Publications by authors named "Jae-Ran Yu"

80 Publications

Radioprotective effects of Cryptosporidium parvum lysates on normal cells.

Int J Biol Macromol 2021 May 23;178:121-135. Epub 2021 Feb 23.

Department of Radiation Oncology, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address:

Two fractions, small and big (CpL-S, CpL-B), from Cryptosporidium parvum lysate (CpL) were prepared and its radioprotective activity was evaluated on normal cells. Both fractions improved cell viability of normal cells in a dose-dependent manner. 20 μg CpL-S and CpL-B improved cell viability of 10 Gy irradiated COS-7 cells by 38% and 34% respectively, while in HaCat cells 16% and 18% improved cell viability was observed, respectively. CpL-S scavenged IR-induced ROS more effectively compared to the CpL-B, 50% more in COS-7 cells and 15% more in HaCat cells. There was a significant reduction of γH2AX, Rad51, and pDNA-PKcs foci in CpL-S treated cells compared to control or CpL-B group at an early time point as well as late time point. In 3D skin tissue, CpL-S reduced the number of γH2AX positive cells by 31%, compared to control, while CpL-B reduced by 9% (p < 0.005) at 1 h post 10 Gy irradiation and 22% vs 6% at 24 h post-IR (p < 0.005). Taken together, CpL-S significantly improved cell viability and prevented radiation-induced DNA damage in normal cells as well as 3D skin tissues by effectively scavenging ROS generated by ionizing radiation. CpL-S can be a candidate for radioprotector development.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.02.151DOI Listing
May 2021

Silencing of FTS increases radiosensitivity by blocking radiation-induced Notch1 activation and spheroid formation in cervical cancer cells.

Int J Biol Macromol 2019 Apr 20;126:1318-1325. Epub 2018 Sep 20.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address:

Increasing evidence(s) suggests that cancer stem cells (CSC) in tumours contribute to radio-resistance and recurrence. Notch plays an important role in the maintenance of CSC in many cancers including cervical cancer. Previously, we have reported the role of Fused Toes Homolog (FTS) in conferring radioresistance in cervical cancer cells in vitro and human subjects. The present study investigated the regulatory role of FTS in Notch signaling and maintenance of CSC upon irradiation of cervical cancer cells. The expression of Notch1, 2, 3, cleaved Notch1 and its downstream target Hes1, and spheroid formation was increased by irradiation. Silencing of FTS prevented the radiation-induced increase in the expression of Notch signaling molecules and spheroid formation. Immunoprecipitation showed FTS binds Notch1 and Hes1. Also in silico structural analysis identified putative residues responsible for the binding between FTS and Notch1. Spheroid formation and the expression of CSC markers, Nanog, Oct4A and Sox2 were greatly reduced by combining silencing of FTS and radiation. Taken together, these results suggest that FTS is involved in the regulation of irradiation-induced Notch signaling and CSC activation and can be used as a target to increase radiosensitivity in cervical cancer.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.09.114DOI Listing
April 2019

Simultaneous Molecular Detection of and from Raw Vegetables in Korea.

Korean J Parasitol 2017 Apr;55(2):137-142

Department of Environmental and Tropical Medicine & International Healthcare Research Institute, Konkuk University School of Medicine, Seoul 05029, Korea.

and are well-known coccidian protozoa that can cause waterborne and foodborne diarrheal illnesses. There have been a few reports regarding contamination in different vegetables with , but no data are available regarding the sources of infections in Korea. In the present study, we collected 6 kinds of vegetables (perilla leaves, winter-grown cabbages, chives, sprouts, blueberries, and cherry tomatoes) from July 2014 to June 2015, and investigated contamination by these 2 protozoa using multiplex quantitative real-time PCR. Among 404 vegetables, and were detected in 31 (7.7%) and 5 (1.2%) samples, respectively. In addition, was isolated from all 6 kinds of vegetables, whereas was detected in 4 kinds of vegetables (except perilla leaves and chives). (17.8%) and (2.9%) had the highest detection rates in chives and winter-grown cabbages, respectively. was detected all year long; however, was detected only from October to January. In 2 samples (sprout and blueberry), both and were detected. Further investigations using I restriction enzyme fragmentation and nested PCR confirmed and , respectively. In conclusion, we detected in vegetables for the first time in Korea. This suggests that screening should be employed to prevent these protozoal infections in Korea.
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http://dx.doi.org/10.3347/kjp.2017.55.2.137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450956PMC
April 2017

Rosiglitazone enhances radiosensitivity by inhibiting repair of DNA damage in cervical cancer cells.

Radiat Environ Biophys 2017 03 9;56(1):89-98. Epub 2017 Feb 9.

Department of Radiation Oncology, Chungbuk National University College of Medicine, 52 Chungdae-ro 1, Seowon-gu, Cheongju, 28644, Republic of Korea.

