IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2022
·Vol. 58
·期 2
·96-108
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IF 2.723
Sun Xiaogang,Hou Zhiyun,Li Ning,Zhang Shuangwei
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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产品关联
DOI
PubMed
高影响因子
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 84
·期 6
·1153-1159
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IF 1.516
Xue Guangpu,Xie Xie,Zhou Yang,Yuan Cai,Huang Mingdong,Jiang Longguang
Peptidic inhibitors of proteases are attracting increasing interest not only as drug candidates but also for studying the function and regulation mechanisms of these enzymes. Previously, we screened out a cyclic peptide inhibitor of human uPA and found that Ala substitution of P2 residue turns upain-1 to a substrate. To further investigate the effect of P2 residue on the peptide behavior transformation, we constructed upain-1-W3F, which has Phe replacement in the P2 position. We determined KD and Ki of upain-1-W3F and found that upain-1-W3F might still exist as an inhibitor. Furthermore, the high-resolution crystal structure of upain-1-W3F·uPA reveals that upain-1-W3F indeed stays as an intact inhibitor bind to uPA. We thus propose that the P2 residue plays a nonnegligible role in the conversion of upain-1 to a substrate. These results also proposed a strategy to optimize the pharmacological properties of peptide-based drug candidates by hydrophobicity and steric hindrance.Abbreviations : uPA: urokinase-type plasminogen activator; SPD: serine protease domain; S1 pocket: specific substrate-binding pocket
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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DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2022
·Vol. 10
·期 41
·15439-15450
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IF 8.067
Jiaqing He,Kaixiang Yang,Qiang Zhou,Yongjun Xie,Gang Zou,Haiyang Yang
As a potential candidate for electronic sensors, mechanically robust and flexible conductive hydrogels or organohydrogels have gained increasing attention in recent years. Herein, a new type of flexible and fully recyclable transparent conductive organogel based on KI-containing glycerol was fabricated by one-pot polymerization of N-hydroxyethyl acrylamide (HEAA) dissolved in KI-containing glycerol. Due to the absence of water, the organogel exhibited outstanding anti-freezing and anti-drying behavior. In fact, the mechanical robustness, conductivity, and transparency of the organogel could be well maintained even at −80 °C or 100 °C. Moreover, the organogel also exhibited high sensitivity and reliability and wide sensing ranges for monitoring and distinguishing various physiological signals and human motions. Of particular interest was that the organogel was sensitive to human sweat, due to the adsorption of salted water. Composed of non-covalent cross-linking sites, the organogel was also fully recyclable in polar solvents and could be remolded accordingly. Our experimental results indicated that organogels, instead of hydrogels or organohydrogels, could also be endowed with excellent mechanical strength, conductivity, and performance even under critical conditions. The design and practical application of transparent, environmental tolerant, and stretchable electronic sensors based on organogels will be enhanced and advanced significantly.
研究领域:
材料科学
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生物医学工程
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DOI
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2023
·
IF 7.5
Nayun Kim,Junhye Kwon,Ui Sup Shin,Joohee Jung
Colorectal cancer (CRC) is associated with high incidence and mortality rates. Targeted therapies for CRC cause various adverse effects, necessitating the development of novel approaches to control CRC progression. In this milieu, we investigated the anti-CRC effects of fisetin, a natural plant flavonoid. Cytotoxicity was performed in CRC patient-derived organoids (30 T and 33 T). Fisetin-induced tumor growth was evaluated in a CRC patient-derived organoid xenograft (PDOX) model. RNA sequencing, immunohistochemistry, and western blotting were performed subsequently. Fisetin significantly decreased organoid viability in a dose-dependent manner. In the PDOX model, fisetin significantly delayed tumor growth, showing a decrease in Ki-67 expression and the induction of apoptosis. In tumor tissues, four genes were identified as differentially expressed between the control and fisetin-treated groups. Among these, A-kinase anchoring protein 12 ( AKAP12 ) level was significantly increased by fisetin treatment (fold change > 2, p < 0.05). Notably, fisetin significantly inhibited vascular endothelial growth factor (VEGF) and epithelial cell adhesion molecule (EpCAM) via upregulation of AKAP12. Our results demonstrate the upregulation of AKAP12 mRNA and inhibition of angiogenesis by fisetin as a therapeutic strategy against CRC.
