The purpose of this study is to clarify the environmental changes and human activities before and after the fortification of the Seongsan Sanseong Fortress (hereinafter mountain fortress) in Haman through using pollen analysis. For this purpose, samples were taken at the Tr-2 site in the Warm-temperate forest. The results of the analysis are as follow. ① Before and after the fortification of the mountain fortress, the area around it has changed from a broad-leaved forest (The HS-I period) into a deciduous broad-leaved forest (The HS-II period) and finally into a the mixed conifer and deciduous broad-leaved forest (The HS-III period). ② The HS-I period (before the middle of the 6th century, compared to the nationwide pollen zone RIIIa during the Postglacial) was covered with cool-temperate southern forests(including some species of Warm-temperate trees) and was very similar to the current climate environment during the Gaya period before the fortification. ③ The HS-II period (mid to late 6th century, pollen zone RIIIa) was covered with typical cool-temperate southern forests after the fortification and the temperature was slightly lower than the first stage. ④ The HS-III period (7th~8th century/9th century, pollen zone RIIIb) is an era of clear human interference, causing the destruction of forests in earnest and paving an active agricultural life.

자외선은 피부 노화를 가속화하여 피부 광노화를 유발하고, 일광 화상, 피부암 등을 유발한다. 자외선 차단제를 사용하더라도 일부 자외선에 의하여 피부 손상은 유발될 수 있기 때문에 자외선에 대한 피부 자체의 방어력을 올려주는 것이 필요하다. 최근, 식물에서 자외선 보호 기능을 하는 것으로 알려진 COP1이 사람의 피부 에서도 자외선에 대한 반응들을 조절한다고 새롭게 밝혀졌다. 본 연구에서는, COP1과 그의 결합 단백질 DET1 이 사람 피부의 각질형성세포에서 자외선에 대한 시그날 조절 물질인 c-Jun 단백질 양을 조절하는 것을 확인하 였다. 자외선에 노출 시 COP1과 DET1 발현이 감소하였고, 그 영향으로 c-Jun 단백질이 증가하였다. 반대로 COP1과 DET1을 발현하는 DNA를 transfection 시켜줄 경우 c-Jun 단백질 양이 감소하였다. 피부 각질형성 세포에서 COP1과 DET1의 발현을 조절할 수 있는 물질을 탐색한 결과, 초피나무 열매 추출물이 COP1과 DET1의 발현을 증가시켜 주었다. 초피나무 열매 추출물은 c-Jun 시그날에 의해서도 조절되는 MMP1이 자외 선에 의해 유도되는 것을 억제하였다. 뿐만 아니라, 초피나무 열매 추출물 PPAR-α 활성이 있어 장벽강화를 통한 피부 보호 효과가 있는데, 자외선에 의하여 염증 유발 물질인 IL-6와 IL-8의 발현이 증가하는 것도 억제 하였다. 사람의 팔에 자외선을 쪼여 준 경우에도 초피나무 열매 추출물이 홍반이 생기는 것을 억제하고 홍반에 의한 색소침착도 억제하였다. 종합적으로, 초피나무 열매 추출물은 다양한 메카니즘을 통하여 자외선으로부터 피부를 보호해 줄 것으로 기대된다.

엑소좀은 세포에서 분비되는 작은 소낭체로서, 기원세포와 조직에 따라 다양한 기능을 수행하며, 세포생 존 및 세포 간 커뮤니케이션에 중요한 역할을 한다. 최근 엑소좀을 활용하여 종양연구, 면역질환 개선, 질병진단 bio-marker 개발 등 다양한 분야에서 연구가 진행되고 있으나, 피부세포에서 분비기전 및 피부 생리적 기능에 대한 연구는 미흡한 실정이다. 따라서 본 연구에서 인체피부 유래 각질형성세포(HaCaT)로부터 분리된 엑소좀 이 피부각질형성세포의 증식과 이주에 미치는 영향을 확인하고자 하였다. HaCaT으로부터 ExoQuick-TC를 활 용하여 엑소좀을 분리하고, 열처리 엑소좀(boiled exosome)과 무처리 엑소좀(unboiled exosome)으로 구분하 였다. HaCaT 유래 엑소좀은 농도 의존적으로(0.1 ∼ 20 μ g/mL) HaCaT의 증식을 유도하였으며, 20 μ g/mL에 서 대조군(control)에 비해 각각 186.96 ± 3.87%(열처리) 또는 193.48 ± 10.48%(무처리)의 증식 유도활성 을 나타내었다. 또한 HaCaT 유래 무처리 엑소좀은 농도 의존적인(0.1 ∼ 20 μ g/mL) HaCaT의 이주활성을 나타내었고, 20 μ g/mL에서 대조군에 비해 179.39 ± 4.89%의 이주를 유도하였다. 그러나 열처리 엑소좀은 이주 유도활성을 나타내지 않았다. 뿐만 아니라 무처리 HaCaT 유래 엑소좀은 collagen sprout outgrowth를 농도 의존적으로 유도함을 확인하였다. 이러한 결과를 통해서 HaCaT 유래 엑소좀은 지질 및 열에 안정한 물질 이 세포의 증식을 유도하고, 단백질 또는 열에 불안정한 물질이 세포의 이동 및 sprout out growth 활성에 관여 하는 것으로 확인되었다. 따라서 피부각질형성세포 유래 엑소좀은 피부의 재상피화 및 상처치유 등의 활성을 나타낼 수 있으며, 향후 화장품소재로서 응용 가능성이 확인되었다.