Radiation therapy (RT) is one of the main treatment modalities for cervical cancer. Rosiglitazone (ROSI) has been reported to have antiproliferative effects against various types of cancer cells and also to induce antioxidant enzymes that can scavenge reactive oxygen species (ROS) and thereby modify radiosensitivity. Here, we explored the effect of ROSI on radiosensitivity and the underlying mechanisms in cervical cancer cells. Three cervical cancer cell lines (ME-180, HeLa, and SiHa) were used. The cells were pretreated with ROSI and then irradiated. Expression of proteins of interest was detected by western blot and immunofluorescence. Intracellular production of ROS was measured by HDCFDA. Radiosensitivity was assessed by monitoring clonogenic survival. Expression of antioxidant enzymes (catalase, superoxide dismutases) was increased by ROSI in HeLa and SiHa cells, but not in ME-180 cells. With ROSI pre-treatment, cell survival after irradiation remained unchanged in HeLa and SiHa cells, but decreased in ME-180 cells. Radiation-induced expression of γ-H2AX was increased and that of RAD51 was decreased by ROSI pre-treatment in ME-180 cells, but not in HeLa cells. ROSI increases radiosensitivity by inhibiting RAD51-mediated repair of DNA damage in some cervical cancer cell lines; therefore, ROSI is a potential inhibitor of RAD51 that can be used to enhance the effect of RT in the treatment of some cervical cancers.
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http://dx.doi.org/10.1007/s00411-016-0679-9DOI Listing
March 2017

Corrigendum to "T0070907 inhibits repair of radiation-induced DNA damage by targeting RAD51" [Toxicol. Vitro 37C (2016) 1-8].

Toxicol In Vitro 2017 04 15;40:347. Epub 2016 Dec 15.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.tiv.2016.11.013DOI Listing
April 2017

T0070907 inhibits repair of radiation-induced DNA damage by targeting RAD51.

Toxicol In Vitro 2016 Dec 18;37:1-8. Epub 2016 Aug 18.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju 28644, Republic of Korea. Electronic address:

T0070907 (T007), a PPARγ inhibitor, can reduce α and β tubulin proteins in some cancer cell lines. Thus, T007 has been suggested as an antimicrotubule drug. We previously reported that T007 increased radiosensitivity by inducing mitotic catastrophe in cervical cancer cells. In this study, we investigated the underlying mechanisms of the T007-mediated increase in radiosensitivity. T007 pre-treatment attenuated RAD51 protein levels and ionising radiation (IR)-induced nuclear foci formation, resulting in more frequent centrosome amplification and multipolar mitotic spindle formation in cervical cancer cells. Furthermore, T007 pre-treatment delayed the clearance of IR-induced γ-H2AX and increased radiosensitivity in cervical cancer cells. In contrast, none of these changes were observed in normal cells. Our data demonstrate for the first time that T007 impairs the repair of IR-induced DNA double-strand breaks by inhibiting RAD51, a key protein in homologous recombination repair, increases IR-induced mitotic catastrophe, and leads to increased death of IR-treated cells. These findings support T007 as a potential RAD51 inhibitor to increase tumour response to radiation therapy.
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http://dx.doi.org/10.1016/j.tiv.2016.08.009DOI Listing
December 2016

Silencing of fused toes homolog enhances cisplatin sensitivity in cervical cancer cells by inhibiting epidermal growth factor receptor-mediated repair of DNA damage.

Cancer Chemother Pharmacol 2016 10 17;78(4):753-62. Epub 2016 Aug 17.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Chungdae-ro 1, Seowon-gu, Cheongju, Chungbuk, 28644, Republic of Korea.

Purpose: Overexpression of epidermal growth factor receptor (EGFR) is related to chemo-/radioresistance and poor prognosis in many cancers. EGFR is activated by cisplatin, and this may lead to resistance to this drug. Fused toes homolog (FTS) is an E2 variant that lacks the active cysteine residue required for ubiquitin transfer. Previously, we reported that FTS interacts with EGFR and activates DNA-dependent protein kinase (DNA-PK) upon irradiation. Here, we investigated the role of FTS in cisplatin sensitivity in ME180 cervical cancer cells.

Methods: Protein expression was assessed using western blot analyses in four cervical cell lines (ME180, CaSki, HeLa, and SiHa). FTS was silenced using a siRNA-based approach. Interactions between proteins were assessed by immunoprecipitation. Immunofluorescence was used to visualize DNA double-strand breaks and the expression of phospho-DNA-PK.

Results: Among the lines tested, ME180 cells showed the highest basal expression of EGFR and increased nuclear phosphorylated EGFR in response to cisplatin. In ME180 cells, the activation of EGFR and DNA-PK by cisplatin was attenuated by silencing FTS. FTS-silencing augmented cisplatin-induced cell death and cisplatin-induced DNA damage assessed by γH2AX. Immunoprecipitation showed binding of FTS with EGFR and DNA-PK.

Conclusion: FTS is involved in EGFR-mediated repair of DNA damage induced by cisplatin in ME180 cells. This suggests that FTS can be a target to increase the efficacy of cisplatin in cervical cancer cells that exhibit increased nuclear phosphorylated EGFR in response to cisplatin.
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http://dx.doi.org/10.1007/s00280-016-3110-yDOI Listing
October 2016

Spatiotemporal Expression Patterns and Antibody Reactivity of Taeniidae Endophilin B1.

J Clin Microbiol 2016 10 3;54(10):2553-62. Epub 2016 Aug 3.

Department of Molecular Parasitology, Sungkyunkwan University School of Medicine, Suwon, South Korea

