JOURNAL OF THE ELECTROCHEMICAL SOCIETY
·
2020
·Vol. 167
·期 2
·027501
·
IF 3.721
Wei Zhang,Jimin Yang,Di Wu
An electrochemical biosensor for direct detection of PIK3CA gene related to lung cancer was developed based on riboflavin 5'-monophosphate sodium salt (FMNs)-functionalized MoS2 nanosheets prepared by simple ultrasonication method. As a highly effective biodispersant, FMNs demonstrated excellent stabilization for obtaining highly dispersed MoS2 nanosheets in an aqueous solution. The prepared FMNs/MoS2 nanocomposite with fine electrochemical redox activity was employed as the platform to immobilize DNA probe and supplied the inherent indicator signal for DNA sensing. The amine-terminated ssDNA probe was covalently immobilized onto the FMNs/MoS2 nanocomposite with rich phosphonate groups. After the hybridization of the probe ssDNA with the complementary target DNA, the self-redox signal of the nanocomposite decreased ascribed to the changes in the conformation of DNA. The results indicated that the proposed self-signal detection platform displayed high sensitivity with a detection limit of 1.2 × 10–17 mol l−1 for PIK3CA gene from lung cancer, accompanied with fine selectivity, outstanding stability and reproducibility. The constructed biosensor was easy to design and had the potential for the detection of different pathogenic DNA without intricate label process.
研究领域:
生物医学工程
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分子生物学
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肿瘤学
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产品关联
DOI
高影响因子
ONCOGENE
·
2020
·Vol. 39
·期 17
·3588-3603
·
IF 7.971
Liu Xiaochen,Cui Jianfeng,Gong Li,Tian Fei,Shen Yangli,Chen Lipeng,Wang Yong,Xia Yangyang,Liu Lei,Ye Xiang,Wang Molin,Liu Guangyi,Jiang Baichun,Shao Changshun,Zou Yongxin,Gong Yaoqin
CUL4B, which acts as a scaffold protein in CUL4B-RING ubiquitin ligase (CRL4B) complexes, participates in a variety of biological processes. Previous studies have shown that CUL4B is often overexpressed and exhibits oncogenic activities in a variety of solid tumors. However, the roles and the underlying mechanisms of CUL4B in bladder cancer (BC) were poorly understood. Here, we showed that CUL4B levels were overexpressed and positively correlated with the malignancy of BC, and CUL4B could confer BC cells increased motility, invasiveness, stemness, and chemoresistance. The PIK3CA/AKT pathway was identified as a critical downstream mediator of CUL4B-driven oncogenicity in BC cells. Furthermore, we demonstrated that CRL4B epigenetically repressed the transcription of miR-372/373, via catalyzing monoubiquitination of H2AK119 at the gene cluster encoding miR-372/373, leading to upregulation of PIK3CA and activation of AKT. Our findings thus establish a critical role for the CUL4B-miR-372/373-PIK3CA/AKT axis in the pathogenesis of BC and have important prognostic and therapeutic implications in BC.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
Analytical Methods
·
2018
·Vol. 11
·期 2
·157-162
·
IF 2.073
Jimin Yang,Xuesong Yin,Wei Zhang
In our study, we report the development of molybdenum disulfide (MoS2) nanosheet-supported poly(indole-6-carboxylic acid) (PIn6COOH) and its usage for the electrochemical determination of circulating tumor DNA (ctDNA) such as PIK3CA gene associated with breast cancer. The MoS2 nanosheets prepared by the solvent exfoliation method from commercial bulk MoS2 were first immobilized on the surface of a carbon paste electrode; then, PIn6COOH, a novel electroactive material, was electropolymerized on the MoS2 substrate by the potentiostatic method to form a unique nanocomposite structure. The physical adsorption between aromatic In6COOH monomers and MoS2 efficiently improved the electropolymerization efficiency, resulting in increased electrochemical response of PIn6COOH. Owing to the presence of abundant carboxyl groups, probe ssDNA was covalently immobilized on the carboxyl-terminated PIn6COOH/MoS2 nanocomposite through free amines of DNA sequences based on 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydrosulfosuccinimide crosslinking reaction. The covalently immobilized probe ssDNA could selectively hybridize with its target DNA to form dsDNA on the surface of the PIn6COOH/MoS2 nanocomposite. The self-signal changes of PIn6COOH induced by DNA immobilization and hybridization could be sensitively recognized via cyclic voltammetry and electrochemical impedance spectroscopy. This developed biosensor showed high performance of DNA hybridization with a detection limit of 1.5 × 10−17 mol L−1 for the detection of PIK3CA gene. The easy construction of this biosensor besides its fine sensitivity and very low time consumption can make this PIn6COOH/MoS2 nanocomposite very highly competitive for further applications in carcinoma diagnostic and therapeutic fields.
