Journal of Neuroinflammation
·
2023
·Vol. 20
·期 1
·1-21
·
IF 9.3
Li Nan,Wang Chunyan,Zhao Yuying,Wang Yigang,Gao Tianyu,Yu Yonghao,Wang Guolin,Zhang Linlin
Background Patients receiving epidural or intrathecal opioids administration for neuraxial analgesia frequently suffer from an irritating itch. STING (stimulator of interferon genes), an innate immune modulator, is strongly implicated in pain pathogenesis via neuron-immune modulation. Given that pain and itch share some common neurocircuits, we evaluate the therapeutic potential of STING agonists in opioid-induced itch and chronic itch.Methods Opioids (morphine, fentanyl and sufentanil) were intrathecally injected to induce acute itch. Chronic itch was induced by dry skin and contact dermatitis. Opioids analgesic effect, itch-induced scratching behavior, spinal expression of STING, phosphorylation of TBK1 (tank-binding kinase 1), IRF3 (interferon regulatory factor-3) and ERK (extracellular signal-regulated kinase), as well as production of IFN-α and IFN-β were examined. STING agonists (DMXAA and ADU-S100), TBK1 inhibitor, recombinant IFN-α and IFN-β elucidated the mechanism and treatment of itch. Whole-brain functional connectivity was evaluated using resting-state fMRI.Results We report the primary expression of STING protein by the spinal dorsal horn neurons. Intraperitoneal injection of DMXAA dose-dependently reduces morphine-induced scratch bouts, without impairing morphine antinociception. Simultaneously, DMXAA alleviates fentanyl- and sufentanil-induced itching-like behavior, and chronic scratching behavior caused by dry skin and contact dermatitis. Furthermore, DMXAA drastically increases spinal phosphorylation of TBK1 and IRF3 following morphine exposure, dry skin and contact dermatitis. DMXAA-induced anti-pruritus effects and spinal productions of IFN-α and IFN-β are compensated by intrathecal delivery of the TBK1 inhibitor. Also, ADU-S100, recombinant IFN-α and IFN-β exhibits remarkable attenuation in scratching behaviors after morphine injection and dermatitis. Recombinant IFN-α inhibits morphine-induced spinal phosphorylation of ERK. Finally, DMXAA prevents dermatitis-induced the increase of cerebral functional connectivity between regions of interests such as primary somatosensory cortex, piriform cortex, retrosplenial cortex, colliculus and ventral thalamus.Conclusion sSTING activation confers protection against opioid-induced itch and chronic itch through spinal up-regulation of TBK1-IRF3-type I interferon cascades in mice, suggesting that STING agonists are promising candidates in translational development for pruritus relief.
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高影响因子
Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 30
·4901-4910
·
IF 0
Wenjie Li,Jing Shi,Chun Zhang,Min Li,Lu Gan,Huibi Xu,Xiangliang Yang
The overexpression of thioredoxin (Trx) 1 is one of the mechanisms for drug resistance in hepatocellular carcinoma (HCC) treatment. The co-delivery of drugs and a short hairpin RNA (shRNA) against Trx1 to silence its expression might provide a promising approach to improve drug sensitivity to chemotherapeutic agents. In this paper, cationic liposomes containing gemini surfactants, soybean lecithin and DOPE were firstly constructed as gene transfection carriers. The length and symmetrical degree of aliphatic chains of gemini surfactants were found to affect gene transfection efficiency of cationic liposomes. Cationic liposome containing gemini surfactants with symmetrical C16 aliphatic chains (L16-2-16) showed the highest transfection efficiency in HCC Bel7402 cells and also displayed the strongest DNA condensation capacity and the highest cellular uptake. Folic acid (FA) targeting further enhanced the transfection efficiency of L16-2-16 by binding to the folate receptor (FR) in FR-overexpressing Bel7402 cells and lipid raft/caveolae-dependent endocytosis might be involved in FA-L16-2-16-mediated gene delivery. Then the multifunctional co-delivery system for doxorubicin (DOX) and Trx1 shRNA was developed via electrostatic interactions between the FA-L16-2-16 and Trx1 shRNA/DOX complex. Co-delivery of Trx1 shRNA and DOX by FA-L16-2-16 inhibited the cell viability and induced apoptosis of Bel7402 cells more efficiently than co-delivery of control shRNA and DOX. The system for co-delivering DOX and Trx1 shRNA could simultaneously achieve gene transfection and drug release in the same cell and increase the intracellular as well as intranuclear DOX concentrations. These results demonstrated that gemini surfactant-based cationic liposomes were promising carriers for the co-delivery of nucleic acids and chemotherapeutic agents to sensitize HCC chemotherapy.
