ACTA PHARMACOLOGICA SINICA
·
2024
·
IF 6.9
Wang Fei,Wang Yu,Zhang Qing-yang,Hu Ke-yu,Song Ying-jie,Yang Lin,Fei Fan,Xu Ceng-lin,Cui Sun-liang,Ruan Ye-ping,Wang Yi,Chen Zhong
Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1 −/− mice but partially terminated SE in IL1R1 −/− mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1β pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.
研究领域:
神经科学
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药理学
·
神经炎症
·
癫痫
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DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2024
·Vol. 21
·期 1
·1-24
·
IF 9.3
Wang Zhimeng,Liu Jing,Han Jing,Zhang Tianyi,Li Shangjin,Hou Yanfei,Su Huili,Han Fangping,Zhang Conggang
Accumulating evidence implicates that herpes simplex virus type 1 (HSV-1) has been linked to the development and progression of Alzheimer’s disease (AD). HSV-1 infection induces β-amyloid (Aβ) deposition in vitro and in vivo, but the effect and precise mechanism remain elusive. Here, we show that HSV-1 infection of the brains of transgenic 5xFAD mice resulted in accelerated Aβ deposition, gliosis, and cognitive dysfunction. We demonstrate that HSV-1 infection induced the recruitment of microglia to the viral core to trigger microglial phagocytosis of HSV-GFP-positive neuronal cells. In addition, we reveal that the NLRP3 inflammasome pathway induced by HSV-1 infection played a crucial role in Aβ deposition and the progression of AD caused by HSV-1 infection. Blockade of the NLRP3 inflammasome signaling reduces Aβ deposition and alleviates cognitive decline in 5xFAD mice after HSV-1 infection. Our findings support the notion that HSV-1 infection is a key factor in the etiology of AD, demonstrating that NLRP3 inflammasome activation functions in the interface of HSV-1 infection and Aβ deposition in AD.
研究领域:
神经科学
·
病毒学
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免疫学
·
病理学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2022
·
IF 15.304
Yu-Xiang Ge,Tai-Wei Zhang,Lei Zhou,Wang Ding,Hai-Feng Liang,Zhi-Chao Hu,Qin Chen,Jian Dong,Feng-Feng Xue,Xiao-Fan Yin,Li-Bo Jiang
Poor immunogenicity and compromised T cell infiltration impede the application of immune-checkpoint blockade (ICB) immunotherapy for osteosarcoma (OS). Although autophagy is involved in enhancing the immune response, the synergistic role of autophagy in ICB immunotherapy and the accurate control of autophagy levels in OS remain elusive and challenging. Here, we designed a pH-sensitive autophagy-controlling nanocarrier, [email protected] @PEG-FA (CBZP), loading a natural derivative, curcumin (CUR), to boost the immunotherapeutic response of PD-1/PD-L1 blockade by activating immunogenic cell death (ICD) via autophagic cell death, and BMS1166 to inhibit the PD-1/PD-L1 interaction simultaneously, enhancing the tumor immunogenicity and sensitizing the antitumor T cell immunity. After entering tumor cells, the pH-sensitive nanoparticles induced autophagy and decreased the intracellular pH , which in turn further facilitated the release of CUR to enhance autophagic activity. Transferring CBZP to orthotopic OS tumor-bearing mice showed powerful antitumor effects and established long-term immunity against tumor recurrence, accompanied by enhanced dendritic cell maturation and tumor infiltration of CD8 + T lymphocytes. Collectively, CBZP exhibited synergistic effects in treating OS by combining ICD induction with checkpoint blockade, thereby shedding light on the use of autophagy control as a potential clinical therapy for OS.
研究领域:
肿瘤学
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免疫疗法
·
纳米技术
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhu Shengjie,Huang Danqing,Luan Qichen,Li Yang,Gan Jingjing,Zhao Yuanjin,Sun Lingyun
Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
研究领域:
药理学
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免疫学
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生物医学工程
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药物递送系统
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自身免疫疾病
✓ 已验证
DOI
高影响因子
PLANT PHYSIOLOGY AND BIOCHEMISTRY
·
2023
·
IF 6.5
Qingwei Jia,Yuqing Yin,Shuting Gai,Lu Tian,Zhihao Zhu,Lei Qin,Yong Wang
Cryptochromes (CRYs), as blue-light photoreceptors, play a crucial role in regulating flowering time and hypocotyl and cotyledon development. Their physiological functions have been extensively studied in various plant species. However, research on onions remains limited. In this study, we identified AcCRY1 and conducted preliminary investigations into its function. Our results demonstrate that AcCRY1 possesses a conserved domain typical of cryptochromes with high homology to those found in monocots. Furthermore, we examined the expression level of AcCRY1 in onion. The green tissues is significantly higher compared to non-green tissues, and it exhibits a significant response to blue-light induction. AcCRY1 demonstrates cytoplasmic localization under blue-light conditions, while it localizes in the nucleus during darkness, indicating a strong dependence on blue-light for its subcellular distribution. In comparison to cry1 , overexpression of AcCRY1 leads to a significant shorten in seedling hypocotyl length, notable expansion of cotyledons, and acceleration of flowering time. The yeast two-hybrid experiment demonstrated the in vitro interaction between AcCRY1, AcCOP1, and AcSPA1. Additionally, BIFC analysis confirmed their interaction in Onion epidermis. Notably, under blue-light conditions, a significantly enhanced binding activity was observed compared to dark conditions. These findings establish a functional foundation for the regulatory role of AcCRY1 in important physiological processes of onion and provide initial insights into the underlying molecular mechanisms.