研究领域:
生物医学工程
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分子诊断学
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癌症研究
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DOI
高影响因子
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
·
2026
·
IF 1.5
Mao Huizi,Li Zhuqing,Lu Chengzhi
The current therapy for myocardial infarction focuses on reestablishing blood flow in the coronary arteries to reduce the ischemic area, but the subsequent damage caused by reperfusion cannot be ignored. Liquiritin, a primary flavonoid compound found in the medicinal plant licorice, exhibits distinct pharmacological properties including neuroprotection, anti-inflammatory, antioxidant, and anti-apoptotic effects. However, further research on its role and mechanism in myocardial ischemia-reperfusion (I/R) injury is needed. The aim of this work was to elucidate the protection of liquiritin against myocardial I/R insult and whether liquiritin-mediated autophagy restoration was associated with phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in vivo and in vitro. Liquiritin administration by oral gavage inhibited pathological injury of myocardial I/R injured rats, evidenced by improved cardiac function and reduced infarct size. Moreover, liquiritin restored excessive autophagy by promoting the phosphorylation of protein kinase B (AKT) and mammalian target of rapamycin (mTOR), which was accompanied by PIK3CA upregulation. Mechanistically, silencing PIK3CA in rat H9c2 cardiomyoblasts diminished the beneficial effects against oxygen-glucose deprivation/reoxygenation (OGD/R) injury reflected by exacerbated apoptosis and dysregulated autophagy mediated by the classical PI3K/Akt/mTOR pathway. Liquiritin inhibited excessive autophagic flux via decreasing autophagosome-lysosome fusion, which was similar to the effect of the autophagy inhibitor chloroquine. Moreover, this phenomenon was enhanced when liquiritin and chloroquine were used in combination. Collectively, our work revealed that the protective effect of liquiritin against myocardial I/R injury may be attributed to its autophagy restoration mediated by PIK3CA.
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2023
·Vol. 9
·期 7
·e17393
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IF 4
Kang Kai,Jiang Han-bing,Cheng Bing-lin,Zhang Shu-jun
Gastric cancer (GC) is a deadly malignant tumor with a high fatality rate and limited curative options. A growing body of research suggests that network pharmacology can replace traditional methods for determining the precise mechanism of action of medicinal substances in conditions such as cancer. The goal of this study was to clarify the biological mechanism of chelerythrine (CHE) and develop a prediction target for CHE against GC using network pharmacology. First, the genes related to GC were identified from the databases Genecards, Disgenet, Online Mendelian Inheritance in Man, Therapeutic Target Database, and Drugbank, and the targets of CHE were obtained from the SwissTargetPrediction database. Fifty linked targets were identified as anti -GC targets of CHE. Functional enrichment and pathway analyses revealed important biological mechanisms mediated by these targets. The core target PIK3CA of CHE anti -GC was obtained using the protein-protein interaction network, CytoHubba plug-in, and Human Protein Atlas. Molecular docking studies revealed that CHE has a strong affinity for PIK3CA (-10.5 kcal/mol). In addition, we used MTT, colony formation, wound-healing, Transwell®, and flow cytometry experiments to confirm that CHE inhibited the proliferation and migration of GC cells and induced cell cycle arrest and apoptosis. Finally, western blotting results showed that CHE downregulated the expression of the PIK3CA protein and inhibited the activation of the PI3K/AKT signaling pathway. Therefore, we concluded that CHE inhibited GC cell proliferation and migration and induced cell cycle arrest and apoptosis by targeting the PIK3CA protein to inhibit the PI3K/AKT pathway activity.
研究领域:
药理学
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肿瘤学
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分子生物学
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DOI
PubMed
高影响因子
TOXICOLOGY AND APPLIED PHARMACOLOGY
·
2025
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IF 3.4
Xing Liu,Mingzhu Xia,Xinyi Wu,Ruobing Chen,Yuting Peng,Yi Fan,Junjie Han,Yichun Zhao,Man Qu
Perfluorooctanoic acid (PFOA), a pervasive environmental contaminant, is implicated in ocular diseases through prenatal/embryonic exposure. This study investigated the protective effects of nomilin, a citrus-derived bioactive compound with therapeutic properties, against PFOA-induced ocular and visual impairments in zebrafish. Integrating network toxicology and molecular docking, we identified seven shared targets (including PIK3CA and mTOR) linking PFOA, nomilin, and ocular diseases. Experimental results demonstrated that PFOA exposure suppressed the PIK3CA/AKT/mTOR/pax6 axis, significantly downregulated (by approximately 0.23- to 0.65-fold) ocular development genes (rx1, vsx1, rpgra, lhx4), and induced structural defects (reduced eye size, lens diameter and retinal layer thickness) and visual dysfunction. Nomilin treatment dose-dependently reversed these effects by activating the PIK3CA/AKT/mTOR/pax6 axis, restoring the expression of ocular developmental related genes by 1.45- to 2.85-fold compared to the PFOA-exposed group, improving ocular morphology, and enhancing visual response behaviors. Furthermore, nomilin attenuated PFOA-induced apoptosis. These findings reveal that nomilin mitigates PFOA-mediated ocular toxicity via PIK3CA activation, offering novel therapeutic insights for environmental pollutant-related ocular disorders.
