NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·579-590
·
IF 4.414
Shen Mengya,Zheng Yuantie,Li Ge,Chen Yinqi,Huang Lili,Wu Jianzhang,Hong Chenglv
Abstract Antioxidants represent a potential therapy for cerebral ischemia–reperfusion injury (CIRI). Compounds which exhibit both direct and indirect antioxidative activity may potentially exert improved effects. Hence, we aimed to assess whether the dual antioxidant DH-217, a derivative of DHAP clinically used to treat coronary heart disease, can reduce oxidative stress damage and elucidate the underlying mechanism. Hydrogen peroxide (H 2 O 2 )-induced and Middle Cerebral Artery Occlusion (MCAO)-induced damages were used to imitate oxidative stress. The antioxidation of DH-217 was determined by MTT, ROS, colony and DPPH assay. Besides, immunofluorescence, Real-Time PCR Analyses, western blotting and si-RNA/Plasmid-induced protein expression were used for mechanism validation. DPPH scavenging assay evidenced DH-217 was a well free radical scavenger. Cell survival assay also showed that DH-217 had a significant cytoprotection through direct and indirect clearance mechanisms. Further, it clearly inhibited oxidative stress-induced IkappaB kinase beta (IKKβ) phosphorylation and increased heme oxygenase-1 (HO-1) expression. Significantly, these antioxidant beneficial effects were reversed by HO-1 inhibitor, si-nuclear erythroid 2-related factor 2 (Nrf2) and IKKβ plasmid. Meanwhile, DH-217 had a good neuroprotective effect on CIRI rats. The dual antioxidant DH-217 has potential reference value for drug development of CIRI. Furthermore, inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 could be a promising antioxidant pathway. Graphical Abstract Dual antioxidant DH-217 not only has the ability of directly scavenging ROS, but also can clear it by targeting IKKβ/Nrf2/HO-1 signal axis. Inhibition of IKKβ phosphorylation and activation of Nrf2/HO-1 may be a promising antioxidant pathway for CIRI.
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Frontiers in Pharmacology
·
2023
·
IF 5.6
Gao Rongyin,Zhang Ximei,Zou Kun,Meng Duo,Lv Jinpeng
Cutaneous pigmentation was recently shown to be an event regulated by clock proteins. Cryptochrome (CRY) is a key protein composing the feedback loop of circadian clock, however, the function of CRY in melanocytes remains unclear. Here, we found that KL001, a synthetic small molecule modulator of CRY1, inhibited melanin synthesis, as well as reduced melanocyte dendrite elongation and melanosome transport. In addition, the dominant role of CRY1 in KL001-induced anti-melanogenesis was revealed by small interfering RNA transfection. Cellular tyrosinase activity and expression level of melanogenic proteins, including tyrosinase, TRP-1, TRP-2, and transport proteins like Rab27a, Cdc42 and Myosin Va induced by α-MSH were remarkably reversed after KL001 treatment. Mechanistically, CRY1 activation inhibited melanogenesis through CREB-dependent downregulation of MITF and CREB phosphorylation was mediated by classical cAMP/PKA pathway. In addition, the other CRY1 activator, KL044 also suppressed cAMP/PKA/CREB pathway and inhibited melanogenesis. Finally, anti-melanogenic efficacy of KL001 was confirmed by determination of melanin contents in UVB-tanning model of brown guinea pigs, which indicated that targeting CRY1 activity, via topical application of small molecule activator, can be utilized therapeutically to manage human pigmentary disorders.
