• Title/Summary/Keyword: Overcoming resistance

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Improvement of Insulin Resistance by Curcumin in High Fat Diet Fed Mice (고지방식이 급여 마우스에서 curcumin의 인슐린 저항성 개선 효능)

  • Kim, Dan Bi;Ahn, Eunyeong;Kim, Eunjung
    • The Journal of the Convergence on Culture Technology
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    • v.4 no.1
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    • pp.315-323
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    • 2018
  • Rapid increase of diabetic population is a major health concern in Korea. In a trial to develop food components which can prevent and/or cure diabetes, we investigated the anti-diabetic activity of curcumin in high fat diet (HFD)-induced type 2 diabetes mellitus (T2DM) animal model. C57BL/6 mice were divided into three groups: normal diet (ND), high fat diet (HFD), and curcumin (CUR, HFD+0.02% curcumin). Mice were fed each diet for 16 weeks. CUR significantly reduced body weight gain, the levels of plasma glucose, insulin, total-cholesterol (T-C), and LDL-C, whereas increased HDL-C compared to those of HFD group. Notably, insulin signaling pathway was activated by CUR. This suggests that CUR improves obesity-associated T2DM by overcoming insulin resistance in part.

Effects of the Insulin Therapy Adherence Program for Patients with Type 2 Diabetes: A Randomized Controlled Trial (제2형 당뇨병 환자를 위한 인슐린치료이행증진 프로그램의 효과: 무작위대조군실험설계)

  • Park, Kyung Min;Son, Jung Tae
    • Journal of Korean Clinical Nursing Research
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    • v.28 no.3
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    • pp.277-288
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    • 2022
  • Purpose: This study was conducted to evaluate the effects of the insulin therapy adherence program (INSTA GRAM) for patients with type 2 diabetes mellitus. Methods: This study examined a total of 63 patients with type 2 diabetes for whom the initiation of insulin therapy is being considered or within 6 months of undergoing insulin therapy. INSTAGRAM is a stage-specific intervention consisting of strategies for motivating patients to initiate and maintain insulin therapy using the transtheoretical model on the stages of change, the process of change, and self-efficacy. The participants were randomly assigned to either the INSTAGRAM group (experimental group, n=32) or the standard diabetes education group (control group, n=31). The INSTAGRAM group received 6 sessions over 8 weeks(face-to-face education was conducted in the first and last sessions, and telephone coaching was conducted from the second to fifth sessions). The outcomes were measured by psychological insulin resistance, self-efficacy, and glycosylated hemoglobin (HbA1c). Results: Psychological insulin resistance (p<.001), self-efficacy (p<.001), and HbA1c (p=.024) of the participants in the INSTAGRAM group significantly improved compared to those in the control group. Conclusion: INSTAGRAM is effective in overcoming psychological insulin resistance and improving self-efficacy and HbA1c. Therefore, the INSTAGRAM can be recommended as a nursing intervention for type 2 diabetic patients who delay the initiation of insulin therapy.

Ginsenoside Rg3 in combination with artesunate overcomes sorafenib resistance in hepatoma cell and mouse models

