• Title/Summary/Keyword: Cathepsin S

검색결과 57건 처리시간 0.034초

A New Class of Potent Cathepsin K Inhibitors; OST-1857 Derivatives

  • Kim, N.C.;Han, T.D.;Hur, Y.;Hwang, H.J.;Shin, Y.A.;Lee, C.H.;Lee, B.Y.;Lee, J.W.;Bae, E.J.;Kim, M.K.;Yang, J.S.;Lim, J.I.;Son, M.H.;Kim, S.H.;Kim, W.B.
    • 대한약학회:학술대회논문집
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    • 대한약학회 2001년도 Proceedings of the Pharmaceutical Society of Korea
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    • pp.121.1-121.1
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    • 2001
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Altered Gene Expression in Cerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis

  • Yu, Ji-Hoon;Lim, Joo-Weon;Kim, Hye-Young
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권6호
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    • pp.409-416
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    • 2009
  • Acute pancreatitis is a multifactorial disease associated with the premature activation of digestive enzymes. The genes expressed in pancreatic acinar cells determine the severity of the disease. The present study determined the differentially expressed genes in pancreatic acinar cells treated with cerulein as an in vitro model of acute pancreatitis. Pancreatic acinar AR42J cells were stimulated with $10^{-8}$ M cerulein for 4 h, and genes with altered expression were identified using a cDNA microarray for 4,000 rat genes and validated by real-time PCR. These genes showed a 2.5-fold or higher increase with cerulein: lithostatin, guanylate cyclase, myosin light chain kinase 2, cathepsin C, progestin-induced protein, and pancreatic trypsin 2. Stathin 1 and ribosomal protein S13 showed a 2.5-fold or higher decreases in expression. Real-time PCR analysis showed time-dependent alterations of these genes. Using commercially available antibodies specific for guanylate cyclase, myosin light chain kinase 2, and cathepsin C, a time-dependent increase in these proteins were observed by Western blotting. Thus, disturbances in proliferation, differentiation, cytoskeleton arrangement, enzyme activity, and secretion may be underlying mechanisms of acute pancreatitis.

위령선(威靈仙)이 RANKL 처리 RAW 264.7 Cell에 미치는 영향 (Effects of Clematidis Radix Extract on Osteoclastogenesis and Gene Expression in RANKL-induced RAW 264.7 Cell)

  • 송영훈;유정은;임현정;유동열
    • 대한한방부인과학회지
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    • 제23권3호
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    • pp.78-90
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    • 2010
  • Purpose: This study was performed to evaluate the effect of Clematidis Radix extract(CB) on osteoclast differentiation and gene expression. The osteocastogenesis and gene expression were determined in RANKL-induced RAW 264.7 cell. Methods: RANKL-induced RAW 264.7 cell with Clematidis Radix extract was stained by TRAP which is expressive marker of osteoclast. The gene expression of RANK, $TNF{\alpha}$, IL-6, iNOS and Cathepsin, those are factors related to bone resorption, was estimated by using Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: Clematidis Radix extract decreased the number of TRAP-positive multi nuclei cell, and decreased the gene expression of RANK, $TNF{\alpha}$, IL-6, iNOS and Cathepsin K in RANKL-induced RAW 264.7 cell. Conclusion: It is concluded that Clematidis Radix extract might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.

Differential expression of the 27 kDa cathepsin L-like cysteine protease in developmental stages of Spirometra erinacei

  • Kong, Yoon;Yun, Doo-Hee;Cho, Seung-Yull;Sohn, Woon-Mok;Chung, Young-Bae;Kang, Shin-Yong
    • Parasites, Hosts and Diseases
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    • 제38권3호
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    • pp.195-199
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    • 2000
  • The 27 kDa cathepsin L-like cysteine protease of Spirometra erinocei plerocercoid is known to play an important function in tissue penetration, nutrient uptake and immune modulation in human sparganosis. In the present study, the expression of this enzyme was examined at different developmental stages of S. erinacei including immature egg, coracidium, plerocercoid in tadpole and rat, and adult Proteolytic activity against carboxybenzoyl-phenylalanyl-arginyl-7-amino-4-rnethylcournarin was do tooted in the extracts of coracidia and plerocercoid while no activity was observed in those of immature egg and adult. The specific activity in coraridial extracts was lower than that in the plerocercoid. Reverse transcription-polymerase chain reaction and Northern biol analysis demonstrated that the gene was expressed in the coracidium and plerocercoid but not in immature egg and adult. These results suggest that the 27 kDa cysteine protease is only expressed in the stages involving active migration of the parasite in the host tissue.

