• Tuberculosis and Respiratory Diseases
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• 제81권3호
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• pp.222-227
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• 2018

Background: Rifampicin (RFP) is one of the principal first-line drugs used in combination chemotherapies against Mycobacterium tuberculosis, and its use has greatly shortened the duration of chemotherapy for the successful treatment of drug-susceptible tuberculosis. Compensatory mutations have been identified in rpoC that restore the fitness of RFP-resistant M. tuberculosis strains with mutations in rpoB. To investigate rpoC mutation patterns, we analyzed 93 clinical M. tuberculosis isolates from patients in South Korea. Methods: Drug-resistant mycobacterial isolates were cultured to determine their susceptibility to anti-tubercular agents. Mutations in rpoC were identified by sequencing and compared with the relevant wild-type DNA sequence. Results: In total, 93 M. tuberculosis clinical isolates were successfully cultured and tested for drug susceptibilities. They included 75 drug-resistant tuberculosis species, of which 66 were RFP-resistant strains. rpoC mutations were found in 24 of the 66 RFP-resistant isolates (36.4%). Fifteen different types of mutations, including single mutations (22/24, 91.7%) and multiple mutations (2/24, 8.3%), were identified, and 12 of these mutations are reported for the first time in this study. The most frequent mutation involved a substitution at codon 452 (nt 1356) resulting in amino acid change F452L. Conclusion: Fifteen different types of mutations were identified and were predominantly single-nucleotide substitutions (91.7%). Mutations were found only in dual isoniazid- and RFP-resistant isolates of M. tuberculosis. No mutations were identified in any of the drug-susceptible strains.

• 한국식품영양과학회지
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• 제30권1호
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• pp.193-195
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• 2001

A radiation-resistant bacterium was isolated from gamma irradiated dried laver (Porphyra tenera) and its microbiological characteristics were examined. As a result of resistance test to gamma irradiation, the isolate was survived $10^{3}$ CFU/mL even at 30 kGy and significant shoulder line zone was shown until 20 kGy. The $D_{10}$ value was 11.27 kGy. The isolate was gram-positive, non-motile coccus and catalase-positive. n culture, the red-pigmented smooth colony was observed. The biochemical test in API (analytical profile index) system showed that the isolate fermented glucose and fructose as the carbon source. Therefore, a radiation-resistant bacterium isolated from laver was potentially identified as Micrococcus roseus sp.

• 대한의생명과학회지
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• 제16권4호
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• pp.229-238
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• 2010

Chicken Mx protein (cMx) induced interferon (IFN) is an antiviral protein to inhibit replication of RNA virus, particularly negative stranded RNA virus, through blockage of transfortation of viral RNA and proteins. In order to determine antiviral effects of cMx from different MHC haplotype chicken, we characterized cMx gene by studying on nucleotide sequencing, antiviral effects to Newcastle disease virus, VSV and MDV, and transcription activities. Three types of eMx genes (2,118 bp) were detected from the different MHC haplotype chickens [B19 (N), B15(F) and B21 (GSP)] chickens, which have showed different susceptible to Marek's disease (MD). Several amino acid substitutions were showed in the cMx. The amino acid 548 and 631 in the cMxs from N and F, chickens susceptible to MD, was Val and Asn which was important on antiviral effects, and showed in resistant cMx. Those in the cMx from GSP, chicken resistant to MD, were same that showed in susceptible cMx. Though every cMx transactivated the expression of the reporter gene, the transcription activation by resistant cMx from N and F was lower compared to that by susceptible cMx from GSP. The decease of the cell growth in the resistant cMx cloned cells was seen in comparison with another cMx clone cells. Replication of NDV and VSV was suppressed in the clones with resistant cMx from N and F. NMx258-transducted cells lack of antiviral effects, and NMx437 or NMx646-transducted cells was showed 60% of antiviral effects compared to NMx705. Mean death time (MDT) and hemaggutination (HA) titer to NDV was long and low in the eggs of N and F lines, but short and high in the egg of GSP line. Interestingly, strong suppression to NDV was observed in the clone with N-Mx and in the eggs of N line. However, the effects of Mx for replication of vvMDV1 have not been. Thus, resistant types of cMx, N- and F-Mx, have showed the anti-viral effects to only RNA virus including NDV and VSV, but not to DNA virus. Antiviral effects of cMx were required whole length of amino acid including Val and Asn in amino acid 548 and 631.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.123-135
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• 2024

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G₀/G₁ phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

• The Plant Pathology Journal
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• 제30권1호
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• pp.75-81
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• 2014