Larval Taeniidae, such as metacestodes of Taenia solium, Echinococcus granulosus, and Echinococcus multilocularis, produce chronic and fatal helminthic diseases. Proper identification of these zoonotic cestodiases is often challenging and is hampered in some clinical settings. Endophilin B1 plays critical roles in the maintenance of membrane contours and endocytosis. We isolated proteins homologous to endophilin B1 from T. solium, Taenia saginata, and Taenia asiatica The three Taeniidae endophilin B1 proteins shared 92.9 to 96.6% sequence identity. They harbored a Bin1/amphiphysin/Rvs (BAR) domain and residues for a dimeric interface but lacked a SRC homology 3 (SH3) domain. Endophilin B1 showed a unique immunological profile and was abundantly expressed in the tegumental syncytium of Taeniidae metacestodes and adults. Bacterially expressed recombinant T. solium endophilin B1 (rTsMEndoB1) demonstrated a sensitivity of 79.7% (345/433 cases) for serodiagnosis of larval Taeniidae infections. The protein showed strong immune recognition patterns against sera from patients with chronic neurocysticercosis, cystic echinococcosis, or advanced-stage alveolar echinococcosis. Adult Taeniidae infections exhibited moderate degrees of positive antibody responses (65.7% [23/35 samples]). rTsMEndoB1 showed some cross-reactivity with sera from patients infected with Diphyllobothriidae (23.6% [25/106 samples]) but not with sera from patients with other parasitic diseases or normal controls. The specificity was 91.7% (256/301 samples). The positive and negative predictive values were 93.6% and 73.4%, respectively. Our results demonstrate that Taeniidae endophilin B1 may be involved in the control of membrane dynamics, thus contributing to shaping and maintaining the tegumental curvature. rTsMEndoB1 may be useful for large-scale screening, as well as for individual diagnosis and follow-up surveillance of Taeniidae infections.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035399PMC
http://dx.doi.org/10.1128/JCM.01135-16DOI Listing
October 2016

Expression of Cryptosporidium parvum thioredoxin peroxidase in COS-7 cells confers radioprotection.

Exp Parasitol 2016 Apr 26;163:8-15. Epub 2016 Jan 26.

Department of Environmental and Tropical Medicine & Research Institute of Medical Science, Konkuk University, School of Medicine, Seoul 143-701, South Korea. Electronic address:

Cryptosporidium parvum is one of the most radioresistant organisms identified to date. In a previous study, we found that thioredoxin peroxidase (CpTPx) was significantly upregulated in this species following exposure to high dose (10 kGy) of γ-irradiation. To assess the potential of CpTPx to confer radioprotection in mammalian cells, it was expressed in COS-7 African green monkey kidney cells (CpTPx-COS7). For comparison, the thioredoxin peroxidase of Cryptosporidium muris (CmTPx) was also expressed in these cells (CmTPx-COS7 cells), which has been confirmed to have lesser antioxidant activity than CpTPx in the previous study. Notably, the survival rates of CpTPx-COS7 cells were significantly higher (12-22%) at 72 h after 8 Gy irradiation than CmTPx-COS7 or non-transfected COS-7 (ntCOS-7) counterparts. In addition, CpTPx revealed a 50% of ROS reduction in irradiated CpTPx-COS7 cells, while γ-H2AX DNA damage marker expression was not significantly changed. Furthermore, the amount of apoptosis only increased to about 120% after 2-8 Gy irradiation compared to 200-300% increase observed in ntCOS-7 cells. CmTPx was shown to have antioxidant and DNA damage protection activities; however, these activities were always lower than those of CpTPx. These results suggest that the potent antioxidant and protective activities of CpTPx are well conserved in this cell-based system and that CpTPx contributed to the radioprotection of mammalian cells through its exceptional antioxidant activity.
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http://dx.doi.org/10.1016/j.exppara.2016.01.012DOI Listing
April 2016

Prevalence of Cryptosporidium Infection among Inhabitants of 2 Rural Areas in White Nile State, Sudan.

Korean J Parasitol 2015 Dec 31;53(6):745-7. Epub 2015 Dec 31.

Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.

Cryptosporidium , a protozoan parasite that causes watery diarrhea, is found worldwide and is common in areas with low water hygiene. In February 2014, 866 stool samples were collected from the inhabitants of 2 rural areas in White Nile State, Sudan. These stool samples were assessed by performing modified acid-fast staining, followed by examination under a light microscope. The overall positive rate of Cryptosporidium oocysts was 13.3%. Cryptosporidium oocysts were detected in 8.6% stool samples obtained from inhabitants living in the area having water purification systems and in 14.6% stool samples obtained from inhabitants living in the area not having water purification systems. No significant difference was observed in the prevalence of Cryptosporidium infection between men and women (14.7% and 14.1%, respectively). The positive rate of oocysts by age was the highest among inhabitants in their 60s (40.0%). These findings suggest that the use of water purification systems is important for preventing Cryptosporidium infection among inhabitants of these rural areas in Sudan.
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http://dx.doi.org/10.3347/kjp.2015.53.6.745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725242PMC
December 2015

Cordycepin increases radiosensitivity in cervical cancer cells by overriding or prolonging radiation-induced G2/M arrest.

Eur J Pharmacol 2016 Jan 10;771:77-83. Epub 2015 Dec 10.

Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address:

Cordycepin (3-deoxyadenosine) has many pharmacological activities. We studied the radiosensitising effect of cordycepin and the underlying mechanisms relating to cell cycle changes in two human uterine cervical cancer cell lines, ME180 and HeLa cells. Cordycepin produced concentration- and time-dependent reductions in cell viability with more pronounced effects in ME180 cells. Cells pre-treated with cordycepin showed lower cell survival than those exposed to irradiation only. Radiation-induced expression of the histone, γ-H2AX, and apoptosis were also increased following cordycepin pre-treatment. In ME180 cells, pre-treatment with cordycepin reduced radiation-induced G2/M arrest and this G2/M checkpoint override was sustained for longer than in HeLa cells, where G2/M arrest was observed earlier and more briefly, the number of HeLa cells in the G2/M phase was subsequently increased. Cordycepin produced different effects on the expression of p53 and cell cycle checkpoint proteins in these two cell lines. It can be assumed that the mechanism underlying cordycepin-mediated radiosensitisation involves multiple effects that are primarily based on the induction of p53-mediated apoptosis and modulation of the expression of cell cycle checkpoint molecules.
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http://dx.doi.org/10.1016/j.ejphar.2015.12.022DOI Listing
January 2016

Who Neglects Neglected Tropical Diseases? - Korean Perspective.

