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Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation
Chu, Kon,Lee, Soon-Tae,Sinn, Dong-In,Ko, Song-Yi,Kim, Eun-Hee,Kim, Jeong-Min,Kim, Se-Jeong,Park, Dong-Kyu,Jung, Keun-Hwa,Song, Eun-Cheol,Lee, Sang Kun,Kim, Manho,Roh, Jae-Kyu Ovid Technologies Wolters Kluwer -American Heart A 2007 Stroke Vol.38 No.1
주건 ( Kon Chu ),신동인 ( Dong In Sin ),노재규 ( Jae Kyu Roh ) 한국조직공학과 재생의학회 2005 조직공학과 재생의학 Vol.2 No.4
Neural stem cells (NSCs) are the most primordial and least committed cells of the nervous system, the cells that exist before regional/functional specification develops. NSCs have the following functional properties: (1) multipotency, (2) the ability to populate a developing region and/or repopulate an ablated or degenerated region of the nervous system with appropriate cell types, (3) the ability to be serially transplanted, and (4) Self-renewal. Recent experiments have shown that NSCs can be transplanted in many neurological disorder models (ischemia, hemorrhage, epilepsy, Parkinsonism, brain tumor, Huntington`s disease, multiple sclerosis, peripheral neuropathy, spinal cord injury, and motor neuron diseases) and can ameliorate the pathogenic insult. This review focuses on the transplantation efficacy in stroke, and optimization strategy for achieving better outcome, considering the pathogenesis of specific diseases.
Chu, Hyosub,Jeong, Jae Cheol,Kim, Wook‐,Jin,Chung, Dong Min,Jeon, Hyo Kon,Ahn, Young Ock,Kim, Sun Ha,Lee, Haeng‐,Soon,Kwak, Sang‐,Soo,Kim, Cha Young Blackwell Publishing Ltd 2013 Physiologia Plantarum Vol.148 No.2
<P>R2R3‐type MYB transcription factors (TFs) play important roles in transcriptional regulation of anthocyanins. The R2R3‐type IbMYB1 is known to be a key regulator of anthocyanin biosynthesis in the storage roots of sweetpotato. We previously showed that transient expression of <I>IbMYB1a</I> led to anthocyanin pigmentation in tobacco leaves. In this article, we generated transgenic <I>Arabidopsis</I> plants expressing the <I>IbMYB1a</I> gene under the control of <I>CaMV 35S</I> promoter, and the sweetpotato <I>SPO</I> and <I>SWPA2</I> promoters. Overexpression of <I>IbMYBa</I> in transgenic <I>Arabidopsis</I> produced strong anthocyanin pigmentation in seedlings and generated a deep purple color in leaves, stems and seeds. Reverse transcription‐polymerase chain reaction analysis showed that <I>IbMYB1a</I> expression induced upregulation of several structural genes in the anthocyanin biosynthetic pathway, including <I>4CL</I>, <I>CHI</I>, <I>F3′H</I>, <I>DFR</I>, <I>AGT</I>, <I>AAT</I> and <I>GST</I>. Furthermore, overexpression of <I>IbMYB1a</I> led to enhanced expression of the <I>AtTT8</I> (<I>bHLH</I>) and <I>PAP1</I>/<I>AtMYB75</I> genes. high‐performance liquid chromatography analysis revealed that <I>IbMYB1a</I> expression led to the production of cyanidin as a major core molecule of anthocyanidins in <I>Arabidopsis</I>, as occurs in the purple leaves of sweetpotato (cv. Sinzami). This result shows that the IbMYB1a TF is sufficient to induce anthocyanin accumulation in seedlings, leaves, stems and seeds of <I>Arabidopsis</I> plants.</P>
A cell‐free extract from human adipose stem cells protects mice against epilepsy
Jeon, Daejong,Chu, Kon,Lee, Soon‐,Tae,Jung, Keun‐,Hwa,Kang, Kyung‐,Mook,Ban, Jae‐,Joon,Kim, Soyun,Seo, Jin Soo,Won, Chong‐,Hyun,Kim, Manho,Lee, Sang Kun,Roh, Jae‐,K Blackwell Publishing Ltd 2011 Epilepsia Vol.52 No.9
