• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.146-152
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• 2013

This study examined the total polyphenol content of eight wild edible plants from Ethiopia and their effect on NO production in Raw264.7 cells. Owing to its relatively high polyphenol concentration and inhibition of NO production, the methanol extract of Adansonia digitata L. leaf (MEAD) was subjected to detailed evaluation of its antioxidant and anti-inflammatory effects. Antioxidant effects were assessed by measuring free-radical-scavenging activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and oxygen-radical-absorbance capacity (ORAC) assays, while anti-inflammatory effects were assessed by measuring inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. In the ORAC assay, MEAD was 10.2 times more potent than vitamin C at eliminating peroxyl radicals. In DPPH assay, MEAD also showed a strong ROS scavenging effect. MEAD significantly inhibited iNOS activity ($IC_{50}=28.6{\mu}g/ml$) of LPS-stimulated Raw264.7 cells. We also investigated the relationship between iNOS expression and nuclear factor kappa B (NF-${\kappa}B$) activation. MEAD inhibited $I{\kappa}B{\alpha}$ degradation and NF-${\kappa}B$ translocation from the cytosol to the nucleus in LPS-induced RAW264.7 cells without significant cytotoxic effects, as confirmed by MTT assay. These results suggest that MEAD inhibits anti-inflammatory iNOS expression, which might be related to the elimination of peroxyl radicals and thus the inhibition of $I{\kappa}B{\alpha}$-mediated NF-${\kappa}B$ signal transduction.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.623-629
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• 2016

(1S,2S,3E,7E,11E)-3,7,11,15-cembratetraen-17,2-olide (LS-1), a marine cembrenolide diterpene, has anticancer activity against colon cancer cells such as HT-29, SNU-C5/5-FU (fluorouracil-resistant SNU-C5) and SNU-C5. However, the action mechanism of LS-1 on SNU-C5 human colon cancer cells has not been fully elucidated. In this study, we investigated whether the anticancer effect of LS-1could result from apoptosis via the modulation of $Wnt/{\beta}$-catenin and the TGF-${\beta}$ pathways. When treated with the LS-1, we could observe the apoptotic characteristics such as apoptotic bodies and the increase of sub-G1 hypodiploid cell population, increase of Bax level, decrease of Bcl-2 expression, cleavage of procaspase-3 and cleavage of poly (ADP-ribose) polymerase in SNU-C5 cells. Furthermore, the apoptosis induction of SNU-C5 cells upon LS-1 treatment was also accompanied by the down-regulation of $Wnt/{\beta}$-catenin signaling pathway via the decrease of GSK-$3{\beta}$ phosphorylation followed by the decrease of ${\beta}$-catenin level. In addition, the LS-1 induced the activation of TGF-${\beta}$ signaling pathway with the decrease of carcinoembryonic antigen which leads to decrease of c-Myc, an oncoprotein. These data suggest that the LS-1 could induce the apoptosis via the down-regulation of $Wnt/{\beta}$-catenin pathway and the activation of TGF-${\beta}$ pathway in SNU-C5 human colon cancer cells. The results support that the LS-1 might have potential for the treatment of human colon cancer.

• The Korean Journal of Emergency Medical Services
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• v.11 no.1
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• pp.27-40
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• 2007

Even now, 119 rescue services have dissatisfactory aspects in operation, system and equipments as discussed above, It is the most urgent subject to systemize rescue services so that they can be suitable for our status, for we will make 21C welfare state come true before long. So, this author suggest that the followings have to be raised to activate 119 rescue service. 1) Bring up experts and offer high-quality rescue service 2) Prepare more up-to-date equipments 3) Operate transfer joint organizations 4) Promote the ability to meet with a press at the time of rescue service activities 5) Adjust regulations related to rescue services 6) Make up for a countermeasure to traffic accidents of ambulances 7) Adjust regulations making it mandatory to establish heliport at the target on hospitals more than a defined scale 8) Install more rescue service teams 9) Educate and train officials belonging to briefing rooms, where the officials with long experiences are arranged 10) Minimize the time for rescue team to reach fields 11) Establish legal protection system for rescue the team Nowadays, our country operates the department of fire fighting and rescue services without great difficulty, even though the circumstances are bad - insufficient members and the inferior circumstances. All of the fire fighting officials are given heavy duties in bad circumstances, and so are the team of rescue service. The rescue service team, taking charge of some emergency medical system, do a fire fighting inspection as a non-duty service, though they are scanty of sleep due to prevention and protection services of the fire fighting service team. But, they can not engage in rescue services completely and have to deal with miscellaneous duties. So they can not offer professional emergency medical services. But now, almost every fire fighting organization, belonging to National Emergency Management Agency, are separating rescue services, which shows a lot of good results. People recognize rescue services to get better and better gradually and the demands for this rescue services increase. So, this is the best time when rescue service teams should offer qualitative services rather than quantitative services. The people will recognize this rescue service team to be an organization sacrificing and serving for them. However well institutes and operation systems should be established, the rescue service team can not come true their aim without strong wills that they will serve and sacrifice themselves for people from their hearts. In addition, it is essential for the officials in charge of policies about emergency medical services to have a concernment on and practice the policy without failure.

