• Title/Summary/Keyword: RAF

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Hyaluronic acid and proteoglycan link protein 1 suppresses platelet-derived growth factor-BB-induced proliferation, migration, and phenotypic switching of vascular smooth muscle cells

  • Dan Zhou;Hae Chan Ha;Goowon Yang;Ji Min Jang;Bo Kyung Park;Bo Kyung Park;In Chul Shin;Dae Kyong Kim
    • BMB Reports
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    • v.56 no.8
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    • pp.445-450
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    • 2023
  • The development of atherosclerotic cardiovascular disease is associated with the phenotypic switching of vascular smooth muscle cells (SMCs) from a contractile to a synthetic state, leading to cell migration and proliferation. Platelet-derived growth factor-BB (PDGF-BB) modulates this de-differentiation by initiating a number of biological processes. In this study, we show that gene expression of hyaluronic acid (HA) and proteoglycan link protein 1 (HAPLN1) was upregulated during differentiation of human aortic SMCs (HASMCs) into a contractile state, but downregulated upon during PDGF-BB-induced dedifferentiation. This is the first study showing that the treatment of HASMCs with full-length recombinant human HAPLN1 (rhHAPLN1) significantly reversed PDGF-BB-induced decrease in the protein levels of contractile markers (SM22α, α-SMA, calponin, and SM-MHC), and inhibited the proliferation and migration of HASMCs induced by PDGF-BB. Furthermore, our results show that rhHAPLN1 significantly inhibited the phosphorylation of FAK, AKT, STAT3, p38 MAPK and Raf mediated by the binding of PDGF-BB to PDGFRβ. Together, these results indicated that rhHAPLN1 can suppress the PDGF-BB-stimulated phenotypic switching and subsequent de-differentiation of HASMCs, highlighting its potential as a novel therapeutic target for atherosclerosis and other vascular diseases.

Understanding the Technical Properties of Delonix regia (HOOK.) RAF. Wood: A Lesser Used Wood Species

  • Funke Grace Adebawo;Olayiwola Olaleye Ajala;Olaoluwa Adeniyi Adegoke;Timileyin Samuel Aderemi
    • Journal of Forest and Environmental Science
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    • v.39 no.1
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    • pp.55-64
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    • 2023
  • Properties of a lesser-used wood species were investigated to determine its potential for structural utilization. Trees of Delonix regia were felled and sampled at the base, middle and top and then sectioned to inner wood, middle wood, and outer wood for variation across the axial and radial directions. Hence, selected physical and mechanical properties as well as natural durability of D. regia along the radial and axial directions were examined. Obtained data were analyzed using analysis of variance (ANOVA) at α0.05. There was no significant difference in the Moisture content (MC) of the wood but specific gravity (SG) decreased from base to top ranging from 0.35-0.44. Water absorption, volumetric swelling, and volumetric shrinkage range from 46.18-51.86%, 2.57-4.02%, and 2.26-3.96% respectively along the axial plane. The weight loss for graveyard exposure and accelerated laboratory decay test ranged from 25.14-48.00% and 32.02-44.45% respectively. Modulus of Rupture and Modulus of Elasticity values range from 29.42-72.68 Nmm2 and 3,834.54-8,830.37 Nmm2 respectively. The SG values has confirmed the species as a medium density wood and values of other properties tested showed that the wood is dimensional stable and moderately resistance to fungi and termite. Hence, it could be used for light construction purposes such as furniture and other interior woodwork.

The Adenylyl Cyclase Activator Forskolin Increases Influenza Virus Propagation in MDCK Cells by Regulating ERK1/2 Activity

  • Sang-Yeon Lee;Jisun Lee;Hye-Lim Park;Yong-Wook Park;Hun Kim;Jae-Hwan Nam
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1576-1586
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    • 2023
  • Vaccination is the most effective method for preventing the spread of the influenza virus. Cell-based influenza vaccines have been developed to overcome the disadvantages of egg-based vaccines and their production efficiency has been previously discussed. In this study, we investigated whether treatment with forskolin (FSK), an adenylyl cyclase activator, affected the output of a cell-based influenza vaccine. We found that FSK increased the propagation of three influenza virus subtypes (A/H1N1/California/4/09, A/H3N2/Mississippi/1/85, and B/Shandong/7/97) in Madin-Darby canine kidney (MDCK) cells. Interestingly, FSK suppressed the growth of MDCK cells. This effect could be a result of protein kinase A (PKA)-Src axis activation, which downregulates extracellular signal-regulated kinase (ERK)1/2 activity and delays cell cycle progression from G1 to S. This delay in cell growth might benefit the binding and entry of the influenza virus in the early stages of viral replication. In contrast, FSK dramatically upregulated ERK1/2 activity via the cAMP-PKA-Raf-1 axis at a late stage of viral replication. Thus, increased ERK1/2 activity might contribute to increased viral ribonucleoprotein export and influenza virus propagation. The increase in viral titer induced by FSK could be explained by the action of cAMP in assisting the entry and binding of the influenza virus. Therefore, FSK addition to cell culture systems could help increase the production efficiency of cell-based vaccines against the influenza virus.

