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Comparison of anticancer activities of Korean Red Ginseng-derived fractions

  • Baek, Kwang-Soo;Yi, Young-Su;Son, Young-Jin;Jeong, Deok;Sung, Nak Yoon;Aravinthan, Adithan;Kim, Jong-Hoon;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.41 no.3
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    • pp.386-391
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    • 2017
  • Background: Korean Red Ginseng (KRG) is an ethnopharmacological plant that is traditionally used to improve the body's immune functions and ameliorate the symptoms of various diseases. However, the antitumorigenic effects of KRG and its underlying molecular and cellular mechanisms are not fully understood in terms of its individual components. In this study, in vitro and in vivo antitumorigenic activities of KRG were explored in water extract (WE), saponin fraction (SF), and nonsaponin fraction (NSF). Methods: In vitro antitumorigenic activities of WE, SF, and NSF of KRG were investigated in the C6 glioma cell line using cytotoxicity, migration, and proliferation assays. The underlying molecular mechanisms of KRG fractions were determined by examining the signaling cascades of apoptotic cell death by semiquantitative reverse transcriptase polymerase chain reaction and Western blot analysis. The in vivo antitumorigenic activities of WE, SF, and NSF were investigated in a xenograft mouse model. Results: SF induced apoptotic death of C6 glioma cells and suppressed migration and proliferation of C6 glioma cells, whereas WE and NSF neither induced apoptosis nor suppressed migration of C6 glioma cells. SF downregulated the expression of the anti-apoptotic gene B-cell lymphoma-2 (Bcl-2) and upregulated the expression of the pro-apoptotic gene Bcl-2-associated X protein (BAX) in C6 glioma cells but had no effect on the expression of the p53 tumor-suppressor gene. Moreover, SF treatment resulted in activation of caspase-3 as evidenced by increased levels of cleaved caspase-3. Finally, WE, SF, and NSF exhibited in vivo antitumorigenic activities in the xenograft mouse model by suppressing the growth of grafted CT-26 carcinoma cells without decreasing the animal body weight. Conclusion: These results suggest that WE, SF, and NSF of KRG are able to suppress tumor growth via different molecular and cellular mechanisms, including induction of apoptosis and activation of immune cells.

Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells

  • Lee, Yoon-Jin;Bae, Jin-Ho;Kim, Soo-A;Kim, Sung-Ho;Woo, Kee-Min;Nam, Hae-Seon;Cho, Moon-Kyun;Lee, Sang-Han
    • Molecules and Cells
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    • v.40 no.8
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    • pp.567-576
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    • 2017
  • The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

Comparative Study of Pneumonia Caused by Streptococcus pneumonia and Legionella pneumophila (레지오넬라 폐렴과 폐렴구균 폐렴 환자의 임상 양상에 대한 비교)

  • Lyu, Ji-Won;Song, Jin-Woo;Choi, Chang-Min;Oh, Yeon-Mok;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Mi-Na;Shim, Tae-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.68 no.2
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    • pp.74-79
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    • 2010
  • Background: Legionella pneumophila has been recognized as an important cause of pneumonia. However, limited data are available in the literature regarding legionella pneumonia in Korea. The objective of this study was to compare epidemiological data and clinical presentation of legionella pneumonia and pneumococcal pneumonia. Methods: We retrospectively compared clinical, radiological, and laboratory data, antimicrobial treatment, and treatment outcomes between 28 cases of legionella pneumonia and 56 cases of pneumococcal pneumonia. Diagnoses of both legionella and pneumococcal pneumonia were based on commercial urinary antigen tests. Results: Legionella pneumonia patients included 23 men and 5 women, with a mean age of 61.6 years (range 36~88). Fifteen were smokers and 26 had some underlying diseases. Legionella pneumonia occurred more frequently in healthcare-associated settings than pneumococcal pneumonia (42.9% vs 21.4%, respectively, p=0.040). There were no significant differences in clinical signs and symptoms. Compared to patients with pneumococcal pneumonia, patients with legionella pneumonia presented more frequently with anemia (39.3% vs 8.9%, p=0.001), increased C-reactive protein (57.1% vs 30.4%, p=0.018) and increased alkaline phosphatase (46.4% vs 16.1%, p=0.003). Also, legionella pneumonia patients more often showed pleural effusion on simple chest X-rays (50.0% vs 12.5%, p<0.001). Conclusion: Legionella pneumonia and pneumococcal pneumonia can not be distinguished by clinical manifestations alone. However, legionella pneumonia occurred as a healthcare-associated pneumonia more frequently and was more often associated with anemia and increased CRP and alkaline phosphatase levels.

