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Morpholine-Functionalized Multicomponent Metallacage as a Vector for Lysosome-Targeted Cell Imaging EI SCIE Scopus
期刊论文 | 2022 , 14 (34) , 38594-38603 | ACS APPLIED MATERIALS & INTERFACES
SCOPUS Cited Count: 18
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Abstract :

Metallacages with suitable cavities and specific functions are promising delivery vectors in biological systems. Herein, we report a morpholine-functionalized metallacage for lysosome-targeted cell imaging. The efficient host-guest interactions between the metallacage and dyes prevent them from aggregation, so their emission in aqueous solutions is well maintained. The fluorescence quantum yield of these hostguest complexes reaches 74.40%. Therefore, the metallacage is further employed as a vector to deliver dyes with different emission colors (blue, green, and red) into lysosomes for targeted imaging. This research affords a type of vector for the delivery of various cargos toward biological applications, which will enrich the usage of metallacages in biomedical engineering.

Keyword :

cell imaging fluorescence host-guest complexation metallacages targeted delivery

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GB/T 7714 Feng, Qian , Yang, Tianfeng , Ma, Lingzhi et al. Morpholine-Functionalized Multicomponent Metallacage as a Vector for Lysosome-Targeted Cell Imaging [J]. | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (34) : 38594-38603 .
MLA Feng, Qian et al. "Morpholine-Functionalized Multicomponent Metallacage as a Vector for Lysosome-Targeted Cell Imaging" . | ACS APPLIED MATERIALS & INTERFACES 14 . 34 (2022) : 38594-38603 .
APA Feng, Qian , Yang, Tianfeng , Ma, Lingzhi , Li, Xiaopeng , Yuan, Hongye , Zhang, Mingming et al. Morpholine-Functionalized Multicomponent Metallacage as a Vector for Lysosome-Targeted Cell Imaging . | ACS APPLIED MATERIALS & INTERFACES , 2022 , 14 (34) , 38594-38603 .
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A fluorescent, chiratity-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery EI SCIE Scopus
期刊论文 | 2022 , 20 (19) , 3998-4005 | ORGANIC & BIOMOLECULAR CHEMISTRY
SCOPUS Cited Count: 7
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Abstract :

In recent years, the rational design and construction of drug delivery systems (DDSs) via a supramolecular approach for improving chemical therapeutics have gained significant attention. Here, we report a host-guest DDS formed from a fluorescent, chirality-responsive, and water-soluble tetraphenylethene-based octacationic cage as a fluorescent/chiral probe, solubilizer, and molecular cargo, which can recognize chiral nucleoside drugs, enhance the solubility of insoluble drugs, and protect drugs from the outside environment by forming host guest complexes in aqueous solution. Given the fluorescence properties and dynamically rotational conformation of tetraphenylethene (TPE) units, this fluorescent and chirality-responsive cage exhibits different responses including turn-on/turn-off fluorescence and negative/positive circular dichroism (CD) when binding with different chiral nucleoside drugs in water, resulting in multiple-responsive photophysical behaviors for these chiral drugs. Furthermore, this water-soluble cationic cage with a hydrophobic cavity can improve the water solubility of insoluble drugs (e.g., CPT) by forming host-guest complexes in water. More importantly, this multifunctional cage exhibits a low toxicity to both human colon and breast cancer cell lines in vitro, and drugs encapsulated by the cage are more effective in killing cancer cells than drugs alone. Finally, the on off -on fluorescence responses in the formation and dissociation processes of the cage superset of drug complexes have been successfully used to monitor drug release and track drug delivery by fluorescence microscopy in vitro. Therefore, this fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container can be used to construct a smart drug delivery system with several functions of fluorescence and CD detection, water solubilization, real-time monitoring, and chemotherapy.

