• International Journal of Oncology
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• v.56 no.2
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• pp.618-629
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• 2020

Bcl2l10, also known as Diva, Bcl-b and Boo, is a member of the Bcl2 family of proteins, which are involved in signaling pathways that regulate cell apoptosis and autophagy. Previously, it was demonstrated that Bcl2l10 plays a crucial role in the completion of oocyte meiosis and is a key regulator of Aurora kinase A (Aurka) expression and activity in oocytes. Aurka is overexpressed in several types of solid tumors and has been considered a target of cancer therapy. Based on these previous results, in the present study, the authors aimed to investigate the regulatory role of Bcl2l10 in A2780 and SKOV3 human ovarian cancer cells. The protein expression of Bcl2l10 was examined in human cancer tissues and cell lines, including the ovaries, using a tissue microarray and various human ovarian cancer cell lines. It was found that Bcl2l10 regulated the protein stability and activities of Aurka in ovarian cancer cells. Although apoptosis was not affected, the cell cycle was arrested at the G0/G1 phase by Bcl2l10 knockdown. Of note, cell viability and motility were markedly increased by Bcl2l10 knockdown. On the whole, the findings of this study suggest that Bcl2l10 functions as tumor suppressor gene in ovarian cancer.

• International Journal of Oncology
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• v.56 no.6
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• pp.1509-1520
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• 2020

The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in human cancer as it regulates critical cellular functions, such as survival, proliferation and metabolism. In the present study, a novel PI3Kα inhibitor (HS-146) was synthesized and its anticancer effects on MCF-7, MDA-MB-231, SKBR3 and BT-474 human breast cancer cell lines were confirmed. HS-146 was found to be most effective in inhibiting the proliferation of MCF-7 cells and in inducing cell cycle arrest in the G0/G1 phase by downregulating cyclin D1, cyclin E, cyclin-dependent kinase (Cdk)2 and Cdk4, and upregulating p21Waf1/Cip1 protein levels in this cell line. The induction of apoptosis by HS-146 was confirmed by DAPI staining and western blot analysis. Cell shrinkage and nuclear condensation, which are typical morphological markers of apoptosis, were increased by HS-146 in the MCF-7 cells in a concentration-dependent manner, and HS-146 also increased the protein expression levels of cleaved poly(ADP-ribose) polymerase (PARP) and decreased the protein expression levels of Mcl-1 and caspase-7. In addition, HS-146 effectively decreased the phosphorylation levels of downstream PI3K effectors, such as Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase 3β (GSK3β), p70S6K1 and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1). Hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression were also suppressed by HS-146 under hypoxic conditions, and HS-146 inhibited the migration and invasion of MCF-7 cells in a concentration-dependent manner. On the whole, the findings of the present study suggest that HS-146, a novel PI3Kα inhibitor, may be an effective novel therapeutic candidate that suppresses breast cancer proliferation and metastasis by inhibiting the PI3K/Akt/mTOR pathway.

• Molecules and Cells
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• v.38 no.7
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• pp.643-650
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• 2015

The use of conditioned medium from mesenchymal stem cells may be a feasible approach for regeneration of bone defects through secretion of various components of mesenchymal stem cells such as cytokines, chemokines, and growth factors. Mesenchymal stem cells secrete and accumulate multiple factors in conditioned medium under specific physiological conditions. In this study, we investigated whether the conditioned medium collected under hypoxic condition could effectively influence bone regeneration through enhanced migration and adhesion of endogenous mesenchymal stem cells. Cell migration and adhesion abilities were increased through overexpression of intercellular adhesion molecule-1 in hypoxic conditioned medium treated group. Intercellular adhesion molecule-1 was upregulated by microRNA-221 in mesenchymal stem cells because microRNAs are key regulators of various biological functions via gene expression. To investigate the effects in vivo, evaluation of bone regeneration by computed tomography and histological assays revealed that osteogenesis was enhanced in the hypoxic conditioned medium group relative to the other groups. These results suggest that behavioral changes of endogenous mesenchymal stem cells through microRNA-221 targeted-intercellular adhesion molecule-1 expression under hypoxic conditions may be a potential treatment for patients with bone defects.

