• Title/Summary/Keyword: Oxa1

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Combination of oxaliplatin and β-carotene suppresses colorectal cancer by regulating cell cycle, apoptosis, and cancer stemness in vitro

  • Junghyeun Lee;Seung Chul Heo;Yuri Kim
    • Nutrition Research and Practice
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    • v.18 no.1
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    • pp.62-77
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    • 2024
  • BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G2/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

Genotyping and Molecular Characterization of Carbapenem-resistant Acinetobacter baumannii Strains Isolated from Intensive Care Unit Patients

  • Abozahra, Rania;Abdelhamid, Sarah M.;Elsheredy, Amel G.;Abdulwahab, Kawther E.;Baraka, Kholoud
    • Microbiology and Biotechnology Letters
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    • v.49 no.2
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    • pp.239-248
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    • 2021
  • The emergence of multidrug-resistant Acinetobacter baumannii has partly increased treatment failure and patient mortality. Class D β-lactamases is an important mechanism of resistance to beta-lactam antibiotics in this species. This study aimed to investigate the relationship between the presence oxacillinase gene and genetic fingerprints of A. baumannii isolates from the intensive care unit of an Egyptian tertiary care hospital. One hundred and twenty A. baumannii clinical isolates were collected. Multiplex PCR was performed to detect genes encoding oxacillinases (OXA-23, OXA-24, OXA-51, OXA-58 and OXA-143). Molecular typing of all collected isolates was performed using random amplified polymorphic DNA (RAPD)-PCR assay. Out of 120 examined isolates, 92, 88 and 84% were resistant to ertapenem, imipenem and meropenem, respectively. The species-specific, commonly present OXA-51 gene was found in all isolates while OXA-23 showed a high prevalence of 88% of isolates. OXA-24 and OXA-143 genes were detected in 3% and 1% of isolates, respectively. No OXA-58 gene was detected. Five clusters consisting of 19 genotypes were detected using RAPD-PCR. Genotype A was the most prevalent, it was observed in 62% of the isolates followed by genotype B (12%). These results revealed that genotypes A and B are common in the hospital. Results also demonstrate that RAPD-PCR is a rapid and reliable method for studying the clonal similarity among A. baumannii isolated from different clinical specimens.

In vitro Evaluation of New Acetylcholinesterase Reactivators as Casual Antidotes against Tabun and Cyclosarin

  • Kuca, Kamil;Jun, Daniel;Kim, Tae-Hyuk;Cabal, Jiri;Jung, Young-Sik
    • Bulletin of the Korean Chemical Society
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    • v.27 no.3
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    • pp.395-398
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    • 2006
  • Nerve agents (sarin, tabun, soman and VX) are class of military important substances able to cause many severe intoxications during few minutes. Currently, the threat of misuse of these agents is daily discussed. Unfortunately, there is no single antidote able to treat intoxication caused by all of these agents. Owing to this fact, new generation of antidotes, especially acetylcholinesterase (AChE; EC 3.1.1.7) reactivators, is still developed. In this study, we have tested four newly developed AChE reactivators: 1-(4-hydroxyiminomethylpyridinium)- 5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (1), 1-(3-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (2), 1,5-bis(2-hydroxyiminomethylpyridinium)-3-oxa-pentane dichloride (3) and 1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxa-pentane dibromide (4) for their potency to reactivate in vitro tabun and cyclosarin-inhibited AChE. Their reactivation efficacy was compared with currently the most promising oxime HI-6 (1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride). According to obtained results, two AChE reactivators 1 and 4 were able to reactivate tabun-inhibited AChE. On the contrary, there was no better AChE reactivator than HI-6 able to reactivate cyclosarin-inhibited AChE.

