• Molecules and Cells
• /
• v.38 no.6
• /
• pp.528-534
• /
• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.

• Journal of Acupuncture Research
• /
• v.29 no.1
• /
• pp.75-87
• /
• 2012

Objectives : The purpose of this study is to inquire into the effect of different concentrations of bee venom pharmacopuncture to inhibit genesis of pro-inflammatory cytokines and to inhibit nuclear factor (NF)-${\kappa}B$ activation on type II collagen induced arthritis. Methods : The experiment was divided into category of the normal group (NOR)-no treated group, control group (CON)-CIA (collagen induced arthritis) induced group, and 4,000 : 1 bee venom group (BV-L)- 4000:1 bee venom pharmacopuncture treated group after CIA, and 2000:1 bee venom group (BV-H)- 2,000 : 1 Bee venom pharmacopuncture treated group after CIA. RA was induced in the mice via injecting $50{\mu}{\ell}$ C II mixed CFA. The bee venom pharmacopuncture was applied on $ST_{35}$ for 19 days from the 3rd day of RA inducement. To research the effect on the expression of IKK ($I{\kappa}B$ kinase), iNOS (inducible nitric oxide synthase) & COX-2 (cyclooxygenase-2) mRNA, RT-PCR was performed on synovial membrane cells from the knee joint of CIA mice. Results : The PMA-induced $I{\kappa}B$ kinase (IKK), inducible nitric oxide synthase (iNOS) and cyclooxygenase -2 (COX-2) mRNA expression were dose-dependantly decreased in bee venom treated with synoviocytes. In mice treated with bee venom pharmacopuncture, foot thickness and the damage of synovial membranes of the joint was lessened, and the activation of RA-related pro-inflammatory cytokines such as MIF, TNF-${\alpha}$ and MMP-9 was significantly decreased. The activation of iNOS and COX-2 was suppressed by the inhibition of NF-${\kappa}B$. In addition, each data was shown that 2,000 : 1 bee venom pharmacopuncture was more effective than 4,000 : 1 bee venom pharmacopuncture. Conclusions : It is speculated that bee venom pharmacopuncture has the therapeutic effect of palliating the damage of the synovial membrane and inflammation on RA by suppressing of NF-${\kappa}B$ activation.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.19 no.1
• /
• pp.202-218
• /
• 2006

Purpose : Because girls at puberty· are lack in sex ability, temporary menstruation disorder can be occured. This disorder is considered that will be disappeared as growing, so people used to leave the disease untreated and just watched. But clinically I frequently experience not to disappear. So I have carried out this study to investigate the actual condition of young girls's menstrual disorders. Methods : I researched 440 high school girls in Pusan by Menstruation Diary which I made about menstrual cycle, duration, amount and pain. The results were managed by the ststistics. Results :1. Menstrual cycle 1) In disorder of menstrual cycle, persons who have Bate menstruation are more than persons who have premature menstruation. 2) Persons who have normal menstrual cycle are in 124 persons(28.51%), the others who have severe premature menstruation or late menstruation more than one time for 4-7 months are in 311 Persons.(71.49%) 2. Menstrual duration and amount 1) Persons who have normal menstrual amount we in 66-89%, hypermenorrhea is in 1-11%, hypomenorrhea is in 5-21%. 2) In the study of menstrual duration, persons more than one thirds are irregular in thier menstrual amount every menstruation. 3) In the study of MMQ, persons who are irregular in thier menstrual amount every menstruation are in 125persons.(29.76%) 3. Menstrual pain 1) Persons who have slight menstrual pain are in 289 persons(65.98%), the middle is in 86 persons(19.63%) the severe is in 34 persons(7.76%) by MMP. 2) Persons who are irregular in thier menstrual pain every menstruation are in 145 persons.(33.11%) Conclusion : In menstrual cycle, there are more persons who have irregular menstrual cycle than normal.(71.49%) In menstrual duration and amount, more persons have normal menstrual amount.(66-89%) In menstrual pain, persons who have slight menstrual pain are the most.(65.98%)