J Korean Med Sci 2015 Nov 6;30 Suppl 2:S122-30. Epub 2015 Nov 6.

Department of Parasitology and Tropical Medicine, Seoul National University College of Medicine, and Institute of Endemic Diseases, Seoul National University Medical Research Center, Seoul, Korea.

Neglected tropical diseases (NTDs) are a group of tropical infectious diseases of poorest people. Of 17 NTDs managed by WHO, two, guinea worm disease (by 2015) and yaws (by 2020) are targeted for eradication, and four (blinding trachoma, human African trypanosomiasis, leprosy, and lymphatic filariasis) for elimination by 2020. The goals look promising but 11 others are still highly prevalent. Soil-transmitted helminths (STHs) are one NTD which prevail over the world including temperate zones. They had been highly prevalent in Korea but are mostly disappearing at present through systematic and sustainable control activity. The successful experience of STH control enables Korean experts to develop many programs of NTD control in developing countries. Several programs of both official development aid and non-governmental organizations are now targeting NTDs. Most NTDs are low in health priority compared to their health threats because they are chronic, insidious, and of low mortality. No one, including the victims, raised priority of NTD control with a loud voice in the endemic field of the diseases. After the millennium development goals declared disease control over the world, NTDs are becoming less neglected globally. Even with limited resources, beginning a sustainable national program is the key for the control and elimination of NTDs. No more neglect, especially no more self-neglect, can eliminate diseases and upgrade quality of life of the neglected people.
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http://dx.doi.org/10.3346/jkms.2015.30.S2.S122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4659863PMC
November 2015

Detection of Encephalitozoon spp. from human diarrheal stool and farm soil samples in Korea.

J Korean Med Sci 2015 Mar 16;30(3):227-32. Epub 2015 Feb 16.

Department of Environmental and Tropical Medicine & Research Institute of Medical Sciences, Konkuk University, School of Medicine, Seoul, Korea.

Microsporidia are eukaryotic organisms that cause zoonosis and are major opportunistic pathogens in HIV-positive patients. However, there is increasing evidence that these organisms can also cause gastrointestinal and ocular infections in immunocompetent individuals. In Korea, there have been no reports on human infections with microsporidia to date. In the present study, we used real-time PCR and nucleotide sequencing to detect Encephalitozoon intestinalis infection in seven of 139 human diarrheal stool specimens (5%) and Encephalitozoon hellem in three of 34 farm soil samples (8.8%). Genotype analysis of the E. hellem isolates based on the internal transcribed spacer 1 and polar tube protein genes showed that all isolates were genotype 1B. To our knowledge, this is the first report on human E. intestinalis infection in Korea and the first report revealing farm soil samples as a source of E. hellem infection. Because microsporidia are an important public health issue, further large-scale epidemiological studies are warranted.
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http://dx.doi.org/10.3346/jkms.2015.30.3.227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330474PMC
March 2015

Detection of Cryptosporidium parvum in environmental soil and vegetables.

J Korean Med Sci 2014 Oct 8;29(10):1367-71. Epub 2014 Oct 8.

Department of Environmental and Tropical Medicine & Research Institute of Medical Science, Konkuk University School of Medicine, Seoul, Korea.

Cryptosporidium parvum is a zoonotic protozoan parasite that causes cryptosporidial enteritis. Numerous outbreaks of cryptosporidiosis have been reported worldwide. Cryptosporidium is transmitted to hosts via consumption of contaminated water and food but also by direct contact with contaminated soil or infected hosts. The present study investigated farm soil collected from 34 locations along the western Korean peninsula and 24 vegetables purchased from local grocery markets in Seoul. The soil and vegetable samples were examined by real-time polymerase chain reaction (qPCR) to estimate the risk of infection. Eleven of 34 locations (32.4%) and 3 of 24 vegetable samples (12.5%) were contaminated with Cryptosporidium parvum, as confirmed by TaqI enzyme digestion of qPCR products and DNA sequencing. It is suggested that Cryptosporidium infection can be mediated via farm soil and vegetables. Therefore, it is necessary to reduce contamination of this organism in view of public health.
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http://dx.doi.org/10.3346/jkms.2014.29.10.1367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214936PMC
October 2014

FTS is responsible for radiation-induced nuclear phosphorylation of EGFR and repair of DNA damage in cervical cancer cells.

J Cancer Res Clin Oncol 2015 Feb 24;141(2):203-10. Epub 2014 Aug 24.

Department of Radiation Oncology, Chungbuk National University College of Medicine, 52 Naesudong-ro, Heungduk-gu, Cheongju, 361-763, Republic of Korea.

Purpose: Radiation-induced nuclear stabilization and phosphorylation of epidermal growth factor receptor (EGFR) confers radioresistance. Understanding of the factor(s) regulating the nuclear stabilization and phosphorylation of EGFR is important for the modulation of radioresistance. Present study was designed to delineate the regulation of EGFR nuclear stabilization and phosphorylation by fused toes homolog (FTS), an oncoprotein, which is responsible for the radioresistance in cervical cancer cells.

Methods: A cervical cancer cell line, ME180 was used. Radiation-induced change in the levels of EGFR, p-EGFR and FTS were evaluated in the cytoplasm and nucleus using Western blot analyses. FTS was silenced using siRNA-based approach. Interaction between EGFR and FTS was assessed using immunofluorescence and immunoprecipitation analyses. Double-strand breaks (DSB) of DNA were assessed using γ H2AX.