진피 상층부 모세혈관은 젊은 사람에 비해 노인에서 그 수와 크기가 감소되어 있어 피부에서 모세혈관이 차지하는 비율이 나이에 따라 급격히 낮아진다. 연교는 물푸레나무과에 속하는 개나리 열매를 건조한 것으로 주로 염증성 또는 항균성 질환에 오랫동안 사용되어져온 약재로서 지금까지 피부 혈관신생과 관련된 효능은 보 고되지 않았다. 따라서 본 연구에서는 연교 추출물이 혈관신생과 관련된 인자들에 미치는 영향을 피부 각질형성 세포주를 이용하여 조사하고자 하였다. 우리는 먼저 연교 추출물이 혈관신생과 관련된 인자들의 발현에 어떤 영향을 주는지 알아보고자 각질형성세포에 연교 추출물을 처리하고 혈관신생과 관련된 55개 단백질의 발현을 분석하였다. 발현 변화를 보인 인자들 중 혈관내피세포 성장인자(VEGF, vascular endothelial growth factor) 는 강력한 혈관신생 촉진인자로서 연교 추출물에 의해 유의하게 발현이 증가되었다. 따라서 연교 추출물이 VEGF 생성에 미치는 영향에 대해 자세히 알아보고자 연교 추출물을 농도별로 세포에 처리하고 단백질 발현과 mRNA 발현 변화를 조사한 결과, 연교 추출물은 VEGF의 유전자 수준뿐만 아니라 단백질 수준의 발현을 2배 이상 농도 의존적으로 증가시켰다. 다음으로 연교 추출물에 의한 VEGF 발현 증가에 관여하는 신호전달 기전을 밝히고자 MAPK 활성을 살펴본 결과, 연교 추출물을 세포에 처리하면 5 min 내 p38 MAPK의 활성이 관찰되었 으며, 특이적 억제제 전처리를 통해 p38 MAPK 활성을 억제하면 연교 추출물을 처리하더라도 VEGF의 유전자 및 단백질 발현이 완전히 억제됨을 확인하였다. 이러한 결과로부터 연교는 피부 각질형성세포에 작용하여 p38 MAPK 활성을 통해 VEGF 생성을 유도함을 알 수 있었고, 피부에서 노화에 따른 표피아래 모세혈관 손상을 개선하는데 도움을 줄 수 있는 후보 물질로서 연교의 새로운 효능을 제안한다.

Purpose - The study sought to examine the relationship between individual characteristics and system features and Human Resource Information System (HRIS) success in Japanese manufacturing companies in Malaysia. Research Design, Data, and Methodology – This study adopt quantitative approach to investigate the relationship between individual characteristics and system features and HRIS. Toward this objective, a total of 700 questionnaires were mailed to a representative of the organization. A total of 187 questionnaires were returned, and only 145 were usable for further analysis, representing a response rate of 20.71%. Result - Results indicated that individual characteristics and two dimensions of system characteristics (ease of use and training) were significantly related to HRIS success. Unexpectedly, the results showed that the third dimension of system features (documentation) was unrelated to HRIS success. Conclusions - The results partially support the underlying arguments that individual characteristics and system characteristics have significant influences on HRIS success. The finding suggests that HRIS success in the organization can be generated as a result of good implementation of system support and employees’ readiness to apply HRIS in their jobs.

