• The Journal of Internal Korean Medicine
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• v.43 no.6
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• pp.1089-1104
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• 2022

Objective: The aim of this study was to identify the efficacy and underlying mechanism of cloves as an osteoarthritis (OA) treatment in a monosodium iodoacetate (MIA)-induced rat OA model. Osteoarthritis (OA) is nowadays one of the most prevalent degenerative joint diseases. Methods: Sprague-Dawley rats treated with MIA (50 μL; 80 mg/mL) were used as in vivo OA models. Cloves (100 and 200 mg/kg b.w.) were administered orally once daily for 2 weeks from 7 days after MIA injection. Changes in hindpaw weight distribution (HWD) were measured as a joint discomfort index. Activation markers related to inflammatory responses and cartilage degeneration in the right knee joints were evaluated by serum analysis and western blotting. Results: HWD decreased in the MIA control group but showed a dose-dependent elevation after clove treatment. Clove treatment inhibited inflammatory factors by PI3K/Akt/NF-κB signaling pathways, while also activating antioxidant factors through Sirt1/AMPK signaling pathways. Clove treatment also suppressed matrix metalloproteinase (MMP) overexpression and significantly increased the levels of tissue inhibitors of metalloproteinases (TIMPs). Conclusions: Treatment with cloves effectively reversed MIA-induced effects. Therefore, clove treatment could have the potential to protect against or treat OA.

• Journal of Korean Medicine Rehabilitation
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• v.33 no.3
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• pp.47-65
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• 2023

Objectives We evaluated the wound healing effects of Dangguijakyak-san (DJ) using C57BL/6 mice that were generated open wound. Methods The study was conducted with seven C57BL/6 mice assigned to each group, divided into the normal group, control group, vitamin E group, DJ low-dose group, DJ high-dose group. We measured total polyphenol, flavonoid contents, the size of the wound, liver function, pro-inflammatory cytokine activity in serum, inflammation-related proteins, adhesion molecules and chemokine proteins, collagen-related proteins in skin tissue and histopathological changes by H&E and Masson's staining. Results DJ treatment significantly reduced the area of the wound compared to the control group. Also, inflammatory cytokines were reduced and the expression of anti-inflammatory-related factors (interleukin-4 [IL-4] and IL-10) was significantly increased in the DJ treatment group. We identified that DJ treatment inhibits both pathways of inflammation, the mitogen-activated protein kinases and nuclear factor-κB pathway. Moreover, the protein expressions of Sirt1 (sirtuin 1), MCP-1 (monocyte chemoattractant protein 1), ICAM-1 (intercellular adhesion molecule 1), and VCAM-1 (vascular cell adhesion molecule 1) were decreased by DJ administration. Also, the expression of α-smooth muscle actin and collagen type I alpha 1, collagen-related proteins, that help skin recovery was significantly increased in the DJ treatment group. Histopathologically, a relatively thin epithelial layer could be observed in the DJ administration group, as well as an increase in fibroblasts and collagen fibers. Conclusions These data suggest that DJ treatment is effective in wound healing, suppressing inflammatory proteins, increasing skin repair factors and improving histopathological changes caused by wounds.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Journal of the Korean Geophysical Society
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• v.9 no.1
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• pp.37-45
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• 2006

Velocity structures were defined in the vicinty of the 140-m deep test borehole in the pungam basin through simultaneous inversion of surface seismic refraction and far-ofset VSP traveltime data. Seismicenergy generated at the surface by a seisgun was recorded both at 42 surface locations at 3-m intervalsalong the profiles in the N20E and its orthogonal directions and at 71 m depth in the borehole. Forthe ofset VSP study, seismic energy was generated by a 5 kg sledgehamer at the surface in the horizontal ofset range of -19.5∼+19.5 m from the borehole. The seismic signals were detected at 9∼99 m depths with 1∼2 m intervals and recorded for 204 ms per shot. After shot static corrections,first-arrival times picked from both the surface refraction and borehole records were simultaneouslyinverted to yield velocity tomograms. The tomograms indicate that a 1.5 m thick soil layer with velocities les than 500 m/s overlies basements having a velocity range of 3,067 ∼5,717 m/s. Within the basements,∼4 m and deeper than 71 m. The high-velocit yzones may be due to conglomerates intercalated with sandstones and siltstones. No evidence for large-scale fracture zones or faults is detected near the borehole

• Journal of Life Science
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• v.30 no.1
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• pp.96-105
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• 2020

