IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2023
·
IF 3.3
Shiling Hu,Jue Wang,Haoyun Bai,Chaohua Feng,Zhenqi Zhou,Zhuoyin Xue,Wen Zhang,Yongjing Zhang,Nan Wang,Langchong He
Background Mast cells (MCs) are important effector cells in anaphylaxis and anaphylactic disease. 3’,4’,5,7-tetrahydroxyflavone (THF) presents in many medicinal plants and exerts a variety of pharmacological effects. In this study, we evaluated the effect of THF on C48/80-induced anaphylaxis and the mechanisms underlying its effects, including the role of secreted phosphoprotein 1 (SPP1), which has not been reported to IgE-independent MC activation.Results THF inhibited C48/80-induced Ca2+ flow and degranulation via the PLCγ/PKC/IP3 pathway in vitro. RNA-seq showed that THF inhibited the expression of SPP1 and downstream molecules. SPP1 is involved in pseudo-anaphylaxis reactions. Silencing SPP1 affects the phosphorylation of AKT and P38. THF suppressed C48/80-induced paw edema, hypothermia and serum histamine, and chemokines release in vivo.Conclusions Our results validated SPP1 is involved in IgE-independent MC activation anaphylactoid reactions. THF inhibited C48/80-mediated anaphylactoid reactions both in vivo and in vitro, suppressed calcium mobilization and inhibited SPP1-related pathways.
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高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 11
·2307
·
IF 6.525
Xueyan Gou,Fenglin Ran,Jinru Yang,Yanrong Ma,Xin’an Wu
Background: Organic anion transporter 1 (OAT1) and OAT3 have an overlapping spectrum of substrates such that one can exert a compensatory effect when the other is dysfunctional. As a result, the knockout of either OAT1 or OAT3 is not reflected in a change in the excretion of organic anionic substrates. To date, only the mOAT1 and mOAT3 individual knockout mouse models have been available. Methods: In this study, we successfully generated aSlc22a6/Slc22a8double-knockout (KO) rat model using CRISPR/Cas9 technology and evaluated its biological properties. Results: The double-knockout rat model did not expressionmRNAfor rOAT1 or rOAT3 in the kidneys. Consistently, the renal excretion ofp-aminohippuric acid (PAH), the classical substrate of OAT1/OAT3, was substantially decreased in theSlc22a6/Slc22a8double-knockout rats. The relativemRNAlevel ofSlco4c1was up-regulated in KO rats. No renal pathological phenotype was evident. The renal elimination of the organic anionic drug furosemide was nearly abolished in theSlc22a6/Slc22a8knockout rats, but elimination of the organic cationic drug metformin was hardly affected. Conclusions: These results demonstrate that this rat model is a useful tool for investigating the functions of OAT1/OAT3 in metabolic diseases, drug metabolism and pharmacokinetics, and OATs-mediated drug interactions.Keywords:OAT1/OAT3;CRISPR/Cas9;gene knockout;pharmacokinetic
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高影响因子
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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高影响因子
COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING
·
2022
·
IF 9.463
Lei Chen,Ruiqi Zhang,Xing Cao,Xuebing Li,Yongtao Qu
High latent heat and thermostatic properties of phase change materials (PCMs) have made them the promising materials. Herein, a novel thermally-induced flexible 1-Hexadecanol/Olefin block copolymer/Hexagonal boron nitride (HD/OBC/h-BN) composite phase change material (CPCM) is proposed. Bio-based non-polluting material of HD is employed innovatively as the phase change component. The triggering of HD phase transition can achieve various deformation modes for CPCM, which is beneficial to reduce the thermal contact resistance between CPCM and device. The electrically insulating property of h-BN not only improves the thermal conductivity and the heating/cooling rate of CPCM, but also further solves the problem of the HD leakage (as low as 0.31 wt%). The prepared CPCM with excellent flexibility and high latent heat (above 150 J/g) has good thermal stability and thermal reliability in the working temperature range. This provides developed CPCM greater potential for thermal energy storage (TES) and thermal management (TM) than conventional PCMs.
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高影响因子
Evidence-based Complementary and Alternative Medicine
·
2022
·
IF 2.65
Guanghua Sun,Yahua Zeng,Fu Luo,Lixian Zhang,Jinqu Tan,Jie Tong,Lu Yang,Danni Liu,Liu Liu,Jun Zhou
Our study aimed to investigate the effect of electroacupuncture pretreatment on the inflammatory response and expression levels of LC3-II/I and Beclin 1 using a model of lipopolysaccharide (LPS)-induced acute lung injury (ALI). Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups: normal control group (NC, n = 6), LSP modeling group (LM, n = 6), and electroacupuncture group (EA, n = 6). Rats in the EA group received electroacupuncture pretreatment at bilateral Zusanli (ST36) and Chize (LU5) points for five days (30 min each time daily, frequency; 3 Hz/15 Hz, intensity; 1 mA). Rats in the EA and LM groups were then injected with 5 mg/kg LPS (Beijing, Solarbio Company, concentration; 5 mg/mL) through the tail vein, while those in the NC group were injected with 5 mg/kg saline. The animals were sacrificed six hours after LPS or saline injection through cervical vertebrae by dislocation under deep anesthesia. Orbital blood was collected for the analysis of serum inflammatory factors including interleukin-1β (IL-1β) and transforming growth factor-β (TGF-β). The lower left lung was excised, stained with hematoxylin-eosin (HE), and subjected to histopathological analysis. The mRNA and protein expression of Beclin 1 and LC3 II/I in the lower right lung tissues were detected via RT-qPCR and Western blot analyses, respectively. The results showed that lung injury score was significantly higher in the LM group than that of the NC group () and EA group (). The IL-1β contents were significantly decreased in the EA group () than in the LM group. In contrast, the GF-β contents were increased in the EA group significantly when compared with the LM group (). RT-qPCR and Western blot detection showed that the relative gene expression of LC3‐II/I and Beclin 1 was significantly lower in the EA group than in the LM group (). However, the relative protein expression level of LC3‐II/I and Beclin 1 was slightly lower in the EA group than the in LM group (). These results show that electroacupuncture pretreatment reduces the inflammatory response in ALI and can protect lung tissue by inhibiting the gene and protein expression levels of LC3‐II/I and Beclin 1.