Results: Radiation increased the levels of EGFR and FTS in the cytoplasm and nucleus. EGFR and FTS are in physical association with each other and are co-localized in the cells. FTS silencing largely reduced the nuclear stabilization and phosphorylation of EGFR and DNA-protein kinase along with increased initial and residual DSBs.

Conclusion: EGFR and FTS physically associate with each other and FTS silencing radiosensitizes ME180 cells through impaired nuclear EGFR signaling.
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http://dx.doi.org/10.1007/s00432-014-1802-4DOI Listing
February 2015

EGF-induced expression of Fused Toes Homolog (FTS) facilitates epithelial-mesenchymal transition and promotes cell migration in ME180 cervical cancer cells.

Cancer Lett 2014 Sep 24;351(2):252-9. Epub 2014 Jun 24.

Department of Radiation Oncology, Chungbuk National University, College of Medicine, Cheongju 361-763, Republic of Korea. Electronic address:

The role of Fused Toes Homolog (FTS) in epidermal growth factor (EGF) induced epithelial-mesenchymal transition (EMT) in cervical cancer cells was studied. EGF treatment induced the change of EMT markers and increased cell migration. EGF treatment also increased phosphorylated EGFR and ERK and nuclear level of ATF-2. The binding of ATF-2 to the promoter region of FTS was evidenced after EGF treatment. Pretreatment with PD98059 and gefitinib prevented EGF-induced FTS expression. FTS silencing reduced EMT and cell migration by EGF treatment. These results demonstrate a novel function for FTS in EGF-mediated EMT process.
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http://dx.doi.org/10.1016/j.canlet.2014.06.007DOI Listing
September 2014

T0070907, a PPAR γ inhibitor, induced G2/M arrest enhances the effect of radiation in human cervical cancer cells through mitotic catastrophe.

Reprod Sci 2014 Nov 18;21(11):1352-61. Epub 2014 Mar 18.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea

Overexpression of peroxisome proliferator activator receptor γ (PPARγ) has been implicated in many types of cancer including cervical cancer. Radiation therapy remains the main nonsurgical modality for the treatment of cervical cancer. The present study reports the impact of pharmacological inhibition of PPARγ in enhancing the radiosensitization of cervical cancer cells in vitro. Three cervical cancer cell lines (HeLa, SiHa, and Me180) were treated with a PPARγ inhibitor, T0070907, and/or radiation. The changes in protein, cell cycle, DNA content, apoptosis, and cell survival were analyzed. The PPARγ is differentially expressed in cervical cancer cells with maximum expression in ME180 cells. T0070907 has significantly decreased the tubulin levels in a time-dependent manner in ME180 cells. The decrease in the tubulin levels after T0070907 in ME180 and SiHa cells was associated with significant increase in the cells at the G2/M phase. The changes in the tubulin and G2/M phase were not evident in HeLa cells. T0070907 reduced the protein levels of PPARγ; however, PPARγ silencing had no effect on the α-tubulin level in ME180 cells suggesting the PPARγ-dependent and -independent actions of T0070907. To ascertain the impact of synergistic effect of T0070907 and radiation, HeLa and ME180 cells were pretreated with T0070907 and subjected to radiation (4 Gy). Annexin V-fluorescein isothiocyanate analysis revealed increased apoptosis in cells treated with radiation and T0070907 when compared to control and individual treatment. In addition, T0070907 pretreatment enhanced radiation-induced tetraploidization reinforcing the additive effect of T0070907. Confocal analysis of tubulin confirmed the onset of mitotic catastrophe in cells treated with T0070907 and radiation. These results strongly suggest the radiosensitizing effects of T0070907 through G2/M arrest and mitotic catastrophe.
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http://dx.doi.org/10.1177/1933719114525265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4212328PMC
November 2014

EGCG suppresses Fused Toes Homolog protein through p53 in cervical cancer cells.

Mol Biol Rep 2013 Oct 25;40(10):5587-96. Epub 2013 Sep 25.

Department of Radiation Oncology, College of Medicine, Chungbuk National University, Cheongju, 361-763, South Korea.

The anticarcinogenic actions of epigallocatechin-3-gallate (EGCG), one of the main ingredients of green tea, against various cancer types including cervical cancer are well documented. Studies pertaining to the exact molecular mechanism by which EGCG induces cancer cell growth inhibition needs to be investigated extensively. In the present study, we observed a stupendous dose dependent reduction in the protein expression of Fused Toes Homolog (FTS) after treatment with EGCG at 1, 10, 25 and 50 μM. Further, we were interested in finding out whether the decrease in the protein expression of FTS was due to decreased mRNA synthesis. Real time reverse transcriptase polymerase chain reaction results revealed a similar dose dependent reduction in the FTS mRNA after EGCG treatment. Chromatin immunoprecipitation analysis revealed the interaction between p53 and the promoter region of FTS. A dose dependent increase in this interaction was evidenced at 25 and 50 μM EGCG treatment. p53 silencing increased the expression of FTS and also decreased the reduction in the levels of FTS expression after EGCG treatment. The decrease in the levels of FTS was more significant at 25 and 50 μM and is associated with reduced physical interaction of FTS with Akt, phosphorylation of Akt and survival of HeLa cells. Collectively, these results conclude that EGCG induced anti-proliferative action in the cervical cancer cell involves reduced mRNA expression of FTS through p53.
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http://dx.doi.org/10.1007/s11033-013-2660-xDOI Listing
October 2013

Cryptosporidium hominis infection diagnosed by real-time PCR-RFLP.

Korean J Parasitol 2013 Jun 30;51(3):353-5. Epub 2013 Jun 30.

Department of Malaria and Parasitic Diseases, National Institute of Health, Chungcheongbuk-do 363-951, Korea.

