turner SD , Farber CR , Rich SS , Wang ET , Williams J , Pisarska MD
Ref : J Clinical Endocrinology Metab , 105 :e4831 , 2020
Abstract : CONTEXT: Crosstalk through receptor ligand interactions at the maternal-fetal interface is impacted by fetal sex. This affects placentation in the first trimester and differences in outcomes. Sexually dimorphic signaling at early stages of placentation are not defined. OBJECTIVE: Investigate the impact of fetal sex on maternal-fetal crosstalk. DESIGN: Receptors/ligands at the maternal-fetal surface were identified from sexually dimorphic genes between fetal sexes in the first trimester placenta and defined in each cell type using single-cell RNA-Sequencing (scRNA-Seq). SETTING: Academic institution. SAMPLES: Late first trimester (~10-13 weeks) placenta (fetal) and decidua (maternal) from uncomplicated ongoing pregnancies. MAIN OUTCOME MEASURES: Transcriptomic profiling at tissue and single-cell level; immunohistochemistry of select proteins. RESULTS: We identified 91 sexually dimorphic receptor-ligand pairs across the maternal-fetal interface. We examined fetal sex differences in 5 major cell types (trophoblasts, stromal cells, Hofbauer cells, antigen-presenting cells, and endothelial cells). Ligands from the CC family chemokine ligand (CCL) family were most highly representative in females, with their receptors present on the maternal surface. Sexually dimorphic trophoblast transcripts, Mucin-15 (MUC15) and notum, palmitoleoyl-protein carboxylesterase (NOTUM) were also most highly expressed in syncytiotrophoblasts and extra-villous trophoblasts respectively. Gene Ontology (GO) analysis using sexually dimorphic genes in individual cell types identified cytokine mediated signaling pathways to be most representative in female trophoblasts. Upstream analysis demonstrated TGFB1 and estradiol to affect all cell types, but dihydrotestosterone, produced by the male fetus, was an upstream regulator most significant for the trophoblast population. CONCLUSIONS: Maternal-fetal crosstalk exhibits sexual dimorphism during placentation early in gestation.
ESTHER : Sun_2020_J.Clin.Endocrinol.Metab_105_e4831
PubMedSearch : Sun_2020_J.Clin.Endocrinol.Metab_105_e4831
PubMedID: 32772088

Title : Chemical Proteomics Reveals Soluble Epoxide Hydrolase as a Therapeutic Target for Ocular Neovascularization - Sulaiman_2018_ACS.Chem.Biol_13_45
Author(s) : Sulaiman RS , Park B , Sheik Pran Babu SP , Si Y , Kharwadkar R , Mitter SK , Lee B , Sun W , Qi X , Boulton ME , Meroueh SO , Fei X , Seo SY , Corson TW
Ref : ACS Chemical Biology , 13 :45 , 2018
Abstract : The standard-of-care therapeutics for the treatment of ocular neovascular diseases like wet age-related macular degeneration (AMD) are biologics targeting vascular endothelial growth factor signaling. There are currently no FDA approved small molecules for treating these blinding eye diseases. Therefore, therapeutic agents with novel mechanisms are critical to complement or combine with existing approaches. Here, we identified soluble epoxide hydrolase (sEH), a key enzyme for epoxy fatty acid metabolism, as a target of an antiangiogenic homoisoflavonoid, SH-11037. SH-11037 inhibits sEH in vitro and in vivo and docks to the substrate binding cleft in the sEH hydrolase domain. sEH levels and activity are up-regulated in the eyes of a choroidal neovascularization (CNV) mouse model. sEH is overexpressed in human wet AMD eyes, suggesting that sEH is relevant to neovascularization. Known sEH inhibitors delivered intraocularly suppressed CNV. Thus, by dissecting a bioactive compound's mechanism, we identified a new chemotype for sEH inhibition and characterized sEH as a target for blocking the CNV that underlies wet AMD.
ESTHER : Sulaiman_2018_ACS.Chem.Biol_13_45
PubMedSearch : Sulaiman_2018_ACS.Chem.Biol_13_45
PubMedID: 29193961

