• Journal of Dental Anesthesia and Pain Medicine
• /
• 제16권4호
• /
• pp.263-271
• /
• 2016

Background: Bone injury is common in many clinical situations, such as surgery or trauma. During surgery, excessive reactive oxygen species (ROS) production decreases the quality and quantity of osteoblasts. Remifentanil decreases ROS production, reducing oxidative stress and the inflammatory response. We investigated remifentanil's protective effects against $H_2O_2$-induced oxidative stress in osteoblasts. Methods: To investigate the effect of remifentanil on human fetal osteoblast (hFOB) cells, the cells were incubated with 1 ng/ml of remifentanil for 2 h before exposure to $H_2O_2$. For induction of oxidative stress, hFOB cells were then treated with $200{\mu}M$ $H_2O_2$ for 2 h. To evaluate the effect on autophagy, a separate group of cells were incubated with 1 mM 3-methyladenine (3-MA) before treatment with remifentanil and $H_2O_2$. Cell viability and apoptotic cell death were determined via MTT assay and Hoechst staining, respectively. Mineralized matrix formation was visualized using alizarin red S staining. Western blot analysis was used to determine the expression levels of bone-related genes. Results: Cell viability and mineralized matrix formation increased on remifentanil pretreatment before exposure to $H_2O_2$-induced oxidative stress. As determined via western blot analysis, remifentanil pretreatment increased the expression of bone-related genes (Col I, BMP-2, osterix, and $TGF-{\beta}$). However, pretreatment with 3-MA before exposure to remifentanil and $H_2O_2$ inhibited remifentanil's protective effects on hFOB cells during oxidative stress. Conclusions: We showed that remifentanil prevents oxidative damage in hFOB cells via a mechanism that may be highly related to autophagy. Further clinical studies are required to investigate its potential as a therapeutic agent.

• Molecules and Cells
• /
• 제46권10호
• /
• pp.592-610
• /
• 2023

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

• IMMUNE NETWORK
• /
• 제1권3호
• /
• pp.230-235
• /
• 2001

Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

• 동의생리병리학회지
• /
• 제28권2호
• /
• pp.154-161
• /
• 2014

The purpose of this study is to evaluate the antioxidant activity and hair growth effects of a natural herbal ethanol extract, Samhwang-Sasimtang(SS). In case of antioxidant ability of SS, the content of phenolic compounds was 28.44mg/g. The extract showed strong electron donating ability and free radical scavenging activity in a concentration-dependent manner. SOD-like activity also rose through increasing the concentrations of SS. In order to estimate the hair growth effects, the extract was applied to the back of seven-week-old C57BL/6 male mice ($150{\mu}{\ell}$ a day, five days a week, for four weeks) in four groups (C, control, saline; PC, positive control, 3% minoxidil; E1, experimental 1, 1% SS; E2, experimental 2, 2% SS). Ten mice were assigned to each group and five mice in each group were sacrificed at weeks 2 and 4, respectively. There was no a significant difference in body weight change among experimental groups. In macroscopic observation of hair growth at week 4, the scores of hair growth on the backs of mice were 80, 60, 40 and 20% in the PC, E2, E1 and C groups. In terms of histological observation, the ratio and thickness of hair follicles, the enzyme activities of ALP and ${\gamma}$-GT, immunohistological examination of IGF-1 and VEGF which are the hair growth factors, in each group were significantly high in this order: PC, E2, E1 and C group, at week 4. Meanwhile, hair growth inhibition factors, TGF-${\beta}1$ and Caspase-3, were reduced in PC, E1 and E2 groups compared with C group. These results indicate that SS extract may be effective in promoting hair growth, and suggest that it can be used practically as a superior natural agent for hair growth promotion.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제32권1호
• /
• pp.69-75
• /
• 2006

