• Molecules and Cells
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• v.41 no.11
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• pp.971-978
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• 2018

The stem cell factor (SCF)/c-KIT axis plays an important role in the hematopoietic differentiation of human pluripotent stem cells (hPSCs), but its regulatory mechanisms involving microRNAs (miRs) are not fully elucidated. Here, we demonstrated that supplementation with SCF increases the hematopoietic differentiation of hPSCs via the interaction with its receptor tyrosine kinase c-KIT, which is modulated by miR-221 and miR-222. c-KIT is comparably expressed in undifferentiated human embryonic and induced pluripotent stem cells. The inhibition of SCF signaling via treatment with a c-KIT antagonist (imatinib) during hPSC-derived hematopoiesis resulted in reductions in the yield and multi-lineage potential of hematopoietic progenitors. We found that the transcript levels of miR-221 and miR-222 targeting c-KIT were significantly lower in the pluripotent state than they were in terminally differentiated somatic cells. Furthermore, suppression of miR-221 and miR-222 in undifferentiated hPSC cultures induced more hematopoiesis by increasing c-KIT expression. Collectively, our data implied that the modulation of c-KIT by miRs may provide further potential strategies to expedite the generation of functional blood cells for therapeutic approaches and the study of the cellular machinery related to hematologic malignant diseases such as leukemia.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.12
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• pp.5173-5177
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• 2016

Acute myeloid leukemia (AML), one of the most prevalent leukemia types in adults, demonstrates great heterogeneity in molecular and clinical terms. Hence, there is a necessity to the mechanisms involved in AML generation in order to determine optimal treatment. This cross sectional study aimed to assess changes in BECN1 gene expression in with blood samples from 30 AML patients, compared with samples from 15 healthy persons. RNA was extracted and cDNA was synthesized and Real Time PCR applied to determine BECN1 gene expression. The results showed no significant differences in BECN1 gene expression between patients with AML and normal controls (P > 0.05). It appears that expression of BECN1 does not play a significant role in genesis of AML leukemia.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.119-125
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• 1999

Mammalian gastric smooth muscles generate spontaneous rhythmic contractions which are associated with slow oscillatory potentials (slow waves) and spike potentials. Spike potentials are blocked by organic $Ca^{2+}-antagonists,$ indicating that these result from the activation of L-type $Ca^{2+}-channel.$ However, the cellular mechanisms underlying the generation of slow wave remain unclear. Slow waves are insensitive to $Ca^{2+}-antagonists$ but are blocked by metabolic inhibitors or low temperature. Recently it has been suggested that Interstitial Cells of Cajal (ICC) serve as pacemaker cells and a slow wave reflects the coordinated behavior of both ICC and smooth muscle cells. Small segments of circular smooth muscle isolated from antrum of the guinea-pig stomach generated two types of electrical events; irregular small amplitude (1 to 7 mV) of transient depolarization and larger amplitude (20 to 30 mV) of slow depolarization (regenerative potential). Transient depolarization occurred irregularly and membrane depolarization increased their frequency. Regenerative potentials were generated rhythmically and appeared to result from summed transient depolarizations. Spike potentials, sensitive to nifedipine, were generated on the peaks of regenerative potentials. Depolarization of the membrane evoked regenerative potentials with long latencies (1 to 2 s). These potentials had long partial refractory periods (15 to 20 s). They were inhibited by low concentrations of caffeine, perhaps reflecting either depletion of $Ca^{2+}$ from SR or inhibition of InsP3 receptors, by buffering $Ca^{2+}$ to low levels with BAPTA or by depleting $Ca^{2+}$ from SR with CPA. They persisted in the presence of $Ca^{2+}-sensitive$ $Cl^--channel$ blockers, niflumic acid and DIDS or $Co^{2+},$ a non selective $Ca^{2+}-channel$ blocker. These results suggest that spontaneous activity of gastric smooth muscle results from $Ca^{2+}$ release from SR, followed by activation of $Ca^{2+}-dependent$ ion channels other than $Cl^-$ channels, with the release of $Ca^{2+}$ from SR being triggered by membrane depolarization.

• Journal of Ginseng Research
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• v.44 no.1
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• pp.96-104
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• 2020

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

• Molecules and Cells
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• v.41 no.5
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• pp.465-475
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• 2018

The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.285-290
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• 2011

Naegleria fowleri, a ubiquitous free-living ameba, causes fatal primary amebic meningoencephalitis in humans. N. fowleri trophozoites are known to induce cytopathic changes upon contact with microglial cells, including necrotic and apoptotic cell death and pro-inflammatory cytokine release. In this study, we treated rat microglial cells with amebic lysate to probe contact-independent mechanisms for cytotoxicity, determining through a combination of light microscopy and scanning and transmission electron microscopy whether N. fowleri lysate could effect on both necrosis and apoptosis on microglia in a time- as well as dose-dependent fashion. A $^{51}Cr$ release assay demonstrated pronounced lysate induction of cytotoxicity (71.5%) toward microglial cells by 24 hr after its addition to cultures. In an assay of pro-inflammatory cytokine release, microglial cells treated with N. fowleri lysate produced TNF-${\alpha}$, IL-6, and IL-$1{\beta}$, though generation of the former 2 cytokines was reduced with time, and that of the last increased throughout the experimental period. In summary, N. fowleri lysate exerted strong cytopathic effects on microglial cells, and elicited pro-inflammatory cytokine release as a primary immune response.

