Molecular Medicine Reports
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2019
·Vol. 20
·期 3
·2135-2142
·
IF 1.851
Ming Yu,Demei Zang,Yuhao Xu,Jie Meng,Shengnan Qian
Advanced glycation end products (AGEs) are important pathogenic substances involved in diabetes mellitus (DM) and its complications. AGEs also serve important roles in promoting the development of Alzheimer's disease (AD). Macrophage migration inhibitory factor (MIF), an inflammatory stimulant and a pathogenic factor involved in DM, was previously reported to be present at increased levels in the cerebrospinal fluid of patients with AD and mild cognitive impairment compared with age‑matched healthy controls. By investigating the association between AGEs and MIF, and the effects of neuroinflammation on AD, the present study aimed to increase understanding of the specific molecular mechanisms involved in the pathogenesis of DM and AD, and the connection between these diseases. PC12 cells were cultured in vitro; the levels of MIF mRNA and protein were determined using reverse transcription‑quantitative (RT‑q)PCR and western blot analyses. The optimal concentrations of AGEs and amyloid β 1‑40 (Aβ1‑40) were also determined in the cell model of AD using Cell Counting Kit‑8 and MTT assays. Cell numbers and morphological changes were observed following the treatment of Aβ1‑40‑stimulated PC12 cells with AGEs and the MIF inhibitor (S,R)‑3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester (ISO‑1). The mRNA expression levels of interleukin (IL)‑1β, IL‑6, tumor necrosis factor‑α (TNF‑α) and MIF were determined via RT‑qPCR analysis. The results showed that the levels of MIF mRNA and protein were significantly increased in cells treated with AGEs compared with the control group. In the AD model group, the inhibition of PC12 cell growth was significantly increased, and the mRNA expression levels of IL‑1β, IL‑6, TNF‑α and MIF were also increased. Compared with treatment with AGEs alone, the combination of AGEs treatment with ISO‑1 significantly improved the survival rate and resulted in the reduced expression of inflammatory mediators in the AD cell model. Thus, ISO‑1 reduced AGEs‑mediated damage in the AD cell model. This may be a consequence of AGEs‑mediated MIF expression promoting neuritis in the AD cell model, whereas ISO‑1 decreased the expression of neuroinflammatory mediators.
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TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2018
·
IF 3.616
Yanzhuo Liu,Chenfan Duan,Honglei Chen,Chenlong Wang,Xiaoxiao Liu,Miao Qiu,Honglin Tang,Feng Zhang,Xiaoyang Zhou,Jing Yang
Cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and microsomal prostaglandin E synthase-1 (mPGES-1)-derived eicosanoids play an essential role in human inflammatory disorders. Here, we investigated whether inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate (MSU) crystal-induced inflammation. Virtual screening assay and in vitro enzyme inhibition assay showed that leonurine was a potential inhibitor of COX-2, mPGES-1 and 5-LOX. Compared with COX-2 inhibitor celecoxib , leonurine (30 mg/kg) significantly decreased ankle perimeter, gait score and neutrophil number in synovial fluid in MSU crystal-treated rats, accompanied with the decreased expression of COX-2, mPGES-1 and 5-LOX and production of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) in the synovial fluid macrophages. In addition, leonurine decreased representative M1 marker (iNOS and CD86) expression, NLRP3 inflammasome activation and M1 cytokine (TNF-α and IL-1β) production. In the in vitro cultured RAW264.7 and human monocyte-derived macrophages (MDMs), blockade of COX-2/mPGES-1 and 5-LOX by leonurine inhibited macrophage M1 polarization and NLRP3 inflammasome activation in response to MSU crystals, and thus down-regulated IL-1β and TNF-α with STAT1 and NF-κB inactivation. Conversely, these effects were partially abolished by overexpression of COX-2, mPGES-1, 5-LOX or STAT1. Furthermore, leonurine prevented a positive feedback loop between COX-2/mPGES-1/5-LOX and IL-1β/TNF-α in MSU crystal-induced inflammation. Together, simultaneous down-regulation of COX-2/mPGES-1 and 5-LOX by leonurine ameliorates MSU crystal-induced inflammation through decreasing IL-1β and TNF-α production. Our study may provide novel multi-target agents toward the arachidonic acid (AA) network for gouty arthritis therapy.