研究领域:
毒理学
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发育生物学
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环境健康
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分子生物学
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眼科学研究
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产品关联
DOI
PubMed
高影响因子
Optoelectronics Letters
·
2024
·Vol. 20
·期 4
·249-256
·
IF 0.8
Liu Jianjun
Breast cancer is the most common malignant tumor in women, which seriously threatens the physical and mental health of women worldwide. The existing detection methods have problems, such as large sample consumption, time-consuming sample preparation, expensive equipment, and low sensitivity. In order to solve these problems, this paper proposes a method for quickly detecting breast cancer using surface-functionalized terahertz metamaterial biosensors. The use of PIK3CA-modified sensors enhances the detection sensitivity and specificity of exosomes. Based on the red shift of the sensor absorption peak caused by exosomes, breast cancer patients can be distinguished from healthy controls. This study demonstrates that exosome detection is effective for the repeatable and non-invasive diagnosis of breast cancer patients. The terahertz metamaterial biosensor designed in this paper has high specificity, repeatability, and sensitivity, and has great potential for application in the development of modern diagnostic instruments.
研究领域:
生物医学工程
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生物化学
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肿瘤学
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分析化学
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纳米技术
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生物物理学
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DOI
高影响因子
MICROCHIMICA ACTA
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2024
·Vol. 191
·期 11
·1-11
·
IF 5.3
Wei Yuxin,Fu Yang,Li Chuanhai,Chen Siyu,Xie Linzhi,Chen Mei
A electrochemical biosensor was designed utilizing a CRISPR Cas9n-driven DNA walker combined with gold-nanosphere-like covalent organic frameworks (COFs-AuNPs) to detect breast cancer markers (PIK3CA E545K ctDNA). The DNA walker probe is activated only in the presence of circulating tumor deoxyribonucleic acid (ctDNA), binding to a support probe to form a double strand that is then specifically cleaved by the Cas9n/sgRNA complex. This cleavage produces numerous DNA fragments for signal amplification. The COF-AuNPs as electrode materials facilitate electronic transfer and provide additional active sites for the immobilization of nucleic acid probes. This setup achieves a detection limit of 1.76 aM, demonstrating high sensitivity. Additionally, Cas9n improves the specificity of the sensor, accurately distinguishing a pair of base-mismatched sequences, and reducing the occurrence of false positives. Overall, the sensor exhibits excellent selectivity, reproducibility, and potential for early diagnosis of breast cancer. Graphical Abstract
研究领域:
生物技术
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癌症生物学
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纳米技术
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电化学
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分子诊断
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产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2023
·Vol. 21
·期 1
·1-14
·
IF 7.4
Chen Shengnan,Li Bo,Chen Lei,Jiang Hongli
Background Diabetic kidney disease (DKD) has been the leading cause of chronic kidney disease in developed countries. Evidence of the benefits of resveratrol (RES) for the treatment of DKD is accumulating. However, comprehensive therapeutic targets and underlying mechanisms through which RES exerts its effects against DKD are limited.Methods Drug targets of RES were obtained from Drugbank and SwissTargetPrediction Databases. Disease targets of DKD were obtained from DisGeNET, Genecards, and Therapeutic Target Database. Therapeutic targets for RES against DKD were identified by intersecting the drug targets and disease targets. GO functional enrichment analysis, KEGG pathway analysis, and disease association analysis were performed using the DAVID database and visualized by Cytoscape software. Molecular docking validation of the binding capacity between RES and targets was performed by UCSF Chimera software and SwissDock webserver. The high glucose (HG)-induced podocyte injury model, RT-qPCR, and western blot were used to verify the reliability of the effects of RES on target proteins.Results After the intersection of the 86 drug targets and 566 disease targets, 25 therapeutic targets for RES against DKD were obtained. And the target proteins were classified into 6 functional categories. A total of 11 cellular components terms and 27 diseases, and the top 20 enriched biological processes, molecular functions, and KEGG pathways potentially involved in the RES action against DKD were recorded. Molecular docking studies showed that RES had a strong binding affinity toward PPARA, ESR1, SLC2A1, SHBG, AR, AKR1B1, PPARG, IGF1R, RELA, PIK3CA, MMP9, AKT1, INSR, MMP2, TTR, and CYP2C9 domains. The HG-induced podocyte injury model was successfully constructed and validated by RT-qPCR and western blot. RES treatment was able to reverse the abnormal gene expression of PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR.Conclusion sRES may target PPARA, SHBG, AKR1B1, PPARG, IGF1R, MMP9, AKT1, and INSR domains to act as a therapeutic agent for DKD. These findings comprehensively reveal the potential therapeutic targets for RES against DKD and provide theoretical bases for the clinical application of RES in the treatment of DKD.