研究领域:
肿瘤学
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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
Oncology Letters
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2016
·Vol. 12
·期 6
·5309-5314
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IF 1.482
Xiao Deng,Qianghong Pu,Erhao Wang,Chao Yu
Human cytochrome P450 (CYP) 2A6 participates in the metabolism of nicotine and precarcinogens, thus the deliberate inhibition of CYP2A6 may reduce cigarette consumption and therefore reduce the risk of developing the types of cancer associated with smoking. The inhibitory effects and mechanisms of celery (Apium graveolens) extract on mouse CYP2A5 and human CYP2A6 activity remain unclear. These effects were investigated in mouse and human liver microsomes using coumarin 7‑hydroxylation in a probe reaction. Celery extract reduced CYP2A5 and CYP2A6 activities in vitro in a dose‑dependent manner. In vivo experiments also showed that celery extract markedly decreased CYP2A5 activity. The inhibition of celery extract on CYP2A5 was time‑ and nicotinamide adenine dinucleotide phosphate (NADPH)‑independent, and was markedly reduced by ultracentrifugation. Additionally, the inhibition of celery extract on CYP2A6 was time and NADPH‑dependent. Levels of inhibition were characterized by a Ki, the measure of the tightness of bonds between the enzyme and its inhibitor, of 266.4 µg/ml for CYP2A5, and a Ki of 1,018 µg/ml and Kinact of 0.3/min for CYP2A6. Kinact is the maximal rate of enzyme inactivation at a saturating concentration of inhibitor. The coumarin derivative 5‑methoxypsoralen present in celery extract did not solely to the inhibition of CYP2A5/6 activity. In conclusion, celery extract inhibited the levels of mouse CYP2A5 and human CYP2A6 activity via different mechanisms: Mixed competitive inhibition for CYP2A5 and mechanism‑based inhibition for CYP2A6.
研究领域:
药理学
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生物化学
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毒理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2024
·
IF 4.9
Qiang Wang,Han Jia,Qiuxia Wang,Jiaxin Li,Chuanqi Li,Han Sun,Ziwei Wei,Xiyang Wang,Wenxin Cao,Pan Huang
Potassium iodide (KI) is regarded as an ideal synergist for typical corrosion inhibitors . However, the synergistic effect of KI may be compromised due to its oxidation in acidic solutions. In this work, the anticorrosion performance of KI with different aging times in HCl solution and their synergistic effect with dodecyltriphenylphosphonium bromide (C 12 TPB) were evaluated via electrochemical tests and surface characterization techniques. The corrosion inhibition efficiency of KI gradually increased from 6.41 % to 38.99 % with increasing aging time to 6 h, while the synergy coefficient between KI and C 12 TPB abnormally decreased from greater than 1.0 to less than 0.4. UV–vis results and quantum chemical calculation demonstrated that the generated I 3 − during the aging process caused negative impact on the adsorption of C 12 TPB, leading to the reduced anticorrosion performance. This study provides valuable insights for the rational utilization of KI as the corrosion inhibitor and synergist.
研究领域:
材料科学
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电化学
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表面科学
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DOI
高影响因子
ChemCatChem
·
2025
·
IF 3.9
Tianao Zhang,Haolong Huang,Yunchong Wang,Qianqian Zhao,Rui Han,Qingling Liu
Graphical CoO x /BCN catalyst with dual active sites was successfully synthesized. This catalyst exhibits excellent selectivity (99%) and a cyclic carbonate yield (98%) in the CO 2 cycloaddition reaction with the nucleophilic reagent KI under solvent-free and mild reaction conditions. This catalyst also has good stability and reusability, providing a new direction for the design of high-performance CO 2 cycloaddition catalysts. The carbon dioxide (CO 2 ) cycloaddition reaction provides an efficient route to achieve resource utilization of CO 2 . However, the inherent chemical stability of CO 2 itself hinders its efficient transformation into cyclic carbonates. Herein, the CoO x /BCN catalyst was successfully prepared by a simple deposition method. The CoO x /BCN exhibited excellent catalytic performance in the CO 2 cycloaddition reaction synergistically catalyzed with the nucleophilic reagent KI under solvent-free and mild reaction conditions (80 °C, 0.8 MPa, 6 h). The yield of cyclic carbonate was 98% and the selectivity was 99%, which was significantly superior to CoO x /CN catalyst (with a cyclic carbonate yield of 73.7%). Furthermore, after six cyclic reactions, CoO x /BCN still maintained a yield of over 93%. It was found that after boron (B) was doped into graphitic carbon nitride (g-C 3 N 4 ), the generated ─NB(OH) 2 group on CoO x /BCN effectively activated the epoxide. Importantly, the interaction between B-doped g-C 3 N 4 and CoO x induced the generation of abundant oxygen vacancies, which provided sufficient active sites for CO 2 adsorption and activation. In addition, carbonates were identified as the main reaction intermediates by in situ DRIFTS, and the possible reaction pathways of the CoO x /BCN catalyst were proposed. Therefore, this work provides new idea for the design of catalysts for CO 2 cycloaddition.