Title : Ocular myasthenia gravis in a person with tetraplegia presenting challenges in diagnosis and management - Gounden_2016_Spinal.Cord.Ser.Cases_2_15037
Author(s) : Gounden S , Lee B , Mellick R , Rutkowski SB , Middleton JW
Ref : Spinal Cord Ser Cases , 2 :15037 , 2016
Abstract : We report the first case of ocular myasthenia gravis (OMG) in a patient with complete tetraplegia, highlighting diagnostic and management challenges. Spinal multidisciplinary rural clinic and specialised inpatient Spinal Cord Injury Unit, NSW, Australia. A 61-year-old man with established C5 AIS A tetraplegia, presented with sudden onset of diplopia and bilateral ptosis, later diagnosed as OMG, in context of other complex co-morbidities, including a cervical cord syrinx, obstructive sleep apnoea and labile blood pressure. Clinical findings were consistent with fluctuating bilateral partial third and sixth nerve palsies. Acetylcholine receptor antibodies were negative, but electromyography demonstrated muscle fatigue. The ocular signs responded well to pyridostigmine. Medications taken before diagnosis, including solifenacin for neurogenic bladder overactivity, were ceased to avoid attenuating the anti-cholinesterase effect. However, the unopposed anti-cholinesterase activity led to frequent and painful abdominal spasms, associated with uncontrolled detrusor hyperreflexia and worsening autonomic dysreflexia (AD). A trans-vesical phenol block to treat this provided only short-lasting benefit. Pyridostigmine was ceased to avoid provoking his abdominal spasms and his regular medications were recommenced. It was decided that the most appropriate treatment for his distressing diplopia was an eye patch. After discharge home, he continued to experience problems with recurrent urinary tract infections, abdominal spasms, episodic postural hypotension and AD. After 5 months, the patient died from an acute myocardial infarction. This case report contributes new knowledge about the rare presentation of OMG in a person with chronic tetraplegia.
ESTHER : Gounden_2016_Spinal.Cord.Ser.Cases_2_15037
PubMedSearch : Gounden_2016_Spinal.Cord.Ser.Cases_2_15037
PubMedID: 28053739

Title : Increased cell proliferation and neural activity by physostigmine in the telencephalon of adult zebrafish - Lee_2016_Neurosci.Lett_629_189
Author(s) : Lee Y , Lee B , Jeong S , Park JW , Han IO , Lee CJ
Ref : Neuroscience Letters , 629 :189 , 2016
Abstract : Physostigmine, an acetylcholinesterase inhibitor, is known to affect the brain function in various aspects. This study was conducted to test whether physostigmine affects cell proliferation in the telencephalon of zebrafish. BrdU-labeled cells was prominently observed in the ventral zone of the ventral telencephalon of zebrafish. The increased number of BrdU- and proliferating cell nuclear antigen-labeled cells were shown in zebrafish treated with 200muM physostigmine, which was inhibited by pretreatment with 200muM scopolamine. iNOS mRNA expression was increased in the brain of zebrafish treated with 200muM physostigmine. Consistently, aminoguanidine, an iNOS inhibitor, attenuated the increase in the number of BrdU-labeled cells by physostigmine treatment. Zebrafish also showed seizure-like locomotor activity characterized by a rapid and abrupt movement during a 30min treatment with 200muM physostigmine. Neural activity in response to an electrical stimulus was increased in the isolated telencephalon of zebrafish continuously perfused with 200muM physostigmine. None of the number of BrdU-labeled cells, neural activity, or locomotor activity was affected by treatment with 20muM physostigmine. These results suggest that 200muM physostigmine increased neural activity and induced cell proliferation via nitric oxide production in zebrafish.
ESTHER : Lee_2016_Neurosci.Lett_629_189
PubMedSearch : Lee_2016_Neurosci.Lett_629_189
PubMedID: 27378362