There are approximately 20 known species of the genus Cryptosporidium, and among these, 8 infect immunocompetent or immunocompromised humans. C. hominis and C. parvum most commonly infect humans. Differentiating between them is important for evaluating potential sources of infection. We report here the development of a simple and accurate real-time PCR-based restriction fragment length polymorphism (RFLP) method to distinguish between C. parvum and C. hominis. Using the CP2 gene as the target, we found that both Cryptosporidium species yielded 224 bp products. In the subsequent RFLP method using TaqI, 2 bands (99 and 125 bp) specific to C. hominis were detected. Using this method, we detected C. hominis infection in 1 of 21 patients with diarrhea, suggesting that this method could facilitate the detection of C. hominis infections.
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http://dx.doi.org/10.3347/kjp.2013.51.3.353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3712111PMC
June 2013

Monthly occurrence of vectors and reservoir rodents of scrub typhus in an endemic area of Jeollanam-do, Korea.

Korean J Parasitol 2012 Dec 26;50(4):327-31. Epub 2012 Nov 26.

Department of Microbiology, Konkuk University School of Medicine, Chungju 380-701, Korea.

Monthly surveys were conducted to investigate the occurrence of chigger mites and seroprevalence of scrub typhus among small mammals in Jeollanam-do, the southwestern part of Korea, from November 2006 through October 2007. Fifty-eight small mammals, including 57 Apodemus agrarius (98.3%) and 1 Crocidura lasiura (1.7%), were captured, and a total of 4,675 chigger mites representing 4 genera and 8 species were collected from them. The chigger infestation rate among small mammals was 69.0%. The most predominant species in A. agrarius was Leptotrombidium scutellare (54.0%), followed by Leptotrombidium pallidum (39.4%), Leptotrombidium orientale (4.4%), Leptotrombidium palpale (1.1%), Neotrombicula tamiyai (0.6%), Eushoengastia koreaensis (0.3%), Neotrombicula gardellai (0.3%), and Cheladonta ikaoensis (<0.1%). The chigger index of A. agrarius was the highest in October (740.0), followed by November (242.0), September (134.6), March (98.3), February (38.2), January (35.3), December (34.5), April (30.8), and May (1.7). The average antibody positive rate of scrub typhus in wild rodents was 50.0%. The seropositive rates were high in October (100.0%) and November (83.3%), whereas those in other months were relatively low (28.6-57.1%). The chigger index of L. scutellare rapidly increased in September to form an acuminate peak in October, followed by a gradual decline. These results suggest that the outbreak of scrub typhus in the southwestern part of Korean peninsula is mostly due to L. scutellare.
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http://dx.doi.org/10.3347/kjp.2012.50.4.327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514424PMC
December 2012

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells.

Radiat Oncol J 2012 Jun 30;30(2):88-95. Epub 2012 Jun 30.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.

Purpose: The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) α and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF).

Materials And Methods: Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay.

Results: In HeLa cells total SOD activity was increased with increasing FF doses up to 30 µM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARα and PPARγ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARα were not increased with FF. However, the mRNA of PPARγ was increased with FF.

Conclusion: FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARα.
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http://dx.doi.org/10.3857/roj.2012.30.2.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429893PMC
June 2012

Effect of troglitazone on radiation sensitivity in cervix cancer cells.

Radiat Oncol J 2012 Jun 30;30(2):78-87. Epub 2012 Jun 30.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Korea.

Purpose: Troglitazone (TRO) is a peroxisome proliferator-activated receptor γ (PPARγ) agonist. TRO has antiproliferative activity on many kinds of cancer cells via G1 arrest. TRO also increases Cu(2+)/Zn(2+)-superoxide dismutase (CuZnSOD) and catalase. Cell cycle, and SOD and catalase may affect on radiation sensitivity. We investigated the effect of TRO on radiation sensitivity in cancer cells in vitro.

Materials And Methods: Three human cervix cancer cell lines (HeLa, Me180, and SiHa) were used. The protein expressions of SOD and catalase, and catalase activities were measured at 2-10 µM of TRO for 24 hours. Cell cycle was evaluated with flow cytometry. Reactive oxygen species (ROS) was measured using 2',7'-dichlorofluorescin diacetate. Cell survival by radiation was measured with clonogenic assay.

Results: By 5 µM TRO for 24 hours, the mRNA, protein expression and activity of catalase were increased in all three cell lines. G0-G1 phase cells were increased in HeLa and Me180 by 5 µM TRO for 24 hours, but those were not increased in SiHa. By pretreatment with 5 µM TRO radiation sensitivity was increased in HeLa and Me180, but it was decreased in SiHa. In Me180, with 2 µM TRO which increased catalase but not increased G0-G1 cells, radiosensitization was not observed. ROS produced by radiation was decreased with TRO.

Conclusion: TRO increases radiation sensitivity through G0-G1 arrest or decreases radiation sensitivity through catalase-mediated ROS scavenging according to TRO dose or cell types. The change of radiation sensitivity by combined with TRO is not dependent on the PPARγ expression level.
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http://dx.doi.org/10.3857/roj.2012.30.2.78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429892PMC
June 2012

Recombinant thioredoxin peroxidase from Cryptosporidium parvum has more powerful antioxidant activity than that from Cryptosporidium muris.

Exp Parasitol 2012 Jul 9;131(3):333-8. Epub 2012 May 9.

Department of Environmental and Tropical Medicine, Konkuk University, School of Medicine, Seoul, Republic of Korea.

