BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2021
·
IF 3.575
Dequan Kong,Baoying Xie,Yuhang Li,Yaping Xu
Palmitoylethanolamide (PEA) offers a strong protection against BBB disruption and neurological deficits after cerebral ischaemic/reperfusion (I/R) injury. To date, these BBB protective effects of PEA are mainly attributed to PPARα-mediated actions. However, whether PEA protects against BBB disruption through direct regulation of cytoskeletal microfilaments remains unknown. Here, we identified PEA as a Rho-associated protein kinase (ROCK2) inhibitor (IC 50 = 38.4 ± 4.8 μM). In vitro data suggested that PEA reduced the activation of ROCK/MLC signaling and stress fiber formation within microvascular endothelial cells (ECs) after oxygen-glucose deprivation (OGD), and consequently attenuated early (0–4 h) EC barrier disruption. These actions of PEA could not be blocked by the PPARα antagonist GW6471. In summary, the present study described a previously unexplored role of PEA as a ROCK2 inhibitor, and propose a PPARα-independent mechanism for pharmacological effects of PEA.
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EXPERIMENTAL NEUROLOGY
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2020
·
IF 4.691
Shuai Zhang,Mei-Ling Yan,Lin Yang,Xiao-Bin An,Hong-Mei Zhao,Sheng-Nan Xia,Zhuo Jin,Si-Yu Huang,Yang Qu,Jing Ai
Chronic cerebral hypoperfusion (CCH) promotes the development of Alzheimer's pathology. However, whether and how CCH impairs the synaptic vesicle trafficking is still unclear. In the present study, we found that the hippocampal glutamatergic vesicle trafficking was impaired as indicated by a significant shortened delayed response enhancement (DRE) phase in CA3-CA1 circuit and decreased synapsin I in CCH rats suffering from bilateral common carotid artery occlusion (2VO). Further study showed an upregulated miR-153 in the hippocampus of 2VO rats. In vitro, overexpression of miR-153 downregulated synapsin I by binding the 3′UTRs of SYN1 mRNAs, which was prevented by its antisense AMO-153 and miRNA-masking antisense oligodeoxynucleotides ( SYN1-ODN ). In vivo , the upregulation of miR-153 elicited similar reduced DRE phase and synapsin I deficiency as CCH. Furthermore, miR-153 knockdown rescued the downregulated synapsin I and shortened DRE phase in 2VO rats. Our results demonstrate that CCH impairs hippocampal glutamatergic vesicle trafficking by upregulating miR-153 , which suppresses the expression of synapsin I at the post-transcriptional level. These results will provide important references for drug research and treatment of vascular dementia .
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RUSSIAN JOURNAL OF INORGANIC CHEMISTRY
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2020
·Vol. 65
·期 8
·1186-1195
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IF 0.94
Xue-Wen Liu,Liu Ning-Yi,Deng Yuan-Qing,Wang Shan,Liu Ting
Abstract Two ruthenium complexes containing nitro-substituted ligand, [Ru(bpy) 2 (hnpip)](PF 6 ) 2 ( 1 ) and [Ru(phen) 2 (hnpip)](PF 6 ) 2 ( 2 ) (bpy = 2,2'-bipyridine; phen = 1,10-phenanthroline; hnpip = 2-(3-hydroxyl- 4-nitrophenyl)imidazo[4,5- f ][1,10-phenanthroline] were synthesized and characterized. DNA binding behaviors were studied by luminescent titration, UV-vis titration, FRET (FRET = Fluorescence resonance energy transfer) and molecular docking experiments. Complex 2 exhibited “light switch” effect upon addition of G-quadruplex DNA and displayed fluorescent selectivity towards G-quadruplex DNA over other DNAs in the presence of K 4 [Fe(CN) 6 ]. Fluorescence experiments, FRET experiments and molecular docking results indicated that the selectivity may be attributed to protection of nitro group from water, DNA affinity and the difference in DNA structures. Furthermore, both complexes were found to cleave DNA under irradiation by the formation of singlet oxygen. DNA topoisomerase inhibition experiments indicated that complex 2 exhibited higher topoisomerase I inhibition activity (IC 50 = 18 μM) than complex 1 (IC 50 = 50 μM). Docking studies revealed that complex 2 stabilized Top1cc complex via π–π interaction and the formation of hydrogen bond.
