• Journal of the Korean Society of Visualization
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• v.13 no.1
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• pp.43-48
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• 2015

Collective cell migration is a fundamental phenomenon observed in various biological processes such as development, wound healing, and cancer metastasis. During the collective migration, cells undergo changes in their phenotypes from those of stable to the migratory state via the process called epithelial-mesenchymal transition (EMT). Recent findings in biology and biochemistry have shown that EMT is closely related to the cancer invasion or metastasis, but not much of the correlations in kinematics and physical forces between the neighboring cells are known yet. In this study, we aim to understand the cell migration and stress distribution within the expanding cell cluster. We constructed the in vitro cell cluster on the hydrogel, employed traction force microscopy (TFM) and monolayer stress microscopy (MSM) to visualize the physical forces within the expanding cell monolayer. During the expansion, cells at the cluster edge exhibited enhanced motility and developed focal adhesions that are the essential features of EMT while cells at the core of the cluster maintained the epithelial characteristics. In the aspect of mechanical stress, the cluster edge had the highest traction force of ~90 Pa directed toward the cluster core, which means that cells at the edge actively pull the substrate to make the cluster expansion. The cluster core of the tightly confined cells by neighboring cells had a lower traction force value (~60 Pa) but the highest intercellular normal stress of ~800 Pa because of the accumulation of traction from the edge of the monolayer.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.3
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• pp.671-676
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• 2005

In this study, we investigated the antioxidant effect of extract from Monascus pillosus, on the human wild-type p53 and p21 expressing A549 lung epithelial cell line and MCF-7 mammary adenocarcinoma cell line stimulated by NO. $P21^{waf/cip1}$ was identified as a gene induced in senescent cells. It is a cyclin-dependent kinase inhibitor and has been shown to cause cell cycle arrest and apoptosis. While p53-regulated stimulation of p21 appears to be central for the permanent growth-arrest, the role of p21 in p53-triggered cell death is unclear. Low dose of sodium nitroprusside (SNP) induced the development of senescence associated with increased expression of p53 and p21 in A549 cells. Inhibition of p21 transactivating activity requires high level correlates with the amount of p53 necessary to cause cell death. Association of p21 and p53 results in inhibition of p21-stimulated transcription. This requires a higher p53 level than is necessary for transcriptional activation of endogenous p53-responsive gene but correlates well with the level of p53 necessary to cause cell death. Exposure to W-1 inhibited oxidative stresses-induced senescence-like arrest, resulting in a significant reduction in p53 and p21 steady state levels. These results suggest that p53 and p21 play a central role in the onset of senescence. Thus, it is important to emphasize control of oxidative balance in tumor prevention and aging.

• Molecules and Cells
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• v.22 no.2
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• pp.189-197
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• 2006

Prolactin (PRL) is a pituitary hormone involved in various physiological processes, including lactation, mammary development, and immune function. To further investigate the in vivo and comparative endocrine roles of PRL, mouse PRL cDNA fused to the cytomegalovirus promoter, was introduced into muscle by direct injection. Previously we studied the function of rat PRL using the same protocol. PRL mRNA was detected in the muscle following injection by RT-PCR and subsequent Southern blot analysis. PRL was also detected and Western blot analysis revealed a relatively high level of serum PRL. In the pCMV-mPRL-injected female mice, the estrous cycle was extended, especially in diestrus stage and the uterus thickening that was shown in normal estrous stage was not observed. In the pCMV-mPRL-injected male mice, new blood vessels were first found at 5 weeks of age and fully developed blood vessels were found after 8 weeks in the testis. The number of Leydig cells increased within the testis and the testosterone level in serum was observed high. Finally, the number of white blood cells (WBCs) increased in the pCMV-mPRL-injected mice. The augmentation of WBCs persisted for at least 20 days after injection. When injection was combined with adrenalectomy, there was an even greater increase in number of WBCs, especially lymphocytes. This increase was returned normal by treatment with dexamethansone. Taken together, our data reveal that intramuscularly expressed mouse PRL influences reproductive functions in female, induces formation of new blood vessels in the testis, and augments WBC numbers. Of notice is that the Leydig cell proliferation with increased testosterone was conspicuously observed in the pCMV-mPRL-injected mice. These results also suggest subtle difference in function of PRL between mouse and rat species.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.197-201
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• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.3
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• pp.194-210
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• 2022