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GB/T 7714 Duan, Yanjuan , Wang, Jingjing , Cheng, Lin et al. A fluorescent, chiratity-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery [J]. | ORGANIC & BIOMOLECULAR CHEMISTRY , 2022 , 20 (19) : 3998-4005 .
MLA Duan, Yanjuan et al. "A fluorescent, chiratity-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery" . | ORGANIC & BIOMOLECULAR CHEMISTRY 20 . 19 (2022) : 3998-4005 .
APA Duan, Yanjuan , Wang, Jingjing , Cheng, Lin , Duan, Honghong , Tian, Ping , Zhang, Yanmin et al. A fluorescent, chiratity-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery . | ORGANIC & BIOMOLECULAR CHEMISTRY , 2022 , 20 (19) , 3998-4005 .
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Intelligent gold nanoparticles for synergistic tumor treatment via intracellular Ca2+ regulation and resulting on-demand photothermal therapy EI SCIE Scopus
期刊论文 | 2022 , 433 | CHEMICAL ENGINEERING JOURNAL
WoS CC Cited Count: 1 SCOPUS Cited Count: 12
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Abstract :

Designing therapeutics to utilize and manipulate the aberrant high concentration of Ca2+ in tumor cells would be a promising approach for effective tumor therapy. Herein, we fabricated a nanohybrid to significantly reduce the intracellular Ca2+ of tumor cells meanwhile to perform Ca2+ triggered photothermal therapy under 660 nm irradiation for synergistic tumor treatment. This nanohybrid contains gold nanoparticle as core, ethylene glycol bis (2-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA, Ca2+ chelating agent) as shell and folic acid (FA, tumor targeting agent) conjugated polyethylene glycol 4000 (PEG) as corona, where the EGTA shell and PEG-FA corona was connected by esterase-cleavable ester bonds. After injection, the nanohybrid maintained a stable "off state " during blood circulation due to the anti-fouling property and EGTA-blocking performed by PEG section. The PEG-FA would be removed by over-expressed esterase in tumor cells after FA mediated tumor accumulation and endocytosis, which activated EGTA to capture Ca2+ in tumor cells, resulting in the truncation of Ca2+ signaling for tumor inhibition. Moreover, the specific chelation between Ca2+ and the nanohybrid would further cause the intracellular assembly of these nanoparticles in tumor cells, which in situ generated an excellent photothermal agent for enhanced tumor therapy under 660 nm irradiation. Both in vitro and in vivo results showed excellent tumor inhibition and high survival rate of tumor-bearing mice after treatment by our AEPF nanohybrid, indicating this synergistic therapy via on-demand Ca2+ manipulation and Ca2+ triggered photo thermal therapy could be a green approach for tumor treatment with high efficiency and minimum side effects.

Keyword :

Accurate tumor treatment via chain activities Ca(2+)dependent photothermal therapy Esterase triggered intracellular Ca2+ regulation Intelligent Gold Nanoparticles Utilization and manipulation of tumor-specific micro-environments

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GB/T 7714 Guo, Xiaoyan , Su, Qi , Liu, Tao et al. Intelligent gold nanoparticles for synergistic tumor treatment via intracellular Ca2+ regulation and resulting on-demand photothermal therapy [J]. | CHEMICAL ENGINEERING JOURNAL , 2022 , 433 .
MLA Guo, Xiaoyan et al. "Intelligent gold nanoparticles for synergistic tumor treatment via intracellular Ca2+ regulation and resulting on-demand photothermal therapy" . | CHEMICAL ENGINEERING JOURNAL 433 (2022) .
APA Guo, Xiaoyan , Su, Qi , Liu, Tao , He, Xiaoning , Yuan, Pingyun , Tian, Ran et al. Intelligent gold nanoparticles for synergistic tumor treatment via intracellular Ca2+ regulation and resulting on-demand photothermal therapy . | CHEMICAL ENGINEERING JOURNAL , 2022 , 433 .
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Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-?B signaling in hepatocellular carcinoma cells SCIE Scopus
期刊论文 | 2022 , 103 | PHYTOMEDICINE
SCOPUS Cited Count: 11
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Abstract :

