JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2024
·
IF 2.8
Liu Shilan,Liu Xiao,Yang Qinghui,Zeng Chunhua,Hu Gang,Ren Bochen
ObjectivesLung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored.MethodsIn this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis.Key findingsThe results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo.ConclusionsOur findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.
研究领域:
肿瘤学
·
分子生物学
·
癌症研究
·
基因组学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Zhiqiang Zhang,Qinglong Wang,Haibo Zhang,Shengchao Wang,Xia Ma,Hui Wang
Mitophagy is a distinct physiological process that can have beneficial or deleterious effects in particular tissues. Prior research suggests that mitophagic activity can be triggered by CaO2-PM-CsPbBr3 QDs, yet the specific role that mitophagy plays in hepatic injury induced by CaO2-PM-CsPbBr3 QDs has yet to be established. Accordingly, in this study a series of mouse model- and cell-based experiments were performed that revealed the ability of CaO2-PM-CsPbBr3 QDs to activate mitophagic activity. Golm1 was upregulated in response to CaO2-PM-CsPbBr3 QDs treatment, and overexpressing Golm1 induced autophagic flux in the murine liver and hepatocytes, whereas knocking down Golm1 had the opposite effect. CaO2-PM-CsPbBr3 QDs were also able to Golm1 expression, in turn promoting the degradation of P53 and decreasing the half-life of this protein. Overexpressing Golm1 was sufficient to suppress the apoptotic death of hepatocytes in vitro and in vivo, whereas the knockdown of Golm1 had the opposite effect. The ability of Golm1 to promote p53-mediated autophagy was found to be associated with the disruption of Beclin-1 binding to Bcl-2, and the Golm1 N-terminal domain was determined to be required for p53 interactions, inducing autophagic activity in a manner independent of helicase activity or RNA binding. Together, these results indicate that inhibiting Golm1 can promote p53-dependent autophagy via disrupting Beclin-1 binding to Bcl-2, highlighting a novel approach to mitigating liver injury induced by CaO2-PM-CsPbBr3 QDs.
研究领域:
细胞生物学
·
分子生物学
·
药理学
·
毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2015
·
IF 8.557
Si Chen,Lei Rong,Qi Lei,Peng-Xi Cao,Si-Yong Qin,Di-Wei Zheng,Hui-Zhen Jia,Jing-Yi Zhu,Si-Xue Cheng,Ren-Xi Zhuo,Xian-Zheng Zhang
To improve the tumor therapeutic efficiency and reduce undesirable side effects, ternary FK/p53/PEG-PLL(DA) complexes with a detachable surface shielding layer were designed. The FK/p53/PEG-PLL(DA) complexes were fabricated by coating the folate incorporated positively charged FK/p53 complexes with charge-switchable PEG-shield (PEG-PLL(DA)) through electrostatic interaction . At the physiological pH 7.4 in the bloodstream, PEG-PLL(DA) could extend the circulating time by shielding the positively charged FK/p53 complexes. After the accumulation of the FK/p53/PEG-PLL(DA) complexes in tumor sites, tumor-acidity-triggered charge switch led to the detachment of PEG-PLL(DA) from the FK/p53 complexes, and resulted in efficient tumor cell entry by folate-mediated uptake and electrostatic attraction . Stimulated by the high content glutathione (GSH) in cytoplasm, the cleavage of disulfide bond resulted in the liberation of proapoptosis peptide C-KLA(TPP) and the p53 gene, which exerted the combined tumor therapy by regulating both intrinsic and extrinsic apoptotic pathways. Both in vitro and in vivo studies confirmed that the ternary detachable complexes FK/p53/PEG-PLL(DA) could enhance antitumor efficacy and reduce adverse effects to normal cells. These findings indicate that the tumor-triggered decomplexation of FK/p53/PEG-PLL(DA) supplies a useful strategy for targeting delivery of different therapeutic agents in synergetic anticancer therapy.
