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41.
Shengying Lin Xiaoyang Wang Roy Wai-Lun Tang Hung Chun Lee Ho Hin Chan Sheyne S. A. Choi Tina Ting-Xia Dong Ka Wing Leung Sarah E. Webb Andrew L. Miller Karl Wah-Keung Tsim 《Molecules (Basel, Switzerland)》2022,27(12)
COVID-19, resulting from infection by the SARS-CoV-2 virus, caused a contagious pandemic. Even with the current vaccines, there is still an urgent need to develop effective pharmacological treatments against this deadly disease. Here, we show that the water and ethanol extracts of the root and rhizome of Polygonum cuspidatum (Polygoni Cuspidati Rhizoma et Radix), a common Chinese herbal medicine, blocked the entry of wild-type and the omicron variant of the SARS-CoV-2 pseudotyped virus into fibroblasts or zebrafish larvae, with IC50 values ranging from 0.015 to 0.04 mg/mL. The extracts were shown to inhibit various aspects of the pseudovirus entry, including the interaction between the spike protein (S-protein) and the angiotensin-converting enzyme II (ACE2) receptor, and the 3CL protease activity. Out of the chemical compounds tested in this report, gallic acid, a phytochemical in P. cuspidatum, was shown to have a significant anti-viral effect. Therefore, this might be responsible, at least in part, for the anti-viral efficacy of the herbal extract. Together, our data suggest that the extracts of P. cuspidatum inhibit the entry of wild-type and the omicron variant of SARS-CoV-2, and so they could be considered as potent treatments against COVID-19. 相似文献
42.
Suvarna H. Pagire Haushabhau S. Pagire Kun-Young Park Eun Jung Bae Kwang-eun Kim Minhee Kim Jihyeon Yoon Saravanan Parameswaran Jun-Ho Choi Sungmi Park Jae-Han Jeon Jin Sook Song Myung Ae Bae In-Kyu Lee Hail Kim Jae Myoung Suh Jin Hee Ahn 《Molecules (Basel, Switzerland)》2022,27(11)
Serotonin (5-hydroxytryptophan) is a hormone that regulates emotions in the central nervous system. However, serotonin in the peripheral system is associated with obesity and fatty liver disease. Because serotonin cannot cross the blood-brain barrier (BBB), we focused on identifying new tryptophan hydroxylase type I (TPH1) inhibitors that act only in peripheral tissues for treating obesity and fatty liver disease without affecting the central nervous system. Structural optimization inspired by para-chlorophenylalanine (pCPA) resulted in the identification of a series of oxyphenylalanine and heterocyclic phenylalanine derivatives as TPH1 inhibitors. Among these compounds, compound 18i with an IC50 value of 37 nM was the most active in vitro. Additionally, compound 18i showed good liver microsomal stability and did not significantly inhibit CYP and Herg. Furthermore, this TPH1 inhibitor was able to actively interact with the peripheral system without penetrating the BBB. Compound 18i and its prodrug reduced body weight gain in mammals and decreased in vivo fat accumulation. 相似文献
43.
X-ray free-electron lasers (XFELs) provide femtosecond X-ray pulses suitable for pump–probe time-resolved studies with a femtosecond time resolution. Since the advent of the first XFEL in 2009, recent years have witnessed a great number of applications with various pump–probe techniques at XFELs. Among these, time-resolved X-ray liquidography (TRXL) is a powerful method for visualizing structural dynamics in the liquid solution phase. Here, we classify various chemical and biological molecular systems studied via femtosecond TRXL (fs-TRXL) at XFELs, depending on the focus of the studied process, into (i) bond cleavage and formation, (ii) charge distribution and electron transfer, (iii) orientational dynamics, (iv) solvation dynamics, (v) coherent nuclear wavepacket dynamics, and (vi) protein structural dynamics, and provide a brief review on each category. We also lay out a plausible roadmap for future fs-TRXL studies for areas that have not been explored yet.Femtosecond X-ray liquidography using X-ray free-electron lasers (XFELs) visualizes various aspects of reaction dynamics. 相似文献
44.
