• Title/Summary/Keyword: therapeutic potential

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Improvement Effect of Sprout of Coix lacryma-jobi var. mayuen Stapf Water Extract on DSS-Induced Ulcerative Colitis in Mice. (DSS로 궤양성 대장염 유발된 동물모델에서 의이아(薏苡芽) 열수 추출물의 개선 효과)

  • Kim, Min Ju;Shin, Mi-Rae;Lee, Jin A;Park, Soon-Ae;Park, Hae-Jin;Lee, Jeong Hoon;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.6
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    • pp.21-28
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    • 2020
  • Objectives : The objective of this study was to investigate the improvement effect of Sprout of Coix lacryma-jobi var. mayuen Stapf water extract (SC) on the dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Methods : The antioxidant activity of SC was measured through total polyphenol and total flavonoid content in vitro. The experiment was conducted with seven-week-old male Balb/c mice. After 1 week adaptation, acute colitis was induced by oral administration of 5% DSS dissolved in drinking water, for 7 days. And normal mice received drinking water without DSS throughout the entire experimental period. For each experiment, the mice were divided into 4 groups and 24 colitis mice were arbitrarily allocated into 3 groups (n = 8/group); Normal group, Control group, SC 100 mg/kg treated group (SCL), SC 200 mg/kg treated group (SCH). Serum and colon tissues were collected after one weeks of drug administration. Results : ROS levels, ONOO- levels, AST, and ALT in serum were decreased in SC treated groups compared to the control group. Western blotting measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2, IL-4, IL-10, and Bcl2 showed that the SC treated groups was increased compared to the Control group. Also, western blot measurements of NF-κBp65, p-IκBα, COX-2, iNOS, TNF-α, IL-1β, Bax, and Caspase-3 showed that the SC treated groups was reduced compared to the Control group. Conclusion : Taken together, these results suggest that SC treatment can attenuate the DSS-induced colitis though inhibiting NF-κB pathway and enhancing Nrf2 pathway. Therefore, SC was the potential to be used as a natural therapeutic drug.

Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson's disease

  • Eom, Seon Ae;Kim, Dae Won;Shin, Min Jea;Ahn, Eun Hee;Chung, Seok Young;Sohn, Eun Jeong;Jo, Hyo Sang;Jeon, Su-Jeong;Kim, Duk-Soo;Kwon, Hyeok Yil;Cho, Sung-Woo;Han, Kyu Hyung;Park, Jinseu;Eum, Won Sik;Choi, Soo Young
    • BMB Reports
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    • v.48 no.7
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    • pp.395-400
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    • 2015
  • Parkinson's disease (PD) is a neurodegenerative disability caused by a decrease of dopaminergic neurons in the substantia nigra (SN). Although the etiology of PD is not clear, oxidative stress is believed to lead to PD. Catalase is antioxidant enzyme which plays an active role in cells as a reactive oxygen species (ROS) scavenger. Thus, we investigated whether PEP-1-Catalase protects against 1-methyl-4-phenylpyridinium (MPP+) induced SH-SY5Y neuronal cell death and in a 1-methyl-4-phenyl-1,2,3,6-trtrahydropyridine (MPTP) induced PD animal model. PEP-1-Catalase transduced into SH-SY5Y cells significantly protecting them against MPP+-induced death by decreasing ROS and regulating cellular survival signals including Akt, Bax, Bcl-2, and p38. Immunohistochemical analysis showed that transduced PEP-1-Catalase markedly protected against neuronal cell death in the SN in the PD animal model. Our results indicate that PEP-1-Catalase may have potential as a therapeutic agent for PD and other oxidative stress related diseases. [BMB Reports 2015; 48(7): 395-400]

Transduced HSP27 protein protects neuronal cell death by enhancing FALS-associated SOD1 mutant activity