Cynanchum wilfordii Radix (CWR), Arctium lappa L (ALL), and Dioscorea opposite (DO) have been known to improve blood lipid profile, blood pressure, and inflammation. To find the optimal combination ratio of CWR, ALL, and DO in terms of vascular health improvement, we compared the effects of various combinations on gene expression of Vascular cell adhesion protein 1 (VCAM-1) in human aortic smooth muscle cells (HASMC). VCAM-1 mediates endothelial leukocyte adhesion and is upregulated in atherosclerosis. Cells was stimulated by TNF-α (10 ng/㎖, 2h) and treated with various combinations for 24 h. A combination (CADM5, CWR:ALL:DO = 2:1:1) showed the strongest suppression of VCAM-1 so that CADM5 was chosen for further experiments. We performed cell viability test with CADM5 (0, 3.125, 12.5, 25, 50, and 100 ㎍/㎖) and no cytotoxicity was found. We also investigated the effect of CADM5 on protein expression of VCAM-1, ICAM-1, Nrf-2, and HO-1 using western blotting. We found that CADM5 diminished the expression of VCAM-1 and increased the expression of Nrf-2 and HO-1. Therefore, we concluded that CADM5 (CWR:ALL:DO = 2:1:1) effectively improves vascular health by regulating the expression of VCAM-1.

Background : Tooth vitality is reflected by the health of dental pulp. Schisandrin C is a natural compound extracted from the fruit of Schisandra chinensis which has anti-inflammatory and anti-oxidant properties. The role of Schisandrin C on human dental pulp cells (HDPCs) has not been studied yet. This study examined the properties of Schisandrin C as an anti-inflammatory and anti-oxidant compound, and whether its characteristics promote mitochondrial biogenesis in HDPCs. Methods and Results : HDPCs were extracted from fresh third molars and cultured. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analyzed by a Muse cell analyzer. Western blotting and gelatin zymography were used to identify the presence of anti-oxidants, as well as inflammatory and mitochondrial biogenesis. Confocal microscopy was used for the detection of mitochondrial activity. Schisandrin C inhibited lipopolysaccharide (LPS)-stimulated inflammatory molecules; intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 and -9 (MMP-2/9), NO production, ROS formation and the mitogen-activated protein (MAPK) pathway through minimizing the nuclear factor kappa B (NF-kB) translocation. Schisandrin C increased the expression of superoxide dismutase (SOD) enzymes as well as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a) through the phosphorylated-protein kinase B (p-AKT) and nuclear factor erythroid 2-related factor-2 (Nrf-2) pathways. The anti-inflammatory and anti-oxidant properties of Schisandrin C promoted mitochondrial biogenesis. Conclusions : These results suggest that Schisandrin C may be used as an anti-inflammatory compound to reduce oral inflammation such as pulpitis.

Background : Lutein, a xanthophyll, consists of chains with 8 conjugated double bounds containing closed rings on each end of the chain. This carotenoid is found in fruits and vegetables, especially dark green leafy vegetables such as green tea. In this study, we investigated the anticancer effects of purified lutein from green tea on human cancer cell lines containing prostate carcinoma cancer cells (LNCaP). Methods and Results : Prostate carcinoma cancer cells (LNCaP) were cultured and evaluated the inhibitory effect of lutein isolated from green tea compared other carotenoids (β-carotene and lycopene) on cell proliferation. Cyclin D1 and PCNA were evaluated as cell differentiation. In results, PCNA/cyclin regulates the initiation of cell proliferation by mediating DNA polymerase. Under cultural conditions, lycopene remarkably suppressed the PCNA expression prostate cancer cell line LNCaP in higher doses (20 μM - 100 μM) statistically. However, β-carotene and lutein presented the less inhibitory effects on PCNA expression. Determination of PCNA expression in control and treated cells demonstrates that lycopene did affect proliferation in LNCaP cancer cells in dose-dependent manner. However, β-carotene and lutein suppressed the cyclin D1 expression in dose-dependent manner but no in lycopene group. These results indicate that differ carotenoids presented the various suppressive ability of PCNA and cyclin D1 expression in cell proliferation. Conclusion : In conclusion, lutein suppressed the carcinogenesis of induced prostate cancer cell line by acting as a suppressor for inhibiting the expression of cyclin D.

