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181.
Hun Ho Park Junseong Park Hye Joung Cho Jin-Kyoung Shim Ju Hyung Moon Eui Hyun Kim Jong Hee Chang Soo Youl Kim Seok-Gu Kang 《Molecules (Basel, Switzerland)》2021,26(2)
Resident cancer cells with stem cell-like features induce drug tolerance, facilitating survival of glioblastoma (GBM). We previously showed that strategies targeting tumor bioenergetics present a novel emerging avenue for treatment of GBM. The objective of this study was to enhance the therapeutic effects of dual inhibition of tumor bioenergetics by combination of gossypol, an aldehyde dehydrogenase inhibitor, and phenformin, a biguanide compound that depletes oxidative phosphorylation, with the chemotherapeutic drug, temozolomide (TMZ), to block proliferation, stemness, and invasiveness of GBM tumorspheres (TSs). Combination therapy with gossypol, phenformin, and TMZ induced a significant reduction in ATP levels, cell viability, stemness, and invasiveness compared to TMZ monotherapy and dual therapy with gossypol and phenformin. Analysis of differentially expressed genes revealed up-regulation of genes involved in programmed cell death, autophagy, and protein metabolism and down-regulation of those associated with cell metabolism, cycle, and adhesion. Combination of TMZ with dual inhibitors of tumor bioenergetics may, therefore, present an effective strategy against GBM by enhancing therapeutic effects through multiple mechanisms of action. 相似文献
182.
Nuri Choi Gabsik Yang Joo Hyeon Jang Han Chang Kang Yong-Yeon Cho Hye Suk Lee Joo Young Lee 《Molecules (Basel, Switzerland)》2021,26(4)
Gout is a type of inflammatory arthritis caused by the deposition of monosodium uric acid (MSU) crystals in tissues. The etiology of gout is directly linked to the NLRP3 inflammasome, since MSU crystals are NLRP3 inflammasome activators. Therefore, we decided to search for a small-molecule inhibitor of the NLRP3 inflammasome for the prevention of gout inflammation. We found that loganin suppressed MSU crystals-induced caspase-1 (p20) and interleukin (IL)-1β production and apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) specks formation in mouse primary macrophages, showing its ability to inhibit the NLRP3 inflammasome. In an air pouch inflammation model, oral administration of loganin to mice prevented MSU crystals-induced production of mature IL-1β and IL-18 in air pouch exudates, resulting in decreased neutrophil recruitment. Furthermore, oral administration of loganin suppressed MSU crystals-induced gout inflammation in a mouse foot gout model, which was accompanied by the inhibition of the NLRP3 inflammasome. Loganin blocked de novo synthesis of mitochondrial DNA in air pouches and foot tissues injected with MSU crystals. Consistently, loganin prevented MSU crystals-induced mitochondrial damage in macrophages, as it increased mitochondrial membrane potential and decreased the amount of mitochondrial reactive oxygen species. These data demonstrate that loganin suppresses NLRP3 inflammasome activation by inhibiting mitochondrial stress. These results suggest a novel pharmacological strategy to prevent gout inflammation by blocking NLRP3 inflammasome activation and mitochondrial dysfunction. 相似文献
183.