  • An, Jae-Jin;Lee, Yeom-Pyo;Kim, Dae-Won;Sohn, Eun-Joung;Jeong, Hoon-Jae;Kang, Hye-Won;Shin, Min-Jae;Kim, Mi-Jin;Ahn, Eun-Hee;Jang, Sang-Ho;Kang, Jung-Hoon;Kang, Tae-Cheon;Won, Moo-Ho;Kwon, Oh-Shin;Cho, Sung-Woo;Lee, Kil-Soo;Park, Jin-Seu;Eum, Won-Sik;Choi, Soo-Young
    • BMB Reports
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    • v.42 no.3
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    • pp.136-141
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    • 2009
  • Familial Amyotrophic lateral sclerosis (FALS) is a progressive neurodegenetative disorder induced by mutations of the SOD1 gene. Heat shock protein 27 (HSP27) is well-defined as a stress-inducible protein, however the its role in ALS protection has not yet been established. To investigate the role HSP27 may have in SOD1 mutant-mediated apoptosis, human SOD1 or HSP27 genes were fused with a PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame fusion protein, which was then transduced into cells. We found the purified PEP-1-HSP27 fusion proteins can be transduced efficiently into neuronal cells and protect against cell death by enhancing mutant SOD1 activity. Moreover, transduced PEP-1-HSP27 efficiently prevents protein aggregation produced by oxidative stress. These results suggest that transduced HSP27 fusion protein may be explored as a potential therapeutic agent for FALS patients.

Sensing the Stress: the Role of the Stress-activated p38/Hog1 MAPK Signalling Pathway in Human Pathogenic Fungus Cryptococcus neoformans

  • Bahn, Yong-Sun;Heitman, Joseph
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2007.05a
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    • pp.120-122
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    • 2007
  • All living organisms use numerous signal-transduction pathways to sense and respond to their environments and thereby survive and proliferate in a range of biological niches. Molecular dissection of these signalling networks has increased our understanding of these communication processes and provides a platform for therapeutic intervention when these pathways malfunction in disease states, including infection. Owing to the expanding availability of sequenced genomes, a wealth of genetic and molecular tools and the conservation of signalling networks, members of the fungal kingdom serve as excellent model systems for more complex, multicellular organisms. Here, we employed Cryptococcus neoformans as a model system to understand how fungal-signalling circuits operate at the molecular level to sense and respond to a plethora of environmental stresses, including osmoticshock, UV, high temperature, oxidative stress and toxic drugs/metabolites. The stress-activated p38/Hog1 MAPK pathway is structurally conserved in many organisms as diverse as yeast and mammals, but its regulation is uniquely specialized in a majority of clinical Cryptococcus neoformans serotype A and D strains to control differentiation and virulence factor regulation. C. neoformans Hog1 MAPK is controlled by Pbs2 MAPK kinase (MAPKK). The Pbs2-Hog1 MAPK cascade is controlled by the fungal "two-component" system that is composed of a response regulator, Ssk1, and multiple sensor kinases, including two-component.like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. We also identified and characterized the Ssk2 MAPKKK upstream of the MAPKK Pbs2 and the MAPK Hog1 in C. neoformans. The SSK2 gene was identified as a potential component responsible for differential Hog1 regulation between the serotype D sibling f1 strains B3501 and B3502 through comparative analysis of their meiotic map with the meiotic segregation of Hog1-dependent sensitivity to the fungicide fludioxonil. Ssk2 is the only polymorphic component in the Hog1 MAPK module, including two coding sequence changes between the SSK2 alleles in B3501 and B3502 strains. To further support this finding, the SSK2 allele exchange completely swapped Hog1-related phenotypes between B3501 and B3502 strains. In the serotype A strain H99, disruption of the SSK2 gene dramatically enhanced capsule biosynthesis and mating efficiency, similar to pbs2 and hog1 mutations. Furthermore, ssk2, pbs2, and hog1 mutants are all hypersensitive to a variety of stresses and completely resistant to fludioxonil. Taken together, these findings indicate that Ssk2 is the critical interface protein connecting the two-component system and the Pbs2-Hog1 pathway in C. neoformans.