Detection of the Carbapenem Resistance Gene in Gram-negative Rod Bacteria Isolated from Clinical Specimens (임상검체에서 분리된 그람음성막대균으로부터 카바페넴 내성 유전자 검출)

  • Yang, Byoung Seon
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.3
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    • pp.179-191
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    • 2022
  • Carbapenem-resistant Enterobacteriaceae (CRE) poses an increasing public health threat and has limited treatment options with high associated mortality. Genotypes of carbapenemase that threaten public health (blaKPC, blaNDM, blaIMP, and blaVIM) and blaOXA-48-like genes were detected by phenotypic and molecular diagnosis, and related gene distribution patterns were investigated. Phenotypic testing using the modified Hodge test confirmed positivity in all 41 strains examined, and carbapenemase inhibitory testing using meropenem+phenyl boronic acid or meropenem+EDTA confirmed positivity in 18 and 8 strains, respectively. Polymerase chain reaction revealed the presence of amplification products in 28 strains of blaKPC, 25 strains of blaNDM, 5 strains of blaIMP, 1 strain of blaVIM, and 13 blaOXA-48-like strains. In addition, 7 strains of blaKPC+blaNDM, 1 strain of blaKPC+blaIMP, 1 strain of blaNDM+blaOXA-48-like, 1 strain of blaNDM+blaVIM, 4 strains of blaKPC+blaNDM+blaIMP, and 4 strains of blaKPC+blaNDM+blaOXA-48-like were identified. Melting curve analysis using real-time PCR was wholly consistent with PCR results. The study shows genetic identification of highly specific CRE by real-time PCR could be used to provide early diagnoses and infection control, improve surveillance, and prevent the transmission of CRE.

Association between Beta-lactam Antibiotic Resistance and Virulence Factors in AmpC Producing Clinical Strains of P. aeruginosa

  • Dehbashi, Sanaz;Tahmasebi, Hamed;Arabestani, Mohammad Reza
    • Osong Public Health and Research Perspectives
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    • v.9 no.6
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    • pp.325-333
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    • 2018
  • Objectives: The purpose of this study was to determine the presence of IMP and OXA genes in clinical strains of Pseudomonas aeruginosa (P. aeruginosa) that are carriers of the ampC gene. Methods: In this study, 105 clinical isolates of P. aeruginosa were collected. Antibiotic resistance patterns were determined using the disk diffusion method. The strains carrying AmpC enzymes were characterized by a combination disk method. Multiplex-PCR was used to identify resistance and virulence genes, chi-square test was used to determine the relationship between variables. Results: Among 105 isolates of P. aeruginosa, the highest antibiotic resistance was to cefotaxime and aztreonam, and the least resistance was to colictin and ceftazidime. There were 49 isolates (46.66%) that showed an AmpC phenotype. In addition, the frequencies of the resistance genes were; OXA48 gene 85.2%, OXA199, 139 3.8%, OXA23 3.8%, OXA2 66.6%, OXA10 3.8%, OXA51 85.2% and OXA58 3.8%. The IMP27 gene was detected in 9 isolates (8.57%) and the IMP3.34 was detected in 11 isolates (10.47%). Other genes detected included; lasR (17.1%), lasB (18%) and lasA (26.6%). There was a significant relationship between virulence factors and the OX and IMP genes ($p{\leq}0.05$). Conclusion: The relationship between antibiotic resistance and virulence factors observed in this study could play an important role in outbreaks associated with P. aeruginosa infections.

Distribution of the extended-spectrum beta-lactamase genes derived from microorganisms in the waterfront environments (주변 수계에서 미생물유래 extended-spectrum beta-lactamase 유전자의 분포)

