BIOINORGANIC CHEMISTRY AND APPLICATIONS
·
2021
·
IF 7.778
Meijuan Chen,Zhousheng Lin,Guangyu Yao,Xi Hong,Xiaolei Xue,Lujia Chen
TTRE, a photosensitizer molecule, has excellent biofluorescence imaging performance and effective antitumor properties for breast cancer. However, its application in breast cancer treatment is limited due to poor tumor selectivity and lack of targeting ability. In this study, TTRE and trastuzumab were combined to synthesize Tra-TTR-A, a novel near-infrared fluorescent nanoprobe for HER2 positive breast cancer. The targeting and antitumor abilities of Tra-TTR-A in breast cancer were also investigated. Like TTRE, Tra-TTR-A has a stable structure with remarkable optical properties and in vivo imaging capacity. However, Tra-TTR-A not only inhibits tumor growth by generating reactive oxygen species but also kills tumor cells by trastuzumab. In this study, Tra-TTR-A, a new type of near-infrared fluorescent nanoprobe that targets HER2-positive breast cancer, was successfully synthesized. Tra-TTR-A could be used in in vivo imaging, targeted photodynamic therapy, and diagnosis and treatment for breast cancer.
研究领域:
癌症研究
·
生物医学工程
·
分子生物学
·
药学
✓ 已验证
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2026
·
IF 7.2
Xiao-Min Ren,Xinxin Liu,Yuwei Ma,Xiaochi Zhang,Huan He,Zhixiang Xu,Gui Yang,Bin Huang,Xuejun Pan
Bisphenol analogues (BPs) are widely used industrial chemicals, raising concern regarding their potential disruption of the thyroid hormone (TH) system. This study systematically evaluated the binding properties and interference potential of 21 structurally diverse BPs toward transthyretin (TTR) and thyroxine-binding globulin (TBG). Fluorescence polarization assays showed that TTR binding was primarily driven by bridging-group rigidity, halogen substitution, and hydroxyl number, whereas TBG affinity was more dependent on molecular polarity and steric volume. Molecular docking supported the roles of halogenation and structural complementarity in stabilizing ligand-protein interactions. A quantitative in vitro to in vivo extrapolation (QIVIVE) model predicted that environmentally relevant exposure levels of most BPs cause negligible alterations in serum free T4, and mixture effects were approximately additive. Toxicological Priority Index (ToxPi) integration identified highly halogenated congeners as dominant high-risk candidates, with substantially greater potential impacts under occupational high-exposure scenarios. Overall, this work establishes a multi-tiered framework linking molecular binding characteristics to in vivo hormone perturbations, providing scientific support for evaluating TH-disrupting risks and guiding the identification of safer BP alternatives.
✓ 已验证
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
·
分子生物学
·
糖尿病
·
肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2017
·
IF 4.9
Mi Deng,Yongming Wu,Chao Xu,Yuanxiang Jin,Xiaoli He,Jinbao Wan,Xiaoling Yu,Hongmin Rao,Wenqing Tu
A Chinese perfluorooctane sulfonate (PFOS) substitute frequently detected in the environment, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), has a similar structure to PFOS and it is proposed to cause thyroid dysfunction. To further confirm this hypothesis, the effects of F-53B on the thyroid endocrine system and underlying mechanisms were investigated in vitro and in vivo using rat pituitary GH3 cells and developing zebrafish, respectively. In GH3 cells, F-53B enhanced cell proliferation in a dose-dependent manner, indicative of thyroid receptor agonistic activity. In zebrafish larvae, F-53B exposure induced significant developmental inhibition and increased thyroxine (T 4 ) but not 3,5,3′-triiodothyronine (T 3 ) levels accompanied by a decrease in thyroglobulin (TG) protein and transcript levels of most genes involved in the hypothalamic-pituitary-thyroid (HPT) axis. Interestingly, T 4 levels remained significantly increased while TG protein and gene transcription levels were markedly upregulated after depuration. Molecular docking studies revealed that F-53B binds to transthyretin (TTR) by forming hydrogen bonds with Lys123 and Lys115, thereby interfering with thyroid hormone homeostasis. Our collective in vitro , in vivo and in silico studies provide novel evidence that F-53B disrupts the thyroid endocrine system at environmentally relevant concentrations, which cannot be recovered after depuration. Given the persistence of F-53B in the environment, the long-term consequences of thyroid hormone disruption by this chemical warrant further investigation.
研究领域:
环境科学
·
毒理学
·
内分泌学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
CONSTRUCTION AND BUILDING MATERIALS
·
2020
·
IF 4.419
Hang Zhang,Miaomiao Hu,Yang Xu,Xiujian Xia,Chi Zhang,Yongjin Yu,Yakai Feng,Jintang Guo
Aberrant thickening of cement slurry caused by polycarboxylate retarders mainly refers to abnormal gelation and thickening time reversal (TTR) when temperature reaches above 120 °C. These phenomena would directly jeopardize cementing operation and hinder the application of polycarboxylate retarders in oil and gas exploitation. Herein, two functionalized polycarboxylate retarders were synthesized to overcome the challenges in complex conditions. The incorporation of isoprenyl oxy poly(ethyleneglycol) ether (TPEG) and [3-(methacryloylamino) propyl] trimethyl ammonium chloride (MAPTAC) was capable of preventing unfavorable “crosslinking and chelation” reaction between cement grains and polymer, thereby avoiding abnormal gelation. It was also found that the hydrophobic association behavior of long side chain in TPEG could cause the gradual release of carboxyl groups at elevated temperature, which was unfavorable for TTR inhibition. When the TPEG was replaced by N-Vinyl-2-Pyrrolidinone (NVP), its retarding effect gradually weakened when temperature rose from 130 °C to 150 °C, and excellent inhibition of TTR was achieved.
研究领域:
石油工程
·
材料科学
·
化学工程
✓ 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）