• International Journal of Stem Cells
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• v.16 no.2
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.

• International Journal of Stem Cells
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• v.15 no.4
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• pp.359-371
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• 2022

Background and Objectives: The goal of this study was to investigate the mechanism of mesenchymal stem cell (MSC)-derived microRNA (miR)-150-5p-expressing exosomes in promoting skin wound healing through activating PI3K/AKT pathway by PTEN. Methods and Results: Human umbilical cord (HUC)-MSCs were infected with miR-150-5p overexpression and its control lentivirus, and HUC-MSCs-derived exosomes (MSCs-Exos) with stable expression of miR-150-5p were obtained. HaCaT cells were induced by H₂O₂ to establish a cellular model of skin injury, in which the expression of miR-150-5p and PTEN and the phosphorylation of PI3K and AKT were evaluated. HaCaT cells were transfected with pcDNA3.1-PTEN or pcDNA3.1 and then cultured with normal exosomes or exosomes stably expressing miR-150-5p. Cell proliferation was inspected by CCK-8. Cell migration was detected by scratch test and cell apoptosis by flow cytometry. The starBase tool was used to predict the binding site of miR-150-5p to PTEN. Dual-luciferase reporter assay and RIP assay were applied to assess the interaction between miR-150-5p and PTEN. In H₂O₂-induced HaCaT cells, the miR-150-5p expression decreased, and PTEN expression increased in a concentration-dependent manner. MSCs-Exos promoted the growth and migration of H₂O₂-induced HaCaT cells and inhibited their apoptosis. In addition, overexpression of exosomal miR-150-5p enhanced the protective effect of MSCs-Exos on H₂O₂-induced HaCaT cells; PTEN overexpression in HaCaT cells partially restrained miR-150-5p-mediated inhibition on H₂O₂-induced injury in HaCaT cells. PTEN was a target gene of miR-150-5p. MiR-150-5p regulated PI3K/AKT pathway through PTEN. Conclusions: MSCs-derived miR-150-5p-expressing exosomes promote skin wound healing by activating PI3K/AKT pathway through PTEN.

• International Journal of Stem Cells
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• v.17 no.3
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• pp.309-318
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• 2024

Nucleotide-binding oligomerization domain 1 (NOD1), a cytosolic pattern recognition receptor protein, plays a crucial role in innate immune responses. However, the functional expression of NOD1 in mesenchymal stem cells (MSCs) derived from endometriosis remains unclear. The aim of this study was to explore the functions of NOD1 in ectopic endometrial lesions. Tissues and MSCs were isolated from both normal endometrium and endometriosis. Immunohistochemistry and real time quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of NOD1 in the tissues/MSCs. Quantification of various cytokines was performed using RT-qPCR and enzyme-linked immunosorbent assay. To confirm the proliferation, invasion/migration, and apoptotic viabilities of the samples, Cell Counting Kit-8, clonogenic formation, transwell assays, and apoptotic experiments were conducted. Higher levels of NOD1 expression were detected in the ectopic-MSCs obtained from endometriosis compared to those from the endometrium. The expression of interleukin-8 was higher in the ectopic-MSCs than in the eutopic-MSCs. Pretreatment with NOD1 agonist significantly enhanced the proliferation and invasion/migration of eutopic-MSCs. Additionally, the NOD1 inhibitor ML-130 significantly reduced the proliferation, clone formation, invasion, and migration abilities of the ectopic-MSCs, having no effect on their apoptosis capacity. Our findings suggest that the expression of NOD1 in ectopic-MSCs may contribute to the progression of ectopic endometrial lesions.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.11 no.4
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• pp.293-301
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• 2013

Borehole Disposal Concept (BDC) was initiated by the South African Nuclear Energy Corporation (NECSA) with the view to improve the radioactive waste management practices in Africa. At a time when geological disposal of radioactive waste is being considered, the need to protect ground water from possible radioactive contamination and the investigation of radionuclides migration through soil and rocks of zone of aeration into ground water has becomes very imperative. This is why the Borehole Disposal Concept (BDC) is being suggested to address the problem. The concept involves the conditioning and emplacement of disused sealed radioactive sources in an engineered facility of a relatively narrow diameter borehole (260 mm). Tanzania is operating a Radioactive Waste Management Facility where a number of spent sealed radioactive sources with long and short half lives are stored. The activity of spent sealed radioactive sources range from (1E-6 to 8.8E+3 Ci). However, the long term disposal solution is still a problem. This study therefore proposing the country to adopt the BDC, since the repository requires limited land area and has a low probability of human intrusion due to the small footprint of the borehole.

