• Biomolecules & Therapeutics
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• v.28 no.2
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• pp.184-194
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• 2020

Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC₅₀ value of MHY4381 was lower in DU145 cells (IC₅₀=0.31 µM) than in LNCaP (IC₅₀=0.85 µM) and PC-3 cells (IC₅₀=5.23 µM). In addition, the IC₅₀ values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.

• Journal of the Korean Society of Radiology
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• v.7 no.5
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• pp.305-311
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• 2013

This study involves an experiment using functional magnetic resonance imaging(fMRI) to delineate brain activation for execution functional performance. Participates to this experiment of the normal adult (man 4, woman 6) of 10 people, is not inserts the metal all closed phobia and 24.5 year-old average ages which the operating surgeon experience which are not they were. The subject for a functional MRI experiment word -color test prosecuting attorney subject rightly at magnetic pole presentation time of 30 first editions and after presenting, uses SPM 99 programs and the image realignment, after executing a standardization (nomalization), a difference which the signal burglar considers the timely order as lattice does, pixel each image will count there probably is, in order to examine rest and active crossroad dividing independence sample t-test (p<.05). Overlapped in this standard anatomic image and got a brain activation image from level of significance 95%. With functional MRI resultant execution function inside being relation, the prefrontal lobe, anterior cingulate gyrus, parietal lobe, orbitofrontal gyrus, temporal lobe, parietal lobe was activated. The execution function promotes a recovery major role from occupational therapy, understanding about the damage mechanism is important. When confirms the brain active area which accomplishes an execution function brain plasticity develops the cognitive therapeutic method which is effective increases usefully very, will be used.

• Toxicological Research
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• v.17
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• pp.47-57
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• 2001

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for ［$^3H$］ cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.275-283
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• 2018

Helicobacter pylori is a causative organism of various gastrointestinal diseases, including chronic gastritis, gastric ulcer, or gastric adenocarcinoma. Pathogenic factors, such as cytotoxin-associated protein A (CagA) and vacuolating cytotoxic protein A (VacA), play a role. This study analyzed qualitatively and quantitatively the effects of zerumbone on the changes in the protein expression levels of various H. pylori proteins, including CagA and VacA. Approximately 200 significant proteins were screened for the H. pylori 60190 (VacA positive / CagA positive; Eastern type) strain, and proteomic analysis was performed on 13 protein molecules that were clinically significant. After two-dimensional electrophoresis (2-DE), $ImageMaster^{TM}$ 2-DE Platinum software was used for quantitative measurements of protein spots. Matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-TOF-MS) and liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) were used for protein identification. After intensive analysis of the proteins that showed significant changes, a reverse transcription-polymerase chain reaction was performed as required to verify the results. In this study, the significance of zerumbone as a therapeutic agent for H. pylori infection was examined by screening a new pharmacological activity mechanism of zerumbone.

• CELLMED
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• v.3 no.2
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• pp.18.1-18.7
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• 2013

Inflammation in rheumatoid arthritis is characterized by immune cell infiltration and cytokine secretion. In particular, mast cells and their cytokines play an important role in the pathogenesis of rheumatoid arthritis. Korean medicine, BaekJeol-Tang (BT) was designed by traditional Korean medicine theory. We already reported therapeutic effect of BT in rheumatoid arthritis. Here, we report the specific underlying mechanism of BT in activated human mast cells, HMC-1 cells. In addition, we report for the first time that BT significantly inhibited the production and mRNA expression of proinflammatory cytokines including thymic stromal lymphopoietin, interleukin (IL)-$1{\beta}$, IL-6, IL-8, and tumor necrosis factor-${\alpha}$ in activated HMC-1 cells. BT also decreased the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and caspapase-1. Taken together, these results indicate that BT has potential as a regulator of inflammatory reactions for the treatment of arthritis such as osteoarthritis and rheumatoid arthritis.

• Journal of Microbiology and Biotechnology
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• v.21 no.12
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• pp.1345-1351
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• 2011

Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and $pep^{27}$ are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and $pep^{27}$ were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in $pep^{27}$ expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, $pep^{27}$ expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in $pep^{27}$ expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.