Most of the commercial devices for vitrification are directly immersed into the warming solution (WS) for increasing of warming rate. However, the previous modified cut standard straw (MCS) which has reported is difficult to immerse into the WS. The aim of this study was to investigate whether the long cut straw (LCS) could be useful as a stable tool for vitrified-warmed human blastocysts. A total of 138 vitrified-warmed cycles were performed between November 2013 and November 2014 (exclusion criteria: women ≥38 years old, poor responder, surgical retrieval sperm, and severe male factor). The artificial shrinkage was conducted using 29-gauge needles. Ethylene glycol and dimethyl sulfoxide (7.5% and 15% (v/v)) were used as cryoprotectants. Freezing and warming were conducted using the LCS tool. The cap of LCS was removed using the forceps in the liquid nitrogen (LN2) and then directly immersed into the first WS for 1 min at 37℃ (1 M sucrose). Only re-expanded blastocysts were transferred after it was cultured in sequential media for 18-20 h. A total of 294 blastocysts were warmed, and all were recovered (100%). Two hundred eighty-five embryos were survived (96.9%). The vitrifiedwarmed blastocysts of all patients were transferred without any cancellation. We were able to achieve a reasonable implantation (24.2%), following by clinical pregnancy (36.2%), which then continued to ongoing pregnancy (36.2%), and live birth (31.2%). Using LCS is achieved the acceptable rates of survival, pregnancy and live birth. Therefore, the LCS could be considered as a stable and simple tool for human embryo vitrificaton.

The natural environment plays an important role not only in ecological sustainability, but also in human health. Growing attention has been focused on the health benefits of natural environments with increasing scientific evidence in this field. Urban green space has positive effects on individual and community health; thus, it is considered as social infrastructure. The natural environment promotes mental health by relieving psychological stress and depression. Physical health can be improved by experiencing nature, which reduces physiological stress and boosts the immune system. Several international initiatives have been undertaken to improve our understanding in this field and to utilize these benefits for health promotion. Interdisciplinary approaches are needed to promote human health through the natural environment in the fields of science, education, planning and policy.

본 연구에서는 방사성폐기물 처분장이 건설·운영되고, 폐쇄 후 제도적 관리기간이 끝나게 되어 그 곳에 처분장이 존재한다 는 사실과 위해(hazard)의 정도가 잊혀 지면서 무의식적인(inadvertent) 처분장 인간침입이 일어날 경우 이를 어떻게 평가할 것인지에 대해 기술하였다. 처분장 인간침입을 평가하기 위한 전제조건을 국내 또는 국제적으로 권고한 사항에 근거하여 설 정하고 처분장 인간침입 평가방법론에 대해 기술하였다. 처분장 인간침입 평가 방법론에서는 사회적요인, 인간침입 시나리 오, 방지대책 도출시 상호 관계에 대해 언급하였으며, 시나리오 도출절차에 대해서도 언급하였다. 인간침입 방지대책을 도 출하기 위한 절차를 네 단계로 구분하여, 기본 정보를 도출하는 방법, 일반방지대책을 도출하는 방법, 후보방지대책을 도출 하는 방법, 정형화된 시나리오를 고려하여 최종적으로 인간침입 방지대책을 도출하는 방법 등에 대해 체계적으로 기술하였 다. 본 연구에서 도출된 인간침입 평가 방법론은 향후 인간침입의 가능성을 감소시키고 인간침입 발생 시 위해를 줄이기 위 한 방지대책 마련 시 유용하게 활용될 것으로 판단된다.

We investigated the antioxidative and protective effects of corn silk (Zea mays L.) ethanol extracts on human HaCaT cells and erythrocytes. The NICS-2 fraction, extracted from corn silk, exhibited favorable 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical scavenging activities with IC50valuesof13.3± 0.3 μg/mL and 14.2 ± 0.1 μg/mL when compared with those of α-tocopherol, a positive control, with IC50=10.4± 02.2 and 22.2 ± 3.6 μg/mL, respectively. In addition, we investigated skin protection effects of NICS extracts of corn silk in HaCaT keratinocytes. To investigate the pharmacological potential of NICS-1 and NICS-2 extracts of corn silk on UV-B-induced damage in HaCaT cells, we measured the activity of interleukin (IL) 1a. Our results showed that all the corn silk extracts inhibited the UV-B-induced activity of IL-1a. In particular, NICS-1 extracts of corn silk significantly suppressed IL-1a activity in a dose-dependent manner without inducing cytotoxicity. These results indicate that the ethanol extracts of corn silk (Zea mays L.) could function as natural cytoprotective agents and antioxidants in biological systems, particularly the skin exposed to UV radiation, by protecting cellular membrane against reactive oxygen species (ROS).

