• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6305-6309
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• 2013

Background: TIAM2, a Rac guanine nucleotide exchange factor, is closely associated with cell adherence and migration. Here, we aimed to investigate the role of TIAM2 in non-small cell lung cancer (NSCLC) cells. Materials and Methods: A small interference RNA (siRNA) was introduced to silence the expression of TIAM2. Invasion and motility assays were then performed to assess the invasion and motility potential of NSCLC cells. GST-pull down assays were used to detect activation of Rac1. Results: TIAM2 was highly expressed in NSCLC cells. Knockdown of TIAM2 inhibited the invasion and motility, and suppressed activation of Rac1. Further experiments demonstrated that knockdown of TIAM2 could up-regulate the expression of E-cadherin, and down-regulate the expression of MMP-3, Twist and Snail. Conclusions: Our data suggest that TIAM2 can promote invasion and motility of NSCLC cells. Activation of Rac1 and regulation of some EMT/invasion-related genes may be involved in the underlying processes.

• Nutrition Research and Practice
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• v.15 no.5
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• pp.579-590
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• 2021

BACKGROUND/OBJECTIVES: Petasites japonicus Maxim (P. japonicus) has been used as an edible and medicinal plant and contains many bioactive compounds. The purpose of this study is to investigate the effect of P. japonicus on osteogenesis. MATERIALS/METHODS: The leaves and stems of P. japonicus were separated and extracted with hot water or ethanol, respectively. The total phenolic compound and total polyphenol contents of each extract were measured, and alkaline phosphatase (ALP) activity of each extract was evaluated to determine their effect on bone metabolism. To investigate the effect on osteoblast differentiation of the aqueous extract of P. japonicus leaves (AL), which produced the highest ALP activity among the tested extracts, collagen content was measured using the Sirius Red staining method, mineralization using the Alizarin Red S staining method, and osteocalcin production through enzyme-linked immunosorbent assay analysis. Also, real-time reverse transcription polymerase chain reaction was performed to investigate the mRNA expression levels of Runt-related transcriptional factor 2 (Runx2) and Osterix. RESULTS: Among the 4 P. japonicus extracts, AL had the highest values in all of the following measures: total phenolic compounds, total polyphenols, and ALP activity, which is a major biomarker of osteoblast differentiation. The AL-treated MC3T3-E1 cells showed significant increases in induced osteoblast differentiation, collagen synthesis, mineralization, and osteocalcin production. In addition, mRNA expressions of Runx2 and Osterix, transcription factors that regulate osteoblast differentiation, were significantly increased. CONCLUSIONS: These results suggest that AL can regulate osteoblasts differentiation, at least in part through Runx2 and Osterix. Therefore, it is highly likely that P. japonicus will be useful as an alternate therapeutic for the prevention and treatment of osteoporosis.

• Korean Circulation Journal
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• v.53 no.6
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• pp.387-403
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• 2023

Background and Objectives: Myocardial ischemia and reperfusion injury (MIRI) has high morbidity and mortality worldwide. We aimed to explore the role of long noncoding RNA lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) in cardiomyocyte pyroptosis. Methods: Hypoxia/reoxygenation (H/R) injury was constructed in human cardiomyocyte (HCM). The level of LOXL1-AS1, miR-761, phosphatase and tensin homolog (PTEN) and pyroptosis-related proteins was monitored by quantitative real-time polymerase chain reaction or western blot. Flow cytometry examined the pyroptosis level. Lactate dehydrogenase (LDH), creatine kinase-MB and cardiac troponin I levels were detected by test kits. Enzyme-linked immunosorbent assay measured the release of inflammatory cytokines. Dual-luciferase assay validated the binding relationship among LOXL1-AS1, miR-761, and PTEN. Finally, ischemia/reperfusion (I/R) animal model was constructed. Hematoxylin and eosin staining assessed morphological changes of myocardial tissue. NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and casepase-1 expression was determined by immunohistochemistry. Results: After H/R treatment, LOXL1-AS1 and PTEN were highly expressed but miR-761 level was suppressed. LOXL1-AS1 inhibition or miR-761 overexpression increased cell viability, blocked the release of LDH and inflammatory cytokines (interleukin [IL]-1β, IL-18), inhibited pyroptosis level, and downregulated pyroptosis-related proteins (ASC, cleaved caspase-1, gasdermin D-N, NLRP3, IL-1β, and IL-18) levels in HCMs. LOXL1-AS1 sponged miR-761 to up-regulate PTEN. Knockdown of miR-761 reversed the effect of LOXL1-AS1 down regulation on H/R induced HCM pyroptosis. LOXL1-AS1 aggravated the MIRI by regulating miR-761/PTEN axis in vivo. Conclusions: LOXL1-AS1 targeted miR-761 to regulate PTEN expression, then enhance cardiomyocyte pyroptosis, providing a new alternative target for the treatment of MIRI.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.145-155
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• 2023

