Nanoscale
·
2021
·Vol. 14
·期 5
·1733-1741
·
IF 7.79
Tingting Zhao,Fengqi Dong,Xinlong Hu,Yanli Xu,Wenmei Wei,Rui Liu,Fang Yu,Weijun Fang,Yuxian Shen,Zhongping Zhang
Monitoring the expression level of the intracellular tumor suppressor gene p21 mRNA is essential to reveal the progress and prognosis of a tumor. Methods widely reported for the detection of p21 mRNA are the real-time polymerase chain reaction and Northern blot. However, these methods only detect mRNA in vitro and cannot realize the in situ monitoring of the p21 mRNA expression level in living cells. Additionally, the sensor for the real-time tracking and monitoring of the p21 mRNA location without the help of a transfection reagent in living cells is still limited. Herein, a novel sticky-flare was constructed for the dynamic monitoring of the temporal and spatial variations of p21 mRNA in living cells. The nanoprobe consists of AuNP, a recognition sequence modified with Cy5, and a thiol-modified DNA sequence. The thiol oligonucleotide strand could act partially complementary to the Cy5-modified oligonucleotide strand to form a double-stranded DNA linked to AuNP, resulting in the fluorescence quenching of Cy5 due to the energy transfer from Cy5 to the gold sphere. In the presence of p21 mRNA, the Cy5-modified recognition nucleic acid specifically bound to p21 mRNA to form a more stable double chain and escaped from the gold sphere, leading to the recovery of red fluorescence. Our method is better than other methods in its ability to quantify the spatial distribution and expression level of p21 mRNA in living cells and discriminate various tumor cell lines with different p21 mRNA expression levels by the naked eye. Particularly, the sticky-flare probe used in this assay could allow the visual evaluation of the tumor treatment effect and the determination of the tumor progression stage by enabling monitoring of the relative expression level of p21 mRNA in tumor cells after cisplatin treatment. The method reported here is accurate, reliable and needs no auxiliary tools (transfection reagent), and thereby provides a promising route for the prognostic evaluation and drug development of cancer treatment in the future.
研究领域:
癌症生物学
·
分子生物学
·
纳米技术
·
生物医学工程
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
·
2024
·
IF 4.2
Lin Lv,Keying Yuan,Jiahao Li,Jing Lu,Qi Zhao,Hongyan Wang,Qiuyu Chen,Xinyu Dong,Siqi Sheng,Mingyu Liu,Yuanqi Shi,Hongquan Jiang,Zengxiang Dong
Myocardial fibroblasts transform into myofibroblasts during the progression of cardiac fibrosis, together with excessive cardiac fibroblast proliferation. Hence, the prevention and treatment of cardiac fibrosis are significant factors for inhibiting the development of heart failure. P-element Induced WImpy testis-interacting RNAs (PiRNA) are widely expressed in the heart, but their involvement in cardiac fibrosis has not yet been confirmed. We identified differentially expressed PiRNAs using Arraystar PiRNA expression profiling in Angiotensin II models of cardiac fibrosis in vivo and in vitro. We then explored cardiac-fibrosis-associated PiRNA-related proteins, RNA-protein interactomes, immunoprecipitation, and pulldown. We detected fibrosis markers and pathway-related proteins using immunofluorescence, qRT-PCR, and Western blot. We uncovered cardiac fibrosis associated PiRNA (CFAPIR) that was obviously dysregulated during cardiac fibrosis, whereas its overexpression reversed fibrosis in vivo and in vitro. Mechanistically, CFAPIR competitively bound muscleblind like protein 2 (MBNL2) and the cyclin-dependent kinase inhibitor P21 to regulate the TGF-β1/SMAD3 signaling pathway.
