• Biomolecules & Therapeutics
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• 제14권2호
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• pp.75-82
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• 2006

Synaptic plasticity, which is a long lasting change in synaptic efficacy, underlies many neural processes like learning and memory. It has long been acknowledged that new protein synthesis is essential for both the expression of synaptic plasticity and memory formation and storage. Most of the research interests in this field have focused on the events regulating transcriptional activation of gene expression from the cell body and nucleus. Considering extremely differentiated structural feature of a neuron in CNS, a neuron should meet a formidable task to overcome spatial and temporal restraints to deliver newly synthesized proteins to specific activated synapses among thousands of others, which are sometimes several millimeters away from the cell body. Recent advances in synaptic neurobiology has found that almost all the machinery required for the new protein translation are localized inside or at least in the vicinity of postsynaptic compartments. These findings led to the hypothesis that dormant mRNAs are translationally activated locally at the activated synapse, which may enable rapid and delicate control of new protein synthesis at activated synapses. In this review, we will describe the mechanism of local translational control at activated synapses focusing on the role of cytoplasmic polyadenylation of dormant mRNAs.

• Biomolecules & Therapeutics
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• 제19권2호
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• pp.181-186
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• 2011

Beta-amyloid (A${\beta}$) is considered as one of the major causes of Alzheimer's disease. This study examined the neuroprotective effects of chlorogenic acid, a naturally occurring polyphenol which is distributed widely in plants, fruits and vegetables, against A${\beta}$-induced toxicity. A${\beta}$ decreased significantly the viability of PC12 cells. This was accompanied by an increase in the intracellular calcium levels and cleaved caspase-3. In addition, A${\beta}$ induced an increase in Bax, and a decrease in Bcl-2 compared to the controls. However, a pre-treatment with chlorogenic acid rescued the PC12 cells from A${\beta}$ by attenuating the elevated intracellular calcium levels and reducing the levels of the apoptosis related proteins, including caspase-3, Bcl-2 and Bax. These results suggest that the protective effects of chlorogenic acid are, at least in parts, by attenuating the intracellular calcium influx and reducing apoptosis induced by A${\beta}$.

• Bulletin of the Korean Chemical Society
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• 제35권10호
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• pp.2985-2989
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• 2014

Autophagy is a self-digestion process in which intracellular structures are degraded in response to stress. Notably, prolonged autophagy leads to cell death. In this study, we investigated whether CX-4945, an orally available protein kinase 2 (CK2) inhibitor, induces autophagic cell death in human cervical cancer-derived HeLa cells and in human prostate cancer-derived LNCaP cells. CX-4945 treatment of both cell lines resulted in the formation of autophagosomes, in the conversion of microtubule-associated protein 1 light chain 3 (LC3), and in down-regulation of the Akt-mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (S6K) signaling cascade. Thus, pharmacologic inhibition of CK2 by CX-4945 induced autophagic cell death in human cancer cells by down-regulating Akt-mTOR-S6K. These results suggest that autophagy-inducing agents have potential as anti-cancer drugs.

• Korean Journal of Acupuncture
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• 제29권2호
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• pp.224-238
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• 2012

Objectives : From mechanism studies using animal models to high-level evidence based research such as randomized controlled trials or systematic reviews, various acupuncture studies have been performed. Nevertheless, the current research appears insufficient to satisfy clinicians' needs. We aimed at investigating clinicians' perception on the translational research and suggesting ways of symbiosis between basic research and clinical practice. Methods : Data were collected using a web-based questionnaire made available to Korean medicine doctors who were informed through social networking service or e-mail. The survey participants indicated their awareness of acupuncture research and their thoughts on the applicability of research in practice. Results : Forty-seven clinicians completed the survey. While most respondents agreed that acupuncture research is very important, only 40% of them answered that the results of acupuncture research are useful to their own practice. In more than half of those who responded to the survey, the current acupuncture research is not viewed as reflecting clinical practice very much. Respondents agreed that acupuncture research should be based on clinical practice, and they recognized the need to collect valid clinical data from real-world practice. Also, as many as 77% of clinicians had no scruple to participate in research programs. Conclusions : There is no doubt among practitioners that acupuncture research is necessary. More importantly, practice-based research remains essential in order to feed-back research outcomes to clinical practice. Communications and academic exchanges between clinicians and researchers can mutually benefit research and practice with better information, resulting in symbiosis.