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Journal of Functional Foods
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2020
·
IF 3.701
Zhenbang Xiao,Shengtao Yang,Jiali Chen,Chengyong Li,Chunxia Zhou,Pengzhi Hong,Shengli Sun,Zhong-Ji Qian
Ultraviolet radiation B cause photoaging of the skin by enhancing the high expression of matrix metalloproteinases (MMPs) to degrade collagen and inhibit the synthesis of procollagen. Trehalose (TRE), a widely occurring natural disaccharide, has been shown to play a cytoprotective role in many pathological processes. However, few studies have evaluated whether it has anti-photoaging potential. In this study, we investigated the anti-photoaging and mechanism of action of TRE using Human immortalized keratinocytes (HaCaT) cells. The results indicated that TRE pretreatment effectively scavenges reactive oxygen species (ROS) accumulation induced by UVB and increases the content of certain endogenous antioxidant factors in HaCaT cells. TRE suppressed UVB-induced MMP expression by blocking mitogen-activated protein kinases (MAPKs), activator protein 1 (AP-1) and NF-κB signaling. TRE treatment increased procollagen I synthesis via activating transforming growth factor-β (TGF-β)/Smad pathway and demonstrated that TRE may be a potential natural disaccharide for photoaging therapy in the future.
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JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Sheng Zhao,Yongyi Qu,Wei Chen,Ruotong Li,Jing Zhu,Yunyun Wu,Lunli Xiang,Lin Li,Hongrui Zhu,Jixi Zhang
Nanocomposite hydrogel enables spatial redox compartmentalization. • Nanoparticle-released neocuproine hijacks endogenous Cu(I) pools. • Mitochondrial Cu(I) redistribution induces immunogenic cuproptosis. • Extracellular antioxidant components buffer ROS to preserve immunity. • Preoperative in situ vaccination elicits durable immune memory. Cuproptosis-based in situ tumor vaccination provides a unique opportunity to transform tumor destruction into systemic antitumor immunity. However, the oxidative stress required for efficient tumor killing simultaneously disrupts immune competence through copper toxicity and immunosuppressive remodeling. Herein, we develop a spatial redox compartmentalized nanocomposite hydrogel platform to resolve this paradox by selectively amplifying intracellular cuproptosis while preserving the extracellular immune niche. Following peritumoral co-injection of gallic acid-grafted chitosan (CS-GA), dopamine-grafted oxidized hyaluronic acid (OHA-DA), and neocuproine-caffeic acid (NCP-CA) nanoparticles, the hydrogel establishes distinct redox microdomains for tumor eradication and immune protection. Specifically, NCP selectively exploits endogenous exchangeable Cu(I) pools and redirects copper toward mitochondria, where copper valence transformation and ferredoxin 1-mediated activation induce dihydrolipoamide S -acetyltransferase oligomerization, mitochondrial proteotoxic stress, and cuproptotic immunogenic cell death. Meanwhile, CA treatment was associated with increased AMPK phosphorylation and a 63.5% reduction in PD-L1 expression. Simultaneously, catechol-mediated redox cycling by CS-GA&OHA-DA continuously scavenges extracellular reactive oxygen species, alleviating oxidative immunosuppression and restoring T-cell viability to 94.4%. After 14 days of treatment, a substantial tumor regression was observed with a tumor volume reduction exceeding 64.2%. In a contralateral tumor rechallenge model, enhanced infiltration of CD8 + T-cells (40.8%) and CD8 + T EM -cells (26.4%) contributed to 75.6% inhibition of tumor recurrence and 93.3% suppression of metastasis. By exploiting endogenous copper resources rather than exogenous copper supplementation and spatially decoupling tumoricidal oxidation from immune-protective antioxidation, this hydrogel platform establishes a new approach for cuproptosis-based in situ vaccination, inducing durable antitumor immune memory and effectively preventing postoperative tumor recurrence and metastasis. Download: Download high-res image (299KB) Download: Download full-size image
