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Associations Between TLR9 Polymorphisms and Cancer Risk: Evidence from an Updated Meta-analysis of 25,685 Subjects

  • Wan, Guo-Xing;Cao, Yu-Wen;Li, Wen-Qin;Li, Yu-Cong;Zhang, Wen-Jie;Li, Feng
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권19호
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    • pp.8279-8285
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    • 2014
  • A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488 controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084, rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk were systematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals (CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphism was significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28), specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CC vs TT: OR=1.31, 95% CI=1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association was significantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphism had a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836 polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98). In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancer risk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breast and digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-control studies are warranted to verify associations between TLR9 polymorphisms and cancer.

연구 실험실 사고의 근본원인분석 Map 개발에 관한 연구 (A Study on Development of Root Cause Analysis Map In Laboratory)

  • 엄석화;이수경
    • 한국가스학회지
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    • 제14권4호
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    • pp.6-11
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    • 2010
  • 연구실험실 사고 방지를 위하여 2005년 연구실 안전환경조성에 관한 법률이 법제화되어 국내 대학 또는 국공립출연연구소나 기업부설 연구소 실험실에서는 안전관리시스템을 구축하고, 안전점검과 정밀안전진단을 실시하고 있음에도 불구하고 폭발, 화재 등 각종 대형 사고가 지속적으로 발생하여 연구 활동 종사자의 인명 피해와 재산 손실이 상당한 수준에 이르고 있다. 또한 연구실험실에서 발생하는 사고는 유사한 내용으로 반복적으로 발생되고 있으므로 이러한 사고의 원인분석과 재발 방지를 위한 안전관리 대책이 시급하다. 따라서 본 논문에서는 국내 해외 대학 또는 국공립출연 연구소나 기업 부설 연구소 실험실에서 발생한 사건 사고에 대해 Root Cause Analysis 기법을 이용하여 사고원인 조사 결과를 보여주고, 이에 따른 실험실 사고원인 조사 분류 Map과 개선사항을 제시하여 연구실험실의 안전관리를 향상시키고자 한다.

Intestinal Parasitic Infections and Environmental Water Contamination in a Rural Village of Northern Lao PDR

  • Ribas, Alexis;Jollivet, Chloe;Morand, Serge;Thongmalayvong, Boupha;Somphavong, Silaphet;Siew, Chern-Chiang;Ting, Pei-Jun;Suputtamongkol, Saipin;Saensombath, Viengsaene;Sanguankiat, Surapol;Tan, Boon-Huan;Paboriboune, Phimpha;Akkhavong, Kongsap;Chaisiri, Kittipong
    • Parasites, Hosts and Diseases
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    • 제55권5호
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    • pp.523-532
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    • 2017
  • A field survey studying intestinal parasites in humans and microbial pathogen contamination at environment was performed in a Laotian rural village to identify potential risks for disease outbreaks. A parasitological investigation was conducted in Ban Lak Sip village, Luang Prabang, Lao PDR involving fecal samples from 305 inhabitants as well as water samples taken from 3 sites of the local stream. Water analysis indicated the presence of several enteric pathogens, i.e., Aeromonas spp., Vibrio spp., E. coli H7, E. coli O157: H7, verocytotoxin-producing E. coli (VTEC), Shigella spp., and enteric adenovirus. The level of microbial pathogens contamination was associated with human activity, with greater levels of contamination found at the downstream site compared to the site at the village and upstream, respectively. Regarding intestinal parasites, the prevalence of helminth and protozoan infections were 68.9% and 27.2%, respectively. Eight helminth taxa were identified in fecal samples, i.e., 2 tapeworm species (Taenia sp. and Hymenolepis diminuta), 1 trematode (Opisthorchis sp.), and 5 nematodes (Ascaris lumbricoides, Trichuris trichiura, Strongyloides stercoralis, trichostrongylids, and hookworms). Six species of intestinal protists were identified, i.e., Blastocystis hominis, Cyclospora spp., Endolimax nana, Entamoeba histolytica/E. dispar, Entamoeba coli, and Giardia lamblia. Questionnaires and interviews were also conducted to determine risk factors of infection. These analyses together with a prevailing infection level suggested that most of villagers were exposed to parasites in a similar degree due to limited socio-economic differences and sharing of similar practices. Limited access to effective public health facilities is also a significant contributing factor.

