• Toxicological Research
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• 제21권4호
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• pp.339-345
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• 2005

Aflatoxins are produced by Aspergillus flavus, parasiticus that grows in improperly stored cereals. Aflatoxin $B_1\;(AFB_1)$ is a potent hepatocarcinogen in a variety of experimental animals including human beings. In spite of a high attention to the hepatocarcinogenecity of aflatoxins, the relative toxicity of other types $(AFB_2,\;AFG_1\;and\;AFG_2)$ of the toxins is not fully clarified. Sprague-Dawley male rats were orally administered with $AFB_1,\;AFB_2,\;AFG_1\;and\;AFG_2$ at the dose of 250, 1250, and $2500\;{\mu}g/kg$ body weight. Animals were then killed at 12, 24 or 48 hrs following aflatoxin adminstration. Subsequently the relative weight of liver was measured and histopathological examination on the liver was performed. Level of 8-OxodG and expression of ras gene in the liver was determined. The relative liver weights at high doses of $AFB_1\;and\;AFG_1$ was significantly low. The treatment of $AFB_1$ at the high dose of $2500\;{\mu}g/kg$ showed vacuolar degeneration and centrilobular hepatic necrosis with inflammatory cells. The pathological changes by $AFB_2\;AFG_1,\;and\;AFG_2$ were not clearly found. The formation of 8-OxodG by $AFB_1$ increased in a dose-dependent manner up to 24 hrs after a single treatment of $AFB_1$ thereafter decreased to the level of the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ showed an inconsistent pattern in the formation of 8-OxodG in the liver of rats with increasing time. The expression of ras oncogene in the liver by $AFB_1$ at the dose of $1250\;{\mu}g/kg$ was increased twice compared to the control. The treatments of $AFB_2\;AFG_1,\;and\;AFG_2$ at all doses decreased the expression of ras in the liver. These results in the present study indicate that $AFB_1$ among aflatoxins with low comparable levels is the most toxic as determined by early biomarkers such as 8-OxodG formation and ras expression. However, the levels of 8-OxodG and ras as biomarkers were not useful to predict the relative hepatocarcinogenicity of aflatoxins to $AFB_1$ in the present model. Further studies are required to look for other biomarkers to predict carcinogenic potency of aflatoxins.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2185-2193
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• 2016

Background: The pathogenesis of sporadic colorectal cancer (CRC) is influenced by the patient genetic background and environmental factors. Based on prior understanding, these are classified in two major pathways of genetic instability. Microsatellite instability (MSI) and CPG island methylator phenotype (CIMP) are categorized as features of the hypermethylated prototype, and chromosomal instability (CIN) is known to be indicative of the non-hypermethylated category. Secreted frizzled related protein 2 (SFRP2), APC1A in WNT signaling pathway and the DNA repair gene, O6-methylguanine-DNA methyltransferase (MGMT), are frequently hypermethylated in colorectal cancer. Detection of methylated DNA as a biomarker by easy and inexpensive methods might improve the quality of life of patients with CRC via early detection of cancer or a precancerous condition. Aim: To evaluate the rate of SFRP2 and MGMT hypermethylation in both polyp tissue and serum of patients in south Iran as compared with matched control normal population corresponding samples. Materials and Methods: Methylation-specific PCR was used to detect hypermethylation in DNA extracted from 48 polypoid tissue samples and 25 healthy individuals. Results: Of total polyp samples, 89.5% had at least one promoter gene hypermethylation. The most frequent methylated locus was SFRP2 followed by MGMT-B (81.2 and 66.6 percent respectively). Serologic detection of hypermethylation was 95% sensitive as compared with polyp tissue. No hypermethylation was detected in normal tissue and serum and its detection in patients with polyps, especially of serrated type, was specific. Conclusions: Serologic investigation for detection of MGMT-B, SFRP2 hypermethylation could facilitate prioritization of high risk patients for colonoscopic polyp detection and excision.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1051-1056
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• 2015