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BIOORGANIC CHEMISTRY
·
2019
·
IF 3.926
Wen-Jin Zhang,Peng-Hui Li,Min-Cong Zhao,Yao-Hao Gu,Chang-Zhi Dong,Hui-Xiong Chen,Zhi-Yun Du
Psoriasis is a chronic inflammatory and immune-mediated skin disease. Although certain agents have shown clinical success in treating psoriasis, development of safe and effective strategies for the treatment of this condition remains important. Research suggests that DNA topoisomerase I (Topo I) inhibitors may have potent psoriasis-ameliorating effects. Here, 25 quinoline derivatives were synthesized and identified as Topo I inhibitors. These compounds inhibited the 12– O –tetradecanoylphorbol-13-acetate-induced mouse ear inflammation. The most potent analogs, 5i and 5l , suppressed the expression of inflammatory cytokines in lipopolysaccharide-stimulated HaCaT cells. Additionally, the lead compounds significantly improved imiquimod-induced psoriasis-like inflammation in mice. Moreover, the expression levels of cytokines and inflammatory mediators, such as interleukin (IL)-17A, IL-22, IL-23, nuclear factor-κB subunit p65, tumor necrosis factor-α, and interferon-γ, were dramatically inhibited in the dorsal skin of 5i - and 5l -treated mice. These findings indicate that the inhibition of Topo I activity may potentially be an effective strategy for psoriasis treatment.
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International Journal of Nanomedicine
·
2023
·
IF 8
Huazhang Qiu,Namei Wu,Yanjie Zheng,Min Chen,Shaohuang Weng,Yuanzhong Chen,Xinhua Lin
A robust and versatile signal-on fluorescence sensing strategy was developed to provide label-free detection of various target analytes. The strategy used SYBR Green I dye and graphene oxide as signal reporter and signal-to-background ratio enhancer, respectively. Multidrug resistance protein 1 (MDR1) gene and mercury ion (Hg2+) were selected as target analytes to investigate the generality of the method. The linear relationship and specificity of the detections showed that the sensitive and selective analyses of target analytes could be achieved by the proposed strategy with low detection limits of 0.5 and 2.2 nM for MDR1 gene and Hg2+, respectively. Moreover, the strategy was used to detect real samples. Analytical results of MDR1 gene in the serum indicated that the developed method is a promising alternative approach for real applications in complex systems. Furthermore, the recovery of the proposed method for Hg2+ detection was acceptable. Thus, the developed label-free signal-on fluorescence sensing strategy exhibited excellent universality, sensitivity, and handling convenience.
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ACS Applied Energy Materials
·
2021
·
IF 6.024
Zheng Jiang,Jun Wang,Enyi Hu,Jingjing Liu,Lei Yu,Faze Wang
The p-i-n junction structure has garnered great interest from researchers due to its increased photoactive area and wider space charger region compared with that of the p-n junction. Herein the ultrawide bandgap (∼6.7 eV) semiconductor alumina (Al2O3) has been introduced to construct a p-i-n junction with ZnO and NiO. ZnO–Al2O3–NiO powders are suitable for electrolyte membrane material of low-temperature solid oxide fuel cells (LT-SOFCs). The insulating Al2O3 brings a doubled depletion region and more effective charge separation compared with the p-n junction consisting of ZnO and NiO. The fuel cell based on the p-i-n junction membrane material delivers an enhanced maximum power density (MPD) of 917 mW cm–2 along with a high open-circuit voltage (OCV) of 1.013 V at 550 °C. An analysis based on the space charge region and energy band alignment in the p-i-n junction is proposed to account for the appreciable cell performance and ionic conductivity, as well as the electron blocking and charge separation ability. This study presents a practical p-i-n junction design based on ZnO–Al2O3–NiO via a solution process for LT-SOFC electrolyte material and sheds light on the extensive exploration of p-i-n junctions applied in LT-SOFCs.
