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  1. Article ; Online: Dual Function of Secreted APE1/Ref-1 in TNBC Tumorigenesis

    Sunga Choi / Yu-Ran Lee / Ki-Mo Kim / Euna Choi / Byeong-Hwa Jeon

    International Journal of Molecular Sciences, Vol 23, Iss 16, p

    An Apoptotic Initiator and a Regulator of Chronic Inflammatory Signaling

    2022  Volume 9021

    Abstract: The simultaneous regulation of cancer cells and inflammatory immune cells in the tumor microenvironment (TME) can be an effective strategy in treating aggressive breast cancer types, such as triple-negative breast cancer (TNBC). Apurinic/apyrimidinic ... ...

    Abstract The simultaneous regulation of cancer cells and inflammatory immune cells in the tumor microenvironment (TME) can be an effective strategy in treating aggressive breast cancer types, such as triple-negative breast cancer (TNBC). Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multi-functional nuclear protein that can be stimulated and then secreted. The extracellular APE1/Ref-1 causes a reduction in disulfide bonds in cytokine receptors, resulting in their conformational changes, thereby inhibiting inflammatory signaling. Furthermore, the secreted APE1/Ref-1 in response to acetylation has been shown to bind to a receptor for the advanced glycation end product (RAGE), initiating the apoptotic cell death of TNBC in vitro and in vivo. This study used PPTLS-APE1/Ref-1 in an adenovirus vector (Ad-PPTLS-APE1/Ref-1) for the constant expression of extracellular APE1/Ref-1, and our results demonstrated its dual function as an apoptotic initiator and inflammation regulator. Injecting MDA-MB 231 orthotopic xenografts with the Ad-PPTLS-APE1/Ref-1 inhibited tumor growth and development in response to acetylation. Moreover, Ad-PPTLS-APE1/Ref-1 generated reactive oxygen species (ROS), and tumor tissues derived from these xenografts exhibited apoptotic bodies. Compared to normal mice, a comparable ratio of anti- and pro-inflammatory cytokines was observed in the plasma of Ad-PPTLS-APE1/Ref-1-injected mice. Mechanistically, the disturbed cytokine receptor by reducing activity of PPTLS-APE1/Ref-1 inhibited inflammatory signaling leading to the inactivation of the p21-activated kinase 1-mediated signal transducer and activator of transcription 3/nuclear factor-κB axis in tumor tissues. These results suggest that the regulation of inflammatory signaling with adenoviral-mediated PPTLS-APE1/Ref-1 in tumors modulates the secretion of pro-inflammatory cytokines in TME, thereby inhibiting aggressive cancer cell progression, and could be considered as a promising and safe therapeutic strategy for treating ...
    Keywords TNBC ; PPTLS-APE1/Ref-1 ; apoptosis ; tumor microenvironment ; cytokines ; anti-inflammatory signaling ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: The Effects of 1- O -Acetylbritannilactone Isolated from Inula britannica Flowers on Human Neutrophil Elastase and Inflammation of RAW 264.7 Cells and Zebrafish Larvae

    Ik Soo Lee / Yu-Ri Lee / Jea Heon Sim / Ki Mo Kim / Young Sook Kim

    Molecules, Vol 28, Iss 4320, p

    2023  Volume 4320

    Abstract: During a search for natural inflammatory inhibitors, 1- O -acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of Inula britannica . ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal ... ...

    Abstract During a search for natural inflammatory inhibitors, 1- O -acetylbritannilactone (ABL), a sesquiterpene lactone, was isolated from the flowers of Inula britannica . ABL significantly inhibited human neutrophil elastase (HNE) with a half-maximal inhibitory concentration (IC 50 ) of 3.2 ± 0.3 µM, thus did so more effectively than the positive control material (epigallocatechin gallate) (IC 50 7.2 ± 0.5 µM). An enzyme kinetic study was performed. ABL noncompetitively inhibited HNE with an inhibition constant K i of 2.4 µM. ABL inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E 2 production by RAW 264.7 cells in a dose-dependent manner, as well as the protein-level expression of inducible nitric oxide synthase and cyclooxygenase-2. The anti-inflammatory effect of ABL was confirmed using a transgenic Tg( mpx :EGFP) zebrafish larval model. The exposure of the larvae to ABL inhibited neutrophil recruitment to the site of injury after tail fin amputation.
    Keywords Inula britannica ; sesquiterpene lactone ; human neutrophil elastase ; RAW 264.7 cells ; zebrafish ; Organic chemistry ; QD241-441
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Efficacy and Safety of GHX02 in the Treatment of Acute Bronchitis and Acute Exacerbation of Chronic Bronchitis

    Su Won Lee / Yee Ran Lyu / Si Yeon Kim / Won Kyung Yang / Seung Hyung Kim / Ki Mo Kim / Sung-Wook Chae / Weechang Kang / In Chul Jung / Yang Chun Park

    Frontiers in Pharmacology, Vol

    A Phase Ⅱ, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

    2022  Volume 12

    Abstract: Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air ... ...