• Biomedical Science Letters
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• v.3 no.2
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• pp.83-88
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• 1997

In septic patients, disseminated intravascula. coagulation (DIC) occurs frequently and is a pathologic condition associated with a variety of critical illness. DIC may complicate the already complex clinical situations and contribute to the high mortality. Nevertheless, its pathogenic mechanisms are not completely elucidated. Present study was prospectively designed to understand the pathogenetic mechanisms involved in the development of DIC. 15 rats were subjected to study and according to the aim, they were divided into three groups： group I, control (not treated-endotoxin, n=5)； group II (12 hours after endotoxin injection, n=5)； group III (24 hours after endotoxin injection, n=5). Experimental DIC was induced in rats by a bolus injection of endotoxin (1mg/kg, E. coli serotype 055:B5). Blood was collected by direct puncture of the heart. Platelet count, fibrinogen and plasminogen concentration, antithrombin III, D-dimer and complement components (C3 and C4) were measured in all subjects. In group II and III, there were apparent signs of DIC, including thrombocytopenia, decreased fibrinogen (but increase in group III), reduced C3 and antithrombin III, and elevated D-dimer. These data indicated that endotoxin might induce the activation of several pathways such as coagulation, fibrinolytic and complement cascade, causing DIC and subsequent multiple organ failures. Ultimately, the increased knowledge of the various pathogenetic mechanisms of coagulation activation and fibrinolysis in endotoxin-induced DIC may have prophylactic or therapeutic implications.

• The Korean Journal of Pharmacology
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• v.23 no.2
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• pp.77-85
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• 1987

This study was carried out to determine the role of cholinoceptors in the ventrolateral medulla on central control of blood pressure (BP) and heart rate (HR). In rats anesthetized with urethane and paralyzed, microinjections of the neuroexcitatory amino acid L-glutamate (300 ng/site) were performed to functionally identity the vasopressor area (VLPA) and the vasodepressor area (VLDA) in the ventrolateral medulla oblongata. 1. The bilateral microinjection of carbachol (300 ng/site) into the VLPA produced significantly an increase in BP and HR which was not blocked by bilateral pretreatment of hexamethoium ($4\;{\mu}g/site$). 2. The bilateral microinjection of physostigmine (200 ng/site) and oxotremorine (300 ng/site) into the VLPA produced significantly an increase in BP respectively. 3. The bilateral microinjection of atropine ($4\;{\mu}g/site$) into the VLPA produced significantly a decrease in BP and HR. 4. The bilateral micro injection of acetylcholine (500 ng/site) and dimethylphenylpiperazinium (500 ng/site) into the VLDA produced significantly a decrease in BP and HR respectively. 5. The depressor and bradycardiac responses elicited by the bilateral microinjection of acetylcholine (500 ng/site) into the VLDA were blocked by bilateral pretreatment of hexamethonium ($4\;{\mu}g/site$). The results suggest that the activation of cholinoceptors in VLPA produce hypertensive and tachycardiac responses which may be mediated by muscarinic receptors, and the activation of cholinoceptors in VLDA produce hypotensive and bradycardiac responses which may be mediated by nicotinic receptors.

• BMB Reports
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• v.33 no.6
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• pp.454-462
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• 2000

