• Journal of Gastric Cancer
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• v.17 no.4
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• pp.295-305
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• 2017

Purpose: We previously found that the histone methyltransferase suppressor of variegation, enhancer of zeste, trithorax and myeloid-nervy-deformed epidermal autoregulatory factor-1 domain-containing protein 3 (SMYD3) is a potential independent predictive factor or prognostic factor for overall survival in gastric cancer patients, but its roles seem to differ from those in other cancers. Therefore, in this study, the detailed functions of SMYD3 in cell proliferation and migration in gastric cancer were examined. Materials and Methods: SMYD3 was overexpressed or suppressed by transfection with an expression plasmid or siRNA, and a wound healing migration assay and Transwell assay were performed to detect the migration and invasion ability of gastric cancer cells. Additionally, an MTT assay and clonogenic assay were performed to evaluate cell proliferation, and a cell cycle analysis was performed by propidium iodide staining. Furthermore, the expression of genes implicated in the ataxia telangiectasia mutated (ATM) pathway and proteins involved in cell cycle regulation were detected by polymerase chain reaction and western blot analyses. Results: Compared with control cells, gastric cancer cells transfected with si-SMYD3 showed lower migration and invasion abilities (P<0.05), and the absence of SMYD3 halted cells in G2/M phase and activated the ATM pathway. Furthermore, the opposite patterns were observed when SMYD3 was elevated in normal gastric cells. Conclusions: To the best of our knowledge, this study provides the first evidence that the absence of SMYD3 could inhibit the migration, invasion, and proliferation of gastric cancer cells and halt cells in G2/M phase via the ATM-CHK2/p53-Cdc25C pathway. These findings indicated that SMYD3 plays crucial roles in the proliferation, migration, and invasion of gastric cancer cells and may be a useful therapeutic target in human gastric carcinomas.

• Journal of Ginseng Research
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• v.41 no.3
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• pp.330-338
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• 2017

Background: Ginsenoside Rh2 (G-Rh2) is a ginseng saponin that is widely investigated because of its remarkable antitumor activity. However, the molecular mechanism by which (20S) G-Rh2 triggers its functions and how target animals avoid its cytotoxic action remains largely unknown. Methods: Phage display was used to screen the human targets of (20S) G-Rh2. Fluorescence spectroscopy and UV-visible absorption spectroscopy were used to confirm the interaction of candidate target proteins and (20S) G-Rh2. Molecular docking was utilized to calculate the estimated free energy of binding and to structurally visualize their interactions. MTT assay and immunoblotting were used to assess whether human serum albumin (HSA), bovine serum albumin (BSA), and bovine serum can reduce the cytotoxic activity of (20S) G-Rh2 in HepG2 cells. Results: In phage display, (20S) G-Rh2-beads and (20R) G-Rh2-beads were combined with numerous kinds of phages, and a total of 111 different human complementary DNAs (cDNA) were identified, including HSA which had the highest rate. The binding constant and number of binding site in the interaction between (20S)-Rh2 and HSA were $3.5{\times}10^5M^{-1}$ and 1, and those in the interaction between (20S) G-Rh2 and BSA were $1.4{\times}10^5M^{-1}$ and 1. The quenching mechanism is static quenching. HSA, BSA and bovine serum significantly reduced the proapoptotic effect of (20S) G-Rh2. Conclusion: HSA and BSA interact with (20S) G-Rh2. Serum inhibited the activity of (20S) G-Rh2 mainly due to the interaction between (20S) G-Rh2 and serum albumin (SA). This study proposes that HSA may enhance (20S) G-Rh2 water solubility, and thus might be used as nanoparticles in the (20S) G-Rh2 delivery process.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.258-266
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• 2020