研究领域:
药学
·
癌症生物学
·
纳米技术
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2017
·
IF 1.9
Li Xu,Caifeng Wan,Jing Du,Hongli Li,Xuesong Liu,Hong Yang,Fenghua Li
Breast cancer is the leading cause of cancer-related deaths in women and earlier detection can substantially reduce deaths from breast cancer. Polymers with targeted ligands are widely used in the field of molecular ultrasound imaging and targeted tumor therapy. In our study, the nanotheranostic agent was fabricated through filling perfluoropropane (C3F8) into poly(d,l-lactic-co-glycolic acid) nanoparticles (PLGA NPs), followed by the formation of gold nanoshell on the surface, then conjugated with anti p53 antibody which has high specificity with the p53 protein overexpressing in breast cancer. The average diameter of the gold nanoshelled PLGA NPs carrying anti p53 antibody (p53-PLGA@Au NPs) was 247 ± 108.2 nm. The p53-PLGA@Au NPs had well-defined spherical morphology and hollow interiors observed by electron microscope, and had a good photothermal effect under the irradiation of an 808 nm laser. The results of laser scanning confocal microscope (LSCM) and flow cytometer (FCM) indicated the specific targeting of p53-PLGA@Au NPs conjugating with breast cancer MCF-7 cells overexpressing p53 protein in vitro. Also the ultrasound imaging experiments in vitro showed that p53-PLGA@Au NPs were suitable for ultrasound contrast imaging. In conclusion, the p53-PLGA@Au NPs are demonstrated to be novel targeted UCAs and may have potential applications in the early diagnosis and targeted near-infrared (NIR) photothermal therapy of breast cancer in the future.
研究领域:
肿瘤学
·
纳米技术
·
生物医学工程
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Zhiyuan Li,Liu Zhang,Quanshun Li
Herein, N -acetyl- l -leucine-modified polyethylenimine was successfully constructed through the EDC/NHS-mediated coupling reaction and employed as vectors to accomplish p53 gene delivery using HeLa (p53wt) and PC-3 cells (p53null) as models. Compared with PEI25K, the derivatives exhibited lower cytotoxicity, protein adsorption and hemolytic activity, together with satisfactory pDNA condensation capability and gene transfection efficiency. After p53 transfection, MTT analysis confirmed that the cell proliferation was inhibited. Flow cytometric analysis showed that the derivative-mediated p53 delivery could induce stronger early apoptosis than PEI25K and Lipofectamine 2000 . Further, PC-3 cells showed higher sensitivity to the exogenous p53 transfection than HeLa cells. The mechanism for inducing apoptosis was determined to be up-regulation of p53 expression at both mRNA and protein levels using RT-PCR and western blotting analysis. Expression level and activity analysis of caspase-3, -8 and -9, and mitochondrial membrane potential measurement revealed that p53 transfection mediated by these derivatives facilitated early apoptosis of tumor cells via a mitochondria-dependent apoptosis pathway. Thus, the derivatives showed potential as biocompatible carriers for realizing effective tumor gene therapy.
研究领域:
癌症生物学
·
分子生物学
·
基因治疗
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2022
·
IF 7.129
Chongshan Dai,Meng Li,Yue Liu,Diem Hong Tran,Haiyang Jiang,Shusheng Tang,Jianzhong Shen
Chronic copper exposure could cause potential nephrotoxicity and effective therapy strategies are limited. This study investigated the protective effects of curcumin on copper sulfate (CuSO 4 )-induced renal damage in a mouse model and the underlying molecular mechanisms. Mice were administrated orally with CuSO 4 (100 mg/kg per day) in combination with or without curcumin (50, 100 or 200 mg/kg per day, orally) for 28 days. Results showed that curcumin supplementation significantly reduce the Cu accumulation in the kidney tissues of mice and improved CuSO 4 -induced renal dysfunction. Furthermore, curcumin supplantation also significantly ameliorated Cu exposure-induced oxidative stress and tubular necrosis in the kidneys of mice. Moreover, compared to the CuSO 4 alone group, curcumin supplementation at 200 mg/kg per day significantly decreased CuSO 4 -induced the expression of p53, Bax, IL-1β, IL-6, and TNF-α proteins, levels of NF-κB mRNA, levels of caspases-9 and − 3 activities, and cell apoptosis, and significantly increased the levels of Nrf2 and HO-1 mRNAs in the kidney tissues. In conclusion, for the first time, our results reveal that curcumin could trigger the inhibition of oxidative stress, mitochondrial apoptotic, p53, and NF-κB pathways and the activation of Nrf2/HO-1 pathway to ameliorate Cu overload-induced nephrotoxicity in a mouse model. Our study highlights that curcumin supplementation may be a promising treatment strategy for treating copper overload-caused nephrotoxicity.
