Kim SY

References (34)

Title : Neuroprotective effects of total alkaloids fraction of Huperzia serrata on scopolamine-induced neurodegenerative animals - Dang_2022_Phytother.Res__
Author(s) : Dang TK , Hong SM , Dao VT , Nguyen DT , Nguyen KV , Nguyen HT , Ullah S , Tran HT , Kim SY
Ref : Phytother Res , : , 2022
Abstract : Huperzia serrata contains Huperzine A (HupA)-an alkaloid used to treat cognitive dysfunction. In this study, we used the total alkaloids (HsAE) to investigate their potential in managing cognitive impairment in comparison with HupA. The antioxidant activity was measured by DPPH assay. In the cellular study, the cell viability and level of ACh of SH-SY5Y cells were evaluated after pretreated with HsAE and scopolamine. For in vivo assay, mice were pre-treated with HsAE, and HupA and undergone scopolamine injection for cognitive impairment. The behavioral tests including the Y-maze and Morris water maze test and the AChE activity, the SOD, CAT, MDA level in the hippocampus and cortex were evaluated. HsAE showed significant scavenging properties on DPPH radicals. HsAE was not toxic to SH-SY5Y cells, and can rescue these cells upon scopolamine treatment. Intriguingly, HsAE showed the neuroprotection against scopolamine-induced amnesia in mice. Moreover, HsAE decreased AChE activity, MDA level, increased antioxidative enzyme activity in the hippocampus as well as cortex of mice, which was relatively better than that of HupA. These findings suggested that HsAE may significantly protect the neurons of mice with scopolamine-induced memory impairment connected to AChE depletion and oxidative stress.
ESTHER : Dang_2022_Phytother.Res__
PubMedSearch : Dang_2022_Phytother.Res__
PubMedID: 36065796

Title : Assessments of the In Vitro and In Vivo Linker Stability and Catabolic Fate for the Ortho Hydroxy-Protected Aryl Sulfate Linker by Immuno-Affinity Capture Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometric Assay - Lee_2021_Pharmaceutics_13_
Author(s) : Lee BI , Park SJ , Park Y , Shin SH , Choi JM , Park MJ , Lim JH , Kim SY , Lee H , Shin YG
Ref : Pharmaceutics , 13 : , 2021
Abstract : Antibody-drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely "bottom-up" and "middle-up" approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker. For comparison, the valine-citrulline-p-aminobenzyloxycarbonyl (VC-PABC) linker was also evaluated under the same experimental conditions. In addition, the catabolite identification experiments at the subunit intact protein level were simultaneously performed to evaluate the catabolic fate of ADCs. As a result, the OHPAS linker was stable in the in vitro mouse/human plasma as well as in vivo pharmacokinetic studies in mice, whereas the VC-PABC linker was relatively unstable in mice in vitro and in vivo. This is because the VC-PABC linker was sensitive to a hydrolytic enzyme called carboxylesterase 1c (Ces1c) in mouse plasma. In conclusion, the OHPAS linker appears to be a good linker for ADC, and further experiments would be warranted to demonstrate the efficacy and toxicity related to the OHPAS linker.
ESTHER : Lee_2021_Pharmaceutics_13_
PubMedSearch : Lee_2021_Pharmaceutics_13_
PubMedID: 33478046
Gene_locus related to this paper: mouse-Ces1c

Title : Dracocephalum moldavica attenuates scopolamine-induced cognitive impairment through activation of hippocampal ERK-CREB signaling in mice - Deepa_2020_J.Ethnopharmacol__
Author(s) : Deepa P , Bae HJ , Park HB , Kim SY , Kim S , Choi JW , Kim DH , Liu XQ , Ryu JH , Park SJ
Ref : J Ethnopharmacol , : , 2020
Abstract : ETHNOPHARMACOLOGICAL RELEVANCE: Dracocephalum moldavica (Moldavian balm) has been traditionally used for the treatment of intellectual disabilities, migraines and cardiovascular problems in East Asia. Recent scientific studies have demonstrated the usefulness of this plant to treat neurodegenerative disorders, including Alzheimer's disease. AIM OF THE STUDY: This study aimed to investigate the effects of the ethanolic extract of D. moldavica leaves (EEDM) on scopolamine-induced cognitive impairment in mice and the underlying mechanisms of action. MATERIALS AND METHODS: The behavioral effects of EEDM were examined using the step-through passive avoidance and Morris water maze tasks. To elucidate the underlying mechanism, we tested whether EEDM affects acetylcholinesterase activity and the expression of memory-related signaling molecules including extracellular signal-regulated kinase (ERK) and cAMP response element-binding protein (CREB) in the hippocampus. RESULTS: EEDM (25, 50 or 100mg/kg) significantly ameliorated the scopolamine-induced step-through latency reduction in the passive avoidance task in mice. In the Morris water maze task, EEDM (50mg/kg) significantly attenuated scopolamine-induced memory impairment. Furthermore, the administration of EEDM increased the phosphorylation levels of ERK and CREB in the hippocampus but did not alter acetylcholinesterase activity. CONCLUSIONS: These findings suggest that EEDM significantly attenuates scopolamine-induced memory impairment in mice and may be a promising therapeutic agent for improving memory impairment.
ESTHER : Deepa_2020_J.Ethnopharmacol__
PubMedSearch : Deepa_2020_J.Ethnopharmacol__
PubMedID: 32035879

Title : Asymmetric Open-Closed Dimer Mechanism of Polyhydroxyalkanoate Synthase PhaC - Chek_2020_iScience_23_101084
Author(s) : Chek MF , Kim SY , Mori T , Tan HT , Sudesh K , Hakoshima T
Ref : iScience , 23 :101084 , 2020
Abstract : Biodegradable polyester polyhydroxyalkanoate (PHA) is a promising bioplastic material for industrial use as a replacement for petroleum-based plastics. PHA synthase PhaC forms an active dimer to polymerize acyl moieties from the substrate acyl-coenzyme A (CoA) into PHA polymers. Here we present the crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, bound to CoA. The structure reveals an asymmetric dimer, in which one protomer adopts an open conformation bound to CoA, whereas the other adopts a closed conformation in a CoA-free form. The open conformation is stabilized by the asymmetric dimerization and enables PhaC to accommodate CoA and also to create the product egress path. The bound CoA molecule has its beta-mercaptoethanolamine moiety extended into the active site with the terminal SH group close to active center Cys291, enabling formation of the reaction intermediate by acylation of Cys291.
ESTHER : Chek_2020_iScience_23_101084
PubMedSearch : Chek_2020_iScience_23_101084
PubMedID: 32388399
Gene_locus related to this paper: 9neis-e1apk1