미생물 실험실에서의 부유 곰팡이 농도의 계절별 변이와 환경영향 (Seasonal and Environmental Influences on Culturable Airborne Fungi Levels in Microbiology Laboratories)

  • 황성호;홍순열;석지원;윤충식
    • 한국환경보건학회지
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    • 제42권1호
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    • pp.19-26
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    • 2016
  • Objectives: This study aimed to assess temporal changes in the level of culturable airborne fungi (CAF) in three microbiology laboratories and determine the environmental factors associated with CAF level. Methods: CAF levels were determined once per month from March 2011 to February 2012 in three microbiology laboratories. An Andersen one-stage sampler was used for five minutes, three times per day to collect the CAF. Arithmetic means of CAF concentrations and standard deviation (SD) were calculated. A Mann-Whitney test was applied to compare the differences between environmental factors such as divided room by structure of laboratory, use of humidifier, and use of air-conditioner. Correlation analysis was also applied to identify the association between CAF concentrations and environmental factors. Results: CAF levels demonstrated an increasing tendency in summer, and the three laboratories showed consistent seasonal patterns. Temperature and relative humidity (RH) were associated with CAF levels. When the humidifier was off, CAF concentrations were significantly higher in study rooms than in study rooms in which the humidifier was on. Conclusion: CAF levels in indoor microbiology laboratories varied greatly depending upon the temperature and RH and whether a humidifier was used.

Purification and Characterization of Recombinant Human Follicle Stimulating Hormone Produced by Chinese Hamster Ovary Cells

  • NA KYU HEUM;KIM SEUNG CHUL;SEO KWANG SEOK;LEE SUNG HEE;KIM WON BAE;LEE KANG CHOON
    • Journal of Microbiology and Biotechnology
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    • 제15권2호
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    • pp.395-402
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    • 2005
  • Biologically active recombinant human follicle stimulating hormone (rhFSH) was produced in Chinese hamster ovary cells and purified by a series of chromatographic steps. The chromatographic steps included anion-exchange chromatography (DEAE Sepharose F/F, Q Sepharose F/F), hydrophobic interaction chromatography (Source 15 PHE), and hydroxyapatite chromatography (Macro-Prep ceramic hydroxyapatite type I). A distinctive step of the purification process developed was the use of ZnCl$_2$ for the removal of non-glycosylated or lowly-glycosylated FSH and impurities through co-precipitation with Zn$^{2+}$. Purified rhFSH was identified and characterized by several physicochemical and biological methods such as gel electrophoresis, high-performance liquid chromatography, amino acid analysis, carbohydrate analysis, and biological activity. The overall yield of the purification was ~$30\%$. The rhFSH preparation obtained showed high purity (>$99\%$) and high in vivo potency (>16,000 IU/mg). Carbohydrate analysis suggested that the purified rhFSH contained approximately $40\%$ (w/w) carbohydrate with di­or tri-antennary structure on average, which is somewhat more heavily sialylated than commercially available rhFSH. In conclusion, the results of these analyses established an identity of the purified rhFSH with natural FSH from human pituitary glands, and furthermore, the purified rhFSH preparation showed higher in vivo potency and was slightly more heavily sialylated than commercially available rhFSH.

Oral Toxicity Study and Skin Sensitization Test of a Cricket

  • Ryu, Hyeon Yeol;Lee, Somin;Ahn, Kyu Sup;Kim, Hye Jin;Lee, Sang Sik;Ko, Hyuk Ju;Lee, Jin Kyu;Cho, Myung-Haing;Ahn, Mi Young;Kim, Eun Mi;Lim, Jeong Ho;Song, Kyung Seuk
    • Toxicological Research
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    • 제32권2호
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    • pp.159-173
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    • 2016
  • Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource.

Gold Nanoparticles Enhance the Anticancer Activity of Gallic Acid against Cholangiocarcinoma Cell Lines

  • Rattanata, Narintorn;Daduang, Sakda;Wongwattanakul, Molin;Leelayuwat, Chanvit;Limpaiboon, Temduang;Lekphrom, Ratsami;Sandee, Alisa;Boonsiri, Patcharee;Chio-Srichan, Sirinart;Daduang, Jureerut
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권16호
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    • pp.7143-7147
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    • 2015
  • Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and $150{\mu}M$ and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (P<0.0001) in both M213 and M214 cells compared to GA alone, indicating that the anticancer activity of GA can be improved by conjugation with GNPs. Moreover, PCA revealed that exposure of the tested cells to GA resulted in significant changes in their cell membrane lipids and fatty acids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways.

Effects of ID-CBT5101 in Preventing and Alleviating Osteoarthritis Symptoms in a Monosodium Iodoacetate-Induced Rat Model

