TOXICOLOGY
·
2021
·
IF 4.221
Shuangyu Guo,Bo Zhang,Wen Qi,Xiaolian Cao,Yixuan Xu,Xueting Zhang,Xu Li,Liting Zhou,Lin Ye
Estrogen receptors are involved in regulating the proliferation and invasion process of neuroblastoma . As a kind of estrogen-like environmental endocrine disruptors (EEDs), whether mono-2-ethylhexyl phthalate (MEHP) can affect the proliferation and invasion of neuroblastoma cells via ERs is unknown. The present study aimed to explore the role of ERα in MEHP-induced proliferation, migration, and invasion of SH-SY5Y cells. SH-SY5Y cells were cultured in DMEM with 10 % FBS. Wild-type SH-SY5Y cells and ERα-knockdown SH-SY5Y cells were treated with MEHP (0, 10, 50, and 250 μM) for 12 h and 24 h. The viability of SH-SY5Y cells was detected with a CCK8 kit and cell cycle was measured by flow cytometry. Cell migration was measured using a scratch assay, and cell invasion was tested using a Transwell migration assay. The expression levels of proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), ERα, and ERβ were detected with real-time qPCR and western blotting . MEHP promoted the proliferation of SH-SY5Y cells. The results also showed that MEHP significantly increased the relative migration distance of wild-type SH-SY5Y cells. Conversely, MEHP treatment did not increase the relative migration distance of ERα-knockdown SH-SY5Y cells, suggesting that MEHP promotes the migration of neuroblastoma through ERα. Similarly, MEHP significantly increased the relative number of invaded wild-type SH-SY5Y cells, while the MEHP-induced invasion effect was significantly decreased in ERα-knockdown SH-SY5Y cells. Moreover, the expression levels of PCNA, MMP-2, MMP-9, and ERα cells were upregulated by MEHP in wild-type SH-SY5Y, and the expression level of its tissue inhibitor TIMP-2 was downregulated. In contrast, the expression of PCNA, MMP-2, MMP-9, and ERα was significantly downregulated in ERα-knockdown SH-SY5Y cells, while the expression of TIMP-2 was significantly upregulated. In conclusion, MEHP can upregulate PCNA, MMP-2, and MMP-9, and downregulate TIMP-2, further promoting proliferation, migration, and invasion of neuroblastoma through ERα.
研究领域:
癌症生物学
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毒理学
·
细胞生物学
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DOI
PubMed
高影响因子
Journal of Healthcare Engineering
·
2021
·
IF 2.682
Yongyan Deng,Hongjin Li,Yujiao Tang
Aim. Taurine is believed to have antioxidant properties and has been implicated in the treatment of neurodegenerative disease, atherosclerosis, coronary heart disease, and prostate cancer. This research focused on taurine inhibition effects of expression related to migration and epithelial-mesenchymal transition- (EMT-) A549 study on related genes of human being non-small-cell lung cancer. Methods. MTT assays assessed cell viability and a RadiusTM assay showed that taurine also inhibited the lung cancer cell migration. Using RT-PCR and Western blot, the migration and EMT markers were identified and evaluated. Results. We found that taurine significantly decreased the expression of migration markers matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF). In contrast, TIMP metallopeptidase inhibitor 1 (TIMP-1) and TIMP metallopeptidase inhibitor 2 (TIMP-2) expressions were increased with taurine treatment. In addition, we found an association between taurine treatment and the expression of EMT markers. The expression of epithelial marker E-cadherin and the mesenchymal marker N-cadherin TWIST-1 was decreased, but the expression of zinc finger protein SNAIL-1 and E-zinc finger homeobox 1 (ZEB-1) was increased. Conclusion. Taken together, our study strongly suggests the therapeutic significance of taurine, which possesses antimigration activity and induces EMT markers expression in lung cancer cells.