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ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2014
·
IF 1.862
Demei Xu,Lihua Hu,Xiaomin Xia,Jianbo Song,Lingrui Li,Erqun Song,Yang Song
Tetrachlorobenzoquinone (TCBQ) is an active metabolite of pentachlorophenol (PCP). Although PCP has been investigated extensively, there are only a few reports describing the toxicity effect of TCBQ, and no report regarding TCBQ-induced liver injury in vivo . In the current study, we aimed to examine the acute hepatic toxicity of TCBQ in the mice model. Chlorogenic acid (CGA) exhibits promising antioxidant activity in the past studies, thus, the second aim of this study was to evaluate the protective effect of CGA on TCBQ-induced liver injury. Our results indicated TCBQ-intoxication caused marked liver cell necrosis and inflammation but not apoptosis, and this damage was alleviated by CGA treatment. Meantime, TCBQ-intoxication enhanced serum ALT, AST activities, TBIL content, hepatic oxidative stress and lipid peroxidation, decreased GSH content and inhibited the activities of antioxidant enzymes. Western blot and immunohistochemical analysis showed that TCBQ marked up-regulated HO-1 and NQO1 expression. On the other hand, pretreatment of CGA reduced TCBQ-induced liver damage remarkably. Taking together, these results revealed that TCBQ has strong hepatic toxic effect, and at least a part of this effect is initiated by free radical and relieved with CGA administration.
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高影响因子
Applied Sciences-Basel
·
2025
·Vol. 15
·期 7
·
IF 2.5
Tianyu Hu,Bingying Liu,Siqian He,Yuanjie Teng,Zaifa Pan
Insulin-like growth factor-1 (IGF-1) is a regulatory factor closely associated with diabetes, obesity, and breast cancer, and it also acts as one of the most abundant growth factors in bovine colostrum. Current methods generally have the problem of low sensitivity, a time-consuming nature, and low stability, which makes it difficult to crack down on the false advertising of IGF-1 content in dairy products. In this work, an ultrasensitive fluorescent enzyme-linked immunosorbent assay (ELISA) is proposed, where the antibody and the target are combined in the form of a “sandwich” to ensure the accuracy and specificity of the assay. IGF-1 is quantified based on an effective hydrogen peroxide (H2O2) probe with 10-acetyl-3,7-dihydroxyphenoxazine (ADHP) as the fluorogenic substrate. The proposed fluorescent sandwich ELISA has a low limit of detection (LOD) of 77.29 pg/mL, fast experimental process within 1 h, and stable signal of 1 h. Furthermore, multi-step pretreatment methods for bovine colostrum powders are established to remove interfering substances, including fat, casein, and binding proteins, achieving the accurate and specific detection of IGF-1. IGF-1 recovery studies on treated bovine colostrum powders exhibit good recovery rates ranging from 91.71% to 102.32%, which proves the feasibility of detecting IGF-1 in real bovine colostrum.
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DOI
高影响因子
CELL CYCLE
·
2021
·
IF 4.534
Yanming Yu,Daoxu Wu,Yongwei Li,Hui Qiao,Zhengfei Shan
Background Ketamine-related cystitis (KC) has been researched in many clinical studies, but its exact mechanism is ambiguous and needs further research. Methods We established a KC rat model and analyzed physiological, biochemical, and urodynamic parameters of ketamine (KET)-related bladder injury. Bladder histologic feature, reactive oxygen species (ROS), autophagy-, apoptosis-, and endoplasmic reticulum stress (ERS)-related markers were examined by hematoxylin and eosin staining, Masson staining, ROS kit, quantitative real-time polymerase chain reaction, and western blot. In vitro, effects of 0.01, 0.1, and 1 mM KET on cell vitality, apoptosis, ROS level, autophagy-, apoptosis-, and ERS-related markers were examined again. Effects of KET-1 and salubrinal on complex formation, autophagy-, apoptosis-, and ERS-related markers were examined by Co-Immunoprecipitation and western blot. After transfection with shIRE1, complex formation, cell biological behaviors, ROS level, autophagy-, apoptosis-, and ERS-related markers were examined again. Results KET induced bladder hyperactivity and injury. KET facilitated urinary frequency, ROS production, and induced bladder histologic injury by activating autophagy-, apoptosis-, and ERS-related markers in rats. In vitro, KET (0.01, 0.1, and 1 mM) restrained cell vitality and elevated apoptosis and ROS level via activating autophagy-, apoptosis-, and ERS-related markers. Moreover, salubrinal reversed the promotion of KET-1 on complex formation, autophagy-, apoptosis-, and ERS-related marker expressions. After transfection with shIRE1, shIRE1 weakened complex formation induced by KET-1, and the effects of KET-1 on cells were offset by shIRE1. Conclusion KET enhanced autophagy and ERS in vivo and in vitro via restraining IRE1-TRAF2-ASK1-JNK pathway.