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Effects of Argon-plasma Jet on the Cytoskeleton of Fibroblasts: Implications of a New Approach for Cancer Therapy (Fibroblasts 세포주의 세포골격에서 아르곤 플라즈마의 효과: Cancer Therapy의 새로운 접근방법)

  • Han, Ji-Hye;Nam, Min-Kyung;Kim, Yong-Hee;Park, Dae-Wook;Choi, Eun Ha;Rhim, Hyangshuk
    • KSBB Journal
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    • v.27 no.5
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    • pp.308-312
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    • 2012
  • Argon-plasma jet (Ar-PJ) is generated by ionizing Ar gas, and the resulting Ar-PJ consists of a mixture of neutral particles, positive ions, negative electrons, and various reactive species. Although Ar-PJ has been used in various biomedical applications, little is known about the biological effects on cells located near the plasma-exposed region. Here, we investigated the effects of the Ar-PJ on actin cytoskeleton of mouse embryonic fibroblasts (MEFs) in response to indirect as well as direct exposure to Ar-PJ. This Ar-PJ was generated at 500 mL/min of flow rate and 100 V electric power by our device mainly consisting of electrodes, dielectrics, and a high-voltage power supply. Because actin cytoskeleton is the key cellular machinery involved in cellular movement and is implicated in regulation of cancer metastasis and thus resulting in a highly desirable cancer therapeutic target, we examined the actin filament architectures in Ar-PJ-treated MEFs by staining with an actin-specific phalloidin labeled with fluorescent dye. Interestingly, the Ar-PJ treatment causes destabilization of actin filament architectures in the regions indirectly exposed to Ar-PJ, but no differences in MEFs treated with Ar gas alone and in untreated cell control, indicating that this phenomenon is a specific cellular response against Ar-PJ in the live cells, which are indirectly exposed to Ar-PJ. Collectively, our study raises the possibility that Ar-PJ may have potential as anti-cancer drug effect through direct destabilization of the actin cytoskeleton.

Effect of Lower Limb Muscle Activity on Balancing through Sprinter Patterns of PNF (PNF의 Sprinter Pattern을 통한 하지의 근 활성도가 균형능력에 미치는 영향)

  • Jeong, Woo-Sik;Jeong, Jae-Young;Kim, Chan-Kyu;Jung, Dae-In;Kim, Kyung-Yoon
    • The Journal of the Korea Contents Association
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    • v.11 no.3
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    • pp.281-292
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    • 2011
  • In this study, for examining an effect of lower limbs' muscle activity on balance capability when applying sprinter pattern among the PNF, the experiment was conducted as followed. Under the object of 24 people diagnosed by hemiplegia, they were divided into control group and experimental group and the experiment was conducted on the experimental group, three times per a week for six weeks. Experimental group received Sprinter pattern of combined PNF upper extremity and lower extremity pattern. For the lower limbs' muscle activity, effective values of Vastus medialis laterails, medial lateral hamstrings, lateral gastrocnemius' action potential were analyzed. The balance ability tests was conducted with FICSIT-4, FSST and MTD-Balance system. For the significance test of control group and experimental group for measuring time by exercise application method, two-way repeated measure ANOVA was conducted and for the significance test among the groups by each measuring time, independent t-test was conducted. Also, for examining the correlation among the measuring item, pearson correlation was used for the analysis. As the result, the application of sprinter pattern increased muscle activity of lower limbs in paretic side and improve static and dynamic balance ability effectively. Therefore, it will be necessary to develop new intervention by combining active application of the therapeutic intervention program for lower limbs' effective muscle mobilizing in paretic side with various exercising patterns.