Background and Objectives: Embryologically, mesodermal development is closely related to the development of various organs such as muscles, blood vessels, and hearts, which are the main organs that make up the body. However, treatment for mesoderm developmental disorders caused by congenital or acquired factors has so far relied on surgery and drug treatment for symptom relief, and more fundamentally, treatment for mesoderm developmental disorders is needed. Methods and Results: In our study, microRNA (miRNA), which plays an important role in the mesoderm development process, was identified and the developmental function was evaluated. miRNAs consist of small nucleotides, which act as transcription factors that bind to the 3' untranslated region and suppressed target gene expression. We constructed the human embryonic stem cell (hESC) knockout cell line and analyzed the function and characteristics of miR-5739, which plays an important role in mesoderm lineage. miR-5739 acts as a transcription factor targeting SMA, Brachyury T, Hand1, which controls muscle proliferation and differentiation, and KDR gene, which regulates vessel formation in vitro. In vivo results suggest a role in regulating muscle proliferation and differentiation. Gene ontology analysis confirmed that the miR-5739 is closely related to genes that regulate muscle and vessel proliferation and differentiation. Importantly, abnormal expression of miR-5739 was detected in somatic cells derived from patients with congenital muscle disease. Conclusions: Our study demonstrate that miR-5739 gene function significantly affects transcriptional circuits that regulate muscle and vascular differentiation during embryonic development.

• International Journal of Oral Biology
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• v.32 no.1
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• pp.1-5
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• 2007

Receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL) induces osteoclast formation from hematopoietic cells via up-regulation of positive regulators, including $NF-{\kappa}B$, c-Fos, microphthalmia transcription factor (Mitf), PU.1, and nuclear factor of activated T cells (NFAT) c1. In addition to the positive regulation by these transcription factors, RANKL appears to regulate negative regulators such as MafB and inhibitors of differentiation (Ids). Ids and MafB are abundantly expressed in osteoclast precursors, bone marrowderived monocyte/macrophage lineage cells (BMMs). Expression levels of these genes are significantly reduced by RANKL during osteoclastogenesis. Overexpression of these genes in BMMs inhibits the formation of tartarate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts by down-regulation of NFATc1 and osteoclast-associated receptor (OSCAR), which are important for osteoclast differentiation. Furthermore, reduced expression of these genes enhances osteoclastogenesis and increases expression of NFATc1 and OSCAR. Taken together, RANKL induces osteoclastogenesis via up-regulation of positive regulators as well as down-regulation of negative regulators.

• YAKHAK HOEJI
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• v.50 no.3
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• pp.184-190
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• 2006

We investigated the effect of fresh Rehmanniae radix methanol extracts (RGMeOH) on the in vitro production of cytokines by splenocytes and peritoneal macrophages isolated from C57BL/6 mice. Peritoneal macrophages and splenocytes were incubated with various concentrations of RGMeOH in the presence of $10\;{\mu}g/ml$ of lipopolysaccharide (LPS) $1\;{\mu}g/ml$ of concanavalin A (Con A) for cytokine assay, These results showed that RGMeOH remarkably attenuated LPS-increased production of $TNF-{\alpha}$ but not IL-6 by peritoneal macrophages and enhanced LPS-stimulated production of IL-10 in a dose-dependent manner RGMeOH significantly augmented the LPS- or Con A-stimulated production of IL-2 and $IFN-{\gamma}$ by splenocytes. These findings suggest that RGMeOH may attenuate inflammatory responses through down-regulation of $TNF-{\alpha}$ and up-regulation of IL-10, and that RGMeOH may up-regulate cell-mediated immune responses through increase in IL-2 and $IFN-{\gamma}$ production.