Head and neck squamous cell carcinoma(HNSCC) is the sixth most common cancer among men in the developed world affecting the tongue, pharynx, larynx and oral cavity. HNSCC is thought to represent a multistep process whereby carcinogen exposure leads to genetic instability in the tissue and accumulation of specific genetic events, which result in dysregulation of proliferation, differentiation, and cell loss and the acquisition of invasive capacity. Despite therapeutic and diagnostic progress in oncology during the past decades, the prognosis of HNSCC remains poor. Thus it seems that finding a biological tumor markers which will increase the early diagnosis and treatment monitoring rates, is of paramount importance in respect to improving prognosis. In an effort to identify gene expression signatures that may serve as biomarkers, this study several genes were selected, such as H3,3A, S100A7, UCHL1, GSTP1, PAI-2, PLK, TGF${\beta}$1 and bFGF, and used 7 HNSCC cell lines that were established various anatomical sites, and also 17 other cancer cell lines were used for control group using real-time quantitative RT-PCR and immunocytochemical analysis with a monoclonal antibody. In this study, S100A7 showed a clearly restricted occurrence in tongue originated cell line, and GSTP1 expression level in the pharynx originated cell line was very increased, relative to corresponding other cell lines. These results suggest that S100A7 and GSTP1 genes' expression can occur during tongue and pharynx originated head and neck tumorigenesis and that genetic change is an important driving force in the carcinogenesis process. This data indicate that S100A7 and GSTP1 expression pattern in HNSCC reflect both diagnostic clue and biological marker. And this is provides a foundation for the development of site-specific diagnostic strategies and treatments for HNSCC.

• Journal of Ginseng Research
• /
• 제44권6호
• /
• pp.790-798
• /
• 2020

Background: Beneficial effects of Korean Red Ginseng (KRG) on polycystic ovarian syndrome (PCOS) remains unclear. Methods: We examined whether pretreatment (daily from 2 hours before PCOS induction) with KRG extract in water (KRGE; 75 and 150 mg/kg/day, p.o.) could exert a favorable effect in a dehydroepian-drosterone (DHEA)-induced PCOS rat model. Results: Pretreatment with KRGE significantly inhibited the elevation of body and ovary weights, the increase in number and size of ovarian cysts, and the elevation of serum testosterone and estradiol levels induced by DHEA. Pretreatment with KRGE also inhibited macrophage infiltration and enhanced mRNA expression levels of chemokines [interleukin (IL)-8, monocyte chemoattractant protein-1), proinflammatory cytokines (IL-1β, IL-6), and inducible nitric oxide synthase in ovaries induced by DHEA. It also prevented the reduction in mRNA expression of growth factors (epidermal growth factor, transforming growth factor-beta (EGF, TGF-β)) related to inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cell pathway and stimulation of the nuclear factor erythroid-derived 2-related factor 2 pathway. Interestingly, KRGE or representative ginsenosides (Rb1, Rg1, and Rg3(s)) inhibited the activity of inflammatory enzymes cyclooxygenase-2 and iNOS, cytosolic p-IκB, and nuclear p-nuclear factor kappa-light-chain-enhancer of activated B in lipopolysaccharide-induced RAW264.7 cells, whereas they increased nuclear factor erythroid-derived 2-related factor 2 nuclear translocation. Conclusion: These results provide that KRGE could prevent DHEA-induced PCOS via antiinflammatory and antioxidant activities. Thus, KRGE may be used in preventive and therapeutic strategies for PCOS-like symptoms.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권1호
• /
• pp.41-44
• /
• 2015

Based on genome-wide association studies (GWAS) a linkage between several variants such as single nucleotide polymorphisms (SNPs) in intron 3 of SMAD7 (mothers against decapentaplegic homolog7) were, rs12953717, rs4464148 and rs4939827 has been noted for susceptibility to colorectal cancer (CRC). In this study we investigated the relationship of rs12953717 and rs4464148 with risk of CRC among 487 Iranian individuals based on a case-control study. Genotyping of SNPs was performed by PCR-RFLP and for confirming the outcomes, 10% of genotyping cases were sequenced with RFLP. Comparing the case and control group, we have found significant association between the rs4464148 SNP and lower risk of CRC. The AG genotype showed decreased risk with and odds ratio of 0.635 (adjusted OR=0.635, 95% CI: 0.417-0.967, p=0.034). There was no significant difference in the distribution of SMAD7 gene rs12953717 TT genotype between two groups of the population evaluated (adjusted OR=1.604, 95% CI: 0.978-2.633, p=0.061). On the other hand, rs12953717 T allele showed a statistically significant association with CRC risk (adjusted OR=1.339, 95% CI: 1.017-1.764, p=0.037). In conclusion, we found a significant association between CRC risk and the rs4464148 AG genotype. Furthermore, the rs12953717 T allele may act as a risk factor. This association may be caused by alternative splicing of pre mRNA. Although we observed a strong association with rs4464148 GG genotype in affected women, we did not detect the same association in CRC male patients.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2006년도 추계학술대회
• /
• pp.32-33
• /
• 2006

