• Journal of Korean Neurosurgical Society
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• 제37권2호
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• pp.129-136
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• 2005

Objective: Currently available therapies for human malignant gliomas have limited efficacy. Toxoplasma gondii, an obligate intracellular protozoan parasite, and Quil-A are nonspecific, potent immune stimulants. T. gondii is shown to have antitumor activity in some types of cancers. Therefore, this study is undertaken to evaluate the antitumor effect of Toxoplasma lysate antigen (TLA), alone or in combination with Quil-A, on human glioma U373MG and U87MG cells. Methods: The in vitro effects of TLA alone or in combination with Quil-A on the proliferation, invasion, and apoptosis of glioma cells were tested using MTT, Matrigel invasion, and DNA fragmentation assays, and the in vivo effects on the growth of gliomas were evaluated in athymic nude mice transplanted with glioma cells. Results: Treatment with TLA resulted in the suppressed proliferation and invasion of both U373MG and U87MG cells, in a dose-dependent manner. In addition, at high concentration, TLA induced glioma cell apoptosis. When TLA was administered in the mouse glioma model, malignant glioma growth was decreased. The combined treatment of TLA with Quil-A significantly inhibited the proliferation and invasion of cultured cells as well as tumor mass of implanted mice. Conclusion: TLA inhibits the proliferation and invasion of glioma cells in vitro and in vivo, and these antitumor effects of TLA are significantly enhanced by the addition of Quil-A.

• 생명과학회지
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• 제22권10호
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• pp.1339-1343
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• 2012

알레르기성 아토피 피부염은 면역적 반응을 포함하는 복잡한 원인을 가진 염증성 질환이다. 본 연구는 ICR mice의 등쪽 부위에 반복적인 DNCB 도포를 통해 유발시킨 알레르기성 아토피 피부염에 있어서 PG-Platycodin D의 효능에 대해 연구하였다. PG-Platycodin D의 효능은 scratching behavior, skin severity score, 그리고 조직병리학적 관찰을 통해서 확인하였다. PG-Platycodin D가 scratching behavior, skin severity score 수준을 감소시킴을 확인할 수 있었다. 또한, 조직병리학적 관찰에 의해 PG-Platycodin D군에서 피부의 부종이 효과적으로 억제됨을 알 수 있었다. 이러한 결과로부터 알레르기성 아토피 피부염에 있어서 Platycodin D가 포함된 도라지 추출물이 유용한 천연 원료 물질로서 가능성을 가짐을 확인하였다.

• Biomolecules & Therapeutics
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• 제20권4호
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• pp.380-385
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• 2012

Glucosamine (GS) is well known for the treatment of inflammation. However, the mechanism and efficacy of GS for skin inflammation are unclear. The aim of this study was to evaluate the effects and mechanism of GS in the mouse 12-O-tetradecanoyl 13-acetate (TPA)-induced ear edema model. TPA-induced ear edema was evoked in ICR or transglutaminase 2 (Tgase-2) (-/-) mice. GS was administered orally (10-100 mg/kg) or topically (0.5-2.0 w/v %) prior to TPA treatment. Orally administered GS at 10 mg/kg showed a 76 or 57% reduction in ear weight or myeloperoxidase, respectively, and a decreased expression of cyclooxygenase-2 (COX-2), NF-${\kappa}B$ and Tgase-2 in TPA-induced ear edema by western blot and immunohistochemistry. Role of Tgase-2 in TPA ear edema is examined using Tgase-2 (-/-) mice and TPA did not induce COX-2 expression in ear of Tgase-2 (-/-) mice. These observations suggested that Tgase-2 is involved in TPA-induced COX-2 expression in the inflamed ear of mice and antiinflammatory effects of glucosamine is mediated through suppression of Tgase-2 in TPA ear edema.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.308-314
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• 2017

Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis. In this study, we evaluated the effects of a newly synthesized UII receptor (UT) antagonist, KR-36996, on the proliferation of SMCs in vitro and neointima formation in vivo in comparison with GSK-1440115, a known potent UT antagonist. In primary human aortic SMCs (HASMCs), UII (50 nM) induced proliferation was significantly inhibited by KR-36996 at 1, 10, and 100 nM which showed greater potency ($IC_{50}$: 3.5 nM) than GSK-1440115 ($IC_{50}$: 82.3 nM). UII-induced proliferation of HASMC cells was inhibited by U0126, an ERK1/2 inhibitor, but not by SP600125 (inhibitor of JNK) or SB202190 (inhibitor of p38 MAPK). UII increased the phosphorylation level of ERK1/2. Such increase was significantly inhibited by KR-36996. UII-induced proliferation was also inhibited by trolox, a scavenger for reactive oxygen species (ROS). UII-induced ROS generation was also decreased by KR-36996 treatment. In a carotid artery ligation mouse model, intimal thickening was dramatically suppressed by oral treatment with KR-36996 (30 mg/kg) which showed better efficacy than GSK-1440115. These results suggest that KR-36996 is a better candidate than GSK-1440115 in preventing vascular proliferation in the pathogenesis of atherosclerosis and restenosis.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.9.1-9.10
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• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

• Journal of Ginseng Research
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• 제43권4호
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• pp.550-561
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• 2019

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU. Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from $Schr{\ddot{o}}dinger$ was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2. Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects. Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.

