BIOMEDICINE & PHARMACOTHERAPY
·
2024
·
IF 6.9
Jaili Li,Ting Luo,Yao Zhao,Dou Wang,Yuanxiang Jin,Zufang Wu,Guiling Yang,Xingjiang Qi
Doxorubicin (DOX) is a commonly used anthracycline in cancer chemotherapy. The clinical application of DOX is constrained by its cardiotoxicity. Myricetin (MYR) is a natural flavonoid widely present in many plants with antioxidant and anti-inflammatory properties. However, MYR's beneficial effects and mechanisms in alleviating DOX-induced cardiotoxicity (DIC) remain unknown. C57BL/6 mice were injected with 15 mg/kg of DOX to establish the DIC, and MYR solutions were administrated by gavage to investigate its cardioprotective potentials. Histopathological analysis, physiological indicators assessment, transcriptomics analysis, and RT-qPCR were used to elucidate the potential mechanism of MYR in DIC treatment. MYR reduced cardiac injury produced by DOX, decreased levels of cTnI, AST, LDH, and BNP, and improved myocardial injury and fibrosis. MYR effectively prevented DOX-induced oxidative stress, such as lowered MDA levels and elevated SOD, CAT, and GSH activities. MYR effectively suppressed NLRP3 and ASC gene expression levels to inhibit pyroptosis while regulating Caspase1 and Bax levels to reduce cardiac cell apoptosis. According to the transcriptomic analysis, glucose and fatty acid metabolism were associated with differential gene expression. KEGG pathway analysis revealed differential gene enrichment in PPAR and AMPK pathways, among others. Following validation, MYR was found to alleviate DIC by regulating glycolipid metabolism and AMPK pathway-related genes. Our findings demonstrated that MYR could mitigate DIC by regulating the processes of oxidative stress, apoptosis, and pyroptosis. MYR is critical in improving DOX-induced myocardial energy metabolism abnormalities mediated by the AMPK signaling pathway. In conclusion, MYR holds promise as a therapeutic strategy for DIC.
研究领域:
药理学
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毒理学
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分子生物学
·
心脏病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL STRESS & CHAPERONES
·
2020
·Vol. 26
·期 2
·367-375
·
IF 2.892
Chen Jun,Li Lihua,Zhou Yun,Zhang Jiahua,Chen Lei
Diabetic retinopathy (DR) is a serious microvascular complication of diabetes. Gambogic acid has been reported to have anti-inflammatory effect. However, the effect of GA on inflammatory response of ARPE-19 cells remains unclear. In our study, ARPE-19 cells were stimulated by palmitic acid (PA) induction in the presence of 30 mM glucose and then treated with 0.5, 1, 2, 5, 10, or 20 μM GA. CCK-8 assay showed that cell viability was increased by GA treatment at doses of 0.5, 1, and 2 μM instead of higher doses. ELISA analysis found that GA dose-dependently reduced the production of pro-inflammatory mediators TNF-α and IL-1β. Western blot indicated that GA downregulated the expression of NLRP3 inflammasome components including TXNIP, NLRP3, ASC, cleaved-caspase-1, and cleaved-IL-1β in a dose-dependent manner. In addition, Western blot and immunofluorescence analysis suggested that GA effectively increased the protein level of nuclear factor E2-related factor-2 (Nrf2). RT-qPCR showed that GA significantly increased the mRNA levels of Heme oxygenase-1 (HO-1) and NADPH:quinone oxidoreductase1 (NQO1). Furthermore, Nrf2 siRNA transfection confirmed the above effects of GA. In total, subtoxic doses of GA significantly flattened the inflammatory response induced by HG and PA in ARPE-19 cells via modulating the Nrf2 signaling pathway.
研究领域:
药理学
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细胞生物学
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糖尿病研究
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炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2023
·Vol. 10
·期 14
·2207448
·
IF 15.1
Jiahui Yan,Jingwen Zhang,Yanan Wang,Hong Liu,Xueping Sun,Aixin Li,Pengfei Cui,Liangmin Yu,Xuefeng Yan,Zhiyu He
Pyroptosis, systemic inflammation, and mitochondrial apoptosis are the three primary contributors to sepsis's multiple organ failure, the ultimate cause of high clinical mortality. Currently, the drugs under development only target a single pathogenesis, which is obviously insufficient. In this study, an acid-responsive hollow mesoporous polydopamine (HMPDA) nanocarrier that is highly capable of carrying both the hydrophilic drug NAD + and the hydrophobic drug BAPTA-AM, with its outer layer being sealed by the inflammatory targeting peptide PEG-LSA, is developed. Once targeted to the region of inflammation, HMPDA begins depolymerization, releasing the drugs NAD + and BAPTA-AM. Depletion of polydopamine on excessive reactive oxygen species production, promotion of ATP production and anti-inflammation by NAD + replenishment, and chelation of BAPTA (generated by BA-AM hydrolysis) on overloaded Ca 2+ can comprehensively block the three stages of sepsis, i.e., precisely inhibit the activation of pyroptosis pathway (NF- κ B-NLRP3-ASC-Casp-1), inflammation pathway (IL-1 β , IL-6, and TNF- α ), and mitochondrial apoptosis pathway (Bcl-2/Bax-Cyt-C-Casp-9-Casp-3), thereby restoring intracellular homeostasis, saving the cells in a state of “critical survival,” further reducing LPS-induced systemic inflammation, finally restoring the organ functions. In conclusion, the synthesis of this agent provides a simple and effective synergistic drug delivery nanosystem, which demonstrates significant therapeutic potential in a model of LPS-induced sepsis.