Cryptosporidium parvum can survive exposure to harsh environmental conditions, various disinfectants, and high doses of γ-irradiation. In an animal study, more than 25kGy of γ-irradiation was necessary to eliminate C. parvum infectivity from mice. In contrast, Cryptosporidium muris (murine Cryptosporidium), which lives in stomach epithelium, lost its infectivity in mice with 1kGy of γ-irradiation. Recently, it was found that thioredoxin peroxidase was highly expressed in C. parvum oocysts irradiated with high doses of γ-irradiation. Therefore we hypothesize that antioxidant activity of the thioredoxin peroxidase is involved in the radioresistance of C. parvum. To verify this, thioredoxin peroxidases of C. parvum (CpTPx) and C. muris (CmTPx) were expressed in Escherichia coli cells, and their antioxidant activities were compared. Both CpTPx and CmTPx belong to the 2-Cys family of peroxiredoxins. Hydrogen peroxide consumption was approximately 2- to 12-fold greater in recombinant CpTPx (rCpTPx) than in recombinant CmTPx (rCmTPx) in the presence of 0.2mM dithioerythritol or glutathione (GSH), respectively. The peroxidase activity of rCpTPx was highly enhanced by GSH, but that of rCmTPx was not. The minimum dose of rCpTPx required to protect supercoiled plasmid DNA from damage by metal-catalyzed oxidation was only 12% of that required with rCmTPx. The results showed that rCpTPx has more powerful antioxidant activity than rCmTPx. Further investigations on the role of CpTPx in the radioresistance of C. parvum are warranted.
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http://dx.doi.org/10.1016/j.exppara.2012.04.018DOI Listing
July 2012

Comparison of resistance to γ-irradiation between Cryptosporidium parvum and Cryptosporidium muris using in vivo infection.

Korean J Parasitol 2011 Dec 16;49(4):423-6. Epub 2011 Dec 16.

Department of Environmental and Tropical Medicine, Konkuk University, School of Medicine, Seoul 143-701, Korea.

In the genus Cryptosporidium, there are more than 14 species with different sizes and habitats, as well as different hosts. Among these, C. parvum and C. hominis are known to be human pathogens. As C. parvum can survive exposure to harsh environmental conditions, including various disinfectants or high doses of radiation, it is considered to be an important environmental pathogen that may be a threat to human health. However, the resistance of other Cryptosporidium species to various environmental conditions is unknown. In this study, resistance against γ-irradiation was compared between C. parvum and C. muris using in vivo infection in mice. The capability of C. muris to infect mice could be eliminated with 1,000 Gy of γ-irradiation, while C. parvum remained infective in mice after up to 1,000 Gy of γ-irradiation, although the peak number of oocysts per gram of feces decreased to 16% that of non-irradiated oocysts. The difference in radioresistance between these 2 Cryptosporidium species should be investigated by further studies.
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http://dx.doi.org/10.3347/kjp.2011.49.4.423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3279683PMC
December 2011

PCR diagnosis of Entamoeba histolytica cysts in stool samples.

Korean J Parasitol 2011 Sep 30;49(3):281-4. Epub 2011 Sep 30.

Division of Malaria and Parasitic Diseases, Korea National Institute of Health, Osong 363-951, Korea.

Amebiasis is a protozoan disease caused by Entamoeba histolytica and a potential health threat in areas where sanitation and hygiene are inappropriate. Highly sensitive PCR methods for detection of E. histolytica in clinical and environmental samples are extremely useful to control amebiasis and to promote public health. The present study compared several primer sets for small subunit (SSU) rDNA and histone genes of E. histolytica cysts. A 246 bp of the SSU rDNA gene of pure cysts contained in phosphate-buffered saline (PBS) and in stool samples was successfully amplified by nested PCR, using the 1,147-246 bp primer set, of the primary PCR products which were pre-amplified using the 1,147 bp primer as the template. The detection limit of the nested PCR using the 1,147-246 primer set was 10 cysts in both groups (PBS and stool samples). The PCR to detect histone gene showed negative results. We propose that the nested PCR technique to detect SSU rDNA can be used as a highly sensitive genetic method to detect E. histolytica cysts in stool samples.
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http://dx.doi.org/10.3347/kjp.2011.49.3.281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3210846PMC
September 2011

Characterization of the thioredoxin peroxidase from Cryptosporidium parvum.

Exp Parasitol 2011 Dec 5;129(4):331-6. Epub 2011 Oct 5.

Department of Environmental and Tropical Medicine, Konkuk University, School of Medicine, Seoul 143-701, Republic of Korea.

Cryptosporidium parvum can survive exposure to harsh environmental conditions, various disinfectants, and high doses of γ-radiation. Recently, it was found that the expression of thioredoxin peroxidase (CpTPx) in C. parvum increased after a high dose of γ-irradiation to the parasite. CpTPx is a two-cysteine peroxiredoxin that contains cysteines at positions 49 and 170. Recombinant CpTPx fused to an N-terminal hexahistidine sequence, (His)(6)-CpTPx, exhibited substantial thiol-dependent peroxidase activity that protected plasmid DNA from damage by metal-catalyzed oxidation in vitro. (His)(6)-CpTPx was used to screen sera from C. parvum-infected mice and humans for antibodies against CpTPx. In Western blots, 10% of the mouse sera and 20% of the human sera reacted with (His)(6)-CpTPx, suggesting that after infection by C. parvum CpTPx can induce a host-immune reaction but is not a major antigen. Immunolocalization studies revealed that CpTPx is expressed mainly in the cytoplasm of C. parvum at various developmental stages.
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http://dx.doi.org/10.1016/j.exppara.2011.09.011DOI Listing
December 2011

Phosphorylation of threonine 190 is essential for nuclear localization and endocytosis of the FTS (Fused Toes Homolog) protein.