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Human umbilical cord blood plasma alleviates age-related olfactory dysfunction by attenuating peripheral TNF-α expression

  • Lee, Byung-Chul;Kang, Insung;Lee, Seung-Eun;Lee, Jin Young;Shin, Nari;Kim, Jae-Jun;Choi, Soon Won;Kang, Kyung-Sun
    • BMB Reports
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    • 제52권4호
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    • pp.259-264
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    • 2019
  • Social requirements are needed for living in an aging society and individual longevity. Among them, improved health and medical cares, appropriate for an aging society are strongly demanded. Human cord blood-derived plasma (hUCP) has recently emerged for its unique anti-aging effects. In this study, we investigated brain rejuvenation, particularly olfactory function, that could be achieved by a systemic administration of young blood and its underlying mechanisms. Older than 24-month-old mice were used as an aged group and administered with intravenous injection of hUCP repetitively, eight times. Anti-aging effect of hUCP on olfactory function was evaluated by buried food finding test. To investigate the mode of action of hUCP, brain, serum and spleen of mice were collected for further ex vivo analyses. Systemic injection of hUCP improved aging-associated olfactory deficits, reducing time for finding food. In the brain, although an infiltration of activated microglia and its expression of cathepsin S remarkably decreased, significant changes of proinflammatory factors were not detected. Conversely, peripheral immune balance distinctly switched from predominance of Type 1 helper T (Th1) cells to alternative regulatory T cells (Tregs). These findings indicate that systemic administration of hUCP attenuates age-related neuroinflammation and subsequent olfactory dysfunction by modulating peripheral immune balance toward Treg cells, suggesting another therapeutic function and mechanism of hUCP administration.

헛개나무와 오리나무 추출물의 간 해독작용 및 체내 알콜 분해능 비교 (Comparison of Hepatic Detoxification activity and reducing Serum Alcohol concentration of Hovenia dulsis $T_{HUNB}$ and Alnus japonica Steud.)

  • 안상욱;김영길;김민회;이병익;이상호;권혁일;황백;이현용
    • 한국약용작물학회지
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    • 제7권4호
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    • pp.263-268
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    • 1999
  • 헛개 나무 추출물과 오리나무 추출물들이 쥐 와 사람을 대상으로 실험한 결과 체내 알콜 분해능이있는 것으로 나타났으며, 쥐 실험의 경우 헛개 나무가 32% 의 알콜 분해능이 증진되었으며 오리나무는 13% 정도로 나타났으며 혼합물인 경우 42% 의 높은 것으로 나타났다. 사람을 대상으로 한 경우도 유사한 경향을 보여 혼합물을 섭취한 경우 4 시간만에 음주 전 알콜 농도로 감소했으나 오리나무는 6 시간에도 0.013% 정도의 알콜이 존재했다. 또한 헛개나무는 6 간 정도 후에 정상 치로 감소된 반면 알콜만 섭취한 경우는 6 시간이 되도 0.04% 의 알콜이 존재하고 있어 이 추출물들이 정도의 차이는 있으나 알콜 분해 효과가 있는 것으로 확인되었다. 간의 해독 증진 및 숙취 해소 기능에서도 혼합물, 헛개 나무, 오리나무 순으로 활성이 좋은 것으로 확인되었다. ADH 효소의 활성의 경우 혼합물의 경우 약 60% 정도 증진되는 것으로 나타났으나 헛개 나무의 경우 35.6% 로 상승되었으며는 것이 확인되었다. 하지만 오리나무의 경우는 약 29% 정도로 별 차이가 없는 것으로 측정되었다. GST 활성 증진의 경우 혼합물을 1 g/L의 농도로 투여해 실험한 결과 최대 180% 의 활성 증진이 가능한 것으로 측정되었다. 이에 비해 각 추출물들이 단독으로 작용하는 경우에 는 유사한 활성 증진을 보여 혼합물의 경우 간의 해독 작용 증진에 synergy 효과가 있을 것으로 예측된다. Cathepsin 활성 저해의 경우 역시 혼합물이 55 % 이상 활성 억제 효과를 보였으며 헛개 나무가 약 40%의 억제 기능을 나타냈다. 하지만 오리나무의 경우는 28% 정도의 낮은 억제 효과를 보였다. 이는 오리나무 추출물은 ADH 효소 활성 증진이나 cethepsin 효소 억제 기능이 아닌 다른 기작에 의해 알콜 분해 및 간 기능 증진에 영향을 주는 것으로 예측된다. 모든 경우 다 혼합물이 여러 활성 효과가 높은 것으로 나타나 이 혼합물을 이용한 기능성 식품 개발이 유용할 것으로 평가된다.

