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161.
Jin Young Kim Kyung Hwa Cho Bo Young Jeong Chang Gyo Park Hoi Young Lee 《Experimental & molecular medicine》2020,52(7):1152
Rab coupling protein (RCP) is upregulated in head and neck squamous cell carcinoma (HNSCC) and is correlated with the progression and survival of patients. However, the role of RCP in one of the aggressive types of HNSCC, oral squamous cell carcinoma (OSCC), remains elusive. In the present study, we identified the important role of Zeb1 in RCP-induced OSCC epithelial-to-mesenchymal transition (EMT) and invasion. RCP induces Zeb1 expression, and silencing Zeb1 expression significantly inhibits RCP-induced OSCC invasion. In addition, Zeb1 upregulates MT1-MMP expression to promote OSCC EMT and invasion. Furthermore, we observed that the β1 integrin/EGFR/β-catenin signaling cascade mediates RCP-induced Zeb1 expression to promote OSCC invasion. Notably, we provide evidence that resveratrol (REV) strongly inhibits RCP-induced Zeb1 expression through blocking β1 integrin endosome recycling and EGFR activation, leading to suppression of RCP-induced OSCC invasion, demonstrating the important role of RCP in OSCC invasion and its reversion by REV. Collectively, the present study provides evidence for the first time that RCP aggravates OSCC invasion through increasing Zeb1 expression and subsequently upregulating MT1-MMP expression and that this process is reversed by REV, providing novel biomarkers and indicating the therapeutic potential of REV in OSCC.Subject terms: Oral cancer, Cell invasion 相似文献
162.
Rapid and sensitive silver-lipopolysaccharide staining using PhastSystem in fast horizontal polyacrylamide gel electrophoresis 总被引:1,自引:0,他引:1
A rapid and sensitive silver-lipopolysaccharide staining method has been developed by using PhastSystem. The total time of the procedure (including time of Phastgel electrophoresis) is within 2 h. It is at least 10 times faster than the previous reported methods and the sensitivity is also increased. 相似文献
163.
Vinayak Juvekar Chang Su Lim Dong Joon Lee Sang Jun Park Gyeong Ok Song Hyuk Kang Hwan Myung Kim 《Chemical science》2021,12(1):427
Two-photon photodynamic therapy (TP-PDT) is a promising approach for the treatment of cancer because of its better penetration depth and superior spatial selectivity. Here, we describe an azo group containing cyclized-cyanine derivatives (ACC1 and ACC2) as a two-photon activated, type I based photosensitizer (PS). These small-molecule and heavy atom-free organic dyes showed marked reactive oxygen species (ROS)-generating ability under physiological conditions, as well as fast loading ability into the cells and negligible dark toxicity. Live cell analyses with one- and two-photon microscopy revealed that these dyes showed higher ROS generation ability upon two-photon excitation than upon one-photon excitation via the type I process. The PSs have superior PDT properties compared to conventional Visudyne and 5-ALA under mild conditions. These characteristics allowed for precise PDT at the target region in mimic tumor spheroids, demonstrating that the developed TP PS could be useful in efficient PDT applications and in designing various PSs.Azo containing dyes as a two-photon selective and type I based photosensitizers (PSs) were developed that exhibit excellent photodynamic therapy properties under mild condition. 相似文献
164.
Salma Kassem Alan T. L. Lee David A. Leigh Augustinas Markevicius Daniel J. Tetlow Naoyuki Toriumi 《Chemical science》2021,12(6):2065
Peptides attached to a cysteine hydrazide ‘transporter module’ are transported selectively in either direction between two chemically similar sites on a molecular platform, enabled by the discovery of new operating methods for a molecular transporter that functions through ratcheting. Substrate repositioning is achieved using a small-molecule robotic arm controlled by a protonation-mediated rotary switch and attachment/release dynamic covalent chemistry. A polar solvent mixtures were found to favour Z to E isomerization of the doubly-protonated switch, transporting cargo in one direction (arbitrarily defined as ‘forward’) in up to 85% yield, while polar solvent mixtures were unexpectedly found to favour E to Z isomerization enabling transport in the reverse (‘backward’) direction in >98% yield. Transport of the substrates proceeded in a matter of hours (compared to 6 days even for simple cargoes with the original system) without the peptides at any time dissociating from the machine nor exchanging with others in the bulk. Under the new operating conditions, key intermediates of the switch are sufficiently stabilized within the macrocycle formed between switch, arm, substrate and platform that they can be identified and structurally characterized by 1H NMR. The size of the peptide cargo has no significant effect on the rate or efficiency of transport in either direction. The new operating conditions allow detailed physical organic chemistry of the ratcheted transport mechanism to be uncovered, improve efficiency, and enable the transport of more complex cargoes than was previously possible.Peptides are transported in either direction between chemically similar sites on a molecular platform, substrate repositioning is achieved using a cysteine hydrazide transporter module and a small-molecule robotic arm controlled by a rotary switch. 相似文献
165.
