• Biomolecules & Therapeutics
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• v.19 no.2
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• pp.174-180
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• 2011

Experiments were carried out to determine the role of Raf-1 kinase in the development of drug resistance to paclitaxel in v-H-ras transformed NIH 3T3 fibroblasts (Ras-NIH 3T3). We established a multidrug-resistant cell line (Ras-NIH 3T3/Mdr) from Ras-NIH 3T3 cells by stepwise increases in paclitaxel. Drug sensitivity assays indicated that the $IC_{50}$ value for drug-resistant Ras-NIH 3T3/Mdr cells was more than 1 ${\mu}M$ paclitaxel, 10- or more-fold higher than for the parental Ras-NIH 3T3 cells. Western blot and RT-PCR analysis showed that the drug efflux pump a P-glycoprotein were highly expressed in Ras-NIH 3T3/Mdr cells, while not being detectable in Ras-NIH 3T3 cells. Additionally, verapamil, which appears to inhibit drug efflux by acting as a substrate for P-glycoprotein, completely reversed resistance to paclitaxel in Ras-NIH 3T3/Mdr cell line, indicating that resistance to paclitaxel is associated with overexpression of the multidrug resistance gene. Interestingly, Ras-NIH 3T3/Mdr cells have higher basal Raf-1 activity compared to Ras-NIH 3T3 cells. Unexpectedly, however, the colocalization of Raf-1 and its negative regulator Spry2 was less observed in cytoplasm of Ras-NIH 3T3/Mdr cells due to translocation of Spry2 around the nucleus in the perinuclear zone, implying that Raf-1 may be released from negative feedback inhibition by interacting with Spry2. We also showed that shRNA-mediated knockdown of Raf-1 caused a moderate increase in cell susceptibility to paclitaxel. Thus, the results presented here suggest that a Raf-1-dependent pathway plays an important role in the development of acquired drug-resistance.

• The Korean Journal of Food And Nutrition
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• v.23 no.1
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• pp.63-69
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• 2010

With the increase of the use of antibiotics and invasive procedures, infections caused by multidrug-resistant Acinetobacter baumannii(MRAB) are increasing. We screened the antibiotic producing strain B-51 for antibacterial activity against MRAB from the soils and studied the effects of culture medium on the antibiotic production of B-51. The medium conditions for maximum antibiotic productivity of B-51 was 2% glycerol, 0.5% soybean meal, 0.01% $CaCl_2$, 0.01% $MgSO_4{\cdot}7H_2O$ and 0.01% $KH_2PO_4$ at an initial pH of 6.0, at $30^{\circ}C$ for 76 h.

• Journal of Korean Critical Care Nursing
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• v.3 no.1
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• pp.67-78
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• 2010

Purpose: This study was done to investigate knowledge of and compliance with the multidrug-resistant organism (MDRO) infection control guidelines among student nurses on clinical practicum, Methods: survey questionnaire on MORO infection control was administered to a convenience sample of 259 nursing students from 3 different nursing schools Results: The mean knowledge score was 28.01/39 (71.82%). The percentages of correct answers for basic concepts, route of transmission, hand washing/ protective devices and environment management, were 55.40, 81.14, 84.94 and 69.17 respectively. The mean compliance score was 3.83/5. The compliance scores for education, communication, contact precaution, environment management, and hand washing were 3.06, 3.33, 3.86, 4.50, 3.92 and 4.29 respectively. 96.9% of subjects knew that they should wash hands after touching MORO patient while only 22.8% of subjects knew how to collect samples for VRE surveillance culture, The highest compliant item was hand washing after touching MORO patient. The Lo-west compliant item was referring to infection control manual. Conclusion: Comprehensive MDRO infection control education programs for nursing students should be developed to decrease MORO infection.