Aberrant expression of genes in de novo lipogenesis (DNL) pathway were associated with various cancers, including hepatocellular carcinoma (HCC). Single nucleotide polymorphisms (SNPs) of DNL genes have been reported to be associated with prognosis of some malignancies. However, the effects of SNPs in DNL genes on overall survival of HCC patients receiving transarterial chemoembolization (TACE) treatment are still unknown. In present study, nine SNPs in three genes (ACLY, ACACA and FASN) in DNL pathway were genotyped using the Sequenom iPLEX genotyping system in a hospital-based cohort with 419 HCC patients treated with TACE, and their associations with HCC overall survival were evaluated by Cox proportional hazard regression analysis under three genetic models (additive, dominant and recessive). Although we did not find any significant results in total analysis (all p>0.05), our stratified data showed that SNP rs9912300 in ACLY gene was significantly associated with overall survival of HCC patients with lower AFP level and SNP rs11871275 in ACACA gene was significantly associated with overall survival of HCC patients with higher AFP level. We further identified the significant interactions between AFP level and SNP rs9912300 or rs11871275 in the joint analysis. Conclusively, our data suggest that genetic variations in genes of DNL pathway may be a potential biomarker for predicting clinical outcome of HCC patients treated with TACE.

• The Korean Journal of Malacology
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• 제25권3호
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• pp.223-230
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• 2009

Metallothioneins (MTs) play a key role in metallic homeostasis and detoxification in most living organisms. In an attempt to study the biological functions and significance of MT in a snail, we cloned and partially characterized the MT gene from the left-handed snail, Physa acutawhich has been regarded as a potential biomonitering species for fresh water. The complete cDNA sequence of PaMT cDNA was identified from the expressed sequence tag (EST) sequencing project of Physa acuta. The coding region of 180 bp gives 60 amino acid residues including the initiation methionine and termination codon. Clustering and phylogenic analysis of PaMT with other MT amino acid sequences show that it has some identities to Helix pomatia (60%), Arianta arbustorum (58%), Perna viridis (49%), Mytilus edulis (49%), Bathymodiolus azoricus (49%), Bathymodiolus azoricus (48%) and Bathymodiolus sp. FD-2002 (48%). Time dependent induction for PaMT from P. acuta exposed with cadmium (50 ppb) indicated that PaMT was induced at 4-8 hr after exposure. It remains to further develop PaMTas a potential biomarker for water contamination in fresh water.

• IMMUNE NETWORK
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• 제21권6호
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• Journal of the Korea Academia-Industrial cooperation Society
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• 제19권9호
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• pp.116-123
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• 2018

The sperm quality is determined by the kinetic characteristics and acrosome integrity of the sperm. In the previous studies, analysis of semen quality had large errors because those experiments by using microscope had been conducted by people. In recent years, the molecular biological methods have been newly developed to complement the previous techniques. The ZAR1 gene is known to be a gene that affects early embryonic development in vertebrates, but there is no study of the association with semen. In this study, we analyzed the association between the kinetic characteristics and ZAR1 single nucleotide polymorphism (SNP) genotype. To detect the SNPs, we performed sequencing using genomic DNA from the whole bloods of Duroc pigs. We identified an SNP in the ZAR1 gene g.2540T>C. ZAR1 SNP genotypeing in 105 pigs revealed that the major and minor alleles were T and C, respectively. After we analyzed the association between the kinetic characteristics of sperm and the ZAR1 SNP genotype, we found a significant association in MOT (p<0.01), VSL (p<0.05) of the kinetic characteristics in the Duroc boars. It was confirmed that the boars with T allele were lower in MOT and VSL than C allele. Therefore, pigs with C allele are judged to be better at the MOT and VSL of semen. Based on these results, ZAR1 SNP genotyping may be a useful molecular biomarker to improve semen quality by applying molecular breeding technology.

• Journal of Life Science
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• 제25권8호
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• pp.861-869
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• 2015

One of the domesticated species; the dog has been selectively bred for various aims by human. The dog has many breeds, which are artificially selected for specific behaviors and morphologies. Dogs contribute their life to human as working dogs for guide, rescue, detection or etc. Working dogs requires good personality, such as gentleness, robustness and patience for performing their special duty. Many studies have concentrated on finding genetic marker for selecting the high-quality working dog. In this study, we confirmed quantitative expression patterns of eight genes (ABAT; 4-Aminobutyrate Aminotransferase, PLCB1; Phospholipase C, Beta 1, SLC10A4; Solute Carrier Family 10, Member 4, WNT1; Wingless-Type MMTV Integration Site Family, Member 1, BARX2; BarH-Like Homeobox 2, NEUROD6; Neuronal Differentiation 6, SEPT9; Septin 9 and TBR1; T-Box, Brain, 1) among brains tissues from four dog breeds (Beagle, Sapsaree, Shepherd and Jindo), because these genes were expressed and have functions in brain mostly. Specially, BARX2, SEPT9, SLC10A4, TBR1 and WNT1 genes were highly expressed in Beagle and Jindo, and Sapsaree and German Shepherd were vice versa. The biological significance of total genes was estimated by database for annotation, visualization and integrated discovery (DAVID) to determine a different gene ontology (GO) class. In these analyses, we suppose to these eight genes could provide influential information for brain development, and intelligence of organisms. Taken together, these results could provide clues to discover biomarker related to functional traits in brain, and beneficial for selecting superior working dogs.

