• Journal of Life Science
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• v.19 no.10
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• pp.1438-1443
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• 2009

Renal fibrosis is a final common manifestation of every type of chronic kidney disease. Plasminogen activator inhibitor (PAI)-1 is induced by lipopolysaccharide (LPS) and is known to play an essential role in the progress of renal fibrosis. In this paper, we found that an isoprenoid antibiotic, ascofuranone (AF), suppresses expression of profibrotic factors, PAI-1 and promoter activity of PAI-1 induced by LPS in rat kidney fibroblast cells. We therefore investigated signaling pathway mediated inhibitory effects of LPS-induced PAI-1 by AF in rNRK-49F cells. PAI-1 expression is suppressed by treatment with kinase inhibitors for MEK-1/2, as it isin inhibition of PAI-1 expression by AF, and AF inhibits phosphorylation of ERK-1/2. This study suggest that AF suppresses expression of PAI-1 through the inhibition of an ERK-1/2-dependent signal transduction pathway. The data indicates the possibility that AF can be used to prevent the development and progression of renal fibrosis.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1499-1506
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• 2016

Background: Crocus sativus and its major constituent crocin are well established to have anti-cancer properties in breast cancer cells (MCF-7). However the role of C. sativus extract (CSE) and crocin on caspase signaling mediated MCF-7 cell death at molecular level is remains unclear. In this study, we tried to unravel role of CSE and crocin on caspase mediated MCF-7 cells death and their in vivo preclinical toxicity profiling and immune stimulatory effect. Materials and Methods: CSE extract was fractionated by HPLC and crocin was isolated and characterized by NMR, IR, and MS. MCF-7 cells were treated with both CSE and crocin and expression of Bcl-2 and Bax was assessed after 24 and 36 hours. Furthermore, caspase 3, caspase 8 and caspase 9 expression was determined by Western blotting after 24 hours of treatment. DNA fragmentation analysis was performed for genotoxicity of CSE and crocin in MCF-7 cells. The in vivo toxicity profile of CSE (300 mg/kg of b.wt) was investigated in normal Swiss albino mice. In addition, peritoneal macrophages were collected from crocin (1, 1.5 and 2 mg/kg body weight) treated mice and analyzed for ex vivo yeast phagocytosis. Results: Immunoblot analysis revealed that there was time dependent decline in anti-apoptotic Bcl-2 with simultaneous upregulation of Bax in CSE and crocin treated MCF-7 cells. Further CSE and crocin treatment downregulated caspase 8 and 9 and cleaved the caspase 3 after 24 hours. Both CSE and crocin elicited considerable DNA damage in MCF-7 cells at each concentration tested. In vivo toxicity profile by histological studies revealed no observable histopathologic differences in the liver, kidney, spleen, lungs and heart in CSE treated and untreated groups. Crocin treatment elicited significant dose and time dependent ex vivo yeast phagocytosis by peritoneal macrophages. Conclusions: Our study delineated involvement of pro-apoptotic and caspase mediated MCF-7 cell death by CSE and crocin at the molecular level accompanied with extensive DNA damage. Further we found that normal swiss albino mice can tolerate the maximum dose of CSE. Crocin enhanced ex vivo macrophage yeast phagocytic ability.

• Journal of Ginseng Research
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• v.42 no.1
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• pp.81-89
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• 2018

Background: BIOGF1K, a compound-K-rich fraction, has been shown to display anti-inflammatory activity. Although Panax ginseng is widely used for the prevention of photoaging events induced by UVB irradiation, the effect of BIOGF1K on photoaging has not yet been examined. In this study, we investigated the effects of BIOGF1K on UVB-induced photoaging events. Methods: We analyzed the ability of BIOGF1K to prevent UVB-induced apoptosis, enhance matrix metalloproteinase (MMP) expression, upregulate anti-inflammatory activity, reduce sirtuin 1 expression, and melanin production using reverse transcription-polymerase chain reaction, melanin content assay, tyrosinase assay, and flow cytometry. We also evaluated the effects of BIOGF1K on the activator protein-1 signaling pathway, which plays an important role in photoaging, by immunoblot analysis and luciferase reporter gene assays. Results: Treatment of UVB-irradiated NIH3T3 fibroblasts with BIOGF1K prevented UVB-induced cell death, inhibited apoptosis, suppressed morphological changes, reduced melanin secretion, restored the levels of type I procollagen and sirtuin 1, and prevented mRNA upregulation of MMP-1, MMP-2, and cyclo-oxygenase-2; these effects all occurred in a dose-dependent manner. In addition, BIOGF1K markedly reduced activator-protein-1-mediated luciferase activity and decreased the activity of mitogen-activated protein kinases (extracellular response kinase, p38, and C-Jun N-terminal kinase). Conclusion: Our results strongly suggest that BIOGF1K has anti-photoaging activity and that BIOGF1K could be used in anti-aging cosmeceutical preparations.

• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.187-194
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• 2011

Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5825-5831
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• 2013

Background/Objectives: Maintenance of cellular function in culture is vital for transfer and development following adoptive immunotherapy. Dual properties of IL-21 in activating T cells and reducing activation induced cell death led us to explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic potential of CIK cells. Method: CIK cells cultured from PBMCs of healthy subjects were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells were measured. To elucidate the mechanism of action of IL-21, mRNA expression of cytotoxic factors was assessed by RT-PCR and protein expression of significantly important cytotoxic factors and cytokine secretion were determined through flow cytometry and ELISA. Western blotting was performed to check the involvement of the JAK/STAT pathway following stimulation. Results: We found that IL-21 did not enhance in vitro proliferation of CIK cells, but did increase the number of cells expressing the CD3+/CD56+ phenotype. Cytotoxic potential was increased with corresponding increase in perforin ($0.9831{\pm}0.1265$ to $0.7592{\pm}0.1457$), granzyme B ($0.4084{\pm}0.1589$ to $0.7319{\pm}0.1639$) and FasL ($0.4015{\pm}0.2842$ to $0.7381{\pm}0.2568$). Interferon gamma and TNF-alpha were noted to increase ($25.8{\pm}6.1ng/L$ to $56.0{\pm}2.3ng/L$; and $5.64{\pm}0.61{\mu}g/L$ to $15.14{\pm}0.93{\mu}g/L$, respectively) while no significant differences were observed in the expression of granzyme A, TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through the STAT-3 and STAT-5b signaling pathway in the CIK cell pool. Conclusion: IL-21 enhances cytotoxic potential of CIK cells through increasing expression of perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the activation of STAT-3 and STAT-5b proteins.

• Herbal Formula Science
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• v.25 no.1
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• pp.51-68
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• 2017

Objectives : Oxidative stress due to excessive accumulation of reactive oxygen species (ROS) is one of the risk factors for the development of several chronic diseases, including neurodegenerative diseases. Methods : In the present study, we investigated the protective effects of cheongnoemyeongsin-hwan (CNMSH) against oxidative stress‑induced cellular damage and elucidated the underlying mechanisms in neuronal-derived SH-SY5Y cells. Results : Our results revealed that treatment with CNMSH prior to hydrogen peroxide (H2O2) exposure significantly increased the SH-SY5Y cell viability, indicating that the exposure of the SH-SY5Y cells to CNMSH conferred a protective effect against oxidative stress. CNMSH also effectively attenuated H2O2‑induced comet tail formation, and decreased the phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V‑positive cells. In addition, CNMSH exhibited scavenging activity against intracellular ROS generation and restored the mitochondria membrane potential (MMP) loss that were induced by H2O2, suggesting that CNMSH prevents H2O2‑induced DNA damage and cell apoptosis. Moreover, H2O2 enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase, a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with CNMSH. Furthermore, CNMSH increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, CNMSH is able to protect SH-SY5Y cells from H2O2-induced apoptosis throughout blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating Nrf2/HO-1 signaling pathway. Conclusions : Therefore, we believed that CNMSH may potentially serve as an agent for the treatment and prevention of neurodegenerative diseases caused by oxidative stress.

• Journal of Broadcast Engineering
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• v.25 no.1
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• pp.25-35
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• 2020

Recently, the development of image processing technology, as well as hardware performance, has been continuing the research on 3D point processing technology that provides users with free viewing angle and stereoscopic effect in various fields. Point cloud technology, which is a type of representation of 3D point, has attracted attention in various fields because it can acquired/expressed point precisely. However, since Hundreds of thousands, millions of point are required to represent one 3D point cloud content, there is a disadvantage that a larger amount of storage space is required than a conventional 2D content. For this reason, the MPEG (Moving Picture Experts Group), an international standardization organization, is continuing to research how to efficiently compress, store, and transmit 3D point cloud content to users. In this paper, a V-PCC bitstream generated by a V-PCC (Video-based Point Cloud Compression) encoder proposed by the MPEG-I (Immersive) group is composed of an MPU (Media Processing Unit) defined by the MMT. In addition, by extending the signaling message defined in the MMT standard, a parameter for a segmented transmission method of the 3D point cloud content by area and quality parameters considering the characteristic of the 3D point cloud content, so that the quality parameters can be selectively determined according to the user's request. Finally, in this paper, we verify the result through design/implementation of the verification platform based on the proposed technology.

