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Suppressive effects of methylthiouracil on polyphosphate‐mediated vascular inflammatory responses
Min, Gahee,Ku, Sae‐,Kwang,Jeong, Seongdo,Baek, Moon‐,Chang,Bae, Jong‐,Sup John Wiley and Sons Inc. 2016 JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Vol.20 No.12
<P><B>Abstract</B></P><P>Drug repositioning is used to discover drug candidates to treat human diseases, through the application of drugs or compounds that are approved for the treatment of other diseases. This method can significantly reduce the time required and cost of discovering new drug candidates for human diseases. Previous studies have reported pro‐inflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti‐inflammatory responses and mechanisms of methylthiouracil (MTU), which is an antithyroid drug, and its effects on PolyP‐induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behaviour of human neutrophils and vascular permeability were determined in PolyP‐activated HUVECs and mice. MTU suppressed the PolyP‐mediated vascular barrier permeability, up‐regulation of inflammatory biomarkers, adhesion/migration of leucocytes, and activation and/or production of nuclear factor‐κB, tumour necrosis factor‐α and interleukin‐6. Furthermore, MTU demonstrated protective effects on PolyP‐mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of MTU on various systemic inflammatory diseases, such as sepsis or septic shock.</P>
Min Jung Lee,Min Soo Park,Soojin Hwang,Yoon Ki Hong,Gahee Choi,Yoon Seak Suh,Seung Yeop Han,Darae Kim,Jungae Jeun,Chun-Taek Oh,이성준,한성준,김동학,김은수,Gilsang Jeong,조경상 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.1
Hempseed, a rich source of polyunsaturated fatty acids (PUFAs) and phytosterols, has been recognized as a po-tential therapeutic food used for cardioprotection, prevent-ing platelet aggregation, and improving atopic dermatitis. Although several studies have revealed the physiological benefits of hempseed on a variety of animals, the effects of dietary hempseed intake on animal development are cur-rently unknown. In this study, we evaluated the develop-mental effects of the addition of hempseed meal (HSM) to the diet of Drosophila. Interestingly, dietary HSM intake was shown to increase the body size of flies by increasing cell numbers, and also truncated the larval period without affecting survival rate or longevity. The oviposition of fe-male flies was also increased by dietary HSM supplemen-tation. Interestingly, the levels of sterols, which are pre-cursors of ecdysone, a molting hormone, were found to be elevated in the larvae fed on HSM. Additionally, the hexane extracts of hempseed mimicked the effects of HSM on growth, developmental timing, and reproduction. Moreover, among the major nonpolar components of HSM, feeding on cholesterol but not PUFA mix or campesterol acceler-ated pupariation and increased body size. These results indicate that the dietary intake of HSM accelerates both body growth and developmental rates in Drosophila via the stimulation of cell growth and ecdysone synthesis. Additionally, nonpolar components of hempseed, such as cholesterol, might be responsible for the effects of HSM on development and reproduction.
Soojin Hwang,Darae Kim,Gahee Choi,Seon Woo An,Yoon Ki Hong,Yoon Seak Suh,Min Jung Lee,조경상 한국분자세포생물학회 2010 Molecules and cells Vol.29 No.6
Parkin is the most prevalent genetic factor in the onset of autosomal recessive juvenile parkinsonism (AR-JP), and mutations in parkin has been reported to cause motor defects, which result from dopamine deficiency caused by dopaminergic neuronal cell death. Activation of c-Jun N-terminal kinase (JNK) has also been implicated in neuronal cell death in Parkinson’s disease (PD). Moreover, Droso-phila models for AR-JP, loss of function mutants of Dro-sophila parkin, also show dopaminergic neural degenera-tion associated with hyperactivation of JNK, increased apoptosis, and mitochondrial defects. However, the mo-lecular mechanism by which Parkin protects cells from apoptosis remains unclear. In the present study, we tested whether Drosophila Parkin suppressed the JNK signaling pathway in developing tissues. Ectopically expressed parkin strongly suppressed the constitutively active form of Hemipterous (HepCA), a Drosophila JNK kinase that in-duces an eye degeneration phenotype and apoptosis in the eye imaginal disc. Moreover, parkin also suppressed extra vein formation induced by Basket (Bsk), a Drosophila JNK. Interestingly, the bsk mRNA level was markedly re-duced by parkin over-expression, suggesting that the ef-fect of parkin on the phenotype induced by activation of JNK signaling was achieved by transcriptional regulation. Furthermore, we found that the expression level of JNK target genes was reduced by parkin over-expression. Taken together, these results suggest that Drosophila Parkin suppresses JNK signaling by reducing bsk transcription.
Kim Hyung Woo,Min Jinsoo,Choi Joon Young,Shin Ah Young,Myong Jun-Pyo,Lee Yunhee,Yim Hyeon Woo,Jeong Hyunsuk,Bae Sanghyuk,Shim Eunhye,In Hyekyung,Chun Chaemin,Kim Gahee,Kang Ji Young,Lee Sung-Soon,Park 대한의학회 2021 Journal of Korean medical science Vol.36 No.36
In 2017, the Korean government launched an unprecedentedly large-scaled latent tuberculosis infection (LTBI) screening project which covered more than a million individuals in congregate settings. A total of 1,047,689 participants of source population (n = 2,336,157) underwent LTBI testing from 2017 to 2018. The overall LTBI test uptake rate during this project was 44.8%. Workers in daycare centers (83.5%) and kindergartens (78.9%) showed high participation rate. A total of 1,012,206 individuals with valid results of interferongamma release assay (IGRA) were selected to constitute the IGRA cohort. Most of the enrolled participants in the IGRA cohort were in their working age. Approximately, threequarters of total enrolled population were female. Investigating the LTBI prevalence, stages of LTBI care cascade, natural history of LTBI, efficacy of LTBI treatment and cost-effectiveness of LTBI screening are feasible within this IGRA cohort.
( Seongdo Jeong ),( Sae Kwang Ku ),( Gahee Min ),( Hyukaje Choi ),( Dong Ho Park ),( Jong Sup Bae ) 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-
Diketopiperazine is a natural products found from bacteria, fungi, marine sponges, gorgonian and red algae. They are cyclic dipeptides possessing relatively simple and rigid structures with chiral nature and various side chains. The compounds in this structure class have been known to possess diverse bio-activities including antibiotic activity, anti-cancer activity, neuroprotective activity, and anti-inflammatory activity. Previous studies have reported proinflammatory responses of endothelial cells to the release of polyphosphate (PolyP). In this study, we examined the anti-inflammatory responses and mechanisms of diketopiperazine and its effects on PolyP-induced septic activities in human umbilical vein endothelial cells (HUVECs) and mice. The survival rates, septic biomarker levels, behavior of human neutrophils, and vascular permeability were determined in PolyP-activated HUVECs and mice. Diketo-piperazine suppressed the PolyP-mediated vascular barrier permeability, upregulation of inflammatory biomarkers, adhesion/migration of leukocytes, and activation and/or production of nuclear factor-ell. tumor necrosis factor-a, and interleukin-6. Furthermore, diketopiperazine demonstrated protective effects on PolyP-mediated lethal death and the levels of the related septic biomarkers. Therefore, these results indicated the therapeutic potential of diketopiperazine on various systemic inflammatory dis-eases, such as sepsis or septic shock.