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ACS Omega
·
2023
·
IF 4.1
Haoyue Hao,MengYao Zhu,Liang Li
In this paper, Er3+/Yb3+ codoped Y2(1–x%)Lu2x %O3 solid solution was prepared through the sol–gel method, and the substitution of Y3+ by Lu3+ ions in Y2O3 was confirmed by X-ray diffraction data. The up-conversion emissions of samples under 980 nm excitation and the relative up-conversion processes are investigated. The emission shapes do not vary with the change in doping concentration due to the unaltered cubic phase. The red-to-green ratio changes from 2.7 to 7.8 and then declines to 4.4 as the doping concentration of Lu3+ increases from 0 to 100. The emission lifetimes of green and red have similar variation: the emission lifetime decreases with doping concentration changing from 0 to 60 and rises as the doping concentration continues to increase. The reason why the emission ratio and lifetime change could be originated to the exacerbation of cross-relaxing process and the change of radiative transition probabilities. The temperature-dependent fluorescence intensity ratio (FIR) shows that all samples can be used in noncontact optical temperature sensing, and the method of local structure distortion can be used to improve sensitivity further. The max sensing sensitivities of FIR based on R538/563 and Rred/green reach 0.011 K–1 (483 K) and 0.21 K–1 (300 K). The results display that Er3+/Yb3+ codoped Y2(1–x %)Lu2x %O3 solid solution can be potential candidates for optical temperature sensing in different temperature ranges.
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Frontiers in Immunology
·
2022
·
IF 8.786
Gu Lingui,Sun Mingjiang,Li Ruihao,Zhang Xingyu,Tao Yihao,Yuan Ye,Luo Xu,Xie Zongyi
Neuroinflammation has been proven to exert an important effect on brain injury after intracerebral hemorrhage (ICH). Previous studies reported that Didymin possessed anti-inflammatory properties after acute hepatic injury, hyperglycemia-induced endothelial dysfunction, and death. However, the role of Didymin in microglial pyroptosis and neuroinflammation after ICH is unclear. The current study aimed to investigate the effect of Didymin on neuroinflammation mediated by microglial pyroptosis in mouse models of ICH and shed some light on the underlying mechanisms. In this study, we observed that Didymin treatment remarkably improved neurobehavioral performance and decreased BBB disruption and brain water content. Microglial activation and neutrophil infiltration in the peri-hematoma tissue after ICH were strikingly mitigated by Didymin as well. At the molecular level, administration of Didymin significantly unregulated the expression of Rkip and downregulated the expression of pyroptotic molecules and inflammatory cytokines such as Nlrp3 inflammasome, GSDMD, caspase-1, and mature IL-1β, TNF-α, and MPO after ICH. Besides, Didymin treatment decreased the number of Caspase-1-positive microglia and GSDMD-positive microglia after ICH. Inversely, Locostatin, an Rkip-specific inhibitor, significantly abolished the anti-pyroptosis and anti-neuroinflammation effects of Didymin. Moreover, Rkip binding with Asc could interrupt the activation and assembly of the inflammasome. Mechanistically, inhibition of Caspase-1 by VX-765 attenuated brain injury and suppressed microglial pyroptosis and neuroinflammation by downregulation of GSDMD, mature IL-1β, TNF-α, and MPO based on Locostatin-treated ICH. Taken together, Didymin alleviated microglial pyroptosis and neuroinflammation, at least in part through the Asc/Caspase-1/GSDMD pathway via upregulating Rkip expression after ICH. Therefore, Didymin may be a potential agent to attenuate neuroinflammation via its anti-pyroptosis effect after ICH.
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 9
·1386-1392
·
IF 7.571
Ling Yang,Ping’an Ma,Xiaorui Chen,Ziyong Cheng,Jun Lin
Sensitive detection of circulating tumor DNA (ctDNA) in vitro has attracted growing attention owing to its potential application in diagnostics of cancer. In this study, we synthesized hydrophilic AgInS2@ZnS core–shell quantum dot nanocrystals and magnetic Fe3O4 nanoparticles, and then the ctDNA triggered hybridization chain reaction was used to detect the CYFRA21-1 DNA associated with lung cancer. In the presence of CYFRA21-1 DNA, three hairpin structures were activated to turn on successively, resulting in the accumulation of quantum dots and eliciting considerable changes of the fluorescence signal. Compared with the conventional fluorescence detection, Fe3O4 provides magnetic adsorption properties and a large surface area for immobilizing and aggregating quantum dot nanoparticles attached to single-stranded DNA. The concentration of CYFRA21-1 is closely related to the number of quantum dots remaining after magnetic adsorption, which provides a promising approach for ctDNA quantification.