Background: Oxidative stress-induced cardiomyocytes apoptosis is a key pathological process in ischemic heart disease. Glutathione reductase (GR) reduces glutathione disulfide to glutathione (GSH) to alleviate oxidative stress. Ginsenoside Rb1 (GRb1) prevents the apoptosis of cardiomyocytes; however, the role of GR in this process is unclear. Therefore, the effects of GRb1 on GR were investigated in this study. Methods: The antiapoptotic effects of GRb1 were evaluated in H9C2 cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, annexin V/propidium iodide staining, and Western blotting. The antioxidative effects were measured by a reactive oxygen species assay, and GSH levels and GR activity were examined in the presence and absence of the GR inhibitor 1,3-bis-(2-chloroethyl)-1-nitrosourea. Molecular docking and molecular dynamics simulations were used to investigate the binding of GRb1 to GR. The direct influence of GRb1 on GR was confirmed by recombinant human GR protein. Results: GRb1 pretreatment caused dose-dependent inhibition of tert-butyl hydroperoxide-induced cell apoptosis, at a level comparable to that of the positive control N-acetyl-L-cysteine. The binding energy between GRb1 and GR was positive (-6.426 kcal/mol), and the binding was stable. GRb1 significantl reduced reactive oxygen species production and increased GSH level and GR activity without altering GR protein expression in H9C2 cells. Moreover, GRb1 enhanced the recombinant human GR protein activity in vitro, with a half-maximal effective concentration of ≈2.317 μM. Conversely, 1,3-bis-(2-chloroethyl)-1-nitrosourea co-treatment significantly abolished the GRb1's apoptotic and antioxidative effects of GRb1 in H9C2 cells. Conclusion: GRb1 is a potential natural GR agonist that protects against oxidative stress-induced apoptosis of H9C2 cells.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.247-257
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• 2020

Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1205-1215
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• 2015

Arbuscular mycorrhizal fungi (AMF) have great potential for assisting heavy metal hyperaccumulators in the remediation of contaminated soils. However, little information is available about the symbiosis of AMF associated with an antimony (Sb) accumulator plant under natural conditions. Therefore, the objective of this study was to investigate the colonization and molecular diversity of AMF associated with the Sb accumulator ramie (Boehmeria nivea) growing in Sb-contaminated soils. Four Sb mine spoils and one adjacent reference area were selected from Xikuangshan in southern China. PCR-DGGE was used to analyze the AMF community composition in ramie roots. Morphological identification was also used to analyze the species in the rhizosphere soil of ramie. Results obtained showed that mycorrhizal symbiosis was established successfully even in the most heavily polluted sites. From the unpolluted site Ref to the highest polluted site T4, the spore numbers and AMF diversity increased at first and then decreased. Colonization increased consistently with the increasing Sb concentrations in the soil. A total of 14 species were identified by morphological analysis. From the total number of species, 4 (29%) belonged to Glomus, 2 (14%) belonged to Acaulospora, 2 (14%) belonged to Funneliformis, 1 (7%) belonged to Claroideoglomus, 1 (7%) belonged to Gigaspora, 1 (7%) belonged to Paraglomus, 1 (7%) belonging to Rhizophagus, 1 (7%) belonging to Sclervocystis, and 1 (7%) belonged to Scutellospora. Some AMF sequences were present even in the most polluted site. Morphological identification and phylogenetic analysis both revealed that most species were affiliated with Glomus, suggesting that Glomus was the dominant genus in this AMF community. This study demonstrated that ramie associated with AMF may have great potential for remediation of Sb-contaminated soils.

• Journal of Korean Neurosurgical Society
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• v.30 no.7
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• pp.831-841
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• 2001

Objective : Somatosensory evoked potentials(SSEPs) have been used widely both experimentally and clinically to monitor the function of central nervous system and peripheral nervous system. Studies of SSEPs have reported the various recording techniques and patterns of SSEP. The previous SSEP studies used scalp recording electrodes, showed mean vector potentials which included relatively constant brainstem potentials(far-field potentials) and unstable thalamocortical pathway potentials(near-field potentials). Even in invasive SSEP recording methods, thalamocortical potentials were variable according to the kinds, depths, and distance of two electrodes. So they were regarded improper method for monitoring of upper level of brainstem. The present study was conducted to investigate the characteristics of somatosensory evoked field potentials(SSEFPs) of the cerebral cortex that evoked by hindlimb stimulation using ball electrode and the pathways of SSEFP by recording the potentials simultaneously in the cortex, VPL nucleus of thalamus, and nucleus gracilis. Methods : In the first experiment, a specially designed recording electrode was inserted into the cerebral cortex perpendicular to the cortical surface in order to recording the constant cortical field potentials and SSEFPs mapped from different areas of somatosensory cortex were analyzed. In the second experiment, SSEPs were recorded in the ipsilateral nucleus gracilis, the contralateral ventroposterolateral thalamic nucleus(VPL), and the cerebral cortex along the conduction pathway of somatosensory information. Results : In the first experiment, we could constantly obtain the SSEFPs in cerebral cortex following the transcutaneous electrical stimulation of the hind limb, and it revealed that the first large positive and following negative waves were largest at the 2mm posterior and 2mm lateral to the bregma in the contralateral somatosensory cortex. The second experiment showed that the SSEPs were conducted by way of posterior column somatosensory pathway and thalamocortical pathway and that specific patterns of the SSEPs were recorded from the nucleus gracilis, VPL, and cerebral cortex. Conclusion : The specially designed recording electrode was found to be very useful in recording the localized SSEFPs and the transcutaneous electrical stimulation using ball electrode was effective in evoking SSEPs. The characteristic shapes, latencies, and conduction velocities of each potentials are expected to be used the fundamental data for the future study of brain functions, including the hydrocephalus model, middle cerebral artery ischemia model, and so forth.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• Journal of Korean Philosophical Society
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• v.148
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• pp.29-47
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• 2018