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高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 29
·期 12
·1806916
·
IF 15.621
Xiaowei Liu,Yanlin Feng,Guangchao Xu,Yang Chen,Ya Luo,Jinen Song,Yu Bao,Jiqiao Yang,Chune Yu,Yanna Li,Haoyu Ye,Bowen Ke,Bo Chen,Jianping Hu,Jie Xu,Huan Meng,Haiyuan Zhang,Hubing Shi
The combination of BRAF/MEK-targeted therapy with immune checkpoint blockade is regarded as a promising regimen for patients with metastatic melanoma due to their complementary advantages. However, MEK-inhibitor-induced T-cell toxicity impedes effective cooperation. In this experiment, a pH-responsive on-demand controlled release mesoporous silica nanoparticles (MSNPs) system is designed. Fluorescein-isothiocyanate-loaded MSNP can be specifically delivered into tumor cells rather than T-cells. MEK-inhibitor-loaded MSNP avoids proliferative and functional inhibitions of T-cells, while preserving growth suppression of tumor cells in vitro. In an in vivo model, MSNP encapsulation reverses the MEK-inhibitor-induced suppression of activated CD8 + T-cells, and enhances the secretion of INF-γ and IL-2. The combination of BRAF inhibitor plus MSNP-loaded MEK inhibitor and anti-PD-1 antibody synergistically inhibits tumor growth via promoting robust immune-related antitumor response. This work provides a novel and generalized framework for combining T-cell-impaired targeted therapy and immune checkpoint blockade by using a nanoparticle-based delivery system.
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高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Yuhang Ge,Fei Zhen,Ziqi Liu,Zhaowei Feng,Gui Wang,Chu Zhang,Xingqi Wang,Ying Sun,Xiaohui Zheng,Yajun Bai,Ruiqin Yao
Preterm white matter injury (PWMI) is the most common form of brain damage in premature infants caused by hypoxia-ischemia (HI), inflammation, or excitotoxicity. It is characterized by oligodendrocyte precursor cell (OPC) differentiation disorder and dysmyelination. Our previous study confirmed that alpha-asarone (α-asaronol), a major compound isolated from the Chinese medicinal herb Acorus gramineus by our lab, could alleviate neuronal overexcitation and improve the cognitive function of aged rats. In the present study, we investigated the effect and mechanism of α-asaronol on myelination in a rat model of PWMI induced by HI. Notably, α-asaronol promoted OPC differentiation and myelination in the corpus callosum of PWMI rats. Meanwhile, the concentration of glutamate was significantly decreased, and the levels of PPARγ and glutamate transporter 1 (GLT-1) were increased by α-asaronol treatment. In vitro, it was also confirmed that α-asaronol increased GLT-1 expression and recruitment of the PPARγ coactivator PCG-1a in astrocytes under oxygen and glucose deprivation (OGD) conditions. The PPARγ inhibitor GW9662 significantly reversed the effect of α-asaronol on GLT-1 expression and PCG-1a recruitment. Interestingly, the conditioned medium from α-asaronol-treated astrocytes decreased the number of OPCs and increased the number of mature oligodendrocytes. These results suggest that α-asaronol can promote OPC differentiation and relieve dysmyelination by regulating glutamate levels via astrocyte PPARγ-GLT-1 signaling. Although whether α -asaronol binds to PPARγ directly or indirectly is not investigated here, this study still indicates that α -asaronol may be a promising small molecular drug for the treatment of myelin-related diseases.
