• BMB Reports
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• v.50 no.12
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• pp.601-609
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• 2017

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrientrich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.65 no.4
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• pp.695-703
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• 2016

The maintenance method for the electrical facility of high speed railway has been evolved from inspection by personnel to the automated way by the detection devices. In particular, the signalling equipment in order to increase the safe and efficient operation of the trains is required to maintain normal operation by periodic maintenance. Because the return current gives the most important effects to the wayside equipment in case of the failures, a method is needed to measure the unbalanced rate of return current on the train at high speed driving. The Hot Box Detector(HBD) device that is installed at track-side has a function to recognize the abnormal axle box by detecting the temperature that occurs in the axle of train passing over its device. In order to implement the measurement equipment for unbalanced rate of return current and axle temperature, the design method is proposed and the experimental test results by test bed are included in the paper.

• Bulletin of the Korean Chemical Society
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• v.32 no.3
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• pp.768-778
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• 2011

Calixpyrroles and related macrocycles are non-planer synthetic anion receptors that have attracted considerable attentions in recent years. Although the synthesis of calix[4]pyrrole (known as meso-octamethylporphyrinogen) was reported more than 100 years ago, the anion binding properties were first discovered in 1996. The simple calix[4]pyrroles can be synthesized in single step in high yield by condensation of pyrrole with acetone. The compounds showed preferential binding for halide anions including fluoride, phosphate, carboxylate, and chloride in organic media. Efforts to improve the anion affinity of calix[4]pyrrole and to enhance its selectivity have led to the synthesis of a variety of new calixpyrrole derivatives. Among the various modifications, introduction of straps on one side of the calix[4]pyrroles are the most effective. Incorporation of aromatic rings other than pyrroles also exhibited interesting binding behaviour. Introduction of signalling units as part of the strapping element enable to detect the anions on chromogenic or fluorogenic fashion. Finding of the anion transport properties across the membrane and cytotoxic effects of the calix[4]pyrroles open new window for calixpyrrole-related research. The polymer-incorporated systems have also been employed as anion complexants in solvent-solvent extraction. These old, yet easy-to-make macrocycles have well advanced more recently with the discovery of the ion-pair complexation properties. In this review, the synthetic developments and anion binding properties of calixpyrroles for the last decades will be discussed and will cover the advances in calixpyrrole chemistry.

• BMB Reports
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• v.51 no.1
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• pp.45-53
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• 2018

Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

• The Journal of Asian Finance, Economics and Business
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• v.8 no.12
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• pp.323-336
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• 2021

The present study aims to examine the impact of real earnings management on the future value of the firm and its persistence. The study also tests suspect firm effects on the relationship between real earnings management and the future value of the firm. The sample of the present study consists of all listed non-financial firms from the year 2011 to 2018. Real earnings management has been measured in three alternative ways viz., abnormal operating cash flows, abnormal discretionary spending, and abnormal production cost. Tobin's Q is used as a measure of firm value. The interaction term of real earnings management and Tobin's Q is used to test firm value persistence. The results of the analysis disclose that out of three measures of real earnings management, abnormal reduction in discretionary spending only has a significant negative impact on the persistence of firm value. Moreover, the suspect firm analysis reveals that when the underlying motive of real earnings management is to meet zero earnings, both abnormal increases in operating cash flows and abnormal reduction in discretionary spending have a significant negative impact on firm value persistence.

• Journal of Digital Convergence
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• v.13 no.12
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• pp.461-467
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• 2015

Saussurea lappa is known for a variety of physiological activities as a component but has not known to show the effect of the cellular signaling pathway. We investigated the anti-inflammatory effects by Saussurea lappa ethanol extract on the LPS(lipopolysaccharide) induced nitric oxide (NO) production by RAW 264.7 cell line. It shows the expressions of iNOS and COX-2 at the transcriptional level (RT-PCR). The Saussurea lappa ethanol extract showed transcriptional expression levels of pro-inflammatory cytokine TNF- and IL-$1{\beta}$ induced by LPS(lipolysaccharide) in RAW264.7 cell line. Saussurea lappa ethanol extract reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the RNA levels in a concentration-dependent manner. The finding that ethanol extract of Saussurea lappa has an influence on NO (nitric oxide) homeostasis in the study of the action mechanism on the macrophage-mediated inflammatory reaction was considered in terms of convergence. And it is to provide an important basis for the prevention and treatment of inflammatory diseases in the future.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.253-261
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• 1993

