This research investigated the immunoenhancing effect through the intracellular MAPKs and NF-B signaling pathways in macrophages activated by crude polysaccharides (YBP) of barley sprouts. YBP extracted from barley sprouts is composed of xylose (25.8%), arabinose (24.1%), galactose (23.4%), and galacturonic acid (11.7%). YBP did not affect the cytotoxicity and showed superior secretion of nitric oxide (NO), interleukin (IL)-6, and tumor necrosis factor (TNF)- by RAW264.7 cells. Also, YBP dose dependently increased IL-6, TNF-, and inducible nitric oxide synthase (iNOS) mRNA gene expression. In the western blot, YBP strongly induced the phosphorylation of the p38, JNK, ERK, and IB pathways in RAW 264.7 cells. In the anti-pattern recognition receptor (anti-PRRs) assay, the effect of YBP on NO secretion strongly decreased toll-like receptor (TLR) 4 and Dectin1 antibodies, whereas IL-6 and TNF- secretion by YBP mainly decreased SR and CD14. Therefore, we concluded that YBPinduced NO, IL-6, and TNF- were secreted via the MAPKs, while NF-B pathways through TLR4, Dectin1, SR, and CD14 receptors existed in a macrophage surface and were involved in the immunoenhancing effect.
In crustaceans, molting is regulated by interactions between ecdysteroid and juvenile hormone (JH) signaling pathway-related genes. Unlike the ecdysteroid signaling pathway, little information on the role of JH signaling pathway-related genes in molting is available in zooplanktonic crustaceans. In this study, three genes (juvenile hormone acid O-methyltransferase (JHAMT ), methoprene-tolerant (Met ), and juvenile hormone epoxide hydrolase (JHEH )) which are involved in the synthesis, receptor-binding, and degradation of JH were identified using sequence and phylogenetic analysis in the brackish water flea, Diaphanosoma celebensis. Transcriptional changes in these genes during the molting cycle in D. celebensis were analyzed. Sequence and phylogenetic analysis revealed that these putative proteins may be functionally conserved along with those of insects and other crustaceans. In addition, the expression of the three genes was correlated with the molting cycle of D. celebensis, indicating that these genes may be involved in the synthesis and degradation of JH, resulting in normal molting. This study will provide information for a better understanding of the role of JH signaling pathwayrelated genes during the molting process in Cladocera.
바이오파울링은 정삼투 공정(FO)에서 비가역성 오염을 야기한다. 바이오파울링 성장과정에서 미생물은 신호전달물질(AHL)의 분비를 통해 의사소통하며, 이를 쿼럼 센싱(QS)이라 한다. 본 연구에서는 Rhodococcus sp. BH4의 용해액에 있는 AHL 분해효소(quorum quencher; QQ)를 이용하여 FO에서의 바이오파울링을 저감하고자 한다. QQ 물질 유무에 따라 P.aeruginosa 종의 막 표면의 바이오필름 성장 및 부착량을 비교한 회분식 실험에서 10mg/L의 QQ 물질이 AHL을 70% 이상 분해함을 확인했다. FO 장치를 이용한 실험실 규모의 연속 실험에서는 10mg/L의 QQ 물질 존재 시 체외 고분자물질(EPS)이 대조군에 비해 80% 이상 감소했다. 위 연구를 통해 QQ가 FO에서 바이오파울링을 저감하는 새로운 방법이 될 수 있음을 확인하였다.
Muscle atrophy is characterized by a decrease in the mass of the muscle. With an increase in life expectancy and chronic illnesses, the incidence of muscle atrophy is increasing and the quality of life of patients is decreasing. Thus, reducing muscle atrophy is of high clinical and socio-economic importance. Mistletoe is a semi-parasitic plant that has been used as a traditional medicine in many countries to treat various human illnesses. It has been reported that Korean mistletoe extract (KME) has diverse biological functions including anti-tumor, anti-oxidant, anti-diabetic, anti-obesity properties, and extension of lifespan. Especially, we have recently reported that KME improves exercise endurance in mice, indicating its beneficial roles in enhancing the capacity of skeletal muscle. In this study, we investigated whether KME could activate the signaling pathway related to protein synthesis in a mouse model of muscle atrophy. Interestingly, KME efficiently activated the Akt/mTOR pathway, and Akt and mTOR are important signaling hub molecules for the acceleration of protein synthesis in muscle cells. In addition, KME also increased the activity of S6 kinase which is involved in the regulation of muscle cell size. Moreover, the ERK activity, required for transcription of ribosomal RNA for protein synthesis, was also enhanced in KME-treated mouse muscle. These data support the idea that KME increases muscle mass via increased protein synthesis. Our findings also suggest that Korean mistletoe might be a promising candidate for the development of functional foods that are beneficial for preventing muscle atrophy.
