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Kang, Dong Hyuk,Yin, Guo Nan,Choi, Min-Ji,Song, Kang-Moon,Ghatak, Kalyan,Minh, Nguyen Nhat,Kwon, Mi-Hye,Seong, Do-Hwan,Ryu, Ji-Kan,Suh, Jun-Kyu Korean Society for Sexual Medicine and Andrology 2018 The World Journal of Men's Health Vol.36 No.2
<P><B>Purpose</B></P><P>Epigenetic modifications, such as histone acetylation/deacetylation and DNA methylation, play a crucial role in the pathogenesis of inflammatory disorders and fibrotic diseases. The aim of this study was to study the differential gene expression of histone deacetylases (HDACs) in fibroblasts isolated from plaque tissue of Peyronie's disease (PD) or normal tunica albuginea (TA) and to examine the anti-fibrotic effect of small interfering RNA (siRNA)-mediated silencing of HDAC7 in fibroblasts derived from human PD plaque.</P><P><B>Materials and Methods</B></P><P>For differential gene expression study, we performed reverse-transcriptase polymerase chain reaction for HDAC isoforms (1–11) in fibroblasts isolated from PD plaque or normal TA. Fibroblasts isolated from PD plaque were pretreated with HDAC7 siRNA (100 pmol) and then stimulated with transforming growth factor-β1 (TGF-β1, 10 ng/mL). Protein was extracted from treated fibroblasts for Western blotting. We also performed immunocytochemistry to detect the expression of extracellular matrix proteins and to examine the effect of HDAC2 siRNA on the TGF-β1-induced nuclear translocation of Smad2/3 and myofibroblastic differentiation.</P><P><B>Results</B></P><P>The mRNA expression of HDAC2, 3, 4, 5, 7, 8, 10, and 11 was higher in fibroblasts isolated from PD plaque than in fibroblasts isolated from normal TA tissue. Knockdown of HDAC7 in PD fibroblasts inhibited TGF-β1-induced nuclear shuttle of Smad2 and Smad3, transdifferentiation of fibroblasts into myofibroblasts, and abrogated TGF-β1-induced production of extracellular matrix protein.</P><P><B>Conclusions</B></P><P>These findings suggest that specific inhibition of HDAC7 with RNA interference may represent a promising epigenetic therapy for PD.</P>
Dual-Responsive Shape Memory and Thermally Reconfigurable Reduced Graphene Oxide-Vitrimer Composites
Guo-kang Chen,Kun Wu,Qian Zhang,Yan-cen Shi,Man-geng Lu 한국고분자학회 2019 Macromolecular Research Vol.27 No.6
In this paper, we have prepared shape memory reduced graphene oxidevitrimer composites via in situ reduction of graphene oxide (GO) during the curing reaction. Because of good compatibility between GO and epoxy resin, reduced graphene oxide (rGO) has a good dispersion in the epoxy matrix. Conventional thermoset shape memory polymers can only maintain one permanent shape, while these obtained composites can be randomly reconfigured into other shapes via dynamic covalent transesterification reaction at 200 °C above transesterification temperature (TV). They can recover quickly from fixed shapes to their initial shapes with shape fixity ratio higher than 95% and shape recovery ratio higher than 97%. Besides, the rGO-vitrimers show good mechanical properties and thermal stabilities. In addition, sequent nearinfrared (NIR) irradiation can control the shape recovery, because rGO can serve as an energy convertor to convert NIR irradiation into thermal energy.
Shen-Kang protects against tacrolimus-induced renal injury
Long Ye Zhang,Jian Jin,Kang Luo,Shang Guo Piao,Hai Lan Zheng,Ji Zhe Jin,임선우,최범순,양철우,Can Li 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5
Background/Aims: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. Methods: Rats were treated daily with TAC (1.5 mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. Results: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/ Bcl2-associated X [Bcl-2/Bax] ratio). Conclusions: SK protects against TAC-induced renal injury.