• Korean Journal of Veterinary Research
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• v.52 no.2
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• pp.133-139
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• 2012

Antimicrobial resistance is one of the most concerns in pig industry. Escherichia (E.) coli have been used for the indicator to monitor the antimicrobial resistance. In this study, 321 E. coli from diarrheic and non-diarrheic piglets were tested for antimicrobial resistance and frequency of $Bla_{TEM}$. In non-diarrheic piglets, they were resistant to oxytetracycline (93%), streptomycin (92%) and sulfadiazine (90%) but susceptible to ceftiofur (99%), colistin (97%), and enrofloxacin (82%). The isolates from diarrheic piglets were resistant to enrofloxacin (72.9%), ceftiofur (17.6%), and colistin (11.3%), whereas the resistance was 1%, 18% and 3% in case of non-diarrheic piglets, respectively. The resistance for amoxicillin/clavulanic acid (54.1%) and ceftiofur (22%) was high in isolates from post-weaning piglets. The resistance for colistin was 15.2% in nursery piglets. Seventy-three percent of isolates from diarrheic piglets showed high multidrug resistance profile (more than 13 antimicrobials) compared to those from non-diarrheic pigs in which 71% of isolates showed moderate multidrug resistance profile (7 to 12 antimicrobials). The frequency of $Bla_{TEM}$ in E. coli from non-diarrheic and diarrheic piglets was 57% and 69%, respectively. The results might provide the basic knowledge to establish the strategies for treatment and reduce antibiotic resistance of E. coli in piglets.

• Journal of Korean Biological Nursing Science
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• v.20 no.1
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• pp.38-46
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• 2018

Purpose: The aim of this study was to verify the effects of daily 2% chlorhexidine gluconate (CHG) bathing on the acquisition of multidrug-resistant organisms (MDRO) and healthcare-associated infection (HAI) in a medical intensive care unit (MICU). Methods: The study was a randomized controlled group posttest only design, involving 91 patients in MICU at a tertiary hospital (47 patients in the experimental group and 44 patients in the control group). The 2% CHG bathing was performed daily according to bathing protocol to the patients in the experimental group, and traditional bath was performed every three days to those in the control group. Fisher's exact test and x2 test were used to analyze the data. Results: MDRO were found in 6 patients of the experimental group and in 15 patients of the control group. The difference was statistically significant (p= .016). HAI occurred in 2 patients of the experimental group and in 7 patients of the control group. The difference was not statistically significant (p= .084). Conclusion: The results confirmed that daily bathing with CHG was effective in reducing the incidence of MDRO acquisition. Therefore, it is expected that daily bathing with CHG will be used as an effective nursing intervention to reduce the incidence of MDRO acquisition.

• Acute and Critical Care
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• v.33 no.4
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• pp.238-245
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• 2018

Background: Infection by multidrug-resistant (MDR) pathogens leads to poor patient outcomes in intensive care units (ICUs). Contact precautions are necessary to reduce the transmission of MDR pathogens. However, the importance of the surrounding environment is not well known. We studied the effects of ICU relocation on MDR respiratory pathogen detection rates and patient outcomes. Methods: Patients admitted to the ICU before and after the relocation were retrospectively analyzed. Baseline patient characteristics, types of respiratory pathogens detected, antibiotics used, and patient outcomes were measured. Results: A total of 463 adult patients admitted to the ICU, 4 months before and after the relocation, were included. Of them, 234 were admitted to the ICU before the relocation and 229 afterward. Baseline characteristics, including age, sex, and underlying comorbidities, did not differ between the two groups. After the relocation, the incidence rate of MDR respiratory pathogen detection decreased from 90.0 to 68.8 cases per 1,000 patient-days, but that difference was statistically insignificant. The use of colistin was significantly reduced from 53.5 days (95% confidence interval [CI], 20.3 to 86.7 days) to 18.7 days (95% CI, 5.6 to 31.7 days). Furthermore, the duration of hospital stay was significantly reduced from a median of 29 days (interquartile range [IQR], 14 to 50 days) to 21 days (IQR, 11 to 39 days). Conclusions: Incidence rates of MDR respiratory pathogen detection were not significantly different before and after ICU relocation. However, ICU relocation could be helpful in reducing the use of antibiotics against MDR pathogens and improving patient outcomes.

