• Title/Summary/Keyword: Synergistic response

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Apoptotic Effects of A Cisplatin and Eugenol Co-treatment of G361 Human Melanoma Cells

  • Park, Jun-Young;Jo, Jae-Beom;Kim, In-Ryoung;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.36 no.3
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    • pp.155-162
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    • 2011
  • Eugenol (4-allyl-2-methoxyphenol) is a naturally occurring phenolic compound that is widely used in dentistry as a component of zinc oxide eugenol cement that is commonly applied to the mouth environment. Cisplatin is one of the most potent known anticancer agents and shows significant clinical activity against a variety of solid tumors. This study was undertaken to investigate the synergistic apoptotic effects of co-treatments with eugenol and cisplatin on human melanoma (G361) cells. To investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment, an MTT assay was conducted. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining and an analysis of DNA hypoploidy. Western blot analysis and immunofluorescent staining were also performed to evaluate the expression levels and the translocation of apoptosis-related proteins following this co-treatment. Furthermore, proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed. The results indicated that a co-treatment with eugenol and cisplatin induced multiple pathways and processes associated with an apoptotic response in G361 cells including nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome activity, the increase and decrease of Bax and Bcl-2, a decreased DNA content, the release of cytochrome c into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of 300 ${\mu}M$ eugenol or 3 ${\mu}M$ cisplatin for 24 h did not induce apoptosis. Our present data thus suggest that a combination therapy of eugenol and cisplatin is a potential treatment strategy for human melanoma.

Apoptotic Effects of Co-Treatment with a Chios Gum Mastic and Eugenol on G361 Human Melanoma Cells

  • Jo, Jae-Beom;Oh, Sang-Hun;Kim, In-Ryoung;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.38 no.3
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    • pp.101-110
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    • 2013
  • We investigated the synergistic apoptotic effects of co-treatments with Chios gum mastic (CGM) and eugenol on G361 human melanoma cells. An MTT assay was conducted to investigate whether this co-treatment efficiently reduces the viability of G361 cells compared with each single treatment. The induction and augmentation of apoptosis were confirmed by DNA electrophoresis, Hoechst staining, and analyses of DNA hypoploidy. Western blot analysis and immunofluorescent staining were also performed to evaluate expression and translocation of apoptosis-related proteins following CGM and eugenol co-treatment. Proteasome activity and mitochondrial membrane potential (MMP) changes were also assayed.The results indicated that the co-treatment of CGM and eugenol induces multiple pathways and processes associated with an apoptotic response in G361 cells. These include nuclear condensation, DNA fragmentation, a reduction in MMP and proteasome activity, an increase of Bax and decrease of Bcl-2, a decreased DNA content, cytochrome c release into the cytosol, the translocation of AIF and DFF40 (CAD) into the nucleus, and the activation of caspase-9, caspase-7, caspase-3, PARP and DFF45 (ICAD). In contrast, separate treatments of $40{\mu}g/ml$ CGM or $300{\mu}M$ eugenol for 24 hours did not induce apoptosis. Our present data thus suggest that a combination therapy of CGM and eugenol is a potential treatment strategy for human melanoma.

Non-Enzymatic Glucose Sensor Based on a Copper Oxide Nanoflowers Electrode Decorated with Pt Nanoparticles (백금 나노입자가 분산된 3차원 산화구리 나노구조체 기반의 글루코스 검출용 비효소적 전기화학 센서 개발)

  • Song, Min-Jung
    • Korean Chemical Engineering Research
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    • v.56 no.5
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    • pp.705-710
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    • 2018
  • An electrochemical glucose sensor with enzyme-free was fabricated using Pt nanoparticles (Pt NPs) decorated CuO nanoflowers (CuO NFs). 3-D CuO nanoflowers film was directly synthesized on Cu foil by a simple hydrothermal method and Pt NPs were dispersed on the petal surface of CuO NFs through electrochemical deposition. This prepared sample was noted to Pt NPs-CuO NF. Morphology of the Pt NPs-CuO NFs layer was analyzed using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). The electrochemical properties and sensing performances were investigated using cyclic voltammetry (CV) and chronoamperometry (CA) under alkaline condition. The sensor exhibited a high sensitivity, wide liner range and fast response time. Its excellent sensing performance was attributed to the synergistic effect of the Pt NPs and CuO nanostructure.

Enhanced Production of Adenosine Triphosphate by Pharmacological Activation of Adenosine Monophosphate-Activated Protein Kinase Ameliorates Acetaminophen-Induced Liver Injury