There is compelling evidence that chronic inflammation predisposes to biliary tract cancer. Previously we found that aspirin use and variants in the PTGS2 gene, both of which are closely linked to inflammation, were associated with biliary tract cancer risk in a population-based study in China. To test the inflammation hypothesis further, we examined the associations of variants in 20 genes involved in the inflammation pathway with risk of biliary tract cancer and stones in a large population-based case-control study in Shanghai, China. We genotyped 56 single nucleotide polymorphisms (SNPs)from 20 inflammation genes in 411 biliary tract cancer cases (237 gallbladder cancers, 127 extrahepatic bile duct cancers, and 47 ampullary cancers), 895 subjects with biliary stones, and 786 population controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (Cls) for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer risk. Of the 56 SNPs examined, 20 showed some associations with biliary cancer and stones. Specifically, variants of the IL8, IL8RB, RNASEL, TGF-beta, and TNF-alpha genes were associated with gallstone risk, while variants in the IL1A, IL10, VEGF, and RNASEL genes were associated with gallbladder cancer risk. Adjustment for multiple comparisons did not materially change these results. Of the 10 genes with multiple SNPs, we inferred halotypes; only one haplotype in the IL8RBgene was associated with gallstones. The haplotype frequency was significantly different between bile dict cancer cases and control (p=0.007). A haplotype comprising 3 SNPs in the IL8RB gene (rs2230054, rs1126579, rs1126580) was associated with a 54% increased risk of bile duct stones (95% CI 1.14-2.07, p=0.02), relative to the most frequent haplotype. In summary, common variants in immune-related genes influencing inflammatory responeses were associated with gallstones and biliary tract cancer, lending further support to the role of inflammation in the pathogenesis of biliary stones and biliary tract cancer. Future larger studies with more complete gene coverage are needed to confirm these results.

• Tuberculosis and Respiratory Diseases
• /
• 제55권5호
• /
• pp.478-487
• /
• 2003

연구배경 : Angiotensin II가 폐포상피세포의 세포사멸을 유도하고 폐섬유모세포에서 TGF-${\beta}$등의 발현을 증가시켜 폐섬유화증을 촉진시킬 수 있다고 알려져 있어 angiotensin II receptor의 차단이 폐섬유화증을 감소시키는 효과가 있을 것으로 예상하고 특발성 폐섬유화증 환자에게 angiotensin II receptor antagonist(AGIIRA)를 투여하여 치료효과를 알아보고자 하였다. 방 법 : 저자들은 가천의대 길병원에서 특발성 폐섬유화증으로 진단된 13명의 환자를 대상으로 하였다. 이들 중 8명 의 환자에게는 angiotensin II type 1 receptor antaginist인 losartan(cozaar$^{(R)}$) 을 투여하였고 나머지 5명의 환자에게는 losartan을 투여 하지 않았으며, 치료 직전과 치료 l년 후에 모든 환자에게 폐기능 검사와 호흡곤란 지수의 정도의 변화를 측정하여 그 결과를 비교하였다. 결 과 : AGIIRA 복용 군에서는 폐기능이 전체적으로 약간의 호전을 보였으며, 미 복용 군에서는 DLco%가 5%로 증가하였으나 TLC가 14%로 감소하는 등 전반적으로 페기능이 감소하는 소견을 보였다. 폐기능 변화가 두 군 모두 통계적으로 유의성이 없었고 두 군간의 변화율의 변화에서도 통계적 유의성은 없었다. 호흡곤란 지수는 AGIIRA 복용한 군에서만 통계적으로 유의하게 더 호전을 보였다. 결 론 : 특발성 폐섬유화증의 치료에 AGIIRA가 일부 환자들에게 임상적 안정화에 도움을 줄 수 있을 것으로 사료된다. 차후 더 많은 환자를 대상으로 오랜 기간의 연구와 함께 폐섬유화에 있어서 anglotensin II와 그 receptor에 대한 기전과 역할에 대하여 더 많은 연구가 필요할 것으로 생각된다.