Title : Lespedeza bicolor Extract Improves Amyloid Beta25 - 35-Induced Memory Impairments by Upregulating BDNF and Activating Akt, ERK, and CREB Signaling in Mice - Ko_2019_Planta.Med_85_1363
Author(s) : Ko YH , Shim KY , Kim SK , Seo JY , Lee BR , Hur KH , Kim YJ , Kim SE , Do MH , Parveen A , Kim SY , Lee SY , Jang CG
Ref : Planta Med , 85 :1363 , 2019
Abstract : Lespedeza bicolor, a traditional herbal medicine widely used in Australia, North America, and Eastern Asia, has various therapeutic effects on inflammation, nephritis, hyperpigmentation, and diuresis. In this study, to evaluate the effects of L. bicolor on cognitive function, we examined whether L. bicolor improved amyloid beta-induced memory impairment and assessed the possible mechanisms in mice. Catechin, rutin, daidzein, luteolin, naringenin, and genistein were identified in the powdered extract of L. bicolor by HPCL-DAD analyses. In behavioral experiments, L. bicolor (25 and 50 mg/kg, p. o.) significantly improved amyloid beta25 - 35 (6 nmol, intracerebroventricular)-induced cognitive dysfunction in the Y-maze, novel recognition, and passive avoidance tests. Our molecular studies showed L. bicolor (25 and 50 mg/kg, p. o.) significantly recovered the reduced glutathione content as well as increased thiobarbituric acid reactive substance and acetylcholinesterase activities in the hippocampus. Furthermore, we found that L. bicolor significantly increased the expression of brain-derived neurotrophic factor, and phospho-Akt, extracellular signal-regulated kinase, and cAMP response element binding caused by amyloid beta25 - 35 in the hippocampus. In conclusion, L. bicolor exerts a potent memory-enhancing effect on cognitive dysfunction induced by amyloid beta25 - 35 in mice.
ESTHER : Ko_2019_Planta.Med_85_1363
PubMedSearch : Ko_2019_Planta.Med_85_1363
PubMedID: 31618776

Title : The memory-enhancing effects of 7,8,4'-trihydroxyisoflavone, a major metabolite of daidzein, are associated with activation of the cholinergic system and BDNF signaling pathway in mice - Ko_2018_Brain.Res.Bull_142_197
Author(s) : Ko YH , Kwon SH , Ma SX , Seo JY , Lee BR , Kim K , Kim SY , Lee SY , Jang CG
Ref : Brain Research Bulletin , 142 :197 , 2018
Abstract : Daidzein is one of the dietary isoflavones present in soybean-based products. After ingestion, daidzein is bioconverted into its major metabolite, 7,8,4'-trihydroxyisoflavone (THIF). Given the pharmacological importance of daidzein, 7,8,4'-THIF has also attracted the interest of researchers. However, there are no reports on the effects of 7,8,4'-THIF on cognition and memory with regard to the cholinergic system. Therefore, this study sought to evaluate the memory-enhancing effects of 7,8,4'-THIF in mice. Treatment with 7,8,4'-THIF ameliorated the cognitive impairments induced by scopolamine, a muscarinic acetylcholine receptor antagonist, in the Y-maze and passive avoidance tests. Interestingly, 7,8,4'-THIF treatment also improved cognitive function in normal mice. This treatment was also able to reverse acetylcholinesterase (AChE) and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus. Finally, 7,8,4'-THIF significantly increased the expression levels of the following molecules in the hippocampus: brain-derived neurotrophic factor (BDNF); phospho extracellular signal-regulated kinase (ERK); phospho cAMP response element binding (CREB); and choline acetyltransferase (ChAT). Our data suggest that 7,8,4'-THIF, a metabolized product of daidzein, improves cognitive function by activating the cholinergic system and the BDNF/ERK/CREB signaling pathway in mice.
ESTHER : Ko_2018_Brain.Res.Bull_142_197
PubMedSearch : Ko_2018_Brain.Res.Bull_142_197
PubMedID: 30031818

Title : Panax ginseng as an adjuvant treatment for Alzheimer's disease - Kim_2018_J.Ginseng.Res_42_401
Author(s) : Kim HJ , Jung SW , Kim SY , Cho IH , Kim HC , Rhim H , Kim M , Nah SY
Ref : J Ginseng Res , 42 :401 , 2018
Abstract : Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid beta-protein (Abeta) formation by inhibiting beta- and gamma-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and Abeta-induced neurotoxicity, and decrease Abeta-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Abeta-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Abeta-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce Abeta formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
ESTHER : Kim_2018_J.Ginseng.Res_42_401
PubMedSearch : Kim_2018_J.Ginseng.Res_42_401
PubMedID: 30337800

Title : PME-1 is regulated by USP36 in ERK and Akt signaling pathways - Kim_2018_FEBS.Lett_592_1575
Author(s) : Kim SY , Choi J , Lee DH , Park JH , Hwang YJ , Baek KH
Ref : FEBS Letters , 592 :1575 , 2018
Abstract : Deubiquitinating enzymes (DUBs) play an important role in the ubiquitin-proteasome system (UPS) by eliminating ubiquitins from substrates and inhibiting proteasomal degradation. Protein phosphatase methylesterase 1 (PME-1) inactivates protein phosphatase 2A (PP2A) and enhances the ERK and Akt signaling pathways, which increase cell proliferation and malignant cell transformation. In this study, we demonstrate that USP36 regulates PME-1 through its deubiquitinating enzyme activity. USP36 increases PME-1 stability, and depletion of USP36 decreases the PME-1 expression level. Furthermore, we demonstrate that USP36 promotes the ERK and Akt signaling pathways. In summary, it is suggested that USP36 regulates PME-1 as a DUB and participates in the ERK and Akt signaling pathways.
ESTHER : Kim_2018_FEBS.Lett_592_1575
PubMedSearch : Kim_2018_FEBS.Lett_592_1575
PubMedID: 29577269
Gene_locus related to this paper: human-PPME1