Rutin은 메밀에 함유되어 있는 것으로 잘 알려져 있는 flavonoid 물질로서, 최근 연구들에서 rutin의 항염증 및 암예 방 활성이 보고되어져 왔다. 그러나, rutin의 암예방 활성과 관련된 분자생물학적 기전에 대한 연구는 아직까지 미비 한 실정이다. 따라서, 본 연구에서는 발암 과정 중 하나인 세포의 악성 변형을 EGF로 유도하여 rutin이 이를 억제하는 지 여부를 확인하는 실험을 진행하였으며, 그 분자생물학적 기전을 규명하고자 하였다. Soft agar assay 실험 결과, rutin은 EGF로 유도된 세포의 악성 변형을 25 μM, 50 μM 100 μM에서 농도별로 감소시켰다. 또한 EGF로 유도된 MEK/ERK 및 MKK4/JNK 신호전달체계의 인산화를 저해하였다. 그러나 이와는 대조적으로 rutin은 EGF로 유도된 MKK3/6/p38 신호전달체계 인산화는 감소시키지 못하는 것으로 확인되었다. 이상의 연구결과들은 rutin이 암화 과정 중 발생되는 세포의 악성변형 과정을 촉진시킨다고 잘 알려져 있는 MEK/ERK 및 MKK4/JNK 신호전달체계의 활성화 를 억제함으로써 암예방 활성을 나타낸다는 것을 제시하고 있으며, 이는 메밀의 생리활성 성분인 rutin의 암예방 생리 활성 소재로서의 이용 가능성을 보여주는 중요한 연구 결과라 할 수 있겠다. 또한 위 연구결과는 MEK/ERK 및 MKK4/JNK 신호전달 체계를 표적으로 하는 생리활성 소재 탐색에도 활용 가능할 것으로 생각되어진다.
이전 연구들에서 rutin과 quercetin을 포함한 여러 flavonoids의 암예방 활성이 보고되었으나, rutin의 경우 섭취 시 체내에서 HVA, HPAA, DHT라는 대사체로 변형되어 흡수된다. 그러나, 이들 대사체와 관련한 암예방 효능 및 그 분자생물학적 작용기작에 대한 연구 결과는 보고된 바가 없어, 본 연구에서 이를 규명하였다. DHT는 EGF로 유도된 세포 변형을 억제하였으며, AP-1 전사인자의 활성 또한 억제하였다. DHT는 Raf-1 효소 활성을 효과적으로 저해하므로서 MEK 및 ERK의 인산화를 억제하였으며, Raf-1과 ATP는 비경쟁적으로 직접 결합하여 Raf-1 효소 활성을 저해한다는 사실을 밝혀내었다. 이와는 대조적으로, rutin은 EGF로 유도된 세포 변형, AP-1 활성, ERK 신호전달체계, Raf-1 효소 활성을 억제하지 못하였다. 이상의 연구결과는 DHT의 암예방 활성이 발암과정과 밀접한 연관이 있는 Raf-1 효소 활성을 억제하여 세포 변형을 억제하는 것과 관련되어 있다는 것을 제시한다.
Oral lichen planus (OLP) is an atypically keratinized and ulcerative lesion, producing severe pain and discomforts in the involved patients. Nevertheless, the etiological factor or the pathogenetic mechanism has not been clearly elucidated. In the present study, the different gene expressions were screened in 21 cases of OLP by immunohistochemical (IHC) array method using 80 antibodies, and found that the pathway of E-cadherin/β-catenin was abnormally expressed compared to the other essential genetic pathways. Particularly, the expressions of eIF5A, DHS, and DOHH, which are the biomarkers of protein translation, were remarkably reduced, nevertheless the expression of β-catenin was strongly positive in the 7 cases among 21 cases of OLP. The other expressions of p53, BCL-2, MDM-2, PAKT, BAX, BAK, BAD, NFkB, HO-1, etc, were usually weak or sparse, while the expressions of PCNA, CDK4, and HSP-70 were markedly increased. Taken together, it is presumed that the overexpression of β-catenin indicates the derangement of E-cad/β-catenin/NFkB pathway, causing the transcription of cellular proliferating genes in downstream events, i.e., PCNA and CDK4, and that it may be eventually relevant to the malignant potential of OLP epithelial cells. It is also suggested that the activation of β-catenin/TCF/LEF1 pathway be closely relevant to the immunological reaction of OLP with the accumulation of T-cells underneath the mucosal epithelium.