Background: Hepatocellular carcinoma (HCC) is a major subtype of liver cancer, with a high mortality rate, and close relation to chronic hepatitis. The components of the NLRP3 inflammasome are poorly expressed or even lost in HCC. Downregulation of the NLRP3 inflammasome expression significantly affects the clinical stages and pathological grade of HCC. According to previous research, Shuanghua decoction (SHD), a traditional folk prescription, has an inhibitory effect on nasopharyngeal cancer. Purpose: This study aimed to reveal the therapeutic potential of the traditional folk recipe, SHD and its demolition recipe for HCC, and to explore the underlying mechanism. Methods: The effect of SHD and its demolition recipe on HCC cell biological behaviors was assessed using the MTT assay, colony formation, LDH release assay, KFluor-Edu staining, annexin V-FITC/PI staining assay, Hoechst staining, wound-healing assay, transwell assay, reactive oxygen species (ROS) release assay, HPLC, nude mice model, HE staining, IHC, western blot, and immunofluorescence staining in vitro and in vivo. Results: SHD was found to inhibit HCC, and Oldenlandia and OP (Oldenlandia: Prunella spike = 2.5:1) were identified as the main ingredients that inhibited the proliferation and migration of HCC cells via the activation of the ROS-mediated NLRP3 inflammasome and inhibition of the NF-kappa B signaling pathway in vitro and in vivo. Conclusion: Overall, Chinese medicine theory and pharmacology research revealed that SHD, Oldenlandia and OP may be promising traditional Chinese medicine for the treatment of HCC.

Keyword :

HCC cells NF-?B signaling NLRP3 inflammasome ROS Shuanghua decoction

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GB/T 7714 Dai, Bingling , Fan, Mengying , Huang, Xiaoyue et al. Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-?B signaling in hepatocellular carcinoma cells [J]. | PHYTOMEDICINE , 2022 , 103 .
MLA Dai, Bingling et al. "Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-?B signaling in hepatocellular carcinoma cells" . | PHYTOMEDICINE 103 (2022) .
APA Dai, Bingling , Fan, Mengying , Huang, Xiaoyue , Gong, Zhengyan , Cao, Hanbing , Hu, Yu et al. Shuanghua decoction exerts anticancer activity by activating NLRP3 inflammasome via ROS and inhibiting NF-?B signaling in hepatocellular carcinoma cells . | PHYTOMEDICINE , 2022 , 103 .
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Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A) SCIE PubMed
期刊论文 | 2021 , 53 | STEM CELL RESEARCH
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Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a two month-old boy and the parents. Jervell and Lange-Nielsen syndrome (JLNS) was diagnosed in the boy carrying combined KCNQ1 frameshift c.431delC (p.I145Sfs*92) and nonsense c.1175G > A(p.W392X) variants inherited from his mother and father respectively. PBMCs were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. IPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carrying identified KCNQ1 variants with corresponding PBMC, and have a normal karyotype. Thus we established three iPSC lines as useful tools for studying the pathophysiological mechanism of JLNS and drug testing.

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GB/T 7714 Zhou, Yafei , Wang, Jie , Li, Huan et al. Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A) [J]. | STEM CELL RESEARCH , 2021 , 53 .
MLA Zhou, Yafei et al. "Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A)" . | STEM CELL RESEARCH 53 (2021) .
APA Zhou, Yafei , Wang, Jie , Li, Huan , Li, Anmao , Wang, Guoxia , Tan, Xiaoqiu et al. Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A) . | STEM CELL RESEARCH , 2021 , 53 .
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Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma SCIE PubMed
期刊论文 | 2021 , 11 (9) | CLINICAL AND TRANSLATIONAL MEDICINE
WoS CC Cited Count: 4
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Abstract :