研究领域:
植物生物学
·
分子生物学
·
遗传学
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DOI
PubMed
高影响因子
Journal of Cell Communication and Signaling
·
2024
·
IF 3.6
Le Cao,Weilu Gao,Haitao Yang,Ran Zeng,Zongsheng Yin
Inflammation promotes the degradation of the extracellular matrix, which contributes to the development of osteoarthritis (OA). Adipocyte enhancer binding protein 1 (AEBP1) participates in multiple pathological processes related to inflammatory diseases. However, the role of AEBP1 in OA development is unknown. We found a higher AEBP1 expression in articular cartilage of OA patients ( n = 20) compared to their normal controls ( n = 10). Thus, we inferred that AEBP1 might affect OA progression. Then mice with destabilization of the medial meniscus (DMM) surgery and chondrocytes with IL-1β treatment (10 ng/mL) were used to mimic OA. The increased AEBP1 expression was observed in models of OA. AEBP1 knockdown in chondrocytes reversed IL-1β-induced inflammation and extracellular matrix degradation, which was mediated by the inactivation of NF-κB signaling pathway and the increased IκBα activity. Co-immunoprecipitation assay indicated the interaction between AEBP1 and IκBα. Importantly, IκBα knockdown depleted the protective role of AEBP1 knockdown in OA. Moreover, AEBP1 knockdown in mice with OA showed similar results to those in chondrocytes. Collectively, our findings suggest that AEBP1 knockdown alleviates the development of OA, providing a novel strategy for OA treatment.
研究领域:
风湿病学
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分子生物学
·
细胞生物学
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病理学
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DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL AND ENGINEERING DATA
·
2015
·
IF 2.037
Xiaopo Wang,Xiaojie Wang,Bo Song
Experimental density and viscosity data for binary mixtures of 2,2,4-trimethylpentane with 1-propanol, 1-pentanol, 1-hexanol, and 1-heptanol at atmospheric pressure over the entire composition range at temperatures from (298.15 to 323.15) K are reported. Excess molar volumes and viscosity deviations of the mixtures were calculated from the experimental data and correlated using the Redlich–Kister equation. The optimized sets of parameters of the equation at each temperature were obtained by the least-squares method.
研究领域:
热力学
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化学工程
·
物理化学
·
流体混合物
✓ 已验证
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2020
·
IF 7.1
Ning Xia,Daohong Wu,Ting Sun,Yilin Wang,Xiaoyu Ren,Feng Zhao,Lin Liu,Xinyao Yi
Poly(ADP-ribose) polymerase-1 (PARP-1), as a highly conserved nuclear enzyme, can catalyze the transfer of multiple ADP-ribose units from β-nicotinamide adenine dinucleotide (NAD + ) to substrate proteins, including PARP-1 itself. In this work, two boronic acid derivatives, ferroceneboronic acid (FcBA) and 4-mercaptophenylboronic acid (MPBA) were used as the signal probes for electrochemical and colorimetric detection of PARP-1, respectively. The detection platform was constructed by modification of double-stranded DNA (dsDNA) on the surface of magnetic beads (MBs). Once PARP-1 was captured by the MB-dsDNA, auto-PARylation was initiated and the PAR products consisting of abundant ribose units were covalently bound to FcBA or MPBA through the formation of boronate ester covalent bonds. Sequestration of FcBA or MPBA by the PAR-covered MBs led to the decrease in the electrochemical signal of FcBA or preventing the MPBA-triggered aggregation of gold nanoparticle indicators. The change of oxidation current or adsorption intensity (color) was dependent upon the concentration and activity of PARP-1. A wide linear range of 0.1 ∼ 50 U was obtained for the electrochemical or colorimetric assays. The methods have been used to evaluate the inhibition efficiency and monitor the PARP-1 activity in living and apoptotic cancer cells.
研究领域:
生物化学
·
分析化学
·
分子生物学
·
癌症研究
✓ 已验证
DOI
高影响因子
JOURNAL OF ELECTROANALYTICAL CHEMISTRY
·
2018
·
IF 3.235
Yang Yuan,Jiaxin Wang,Xinjiong Ni,Yuhua Cao
A biosensor for determination of 3-chloro-1, 2-propandiol (3-MCPD) was developed based on the electrochemically catalytic reduction by hemoglobin (Hb). Hb was concentrated and immobilized with magnetic molecularly imprinted nanoparticles (MMIPs NPs). The MMIP NPs had a core-shell structure, with magnetic Fe 3 O 4 NPs as the core and SiO 2 as the shell. MMIPs NPs were modified on the surface of a magnetic electrode to constitute the Hb enzyme-like sensor. The biosensor could catalyze the electrochemical reduction of 3-MCPD, and a direct electrochemical determination of 3-MCPD could be achieved for the first time. The biosensor, where Hb immobilized with MMIPs NPs had high electrochemical response for 3-MCPD, increased by 37.5% compared with Hb immobilized with magnetic non-imprinted nanoparticle (MNIPs NPs). The biosensor increased the response by 19.56% again under an external magnetic field . The reduction peak current had a linear relationship with 3-MCPD concentration ranging from 1.0 mg·L −1 to 160 mg·L −1 with a detection limit (S/N = 3) of 0.25 mg·L −1 . The biosensor was applied to the determination of 3-MCPD in soy sauce samples successfully with recoveries between 97.4% and 99.6%.