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Small Methods
·
2022
·Vol. 6
·期 4
·2101509
·
IF 15.367
Xiaojie Zhou,Yichen Cai,Mingsheng Xu,Jianping Li,Chenxu Sheng,Qiuyi Zhang,Xinxia Qiu,Wenchong Wang,Shisheng Xiong,Chunxiao Cong,Zhi-Jun Qiu,Ran Liu,Laigui Hu
The emergence of near-eye displays, such as head-mounted displays, is triggering a requirement for highly enhanced display resolution. High-resolution micro-displays with micro-organic light-emitting diodes (micro-OLEDs) can be a preferential candidate, owing to the mature industrialization of OLEDs along with the advantages of flexibility, light weight, and ease of processing. However, micro-OLEDs with pixel sizes down to micrometers are difficult to be achieved using conventional techniques such as fine metal mask evaporation and lithography. Here, a solution-processing approach to pattern organic semiconductors (OSCs) for micro-OLED arrays with the assistance of templated dewetting is demonstrated. Solvents containing organic functional materials are dewetted on the surface with hydrophobic/hydrophilic patterns to form ordered droplet arrays using dip-coating. Subsequently, patterned OSC films are produced by effectively controlling solvent evaporation. Micro-OLED arrays with a pixel size down to 1 µm are successfully fabricated by further deposition of emitting/electron transport layers and top electrodes. This approach can open an avenue for low-cost manufacturing of flexible and high-resolution micro-displays.
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SEPARATION AND PURIFICATION TECHNOLOGY
·
2022
·
IF 9.136
Fei Yu,Xueting Bai,Mingxing Liang,Jie Ma
Considering the increasingly serious levels of antibiotic pollution, it is necessary to find new and efficient adsorbents. In this study, the adsorptive removal of a model quinolone antibiotic, ciprofloxacin (CIP), from wastewater is presented using a metal–organic framework (MOF)-derived carbon. HKUST-1-derived carbon (HDC-1100) was obtained by high-temperature carbonization of the HKUST-1 precursor at 1100 °C. HDC-1100 has a regular octahedron shape decorated with Cu/Cu 2 O particles and has a microporous and mesoporous structure with abundant oxygen-containing functional groups on the surface. Within 48 h, HDC-1100 could reach adsorption equilibrium for 30 mg·L -1 CIP, and the kinetic data were fitted with a pseudo-first-order model and a pseudo-second-order model. In this study, the maximum adsorption capacity of HDC-1100 for CIP was as high as 592 mg·g −1 . The high adsorption capacity is attributed mainly to metal–organic complexation, electrostatic interactions, and hydrogen bonding. Also, the effects of environmental factors, such as pH, ionic strength, and humic acid, on the adsorption capacity were considered. This study is significant for the treatment of high-concentration antibiotic-polluted wastewater.
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EUROPEAN JOURNAL OF PHARMACOLOGY
·
2022
·
IF 5.195
Huizhen Sun,Anyong Zhang,Yanchun Gong,Wei Sun,Baiyi Yan,Shuihong Lei,Li-Hua Yao
Diabetes mellitus (DM) has recently become one of the major diseases that have received attention. Cordycepin (molecular formula: C 10 H 13 N 5 O 3 ), is one of the major bioactive components of Cordyceps militaris , decreases blood glucose levels. In this study, the effect and mechanism of cordycepin in normal and oxidative-damaged INS-1 cells were explored by using cell and molecular biology methods. Results showed that cordycepin could enhance insulin synthesis and secretion. The mechanism is possibly related to the elevated ATP content induced membrane depolarisation and increased Ca 2+ concentration. At the genetic level, cordycepin upregulated the mRNA level of insulin, pancreatic duodenal homeobox factor-1 (PDX-1) and glucose transporter 1 (GLUT1). At the protein level, cordycepin promoted the expression of PDX-1, GLUT1, serine threonine kinase (Akt) and phosphorylated Akt (P-Akt). These effects may also contribute to the enhancement of insulin synthesis and secretion. Further analysis revealed that cordycepin protected against H 2 O 2 -induced damage on INS-1 cells and improved their viability and insulin synthesis/secretion. This effect should be attributed to the reduced intracellular reactive oxygen species (ROS), enhanced mitochondrial membrane potential (MMP), increased activity of superoxide dismutase (SOD) and upregulated genetic and protein expression of catalase (CAT), PDX-1, GLUT1 and P-Akt. In conclusion, cordycepin promotes insulin synthesis and secretion in normal islet β cells and improves this function in oxidative-damaged islet β cells. Given that islet β cells are vulnerable to oxidative stress , the improving effect of cordycepin on the antioxidant capacity and insulin synthesis/secretion of INS-1 cells may be an important mechanism for its hypoglycaemic effect.