Sirtuin inhibitors are pharmaceutically and therapeutically valuable compounds that inhibit sirtuin, a type III histone deacetylase. Synthetic sirtuin inhibitors were discovered and characterized using cell-based screens in yeast (Saccharomyces cerevisiae) and have been used in the study of aging, carcinogenesis, and diabetes, all of which are related to sirtuin function. For medical applications, synthetic inhibitors have been further developed for increased potency and specificity, including compounds containing nicotinamide, thioacetyl lysine, β-naphthol, and indole derivatives. Suramin, tenovin, and their analogues were developed as a result. Sirtuin inhibitors were found to affect organic development and have been used to genetically modify plants, although a sirtinol-resistant mutation in the biosynthesis of a molybdopterin cofactor for an aldehyde oxidase has been identified. Some natural flavonoids, and catechin and quercetin derivatives also act as sirtuin inhibitors have been studied to identify a more potent inhibitor for therapeutic purposes. In this review, sirtuin is introduced and the therapeutic inhibitors that have been developed are presented, particularly sirtinol which has been used for genetic modification in plants though it was not designed to be so. Sirtuin inhibitors with greater potency and selectivity are required and those developed in pharmaceutics should be used in plant research to identify more authentic sirtuins in plants.

• 한국지구물리탐사학회:학술대회논문집
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• 2000.09a
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• pp.132-146
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• 2000

Seismic refraction survey was performed for 10 lines along NE-SW and NW-SE directions above Nampoong gallery at Makyo-ri, Dogye, Samcheok, Kangwon-do. 48 geophones were laid in line with the interval of 1m, and a 5Kg hammer was used as a source at 5 points for each line. Data processing was done using reciprocal time method, GRM, and traveltime tomography which utilizes wavefront expansion method for forward process and STRT for inversion. The result shows that the first layer has its lower boundary between 3.49m and 8.88m. The P-wave velocity of the first and the second layer were estimated as 270${\~}$360m/s and 1550${\~}$1940m/s respectively. When the boundary of the first and second layer is smooth enough and the velocity difference is large enough, GRM has little advantage over reciprocal time method. The result of reciprocal method and traveltime tomography shows consistency. The northeast part of the boundary has syncline structure, which is similar to the topography above. This implies that the collapse of the cavities of Nampoong gallery result in the subsidence of the ground surface. The subsidence is in progress across the Youngdong railroad, therefore a proper reinforcement work is required.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7619-7625
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• 2015

Background: Aberrant microRNA expression has been associated with the pathogenesis of a variety of human malignancies including oral squamous cell carcinoma (SCC). In this study, we examined primary oral SCCs for the expression of 6 candidate miRNAs, of which five (miR-34a, miR-143, miR-373, miR-380-5p, and miR-504) regulate the tumor suppressor TP53 and one (miR-99a) is involved in AKT/mTOR signaling. Materials and Methods: Tumor tissues (punch biopsies) were collected from 52 oral cancer patients and as a control, 8 independent adjacent normal tissue samples were also obtained. After RNA isolation, we assessed the mature miRNA levels of the 6 selected candidates against RNU44 and RNU48 as endogenous controls, using specific TaqMan miRNA assays. Results: miR-34a, miR-99a, miR-143 and miR-380-5p were significantly down-regulated in tumors compared to controls. Moreover, high levels of miR-34a were associated with alcohol consumption while those of miR-99a and miR-143 were associated with advanced tumor size. No significant difference was observed in the levels of miR-504 between the tumors and controls whereas miR-373 was below the detection level in all but two tumor samples. Conclusions: Low levels of miR-380-5p and miR-504 that directly target the 3'UTR of TP53 suggest that p53 may not be repressed by these two miRNAs in OSCC. On the other hand, low levels of miR-34a or miR-143 may relieve MDM4 and SIRT1 or MDM2 respectively, which will sequester p53 indicating an indirect mode of p53 suppression in oral tumors.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.911-917
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• 2016

Lespedeza cuneata G. Don is an edible perennial herb used in traditional Korean medicine. We investigated the anti-proliferative properties and mechanism of L. cuneata extract. The ethanolic extract of L. cuneata dose-and time-dependently inhibited human colorectal cancer cell proliferation. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to test the effect of the extract on proliferation of HT-29 colorectal cancer cells. The extract inhibited HT-29 cell proliferation with an $IC_{50}$ value of $554.26{\pm}8.81{\mu}g/mL$. L. cuneata extract suppressed production of pro-inflammatory cytokines interleukin-6 and tumor necrosis $factor-{\alpha}$. Apoptosis was evaluated by analysis of DNA fragmentation, poly(ADP-ribose) polymerase cleavage, caspase-3 activity, and protein expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2). Our results demonstrated that the extract induced DNA fragmentation and characteristic morphological changes associated with apoptosis in HT-29 colorectal cancer cells. The extract also time- and dose-dependently up-regulated expression of the Bax and down-regulated expression of the Bcl-2. Furthermore, the extract dose- and time-dependently enhanced caspase-3 activity. Our findings provide evidence that L. cuneata extract may mediate its anti-proliferative effect via modulation of apoptosis.