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SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Yanna Lin,Xueying Wang,Yuanling Sun,Yuxue Dai,Weiyan Sun,Xiaodong Zhu,Hao Liu,Rui Han,Dandan Gao,Chuannan Luo
In this work, target-responsive DNA hydrogel with high loading and good biocompatibility was used to construct chemiluminescent biosensor for specific detection of adenosine. Acrydite-modified adenosine aptamer (Acry-A-Apt), acrydite-modified single-strand DNA (Acry-ssDNA) and hemin aptamer (H-Apt) were used to prepared the DNA hydrogel, and the three single-strand DNA were partially complementary to each other. Thus, the DNA hydrogel only dissolved when adenosine and hemin were present simultaneously. HKUST-1 is a Cu-based MOFs with peroxidase-like activity. Au NPs were coated into cavities of HKUST-1 to obtain [email protected] , and the [email protected] had a stronger peroxidase-like activity than HKUST-1. [email protected] was coated in the DNA hydrogel. When only hemin was present, hemin bound to the H-Apt to form the G-quadruplex/hemin and the DNA hydrogel remained in the gel state. Therefore, the G-quadruplex/hemin was formed in the hydrogel and the excess hemin can be removed, avoiding background signal interference. Adenosine was then added and the preferential interaction between adenosine and adenosine aptamer resulted in complete dissolution of the DNA hydrogel. Subsequently, G-quadruplex/hemin and [email protected] were released simultaneously, enabling dual signal amplification of chemiluminescent biosensor, yielding a “signal on” readout. As a result, the biosensor could quantify adenosine from 4 × 10 −13 – 1.5 × 10 -10 mol/L with a detection limit as low as 1.04 × 10 −13 mol/L. The DNA hydrogel system provides a simple, sensitive and biocompatible method for the detection of adenosine which is useful in the field of biotechnology.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2019
·
IF 3.407
Li-Ming Yu,Xue Dong,Xiao-Dong Xue,Jian Zhang,Zhi Li,Hong-Jiang Wu,Zhong-Lu Yang,Yang Yang,Hui-Shan Wang
Punicalagin has been found to exert cardiac protective effects against myocardial ischemia/reperfusion (MI/R) injury, although the detailed mechanisms remain largely unknown. This experiment was performed to explore the potential involvement of silent information regulator 1 (SIRT1)-NFE2-related factor 2 (NRF-2)-heme oxygenase-1 (HO-1) pathway in the cardiac protective actions of punicalagin. Sprague-Dawley (SD) rats were subjected to MI/R operation with or without punicalagin treatment (40 mg kg −1 d −1 ). We showed that punicalagin-treated group exhibited enhanced cardiac function, reduced myocardial infarction and decreased cleaved caspase-3 level. Furthermore, myocardial oxidative/nitrosative stress was ameliorated by punicalagin as evidenced by suppressed superoxide generation, gp91 phox and iNOS expressions, NO metabolites as well as myocardial nitrotyrosine level. Additionally, punicalagin decreased myocardial IL-6, TNF-α and the levels of ICAM-1, VCAM-1 and IKK-β expressions as well as IκB-α phosphorylation and NF-κB nuclear translocation. However, these effects were abolished by EX527 (5 mg kg −1 d −1 , a selective SIRT1 inhibitor). We further found that punicalagin dose-dependently enhanced SIRT1 nuclear distribution and NRF-2-HO-1 signaling. While EX527 treatment not only reduced SIRT1 activity, but also reversed the activation of NRF-2-HO-1 pathway. Collectively, these results revealed that punicalagin reduced cardiac oxidative/nitrosative stress and inflammatory response induced by MI/R operation through SIRT1-mediated activation of NRF-2-HO-1 signaling.