• IMMUNE NETWORK
• /
• v.14 no.1
• /
• pp.45-53
• /
• 2014

Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

• Toxicological Research
• /
• v.34 no.2
• /
• pp.103-110
• /
• 2018

Environmental stimuli can lead to the excessive accumulation of reactive oxygen species (ROS), which is one of the risk factors for premature skin aging. Here, we investigated the protective effects of $7-MEGA^{TM}$ 500 (50% palmitoleic acid, 7-MEGA) against oxidative stress-induced cellular damage and its underlying therapeutic mechanisms in the HaCaT human skin keratinocyte cell line (HaCaT cells). Our results showed that treatment with 7-MEGA prior to hydrogen peroxide ($H_2O_2$)-induced damage significantly increased the viability of HaCaT cells. 7-MEGA effectively attenuated generation of $H_2O_2$-induced reactive oxygen species (ROS), and inhibited $H_2O_2$-induced inflammatory factors, such as prostaglandin $E_2$ ($PGE_2$), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), and $interleukin-1{\beta}$ ($IL-1{\beta}$). In addition, cells treated with 7-MEGA exhibited significantly decreased expression of matrix metalloproteinase-1 (MMP-1) and increased expression of procollagen type 1 (PCOL1) and Elastin against oxidative stress by $H_2O_2$. Interestingly, these protective activities of 7-MEGA were similar in scope and of a higher magnitude than those seen with 98.5% palmitoleic acid (PA) obtained from Sigma when given at the same concentration (100 nL/mL). According to our data, 7-MEGA is able to protect HaCaT cells from $H_2O_2$-induced damage through inhibiting cellular oxidative stress and inflammation. Moreover, 7-MEGA may affect skin elasticity maintenance and improve skin wrinkles. These findings indicate that 7-MEGA may be useful as a food supplement for skin health.

• Korean Journal of Medicinal Crop Science
• /
• v.24 no.1
• /
• pp.38-46
• /
• 2016

Background : The white jelly mushroom (Tremella fuciformis), one of the most popular edible fungi, has medicinal properties. However, the effects of T. fuciformis in skin whitening or anti-wrinkle efficacy has not been defined to date. The aim of the present study was to investigate the effects of T. fuciformis extracts on whitening and anti-wrinkle efficacy in skin cells. Methods and Results :We prepared T. fuciformis extracts with water. The extracts ($80^{\circ}C$) contained 12.11 mg/g polyphenol and 8.54 mg/g flavonoid concentration. T. fuciformis extracts markedly decreased melanin contents and tyrosinase activity in ${\alpha}$-MSH-stimulated melanocytes (B16F10 cells). In addition, the mRNA expression of melanin formation factors, such as microphthalmia-associated transcription factor (MITF), tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were significantly down-regulated in ${\alpha}$-MSH-stimulated melanocyte. Furthermore, T. fuciformis extracts increased the synthesis of type I procollagen and reduced mRNA expression of matrix metalloproteinase 1 (MMP-1) in the human dermal fibroblast (HDFn cells). These data indicated that T. fuciformis extracts induce repression of cellular melanogenesis and protect against wrinkles caused by UVB-stimulated damage. Conclusions : Thus T. fuciformis extracts could be a cosmetic candidate for skin whitening and anti-wrinkle effects.

• International Journal of Oral Biology
• /
• v.33 no.4
• /
• pp.205-211
• /
• 2008

Gingival overgrowth can cause dental occlusion and seriously interfere with mastication, speech, and dental hygiene. It is observed in 25 to 81% of renal transplant patients treated with cyclosporine A (CsA). CsA-induced gingival overgrowth (CIGO) is caused by quantitative alteration of the extracellular matrix components, particularly collagen. However, the molecular mechanisms involved in the pathogenesis of CIGO remain poorly understood, despite intense clinical and laboratory investigations. The aim of the present work is to identify differentially expressed genes closely associated with CIGO. Human gingival fibroblasts were isolated by primary explant culture of gingival tissues from five healthy subjects (HGFs) and two patients with the CIGO (CIGO-HGFs). The proliferative activity of CsA-treated HGFs and CIGO-HGFs was examined using the MTT assay. The identification of differentially expressed genes in CsA-treated CIGO-HGF was performed by differential display reverse transcriptase-polymerase chain reaction (RT-PCR) followed by DNA sequencing. CsA significantly increased the proliferation of two HGFs and two CIGO-HGFs, whereas three HGFs were not affected. Seven genes, including the beta subunit of prolyl 4-hydroxylase (P4HB) and testican 1, were upregulated by CsA in a highly proliferative CIGO-HGF. The increased P4HB and testican-1 mRNA levels were confirmed in CsA-treated CIGO-HGFs by semiquantitative RT-PCR. Furthermore, CsA increased type I collagen mRNA levels and suppressed MMP-2 mRNA levels, which are regulated by P4HB and testican-1, respectively. These results suggest that CsA may induce gingival overgrowth through the upregulation of P4HB and testican-1, resulting in the accumulation of extracellular matrix components.

• Restorative Dentistry and Endodontics
• /
• v.25 no.4
• /
• pp.509-526
• /
• 2000