Title : Oral administration of squid lecithin-transphosphatidylated phosphatidylserine improves memory impairment in aged rats - Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
Author(s) : Lee B , Sur BJ , Han JJ , Shim I , Her S , Lee YS , Lee HJ , Hahm DH
Ref : Prog Neuropsychopharmacol Biological Psychiatry , 56C :1 , 2014
Abstract : Recently, lecithin-derived phosphatidylserine (PS), which originates from marine life, has received much attention as a viable alternative to bovine cerebral cortex PS. In this study, the use of squid phosphatidylcholine-transphosphatidylated PS (SQ-PS) was evaluated through examination of its ameliorating effects on age-associated learning and memory deficits in rats. Aged rats were orally administered SQ-PS (10, 20, or 50mg/kg per day) once a day for seven days 30min prior to behavioral assessment in a Morris water maze. SQ-PS administration produced significant dose-dependent improvements in escape latency for finding the platform in the Morris water maze in the aged rats even though Soy-PS administration also exhibited comparable improvements with SQ-PS. Biochemical alterations in the hippocampal cholinergic system, including changes in choline acetyltransferase and acetylcholinesterase immunoreactivity, were consistent with the behavioral results. In addition, SQ-PS treatment significantly restored age-associated decreases of choline transporter and muscarinic acetylcholine receptor type 1 mRNA expression in the hippocampus. These results demonstrate that orally administered SQ-PS dose-dependently aids in the improvement of memory deficits that occur during normal aging in rats. This suggests that SQ-PS may be a useful therapeutic agent in the treatment of diminished memory function in elderly people.
ESTHER : Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
PubMedSearch : Lee_2014_Prog.Neuropsychopharmacol.Biol.Psychiatry_56C_1
PubMedID: 25058912

Title : Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models - Huh_2014_Biomol.Ther.(Seoul)_22_176
Author(s) : Huh E , Kim HG , Park H , Kang MS , Lee B , Oh MS
Ref : Biomol Ther (Seoul) , 22 :176 , 2014
Abstract : Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Abeta) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Abeta-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Abeta-induced neurotoxicity. In mice with Abeta-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Abeta-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 mug/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.
ESTHER : Huh_2014_Biomol.Ther.(Seoul)_22_176
PubMedSearch : Huh_2014_Biomol.Ther.(Seoul)_22_176
PubMedID: 25009697

Title : Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV - Zhang_2011_J.Med.Chem_54_510
Author(s) : Zhang Z , Wallace MB , Feng J , Stafford JA , Skene RJ , Shi L , Lee B , Aertgeerts K , Jennings A , Xu R , Kassel DB , Kaldor SW , Navre M , Webb DR , Gwaltney SL
Ref : Journal of Medicinal Chemistry , 54 :510 , 2011
Abstract : The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.
ESTHER : Zhang_2011_J.Med.Chem_54_510
PubMedSearch : Zhang_2011_J.Med.Chem_54_510
PubMedID: 21186796
Gene_locus related to this paper: human-DPP4

Title : Complete genome sequence of Burkholderia gladioli BSR3 - Seo_2011_J.Bacteriol_193_3149
Author(s) : Seo YS , Lim J , Choi BS , Kim H , Goo E , Lee B , Lim JS , Choi IY , Moon JS , Kim J , Hwang I
Ref : Journal of Bacteriology , 193 :3149 , 2011
Abstract : We report the complete genome sequence of Burkholderia gladioli BSR3, isolated from a diseased rice sheath in South Korea.
ESTHER : Seo_2011_J.Bacteriol_193_3149
PubMedSearch : Seo_2011_J.Bacteriol_193_3149
PubMedID: 21478339
Gene_locus related to this paper: burgs-f2lad2 , burgs-f2lc33 , burgs-f2lje5 , burgs-f2lka6 , burgs-f2lp50 , burgs-f2lkq2 , burgs-f2l922 , burgs-f2ld85 , burgs-f2lqm0 , burgs-f2la46 , burgs-f2ljj1