• The Transactions of the Korean Institute of Power Electronics
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• v.13 no.2
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• pp.79-87
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• 2008

Boost Converters have been used to step up and regulate the low and widely varing voltage from the fuel cell. A transformer-less boost converter which does not have lossy, bulky, and costly high frequency transformers has an advantage in applications where galvanic isolation is not required. In this paper a new transformer-less boost converter is proposed. The proposed boost converter has practically usuable 6 to 8 times of step up ratio and is suitable for fuel cell applications due to very low input and output current ripples. The proposed converter is verified through the theorical analysis, simulation and experimental waveform.

• Journal of Plant Biotechnology
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• v.37 no.3
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• pp.327-336
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• 2010

Cysteine proteases have been known as a critical factor in plant defense mechanisms in pineapple, papaya, or wild fig. Papain or ficin is one kind of cysteine proteases that shows toxic effects to herbivorous insects and pathogenic bacteria. However, resistance to bacterial soft rot of plants genetically engineered with cysteine protease has been little examined thus far. We cloned a cysteine protease cDNA from Ananas comosus and introduced the gene into Chinese cabbage (Brassica rapa) under the control of the cauliflower mosaic virus 35S promoter. The transgene was stably integrated and actively transcribed in transgenic plants. In comparisons with wild-type plants, the $T_2$ and $T_3$ transgenic plants exhibited a significant increase in endo-protease activity in leaves and enhanced resistance to bacterial soft rot. A cDNA microarray analysis revealed that several genes were more abundantly transcribed in the transgenic than in the wild type. These genes encode a glyoxal oxidase, PR-1 protein, PDF1, protein kinase, LTP protein, UBA protein and protease inhibitor. These results suggest an important role for cysteine protease as a signaling regulator in biotic stress signaling pathways, leading to the build-up of defense mechanism to pathogenic bacteria in plants.

• Journal of Microbiology and Biotechnology
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• v.25 no.11
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• pp.1787-1795
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• 2015

The transition from primary to secondary metabolism in antibiotic-producing Streptomyces correlates with expression of genes involved in stress responses. Consequently, regulatory pathways that regulate specific stress responses are potential targets to manipulate to increase antibiotic titers. In this study, genes encoding key proteins involved in regulation of the osmotic stress response in Streptomyces avermitilis, the industrial producer of avermectins, are investigated as targets. Disruption of either osaB_Sa, encoding a response regulator protein, or osaC_Sa, encoding a multidomain regulator of the alternative sigma factor SigB, led to increased production of both oligomycin, by up to 200%, and avermectin, by up to 37%. The mutations also conditionally affected morphological development; under osmotic stress, the mutants were unable to erect an aerial mycelium. In addition, we demonstrate the delivery of DNA into a streptomycete using biolistics. The data reveal that information on stress regulatory responses can be integrated in rational strain improvement to improve yields of bioactive secondary metabolites.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.885-889
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• 2013

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression through post-transcriptional interactions with mRNA. miRNAs have recently emerged as key regulators of various cancers. Although miR-27a has been implicated in several other cancers, its role in hepatitis B virus-related hepatocellular carcinoma (HCC) is unknown. In this study, we showed miR-27a to be frequently up-regulated in HCC tissues and HCC cell lines (HepG2 and Huh7). Overexpression of miR-27a enhanced cell proliferation, promoted migration and invasion, and activated cell cycling in HepG2 and Huh7 cells. In summary, our results suggest that up-regulation of miR-27a may play an oncogenic role in the development of HCC and might thus be a new therapeutic target in HCC patients.