To analyze human thermal environments in protected horticultural houses (plastic houses), human thermal sensations estimated using measured microclimatic data (air temperature, humidity, wind speed, and solar and terrestrial radiation) were compared between an outdoor area and two indoor plastic houses, a polyethylene (PE) house and a polycarbonate (PC) house. Measurements were carried out during the daytime in autumn, a transient season that exhibits human thermal environments ranging from neutral to very hot. The mean air temperature and absolute humidity of the houses were 14.6-16.8℃ (max. 22. 3℃) and 7.0-12.0 g∙m-3 higher than those of the outdoor area, respectively. Solar (K) and terrestrial (L) radiation were compared directionally from the sky hemisphere (↓) and the ground hemisphere (↑). The mean K↓ and K↑ values for the houses were respectively 232.5-367.8 W∙m-2 and 44.9-55.7 W∙m-2 lower than those in the outdoor area; the mean L↓ and L↑ values were respectively 150.4-182.3 W∙m-2 and 30.5-33.9 W∙m-2 higher than those in the outdoor area. Thus, L was revealed to be more influential on the greenhouse effect in the houses than K. Consequently, mean radiant temperature in the houses was higher than the outdoor area during the daytime from 10:45 to 14:15. As a result, mean human thermal sensation values in the PMV, PET, and UTCI of the houses were respectively 3.2-3.4℃ (max. 4.7℃), 15.2-16.4℃ (max. 23.7℃) and 13.6-15.4℃ (max. 22.3℃) higher than those in the outdoor area. The heat stress levels that were influenced by human thermal sensation were much higher in the houses (between hot and very hot) than in the outdoor (between neutral and warm). Further, the microclimatic component that most affected the human thermal sensation in the houses was air temperature that was primarily influenced by L↓. Therefore, workers in the plastic houses could experience strong heat stresses, equal to hot or higher, when air temperature rose over 22℃ on clear autumn days.

천연자원으로부터 항노화 화장품 신소재를 탐색하던 중, 국내 자생버섯의 일종인 붉은싸리버섯 자실체 추출물이 항산화 활성과 인체 호중구 엘라스타제 저해활성이 우수함을 확인하고 일련의 연구를 수행하였다. 붉 은싸리버섯 추출물의 DPPH 라디칼 소거활성은 붉은싸리버섯 추출물 500 μ g/mL 처리시 117.0 mg/mL (ascorbic acid 환산값)의 매우 우수한 소거활성을 나타냈다. Peroxy 라디칼 소거활성을 oxygen radical absorbance capacity (ORAC) assay 를 통하여 측정한 결과 붉은싸리버섯 추출물 1, 10, 20 μ g/mL 처리 시, 각각 0.8, 5.2, 7.8 ORACRoo (trolox equivalents, 1 μ M)로 농도 의존적으로 높은 소거활성을 나타냈다. 뿐만 아니라 cellular antioxidant capacity를 DCF fluorescence intensity (% of control)로 조사한 결과에서도 붉은싸리버섯 추출물 20 μ g/mL 처리시 약 30% 이상 높은 항산화 활성을 나타냈다. Human neutrophil elastase 저해활성은 농도 의존적으로 저해활성을 나타냈으며 특히 에탄올 추출분획에서 ED50 값은 42.9 μ g/mL이 었다. 붉은싸리버섯 추출물은 Bacillus subtilis (B. subtilis), Escherichia coli (E. coli), Candida albicans (C. albicans), Aspergillus oryzae (A. oryzae) 균주 모두에서 항균활성은 나타나지 않았다. 또한 염증성 cytokine인 interleukin-10 및 interferon-γ (IFN-γ)의 생산 또는 분비 조절에는 영향을 미치지 않았다. 이상 의 결과로 붉은싸리버섯 추출물은 항산화활성과 elastase 저해활성을 우수하여 피부에 자극이 없는 항노화 화장 품 조성물로 유용하게 사용될 수 있음을 확인하였다.

This study surveyed the human thermal responses according to the green space types. Three green space type (forest trail, residential area and central building district) were set the research sites in Dongdaemun-gu, Seoul. The physical thermal environment factors were measured while the human thermal responses were investigated. The air temperature and radiant temperature showed higher in central building area where sky view factor was 0.799 than in forest trail where sky view factor was 0.651. The skin temperatures increased according to green space type and rectal temperatures showed the highest value in central building area. The thermal sensation vote and thermal comfort showed the differences only between forest trail and central building area. These results will use as base line data on the green space type management plan for thermal environment amenity.