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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产品关联
DOI
PubMed
高影响因子
BMC Complementary and Alternative Medicine
·
2015
·Vol. 15
·期 1
·1-10
·
IF 2.02
Li Wei,Luo Zhenhua,Liu Xingde,Fu Lingyun,Xu Yini,Wu Lirong,Shen Xianchun
Background To investigate the ameliorated effects of an extract of Ginkgo biloba extract (GBE) on experimental cardiac remodeling in rats induced by acute cardiac infarction, and further explore the mechanism concentrated on myocardial type I collagen, transforming growth factor beta 1 (TGF-β1), matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9), and provide the experimentaldata for clinical application of GBE.Methods Rats were divided into five groups (n = 20) as following: sham operation group (group A), acute myocardial infarction model group (group B), acute myocardial infarction model + aspirin (10 mg/kg) treatment group (group C), acute myocardial infarction model + captopril (20 mg/kg) treatment group (group D) and acute myocardial infarction model + Ginkgo biloba extract (100 mg/kg) treatment group (group E). The rat acute myocardial infarction model was reproduced by ligaturing the left anterior descending artery excluding the sham operation group which did not ligation only completed the operational process. Each group was further subdivided into treatment regimens lasting 4 weeks and 8 weeks. Immunohistochemistry and real-time polymerase chain reaction (PCR) methods were used to detect the protein expression and mRNA transcriptional levels of rat myocardial TGF-β1, type I collagen, MMP-2 and MMP-9.Results Compared with group B, regardless of the length of treatment (4 or 8 weeks), the TGF-β1, MMP-2 and MMP-9 mRNA transcriptional levels, and the protein expression levels of type I collagen, MMP-2 and MMP-9 in groups D, C and E were significantly decreased (P < 0.01). Furthermore, the mRNA expression levels of TGF-β1 in groups D, C and E were significantly lower after 8 weeks compared to after 4 weeks (P < 0.01), as were the expression levels of type I collagen in groups D, C and E (P < 0.05). There was no statistically significant difference in the protein expression levels of MMP-2 and MMP-9 between groups E and C.Conclusion sGBE could inhibit experimental rat myocardial remodeling after acute myocardial infarction via reduced transcription of TGF-β1, MMP-2 and MMP-9 genes and by the decreased expression of type I collagen, MMP-2 and MMP-9 proteins in myocardial cells.
研究领域:
心脏病学
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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
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 408
·期 25
·7067-7075
·
IF 3.125
Dang Qian,Gao Hongfang,Li Zhejian,Qi Honglan,Gao Qiang,Zhang Chengxiao
A simple and sensitive electrogenerated chemiluminescence biosensor was developed to monitor matrix metalloproteinase 2 (MMP-2) by employing a specific peptide (CGPLGVRGK) as a molecular recognition substrate. Bis(2,2′-bipyridine)-4′-methyl-4-carboxybipyridine-ruthenium N -succinimidyl ester-bis(hexafluorophosphate) (Ru(bpy) 2 (mcbpy-O-Su-ester)(PF 6 ) 2 (Ru1) was used as ECL-emitting species and covalently labeled onto the peptide through NH 2 -containing lysine on the peptide via acylation reaction to form Ru1-peptide as an ECL probe. An ECL peptide-based biosensor was fabricated by self-assembling the ECL probe onto the surface of gold electrode. MMP-2 can specifically cleave the Ru1-peptide on the electrode surface, which led the partly Ru1-peptide to leave the electrode surface and resulted in the decrease of the ECL intensity obtained from the resulted electrode in 0.1 M phosphate-buffered saline (pH 7.4) containing tri- n -propylamine. The decreased ECL intensity was piecewise linear to the concentration of MMP-2 in the range from 1 to 500 ng/mL. Moreover, the ECL biosensor is successfully applied to detection of MMP-2 secreted by living cell, such as HeLa cells. Additionally, the biosensor was also applied to the evaluation of matrix metalloproteinase inhibitors. The strategy presented here is promising for other disease-related matrix metalloproteinase assay and matrix metalloproteinase inhibitor profiling with sensitivity and simplicity.
Detection of MMP-2 released from living cells by ECL peptide-based biosensor
研究领域:
生物化学
·
分析化学
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生物技术
·
癌症研究
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产品关联
DOI
PubMed
高影响因子
PHOTOCHEMISTRY AND PHOTOBIOLOGY
·
2023
·
IF 3.3
Xiaoying Mo,Xiaochun Chen,Xiaojiao Pan,Yantong Lu,Guangjuan Pan,Jielan Xie,Zhenzhen Pan,Li Li,Hui Tian,Yaohua Li
Helianthus annuus seed byproduct is a residual product obtained after seed oil extraction. The present study investigated the preventive and repair effects of the H. annuus seed byproduct ethanol extract (HSE) on ultraviolet radiation (UVR)-induced injury in human immortalized keratinocytes (HaCaTs) and human skin fibroblasts (HSFs). Results revealed that the total phenolic acid and oligosaccharide content in HSE was >50%. HSE had a stronger preventive effect on UVR-induced injury than the repair effect. Moreover, phenolic acids were the main active component of HSE mediating the preventative effect. In HaCaTs and HSFs, HSE prevented UVR-induced injury by inhibiting excessive ROS production. It reduced the secretion of tumor necrosis TNF-α, IL-1α, IL-1β, IL-6, and IL-8 by inhibiting the level of ROS, thus reducing inflammation-mediated injury to skin cells. In addition, HSE inhibited the expression of various mRNA kinases in the MAPK–ERK/p38/JNK pathway. This downregulated the expression of activator protein-1 (AP-1) mRNA and further reduced the secretion of matrix metalloproteinase (MMP)-1, MMP-3, and MMP-9 as well as reduced UVR-induced injury to the cells. In conclusion, HSE is a broad-spectrum, natural UV filter with high efficiency and low toxicity that has the potential to be used in sunscreen products.