• Biomolecules & Therapeutics
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• 제30권1호
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• pp.80-89
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• 2022

The targeting of DNA methylation in cancer using DNA hypomethylating drugs has been well known to sensitize cancer cells to chemotherapy and immunotherapy by affecting multiple pathways. Herein, we investigated the combinational effects of DNA hypomethylating drugs and ionizing radiation (IR) in human sarcoma cell lines both in vitro and in vivo. Clonogenic assays were performed to determine the radiosensitizing properties of two DNA hypomethylating drugs on sarcoma cell lines we tested in this study with multiple doses of IR. We analyzed the effects of 5-aza-dC or SGI-110, as DNA hypomethylating drugs, in combination with IR in vitro on the proliferation, apoptosis, caspase-3/7 activity, migration/invasion, and Western blotting using apoptosis- or autophagy-related factors. To confirm the combined effect of DNA hypomethylating drugs and IR in our in vitro experiment, we generated the sarcoma cells in nude mouse xenograft models. Here, we found that the combination of DNA hypomethylating drugs and IR improved anticancer effects by inhibiting cell proliferation and by promoting synergistic cell death that is associated with both apoptosis and autophagy in vitro and in vivo. Our data demonstrated that the combination effects of DNA hypomethylating drugs with radiation exhibited greater cellular effects than the use of a single agent treatment, thus suggesting that the combination of DNA hypomethylating drugs and radiation may become a new radiotherapy to improve therapeutic efficacy for cancer treatment.

• 한국정보전자통신기술학회논문지
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• 제15권5호
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• pp.396-404
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• 2022

쑥갓(Chrysanthemum coronarium L.)에는 베타카로틴을 비롯한 비타민 A,C, 폴리페놀 성분 등 여러 항산화 물질들이 포함되어 있고 항염증 효능을 보유한다고 알려져 있다. 추출물에 포함되는 PDRN이 항염증 반응을 매개할 수 있다는 가정하에, 마우스 대식세포인 RAW264.7 세포를 Lipopolysaccharides(LPS)로 자극하여 염증세포로의 전환을 유도한 다음, 쑥갓에서 추출한 PDRN의 첨가가 염증 억제 효능이 있는지를 분석하였다. 항염증의 지표로는 IL-1β, TNF-α의 유전자 발현을 사용하였으며, RT-PCR로 각 유전자의 상대적인 발현량을 확인하였다. 분걱 결과, RT-PCR에서는 IL-1β, TNF-α 두 유전자에서 PDRN에 의한 염증 억제의 효과를 확인하였다. 따라서, 본 연구를 토대로 염증 질환의 치료제로 개발될 수 있는 선행자료라 사료되며, 염증억제 기전을 개선할 수 있는 치료제의 연구개발에 도움이 될 것이다.

• Archives of Plastic Surgery
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• 제37권3호
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• pp.220-226
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• 2010

Purpose: Many topical agents had been used for burn or wound treatment. An awareness of topical agents on various aspects of wound healing permits the clinician to choose the most appropriate material to advantageously control the wound process and final results. Although polydeoxyribonucleotide (PDRN) was used as a tissue repair stimulating agent in a number of human diseases, such as ulcers and burns, its wound healing effects were largely unreported. We aimed to compare the woundhealing effects of PDRN and common dressing materials on full-thickness skin defect in the mouse. Methods: Full-thickness skin defects were made on the back of mice (N=60). The mice were divided into the following 4 groups according to the dressing used for the wounds: group O (Polydeoxyribonucleotide cream), group I (Polydeoxyribonucleotide solution), group M (Medifoam$^{(R)}$), and group G (dry gauze, control group). We analyzed the gross findings, wound sizes and histological findings for the groups. Results: The rate of wound size was decreased in order of group I, group O, group M and group G. The histological findings revealed that the I group showed more reepithelialization and granulation tissue formation and less inflammatory cell infiltration than the other materials. The grade score of wound healing was increased in order of group I, group O, group M and group G. Conclusion: PDRN applicated wound dressings can be used for treating a full-thickness skin defect wounds. Considering its superior efficacy in comparison to the efficacies of other wound dressings, PDRN soaked gauze dressing should be preferentially used for the treatment of fullthickness skin wounds.

• Archives of Plastic Surgery
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• 제37권2호
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• pp.115-121
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• 2010

Purpose: Many topical agents had been used for contaminated wound treatment. Although antimicrobial ointments were widely used as topical agents, their comparative antibacterial and wound healing effects were largely unreported. The purpose of this study was to compare antibacterial effects and wound healing effects of common topical ointments on infected full thickness skin defect in the mouse. Methods: One full thickness skin defects in the mice (n=60) were developed on the back and left open for twenty-four hours. Sixty mice were divided into four groups: group B (dressing with Bactroban$^{(R)}$, n=15), group I (dressing with Iodosorb$^{(R)}$, n=15), group T (dressing with Terramycin$^{(R)}$, n=15), group G (control group, dressing with dry gauze, n=15). The size of wound defects and the grades of wound healing were evaluated at 4, 7, 10 days, and antibacterial effect was evaluated with restricted zone in Mueller Hinton agar by disk diffusion method. After the wound was left open for twenty-four hours, many Staphylococcus aureus was cultured. The wound defect size was decreased in order of Bactroban$^{(R)}$ (B), Iodosorb$^{(R)}$ (I), Terramycin$^{(R)}$ and gauze dressing group in all days, but difference among experimental groups was not statistically significant. The grade score of wound healing was increased in order of Bactroban$^{(R)}$, Iodosorb$^{(R)}$, Terramycin$^{(R)}$ and gauze dressing group, and the difference was statistically significant. Antibacterial effect for was increased in order of Bactroban$^{(R)}$, Iodosorb$^{(R)}$, Terramycin$^{(R)}$ and gauze dressing group, and the difference was statistically significant. Conclusion: Topical antimicrobial ointments application was effective against wound infections by S. aureus. Bactroban$^{(R)}$ may be an optimal topical treatment for infected wounds according to this study. However, further study is necessary to evaluate the clinical efficacy of antimicrobial ointments and to search for the mechanisms that explain their effects.