Choi, Hyeong Sim;Jeong, Eun-Hui;Lee, Tae-Gul;Kim, Seo Yun;Kim, Hye-Ryoun;Kim, Cheol Hyeon
Tuberculosis and Respiratory Diseases
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v.75
no.1
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pp.9-17
/
2013
Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.
In order to isolate novel oligotrophic bacteria exhibiting antifungal activities, soils were collected from pepper-cultivated fields of Yeongyang, Jecheon, Nonsan, Eumsong and Goesan area in Korea. From soils in pepper cultivated area, a total of 9,354 strains were isolated as oligotrophic bacteria by the R2A dilution method. Among 9,354 oligotrohic bacteria candidates, 1A strain was selected by screening against Phytophthora capsici causing phytophthora blight of hot pepper in the greenhouse and field. The strain was identified as Bacillus vallismortis based on its 16S rDNA sequence and key characteristics as compared with those of authentic cultures of B. vallismortis(KACC 12149) and B. mojavensis(KACC 12096). The strain showed broad spectrum of antibiotic activity in vitro test, as revealed in its strong inhibitory activity to the genera Phytophthora, Collectotrichum, Botrytis and Fusarium, but not to Rhizoctonia and Magnaporthe. In pot experiments, infection rate of hot pepper in the non-treated pots was about 89%, while it was only 29% in the pots treated with 1A strain. The result indicated B. vallismortis 1A is a potential biocontrol agent for phytophthora blight of hot pepper
This study evaluated the effects of dietary anticoccidial drugs plus antibiotic growth promoters (AGPs) on parameters of immunity in commercial broiler chickens. Day-old chicks were raised on used litter from a farm with endemic gangrenous dermatitis to simulate natural pathogen exposure and provided with diets containing decoquinate (DECX) or monensin (COBN) as anticoccidials plus bacitracin methylene disalicylate and roxarsone as AGPs. As a negative control, the chickens were fed with a non-supplemented diet. Immune parameters examined were concanavalin A (ConA)-stimulated spleen cell proliferation, intestine intraepithelial lymphocyte (IEL) and spleen cell subpopulations, and cytokine/chemokine mRNA levels in IELs and spleen cells. ConA-induced proliferation was decreased at 14 d post-hatch in DECX-treated chickens, and increased at 25 and 43 d in COBN-treated animals, compared with untreated controls. In DECX-treated birds, increased percentages of $MHC2^+$ and $CD4^+$ IELS were detected at 14 d, but decreased percentages of these cells were seen at 43 d, compared with untreated controls, while increased $TCR2^+$ IELs were evident at the latter time. Dietary COBN was associated with decreased fractions of $MHC2^+$ and $CD4^+$ IELs and reduced percentages of $MHC2^+$, $BU1^+$, and $TCR1^+$ spleen cells compared with controls. The levels of transcripts for interleukin-4 (IL-4), IL-6, IL-17F, IL-13, CXCLi2, interferon-${\gamma}$ (IFN-${\gamma}$), and transforming growth factor${\beta}$4 were elevated in IELs, and those for IL-13, IL-17D, CXCLi2, and IFN-${\gamma}$ were increased in spleen cells, of DECX- and/or COBN-treated chickens compared with untreated controls. By contrast, IL-2 and IL-12 mRNAs in IELs, and IL-4, IL-12, and IL-17F transcripts in spleen cells, were decreased in DECX- and/or COBN-treated chickens compared with controls. These results suggest that DECX or COBN, in combination with bacitracin and roxarsone, modulate the development of the chicken post-hatch immune system.
Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.