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高影响因子
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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高影响因子
Nanomaterials
·
2022
·Vol. 12
·期 12
·2094
·
IF 5.719
Hongming Liu,Qin Zhou,Yongfu Lian
Individual single–walled carbon nanotubes (SWNTs) with distinct electronic types are crucial for the fabrication of SWNTs–based electronic and magnetic devices. Herein, the water–soluble polymethyl(1–butyric acidyl)silane (BA–PMS) was synthesized via the hydrosilylation reaction between 3–butenoic acid and polymethylsilane catalyzed by 2,2′–azodibutyronitrile. As a new dispersant, BA–PMS displayed a quite good dispersing capacity to arc–discharged SWNTs and moderate selectivity for metallic species. The application of sucrose–DGU, the density gradient ultracentrifugation with sucrose as the gradient medium, to the co–surfactants (BA–PMS and sodium dodecyl sulfonate) individually dispersed SWNTs yielded metallic SWNTs of 85.6% purity and semiconducting SWNTs of 99% purity, respectively. This work paves a path to the DGU separation of the SWNTs dispersed by polymer–based dispersants with hydrophobic alkyl chains.Keywords:polymethyl(1–butyric acidyl)silane;dispersion;density gradient ultracentrifugation
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高影响因子
GENE
·
2022
·
IF 3.913
Xiaohong Chen,Yueya Zhang,Haifeng Yan,Meiyun Niu,Yuping Xiong,Xinhua Zhang,Yuan Li,Jaime A. Teixeira da Silva,Guohua Ma
The commercial value of Santalum album L. lies in its aromatic heartwood and essential oil. Sesquiterpenes are the main components of sandal essential oil, and these are synthesized through the plant’s mevalonate (MVA) and methylerythritol phosphate (MEP) pathways. In this study, the first key rate-limiting enzyme, 1-deoxy- d -xylulose-5-phosphate synthase (SaDXS), was investigated to provide a theoretical molecular basis for the sandalwood MEP sesquiterpene biosynthetic pathway. The biofunctions of SaDXS were also analyzed. SaDXS promoters were successfully cloned from a seven-year-old S. album tree. SaDXS1A/1B promoter activity was verified by a β-glucuronidase (GUS) assay and by analyzing cis -acting elements of the promoters, which carried light- and methyl jasmonate (MeJA)-responsive signals. In an experiment involving yellow S. album seedlings, exposure to light upregulated SaDXS1A/1B expression and increased chlorophyll and carotenoid contents when overexpressed in Arabidopsis thaliana . Analysis of the expression of SaDXS1A/1B and SaSSy , key genes of santalol biosynthesis, revealed SaDXS1A expression in all tissues whereas SaDXS1B was expressed in tissues that contained photosynthetic pigments, such as stems, leaves and flowers. Sandal seedlings exogenously treated with two hormones, MeJA and ethylene, revealed similar expression patterns for SaDXS1A/1B and SaSSy . Sandal seedlings were treated with an inhibitor of DXS, clomazone, but showed no significant changes in the contents of α-santalene, β-santalene and α-santalol between treatment and control groups. These results suggest that SaDXS1A/1B play a role in the synthesis of sandalwood sesquiterpenes, providing carbon for downstream secondary metabolites. SaDXS1A/1B also play a role in the biosynthesis of chlorophyll, carotenoids, and primary metabolites.
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高影响因子
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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IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2022
·
IF 3.712
Sa-sa Zhang,Yi-jin Wu,Shu Pan,Qi-hai Wang,Wen-gang Chen,Zhong-fang Wang,Jin-ying Xu,Jian Zuo,Qin Yin
Background The first-line anti-rheumatic drug methotrexate (MTX) is used in the combination. Because of the unpredictable adverse reactions, optimization of relevant regimens is necessary and meaningful. This study aimed to study the possible interaction between Securidaca inappendiculate Hassk. Derived xanthones and MTX.Methods We established adjuvant-induced arthritis (AIA) model, which was treated with MTX and MTX + xanthone-rich fraction (XRF). The clinical efficacy was evaluated by histopathological examination, and LC-MS was used to monitor the blood concentration of MTX. Western blotting and immunohistochemistry were used to detect protein expression. In vitro, we assessed the activity of related transporters by cellular uptake assay based on HEK-293T cells.Results Compared with MTX-treated rats, inflammation in the immunized rats in the MTX + XRF group was obvious, indicating that XRF antagonized the anti-rheumatic effect of MTX. Meanwhile, XRF reduced liver and kidney injuries caused by MTX in addition to MTX. Results from immunohistochemical and nappendiculat assays suggested that XRF may reduce uptake of MTX by down-regulating reduced folate carrier 1 (RFC1).Conclusion This study indicated that XRF could reduce the plasma concentration of MTX by inhibiting the expression of RFC1, antagonize the therapeutic effect of MTX on AIA rats, and reduce its oral bioavailability. The combination of S. inappendiculate and MTX should be further optimized to achieve the goal of increasing efficiency and reducing toxicity.
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高影响因子
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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高影响因子
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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