Human milk contains a number of nutritional and bioactive molecules including microorganisms that constitute the so-called "Human Milk Microbiota (HMM)". Recent studies have shown that not only bacterial but also viral, fungal, and archaeal components are present in the HMM. Previous research has established, a "core" microbiome, consisting of Firmicutes (i.e., Streptococcus, Staphylococcus), Proteobacteria (i.e., Serratia, Pseudomonas, Ralstonia, Sphingomonas, Bradyrhizobium), and Actinobacteria (i.e., Propionibacterium, Corynebacterium). This review aims to summarize the main characteristics of HMM and the role it plays in shaping a child's health. We reviewed the most recent literature on the topic (2019-2021), using the PubMed database. The main sources of HMM origin were identified as the retrograde flow and the entero-mammary pathway. Several factors can influence its composition, such as maternal body mass index and diet, use of antibiotics, time and type of delivery, and mode of breastfeeding. The COVID-19 pandemic, by altering the mother-infant dyad and modifying many of our previous habits, has emerged as a new risk factor for the modification of HMM. HMM is an important contributor to gastrointestinal colonization in children and therefore, it is fundamental to avoid any form of perturbation in the HMM that can alter the microbial equilibrium, especially in the first 100 days of life. Microbial dysbiosis can be a trigger point for the development of necrotizing enterocolitis, especially in preterm infants, and for onset of chronic diseases, such as asthma and obesity, later in life.

• Proceedings of the KSAR Conference
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• 2001.03a
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• pp.60-60
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• 2001

Human thrombopoietin (hTPO) is a cytokine that plays a central role in megakaryopoiesis by influencing on the development and maturation of megakaryocyte and platelet production. To induce hTPO production in the mammary gland, expression vector was constructed by combining the promoter of bovine beta-casein gene, cDNA of hTPO and neomycine resistance gene for transfection into fibroblasts. Bovine fibroblast cells derived from female ear skin were transfercted with the expression vector using Lipofectamine (Life Technology, NY). Transected cells resistant to G4l8 treatment (600 $\mu\textrm{g}$/$m\ell$) were recovered and colony formation was initiated at 13 days. The colonies with about 1 cm diameter were picked and analysed by PCR. Single transfected cells were individually transferred to enucleated oocytes. After electrofusion, the reconstructed embryos were exposed to calcium ionophore (5uM) for 5 min followed by treatment with 6-DMAP (2.5 mM) for 4h. The nuclear transfer embryos were cultured in CRlaa medium at 38.5C, 5% $CO_2$ for 7 days. Twenty three of 29 (79.3%) colonies were proved to be hTPO transfectants by PCR. The colonies were further passaged and used to produce transgenic embryos using nuclear transfer. Cleavage and developmental rates of reconstructed embryos to the blastocyst stage were 65.1% and 39.4%, respectively Of 22 blastocysts that developed from reconstructed embryos with the transfected cell, 20 embryos (90.9%) were positive for hTPO by using PCR analysis. The results suggest that somatic cell nuclear transfer is efficient for production of transgenic embryos.

• Genomics & Informatics
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• v.21 no.2
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• pp.19.1-19.13
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• 2023

Liver cancer, particularly hepatocellular carcinoma (HCC), poses a significant global threat to human lives. To advance the development of innovative diagnostic and treatment approaches, it is essential to examine the hidden features of HCC, particularly its 3D genome architecture, which is not well understood. In this study, we investigated the 3D genome organization of four HCC cell lines-Hep3B, Huh1, Huh7, and SNU449-using in situ Hi-C and assay for transposase-accessible chromatin sequencing. Our findings revealed that HCC cell lines had more long-range interactions, both intra-and interchromosomal, compared to human mammary epithelial cells (HMECs). Unexpectedly, HCC cell lines displayed cell line-specific compartmental modifications at the megabase (Mb) scale, which could potentially be leveraged in determining HCC subtypes. At the sub-Mb scale, we observed decreases in intra-TAD (topologically associated domain) interactions and chromatin loops in HCC cell lines compared to HMECs. Lastly, we discovered a correlation between gene expression and the 3D chromatin architecture of SLC8A1, which encodes a sodium-calcium antiporter whose modulation is known to induce apoptosis by comparison between HCC cell lines and HMECs. Our findings suggest that HCC cell lines have a distinct 3D genome organization that is different from those of normal and other cancer cells based on the analysis of compartments, TADs, and chromatin loops. Overall, we take this as evidence that genome organization plays a crucial role in cancer phenotype determination. Further exploration of epigenetics in HCC will help us to better understand specific gene regulation mechanisms and uncover novel targets for cancer treatment.