研究领域:
心脏病学
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分子生物学
·
基因组学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2018
·
IF 3.04
Qi Wan,Hui Chen,Xiaolei Li,Lianqi Yan,Yu Sun,Jingcheng Wang
Fibroblast proliferation is considered to be a major cause in the process of epidural fibrosis formation. Autophagy is a tightly-regulated catabolic process in charge of degrading intracellular components. Although autophagy has been associated with fibrosis of different tissues, the effect of autophagy on epidural fibrosis is still unknown. The aim of this study was to investigate the function and mechanism of autophagy induced by Artesunate (ART), a classical antimalarial agent extracted from the Chinese medicinal herb. In vitro, the effect of ART on inducing fibroblast autophagy was evaluated via LC3 immunofluorescent staining , Transmission Electron Microscopy (TEM) and western blotting analysis. Moreover, the effect of ART on inhibiting fibroblast proliferation was investigated by CCK-8 assay, EdU incorporation assay, flow cytometry and western blotting analysis. Results indicated that ART could induce autophagy and inhibit proliferation in fibroblasts. The inhibitory effect of ART on fibroblast proliferation was associated with the upregulation of p53 and p21 waf1/cip1 proteins. Intriguingly, 3-MA, a classical autophagy inhibitor, attenuated ART-induced p53/p21 waf1/cip1 pathway activation and fibroblast proliferation inhibition. In vivo, the effect of ART on reducing epidural fibrosis was detected by histological macroscopic assessment, hydroxyproline content analysis, histological and immunohistochemical staining. The results revealed that ART had significant suppressive effects on epidural fibrosis following laminectomy in rats. In conclusion, this research demonstrated that ART could inhibit fibroblast proliferation and reduce epidural fibrosis formation after laminectomy, and the potential mechanism might through autophagy cascade-mediated p53/p21 waf1/cip1 pathway. It might provide a novel reagent for reducing epidural fibrosis after spinal laminectomy surgery.
研究领域:
药理学
·
神经外科
·
细胞生物学
·
分子生物学
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2023
·
IF 4.8
Haiyan Zhao,Fangfang Bi,Mengyuan Li,Yuhan Diao,Chen Zhang
RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV. Here, we explored the potential signaling pathways related to RNF180 and IPO4. It was first verified that RNF180 is downregulated and IPO4 is upregulated in OV. By overexpressing or knocking down RNF180 in OV cells, we confirmed that RNF180 inhibited the malignant behaviors of OV cells both in vitro and in vivo . Bioinformatics analysis and proteomics experiments found that RNF180 could interact with IPO4 and promote the degradation of IPO4 through ubiquitination. In addition, overexpression of IPO4 removed the inhibitory effect of RNF180 on OV. We subsequently found that IPO4 could bind to the oncogene Sex determining Region Y-box 2 (SOX2). Knockdown of IPO4 in OV cells decreased SOX2 protein level in nucleus and promoted cyclin-dependent kinase inhibitory protein-1 (p21) expression. Overexpression of RNF180 also inhibited the expression of SOX2 in nucleus. All these results indicated that RNF180 inhibited the nuclear translocation of SOX2 by promoting ubiquitination of IPO4, which ultimately promoted the expression of p21 and then suppressed the progression of OV. This study verified the tumor suppressor effect of RNF180 on OV, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in OV and identified for OV.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2026
·Vol. 15
·期 3
·
IF 8.2
Jianhong Wang,Ting Jiang,Siqi Chen,Yajing Li,Qing Li,Lan Xiang,Jianhua Qi
Traditional Chinese medicine plays an important role in human health, but due to the complexity of its active fraction, its therapeutic mechanism still needs further clarification.Polygalae Radixis one of the traditional Chinese medicines, which was recorded inShennong Classic of Materia Medicawith the effect of prolonging life. In the present study, we isolated a small molecule compound with anti-aging effects, 3,6′-disinapoyl sucrose (DISS), fromPolygalae Radixunder the guidance of the replicative lifespan assay of K6001 yeast strain. It extended the lifespan of yeast and alleviated etoposide-induced aging in 3T3 cells. Furthermore, this compound increased the telomerase activity and the length of telomeres, and targeted the SIRT1 signaling pathway, respectively. In addition, it improved the survival ability of yeast under oxidative stress conditions, decreased ROS and MDA levels, and increased the activity of SOD, CAT and GPx enzymes. Moreover, DISS enhanced autophagic flux, as demonstrated by assay of the YOM38-GFP-ATG8 yeast strain. In conclusion, DISS fromPolygalae Radixexerts anti-aging effects by protecting telomeres, regulating the SIRT1/p53/p21 signaling pathway, mitigating oxidative stress and modulating autophagy. Thus, this study provides scientific evidence for the use ofPolygalae Radixas an anti-aging herb.