Background Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. Overexpression of pleomorphic adenoma gene like-2 (PLAGL2) is associated with tumorigenesis. However, its function in HCC is unclear, and there are currently no anti-HCC drugs that target PLAGL2. Drug repositioning may facilitate the development of PLAGL2-targeted drug candidates. Methods The expression of PLAGL2 in HCC clinical tissue samples and HCC cell lines was analyzed by western blotting. The constructed HCC cell models were used to confirm the underlying function of PLAGL2 as a therapeutic target. Multiple in vitro and in vivo assays were conducted to determine the anti-proliferative and apoptosis-inducing effects of selenium sulfide (SeS2), which is clinically used for the treatment of seborrheic dermatitis and tinea versicolor. Results PLAGL2 expression was higher in HCC tumor tissues than in normal adjacent tissues. Its overexpression promoted the resistance of HCC cells of mitochondrial apoptosis through the regulation of the downstream C-MET/STAT3 signaling axis. SeS2 exerted significant anti-proliferative and apoptosis-inducing effects on HCC cells in a PLAGL2-dependent manner. Mechanistically, SeS2 suppressed C-MET/STAT3, AKT/mTOR, and MAPK signaling and triggered Bcl-2/Cyto C/Caspase-mediated intrinsic mitochondrial apoptosis both in vitro and in vivo. Conclusions Our data reveal an important role of PLAGL2 in apoptosis resistance in HCC and highlight the potential of using SeS2 as a PLAGL2 inhibitor in patients with HCC.

Keyword :

C-MET HCC PLAGL2 selenium sulfide STAT3

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GB/T 7714 Yang, Tianfeng , Huo, Jian , Xu, Rui et al. Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma [J]. | CLINICAL AND TRANSLATIONAL MEDICINE , 2021 , 11 (9) .
MLA Yang, Tianfeng et al. "Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma" . | CLINICAL AND TRANSLATIONAL MEDICINE 11 . 9 (2021) .
APA Yang, Tianfeng , Huo, Jian , Xu, Rui , Su, Qi , Tang, Wenjuan , Zhang, Dongdong et al. Selenium sulfide disrupts the PLAGL2/C-MET/STAT3-induced resistance against mitochondrial apoptosis in hepatocellular carcinoma . | CLINICAL AND TRANSLATIONAL MEDICINE , 2021 , 11 (9) .
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Near-infrared and tumor environment Co-activated nanoplatform for precise tumor therapy in multiple models EI SCIE
期刊论文 | 2021 , 24 | APPLIED MATERIALS TODAY
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Chemotherapy based on anti-tumor drugs is one of the most commonly utilized approaches for tumor treatment. However, the uncontrollable toxicity of these drugs to healthy tissue, insufficient therapeutic efficiency and chemotherapeutic resistance induced by hypoxic environment in most types of solid tumors still limited the clinical application of chemotherapy. Herein, a smart nanoplatform responsive to near-infrared (NIR) light and tumor-specific microenvironment is developed for precise and effective tumor therapy via chain procedures of rapid hypoxia inhibition, promoted catalytic medicine and low-resistance chemotherapy. The concept is demonstrated by co-encapsulating ferroferric oxide nanoparticles (Fe3O4 NPs, photothermal agent and catalyst), calcium peroxide (CaO2, H2O2/O-2 generator) and pa-clitaxel (PTX, anticancer drug) into an enzyme and thermal breakable capsule, which contained a bi-layer shell of hyaluronic acid (HA) and lauric acid (LA). The HA layer serves as tumor target agent to guide the nanoplatform to accumulate in tumor tissue, which would be subsequently degraded by the over-expressed hyaluronidase to expose LA layer for further activation by NIR irradiation. Due to the well-defined melting point of LA at 44 degrees C and excellent photothermal property of Fe3O4, the LA layer un-dertakes a NIR-triggered phase-change to release the encapsulated therapeutic agents (CaO2, Fe3O4 and PTX) for controllable tumor therapy. The exposed CaO2 would react with water or acid in tumor cells to produce O-2 and H2O2, where the O-2 not only press PTX out of the capsule to accelerate its release, but reverse the hypoxic environment to inhibit the hypoxia-induced drug resistance for enhanced chemother-apy. The H2O2 would be further converted to cytotoxic hydroxyl radical by Fe3O4 via catalytic medicine (Fenton reaction), resulting in an enhanced anticancer activity. Near-infrared and tumor environment co-activated nanoplatform, Effective hypoxia inhibition, Promoted catalytic medicine, Low-resistance chemotherapy, Precise tumor therapy via chain activities (C) 2021 Elsevier Ltd. All rights reserved.