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TETRAHEDRON
·
2019
·
IF 2.379
Jingyuan Li,Qingwen Song,Hengxuan Zhang,Ping Liu,Kan Zhang,Junwen Wang,Dengsong Zhang
Chemical fixation of carbon dioxide under mild reaction conditions e.g. atmospheric pressure and low temperature depends upon the ability of catalyst. Herein, a synergistic catalytic scheme of silver sulfadiazine/ n Bu 4 NBr was described for the three-component reaction of propargylic alcohols, CO 2 , and monohydric alcohols. This catalytic system was demonstrated effectively to provide β-oxopropyl carbonates in excellent yields (up to 99% yield with 5 mol% catalyst). The method tolerated a wide scope of propargylic alcohols and monohydric alcohols under atmospheric CO 2 pressure and solvent-free conditions. The excellent catalytic performance was attributed to the synergistic catalysis confirmed by the careful experiments.
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BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
·
IF 3.5
Guiying Wu,Hui Zhong,Ying Wang,Li Chen,Jianbo Sun
A number of NO-releasing quinoline derivatives have been designed and synthesized by introducing NO donor to quinoline carboxylic acid fragment. The anti-proliferation of all target compounds was evaluated against human cancer cell lines (HCT-116, MCF-7, and A549), MCF-7/ADR and normal cell (MCF-10A). Most compounds showed cytotoxic activity on cancer cells and drug-resistant cells with IC 50 values in the range of 0.62–5.51 μM. Importantly, these compounds showed low toxicity to normal cells (4.21–34.08 μM). Further mechanism studies showed that the most potent compound 9 could release high concentration of NO and inhibit the activity of topoisomerase I. In addition, 9 regulated apoptosis-related proteins, generated ROS and blocked MCF-7 cells in G2/M phase to induce cell apoptosis. Furthermore, the P-gp-mediated transport was also influenced by 9 . And 9 could significantly inhibit the growth of tumor in vivo without observable organ-related toxicities. Overall, as a novel NO-releasing quinoline derivative, 9 was worthy for further in-depth study.
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INORGANICA CHIMICA ACTA
·
2021
·
IF 2.545
Dan Zheng,Ting-Hong Huang,Cheng Luo,Jing Tang
Three dinuclear Cu(I) complexes, [Cu 2 (pnd)(PPh 3 ) 4 ](BF 4 ) 2 (1) , [Cu 2 (pnd)(dppp) 2 ] (BF 4 ) 2 (2) , and [Cu 2 (pnd)(DPEphos) 2 ](BF 4 ) 2 (3) (PPh 3 = triphenylphosphine , dppp = 1, 3-bis (diphenylphosphino)propane, DPEphos = bis(2-diphenylphosphinophenyl)ether, pnd = N , N ’-bis (pyridin-2-ylmethylene)naphthyl-1, 5-diimine), have been prepared and characterized by IR, 1 H NMR, 31 P NMR, 13 C NMR, XRD , elemental analysis and X-ray crystal structure analysis. The structural analysis reveals that the flexible pnd in 1 – 3 acts in a trans bridging coordination mode to connect two Cu + ions, forming a S-shape conformation, while each of Cu (I) ion is four-coordinate N2P2, adopting a distorted-tetrahedral geometry. DFT calculations show that the HOMOs of complexes 1 – 3 are primarily located on the copper d -orbital and the phosphine ligand, together with a specific contribution of pnd, while LUMOs are mostly composed of pnd with admixed Cu(I) d-orbital character. Corresponding calculations of atomic charges indicate that the charge of the copper atom in complexes 1 – 3 is below + 1, while the total charges of the coordinated atoms are 0.743–0.786. Moreover, the solid-state emission spectra of complexes 1 – 3 show the existence of broad emission bands at 350–550 nm.
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SYNLETT
·
2021
·Vol. 32
·期 14
·1437-1446
·
IF 2.454
Haifei Wang,Chuliang Gong,Chen Zhang,Xiaojun Zheng,Qinglin Hou,Qingxia Zhou,Guiyin Zhou,Yao Chen
In this work, we introduced a multifunctional Ag(I)/CAAA-amidphos complex catalyzed asymmetric 1,3-dipolar cycloaddition of acrylates with α-imino esters, affording a series of 2,4,5-trisubstituted endo-pyrrolidines in good yields (up to 97%) with high enantioselectivities (up to 98% ee). Meanwhile, the catalytic system was also applied in the three-component one-pot reaction of α-imino esters formed in situ under the action of N,N′-diisopropylcarbodiimide. In addition, the gram-scale reaction was realized for the formal synthesis of (+)-ibophyllidine in eight steps.
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