  • Chen, Ying-Jie;Wu, Jia-Ying;Deng, Yu-Yi;Wu, Ying;Wang, Xiao-Qi;Li, Amy Sze-man;Wong, Lut Yi;Fu, Xiu-Qiong;Yu, Zhi-Ling;Liang, Chun
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.418-425
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    • 2022
  • Background: Sorafenib is effective in treating hepatoma, but most patients develop resistance to it. STAT3 signaling has been implicated in sorafenib resistance. Artesunate (ART) and 20(R)-ginsenoside Rg3 (Rg3) have anti-hepatoma effects and can inhibit STAT3 signaling in cancer cells. This study aimed to evaluate the effects of Rg3 in combination with ART (Rg3-plus-ART) in overcoming sorafenib resistance, and to examine the involvement of STAT3 signaling in these effects. Methods: Sorafenib-resistant HepG2 cells (HepG2-SR) were used to evaluate the in vitro anti-hepatoma effects of Rg3-plus-ART. A HepG2-SR hepatoma-bearing BALB/c-nu/nu mouse model was used to assess the in vivo anti-hepatoma effects of Rg3-plus-ART. CCK-8 assays and Annexin V-FITC/PI double staining were used to examine cell proliferation and apoptosis, respectively. Immunoblotting was employed to examine protein levels. ROS generation was examined by measuring DCF-DA fluorescence. Results: Rg3-plus-ART synergistically reduced viability of, and evoked apoptosis in HepG2-SR cells, and suppressed HepG2-SR tumor growth in mice. Mechanistic studies revealed that Rg3-plus-ART inhibited activation/phosphorylation of Src and STAT3 in HepG2-SR cultures and tumors. The combination also decreased the STAT3 nuclear level and induced ROS production in HepG2-SR cultures. Furthermore, overactivation of STAT3 or removal of ROS diminished the anti-proliferative effects of Rg3-plus-ART, and removal of ROS diminished Rg3-plus-ART's inhibitory effects on STAT3 activation in HepG2-SR cells. Conclusions: Rg3-plus-ART overcomes sorafenib resistance in experimental models, and inhibition of Src/STAT3 signaling and modulation of ROS/STAT3 signaling contribute to the underlying mechanisms. This study provides a pharmacological basis for developing Rg3-plus-ART into a novel modality for treating sorafenib-resistant hepatoma.

Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa - Combination therapy against resistant bacteria -

  • Bazzaz, Bibi Sedigheh Fazly;Sarabandi, Sahar;Khameneh, Bahman;Hosseinzadeh, Hossein
    • Journal of Pharmacopuncture
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    • v.19 no.4
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    • pp.312-318
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    • 2016
  • Objectives: Bacterial resistant infections have become a global health challenge and threaten the society's health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). Methods: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). Results: The MICs of gentamicin against bacterial strains were in the range of $0.312-320{\mu}g/mL$. The MIC values of both types of catechins were $62.5-250{\mu}g/mL$. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance.

Characterization of Wild-Type and Mutated RET Proto-Oncogene Associated with Familial Medullary Thyroid Cancer

  • Masbi, Mohammad Hosein;Mohammadiasl, Javad;Galehdari, Hamid;Ahmadzadeh, Ahmad;Tabatabaiefar, Mohammad Amin;Golchin, Neda;Haghpanah, Vahid;Rahim, Fakher
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.5
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    • pp.2027-2033
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    • 2014
  • Background: We aimed to assess RET proto-oncogene polymorphisms in three different Iranian families with medullary thyroid cancer (MTC), and performed molecular dynamics simulations and free energy stability analysis of these mutations. Materials and Methods: This study consisted of 48 patients and their first-degree relatives with MTC confirmed by pathologic diagnosis and surgery. We performed molecular dynamics simulations and free energy stability analysis of mutations, and docking evaluation of known RET proto-oncogene inhibitors, including ZD-6474 and ponatinib, with wild-type and mutant forms. Results: The first family consisted of 27 people from four generations, in which nine had the C.G2901A (P.C634Y) mutation; the second family consisted of six people, of whom three had the C.G2901T (P.C634F) mutation, and the third family, who included 12 individuals from three generations, three having the C.G2251A (P.G691S) mutation. The automated 3D structure of RET protein was predicted using I-TASSER, and validated by various protein model verification programs that showed more than 96.3% of the residues in favored and allowed regions. The predicted instability indices of the mutated structures were greater than 40, which reveals that mutated RET protein is less thermo-stable compared to the wild-type form (35.4). Conclusions: Simultaneous study of the cancer mutations using both in silico and medical genetic procedures, as well as onco-protein inhibitor binding considering mutation-induced drug resistance, may help in better overcoming chemotherapy resistance and designing innovative drugs.