Development of the transgenic silkworm producing a improved green fluorescence cocoon (실용형질이 우수한 녹색 형광실크 형질전환 누에 개발)

  • Piao, Yulan;Kim, Sung-Wan;Kim, Seong-Ryul;Kim, Kee-Young;Kang, Seok-Woo;Goo, Tae-Won;Choi, Kwang-Ho
    • Journal of Sericultural and Entomological Science
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    • v.52 no.2
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    • pp.117-122
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    • 2014
  • On previous studies, we constructed a transgenic silkworm which produces the chimeric silk fused green fluorescent protein (EGFP), but the transgenic silkworm has decreased commercial feasible traits such as convenience of breeding and productivity of silk. In this study, we performed cross fertilization between green fluorescent silk transgenic silkworm and colored cocoon silkworm descents to make the transgenic the transgenic silkworm producing improved fluorescence cocoon. In the result, we found out a bit valuable cross fertilization manners ($female{\times}male$) in respect of silk productivity such as $T59B{\times}Jam26$, $Jam329{\times}T59W$, $T59W{\times}Jam329$, and $T59W{\times}Jam178$. The color-difference of offspring cocoons were measured according to different cross manners using by CIE Lab-based formulae with a X-rite VS450. In the result, the depth of green color of cocoons was a little high at cross manners as $Jam329{\times}T59W$, $T59W{\times}Jam178$. Meanwhile, the depth of yellow clolor of cocoons was remarkable at cross manners as $Jam178{\times}T59W$, $T59W{\times}Jam178$, respectively.

Glioblastoma in a Pekingese (페키니즈견의 아교모세포종 증례)

  • Cho, Hyun-kee;Yoo, Dae-Young;Kang, Joo-yeon;Lee, Kwon-Young;Hwang, In-Koo;Choi, Jung-Hoon;Chung, Jin-Young
    • Journal of Veterinary Clinics
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    • v.32 no.6
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    • pp.544-547
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    • 2015
  • An 11-year-old, intact male Pekingese was brought to the Veterinary Teaching Hospital of Kangwon National University with a 10-day history of seizures. Fifteen days before coming to Kangwon National University, the dog had visited a local animal hospital for lameness, and non-steroidal anti-inflammatory drugs were prescribed to treat this symptom. However, 10 days before coming to our hospital, the dog experienced generalized seizures. Two days before his arrival, generalized ataxia and mental dullness also occurred. Our examinations revealed no remarkable findings on a routine blood test or X-ray. However, the neurological examinations confirmed mental dullness, generalized ataxia, and a lack of menace response and pupillary light reflexes. Nine hours later, dyspnea occurred, and 12 hours after that, the patient was euthanized per the client's request. A necropsy of transverse sections confirmed the presence of a prominent midline shift due to extended tumor growth. On histopathological analyses, pseudopalisading necrosis of the glial cells and microvascular proliferation were observed. In immunohistochemical analysis, glial fibrillary acidic protein, proliferating cell nuclear antigens, and ionized calcium binding adaptor molecule 1 immunoreactive cells were observed in the tumor area. Based on the results, the tumor was confirmed to be a glioblastoma. Primary intracranial tumors are rare in the veterinary field. This case report describes the clinical and histopathological findings of glioblastoma in a Pekingese.