Title : 6,7,4'-Trihydroxyisoflavone, a major metabolite of daidzein, improves learning and memory via the cholinergic system and the p-CREB\/BDNF signaling pathway in mice - Ko_2018_Eur.J.Pharmacol_826_140
Author(s) : Ko YH , Kim SY , Lee SY , Jang CG
Ref : European Journal of Pharmacology , 826 :140 , 2018
Abstract : Daidzein is one of the major isoflavfones found in soy food and plants. Following ingestion, daidzein is readily converted to hydroxylated metabolites in the human body. 6,7,4'-Trihydroxyisoflavone (THIF), one of the metabolites of daidzein, has several pharmacological activities, including anti-cancer and anti-obesity properties. However, no reports exist on the effects of 6,7,4'-THIF for cognitive function in mice. The present study aimed to investigate the effects of 6,7,4'-THIF against scopolamine-induced learning and memory impairments using the Y-maze and passive avoidance test. A single administration of 6,7,4'-THIF significantly improved scopolamine-induced cognitive dysfunction in these in vivo tests. Moreover, treatment with 6,7,4'-THIF alone enhanced learning and memory performance in the same behavioral tests. Molecular studies showed that 6,7,4'-THIF significantly inhibited acetylcholinesterase and thiobarbituric acid reactive substance (TBARS) activities in the hippocampus of scopolamine-induced mice. In addition, immunohistochemistry and Western blot results revealed that 6,7,4'-THIF significantly increased brain-derived neurotrophic factor (BDNF) and phosphor cAMP response element binding (CREB) in the hippocampus of mice. Taken together, these findings suggest that 6,7,4'-THIF improves cognitive dysfunction induced by scopolamine and enhances learning and memory by activation of the cholinergic system and the p-CREB/BDNF signaling pathway in mice.
ESTHER : Ko_2018_Eur.J.Pharmacol_826_140
PubMedSearch : Ko_2018_Eur.J.Pharmacol_826_140
PubMedID: 29510125

Title : Identification of novel acetylcholinesterase inhibitors designed by pharmacophore-based virtual screening, molecular docking and bioassay - Jang_2018_Sci.Rep_8_14921
Author(s) : Jang C , Yadav DK , Subedi L , Venkatesan R , Venkanna A , Afzal S , Lee E , Yoo J , Ji E , Kim SY , Kim MH
Ref : Sci Rep , 8 :14921 , 2018
Abstract : In this study, pharmacophore based 3D QSAR models for human acetylcholinesterase (AChE) inhibitors were generated, with good significance, statistical values (r(2)training = 0.73) and predictability (q(2)training = 0.67). It was further validated by three methods (Fischer's test, decoy set and Guner-Henry scoring method) to show that the models can be used to predict the biological activities of compounds without costly and time-consuming synthesis. The criteria for virtual screening were also validated by testing the selective AChE inhibitors. Virtual screening experiments and subsequent in vitro evaluation of promising hits revealed a novel and selective AChE inhibitor. Thus, the findings reported herein may provide a new strategy for the discovery of selective AChE inhibitors. The IC50 value of compounds 5c and 6a presented selective inhibition of AChE without inhibiting butyrylcholinesterase (BChE) at uM level. Molecular docking studies were performed to explain the potent AChE inhibition of the target compounds studies to explain high affinity.
ESTHER : Jang_2018_Sci.Rep_8_14921
PubMedSearch : Jang_2018_Sci.Rep_8_14921
PubMedID: 30297729

Title : Malathion increases apoptotic cell death by inducing lysosomal membrane permeabilization in N2a neuroblastoma cells: a model for neurodegeneration in Alzheimer's disease - Venkatesan_2017_Cell.Death.Discov_3_17007
Author(s) : Venkatesan R , Park YU , Ji E , Yeo EJ , Kim SY
Ref : Cell Death Discov , 3 :17007 , 2017
Abstract : Malathion is an organophosphate with severe neurotoxic effects. Upon acute exposure, malathion initially enhances cholinergic activity by inhibition of acetylcholinesterase, which is its major pathological mechanism. Malathion also induces non-cholinergic neuronal cell death in neurodegenerative conditions; the associated molecular mechanism is not well-characterized. To investigate the molecular mechanism of malathion-induced cell death, N2a mouse neuroblastoma cells were exposed to malathion and cell death-related parameters were examined. Malathion reduced cell viability mainly by apoptosis through mitochondrial dysfunction in N2a cells, as judged by an increase in the level of the pro-apoptotic protein Bax and decrease in the levels of the anti-apoptotic proteins p-Akt and Bcl2, resulting in cytochrome c release and caspase-dependent DNA fragmentation and condensation. Malathion treatment also induced autophagy and lysosomal membrane permeabilization (LMP) in N2a cells. LMP caused a lessening of autophagic flux via inhibition of lysosomal fusion with the autophagosome. LMP-induced cathepsin B release and its proteolytic effect may intensify apoptotic insults. Moreover, malathion-exposed N2a cells showed a marked reduction in the levels of the neuronal marker proteins vascular endothelial growth factor and heart fatty acid binding protein 3, along with diminished neuritogenesis in N2a cells and nerve growth factor secretion in C6 glioma cells. Our data suggest that the non-cholinergic effect of malathion may be mediated by apoptotic cell death via LMP induction in N2a cells. Malathion-treated N2a cells can be utilized as an in vitro model system to screen natural and new chemical drug candidates for neurodegenerative diseases such as Alzheimer's disease.
ESTHER : Venkatesan_2017_Cell.Death.Discov_3_17007
PubMedSearch : Venkatesan_2017_Cell.Death.Discov_3_17007
PubMedID: 28487766

Title : Lactucopicrin potentiates neuritogenesis and neurotrophic effects by regulating Ca2+\/CaMKII\/ATF1 signaling pathway - Venkatesan_2017_J.Ethnopharmacol_198_174
Author(s) : Venkatesan R , Shim WS , Yeo EJ , Kim SY
Ref : J Ethnopharmacol , 198 :174 , 2017
Abstract : ETHNO-PHARMACOLOGICAL RELEVANCE: Lactucopicrin is one of constitutes in Cichorium intybus L, which is commonly known as chicory in worldwide. It has been used for traditional usage such as antianalgesics, antidepressants and antihyperglycemics AIM OF STUDY: We investigated the neurotrophin-mediated neuroprotective effect of lactucopicrin in in vitro and examined for the underlying mechanism. MATERIALS AND METHOD: To verify the neuroprotective effect of lactucopicrin, we investigated the inhibitory AChE activity, neurite outgrowth-related downstream signaling in murine neuroblastoma N2a and neurotrophins secretion in rat C6 glioma cells.
RESULTS: Lactucopicrin inhibited the AChE activity and increased intracellular Ca2+ levels with a substantial rise in muscarinic acetylcholine receptor M1 (CHRM1) expression in N2a cells. Moreover, lactucopicrin actively promoted neurite outgrowth via Ca2+-mediated activation of Ca2+/calmodulin-dependent protein kinase-II (CaMKII). It further activates transcription factor 1 (ATF1) along with modulating the levels of tropomyosin receptor kinase A, extracellular signal-regulated kinase 1 and 2, AKT, and synaptophysin 1 in N2a cells. Additionally, the levels of neurotrophins including NGF, BDNF, and NT3 were increased by treatment of lactucopicrin in C6 cells. The effects of lactucopicrin on NGF secretion and neuritogenesis were maintained even in the presence of phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002, indicating that lactucopicrin exerts its effect on neuritogenesis in a PI3K-independent manner. CONCLUSION: Our results suggest that the natural compound lactucopicrin may be a promising neurotrophin-mediated neuroprotective candidate for neurodegenerative diseases.
ESTHER : Venkatesan_2017_J.Ethnopharmacol_198_174
PubMedSearch : Venkatesan_2017_J.Ethnopharmacol_198_174
PubMedID: 28011163

