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Park, Jin Seok,Yi, Tac-Ghee,Park, Jong-Min,Han, Young Min,Kim, Jun-Hyung,Shin, Dong-Hee,Tak, Seon Ji,Lee, Kyuheon,Lee, Youn Sook,Jeon, Myung-Shin,Hahm, Ki-Baik,Song, Sun U,Park, Seok Hee the Society for Free Radical Research Japan 2015 Journal of clinical biochemistry and nutrition Vol.57 No.3
<P>Mouse bone marrow-derived clonal mesenchymal stem cells (mcMSCs), which were originated from a single cell by a subfractionation culturing method, are recognized as new paradigm for stem cell therapy featured with its homogenous cell population. Next to proven therapeutic effects against pancreatitis, in the current study we demonstrated that mcMSCs showed significant therapeutic effects in dextran sulfate sodium (DSS)-induced experimental colitis model supported with anti-inflammatory and restorative activities. mcMSCs significantly reduced the disease activity index (DAI) score, including weight loss, stool consistency, and intestinal bleeding and significantly increased survival rates. The pathological scores were also significantly improved with mcMSC. We have demonstrated that especial mucosal regeneration activity accompanied with significantly lowered level of apoptosis as beneficiary actions of mcMSCs in UC models. The levels of inflammatory cytokines including TNF-α, IFN-γ, IL-1β, IL-6, and IL-17 were all significantly concurrent with significantly repressed NF-κB activation compared to the control group and significantly decreased infiltrations of responsible macrophage and neutrophil. Conclusively, our findings provide the rationale that mcMSCs are applicable as a potential source of cell-based therapy in inflammatory bowel diseases, especially contributing either to prevent relapse or to accelerate healing as solution to unmet medical needs in IBD therapy.</P>
Yun, Jaesuk,Gu, Sun Mi,Lee, Tac-hyung,Song, Yun Jeong,Seong, Seonhwa,Kim, Young-Hoon,Cha, Hye Jin,Han, Kyoung Moon,Shin, Jisoon,Oh, Hokyung,Jung, Kikyung,Ahn, Chiyoung,Park, Hye-Kyung,Kim, Hyung Soo The Korean Society of Applied Pharmacology 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) $3{\varepsilon}$, $CD3{\gamma}$, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.
( Jaesuk Yun ),( Sun Mi Gu ),( Tac-hyung Lee ),( Yun Jeong Song ),( Seonhwa Seong ),( Young-hoon Kim ),( Hye Jin Cha ),( Kyoung Moon Han ),( Jisoon Shin ),( Hokyung Oh ),( Kikyung Jung ),( Chiyoung Ah 한국응용약물학회 2017 Biomolecules & Therapeutics(구 응용약물학회지) Vol.25 No.3
Synthetic cannabinoids are one of most abused new psychoactive substances. The recreational use of abused drug has aroused serious concerns about the consequences of these drugs on infection. However, the effects of synthetic cannabinoid on resistance to tetanus toxin are not fully understood yet. In the present study, we aimed to determine if the administration of synthetic cannabinoids increase the susceptibility to tetanus toxin-induced motor behavioral deficit and functional changes in cerebellar neurons in mice. Furthermore, we measured T lymphocytes marker levels, such as CD8 and CD4 which against tetanus toxin. JWH-210 administration decreased expression levels of T cell activators including cluster of differentiation (CD) 3ε, CD3γ, CD74p31, and CD74p41. In addition, we demonstrated that JWH-210 induced motor impairment and decrement of vesicle-associated membrane proteins 2 levels in the cerebellum of mice treated with tetanus toxin. Furthermore, cerebellar glutamatergic neuronal homeostasis was hampered by JWH-210 administration, as evidenced by increased glutamate concentration levels in the cerebellum. These results suggest that JWH-210 may increase the vulnerability to tetanus toxin via the regulation of immune function.
Synthetic cannabinoid, JWH-030, induces QT prolongation through hERG channel inhibition
Yun, Jaesuk,Yoon, Kyung Sik,Lee, Tac-Hyung,Lee, Hyunjin,Gu, Sun Mi,Song, Yun Jeong,Cha, Hye Jin,Han, Kyoung Moon,Seo, Hyewon,Shin, Jisoon,Park, Hye-Kyung,Kim, Hyung Soo,Kim, Young-Hoon Oxford University Press 2016 Toxicology research Vol.5 No.6
<P>The problem of new psychoactive substance (NPS) abuse, which includes synthetic cannabinoids, is emerging globally, and the cardiotoxicity of these synthetic cannabinoids has not yet been evaluated extensively. In the present study, we investigated the effects of synthetic cannabinoids on the cytotoxicity, human Ether-à-go-go-related gene (hERG) channel, action potential duration (APD), and QT interval. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that JWH-030 was more cytotoxic than JWH-210, JWH-250, and RCS4 in H9c2 cells at 0.1 μM. In addition, the cytotoxicity was associated with its pro-apoptotic effects as evidenced by the increase in caspase-3 levels. We demonstrated that a cannabinoid receptor type 2 (CB2) antagonist, AM630, inhibited JWH-030-induced cytotoxicity, whereas a CB1 antagonist, rimonabant, did not. Furthermore, fluorescence polarization assay showed JWH-030 to block the hERG channel (half-maximal inhibitory concentration, IC50 was 88.36 μM). JWH-030 significantly reduced the APD at 90% repolarization (APD90) in rabbit Purkinje fibers and decreased the left ventricular end diastolic pressure (LVEDP) in Langendorff-perfused Sprague-Dawley (SD) rat hearts at 30 μM. In addition, the electrocardiogram (ECG) measurement revealed that the intravenous injection of JWH-030 (0.5 mg kg<SUP>−1</SUP>) prolonged the QT interval in SD rats. These results suggest that JWH-030 is cytotoxic and its cytotoxicity is mediated by its action on the CB2 receptor; it prolongs the QT interval by regulating ion current channels and APD.</P>