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DNA Vaccines Encoding Toxoplasma gondii Cathepsin C 1 Induce Protection against Toxoplasmosis in Mice

  • Han, Yali;Zhou, Aihua;Lu, Gang;Zhao, Guanghui;Sha, Wenchao;Wang, Lin;Guo, Jingjing;Zhou, Jian;Zhou, Huaiyu;Cong, Hua;He, Shenyi
    • Parasites, Hosts and Diseases
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    • 제55권5호
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    • pp.505-512
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    • 2017
  • Toxoplasma gondii cathepsin C proteases (TgCPC1, 2, and 3) are important for the growth and survival of T. gondii. In the present study, B-cell and T-cell epitopes of TgCPC1 were predicted using DNAstar and the Immune Epitope Database. A TgCPC1 DNA vaccine was constructed, and its ability to induce protective immune responses against toxoplasmosis in BALB/c mice was evaluated in the presence or absence of the adjuvant ${\alpha}-GalCer$. As results, TgCPC1 DNA vaccine with or without adjuvant ${\alpha}-GalCer$ showed higher levels of IgG and IgG2a in the serum, as well as IL-2 and $IFN-{\gamma}$ in the spleen compared to controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). Upon challenge infection with tachyzoites of T. gondii (RH), $pCPC1/{\alpha}-GalCer$ immunized mice showed the longest survival among all the groups. Mice vaccinated with DNA vaccine without adjuvant (pCPC1) showed better protective immunity compared to other controls (PBS, pEGFP-C1, and ${\alpha}-GalCer$). These results indicate that a DNA vaccine encoding TgCPC1 is a potential vaccine candidate against toxoplasmosis.

A network pharmacology and molecular docking approach in the exploratory investigation of the biological mechanisms of lagundi (Vitex negundo L.) compounds against COVID-19

  • Robertson G. Rivera;Patrick Junard S. Regidor;Edwin C. Ruamero Jr;Eric John V. Allanigue;Melanie V. Salinas
    • Genomics & Informatics
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    • 제21권1호
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    • pp.4.1-4.18
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    • 2023
  • Coronavirus disease 2019 (COVID-19) is an inflammatory and infectious disease caused by severe acute respiratory syndrome coronavirus 2 virus with a complex pathophysiology. While COVID-19 vaccines and boosters are available, treatment of the disease is primarily supportive and symptomatic. Several research have suggested the potential of herbal medicines as an adjunctive treatment for the disease. A popular herbal medicine approved in the Philippines for the treatment of acute respiratory disease is Vitex negundo L. In fact, the Department of Science and Technology of the Philippines has funded a clinical trial to establish its potential as an adjunctive treatment for COVID-19. Here, we utilized network pharmacology and molecular docking in determining pivotal targets of Vitex negundo compounds against COVID-19. The results showed that significant targets of Vitex negundo compounds in COVID-19 are CSB, SERPINE1, and PLG which code for cathepsin B, plasminogen activator inhibitor-1, and plasminogen, respectively. Molecular docking revealed that α-terpinyl acetate and geranyl acetate have good binding affinity in cathepsin B; 6,7,4-trimethoxyflavanone, 5,6,7,8,3',4',5'-heptamethoxyflavone, artemetin, demethylnobiletin, gardenin A, geranyl acetate in plasminogen; and 7,8,4-trimethoxyflavanone in plasminogen activator inhibitor-1. While the results are promising, these are bound to the limitations of computational methods and further experimentation are needed to completely establish the molecular mechanisms of Vitex negundo against COVID-19.