Title : Krill phosphatidylserine improves learning and memory in Morris water maze in aged rats - Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
Author(s) : Lee B , Sur BJ , Han JJ , Shim I , Her S , Lee HJ , Hahm DH
Ref : Prog Neuropsychopharmacol Biological Psychiatry , 34 :1085 , 2010
Abstract : The ameliorating effect of phosphatidylserine (PS) isolated from krill (KR-PS) on the learning and memory deficits associated with normal aging in rats was investigated, as compared with soybean PS (SOY-PS). Rats were orally administered with KR-PS (20, 50 mg kg-1) and SOY-PS (50 mg kg-1) daily, for 7 days, 30 min before behavioral assessment using the Morris water maze (MWM). Changes in the cholinergic system were examined by measuring choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) immunoreactivity in the hippocampus. The daily administration of KR-PS produced a significant improvement in the escape latency for finding the platform in the MWM, as compared with SOY-PS. Consistent with the behavioral results, KR-PS treatments significantly alleviated age-associated losses of cholinergic immunoreactivity, and muscarinic acetylcholine receptor type 1 (mAChR-M1) and choline transporter (CHT) mRNA expression in the hippocampus. These findings demonstrate that KR-PS showed significant neuroprotective activity against the neuronal and cognitive impairments that occur with normal aging in rats; comparable results were obtained with SOY-PS. These data indicate that oral administration of PS derived from marine life could substitute for bovine cerebral cortex PS (BC-PS) as therapy for the improvement of diminished memory function in elderly people.
ESTHER : Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
PubMedSearch : Lee_2010_Prog.Neuropsychopharmacol.Biol.Psychiatry_34_1085
PubMedID: 20677367

Title : Effect of wild ginseng on scopolamine-induced acetylcholine depletion in the rat hippocampus - Lee_2010_J.Pharm.Pharmacol_62_263
Author(s) : Lee B , Park J , Kwon S , Park MW , Oh SM , Yeom MJ , Shim I , Lee HJ , Hahm DH
Ref : J Pharm Pharmacol , 62 :263 , 2010
Abstract : OBJECTIVES: The ameliorating effects of wild ginseng on learning and memory deficits were investigated in rats. METHODS: Rats were treated daily with wild ginseng or cultivated ginseng for 7 days at 30 min before scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment by the administration of scopolamine, behavioural assessment using the Morris water maze was performed. Changes in cholinergic system reactivity were also examined by measuring the immunoreactive neurons of choline acetyltransferase and the reactivity of acetylcholinesterase in the hippocampus. KEY FINDINGS: Scopolamine injection induced impaired performance in the water maze test and severe cell losses in hippocampal cholinergic neurons, as indicated by decreased choline acetyltransferase immunoreactivity and increased acetylcholinesterase reactivity. Daily administration of wild ginseng produced a significant improvement in the escape latency for finding the platform in the Morris water maze and reduced the loss of cholinergic immunoreactivity in the hippocampus. The reduced expression of brain-derived neurotrophic factor mRNA due to the scopolamine injection was recovered to normal levels by the administration of wild ginseng. CONCLUSIONS: Wild ginseng demonstrates a significant neuroprotective effect against scopolamine-induced neuronal and cognitive impairment.
ESTHER : Lee_2010_J.Pharm.Pharmacol_62_263
PubMedSearch : Lee_2010_J.Pharm.Pharmacol_62_263
PubMedID: 20487207