• Molecules and Cells
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• 제41권5호
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• pp.486-494
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• 2018

Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors-symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphorylated $CaMKII{\alpha}$ were significantly decreased while the expression level of $CaMKII{\alpha}$ was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.

• Nutrition Research and Practice
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• 제8권4호
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• pp.404-409
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• 2014

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

• 한국생물물리학회:학술대회논문집
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• 한국생물물리학회 1999년도 학술발표회 진행표 및 논문초록
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• pp.29-29
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• 1999

Diabetic cardiomyopathy has been suggested to be caused by the intracellular Ca$\^$2＋/ overload in the myocardium. We have investigated the possible mechanism of the functional defect of cardiac sarcoplasmic reticulum (SR) in diabetic rats with respect to Ca$\^$2＋/-ATPase and phospholamban (PLB) at the transcriptional and translational levels.(omitted)

• 대한병리학회지
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• 제52권6호
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• pp.420-424
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• 2018

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.5977-5982
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• 2014

Research over the years has progressively shown substantial broadening of the tumor necrosis factor alpha-related apoptosis-inducing ligand (TRAIL)-mediated signaling landscape. Increasingly it is being realized that pancreatic cancer is a multifaceted and genomically complex disease. Suppression of tumor suppressors, overexpression of oncogenes, epigenetic silencing, and loss of apoptosis are some of the extensively studied underlying mechanisms. Rapidly accumulating in vitro and in vivo evidence has started to shed light on the resistance mechanisms in pancreatic cancer cells. More interestingly a recent research has opened new horizons of miRNA regulation by DR5 in pancreatic cancer cells. It has been shown that DR5 interacts with the core microprocessor components Drosha and DGCR8, thus impairing processing of primary let-7. Xenografting DR5 silenced pancreatic cancer cells in SCID-mice indicated that there was notable suppression of tumor growth. There is a paradigm shift in our current understanding of TRAIL mediated signaling in pancreatic cancer cells that is now adding new layers of concepts into the existing scientific evidence. In this review we have attempted to provide an overview of recent advances in TRAIL mediated signaling in pancreatic cancer as evidenced by findings of in vitro and in vivo analyses. Furthermore, we discuss nanotechnological advances with emphasis on PEG-TRAIL and four-arm PEG cross-linked hyaluronic acid (HA) hydrogels to improve availability of TRAIL at target sites.

• Molecules and Cells
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• 제41권2호
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• pp.127-133
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• 2018

Chromatin remodeling factors are involved in many cellular processes such as transcription, replication, and DNA damage response by regulating chromatin structure. As one of chromatin remodeling factors, remodeling and spacing factor 1 (RSF1) is recruited at double strand break (DSB) sites and regulates ataxia telangiectasia mutated (ATM) -dependent checkpoint pathway upon DNA damage for the efficient repair. RSF1 is overexpressed in a variety of cancers, but regulation of RSF1 levels remains largely unknown. Here, we showed that protein levels of RSF1 chromatin remodeler are temporally upregulated in response to different DNA damage agents without changing the RSF1 mRNA level. In the absence of SNF2h, a binding partner of RSF1, the RSF1 protein level was significantly diminished. Intriguingly, the level of RSF1-3SA mutant lacking ATM-mediated phosphorylation sites significantly increased, and upregulation of RSF1 levels under DNA damage was not observed in cells overexpressing ATM kinase. Furthermore, failure in the regulation of RSF1 level caused a significant reduction in DNA repair, whereas reconstitution of RSF1, but not of RSF1-3SA mutants, restored DSB repair. Our findings reveal that temporal regulation of RSF1 levels at its post-translational modification by SNF2h and ATM is essential for efficient DNA repair.