JOURNAL OF FLUORESCENCE
·
2013
·Vol. 24
·期 2
·533-539
·
IF 1.789
Liu Chengxuan,Liang Gaiting,Liu Zhen,Zu Lily
Time-resolved fluorescence anisotropy spectroscopy was applied to study the interaction between a peptide truncated from the binding site of tumor suppressor p53 protein and the DNAs covalently labeled with 6-carboxyfluorescein (FAM) dye. Fluorescence intensity quenching and changes of anisotropy decay lifetime were monitored when FAM labeled DNA formed complex with the peptide. The results demonstrated that the sequence of DNA could not define the binding specificity between the peptide and DNA. But the anisotropy decay of FAM can be used to examine the binding affinity of the peptide to DNA. The fluorescent dynamics of FAM can also be used to represent the rigidity of the complex formed between the peptide and DNA.
研究领域:
生物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
IUBMB LIFE
·
2022
·Vol. 74
·期 6
·508-518
·
IF 4.709
Qin Guo,Yujia Li,Yuan Chen,Jin Ji,Shizhong Zheng,Xuefen Xu,Biyun Zhang,Jianzhou Ye
Hypertrophic scar (HS) is a condition characterized by excessive synthesis and deposition of collagen. There are many clinical methods to alleviate HS, but most of them are accompanied by many complications. To investigate the effects of β-Elemene, extracted from the ginger family plant Wenyujin, on human hypertrophic scar fibroblast (hHSFs). Cultured hHSFs and human normal fibroblasts, observed the effect of β-Elemene on apoptosis, extracellular matrix, and endoplasmic reticulum stress (ERS) by western blot, Real Time-Polymerase Chain Reaction (RT-PCR), and flow cytometry. Based on our findings, it is clear that β-Elemene could inhibit the expression of α-smooth muscle actin (α-SMA), collagen I, and fibronectin, reduced collagen deposition. Further studies had found that β-Elemene could increase the expression of ERS-related proteins CHOP and Calnexin in a dose-dependent manner, thereby promoting the aggregation of cleaved-caspase-3 and inducing hHSFs to undergo poptosis. This process may depend on the regulation of P53. The results of our study indicates that β-Elemene induced hHSFs to undergo apoptosis though ERS pathway in a P53-dependent manner, which means that our research provided a new strategy for the development of drugs for the treatment of HS.
研究领域:
药理学
·
细胞生物学
·
皮肤科
✓ 已验证
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Guanyu Huang,Jiajun Zhang,Yu Xu,Fei Wu,Yiwei Fu,Xuelin Zhang,Hanxiao Yin,Yuanyuan You,Peng Zhao,Weihai Liu,Jingnan Shen,Junqiang Yin
LACTB is identified as a tumor suppressor in several tumors. However, preliminary study reveals that LACTB is overexpressed in osteosarcoma and indicates poor prognosis. Two missense mutations (rs34317102 and rs2729835) exist simultaneously in 92.31% of osteosarcoma patients and cause M5L and R469K double mutations in LACTB, suggesting the biologic function of LACTB protein may be altered in osteosarcoma. Moreover, LACTB M5L+R469K overexpression can promote malignant progression in different tumors, which suggests that the M5L and R469K mutations confer oncogene-like functions to LACTB. Mechanistically, LACTB M5L+R469K not only reduces the wild type p53 via enhancing PSMB7 catalytic activity, but also protects p53 R156P protein from lysosomal degradation, which suggesting LACTB M5L+R469K is a dual-regulator for wt-p53 and mutant p53, and derive oncogene-like functions. More importantly, clavulanate potassium, a bacterial β -lactamase inhibitor, can inhibit osteosarcoma proliferation and sensitize osteosarcoma to cisplatin by binding and blocking LACTB M5L+R469K . These findings revealed that the M5L and R469K double mutations can diminish the tumor suppressive ability of wild type LACTB and provide oncogene-like functions to LACTB. Inhibiting LACTB M5L+R469K can suppress the progression of osteosarcoma harbouring wild-type or mutant p53. Clavulanate potassium is a promising drug by targeting LACTB M5L+R469K -p53 pathway for the treatment of osteosarcoma patients.
