• Title/Summary/Keyword: Aberrant

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Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation

  • Seok, Ju Hyung;Kim, Dae Hyun;Kim, Hye Jih;Jo, Hang Hyo;Kim, Eun Young;Jeong, Jae-Hwang;Park, Young Seok;Lee, Sang Hun;Kim, Dae Joong;Nam, Sang Yoon;Lee, Beom Jun;Lee, Hyun Jik
    • Journal of Veterinary Science
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    • v.23 no.5
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    • pp.74.1-74.16
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    • 2022
  • Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

11S and 7S Globulin Fractions in Soybean Seed and Soycurd Characteristics (콩 종실 단백질 분획(7S, 11S)과 두부특성)

  • Kim, Yong-Ho;Kim, Seok-Dong;Hong, Eun-Hi
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.39 no.4
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    • pp.348-352
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    • 1994
  • Soybean seed consists of two major storage protein, the 7S and 11S globulins. For improving the quality of soybean seed protein, an increase of 11S/7S ratio would be a desirable objective because the 11S globulin contains much more the sulfur-containing amino acids than the 7S globulin. In this study, some soybean varieties were used to investigate the analyzing method for 7S and 11S globulins. 7S and 11S globulins couble be fractionated by their different solubilities in tris buffers. Adjusting the pH and tris concentration were major factors affecting the precipitation of the two globulins. And it was possible to screen the soybean genotypes having aberrant subunit compositions of the two globulins by an sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of total soybean proteins. The ratio of 11S to 7S globulin ranged from 1.29 to 1.38. This paper also dealed with the contribution of protein components in soybean seeds to the physical properties of soycurd. It indicated that the soycurd from crude 11S was remarkably harder than that from crude 7S, and springiness and cohesiveness were slightly higher in soycurd having higher proportion of 11S. So, it may concluded that proportion of protein components in soybean seed can be important factor which controls the suitability for soycurd or other foods.

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Morphological Characteristics of Pig Blastocysts Produced by Somatic Cell Nuclear Transfer

  • Y.M. Han;D.B. Koo;Park, Y.H.;Park, J.S.;Kim, H.N.;Y.K. Kang;W.K. Chang;Lee, K.K.
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.68-68
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    • 2001
  • Blastocyst formation, consisting of the inner cell mass (ICM) and trophectoderm (TE), is the first differentiation process during embryonic development in mammals. It has been hypothesized that the proportion of ICM to TE in the blastocyst may be crucial for subsequent developmental competence of early embryos, which it may be expressed as a sensitive indicator for evaluating in vitro systems. In this study ICM/total cell ratio of nuclear transfer (NT) embryos was compared with IVF-derived and in vivo embryos. Somatic cell nuclei obtained from a fetus at Day 40 of gestation were transferred into the enucleated oocyte and then cultured in NCSU 23 medium for 6 days as previously described (Koo et al., Biol. Reprod. 2000; 63:986-992). ICM and TE cells of blastocysts were determined by using a differential staining method (Han et al., Biol. Reprod. 1999; 60:1110-1113). Development rate (9.8$\pm$2.5%, 23/225) to the blastocyst stage of NT embryos was lower than IVF embryos (23.8$\pm$2.7%, 53/223). Thus, a difference was detected in the in vitro developmental rate to blastocyst stage between NT and IVF-derived embryos (P<0.05). In the next experiment, we investigated ICM and TE nuclei to assess the quality of blastocysts that produced by NT, IVF and in vivo, respectively. NT blastocysts (27.6$\pm$8.3) showed a smaller total cell number than IVF-derived (42.6$\pm$17.4) and in vivo embryos (283.9$\pm$103.5) (P<0.05). Ratios of ICM/total cells in NT, IVF and in vivo blastocysts were 15.1$\pm$ 18.6% (n=56), 12.3$\pm$9.2% (n=57) and 30.4$\pm$6.8% (n=40), respectively. Individual blastocysts for the ratio of ICM/total cells were assigned to 3 groups (I; <20%, II; 20 to 40% and III;>40%). As the results, most in vivo blastocysts (97.5%, 39/40) were distributed into group II while most NT (78.6%, 44/56) and IVF-derived blastocysts (82.5%, 47/57) were allocated to group I. Thus, our data show that NT or IVF-derived embryos have aberrant morphology during early development in vitro systems, suggesting that these anomalies may result in developmental failures of the NT embryos to term.