Ryu, Junghyun;Kim, Minjeong;Ahn, Jin Seop;Ahn, Kwang Sung;Shim, Hosup
Journal of Embryo Transfer
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v.31
no.1
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pp.1-7
/
2016
Xenotransplantation involves multiple steps of immune rejection. The present study was designed to produce nuclear transfer embryos, prior to the production of transgenic pigs, using fibroblasts carrying transgenes human complement regulatory protein hCD59 and interleukin-18 binding protein (hIL-18BP) to reduce hyperacute rejection (HAR) and cellular rejection in pig-to-human xenotransplantation. In addition to the hCD59-mediated reduction of HAR, hIL-18BP may prevent cellular rejection by inhibiting the activation of natural killer cells, activated T-cell proliferation, and induction of $IFN-{\gamma}$. Transgene construct including hCD59 and ILI-18BP was introduced into miniature pig fetal fibroblasts. After antibiotic selection of double transgenic fibroblasts, integration of the transgene was screened by PCR, and the transgene expression was confirmed by RT-PCR. Treatment of human serum did not affect the survival of double-transgenic fibroblasts, whereas the treatment significantly reduced the survival of non-transgenic fibroblasts (p<0.01), suggesting alleviation of HAR. Among 337 reconstituted oocytes produced by nuclear transfer using the double transgenic fibroblasts, 28 (15.3%) developed to the blastocyst stage. Analysis of individual embryos indicated that 53.6% (15/28) of embryos contained the transgene. The result of the present study demonstrates the resistance of hCD59 and IL-18BP double-transgenic fibroblasts against HAR, and the usefulness of the transgenic approach may be predicted by RT-PCR and cytolytic assessment prior to actual production of transgenic pigs. Further study on the transfer of these embryos to surrogates may produce transgenic clone miniature pigs expressing hCD59 and hIL-18BP for xenotransplantation.
The aim of this study was to investigate the prevalence of CTX-M β-lactamase and plasmid-mediated quinolone resistance (PMQR) genes, and the pattern of antibiotic resistance in cefotaxime-resistant gramnegative bacteria. A total 126 gram-negative bacteria were isolated from hospitalized dogs and cats between 2018 and 2019. The most predominant isolates were E. coli (n=41), followed by Pseudomonas aeruginosa (n=25), Proteus mirabilis (n=14), Klebsiella pneumoniae (n=9), Sphingomonas paucimobilis (n=7), and Enterobacter cloacae and Serratia marcescens (respectively, n=5). Cefotaxime-resistant isolates were identified in 26.2% (33 isolates) of 126 gram-negative bacteria. CTX-M type β-lactamase were found in 15 isolates (10 E. coli, 1 Ent, cloacae and 4 K. pneumoniae, respectively). Among the CTX-M producing gram-negative bacteria, CTX-M-1 and CTX-M-9 were detected in 10 (66.7%) and 5 (33.3%) isolates, respectively. While, CTX-M-2 and CTX-M-8 were not found. PMQR genes were detected in 12 (36.4%) isolates (4 E. coli, 2 Ent, cloacae and 6 K. pneumoniae, respectively), and the predominant PMQR gene was aac(6')-lb-cr (n=9), followed by qnrB (n=8) and qnrS (n=1) alone or in combination. qnrA and qepA were not found. Additionally, 9 (60%) of 12 PMQR positive isolates were co-existence with CTX-M-1 or CTX-M-9. CTX-M or PMQR producing isolates showed highly resistance to penicillins (100%), cephalosporins (100~66.7%), monobactams (72.2%), and non-β-lactam antibiotics (94.4~61.1%) such as quinolones, trimethoprim/sulfamethoxazole, tetracycline and gentamicin. These findings showed CTX-M-1, CTX-M-9, aac(6')-lb-cr and qnrB were highly prevalent in cefotaxime-resistant Enterobacteriaceae isolates from companion animals in our region. Moreover, PMQR genes were closely associated with CTX-M type β-lactamase.
Onion has been reported to contain various organosulfur compounds which have antibiotic and anticarcinogenic properties and flavonoid like quercetin which is a valuable natural source of antioxidants. Carbohydrates in onion constitute about 80% of dry matter, and the major non-structural carbohydrate of onion bulb is fructo-oligosaccharides, well known as fructan, followed by glucose, fructose, and sucrose. The sugar concentration is associated with dormancy and storage life of onion, occurring as decrease in glucose, fructose and fructan, particularly towards the end of storage. Forced air pre-drying for 15-20 days at room temperature is an essential procedure to reduce freezing injury and sprouting, then onion bulbs can be stored at $0^{\circ}C$ for 6 months to control sprouting and decay. Bacterial soft rot caused by $Erwinia$ and $Pseudomonas$ is the main postharvest disease when the bulbs are infected with the bacteria and stored at room temperature. Browning in sliced onion is due to oxidation of phenolic compounds by polyphenol oxidase and it can be inhibited by citric acid treatment, packing with nitrogen gas, and polyethylene film.