Wu, Zhen-Guo,Li, Jun-Tao,Zhong, Yan-Jun,Guo, Xiao-Dong,Huang, Ling,Zhong, Ben-He,Agyeman, Daniel-Adjei,Lim, Jin-Myoung,Kim, Du-ho,Cho, Maeng-hyo,Kang, Yong-Mook American Chemical Society 2017 ACS APPLIED MATERIALS & INTERFACES Vol.9 No.25
<P>A synergistic approach for advanced cathode materials is proposed. Sodium manganese oxide with a layered-tunnel hybrid structure was designed, synthesized, and subsequently investigated. The layered-tunnel hybrid structure provides fast Na ion diffusivity and high structural stability thanks to the tunnel phase, enabling high rate capability and greatly improved cycling stability compared to that of the pure P2 layered phase while retaining the high specific capacity of the P2 layered phase. The hybrid Structure provided a decent discharge capacity of 133.4 mAh g(-1) even at 8 C, which exceeds the reported hest rate capability for Mn-based cathodes. It also displayed an impressive cycling stability, maintaining 83.3 mAh g(-1) after 700 cycles at 10 C. Theoretical calculation and the potentiostatic intermittent titration technique (PITT) demonstrated that this hybrid structure helps enhance Na ion diffusivity during charge and discharge, attaining, as a result, an unprecendented electrochemical performance.</P>
Lee, Minji,Kim, Jong Hyun,Yoon, Ina,Lee, Chulho,Fallahi Sichani, Mohammad,Kang, Jong Soon,Kang, Jeonghyun,Guo, Min,Lee, Kang Young,Han, Gyoonhee,Kim, Sunghoon,Han, Jung Min National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.23
<P>A protein synthesis enzyme, leucyl-tRNA synthetase (LRS), serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which is a central effector for protein synthesis, metabolism, autophagy, and cell growth. However, its significance in mTORC1 signaling and cancer growth and its functional relationship with other suggested leucine signal mediators are not well-understood. Here we show the kinetics of the Rag GTPase cycle during leucine signaling and that LRS serves as an initiating 'ON' switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an 'OFF' switch by controlling GTP hydrolysis of RagB in the Rag GTPase-mTORC1 axis. The LRS-RagD axis showed a positive correlation with mTORC1 activity in cancer tissues and cells. The GTP-GDP cycle of the RagD-RagB pair, rather than the RagC-RagA pair, is critical for leucine-induced mTORC1 activation. The active RagD-RagB pair can overcome the absence of the RagC-RagA pair, but the opposite is not the case. This work suggests that the GTPase cycle of RagD-RagB coordinated by LRS and Sestrin2 is critical for controlling mTORC1 activation, and thus will extend the current understanding of the amino acidsensing mechanism.</P>
Guo, Hong-Yan,Xing, Yue,Sun, Yu-Qiao,Liu, Can,Xu, Qian,Shang, Fan-Fan,Zhang, Run-Hui,Jin, Xue-Jun,Chen, Fener,Lee, Jung Joon,Kang, Dongzhou,Shen, Qing-Kun,Quan, Zhe-Shan The Korean Society of Ginseng 2022 Journal of Ginseng Research Vol.46 No.6
Background: Ginseng possesses antitumor effects, and ginsenosides are considered to be one of its main active chemical components. Ginsenosides can further be hydrolyzed to generate secondary saponins, and 20(R)-panaxotriol is an important sapogenin of ginsenosides. We aimed to synthesize a new ginsengenin derivative from 20(R)-panaxotriol and investigate its antitumor activity in vivo and in vitro. Methods: Here, 20(R)-panaxotriol was selected as a precursor and was modified into its derivatives. The new products were characterized by <sup>1</sup>H-NMR, <sup>13</sup>C-NMR and HR-MS and evaluated by molecular docking, MTT, luciferase reporter assay, western blotting, immunofluorescent staining, colony formation assay, EdU labeling and immunofluorescence, apoptosis assay, cells migration assay, transwell assay and in vivo antitumor activity assay. Results: The derivative with the best antitumor activity was identified as 6,12-dihydroxy-4,4,8,10,14-pentamethyl-17-(2,6,6-trimethyltetrahydro-2H-pyran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthren-3-yl(tert-butoxycarbonyl)glycinate (A11). The focus of this research was on the antitumor activity of the derivatives. The efficacy of the derivative A11 (IC<sub>50</sub> < 0.3 µM) was more than 100 times higher than that of 20(R)- panaxotriol (IC<sub>50</sub> > 30 µM). In addition, A11 inhibited the protein expression and nuclear accumulation of the hypoxia-inducible factor HIF-1α in HeLa cells under hypoxic conditions in a dose-dependent manner. Moreover, A11 dose-dependently inhibited the proliferation, migration, and invasion of HeLa cells, while promoting their apoptosis. Notably, the inhibition by A11 was more significant than that by 20(R)-panaxotriol (p < 0.01) in vivo. Conclusion: To our knowledge, this is the first study to report the production of derivative A11 from 20(R)-panaxotriol and its superior antitumor activity compared to its precursor. Moreover, derivative A11 can be used to further study and develop novel antitumor drugs.