Opuntia humifusa stems rich in quercetin and isorhamnetin alleviate insulin resistance in high-fat diet-fed rats

  • Young-Min Lee;Yeonjeong Choi;Eunseo Kim;In-Guk Hwang;Yoona Kim
    • Nutrition Research and Practice
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    • v.18 no.4
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    • pp.498-510
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    • 2024
  • BACKGROUND/OBJECTIVES: Obesity, characterized by abnormal fat accumulation and metabolic disturbances, presents a significant health challenge. Opuntia humifusa Raf., commonly known as Korean Cheonnyuncho, is rich in various beneficial compounds and has demonstrated antioxidant and anti-inflammatory effects. However, its potential impact on glucose and lipid metabolism, particularly in obese rats, remains unexplored. We aimed to investigate whether O. humifusa stems and fruits could beneficially alter glucose metabolism and lipid profiles in a rat model of high-fat diet (HFD)-induced obesity. MATERIALS/METHODS: Thirty-two rats were allocated into 4 groups: normal diet (NF), HFD control (HF), HFD treated with 2% O. humifusa stems (HF-OS), and HFD treated with 2% O. humifusa fruits (HF-OF). Experimental diets were administered for 6 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. The major flavonoid from O. humifusa stems and fruits was identified and quantified. RESULTS: After 6 weeks of treatment, the serum fasting glucose concentration in the HF-OS group was significantly lower than that in the HF group. Serum fasting insulin concentrations in both HF-OS and HF-OF groups tended to be lower than those in the HF group, indicating a significant improvement in insulin sensitivity in the HF-OS group. Additionally, the HF-OS group exhibited a tendency towards the restoration of adiponectin levels to that of the NF group. CONCLUSION: The 2% O. humifusa stems contain abundant quercetin and isorhamnetin, which alter fasting blood glucose levels in rats fed a HFD, leading to a favorable improvement in insulin resistance.

Apoptosis-related Genes Altered in Bovine Cystic Ovary (난소낭종 시 변화되는 세포사멸 관련 유전자)

  • Tak, Hyun-Min;Kim, Gyu-Tae;Kim, Eun-Jin;Mun, Yun-Ja;Choe, Chang-Yong;Son, Dong-Soo;Han, Jae-Hee;Kang, Da-Won
    • Journal of Embryo Transfer
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    • v.24 no.1
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    • pp.57-64
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    • 2009
  • This study was carried out to investigate expression of apoptosis-related differentially expressed gene (DEG) in ovaries of Korean cattle with follicular and luteal cysts and to identify the relationship between cyst and apoptosis using microarray, real-time PCR, TUNEL staining, and Western blot analysis. Microarray data showed that PIK3R2 and AKT1 were significantly up-regulated in follicular cyst, and TNF-RAF2, PRLR, FOXL2, STK4, and COL4A3 were up-regulated whereas INHA, CIDEB, BCL10, and FASLG were down-regulated in luteal cyst. Real-time PCR was performed to validate DEGs altered in luteal cyst. Of nine DEGs, four DEGs down-regulated in luteal cyst showed a positive corelation between microarray data and real-time PCR data. In this study, we focused on INHA, among many DEGs, which was highly down-regulated in both follicular and luteal cysts. Real-time PCR and micro array data showed that INHA was down-regulated by 12.3-fold and by 1.4-fold, respectively, in the bovine follicular cyst. TUNEL assay and Western blot analysis for ERK, JNK, p38, PI3K, and Akt, which were used to detect whether apoptosis is occurred, showed no significant changes in cystic ovaries (p>0.05). In the expression and activity of caspase-3, Bax, Bel-2, and Bel-xL, there was no significant changes between follicular cystic ovary and normal ovary. Rather, the expression levels of PI3K and p-Akt were decreased in follicular cystic ovary. These results suggest that deficiency of apoptosis in cystic ovary is associated with decreased expression of apoptotic effectors.