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Angioimmunoblastic T-Cell Lymphoma with Polyclonal Proliferation of Plasma Cells: A Cautionary Note for Flow Cytometry Interpretations (유세포 분석의 주의사항: 혈관면역모세포성 T세포 림프종에서 관찰된 다클론성 형질세포)

  • Shin, Woo Yong;Bang, Hae In;Kim, Jung-Ah;Kim, Jieun;Park, Rojin
    • Korean Journal of Clinical Laboratory Science
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    • v.54 no.1
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    • pp.68-72
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    • 2022
  • Angioimmunoblastic T-cell lymphoma (AITL) is a lymphoproliferative disorder of mature T follicular helper cells. Atypical lymphoid cells were observed in the bone marrow of an 80-year-old woman, and the flow cytometric determined immunophenotypes of B-cells were unusual, that is, CD19+, CD20-, and CD22- with lambda light chain restriction. Initially, we suspected BM involvement of B-cell lymphoma based on the presence of abnormal B-cells. However, the patient was diagnosed with AITL involving BM. A re-analysis of flow cytometric immunophenotyping revealed a minor, aberrant T-cell population, and the lambda light chain restriction observed by surface staining was considered non-specific binding. This case demonstrates B-cells in patients with EBV-positive T-cell lymphoma may exhibit immunophenotypes resembling those of plasma cells, and that proliferation of abnormal B-cells or plasma cells could also potentially mask underlying T-cell lymphoma. A more integrated approach is required for accurate diagnosis.

Idea of Persecution and Psychological Factors Associated With Idea of Persecution in Patients With PTSD (PTSD 환자의 피해 사고 및 피해 사고에 기여하는 심리학적 요인)

  • Seungyun Lee;Young Kyung Moon;Sora Lee;Hayun Choi
    • Korean Journal of Psychosomatic Medicine
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    • v.31 no.2
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    • pp.155-164
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    • 2023
  • Objectives : The aim of this study was to identify the factors affecting ideas of persecution in post-traumatic stress disorder (PTSD) patients who underwent Clinician-Administered PTSD Scale (CAPS) and Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Methods : We retrospectively reviewed 116 patients who underwent CAPS and MMPI 2 between May 2013 and April 2020 at Veteran Health Service Medical Center. Based on the CAPS score, the patients were divided into the PTSD group (n=63, age: 58.16±17.84) and the trauma exposed without PTSD group (n=53, age: 67.34±12.05). After checking the correlation between Ideas of persecution, CAPS, and MMPI-2 scales, linear regression analysis was performed to identify the risk factors for clinically relevant symptoms. Results : The PTSD group showed significant differences in Schizophrenia, Ideas of persecution, Dysfunctional negative emotions, Aberrant Experiences, Psychoticism, Negative Emotionality/Neuroticism, Anxiety, Depression, and Anger scales compared to the trauma-exposed without PTSD group. When analyzing the correlation between Idea of persecution, CAPS and MMPI-2 scales, there was a strong association with most of the scales in MMPI-2 and Idea of persecution except Disconstraint. Multiple linear regression analysis performed in PTSD group identified that risk factors for Idea of persecution were Dysfunctional negative emotions and Anger scale. Conclusions : The PTSD group had increased idea of persecution compared to the trauma exposed without PTSD group. Dysfunctional negative emotions and anger may be risk factors for idea of persecution in trauma exposed population.

Deciphering the DNA methylation landscape of colorectal cancer in a Korean cohort

  • Seok-Byung Lim;Soobok Joe;Hyo-Ju Kim;Jong Lyul Lee;In Ja Park;Yong Sik Yoon;Chan Wook Kim;Jong-Hwan Kim;Sangok Kim;Jin-Young Lee;Hyeran Shim;Hoang Bao Khanh Chu;Sheehyun Cho;Jisun Kang;Si-Cho Kim;Hong Seok Lee;Young-Joon Kim;Seon-Young Kim;Chang Sik Yu
    • BMB Reports
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    • v.56 no.10
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    • pp.569-574
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    • 2023
  • Aberrant DNA methylation plays a pivotal role in the onset and progression of colorectal cancer (CRC), a disease with high incidence and mortality rates in Korea. Several CRC-associated diagnostic and prognostic methylation markers have been identified; however, due to a lack of comprehensive clinical and methylome data, these markers have not been validated in the Korean population. Therefore, in this study, we aimed to obtain the CRC methylation profile using 172 tumors and 128 adjacent normal colon tissues of Korean patients with CRC. Based on the comparative methylome analysis, we found that hypermethylated positions in the tumor were predominantly concentrated in CpG islands and promoter regions, whereas hypomethylated positions were largely found in the open-sea region, notably distant from the CpG islands. In addition, we stratified patients by applying the CpG island methylator phenotype (CIMP) to the tumor methylome data. This stratification validated previous clinicopathological implications, as tumors with high CIMP signatures were significantly correlated with the proximal colon, higher prevalence of microsatellite instability status, and MLH1 promoter methylation. In conclusion, our extensive methylome analysis and the accompanying dataset offers valuable insights into the utilization of CRC-associated methylation markers in Korean patients, potentially improving CRC diagnosis and prognosis. Furthermore, this study serves as a solid foundation for further investigations into personalized and ethnicity-specific CRC treatments.