It is known that injuries to the dentin have a corresponding inflammatory effect on the pulp and these inflammatory effects frequently result in pulpal pathoses due to progressive degradation of pulpal connective tissue. It was supposed that the tissue degradation in different inflammatory process was controlled by proteinase activity and antiproteinase activity. Therefore, the purpose of this study was to examine the pulp and periapical pathoses in terms of the activities of proteinase and proteinase inhibitor, 37 pulpal tissues were divided by clinical diagnostic criteria into normal pulp, acute inflamed pulp, and chronic inflamed pulp, and then those groups were subdivided by histopathological findings into 5 pulpal pathoses groups, i.e. normal pulp (P1, n=8), chronic pulpitis with fibrotic change (P2, n=2), chronic pulpitis with dystrophic calcification (P3, n=11), chronic pulpitis with pulp abscess (P4, n=7), acute pulpitis with necrotic change (P5, n=4), 26 periapical tissues were also divided by ordinary histopathological findings into 3 periapical pathoses group, i.e., granuloma (A1, n=17), cyst (A2, n=2) and abscess (A3, n=7). The activities of proteinases (cathepsin G, MMP-3) and proteinase inhibitors (${\alpha}1$-AT, TIMP-1 and, SLPI) were evaluated by RT-PCR and immunohistochemical methods. The results were as follows. 1. Generally, the intensity of immunohistochemical staining of proteinases and proteinase inhibitors increased in P2 and P5 groups compared to P1 group. 2. The immunohistochemical stain of proteinases and proteinase inhibitors was intensely detected in P2 group, showing low inflammatory reaction and low tissue degradation, but it was reduced in P3 and P4 groups, showing severe tissue degradation. 3. The distribution of proteinases and proteinase inhibitors in pulpal pathoses was consistently presented by immunohistochemical staining, while the expression of proteinase and/or proteinase inhibitors mRNAs in pulpal pathoses was occasionally detected by RT-PCR methods. 4. RT-PCR of proteinase and proteinase inhibitors was usually positive in P2, showing rare tissue degradation, but it was almost negative in P3 and P4, showing severe tissue degradation. 5. We presume that the reason why the level of proteinase and proteinase inhibitors was so sparse in RT-PCR method is due to the abrupt decrease of mRNA synthesis or degradation of synthesized mRNA of proteinase and/or proteinase inhibitors depend on the inflammatory reaction and/or on the degradation of pulp tissues(P3, P4). 6. Pulpal pathoses groups showed significant lower RT-PCR detection of proteinases and proteinase inhibitors than the periapical pathoses group(p<0.05), and there is no significant difference among the periapical pathoses groups(p>0.05).

• International Journal of Stem Cells
• /
• v.16 no.1
• /
• pp.52-65
• /
• 2023

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.10a
• /
• pp.118-118
• /
• 2018

인삼은 우리나라에서 오랜 역사동안 많은 연구가 진행되어 왔으며, 현재는 다양한 방법으로 홍삼과 흑삼으로 만들어 식품, 화장품, 의약품 등 다양한 방면으로 사용하고 있다. 본 연구에서 시중에서 구매한 새싹삼(인삼새싹) 잎/줄기에 함유된 진세노사이드(Re, Rg1, Rb1, Rg3, Rh1) 함량을 높이기 위하여 증숙과 초음파 추출조건에 관한 연구를 수행하여 우수한 항노화 소재를 개발하기 위하여 실시하였다. 실험은 새싹삼 잎/줄기를 증숙 온도와 시간의 조건에서 진세노사이드 함량이 가장 높은 조건을 선정하였으며, 선정된 조건의 새싹삼 잎/줄기에 파장과 출력에 대한 조건으로 초음파 추출을 진행하여 진세노사이드가 가장 높은 함량을 보이는 조건을 선정하였다. 그 결과 새싹삼 잎/줄기추출물(GSE; Ginseng Sprout Extract)의 진세노사이드 함량은 4.8 mg/g으로 확인되었으나 증숙공정을 통해 8.82 mg/g으로 함량이 증가되었으며, 상기 증숙된 새싹삼 잎/줄기에 초음파공정을 적용하여 추출한 새싹삼 잎/줄기초음파추출물(SU-GSE; Steaming & dry Ultrasonication-Ginseng Sprout Extract)에서는 최대 10.65 mg/g으로 함량이 증가되었다. 반면, 새싹삼 뿌리의 진세노사이드는 2.30 mg/g으로 확인되었으나 증숙공정을 통해 4.95 mg/g으로 함량이 증가되었으며, 초음파추출공정을 통해 최대 5.82 mg/g으로 함량이 증가된 것을 확인할 수 있었으나, 새싹삼 잎/줄기에 비해 진세노사이드 함량이 낮은 것을 확인하였다. 항노화 소재로의 활용가능성을 평가하기 위하여 새싹삼 잎/줄기추출물 GSE와 SU-GSE에 대한 세포생존률, 항산화 및 항노화에 대한 효능평가를 진행하였으며 GSE의 경우 $100{\mu}g/ml$에서 세포생존률이 82.4%를 보인 반면 SU-GSE에서는 $1,000{\mu}g/ml$의 농도에서 101.8%의 세포 생존률을 보였다. 항산화 활성의 경우 GSE와 SU-GSE $100{\mu}g/ml$ 농도에서 각각 52%와 81%의 항산화 활성을 나타냄으로써 SU-GES의 조건에서 항산화 활성이 우수한 것으로 확인되었다. 또한, 항노화 활성에 대한 실험결과 MMP-1 유전자 발현에 대한 억제율을 비교한 결과 GSE와 SU-GES $100{\mu}g/ml$의 농도에서 각각 18%와 29%의 억제율을 보임에 항노화 소재로의 활용가능성을 확인하였다.