  • Hwang, Jung Hwan;Kim, Yong-Hoon;Noh, Jung-Ran;Choi, Dong-Hee;Kim, Kyoung-Shim;Lee, Chul-Ho
    • Molecules and Cells
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    • v.38 no.10
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    • pp.843-850
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    • 2015
  • The1hepatic cell death induced by acetaminophen (APAP) is closely related to cellular adenosine triphosphate (ATP) depletion, which is mainly caused by mitochondrial dysfunction. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a key sensor of low energy status. AMPK regulates metabolic homeostasis by stimulating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. We found that the decrease in active phosphorylation of AMPK in response to APAP correlates with decreased ATP levels, in vivo. Therefore, we hypothesized that the enhanced production of ATP via AMPK stimulation can lead to amelioration of APAP-induced liver failure. A769662, an allosteric activator of AMPK, produced a strong synergistic effect on AMPK Thr172 phosphorylation with APAP in primary hepatocytes and liver tissue. Interestingly, activation of AMPK by A769662 ameliorated the APAP-induced hepatotoxicity in C57BL/6N mice treated with APAP at a dose of 400 mg/kg intraperitoneally. However, mice treated with APAP alone developed massive centrilobular necrosis, and APAP increased their serum alanine aminotransferase and aspartate aminotransferase levels. Furthermore, A769662 administration prevented the loss of intracellular ATP without interfering with the APAP-mediated reduction of mitochondrial dysfunction. In contrast, inhibition of glycolysis by 2-deoxy-glucose eliminated the beneficial effects of A769662 on APAP-mediated liver injury. In conclusion, A769662 can effectively protect mice against APAP-induced liver injury through ATP synthesis by anaerobic glycolysis. Furthermore, stimulation of AMPK may have potential therapeutic application for APAP overdose.

Synergistic Induction of iNOS by IFN-${\gamma}$ and Glycoprotein Isolated from Dioscorea batatas

  • Pham, Thi Thu Huong;Lee, Min Young;Lee, Kun Yeong;Chang, In Youp;Lee, Seog Ki;Yoon, Sang Pil;Lee, Dong-Cheol;Jeon, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.6
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    • pp.431-436
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    • 2012
  • Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-${\gamma}$, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-${\gamma}$, but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-${\gamma}$-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

Nitric oxide modulates antioxidant defense and the methylglyoxal detoxification system and reduces salinity-induced damage of wheat seedlings

  • Hasanuzzaman, Mirza;Hossain, Mohammad Anwar;Fujita, Masayuki
    • Plant Biotechnology Reports
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    • v.5 no.4
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    • pp.353-365
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    • 2011
  • The present study investigates the possible regulatory role of exogenous nitric oxide (NO) in antioxidant defense and methylglyoxal (MG) detoxification systems of wheat seedlings exposed to salt stress (150 and 300 mM NaCl, 4 days). Seedlings were pre-treated for 24 h with 1 mM sodium nitroprusside, a NO donor, and then subjected to salt stress. The ascorbate (AsA) content decreased significantly with increased salt stress. The amount of reduced glutathione (GSH) and glutathione disulfide (GSSG) and the GSH/GSSG ratio increased with an increase in the level of salt stress. The glutathione S-transferase (GST) activity increased significantly with severe salt stress (300 mM). The ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), catalase (CAT) and glutathione peroxidase (GPX) activities did not show significant changes in response to salt stress. The glutathione reductase (GR), glyoxalase I (Gly I), and glyoxalase II (Gly II) activities decreased upon the imposition of salt stress, especially at 300 mM NaCl, with a concomitant increase in the $H_2O_2$ and lipid peroxidation levels. Exogenous NO pretreatment of the seedlings had little influence on the nonenzymatic and enzymatic components compared to the seedlings of the untreated control. Further investigation revealed that NO pre-treatment had a synergistic effect; that is, the pre-treatment increased the AsA and GSH content and the GSH/GSSG ratio, as well as the activities of MDHAR, DHAR, GR, GST, GPX, Gly I, and Gly II in most of the seedlings subjected to salt stress. These results suggest that the exogenous application of NO rendered the plants more tolerant to salinity-induced oxidative damage by enhancing their antioxidant defense and MG detoxification systems.

Synthesis of CdxZn1-xS@MIL-101(Cr) Composite Catalysts for the Photodegradation of Methylene Blue

  • Yang, Shipeng;Peng, Siwei;Zhang, Chunhui;He, Xuwen;Cai, Yaqi
    • Nano
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    • v.13 no.10
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    • pp.1850118.1-1850118.17
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    • 2018
  • Nanoparticles of the semiconductor catalyst $Cd_xZn_{1-x}S$ were embedded into the metal organic framework MIL-101(Cr) to obtain $Cd_xZn_{1-x}S@MIL-101$(Cr) nanocomposites. These materials not only possess high surface areas and mesopores but also show good utilization of light energy. The ultraviolet-visible diffuse reflectance patterns of $Cd_xZn_{1-x}S@MIL-101$(Cr) nanocomposites showed that $Cd_{0.8}Zn_{0.2}S@MIL-101$(Cr) possessed good visible light response ability among the synthesized nanocomposites. The photocatalytic performance of the $Cd_xZn_{1-x}S@MIL-101$(Cr) nanocomposites were tested via degradation and mineralization of methylene blue in neutral water solution under light irradiation using a 300W xenon lamp. As a result, using $Cd_{0.8}Zn_{0.2}S@MIL-101$(Cr) as a catalyst, 99.2% of methylene blue was mineralized within 30 min. Due to the synergistic effect of adsorption by the MIL-101(Cr) component and photocatalytic degradation provided by the $Cd_{0.8}Zn_{0.2}S$ component, the $Cd_{0.8}Zn_{0.2}S@MIL-101$(Cr) catalyst displayed superior photocatalytic performance relative to $Cd_{0.8}Zn_{0.2}S$ and MIL-101(Cr). Furthermore, $Cd_{0.8}Zn_{0.2}S@MIL-101$(Cr) possessed excellent stability during photodegradation and exhibited good reusability. The remarkable photocatalytic performance of $Cd_{0.8}Zn_{0.2}S@MIL-101$(Cr) is likely due to the effective transfer of electrons and holes at the heterojunction interfaces.

