Molecular Medicine Reports
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2019
·Vol. 19
·期 6
·4579-4588
·
IF 1.851
Shiqi Wang,Fuwei He,Zhenwei Li,Yewen Hu,Ning Huangfu,Xiaomin Chen
Oxidative stress serves important roles in cardiac injury during the process of ischemia/reperfusion (I/R). Y‑box protein 1 (YB1), a member of the highly conserved Y‑box protein family, is closely associated with inflammation and stress responses by regulating gene transcription, RNA splicing and mRNA translation. However, the roles of YB1 in oxidative stress‑induced myocardial‑I/R (M‑I/R) injury are unknown. The aim of the present study was to examine the effects of YB1 on H2O2‑induced cardiomyocyte injury and its underlying mechanism. The results demonstrated that YB1 expression was upregulated during H2O2‑induced myocardial injury. YB1 knockdown through transfection of small interfering RNA significantly aggravated cardiac cell apoptosis. Furthermore, YB1 knockdown significantly reversed the H2O2‑mediated increase in phosphorylated signal transducer and activator of transcription (STAT)3, but did not affect the phosphorylation of P38, extracellular signal‑regulated kinases 1/2, c‑Jun N‑terminal kinases, P65, Janus kinase 1 and 2 or STAT1. Moreover, protein co‑immunoprecipitation and RNA‑binding protein immunoprecipitation assays revealed that YB1 interacted with protein inhibitor of activated STAT 3 (PIAS3) mRNA but not its translated protein. YB1 overexpression may have promoted PIAS3 mRNA decay, decreasing PIAS3 protein levels, and therefore increased the levels of phosphorylated STAT3. Finally, YB1 knockdown, mediated by a lentivirus carrying YB1 targeted short hairpin RNA, significantly decreased left ventricle percentage fractional shortening and ejection fraction values, while increasing the infarct sizes in a rat model of M‑I/R injury. These results demonstrated for the first time (to the best of our knowledge) that YB1 may protect cardiac myocytes against H2O2 or M‑I/R‑induced injury by binding to PIAS3 mRNA and resulting in the phosphorylation of STAT3.
研究领域:
心脏病学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2024
·
IF 4.2
Minghui Cai,Qiuyuan Li,Yang Cao,Yujia Huang,Haixu Yao,Chen Zhao,Jiao Wang,Hui Zhu
Autophagy is closely related to the aging of various organ systems, including ovaries. Quercetin has a variety of biological activities , including potential regulation of autophagy. However, whether quercetin-regulated autophagy activity affects the process of ovarian aging and injury has not been clarified yet. This study explores whether quercetin can resist H 2 O 2 -induced aging and injury of granulosa cells by regulating autophagy and its related molecular mechanisms in vitro experiments. The cell viability , endocrine function, cell aging , and apoptosis were detected to evaluate the effects of quercetin and autophagy regulators like 3-methyladenine and rapamycin . The levels of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 were determined by Western blot to assess the effects of quercetin, 3-methyladenine and rapamycin on autophagy. Our results showed quercetin resisted H 2 O 2 -induced granulosa cell aging and injury by activating protective autophagy. The treatment of 3-methyladenine and rapamycin confirmed the protective function of autophagy in H 2 O 2 -induced granulosa cells. 3-methyladenine treatment inhibited the expression of autophagy markers Atg5, Atg12, Atg16L, Lc3B II/I, and Beclin1 and abolished the positive effects on cell viability , estradiol secretion, and cell apoptosis activated by quercetin. In conclusion, quercetin activates autophagy by upregulating the expression of autophagy-related proteins to resist H 2 O 2 -induced aging and injury, which is crucial for stabilizing the function of granulosa cells under oxidative injury conditions and delaying aging. This study may explain the protective effects of quercetin on ovarian aging and injury from the perspective of regulating autophagy.
