• BMB Reports
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• 제55권4호
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• pp.198-203
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• 2022

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

• 대한통합의학회지
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• 제12권1호
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• pp.27-39
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• 2024

Purpose : Smoking is a major factor in chronic obstructive pulmonary disease (COPD), but the effect of electrical cigarette smoking on COPD development is still uncertain. This study aimed to compare the functions of airways and lungs exposed to combustible cigarettes and electrical cigarettes based on the pulmonary function test (PFT) results from the Korean National Health and Nutrition Examination Survey (NHANES). Methods : This study used data from 8,942 participants with PFT results out of 47,309 total subjects from the 6th to 8th Korean NHANES (2014-2015, 2016-2018, and 2019, respectively). Individuals with diseases such as cancer, ex-smokers, and dual tobacco users were excluded. The PFT results were analyzed according to the COPD diagnostic criteria. After adjusting for confounding variables, a complex sample generalized linear model ANOVA test was performed to investigate the association between PFT results and combustible smoker or electrical cigarette user groups. Results : In an analysis based on the obstructive ventilatory disorders (forced expiratory volume in 1 second[FEV₁]/forced vital capacity[FVC]<.7), combustible cigarette smokers showed a 3.46 times higher risk of COPD compared to non-smokers, while electrical cigarette smokers exhibited no significant difference in terms of COPD-related risks compared to non-smokers. FEV₁ showed a negative relation with combustible cigarette smokers as reported elsewhere (B=-.07, p<.001). FEV₁/FVC was negatively related to both combustible cigarette smokers (B=-.03, p<.001) and electrical cigarette smokers (B=-.02, p<.001). Conclusion : FEV₁/FVC decreases were observed in the long-term exposure to both combustible and electrical cigarettes. The lower FEV₁ in the combustible cigarette group implies the worsening of the severity of COPD, suggesting more damage to the airways and lungs in the short term. Therefore, the temporary electrical cigarettes use for the transition period in order to smoking cessation potentially aids to reduce the harmful effect of combustible cigarettes in COPD development.

• Korean Journal of Mathematics
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• 제28권4호
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• pp.889-906
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• 2020

In this article, we consider the uniqueness problem of the shift polynomials $f^n(z)(f^m(z)-1){\prod\limits_{j=1}^{s}}f(z+c_j)^{{\mu}_j}$ and $f^n(z)(f(z)-1)^m{\prod\limits_{j=1}^{s}}f(z+c_j)^{{\mu}_j}$, where f(z) is a transcendental entire function of finite order, cj (j = 1, 2, …, s) are distinct finite complex numbers and n(≥ 1), m(≥ 1), s and µj (j = 1, 2, …, s) are integers. With the concept of weakly weighted sharing and relaxed weighted sharing we obtain some results which extend and generalize some results due to P. Sahoo [Commun. Math. Stat. 3 (2015), 227-238].

• Journal of Microbiology and Biotechnology
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• 제21권2호
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• pp.176-182
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• 2011

The study objective was to prepare biodegradable branched dextran microspheres encapsulated with His-tagged interferon-alpha (BDM-hIFN-${\alpha}$) and evaluate its activity in vitro and in vivo. The glycidyl methacrylate derivatized dextrans (Dex-GMA) as precursor was primarily synthesized by substituting hydroxyl groups of either the branched or linear type of dextran with GMA. Dex-GMA microspheres loaded with hIFN-${\alpha}$ was then prepared by the water-in-water emulsion technique. In vitro release and Western blotting experiments demonstrated the retained activity of hIFN-${\alpha}$ released from branched dextran microspheres at 24 h by inducing phosphorylation of signal transducer and activator transcription-1 (STAT-1), a down-stream effector of IFN-${\alpha}$, in HepG2 cells. Animal data further revealed a peak of plasma levels of IFN-${\alpha}$ in rats injected intravenously with BDM-hIFN-${\alpha}$ at 10 min post-injection, but a sharp decline at 2 h. High plasma levels of neopterin, a plasma protein induced by IFN-${\alpha}$, were also detected in rats injected with BDM-hIFN-${\alpha}$ at 10 min post-injection. Notably, plasma levels of neopterin remained high at 4 h, but largely declined thereafter.

