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41.
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
42.
A highly sensitive nanomechanical cantilever sensor assay based on an electrical measurement has been developed for detecting activated cyclic adenosine monophosphate (cyclic AMP)-dependent protein kinase (PKA). Employing a peptide derived from the heat-stable protein kinase inhibitor (PKI), a magnetic bead system was first selected as a vehicle to immobilize the PKI-(5-24) peptide for capturing PKA catalytic subunit and the activity assay was applied for indirectly assessing the binding. Synergistic interactions of adenosine triphosphate (ATP) and the peptide inhibitor with the kinase were then investigated by a solution phase capillary electrophoretic assay, and by surface plasmon resonance technology which involved immobilization of the peptide inhibitor. After systemically evaluated by a homogeneous direct binding assay, the ATP-dependent recognition of the catalytic subunit of PKA by PKI-(5-24) was successfully transferred on to the nanomechanical cantilevers at protein concentrations of 6.6 pM-66 nM, exhibiting much higher sensitivity and wider dynamic range than the conventional activity assay. Thus, direct assessment of activated kinases using the cantilever sensor system functionalized with specific peptide inhibitors holds great promise in analytical applications and clinical medicine. 相似文献
43.
H. C. Eun Y. Z. Cho H. S. Park I. T. Kim H. S. Lee 《Journal of Radioanalytical and Nuclear Chemistry》2012,292(2):531-535
In this paper, a separation method of radionuclides (Ba, Sr) from LiCl salt wastes generated from the electroreduction process
of spent nuclear fuel was studied to recover pure LiCl salts and reduce radioactive wastes. The method consisted of chemical
conversion process of BaCl2 and SrCl2 in LiCl molten salts by using lithium compounds and vacuum distillation process of LiCl salts. In the chemical conversion,
BaCl2 and SrCl2 in LiCl molten salts were mainly converted into (Ba,Sr)CO3 or (Ba,Sr)SO4. Contents of Ba and Sr in LiCl salts recovered from the vacuum distillation process were equal to about 0.01 of initial concentrations
of Ba and Sr in LiCl molten salts. These results will be utilized to recycle the LiCl salt wastes. 相似文献
44.
Conrad T. Pfeiffer Justin D. Northrup Jae Eun Cheong Melody A. Pham Matthew F.L. Parker Christian E. Schafmeister 《Tetrahedron letters》2018,59(30):2884-2888
Spiroligomers are a class of peptidomimetics that connect interchangeable, stereochemically pure, cyclic monomers through pairs of amide bonds to form diketopiperazines between the monomers. This enables them to adopt predictable and programmable structure due to the rigidity of the final molecule. We present a new method for the solid phase synthesis of highly functionalized spiroligomers that incorporates the use of the p-nitrobenzyloxycarbonyl (pNZ) as a temporary amine protecting group and the pentafluorophenyl ester for monomer activation. This new method allows for the synthesis of spiroligomers with higher purity and increased yields when compared to previous methods. This improved method of synthesis of functionalized spiroligomers will facilitate the development of applications as catalysts, therapeutics and membrane channels. 相似文献
45.
Nb2O5/C nanosheets are successfully prepared through a mixing process and followed by heating treatment.Such Nb2O5/C based electrode exhibits high rate performance and remarkable cycling ability, showing a high and stable specific capacity of ~380 mAh g-1 at the current density of 50 mA g-1(much higher than the theoretical capacity of Nb2O5).Further more,at a current density of 500 mA g-1,the nanocomposites electrode still exhibits a specific capacity of above 150 mAh g-1 after 100 cycles.These results suggest the Nb2O5/C nanocomposite is a high performance anode material for lithium-ion batteries. 相似文献
46.
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
47.
Understanding the congener-specific toxicity in polychlorinated dibenzo-p-dioxins: chlorination pattern and molecular quadrupole moment. 总被引:2,自引:0,他引:2
Byung Jin Mhin Jung Eun Lee Wonyong Choi 《Journal of the American Chemical Society》2002,124(1):144-148
It is well known that the biological activities and toxicities of planar polychlorinated aromatic compounds are extremely sensitive to chlorination pattern. Although their toxic responses have been correlated with the relative affinity for the receptor, the origin of this congener specificity is not well understood. We present a general interpretation of the congener-specific activity in polychlorinated dibenzo-p-dioxins, which concludes that molecular electrostatics is the principal factor determining the structure-activity relationship in this highly controversial environmental pollutant even though this electrostatic interaction represents only a part of the total interaction energy. Through calculations of the molecular charge distribution in the complete set of 76 dioxin congeners, we show that all active congeners share a unique charge distribution pattern, which is quantitatively described in terms of the molecular quadrupole moment (QM). The QM of dioxins changes sensitively and systematically with chlorination pattern. The three-dimensional electrostatic interactions at the receptor-binding site, which are optimized at a specific QM pattern represented by that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, could explain the congener specificity in the binding affinity and toxicity. Although the polarizability also changes systematically with chlorination, it can only account for the effect of the degree of chlorination, not the congener specificity. 相似文献
48.
Eun Hee-Chul Yang Hee-Chul Kim Hyung-Ju Kim Sung-Jun Jeon Min-Ku Lee Keun-Young Seo Bum-Kyoung 《Journal of Radioanalytical and Nuclear Chemistry》2022,331(9):3735-3744
Journal of Radioanalytical and Nuclear Chemistry - CaCO3 powder containing C-14, which has a long half-life, is generated from the treatment process of spent activated carbons from the air cleaning... 相似文献
49.
50.
Diabetes is a chronic metabolic disease that is a constant problem. Previous studies have reported that Benincasa cerifera Savi. extracts are effective in treating diabetes and its complications. Benincasae Exocarpium (BE) is a fruit peel of B. cerifera that has been reported to be used for the prevention and treatment of metabolic diseases such as hyperglycemia, obesity, and hyperlipidemia. However, there are not enough studies on the compounds and bioassays to support the efficacy of BE. The inhibitory activity of the BE extracts and fractions against advanced glycation end-products (AGE) formation and α-glucosidase activity was evaluated. These assays are relevant for the treatment of type 2 diabetes and its complications. Based on these results, compounds 1–11 were isolated through bioassay-guided isolation. In addition, we developed a high-performance liquid chromatography (HPLC) method that can simultaneously analyze these 11 compounds. Activity evaluation of the compounds was also conducted, and eight compounds exhibited significant activity. Among these, flavonoid compounds showed strong activity. A quantitative evaluation of eight bioactive compounds (2, 5–11) was conducted. In conclusion, this study demonstrated the potential of BE for prevention and treatment of type 2 diabetes and its complications. 相似文献