• Title/Summary/Keyword: Target Disease

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Non-classical role of Galectin-3 in cancer progression: translocation to nucleus by carbohydrate-recognition independent manner

  • Kim, Seok-Jun;Chun, Kyung-Hee
    • BMB Reports
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    • v.53 no.4
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    • pp.173-180
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    • 2020
  • Galectin-3 is a carbohydrate-binding protein and regulates diverse functions, including cell proliferation and differentiation, mRNA splicing, apoptosis induction, immune surveillance and inflammation, cell adhesion, angiogenesis, and cancer-cell metastasis. Galectin-3 is also recommended as a diagnostic or prognostic biomarker of various diseases, including heart disease, kidney disease, and cancer. Galectin-3 exists as a cytosol, is secreted in extracellular spaces on cells, and is also detected in nuclei. It has been found that galectin-3 has different functions in cellular localization: (i) Extracellular galectin-3 mediates cell attachment and detachment. (ii) cytosolic galectin-3 regulates cell survival by blocking the intrinsic apoptotic pathway, and (iii) nuclear galectin-3 supports the ability of the transcriptional factor for target gene expression. In this review, we focused on the role of galectin-3 on translocation from cytosol to nucleus, because it happens in a way independent of carbohydrate recognition and accelerates cancer progression. We also suggested here that intracellular galecin-3 could be a potent therapeutic target in cancer therapy.

Antimicrobial Cyclic Peptides for Plant Disease Control

  • Lee, Dong Wan;Kim, Beom Seok
    • The Plant Pathology Journal
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    • v.31 no.1
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    • pp.1-11
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    • 2015
  • Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

Structural Basis of the Disease-related Proteins: Target Oriented Structural Proteomics

  • Jinho Moon;Heo, Yong-Suk;Kim, Young-Kwan;Kim, Hye-Yeon;Park, Min-Hye;Hwang, Kwang-Yeon
    • Proceedings of the Korea Crystallographic Association Conference
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    • 2003.05a
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    • pp.15-15
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    • 2003
  • To discover new drugs more quickly and more efficiently, pharmaceutical companies and biotechnology firms are increasingly turning to the genomics and the structural proteomics technologies. Structural-proteomics can provide a foundation for this through the determination and analysis for protein structure on a genomics scale. Among many structures determined by CGI, we will present with the representative examples drawn from our work on novel structures or complex structures of the disease-related proteins. The alpha subunit of Hypoxia-inducible factor (HIF) is targeted for degradation under normoxic conditions by an ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF. Hydroxylation is catalysed by HIF prolyl 4-hydroxylases (HIFPH) which are fe(II) and 2-oxoglutarate (2-OG) dependent oxygenases. Here, we discuss the first crystal structure of the catalytic domain of HIFPH in complexes, with the Fe(II)/2-OG at 1.8Å. These structures suggest that the Ll region (residues 236-253), which is also conserved in mammals, form a 'lid' that closes over the active site. The structural and mutagenesis analyses allow us to provide a focus for understanding cellular responses to hypoxia and a target for the therapeutic manipulation.

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Structural Basis of the Disease-related Proteins: Target Oriented Structural Proteomics

  • Hwang, Kwang-Yeon;Lee, Tae-Gyu;Kim, Jin-Hwan;Jeon, Young-Ho;Seonggu Ro;Cho, Joong-Myung
    • Proceedings of the Korean Biophysical Society Conference
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    • 2003.06a
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    • pp.28-28
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    • 2003
  • To discover new drugs more quickly and more efficiently, pharmaceutical companies and biotechnology firms are increasingly turning to the genomics and the structural proteomics technologies. Structural-proteomics can provide a foundation for this through the determination and analysis for protein structure on a genomics scale. Among many structures determined by CGI, we will present with the representative examples drawn from our work on novel structures or complex structures of the disease-related proteins. The alpha subunit of Hypoxia-inducible factor (HIF) is targeted for degradation under normoxic conditions by an ubiquitin-ligase complex that recognizes a hydroxylated proline residue in HIF, Hydroxylation is catalysed by HIF prolyl 4-hydroxylases (HIFPH) which are Fe(II) and 2-oxoglutarate (2-OG) dependent oxygenases. Here, we discuss the first crystal structure of the catalytic domain of HIFPH in complexes, with the Fe(II)/2-OG at 1.8 ${\AA}$. These structures suggest that the L1 region (residues 236-253), which is also conserved in mammals, form a ‘lid’ that closes over the active site. The structural and mutagenesis analyses allow us to provide a focus for understanding cellular responses to hypoxia and a target for the therapeutic manipulation.