<P><B>Summary</B></P><P><B>Purpose: </B> Stem cell–based therapies are being considered for various neurologic diseases, such as epilepsy. Recent studies have suggested that some effects of transplanted stem cells are due to bystander effects that modulate the host environment, rather than direct effects of cell replacement. The extract from human adipose stem cells (ASCs) that secrete multiple growth factors including cytokines and chemokines may be a potential source of bystander effects for the treatment of epilepsy, in which inflammation is thought to play an important role. Here, we investigated the effects of a cytosolic extract of human ASCs (ASCs‐E) in a mouse model of epilepsy.</P><P><B>Methods: </B> Human ASCs‐E, boiled ASCs‐E, or fibroblast‐extract (fibroblast‐E) was intraperitoneally administrated to C57BL/6 mice 15 min before pilocarpine‐induced status epilepticus (SE) or during chronic epileptic stage. Blood–brain barrier (BBB) leakage was evaluated by measuring Evans blue dye extravasation. Spontaneous recurrent seizure (SRS) was investigated by long‐term video–electroencephalography (EEG) monitoring. The mice performed elevated plus maze, open‐field, light/dark transition, and novel object recognition tasks.</P><P><B>Key Findings: </B> Acute application of human ASCs‐E before SE led to earlier attenuation of seizure spike activities after treatment with diazepam, reduction of BBB leakage, and inhibition of the development of epilepsy. Human ASCs‐E treatment (for 7 days) during the chronic epileptic stage suppressed SRS and reduced abnormal epileptic behavioral phenotypes. However, neither boiled ASCs‐E nor fibroblast‐E had any effects in the experimental epilepsy model.</P><P><B>Significance: </B> Our results demonstrate that human ASCs‐E prevents or inhibits epileptogenesis and SRS in mice. They also suggest a stem cell–based, noninvasive therapy for the treatment of epilepsy.</P>
Circulating endothelial microparticles as a marker of cerebrovascular disease
Jung, Keun-Hwa,Chu, Kon,Lee, Soon-Tae,Park, Hee-Kwon,Bahn, Jae-Jun,Kim, Dong-Hyun,Kim, Jin-Hee,Kim, Manho,Kun Lee, Sang,Roh, Jae-Kyu Wiley Subscription Services, Inc., A Wiley Company 2009 Annals of Neurology Vol.66 No.2
<B>Objective</B><P>Circulating endothelial microparticles (EMPs) have been reported to reflect vascular damage. Detailed profiling of these blood endothelial markers may adumbrate the pathogenesis of stroke or enable determination of the risk for stroke. We investigated EMP profiles in patients at risk for cerebrovascular disease.</P><B>Methods</B><P>We prospectively examined 348 consecutive patients: 73 patients with acute stroke and 275 patients with vascular risk factors but no stroke events. We quantified various types of EMPs by flow cytometry using CD31, CD42b, annexin V (AV), and CD62E antibodies in the peripheral blood of patients. This method allowed fractionation of CD31<SUP>+</SUP>/CD42b<SUP>−</SUP>, CD31<SUP>+</SUP>/AV<SUP>+</SUP>, and CD62E<SUP>+</SUP> EMPs. Clinical and laboratory factors associated with EMPs were assessed.</P><B>Results</B><P>Recent ischemic episodes were found to be more strongly associated with greater CD62E<SUP>+</SUP> EMP levels than with levels of other phenotypes. Increased National Institutes of Health Stroke Scale scores and infarct volumes in acute stroke patients were significantly associated with greater CD62E<SUP>+</SUP> EMP levels. In the risk factor group, patients with extracranial arterial stenosis had greater CD62E<SUP>+</SUP> EMP levels, whereas those with intracranial arterial stenosis had greater CD31<SUP>+</SUP>/CD42b<SUP>−</SUP> and CD31<SUP>+</SUP>/AV<SUP>+</SUP> EMP levels. The ratio of CD62E<SUP>+</SUP> to CD31<SUP>+</SUP>/CD42b<SUP>−</SUP> or CD31<SUP>+</SUP>/AV<SUP>+</SUP> EMP level significantly discriminated extracranial and intracranial arterial stenosis.</P><B>Interpretation</B><P>Circulating EMP phenotypic profiles reflect distinct phenotypes of cerebrovascular disease and are markers of vascular pathology and an increased risk for ischemic stroke. Ann Neurol 2009;66:191–199</P>