• Journal of Food Hygiene and Safety
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• v.13 no.2
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• pp.106-111
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• 1998

This study has been focused on both estrogenic and proliferating activity of genistein (GEN) and bisphenol A (BPA). GEN and BPA enhance the proliferation of estrogen-dependent MCF-7 human breast cancer cells at concentrations as low as 100 nM of GEN and 8 ng/ml of BP A achieving similar effect to that of estradiol at 1 nM. Expression of the estrogen responsive gene, pS2 was also induced in MCF-7 cells by treatment with genistein at dose as low as 1 nM and BPA at dose as low as 4 ng/ml. Using 21 day-old ovariectomized nude mice, we examined end-bud formation and mammary gland development after treatment with bisphenol A or genistein. Compared with untreated control, mammary gland development and end-bud formation were significantly increased in mice fed genistein or bisphenol A (p<0.05). Taken together, it is concluded that GEN and BP A can act as an estrogen agonist resulting in cell proliferation and induction of the estrogen responsive pS2 gene in MCF-7 cells in vitro and in athymic mice in vivo, respectively. Therefore, it is suggested that GEN and BP A might modulate human endocrine system and these compounds might be considered as a endocrine modulator at the low levels of doses.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.41 no.spc1
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• pp.25-45
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• 1996

Soyfoods have potential roles in the prevention and treatment of chronic diseases, most notably cancer, osteoporosis, and heart disease. There is evidence that carcinogenesis are supressed by isolated soybean derived products in vivo such as a protease inhibitor, phytic acid, saponins and isoflavones. It is believed that supplementation of human diets with soybean products markedly reduces human cancer mortality rates. Especially, recent papers recognize the potential benefit of soybean isoflavone components for reducing the risk of various cancers. Isoflavones exhibit a multitude of medicinal effects that influence cell growth and regulation, which may have potential value in the prevention and treatment of cancer. In addition to potential biological effects, soybean isoflavones have the important physiological functions such as the induction of Bradyrizobium japonicum nod genes and the responses of soybean tissues to infection by Phytophthora megasperma as well as biochemical activities such as antifungal and antibacterial actions. Genistin, daidzin, glycitin and their aglycone (genistein, daidzein, glycitein) are the principal isoflavones found in soybean. Malonyl and acetyl forms have also been detected but they are thermally unstable and are usually transformed during the processing in glucoside form. Most soy products, with the exception of soy sauce, alcohol-extracted soy protein concentrate, and soy protein isolate, have total isoflavone concentrations similar to those in the whole soybean. Soybean-containing diets inhibit mammary tumorigenesis in animal models of breast cancer, therefore, it is possible that dietary isoflavones are an important factor accounting for the lower incidence and mortality from breast cancer. Of the total soybean seed isoflavones, $80\~90\%$ were located in cotyledons, with the remainder in the hypocotyls. The hypocotyls had a higher concentrations of isoflavones on a weight basis compared with cotyledons. Isoflavone contents were influenced by genetics, crop years, and growth locations. The effect of crop year had a greater impact on the isoflavone contents than that of location. The climate condition might be the attribution factor to variation in isoflavone contents. Also, while the isoflavone content of cotyledons exhibited large variations in response to high temperature during seed development, hypocotyls showed high concentration in isoflavone content. So, it is concluded that one of the factors affecting isoflavone content in soybean seeds is temperature during seed development. High temperature, especially in maturity stage, causes lower isoflavone content in soybean seed. It is also suggested that there may exist a different mechanism to maintain isoflavone contents between cotyledon and seed hypocotyls. In a conclusion, soy foods may be able to have a significant beneficial impact on public health.

• Journal of Chest Surgery
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• v.39 no.10 s.267
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• pp.754-758
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• 2006

Background: Surgical role for acute coronary syndrome has been reduced in recent years due to development of drug eluting stent. We evaluated the surgical results of acute coronary syndrome in our hospital. Material and Method: Between January 2001 and August 2005, 416 patients underwent coronary artery bypass grafting (CABG) under diagnosis of non-ST-elevation acute coronary syndrome (NSTE ACS). Mean age was $61.8{\pm}9.0$ years and 276 (66.3%) patients were male. 324 (77.9%) patients had triple vessel disease and 92 (22.1%) had left main disease at angiographic study. 236 (56.7%) patients had hypertension and 174 (41.8%) had diabetes mellitus. Conventional on-pump CABG was performed in 194 patients (46.6%) and off-pump CABG in 222 (53.4%). Total arterial revascularization with no touch technique was done in 97 patients (23.3%). The number of total distal anastomosis was 1,306 and the number per patient was $3.21{\pm}1.71$. Result: Surgical mortality rate was 1.0% (4 patients) and postoperative complication rate was 15.6% (65 patients). Graft patency was checked at mean $3.7{\pm}7.6$ months (from 1 to 37 months) postoperatively with multi-directional computed tomography in 152 patients. Left internal mammary artery was patent in 95.3%, right internal mammary artery in 98.1%, radial artery in 92.2% and saphenous vein in 89.0%. Conclusion: The surgical treatment of NSTE ACS showed relatively low mortality rate and good graft patency rate. Further study is needed to compare the long term results with drug eluting stent.