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GB/T 7714 Chen, Li , Yang, Tianfeng , Tian, Ran et al. Near-infrared and tumor environment Co-activated nanoplatform for precise tumor therapy in multiple models [J]. | APPLIED MATERIALS TODAY , 2021 , 24 .
MLA Chen, Li et al. "Near-infrared and tumor environment Co-activated nanoplatform for precise tumor therapy in multiple models" . | APPLIED MATERIALS TODAY 24 (2021) .
APA Chen, Li , Yang, Tianfeng , Tian, Ran , Yin, Tian , Weng, Lin , Bai, Yongkang et al. Near-infrared and tumor environment Co-activated nanoplatform for precise tumor therapy in multiple models . | APPLIED MATERIALS TODAY , 2021 , 24 .
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Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K SCIE PubMed
期刊论文 | 2021 , 36 (10) , 1525-1535 | HEART AND VESSELS
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The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 +/- 18.65 vs 62.33 +/- 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.

Keyword :

E334K Gender differences genotype correlation Incomplete penetrance MYBPC3&#8211 Phenotype&#8211

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GB/T 7714 Yang, Qian-Li , Zuo, Lei , Ma, Zhi-Ling et al. Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K [J]. | HEART AND VESSELS , 2021 , 36 (10) : 1525-1535 .
MLA Yang, Qian-Li et al. "Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K" . | HEART AND VESSELS 36 . 10 (2021) : 1525-1535 .
APA Yang, Qian-Li , Zuo, Lei , Ma, Zhi-Ling , Lei, Chang-Hui , Zhu, Xiao-Li , Wang, Xuan-Ying et al. Gender- and age-related differences in distinct phenotypes of hypertrophic cardiomyopathy-associated mutation MYBPC3-E334K . | HEART AND VESSELS , 2021 , 36 (10) , 1525-1535 .
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beta(2)-adrenergic receptor affinity chromatography with an interaction force analysis model: A method for analysis of active compounds targeting beta(2)-adrenergic receptor EI SCIE PubMed
期刊论文 | 2021 , 1652 | JOURNAL OF CHROMATOGRAPHY A
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Asthma is one of the most prevalent diseases worldwide, and beta(2)-adrenergic receptor (beta(2)AR) agonists have been reported to be highly effective bronchodilators against this disease. In this study, we successfully constructed a novel CHO-beta(2)AR affinity chromatography (CHO-beta(2)AR/AC), which was evaluated by infrared spectroscopic and scanning electron microscope (SEM) analysis. In addition, CHO-beta(2)AR/AC model exhibited good selectivity and reliability with the relative standard deviation smaller than 5.6% after 30 days. Furthermore, an interaction force analysis model was developed based on CHO-beta(2)AR/AC. The results showed that the interaction force analysis model (Phi center dot E center dot pKa) exhibited a strong correlation with equilibrium dissociation constant (K-D) (r(2)=0.9284, p=0.002) and a good correlation with logarithm of half-maximum effective concentration (pEC(50)) values (r(2)=0.7135, p=0.034). In addition, a pool of clinically approved drugs was screened by this CHO-beta(2)AR/AC model. Codeine was found to bind to and activate beta(2)AR with K-D value of 4.10 x 10(-7) M, leading to increased cyclic adenosine monophosphate (cAMP) production with EC50 of 6.49 x 10(-7) M and reduction of intracellular Ca-2 + concentration, which in turn relaxes bronchial contraction with EC50 of 2.62 x 10(- 6) M. Furthermore, the K-D value and pEC(50) of codeine were within the 95% prediction range of the interaction force analysis model. The results indicate that the CHO-beta(2)AR/AC with interaction force analysis model constructed in this study can be used to effectively and rapidly screen active compounds targeting beta(2)AR. (C) 2021 Elsevier B.V. All rights reserved.