Cytotaxonomic study of Korean Euphorbia L. (Euphorbiaceae) (한국산 대극속(Euphorbia L., Euphorbiaceae)의 세포분류학적 연구)

  • Chung, Gyu Young;Oh, Byoung-Un;Park, Ki-Ryong;Kim, Joo-Hwan;Kim, Mi Suk;Nam, Gi-Heum;Jang, Chang-Gee
    • Korean Journal of Plant Taxonomy
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    • v.33 no.3
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    • pp.279-293
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    • 2003
  • Somatic chromosomes about 13 taxa of Korean Euphorbia L. was investigated to estimate its taxonomic significance. Somatic chromosome numbers of treated taxa were 2n= 12, 20, 22, 28, 40, 42, 56, therefore basic chromosome numbers of those were x=6, 7, 10, 11. The chromosome numbers of E. pallasii Turcz. (2n=20), E. hylonoma Hand.-Mazz (2n=20.), E. fauriei H. L$\acute{e}$v. & Vaniot ex H. L$\acute{e}$v (2n=28) and E. jolkini Boiss. (2n=28) were determined for the first time in this study. The chromosome numbers of four taxa were same as previous ones; E. sieboldiana Moor. & Decne. (2n=20), E. ebracteolata Hayata (2n=20), E. humifusa Willd. ex Schlecht. (2n=22). But those of six taxa were different; E. esula L (2n= 16, 20, 60, 64 vs 2n=20), E. helioscopia L. (2n=12, 42 vs 2n=42), E. lucorum Rupr. (2n=28, 40 vs 2n=56), E. pekinensis Rupr. in Maxim. (2n=24 vs 2n=28, 56), E. maculata L. (2n=28, 42 vs 2n=12), E. supina Raf. (n=7 vs 2n=40). E. ebracteolata, E. pallasii and E. hylonoma were distingushcd from the other taxa by the chromosome numbers, size and satellites, E. maculata, E. humifusa, E. supina had the different basic and somatic chromosome numbers in spite of the similar morphological. anatomical and palynological chracters. The chromosomal character of Korean Euphorbia was supported the Ma and Hu's systems, and as above results, it was found to be a good character in delimiting above sections and estimating relationships for some species.

Polymorphisms in RAS Guanyl-releasing Protein 3 are Associated with Chronic Liver Disease and Hepatocellular Carcinoma in a Korean Population

  • Oh, Ah-Reum;Lee, Seung-Ku;Kim, Min-Ho;Cheong, Jae-Youn;Cho, Sung-Won;Yang, Kap-Seok;Kwack, Kyu-Bum
    • Genomics & Informatics
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    • v.6 no.4
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    • pp.181-191
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    • 2008
  • RAS guanyl-releasing protein 3 (RasGRP3), a member of the Ras subfamily of GTPases, functions as a guanosine triphosphate (GTP)/guanosine diphosphate (GDP)-regulated switch that cycles between inactive GDP- and active GTP-bound states during signal transduction. Various growth factors enhance hepatocellular carcinoma (HCC) proliferation via activation of the Ras/Raf-1/extracellular signal-regulated kinase (ERK) pathway, which depends on RasGRP3 activation. We investigated the relationship between polymorphisms in RasGRP3 and progression of hepatitis B virus (HBV)-infected HCC in a Korean population. Nineteen RasGRP3 SNPs were genotyped in 206 patients with chronic liver disease (CLD) and 86 patients with HCC. Our results revealed that the T allele of the rs7597095 SNP and the C allele of the rs7592762 SNP increased susceptibility to HCC (OR=1.55, p=0.04 and OR=1.81${\sim}$2.61, p=0.01${\sim}$0.03, respectively). Moreover, patients who possessed the haplotype (ht) 1 (A-T-C-G) or diplotype (dt) 1 (ht1/ht1) variations had increased susceptibility to HCC (OR=1.79${\sim}$2.78, p=0.01${\sim}$0.03). In addition, we identified an association between haplotype1 (ht1) and the age of HCC onset; the age of HCC onset are earlier in ht1 +/+ than ht1 +/- or ht1 -/- (HR=0.42${\sim}$0.66, p=0.006${\sim}$0.015). Thus, our data suggest that RasGRP3 SNPs are significantly associated with an increased risk of developing HCC.