Surface Characteristics and Photocatalytic Propertiy of B Doped TiO2 Layer Synthesized by Plasma Electrolytic Oxidation Process (Plasma Electrolytic Oxidation 방식으로 제조된 B Doped TiO2의 표면특성과 광촉매 특성)

  • Lee, Jong-Ho;Lee, Young-Ki;Kim, Young-Jig;Oh, Han-Jun
    • Korean Journal of Materials Research
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    • v.31 no.10
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    • pp.552-561
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    • 2021
  • For the purpose of manufacturing a high efficiency TiO2 photocatalyst, B-doped TiO2 photocatalysts are synthesized using a plasma electrolytic oxidation method in 0.5 M H2SO4 electrolyte with different concentrations of H3BO3 as additive. For the B doped TiO2 layer fabricated from sulfuric electrolyte having a higher concentration of H3BO3 additive, the main XRD peaks of (101) and (200) anatase phase shift gradually toward the lower angle direction, indicating volume expansion of the TiO2 anatase lattice by incorporation of boron, when compared with TiO2 layers formed in sulfuric acid with lower concentration of additive. Moreover, XPS results indicate that the center of the binding energy peak of B1s increases from 191.45 eV to 191.98 eV, which suggests that most of boron atoms are doped interstitially in the TiO2 layer rather than substitutionally. The B doped TiO2 catalyst fabricated in sulfuric electrolyte with 1.0 M H3BO3 exhibits enhanced photocurrent response, and high efficiency and rate constant for dye degradation, which is ascribed to the synergistic effect of the new impurity energy band induced by introducing boron to the interstitial site and the improvement of charge transfer reaction.

An In sight into Novel Drug Delivery System: In Situ Gels

  • Bashir, Rabiah;Maqbool, Mudasir;Ara, Irfat;Zehravi, Mehrukh
    • CELLMED
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    • v.11 no.1
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    • pp.6.1-6.7
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    • 2021
  • In situ gelling devices, as they enter the body, are dosage forms in the shape of the sol but turn into gel types under physiological circumstances. Transition from sol to gel is contingent on one or a mixture of diverse stimuli, such as transition of pH control of temperature, irradiation by UV, by the occurrence of certain ions or molecules. Such characteristic features may be commonly employed in drug delivery systems for the production of bioactive molecules for continuous delivery vehicles. The technique of in situ gelling has been shown to be impactful in enhancing the potency of local or systemic drugs supplied by non-parenteral pathways, increasing their period of residence at the absorption site. Formulation efficacy is further improved with the use of mucoadhesive agents or the use of polymers with both in situ gelling properties and the ability to bind with the mucosa/mucus. The most popular and common approach in recent years has provided by the use of polymers with different in situ gelation mechanisms for synergistic action between polymers in the same formulation. In situ gelling medicine systems in recent decades have received considerable interest. Until administration, it is in a sol-zone and is able to form gels in response to various endogenous factors, for e.g elevated temperature, pH changes and ions. Such systems can be used in various ways for local or systemic supply of drugs and successfully also as vehicles for drug-induced nano- and micro-particles. In this review we will discuss about various aspects about use of these in situ gels as novel drug delivery systems.

Helicobacter pylori GroEL Seropositivity Is Associated with an Increased Risk of Opisthorchis viverrini-Associated Hepatobiliary Abnormalities and Cholangiocarcinoma

  • Jala, Isabelle;Almanfaluthi, Muhammad Luthfi;Laha, Thewarach;Kanthawong, Sakawrat;Tangkawattana, Sirikachorn;Saichua, Prasert;Suttiprapa, Sutas;Sripa, Banchob
    • Parasites, Hosts and Diseases
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    • v.59 no.4
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    • pp.363-368
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    • 2021
  • Despite the synergistic effect of Opisthorchis viverrini and Helicobacter pylori co-infection on pathogenesis of severe hepatobiliary abnormalities (HBA) including advanced periductal fibrosis and replace with cholangiocarcinoma (CCA) have been established, the immune response to H. pylori in O. viverrini infected population has never been explored. Hence, this study aimed to investigate the antibody responses to 2 immunogenic H. pylori proteins in O. viverrini-infected patients with HBA and CCA. The risk analysis by multinomial logistic regression revealed that GroEL seropositivity was associated with higher risks of hepatobiliary abnormalities and CCA with adjusted odds ratios (95% confidence intervals) of 2.11 (95% CI=1.20-3.71, P=0.008) and 2.13 (95% CI=1.21-3.75, P=0.009), respectively. These findings indicate that GroEL seropositivity might be a biomarker for early detection of O. viverrini associated HBA and CCA.