Influences of Electrodeposition Variables on the Internal Stess of Nanocrystalline Ni-W Films (나노결정질 Ni-W 합금전착의 내부응력에 미치는 공정조건 변수의 영향)

  • Kim, Kyung-Tae;Lee, Jung-Ja;Hwang, Woon-Suk
    • Corrosion Science and Technology
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    • v.11 no.6
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    • pp.275-279
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    • 2012
  • Ni-W alloy deposits have lately attracted the interest as an alternative surface treatment method for hard chromium electrodeposits because of higher wear resistance, hardness at high temperature, and corrosion resistance. This study deals with influences of process variables, such as electodeposition current density, plating temperature and pH, on the internal stress of Ni-W nanocrystalline deposits. The internal stress was increased with increasing the applied current density. With increasing applied current density, the grain size of the deposit decreases and concentration of hydrogen in the deposit increases. The subsequent release of the hydrogen results in shrinkage of the deposit and the introduction of tensile stress in the deposit. Consequently, for layers deposited at high current density, cracking occurs readily owing to high tensile stress value. By increasing the temperature of the electrodeposition from $60^{\circ}C$ to $80^{\circ}C$, the internal stress was decreased. It seems that an increase in the number of active ions overcoming the activation energy at elevated temperature caused a decline in the concentration polarization and surface diffusion. It decreased the level of hydrogen absorption due to the lessened hydrogen evolution reaction. Therefore, the lower level of hydrogen absorption degenerated the hydride on the surface of the electrode, resulting in the reduction of the internal stress of the deposits. By increasing the pH of the electrodeposition from 5.6 to 6.8, the internal stress in the deposits were slightly decreased. It is considered that the decrease in internal stess of deposits was due to supply of W complex compound in cathode surface, and hydrogen ion resulted from decrease of activity.

Picropodophyllotoxin Inhibits Cell Growth and Induces Apoptosis in Gefitinib-Resistant Non-Small Lung Cancer Cells by Dual-Targeting EGFR and MET

  • Jin-Young, Lee;Bok Yun, Kang;Sang-Jin, Jung;Ah-Won, Kwak;Seung-On, Lee;Jin Woo, Park;Sang Hoon, Joo;Goo, Yoon;Mee-Hyun, Lee;Jung-Hyun, Shim
    • Biomolecules & Therapeutics
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    • v.31 no.2
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    • pp.200-209
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    • 2023
  • Patients with non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) amplification or sensitive mutations initially respond to the tyrosine kinase inhibitor gefitinib, however, the treatment becomes less effective over time by resistance mechanism including mesenchymal-epithelial transition (MET) overexpression. A therapeutic strategy targeting MET and EGFR may be a means to overcoming resistance to gefitinib. In the present study, we found that picropodophyllotoxin (PPT), derived from the roots of Podophyllum hexandrum, inhibited both EGFR and MET in NSCLC cells. The antitumor efficacy of PPT in gefitinib-resistant NSCLC cells (HCC827GR), was confirmed by suppression of cell proliferation and anchorage-independent colony growth. In the targeting of EGFR and MET, PPT bound with EGFR and MET, ex vivo, and blocked both kinases activity. The binding sites between PPT and EGFR or MET in the computational docking model were predicted at Gly772/Met769 and Arg1086/Tyr1230 of each ATP-binding pocket, respectively. PPT treatment of HCC827GR cells increased the number of annexin V-positive and subG1 cells. PPT also caused G2/M cell-cycle arrest together with related protein regulation. The inhibition of EGFR and MET by PPT treatment led to decreases in the phosphorylation of the downstream-proteins, AKT and ERK. In addition, PPT induced reactive oxygen species (ROS) production and GRP78, CHOP, DR5, and DR4 expression, mitochondrial dysfunction, and regulated involving signal-proteins. Taken together, PPT alleviated gefitinib-resistant NSCLC cell growth and induced apoptosis by reducing EGFR and MET activity. Therefore, our results suggest that PPT can be a promising therapeutic agent for gefitinib-resistant NSCLC.