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产品关联
DOI
PubMed
高影响因子
ORAL DISEASES
·
2026
·
IF 3.1
Jiaying Shi,Shuxian Lin,Jiayu Yan,Wanyi Tang,Xiaohua Wu,Shuwen Ding,Siyi Chen,Ruowen Zhao,Junhua Wu
Background Osteoradionecrosis of the jaw (ORNJ) is a severe radiotherapy complication with unclear molecular drivers. CDKN1A/p21 is upregulated by radiation-induced DNA damage, but its role in ORNJ remains unknown. Methods An ORNJ mouse model was established. Single-cell RNA-sequencing of irradiated mandibles was analyzed and validated in vivo. Irradiated jaw bone marrow mesenchymal stem cells (JBMMSCs) were characterized. p21 was inhibited using UC2288 and siRNA. A UC2288-loaded AlgMA hydrogel was developed for local delivery. Results Bone healing was compromised in ORNJ. Radiation induced p21 upregulation in osteogenic lineage cells, which promoted Rb dephosphorylation and aberrant Smad2/3 phosphorylation, thereby suppressing Runx2-mediated osteogenesis. p21 inhibition reversed this cascade and restored osteogenic differentiation. Local delivery of UC2288@AlgMA significantly enhanced bone regeneration. Conclusion p21-related signaling impairs bone healing after irradiation, and local UC2288 delivery via AlgMA hydrogels represents a viable strategy to enhance ORNJ regeneration.
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Xueying An,Hanjie Zhang,Xujing Zhang,Minyi Cai,Yining Zhou,Hantao Cai,Tao Shen,Sheng zhao,Zhihong Xu,Hui Wei,Qing Jiang
A lycopene-loaded CeO₂ nanozyme (Ly@Ce) is developed to combat chondrocyte senescence for osteoarthritis therapy • Ly@Ce efficiently scavenges mitochondrial ROS, restores mitochondrial dynamics, and elevates NAD + levels • Ly@Ce reverses H₂O₂-induced dysregulation of the p53-p21 signaling axis • Ly@Ce suppresses SASP expression and shifts ECM metabolism toward an anabolic program • The nanozyme integrates redox/NAD + reprogramming with senescence pathway inhibition, offering a disease-modifying strategy for OA Osteoarthritis (OA) is strongly associated with chondrocyte senescence, driven by oxidative stress, mitochondrial dysfunction, and the ensuing senescence-associated secretory phenotype (SASP). Herein, we report a lycopene-loaded ceria nanozyme (Ly@Ce) designed to simultaneously address these interconnected pathogenic cues. Ly@Ce markedly reduced intracellular and mitochondrial reactive oxygen species (ROS), mitigated excessive mitochondrial fragmentation, and restored mitochondrial membrane potential in senescent chondrocytes, indicating robust recovery of mitochondrial fitness. Notably, Ly@Ce also elevated intracellular nicotinamide adenine dinucleotide (NAD + ) levels, making it an active metabolic modulator rather than a passive ROS scavenger. Transcriptomic profiling revealed that Ly@Ce reversed H 2 O 2 -induced dysregulation of the p53-p21 signaling pathway, accompanied by suppression of SASP-related genes and a shift of extracellular matrix metabolism toward an anabolic program, thus delaying OA progression. Collectively, these findings establish Ly@Ce as a bioinspired, catalytic antioxidant nanoplatform that combines redox and NAD + reprogramming with p53-p21 inhibition, offering a disease-modifying strategy for senescence-associated OA and a potential framework for targeting other age-related pathologies characterized by mitochondrial decline and cellular senescence.
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DOI
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Qingqiu Chen,Guang Xin,Shiyi Li,Yuman Dong,Xiuxian Yu,Chengyu Wan,Zeliang Wei,Yuda Zhu,Kun Zhang,Yilan Wang,Fan Li,Cuicui Zhang,E Wen,Yulong Li,Hai Niu,Wen Huang
Background Accumulation of age-associated senescent cells accompanied with increased reactive oxygen species (ROS) and inflammatory factors contributes to the progression of age-related macular degeneration (AMD), the main cause of blindness in the elderly. Berberine (BBR) has shown efficacy in the treatment of age-related diseases including diabetes and obesity by decreasing ROS. However, the pharmacological effect of BBR on alleviating retinal aging remains largely unknown. Purpose Our study aimed to investigate the pharmacological effect of BBR as an anti-aging agent in retinal aging and its further molecular mechanisms. Methods D-galactose (DG)-induced ARPE-19 cell senescence and retinal aging were employed to evaluate the anti-aging effect of BBR in vivo and in vitro . The siRNA transfection, Western-Blot analyses, SA-β-Gal assay and immunofluorescence were performed to investigate the potential mechanisms of BBR on anti-aging of RPE . Results In RPE-choroid of both natural aged and DG-induced accelerated aged mice, oxidative stress was increased along with the up-regulation of p21 expression, which was ameliorated by BBR treatment. BBR down-regulated the expression of REDD1 to decrease intracellular ROS content, attenuating DG-induced senescence in vitro and in vivo . Furthermore, p53 instead of HIF-1α was identified as the transcriptional regulator of REDD1 in DG-induced premature senescence. Importantly, NAC and BBR reversed the expression of p53 and the content of 8-OHdG, indicating that the positive feedback loop of ROS-DNA damage response (DDR) was formed, and BBR interrupted this feedback loop to alleviate DG-induced premature senescence by reducing REDD1 expression. In addition, BBR restored DG-damaged autophagy flux by up-regulating TFEB-mediated lysosomal biosynthesis by inhibiting REDD1 expression, thereby attenuating cellular senescence . Conclusion BBR down-regulates REDD1 expression to interrupt the ROS-DDR positive feedback loop and restore autophagic flux, thereby reducing premature senescence of RPE. Our findings elucidate the promising effects of REDD1 on cellular senescence and the great potential of BBR as a therapeutic approach.