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高影响因子
Autophagy
·
2018
·
IF 11.1
Zhen Yang,Qi Sun,Junfei Guo,Shixing Wang,Ge Song,Weiying Liu,Min Liu,Hua Tang
Emerging evidence has revealed that miRNAs could upregulate the expression levels of target genes. However, the molecular mechanism underlying upregulation of targets mediated by miRNAs remains unclear. In this study, we found a novel miRNA named MIR-G-1 by GRSF1-RNA immunoprecipitation (RIP)-deep sequencing, which could directly target and upregulate LMNB1 and TMED5 in a GRSF1-dependent manner in cervical cancer cells. In addition, upregulated MIR-G-1 in cervical cancer promoted a malignant phenotype in vitro and in vivo. TMED5 could interact with WNT7B and thus activated the canonical WNT-CTNNB1/β-catenin signaling pathway. MIR-G-1 mediated the activation of this pathway. Furthermore, MIR-G-1 promoted serum starvation-induced nuclear macroautophagy/autophagy, and accelerated taxol (TAX)-induced DNA-damage repair in cervical cancer cells. Collectively, these findings may provide a new insight into the upregulation mechanism and nuclear autophagy mediated by miRNAs and provide a potential biomarker for cervical cancer.Abbreviations: 3ʹUTR: 3′ untranslated region; EMSA: electrophoretic mobility shift assay; EMT: epithelial-mesenchymal transition; GRSF1: G-rich RNA sequence binding factor 1; IF: immunofluorescence; IP: immunoprecipitation; IHC: immunohistochemistry; lnc: long noncoding; miRNA:microRNA; TAX: taxol; TMED5: transmembrane p24 trafficking protein 5
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高影响因子
International Journal of Biological Sciences
·
2020
·
IF 4.858
Yiliang Wang,Lianzhou Huang,Yun Wang,Weisheng Luo,Feng Li,Ji Xiao,Shurong Qin,Zhaoyang Wang,Xiaowei Song,Yuan Wang,Fujun Jin,Yifei Wang
Herpes simplex virus (HSV) type 1 (HSV-1) infection exhibited high heterogeneity at individual cells level, including the different gene expression patterns and varying amounts of progeny virus. However, the underlying mechanism of such variability remains obscure. The importance of host long noncoding RNAs (lncRNAs) in virus infection had been recognized, while the contribution of lncRNAs to the heterogeneous infection remains unknown. Herein, a prior single-cell RNA sequencing data using HSV-1 reporter strain expressing ICP4-YFP was re-analyzed to obtain the differentially expressed lncRNA between the successfully initiated viral gene expression (ICP4-YFP + ) cells and the aborted infection cells (ICP4-YFP - ). The ICP4-YFP + population show a higher abundance of MAMDC2 antisense 1 (MAMDC2-AS1) lncRNA than ICP4-YFP - population. MAMDC2-AS1 silencing reduces the expression of HSV-1 immediate early (IE) genes and limit HSV-1 infection in human host cells. Consistently, ectopic expression of MAMDC2-AS1 enhances HSV-1 IE genes transcription and facilitates the formation of HSV-1-induced plaques. Mechanically, both RNA-pull down and RNA immunoprecipitation assays show that MAMDC2-AS1 interacts with the RNA binding protein heat shock protein 90α (Hsp90α), a molecular chaperone involving in the nuclear import of HSV-1. The MAMDC2-AS1-Hsp90α interaction facilitates the nuclear transport of viral tegument protein VP16, the core factor initiating the expression of HSV-1 IE genes. The transcription factor YY1 mediates the induction of MAMDC2-AS1 upon HSV-1 infection. Our study elucidates the contribution of lncRNA to HSV-1 infection susceptibility in human cells and the role of Hsp90α RNA binding activity in HSV-1 infection.