研究领域:
药理学
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纳米技术
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免疫学
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细胞生物学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CRYSTENGCOMM
·
2023
·Vol. 25
·期 20
·3066-3078
·
IF 3.1
Jinyu Ma,Qing Sun,Chuan Jing,Faling Ling,Xiao Tang,Yanhong Li,Yongjie Wang,Sha Jiang,Kexin Yao,Xianju Zhou
Since the energy density and voltage window of supercapacitors cannot match that of lithium-ion batteries, supercapacitors are far from replacing batteries but can only be seen as a supplement to battery charge storage or transmission devices. The design of transition metal oxide-based electrodes with high cycling capacitance retention is very important for the development of supercapacitors. In this study, flower-like SAC@NiCoMn-LDH electrode materials with different Mn doping ratios were prepared by a hydrothermal method with mesoporous carbon (SAC) as the substrate. Density functional theory (DFT) calculations confirm that Mn doping can enhance the adsorption of OH− and the desorption of the H proton. In addition, Mn doping increases the density of states of LDH near the Fermi level and increases the number of active electrons, which is conducive to the occurrence of electrochemical reactions. In the three-electrode system, SAC@Ni2Co0.95Mn0.05-LDH with optimal doping ratio increased the specific capacitance by three times compared to that of NiCo-LDH and displayed an excellent cycling stability (83.76% capacitance retention after 50 000 cycles). Moreover, the prepared SAC@Ni2Co0.95Mn0.05-LDH and commercial activated carbon (AC) were made into electrode plates and then assembled into a SAC@Ni2Co0.95Mn0.05-LDH//AC asymmetric supercapacitor (ASC). The ASC exhibited high energy density (23.68 W h kg−1 at 325 W kg−1) and excellent specific capacitance retention (85.32% after 50 000 cycles), making it well suited for efficient wind energy storage and conversion with promising practical applications.
研究领域:
材料科学
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电化学
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能源存储
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纳米技术
✓ 已验证
产品关联
DOI
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2022
·
IF 5.204
Yumin Wu,Yizhi Jiao,Zhihao Rong,Chuanhui Gao,Yuetao Liu
Manufacturing organosilicon elastomers that have combined reprocessability, self-healing, and high stretchable properties, this remains a significant challenge. Herein, we proposed a simple one-pot method to synthesize thermoset organosilicon elastomers which could be self-healed and had good mechanical properties. The elastomers were capped with the α,ω-hydroxypolydimethylsiloxane and isophorone diisocyanate, following chain expansion with adipic dihydrazide, and cross-linked by triethanolamine. The average elongation of the elastomers was 1145%, with the largest strain of 4.1 MPa. Due to the highly flexible Si-O chain and the large number of hydrogen bonds formed by the dynamic acyl semicarbazide (ASC) groups, the elastomers had good self-healing ability. It was noted that the elastomers could be recycled entirely under the synergistic dynamic effect of ASC groups without chemical treatment, and the elastomers could achieve 91% of the initial mechanical strength even after ten times of dissolution recycling. And through three times of hot pressing recovery, 86% of the mechanical properties were also maintained. In addition, the self-healing flexible electronic devices were prepared by compounding multi-walled carbon nanotubes (MWCNTs), and they could monitor the subtle movements of the human body. This work fabricated the reprocessable and self-healing organosilicon elastomers for flexible electronic devices, which might have essential inspiration for the sustainable development of organosilicon materials.