Interleukin-4(IL-4) is known to be a major cytokine regulating immunoglobulin E(IgE) response by the induction of IgE production and type II IgE receptor(IgER II: CD23) expression. Recently, however, the role of neuroendocrine factors has been implicated in modulating the IgE response. Among various neuroendocrine growth factors, we investigated the effects of the insulin-like growth factor-1(IGF-1) since IL-4 and IGF-1 share common intracellular signaling molecules, such as the insulin receptor substrate-1/2(IRS-1/2) to induce a specific cellular response. In the human peripheral blood mononuclear cell (PBMC) cultures, IGF-1 was capable of inducing a substantial level of IgE production in a dose-dependent manner. It also noticeably upregulated the IL-4-induced or IL-4 plus anti-CD40-induced IgE production. Similarly, the IGF-1-induced IgE production was enhanced by IL-4 or anti-CD40 in an additive manner, which became saturated at high concentrations of IGF-1. Although IGF-1 alone did not induce IgER II (CD23) expression, it augmented the IL-4-induced surface CD23 expression in a manner similar to the action of anti-CD40. These results imply that IGF-1 is likely to utilize common signaling pathways with IL-4 and anti-CD40 to induce IgE and IgER II expression. In support of this notion, we observed that IGF-1 enhanced the IL-4-induced signal transducers and activators of transcription 6(STAT6) activation and independently induced $NF-{\kappa}B$ activation. Both of these bind to the IgE(C) or IgER II (CD23) promoters. Together, our data suggest that IL-4 and IGF-1 work cooperatively to activate STAT6 and $NF-{\kappa}B$. This leads to the subsequent binding of these transcription factors to the $C{\varepsilon}$ and CD23 promoters to enhance the expression of IgE and IgER II. The observed differential ability of IGF-1 on the induction of IgE vs. IgER II is discussed based on the different structure of the two promoters.

• Journal of Ginseng Research
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• v.41 no.1
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• pp.23-30
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• 2017

Background: Ginsenoside Rg1 is a class of steroid glycoside and triterpene saponin in Panax ginseng. Many studies suggest that Rg1 suppresses adipocyte differentiation in 3T3-L1. However, the detail molecular mechanism of Rg1 on adipogenesis in 3T3-L1 is still not fully understood. Methods: 3T3-L1 preadipocyte was used to evaluate the effect of Rg1 on adipocyte development in the differentiation in a stage-dependent manner in vitro. Oil Red O staining and Nile red staining were conducted to measure intracellular lipid accumulation and superoxide production, respectively. We analyzed the protein expression using Western blot in vitro. The zebrafish model was used to investigate whether Rg1 suppresses the early stage of fat accumulation in vivo. Results: Rg1 decreased lipid accumulation in early-stage differentiation of 3T3-L1 compared with intermediate and later stages of adipocyte differentiation. Rg1 dramatically increased CAAT/enhancer binding protein (C/EBP) homologous protein-10 (CHOP10) and subsequently reduced the $C/EBP{\beta}$ transcriptional activity that prohibited the initiation of adipogenic marker expression as well as triglyceride synthase. Rg1 decreased the expression of extracellular signal-regulated kinase 1/2 and glycogen synthase kinase $3{\beta}$, which are also essential for stimulating the expression of $CEBP{\beta}$. Rg1 also reduced reactive oxygen species production because of the downregulated protein level of nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase 4 (NOX4). While Rg1 increased the endogenous antioxidant enzymes, it also dramatically decreased the accumulation of lipid and triglyceride in high fat diet-induced obese zebrafish. Conclusion: We demonstrated that Rg1 suppresses early-stage differentiation via the activation of CHOP10 and attenuates fat accumulation in vivo. These results indicate that Rg1 might have the potential to reduce body fat accumulation in the early stage of obesity.

• Molecules and Cells
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• v.38 no.2
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• pp.138-144
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• 2015

Raloxifene is a selective estrogen receptor modulator (SERM) that binds to the estrogen receptor (ER), and exhibits potent anti-tumor and autophagy-inducing effects in breast cancer cells. However, the mechanism of raloxifene-induced cell death and autophagy is not well-established. So, we analyzed mechanism underlying death and autophagy induced by raloxifene in MCF-7 breast cancer cells. Treatment with raloxifene significantly induced death in MCF-7 cells. Raloxifene accumulated GFP-LC3 puncta and increased the level of autophagic marker proteins, such as LC3-II, BECN1, and ATG12-ATG5 conjugates, indicating activated autophagy. Raloxifene also increased autophagic flux indicators, the cleavage of GFP from GFP-LC3 and only red fluorescence-positive puncta in mRFP-GFP-LC3-expressing cells. An autophagy inhibitor, 3-methyladenine (3-MA), suppressed the level of LC3-II and blocked the formation of GFP-LC3 puncta. Moreover, siRNA targeting BECN1 markedly reversed cell death and the level of LC3-II increased by raloxifene. Besides, raloxifene-induced cell death was not related to cleavage of caspases-7, -9, and PARP. These results indicate that raloxifene activates autophagy-dependent cell death but not apoptosis. Interestingly, raloxifene decreased the level of intracellular adenosine triphosphate (ATP) and activated the AMPK/ULK1 pathway. However it was not suppressed the AKT/mTOR pathway. Addition of ATP decreased the phosphorylation of AMPK as well as the accumulation of LC3-II, finally attenuating raloxifene-induced cell death. Our current study demonstrates that raloxifene induces autophagy via the activation of AMPK by sensing decreases in ATP, and that the overactivation of autophagy promotes cell death and thereby mediates the anti-cancer effects of raloxifene in breast cancer cells.