CHIP-mediated hyperubiquitylation of tau promotes its self-assembly into the insoluble tau filaments
Ji Hyeon Kim Jeeyoung Lee Won Hoon Choi Seoyoung Park Seo Hyeong Park Jung Hoon Lee Sang Min Lim Ji Young Mun Hyun-Soo Cho Dohyun Han Young Ho Suh Min Jae Lee 《Chemical science》2021,12(15):5599
The tau protein is a highly soluble and natively unfolded protein. Under pathological conditions, tau undergoes multiple post-translational modifications (PTMs) and conformational changes to form insoluble filaments, which are the proteinaceous signatures of tauopathies. To dissect the crosstalk among tau PTMs during the aggregation process, we phosphorylated and ubiquitylated recombinant tau in vitro using GSK3β and CHIP, respectively. The resulting phospho–ub-tau contained conventional polyubiquitin chains with lysine 48 linkages, sufficient for proteasomal degradation, whereas unphosphorylated ub-tau species retained only one–three ubiquitin moieties. Mass-spectrometric analysis of in vitro reconstituted phospho–ub-tau revealed seven additional ubiquitylation sites, some of which are known to stabilize tau protofilament stacking in the human brain with tauopathy. When the ubiquitylation reaction was prolonged, phospho–ub-tau transformed into insoluble hyperubiquitylated tau species featuring fibrillar morphology and in vitro seeding activity. We developed a small-molecule inhibitor of CHIP through biophysical screening; this effectively suppressed tau ubiquitylation in vitro and delayed its aggregation in cultured cells including primary cultured neurons. Our biochemical findings point to a “multiple-hit model,” where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process, thus indicating that targeting tau ubiquitylation may be an effective strategy to alleviate the course of tauopathies.Multiple-hit model for tau aggregation, where sequential events of tau phosphorylation and hyperubiquitylation function as a key driver of the fibrillization process. 相似文献
166.
The thermal expansion properties of crystalline organic compounds are investigated by data mining of the Cambridge Structural Database (CSD). The mean volumetric thermal expansion coefficient is 168.8 × 10−6 K−1 and the mean uniaxial thermal expansion coefficient is 71.4 × 10−6 K−1, based on 745 and 1129 different observations, respectively. Normal and anomalous coefficients can be identified using these values and the associated standard deviations. The anisotropy of the thermal expansion is also evaluated and found to have a very broad distribution. 4719 different structures, comprising 4093 different molecular compounds and 626 additional polymorphs have been analyzed on their thermal expansion properties. Approximately 34% of these structures may have at least one orthogonal axis with negative thermal expansion, much more than generally believed. Moreover 127 structures have been identified which could have negative volumetric thermal expansion. Experimental validation using a robust protocol with data collected at more than 2 different temperatures is required to validate these cases.The thermal expansion properties of crystalline organic compounds are investigated by data mining of the Cambridge Structural Database (CSD). Negative uniaxial thermal expansion is much more common than generally believed. 相似文献
167.
Kim HG Lee CW Yun S Hong BH Kim YO Kim D Ihm H Lee JW Lee EC Tarakeshwar P Park SM Kim KS 《Organic letters》2002,4(22):3971-3974
[formula: see text] A new molecular system, 2,11-dithio[4,4]metametaquinocyclophane containing a quinone moiety, was designed and synthesized. As the quinone moiety can readily be converted into an aromatic pi-system (hydroquinone) upon reduction, the nanomechanical molecular cyclophane system exhibits a large flapping motion like a molecular flipper from the electrochemical redox process. The conformational changes upon reduction and oxidation are caused by changes of nonbonding interaction forces (devoid of bond formation/breaking) from the edge-to-face to face-to-face aromatic interactions and vice versa, respectively. 相似文献
168.
Applied Biochemistry and Biotechnology - By inserting metallocatalysts (such as platinum, osmium, or ruthenium) at the reducing site of photosystem I (PSI), electrons that emerge from PSI can be... 相似文献
169.
[reaction: see text] A new iterative strategy for the synthesis of unsymmetrically substituted polyynes has been developed. The starting bromoalkyne is homologated by one acetylene unit through palladium-catalyzed cross-coupling with a TIPS-protected terminal acetylene and a subsequent in situ one-pot AgF-mediated desilylative bromination. The utility of this new synthetic method is demonstrated by its application to the total synthesis of (S)-(E)-15,16-dihydrominquartynoic acid. 相似文献
170.
W. Lyoo C. Park J. Yeum B. Ji C. Lee S. Lee J. Lee 《Colloid and polymer science》2002,280(12):1075-1083
To prepare ultrahigh molecular weight (UHMW) poly(vinyl pivalate) (PVPi) with high conversion and high linearity for a precursor of syndiotacticity-rich UHMW poly(vinyl alcohol) (PVA), vinyl pivalate (VPi) was suspension polymerized using a low-temperature initiator, 2,2'-azobis(2,4-dimethylvaleronitrile) (ADMVN), and the effects of polymerization conditions on the polymerization behavior and molecular structures of PVPi and PVA prepared by saponifying PVPi were investigated. Suspension polymerization was slightly inferior to bulk polymerization in increasing the molecular weight of PVA. In contrast, the former was superior in increasing the conversion of the polymer. Suspension polymerization of VPi at 25 °C by controlling various polymerization factors proved to be successful in obtaining PVA of UHMW (number-average degree of polymerization (Pn): 14,700-16,700), high syndiotactic diad content (62%), and of high yield (ultimate conversion of VPi into PVPi: 85-90%). In the case of bulk polymerization of VPi under the same conditions, maximum Pn, conversion of 15,800-17,000, and 25-35% were obtained, respectively. The degree of branching was lower and the Pn and syndiotacticity were higher with PVA prepared from PVPi polymerized at lower temperatures. All PVAs from PVPi suspension-polymerized at 25 °C were fibrous, with a high degree of crystallinity and orientation of the crystallites. 相似文献