Respiratory Protective Effect of Salvia plebeia R. Br. Extracts against Ambient Particulate Matter-induced Airway Inflammation (미세먼지 유도 기도염증에 대한 배암차즈기 추출물의 호흡기 보호 효과)

  • Song, Hyeongwoo;Ji, Kon Young;Kim, Bok Kyu;Yang, Won Kyung;Han, Chang Kyun;Shin, Han Jae;Park, Yang Chun;Hwang, Ji Sook;Kang, Hyung Sik;Kim, Seung Hyung
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.5
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    • pp.269-281
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    • 2017
  • Background: Small particles increase airway inflammation upon reaching the alveoli. Here, we investigated the protective or therapeutic effects of Salvia plebeia R. Br. (SP_R) extracts on airway inflammation. Methods and Results: To investigate the anti-inflammatory activity of SP_R extracts, we measured their inhibitory effect on the production of reactive oxygen species (ROS) expression of inflammatory mediators, and immune cell infiltration in MH-S alveolar macrophage cells and in the ambient particulate matter (APM)-exposed airway inflammation mice model. The SP_R extracts inhibited the production of ROS and expression of IL-4, IL-10, IL-15, and IL-17A mRNA in APM-stimulated MH-S cells. Oral administration of SP_R extracts suppressed APM-induced inflammatory symptoms, such as high alveolar wall thickness, excess collagen fibers, decreased mRNA expression of chemokines (Ccr9, Ccl5, Ccr3), inflammatory cytokines (IL-15, TNF-${\alpha}$), and IL-4 Th2 cytokine in the lung. The SP_R extracts also inhibited ROS production, granulocyte ($CD11b^+Gr-1^+$) infiltration, IL-17A, TNF-${\alpha}$, macrophage inflammatory protein (Mip-2), and chemokine (C-X-C motif) ligand 1 (Cxcl-1) production in the airway. The specific compounds in the SR-R extracts that mediate the anti-inflammatory effects were identified. Conclusions: In this study, SP_R extracts effectively inhibited airway inflammatory responses, such as ROS production and granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines.

Isolation of an Rx homolog from C. annuum and the evolution of Rx genes in the Solanaceae family

  • Shi, Jinxia;Yeom, Seon-In;Kang, Won-Hee;Park, Min-Kyu;Choi, Do-Il;Kwon, Jin-Kyung;Han, Jung-Heon;Lee, Heung-Ryul;Kim, Byung-Dong;Kang, Byoung-Cheorl
    • Plant Biotechnology Reports
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    • v.5 no.4
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    • pp.331-344
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    • 2011
  • The well-conserved NBS domain of resistance (R) genes cloned from many plants allows the use of a PCR-based approach to isolate resistance gene analogs (RGAs). In this study, we isolated an RGA (CapRGC) from Capsicum annuum "CM334" using a PCR-based approach. This sequence encodes a protein with very high similarity to Rx genes, the Potato Virus X (PVX) R genes from potato. An evolutionary analysis of the CapRGC gene and its homologs retrieved by an extensive search of a Solanaceae database provided evidence that Rx-like genes (eight ESTs or genes that show very high similarity to Rx) appear to have diverged from R1 [an NBS-LRR R gene against late blight (Phytophthora infestans) from potato]-like genes. Structural comparison of the NBS domains of all the homologs in Solanaceae revealed that one novel motif, 14, is specific to the Rx-like genes, and also indicated that several other novel motifs are characteristic of the R1-like genes. Our results suggest that Rx-like genes are ancient but conserved. Furthermore, the novel conserved motifs can provide a basis for biochemical structural. function analysis and be used for degenerate primer design for the isolation of Rx-like sequences in other plant species. Comparative mapping study revealed that the position of CapRGC is syntenic to the locations of Rx and its homolog genes in the potato and tomato, but cosegregation analysis showed that CapRGC may not be the R gene against PVX in pepper. Our results confirm previous observations that the specificity of R genes is not conserved, while the structure and function of R genes are conserved. It appears that CapRGC may function as a resistance gene to another pathogen, such as the nematode to which the structure of CapRGC is most similar.

