• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3961-3968
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• 2015

Background: Variants of human papillomavirus (HPV) show more oncogenicity than do prototypes. The HPV16 Asian variant (HPV16As) plays a major role in cervical cancer of Asian populations. Some amino acid changes in the E6 protein of HPV16 variants affect E6 functions such as p53 interaction and host immune surveillance. This study aimed to investigate activities of HPV16As E6 protein on modulation of expression of miRNA-21 as well as interferon regulatory factors (IRFs) 1, 3, 7 and c-fos. Materials and Methods: Vectors expressing E6 protein of HPV16As (E6D25E) or HPV16 prototype (E6Pro) were constructed and transfected into C33A cells. HCK1T cells expressing E6D25E or E6Pro were established by transducing retrovirus-containing E6D25E or 16E6Pro. The E6AP-binding activity of E6 and proliferation of the transfected C33A cells were determined. MiR-21 and mRNA of interesting genes were detected in the transfected C33A cells and/or the HCK1T cells, with or without treatment by culture medium from HeLa cells (HeLa-CM). Results: E6D25E showed binding activity with E6AP similar to that of E6Pro. Interestingly, E6D25E showed a higher activity of miR-21 induction than did E6Pro in C33A cells expressing E6 protein. This result was similar to the HCK1T cells expressing E6 protein, with HeLa-CM treatment. The miR-21 up-regulation significantly corresponded to its target expression. Different levels of expression of IRFs were also observed in the HCK1T cells expressing E6 protein. Interestingly, when treated with HeLa-CM, IRFs 1, 3 and 7 as well as c-fos were significantly suppressed in the HCK1T cells expressing E6D25E, whereas those in the HCK1T cells expressing E6Pro were induced. A similar situation was seen for IFN-${\alpha}$ and IFN-${\beta}$. Conclusions: E6D25E of the HPV16As variant differed from the E6 prototype in its activities on epigenetic modulation and immune surveillance and this might be a key factor for the important role of this variant in cervical cancer progression.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2000.12a
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• pp.79-79
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• 2000

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.17-20
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• 1993

As a step toward a more complete understanding of the molecular actions of TNF, we prepared a cDNA library from TNF-treated human FS-4 fibroblasts and used differential hybridization to identify cDNA clones corresponding to mRNAs enriched in TNF-treated eells. In Quiescent FS-4 cells n induces an increase in the level of some mRNAs within 20 to 30 min. Some of these immediate-early response mRNAs are elevated only transiently for about 30 to 120 min, e. g., c-fos and c-myc (Lin and Vilcek,1987) or the transcription factor IRF-1 (Fujita et al.1989). Such immediate-early gene products may be important for the activation of other genes, but their transient induction suggests that they are not the actual effector molecules responsible for the phenotypic changes induced by TNF. We chose a 3-h incubation with W because we were seeking cDNAs corresponding to messages that are more stably elevated after TNF treatment. Indeed, the results shown in Figure 8 and 9 indicate that all of the mRNAs corresponding to the eight TSG cDNAs isolated remained significantly elevated after 16h of continuous treatment with TNF, and their kinetics of induction were clearly different from those of the immediate-early response mRNAs such as c-fos, c-myc or IRF-1. Nevertheless, only the induction of TSG-21 (collagenase) and TSG-27 (stromelysin) nNAs was completely inhibited by cycloheximide and the induction of TSG-37 (metallothionein-II) was reduced in the presence of this inhibitor of protein synthesis. Induction of the other five TSG mRNAs by TNF was completelyresistant to cycloheximide, suggest ins that no protein intermediate is needed for the upregulation of these mRNAs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.5
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• pp.848-853
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• 2010

Bone maintains its homeostasis through balance between bone resorbing osteoclasts and bone forming osteoblasts. Thus, unusual balance between osteoclasts and osteoblasts leads to pathological bone diseases, such as osteoporosis, rheumatoid arthritis, autoimmune arthritis, periodontitis. Schisandra chinensis well known traditional herbal has been used for treatment of diseases in China, Korea, Japan, andothers. Recently, research studies have demonstrated that the lignans found in Schisandra chinensis stimulate osteoblasts and suggest that it may be helpful against osteoporosis. However, the inhibitory effect of water extract of Schisandra chinensis on osteoclast differentiation remains largely unknown. In this study, Water extract of Schisandra chinensis markedly suppressed RANKL-induced osteoclast differentiation in cultures of BMMs without cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP induced by RANKL was inhibited by water extract of Schisandra chinensis. It also suppressed c-Fos and NFATc1 protein expression. Taken together, these results suggest that water extract of Schisandra chinensis has the potential to serve as a treatment of bone disease such as osteoporosis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.796-801
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• 2008

Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated $I-{\kappa}B$ degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.766-770
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• 2008

Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated $I-{\kappa}B$ degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.1035-1048
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• 2017

Objectives: This study was performed to investigate the effects of Gardenia jasminoides extract (GJ) on osteoclast differentiation and bone resorption in vitro. Methods: To investigate the effect of GJ on osteoclast differentiation, the mouse leukemic myeloid cell line RAW 264.7 was stimulated by RANKL (receptor activator of nuclear factor kB ligand). Osteoclast differentiation was measured by counting TRAP (+) MNC in the presence of RANKL. To elucidate the mechanism of the inhibitory effect of GJ on osteoclast differentiation, gene expression of TRAP, Cathepsin K, MMP-9, NFATc1, c-Fos, MITF, DC-STAMP, CTR, OC-STAMP and Atp6v0d2 was measured using reverse transcription-PCR (RT-PCR). Bone resorption was measured using the bone pit formation assay. Results: GJ decreased the number of TRAP (+) MNCs in the presence of RANKL. GJ inhibited the expression of cathepsin K, MMP-9, TRAP, MITF, NFATc1, c-Fos, iNON, OC-STAMP, Atp6v0d2, and DC-STAMP in the osteoclast, and inhibited bone pit formation in vitro. Conclusions: The results suggest that GJ has inhibitory effects on bone resorption resulting from inhibition of osteoclast differentiation and gene expression.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.390-395
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• 2017

The present study investigated the sedative effects of Sophora flavescens (SF) and its bioactive compound, matrine through performing locomotor activity test and the electroencephalography (EEG) analysis in the rat. The underlying neural mechanism of their beneficial effects was determined by assessing c-Fos immunoreactivity and serotonin (5-HT) in the brain utilizing immunohistochemical method and enzyme-linked immunosorbent assay. The results showed that SF and matrine administration had an effect on normalization of caffeine-induced hyperactivity and promoting a shift toward non-rapid eye movement (NREM) sleep. c-Fos-immunoreactivity and 5-HT level in the ventrolateral preoptic nucleus (VLPO), a sleep promoting region, were increased in the both SF and matrine-injected groups. In conclusion, SF and its bioactive compound, matrine alleviated caffeine-induced hyperactivity and promoted NREM sleep by activating VLPO neurons and modulating serotonergic transmission. It is suggested that SF might be a useful natural alternatives for hypnotic medicine.

• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.107-119
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• 2002

This study was performed to evaluate the effects of Koamsimsinwhan (without Cinnabarite) on depression in CMS-treated rats. Rats of trial groups were exposured to chronic mild unpredictable stress for 4 weeks. These CMS-treated rats were stratified into Koamsimsinwhan(without Cinnabarite) group and vehicle(non-drug) group. And there were control rats excluding both CMS and Koamsimsinwhan(without Cinnabarite). Forced swimming test, general activity test and immunohistochemical test(measuring the level of manifestation of c-Fos in PVN) were executed to evaluate the effects of Koamsimsinwhan(without Cinnabarite) on depression after 4 weeks of CMS treatment. The results were as follows 1. In FST, depression was induced from CMS treatment and was supressed with Koamsimsinwhan(without Cinnabarite). 2. The increased activity of nerve cell in PVN, which refers to stress, was induced from CMS treatment and normalized with Koamsimsinwhan (without Cinnabarite).

• The Journal of Korean Medicine
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• v.30 no.6
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• pp.53-68
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• 2009

Objectives: This study demonstrates the neurological effects of Bojungikki-tang and Bojungikki-tang-gamibang on the focal cerebral ischemia of rats with ischemic damage caused by middle cerebral artery occlusion (MCAO). Methods: Rats were treated with Bojungikki-tang and Bojungikki-tang-gamibang extracts for about five days after MCAO, and the size and volume of cerebral infarction and the ratio of cerebral edema were observed. From the immunohistochemical view, significant changes of outbreak of Bax, Bcl-2, c-Fos, HSP72, and iNOS were observed in the brain tissues. Results: Bojungikki-tang repressed only brain edema and iNOS revelation led by focal cerebral ischemia, when considering significance. In contrast, Bojungikki-tang-gamibang demonstrated significant suppression of cerebral infarction, brain edema, Bax, c-Fos, HSP72, and iNOS induced by focal cerebral ischemia. Conclusions: Bojungikki-tang is considered functional treatment for cerebral ischemic damage; it can be effective to relieve secondary brain edema and immune response. Bojungikki-tang-gamibang can have a direct function to alleviate brain infarct and to control the natural death of nerve cells which cerebral ischemic damage brings about.