Title : Structure of polyhydroxyalkanoate (PHA) synthase PhaC from Chromobacterium sp. USM2, producing biodegradable plastics - Chek_2017_Sci.Rep_7_5312
Author(s) : Chek MF , Kim SY , Mori T , Arsad H , Samian MR , Sudesh K , Hakoshima T
Ref : Sci Rep , 7 :5312 , 2017
Abstract : Polyhydroxyalkanoate (PHA) is a promising candidate for use as an alternative bioplastic to replace petroleum-based plastics. Our understanding of PHA synthase PhaC is poor due to the paucity of available three-dimensional structural information. Here we present a high-resolution crystal structure of the catalytic domain of PhaC from Chromobacterium sp. USM2, PhaC Cs -CAT. The structure shows that PhaC Cs -CAT forms an alpha/beta hydrolase fold comprising alpha/beta core and CAP subdomains. The active site containing Cys291, Asp447 and His477 is located at the bottom of the cavity, which is filled with water molecules and is covered by the partly disordered CAP subdomain. We designated our structure as the closed form, which is distinct from the recently reported catalytic domain from Cupriavidus necator (PhaC Cn -CAT). Structural comparison showed PhaC Cn -CAT adopting a partially open form maintaining a narrow substrate access channel to the active site, but no product egress. PhaC Cs -CAT forms a face-to-face dimer mediated by the CAP subdomains. This arrangement of the dimer is also distinct from that of the PhaC Cn -CAT dimer. These findings suggest that the CAP subdomain should undergo a conformational change during catalytic activity that involves rearrangement of the dimer to facilitate substrate entry and product formation and egress from the active site.
ESTHER : Chek_2017_Sci.Rep_7_5312
PubMedSearch : Chek_2017_Sci.Rep_7_5312
PubMedID: 28706283
Gene_locus related to this paper: 9neis-e1apk1

Title : Rapid Return of Spontaneous Respiration after General Anesthesia with Sugammadex in a Patient with Myasthenia Gravis - Kim_2016_J.Lifestyle.Med_6_43
Author(s) : Kim RK , Kim SY
Ref : J Lifestyle Med , 6 :43 , 2016
Abstract : Myasthenia gravis causes weakness and fatigue of the skeletal muscles, including respiratory muscles. When immobile surgical fields are needed, neuromuscular blocking agents (NMBAs) are often administered to block muscle activity, leading to an immobile surgical field and respiratory arrest. Acetylcholinesterase inhibitors are administered to reverse the muscle block, promoting spontaneous respiration for patient recovery. If immobile surgical fields are required in myasthenic patient operations, NMBAs should be administered. However, recovery from NMBAs using acetylcholinesterase inhibitors might be delayed in myasthenic patients due to their intake of medicines that already inhibit cholinesterase, resulting in a delay in spontaneous respiration. Sugammadex is a recently introduced medicine that reverses muscle blocks through a different mechanism from acetylcholinesterase inhibitors and can be administered to facilitate the return of spontaneous respiration in myasthenic patients. Our experience of the rapid return to spontaneous respiration of a myasthenic patient with Sugammadex is reported in this paper.
ESTHER : Kim_2016_J.Lifestyle.Med_6_43
PubMedSearch : Kim_2016_J.Lifestyle.Med_6_43
PubMedID: 27358839

Title : Alzheimer's disease with cerebrovascular disease: current status in the Asia-Pacific region - Chen_2016_J.Intern.Med_280_359
Author(s) : Chen C , Homma A , Mok VC , Krishnamoorthy E , Alladi S , Meguro K , Abe K , Dominguez J , Marasigan S , Kandiah N , Kim SY , Lee DY , De Silva HA , Yang YH , Pai MC , Senanarong V , Dash A
Ref : J Intern Med , 280 :359 , 2016
Abstract : BACKGROUND: There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well-defined criteria and treatment guidelines AD+CVD may be underdiagnosed in Asia.
METHODS: Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available.
RESULTS: AD accounts for up to 60% and AD+CVD accounts for 10-20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First-line therapy is usually an acetylcholinesterase inhibitor such as donepezil. CONCLUSION: AD+CVD is likely to be under-recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.
ESTHER : Chen_2016_J.Intern.Med_280_359
PubMedSearch : Chen_2016_J.Intern.Med_280_359
PubMedID: 26992016

Title : Clinical Predictors for Mild Cognitive Impairment Progression in a Korean Cohort - Shim_2016_Dement.Neurocogn.Disord_15_68
Author(s) : Shim YS , Yang DW , Yoon B , Lee Y , Hong CH , Seo SW , Yoon SJ , Jeong JH , Park MH , Choi SH , Kim SY
Ref : Dement Neurocogn Disord , 15 :68 , 2016
Abstract : Background and Purpose: Patients with mild cognitive impairment (MCI) and their caregivers are concerned with the likelihood and time course of progression to dementia. This study was performed to identify the clinical predictors of the MCI progression in a Korean registry, and investigated the effects of medications without evidence, frequently prescribed in clinical practice. Methods: Using a Korean cohort that included older adults with MCI who completed at least one follow-up visit, clinical characteristics and total medical expenses including prescribed medications were compared between two groups: progressed to dementia or not. Cox proportional hazards regression analysis was conducted. Results: During the mean 1.42+/-0.72 years, 215 (27.63%) of 778 participants progressed to dementia. The best predictors were age [hazard ratio (HR), 1.036; 95% confidence interval (CI), 1.006-1.067; p=0.018], apolipoprotein epsilon4 allele (HR, 2.247; 95% CI, 1.512-3.337; p<0.001), Clinical Dementia Rating scale-sum of boxes scores (HR, 1.367; 95% CI, 1.143-1.636; p=0.001), Instrumental Activities of Daily Living scores (HR, 1.035; 95% CI, 1.003-1.067; p=0.029), and lower Mini-Mental State Examination scores (HR, 0.892; 95% CI, 0.839-0.949; p<0.001). Total medical expenses were not different. Conclusions: Our data are in accordance with previous reports about clinical predictors for the progression from MCI to dementia. Total medical expenses were not different between groups with and without progression.
ESTHER : Shim_2016_Dement.Neurocogn.Disord_15_68
PubMedSearch : Shim_2016_Dement.Neurocogn.Disord_15_68
PubMedID: 30906345