There is considerable evidence that ionizing radiation (IR) mediates checkpoint control, repair and cell death. In this study, we have used a high density microarray hybridization approach to characterize the transcriptional response of human breast carci
본 연구에서 상동나무 가지 추출물(STB-E100)은 대장암 세포에서 세포사멸을 유도하여 세포생육을 억제하였다. 또한 Iκ B-α 인산화를 통한 IκB-α 단백질 분해를 유도하며 이로 인해 P65 핵내 전이를 유도하여 NF-κB 신호전달을 활성화시킨다. NF-κB 신호전달 활성화는 GSK3β 활성화를 통해 P65 핵내 전 이를 유도에 의한 것이지만 IκB-α분해는 GSK3β 의존성이 아니다. 상동나무 가지 추출물은 이러한 신호전달 활성화를 통해 세포사멸을 유도하여 대장암의 세포생육을 억제한다. 본 결과를 바탕으로 상동나무 가지가 암 예방 및 치료를 목적으로한 표적 요법에서 항암제 개발의 잠재적 활용 소재로서 이용 가능하다고 사료된다. 그러나 대장암 세포에서 상동나무 가지 추출물에 의해 유도된 NF-κB 신호전달 작용기전을 좀 더 구체적으로 구명할 필요가 있고 대장암에 대한 세포사멸과 작용기전의 정확한 관련성을 조사하기 위해 추가적인 연구가 필요하다.
Particulate matter with an aerodynamic diameter of less than 2.5 μM (PM2.5) is one of the major environmental pollutants. Di(2-ethylhexyl) phthalate (DEHP), an endocrine disrupting chemical in PM2.5, has been utilized for the manufacturing of polyvinyl chloride to increase the flexibility of final products. In the present study, we investigated the ecotoxicological effect of DEHP on the viability of skin keratinocytes (HaCaT). DEHP induced apoptotic cell death mediated by phosphorylation of extracellular signal-regulated kinase through the production of intracellular Reactive Oxygen Species (ROS). Interestingly, we found that DEHP induces the phosphorylation of the nuclear factor-kappa B responsible for the expression of cleaved caspase-3 as an executional cell death protease in HaCaT cells. On the basis of these results, we suggest that DEHP in PM2.5 induces the apoptotic death of human keratinocytes via ROS-mediated signaling events.
In patients with acute cerebral infarction, taranscranial ultrasonography is helpful in assessing blood flow, but in some patients, failure to detect cerebral blood flow through the temporal window is an important problem in expansion of clinical indications for transcranial ultrasonography. This study was performed between May 2016 and September 2016 in patients admitted to the neurology department of Chosun University Hospital with cerebral infarction and underwent transcranial ultrasonography and brain magnetic resonance image. Of the 129 patients, 47 were female (36.4%). The mean age of the patients was 80.7±8.0 years. Fifty patients (38.8%) did not showed any blood flow signal due to poor temporal window. The mean age of patients with temporal window failure (83.8±6.0 years) was significantly higher than without temporal window failure (78.7±8.5), and the temporal window failure was significantly higher in women. In conclusion, temporal window failure was more common in elderly and women in this study. In addition to temporal bone thickness and heterogeneity of temporal bone due to osteoporosis, hyperlipidemia may also be associated with temporal window failure and future prospective studies will be needed.
Background : Ginseng (Panax ginseng) has been reported to exert an anti-inflammatory activity in a variety of inflammatory. However, inflammation-regulatory activity of wood-cultivated ginseng has not been thoroughly evaluated. In this study, we evaluated the anti-inflammatory effect of wood-cultivated ginseng and elucidated the potential mechanisms in LPS-stimulated RAW264.7 cells.