研究领域:
药理学
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皮肤病学
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植物科学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Biosystems
·
2018
·Vol. 2
·期 10
·1800115
·
IF 0
Jin Hong,Yu-Feng Chen,Yu Ma,Fen-Fen Zhang,Chun-Ming Wang,Ya Ding
To directly compare the surface modifier effects on the property regulation of nanoparticle (NP)-based systems, a fluorescence quenched nanoprobe (GpF) responsive to matrix metalloproteinases (MMPs) is employed as a demonstration. Polyethylene glycol (PEG) and bovine serum albumin (BSA) are modified on the surface of GpF via different modes, the S Au covalent bond and nonspecific interaction, respectively. PEG and BSA display similarly protective capability to GpF and increase their biocompatibility that are demonstrated in stability, cytotoxicity, and hemolysis studies. Although PEGylated NPs show better in vivo long circulation property than BSA-decorated ones, the merit of BSA in controlling the system size in a relatively small range improves the penetration of GpF-BSA in tumor tissues and reduces the accumulation in normal tissues. Through an MMP-dominated catalysis and then a glutathione-assisted replacement process, the fluorescence recovery of GpF-BSA shows higher efficiency than PEG-modified NPs. It can be explained by the low steric hindrance and exchangeable manner of BSA on the surface of GpF. The results in this work demonstrate that an endogenous protein having dysopsonization function will be a promising material for the construction and surface modification of nanosystems for biomedical applications.
研究领域:
生物医学工程
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纳米医学
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分子生物学
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产品关联
DOI
Experimental and Therapeutic Medicine
·
2023
·Vol. 26
·期 6
·1-12
·
IF 2.7
Jun Li,Changjun Yu,Kangmin Yu,Zhiyong Chen,Dan Xing,Binshan Zha,Wentao Xie,Huan Ouyang
Thoracic aortic dissection (TAD) is a severe and extremely dangerous cardiovascular disease. Proliferation, migration and phenotypic switching of vascular smooth muscle cells (SMCs) are major pathogenetic mechanisms involved in the development of TAD. The present study was designed to investigate the expression and potential function of serine peptidase inhibitor Kunitz type 2 (SPINT2) in TAD. The gene expression profile data for ascending aorta from patients with TAD were downloaded from the GEO database with the accession number GSE52093. Bioinformatics analysis using GEO2R indicated that the differentially expressed SPINT2 was prominently decreased in TAD. The expression levels of SPINT2 mRNA and protein in aortic dissection specimens and normal aorta tissues were measured using reverse transcription‑quantitative PCR and western blotting. SPINT2 expression was downregulated in clinical samples from aortic dissection specimens of patients with TAD compared with the corresponding expression noted in tissues derived from patients without TAD. In vitro, platelet‑derived growth factor BB (PDGF‑BB) was applied to induce the isolated primary mouse aortic SMC phenotypic modulation (a significant upregulation in the expression levels of synthetic markers), and the SMCs were infected with the adenoviral vector, Ad‑SPINT2, to construct SPINT2‑overexpressed cell lines. SMC viability was detected by an MTT assay and SMC proliferation was detected via the presence of Ki‑67‑positive cells (immunofluorescence staining). To explore the effects of SPINT2 on SMC migration, a wound healing assay was conducted. ELISA and western blotting assays were used to measure the content and expression levels of MMP‑2 and MMP‑9. The expression levels of vimentin, collagen I, α‑SMA and SM22α were measured using western blotting. The PDGF‑BB‑induced proliferation and migration of SMCs were recovered by SPINT2 overexpression. The increase in the expression levels of SPINT2 reduced the expression levels of active matrix metalloproteinases (MMPs), MMP‑2 and MMP‑9. Overexpression of SPINT2 suppressed SMC switching from a contractile to a synthetic type, as evidenced by decreased vimentin and collagen I expression levels along with increased α‑smooth muscle actin and smooth muscle protein 22‑α expression levels. Furthermore, activation of ERK was inhibited in SPINT2‑overexpressing SMCs. A specific ERK agonist, 12‑O‑tetradecanoylphorbol‑13‑acetate, reversed the SPINT2‑mediated inhibition of SMC migration and the phenotypic switching. Collectively, the data indicated that SPINT2 was implicated in the proliferation, migration and phenotypic switching of aortic SMCs, suggesting that it may be involved in TAD progression.