Butyric acid and prospects for creation of new medicines based on its derivatives: a literature review

  • Lyudmila K. Gerunova;Taras V. Gerunov;Lydia G. P'yanova;Alexander V. Lavrenov;Anna V. Sedanova;Maria S. Delyagina;Yuri N. Fedorov;Natalia V. Kornienko;Yana O. Kryuchek;Anna A. Tarasenko
    • Journal of Veterinary Science
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    • v.25 no.2
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    • pp.23.1-23.15
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    • 2024
  • The widespread use of antimicrobials causes antibiotic resistance in bacteria. The use of butyric acid and its derivatives is an alternative tactic. This review summarizes the literature on the role of butyric acid in the body and provides further prospects for the clinical use of its derivatives and delivery methods to the animal body. Thus far, there is evidence confirming the vital role of butyric acid in the body and the effectiveness of its derivatives when used as animal medicines and growth stimulants. Butyric acid salts stimulate immunomodulatory activity by reducing microbial colonization of the intestine and suppressing inflammation. Extraintestinal effects occur against the background of hemoglobinopathy, hypercholesterolemia, insulin resistance, and cerebral ischemia. Butyric acid derivatives inhibit histone deacetylase. Aberrant histone deacetylase activity is associated with the development of certain types of cancer in humans. Feed additives containing butyric acid salts or tributyrin are used widely in animal husbandry. They improve the functional status of the intestine and accelerate animal growth and development. On the other hand, high concentrations of butyric acid stimulate the apoptosis of epithelial cells and disrupt the intestinal barrier function. This review highlights the biological activity and the mechanism of action of butyric acid, its salts, and esters, revealing their role in the treatment of various animal and human diseases. This paper also discussed the possibility of using butyric acid and its derivatives as surface modifiers of enterosorbents to obtain new drugs with bifunctional action.

Exploring the DNA methylome of Korean patients with colorectal cancer consolidates the clinical implications of cancer-associated methylation markers

  • Sejoon Lee;Kil-yong Lee;Ji-Hwan Park;Duck-Woo Kim;Heung-Kwon Oh;Seong-Taek Oh;Jongbum Jeon;Dongyoon Lee;Soobok Joe;Hoang Bao Khanh Chu;Jisun Kang;Jin-Young Lee;Sheehyun Cho;Hyeran Shim;Si-Cho Kim;Hong Seok Lee;Young-Joon Kim;Jin Ok Yang;Jaeim Lee;Sung-Bum Kang
    • BMB Reports
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    • v.57 no.3
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    • pp.161-166
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    • 2024
  • Aberrant DNA methylation plays a critical role in the development and progression of colorectal cancer (CRC), which has high incidence and mortality rates in Korea. Various CRC-associated methylation markers for cancer diagnosis and prognosis have been developed; however, they have not been validated for Korean patients owing to the lack of comprehensive clinical and methylome data. Here, we obtained reliable methylation profiles for 228 tumor, 103 adjacent normal, and two unmatched normal colon tissues from Korean patients with CRC using an Illumina Infinium EPIC array; the data were corrected for biological and experiment biases. A comparative methylome analysis confirmed the previous findings that hypermethylated positions in the tumor were highly enriched in CpG island and promoter, 5' untranslated, and first exon regions. However, hypomethylated positions were enriched in the open-sea regions considerably distant from CpG islands. After applying a CpG island methylator phenotype (CIMP) to the methylome data of tumor samples to stratify the CRC patients, we consolidated the previously established clinicopathological findings that the tumors with high CIMP signatures were significantly enriched in the right colon. The results showed a higher prevalence of microsatellite instability status and MLH1 methylation in tumors with high CMP signatures than in those with low or non-CIMP signatures. Therefore, our methylome analysis and dataset provide insights into applying CRC-associated methylation markers for Korean patients regarding cancer diagnosis and prognosis.