研究领域:
药理学
·
眼科学
·
衰老
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cancer Cell International
·
2021
·Vol. 21
·期 1
·1-15
·
IF 5.722
Lv Minchao,Xu Qingxin,Zhang Bei,Yang Zhiqiang,Xie Jun,Guo Jinku,He Feixiong,Wang Wei
Background Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma still remains unsatisfactory in the past decades. Therefore, development of novel therapeutic agents which are effective to osteosarcoma and are safe to normal tissue simultaneously is quite essential and urgent. Methods Firstly, MTT assay, cell colony formation assay, cell migration and invasion assays were conducted to evaluate the inhibitory effects of imperatorin towards human osteosarcoma cells. RNA-sequence assay and bioinformatic analysis were then performed to filtrate and assume the potential imperatorin-induced cell death route and signaling pathway. Moreover, quantitative real-time PCR assay, western blot assay and rescue experiments were conducted to confirm the assumptions of bioinformatic analysis. Finally, a subcutaneous tumor-transplanted nude mouse model was established and applied to evaluate the internal effect of imperatorin on osteosarcoma by HE and immunohistochemistry staining. Results Imperatorin triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, imperatorin treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued imperatorin-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Conclusions This work firstly revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ZEITSCHRIFT FUR KRISTALLOGRAPHIE-NEW CRYSTAL STRUCTURES
·
2023
·Vol. 238
·期 4
·799-800
·
IF 0.3
Yu-Pei Xia
C 4 H 13 Cl 2 N 5 , monoclinic, P 2 1 (no. 4), a = 7.1868(6) Å, b = 5.8408(4) Å, c = 12.6534(11) Å, β =
105.134
(
2
)
∘
, V = 512.73(7) Å 3 , Z = 2, R
gt ( F ) = 0.0354, wR
ref ( F
2 ) = 0.0961, T = 298 K.
研究领域:
化学晶体学
·
材料科学
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产品关联
DOI
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2020
·Vol. 47
·期 6
·1083-1091
·
IF 2.456
Zhu Wang,Qianqian Wang,Tao He,Wen Li,Yan Liu,Yuan Fan,Yanping Wang,Qi Wang,Jie Chen
Carboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi-drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti-malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non-small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle-related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G 2 /M phase, and induced the expression of the cell cycle and apoptosis-related proteins BAX, p21, p53, and Caspase-3, while decreasing Bcl-2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti-tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria-dependent manner.
研究领域:
肿瘤学
·
药理学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Ruijie Xu,Zhijie Yao,Hao Zhang,Haitao Li,Wei Chen
Loss of susceptibility to anoikis signals is a crucial step in metastasis. Anoikis resistance therefore represents a promising adjuvant therapeutic target for cancer management. In this study, we have conducted a rationalized screening to search for novel leading anoikis sensitizer from daily foods. Among 19 tested dietary phytochemicals, the best results were obtained with apigenin, a natural component of celery. Phenotypically, apigenin sensitized breast cancer cells to anoikis, lowered the number of circulating tumor cells, and protected against breast cancer metastasis to lung in mice. Mechanistically, we demonstrated that the thromboxane A 2 (TXA 2 )-TXA 2 receptor (TP) axis has a critical role in acquired anoikis resistance by activating PI3K-Akt signaling pathway. Blockage of TXA 2 signaling up-regulated p53 as well as its target gene p21, caused a G1 phase arrest, and finally led to apoptosis in breast cancer cells. TXA 2 level was positively correlated with breast cancer cell anoikis rate, and apigenin significantly inhibited TXA 2 biosynthesis in vitro and in vivo. Collectively, we identified apigenin as a potent anoikis sensitizer with anti-metastatic properties in a mouse model of breast cancer, and these findings might provide a rationale for introducing apigenin supplementation to breast cancer patients.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）