Title : Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia - Kwon_2014_J.Neurol.Sci_347_66
Author(s) : Kwon KJ , Kim MK , Lee EJ , Kim JN , Choi BR , Kim SY , Cho KS , Han JS , Kim HY , Shin CY , Han SH
Ref : Journal of Neurology Sci , 347 :66 , 2014
Abstract : Vascular dementia (VaD) is the second most common form of dementia caused by cerebrovascular disease. Several recent reports demonstrated that cholinergic deficits are implicated in the pathogenesis of VaD and that cholinergic therapies have shown improvement of cognitive function in patients with VaD. However, the precise mechanisms by which donepezil achieves its effects on VaD are not fully understood. Donepezil hydrochloride is an acetylcholinesterase inhibitor (AChEI) currently used for the symptomatic treatment of Alzheimer's disease (AD). Several lines of evidence have demonstrated that AChEIs such as donepezil promote neurogenesis in the central nervous system. We investigated whether donepezil regulated hippocampal neurogenesis after bilateral common carotid artery occlusion (BCCAO) in rats, a commonly used animal model of VaD. To evaluate the effect of donepezil on neurogenesis, we orally treated rats with donepezil (10mg/kg) once a day for 3weeks, and injected BrdU over the same 3-week period to label newborn cells. The doses of donepezil that we used have been reported to activate cholinergic activity in rats. After 3weeks, a water maze task was performed on these rats to test spatial learning, and a subsequent histopathological evaluation was conducted. Donepezil improved memory impairment and increased the number of BrdU-positive cells in the dentate gyrus (DG) of BCCAO animals. These results indicated that donepezil improves cognitive function and enhances the survival of newborn neurons in the DG in our animal model of VaD, possibly by enhancing the expression of choline acetyltransferase and brain-derived neurotropic factor.
ESTHER : Kwon_2014_J.Neurol.Sci_347_66
PubMedSearch : Kwon_2014_J.Neurol.Sci_347_66
PubMedID: 25266713

Title : Val-boroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors - Walsh_2013_PLoS.One_8_e58860
Author(s) : Walsh MP , Duncan B , Larabee S , Krauss A , Davis JP , Cui Y , Kim SY , Guimond M , Bachovchin W , Fry TJ
Ref : PLoS ONE , 8 :e58860 , 2013
Abstract : Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine.
ESTHER : Walsh_2013_PLoS.One_8_e58860
PubMedSearch : Walsh_2013_PLoS.One_8_e58860
PubMedID: 23554941

Title : Structures of D14 and D14L in the strigolactone and karrikin signaling pathways - Kagiyama_2013_Genes.Cells_18_147
Author(s) : Kagiyama M , Hirano Y , Mori T , Kim SY , Kyozuka J , Seto Y , Yamaguchi S , Hakoshima T
Ref : Genes Cells , 18 :147 , 2013
Abstract : Strigolactones (SLs) are plant hormones that inhibit shoot branching. DWARF14 (D14) inhibits rice tillering and is an SL receptor candidate in the branching inhibition pathway, whereas the close homologue DWARF14-LIKE (D14L) participates in the signaling pathway of karrikins (KARs), which are derived from burnt vegetation as smoke stimulants of seed germination. We provide the first evidence for direct binding of the bioactive SL analogue GR24 to D14. Isothermal titration calorimetry measurements show a D14-GR24 binding affinity in the sub-micromolar range. Similarly, bioactive KAR1 directly binds D14L in the micromolar range. The crystal structure of rice D14 shows a compact alpha-/beta-fold hydrolase domain forming a deep ligand-binding pocket capable of accommodating GR24. Insertion of four alpha-helices between beta6 strand and alphaD helix forms the helical cap of the pocket, although the pocket is open to the solvent. The pocket contains the conserved catalytic triad Ser-His-Asp aligned with the oxyanion hole, suggesting hydrolase activity. Although these structural characteristics are conserved in D14L, the D14L pocket is smaller than that of D14. The KAR-insensitive mutation kai2-1 is located at the prominent long beta6-alphaD1 loop, which is characteristic in D14 and D14L, but not in related alpha-/beta-fold hydrolases.
ESTHER : Kagiyama_2013_Genes.Cells_18_147
PubMedSearch : Kagiyama_2013_Genes.Cells_18_147
PubMedID: 23301669
Gene_locus related to this paper: arath-KAI2.D14L , orysj-Q10QA5

Title : Genome sequence of the leaf-colonizing Bacterium Bacillus sp. strain 5B6, isolated from a cherry tree - Kim_2012_J.Bacteriol_194_3758
Author(s) : Kim BK , Chung JH , Kim SY , Jeong H , Kang SG , Kwon SK , Lee CH , Song JY , Yu DS , Ryu CM , Kim JF
Ref : Journal of Bacteriology , 194 :3758 , 2012
Abstract : Plant growth-promoting bacteria colonize various habitats, including the phyllosphere. Here, we present the high-quality draft genome sequence of Bacillus sp. strain 5B6, which was isolated from the leaf of a cherry tree. The 3.9-Mb genome uncovers its potential for understanding the nature of leaf colonization as well as antibiosis against plant pathogens.
ESTHER : Kim_2012_J.Bacteriol_194_3758
PubMedSearch : Kim_2012_J.Bacteriol_194_3758
PubMedID: 22740678
Gene_locus related to this paper: baca2-a7z924 , bacsu-YVAK

Title : Genome sequence of the plant growth-promoting rhizobacterium Bacillus sp. strain JS - Song_2012_J.Bacteriol_194_3760
Author(s) : Song JY , Kim HA , Kim JS , Kim SY , Jeong H , Kang SG , Kim BK , Kwon SK , Lee CH , Yu DS , Kim BS , Kim SH , Kwon SY , Kim JF
Ref : Journal of Bacteriology , 194 :3760 , 2012
Abstract : Volatile and nonvolatile compounds emitted from the plant growth-promoting rhizobacterium Bacillus sp. strain JS enhance the growth of tobacco and lettuce. Here, we report the high-quality genome sequence of this bacterium. Its 4.1-Mb genome reveals a number of genes whose products are possibly involved in promotion of plant growth or antibiosis.
ESTHER : Song_2012_J.Bacteriol_194_3760
PubMedSearch : Song_2012_J.Bacteriol_194_3760
PubMedID: 22740679
Gene_locus related to this paper: bacsu-pnbae , bacsu-YVAK

Title : Complete genome sequence of the endophytic bacterium Burkholderia sp. strain KJ006 - Kwak_2012_J.Bacteriol_194_4432
Author(s) : Kwak MJ , Song JY , Kim SY , Jeong H , Kang SG , Kim BK , Kwon SK , Lee CH , Yu DS , Park SH , Kim JF
Ref : Journal of Bacteriology , 194 :4432 , 2012
Abstract : Endophytes live inside plant tissues without causing any harm and may even benefit plants. Here, we provide the high-quality genome sequence of Burkholderia sp. strain KJ006, an endophytic bacterium of rice with antifungal activity. The 6.6-Mb genome, consisting of three chromosomes and a single plasmid, contains genes related to plant growth promotion or degradation of aromatic compounds.
ESTHER : Kwak_2012_J.Bacteriol_194_4432
PubMedSearch : Kwak_2012_J.Bacteriol_194_4432
PubMedID: 22843575
Gene_locus related to this paper: 9burk-i2dyd7 , burvg-a4jmy2