Keyword :

Affinity chromatography beta(2) AR Codeine Drug-receptor interaction Interaction force analysis model

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GB/T 7714 Ma, Weina , Yang, Liu , Liu, Yanhong et al. beta(2)-adrenergic receptor affinity chromatography with an interaction force analysis model: A method for analysis of active compounds targeting beta(2)-adrenergic receptor [J]. | JOURNAL OF CHROMATOGRAPHY A , 2021 , 1652 .
MLA Ma, Weina et al. "beta(2)-adrenergic receptor affinity chromatography with an interaction force analysis model: A method for analysis of active compounds targeting beta(2)-adrenergic receptor" . | JOURNAL OF CHROMATOGRAPHY A 1652 (2021) .
APA Ma, Weina , Yang, Liu , Liu, Yanhong , Lei, Panpan , Zhang, Yanmin . beta(2)-adrenergic receptor affinity chromatography with an interaction force analysis model: A method for analysis of active compounds targeting beta(2)-adrenergic receptor . | JOURNAL OF CHROMATOGRAPHY A , 2021 , 1652 .
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Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1 alpha pathways in breast cancer SCIE PubMed
期刊论文 | 2021 , 84 | PHYTOMEDICINE
WoS CC Cited Count: 3
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Background: Breast cancer is the most common female cancer worldwide. Large hypoxic area is one of the features of tumor microenvironment. Highly activated hypoxia-induced pathways positively correlate with poor clinical response to chemo- and radiotherapy and high mortality in breast cancer patients. Purpose: We explore the effect of sanguinarine on hypoxia-induced activation of Ephrin type-B receptor 4 (EphB4) and hypoxia inducible factor-1 alpha (HIF-1 alpha) pathways in breast cancer. Results: Hypoxia-induced expression of a receptor tyrosine kinase EphB4 was observed in hypoxic breast cancer cell models. Sanguinarine, a natural alkaloid, could effectively combat hypoxia-induced EphB4 and HIF-1 alpha expression. Sanguinarine inhibited the activation of downstream protein signal transducer and activator of transcription-3 (STAT3), thereby blocking hypoxia-induced HIF-1 alpha/STAT3 interaction and downregulating the mRNA levels of their target genes. Mechanically, sanguinarine attenuated HIF-1 alpha protein levels via inhibition of MAPK/ERK pathways and promotion of HIF-1 alpha proteasome degradation. Sanguinarine inhibited STAT3 activation through targeting its upstream EphB4 and accelerating STAT3 dephosphorylation. Correspondingly, xenograft models confirmed that sanguinarine treatment disrupted hypoxia-induced pathways and inhibited tumor growth in vivo. Conclusions: Our results may bring insights to the hypoxia-induced pathways in breast cancers, and suggest sanguinarine as a promising candidate for EphB4 and HIF-1 alpha-targeted inhibition.

Keyword :

Breast cancer Ephrin type-B receptor 4 Hypoxia inducible factor-1 alpha Sanguinarine Signal transducer and activator of transcription-3

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GB/T 7714 Su, Qi , Wang, Jingjing , Wu, Qing et al. Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1 alpha pathways in breast cancer [J]. | PHYTOMEDICINE , 2021 , 84 .
MLA Su, Qi et al. "Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1 alpha pathways in breast cancer" . | PHYTOMEDICINE 84 (2021) .
APA Su, Qi , Wang, Jingjing , Wu, Qing , Ullah, Asmat , Ghauri, Mohsin Ahmad , Sarwar, Ammar et al. Sanguinarine combats hypoxia-induced activation of EphB4 and HIF-1 alpha pathways in breast cancer . | PHYTOMEDICINE , 2021 , 84 .
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