研究领域:
心血管疾病
·
分子生物学
·
细胞生物学
·
病理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Hao Zhang,Wenjing Yan,Jinhui Wang,Shuqian Xie,W. Andy Tao,Chien-Wei Lee,Xing Zhang,Guiyuan Zhang,Yufeng Liu,Dong Wei,Jing Hu,Haohan Liu,Fengying Liu,Yamei Nie,Xue Chen,Hongtao Xu,Jiang Xia,Shizhi Wang
Osteoarthritis (OA) is the most prevalent degenerative cartilage disease, but no effective treatment is currently available to ameliorate the dysregulation of cartilage catabolism. Cartilage degeneration is closely related to the change in the physiology of chondrocytes: for example, chondrocytes of the OA patients overexpress matrix metallopeptidase 13 (MMP13), a.k.a. collagenase 3, which damages the extracellular matrix (ECM) of the cartilage and deteriorate the disease progression. Inhibiting MMP13 has shown to be beneficial for OA treatments, but delivering therapeutics to the chondrocytes embedded in the dense cartilage is a challenge. Here, we engineered the exosome surface with the cartilage affinity peptide (CAP) through lipid insertion to give chondrocyte-targeting exosomes, CAP-Exo, which was then loaded with siRNA against MMP13 (siMMP13) in the interior to give CAP-Exo/siMMP13. Intra-articular administration of CAP-Exo/siMMP13 reduced the MMP13 level and increased collagen COL2A1 and proteoglycan in cartilage in a rat model of anterior cruciate ligament transection (ACLT)-induced OA. Proteomic analysis showed that CAP-Exo/siMMP13 treatment restored the altered protein levels in the IL-1β-treated chondrocytes. Taken together, a facile exosome engineering method enabled targeted delivery of siRNA to chondrocytes and chondrocyte-specific silencing of MMP13 to attenuate cartilage degeneration.
研究领域:
医学
·
分子生物学
·
再生医学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2019
·Vol. 18
·期 3
·1793-1799
·
IF 1.448
Huijuan Zhai,Teng Pan,Haiyan Yang,Haiyu Wang,Yadong Wang
Cadmium (Cd) is an established carcinogen that is involved in the progression of lung cancer. However, the mechanisms underlying this Cd‑induced process have yet to be fully elucidated. The present study explored the potential roles of phosphorylated (p)‑ERK in the Cd‑induced migration and invasion of lung cancer cells. An MTT assay was performed to evaluate cell viability whilst western blot analysis and reverse transcription‑quantitative PCR were used to detect the expression of protein and mRNA, respectively. Migration and invasion assays were performed to assess cell migratory and invasive abilities. The results demonstrated that exposure to Cd increased the expression of p‑ERK in A549 cells. Cd also enhanced the migration and invasion of A549 cells, which could be blocked via U0126 treatment (an inhibitor of mitogen activated protein kinase). In addition, it was identified that Cd‑induced expression of matrix metalloproteinases 2 mRNA was mediated by p‑ERK. In conclusion, the present findings indicated that Cd induced A549 cell migration and invasion by activating ERK, and it was hypothesized that p‑ERK could serve as a target in the clinical treatment of Cd‑induced lung cancer.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Reproductive and Developmental Medicine
·
2022
·
IF 0
Wang Xian-Li,Tang Jing
Objective: Hydrogen sulfide (H 2 S) has been elucidated that it promotes migration and invasion in human placenta trophoblasts. However, the signaling pathway underlying H 2 S-based regulation of trophoblasts remains unknown. Hence, we investigated the potential effect of sodium hydrosulfide (NaHS), an exogenous H 2 S donor, on extravillous trophoblasts. Methods: The Cell Counting Kit-8 was used to detect the proliferative activity of trophoblasts and to screen the optimal concentration of NaHS. The migration and invasion of HTR8/SVneo cells were measured by Transwell assays. Gene expression was determined by quantitative real-time PCR analysis. Protein expression was determined by western blot. Results: We found that NaHS could promote the proliferation , migration , and invasion of HTR8/SVneo cells. The phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK) were activated by NaHS. Moreover, NaHS also upregulated the expression of matrix metalloproteinase-2(MMP-2) and MMP-9, downregulated the expression of E-cadherin in HTR8/SVneo cells. The application of NaHS could increase the expression of cystathionine-β-synthase. Conclusion: Both FAK–Src signaling and the upstream signaling cascade of ERK activation play a significant important role in NaHS-induced proliferation , migration , and invasion via upregulating activity of MMP-2, MMP-9, and downregulating E-cadherin in HTR8/SVneo cells. These novel findings may provide a strong foundation for the clinical application of H 2 S donor drugs.