Title : Neuroprotective effects of Eucommia ulmoides Oliv. Bark on amyloid beta(25-35)-induced learning and memory impairments in mice - Kwon_2011_Neurosci.Lett_487_123
Author(s) : Kwon SH , Lee HK , Kim JA , Hong SI , Kim SY , Jo TH , Park YI , Lee CK , Kim YB , Lee SY , Jang CG
Ref : Neuroscience Letters , 487 :123 , 2011
Abstract : In the present study, we examined whether aqueous extract of Eucommia ulmoides Oliv. Bark (EUE) with graded doses exerted its neuroprotective effects on amyloid beta(25-35) (Abeta(25-35))-induced learning and memory impairments in mice. Mice received a single intracerebroventricular (i.c.v.) injection of Abeta(25-35) 6 nmol as the critical factor in Alzheimer's disease (AD), cognition was evaluated using Y-maze, passive avoidance, and Morris water maze tests. EUE significantly improved the Abeta(25-35)-induced memory deficit in the Y-maze test. Also, EUE increased step-through latency time with Abeta(25-35)-induced learning and memory deficits in the passive avoidance test. In addition, EUE decreased the escape latencies with Abeta(25-35)-induced cognitive impairments in the Morris water maze test. In the probe trial session, EUE increased time spent in the target quadrant. In the in vitro study, EUE was found to inhibit acetylcholinesterase (AChE) activity in a dose-dependent manner (IC50 value; 172 mug/ml). Ex vivo study, EUE significantly inhibited AChE activity in the hippocampus and frontal cortex. These results demonstrate that EUE possesses potent neuroprotective effects and that its beneficial effects are mediated, in part, by AChE inhibition, and therefore, might be a potential candidate in neurodegenerative diseases such as AD.
ESTHER : Kwon_2011_Neurosci.Lett_487_123
PubMedSearch : Kwon_2011_Neurosci.Lett_487_123
PubMedID: 20974223

Title : Genome sequence of strain IMCC9480, a xanthorhodopsin-bearing betaproteobacterium isolated from the Arctic Ocean - Oh_2011_J.Bacteriol_193_3421
Author(s) : Oh HM , Lee K , Jang Y , Kang I , Kim HJ , Kang TW , Kim SY , Cho JC
Ref : Journal of Bacteriology , 193 :3421 , 2011
Abstract : Strain IMCC9480 is a novel member of the family Oxalobacteraceae of the Betaproteobacteria, isolated from the Arctic Ocean by dilution-to-extinction culturing. Here we present the draft genome sequence of strain IMCC9480. The genome is predicted to contain genes for xanthorhodopsin, retinoid biosynthesis, carbon monoxide dehydrogenase, and C(1) metabolism.
ESTHER : Oh_2011_J.Bacteriol_193_3421
PubMedSearch : Oh_2011_J.Bacteriol_193_3421
PubMedID: 21572000
Gene_locus related to this paper: 9burk-f1vv61 , 9burk-f1vzd3 , 9burk-f1w2e1 , 9burk-f1w0q2

Title : Genome sequence of strain IMCC2047, a novel marine member of the Gammaproteobacteria - Kang_2011_J.Bacteriol_193_3688
Author(s) : Kang I , Kang D , Oh HM , Kim H , Kim HJ , Kang TW , Kim SY , Cho JC
Ref : Journal of Bacteriology , 193 :3688 , 2011
Abstract : Strain IMCC2047 was isolated from the Yellow Sea using dilution-to-extinction culturing. The strain was shown to occupy a distinct phylogenetic position within the Gammaproteobacteria. Here we present the genome sequence of strain IMCC2047, which harbors genes for various metabolic pathways, including proteorhodopsin and ribulose bisphosphate carboxylase.
ESTHER : Kang_2011_J.Bacteriol_193_3688
PubMedSearch : Kang_2011_J.Bacteriol_193_3688
PubMedID: 21602327
Gene_locus related to this paper: 9gamm-f3kbt3 , 9gamm-f3kec2

Title : NDRG2 expression decreases with tumor stages and regulates TCF\/beta-catenin signaling in human colon carcinoma - Kim_2009_Carcinogenesis_30_598
Author(s) : Kim YJ , Yoon SY , Kim JT , Song EY , Lee HG , Son HJ , Kim SY , Cho D , Choi I , Kim JH , Kim JW
Ref : Carcinogenesis , 30 :598 , 2009
Abstract : NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular beta-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of beta-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/beta-catenin signaling for the maintenance of healthy colon tissues.
ESTHER : Kim_2009_Carcinogenesis_30_598
PubMedSearch : Kim_2009_Carcinogenesis_30_598
PubMedID: 19237607

Title : Effect of ApoE genotype on response to donepezil in patients with Alzheimer's disease - Choi_2008_Dement.Geriatr.Cogn.Disord_25_445
Author(s) : Choi SH , Kim SY , Na HR , Kim BK , Yang DW , Kwon JC , Park MY
Ref : Dementia & Geriatric Cognitive Disorders , 25 :445 , 2008
Abstract : BACKGROUND/AIMS: The possible influence of apolipoprotein E (ApoE) genotype on the response to acetylcholinesterase inhibitor therapy in patients with Alzheimer's disease (AD) remains a matter of controversy. In order to address this issue, we investigated the effects of ApoE genotype on the clinical response to donepezil in patients with mild to moderate AD.
METHODS: An open study was carried out in 51 patients with probable AD who were treated with 5-10 mg of donepezil per day for 48 weeks.
RESULTS: Eighteen (35.3%) of the 51 patients had 1 or 2 ApoE epsilon4 alleles. ApoE epsilon4 carriers with AD showed a mean 1.1-point increase from the baseline score of 23.9 on the 70-point Alzheimer's Disease Assessment Scale-Cognitive Component at 48 weeks, while the ApoE epsilon4 noncarrier group showed a 3.1-point increase from the baseline score of 22.5 (p = 0.03). The ApoE epsilon4 carrier group exhibited a mean 0.13-point worsening from the baseline score of 0.97 on the Korean Instrumental Activities of Daily Living at 48 weeks, while the ApoE epsilon4 noncarrier group exhibited a 0.17-point worsening from the baseline score of 0.64 (p = 0.05). CONCLUSION: AD patients who carry the ApoE epsilon4 allele may respond more favorably to donepezil than epsilon4 noncarriers.
ESTHER : Choi_2008_Dement.Geriatr.Cogn.Disord_25_445
PubMedSearch : Choi_2008_Dement.Geriatr.Cogn.Disord_25_445
PubMedID: 18401173

