ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Xiancheng Wan,Huili Wang,Qiuhui Qian,Jin Yan
As a commonly used antibacterial agent in daily consumer products, triclosan (TCS) has attracted significant attention due to its potential environmental risks. In this study, we investigated the toxic effects of TCS exposure (1.4 μM) on heart development in zebrafish embryos. Our findings revealed that TCS exposure caused significant cardiac dysfunction, characterized by pericardial edema, malformations in the heart structure, and a slow heart rate. Additionally, TCS exposure induced oxidative damage and abnormal apoptosis in heart cells through the up-regulation of β-adrenergic receptor (β-AR) signaling pathway genes ( adrb1 , adrb2a , arrb2b ), similar to the effects induced by β-AR agonists. Notably, the adverse effects of TCS exposure were alleviated by β-AR antagonists. Using high-throughput transcriptome miRNA sequencing and targeted miRNA screening, we focused on miR-133b, which targets adrb1 and was down-regulated by TCS exposure, as a potential contributor to TCS-induced cardiotoxicity. Inhibition of miR-133b produced similar toxic effects as TCS exposure, while overexpression of miR-133b down-regulated the β-AR signaling pathway and rescued heart defects caused by TCS. In summary, our findings provide new insights into the mechanisms underlying the cardiotoxic effects of TCS. We suggest that targeting the β-AR pathway and miR-133b may be effective strategies for pharmacotherapy in cardiotoxicity induced by environmental pollutants such as TCS.
研究领域:
毒理学
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心脏病学
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分子生物学
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环境科学
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PubMed
高影响因子
Biomedical Materials
·
2024
·Vol. 19
·期 3
·035009
·
IF 3.9
Guancheng Zhan,Lixia Yu,Qiqi Wang,Longyang Jin,Xiaohong Yin,Xiaodong Cao,Huichang Gao
Corneal stromal injury is a common surgical disease. With the development of tissue engineering materials, many artificial corneal scaffolds have been developed to replace allograft corneal transplantation and solve the problem of corneal donor shortage. However, few researchers have paid attention to corneal stromal wound healing. Herein, a nanocomposite of amino modified mesoporous bioactive glass (MBG-NH2) and microRNA-133b (miR-133b) was introduced into the patterned collagen films to achieve corneal stromal injury repair. MBG-NH2 nanoparticles as a nano delivery carrier could efficiently load miR-133b and achieve the slow release of miR-133b. The physicochemical properties of collagen films were characterized and found the microgrooved collagen films loaded with miR-133b@MBG-NH2 nanoparticles possessed similar swelling properties, optical clarity, and biodegradability to the natural cornea. In vitro cell experiments were also conducted and proved that the patterned collagen films with miR-133b@MBG-NH2 possessed good biocompatibility, and miR-133b@MBG-NH2 nanoparticles could be significantly uptake by rabbit corneal stromal cells (RCSCs) and have a significant impact on the orientation, proliferation, migration, and gene expression of RCSCs. More importantly, the patterned collagen films with miR-133b@MBG-NH2 could effectively promote the migration of RCSCs and accelerate wound healing process, and down-regulate the expression levels of α-SMA, COL-I, and CTGF genes associated with myofibroblast differentiation of corneal stromal cells, which has a potential application prospect in the repair of corneal stromal injury.
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高影响因子
Molecular Medicine Reports
·
2021
·Vol. 25
·期 2
·1-13
·
IF 2.952
Hongbin Peng,Pingjiang Ge
It has been reported that long non‑coding RNA HLA complex group 18 (HCG18) is involved in the progression of cancer, acting as an oncogenic gene. The aim of the present study was to investigate the mechanism underlying the action of HCG18 in laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC). The expression levels of HCG18, microRNA (miR)‑133b and fibroblast growth factor receptor 1 (FGFR1) in LHSCC tissues and transfected LHSCC cells were evaluated by reverse transcription‑quantitative PCR or immunohistochemistry. The viability, migration and invasion of transfected LHSCC cells were detected by Cell Counting Kit‑8, wound healing and Transwell assays, respectively. The targeting relationships of HCG18, miR‑133b and FGFR1 were predicted by bioinformatics analysis and confirmed using a dual‑luciferase reporter assay. Moreover, the expression levels of FGFR1, phosphorylated (p)‑PI3K, PI3K, p‑AKT, AKT, p53, Bax and Bcl‑2 in transfected LHSCC cells were measured by western blotting. It was found that the expression levels of HCG18 and FGFR1 were upregulated, but those of miR‑133b were downregulated in LHSCC tissues. Short hairpin RNA (sh) HCG18 and miR‑133b mimic inhibited LHSCC cell viability, while enhancing miR‑133b expression. HCG18 could competitively bind with miR‑133b. Moreover, the miR‑133b inhibitor promoted cell viability, migration, invasion and the expression levels of Bcl‑2, p‑PI3K and p‑AKT, but inhibited the expression levels of p53 and Bax, which were abrogated by shHCG18. miR‑133b could competitively bind with FGFR1, and the miR‑133b mimic decreased the expression level of FGFR1 in transfected LHSCC cells. shFGFR1 promoted the expression levels of p53 and Bax, while inhibiting viability, migration, invasion and Bcl‑2, p‑PI3K and p‑AKT expression in LHSCC cells. In conclusion, the current results indicated that HCG18 facilitated the progression of LHSCC by upregulating FGFR1 via miR‑133b. The present study evaluated the mechanism with regards to the action of HCG18 in LHSCC, and these experimental results may provide novel evidence for targeted therapy of LHSCC.
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高影响因子
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