• Korean Journal of Food Science and Technology
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• 제50권5호
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• pp.480-485
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• 2018

In this study, to identify single nucleotide polymorphisms (SNPs) associated with meat quality in Berkshire pigs, we performed RNA sequencing. A non-synonymous SNP (nsSNP) in the Complement component 9 (C9) gene was identified, and the association between meat quality traits and the C9 genotype was analyzed. The nsSNP in the C9 gene was located at c.942 G>T. In the dominant model, significant associations were observed between the SNP and meat quality traits such as CIE L, collagen content, moisture level, and $pH_{24h}$, whereas in the co-dominant model, significant associations were observed between the SNP and CIE L, collagen content, and protein content. In the recessive model, a significant association between the C9 genotype and the collagen content was observed. In addition, we identified the significant relationship between the C9 genotype and meat quality according to sex. These results indicate that the C9 SNP can be used as a genetic marker for improving pork quality.

• The Korean Journal of Malacology
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• 제32권4호
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• pp.263-268
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• 2016

Metallothionein (MT) family of metal-binding proteins are involved in maintaining homeostasis and heavy metal poisoning. Recently, MT has been considered as a biomarker that can identify a particular species, very similar to the use of cytochrome oxidase I (COI) gene. Satsuma myomphala species of land snails have been reported from North-East Asia, including South Korea and Japan. In particular, the land snail species have been known from only a limited area of Geoje Island, Gyeongsangnam-do province of South Korea. Genetic studies of S. myomphala has been limited with only 6 nucleotide, 2 protein registered on the NCBI server. For elucidating the genetic information of S. myomphala, we conducted RNA sequencing analysis using Illumina HiSeq 2500 next-generation platform. We screened the MT gene from the RNA-Seq database to confirm the molecular phylogenetic relationship. After sequencing, the de novo analysis and clustering generated 103,774 unigenes. After annotation against PANM database using BLAST program, we obtained MT sequence of 74 amino acid residues containing the coding region of 222 bp. Based on this sequence, we found about 53 sequences using the BLAST program in NCBI nr database. Using ClustalX alignment, Maximum-Likehood Tree of MEGA program, we confirmed the molecular phylogenetic relationships that showed similarity with mollusks such as Helix pomatia and H. aspersa, Megathura crenulata.

• Journal of Embryo Transfer
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• 제33권3호
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• pp.177-183
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• 2018

The identification of biomarkers of a living tissues is essentially required to understand specific functions of the cells. In previous study, we reported IGFBP 3 as one of the putative biomarkers, by showing specific expression at porcine spermatogonial stem cells (SSCs) of early stage of porcine testis. In this study, we analyzed the expression of seven members of IGFBP family (IGFBPs) in SSCs and histological expression pattern of pregnancy-associated plasma protein-A (PAPP-A), which plays a role on the growth promoting enzyme by cleavage of IGFBPs in testis of 5 days old pig. RT-PCR analysis showed that IGFBP 1, 2, 3, 4, and 6 were expressed at high level specifically in porcine SSCs compared with whole testis. We performed immunohisotochemical staining of testis sections with PAPP-A and protein gene product 9.5 (PGP9.5) which are the known biomarkers for SSCs. We were not able to find co-expression of PAPP-A and PGP9.5; PAPP-A was expressed only in Sertoli cells and PGP9.5 expression was confirmed in spermatogonium. Additionally, we were able to confirm the GATA4 expression in Sertoli and Leydig cells as a regulator of Sertoli cell function was not detected PGP9.5 expressing cells, indicating indirect evidence of that cytolocalization of PAPP-A expression is limited in Sertoli cells. These results suggested that the PAPP-A expressed in Sertoli cells may play role on regulation of development and differentiation of testicular cells through the IGF axis in neonatal porcine testis.