Title : Synthesis and biological evaluation of homopiperazine derivatives with beta-aminoacyl group as dipeptidyl peptidase IV inhibitors - Ahn_2008_Bioorg.Med.Chem.Lett_18_6525
Author(s) : Ahn JH , Park WS , Jun MA , Shin MS , Kang SK , Kim KY , Rhee SD , Bae MA , Kim KR , Kim SG , Kim SY , Sohn SK , Kang NS , Lee JO , Lee DH , Cheon HG , Kim SS
Ref : Bioorganic & Medicinal Chemistry Lett , 18 :6525 , 2008
Abstract : Compounds with homopiperazine skeleton are designed to find a potent DPP-IV inhibitor without inhibiting CYP. Thus a series of beta-aminoacyl-containing homopiperazine derivatives was synthesized and evaluated. Compounds with acid moiety were found to be potent inhibitors of DPP-IV without inhibiting CYP 3A4. More specifically, compound 7m showed nanomolar activity with no inhibition towards five subtypes of CYPs, was considered as a prototype for further derivatization. Based on its X-ray co-crystal structure with human DPP-IV, we identified compounds 7s and 7t which showed good in vitro activity, no CYP inhibition, and good selectivity.
ESTHER : Ahn_2008_Bioorg.Med.Chem.Lett_18_6525
PubMedSearch : Ahn_2008_Bioorg.Med.Chem.Lett_18_6525
PubMedID: 18996694
Gene_locus related to this paper: human-DPP4

Title : The Orientia tsutsugamushi genome reveals massive proliferation of conjugative type IV secretion system and host-cell interaction genes - Cho_2007_Proc.Natl.Acad.Sci.U.S.A_104_7981
Author(s) : Cho NH , Kim HR , Lee JH , Kim SY , Kim J , Cha S , Darby AC , Fuxelius HH , Yin J , Kim JH , Lee SJ , Koh YS , Jang WJ , Park KH , Andersson SG , Choi MS , Kim IS
Ref : Proc Natl Acad Sci U S A , 104 :7981 , 2007
Abstract : Scrub typhus is caused by the obligate intracellular rickettsia Orientia tsutsugamushi (previously called Rickettsia tsutsugamushi). The bacterium is maternally inherited in trombicuid mites and transmitted to humans by feeding larvae. We report here the 2,127,051-bp genome of the Boryong strain, which represents the most highly repeated bacterial genome sequenced to date. The repeat density of the scrub typhus pathogen is 200-fold higher than that of its close relative Rickettsia prowazekii, the agent of epidemic typhus. A total of 359 tra genes for components of conjugative type IV secretion systems were identified at 79 sites in the genome. Associated with these are >200 genes for signaling and host-cell interaction proteins, such as histidine kinases, ankyrin-repeat proteins, and tetratrico peptide-repeat proteins. Additionally, the O. tsutsugamushi genome contains >400 transposases, 60 phage integrases, and 70 reverse transcriptases. Deletions and rearrangements have yielded unique gene combinations as well as frequent pseudogenization in the tra clusters. A comparative analysis of the tra clusters within the genome and across strains indicates sequence homogenization by gene conversion, whereas complexity, diversity, and pseudogenization are acquired by duplications, deletions, and transposon integrations into the amplified segments. The results suggest intragenomic duplications or multiple integrations of a massively proliferating conjugative transfer system. Diversifying selection on host-cell interaction genes along with repeated population bottlenecks may drive rare genome variants to fixation, thereby short-circuiting selection for low complexity in bacterial genomes.
ESTHER : Cho_2007_Proc.Natl.Acad.Sci.U.S.A_104_7981
PubMedSearch : Cho_2007_Proc.Natl.Acad.Sci.U.S.A_104_7981
PubMedID: 17483455

Title : The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice - Kim_2007_J.Pharmacol.Sci_105_82
Author(s) : Kim DH , Yoon BH , Kim YW , Lee S , Shin BY , Jung JW , Kim HJ , Lee YS , Choi JS , Kim SY , Lee KT , Ryu JH
Ref : J Pharmacol Sci , 105 :82 , 2007
Abstract : In the present study, we assessed the effect of the ethanolic extract of the seeds of Cassia obtusifolia (COE) on the learning and memory impairments induced by scopolamine or transient bilateral common carotid artery occlusion (2VO). In a study of the cholinergic dysfunction induced by scopolamine, single COE (25, 50, or 100 mg/kg, p.o.) administration significantly attenuated scopolamine-induced cognitive impairments as determined by the passive avoidance and Y-maze tasks (P<0.05) and also reduced escape-latency on the Morris water maze task (P<0.05). In the 2VO study, COE (50 mg/kg, p.o.) significantly reversed 2VO-induced cognitive impairments in mice by the passive avoidance and the Y-maze tasks (P<0.05). Moreover, COE (50 mg/kg, p.o.) also reduced escape-latency and prolonged swimming time in the target quadrant during a probe trial of the Morris water maze task (P<0.05). In an in vitro study, COE was found to inhibit acetylcholinesterase activity in a dose-dependent manner (IC(50) value: 81.6 microg/ml). Furthermore, COE also inhibited acetylcholinesterase activity in an ex vivo study. These results suggest that COE attenuates memory impairment induced by scopolamine or 2VO and that these effects are mediated by enhancing the cholinergic nervous system via acetylcholinesterase inhibition.
ESTHER : Kim_2007_J.Pharmacol.Sci_105_82
PubMedSearch : Kim_2007_J.Pharmacol.Sci_105_82
PubMedID: 17895591

Title : In vitro evolution of lipase B from Candida antarctica using surface display in hansenula polymorpha - Kim_2007_J.Microbiol.Biotechnol_17_1308
Author(s) : Kim SY , Sohn JH , Pyun YR , Yang IS , Kim KH , Choi ES
Ref : J Microbiol Biotechnol , 17 :1308 , 2007
Abstract : ALipase B from Candida antarctica (CalB) displayed on the cell surface of H. polymorpha has been functionally improved for catalytic activity by molecular evolution. CalB was displayed on the cell surface by fusing to a cell-wall anchor motif (CwpF). A library of CalB mutants was constructed by in vivo recombination in H. polymorpha. Several mutants with increased whole-cell CalB activity were acquired from screening seven thousand transformants. The two independent mutants CalB10 and CalB14 showed an approximately 5 times greater whole-cell activity than the wild-type. When these mutants were made as a soluble form, CalB 10 showed 6 times greater activity and CalB14 showed an 11 times greater activity compared with the wild-type. Sequence analyses of mutant CALB genes revealed amino acid substitutions of Leu278Pro in CalB10 and Leu278Pro/Leu219Gln in CalB14. The substituted Pro278 in both mutants was located near the proline site of the alpha10 helix. This mutation was assumed to induce a conformational change in the alpha10 helix and increased the k(cat) value of mutant CalB approximately 6 times. Site-directed mutagenized CalB, LQ (Leu219Gln) was secreted into the culture supernatant at an amount of approximately 3 times more without an increase in the CalB transcript level, compared with the wild-type.
ESTHER : Kim_2007_J.Microbiol.Biotechnol_17_1308
PubMedSearch : Kim_2007_J.Microbiol.Biotechnol_17_1308
PubMedID: 18051599