研究领域:
生物传感器
·
分析化学
·
食品科学
·
电化学
·
分子生物学
·
纳米医学
✓ 已验证
DOI
高影响因子
Energy Storage Materials
·
2021
·
IF 17.789
Weibo Huang,Yan Wang,Linze Lv,Wei Wang,Chengchang Jin,Guobin Zhu,Qiang Shi,Qunting Qu,Chao Jin,Honghe Zheng
Fluoroethylene carbonate (FEC) is an important electrolyte additive in silicon (Si) anodes. However, it is easily defluorinated by Lewis acids (PF 5 − ) to form harmful corrosive substances (HF). To overcome this problem, 1-Hydroxyethylidene-1, 1-diphosphonic acid (HEDP), a novel multifunctional surface modifier is developed on the Si surface. It can not only consume HF, but also participate in the formation of a solid electrolyte interphase (SEI) film with excellent electrochemical stability, high lithium conductivity, and good thermal stability. In addition, Si@HEDP anode with polyvinylidene fluoride (PVDF) binder exhibits much improved electrochemical performance. After 500 cycles at 30 °C, a high reversible capacity of 1831.8 mAh g − 1 is obtained; and after 200 cycles at 60 °C, it still maintains 2163.8 mAh g − 1 ; which are in sharp contrast to the reference Si anode of almost zero capacity after 25 cycles. This work overcomes the fundamental challenges of using FEC electrolyte additive and PVDF binder in Si-based batteries.
✓ 已验证
产品关联
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Jing Zhu,Liutao Chen
Fluorescent dye DITO-1 has almost no fluorescence in the absence of nucleic acid . G bases in single strand DNA can induce maximum fluorescent enhancement followed by the A bases when it binds the DITO-1. However, the incorporation efficiency of the dATP was higher than dGTP in terminal transferase (TdT) polymerization. As a consequence, ploy (A) n , rather than ploy (G) n via TdT polymerization had the superior photoluminance when it binded DITO-1 fluorescent dye. Here, we developed a high selective and sensitive sensing strategy for assaying TdT and T4 polynucleotide kinase activity (T4 PNK) based on the ploy (A) n -DITO-1 fluorescent probe. An increasing amounts of TdT enzyme could promote the distinct incorporation of dATP on the DNA primer and form poly (A) n ssDNA with a difference in length. A good linear relationship between the ΔF and the concentrations of TdT in a range of 0.2–50 U/mL was obtained and the detection limit was 0.05 U/mL. Based on the experimental results for TdT, we further expanded the application of this method for detection of a series of concentrations of T4 PNK. The ΔF and the logarithm concentrations of T4 PNK in the range of 0.1–10 U/mL showed a good linear response and the detection limit of 0.02 U/mL was obtained. In addition, the detection of T4 PNK in Hela cell lysate was achieved, demonstrating that the proposed method had the potential application in complex system. The ploy (A) n -DITO-1 fluorescent probe had the excellent properties of one-step readout, robustness for target detection in complex system, and easiness operation, and showed the great potential in clinical diagnostics, inhibitor screening, and drug discovery.
研究领域:
分子生物学
·
生物化学
·
分析化学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2020
·
IF 4.831
Shiyang Zhou,Gangliang Huang
In this study, a series of novel 7 H -benzo [ c ] [1,3] dioxolo [4, 5- f ] chromen-7-one derivatives were obtained by structural modification of the lead compounds with Fissitungfine B. A total 15 compounds were designed, synthesized and evaluated as inhibitors of tumor. These target compounds have the novel chemical structures that named three six-membered rings including one lactone six-membered ring. In vitro assay, the results showed that the target compounds have a broad spectrum and strong of anti-tumor activity. Such as the target compound 4n to MCF-7 was IC 50 = 0.35 ± 0.01 μM, to A-549 was IC 50 = 0.37 ± 0.01 μM, to Hela was IC 50 = 0.56 ± 0.02 μM, to MDC-803 was IC 50 = 0.53 ± 0.02 μM and COLO-205 was IC 50 = 0.50 ± 0.02 μM in vitro . At the same time, in vivo anti-tumor activity assay results showed that the target compounds had a good inhibitory effect on tumor growth. Among them, the target compound 4n had the best anti-tumor activity, it could inhibit tumor growth well at a low dose. The target compound 4n could be used as a candidate drug for further research and development, in order to be used as early as application in the clinical treatment of tumors.
研究领域:
药物化学
·
肿瘤学
·
有机合成
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）