研究领域:
材料科学
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聚合物化学
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柔性电子
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可持续材料
✓ 已验证
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2021
·
IF 4.36
Xing-Jie Zhang,Kun Shang,Yu-Kun Pu,Qi Wang,Ting-Ting Wang,Yan Zou,Yong-Mei Wang,Yao-Jun Xu,Xiao-Li Li,Rui-Han Zhang,Wei-Lie Xiao
Ethnopharmacological relevance Duan Teng Yimu decoction is a Chinese herbal medicine compound with proven therapeutic effects on inflammasome-related diseases, such as rheumatoid arthritis . This decoction consists of three Chinese herbal medicines, including Leonurus japonicus ( L. japonicus ), which promotes the blood circulation and exhibits detumescence activity, traditionally curing gynecologic and inflammasome diseases. Aim of the study To explore the anti-inflammasome activity and the underlying mechanisms of action of the compounds from L. japonicus . Materials and methods A series of compounds were isolated from L. japonicus . Their anti-inflammasome activities were evaluated in macrophages that were co-stimulated by lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. NLRP3 inflammasome formation and apoptosis speck like containing a CARD (ASC) oligomerization were evaluated by immunofluorescent microscopy and Western blot analysis . The regulation of autophagy after treatment of this compound was also evaluated. Lastly, in vivo activity of Leojaponin was analyzed in a mouse acute gouty arthritis model. Results Here we show that Leojaponin, a diterpenoid compound from L. japonicus , suppressed lactate dehydrogenase and IL-1β release in Nigericin-stimulated macrophages in a pyroptosis model. Leojaponin inhibits NLRP3 inflammasome activation in both J774A.1 cells and bone marrow-derived macrophages in a dose dependent manner. Moreover, Leojaponin suppressed NLRP3-mediated ASC specks formation and ASC oligomerization. These activities of Leojaponin depend on restoration of autophagy via promoting RAPTOR phosphorylation. Furthermore, Leojaponin ameliorated monosodium urate (MSU)-induced acute gouty arthritis in vivo . Conclusion Our findings suggest that Leojaponin inhibits NLRP3 inflammasome activation through enhancing autophagy via RAPTOR phosphorylation, thereby highlighting Leojaponin as a potent drug for inflammasome-related diseases.
研究领域:
药理学
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免疫学
·
传统中药
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分子生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2022
·Vol. 13
·期 16
·8593-8604
·
IF 6.317
Yanfang Yu,Yuhuan Chen,Xuping Shi,Chuan Ye,Junwen Wang,Jinzhi Huang,Bing Zhang,Zeyuan Deng
This study investigated the hepatoprotective effects of various mulberry (Morus alba L.) leaf extracts (MLEs), including mulberry ethanol extract (MEE), aqueous extract (MAE) and a combination extract (MCE) against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in rats. It aimed to explore the possible molecular mechanism of the liver-protecting function of mulberry leaves and provide a reference for choosing the appropriate extraction method. The results showed that the three extracts contained different amounts of phenolic compounds, 1-deoxynojirimycin (DNJ) and polysaccharides. MLEs markedly improved the pathological status of rat liver tissue, decreased the levels of AST, ALT, TNF-α, IL-1β, IL-6 and MDA, while increased the levels of GSH, SOD and CAT in the D-GalN/LPS-treated rats at the same time. MEE, with the highest amount of total phenolics, exhibited the highest antioxidant activity corresponding to the protein expression level of Nrf2 and HO-1. MCE significantly suppressed the expression of apoptosis-related dot-like protein (ASC) and Caspase-1 and inhibited the phosphorylation of p38 MAPK and ERK1/2, thereby showing high anti-inflammatory activity. These results indicated that the active components from mulberry leaves protected rats against acute liver injury, attributed to a reduction in both oxidative stress and inflammatory response. The protective effect may be implicated in regulating the Nrf2, NLRP3 and MAPK signaling pathways.
研究领域:
药理学
·
肝病学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2021
·
IF 13.273
Jiahui Zhang,Wei Xin,Yechi Qin,Yuhao Hong,Zijie Xiahou,Kunxi Zhang,Peiliang Fu,Jingbo Yin
Based on “bottom-up” strategy, cell-laden 3D bioprinting is an important process of fabricating sophisticated biomimetic structures. Stem cell spheroids possess better biological properties and are advanced as printing units. However, efficient and convenient preparation, collection and printing of cell spheroids remains a challenge. The present study developed a composite granular hydrogel acted as “all-in-one” multi-functional bioink to realize Adipose-derived stem cell (ASC) spheroids Production and reorganization. Poly(sulfobetaine methacrylate) (PSBMA) based microspheres were fabricated and self-assembled to a granular hydrogel. Then, N -isopropylacrylamide (NIPAM) and SBMA were co-polymerized in-situ inside of assembled PSBMA microspheres to further crosslink the assembled microspheres, forming a composite granular hydrogel, which possesses bulk feature and shear-thinning, self-healing properties. Caves were created by compressing composite granular hydrogels into sugar particles that removed via dissolution in water. Due to the non-fouling feature and the porous structure, numerous ASC spheroids were formed spontaneously inside the porous composite granular hydrogel, which were transferred conveniently to 3D printer. The spheroids-laden composite granular hydrogels showed well-performed extrudability and fidelity, realizing reorganization of the produced spheroids to the stable 3D constructs for further in vitro culture . ASC spheroids in granular hydrogel after 3D printing showed high level of viability and stemness, as well as efficient chondrogenic/osteogenic/adipogenic differentiation. The composite granular hydrogel thus shows potential toward stem cell researches such as organoids construction. The results of both in vitro drug toxicity and in vivo cartilage regeneration experiments showed spheroids-laden granular hydrogel is promising in drug screening and tissue regeneration.