Shanru He Yuanyuan Chen Lulu Wang Xue Bai Tingting Bu Jie Zhang Ming Lu Nam-Chul Ha Chunshan Quan Ki Hyun Nam Yongbin Xu 《Molecules (Basel, Switzerland)》2022,27(15)
Pyridoxal 5′-phosphate (PLP) is the active form of vitamin B6, but it is highly reactive and poisonous in its free form. YggS is a PLP-binding protein found in bacteria and humans that mediates PLP homeostasis by delivering PLP to target enzymes or by performing a protective function. Several biochemical and structural studies of YggS have been reported, but the mechanism by which YggS recognizes PLP has not been fully elucidated. Here, we report a functional and structural analysis of YggS from Fusobacterium nucleatum (FnYggS). The PLP molecule could bind to native FnYggS, but no PLP binding was observed for selenomethionine (SeMet)-derivatized FnYggS. The crystal structure of FnYggS showed a type III TIM barrel fold, exhibiting structural homology with several other PLP-dependent enzymes. Although FnYggS exhibited low (<35%) amino acid sequence similarity with previously studied YggS proteins, its overall structure and PLP-binding site were highly conserved. In the PLP-binding site of FnYggS, the sulfate ion was coordinated by the conserved residues Ser201, Gly218, and Thr219, which were positioned to provide the binding moiety for the phosphate group of PLP. The mutagenesis study showed that the conserved Ser201 residue in FnYggS was the key residue for PLP binding. These results will expand the knowledge of the molecular properties and function of the YggS family. 相似文献
45.
Ye Seul Kim Jung Won Yoon Dasol Kim Seunghak Choi Hyoung Kyu Kim Jae Boum Youm Jin Han Soon Chul Heo Sung-Ae Hyun Jung-Wook Seo Deok-Ho Kim Jae Ho Kim 《Experimental & molecular medicine》2022,54(4):493
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) have been reported to exhibit immature embryonic or fetal cardiomyocyte-like phenotypes. To enhance the maturation of hESC-CMs, we identified a natural steroidal alkaloid, tomatidine, as a new substance that stimulates the maturation of hESC-CMs. Treatment of human embryonic stem cells with tomatidine during cardiomyocyte differentiation stimulated the expression of several cardiomyocyte-specific markers and increased the density of T-tubules. Furthermore, tomatidine treatment augmented the number and size of mitochondria and enhanced the formation of mitochondrial lamellar cristae. Tomatidine treatment stimulated mitochondrial functions, including mitochondrial membrane potential, oxidative phosphorylation, and ATP production, in hESC-CMs. Tomatidine-treated hESC-CMs were more sensitive to doxorubicin-induced cardiotoxicity than the control cells. In conclusion, the present study suggests that tomatidine promotes the differentiation of stem cells to adult cardiomyocytes by accelerating mitochondrial biogenesis and maturation and that tomatidine-treated mature hESC-CMs can be used for cardiotoxicity screening and cardiac disease modeling.Subject terms: Heart failure, Embryonic stem cells, Stem-cell differentiation 相似文献
46.
Shofiul Azam Md. Ezazul Haque Duk-Yeon Cho Joon-Soo Kim Md. Jakaria In-Su Kim Dong-Kug Choi 《Molecules (Basel, Switzerland)》2022,27(9)
Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson’s disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect neuronal cells in PD via reducing apoptosis and enhancing neurogenesis. In this study, the 1-methyl-4-phenylpyridinium ion (MPP+) was used to induce neurotoxicity and impair autophagic flux in a human neuroblastoma cell line (SH-SY5Y). The result showed that dioscin pre-treatment counters MPP+-mediated autophagic flux impairment and alleviates MPP+-induced apoptosis by downregulating activated caspase-3 and BCL2 associated X, apoptosis regulator (Bax) expression while increasing B-cell lymphoma 2 (Bcl-2) expression. In addition, dioscin pre-treatment was found to increase neurotrophic factors and tyrosine hydroxylase expression, suggesting that dioscin could ameliorate MPP+-induced degeneration in dopaminergic neurons and benefit the PD model. To conclude, we showed dioscin’s neuroprotective activity in neuronal SH-SY5Y cells might be partly related to its autophagy induction and suppression of the mitochondrial apoptosis pathway. 相似文献
47.