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Deoxypodophyllotoxin Induces ROS-Mediated Apoptosis by Modulating the PI3K/AKT and p38 MAPK-Dependent Signaling in Oral Squamous Cell Carcinoma

  • Seo, Ji-Hye;Yoon, Goo;Park, Seryoung;Shim, Jung-Hyun;Chae, Jung-Il;Jeon, Young-Joo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.9
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    • pp.1103-1109
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    • 2022
  • Deoxypodophyllotoxin (DPT), a naturally occurring flavonolignan, possesses several pharmacological properties, including anticancer property. However, the mechanisms underlying DPT mode of action in oral squamous cell carcinoma (OSCC) remain unknown. This study aimed to investigate the anticancer effects of DPT on OSCC and the underlying mechanisms. Results of the MTT assay revealed that DPT significantly reduced the cell viability in a time- and dose-dependent manner. Flow cytometry analysis revealed that DPT induces apoptosis in OSCC cells in a dose-dependent manner. Moreover, DPT enhanced the production of mitochondrial reactive oxygen species (ROS) in OSCC cells. Mechanistically, DPT induced apoptosis in OSCC cells by suppressing the PI3K/AKT signaling pathway while activating the p38 MAPK signaling to regulate the expression of apoptotic proteins. Treatment with SC79, an AKT activator, reversed the effects of DPT on AKT signaling in OSCC cells. Taken together, these results provide the basis for the use of DPT in combination with conventional chemotherapy for the treatment of oral cancer.

No excessive mutations in transcription activator-like effector nuclease-mediated α-1,3-galactosyltransferase knockout Yucatan miniature pigs

  • Choi, Kimyung;Shim, Joohyun;Ko, Nayoung;Park, Joonghoon
    • Asian-Australasian Journal of Animal Sciences
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    • v.33 no.2
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    • pp.360-372
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    • 2020
  • Objective: Specific genomic sites can be recognized and permanently modified by genome editing. The discovery of endonucleases has advanced genome editing in pigs, attenuating xenograft rejection and cross-species disease transmission. However, off-target mutagenesis caused by these nucleases is a major barrier to putative clinical applications. Furthermore, off-target mutagenesis by genome editing has not yet been addressed in pigs. Methods: Here, we generated genetically inheritable α-1,3-galactosyltransferase (GGTA1) knockout Yucatan miniature pigs by combining transcription activator-like effector nuclease (TALEN) and nuclear transfer. For precise estimation of genomic mutations induced by TALEN in GGTA1 knockout pigs, we obtained the whole-genome sequence of the donor cells for use as an internal control genome. Results: In-depth whole-genome sequencing analysis demonstrated that TALEN-mediated GGTA1 knockout pigs had a comparable mutation rate to homologous recombination-treated pigs and wild-type strain controls. RNA sequencing analysis associated with genomic mutations revealed that TALEN-induced off-target mutations had no discernable effect on RNA transcript abundance. Conclusion: Therefore, TALEN appears to be a precise and safe tool for generating genomeedited pigs, and the TALEN-mediated GGTA1 knockout Yucatan miniature pigs produced in this study can serve as a safe and effective organ and tissue resource for clinical applications.