Title : High-throughput genome sequencing of two Listeria monocytogenes clinical isolates during a large foodborne outbreak - Gilmour_2010_BMC.Genomics_11_120
Author(s) : Gilmour MW , Graham M , Van Domselaar G , Tyler S , Kent H , Trout-Yakel KM , Larios O , Allen V , Lee B , Nadon C
Ref : BMC Genomics , 11 :120 , 2010
Abstract : BACKGROUND: A large, multi-province outbreak of listeriosis associated with ready-to-eat meat products contaminated with Listeria monocytogenes serotype 1/2a occurred in Canada in 2008. Subtyping of outbreak-associated isolates using pulsed-field gel electrophoresis (PFGE) revealed two similar but distinct AscI PFGE patterns. High-throughput pyrosequencing of two L. monocytogenes isolates was used to rapidly provide the genome sequence of the primary outbreak strain and to investigate the extent of genetic diversity associated with a change of a single restriction enzyme fragment during PFGE.
RESULTS: The chromosomes were collinear, but differences included 28 single nucleotide polymorphisms (SNPs) and three indels, including a 33 kbp prophage that accounted for the observed difference in AscI PFGE patterns. The distribution of these traits was assessed within further clinical, environmental and food isolates associated with the outbreak, and this comparison indicated that three distinct, but highly related strains may have been involved in this nationwide outbreak. Notably, these two isolates were found to harbor a 50 kbp putative mobile genomic island encoding translocation and efflux functions that has not been observed in other Listeria genomes.
CONCLUSIONS: High-throughput genome sequencing provided a more detailed real-time assessment of genetic traits characteristic of the outbreak strains than could be achieved with routine subtyping methods. This study confirms that the latest generation of DNA sequencing technologies can be applied during high priority public health events, and laboratories need to prepare for this inevitability and assess how to properly analyze and interpret whole genome sequences in the context of molecular epidemiology.
ESTHER : Gilmour_2010_BMC.Genomics_11_120
PubMedSearch : Gilmour_2010_BMC.Genomics_11_120
PubMedID: 20167121
Gene_locus related to this paper: lismo-LMO0110 , lismo-LMO0493 , lismo-LMO0580 , lismo-LMO0857 , lismo-LMO0950 , lismo-LMO0951 , lismo-LMO0977 , lismo-LMO1128 , lismo-LMO1258 , lismo-LMO1674 , lismo-LMO2089 , lismo-LMO2433 , lismo-LMO2450 , lismo-LMO2452 , lismo-LMO2578 , lismo-LMO2755 , lismo-metx

Title : LMO4 controls the balance between excitatory and inhibitory spinal V2 interneurons - Joshi_2009_Neuron_61_839
Author(s) : Joshi K , Lee S , Lee B , Lee JW , Lee SK
Ref : Neuron , 61 :839 , 2009
Abstract : Multiple excitatory and inhibitory interneurons form the motor circuit with motor neurons in the ventral spinal cord. Notch signaling initiates the diversification of immature V2-interneurons into excitatory V2a-interneurons and inhibitory V2b-interneurons. Here, we provide a transcriptional regulatory mechanism underlying their balanced production. LIM-only protein LMO4 controls this binary cell fate choice by regulating the activity of V2a- and V2b-specific LIM complexes inversely. In the spinal cord, LMO4 induces GABAergic V2b-interneurons in collaboration with SCL and inhibits Lhx3 from generating glutamatergic V2a-interneuons. In LMO4;SCL compound mutant embryos, V2a-interneurons increase markedly at the expense of V2b-interneurons. We further demonstrate that LMO4 nucleates the assembly of a novel LIM-complex containing SCL, Gata2, and NLI. This complex activates specific enhancers in V2b-genes consisting of binding sites for SCL and Gata2, thereby promoting V2b-interneuron fate. Thus, LMO4 plays essential roles in directing a balanced generation of inhibitory and excitatory neurons in the ventral spinal cord.
ESTHER : Joshi_2009_Neuron_61_839
PubMedSearch : Joshi_2009_Neuron_61_839
PubMedID: 19323994

Title : Mangiferin ameliorates scopolamine-induced learning deficits in mice - Jung_2009_Biol.Pharm.Bull_32_242
Author(s) : Jung K , Lee B , Han SJ , Ryu JH , Kim DH
Ref : Biol Pharm Bull , 32 :242 , 2009
Abstract : The aim of this study was to evaluate the effects of Anemarrhena asphodeloides BUNGE (AA) on cholinergic memory deficits in mice. This agent has previously been used as an antipyretic, anti-inflammatory, anti-diabetic, and antidepressant in traditional Chinese medicine. Mangiferin was isolated from AA and showed a dose-dependent inhibition of acetylcholinesterase (AChE) activity (IC(50) value, 62.8 microM). Cholinergic dysfunction was induced in mice by administering scopolamine, and the animals were then tested using the passive avoidance test as well as the Morris water maze test. Mangiferin (20 mg/kg, p.o.) significantly reversed scopolamine-induced deficits in the passive avoidance test, and also improved escape latencies in training trials and increased swimming times in the Morris water maze test (p<0.05). Mangiferin also reduced acetylcholine and tumor necrosis factor (TNF)-alpha levels induced by scopolamine in mice brain (p<0.05) and inhibited nuclear factor (NF)-kappaB activation in scopolamine or TNF-alpha-stimulated BV-2 microglial cells. These results suggest that mangiferin can improve long-term cholinergic memory deficits by AChE inhibition or cholinergic receptor stimulation and inhibition of NF-kappaB activation.
ESTHER : Jung_2009_Biol.Pharm.Bull_32_242
PubMedSearch : Jung_2009_Biol.Pharm.Bull_32_242
PubMedID: 19182383