研究领域:
催化
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二氧化碳利用
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材料科学
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化学反应工程
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环境化学
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产品关联
DOI
高影响因子
Food & Function
·
2023
·
IF 6.1
Yichun Liu,Kaimin Niu,Ruxia Wang,Xiaoxiao Liang,Chong Lin,Xin Wu,Zhenya Zhai
Bile acids, such as taurochenodeoxycholic acid (TCDCA), are considered as functional small molecules involved in nutrition regulation or acting with adjuvant therapeutic effects against metabolic or immune diseases. The homeostasis of the intestinal epithelium depends on the conventional cellular proliferation and apoptosis of cells. Herein, mice and normal intestinal epithelial cells (IPEC-J2, a widely used normal intestinal epithelial cell line derived from porcine) were used as models to explore the regulatory effect of TCDCA on the proliferation of intestinal epithelial cells (IECs). In the mouse study, the oral gavage of TCDCA led to a significant reduction in weight gain, small intestinal weight, and the villus height of the intestinal epithelium while inhibiting the gene expression of Ki-67 in the intestinal epithelial crypts of mice (P < 0.05). TCDCA significantly downregulated the expression of the farnesoid X receptor (FXR) and upregulated the expression of caspase-9 in the jejunum (P < 0.05). The results of real-time quantitative PCR (RT-qPCR) suggested that TCDCA significantly inhibited the expression of tight junction proteins zonula occludens (ZO)-1, occludin, claudin-1, and mucin-2 (P < 0.05). In terms of apoptosis-related genes, TCDCA significantly inhibited the expression of Bcl2 and increased the expression of caspase-9 (P < 0.05). At the protein level, TCDCA decreased the expression of Ki-67 and PCNA, as well as FXR (P < 0.05). Caspase inhibitor Q-VD-OPh and guggulsterone, an FXR antagonist, significantly improved the inhibition of TCDCA-induced cell proliferation. Moreover, guggulsterone enhanced TCDCA-induced cell late apoptosis through flow cytometry and significantly lowered the TCDCA-induced up-regulated gene expression of caspase 9, despite both TCDCA and guggulsterone down-regulating the expression of FXR (P < 0.05). Overall, the effect of TCDCA on the induction of apoptosis is not dependent on FXR, whereas it would function via the activation of the caspase system. This provides a new perspective for the application of TCDCA or bile acid as functional small molecules in food, additives, and medicine.
研究领域:
胃肠病学
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分子生物学
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细胞生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2024
·
IF 5.4
Mingyue Ruan,Xinran Wang,Mingxue Guo,Zucheng Hu,Wenjun Hu,Zishuo Guo,Wanling Chen,Shiyan Li,Kai Wu,Shouying Du,Ning Han
Combined chemo-phototherapy has shown considerable advantages and potential in cancer treatment. For this purpose, self-assembled nanoparticles by gambogic acid (GA) and IR780 (referred to as GA-IR780 NPs) were prepared. Herein, GA, an active compound derived from Garcinia hanburyi Hook.f, was selected as a chemo-agent. IR780 was used as a photothermal agent as well as a photosensitizer, which could kill tumor cells via photothermal effect and photodynamic effect. The obtained GA-IR780 NPs were uniform spheres with particle size of ca. 50 nm. The drug loading efficiency of GA and IR780 was 38.42 % and 56.64 %, respectively. The GA-IR780 NPs exhibited excellent photothermal properties as well as photodynamic effect when irradiated by near infrared (NIR) light (808 nm, 2.0 W/cm 2 ). Moreover, the GA-IR780 NPs showed enhanced cytotoxicity with NIR light activation. Results of animal experiments showed that GA-IR780 NPs had the most significant tumor inhibition when irradiated by laser, and the results of H&E , Ki-67 and TUNEL staining confirmed that the GA-IR780 NPs+Laser group caused the most severe tumor tissue damage. The above results indicated that GA-mediated chemotherapy combining with IR780-based phototherapy could significantly improve the anti-tumor efficacy.