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LIFE SCIENCES
·
2018
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IF 3.234
Runxiao Lv,Lili Du,Lixin Zhang,Zhiqiang Zhang
Aims Spinal cord injury (SCI) is one of the most devastating central lesions, resulting in serious locomotor deficit. Polydatin is a glucoside of resveratrol with proven anti-cardiovascular, anti-inflammatory and anti-oxidative properties. The main purpose of this study was to investigate whether polydatin could alleviate SCI in rats and explore the underlying mechanisms. Materials and methods SCI rats induced by a weight-drop device were treated with intraperitoneal injection of 20 or 40 mg/kg polydatin. Then the locomotor function of SCI rats was evaluated by the Basso, Beattie and Bresnahan locomotor rating scale, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers were detected by commercial kits and cell apoptosis status was measured by TUNEL staining. In addition, reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) production and apoptosis status were detected in murine microglia BV2 cells treated with 100 ng/ml lipopolysaccharides (LPS) and 4.0 μM polydatin. The expression of apoptosis-related proteins involved in nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway was measured by western blot. Key findings Our data showed that polydatin treatment improved locomotor performance of SCI rats, as well as reduced oxidative stress and inhibited apoptosis by enhancing Nrf2/HO-1 signaling. In addition, polydatin was found to up-regulate Nrf2 activity and the inhibitory effects of polydatin on oxidative stress and apoptosis in LPS-stimulated BV2 microglia was neutralized by silencing Nrf2 using specific siRNA. Significance We demonstrate that polydatin may protect the spinal cord from SCI by suppression of oxidative stress and apoptosis via improving Nrf2/HO-1 signaling in microglia.
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JOURNAL OF HAZARDOUS MATERIALS
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2021
·
IF 10.588
Yuhao Wu,Junke Wang,Tianxin Zhao,Jiadong Chen,Lian Kang,Yuexin Wei,Lindong Han,Lianju Shen,Chunlan Long,Shengde Wu,Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is an extensively used plasticizer and has been shown to cause reproductive dysfunction in humans and model animals. However, the exact mechanisms of testicular injury induced by DEHP exposure have not been fully clarified. Using gas chromatography-mass spectrometry, we found that mono-2-ethylhexyl ester (MEHP, a major biometabolite of DEHP) and DEHP concentrations were elevated in mouse serum after DEHP exposure. Using RNA-seq, we found that ferroptosis and HIF-1 signaling pathways might be involved in testicular injury due to prepubertal DEHP exposure. Subsequent Western blotting, ferrous iron and MDA measurements, and immunofluorescence of testicular sections verified the RNA-seq findings. Consistently, based on the RNA-seq findings, we found that ferroptosis and HIF-1 signaling pathways might play crucial roles in Leydig and Sertoli cell injury due to MEHP exposure in vitro. Further experiments also confirmed ferroptosis in Leydig and Sertoli cells. Using Western blotting, cellular immunofluorescence and ChIP-qPCR, we found that MEHP exposure caused HIF-1α accumulation and stabilization, resulted in HIF-1α translocation into the nucleus, and induced HIF-1α/ Hmox1 binding in Leydig and Sertoli cells. To clarify whether HIF-1α plays a pivotal role in MEHP-induced ferroptosis, we knocked out Hif-1α using the CRISPR/Cas9 technique. We found that Hif-1α knockout rescued MEHP-induced ferroptosis. In summary, our findings certified that prepubertal DEHP exposure led to ferroptosis in mouse testes via the HIF-1α/HO-1 signaling pathway.
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JOURNAL OF CHEMICAL NEUROANATOMY
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2020
·
IF 2.353
Hongqing Liu,Shiqi Li,Cuizhu Yang,Hui Jia,Ziting Gu,Xing Tu,Sumin Tian,Jing Liu,Guoying Li,Yuxin Ma
The senile plaque formed by β-amyloid (Aβ) deposition in the brain is one of the main pathological features of Alzheimer’s disease (AD), and the c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the pathogenesis of AD. This study aimed to investigate that D-serine may ameliorate motor and cognitive impairment in Aβ injected mice by inhibiting JNK signaling pathway. Firstly, Kunming mice were injected intrahippocampally with Aβ 1-42 to build AD model. The mice were injected intraperitoneally with saline, D-serine, D-amino acid oxidase (DAAO), and Sodium benzoate (BE) for 10 consecutive days, respectively. Subsequently, the motor and cognitive functions of mice were detected by behavioral tests. The silver staining and immunohistochemical methods were used to detect the distributions of Aβ in the hippocampus of mice. 18 F-2-Fluro-D-deoxy-glucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) scans were performed to detected glucose metabolism of Aβ 1-42 induced lesions. The expressions of relative JNK factors were detected by immunohistochemistry and Western blot methods. These results showed that Aβ severely impaired the motor and memory abilities of mice. The expressions of glial fibrillary acidic protein (GFAP), tumor necrosis factor (TNF-α), N-methyl-D-aspartate receptor 1 (NMDAR1), phospho-JNK (p-JNK), p-c-Jun and activating transcription factor 2 (ATF2) increased significantly. After D-serine treatment, the abilities of movement and memory of mice were improved, and the clearance rate of Aβ was accelerated. The expressions of GFAP, TNF-α, NMDAR1, p-JNK, p-c-Jun and ATF2 decreased significantly. DAAO and BE were administered to further validate these results. Therefore, this study showed that D-serine could alleviate the cognitive impairment of Aβ 1-42 injected mice by inhibiting JNK signaling pathway. These results provide more evidences for the effect of D-serine on AD and relevant mechanism to treat AD.