  • Young-Min Bae
    • Journal of the Korean Applied Science and Technology
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    • v.39 no.6
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    • pp.916-923
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    • 2022
  • Water samples were collected from three spots(Namcheon, Changwoncheon and Cheongwoonji) in Changwon and genomic DNA was isolated from them. Quantitative PCR was performed with the isolated DNA as template and primers targeting five different class A extended-spectrum beta-lactamase(ESBL) genes(blaOXA-1, blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9). The number of total ESBL genes from each sample showed large variations between each sample. Thirty nanograms of DNA from Namcheon contained 1.93×106 copies of ESBL genes whereas the same amount of DNA from Changwoncheon contained 1.47×105 copies of ESBL genes. However, the same amount of DNA from Cheongwoonji pond contained only 9.5×103 copies of ESBL genes. The ratio of each ESBL genes showed little difference between Namcheon river and Changwoncheon river, but DNA from Cheongwoonji pond showed a large difference from the rest. blaOXA-1 gene was present at 65.3%, and blaCTX-M-1 gene 33.6% for Namcheon comprising together almost 99%. blaOXA-1 gene was present at 64.1%, and blaCTX-M-1 gene 19.1% for Changwoncheon comprising together over 83%. blaCTX-M-1 gene was present at 87.5% and blaCTX-M-9 genes 9.8% for Cheongwoonji, a pond which is a closed and isolated environment.

Distribution of Quinolones (Ciprofloxacin, Norfloxacin and Oxolinic acid) after Oral Administration in Carp (Cyprinus carpio) (잉어에 있어서 Quinolones (Ciprofloxacin, Norfloxacin 및 Oxolinic acid)의 경구투여에 따른 장기내 분포상)

  • Choi, Min-Soon;Park, Kwan-Ha
    • Journal of fish pathology
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    • v.18 no.3
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    • pp.269-276
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    • 2005
  • The concentrations of quinolones (oxolinic acid; OXA, norlloxacin: NRF & ciprofloxacin: CPF) after oral administration of single doses (20 mg/kg B.W.) were investigated in carp (Cyprinus carpio) kept in freshwater at 20-23$^{\circ}C$. The distribution of the drug was studied after treatment. At points timed, from 1 h to 96 hrs after administration, blood (B), liver (L), kidney (K) and muscle (M) from 5 individuals in each group were collected for analyse with microbiological bioassay method. The peak concentrations were measured at 8 h (L), 12 h (B and K) and 24 h (M) after administration regardless of treated drugs. Considerably high concentrations of CPF (13.8-19.6${\mu}g/m{\ell}$) NRF (11.8-16.9${\mu}g/m{\ell}$) and OXA (10.8-13.9 ${\mu}g/m{\ell}$) were revealed during the 24 h. At the last time point of the experiment (96 h), concentrations of all three quinolones were: OXA, 2.3-6.3 ${\mu}g/m{\ell}$ ; NRF, 3.1-4.5 ${\mu}g/m{\ell}$ ; CPF, 3.0-5.5${\mu}g/m{\ell}$ in samples. The concentrations decreased subsequently, indicating a first rapid redistribution, followed by a slow phase of elimination. The steady state was observed in blood (12-36 h), liver (12-96 h) and muscle (36-96 h) after the initiation of treatment with OXA. Concerning the compartmental concentrations, (L, K. and M/B concentration ratio), the fluctuation of the ratio was founded at different time points, among drugs. For CPF, highest tissue ratios were prolonged in the order of L>K>M (0.65-1.2/0.82-0.93/1.0-1.7) during the experiments. On the other hand, NRF presented L>K>M (0.65-1.3/0.86-1.0) till 24 h, but L>M>K (0.89-1.26) at 36-96 h. OXA showed L>K>M (0.95-2.1) at 1-8 h, M>K>L (0.51-1.0) at 12-36 hand M>L>K (1.0-2.3) at 48-96 h, respectively.

Intramolecular Oxa-Mannich Reaction of 1,3-Dihydro-2-benzofuran-1-ol for Efficient Synthesis of 1-Aminophthalan Derivatives

  • Kim, Heebum;Kim, Sung-Gon
    • Journal of the Korean Chemical Society
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    • v.66 no.1
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    • pp.9-14
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    • 2022
  • An efficient method for the synthesis of 1-aminophthalans has been developed. The intramolecular oxa-Mannich reaction of 1,3-dihydro-2-benzofuran-1-ols with p-toluenesulfonylamine in the presence of Cs2CO3 as a base, without using any catalyst, provided the desired 1-aminophthalans in moderate to good yields.