Streptococcosis caused by Streptococcus parauberis is a very important disease in farmed olive flounder Paralichthys olivaceus. For most fish pathogens, including S. parauberis, there are no analytical criteria to distinguish antibioticsusceptible strains from antibiotic-resistant strains. In this study, epidemiological cut-off ($CO_{WT}$) values were generated to classify 75 strains of S. parauberis isolated from 1999 to 2018 as wild type (WT) and non-wild type (NWT) using disc diffusion data and normalized resistance interpretation (NRI) analysis. The susceptibility of the isolates to 16 antibiotics was evaluated using CLSI guideline M42-A. The wild-type cut-off values for amoxicillin, erythromycin, oxytetracycline, and florfenicol for S. parauberis were ${\geq}35$, 31, 28, and 27 mm, respectively. The NWT ratios of S. parauberis strains to treatment with GEN, FFC, ENR, SXT, EFT, VAN, and CHL were 17% or less, indicating that these antibiotics may be used to treat streptococcosis caused by S. parauberis. For recent S. parauberis isolates, the NWT ratios for AMX, ERY, OTC and FFC are much higher than for strains isolated from 1999-2007. The $CO_{WT}$ data from this study will assist aquatic animal disease professionals in prescribing appropriate antibiotics for the treatment of streptococcosis caused by S. parauberis, which will help reduce the misuse and abuse of antibiotics in the aquaculture sector.
Kwak, Shinhyeung;Kim, Dongsub;Choi, Joon-sik;Yoon, Yoonsun;Kim, Eun Sil;Kim, Mi Jin;Yoo, So-Young;Shim, Jong Sup;Choe, Yon Ho;Kim, Yae-Jean
Pediatric Infection and Vaccine
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v.29
no.2
/
pp.96-104
/
2022
Chronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory bone disorder presenting with sterile osteomyelitis, most often presenting in childhood. Although the etiology is understood incompletely, its association with other auto-inflammatory diseases including inflammatory bowel disease (IBD); psoriasis; Wegener's disease; arthritis; and synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome suggests that dysregulated innate immunity may play an important role in the pathogenesis. We report a case of a 13-year-old boy with CRMO associated with Crohn's disease (CD) successfully treated with infliximab after failure of non-steroidal anti-inflammatory drug (NSAID) treatment. He initially was diagnosed with CRMO based on symmetric and aseptic bone lesions with no fever, lack of response to antibiotic treatment, vertebral involvement, and normal blood cell counts. Despite five months of NSAID treatment, his musculoskeletal symptoms were aggravated, and he developed gastrointestinal symptoms. Finally, he was diagnosed with CRMO associated with CD. Due to the severity of symptoms, infliximab was initiated and produced symptom improvement. This case supports infliximab as another choice for treatment of bowel symptoms in addition to the bone and joint symptoms of CRMO when other first-line treatments are ineffective.
Bacteriocins are antimicrobial peptides synthesized on ribosomes, produced by bacteria, that inhibit the growth of similar or closely related bacterial strains. Since the discovery of nisin, many bacteriocins with unique structures and various modes of antibacterial activity have been described, and genes encoding production, secretion, and immunity have been reported. Nisin is one of the bacteriocins applied in cheese, liquid eggs, sauces and canned foods. Many of the bacteriocins of the genus Bacillus belong to lantibiotics, which are modified peptides after translation. Other genus Bacillus also produce many non-lantibiotic bacteriocins. Bacteriocins of the genus Bacillus are sometimes becoming more important because of their broader antibacterial spectrum. Bacteriocins are considered attractive compounds in the food and pharmaceutical industries to prevent food spoilage and growth of pathogenic bacteria. Bacteriocins can be used as biological preservatives in a variety of ways in the food system. Biopreservation refers to extending shelf life and improving safety of foods using microorganisms and/or their metabolites. The demand for new antimicrobial compounds has generated great interest in new technologies that can improve food microbiological safety. Applications of bacteriocins are expanding from food to human health. Today, many researchers are shifting their interest in bacteriocins from food preservation to the treatment of bacteria that cause infections and antibiotic-resistant diseases. This exciting new era in bacteriocin research will undoubtedly lead to new inventions and new applications. In this review, we summarize the various properties and applications of bacteriocins produced by the genus Bacillus.
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