• KSBB Journal
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• 제29권1호
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• pp.50-57
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• 2014

NF-${\kappa}B$ is a transcriptional factor which is involved in many biological processes including immunity, inflammation, and cell survival. Many investigators studied on the mechanism involved in activation of NF-${\kappa}B$ signalling pathway via ubiquitination and degradation of $I{\kappa}B$ regarding skin disease. Some specific molecules including Akt, MEK, p38 MAP Kinase, Stat3, et al. represent convergence points and key regulatory proteins in signaling pathways controlling cellular events such as growth and differentiation, energy homeostasis, and the response to stress and inflammation. Ultraviolet (UV) irradiation has many adverse effects on skin, including inflammation, alteration in the extracellular matrix, cellular senescence, apoptosis and skin cancer. Prunus mume, a naturally derived plant extract, has beneficial biological activities as blood fluidity improvement, anti-fatigue action, antioxidative and free radical scavenging activities, inhibiting the motility of Helicobacter pyolri. Previous reports on various beneficial function prompted us to investigate UVB-induced or other immunostimulated biological marker regarding P. mume extract. P. mume extract suppresses UVB-induced cyclooxygenase-2 (COX-2) expression in mouse skin epidermal JB6 P+ cells. The activation of activator protein-1 and nuclear factor-${\kappa}B$ induced by UVB was dose-dependently inhibited by P. mume extract treatment. This results suggest that P. mume extracts might be used as a potential agents for protection of inflammation or UVB induced skin damage.

• Natural Product Sciences
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• 제26권2호
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• pp.136-143
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• 2020

Psoriasis is one of the most common inflammatory skin disorders, with a global prevalence of 2% - 3%. It is an autoimmune skin disorder characterized by excessive generation of plaques on the skin with typical long-lasting red, itchy, and scaly lesions. In this study, we aimed to elucidate the anti-psoriatic effect of the methanolic extract of Persicaria senticosa (PS), a bioactive edible plant extract used in traditional medicine, using a mouse model of imiquimod (IMQ)-induced psoriasis. The daily topical application of IMQ could induce human psoriasis-like lesion. The extract ameliorated IMQ-induced psoriasis. Furthermore, hematoxylin and eosin staining and the Psoriasis Area and Severity Index (PASI) scores indicated that topical application of PS led to an improvement in erythema, scaling, and thickness scores of the mouse dorsal skin and a considerable decrease in the epidermal thickness of the ear and dorsal skin in the IMQ-induced psoriatic mouse model. We also studied the effect of PS on the proliferation of keratinocytes using HaCaT cells. The extract inhibited cell proliferation and IL-6 and pSTAT3 expression induced by M5 cocktail (comprising interleukin [IL]-1α, IL-17A, IL-22, oncostatin M, and tumor necrosis factor-α) in HaCaT cells. Thus, PS might serve as a potential therapeutic agent for the treatment of psoriasis.

• 한국발생생물학회지:발생과생식
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• 제12권2호
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• pp.159-168
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• 2008

Nanog is a newly identified member of the homeobox family of DNA binding transcription factors that functions to maintain the undifferentiated state of stem cells. However, molecular mechanisms underlying the function of Nanog remain largely unknown. To elucidate the regulatory roles of Nanog involved in maintenance of P19 embryonal carcinoma (EC) stem cells, we transfected three small interfering RNA (siRNA) duplexes targeted against different regions of the Nanog gene into P19 cells. The Nanog siRNA-100 duplexes effectively decreased the expression of Nanog up to 30.7% compared to other two Nanog siRNAs, the Nanog siRNA-400 (67.9 %) and -793 (53.0%). When examined by RT-PCR and real-time PCR, the expression of markers for pluripotency such as Fgf4, Oct3/4, Rex1, Sox1 and Yes was downregulated at 48 h after transfection with Nanog siRNA-100. Furthermore, expression of the ectodermal markers, Fgf5 and Isl1 was reduced by Nanog knockdown. By contrast, the expression of other markers for pluripotency such as Cripto, Sox2 and Zfp57 was not affected by Nanog knockdown at this time. On the other hand, the expression of Lif/Stat3 pathway molecules and of the endoderm markers including Dab2, Gata4, Gata6 and the germ cell nuclear factor was not changed by Nanog knockdown. The results of this study demonstrated that the knockdown of Nanog expression by RNA interference in P19 cells was sufficient to modulate the expression of pluripotent markers involved in the self-renewal of EC stem cells. These results provide the valuable information on potential downstream targets of Nanog and add to our understanding of the function of Nanog in P19 EC stem cells.