研究领域:
药理学
·
毒理学
·
分子生物学
·
肾脏生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Jieyu Hu,Xingxing Yu,Xiumei Zhuang,Yan Sun,Junjie Wang,Haiting Ren,Shenghao Zhang,Yueshou Zhang,Hongxing Qiu,Yongjun Hu
The p53 gene is a known cancer marker. We report a novel protocol for the SERS tandem strategy to detect the p53 gene with high sensitivity. Herein, the click reaction between azide and alkyne was catalyzed by utilizing copper oxide nanoparticles (CuONPs), which were enriched by a T-DNA-triggered hybridization chain reaction (HCR). The T-DNA signal was amplified by establishing the correlation between the T-DNA signal and the concentration of CuONPs in a nonenzymatic isothermal environment. In contrast to other Raman reporters, we used alkynyl compounds as Raman reporters, which showed excellent characteristics in the Raman-silent region (1800–2800 cm −1 ). Therefore, the highly sensitive and highly selective SERS signals could be obtained in complex biological matrices. Due to utilizing multistep amplification strategies, including the nanoparticle-modified HCR polymer and “click” reaction, the limit of detection (LOD) and the limit of quantification (LOQ) of this sensor could be as low as 0.0174 pM and 0.0583 pM, respectively. The accuracy of the strategy expressed as the RSD was in the range of 3.14%–6.21%. The results indicated that the constructed sensor has excellent performance for the detection of the p53 gene in serum samples in a low concentration range, which suggests that the proposed enzyme-free SERS analytical sensor has good clinical application prospects.
研究领域:
生物技术
·
纳米技术
·
癌症研究
·
分析化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Jiajian Wang,Lanqing Zhang,Runfang Li,Rui Yang,Fan Yang,Fei Yu,Jihong Zhang
TP53, the most frequently mutated gene in human cancers, undergoes a functional transformation from a tumor suppressor to an oncoprotein, thereby enhancing tumor aggressiveness, metastatic potential, and resistance to therapy. Given the prevalence of p53 mutations in cancer, the reactivation of wild-type p53 function presents a compelling therapeutic strategy for these malignancies. In this study, we identified gambogic acid (GA), a natural compound, as a potent reactivator of mutant p53 transcriptional activity. Immunofluorescence and co-immunoprecipitation assays revealed that GA treatment upregulates wild-type p53 expression while depleting mutant p53 in cancer cells. The time-dependent restoration of p53′s DNA-binding capacity and transcriptional regulatory activity by GA was further demonstrated through EMSA and ChIP. Consequently, GA robustly induced the expression levels of canonical p53 downstream target genes, confirming functional restoration of p53 signaling. In addition, GA synergizes with RSL3, a GPX4 inhibitor, to promote ferroptosis in mutant p53 cancer cells in both cellular and animal studies. In summary, our findings identify GA as a promising compound that reactivates mutant p53 through thiol modification, restoring its wild-type function and inducing ferroptosis in p53-mutant cancer cells. The findings of this study establish a foundational rationale and new perspectives for a mutant p53-directed therapeutic paradigm in oncology.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
癌症生物学
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Min Li,Xueqin Wu,Jixing Zou,Yingqian Lai,Jiawen Zhang,Xiumei Chen,Xiaotian Niu,Yidi Kong,Guiqin Wang
This study was aimed to evaluate the ameliorative effects of thymol-supplemented diets on the toxicity damage of Channa argus induced by deltamethrin (DEL). After 28 d, the results are as follows: thymol can attenuate DEL-induced oxidative stress by reversing the decrease of the activities of antioxidant enzyme (SOD, CAT , GSH , GST and GSH-Px) and the increase of the MDA content in the tissues (liver and spleen), and also by reversing the decrease of the mRNA expression levels of Nrf2, Cu/Zn SOD and HO-1, and the increase of the Keap1 mRNA expression level in the tissues (liver and spleen). Thymol can attenuate DEL-induced immunotoxicity of fish by reverse the decrease of the levels of humoral immune parameters (C4, C3, IgM and LYS) in the serum, and by reversing the increase of the expression levels of NF-κB p65, TNF-α, IL-1β, IL-8 and IL-6, and the decrease of the IL-10 expression level in the tissues (liver and spleen). Thymol can attenuate DEL-caused apoptosis reversing the increase of the expression levels of pro-apoptosis (p53, Bax and Apaf-1) and the decrease of the expression level of anti-apoptosis Bcl-2 in the tissues (liver and spleen). Therefore, this study reveals that dietary supplementation of thymol alleviates DEL-caused immunotoxicity, oxidative stress, and apoptosis of C. argus in association with the NF-κB/Nrf2/p53 pathway.