• Natural Product Sciences
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• v.27 no.2
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• pp.86-98
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• 2021

This study was designed to characterize the effect of ginsenoside-Rg2 (Rg2), one of panaxatriol saponins isolated from Korean ginseng root, on the release of catecholamines (CA) in the perfused model of the rat adrenal medulla, and also to establish its mechanism of action. Rg2 (3~30 µM), administered into an adrenal vein for 90 min, depressed acetylcholine (ACh)-induced CA secretion in a dose- and time-dependent manner. Rg2 also time-dependently inhibited the CA secretion induced by 3-(m-chloro-phenyl-carbamoyl-oxy)-2-butynyltrimethyl ammonium chloride (McN-A-343), 1.1-dimethyl-4-phenyl piperazinium iodide (DMPP), and angiotensin II (Ang II). Also, during perfusion of Rg2, the CA secretion induced by high K⁺, veratridine, cyclopiazonic acid, methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644) depressed, respectively. In the simultaneous presence of Rg2 and N^ω-nitro-L-arginine methyl ester hydrochloride ʟ-NAME), the CA secretion induced by ACh, Ang II, Bay-K-8644 and veratridine was restored nearly to the extent of their corresponding control level, respectively, compared to those of inhibitory effects of Rg2-treatment alone. Virtually, NO release in adrenal medulla following perfusion of Rg2 was significantly enhanced in comparison to the corresponding spontaneous release. Also, in the coexistence of Rg2 and fimasartan, ACh-induced CA secretion was markedly diminished compared to the inhibitory effect of fimasartan-treated alone. Collectively, these results demonstrated that Rg2 suppressed the CA secretion induced by activation of cholinergic as well as angiotensinergic receptors from the perfused model of the rat adrenal gland. This Rg2-induced inhibitory effect seems to be exerted by reducing both influx of Na⁺ and Ca²⁺ through their ionic channels into the adrenomedullary cells as well as by suppressing Ca²⁺ release from the cytoplasmic calcium store, at least through the elevated NO release by activation of NO synthase, which is associated to the blockade of neuronal cholinergic and AT₁-receptors. Based on these results, the ingestion of Rg2 may be helpful to alleviate or prevent the cardiovascular diseases, via reduction of CA release in adrenal medulla and consequent decreased CA level in circulation.

• Quality Improvement in Health Care
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• v.27 no.2
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• pp.18-29
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• 2021

Purpose: Patients with hematologic malignancy (HM) typically have a high mortality rate when their condition deteriorates. The chronic progressive course of the disease makes it difficult to assess the effect of intervention on acute events. We investigated the effectiveness of a rapid response team (RRT) on in-hospital mortality in patients with HM. Methods: We retrospectively analyzed the data of patients with HM who admitted to the medical intensive care unit between 2006 and 2015. Clinical outcomes before and after RRT implementation were evaluated. Results: A total of 228 patients in the pre-RRT period and 781 patients in the post-RRT period were included. The overall in-hospital mortality was 55.4%. Patients in the post-RRT period had improved survival; however, they required more vasopressor therapy, continuous renal replacement therapy, and extracorporeal membrane oxygenation. Multivariate analysis revealed that in-hospital mortality was associated with RRT activation (hazard ratio [HR], 0.634; 95% confidence interval [CI], 0.498-0.807; p < .001), neurological disease (HR, 2.007; 95% CI, 1.439-2.800; p < .001), sequential organ failure assessment score (HR, 1.085; 95% CI, 1.057-1.112; p < .001), need for continuous renal replacement therapy (HR, 1.608; 95% CI, 1.206-1.895; p< .001), mechanical ventilation (HR, 1.512; 95% CI, 1.206-1.895; p< .001), vasopressor (HR, 1.598; 95% CI, 1.105-2.311; p = .013), and extracorporeal membrane oxygenation (HR, 1.728; 95% CI, 1.105-2.311; p = .030). Conclusion: RRT activation may be associated with improved survival in patients with HM.