Title : Timosaponin AIII, a saponin isolated from Anemarrhena asphodeloides, ameliorates learning and memory deficits in mice - Lee_2009_Pharmacol.Biochem.Behav_93_121
Author(s) : Lee B , Jung K , Kim DH
Ref : Pharmacol Biochem Behav , 93 :121 , 2009
Abstract : Anemarrhena asphodeloides Bunge (AA, family Liliaceae), which primarily contains xantones, such as mangiferin, and steroidal saponins, such as timosaponin AIII and sarsasapogenin, has been used as an anti-pyretic, anti-inflammatory, anti-diabetic, anti-platelet aggregation, and anti-depressant agent in traditional Chinese medicine. In the present study, the memory-enhancing effects of these saponins were investigated in scopolamine-treated mice. Among saponins, timosaponin AIII (TA3) significantly reversed the scopolamine-induced deficits in a passive avoidance test and in the Morris water maze test. TA3 also increased hippocampal acetylcholine levels in scopolamine-treated mice and dose-dependently inhibited acetylcholinesterase (AChE) activity (IC(50) value, 35.4 microM). When TA3 (50 mg/kg) was orally administered to mice and its blood concentration was measured by liquid chromatography and tandem mass spectrometry, the C(max) of TA3 occurred 4-6 h after TA3 treatment. The memory-enhancing effect of TA3 was greater when it was administered 5 h before the acquisition trial than 1 h before. Scopolamine treatment in mice increased brain levels of TNF-alpha and IL-1beta expression. However, treatment with TA3 and scopolamine inhibited the increase of TNF-alpha and IL-1beta expression. These results suggest that scopolamine may cause learning and memory deficits that are further complicated by inflammation. TA3 also inhibited the activation of NF-kappaB signaling in BV-2 microglia and in SK-N-SH neuroblastoma cells induced with TNF-alpha or scopolamine. Nevertheless, TA3 may ameliorate memory deficits, mainly by inhibiting AChE.
ESTHER : Lee_2009_Pharmacol.Biochem.Behav_93_121
PubMedSearch : Lee_2009_Pharmacol.Biochem.Behav_93_121
PubMedID: 19426756