研究领域:
肿瘤学
·
遗传学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACTA PHARMACOLOGICA SINICA
·
2020
·Vol. 41
·期 9
·1208-1222
·
IF 5.064
Almoiliqy Marwan,Wen Jin,Xu Bin,Sun Yu-chao,Lian Meng-qiao,Li Yan-li,Qaed Eskandar,Al-Azab Mahmoud,Chen Da-peng,Shopit Abdullah,Wang Li,Sun Peng-yuan,Lin Yuan
Our preliminary study shows that cinnamaldehyde (CA) could protect against intestinal ischemia/reperfusion (I/R) injuries, in which p53 and NF-κB p65 play a synergistic role. In this study, we conducted in vivo and in vitro experiments to verify this proposal. SD rats were pretreated with CA (10 or 40 mg · kg −1 · d −1 , ig) for 3 days, then subjected to 1 h mesenteric ischemia followed by 2 h reperfusion. CA pretreatment dose-dependently ameliorated morphological damage and reduced inflammation evidenced by decreased TNF-α, IL-1β, and IL-6 levels and MPO activity in I/R-treated intestinal tissues. CA pretreatment also attenuated oxidative stress through restoring SOD, GSH, LDH, and MDA levels in I/R-treated intestinal tissues. Furthermore, CA pretreatment significantly reduced the expression of inflammation/apoptosis-related NF-κB p65, IKKβ, IK-α, and NF-κB p50, and downregulated apoptotic protein expression including p53, Bax, caspase-9 and caspase-3, and restoring Bcl-2, in I/R-treated intestinal tissues. We pretreated IEC-6 cells in vitro with CA for 24 h, followed by 4 h hypoxia and 3 h reoxygenation (H/R) incubation. Pretreatment with CA (3.125, 6.25, and 12.5 μmol · L −1 ) significantly reversed H/R-induced reduction of IEC-6 cell viability. CA pretreatment significantly suppressed oxidative stress, NF-κB activation and apoptosis in H/R-treated IEC-6 cells. Moreover, CA pretreatment significantly reversed mitochondrial dysfunction in H/R-treated IEC-6 cells. CA pretreatment inhibited the nuclear translocation of p53 and NF-κB p65 in H/R-treated IEC-6 cells. Double knockdown or overexpression of p53 and NF-κB p65 caused a synergistic reduction or elevation of p53 compared with knockdown or overexpression of p53 or NF-κB p65 alone. In H/R-treated IEC-6 cells with double knockdown or overexpression of NF-κB p65 and p53, CA pretreatment caused neither further decrease nor increase of NF-κB p65 or p53 expression, suggesting that CA-induced synergistic inhibition on both NF-κB and p53 played a key role in ameliorating intestinal I/R injuries. Finally, we used immunoprecipitation assay to demonstrate an interaction between p53 and NF-κB p65, showing the basis for CA-induced synergistic inhibition. Our results provide valuable information for further studies.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
病理生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Medicine
·
2019
·Vol. 8
·期 11
·5313-5326
·
IF 3.357
Han-Qing Zhu,Chao Zhang,Zhu-Ying Guo,Jun-Mei Yang,Jia-Hui Guo,Chen Chen,Qiang-Hua Yao,Feng Liu,Quan-Wu Zhang,Feng-Hou Gao
Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- and cell cycle arrest-related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53-induced Mdm2 (E3 ubiquitin-protein ligase Mdm2) to generate Mdm2-p60. The generation of Mdm2-p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2017
·
IF 2.764
Bei Xie,Jipeng Yi,Jian Peng,Xing Zhang,Lei Lei,Dapeng Zhao,Zhixin Lei,Hemin Nie
Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxide-polyethyleneimine/p53 plasmid (Dox/GO-PEI/p53) were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of HeLa cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction . The nanoparticles efficiently mediated the transfection of DNA in HeLa cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner, and showed successive inhibition of the in vitro growth of HeLa cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.