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高影响因子
Analytical Methods
·
2019
·Vol. 11
·期 41
·5250-5259
·
IF 2.378
Chenlei Gu,Xinwei Wei,Yuxiang Pan,Tao Liang,Ying Gan,Keqiang Gao,Yong Qiu,Hao Wan,Ping Wang
Drug-induced cardiac side-effects remain a major cause for the removal of drugs from the market and the termination of significant numbers of drug development projects. Many of the physiological and pharmacological reasons are still unclear. In this study, to comprehensively evaluate the cardiac side-effects of drugs, high-temporal-range evaluation with an HL-1-based impedance and long-term electrophysiology recording platform was proposed. Integrated with microscale interdigitated electrodes (IDEs) and planar microelectrodes, the platform could get reliable cell viability monitoring and extracellular electrophysiology recording simultaneously for low system signal drifting and noise (10 μV) in long-term experiments. HL-1 cardiac muscle cells were used as a target cardiac electrophysiology model because they are, by far, the only cardiomyocytes that can continuously divide while maintaining specific characteristics of adult cardiomyocytes. Vinblastine and nifedipine were introduced to verify the performance of this platform in a different time-dependent manner. According to the extracted cell viability and electrophysiological characteristics including cell impedance (namely, cell index, CI), extracellular field potential (EFP), firing rate (FR), inner-period and period-to-period intervals, the results showed that vinblastine exhibited a relatively strong effect on cell viability (maximum 79.83% decrease after 24 hours) and led to the fluctuation of inner-period intervals in long-term monitoring. In contrast, nifedipine presented a negligible effect on cell viability compared to control groups (maintaining minimum 86.20% of viability on an average after 24 hours), but a shortened QT interval (15.2% at least) was observed immediately. In summary, all the two time-dependent drug-induced results indicated that this HL-1-based impedance and long-term electrophysiology recording platform can not only monitor cell viability through the whole experiment but also possess both quick-reaction and long-term tracking ability for identical requirements, thus providing a promising and useful way for drug-induced cardiac side-effect evaluation in a high temporal range.
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高影响因子
ACS Applied Optical Materials
·
2024
·
IF 0
Yuhang Zheng,Shoujun Ding,Yong Zou,Xubing Tang,Wenpeng Liu
Sc(NbO4)x(TaO4)1–x is composed of ScNbO4 and ScTaO4 matrices, containing [NbO4]3– and [TaO4]3– self-activating luminescent groups, and is a series of potential high-performance luminescent matrixes. In this work, trivalent samarium (Sm3+)-doped Sc(NbO4)x(TaO4)1–x (SNTO) phosphors have been synthesized through a traditional solid-state reaction method. The quenching concentration of Sm3+ in the SNTO matrix was 2 atom %, and the quenching mechanism was analyzed. Especially, the effects of [NbO4]3–/[TaO4]3– component ratios on luminescent properties and thermal stability were studied. The temperature-dependent fluorescence spectra and decay curves of Sm:SNTO phosphors, spanning from 300 to 510 K, have unveiled their luminescent thermal stability. The activation energy Ea representing luminescent thermal stability was found to be sensitive to the [NbO4]3–/[TaO4]3– component ratios, and the maximum Ea value was 0.272 eV. The findings suggest that the luminescent thermal stability of Sm3+-doped Sc(NbO4)x(TaO4)1–x orange-reddish phosphors can be regulated by the host component. Thus, this study can provide a reference for achieving high luminescent thermal stability phosphors through cosubstitution component regulation.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Ruiting Fan,Li Song,Yongsheng Hu,Xiaoyang Guo,Xingyuan Liu,Lishuang Wang,Chong Geng,Shu Xu,Yonghui Zhang,Zihui Zhang,Nannan Luan,Wengang Bi
Properties of the underlying hole transport layer (HTL) in perovskite light-emitting devices (PeLEDs) play a critical role in determining the optoelectronic performance through influencing both the charge transport and the quality of the active perovskite emission layer (EML). This work focuses on manipulating the carrier transport behavior and obtaining a high-quality EML film by tailoring the poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) HTL with previously unused amino alcohol 3-amino-1-propanol (3AP). The modified PEDOT:PSS rendered a deeper work function that is more suitable for the hole injection from the HTL to EML. More importantly, the 3AP-modified PEDOT:PSS film can induce a low-dimensional perovskite phase that can passivate the defects in the EML, resulting in a significantly improved light emission. Such ameliorations consequently result in a dramatical enhancement in performance of PeLED with a low turn-on voltage of 2.54 V, a maximum luminance of 23033 cd/m2, a highest current efficiency of 29.38 cd/A, a corresponding maximum external quantum efficiency of 9.4%, and a prolonged lifetime of 6.1 h at a proper Cs/Pb ratio.
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高影响因子
危险品化学品经营许可证（带存储）