Wang XL Yuan CZ Shen CP Wang P Adachi I Aihara H Arinstein K Aushev T Bakich AM Barberio E Bedny I Bhardwaj V Bitenc U Blyth S Bondar A Bozek A Bracko M Brodzicka J Browder TE Chang P Chen A Chen KF Cheon BG Chiang CC Chistov R Cho IS Choi SK Choi Y Dalseno J Danilov M Dash M Drutskoy A Eidelman S Epifanov D Gabyshev N Go A Gokhroo G Ha H Hayasaka K Hayashii H Hazumi M Heffernan D Hoshi Y Hou WS Hyun HJ Iijima T Inami K Ishikawa A Ishino H Itoh R Iwasaki Y Kah DH Kang JH Kawai H Kawasaki T 《Physical review letters》2007,99(14):142002
The cross section for e+ e- --> pi+ pi- psi(2S) between threshold and sqrt[s]=5.5 GeV is measured using 673 fb(-1) of data on and off the Upsilon(4S) resonance collected with the Belle detector at KEKB. Two resonant structures are observed in the pi+ pi- psi(2S) invariant-mass distribution, one at 4361 +/- 9 +/- 9 MeV/c2 with a width of 74 +/- 15 +/- 10 MeV/c2, and another at 4664 +/- 11 +/- 5 MeV/c2 with a width of 48 +/- 15 +/- 3 MeV/c2, if the mass spectrum is parametrized with the coherent sum of two Breit-Wigner functions. These values do not match those of any of the known charmonium states. 相似文献
184.
Thin-film-based sensitivity enhancement for total internal reflection fluorescence live-cell imaging
We investigated experimentally the evanescent field enhancement based on dielectric thin films in total internal reflection microscopy. The sample employed two layers of Al2O3 and SiO2 deposited on an SF10 glass substrate. Field intensity enhancement measured by fluorescent excitation of microbeads relative to that of a control sample without dielectric films was polarization dependent, determined as 4.2 and 2.4 for TE and TM polarizations, respectively, and was in good agreement with numerical results. The thin-film-based field enhancement was also applied to live-cell imaging of quantum dots, which confirmed the sensitivity enhancement qualitatively. 相似文献
185.
Bongki Cho Hyo Min Cho Hyun Jung Kim Jaehoon Jeong Sang Ki Park Eun Mi Hwang Jae-Yong Park Woon Ryoung Kim Hyun Kim Woong Sun 《Experimental & molecular medicine》2014,46(7):e105
Mitochondrial functions are essential for the survival and function of neurons. Recently, it has been demonstrated that mitochondrial functions are highly associated with mitochondrial morphology, which is dynamically changed by the balance between fusion and fission. Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. Drp1 activity is regulated by several post-translational modifications, thereby modifying mitochondrial morphology. Here, we found that phosphorylation of Drp1 at serine 616 (S616) is mediated by cyclin-dependent kinase 5 (CDK5) in post-mitotic rat neurons. Perturbation of CDK5 activity modified the level of Drp1S616 phosphorylation and mitochondrial morphology in neurons. In addition, phosphorylated Drp1S616 preferentially localized as a cytosolic monomer compared with total Drp1. Furthermore, roscovitine, a chemical inhibitor of CDKs, increased oligomerization and mitochondrial translocation of Drp1, suggesting that CDK5-dependent phosphorylation of Drp1 serves to reduce Drp1''s fission-promoting activity. Taken together, we propose that CDK5 has a significant role in the regulation of mitochondrial morphology via inhibitory phosphorylation of Drp1S616 in post-mitotic neurons. 相似文献
186.
Soo Chool Lee Min Sun Cho Suk Yong Jung Chong Kul Ryu Jae Chang Kim 《Adsorption》2014,20(2-3):331-339
A range of potassium-based alumina sorbents were fabricated by impregnation of alumina with K2CO3 to examine the effects of the structural and textural properties of alumina on the CO2 sorption and regeneration properties. Alumina materials, which were used as supports, were prepared by calcining alumina at various temperatures (300, 600, 950, and 1,200 °C). The CO2 sorption and regeneration properties of these sorbents were examined during multiple tests in a fixed-bed reactor in the presence of 1 vol% CO2 and 9 vol% H2O. The regeneration capacities of the potassium-based alumina sorbents increased with increasing calcination temperature of alumina. The formation of KHCO3 increased with increasing calcination temperature during CO2 sorption, whereas the formation of KAl(CO3)(OH)2, which is an inactive material, decreased. These results is due to the fact that the structure of alumina by the calcination temperature is related directly to the formation of the by-product [KAl(CO3)(OH)2]. The structure of alumina plays an important role in enhancing the regeneration capacity of the potassium-based alumina sorbent. Based on these results, a new potassium-based sorbent using δ-Al2O3 as a support was developed for post-combustion CO2 capture. This sorbent maintained a high CO2 capture capacity of 88 mg CO2/g sorbent after two cycles. In particular, it showed a faster sorption rate than the other potassium-based alumina sorbents examined. 相似文献
187.