    Abstract Acute bronchitis and acute exacerbations of chronic bronchitis (AECB) have cough and sputum as the main symptoms with a high prevalence and substantial economic burden. Although the demand for bronchitis treatment increases due to causes, such as air pollution, the appropriateness of antibiotic prescriptions and the effects of current symptomatic treatments for bronchitis are unclear. GHX02, which is a combined formulation containing four herbs, and has been clinically used for bronchitis in South Korea. We conducted a phase II, randomized, double-blind, and placebo-controlled, multicenter trial to evaluate its efficacy and safety. Patients with acute bronchitis or AECB were recruited and randomized to receive high-dose GHX02 (1920 mg/day), standard-dose GHX02 (960 mg/day), or placebo for 7 days. The primary outcome measure was the change in Bronchitis Severity Score (BSS) from baseline to Day 7. The secondary outcomes were the frequency of coughing fits, Questionnaire of Clinical Symptoms of Cough and Sputum (QCSCS), Leicester Cough Questionnaire (LCQ), Integrative Medicine Outcome Scale (IMOS), and Integrative Medicine Patient Satisfaction Scale (IMPSS). A total of 117 patients were randomized to parallel groups (38 in the high-dose GHX02, 41 in the standard-dose GHX02 group, and 38 in the placebo group). The mean differences in BSS from baseline to Day 7 in the treatment groups (4.2 ± 2.0 and 4.5 ± 1.8 in the high-dose GHX02 and standard-dose GHX02 groups, respectively) were higher than the placebo group (3.8 ± 2.1), p = 0.028. The mean differences in the frequency of coughing fits from baseline to Day 7 and IMPSS were better in the GHX02 treatment group than in the placebo group (standard-dose GHX02 group vs placebo group, p = 0.036). The QCSCS, LCQ, IMOS, and GHX02 of the treatment groups also showed more improvement than the placebo group, but there were no statistically significant differences between the groups. There were no severe adverse effects during the trial. This study supports that GHX02 is ...
    Keywords acute bronchitis ; acute exacerbation of chronic bronchitis ; Ghx02 ; herbal drug ; Korean medicine ; Therapeutics. Pharmacology ; RM1-950
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Protective effects of Oxya chinensis sinuosa Mishchenko against ultraviolet B-induced photodamage in hairless mice

    A-Rang Im / InWha Park / Kon-Young Ji / Joo Young Lee / Ki Mo Kim / MinKyun Na / Sungwook Chae

    BMC Complementary and Alternative Medicine, Vol 19, Iss 1, Pp 1-

    2019  Volume 9

    Abstract: Abstract Background Edible insects, including Oxya chinensis sinuosa Mishchenko (Oc), which is consumed as food in Asia, are considered as a human food shortage alternative, and also as a preventive measure against environmental destruction. Ultraviolet ... ...

    Abstract Abstract Background Edible insects, including Oxya chinensis sinuosa Mishchenko (Oc), which is consumed as food in Asia, are considered as a human food shortage alternative, and also as a preventive measure against environmental destruction. Ultraviolet B (UVB) irradiation, which causes skin photodamage, is considered as an extrinsic skin aging factor. It reduces skin hydration, and increases wrinkle formation and reactive oxygen species (ROS) and inflammatory cytokine expression. Thus, the objective of this study was to investigate the anti-aging effects of an ethanol extract of Oc (Oc.Ex). Methods A UVB-irradiated hairless mouse model was used to examine relevant changes in skin hydration, wrinkle formation, and skin epidermal thickness. Also, antioxidant markers such as superoxide dismutase (SOD) and catalase (CAT) were analyzed, and Oc. Ex skin protective effects against UVB irradiation-induced photoaging were examined by determining the levels of skin hydration factors. Results Oc.Ex improved epidermal barrier dysfunctions such as increased transepidermal water loss (TEWL) and capacitance reduction in UVB-irradiated mice. It upregulated skin hydration-related markers, including hyaluronic acid (HA), transforming growth factor (TGF)-β, and pro-collagen, in UVB-irradiated mice, compared with the vehicle control group. It also reduced UVB-induced wrinkle formation, collagen degradation, and epidermal thickness. Additionally, it remarkably suppressed the increased expression of matrix metalloproteinases (MMPs), and restored the activity of SOD and CAT in UVB-irradiated mice, compared with the vehicle control group. Furthermore, Oc. Ex treatment downregulated the production of inflammatory cytokines and phosphorylation of the mitogen-activated protein kinases (MAPKs) signaling pathway activated by UVB irradiation. Conclusion This study revealed that Oc. Ex reduced skin thickness and the degradation of collagen fibers by increasing hydration markers and collagen-regulating factors in the skin of UVB-irradiated ...
    Keywords Oxya chinensis sinuosa Mishchenko ; UVB irradiation ; Matrix metalloproteinases ; Mitogen-activated protein kinase ; Photoprotective effect ; Other systems of medicine ; RZ201-999
    Subject code 571
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Therapeutic positioning of secretory acetylated APE1/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo

    Yu Ran Lee / Myoung Soo Park / Hee Kyoung Joo / Ki Mo Kim / Jeryong Kim / Byeong Hwa Jeon / Sunga Choi

    Scientific Reports, Vol 8, Iss 1, Pp 1-

    2018  Volume 16

    Abstract: Abstract Triple-negative breast cancer (TNBC) represents a relatively small proportion of all BCs but a relatively large proportion of BC-related death. Thus, more effective therapeutic strategies are needed for the management of TNBC. We demonstrated ... ...

    Abstract Abstract Triple-negative breast cancer (TNBC) represents a relatively small proportion of all BCs but a relatively large proportion of BC-related death. Thus, more effective therapeutic strategies are needed for the management of TNBC. We demonstrated that the stimulation of apoptosis by the binding of secreted acetylated-apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1) to the receptor for advanced glycation end products (RAGE) was essential for TNBC cell death in response to hyperacetylation. The aim of the present study was to assess the potential therapeutic efficacy of secretory Ac-APE1/Ref-1 in orthotopic TNBC xenografts in vivo. We found that hyperacetylation in xenografts caused secretion of Ac-APE1/Ref-1 into the blood, where the factor bound directly to RAGE in hyperacetylated tumor tissues. Hyperacetylation in the TNBC xenografts induced strong inhibition of tumor growth and development, leading to apoptotic cell death, accompanied by increased RAGE expression and generation of reactive oxygen species. Tissues exhibited markedly higher counts of apoptotic bodies, a reduced proliferation index, and reduced neovascularization compared with control tumors. Ac-APE1/Ref-1-stimulated apoptosis was markedly reduced in RAGE-knockdown tumors compared with RAGE-overexpressing tumors, even in the presence of hyperacetylation. The function of secreted Ac-APE1/Ref-1 was confirmed in other hyperacetylated TNBCs xenografts using BT-549 and MDA-MB-468 cells, demonstrating its relevance as an anti-cancer molecule.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2018-06-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: High–efficiency generation of induced pluripotent stem cells from human foreskin fibroblast cells using the Sagunja-tang herbal formula

    Ki Mo Kim / Deok Rim Heo / Joo Young Lee / Chang-Seob Seo / Sun-Ku Chung

    BMC Complementary and Alternative Medicine, Vol 17, Iss 1, Pp 1-

    2017  Volume 9

    Abstract: Abstract Background Sagunja-Tang (SGT-4) is a traditional herbal formula in Korean medicine that is used to treat anti-metabolic syndrome, and has antioxidant activity. In this study, we evaluated the effects of SGT-4 on the formation efficiency of ... ...

    Abstract Abstract Background Sagunja-Tang (SGT-4) is a traditional herbal formula in Korean medicine that is used to treat anti-metabolic syndrome, and has antioxidant activity. In this study, we evaluated the effects of SGT-4 on the formation efficiency of induced pluripotent stem cells (iPSCs) from human foreskin fibroblasts (HFFs) by four reprogramming transcription factors: Oct4, Sox2, KIf4, and c-Myc (OSKM). Methods SGT-4 contained four different herbal medicines that are composed of Ginseng Radix, Glycyrrhizae Radix et Rhizoma, Atractylodis Rhizoma Alba, and Poria Sclerotium. The composition of SGT-4 was analyzed by high-performance liquid chromatography (HPLC). HFFs were transfected with episomal vectors contained by four OSKM. Western blotting, RT-PCR, immunofluroescence, and in vitro differentiation were used to assess the pluripotency of the iPSC cells. Results SGT-4 exhibited antioxidant activity against the generation of intracellular reactive oxygen species (ROS) as well as promoted the activation of superoxide dismutase 1 (SOD1), catalase, gluthathione peroxidase 1 (GPX1), and glutathione (GSH). Moreover, the ATP level was not significantly fluctuated depending on the concentration of SGT-4 in the hiPSCs. Conclusion Our results indicate that the SGT-4, herbal formula significantly increases the efficiency of human iPSC generation via the transcription factors (Oct4, Sox2, KIf4, and c-Myc).
    Keywords Sagunja-tang ; Induced pluripotent stem cells ; Reactive oxygen species ; Human foreskin fibroblast ; Alkaline phosphatase staining ; Other systems of medicine ; RZ201-999
    Subject code 500
    Language English
    Publishing date 2017-12-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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