The effect of PDGF-BB loaded TCP/chitosan microgranules on new bone formation (혈소판유래성장인자를 함유한 TCP-chitosan 미세과립이 신생골조직 형성에 미치는 영향에 관한 연구)

  • Seol, Yang-Jo;Lee, Jue-Yeon;Kye, Seung-Beom;Lee, Young-Kyu;Kim, Won-Kyeong;Lee, Yong-Moo;Ku, Young;Han, Soo-Boo;Lee, Seung-Jin;Chung, Chong-Pyoung;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.32 no.3
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    • pp.489-500
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    • 2002
  • The purpose of this study was to evaluate newly fabricated tricalcium phosphate(TCP)/chitosan microgranuls as bone substitutes. TCP/chitosan microgranules were fabricated by dropping TCP-chitosan suspension into the NaOH/ethanol solution. The size of microgranules could be controllable via airflow rate. PDGF-BB was loaded into the fabricated granules via freeze-drying methods(300 ng/20 mg). To evaluate cell proliferation, cultured osteoblasts cell lines(MC3T3-El) was dropped on the BioOss(R), chitosan microgranules, TCP/chitosan microgranules and cultured for 1, 7 , 14, and 28 days. Scanning electron microscopic observation was done after 7 days of culture and light microscopic examination was done after 28 days of culture. PDGF-BB release from the microgranules was tested. Rabbit calvarial defects(8 mm in diameter) were formed and chitosan, TCP/chitosan, PDGF-TCP/chitosan microgranules, and BioGran(R) were grafted to test the ability of new bone formation. At SEM view, the size of prepared microgranules was 250-1000 um and TCP powders were observed at the surface of TCP/chitosan microgranules. TCP powders gave roughness to the granules and this might help the attachment of osteoblasts. The pores formed between microgranules might be able to allow new bone ingrowth and vascularization. There were no significant differences in cell number among BioOss(R) and two microgranules at 28 day. Light and scanning electron microscopic examination showed that seeded osteoblastic cells were well attached to TCP/chitosan microgranules and proliferated in a multi-layer. PDGF-BB released from TCP/chitosan microgranules was at therapeutic concentration for at least 1 week. In rabbit calvarial defect models, PDGF-TCP/chitosan microgranules grafted sites showed thicker bone trabeculae pattern and faster bone maturation than others. These results suggested that the TCP/chitosan microgranules showed the potential as bone substitutes.

Luteolin reduces fluid hypersecretion by inhibiting TMEM16A in interleukin-4 treated Calu-3 airway epithelial cells

  • Kim, Hyun Jong;Woo, JooHan;Nam, Yu-Ran;Seo, Yohan;Namkung, Wan;Nam, Joo Hyun;Kim, Woo Kyung
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.4
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    • pp.329-338
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    • 2020
  • Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl- and HCO3- is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl- channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Cisplatin and Extract of Tissue Cultured Mountain Ginseng-Induced Apoptosis in Human Cervical Cancer Cells (인체 자궁암세포에서 cisplatin과 산삼배양근추출물에 의한 apoptosis유도)

  • Lee, Myeong-Seon
    • Applied Microscopy
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    • v.40 no.3
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    • pp.133-138
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    • 2010
  • Mountain ginseng is a perennial crop rarely found in the deep mountains of Korea. The medicinal effect of the mountain ginseng is well known as a panacea in traditional Chinese medicine for a long time. But scientific studies to elucidate the medicinal effect of the mountain ginseng have never been made on account of lack of sample. Recently an improved method of adventitious root culture system through the use of bioreactor has been developed in Panax ginseng that seems to be a reliable way of commercialization of root derived secondary metabolites. This experiment was conducted to evaluated chemotherapeutic effect against human cervical cancer cells by cisplatin (CDDP) and extract of tissue cultured mountain ginseng (ETCMG). CDDP and ETCMG-induced apoptotic cell death in human cervical cancer cell line, HeLa was confirmed by the analysis of cell growth, morphological changes, DNA fragmentation, flow cytometry showed that ETCMG is an inducer of apoptosis and synergizes with CDDP. These results suggest that ETCMG present evidence of anticancer effect and could have a possibly natural therapeutic potential in cervical cancer patients.

Effect of the Paclitaxel and Radiation in the Mucosa of the Small Bowel of Rat (흰쥐의 소장점막에 Paclitaxel(Taxol)과 방사선조사의 효과)

  • Lee Kyung-Ja
    • Radiation Oncology Journal
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    • v.14 no.4
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    • pp.255-264
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    • 1996
  • Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

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