Simultaneous In Situ Quantification of Two Cellular Lipid Pools Using Orthogonal Fluorescent Sensors
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Dr. Shu‐Lin Liu Dr. Ren Sheng Matthew J. O'Connor Yang Cui Dr. Youngdae Yoon Svetlana Kurilova Dr. Daesung Lee Dr. Wonhwa Cho 《Angewandte Chemie (International ed. in English)》2014,53(52):14387-14391
Lipids regulate a wide range of biological activities. Since their local concentrations are tightly controlled in a spatiotemporally specific manner, the simultaneous quantification of multiple lipids is essential for elucidation of the complex mechanisms of biological regulation. Here, we report a new method for the simultaneous in situ quantification of two lipid pools in mammalian cells using orthogonal fluorescent sensors. The sensors were prepared by incorporating two environmentally sensitive fluorophores with minimal spectral overlap separately into engineered lipid‐binding proteins. Dual ratiometric analysis of imaging data allowed accurate, spatiotemporally resolved quantification of two different lipids on the same leaflet of the plasma membrane or a single lipid on two opposite leaflets of the plasma membrane of live mammalian cells. This new imaging technology should serve as a powerful tool for systems‐level investigation of lipid‐mediated cell signaling and regulation. 相似文献
188.
Enhanced solubility of galangin based on the complexation with methylated microbial cyclosophoraoses
Hwanhee Kim Jae Min Choi Youngjin Choi Muhammad Nazir Tahir Yung-Hun Yang Eunae Cho Seunho Jung 《Journal of inclusion phenomena and macrocyclic chemistry》2014,79(3-4):291-300
Methylated cyclosophoraoses (M-Cys) were synthesized by reaction using dimethyl sulfate with native Cys (unbranched cyclic β-1,2-d-glucans) isolated from Rhizobium leguminosarum biovar viciae VF-39. Its structure was proven using nuclear magnetic resonance (1H NMR) spectroscopy, Fourier-transform infrared (FT-IR) spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Based on the enhanced hydrophobicity by methylation of Cys, we investigated the inclusion property with the water-insoluble flavonoid, galangin, through a phase solubility study using ultraviolet–visible spectroscopy. The solubility of galangin was enhanced 5.6-fold according to the added concentrations (1 mM) of M-Cys, compared to the 1.9-fold and 3.4-fold enhancements by β-Cyclodextrin (β-CD) and heptakis (2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD), respectively. M-Cys was also shown to have the highest binding constant (5,534 M?1) with galangin among the tested host molecules (β-CD, DM-β-CD, Cys, and M-Cys). From this result, we can infer that the complex of galangin with M-Cys is more stable than any of the other host molecules. The continuous variation method showed that the galangin/M-Cys complex was suitable for 1:1 stoichiometry. The formation of the complex was confirmed with 1H NMR, FT-IR, differential scanning calorimetry, and scanning electron microscopy. Furthermore, the hypothetical molecular model of 1:1 galangin/M-Cys complex was suggested by molecular docking simulations. The cytotoxicity to the human cervical adenocarcinoma cell lines was enhanced by the galangin/M-Cys complex compared with free galangin. The obtained results indicate that M-Cys can be utilized as an effective complexing agent for galangin. 相似文献
189.
Transition Metal Chemistry - A facile synthetic approach has been adopted towards the synthesis of (2R,3R)-N2,N3-bis((S)-1-phenylethyl)butane-2,3-diamine via demetalation of its dichloro Zn(II)... 相似文献