Cognitive improvement by ginseng in Alzheimer's disease
Lee, Soon-Tae,Chu, Kon,Kim, Jeong-Min,Park, Hyun-Jeong,Kim, Man-Ho The Korean Society of Ginseng 2007 Journal of Ginseng Research Vol.31 No.1
Ginseng shows protective and trophic effects in neurodegenerative diseases in experimental models, and showed cognitive improvement in normal population. To investigate the efficacy of ginseng in patients with Alzheimer's disease, patients, who met NINDS-ADRDA criteria for AD were studied Subjects were randomly assigned to ginseng group and control group, and ginseng group was treated with Korean white ginseng powder (4.5 g/day) for 12 weeks. Efficacy variables included changes in mini-mental status exam (MMSE) and cognitive subscales of Alzheimer's disease assessment scale (ADAS-cog) at 4 weeks and 12 weeks. Baseline MMSE and ADAS scores showed no difference between the two groups. Results showed that ginseng improved ADAS-cog compared to the control group at 12 weeks (p<0.05). MMSE was also increased by ginseng treatment compared to the control at 12 weeks (p<0.01). This study suggests the symptomatic efficacy of ginseng in patients with Alzheimer's disease.
Risk of Macrovascular Complications in Type 2 Diabetes Mellitus: Endothelial Microparticle Profiles
Jung, Keun-Hwa,Chu, Kon,Lee, Soon-Tae,Bahn, Jae-Jun,Kim, Jin-Hee,Kim, Manho,Lee, Sang Kun,Roh, Jae-Kyu S. Karger AG 2011 Cerebrovascular Diseases Vol.31 No.5
<P><I>Background:</I> While the adverse impact of diabetes on microvessels is well known, the risks of macroangiopathy are less well recognized. Here, we determine the differential risk and endothelial microparticle (EMP) profile of vascular complications in type 2 diabetes mellitus. <I>Methods:</I> Macroangiopathy was evaluated for cerebrovascular disease, coronary artery disease and peripheral artery disease; microangiopathy was evaluated for retinopathy, nephropathy and peripheral neuropathy. Clinical and laboratory factors were compared among 149 patients with no vascular complications or with microangiopathic and/or macroangiopathic complications. EMPs were also examined by flow cytometry using CD31, CD42b, annexin V (AV), and CD62E antibodies in the peripheral blood of patients. <I>Results:</I> Diabetes of long duration, an elevated hemoglobin A1c (HbA1c) and concomitant hypertension were significantly associated with the occurrence of vascular complications. Dyslipidemia and a high body mass index were significantly associated with macroangiopathy, while diabetes of long duration and a high concentration of HbA1c were associated with microangiopathy. The EMP (CD31+/CD42b-, CD31+/AV+) levels were higher in patients with macroangiopathy than in patients with microangiopathy and no complications. The EMP level was also independently associated with macroangiopathy in diabetic patients. <I>Conclusions:</I> Microangiopathy and macroangiopathy in diabetic patients appear to have a different pathophysiological basis. The measurement of EMP would be helpful to differentiate the risk of diabetic vascular complications.</P><P>Copyright © 2011 S. Karger AG, Basel</P>