研究领域:
生殖生物学
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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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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Youlu Chen,Ruihao Li,Xue Fu,Yaming Guo,Suling Yan,Lei Tian,Qinxia Zhou,Yongpeng Diao,Wei Chen
Gene therapy offers a promising avenue for treating ischemic diseases, yet its clinical efficacy is hindered by the limitations of single gene therapy and the high oxidative stress microenvironment characteristic of such conditions. Lipid-polymer hybrid vectors represent a novel approach to enhance the effectiveness of gene therapy by harnessing the combined advantages of lipids and polymers. In this study, we engineered lipid-polymer hybrid nanocarriers with tailored structural modifications to create a versatile membrane fusion lipid-nuclear targeted polymer nanodelivery system (FLNPs) optimized for gene delivery. Our results demonstrate that FLNPs facilitate efficient cellular uptake and gene transfection via membrane fusion, lysosome avoidance, and nuclear targeting mechanisms. Upon encapsulating Hepatocyte Growth Factor plasmid (pHGF) and Catalase plasmid (pCAT), HGF/CAT-FLNPs were prepared, which significantly enhanced the resistance of C2C12 cells to H 2 O 2 -induced injury in vitro. In vivo studies further revealed that HGF/CAT-FLNPs effectively alleviated hindlimb ischemia-induced gangrene, restored motor function, and promoted blood perfusion recovery in mice. Metabolomics analysis indicated that FLNPs didn't induce metabolic disturbances during gene transfection. In conclusion, FLNPs represent a versatile platform for multi-dimensional assisted gene delivery, significantly improving the efficiency of gene delivery and holding promise for effective synergistic treatment of lower limb ischemia using pHGF and pCAT.
研究领域:
基因治疗
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纳米技术
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分子生物学
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药学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2015
·
IF 4.074
Wuxia Zhang,Dan Song,Dan Xu,Tingting Wang,Lu Chen,Jinyou Duan
Rhizoma Acori Tatarinowii is widely used in traditional Chinese medicine. In this study, three novel polysaccharides designated RATPW, RATPS1 and RATPS2 were isolated from Rhizoma Acori Tatarinowii by DEAE-52 cellulose chromatography. Their structures were characterized using physicochemical and spectral methods. Chemical analysis indicated that RATPW (6.5 × 10 3 Da) mainly composed of glucose and fructose. RATPS1 (1.5 × 10 5 Da) contained galactose and arabinose, while RATPS2 (5.3 × 10 4 Da) contained ∼49.5% galacturonic acid along with rhamnose, fructose, galactose, and arabinose. In vitro , RATPS2 showed the most significant scavenging activity on DPPH and hydroxyl radical. Three polysaccharides could protect the PC12 cells from H 2 O 2 -induced damage. Immunological tests indicated that both RATPW and RATPS2 significantly stimulated NO production and phagocytic activity in RAW264.7, and promoted splenocyte proliferation. These data suggested that polysaccharides RATPW and RATPS2 had the potential as novel natural sources of antioxidative and immunopotentiating agents.
研究领域:
药理学
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生物化学
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免疫学
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传统中药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2022
·
IF 5.318
Jiaqi Lu,Jinxia Chen,Chunyan Yang,Chen Xia,Junling Deng,Zuoya Xiang,Jian Chen,Yong Wu
Epigallocatechin-3-gallate (EGCG) is a polyphenol naturally sourced in green tea with extensive bioactivities, including antioxidant, anti-carcinogenic, anti-microbial, anti-obesity, and neuroprotection. However, EGCG is unstable in neutral or alkaline conditions and has poor lipid solubility , leading to inadequate systemic absorption, reduced pharmacokinetics , limited biodistribution , and first-pass metabolism. The aim of this study is to solve these problems, thus two novel EGCG-glucose conjugates , Glu-EGCG and 2Glu-EGCG possessing one and two glucose, respectively, were designed, synthesized, and characterized. The EGCG-glucose conjugates’ chemical stability, cytotoxicity and alleviation H 2 O 2 -induced antioxidative damage to neuronal cell and antioxidative neuroprotection activities were examined. Compared with their precursor EGCG, Glu-EGCG and 2Glu-EGCG are more stable, less toxic to PC12 and bEnd.3 cell, stronger ability to attenuate H 2 O 2 -induced injury to PC12 cells resulting higher cell viability and lower reactive oxygen species (ROS) in the cell. Animal study results further proved that Glu-EGCG and 2Glu-EGCG possess higher antioxidative activities than EGCG, through decreasing the ischemia area, inhibiting morphological changes and neuronal loss in brain tissues, and modulating the oxidative factor and antioxidant factor. In conclusion, 2Glu-EGCG shows stronger antioxidant activities than Glu-EGCG does. Both EGCG-glucose conjugates are promising brain target antioxidative neuroprotection agents.
研究领域:
药理学
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神经科学
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生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
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