소핵시험은 세포분열 단계 중 간기 세포의 세포질 내 소핵 유무를 조사함으로써 유전독성을 평가하는 시험법이다. 최근 화장품 안전성 평가에 동물실험을 금지하거나 최소화하려는 노력이 확산되고 있어 유전독성 평가에 있어서도 기존의 동물실험이 아닌 새로운 in vitro 시험법이 요구되고 있다. 본 연구에서는 3차원 배양 인공피부모델인 KeraSkinTM을 이용하여 도포 처치된 물질의 유전독성을 평가하였다. 2종의 유전독성물질인 mitomycin C (MMC)와 methyl methanesulfonate (MMS)는 농도 의존적으로 세포독성과 소핵 형성이 유도 된 반면, 대조물질인 4-nitrophenol (4-NP)와 trichloroethylene (TCE)에서는 농도 의존적으로 세포독성은 관찰되었으나 소핵은 형성되지 않았다. 따라서 인공피부모델을 이용한 소핵시험이 화장품과 같은 피부적용물질 의 in vitro 유전독성 평가에 유용할 것으로 사료된다.

본 연구는 루터가 가르친 인간의 죄에 대한 제어로서 하나님의 숨어계 심의 세 종류를 제시하고, 한국 개신교에 대한 적용점을 살펴보기 위한 것 이다. 루터에게서 하나님은 첫 번째로, 신자에게는 자신을 드러내시지만, 불신자로부터 자신을 숨기신다. 참된 기독교 신자가 되는 길은 성령의 도 우심 가운데 율법과 복음을 바르게 이해하는 데 있다. 두 번째로, 하나님은 영광의 신학자로부터는 자신을 감추시지만, 십자가의 신학자에게는 자신을 드러내신다. 신자는 탐욕을 추구하여 하나님을 우상화 하는 영광의 신학을 버리고, 인간의 죄를 드러내고 극복하게 하는 십자가의 신학을 가질 때 참 된 하나님을 섬길 수 있다. 세 번째로, 하나님은 모든 신자로부터 숨어계신 다. 참된 신자는 숨어계신 하나님의 위엄을 알고, 하나님의 계시하신 뜻을 붙드는 신앙을 가져야 한다.

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

Apoptosis has been regarded as a therapeutic target because apoptosis is typically disturbed in human cancer. Silymarin found in the seeds of the milk thistle (Silybum marianum) has been reported to exert anti-cancer properties through apoptosis. This study was performed to investigate the molecular target for silymarin-mediated apoptosis in human colorectal cancer cells. Silymarin reduced the cell viability and induced an apoptosis in human colorectal cancer cells. ATF3 overexpression increased PARP cleavage by silymarin. Increased ATF3 expression in both protein and mRNA was observed in silymarin-treated cells. In addition, silymarin increased the luciferase activity of ATF3 promoter. Inhibition of JNK and IκK-α blocked silymarin-mediated ATF3 expression. The results suggest that silymarin induces apoptosis through JNK and IκKα-dependent ATF3 expression in human colorectal cancer cells.

Previously we observed that human adipose-derived stem cells (hADSCs) could form aggregation during culture in the presence of human serum (HS). In the present study, we have examined if the aggregation might result from the cell migration and analyzed the difference of cell adhesivity after culture in various conditions. When cells were cultured in fetal bovine serum (FBS) alone, there was no morphological change. Similarly, cells pretreated with FBS for 1 day or cultured in a mixture of FBS and HS showed little change. In contrast, cells cultured in HS alone exhibited formation of cell-free area (spacing) and/or cell aggregation. When cells cultured in FBS or pretreated with FBS were treated with 0.06% trypsin, almost cells remained attached to the dish surfaces. In contrast, when cells cultured in HS alone were examined, most cells detached from the dish by the same treatment. Treatment of cells with forskolin, isobutylmethyl xanthine (IBMX) or LY294002 inhibited the formation of spacing whereas H89 or Y27632 showed little effect. When these cells were treated with 0.06% trypsin after culture, most cells detached from the dishes as cells cultured in HS alone did. However, cells treated with IBMX exhibited weaker adhesivity than HS alone. Based on these observations, it is suggested that HS treatment might decrease the adhesivity and induce three-dimensional migration of hADSCs, in the latter of which cAMP signaling could be involved.