The relationship between Confucian tradition and modern China has been discussed since the last century only on a preconceived level of "pre-modernization" without practical orientation, since the discussion has been referred to the modern West while China has not yet commenced modernization. Such being the case, it is of great significance to revert to this topic in the contemporary context of China's modernization. In other words, such new discussions are concerned with a series of difficulties China is presently confronted. To put it brief, the profit-oriented market economy has bit by bit undermined the traditional customs of the mild agricultural society, resulting in the emotional apathy among people, crush of the ethical order, discard of morality in life, ignorance of man's spiritual existence, and ultimately the extremely unbalanced development of "beggar-thy-neighbor" situation among ethnic groups, countries and regions. Since Confucius time, the Confucian tradition has always been attaching great importance to purify customs through social rules for etiquette and harmony, in the process of which, the ethic order is arranged to promote the emotional communication among group members, the individuals are cultivated to enhance their spiritual realms, and most importantly, those social rules for etiquette and harmony are casted as forms of civilization so as to achieve peace and harmony of the whole world. The integration of these three aspects of the Confucian tradition can undoubtedly provide a reference for solving considerable problems confronted by modern China.

• Journal of Microbiology and Biotechnology
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• v.29 no.10
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• pp.1644-1655
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• 2019

Saccharomyces cerevisiae (S. cerevisiae) and glucagon-like peptide-2 (GLP-2) have been employed to improve the intestinal development of weaned animals. The goal of this study was to determine whether either exogenous S. cerevisiae or GLP-2 elicits major effects on fecal microbiotas and cytokine responses in weaned piglets. Ninety-six piglets weaned at 26 days were assigned to one of four groups: 1) Basal diet (Control), 2) empty vector-harboring S. cerevisiae (EV-SC), 3) GLP-2-expressing S. cerevisiae (GLP2-SC), and 4) recombinant human GLP-2 (rh-GLP2). At the start of the post-weaning period (day 0), and at day 28, fecal samples were collected to assess the bacterial communities via sequencing the V1-V2 region of the 16S-rRNA gene, and piglets' blood was also sampled to measure cytokine responses (i.e., IL-$1{\beta}$, TNF-${\alpha}$, and IFN-${\gamma}$). This study revealed that, on the one hand, although S. cerevisiae supplementation did not significantly alter the growth of weaned piglets, it induced increases in the relative abundances of two core genera (Ruminococcaceae_norank and Erysipelotrichaceae_norank) and decreases in the relative abundances of two other core genera (Lachnospiraceae_norank and Clostridiale_norank) and cytokine levels (IL-$1{\beta}$ and TNF-${\alpha}$) (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). On the other hand, GLP-2 supplementation had no significant influence on fecal bacterial communities and cytokine levels, but it produced better body weight and average daily gain (p < 0.05, Control vs EV-SC; p < 0.05, rh-GLP2 vs GLP2-SC). Therefore, altered fecal microbiotas and cytokine response effects in weaned piglets were due to S. cerevisiae rather than GLP-2.

• Journal of the Korea Convergence Society
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• v.12 no.12
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• pp.509-518
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• 2021

This study was conducted to examine the effects of auricular acupressure on quality of sleep and depression. Adults who had insomnia for over 1 month were recruited. Participants were distributed randomly to the experimental group(n=22) and the control group(n=22). The experimental group received auricular acupressure on Shen men(TF2), insomnia 1(SF4), insomnia 2(SF1), and anti-depression(LO8) for 1 week. The contrast group received sleep hygiene education. The mean differences of the quality of sleep were 4.05±2.52 in the experimental group and 1.45±3.77 in the control group. Auricular acupressure significantly decreased insomnia in the experimental group compared to the control group(t=3.07, p=.004). Depression scores after acupressure were not different between the experimental group and the control group. After controlling the religion as a covariate, the mean difference of depression in the experimental group was higher than the control group(F=4.22, p=.046). In conclusion, auricular acupressure decreased insomnia and depression. Therefore, further studies on different acupressure points such as shen men, jiao gan, heart, pi zhi xia, and endocrine are recommended.