BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
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2025
·Vol. 136
·期 5
·e70027
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IF 3.3
Mengjie Guo,Han Meng,Yi Sun,Lianxin Zhou,Tingting Hu,Tianyi Yu,Haowen Bai,Yuanjiao Zhang,Chunyan Gu,Ye Yang
Multiple myeloma (MM) is an incurable hematologic malignancy, driving significant interest in the discovery of novel therapeutic strategies. Bruceine A (BA), a tetracyclic triterpene quassinoid derived from Brucea javanica , has shown anticancer properties by modulating multiple intracellular signalling pathways and exhibiting various biological effects. However, the specific pharmacological mechanisms by which it combats MM remain unclear. In this study, we identified USP13 as a potential target of BA. We observed a significant increase in USP13 expression in patients with MM, which was strongly associated with a poorer prognosis. Furthermore, enhanced USP13 expression can stimulate MM cell proliferation both in vitro and in vivo. Mass spectrometry analysis, combined with co-immunoprecipitation and in vitro ubiquitination experiments, revealed PARP1 as a critical downstream target of USP13. USP13 can stabilize PARP1 protein through deubiquitination, promoting PARP1-mediated DNA damage repair (DDR) and facilitating MM progression. Notably, we utilized MM cell lines, an MM Patient-Derived Tumour Xenograft model, and a 5TMM3VT mouse model to determine the anticancer effects of BA on MM progression, revealing its potential to target USP13/PARP1 signalling and disrupt DDR in MM cells. In conclusion, these findings suggest that BA inhibiting USP13/PARP1-mediated DDR might be a promising therapeutic strategy for MM.
研究领域:
肿瘤学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2018
·
IF 3.716
Qian-Yu Zhao,Hai-Tian Zhao,Xin Yang,Hua Zhang,Ai-Jun Dong,Jing Wang,Bin Li
In this work, a novel synthetic strategy for separation media which quickly specific recognize anthocyanins was developed by dummy molecular imprinting technology and magnetic separation technology. Rutin, similar to cyanidin-3-O-rutinoside structure, was selected as a virtual template. The appropriate molecular imprinting system was selected by NIP library screening method, 4-vinyl pyridine and acetonitrile as functional monomer and solvent respectively. The molecularly imprinted layer was formed on the surface of the magnetic carrier to prepare dummy magnetic molecularly imprinted polymers. The microstructures of prepared composites were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), thermal gravimetric analysis (TGA) and X-ray diffraction (XRD). Adsorption kinetics, isothermal adsorption curves and selective specificity were investigated to further reveal the specific recognition mechanism of the adsorbents on anthocyanins. The dummy molecularly imprinted polymers showed a short kinetic equilibrium time, high selectivity (comparing with quercetin and naringin), and satisfying adsorption capacity for anthocyanins. The binding capacity and the imprinting factor of dummy molecularly imprinted polymers can reach 15.69 mg g −1 and 2.05, respectively. In addition, the purity of cyanidin-3- O -rutinoside in the crude extract from Lonicera caerulea increased to 89% after the adsorption of dummy magnetic molecular imprinted polymers. Many favorable capabilities of the prepared molecularly imprinted polymers also provided the basis for further application for separation and purification of anthocyanins in the future.
研究领域:
食品科学
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材料科学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Xudan Xing,Zunlei Gong,Chuke Chen,Yeyin Lin,Peiyi Liu,Tianhua Xiao,Hui Yu,Yuanxin Li,Yucong Lin,Guoxin Tan,Chengyun Ning,Zenghui Wu,Le Wang,Lei Zhou
Diabetes is associated with excessive inflammation, which negatively impacts the fracture healing process and delays bone repair. Previously, growing evidence indicated that activation of the nod-like receptor (NLR) family, such as nod-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome induces a vicious cycle of chronic low-grade inflammatory responses in diabetic fracture. Here, we describe the synthesis of a bone adhesive hydrogel that can be locally injected into the fracture site and releases a natural inhibitor of NLRP3 (rutin) in response to pathological cue reactive oxygen species activity (ROS). The hydrogel (denoted as RPO) was facilely formed by the cross-linking of rutin-functionalized gelatin, poly(vinyl alcohol), and oxidized starch based on the dynamic schiff base and boronate ester bond. Specifically, rutin is conjugated in the RPO hydrogel via a ROS linker and is released as the linker is cleaved by active ROS. In vitro studies demonstrate that RPO hydrogel effectively mitigates oxidative stress, alleviates mitochondrial dysfunction, and limits the overactivation of NLRP3 inflammasome in bone marrow derived macrophages, thereby promoting osteogenic differentiation of bone marrow mesenchymal stem cells. In a diabetic rat fracture model, RPO hydrogel significantly accelerates bone repair by modulating the inflammatory microenvironment. Our results demonstrate that local, on-demand NLRP3 inhibition for the treatment of diabetic fracture is achievable by using an injectable bioresponsive adhesive RPO hydrogel.
