• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.6.1-6.12
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• 2018

Morphine tolerance remains a challenge in the management of chronic pain in the clinic. As shown in our previous study, the dopamine D2 receptor (D2DR) expressed in spinal cord neurons might be involved in morphine tolerance, but the underlying mechanisms remain to be elucidated. In the present study, selective spinal D2DR blockade attenuated morphine tolerance in mice by inhibiting phosphatidylinositol 3 kinase (PI3K)/serine-threonine kinase (Akt)-mitogen activated protein kinase (MAPK) signaling in a ${\mu}$ opioid receptor (MOR)-dependent manner. Levo-corydalmine (l-CDL), which exhibited micromolar affinity for D2DR in D2/CHO-K1 cell lines in this report and effectively alleviated bone cancer pain in our previous study, attenuated morphine tolerance in rats with chronic bone cancer pain at nonanalgesic doses. Furthermore, the intrathecal administration of l-CDL obviously attenuated morphine tolerance, and the effect was reversed by a D2DR agonist in mice. Spinal D2DR inhibition and l-CDL also inhibited tolerance induced by the MOR agonist DAMGO. l-CDL and a D2DR small interfering RNA (siRNA) decreased the increase in levels of phosphorylated Akt and MAPK in the spinal cord; these changes were abolished by a PI3K inhibitor. In addition, the activated Akt and MAPK proteins in mice exhibiting morphine tolerance were inhibited by a MOR antagonist. Intrathecal administration of a PI3K inhibitor also attenuated DAMGO-induced tolerance. Based on these results, l-CDL antagonized spinal D2DR to attenuate morphine tolerance by inhibiting PI3K/Akt-dependent MAPK phosphorylation through MOR. These findings provide insights into a more versatile treatment for morphine tolerance.

• Animal Bioscience
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• v.34 no.11
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• pp.1739-1748
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• 2021

Objective: In recent years, long noncoding RNAs (lncRNAs) have been identified in many species, and some of them have been shown to play important roles in muscle development and myogenesis. However, the differences in lncRNAs between Kazakh cattle and Xinjiang brown cattle remain undefined; therefore, we aimed to confirm whether lncRNAs are differentially expressed in the longissimus dorsi between these two types of cattle and whether differentially expressed lncRNAs regulate muscle differentiation. Methods: We used RNA-seq technology to identify lncRNAs in longissimus muscles from these cattle. The expression of lncRNAs were analyzed using StringTie (1.3.1) in terms of the fragments per kilobase of transcript per million mapped reads values of the encoding genes. The differential expression of the transcripts in the two samples were analyzed using the DESeq R software package. The resulting false discovery rate was controlled by the Benjamini and Hochberg's approach. KOBAS software was utilized to measure the expression of different genes in Kyoto encyclopedia of genes and genomes pathways. We randomly selected eight lncRNA genes and validated them by quantitative reverse transcription polymerase chain reaction (RT-qPCR). Results: We found that 182 lncRNA transcripts, including 102 upregulated and 80 downregulated transcripts, were differentially expressed between Kazakh cattle and Xinjiang brown cattle. The results of RT-qPCR were consistent with the sequencing results. Enrichment analysis and functional annotation of the target genes revealed that the differentially expressed lncRNAs were associated with the mitogen-activated protein kinase, Ras, and phosphatidylinositol 3-kinase (PI3k)/Akt signaling pathways. We also constructed a lncRNA/mRNA coexpression network for the PI3k/Akt signaling pathway. Conclusion: Our study provides insights into cattle muscle-associated lncRNAs and will contribute to a more thorough understanding of the molecular mechanism underlying muscle growth and development in cattle.