Ji-Myung Choi Huong Thu Vu Seong-Jin Shin Jun-Yong Ahn You-Jin Kim Sol Song Mi-Ran Han Jun-Haeng Lee Jong-Soo Kim Jonathan C. Knowles Hae-Hyoung Lee Ji-Sun Shin Jong-Bin Kim Jung-Hwan Lee 《Molecules (Basel, Switzerland)》2022,27(9)
Therapeutic iodoform (CHI3) is commonly used as a root-filling material for primary teeth; however, the side effects of iodoform-containing materials, including early root resorption, have been reported. To overcome this problem, a water-soluble iodide (NaI)-incorporated root-filling material was developed. Calcium hydroxide, silicone oil, and NaI were incorporated in different weight proportions (30:30:X), and the resulting material was denoted DX (D5~D30), indicating the NaI content. As a control, iodoform instead of NaI was incorporated at a ratio of 30:30:30, and the material was denoted I30. The physicochemical (flow, film thickness, radiopacity, viscosity, water absorption, solubility, and ion releases) and biological (cytotoxicity, TRAP, ARS, and analysis of osteoclastic markers) properties were determined. The amount of iodine, sodium, and calcium ion releases and the pH were higher in D30 than I30, and the highest level of unknown extracted molecules was detected in I30. In the cell viability test, all groups except 100% D30 showed no cytotoxicity. In the 50% nontoxic extract, D30 showed decreased osteoclast formation compared with I30. In summary, NaI-incorporated materials showed adequate physicochemical properties and low osteoclast formation compared to their iodoform-counterpart. Thus, NaI-incorporated materials may be used as a substitute for iodoform-counterparts in root-filling materials after further (pre)clinical investigation. 相似文献
48.
Abstract A continuum-based configuration design sensitivity analysis method is presented for kinematically driven mechanical systems. Configuration design variable for mechanical systems are defined. The 3-1-3 Euler angle is used as the orientation design variable. The reassembly process for a mechanical system after a configuration design change is eliminated by imposing kinematic admissibility conditions of the velocity field. The direct differentiation method is used to derive design sensitivity equations. Numerical examples are presented to demonstrate the validity and effectiveness of the proposed method. 相似文献
49.
Dr. Chi Kyung Kim Taeho Kim In‐Young Choi Min Soh Dr. Dohoung Kim Young‐Ju Kim Dr. Hyunduk Jang Hye‐Sung Yang Dr. Jun Yup Kim Dr. Hong‐Kyun Park Dr. Seung Pyo Park Sangseung Park Dr. Taekyung Yu Prof. Byung‐Woo Yoon Prof. Seung‐Hoon Lee Prof. Taeghwan Hyeon 《Angewandte Chemie (International ed. in English)》2012,51(44):11172-11172
50.
Hyoung Gwon Choi 《国际流体数值方法杂志》2012,68(7):887-904
In this paper, a least‐square weighted residual method (LSWRM) for level set (LS) formulation is introduced to achieve interface capturing in two‐dimensional (2D) and three‐dimensional (3D) problems. An LSWRM was adopted for two semi‐discretized advection and reinitialization equations of the LS formulation. The present LSWRM provided good mathematical properties such as natural numerical diffusion and the symmetry of the resulting algebraic systems for the advection and reinitialization equations. The proposed method was validated by solving some 2D and 3D benchmark problems such as those involving a rotating slotted disk, the rotation of a slotted sphere, and a time‐reversed single‐vortex flow and a deformation problem of a spherical fluid. The numerical results were compared with those obtained from essentially non‐oscillatory type formulations and particle LS methods. Further, the proposed LSWRM for the LS formulation was coupled with a splitting finite element method code to solve the incompressible Navier–Stokes equations, and then, the collapse of a 3D broken dam flow was well simulated; in the simulation, the entrapping of air and the splashing of the surge front of water were reproduced. The mass conservation of the present method was found to be satisfactory during the entire simulation. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献