In total, 170 carrot lines developed in Korea were screened for resistance to Meloidogyne incognita race 1 to select parental genetic resources useful for the development of nematode-resistant carrot cultivars. Using the gall index (GI), gall formation was examined on carrot roots inoculated with approximately 1,000 second-stage juveniles of the nematode 7 weeks after inoculation. Sixty-one carrot lines were resistant (GI ${\leq}1.0$), while the other 109 were susceptible (GI > 1.0) with coefficient of variance (CV) of GI for total carrot lines 0.68, indicating low-variation of GI within the lines examined. The histopathological responses of two carrot plants from resistant and susceptible lines were examined after nematode infection. In susceptible carrots, giant cells formed with no discernible necrosis around the infecting nematodes. In the resistant carrot line, however, no giant cells formed, although modified cells were observed with extensive formation of necrotic layers through their middle lamella and around the infecting nematodes. This suggested that these structural modifications were related to hypersensitive responses governed by the expression of true resistance genes. Therefore, the Korean carrot lines resistant to the nematode infection are potential genetic resources for the development of quality carrot cultivars resistant to M. incognita race 1.

• Asian Pacific Journal of Cancer Prevention
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• 제16권13호
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• pp.5191-5197
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• 2015

A partial response or resistance to chemotherapeutic agents is considered as a main obstacle in treatment of patients with cancer, including breast cancer. Refining taxane-based treatment procedures using adjuvant or combination treatment is a novel strategy to increase the efficiency of chemotherapy. PPM1D is a molecule activated by reactive oxygen species. whose expression is reported to modulate the recruitment of DNA repair molecules. In this study we examined the impact of arsenic trioxide on efficacy of paclitaxel-induced apoptosis in paclitaxel-resistant MCF-7 cells. We also investigated the expression of PPM1D and TP53 genes in response to this combination treatment. Resistant cells were developed from the parent MCF-7 cell line by applying increasing concentrations of paclitaxel. MTT assays were applied to determine the rate of cell survival. DAPI staining using fluorescent microscopy was employed to study apoptotic bodies. Real-time RT-PCR analysis was also applied to determine PPM1D mRNA levels. Our results revealed that combination of arsenic trioxide and paclitaxel elevates the efficacy of the latter in induction of apoptosis in MCF-7/PAC resistant cells. Applying arsenic trioxide also caused significant decreases in PPM1D mRNA levels (p<0.05). Our findings suggest that arsenic trioxide increases paclitaxel-induced apoptosis by down regulation of PPM1D expression. PPM1D dependent signaling can be considered as a novel target to improve the efficacy of chemotherapeutic agents in resistant breast cancer cells.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.265-273
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• 2022

Resistance to chemotherapeutic drugs is a significant problem in the treatment of colorectal cancer, resulting in low response rates and decreased survival. Recent studies have shown that shikonin, a naphthoquinone derivative, promotes apoptosis in colon cancer cells and cisplatin-resistant ovarian cells, raising the possibility that this compound may be effective in drug-resistant colorectal cancer. The aim of this study was to characterize the molecular mechanisms underpinning shikonin-induced apoptosis, with a focus on endoplasmic reticulum (ER) stress, in a 5-fluorouracil-resistant colorectal cancer cell line, SNU-C5/5-FUR. Our results showed that shikonin significantly increased the proportion of sub-G₁ cells and DNA fragmentation and that shikonin-induced apoptosis is mediated by mitochondrial Ca²⁺ accumulation. Shikonin treatment also increased the expression of ER-related proteins, such as glucose regulatory protein 78 (GRP78), phospho-protein kinase RNA-like ER kinase (PERK), phospho-eukaryotic initiation factor 2 (eIF2α), phospho-phosphoinositol-requiring protein-1 (IRE1), spliced X-box-binding protein-1 (XBP-1), cleaved caspase-12, and C/EBP-homologous protein (CHOP). In addition, siRNA-mediated knockdown of CHOP attenuated shikonin-induced apoptosis, as did the ER stress inhibitor TUDCA. These data suggest that ER stress is a key factor mediating the cytotoxic effect of shikonin in SNU-C5/5-FUR cells. Our findings provide an evidence for a mechanism in which ER stress leads to apoptosis in shikonin-treated SNU-C5/5-FUR cells. Our study provides evidence to support further investigations on shikonin as a therapeutic option for 5-fluorouracil-resistant colorectal cancer.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.335-335
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• 2017