• Molecules and Cells
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• v.26 no.2
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• pp.121-130
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• 2008

Methamphetamine, a commonly used addictive drug, is a powerful addictive stimulant that dramatically affects the CNS. Repeated METH administration leads to a rewarding effect in a state of addiction that includes sensitization, dependence, and other phenomena. It is well known that susceptibility to the development of addiction is influenced by sources of reinforcement, variable neuroadaptive mechanisms, and neurochemical changes that together lead to altered homeostasis of the brain reward system. These behavioral abnormalities reflect neuroadaptive changes in signal transduction function and cellular gene expression produced by repeated drug exposure. To provide a better understanding of addiction and the mechanism of the rewarding effect, it is important to identify related genes. In the present study, we performed gene expression profiling using microarray analysis in a reward effect animal model. We also investigated gene expression in four important regions of the brain, the nucleus accumbens, striatum, hippocampus, and cingulated cortex, and analyzed the data by two clustering methods. Genes related to signaling pathways including G-protein-coupled receptor-related pathways predominated among the identified genes. The genes identified in our study may contribute to the development of a gene modeling network for methamphetamine addiction.

• Asian-Australasian Journal of Animal Sciences
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• v.20 no.2
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• pp.153-159
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• 2007

In our previous study, overexpression of extracellular proteinase inhibitor (Expi) gene accelerated apoptosis of mammary epithelial cells, and induced expression of B cell activating factor (BAFF) gene. In this study, we found induction of BAFF-receptor (BAFF-R) gene expression in the Expi-transfected cells. A proliferation-inducing ligand (APRIL) gene is another TNF family member and the closest known relative of BAFF. We found induction of APRIL gene expression in the Expi-overexpressed apoptotic cells. NF-${\kappa}$B gene was also induced in the Expi-overexpressed cells. Expression patterns of BAFF and APRIL pathway-related genes were examined in in vivo mouse mammary gland at various reproductive stages. Expression levels of BAFF gene were very low at early pregnancy, increased from mid-pregnancy, and peaked at lactation, and thereafter decreased at involution stages of mammary gland. Expression of BAFF-R gene was highly induced in involution stages compared to lactation stages. Thus, expression patterns of BAFF-R gene were correlated to apoptotic status of mammary gland: active apoptosis of mammary epithelial cells occurs at involution stage of mammary gland. Expression levels of NF-${\kappa}$B gene were higher in involution stages compared to lactation stages. We analyzed mRNA levels of bcl-2 family genes from different stages of mammary development. Bcl-2 gene expression was relatively constant during lactation and involution stages. There was a slight increase in bcl-xL gene expression in involution stages compared to lactation state. Bax gene expression was highly induced in involution stage. Our results suggest that signaling pathways activated by both BAFF and ARRIL in mammary gland point towards NF-${\kappa}$B activation which causes upregulation of bax.

• Proceedings of the KSR Conference
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• 2011.10a
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• pp.165-171
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• 2011

A Consider the dead man's switch installed in each and every locomotive cab, which support operational safety on railways around the world. The concept is very simple - every 150 to 180 seconds an illuminated push-button demands to be acknowledged so as to know that the Train Driver is alive and active. In the absence of a response over a period of minutes, the vigilance control will automatically apply the train brakes and bring the train to a stand. If we multiply the resetting of the vigilance control 60 times per hour by a 10-hour shift it equals 600 presses of the button during the shift that a Train Driver must pay attention to and acknowledge. This adds a fair bit of pressure on the train driver's job, particularly when he/she is driving through stations, with passengers moving about on platforms in an environment of complex signaling arrangements - all the while looking out for restricting signals. From this perspective, the Vigilance System's demand to be acknowledged every 150/180 seconds is disturbing and can unnecessarily take a driver's attention away from what is happening outside the confines of the cab. A much more dramatic situation can happen when a train driver is driving hour after hour at night when, by Mother's Nature request - people need to sleep. Experience and research shows that the the dead man's switch can be pressed by train driver in a state of deep relaxation and 'micro-sleep'. The vigilance control system which is applied to reduce the drive load considering bio-response multiple unit train is proposed.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.69-79
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• 2020

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

• Korean Journal of Plant Resources
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• v.31 no.3
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• pp.268-273
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• 2018

