Seo-Na Chang

High animal fat intake enhances prostate cancer progression and reduces glutathione peroxidase 3 expression in early stages of TRAMP mice.

Prostate cancer is the most frequently diagnosed cancer in Western men, and more men have been diagnosed at younger ages in recent years. A high‐fat Western‐style diet is a known risk factor for prostate cancer and increases oxidative stress.

The First Case of Capillaria hepatica Infection in a Nutria (Myocastor coypus) in Korea

This study reports the first case of Capillaria hepatica infection in a nutria in Korea. Ten nutrias, captured near the Nakdong River, were submitted to our laboratory for necropsy. White-yellowish nodules were found in the liver of 1 of the nutrias at necropsy. Histologically, the lesions were granulomatous, and infiltrations of lipid-laden macrophages, eosinophils, and several multinucleated giant cells were observed. The lesions consisted of numerous eggs and necrotic hepatocytes. The eggs were lemon-shaped and had polar plugs at the ends of both long sides. The eggs were morphologically identified as those of C. hepatica. Worldwide, C. hepatica infection in nutrias is very rare. Nutrias are a kind of livestock, as well as wildlife; therefore, an epidemiological study for parasitic infections needs to be conducted.

Effects of dietary high fat on prostate intraepithelial neoplasia in TRAMP mice.

Increased fat intake is known to be a major cause of prostate cancer. In this study, we investigated the effect of dietary high fat on prostate intraepithelial neoplasia using transgenic adenocarcinoma mouse prostate (TRAMP) mice. Six-week-old male TRAMP mice were fed AIN93G (control group, 4.0 kcal/kg, n=6) and AIN93G-HFD (experimental group, 4.8 kcal/kg, n=7) for 10 weeks. Prostate histopathology, urogenital tract (UGT) weight, epididymal white adipose tissue weight, argyrophilic nucleolar organizer regions (AgNORs) counts, and serum leptin levels were examined. AIN93G-HFD fed group showed progressed neoplastic lesions in the prostate (P<0.05) compared to AIN93G fed group. AIN93G-HFD intake resulted in a increase in the weight of UGT (P<0.05) and epididymal white adipose tissue. The number of Ag-NOR positive dots significantly increased in each prostate lobe and final serum leptin levels in AIN93G-HFD fed group were about twice those of AIN93G fed group (P<0.05). Dietary high fat was related to the prostate cancer progression in the early stage of TRAMP mice and increased serum leptin levels, suggesting that the regulation of dietary components could delay the progression of prostate cancer.

Adiaspiromycosis of an Apodemus agrarius captured wild rodent in Korea

Adiaspiromycosis is caused by pulmonary infection with Emmonsia. Inhalated spores of Emmonsia cause asymptomatic infection to necrogranulomatous pneumonia, depending on the burden of adiaspore and host immunity. For disease monitoring of wild rodents captured on Jeju Island in Korea, we examined the lung tissue of wild rodents histopathologically. Spores composed of thick three-layered walls were found following histopathological examination and were diagnosed as adiaspiromycosis. Adiaspiromycosis has been found in mammals in many parts of the world. To our knowledge, this is the first report of adiaspiromycosis of an Apodemus agrarius captured in Korea.

Detection and Molecular Characterization of Cryptosporidium spp. from Wild Rodents and Insectivores in South Korea

In order to examine the prevalence of Cryptosporidium infection in wild rodents and insectivores of South Korea and to assess their potential role as a source of human cryptosporidiosis, a total of 199 wild rodents and insectivore specimens were collected from 10 regions of South Korea and screened for Cryptosporidium infection over a period of 2 years (2012-2013). A nested-PCR amplification of Cryptosporidium oocyst wall protein (COWP) gene fragment revealed an overall prevalence of 34.2% (68/199). The sequence analysis of 18S rRNA gene locus of Cryptosporidium was performed from the fecal and cecum samples that tested positive by COWP amplification PCR. As a result, we identified 4 species/genotypes; chipmunk genotype I, cervine genotype I, C. muris, and a new genotype which is closely related to the bear genotype. The new genotype isolated from 12 Apodemus agrarius and 2 Apodemus chejuensis was not previously identified as known species or genotype, and therefore, it is supposed to be a novel genotype. In addition, the host spectrum of Cryptosporidium was extended to A. agrarius and Crosidura lasiura, which had not been reported before. In this study, we found that the Korean wild rodents and insectivores were infected with various Cryptosporidium spp. with large intra-genotypic variationa, indicating that they may function as potential reservoirs transmitting zoonotic Cryptosporidium to livestock and humans.