研究领域:
生物材料学
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炎症生物学
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骨科医学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 39
·7734-7744
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IF 4.726
Yiyin Chen,Angelina Angelova,Borislav Angelov,Markus Drechsler,Vasil M. Garamus,Regine Willumeit-Römer,Aihua Zou
Multidrug delivery devices are designed to take advantage of the synergistic effects of anticancer agents in combination therapies. Here we report novel liquid crystalline self-assembled nanocarriers enhancing the activity of the phytochemical anticancer agent baicalin (BAI) in combination with Brucea javanica oil (BJO), which ensures safe formulations for clinical applications. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) evidenced the multicompartment, sponge-type nano-organization of the blank and multidrug-loaded liquid crystalline carriers. Physico-chemical stability of the sponge nanoparticles was achieved through PEGylation of the lipid membranes, which make up the drug nanocarriers. The proposed green nanotechnology for nanocarrier preparation by supramolecular self-assembly provided a multidrug encapsulation efficiency as high as 75%. The apoptosis study with the human lung carcinoma cell line A549 demonstrated improved efficacy of the multidrug delivery nanocarriers in comparison to the single-drug reservoirs. The obtained results evidenced the synergistic anticancer apoptotic effects of the multidrug-loaded nanosponge carriers and suggested the opportunity for in vivo translation towards the treatment of lung, gastrointestinal, and ovarian cancers.
研究领域:
药剂学
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癌症治疗
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纳米技术
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2025
·Vol. 31
·期 1
·1-17
·
IF 6.4
Liu Jing,Li Wenqi,Jiao Ran,Liu Zhigang,Zhang Tiantian,Chai Dan,Meng Lingxin,Yang Zhongyi,Liu Yuming,Wu Hongliang,Gu Xiaoting,Li Xiaohe,Yang Cheng
Background Cardiac fibrosis is significant global health problem, which is associated with numerous cardiovascular diseases, and ultimately leads to the progression to heart failure. β-adrenergic receptor (β-AR) overactivation play a role in the development of cardiac fibrosis. Miglustat (Mig) has shown anti-fibrosis effects in multiple fibrotic diseases. However, it is unclear whether and how Mig can ameliorate cardiac fibrosis induced by β-AR overactivation. Methods In vivo, mice were injected with isoproterenol (ISO) to induce cardiac fibrosis and treated with Mig. In vitro, primary cardiac fibroblasts were stimulated by ISO and treated with Mig. Levels of cardiac fibrosis, cardiac dysfunction, activation of cardiac fibroblasts were evaluated by real-time polymerase chain reaction, western blots, sirius red staining, immunohistochemistry staining and echocardiography. Through GEO data and knockdown UDP-glucose ceramide glycosyltransferase (UGCG) in primary cardiac fibroblasts, whether Mig alleviates cardiac fibrosis by targeting UGCG was explored. Results The results indicated that Mig alleviated ISO-induced cardiac dysfunction. Consistently, Mig also suppressed ISO-induced cardiac fibrosis. Moreover, Mig attenuated ISO-induced cardiac fibroblasts (CFs) activation. To identify the protective mechanism of Mig on cardiac fibrosis, several classical β-AR downstream signaling pathways, including ERK, STAT3, Akt and GSK3β, were further analyzed. As expected, ISO activated the ERK, STAT3, Akt and GSK3β in both CFs and mouse hearts, but this effect was reversed pretreated with Mig. Besides, Mig ameliorates ISO-induced cardiac fibrosis by targeting UDP-glucose ceramide glycosyltransferase (UGCG) in CFs. Conclusions Mig ameliorates β-AR overactivation-induced cardiac fibrosis by inhibiting ERK, STAT3, Akt and GSK3β signaling and UGCG may be a potential target for the treatment of cardiac fibrosis.
研究领域:
心血管疾病
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药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2021
·
IF 7.086
Yan Cao,Linfeng Zhang,Yingxue Geng,Yingjie Li,Qun Zhao,Jianhong Huang,Ping Ning,Senlin Tian
Polycyclic aromatic hydrocarbons (PAHs) can penetrate and accumulate in the pulmonary surfactant (PS) membranes, leading to abnormalities of biological macromolecules and the destruction of membrane structure and properties. In the present study, the bioavailability , apparent permeability, effective permeability and residual coefficient of 10 PAHs on PS membrane was assessed by the parallel artificial membrane permeability assay (PAMPA). The influence of various forces on permeability is obtained by analyzing the correlation between parameters and physicochemical properties . Research shows that octanol-water partition coefficient ( K ow ) cannot directly predict permeability, and permeability has no significant relationship with polarity. Dispersion, induction, coupling/polarization promote permeation, while hydrogen bonded acid and n-n electron pair inhibit permeation. Further surface pressure-area (π-A) isotherms test and Brewster angle microscope observation manifested that there are huge differences in the transmembrane ability and effects on the membrane of PAHs with different structures. This work has considerable significance that will help to evaluate the bioavailability and human health risk of PAHs.
研究领域:
环境科学
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毒理学
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生物物理学
·
化学
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DOI
高影响因子
危险品化学品经营许可证（带存储）