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PHYTOMEDICINE
·
2022
·
IF 6.656
Ying-kun Zhi,Jing Li,Lang Yi,Rui-li Zhu,Jin-fang Luo,Qing-ping Shi,Sha-sha Bai,Yan-wu Li,Qun Du,Jia-zhong Cai,Liang Liu,Pei-xun Wang,Hua Zhou,Yan Dong
Background Sinomenine (SIN) is an anti-inflammatory drug that has been used for decades in China to treat arthritis . In a previous study, SIN acted on α7 nicotinic acetylcholine receptor (α7nAChR) to inhibit inflammatory responses in macrophages, which indicates a new anti-inflammatory mechanism of SIN. However, the level of α7nAChR was increased in the inflammatory responses and was downregulated by SIN in vitro, so the underlying mechanisms of SIN acting on α7nAChR remain unclear. Purpose To analyze the role of α7nAChR in inflammation and the effect and mechanism of SIN regulation of α7nAChR. Methods The effects of SIN on α7nAChR in endotoxemic mice and LPS-stimulated macrophages were observed. Nicotine (Nic) was used as a positive control, and berberine (Ber) was used as a negative control targeting α7nAChR. The antagonists of α7nAChR, α-bungarotoxin (BTX) and mecamylamine (Me), were used to block α7nAChR. In RAW264.7 macrophage cells in vitro , α7nAChR short hairpin RNA (shRNA) was used to knock down α7nAChR. Macrophage polarization was analyzed by the detection of TNF-α, IL-6, iNOS, IL-10, Arg-1, and Fizz1. U0126 was used to block ERK phosphorylation. The cytokines α7nAChR, ERK1/2, p-ERK1/2 and Egr-1 were detected. Results SIN decreased the levels of TNF-α, IL-6 and the expression of α7nAChR increased by LPS in endotoxemic mice. The above effects of SIN were attenuated by BTX. In the α7nAChR shRNA transfected RAW264.7 cells, compared with the control, α7nAChR was knocked down, and M1 phenotype markers (including TNF-α, IL-6, and iNOS) were significantly downregulated, whereas M2 phenotype markers (including IL-10, Arg-1, and Fizz1) were significantly upregulated when stimulated by LPS. SIN inhibited the expression of p-ERK1/2 and the transcription factor Egr-1 induced by LPS in RAW264.7 cells, and the above effects of SIN were attenuated by BTX. The expression of α7nAChR was suppressed by U0126, which lessened the expression of p-ERK1/2 and Egr-1. Conclusions SIN acts on α7nAChR to inhibit inflammatory responses and downregulates high expression of α7nAChR in vivo and in vitro . The increase of α7nAChR expression is correlated with inflammatory responses and participates in macrophage M1 polarization. SIN downregulates α7nAChR via a feedback pathway of α7nAChR/ERK/Egr-1, which contributes to inhibiting macrophage M1 polarization and inflammatory responses.
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APPLIED ORGANOMETALLIC CHEMISTRY
·
2022
·Vol. 36
·期 6
·e6693
·
IF 4.072
Jiale Liu,Mengyao Huang,Zhongyu Hua,Jiatong Ni,Yi Dong,Zeran Feng,Tiedong Sun,Chunxia Chen
Chemodynamic therapy (CDT) uses the conversion of H 2 O 2 to ·OH triggered by Fenton-like reactions to treat tumors, but the treatment is not complete due to insufficient intracellular H 2 O 2 content. Photothermal therapy (PTT) uses photothermal materials for photothermal conversion to kill tumors, but it is limited by the extent of exogenous light transmission and cannot achieve satisfactory therapeutic effects. Therefore, designing a composite nanomaterial that amplifies CDT and couples it with PTT for tumor treatment is a major challenge. Herein, we designed a W-POM NCs@HKUST-1 nanoplatform that combines PTT and CDT and has better targeting properties. It shows high stability and photothermal conversion efficiency under the irradiation of near-infrared light and efficiently catalyzes the generation of intracellular hydroxyl radicals, this composite material exhibits higher lethality than single therapeutic strategies. This study expands the application area of POM@MOF composite nanomaterials and provides a promising means of enhanced tumor therapy.