Recently NERICA (New Rice for Africa) was developed by a crossing of African rice (Oryza glaberrima Steud.) and Asian rice (Oryza sativa L.) in West Africa, and is considered to be drought resistant, but drought resistance of NERICA and differences between Asian rice are not clarified enough. In this research, NERICA (four cultivars and two lines), Asian rice (three cultivars and sativa parent of NERICA) and African rice (glaberrima parent of NERICA) were cultivated in the field in Shizuoka University under drought and traits of each cultivar and line relevant to drought resistance, stomatal conductance by porometer, soil water content of individual depths by TDR method, SPAD values by SPAD meter and leaf thickness by micrometer, were measured and compared with dry matter production and yield. Effects of compost were also compared among sativa parent, one NERICA cultivar and two NERICA lines. Glaberrima parent showed highest top dry weight. One NERICA line, one drought resistant Asian rice cultivar and sativa parent, showed higher top dry weight and yield (ear weight) than other Asian rice cultivars and NERICA cultivars and line tested. Compost tended to increase top dry weight and yield in one of NERICA line and sativa parent. But in one NERICA cultivar and line, top dry weight and yield were not increased. In one of Asian rice, one of NERICA line and sativa parent that showed high top dry weight and yield, stomatal conductance was high. On the contrary the glaberrima parent and in other NERICA cultivars and line it was low. In sativa parent compost increased stomatal conductance but in NERICA cultivar and lines it was not. Among cultivars and lines that showed high top dry weight and yield sativa parent and one of NERICA line SPAD value and leaf thickness were high but in one of Asian rice and glaberrima parent they were low. Cultivar and line differences in yield and top dry weight among Asian rice and NERICA were significantly correlated with those in stomatal conductance ($r=0.778^{**}$ and $r=0.654^*$, respectively) and those in leaf thickness ($r=0.600^*$ and $r=0.640^*$, respectively). In Asian rice cultivars average soil water content was significantly correlated with yield ($r=0.886^*$) but in NERICA cultivars and lines it was not significant correlated (r= -0.256). Cultivar and line differences in leaf thickness were significantly correlated with SPAD value ($r=0.773^{**}$). In Asian rice cultivars it was significantly correlated ($r=0.962^{**}$), but in NERICA cultivars and lines it was not significantly correlated (r=0.559). Asian rice cultivars tended to consume soil water to increase yield but in NERICA cultivars and lines the tendency was not clear. Correlation between SPAD value and leaf thickness was different between Asian rice and NERICA cultivars and lines, and in Asian rice cultivars it was significantly correlated but in NERICA cultivars and lines it was not significant. Importance of maintaining high stomatal conductance by high leaf thickness was clarified.

• 대한수의학회지
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• 제38권4호
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• pp.784-792
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• 1998

This study was conducted to select resistant chicken-line between Brown and White layer lines against Salmonella gallinarum infection. The Brown and White layer chickens allocated into different age groups were inoculated with S gallinarum (WJO-126) either orally($1{\times}10^7cfu$) or intramusculaly($5{\times}10^6cfu$) and clinical observations were made for 2 weeks. All dead birds were necropsied and culture was made to recover the inoculated organinsm from liver, spleen, brain, bone marrow and cecal contents. Serum was isolated from all live birds after 2 weeks experiment and these birds were also necropsied and cultured to reisolate S gallinarum. The brown layers showed very high mortality to S gallinarum infection regardless of their ages and routes of inoculation, while white layers did not shown any mortality by the direct effects of S gallinarum. The mortality rate of 2 week old brown layers, in particular, were 82.6% (19/23) in peroral group and 86.9% in intramuscularly inoculated group, while those of white layer groups were only 0.0% in both groups. S gallinarum could be reisolated from all dead birds, especially, from liver and spleen. This result was inferred that the organism is highly invasive on the chicken. The intramuscularly challenged birds showed more seropositive-reactors(86.9%) than orally inoculated groups(61.9%). The overall results of present study suggested that white layers are much more resistant than brown layers against the experimental infection of S gallinarum and shown experimentally that resistance to S gallinarum is a characteristic of the White-line layers.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7421-7426
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• 2013

Background: Colorectal cancer is the fourth most common cancer worldwide and the second leading cause of cancer-related death. FOLFOX is the most common regimen used in the first-line chemotherapy in advanced colorectal cancer, but only half of the patients respond to this regimen and we have almost no clue in predicting resistance in such first-line application. Methods: To explore the potential molecular biomarkers predicting the resistance of FOLFOX regimen as the first-line treatment in advanced colorectal cancer, we screened microRNAs in serum samples from drug-responsive and drug-resistant patients by microarrays. Then differential microRNA expression was further validated in an independent population by reverse transcription and quantitative real-time PCR. Results: 62 microRNAs expressing differentially with fold-change >2 were screened out by microarray analysis. Among them, 5 (miR-221, miR-222, miR-122, miR-19a, miR-144) were chosen for further validation in an independent population (N=72). Our results indicated serum miR-19a to be significantly up-regulated in resistance-phase serum (p=0.009). The ROC curve analysis showed that the sensitivity of serum miR-19a to discriminate the resistant patients from the response ones was 66.7%, and the specificity was 63.9% when the AUC was 0.679. We additionally observed serum miR-19a had a complementary value for cancer embryonic antigen (CEA). Stratified analysis further revealed that serum miR-19a predicted both intrinsic and acquired drug resistance. Conclusions: Our findings confirmed aberrant expression of serum miR-19a in FOLFOX chemotherapy resistance patients, suggesting serum miR-19a could be a potential molecular biomarker for predicting and monitoring resistance to first-line FOLFOX chemotherapy regimens in advanced colorectal cancer patients.