  • Sim, Boo-Yong;Choi, Hak-Joo;Kim, Min-Goo;Jeong, Dong-Gu;Lee, Don-Gil;Yoon, Jong-Min;Kang, Dae-Jung;Park, Soobong;Ji, Joong-Gu;Joo, In-Hwan;Kim, Dong-Hee
    • Journal of Microbiology and Biotechnology
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    • 제28권7호
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    • pp.1199-1208
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    • 2018
  • Osteoarthritis is a disease that affects the articular cartilage and osseous tissue, and can be worsened by aging, overweight status, and post-traumatic arthritis. The present study aimed to evaluate the effect of ID-CBT5101 (tyndallized Clostridium butyricum) on bone metabolism and the inflammatory response in a monosodium iodoacetate-induced rat model of osteoarthritis. ID-CBT5101 was administered orally at doses of $10^8$ or $10^{10}CFU/day$ for 2 weeks before direct injection of monosodium iodoacetate ($3mg/50{\mu}l$ of 0.9% saline) into the intra-articular space of the rats' right knees. The rats subsequently received the same doses of oral ID-CBT5101 for another 4 weeks. We evaluated the treatment effects based on serum biomarkers, mRNA expression, morphological and histopathological analyses of the knee joints, and weight-bearing distribution analysis. Compared with those in control rats, the ID-CBT5101 treatments significantly reduced the serum concentration of inflammation and bone metabolism markers (i.e., COX-2, IL-6, $LTB_4$, and COMP), and significantly increased the concentration of $IFN-{\gamma}$ and glycosaminoglycans. In addition, the ID-CBT5101 treatments inhibited the mRNA expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases (i.e., MMP-2, MMP-3, MMP-9, MMP-13, TIMP-1, and TIMP-2). Furthermore, the ID-CBT5101 treatments effectively preserved the knee cartilage and synovial membrane, and significantly decreased the amount of fibrous tissue. Moreover, compared with that of the negative control group, the ID-CBT5101 treatments increased the weight-bearing distribution by ${\geq}20%$. The results indicate that ID-CBT5101 prevented and alleviated osteoarthritis symptoms. Thus, ID-CBT5101 may be a novel therapeutic option for the management of osteoarthritis.

DA-7911, $^{188}Rhenium-tin$ Colloid, as a New Therapeutic Agent of Rheumatoid Arthritis

  • Shin, Chang-Yell;Son, Miwon;Ko, Jun-Il;Jung, Mi-Young;Lee, In-Ki;Kim, Soon-Hoe;Kim, Won-Bae;Jeong, Jae-Min;Song, Yeong-Wook
    • Archives of Pharmacal Research
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    • 제26권2호
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    • pp.168-172
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    • 2003
  • Radiation synovectomy is one of the most useful methods for treating patients with refractory synovitis because of its convenience, long-term effects, repeatability and the avoidance of surgery. In this study, we investigated the toxicity, stability and biodistribution of a rhenium-188 ($^{188}$Re)-tin colloid to evaluate its suitability as a synovectomy agent. Twenty four hours after injecting the $^{188}$Re-tin colloids (74 KBq/0.1 mL) into the tail vein of ICR mice, most of the $^{188}$Retin colloidal particles was found in the lungs. In addition, there were no particle size changes at either room temperature or at $37^{\circ}C$ after injecting the $^{188}$Re-tin colloids in human plasma and synovial fluid. In vitro stability tests showed that the $^{188}$Re-tin colloid remained in a colloidal form without a critical size variation over a 2-day period. We investigated the leakage of $^{188}$Retin colloids from the intraarticular injection site with gamma counting in New Zealand white rabbits. The $^{188}$Re-tin colloids (55.5 MBq/0.15 mL) were injected at the cavum articular and the mean retention percentage of the $^{188}$Re-tin colloid was 98.7% for 1 day at the injection site, which suggests that there was neither change in the particle size nor leakage at the injection sites. In the biodistribution study with the SD rats, the liver showed the highest radioactivity (0.0427% ID/organ) except for the injected knees (99.49%). In the SD rats, mild toxicities including the skin or a synovium inflammation were observed as a result of a radioactivity of 15 mCi/kg at the intraarticular injection site. However, there was no systemic toxicity. In the Ovalbumin (OVA)-induced arthritic rabbits, the $^{188}$Re-tin colloid improved the macroscopic, the histological score and reduced the knee joint diameter when compared to the arthritic control. In conclusion, a $^{188}$Re-tin-colloid is considered as a strong candidate for radiation synovectomy with a superior efficacy and safety.

Five Most Common Prognostically Important Fusion Oncogenes are Detected in the Majority of Pakistani Pediatric Acute Lymphoblastic Leukemia Patients and are Strongly Associated with Disease Biology and Treatment Outcome

  • Awan, Tashfeen;Iqbal, Zafar;Aleem, Aamer;Sabir, Noreen;Absar, Muhammad;Rasool, Mahmood;Tahir, Ammara H.;Basit, Sulman;Khalid, Ahmad Mukhtar;Sabar, Muhammad Farooq;Asad, Sultan;Ali, Agha Shabbir;Mahmood, Amer;Akram, Muhammad;Saeed, Tariq;Saleem, Arsalan;Mohsin, Danish;Shah, Ijaz Hussain;Khalid, Muhammad;Asif, Muhammad;Haq, Riazul;Iqbal, Mudassar;Akhtar, Tanveer
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5469-5475
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    • 2012
  • Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.