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Chinese Medicine
·
2022
·Vol. 17
·期 1
·1-21
·
IF 4.546
Huang Qianqian,Zhang Chen,Dong Shi,Han Junwen,Qu Sihao,Xie Tianshu,Zhao Haibin,Shi Yuanyuan
Background Alzheimer's Disease (AD) is a serious neurodegenerative disease and there is currently no effective treatment for AD progression. The use of TCM as a potential treatment strategy for AD is an evolving field of investigation. Asafoetida (ASF), an oleo-gum-resin isolated from Ferula assa-foetida root, has been proven to possess antioxidative potential and neuroprotective effects, which is closely associated with the neurological disorders. However, the efficacy and further mechanisms of ASF in AD experimental models are still unclear. Methods A cognitive impairment of mouse model induced by scopolamine was established to determine the neuroprotective effects of ASF in vivo , as shown by behavioral tests, biochemical assays, Nissl staining, TUNEL staining, Immunohistochemistry, western blot and qPCR. Furthermore, the PC12 cells stimulated by H 2 O 2 were applied to explore the underlying mechanisms of ASF-mediated efficacy. Then, the UPLCM analysis and integrated network pharmacology approach was utilized to identified the main constitutes of ASF and the potential target of ASF against AD, respectively. And the main identified targets were validated in vitro by western blot, qPCR and immunofluorescence staining. Results In vivo , ASF treatment significantly ameliorated cognitive impairment induced by scopolamine, as evidenced by improving learning and memory abilities, and reducing neuronal injury, cholinergic system impairment, oxidative stress and apoptosis in the hippocampus of mice. In vitro , our results validated that ASF can dose-dependently attenuated H 2 O 2 -induced pathological oxidative stress in PC12 cells by inhibiting ROS and MDA production, as well as promoting the activities of SOD, CAT, GSH. We also found that ASF can significantly suppressed the apoptosis rate of PC12 cells increased by H 2 O 2 exposure, which was confirmed by flow cytometry analysis. Moreover, treatment with ASF obviously attenuated H 2 O 2 -induced increase in caspase-3 and Bax expression levels, as well as decrease in Bcl-2 protein expression. KEGG enrichment analysis indicated that the PI3K/Akt/GSK3β/Nrf2 /HO-1pathway may be involved in the regulation of cognitive impairment by ASF. The results of western blot, qPCR and immunofluorescence staining of vitro assay proved it. Conclusions Collectively, our work first uncovered the significant neuroprotective effect of ASF in treating AD in vivo . Then, we processed a series of vitro experiments to clarify the biological mechanism action. These data demonstrate that ASF can inhibit oxidative stress induced neuronal apoptosis to foster the prevention of AD both in vivo and in vitro , and it may exert the function of inhibiting AD through PI3K/Akt/GSK3β/Nrf2/HO-1pathway.
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CATALYSIS LETTERS
·
2022
·Vol. 153
·期 4
·1215-1226
·
IF 2.936
Wang Shiqing,Li Yafei,Lan Xiaocheng,Liu Boyang,Wang Tiefeng
Ni phosphide and Lewis acid–base pair site of Al 2 O 3 were combined as highly efficient catalyst for direct amination of 1-octanol to 1-octylamine. Due to the higher dehydrogenation activity and the site isolation effect, Ni 3 P/Al 2 O 3 -TPP prepared by organophosphorus was 4.0 times more active than Ni/Al 2 O 3 and increased the selectivity to 1-octylamine from 71.4 to 92.8% at 0.4 MPa NH 3 . Graphical Abstract
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危险品化学品经营许可证（带存储）