Methods and Results : Inhibitory effects of the old wood-cultivated ginseng (WCG-O), young wood-cultivated ginseng (WCG-Y) and ginseng (G) on NO and PGE2 production were examined using the Griess assay and ELISA kit. Suppressive effects of WCG-O on inflammatory gene expression, transcriptional activation, and inflammation signaling events were investigated using Western blot analysis, RT-PCR analysis and luciferase activity reporter gene assay. WCG-O dose-dependently suppressed nitric oxide (NO) and Prostaglandin E2 (PGE2) production in LPS-stimulated RAW264.7 cells. In addition, WCG-O attenuated LPS-mediated overexpression of iNOS and COX-2. In addition, WCG-O blocked the expression of TNF-α and IL-1β in LPS-stimulated RAW264.7 cells. In elucidation of the potential mechanisms for anti-inflammatory effect, WCG-O inhibited the activation of IκK-α/β, the phosphorylation of IκB-α, and degradation of IκB-α, which results in the inhibition of p65 nuclear accumulation and NF-κB activation. In addition, WCG-O suppressed the activation of ERK1/2, p38 and JNK, which results in the inhibition of ATF2 nuclear accumulation.
Conclusion : These results indicate that WCG-O may exert anti-inflammatory activity through the inhibiting NF-κB and MAPK signaling. From these findings, WCG-O has potential to be a candidate for the development of chemoprevention or therapeutic agents for the inflammatory diseases.
ABA는 식물에서 비 생물학적 스트레스 내성에 관여하는 중 요한 식물 호르몬이다. 애기장대의 group A bZIP 전사인자는 ABA 신호전달 과정에 중요한 역할을 한다고 알려져 있다. 그러나 벼에서는 group A bZIP 전사인자의 기능이 잘 알려져 있지 않다. 따라서 우리는 벼에서 group A bZIP 전사인자인 OsABF3 (Oryza sativa ABA responsive element binding factor 3)를 연 구하였다. 이를 위해 벼의 다양한 조직과 다양한 스트레스(가 뭄, 염분, 저온, ABA, 산화 스트레스)에 따른 OsABF3 발현 패턴을 분석하였다. 또한 maize의 원형질체에서 GFP fusion 벡터를 사용한 세포 내 위치 분석을 통해 OsABF3가 핵단백질이라는 것을 확인하였다. Yeast one-hybrid 실험을 통해 OsABF3의 Cterminal 부분이 ABREs에 결합한다는 것과 N-terminal 부분 이 하위 유전자의 transactivation 하는데 필요하다는 것을 알수 있었다. 그리고 T-DNA가 삽입된 OsABF3의 homozygous 돌연변이체가 야생형과 과발현체에 비해 발아와 발아 후 단계 에서 고농도의 ABA에 대한 민감도가 더 감소한 것을 알 수 있었다. 결과적으로 종합해 볼 때 OsABF3는 ABA의 의존적인 경로를 통해 비 생물학적 스트레스에 반응하는 유전자의 발현을 조절하는 기능을 하는 전사 조절자이다. 또한 OsABF3의 transactivation을 측정하는 실험에 있어서 억제 domain이 존 재한다는 결과를 얻었다.
The Wnt/β-catenin signaling pathway is mandatory in adipogenesis. In this study, we investigated the applicability of functional materials for the treatment of obesity by examining Wnt/β-catenin pathway reporter activity related to adipocyte differentiation inhibiting with korean native plant extracts. The luciferase activity of HEK 293-TOP cells increased the reporter activity approximately 152% and 130% by treatment with Sanguisorba officinalis and Thuja orientalis, respectively. Ricinus communis were represented about 90% higher activity, two samples(Rosa rugosa and Sophorae Flos) showed 80% higher activity than the control. Three samples of plant extracts (Zanthoxylum piperitum, Pueraria thunbergiana, Solanum nigrum) were about 70% higher activity compared with the non-treated control. Cytotoxicity of plant extracts was not detected in the rat neural stem cells. These results suggest that the selected eight plant extracts are safe compounds. Our findings indicate that Wnt/β-catenin pathway reporter activity could be used for high throughput screening system. In addition, the plant extracts selected as candidates for adipocyte differentiation inhibiting may be potential therapeutic agents for obesity, it will be exploring the possibility of developing an anti-obesity materials through further experiments with selected plant extracts.
Abscisic acid (ABA) is a stress hormone that functions in abiotic stress adaptation in plants. Thus many efforts have been made to identify the molecular mechanisms of ABA signal transduction pathways. Recently there were big advances in understanding molecular mechanisms of ABA dependent expression. From the ABA receptors to the transcription factors, signaling components were discovered and the biological networks among the components were identified. In this review, we describe the ABA signaling components and the rice orthologues identified. These show that signaling network systems of ABA are highly conserved in dicot and monocot plants and we are able to manipulate the ABA signaling components to develop the abiotic stress tolerant crops.