• Smart Structures and Systems
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• v.23 no.6
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• pp.627-639
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• 2019

Passive control may not provide enough damping for a stay cable since the control devices are often restricted to a low location level. In order to enhance control performance of conventional passive dampers, a new type of damper integrated with a rotary electromagnetic damper providing variable damping force and a flywheel serving as an inertial mass, called the rotary electromagnetic inertial mass damper (REIMD), is presented for suppressing the cable vibrations in this paper. The mechanical model of the REIMD is theoretically derived according to generation mechanisms of the damping force and the inertial force, and further validated by performance tests. General dynamic characteristics of an idealized taut cable with a REIMD installed close to the cable end are theoretically investigated, and parametric analysis are then conducted to investigate the effects of inertial mass and damping coefficient on vibration control performance. Finally, vibration control tests on a scaled cable model with a REIMD are performed to further verify mitigation performance through the first two modal additional damping ratios of the cable. Both the theoretical and experimental results show that control performance of the cable with the REIMD are much better than those of conventional passive viscous dampers, which mainly attributes to the increment of the damper displacement due to the inertial mass induced negative stiffness effects of the REIMD. Moreover, it is concluded that both inertial mass and damping coefficient of an optimum REIMD will decrease with the increase of the mode order of the cable, and oversize inertial mass may lead to negative effect on the control performance.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.62-62
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• 2003

It is now convincing that free radical generation is involved in the pathophy siological mechanisms of ischemic stroke, particularly in ischemia-reperfusion injury. The present study, therefore, examined neuroprotective effect of aloesin isolated from Aloe vera, which was known to have antioxidative activity, in a rat model of transient focal cerebral ischemia. Transient focal cerebral ischemia was induced by occlusion of middle cerebral artery for 2 hr with a silicone-coated 4-0 nylon monofilament in male Sprague-Dawley rats under isoflurane anesthesia Aloesin (1, 3, 10, 30 and 50 mg/kg/injection) was administered intravenously 3 times at 0.5, 2 and 4 hr after onset of ischemia. Neurological score was measured 24 hr after onset of ischemia immediately before sacrifice. Seven serial coronal slices of the brain were stained with 2,3,5-triphenyltetrazolium chloride and infarct size was measured using a computerized image analyzer. Treatment with the close of 1 or 50 mg/kg did not significantly reduce infarct volume compared with the saline vehicle-treated control group. However, treatments with the closes of 3 and 10 mg/kg significantly reduced both infarct volume and edema by approximately 47% compared with the control group, producing remarkable behavioral recovery effect. Treatment with the close of 30 mg/kg also significantly reduced infarct volume to a lesser extent by approximately 33% compared with the control group, but produced similar degree of behavioral recovery effect. In addition, general pharmacological studies showed that aloesin was a quite safe compound. The results suggest that aloesin can serve as a lead chemical for the development of neuroprotective agents by providing neuroprotection against focal ischemic neuronal injury.

• Journal of Microbiology and Biotechnology
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• v.24 no.6
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• pp.869-878
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• 2014

In this study, we performed two-dimensional electrophoresis with protein extracts from lizard tails, and analyzed the protein expression profiles during the tissue regeneration to identify the dedifferentiation factor. As a result, we identified 18 protein spots among total of 292 spots, of which proteins were specifically expressed during blastema formation. We selected lactoferrin as a candidate because it is the mammalian homolog of leech-derived tryptase inhibitor, which showed the highest frequency among the 18 proteins. Lactoferrin was specifically expressed in various stem cell lines, and enhanced the efficiency of iPSC generation upto approximately 7-fold relative to the control. Furthermore, lactoferrin increased the efficiency by 2-fold without enforced expression of Klf4. These results suggest that lactoferrin may induce dedifferentiation, at least partly by increasing the expression of Klf4.

• The Korean Journal of Food And Nutrition
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• v.31 no.4
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• pp.495-501
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• 2018

Ultraviolet B (UVB) exposure is a risk factor for skin damage resulting in oxidative stress, inflammation, and cell death. The purpose of this study was to investigate the physicochemical properties of Platycodon grandiflorum (PG) to improve its biological activities using a three-step steaming process. We investigated the protective effects of PG and steamed PG extracts on human dermal fibroblasts (HDFs) against UVB radiation-induced oxidative stress and inflammation as well as the underlying mechanisms. The antioxidant potential of the PG extracts was evaluated by measuring the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) scavenging activity. ABTS and DPPH were shown by the 0, 30, and 70% ethanol extracts of 2S-PG and 3S-PG ($IC_{50}$, 28~45 and $27{\sim}30{\mu}g/mL$, respectively). Treatment of UVB-irradiated cells with steamed PG ($25{\sim}400{\mu}g/mL$) did not affect their viability. The streamed PG extract suppressed UVB-induced generation of reactive oxygen species (ROS). In addition, streamed PG extract reduced cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in UVB-irradiated HDF, regulating nuclear factor $(NF)-{\kappa}B$ expression. These findings suggest that steamed PG extract may be potentially effective against inflammation associated with UVB-induced oxidation stress.