研究领域:
水产养殖
·
毒理学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY
·
2025
·Vol. 51
·期 3
·1070-1082
·
IF 1.7
Liu Xing,He Jingliang,Cheng Wenhao,Wang Xiaoshuo,Zhang Meiqi,Wang Sen,Chen Lu,Zhang Siyi,Zhou Chongyun,Zhou Lili,Zhang Boyu,Wang Dan,Song Yizhuo,Wang Xiujun,Ji Jing
Objective: To design and synthesize a novel piperine derivative with enhanced antitumor efficacy compared to the natural compound piperine. Methods: Compound NOHJ was synthesized via the condensation of ( E )-3-(4,5-dimethoxy-2-nitrophenyl)acrylic acid with 4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)aniline. Its antitumor activity was evaluated using both in vitro and in vivo models. Potential molecular targets of NOHJ were identified through molecular docking, Western blotting, and immunofluorescence assays. Results and Discussion: NOHJ exhibited significant antitumor activity and demonstrated greater efficacy than piperine in inhibiting cell adhesion, migration, invasion, and colony formation in MDA-MB-231 and MCF-7 breast cancer cell lines. Additionally, NOHJ effectively suppressed tumor growth in vivo and inhibited angiogenesis in the chick embryo chorioallantoic membrane (CAM) assay. Mechanistic studies revealed that NOHJ treatment upregulated the expression of p53 and p21, while downregulating CDK1 and CCNB1, indicating cell cycle disruption. Conclusions: NOHJ exerts its antibreast cancer effects by targeting and inhibiting MDM2, stabilizing p53, and modulating key regulators of the cell cycle, ultimately leading to G 2 /M phase arrest and apoptosis. These findings suggest that NOHJ is a promising therapeutic candidate for breast cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
DOI
高影响因子
ACS Pharmacology & Translational Science
·
2024
·
IF 4.9
Quan Wang,Xinyue Liu,Han Yuan,Fengcai Zhang,Jiafei Wu,Dongjing Yang,Jiang Qian,Yi-You Huang,Guihong Chai,Hai-Bin Luo,Lei Guo
Idiopathic pulmonary fibrosis (IPF) is a debilitating, incurable, and life-threatening disease that lacks effective therapy. The overexpression of phosphodiesterase 10A (PDE10A) plays a vital role in pulmonary fibrosis (PF). However, the impact of selective PDE10A inhibitors on the tumor growth factor-β (TGF-β)/small mother against decapentaplegic (Smad) signaling pathway remains unclear. Herein, we have exploited a novel carbonyl sulfide (COS)/hydrogen sulfide (H2S)-donor hybrid PDE10A inhibitor called COS-2080 with a well-defined mechanism of H2S-releasing action. It exhibited highly potent inhibitory activity against PDE10A and excellent PDE subfamily selectivity. Moreover, COS-2080 demonstrated significant antifibrotic effects by inhibiting cell proliferation and mitigating fibroblast-to-myofibroblast transition (FMT). A dry powder inhalation formulation called COS-2080-DPI has been developed using the ultrasonic spray freeze drying (USFD) technique, demonstrating significant antifibrotic efficacy in mice with bleomycin-induced PF at a dosage approximately 600 times lower than pirfenidone. This remarkable antifibrotic efficacy of COS-2080 on TGF-β1-induced FMT could be primarily attributed to its inhibition of the Smad2/Smad3 phosphorylation. Moreover, COS-2080 effectively attenuated fibrosis in MRC-5 cells by activating the cAMP/protein kinase A (PKA)/CREB pathway and potentially increasing levels of p53 protein. Our findings suggest that effective inhibition of PDE10A potentially confers a protective effect on FMT in PF by impeding TGF-β signaling and activating the cAMP/PKA/CREB/p53 axis.
研究领域:
肺病学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 19
·8783
·
IF 5.6
Chen-Yang Jiang,Yan-Li Wang,Nan Lv,Bing-Kun Cai,Tian-Xia Jiang
Tumor incidence increases markedly with advancing age, yet the molecular mechanisms linking aging-driven senescence to tumorigenesis remain incompletely understood. The proteasome activator PA200 preserves genomic stability by mediating the degradation of acetylated histones during aging. However, its function in age-associated tumor progression is poorly defined. Here, we demonstrate that PA200 promotes aging-associated tumorigenesis independent of its histone-degrading activity. Elevated PA200 correlates with poor prognosis and advancing age in human lung cancer. PA200-deficient tumor cells exhibit suppressed proliferation and migration, accompanied by aggravated oxidative-stress-triggered cellular senescence. Mechanistically, p53 directly binds and repressesPSME4transcription at its promoter. Reciprocally, PA200 facilitates proteasomal degradation of β-catenin, thereby sustaining p53 activity and forming a negative feedback loop. In the urethane-induced mouse lung tumor model, PA200 ablation markedly reduces tumor burden, especially in middle-aged mice. This effect is coupled with β-catenin accumulation, lowered p53 levels, and partial remodeling of the pro-inflammatory tumor microenvironment. Our findings uncover the p53-PA200-β-catenin feedback axis as a key driver of age-dependent lung tumorigenesis and highlight PA200 as a potential therapeutic target for elderly patients with lung cancer.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）