Title : Pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel inhibitor of dipeptidyl peptidase-4, in rats, dogs, and monkeys - Lee_2008_Eur.J.Pharmacol_589_306
Author(s) : Lee B , Shi L , Kassel DB , Asakawa T , Takeuchi K , Christopher RJ
Ref : European Journal of Pharmacology , 589 :306 , 2008
Abstract : The aim of the present research was to characterize the pharmacokinetic, pharmacodynamic, and efficacy profiles of alogliptin, a novel quinazolinone-based dipeptidyl peptidase-4 (DPP-4) inhibitor. Alogliptin potently inhibited human DPP-4 in vitro (mean IC(50), ~ 6.9 nM) and exhibited > 10,000-fold selectivity for DPP-4 over the closely related serine proteases DPP-2, DPP-8, DPP-9, fibroblast activation protein/seprase, prolyl endopeptidase, and tryptase (IC(50) > 100,000 nM). Absolute oral bioavailability of alogliptin in rats, dogs, and monkeys was 45%, 86%, and 72% to 88%, respectively. After a single oral dose of alogliptin, plasma DPP-4 inhibition was observed within 15 min and maximum inhibition was > 90% in rats, dogs, and monkeys; inhibition was sustained for 12 h in rats (43%) and dogs (65%) and 24 h in monkeys (> 80%). From E(max) modeling, 50% inhibition of DPP-4 activity was observed at a mean alogliptin plasma concentration (EC(50)) of 3.4 to 5.6 ng/ml (10.0 to 16.5 nM) in rats, dogs, and monkeys. In Zucker fa/fa rats, a single dose of alogliptin (0.3, 1, 3, and 10 mg/kg) inhibited plasma DPP-4 (91% to 100% at 2 h and 20% to 66% at 24 h), increased plasma GLP-1 (2- to 3-fold increase in AUC(0-20 min)) and increased early-phase insulin secretion (1.5- to 2.6-fold increase in AUC(0-20 min)) and reduced blood glucose excursion (31%-67% decrease in AUC(0-90 min)) after oral glucose challenge. Alogliptin (30 and 100 mg/kg) had no effect on fasting plasma glucose in normoglycemic rats. In summary, these data suggest that alogliptin is a potent and highly selective DPP-4 inhibitor with demonstrated efficacy in Zucker fa/fa rats and potential for once-daily dosing in humans.
ESTHER : Lee_2008_Eur.J.Pharmacol_589_306
PubMedSearch : Lee_2008_Eur.J.Pharmacol_589_306
PubMedID: 18538760

Title : Novel assay utilizing fluorochrome-tagged physostigmine (Ph-F) to in situ detect active acetylcholinesterase (AChE) induced during apoptosis - Huang_2005_Cell.Cycle_4_140
Author(s) : Huang X , Lee B , Johnson G , Naleway J , Guzikowski A , Dai W , Darzynkiewicz Z
Ref : Cell Cycle , 4 :140 , 2005
Abstract : It was recently reported that acetylcholinesterase (AChE) is expressed in cells undergoing apoptosis and that its presence is essential for assembly of the apoptosome and subsequent caspase-9 activation. To obtain a marker of active AChE that could assay this enzyme in live intact cells and be applicable to fluorescence microscopy and cytometry, the fluorescein-tagged physostigmine (Ph-F), high affinity ligand (inhibitor) reactive with the active center of AChE, was constructed and tested for its ability to in situ label AChE and measure its induction during apoptosis. Ph-F inhibited cholinesterase activity in vitro (IC50 = 10(-6) and 5 x 10(-6) M for equine butyrylcholinesterase and human erythrocyte AChE, respectively) and was a selective marker of cells and structures that were AChE-positive. Thus, exposure of mouse bone marrow cells to Ph-F resulted in the exclusive labeling of megakaryocytes, and of the diaphragm muscle, preferential labeling of the nerve-muscle junctions (end-plates). During apoptosis of carcinoma HeLa cells and leukemic HL-60 or Jurkat cells triggered either by the DNA topoisomerase 1 inhibitor topotecan (TPT) or by oxidative stress (H2O2), the cells become reactive with Ph-F. Their Ph-F derived fluorescence was measured by flow and laser scanning cytometry. The appearance of Ph-F binding sites during apoptosis was preceded by the loss of mitochondrial potential, was concurrent with the presence of activated caspases, and was followed by loss of membrane integrity. At a very early stage of apoptosis, when nucleolar segregation was apparent, the Ph-F binding sites were distinctly localized within the nucleolus and at later stages of apoptosis in the cytoplasm. During apoptosis triggered by TPT, Ph-F binding was preferentially induced in S-phase cells. Our data on megakaryocytes and end-plates indicate that Ph-F reacts with active sites of AChE, and can be used to reveal the presence of this enzyme in live cells and possibly to study its expression in disorders of the neurological cholinergic system. The findings are also compatible with the reports that AChE may be induced during apoptosis. In fact, the simple and rapid Ph-F binding assay may serve as a convenient marker of apoptotic cells. However, the proposed role of active AChE as an essential factor for assembly of the apoptosome and caspase activation is in question because the AChE inhibitors Ph, Ph-F and BW284c51 did not protect the cells from apoptosis induced by TPT or H2O2. Further studies are thus needed to ascertain the induction and role of AChE in apoptosis.
ESTHER : Huang_2005_Cell.Cycle_4_140
PubMedSearch : Huang_2005_Cell.Cycle_4_140
PubMedID: 15611638