Title : Synthesis, biological evaluation and structural determination of beta-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors - Ahn_2007_Bioorg.Med.Chem.Lett_17_2622
Author(s) : Ahn JH , Shin MS , Jun MA , Jung SH , Kang SK , Kim KR , Rhee SD , Kang NS , Kim SY , Sohn SK , Kim SG , Jin MS , Lee JO , Cheon HG , Kim SS
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :2622 , 2007
Abstract : Inhibitors of dipeptidyl peptidase IV (DPP-IV) have been shown to be effective treatments for type 2 diabetes. A series of beta-aminoacyl-containing cyclic hydrazine derivatives were synthesized and evaluated as DPP-IV inhibitors. One member of this series, (R)-3-amino-1-(2-benzoyl-1,2-diazepan-1-yl)-4-(2,4,5-trifluorophenyl)butan-1-one (10f), showed potent in vitro activity, good selectivity and in vivo efficacy in mouse models. Also, the binding mode of compound 10f was determined by X-ray crystallography.
ESTHER : Ahn_2007_Bioorg.Med.Chem.Lett_17_2622
PubMedSearch : Ahn_2007_Bioorg.Med.Chem.Lett_17_2622
PubMedID: 17331715
Gene_locus related to this paper: human-DPP4

Title : Molecular characterization of extracellular medium-chain-length poly(3-hydroxyalkanoate) depolymerase genes from Pseudomonas alcaligenes strains - Kim_2005_J.Microbiol_43_285
Author(s) : Kim DY , Kim HC , Kim SY , Rhee YH
Ref : J Microbiol , 43 :285 , 2005
Abstract : A bacterial strain M4-7 capable of degrading various polyesters, such as poly(epsilon-caprolactone), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(3-hydroxyoctanoate), and poly(3-hydroxy-5-phenylvalerate), was isolated from a marine environment and identified as Pseudomonas alcaligenes. The relative molecular mass of a purified extracellular medium-chain-length poly(3-hydroxyalkanoate) (MCL-PHA) depolymerase (PhaZ(PalM4-7)) from P. alcaligenes M4-7 was 28.0 kDa, as determined by SDS-PAGE. The PhaZ(PalM4-7) was most active in 50 mM glycine-NaOH buffer (pH 9.0) at 35 degrees C. It was insensitive to dithiothreitol, sodium azide, and iodoacetamide, but susceptible to p-hydroxymercuribenzoic acid, N-bromosuccinimide, acetic anhydride, EDTA, diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, Tween 80, and Triton X-100. In this study, the genes encoding MCL-PHA depolymerase were cloned, sequenced, and characterized from a soil bacterium, P. alcaligenes LB19 (Kim et al., 2002, Biomacromolecules 3, 291-296) as well as P. alcaligenes M4-7. The structural gene (phaZ(PalLB19)) of MCL-PHA depolymerase of P. alcaligenes LB19 consisted of an 837 bp open reading frame (ORF) encoding a protein of 278 amino acids with a deduced M((r)) of 30,188 Da. However, the MCL-PHA depolymerase gene (phaZ(PalM4-7)) of P. alcaligenes M4-7 was composed of an 834 bp ORF encoding a protein of 277 amino acids with a deduced Mr of 30,323 Da. Amino acid sequence analyses showed that, in the two different polypeptides, a substrate-binding domain and a catalytic domain are located in the N-terminus and in the C-terminus, respectively. The PhaZ(PalLB19) and the PhaZ(PalM4-7) commonly share the lipase box, GISSG, in their catalytic domains, and utilize 111Asn and 110Ser residues, respectively, as oxyanions that play an important role in transition-state stabilization of hydrolytic reactions.
ESTHER : Kim_2005_J.Microbiol_43_285
PubMedSearch : Kim_2005_J.Microbiol_43_285
PubMedID: 15995648
Gene_locus related to this paper: pseac-q6ufw4 , pseal-PHAZ , psefl-phaz

Title : Effects of physostigmine on the pharmacokinetics of intravenous parathion in rats - Hurh_2000_Biopharm.Drug.Dispos_21_331
Author(s) : Hurh E , Lee EJ , Kim YG , Kim SY , Kim SH , Kim YC , Lee MG
Ref : Biopharmaceutics & Drug Disposition , 21 :331 , 2000
Abstract : It was reported that the area under the plasma concentration-time curve from time zero to time infinity (AUC) of parathion was significantly smaller, and the time-averaged total body clearance (Cl) of parathion was significantly faster after intravenous administration of parathion to rats pretreated with dexamethasone than those in control rats. This was supported by significantly faster intrinsic clearance of parathion to form paraoxon in hepatic microsomal fraction of rats pretreated with dexamethasone. The above data suggested that parathion was metabolized to paraoxon by dexamethasone-inducible hepatic cytochrome P450 (CYP) 3A in rats. The purpose of this study is to explain the protective effects of physostigmine against paraoxon toxicity by suppressing CYP3A, and hence, decreasing formation of a toxic metabolite, paraoxon. The pharmacokinetic changes of parathion and paraoxon were investigated after intravenous administration of parathion, 3 mg/kg, to control Sprague-Dawley rats, and the rats pretreated with physostigmine (100 microg/kg, intraperitoneal injection 30 min before parathion administration). After a 1-min intravenous infusion of parathion to rats pretreated with physostigmine, the AUC of parathion (60.4 compared with 73.7 microg min/mL) was significantly greater, Cl of parathion (49.7 compared with 40.7 mL/min/kg) was significantly slower, and amount of paraoxon recovered from liver, mesentery and large intestine at 5 min was smaller than those in control rats. Based on in vitro rat hepatic microsomal studies, physostigmine inhibited significantly the erythromycin N-demethylase activity (1.03 compared with 0.924 nmol/mg protein/min), mainly mediated by hepatic cytochrome P450 3A in rats. The above data suggested that the formation of paraoxon was inhibited in rats pretreated with physostigmine by inhibiting CYP3A.
ESTHER : Hurh_2000_Biopharm.Drug.Dispos_21_331
PubMedSearch : Hurh_2000_Biopharm.Drug.Dispos_21_331
PubMedID: 11514953