• 한국시조학회지:시조학논총
• /
• 제23집
• /
• pp.161-188
• /
• 2005

사설시조의 형태구조를 알아보기 위하여 시조의 형태를 종류별로 알아보고, 평시조, 엇시조, 사설시조를 형태적으로 구분하는 기준을 제시하였다. 그래서 평시조는 3장 6구 12절 이상이라 하였고, 엇시조는 3장 7구 14철 이상이라 하였고, 사설시조는 3장 8구 16절 이상이라 하였다. 이 연구는 1) 시조와 비시조, 2) 엇시조와 사설시조의 구분, 3) 서설시조의 구조 순으로 논의하였다. 1)에서는 2음보에 44조로 된 작품, 시조와 마찬가지로 3장의 형식은 갖추었지만 시조의 틀과 율조에 거리가 먼 작품, 쓰여진 말이나 어구가 우리말이 아니고 한시나 한문 문장으로 되어 있는 작품들은 비시조로 보아서 시조의 범주에서 제외시켰다. 2)에서는 엇시조는 형식을 장별로 보아 1구 2절 이상 늘어난 것만 엇시조로 간주하였고, 사설시조의 경우는 장별로 따졌을 때 어느 한 장에서 2구 4절 이상 늘어나면 사설시조로 간주하였다. 엇시조는 3장 중 어느 한 장에 구 한 개가 늘어난 경우, 사설시조는 3장 중 어느 한 장에 장 한 개가 늘어난 경우라 보면 된다. 3)에서 사설시조의 구조는 시조 1편이 3장 8구 16절 이상 된 것이라 하였다. 시조의 3장중에서 어느 한 장이 2구 4절 이상 늘어났으면 사설시조의 요건을 갖추었다고 본 것이다. 이러한 구절 첨가 현상은 (1) 초장에서 절(음보) 첨가 현상이 일어난 경우 (2) 중장에서 절 첨가 현상이 일어난 경우 (3) 종장에서 절 첨가 현상이 일어난 경우 (4) 초장과 중장에서 동시에 절 첨가 현상이 일어난 경우(5) 중장과 종장에서 동시에 절 첨가 현상이 일어난 경우 (6) 초 중 종 3장 모두에서 동시에 절 첨가 현상이 일어난 경우 등 다양하기 이를 데 없었다. 그리고 사설시조의 구절 수는 3장중 어느 한 장에서 최소 8절부터 최다 87절까지 늘어난 경우가 있어서 그 격차가 너무 크다는 것을 확인하였다.보 20, 검설뽕과 비슷한 성적을 나타내었으나 특이하게 pH 4.7로 단맛과 신맛을 함께 지니고 있었다. 7. NK-T2의 사료가치 검정평가 결과 개량뽕과 비교하여 유충기간과 화용비율, 견충비율은 거의 비슷하였으나, 단견중, 견층중. 2만두 수견량은 약간 떨어지는 결과를 보여 엽질이 비교적 우량하다고 평가되었다. 8. MK-T2로 사육한 5령3일차 누에의 아미노산을 분석한 결과 개량뽕을 급이한 대조구 간에는 서로 거의 유사한 아미노산 조성을 보여주었으나 MK-T2를 급이한 시험구의 경우 대조구와 비교하여 Leu에서 차이를 보여주었으며 Ile는 대조구에서는 검출되지 않았으나 MK-T2 시험구에서는 검출되었다. 9. MK-T2로 사육한 5령3일차 누에 에탄올 추출물의 약리효과 검정결과 누에 에탄을 추출물을 투여한 쥐에서 적출한 신장조직에 대한 HE 염색 및 조직면역화학염색 모두에서 조직학적 병징이 나타나지 않았고 $TGF-{\beta}1$ 단백 발현이 거의 확인되지 않는 수준으로 낮아졌다.며, 앞으로 LTCC가 발전 해야할 방향을 제시하고자 한다.e 121.9 ${\mu}g/100mg$ 함유되어 있었다. 버뮤다그라스(Cynodon dactylon)에서 발견되었다.이 설치 운영하고 있는 측정 장비에 의해 취득한 기상자료를 공동 활용하여 표출하면 더욱 상세한 자료의 획득과 활용이 기대되어 진다. 또한, 금번 논문에서는 산불위험지역의 격자점(15km)내에 최소한 1대의 AWS 설치방안을 제시하였지만, 금후에는 15km내에서도 능선, 계곡 등 구체적인 위치확정을 위한 선행연구가 실시되어야할 것으로 판단된다.의해 원고는 결과발생지인 미국법원의 재판관할을 강제할 수 없을 것이다. 지적재산권을 둘러싼 분쟁에 관한 재판관할과 국제법상의 판결의 승인 및 집행의 통일성을 기하기 위하여 2001년 1월 세계지적재산권기구(World