• Microbiology and Biotechnology Letters
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• v.41 no.1
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• pp.105-111
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• 2013

Biofilm formation of multifunctional plant growth promoting rhizobacterium (PGPR), Pseudomonas fluorescens 2112 is necessary for P. fluorescens 2112 to have a positive impact on the rhizosphere of red-pepper. This study investigated whether signal molecules of the quorum sensing AHLs are produced in order to confirm biofilm formative ability. Through the use of Petri dish bioassays a blue circle formed evidence of AHLs. It was confirmed that P. fluorescens 2112 produced six-carbon-chain-long AHLs by TLC bioassay. The bacterial density of P. fluorescens 2112 on the top and bottom of pepper plant roots was estimated as $3{\times}10^5$ and $8{\times}10^3$ CFU/g root, respectively. P. fluorescens 2112 exist more with high-density of $3.5{\times}10^6$ CFU/g soil at a depth of 1 cm but at a low-density of $1.1{\times}10$ CFU/g soil at a depth of 5 cm, from the surface of rhizosphere soil. In addition, biofilm formation of P. fluorescens 2112 on the epidermises and the tips of the red-pepper roots were confirmed visually by SEM. Thus, the production of AHLs by P. fluorescens 2112 brings about quorum sensing signaling and the formation of biofilm on the roots which has a positive effect on economically important crops such as red-pepper by additionally producing a variety of antifungal substances and auxin.

• Reproductive and Developmental Biology
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• v.30 no.4
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• pp.271-277
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• 2006

Transforming growth $factor-{\beta}\;(TGF-{\beta})$ has been shown to have a positive effect on in vitro fertilization (IVF) and has been reported to stimulate meiosis at follicular level in variety of species. The study was designed to determine the expression patterns of $TGF-{\beta}1,\;TGF-{\beta}$ receptors type I, II and Smads gene in bovine oocytes and embryos. $TGF-{\beta}1$ and their receptors were observed in the unfertilized oocytes. $TGF-{\beta}1$ and type II receptor were not expressed at the blastocyst stage, however, only type I receptor was exclusively observed at the same stage. The blastocyst stage, in particular, showed high levels of mRNA expression patterns containing a $TGF-{\beta}1$ type I receptor. The mRNA expression pattern of Smad 2 at all stages of embryonic development was similar in all respect with $TGF-{\beta}1$ type I receptor. On the contrary, Smad 3 and 4 were expressed with high and low level mRNA at the blastocyst stage. In conclusion. it is suggested that $TGF-{\beta}1$ signaling may be regarded as an important entity during the preimplantation embryo development.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.25-33
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• 2016

Ion channels in carcinoma and their roles in cell proliferation are drawing attention. Intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$)-dependent signaling affects the fate of cancer cells. Here we investigate the role of $Ca^{2+}$-activated $K^+$ channel (SK4) in head and neck squamous cell carcinoma cells (HNSCCs) of dif-ferent cell lines; SNU-1076, OSC-19 and HN5. Treatment with $1{\mu}M$ ionomycin induced cell death in all the three cell lines. Whole-cell patch clamp study suggested common expressions of $Ca^{2+}$-activated $Cl^-$ channels (Ano-1) and $Ca^{2+}$-activated nonselective cation channels (CAN). 1-EBIO, an activator of SK4, induced outward $K^+$ current (ISK4) in SNU-1076 and OSC-19. In HN5, ISK4 was not observed or negligible. The 1-EBIO-induced current was abolished by TRAM-34, a selective SK4 blocker. Interestingly, the ionomycin-induced cell death was effectively prevented by 1-EBIO in SNU-1076 and OSC-19, and the rescue effect was annihilated by combined TRAM-34. Con-sistent with the lower level of ISK4, the rescue by 1-EBIO was least effective in HN5. The results newly demonstrate the role of SK4 in the fate of HNSCCs under the $Ca^{2+}$ overloaded condition. Pharmacological modulation of SK4 might provide an intriguing novel tool for the anti-cancer strategy in HNSCC.