Ten-eleven translocation 1 mediating DNA demethylation regulates the proliferation of chicken primordial germ cells through the activation of Wnt4/β-catenin signaling pathway

  • Yinglin Lu;Ming Li;Heng Cao;Jing Zhou;Fan Li;Debing Yu;Minli Yu
    • Animal Bioscience
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    • v.37 no.3
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    • pp.471-480
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    • 2024
  • Objective: The objective of this study was to investigate the regulation relationship of Ten-eleven translocation 1 (Tet1) in DNA demethylation and the proliferation of primordial germ cells (PGCs) in chickens. Methods: siRNA targeting Tet1 was used to transiently knockdown the expression of Tet1 in chicken PGCs, and the genomic DNA methylation status was measured. The proliferation of chicken PGCs was detected by flow cytometry analysis and cell counting kit-8 assay when activation or inhibition of Wnt4/β-catenin signaling pathway. And the level of DNA methylation and hisotne methylation was also tested. Results: Results revealed that knockdown of Tet1 inhibited the proliferation of chicken PGCs and downregulated the mRNA expression of Cyclin D1 and cyclin-dependent kinase 6 (CDK6), as well as pluripotency-associated genes (Nanog, PouV, and Sox2). Flow cytometry analysis confirmed that the population of PGCs in Tet1 knockdown group displayed a significant decrease in the proportion of S and G2 phase cells, which meant that there were less PGCs entered the mitosis process than that of control. Furthermore, Tet1 knockdown delayed the entrance to G1/S phase and this inhibition was rescued by treated with BIO. Consistent with these findings, Wnt/β-catenin signaling was inactivated in Tet1 knockdown PGCs, leading to aberrant proliferation. Further analysis showed that the methylation of the whole genome increased significantly after Tet1 downregulation, while hydroxyl-methylation obviously declined. Meanwhile, the level of H3K27me3 was upregulated and H3K9me2 was downregulated in Tet1 knockdown PGCs, which was achieved by regulating Wnt/β-catenin signaling pathway. Conclusion: These results suggested that the self-renewal of chicken PGCs and the maintenance of their characteristics were regulated by Tet1 mediating DNA demethylation through the activation of Wnt4/β-catenin signaling pathway.

Antigenotoxic and Anticarcinogenic Effects of Styela plicata (오만둥이(Styela plicata)의 항유전독성 및 대장암 억제효과에 관한 연구)

  • Seo, Bo-Young;Kim, Jung-Mi;Lee, Seung-Cheol;Park, Eun-Ju
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.7
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    • pp.839-845
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    • 2009
  • Colorectal cancer is the third most common malignant neoplasm in the world. Much attention has been focused on reducing colon cancer risk through medical properties of natural compound that could act as anticarcinogens. In this study, we evaluated the antioxidant and antigenotoxic effects of Styela plicata (S. plicata) from in vitro experiments. S. plicata extracts showed antioxidant activity measured by TRAP assay and antigenotoxic effect in $200{\mu}M$ $H_2O_2$ induced DNA damage in human leukocytes. Especially, freeze-dried S. plicata extracted with methanol showed the highest level of TRAP (0.225 mM) and inhibition of DNA damage (66.8%). Additionally we observed the effect of S. plicata on the formation of aberrant crypt foci (ACF) induced by dimethylhydrazine (DMH) and DMH induced DNA damage (by comet assay) in male SD rats. The animals were divided into three groups and fed high-fat and low fiber diet (100 g lard+20 g cellulose/kg diet) without (normal control and DMH control) or with a 3% (w/w) of lyophilized S. plicata powder (DMH+S. plicata). One week after beginning the diets, rats were treated with DMH (30 mg/kg, s.c.) for 6 weeks except for normal control group, which was treated saline instead; dietary treatments were continued for the entire experiment. Nine weeks after DMH injection, administration of S. plicata resulted in reduction of ACF numbers, to 82.7% of the carcinogen control value ($7.67{\pm}2.04$ vs. $1.33{\pm}0.53$: p<0.01). S. plicata supplementation induced antigenotoxic effect on DMH-induced DNA damage in the blood cell (% tail intensity: $6.79{\pm}0.26$ vs. $6.13{\pm}0.22$). These data indicate that S. plicata extract has antigenotoxic and anticarcinogenic effects from in vitro experiments and S. plicata exerts a protective effect on the process of colon carcinogenesis, possibly by suppressing the DMH-induced DNA damage in blood cell and the development of preneoplastic lesions in colon.