研究领域:
组织工程
·
干细胞生物学
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生物打印
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材料科学
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再生医学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 74
·期 2
·216-226
·
IF 3.765
Huang Rui,Zhao Zizuo,Jiang Xujie,Li Weiwei,Zhang Lidan,Wang Bin,Tie Hongtao
ObjectivesThe chrysin has properties of low aqueous solubility, bioavailability and absorption, and its effect on hepatic ischaemia-reperfusion (HIR) remains unclear. Thus, we prepared a liposomal chrysin (LC) and explored its effect and potential mechanism on HIR.MethodsA thin-film dispersion method was used to prepare LC, and a mouse HIR model was used. Mice were pre-treated with LC (100 mg/kg) or placebo by gavage feeding at 16.5 h, 8.5 h, 0.5 h before modelling.ResultsThe average particle sizes, polydispersity index, zeta potential, encapsulation efficiency and drug loading of LC were 129 ± 13.53 nm, 0.265 ± 0.021, −34.46 ± 4.14 mV, 95.03 ± 2.17%, 16.4 ± 0.8%. The concentration of chrysin in plasma and liver tissue by LC administration increased 2.54 times and 1.45 times. LC pre-treatment reduced HIR-induced liver injury and inhibited cell apoptosis. Besides, LC pre-treatment decreased reactive oxygen species and malondialdehyde and inhibited the inflammation response indicated by lower IL-6, TNF-α, infiltration of neutrophils. Further, LC pre-treatment significantly decreased NLRP3 activation, evidenced by reduced cleaved caspase-3, NLRP3, ASC, cleaved caspase-1 and IL-1β expression.ConclusionsLC has good biocompatibility, and it could attenuate HIR-induced injury. Its mechanism was associated with NLRP3 inflammasome inhibition, and LC might be an effective drug for treating and preventing HIR-induced injury.
研究领域:
药理学
·
肝病学
·
炎症研究
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
METABOLISM-CLINICAL AND EXPERIMENTAL
·
2021
·
IF 8.697
Suling Huang,Yanwei Wu,Zhuohui Zhao,Bing Wu,Kai Sun,Haoyu Wang,Li Qin,Fang Bai,Ying Leng,Wei Tang
Objective Obeticholic acid (OCA) has been proved to play potential therapeutic effect on nonalcoholic steatohepatitis (NASH). Up to now, the study of OCA on NLRP3 inflammasome activation in macrophage is still blank and merits great attention. Here, we aimed to better characterize the role and mechanism of OCA on NASH treatment focusing on NLRP3 inflammasome activation in macrophages. Methods The effects of OCA on inflammasome activation were investigated in BMDM , Kupffer cell , BMDC and LX2 cell. Preconditioned media from BMDM culture was used to treat primary hepatocytes to explore the effects of macrophage NLRP3 inflammasome activation on the function of hepatocytes. In vivo, high fat diet plus CCl 4 (DIO + CCl 4 ) induced murine NASH model and choline-deficient and amino acid-defined (CDA) diet-induced NASH mice were used to verify the inhibitory effect of OCA on inflammasome activation in liver macrophages and recapitulate its protective role on NASH progressing. To clear up the effect of OCA on macrophage is FXR dependent or not, FXR siRNA was introduced into BMDMs. Results OCA blockaded NLRP3 inflammasome in BMDMs by impacting on the activation stage and disrupting ASC oligomerization . Preconditioned supernatant from LPS + ATP treated BMDMs increased mRNA expression of lipogenic enzymes and lipid content, whereas preconditioned supernatant from OCA treated BMDM blocked these effects in both normal and the FXR knockdown hepatocytes. In DIO + CCl 4 mice, the population of inflammatory myeloid lineage cells in livers was decreased upon OCA treatment. Accordingly, the level of IL-1β and IL-18 in liver, the hepatic expression of ASC, pro-caspase-1 and active caspase-1, the expression of caspase 1 p20 in liver macrophages were also reduced. Similar results were obtained in CDA diet-fed mice. Furthermore, OCA maintained the inhibition on NLRP3 inflammasome activation in FXR knockdown BMDMs, suggesting FXR could be dispensable in this effect. Conclusions This finding brings up a new mechanism of OCA on NASH treatment, suggested by direct inhibition on NLRP3 inflammasome activation in macrophage, further suppression on inflammasome activation-elicited hepatic lipid accumulation , and contributing to the amelioration of NASH.
研究领域:
药理学
·
免疫学
·
肝病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）