Flora Distributed in Mt. Geumgok, Gyeongju-si, Gyeongsangbuk-do (경상북도 경주시 금곡산에 분포하는 관속식물상)

  • You, Ju Han
    • Korean Journal of Plant Resources
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    • v.26 no.2
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    • pp.248-270
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    • 2013
  • The purpose of this study is to collect the raw data for conservation of plant ecosystem by surveying and analysing the flora of Mt. Geumgok located in Gyeongju-si, Gyeongsangbuk-do, Korea. The flora were summarized as 453 taxa including 91 families, 298 genera, 397 species, 4 subspecies, 46 varieties and 6 forms. The rare plants designated by Korea Forest Service were 3 taxa such as Eranthis byunsanensis B.Y.Sun, Potentilla discolor Bunge and Iris odaesanensis Y.N.Lee. The Korean endemic plants were 6 taxa such as Carpinus laxiflora (Siebold & Zucc.) Blume, Eranthis byunsanensis B.Y.Sun, Philadelphus schrenkii Rupr., Lespedeza maritima Nakai, Vicia chosenensis Ohwi and Weigela subsessilis (Nakai) L.H.Bailey. The specific plants by floristic region were 36 taxa such as Pinus koraiensis Siebold & Zucc., Salix chaenomeloides Kimura, Anemone raddeana Regel, Chloranthus japonicus Siebold, Euphorbia pekinensis Rupr., Ilex macropoda Miq., Ajuga multiflora Bunge, Saussurea odontolepis Sch.Bip. ex Herd, Viola orientalis (Maxim.) W.Becker, Betula davurica Pall., Vitex negundo var. incisa (Lam.) C.B.Clarke and Cimicifuga heracleifolia Kom.. The naturalized plants were 36 taxa such as Fallopia dumetorum (L.) Holub, Lepidium apetalum Willd., Robinia pseudoacacia L., Trifolium repens L., Euphorbia supina Raf., Ipomoea purpurea Roth, Veronica persica Poir., Bidens pilosa L., Carduus crispus L., Xanthium canadense Mill., Bromus unioloides H.B.K. and Festuca arundinacea Schreb.. The invasive alien plants were 2 taxa such as Ambrosia artemisiifolia L. and Aster pilosus Willd.. The ratios of the urbanized index(UI), the naturalized index(NI) and the disturbed index(DI) were 11.2%, 7.9% and 18.2% each.

Flora of Sumeunmulbaengdui wetland in Jeju-do, Korea (숨은물뱅듸 습지(제주도)의 식물 다양성)

  • Ko, Sung Chul;Son, Dong Chan;Park, Beom Kyun
    • Korean Journal of Plant Taxonomy
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    • v.44 no.3
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    • pp.222-232
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    • 2014
  • The flora of vascular plants in Sumeunmulbaengdui wetland located in Hallasan National Park was surveyed 9 times from September, 2010 to May, 2014. This survey resulted in 236 taxa in total composed of 202 species, 2 subspecies, 27 varieties and 5 forms of 148 genera under 69 families. They were categorized by their life forms into 8 groups of 37 megaphanerophytes, 26 nanophanerophytes, 2 epiphytes, 3 chamaephytes, 84 hemicryptophytes, 33 geophytes, 21 hydrophytes, 30 therophytes. Among them, 10 taxa of Korean endemic plants and 9 taxa of rare and endangered plants were included. In addition, the floristic regional indicator plants were 43 taxa comprised of 3 taxa of grade V, 7 taxa of grade IV, 12 taxa of grade III, 8 taxa of grade II and 13 taxa of grade I. 2 species of alien plants, Erechtites hieracifolia Raf. and Taraxacum officinale Weber were found. Sustainable interest and protective measures to Sumeunmulbaengdui wetland are required, since this area is comparatively larger in size and higher in plant diversity than other Ramsar wetlands in Jeju-do Province.

Impact of Cellular Genetic Make-up on Colorectal Cancer Cell Lines Response to Ellagic Acid: Implications of small interfering RNA

  • Yousef, Amany I;El-Masry, Omar S;Abdel Mohsen, Mohamed A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.2
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    • pp.743-748
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    • 2016
  • Background: $K^-Ras$ activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. Purpose: To evaluate the impact of cellular genetic makeup of two colon cancer cell lines with different genetic backgrounds, HCT-116 ($K^-Ras^-/p53^+$) and Caco-2 ($K^-Ras^+/p53^-$), on response to potential anti-tumour effects of EA. In addition, the influence of $K^-Ras$ silencing in HCT-116 cells was investigated. Materials and Methods: Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of $K^-Ras$ siRNA or incubated with ellagic acid following transfection. Results: The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce $K^-Ras$ protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected. Conclusions: Cellular genetic makeup ($K^-Ras^-/p53^-$) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant $K^-Ras$).