Suggestion and Design of GaN on Diamond Structure for an Ideal Heat Dissipation Effect and Evaluation of Heat Transfer Simulation as Different Adhesion Layer (이상적인 열방산 효과를 위한 GaN on Diamond 구조의 제안과 접합매개층 종류에 따른 열전달 시뮬레이션 비교)

  • Kim, Jong Cheol;Kim, Chan Il;Yang, Seung Han
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.30 no.5
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    • pp.270-275
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    • 2017
  • Current progress in the development of semiconductor technology in applications involving high electron mobility transistors (HEMT) and power devices is hindered by the lack of adequate ways todissipate heat generated during device operation. Concurrently, electronic devices that use gallium nitride (GaN) substrates do not perform well, because of the poor heat dissipation of the substrate. Suggested alternatives for overcoming these limitations include integration of high thermal conductivity material like diamond near the active device areas. This study will address a critical development in the art of GaN on diamond (GOD) structure by designing for ideal heat dissipation, in order to create apathway with the least thermal resistance and to improve the overall ease of integrating diamond heat spreaders into future electronic devices. This research has been carried out by means of heat transfer simulation, which has been successfully demonstrated by a finite-element method.

Fungal Infection Occurrence on New Cultivars of Kiwifruit Correlated with Fruit Soluble Solids Content and Firmness

  • Kim, Min-Jung;Kwon, Youngho;Shin, Mi Hee;Kim, Jin Gook;Kwak, Youn-Sig;Kwack, Yong-Bum
    • Korean Journal of Soil Science and Fertilizer
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    • v.50 no.4
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    • pp.215-225
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    • 2017
  • Kiwifruit is prone to damage by frost in the harvest season and the occurrence of postharvest diseases. Accordingly, new cultivars overcoming these disadvantages have been developed. Compared to existing cultivars, studies on diseases in new cultivars are very limited. Thus, goal of this study was investigation of fungal infection occurrences in new cultivars. Kiwifruit was harvested in 2014 and 2015 year, respectively. In both years, cvs. Goldone and Redvita showed more resistance against fungal infection but cv. Gamrok was more sensitive compared with cv. Hayward. Major fungi were identified as Botryosphaeria dothidea, Phomopsis sp., Alternaria alternata and Nigrospora sp. Firmness and soluble solids content were also influenced by the occurrences. This study's findings are important for providing practical information on new cultivars in the kiwifruit industry.

The Effect of overcoming the TRAIL resistance through bufalin in EJ human bladder cancer cell (EJ 인간 방광암 세포에서 bufalin 의 TRAIL 저항성 극복 효과)

  • Hong, Su Hyun
    • Herbal Formula Science
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    • v.25 no.2
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    • pp.145-154
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    • 2017
  • Objectives : Bufalin is one of the bioactive component of 'Sum Su (蟾酥)', which is obtained from the skin and parotid venom gland of toad. Bufalin has been known to possess the inhibitory effects on cell proliferation and inducing apoptosis in various cancer cells. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has concerned, because it can selectively induce apoptotic cell death in many types of malignant cells, while it is relatively non-toxic to normal cells. Here, we investigated whether bufalin can trigger TRAIL-induced apoptotic cell death in EJ human bladder cancer cells. Methods : Effects on the cell viability and apoptotic activity were quantified using MTT assay and flow cytometry analysis, respectively. To investigate the morphological change of nucleus, DAPI staining was performed. Protein expressions were measured by immunoblotting. Results : A combined treatment with bufalin (10 nM) and TRAIL (50 ng/ml) significantly promoted TRAIL-mediated growth inhibition and apoptosis in EJ cells. The apoptotic effects were associated with the up-regulation of death receptor proteins, and the down-regulation of cFLIP and XIAP. Moreover, our data showed that bufalin and TRAIL combination activated caspases and subsequently increased degradation of poly(ADP-ribose) polymerase. Conclusions : Taken altogether, the nontoxic doses of bufalin sensitized TRAIL-mediated apoptosis in EJ cells. Therefore, bufalin might be an effective therapeutic strategy for the safe treatment of TRAIL-resistant bladder cancers.