Spectroscopic Comparison of Photo-oxidation of Outside and Inside of Hair by UVB Irradiation (자외선B 조사에 의한 모발 외부와 내부의 광산화에 관한 분광학적 비교)

  • Ha, Byung-Jo
    • Applied Chemistry for Engineering
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    • v.31 no.2
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    • pp.220-225
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    • 2020
  • Hair is made of proteins containing various amino acids. Ultraviolet (UV) radiation is believed to be responsible for the most damaging effects of sunlight, and also plays an important role in hair aging. The purpose of this study was to investigate the changes in morphological and chemical structures after ultraviolet B (UVB) irradiation of human hair. The UVB-irradiated hair showed characteristic morphological and structural changes, compared to those of the normal hair. The result from a scanning electron microscope (SEM) equipped with an energy dispersive X-ray diffractometer (EDX) showed that the scale of UV-irradiated hair appeared to be rough and the amount of oxygen element was higher than that of the normal hair. Fluorescence and three dimensional (3D) topographical images were obtained by a confocal laser scanning microscope (CLSM). In 3D images, the green emission intensity of normal hair was much higher than that of fluorescing UVB-irradiated hair. The intensity of green emission reflects the intrinsic fluorescence of hair protein. Also, a fluorescent imaging method using fluorescamine reagent was used to identify the free amino groups resulting from a peptide bond breakage in UVB-irradiated hair. Strong blue fluorescence of UVB-irradiated hair, which indicates a very high level of amino groups, was observed by CLSM. Therefore, the fluorescamine as an extrinsic fluorescence could provide a useful tool to identify the peptide bond breakage in UVB-irradiated hair. Infrared image mapping was also employed to assess the cross-sections of normal and UVB-irradiated specimens to examine the oxidation of disulfide bonds. The degree of peak areas with strong absorbance for the disulfide mono-oxide was spread from the outside to the inside of hair. The spectroscopic techniques used alone, or in combination, launch new possibilities in the field of hair cosmetics.

Gene Therapy Using GM-CSF Gene Transferred by a Defective Infectious Single-cycle Herpes Virus in Micro-residual Organotropic Head and Neck Squamous Cell Cancer Model (향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료)

  • Kim Se-Heon;Choi Eun-Chang;Kim Han-Su;Chang Jung-Hyun;Kim Ji-Hoon;Kim Kwang-Moon
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.1
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    • pp.25-33
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    • 2003
  • Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

Development and Hypoglycemic Effect of Low-fat and Sugar-free Cookie (저지방 무설탕 쿠키의 제조와 혈당 강하 효과)

  • Park, Sun-Min;Kim, Young-Soon;Yoon, In-Chul;Seo, Eun-Hae;Ko, Byoung-Seob;Choi, Soo-Bong
    • Korean Journal of Food Science and Technology
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    • v.34 no.3
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    • pp.487-492
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    • 2002
  • Low-fat and sugar-free (LFSF) cookies were developed for patients with metabolic syndrome X, such as obesity, diabetes, coronary heart disease, and hypertention, using artificial sweeteners (mixture of aspartame and saccharin), pectin and herb extracts such as Polygonatum Odoratum (Mill) Druce, Schizandrae Fructus and Lycii Fructus, without sugar and fats. LFSF cookies were composed of 7.5 : 1 of aspartame and saccharin, 5% pectin, 49% protein, and 5% herb extracts, with reduced fat level. The values for area under the curve in oral glucose tolerance tests were significantly lower in 90% pancreatomized-(Px, n = 8) and sham - operated (Sham, n = 8) rats which consumed LFSF cookies, than the control, which consumed regular cookies. Blood glucose levels were higher and the peak levels were significantly lower in the LFSF cookies group than the control group of Px and Sham rats. Blood glucose levels of healthy female college students (n = 10) at 30 and 60 min after the consumption of 30 g LFSF and regular cookies were not different, but they were significantly lower in the LFSF-cookies group in diabetes patients (n = 10). In conclusions, LFSF cookies was considered as a good snack for diabetic patients.