• Biomolecules & Therapeutics
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• 제31권2호
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• pp.219-226
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• 2023

Furanocoumarin 8-methoxypsoralen (8-MOP) is the parent compound that naturally occurs in traditional medicinal plants used historically. 8-MOP has been employed as a photochemotherapeutic component of Psoralen + Ultraviolet A (PUVA) therapy for the treatment of vitiligo and psoriasis. Although the role of 8-MOP in PUVA therapy has been studied, little is known about the effects of 8-MOP alone on human gastric cancer cells. In this study, we observed anti-proliferative effect of 8-MOP in several human cancer cell lines. Among these, the human gastric cancer cell line SNU1 is the most sensitive to 8-MOP. 8-MOP treated SNU1 cells showed G1-arrest by upregulating p53 and apoptosis by activating caspase-3 in a dose-dependent manner, which was confirmed by loss-of-function analysis through the knockdown of p53-siRNA and inhibition of apoptosis by Z-VAD-FMK. Moreover, 8-MOP-induced apoptosis is not associated with autophagy or necrosis. The signaling pathway responsible for the effect of 8-MOP on SNU1 cells was confirmed to be related to phosphorylated PI3K, ERK2, and STAT3. In contrast, 8-MOP treatment decreased the expression of the typical metastasis-related proteins MMP-2, MMP-9, and Snail in a p53-independent manner. In accordance with the serendipitous findings, treatment with 8-MOP decreased the wound healing, migration, and invasion ability of cells in a dose-dependent manner. In addition, combination treatment with 8-MOP and gemcitabine was effective at the lowest concentrations. Overall, our findings indicate that oral 8-MOP has the potential to treat early human gastric cancer, with fewer side effects.

• 한방안이비인후피부과학회지
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• 제35권2호
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• pp.1-12
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• 2022

Objectives : This study was conducted to verify the anti-inflammatory effects of Aster glehni water extracts in HaCaT keratinocytes. Methods : In this study, cell viability was confirmed by MTT assay. Production of TNF-α and IL-6 was determined by ELISA. mRNA expression of TARC and MDC were measusred by qRT-PCR. Also, expressions of p-JNK, JNK, p-ERK, ERK, p-p38, and p-38 were investigated by using western blot assay. Results : Aster glehni water extracts were not shown any significant cytotoxicity at 15.625-500㎍/㎖ in HaCaT keratinocytes. Aster glehni extracts inhibited the TNF-α and IL-6 production in HaCaT keratinocytes treated with TNF-α and IFN-γ. Also, expression of TARC, MDC, p-ERK, and p-STAT1 was decreased. Conclusions : These results suggest that Aster glehni water extracts have anti-inflammatory effects in HaCaT keratinocytes and can be applied to the development of anti-inflammatory treatment substances.

• 농업과학연구
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• 제41권3호
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• pp.237-243
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• 2014

Human Glucagon like peptide-1 (GLP-1) is an incretin hormone that promotes secretion of insulin. In order to eliminate the formation of the soluble aggregate, Ala19 in GLP-1 was substituted with Thr, resulting in a GLP-1 mutant GLP-1A19T. The gene synthesis of GLP-1A19T and the fusion of 6-lysine tagged ubiquitin gene were accomplished by using the overlap extension polymerase chain reaction. The ubiquitin fused GLP-1A19T (K6UbGLP-1A19T) is expressed as form of inclusion body with little formation of the soluble aggregation in recombinant E. coli. In order to produce K6UbGLP-1A19T in large amounts, fed-batch fermentation was carried out in a pH-stat feeding strategy. Maximum dry cell weight of 87.7 g/L and 20.4% of specific K6UbGLP-1A19T content were obtained. Solid-phase refolding using a cation exchanger was carried out to renature K6UbGLP-1A19T. The refolded K6UbGLP-1A19T aggregated little and was released GLP-1A19T by on-column cleavage with ubiquitin-specific protease-1. The molecular mass of GLP-1A19T showed an accurate agreement with its theoretical molecular mass.