CHEMOSPHERE
·
2019
·
IF 5.108
Yan Ma,Luxiu Zang,Danting Wang,Jiahui Jiang,Caihong Wang,Xuedong Wang,Fang Fang,Huili Wang
Triclosan (TCS), one of the important bactericides , is widely used in personal care products, and its chronic exposure leads to severe toxic effects on the growth and development of blood vessels in zebrafish ( Danio rerio ). Herein, we screened out three differentially expressed miRNAs (miR-181a-5p, miR-132-3p and miR-128-3p) by sequencing and qRT-PCR analyses of 4–96-hpf TCS-exposed zebrafish, among which miR-181a-5p was found to regulate many signaling pathways involved in fatty acid biosynthesis and phosphatidylimositol signaling systems. By O-dianisidine staining, TCS-exposure resulted in decreased distribution of red blood cells and induced blood hypercoagulable state and thrombotic effects. Defective subintestinal veins (SIVs), and decreased branching and curvature of blood vessels were observed with increasing TCS-exposure concentrations. After microinjection of miR-181a-5p mimic and inhibitor, zebrafish malformation type and percentage were prominently increased such as distorted SIV vessels along with reduced venation and abnormal branches by ALP staining. Overexpressed miR-181a-5p had a greater effect on development and branching patterns of arteries and veins than its knockdown. By laser confocal microscopy observation, the 72-hpf Tg (flk1: mCherry) zebrafish obviously displayed vascular proliferation and ablation in the miR-181a-5p mimic group. Microinjection of miR-181a-5p mimics and inhibitors led to abnormal expressions (20–50%) of two key target genes ( pax2a and vash2 ) by WISH, and increased malformation percentages (18–45%) by IOD analysis. Overexpression of vash2 led to the inhibitory or promoting effects on the expression of PI3K signaling pathway-related genes, proving that the effect of vash2 on development of blood vessels could be realized by inhibiting PI3K signaling pathway. These observations lay theoretical foundation for deep insight into the molecular mechanisms on TCS-induced cardiovascular diseases.
研究领域:
毒理学
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发育生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Guoqiang Xu,Xiaona Song,Xiaotang Wang,Rui Xue,Xiaoru Yan,Litao Qin,Xiaoqi Chang,Jiping Gao,Zhaoyang Chen,Guohua Song
Purpose Oral squamous cell carcinoma is the most common type of malignant tumor in the head and neck region. Despite advancements, metastasis and recurrence rates remain high, and patient survival has not significantly improved. Although miRNA therapies are promising for cancer gene therapy, their applications in treating oral cancer are limited. Targeted medication delivery systems based on nanotechnology offer an efficient way to enhance oral cancer treatment efficacy.Methods We synthesized nanosilver (AgNPs) and loaded them with the tumor suppressor miR-181a-5p. In vitro experiments were conducted to investigate the inhibitory effects of AgNPs and their composites on the malignant behavior of oral cancer cell lines. The xenograft experiment was utilized to examine their effects on tumorigenesis and the potential molecular mechanisms involved.Results The nanosilver exhibited a spherical morphology with a size distribution ranging from 50 to 100 nm. They exhibited a distinct absorption peak at 330 nm and could be excited to emit green fluorescence. The biocompatible AgNPs effectively shielded miRNA from degradation by RNase and serum. The nanocomposites significantly inhibited the proliferation, invasion, migration, and colony formation of oral cancer cell lines. Notably, treatment with the nanocomposites resulted in substantial tumor growth suppression in the xenograft model. Mechanistically, these composites directly targeted BCL2 and exerted their antitumor effects by suppressing the β-catenin signaling pathway and other downstream genes without inducing acute toxicity.Conclusion Collectively, the findings demonstrate that the miR-181a-5p/AgNPs combination significantly impedes the growth and progression of oral cancer both in vitro and in vivo, highlighting a pivotal role for the β-catenin signaling pathway. This multifaceted approach holds promise as a prospective therapeutic strategy for oral cancer management in the future.
研究领域:
肿瘤学
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分子生物学
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纳米医学
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癌症治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL ANIMALS
·
2020
·
IF 1.574
Yongxia Cheng,Jingchao Li,Chong Wang,Heran Yang,Ying Wang,Tao Zhan,Sufen Guo,Jun Liang,Yuxin Bai,Jianbo Yu,Guibo Liu
Diabetic cardiomyopathy (DCM) is one of the cardiovascular complications of diabetes mellitus independent of hypertension, coronary disease, and other heart diseases. The development of DCM is multifactorial and hard to detect at an early stage. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is emerging as a regulator of DCM, the underlying mechanism of its role in DCM has not been elaborated yet. In this study, we established a mouse DCM model via streptozocin injection as evidenced by cell hypertrophy and cell apoptosis of myocardial tissue, and found that Malat1 expression was upregulated in the myocardium in DCM mice. Meanwhile, elevated expression of pro-apoptotic factors p53, p21, cleaved caspase 3, cleaved caspase 9 and BAX, and down-regulation of anti-apoptotic BCL-2 were observed in DCM myocardium. We further investigated the effect of Malat1 on cardiomyocytes under high glucose condition by silencing Malat1 with its specific short-hairpin RNA. Like in vivo, expression of Malat1 in cardiomyocytes was notably raised, remarkable cell apoptosis and changes in apoptosis-related factors were also observed following high glucose treatment. Besides, we validated that Malat1 acted as a sponge of miR-181a-5p. Inhibition of miR-181a-5p could, at least partially, abolish Malat1 knockdown-induced alteration in cardiomyocytes. In addition, p53, a critical regulator of apoptosis, was validated to be a downstream target of miR-181a-5p. In summary, our findings reveal that Malat1 knockdown attenuates high glucose-induced cardiomyocyte apoptosis via releasing miR-181a-5p, and this mechanism may provide us with new diagnosis target of DCM.