Effect of fluorescent whitening agent on the transcription of cell damage-related genes in zebrafish embryos

7‐Diethylamino‐4‐methylcoumarin (DEMC) is a fluorescent whitening agent (FWAs). There have been some studies on DEMCs protective effects against biological activity but there are few papers about the in vivo toxicity of DEMC. In this study, we used wild‐type zebrafish embryos 3 days post fertilization (dpf). Test solutions with DEMC concentrations were negative control (without vehicle), 0 (with vehicle, 0.01% v/v ethanol), 0.25, 0.5, 0.75, 1.0, 1.25, 1.5 and 2 ppm. Embryos and larvae were counted for survival rate and hatching rate. Heart rates were also counted at 2.5 and 3.0 dpf. At 3.0 dpf, quantitative RT‐PCR was performed with some samples (0, 0.25, 0.75 and 1.25 ppm) to determine the toxic effect to DEMC by detecting the expression levels of toxic‐responsive genes. We used 11 genes, which included oxidative stress‐related genes [sod(Mn), sod(Cu,Zn) and hsp70], mitochondrial metabolism‐related genes (coxI, pyc, cyt and cyclinG1) and apoptosis‐related genes (c‐jun, bcl2, bax and p53). High‐concentration DEMC‐treated groups showed significant different survival rate, hatching rate and heart rate compared with low‐concentration DEMC‐treated groups. The LC50 of this chemical, 0.959 ppm, was calculated. We also confirmed that some genes in the DEMC exposure groups showed significantly up‐regulations in expression levels compared with control groups. We concluded that the fluorescence agent, DEMC, has possible developmental toxicities and alteration effect of gene expression, which are related to oxidative stress, mitochondrial metabolism and apoptosis in zebrafish embryos. Copyright

Glutathione Peroxidase 3 Inhibits Prostate Tumorigenesis in TRAMP Mice.

Glutathione peroxidase 3 (GPx3) is involved in protecting cells from oxidative damage, and down‐regulated levels of expression have been found in prostate cancer samples. We hypothesize that loss of the GPx3 increases the rate of prostate carcinogenesis and generated GPx3‐deficient transgenic adenocarcinoma of the mouse prostate (TRAMP) mice.

Decreased expression of Toll-like receptor 4 and 5 during progression of prostate transformation in transgenic adenocarcinoma of mouse prostate mice

Chronic inflammation has been considered an important risk factor for development of prostate cancer. Toll-like receptors (TLRs) recognize microbial moieties or endogenous molecules and play an important role in the triggering and promotion of inflammation. In this study, we examined whether expression of TLR4 and TLR5 was associated with progression of prostate transformation in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The expression of TLR4 and TLR5 was evaluated by immunohistochemisty in formalin-fixed paraffin-embedded prostate tissue from wild-type (WT) and TRAMP mice. Normal prostate tissue from WT mice showed strong expression of TLR4 and TLR5. However, TLR4 expression in the prostate tissue from TRAMP mice gradually decreased as pathologic grade became more aggressive. TLR5 expression in the prostate tissue from TRAMP mice also decreased in low-grade prostate intraepithelial neoplasia (PIN), high-grade PIN and poorly differentiated adenocarcinoma. Overall, our results suggest that decreased expression of TLR4 and TLR5 may contribute to prostate tumorigenesis.

Detection of sarcocystic infection in a wild rodent (Apodemus agrarius chejuensis) captured on Jeju island

Sarcocystis spp is a causative agent of sarcocystosis. They have a characteristic life cycle infecting both prey and predator. Sarcocystis can cause myositis, atrophy of the adjacent cells and abortion in cattle. In mice, sarcocystosis causes mild cellular reactions without clinical disease. Severe haemorrhage and abortion were also reported. For monitoring the disease in wild rodents of the Korean peninsula, we captured Apodemus agrarius chejuensis on Jeju island and examined the specimen histopathologically. Intramuscular cysts were found and diagnosed as Sarcocystis. Sarcocystic infection has been reported in worldwide. There have been many reported infections in cattle and pigs in Korea. To our knowledge, this is the first report of Sarcocystis in Apodemus agrarius chejuensis captured in Korea.

Development of an alternative zebrafish model for drug-induced intestinal toxicity

An evaluation of intestinal toxicity is important because the mucosal lining of the gastrointestinal tract is the first barrier for oral xenobiotics. Until now, a rat model has been recommended as the standard intestinal toxicity model and the Caco‐2 cell line, originated from a human colon adenocarcinoma, has been used as an alternative to this model, but there are limitations regarding cost‐effectiveness and the need for mimicry of the human system. In this study, we investigated whether zebrafish could be a valid alternative to rats and Caco‐2 cells as an intestinal toxicity model. We focused on intestinal gene expression of cytochrome P450 3A65, oxidative stress, apoptosis, inflammation, and intestinal function. Reverse transcription–quantitative polymerase chain reaction analysis was conducted using three models: zebrafish, Sprague–Dawley rats and Caco‐2 cells, and the transcript levels and patterns of indicator genes were analyzed in conjunction with histopathological changes. Our results suggested that representative intestinal toxicants, indomethacin, diclofenac and methotrexate, induced significant transcript level changes in marker genes such as CYP3A, inducible nitric oxide synthase, heme oxygenase 1, superoxide dismutase 1, glutathione peroxidase 1, BCL2 associated X, B‐cell lymphoma 2, caspase 9, tumor protein p53, nuclear factor‐κB, interleukin‐1β, tumor necrosis factor‐alphaα and toll‐like receptor 2 in the zebrafish model as in the rat and Caco‐2 cells models. These results suggest that zebrafish model is sufficiently worth developing as an intestinal toxicity model that can replace or compensate the rat model or Caco‐2 cell model.