研究领域:
药学
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癌症研究
·
纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2020
·Vol. 15
·期 1
·1-18
·
IF 2.96
Qin Zifei,Jia Mengmeng,Yang Jing,Xing Han,Yin Zhao,Yao Zhihong,Zhang Xiaojian,Yao Xinsheng
Background Kang-Ai injection is widely used as an adjuvant therapy drug for many cancers, leukopenia, and chronic hepatitis B. Circulating alkaloids and saponins are believed to be responsible for therapeutic effects. However, their pharmacokinetics (PK) and excretion in vivo and the risk of drug–drug interactions (DDI) through inhibiting human cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes remain unclear.Methods PK and excretion of circulating compounds were investigated in rats using a validated ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS) method. Further, the inhibitory effects of nine major compounds against eleven CYP and UGT isozymes were assayed using well-accepted specific substrate for each enzyme.Results After dosing, 9 alkaloids were found with Cmax and t1/2 values of 0.17–422.70 μmol/L and 1.78–4.33 h, respectively. Additionally, 28 saponins exhibited considerable systemic exposure with t1/2 values of 0.63–7.22 h, whereas other trace saponins could be negligible or undetected. Besides, over 90% of alkaloids were excreted through hepatobiliary and renal excretion. Likewise, astragalosides and protopanaxatriol (PPT) type ginsenosides also involved in hepatobiliary and/or renal excretion. Protopanaxadiol (PPD) type ginsenosides were mainly excreted to urine. Furthermore, PPD-type ginsenosides were extensively bound (fu-plasma approximately 1%), whereas astragalosides and PPT-type ginsenosides displayed fu-plasma values of 12.35% and 60.23–87.36%, respectively. Moreover, matrine, oxymatrine, astragaloside IV, ginsenoside Rg1, ginsenoside Re, ginsenoside Rd, ginsenoside Rc, and ginsenoside Rb1 exhibited no inhibition or weak inhibition against several common CYP and UGT enzymes IC50 values between 8.81 and 92.21 μM. Through kinetic modeling, their inhibition mechanisms towards those CYP and UGT isozymes were explored with obtained Ki values. In vitro-in vivo extrapolation showed the inhibition of systemic clearance for CYP or UGT substrates seemed impossible due to [I]/Ki no more than 0.1.Conclusion sWe summarized the PK behaviors, excretion characteristics and protein binding rates of circulating alkaloids, astragalosides and ginsenosides after intravenous Kang-Ai injection. Furthermore, weak inhibition or no inhibition towards these CYP and UGT activities could not trigger harmful DDI when Kang-Ai injection is co-administered with clinical drugs primarily cleared by these CYP or UGT isozymes.
研究领域:
药理学
·
药剂学
·
药物代谢
·
毒理学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2021
·
IF 0
Linzhi Jing,Xiang Wang,Bin Leng,Ningping Zhan,Hang Liu,Shifei Wang,Yuyun Lu,Jie Sun,Dejian Huang
Scaffold-based three-dimensional (3D) cell culture systems have gained increased interest in cell biology, tissue engineering, and drug screening fields as a replacement of two-dimensional (2D) monolayer cell culture and as a way to provide biomimetic extracellular matrix environments. In this study, microscale fibrous scaffolds were fabricated via electrohydrodynamic printing, and nanoscale features were created on the fiber surface by simply leaching gliadin of poly(ε-caprolactone) (PCL)/gliadin composites in ethanol solution. The microstructure of the printed scaffolds could be precisely controlled by printing parameters, and the surface nanotopography of the printed fiber could be tuned by varying the PCL/gliadin ratios. By seeding mouse embryonic fibroblast (NIH/3T3) cells and human nonsmall cell lung cancer (A549) cells on the printed scaffolds, the cellular responses showed that the fiber nanotopography on printed scaffolds efficiently favored cell adhesion, migration, proliferation, and tissue formation. Quantitative analysis of the transcript expression levels of A549 cells seeded on nanoporous scaffolds further revealed the upregulation of integrin-β1, focal adhesion kinase, Ki-67, E-cadherin, and epithelial growth factor receptors over what was observed in the cells grown on the pure PCL scaffold. Furthermore, a significant difference was found in the relevant biomarker expression on the developed scaffolds compared with that in the monolayer culture, demonstrating the potential of cancer cell-seeded scaffolds as 3D in vitro tumor models for cancer research and drug screening.
研究领域:
组织工程
·
细胞生物学
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癌症研究
·
药物筛选
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产品关联
DOI
PubMed
ANALYTICAL SCIENCES
·
2023
·Vol. 39
·期 6
·935-943
·
IF 1.6
Wang Jingyu,Cui Yunyi,Lin Ying,He Yi
Abstract A long-standing challenge in colorimetric detection of triacetone triperoxide (TATP) explosive is low sensitivity. We herein developed an iodine-mediated photoinduced auto-inductive tandem chromogenic system to achieve exponential signal amplification. The strategy employs the KI-TATP reaction and photo-induced autocatalytical oxidation of o-phenylenediamine (OPD) that work in tandem. The resulting I 3 − from the KI-TATP reaction oxidizes OPD to yellow 2,3-diaminophenazine (DAP) that is further excited by blue light illumination to produce reactive oxygen species (ROS). The obtained ROS, in turn, promotes the oxidation of OPD to gain more DAP, causing the auto-inductive chromogenic reaction processes. This tandem chromogenic system is applied for visual colorimetric detection of TATP, allowing the selective and sensitive detection of TATP down to 42.8 μM. Moreover, analyses of TATP in real samples are performed, and the satisfactory recovery results are achieved. Furthermore, a field detection kit is also developed. Graphical abstract
研究领域:
分析化学
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爆炸物检测
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光化学
·
比色传感器
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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）