• The Journal of the Korea Contents Association
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• v.15 no.1
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• pp.276-285
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• 2015

The aim of this study was to identify the impact of community factors on the community-level Health-Related Quality of Life (HRQOL) in Korea. This was a cross-sectional study conducted in 2012 using secondary data(n=209) of the Korean Statistical Information Service. The framework was based on community factors provided by the International Council of Science (ICSU) and community factors were categorized based on six aspects. Multiple regression was applied to community factors depending on the community EQ-5D index. Smoking rate, "Good" self-rated health rate, water and wastewater coverage rate, and financial independency rate were significantly and positively associated with the EQ-5D score. Net migration rate(more move out than move in), obesity rate, unmet needed health care rate, and community type(rural than urban) were significantly and negatively associated with the EQ-5D score. This study identifies association for the impact of community factors on the community-level HRQOL and can provide useful evidence for development of community health promotion policies.

• Clinical and Experimental Reproductive Medicine
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• v.45 no.1
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• pp.10-16
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• 2018

Objective: Placental oxidative stress is known to be a factor that contributes to pregnancy failure. The aim of this study was to determine whether selenium could induce antioxidant gene expression and regulate invasive activity and mitochondrial activity in trophoblasts, which are a major cell type of the placenta. Methods: To understand the effects of selenium on trophoblast cells exposed to hypoxia, the viability and invasive activity of trophoblasts were analyzed. The expression of antioxidant enzymes was assessed by reverse-transcription polymerase chain reaction. In addition, the effects of selenium treatment on mitochondrial activity were evaluated in terms of adenosine triphosphate production, mitochondrial membrane potential, and reactive oxygen species levels. Results: Selenium showed positive effects on the viability and migration activity of trophoblast cells when exposed to hypoxia. Interestingly, the increased heme oxygenase 1 expression under hypoxic conditions was decreased by selenium treatment, whereas superoxide dismutase expression was increased in trophoblast cells by selenium treatment for 72 hours, regardless of hypoxia. Selenium-treated trophoblast cells showed increased mitochondrial membrane potential and decreased reactive oxygen species levels under hypoxic conditions for 72 hours. Conclusion: These results will be used as basic data for understanding the mechanism of how trophoblast cells respond to oxidative stress and how selenium promotes the upregulation of related genes and improves the survival rate and invasive ability of trophoblasts through regulating mitochondrial activity. These results suggest that selenium may be used in reproductive medicine for purposes including infertility treatment.

• International Journal of Advanced Culture Technology
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• v.8 no.2
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• pp.96-100
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• 2020

In this paper, I try to help the business operation so that they could continue the desirable operation despite the unfavorable conditions. It is important to reinforce for corporate growth various support measures to generate profits. However, if they are involved in criminal activities such as slush fund creation, they will have to deal with them separately. As a result, To raise awareness helps to keep the company running. Recently, the companies are in a poor condition due to overseas migration. If a company does not create profits by doing business, it is a burden to continue operating and it will eventually be hard to support and destroy. The corporate crime and white-collar crime are mostly similar types, mainly because they occur in the industry. The corporate crime proceeds throughout the company and ultimately translates into corporate profits. The white-collar crime, on the other hand, is a profitable part of the individual. In the process of generating profits, the purpose and management method of slush funds is an important issue in judging whether illegal immorality of business is intended or not. In addition, in the case of the corporate crime, it seems necessary to identify the types of slush fund raising activities in addition to the investigations of the accomplices and clinical investigations, and to apply efficient investigation methods on a case-by-case basis. At present, many companies frequently migrate overseas due to the influence of domestic regulations. In this process, if it is involved in crime such as a borrowing accounts or the purpose of slush fund creation should be treated separately.