Title : Physiological role of S-formylglutathione hydrolase in C(1) metabolism of the methylotrophic yeast Candida boidinii - Yurimoto_2003_Microbiology_149_1971
Author(s) : Yurimoto H , Lee B , Yano T , Sakai Y , Kato N
Ref : Microbiology , 149 :1971 , 2003
Abstract : The methylotrophic yeast Candida boidinii exhibits S-formylglutathione hydrolase activity (FGH, EC 3.1.2.12), which is involved in the glutathione-dependent formaldehyde oxidation pathway during growth on methanol as the sole carbon source. The structural gene, FGH1, was cloned from C. boidinii, and its predicted amino acid sequence showed more than 60 % similarity to those of FGHs from Paracoccus denitrificans and Saccharomyces cerevisiae, and human esterase D. FGH from C. boidinii contained a C-terminal tripeptide, SKL, which is a type I peroxisome-targeting signal, and a bimodal distribution of FGH between peroxisomes and the cytosol was demonstrated. The FGH1 gene was disrupted in the C. boidinii genome by one-step gene disruption. The fgh1Delta strain was still able to grow on methanol as a carbon source under methanol-limited chemostat conditions with low dilution rates (D<0.05 h(-1)), conditions under which a strain with disruption of the gene for formaldehyde dehydrogenase (another enzyme involved in the formaldehyde oxidation pathway) could not survive. These results suggested that FGH is not essential but necessary for optimal growth on methanol. This is believed to be the first report of detailed analyses of the FGH1 gene in a methylotrophic yeast strain.
ESTHER : Yurimoto_2003_Microbiology_149_1971
PubMedSearch : Yurimoto_2003_Microbiology_149_1971
PubMedID: 12904537
Gene_locus related to this paper: canbo-q7z7w4

Title : A new therapeutic target in Alzheimer's disease treatment: attention to butyrylcholinesterase - Greig_2001_Curr.Med.Res.Opin_17_159
Author(s) : Greig NH , Utsuki T , Yu Q , Zhu X , Holloway HW , Perry T , Lee B , Ingram DK , Lahiri DK
Ref : Curr Med Res Opin , 17 :159 , 2001
Abstract : Alzheimer's disease (AD) is a progressive neurodegenerative disorder of the elderly, characterised by widespread loss of central cholinergic function. The only symptomatic treatment proven effective to date is the use of cholinesterase (ChE) inhibitors to augment surviving cholinergic activity. ChE inhibitors act on the enzymes that hydrolyse acetylcholine (ACh) following synaptic release. In the healthy brain, acetylcholinesterase (AChE) predominates (80%) and butyrylcholinesterase (BuChE) is considered to play a minor role in regulating brain ACh levels. In the AD brain, BuChE activity rises while AChE activity remains unchanged or declines. Therefore both enzymes are likely to have involvement in regulating ACh levels and represent legitimate therapeutic targets to ameliorate the cholinergic deficit. The two enzymes differ in location, substrate specificity and kinetics. Recent evidence suggests that BuChE may also have a role in the aetiology and progression of AD beyond regulation of synaptic ACh levels. Experimental evidence from the use of agents with enhanced selectivity for BuChE (cymserine, MF-8622) and ChE inhibitors such as rivastigmine, which have a dual inhibitory action on both AChE and BuChE, indicate potential therapeutic benefits of inhibiting both AChE and BuChE in AD and related dementias. The development of specific BuChE inhibitors and the continued use of ChE inhibitors with the ability to inhibit BuChE in addition to AChE should lead to improved clinical outcomes.
ESTHER : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedSearch : Greig_2001_Curr.Med.Res.Opin_17_159
PubMedID: 11900310