研究领域:
生物医学工程
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
高影响因子
Aging-US
·
2021
·
IF 5.682
Jianhao Xu,Liwei Ni,Fenglun Zhao,Xiaoxiao Dai,Jialong Tao,Jia Pan,Aiming Shi,Zhu Shen,Cunjin Su,Yusong Zhang
Background: This study aimed to investigate the aberrant expression of hsa_circ_0002874 in non-small cell lung cancer (NSCLC) and elucidate associated molecular mechanisms that influence apoptosis and induce paclitaxel (PTX) resistance. Methods: Inhibitors were used to downregulate circRNA or miRNA expression. pCDNA plasmid transfection and mimics were used to upregulate circRNA or miRNA expression. Dual-luciferase reporter assays were conducted to evaluate interactions between miR1273f and MDM2. Xenograft tumor models were used to assess the effect of hsa_circ_0002874 and miR1273f on tumor growth. NSCLC tissues and matched non-cancerous tissues were also collected for correlation analysis. Results: hsa_circ_0002874 acts as a sponge for miR1273f which targets MDM2/P53. The stability of the hsa_circ_0002874/miR1273f/MDM2/P53 pathway was verified by upregulating and downregulating the expression of hsa_circ_0002874 and miR1273f. hsa_circ_0002874 downregulation or miR1273f upregulation reversed the resistance of the A549/Taxol cells in xenograft models. The expression of hsa_circ_0002874 was high, and the level of MDM2 was low in NSCLC tissues. P53 was only weakly expressed in NSCLC tissues with high expression of MDM2. Conclusions: hsa_circ_0002874 is strongly expressed in NSCLC tissues and maybe a potential marker for PTX resistance. hsa_circ_0002874 downregulation could regulate miR1273f/MDM2/P53 signaling pathway to reverse the PTX resistance of NSCLC and induce apoptosis in vitro and vivo .
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heart Lung and Circulation
·
2025
·
IF 2.2
Dan-Qing Duan,Ming-Rui Li,Li-Qun Lu,Bi-Feng Yao,Lin-Lu Huang,Xiu-Ju Luo,Jun Peng
Background & Aim Ferroptosis is an iron-dependent cell death and contributes to myocardial ischaemia/reperfusion (I/R) injury. Downregulation of glutathione peroxidase 4 (GPX4) is a key factor to accelerate ferroptosis, but the underlying mechanisms are not fully elucidated. Solute carrier family 7A member 11 (SLC7A11) plays a key role in maintaining the normal level of GPX4, and its transcription is suppressed by p53, whose level is controlled by spermatogenesis-associated protein 2 (SPATA2)/cylindromatosis (CYLD) pathway in a de-ubiquitination-dependent way. This study aims to explore whether SPATA2/CYLD pathway promotes myocardial ferroptosis in rat hearts after I/R through p53-dependent inhibition of SLC7A11. Methods The rat hearts were subjected to 1 h-ischaemia plus 3 h-reperfusion to establish a myocardial I/R injury model, and H9c2 cells were subjected to 8 h-hypoxia plus 12 h-re-oxygenation (H/R) to mimic myocardial I/R injury in vitro. Results Both the rat hearts and the cultured cardiomyocytes showed elevated levels of SPATA2 and CYLD, concomitant with the increased p53 levels and the enhanced interaction between SPATA2 and CYLD; these phenomena were reversed by knockdown of SPATA2. Mechanistically, knockdown of SPATA2 restored the ubiquitination of p53 and decreased p53 level in the H/R-treated cardiomyocytes, accompanied by increases in the levels of SLC7A11 and GPX4, and reduction of ferroptosis. Furthermore, suppression of SPATA2 by lurasidone, a predicted inhibitor of SPATA2, in the I/R-treated rat hearts also achieved similar results. Conclusion SPATA2/CYLD pathway-dependent de-ubiquitylation of p53 promotes ferroptosis in rat heart after I/R through a mechanism involving suppression of SLC7A11.
研究领域:
分子生物学
·
心血管医学
·
细胞信号传导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL CELL
·
2023
·
IF 11.8
Xue-Lian Sun,Zhen-Hua Chen,Xize Guo,Jingjing Wang,Mengmeng Ge,Samuel Zheng Hao Wong,Ting Wang,Si Li,Mingze Yao,Laura A. Johnston,Qing-Feng Wu
Cell competition acts as a quality-control mechanism that eliminates cells less fit than their neighbors to optimize organ development. Whether and how competitive interactions occur between neural progenitor cells (NPCs) in the developing brain remains unknown. Here, we show that endogenous cell competition occurs and intrinsically correlates with the Axin2 expression level during normal brain development. Induction of genetic mosaicism predisposes Axin2-deficient NPCs to behave as "losers" in mice and undergo apoptotic elimination, but homogeneous ablation of Axin2 does not promote cell death. Mechanistically, Axin2 suppresses the p53 signaling pathway at the post-transcriptional level to maintain cell fitness, and Axin2-deficient cell elimination requires p53-dependent signaling. Furthermore, mosaic Trp53 deletion confers a "winner" status to p53-deficient cells that outcompete their neighbors. Conditional loss of both Axin2 and Trp53 increases cortical area and thickness, suggesting that the Axin2-p53 axis may coordinate to survey cell fitness, regulate natural cell competition, and optimize brain size during neurodevelopment.