Hepatic ischemia-reperfusion injury (HIRI) is linked with high mortality rate. Several agents have been developed so far to reduce the risk of HIRI. In this study, we investigated the effects of combined treatment of Ginko biloba leaves extract and vitamin C (GLEVC) on hepatic ischemia-reperfusion injury. To explore the protective effects of GLEVC on HIRI rats model were tested. After the development of HIRI by using clamping method rats were then randomly divided into four groups. Different doses of GLEVC were administered in HIRI rat model. The level of ALT, AST, SOD and MDA content in serum were detected in HIRI groups. Moreover, the activity of SOD, content of MDA, and GSH in hepatic tissue were also examined. Bcl-2 and Bax protein expression were detected by immunohistochemical staining method. Compared with sham group, GLEVC has the protective effect on the HIRI-induced model. Level of ALT, AST, and MDA in blood were significantly lower in GLEVC group compared with HIRI-induced group. Moreover, SOD activity and GSH were increased in GLEVC group whereas MDA content was reduced by GLEVC treatment. Furthermore, HIRI-induced Bax protein was reduced upon GLEVC treatment, whereas Bcl-2 protein expression was enhanced. These results demonstrate that GLEVC treatment may provide potential ameliorative therapy by reducing damaged signaling mechanism in hepatic ischemia/reperfusion injury model.

• Journal of Korea Multimedia Society
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• v.8 no.3
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• pp.372-378
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• 2005

When a mobile node changes a sub network using Mobile IP, it must register its current location to the home agent. If a mobile node is far from its home network, the Binding Update (BU) time delay is longer and affects its connection state. To solve such a BU delay problem, a new component in HMIPv6, called MAP, supports the mobility of mobile node to reduce the signaling delay in handover However, in hierarchical MAP architecture, the register concentration to a specific MAP may be occurred, which affects the network management wholly. In this paper, we propose a MAP selection scheme based on ioad balancing by the mobility factor and the traffic property. By the mobility factor and the traffic property, a mobile node can select a adequate MAP on its mobility factor and traffic characteristic.

• BMB Reports
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• v.44 no.4
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• pp.267-272
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• 2011

ZAS3 is a large zinc finger transcription repressor that binds the ${\kappa}B$-motif via two signature domains of ZASN and ZASC. A loss-of-function study showed that lack of ZAS3 protein induced accelerated cell proliferation and tumorigenesis. Conversely, gain-of-function studies showed that ZAS3 repressed $NF{\kappa}B$-activated transcription by competing with $NF{\kappa}B$ for the ${\kappa}B$-motif. Based on these observations, we hypothesize that ZAS3 promotes apoptosis by interrupting anti-apoptotic activity of $NF{\kappa}B$. Here, we present evidence that upon $TNF{\alpha}$ stimulation, ZAS3 inhibits $NF{\kappa}B$-mediated cell survival and promotes caspase-mediated apoptosis. The inhibitory effect of ZAS3 on $NF{\kappa}B$ activity is mediated by neither direct association with $NF{\kappa}B$ nor disrupting nuclear localization of $NF{\kappa}B$. Instead, ZAS3 repressed the expression of two key anti-apoptotic genes of $NF{\kappa}B$, TRAF1 and TRAF2, thereby sensitizing cells to $TNF{\alpha}$-induced cell death. Taken together, our data suggest that ZAS3 is a tumor suppressor gene and therefore serves as a novel therapeutic target for developing anti-cancer drugs.

• The Journal of the Korea institute of electronic communication sciences
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• v.14 no.6
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• pp.1061-1068
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• 2019

Cooperative networks transmit signals form the source node to the destination node via several relay node where the combining and demodulation of relay aided signals provide the benefit of performance enhancement and data rate increment. In general, a repetitive manner transmission scheme in which the received signal from the source node is amplified/re-generated and forward to the destination node is widely used. In this paper, we analyzed the performance of cooperative networks using the mixed transmission scheme. The conventional modulation scheme is used in the source-relay links, and space-time code is applied in the relay-destination links. To reduce the complexity of the overall system, we adopt differential modulation which bypasses channel state information. We analyze bit error rate (BER) of the proposed system by considering the number of relay nodes, and the performances depending on the strength of transmission signal in the source-relays and rely-destination links are compared. In addition, we also discuss the system performance with the signal strength and the number of relay nodes simultaneously.