Int J Biol Macromol 2011 Nov 12;49(4):721-8. Epub 2011 Jul 12.

Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.

Fused Toes Homolog (FTS) is a member of a group of proteins termed as E2 variants and this group of proteins lacks an active cysteine residue that is required for ubiquitin transfer. We have identified the expression of this protein in early neoplastic stages of cervical cancer and its translocation into nucleus from cytoplasm upon irradiation. Here we have reported that a threonine residue at position 190 is essential for its nucleocytoplasmic shuttling and function. Upon LMB treatment we found that FTS was located in the nucleus and it suggests that direct role of nuclear export signal (NES) is required for the binding to CRM1 and facilitates nuclear export. The threonine residue was phosphorylated and promoted the phosphorylation of EGFR, p38 and JNK facilitating vesicular trafficking of early to late endosomes. Mutational change of the threonine into alanine resulted in the cytoplasmic localization of FTS and failed to phosphorylate EGFR and its downstream effector proteins. In addition the mutation also reduced the number of early endosomes formed and also resulted in the clustering of late endosomes around the perinuclear region. These data suggest that threonine residue of FTS at position 190 is not only essential for its function but also for the formation, maturation and trafficking of early endosomes to late endosome/lysosome, as well as we speculate that FTS may function at a connection point in the vesicle tethering.
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http://dx.doi.org/10.1016/j.ijbiomac.2011.07.005DOI Listing
November 2011

5-Methoxyflavanone induces cell cycle arrest at the G2/M phase, apoptosis and autophagy in HCT116 human colon cancer cells.

Toxicol Appl Pharmacol 2011 Aug 15;254(3):288-98. Epub 2011 May 15.

SMART Institute of Advanced Biomedical Science, Konkuk University Medical Center, Seoul 143-701, Republic of Korea.

Natural flavonoids have diverse pharmacological activities, including anti-oxidative, anti-inflammatory, and anti-cancer activities. In this study, we investigated the molecular mechanism underlying the action of 5-methoxyflavanone (5-MF) which has a strong bioavailability and metabolic stability. Our results show that 5-MF inhibited the growth and clonogenicity of HCT116 human colon cancer cells, and that it activated DNA damage responses, as revealed by the accumulation of p53 and the phosphorylation of DNA damage-sensitive proteins, including ataxia-telangiectasia mutated (ATM) at Ser1981, checkpoint kinase 2 (Chk2) at Thr68, and histone H2AX at Ser139. 5-MF-induced DNA damage was confirmed in a comet tail assay. We also found that 5-MF increased the cleavage of caspase-2 and -7, leading to the induction of apoptosis. Pretreatment with the ATM inhibitor KU55933 enhanced 5-MF-induced γ-H2AX formation and caspase-7 cleavage. HCT116 cells lacking p53 (p53(-/-)) or p21 (p21(-/-)) exhibited increased sensitivity to 5-MF compared to wild-type cells. 5-MF further induced autophagy via an ERK signaling pathway. Blockage of autophagy with the MEK inhibitor U0126 potentiated 5-MF-induced γ-H2AX formation and caspase-2 activation. These results suggest that a caspase-2 cascade mediates 5-MF-induced anti-tumor activity, while an ATM/Chk2/p53/p21 checkpoint pathway and ERK-mediated autophagy act as a survival program to block caspase-2-mediated apoptosis induced by 5-MF.
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http://dx.doi.org/10.1016/j.taap.2011.05.003DOI Listing
August 2011

DHS-21, a dicarbonyl/L-xylulose reductase (DCXR) ortholog, regulates longevity and reproduction in Caenorhabditis elegans.

FEBS Lett 2011 May 6;585(9):1310-6. Epub 2011 Apr 6.

Department of Life Science, Hanyang University, Seoul, Republic of Korea.

Dicarbonyl/L-xylulose reductase (DCXR) converts l-xylulose into xylitol, and reduces various α-dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. In this study, we identified DHS-21 as the only DCXR ortholog in Caenorhabditis elegans. The dhs-21 gene is expressed in various tissues including the intestine, gonadal sheath cells, uterine seam (utse) cells, the spermathecal-uterus (sp-ut) valve and on the plasma membrane of spermatids. Recombinant DHS-21 was shown to convert L-xylulose to xylitol using NADPH as a cofactor. Dhs-21 null mutants of C. elegans show defects in longevity, reproduction and egg-laying. Knock-down of daf-16 and elt-2 transcription factors affected dhs-21 expression. These results suggest that DHS-21 is a bona fide DCXR of C. elegans, essential for normal life span and reproduction.
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http://dx.doi.org/10.1016/j.febslet.2011.03.062DOI Listing
May 2011

Risk factors associated with head louse infestation in Korea.

Korean J Parasitol 2011 Mar 18;49(1):95-8. Epub 2011 Mar 18.

Department of Environmental and Tropical Medicine, School of Medicine, Konkuk University, Chungju 380-701, Korea.

Head louse infestation (HLI) is one of the most frequently occurring parasitic diseases in children. This study was conducted to investigate the socioeconomic and personal factors influencing HLI in the Republic of Korea. A total of 2,210 questionnaires about various factors related to HLI were obtained from children in 17 primary schools throughout the country. The rate of HLI was significantly lower in children who lived together with mother or in a family where both parents worked. In addition, HLI was lower in children whose fathers or mothers were public officers or teachers. However, HLI was higher in children who had small families and washed their hair less often. Education levels of parents and the number of children in family were not significant. Improvement of socioeconomic factors and personal hygiene will be helpful for reducing HLI.
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http://dx.doi.org/10.3347/kjp.2011.49.1.95DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063935PMC
March 2011
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