研究领域:
分子生物学
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心脏病学
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糖尿病
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非编码RNA
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioengineered
·
2022
·
IF 6.832
Ning Han,Fei Qian,Xianping Niu,Guoting Chen
Osteonecrosis of the femoral head (ONFH) caused by steroids is a severe orthopedic disorder resulting from the use of high-dose steroid drugs, characterized by structural changes in the bone, joint dysfunction, and femoral head collapse. CircRNAs and miRNAs have increasingly been suggested to play pivotal roles in osteogenic differentiation and osteogenesis. Significant upregulation of circ_0058792 was observed in patients with steroid-induced ONFH. Bioinformatic analysis showed that circ_0058792 might act as a sponge for miR-181a-5p. This study further investigated the mechanisms underlying the role of circ_0058792 and miR-181a-5p in osteogenic differentiation in methylprednisolone-induced ONFH rats and MC3T3-E1 cells. The results showed a notable decrease in the serum of miR-181a-5p in methylprednisolone-induced ONFH rats. Silencing of circ_0058792 using siRNAs and overexpression of miR-181a-5p significantly increased alkaline phosphatase activity and matrix mineralization capacity. Additionally, markers for osteogenic differentiation were significantly upregulated in miR-181a-5p-transfected cells. However, overexpression of circ_0058792 and the addition of the miR-181a-5p inhibitor reversed this increase. Smad7 was identified to be miR-181a-5p’s direct target and circ_0058792 was confirmed to be miR-181a-5p’s competing endogenous RNA (ceRNA). Upregulation of miR-181a-5p promotes phosphorylation of Smad2 and Smad3. Furthermore, circ_0058792 and miR-181a-5p had opposing effects on Smad7 expression. Collectively, these findings indicate that circ_0058792 regulates osteogenic differentiation by sponging miR-181a-5p via the TGF-β/Smad7 pathway. These findings elucidated the functions of circ_0058792 and miR-181a-5p in the regulation of steroid-induced ONFH. Our findings also indicated that circ_0058792 and miR-181a-5p are possible diagnostic markers and therapeutic targets for treating steroid-induced ONFH.
研究领域:
骨科
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分子生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
LABORATORY INVESTIGATION
·
2020
·Vol. 100
·期 9
·1223-1237
·
IF 4.197
Kong Huimin,Wang Huaili,Zhuo Zhihong,Li Zhenbiao,Tian Peichao,Wu Jing,Liu Jian,Chen Zheng,Zhang Jiyao,Luo Qiang
MicroRNAs regulate gene expression at the posttranscriptional level, and this process has been shown to be implicated in the pathological processes of temporal lobe epilepsy. At present, studies about the impact of microRNA-181a (miR-181a) on epilepsy have focused on hippocampal neurons, and the effect of miR-181a on other cells in the hippocampus remains poorly understood. Herein, we explored the role of miR-181a-5p in a lithium-pilocarpine model of epilepticus in immature rats. We found that the hippocampal expression level of miR-181a-5p was increased. Inhibition of miR-181a-5p protected the hippocampus against epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, oxidative stress, mitochondrial function, and cognitive dysfunction. Moreover, miR-181a-5p inhibition exerted a seizure-suppressing effect via SIRT1 upregulation. Overall, our findings reveal the potential role of the miR-181a-5p/SIRT1 pathway in the development of temporal lobe epilepsy, and this pathway may represent a novel target for ameliorating epilepsy and its sequelae.
研究领域:
神经科学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Stem Cells International
·
2026
·Vol. 2026
·期 1
·6997518
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IF 3.6
Fengshan Gan,Fan Zheng,Qingzhu Zhou,Boyan Liu,Bin Yang,Lianzhu Ou,Wenli Huang,Xinxin Yang,Zhuo Gong,Yunyu Xiong,Xian Zhao,Jia He
Background Soft tissue defects refer to defects in or damage to human soft tissue, which may affect the appearance, function, and health of the human body and cause physical and psychological distress to the patient. Hyaluronic acid (HA), a fillable material in the field of plastic medicine, could play a crucial role in reconstructing soft tissues and enhancing the adipogenic differentiation of adipose-derived stem cells (ADSCs). Methods We isolated ADSCs from human subcutaneous adipose tissue and cultured them in HA hydrogel at a density of 2.1 × 10 6 /mL, followed by subcutaneous injections of ADSCs (0.2 mL, 1 × 10 7 cells/mL with 0.2 mL of DMEM) and HA hydrogel (0.2 mL) into the dorsal side of nude mice. The expression of related genes and proteins was detected using RT‒qPCR and western blotting. The adipogenic differentiation of ADSCs and adipogenesis in nude mice were assessed using CCK-8, Oil Red O, and HE staining. Results The results revealed an increase in the levels of miR-181a-5p and adipocyte differentiation-related proteins (PPARγ, C/EBPα, FABP4, and adiponectin) and a decrease in the levels of autophagy-related proteins (LC3II/I, Beclin-1, and ATG5) in ADSCs cocultured with HA hydrogel. The adipogenic differentiation ability of ADSCs was enhanced. From a mechanistic standpoint, HA hydrogel inhibited the expression of ATG5 by promoting the expression of miR-181a-5p, thus inhibiting autophagy, promoting the adipogenic differentiation of ADSCs, and promoting the formation of adipose tissue in vivo. Conclusions Our findings suggest that a combined culture of ADSCs and HA hydrogel may be a new method to enhance the adipogenic differentiation of ADSCs.
✓ 已验证
DOI
PubMed
高影响因子
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