研究领域:
神经科学
·
发育生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Zheng-Meng Jiang,Zhi-Yue Fang,Xing Yang,Xing-Xing Ji,Yuan-Yuan Zhao,Bin-Yan Lin,Ze-Bin Weng,E-Hu Liu
Background Dysbiosis of the gut microbiota is pivotal in the development of gastric mucosa injury (GMI). Glycyrrhetinic acid (GA) is a bioactive triterpenoid compound abundantly present in licorice roots. Although GA's potential in mitigating GMI is recognized, its precise mechanism remains elusive, particularly concerning the role of gut microbiota. Purpose This study aimed to explore the protective effects and mechanisms of GA in preventing HCl/ethanol-induced GMI in rats. Results This study demonstrated the protective effects of GA on gastric mucosa, evidenced by enhanced morphology and structure as revealed through H&E staining. Utilizing fecal microbiota transplantation, GA was found to significantly mitigate oxidative damage, inflammation, and expression of apoptosis-related genes in GMI rats by a gut microbiota-dependent mechanism. 16S rRNA sequencing and metabolomics profiling revealed that GA ameliorated HCl/ethanol-triggered intestinal dysbiosis and imbalances in sphingolipid, arginine, and tryptophan metabolism. By promoting the prevalence of Bifidobacterium longum subsp. infantis ( B. infantis ) in the gut microbiota, GA improved metabolic disturbances linked to injury. Furthermore, its action mechanism was related to the inhibition of the Thbs1/PI3K-Akt/p53 signaling pathway. Conclusion The administration of GA improves GMI by mitigating intestinal dysbiosis and fostering colonization of B. infantis . GA offers therapeutic potential for GMI by modulating the Thbs1/PI3K-Akt/p53 pathway, thus alleviating inflammatory responses associated with gut microbiota imbalance.
研究领域:
药理学
·
微生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2018
·Vol. 8
·期 45
·25611-25616
·
IF 2.936
Dan Han,Chunying Wei
In this paper, we construct a fluorescence nucleic acid probe based on DNA-templated silver nanoclusters (DNA-Ag NCs) for the detection of the p53 gene. The fluorescence biosensing of the “turn-on” model is successfully implemented as a result of the target-triggered configurational change in the hairpin DNA probe and the synthesis of fluorescent Ag NCs. With this biosensor, the limit of detection (LOD) for the p53 gene is 3.57 nM and the linear range is 250–2500 nM in phosphate buffer solution, while a LOD of 6.06 nM in the linear range of 250–2500 nM is obtained in 1% diluted fetal calf serum. So this probe, with its advantages of specificity, practical application, easy operation and low cost, will have favourable development prospects in biological sensing and imaging.
研究领域:
生物化学
·
分子生物学
·
纳米生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
·
IF 3.973
Jian-Tao Lin,Hua Chen,Dan Wang,Liang Xiong,Jia-Zhu Li,Gui-hong Chen,Guang-Bin Chen
The nucleus is one of the most important cellular organelles. Chitosan-grafted poly-(N-3-carbobenzyloxy-lysine) (CCL) decorated with human immunodeficiency virus-1 transactivator of transcription (TAT) can co-deliver p53 and doxorubicin into the nucleus simultaneously, such that their antitumor functions are exerted. However, TAT-CCL has been shown to have an anti-tumor effect only in vitro; the effect in vivo was unsatisfactory. Here, a unique nucleus-targeted delivery system based on amidized TAT (aTAT)-CCL with aTAT functional on the surface was designed to achieve a highly efficient nucleus-targeting gene and drug delivery system for effective cancer cell elimination in vitro and in vivo. In this delivery system, TAT is amidized to inhibit its nonspecific interactions. Confocal laser scanning microscopy observations revealed that if aTAT-CCL was incubated in pH 5.0 acetate buffer solution for 24 h before use (named aTAT-CCL-HB), more aTAT-CCL-HB entered the nucleus compared with aTAT-CCL or CCL. aTAT-CCL-HB can also achieve high gene transfection and drug delivery efficiencies and low viability in HepG2 cells. However, only aTAT-CCL achieved extensive circulation in the blood compartment and high antitumor activity in vivo. Amidization of TAT in vectors may become a promising strategy for nucleus-targeted delivery systems, especially in in vivo applications.
研究领域:
癌症研究
·
药剂学
·
分子生物学
·
药物递送系统
✓ 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）