Possible changes in the role of insulin-sensitive cyclic nucleotide phosphodiesterase(PDE) in mediating the antilipolytic action of insulin were investigated in adipocytes from streptozotocin-induced diabetic rats. Isolated adipocytes prepared from epididymal adipose tissue were incubated, with or without insulin, at $37^{\circ}C$ for 15 min following pretreatment with various drugs or toxins, and three (plasma membranes, microsomal membranes, and cytosol) fractions prepared by differential centrifugation were then assayed for cAMP phosphodiesterase activity. The PDE activities only in the crude microsomal (P2) fractions were activated by insulin both in diabetic and control rats. The basal PDE activities in P2 fractions of adipocytes from diabetic rats were higher than those from control rats, although the maximal effects observed at 2 nM of insulin, $100\;{\mu}M$ of isoproterenol or the combination of both were not significantly different from each other. The insulin-stimulated PDE activities in P2 fractions of adipocytes from diabetic rats were not changed by PIA, a $A_{1}$ adenosine receptor agonist, whereas they were decreased to the basal PDE activities in those from control rats. In addition, the adipocytes from diabetic rats showed an increased sensitivity to pertussis toxin compared to those from controls. There were no differences between diabetic and control rats in the sensitivity of adipocytes to cholera toxin. These data indicate that the impaired signalling through inhibitory receptors such as adenosine receptors in adipocytes from streptozotocin-induced diabetes relates to the loss or the decreased function of $G_i$ proteins, and leads to the increased activity of the insulin-dependent PDE at the basal states.

• CELLMED
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• v.3 no.2
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• pp.10.1-10.8
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• 2013

Cancer is one of the major dreaded diseases causing high mortality. Lung cancer is second in position of all cancer related deaths and mainly divided into two morphologic sub-types: small-cell lung cancer and non-small cell lung cancer (NSCLC). NSCLC is an aggressive neoplasm which hardly responds to any conventional chemotherapy. Epidermal growth factor receptor (EGFR) belongs to the ErbB family of receptor tyrosine kinase that is mainly over-expressed in NSCLC. EGFR is mainly involved in the pathogenesis and progression of different carcinoma. In vivo and in vitro studies suggest that EGFR and EGF like peptides are often over-expressed in human NSCLC and these proteins are able to induce cell transformation. The conventional therapies mostly inhibit the EGFR activity and expression level in human NSCLC with the use of some EGFR-inhibitors like HKI-272, EKB569, CL-387785 etc. and some synthetic chemotherapeutic drugs like erlotinib, gefitinib, plumbagin, docetaxel, cisplatin etc., alone or in combination of two or more drugs. These therapies selectively act by competitive inhibition of the binding of adenosine triphosphate to the tyrosine kinase domain of the EGFR, resulting in inhibition of the EGFR signaling pathway. But these chemotherapeutic drugs have some cytotoxic activities to the normal cells and have some adverse side-effects. Recent studies on some traditional alternative therapies including some herbal and plant extracts, active ingredients like curcumin, different homeopathic drugs, etc. can target EGFR-signalling in NSCLC with less toxic side-effects are being currently developed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2453-2459
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• 2014

Ginsenoside Rg1 is one effective anticancer and antioxidant constituent of total saponins of Panax ginseng (TSPG), which has been shown to have various pharmacological effects. Our previous study demonstrated that Rg1 had anti-tumor activity in K562 leukemia cells. The aim of this study was designed to investigate whether Rg1 could induce apoptosis in TF-1/Epo cells and further to explore the underlying molecular mechanisms. Here we found that Rg1 could inhibit TF-1/Epo cell proliferation and induce cell apoptosis in vitro in a concentration and time dependent manner. It also suppressed the expression of EpoR on the surface membrane and inhibited JAK2/STAT5 pathway activity. Rg1 induced up-regulation of Bax, cleaved caspase-3 and C-PAPR protein and down-regulation of Bcl-2 and AG490, a JAK2 specific inhibitor, could enhance the effects of Rg1. Our studies showed that EpoR-mediated JAK2/STAT5 signaling played a key role in Rg1-induced apoptosis in TF-1/Epo cells. These results may provide new insights of Rg1 protective roles in the prevention a nd treatment of leukemia.

• Journal of Nutrition and Health
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• v.39 no.8
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• pp.748-755
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• 2006

The purpose of this study was to find out effects of treatment of ginsenoside Re, Rc and EGCG on mRNA expressions of leptin, hormone sensitive lipase (HSL) and resistin in 3T3-L1 adipocytes. The concentrations of EGCG were treated with $0.01{\times}10^{-7},\;0.1{\times}10^{-7},\;1{\times}10^{-7}\;and\;1{\times}10^{-6}\;or\;100{\mu}g/ml$ ginsenoside Re, Rc in culture cell for 13 days. mRNA expression of leptin wasn't expressed in preadipocyte but according to differentiation of adipocyte, the that of mRNA expression was decreased at gensenosids or EGCG treated cells compared with non treated adipocyte. Expression of HSL mRNA was increased in G-Re, G-Rc and EGCG treated cells compared with non treated cells. The resistin level was significantly decreased in adipocytes treated with G-Re, G-Rc and EGCG. These pattern was similar to leptin expression. These results support that treatment of gensenosides or EGCG in 3T3-L1 adipocyte resulted to affect of leptin and resistin as well as HSL mRNA levels, accordingly, levels of leptin and HSL will be acted by signalling body fat stores to the hypothalamus which in turn regulates food intake andenergy expenditure to maintain body weight homeostasis. And also regulation of resistin mRNA will prevent to diabetics attacked with obesity. In conclusion, we suggest that consumption of ginseng saponine or EGCG might prevent human diabetics or/and obesity.