研究领域:
药理学
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分子生物学
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糖尿病
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肾病学
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产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 9
·4191-4203
·
IF 6.1
Qiang Zhang,Xuehan Yang,Jingyue Liu,Jiayi Song,Siwei Zhang,Li Chen,Ming Zhang
Neurogenesis in Alzheimer's disease (AD) is impaired, and thus promoting neurogenesis is a promising strategy for treating AD-related cognition impairment. Here, we found that 20S-protopanaxatriol (PPT) can alleviate cognitive deficits in an AlCl3-induced AD zebrafish model in Y and T maze tests and increase the HUC expression of the telencephalon. PPT promotes neural stem cell (NSC) line differentiation into neurons under AD condition. PPT significantly alleviated the apoptosis and cell cycle arrest of NSCs induced by amyloid-beta. Next, we investigated the molecular mechanism of PPT in treating AD by network pharmacology and molecular docking. PPT could target PIK3CA and PI3K/AKT signaling pathways. PPT significantly reversed the reduced expression level of PIK3CA (PI3K p110), p-PI3Kp85 and p-AKT of NSCs under AD condition. These results suggested that PPT alleviated the cognitive dysfunction of AD and promoted NSC proliferation and neurogenesis through the PI3K/AKT pathway. Therefore, PPT might be a potential candidate to treat AD-related cognitive decline via enhancing endogenous neurogenesis.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Arabian Journal of Chemistry
·
2024
·
IF 5.3
Dong Xie,Guangfu Lv,Yuchen Wang,Wenjing Zhang,Nian Li,Yao Duan,Qing Huang,Ge Chen,Zifeng Pi,Hao Yue
Tenghuang Jiangu Wan (THJGW) is a commonly utilized treatment for osteoarthritis (OA), yet its pharmacodynamic material basis and molecular mechanism remain inadequately understood. This study systematically characterized the in vitro and in vivo chemical components of THJGW using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The pharmacodynamic material basis of THJGW in the treatment of OA was explored through a target network pharmacology approach and molecular docking technology. Cellular experiments were subsequently employed to validate the molecular mechanisms. Consequently, a total of 134 components from THJGW were identified in vitro , comprising 45 flavonoids, 10 iridoid glycosides, 39 phenylethanoid glycosides, 9 phenylpropanoids, 11 organic acids, 4 phenolics, and 16 other compounds. Additionally, 38 prototype absorbed components in serum were characterized for the purpose of network construction. 11 key components and 10 core targets (VEGFA, STAT3, RELA/NF-κB p65, PIK3R1, PIK3CA, MMP9, MMP1, IL-6, HDAC1, and FGF2) were determined by the target network pharmacology. Through Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it was found that these intersection targets are associated with various signaling pathways such as pathways in cancer, lipid and atherosclerosis, and prostate cancer. Notably, the lipid and atherosclerosis pathway was closely linked to OA. The molecular docking results demonstrated strong binding affinities of the three core targets: IL-6, STAT3, and RELA/NF-κB p65. These results suggest that these targets may play a significant role for THJGW in treating OA. In vitro experiments showed that THJGW had notable protective effects on LPS-induced RAW264.7 macrophages by reducing levels of TNF-α and IL-6, and inhibiting phosphorylation expression of STAT3 and NF-κB p65 proteins related to the lipid and atherosclerosis pathway. This study provides insight into the pharmacodynamic material basis and mechanism of action for THJGW in the treatment of OA, which provide scientific evidence for the scientific application and improvement of quality standards for THJGW.
研究领域:
药理学
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生物化学
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分子生物学
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中医药
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Qingshuang Zou,Ke Liao,Guangchao Li,Xin Huang,Yongwei Zheng,Gun Yang,Min Luo,Evelyn Y. Xue,Chuanqing Lan,Shuai Wang,Yao Shen,Dixian Luo,Dennis K. P. Ng,Quan Liu
The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can “warm” the “cold” tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr 3+ ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
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生物医学工程
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癌症生物学
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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）