• Journal of Korean Academy of Nursing
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• v.51 no.4
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• pp.414-429
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• 2021

Purpose: This systematic review and meta-analysis analyzed the effects of 2% chlorhexidine bathing on the incidence of hospital-acquired infection (HAI) and multidrug-resistant organisms (MDRO) in adult intensive care units. Methods: PubMed, CINAHL, Cochrane library, and RISS database were systematically searched, and 12 randomized studies were included in the analysis. Comprehensive Meta-Analysis version 3.0 was used to calculate the effect size using the odds ratio (OR) and a 95% confidence interval (CI). Subgroup analysis was performed according to the specific infection and intervention types. Results: In general, 2% chlorhexidine bathing has a significant effect on the incidence of HAI (OR, 0.59; 95% CI, 0.40~0.86) and MDRO (OR, 0.52; 95% CI, 0.34~0.79). Subgroup analyses show 2% chlorhexidine bathing is effective in bloodstream infections (OR, 0.51; 95% CI, 0.39~0.66) but not for urinary tract infections, ventilator-associated pneumonia infections, and Clostridium difficile infections. Moreover, 2% chlorhexidine bathing alone or its combination with other interventions has a significant effect on the incidence of HAI and MDRO (OR, 0.59; 95% CI, 0.38~0.92). Conclusion: This meta-analysis reveals that 2% chlorhexidine bathing significantly reduces the incidence of HAI and MDRO in intensive care units. The effect of 2% chlorhexidine bathing on pediatric patients or patients at general wards should be further assessed as a cost-effective intervention for infection control.

• Journal of Microbiology and Biotechnology
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• v.33 no.1
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• pp.61-74
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• 2023

The global increase in multidrug-resistant (MDR) bacteria has inspired researchers to develop new strategies to overcome this problem. In this study, 23 morphologically different, soil-isolated actinomycete cultures were screened for their antibacterial ability against MDR isolates of ESKAPE pathogens. Among them, isolate BOGE18 exhibited a broad antibacterial spectrum, so it was selected and identified based on cultural, morphological, physiological, and biochemical characteristics. Chemotaxonomic analysis was also performed together with nucleotide sequencing of the 16S rRNA gene, which showed this strain to have identity with Streptomyces lienomycini. The ethyl acetate extract of the cell-free filtrate (CFF) of strain BOGE18 was evaluated for its antibacterial spectrum, and the minimum inhibitory concentration (MIC) ranged from 62.5 to 250 ㎍/ml. The recorded results from the in vitro anti-biofilm microtiter assay and confocal laser scanning microscopy (CLSM) of sub-MIC concentrations revealed a significant reduction in biofilm formation in a concentration-dependent manner. The extract also displayed significant scavenging activity, reaching 91.61 ± 4.1% and 85.06 ± 3.14% of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), respectively. A promising cytotoxic ability against breast (MCF-7) and hepatocellular (HePG2) cancer cell lines was obtained from the extract with IC₅₀ values of 47.15 ± 13.10 and 122.69 ± 9.12 ㎍/ml, respectively. Moreover, based on gas chromatography-mass spectrometry (GC-MS) analysis, nine known compounds were detected in the BOGE18 extract, suggesting their contribution to the multitude of biological activities recorded in this study. Overall, Streptomyces lienomycini BOGE18-derived extract is a good candidate for use in a natural combating strategy to prevent bacterial infection, especially by MDR pathogens.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.25.1-25.13
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• 2020

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP^-/- mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP^-/- mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP^-/- neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP^-/- neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

• BMB Reports
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• v.53 no.2
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• pp.88-93
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• 2020

Cisplatin is a widely used anti-cancer agent. However, the effectiveness of cisplatin has been limited by the commonly developed drug resistance. This study aimed to investigate the potential effects of endoplasmic reticulum (ER) stress to overcome drug resistance using the cisplatin-resistant A2780/CisR ovarian cancer cell model. The synthetic chalcone derivative (E)-3-(3,5-dimethoxyphenyl)-1-(2-methoxyphenyl)prop-2-en-1-one (named DPP23) is an ER stress inducer. We found that DPP23 triggered apoptosis in both parental cisplatin-sensitive A2780 and cisplatin-resistant A2780/CisR ovarian cancer cells due to activation of reactive oxygen species (ROS)-mediated unfolded protein response (UPR) pathway in the endoplasmic reticulum. This result suggests that ROS-mediated UPR activation is potential in overcoming drug resistance. DPP23 can be used as a target pharmacophore for the development of novel chemotherapeutic agents capable of overcoming drug resistance in cancer cells, particularly ovarian cancer cells.