• Journal of Pharmaceutical Investigation
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• v.32 no.3
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• pp.223-229
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• 2002

Metformin is an oral antihyperglycemic agent used in the therapy of noninsulin-dependent diabetes mellitus and does not cause hypoglycemia at the therapeutic dose. Its mechanism of action may involve an increased binding of insulin to its receptors and glucose uptake at the post-receptor level. The purpose of the present study was to evaluate the bioequivalence of two metformin tablets, Glucophage (Daewoong Pharmaceutical Co., Ltd.) and Glycomin (Ilsung Pharmaceuticals Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The metformin release from the two metformin tablets in vitro was tested using KP VII Apparatus II method with various dissolution media (pH 1.2, 4.0, 6.8 buffer solution and water). Twenty four normal male volunteers, $23.75{\pm}1.96$ years in age and $68.77{\pm}10.41\;kg$ in body weight, were divided into two groups with a randomized $2{\times}2$ cross-over study. After one tablet containing 500 mg as metformin was orally administered, blood was taken at predetermined time intervals and the concentrations of metformin in serum were determined using HPLC with UV detector. Besides, the dissolution profiles of two metformin tablets were very similar at 떠1 dissolution media. The pharmacokinetic parameters such as $AVC_t,\;C_{max}\;and\;T_{max}$ were calculated. The ANOVA test was performed for the statistical analysis of the logarithmically transformed $AVC_t\;and\;C_{max}$, untransformed $T_{max}$. The results showed that the differences in $AVC_t,\;C_{max}\;and\;T_{max}$ between two tablets based on the Glucophage were 0.09%, 6.09% and -8.22%, respectively. There were no sequence effects between two tablets in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25) $(e.g.,\;log(0.94){\sim}log(1.09)\;and \;log(1.01){\sim}log(1.15)$\;for\;AVC_t\;and\;C_{max},\;respectively)$, indicating that Glycomin tablet is bioequivalent to Glucophage tablet.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.309-316
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• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• Journal of Yeungnam Medical Science
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• v.3 no.1
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• pp.261-267
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• 1986

Development of supervoltage treatment machine may minimize skin reaction by skin-sparing effect, but skin damage is still one of "the dose limiting factor" in radiation therapy. In spite of these importance, systemic histopathologic studies of skin in similar conditions which used in clinical treatment has not been performed so far. 60mice were irradiated with conventional fraction ($200{\times}5/wk$) and whole abdominal field ($2{\times}3cm$, from symphysis pubis to xyphoid process). Used machine was 250KV, 24mA, orthovoltage x-ray machine. Histopathological changes of acute skin reaction at the level of total irradiation dose were analyzed and the possible mechanism of later chronic changes were investigated. Obtained results are as follows: 1. In 1,000 rad irradiated group, only mild epidermal edema is noted. 2. In 2,000 rad irradiated group, slightly decreased number and size of hair follicles and appendages, dermal edema and scanty infiltration of inflammatory cells are visible. 3. In 3,000 rad irradiated group, marked increased capillary congestion and prominant infiltration of inflammatory cells are observed. 4. In 4,000 rad irradiated group, vascular wall thickening with proliferation of endothelial cells are prominant. Dermal thinning and hyalinization are newly developed. 5. In 5,000 rad irradiated group, complete desquamation of epidermis is not seen, despite of acceleration of all above mentioned changes.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7179-7186
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• 2013

Background and Aims: Scutellaria is one of the most popular traditional Chinese herbal remedies against various human diseases, including cancer. In this study, we examined the active effects of Scutellaria extract and its main flavonoid constituents on the proportion of side population cells within human multiple myeloma cell line RPMI8226 in vitro and explored the potential molecular mechanisms involved. Materials and Methods: The contents of flavonoids in ethanolic extract of Scutellaria baicalensis Georgi were determined using high performance liquid chromatography. The antiproliferative effect of the ethanolic extract on RPMI-8226 was determined by CCK assay. Apoptosis was measured by annexin combining with propidium iodide in a flow cytometer. Cell cycle analysis was performed by propidium iodide staining in combination with flow cytometry analysis. Hoechst 33342 exclusion assay was used for the identification of side population within RPMI8226 cells. The expression of ABCG2 protein was assessed by Western blotting assay. Results: The content of major flavonoids constitutents of Scutellaria extract was baicalin (10.2%), wogonoside (2.50%), baicalein (2.29%), and wogonin (0.99%), respectively. The crude Scutellaria extract did not show significant anti-proliferative effect, apoptosis induction and cell cycle arrest in RPMI-8226 within the concentrations of $1-75{\mu}g/mL$. However, the ethanolic extract, baicalein, wogonin and baicalin reduced the side population cells in RPMI-8226, and data showed that baicalein and wogonin had stronger inhibitory effects. Correspondingly, they also exhibited significant effects on decreasing the expression level of ABCG2 protein in RPMI-8226 in vitro. Conclusions: Our results for the first time demonstrated a novel mechanism of action for Scutellaria extract and its main active flavonoids, namely targeting SP cells by modulating the expression of ABCG2 protein. This study provides an insight for new therapeutic strategies targeting cancer stem cells of multiple myeloma.