Overview of RCT for Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis

  • Son, Chang-Gue
    • The Journal of Korean Medicine
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    • v.32 no.3
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    • pp.44-49
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    • 2011
  • Objective: This study aimed to get information on the current status of therapies to date for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Methods: All randomized clinical controlled trial (RCT)-derived papers for NAFLD or NASH were reviewed via PubMed Database. Results: 39 RCTs met the review criteria, of which 15 and 24 papers were for NAFLD and NASH, respectively. 83% of the papers were released since 2006, and 30 studies were conducted for western medicines, antioxidants and lifestyle intervention whereas nine trials were done using herbal medicine or acupuncture which showed positive outcome. Conclusions: NAFLD and NASH are new epidemic disorders which can be a target of traditional Oriental medicine. This study will be helpful for the Oriental medicine-based strategies or therapeutic development for them.

Animal Models of Arthritis: Pharmacological Intervention

  • Ryn, Joanne van
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.41-76
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    • 2001
  • Rheumatoid arthritis is an incurable chronic inflammatory and destructive arthopathy that affects 1% of the population world-wide. It has substantial personal, social and economic costs. The long-term prognosis is poor: 80 percent of affected patients will become disabled within 20 years after onset of disease. Medical costs of rheumatoid arthritis average ∼$ 6000 (US) per patient (1), Current antirheumatic drugs have limited efficacy and many side effects and more importantly they do not improve the long-term prognosis of rheumatoid arthritis (2). After a decade of few notable advances in therapy, several biological response modifiers that target pathophysiological processes in the disease have now emerged in the clinic. These new drugs are termed biological agents, and although information about their use in the clinic is still limited to short term treatment, they appear to have the ability to modify disease progress. In addition, COX-2 selective agents have now been approved that have comparable efficacy with standard NSAIDs, but fewer gastrointestinal side effects (3). Thus today many more therapeutic options are suddenly open to patients that even five years ago had little hope of relief from chronic pain and inflammation.

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Alzheimer Disease detection and analysis using P300 componenet of ERP in Alzheimer type Dementia (사상관련전위 P300 요소를 이용한 알츠하이머형 치매의 탐지와 분석)

  • 박은혜;이영혁;임재환;김종우;황의완;김현택
    • Proceedings of the Korean Society for Emotion and Sensibility Conference
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    • 2002.11a
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    • pp.148-152
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    • 2002
  • This study is to develop the Alzheimers disease (AD) detection and analysis system using event-related potential (ERP) of AD patients. We recorded ERP in an auditory oddball paradigm in mild AD (n=25), severe AD (n=12), age-matched normal aged controls (n=17), and young controls (n=7). The amplitude and latency of target P300 components were compared among 4 groups. The relationship between P300 measures and neuro psychological test (K-DRS) scores were evaluated by correlations. The latency of P300 was prolonged in AD and the effects were correlated with the severity of dementia. The P300 amplitude was not affected significantly in AD. Theres no difference between normal aged group and young group. These results suggest that the P300 component is specifically affected by Alzheimer type dementia.

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Importance of Microglial Cytoskeleton and the Actin-interacting Proteins in Alzheimer's Disease

  • Choi, Go-Eun
    • Biomedical Science Letters
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    • v.26 no.1
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    • pp.1-7
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    • 2020
  • Alzheimer's disease (AD) is the most common neurodegenerative disorder and is expected to become more and more widespread as life expectancy increases. New therapeutic target, as well as the identification of mechanisms responsible for pathology, is urgently needed. Recently, microglial actin cytoskeleton has been proposed as a beneficial role in axon regeneration of brain injury. This review highlights in understanding of the characteristics of microglial actin cytoskeleton and discuss the role of specific actin-interacting proteins and receptors in AD. The precise mechanisms and functional aspects of motility by microglia require further study, and the regulation of microglial actin cytoskeleton might be a potential therapeutic strategy for neurological diseases.