研究领域:
细胞生物学
·
分子生物学
·
生殖生物学
·
药理学
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DOI
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 11
·5720-5731
·
IF 4.302
Jianle Wang,Chongan Huang,Zongze Lin,Xiangxiang Pan,Jiaoxiang Chen,Gang Zheng,Naifeng Tian,Yingzhao Yan,Zengjie Zhang,Jianing Hu,Pu Cheng,Xiangyang Wang,Xiaolei Zhang
Intervertebral disc degeneration (IVDD) is one of the major causes of low back pain. Polydatin (PD) has been shown to exert multiple pharmacological effects on different diseases; here, we test the therapeutic potential of PD for IVDD. In in-vitro experiments, we confirmed PD is nontoxic to nucleus pulposus cells (NPCs) under the concentration of 400 μmol/L. Furthermore, PD was able to decrease the level of senescence in TNF-α-treated NPCs, as indicated by β-gal staining as well as senescence markers p53 and p16 expression. In the aspect of extracellular matrix (ECM), PD not only reduced metalloproteinase 3 (MMP-3), metalloproteinase 13 (MMP-13) and a disintegrin-like and metalloproteinase thrombospondin type 1 motif 4 (ADAMTS-4) expression, but also increased aggrecan and collagen II levels. Mitochondrion is closely related to cellular senescence and ECM homeostasis; mechanistically, we found PD may rescue TNF-α-induced mitochondrial dysfunction, and it may also promote Nrf2 expression and activity. Silencing Nrf2 partly abolished the protective effects of PD on mitochondrial homeostasis, senescence and ECM homeostasis in TNF-α-treated NPCs. Correspondingly, PD ameliorated IVDD in rat model by promoting Nrf2 activity, preserving ECM and inhibiting senescence in nucleus pulposus cells. To sum up, our study suggests that PD exerts protective effects in NPCs against IVDD and reveals the underlying mechanism of PD on Nrf2 activation in NPCs.
研究领域:
药理学
·
骨科
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2022
·Vol. 50
·期 5
·1-14
·
IF 5.314
Weichao Sun,Wei Xie,Dixi Huang,Yinxing Cui,Jiaji Yue,Qifei He,Luoyong Jiang,Jianyi Xiong,Wei Sun,Qian Yi
Osteoarthritis (OA) is the most common degenerative disease affecting the joints, and inflammation appears to play a critical role in the initiation and progression of OA. Caffeic acid phenethyl ester (CAPE), a natural flavonoid compound, has anti‑inflammatory and antioxidant functions. However, its anti‑inflammatory effects on OA and the underlying mechanisms of action of CAPE in the treatment of OA remain elusive. Therefore, the present study investigated the anti‑inflammatory effects of CAPE on IL‑1β‑stimulated chondrocytes in vitro and surgically induced rat models of OA in vivo. In vitro, CAPE reduced the expression of inducible nitric oxide synthase and cyclooxygenase‑2 in IL‑1β‑stimulated chondrocytes, as well as the extracellular secretion of nitric oxide and prostaglandin E2 in the cell culture supernatants. In addition, CAPE attenuated the degradation of extracellular matrix by increasing the expression of aggrecan and collagen II, and decreasing the expression of MMP3, MMP13 and a disintegrin and metalloproteinase with thrombospondin motif‑5. Furthermore, CAPE attenuated NF‑κB signaling and activated the nuclear factor erythroid 2‑related factor 2/heme oxygenase‑1 signaling pathway in IL‑1β‑stimulated chondrocytes. In vivo, CAPE protected cartilage from destruction and delayed the progression of OA in rats. Taken together, the findings of the present study indicated that CAPE may be a potential therapeutic agent for the prevention or treatment of OA.
研究领域:
药理学
·
风湿病学
·
分子生物学
·
细胞生物学
✓ 已验证
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）