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CERAMICS INTERNATIONAL
·
2024
·
IF 5.1
Meng-Han Yan,Zhi-Fei Zhang,Hai-Hua Huang,Zi-Liang Li,Peng Li,Ji-Gong Hao,Wei Li,Juan Du,Mahesh Kumar Joshi,Peng Fu
In this work, a series of x Sm 2 O 3 -(1- x ) CaCu 3 Ti 4 O 12 ( x Sm 2 O 3 -(1- x )CCTO, x = 0.00–0.05) negative temperature coefficient (NTC) ceramics were prepared by a solid-state method. The influence of Sm 2 O 3 content on electrical properties was examined using microstructural, band gap, morphological, Direct Current (DC) resistivity, and impedance spectroscopy analysis. The increase in Sm 2 O 3 content resulted in a gradual decrease of the resistivities ( ρ 25 ), thermal constants ( B 25/75 ), activation energies for electrical conduction ( E a ) and activation energies of the relaxation process ( E relax ) from 1.16 × 10 7 Ω cm, 6387 K, 0.5456 eV and 0.5592 eV to 3.43 × 10 5 Ω cm, 4149 K, 0.4088 eV and 0.4115 eV respectively. First-principles calculations revealed a reduction in the band gap by adding Sm 2 O 3 , partially explaining the decrease in electrical resistivity. In-situ XPS analysis elucidated a relationship between conduction mechanism of Sm 2 O 3 -doped CCTO ceramics and electron hopping. Impedance analyses showed that both grains and grain boundaries contributed to the NTC effect of ceramics. The electrical inhomogeneity arose from grains and grain boundaries, while local relaxation was due to the short-range motion of charge carriers.
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Nature Communications
·
2024
·Vol. 15
·期 1
·1-12
·
IF 14.7
An Hanwen,Li Menglu,Liu Qingsong,Song Yajie,Liu Jiaxuan,Yu Zhihang,Liu Xingjiang,Deng Biao,Wang Jiajun
Polyethylene oxide (PEO) based electrolytes critically govern the security and energy density of solid-state batteries, but typically suffer from poor oxidation resistance at high voltages, which limits the energy density of batteries. Here, we report a Lewis-acid coordinated strategy to significantly improve the cyclic stability of 4.8 V-class PEO-based battery. The introduced Mg 2+ and Al 3+ with strong electron-withdrawing capability weaken the electron density of ether oxygen (EO) chains via chelation in the coordination structure, resulting in a locally limited interaction between the EO chains and the surface of cathodes at high state of charge. The batteries using Lewis-acid coordinated electrolytes and Ni-rich cathodes achieve high voltage stability of 4.8 V over 300 cycles. Further, the realization of industrial-scale electrolyte membranes, and Ah-level pouch cells over 586 Wh kg ‒1 with good cyclic stability, suggests the potential of our strategy in practical applications of all-solid-state batteries.
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JOURNAL OF ENVIRONMENTAL MANAGEMENT
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2024
·
IF 8
Meichen Liu,Meichen Gao,Xu Shi,Yilin Yin,Huanyi Liu,Ruirui Xie,Chenxi Huang,Wenwen Zhang,Shiwen Xu
With the increasing development of the society, silicon dioxide (SiO 2 ) has been used in various fields, such as agriculture, food industry, etc., and its residues can pose a potential health threat to organisms. Quercetin (Que) is a potent free radical scavenger commonly found in plants. C57BL/6 mice were chosen to established a mouse model of SiO 2 exposure and Que antagonism to investigate the mechanism of action of Que in rescuing the toxic damage of SiO 2 on mouse cerebellum tissue. The results showed that cytoplasmic vacuolization, and inflammatory cell infiltration caused by SiO 2 were alleviated by the addition of Que, and reduced oxidative stress in mouse cerebellum, alleviated the activation of TLR4 pathway induced by SiO 2 , and substantially reduced the occurrence of ZBP-1-mediated PANoptosis induced by SiO 2 exposure in mouse cerebellum. In NS20Y cells, the oxidative stress activator (Elesclomol) and inhibitor N-acetyl cysteine (NAC), and the NF-κB activator 2 (NA2) were added. Elesclomol and NAC confirm the involvement of ROS in regulating the TLR4/NF-κB pathway, the TLR4/NF-κB pathway regulated ZBP-1-mediated PANoptosis in cerebellum and NS20Y cells induced by SiO 2 exposure. In conclusion, the present experimental data suggest that Que mitigates the onset of ZBP-1-mediated PANoptosis in neuronal cells induced by SiO 2 through the ROS/TLR4/NF-κB pathway. The present experimental findings help to understand the detoxification effect of Que in more tissues and provide an important reference for the rescue of organisms in long-term SiO 2 environment.
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ELECTROCHIMICA ACTA
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2011
·
IF 3.65
Xiaofang Shen,Yan Cui,Yuehong Pang,He Qian
1-Hydroxypyrene (1-OHP) is a ubiquitous metabolite of polycyclic aromatic hydrocarbons (PAHs) and has been widely used as a biomarker for evaluation of human exposure to PAHs. In this paper, an electrochemical sensor consisted of graphene oxide nanoribbon (GON)/octa(3-aminopropyl)octasilae quioxane octahydrochloride (OA-POSS) framework films (GON/OA-POSS) modified electrode for pre-concentrating and sensing of 1-OHP was described. The GON/OA-POSS composite films were prepared by hierarchically layer-by-layer assembly via electrostatic interactions. GON, which has higher electrical conductivity than that of graphene oxide, offers residual π-conjugated systems for adsorption of 1-OHP via π–π stacking interaction. Meanwhile, OA-POSS nanocages make the GON layers frameworked to enhance contacting between GON and 1-OHP. When 1-OHP was pre-concentrated on GON/OA-POSS frameworks modified electrode, the response signal and adsorption stability was enhanced significantly. Differential pulse voltammetry was used for direct determination of 1-OHP. The electrochemical sensor calibration curve had a range of 0.1–12.55 μM ( R = 0.995) with a detection limit of 0.04 μM. The results showed that the GON/OA-POSS framework films modified electrode established a new way for simple and sensitive analysis of 1-OHP.
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CERAMICS INTERNATIONAL
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2024
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IF 5.1
Yajie Wang,Ziyi Zhang,Jie Li,Ying Tang,Liang Fang
Excellent spinel microwave dielectric ceramics (1- x )Zn 2 TiO 4 - x Li 2 MgTi 3 O 8 (ZTLMT x , x = 1/3 and 2/3) were prepared at relatively low densification temperatures of 1100 °C and 1080 °C, respectively. A disordered cubic phase with space group Fd -3 m was formed at x = 1/3, whereas an ordered cubic phase with space group P 4 3 32 was formed at x = 2/3. The ceramics at x = 1/3 and 2/3 exhibited promising microwave dielectric properties of ɛ r = 18.27 and 22.96, Q × f = 91,877 GHz and 75,186 GHz, and τ f = −42.3 ppm/°C and −21.05 ppm/°C, respectively. The large deviation between the experimental ԑ r and theoretical ε th of 1/3 and 2/3 ceramics were 18.3 % and 57 %, respectively, due to the underestimation of the ionic polarizability of Ti 4+ . The difference in their ɛ r , Q × f , and τ f were discussed by the structure, FWHM of A 1g , lattice energy and bond energy in detail.
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