INTERNATIONAL IMMUNOPHARMACOLOGY
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2022
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IF 5.714
Yaojian Rao,Junjie Li,Ruofei Qiao,Jinxin Luo,Yan Liu
Background Both Tetramethylpyrazine (TMPZ) and Astragaloside IV (AGS-IV) can ameliorate neuronal apoptosis and neuroinflammation in CNS diseases. This study revolves around the underlying mechanism of TMPZ and AGS-IV in spinal cord injury (SCI)-associated neuropathic pain (NP). Materials and methods An in-vivo NP model was constructed in Sprague-Dawley (SD) rats via SCI. qRT-PCR was employed to detect OIP5-AS1 and miR-34a. The paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of the rats were evaluated. Neuronal apoptosis in the spinal cord of rats was examined by Nissl staining and TUNEL staining. The interactions between OIP5-AS1 and miR-34a as well as miR-34a and Sirt1 were investigated through dual luciferase assay and RIP assay. The protein expressions of Bad, Bax, Caspase-3, iNOS, COX2, NF-κB, and Sirt1 were examined by western blot. Results TMPZ and AGS-IV combination relieved behavioral symptoms of neuropathic pain in the SCI rat model, enhanced the levels of OIP5-AS1 and Sirt1, and lowered the profile of miR-34a. OIP5-AS1 downregulation weakened the neuroprotective function of TMPZ and AGS-IV in SCI rats and reversed their anti-inflammatory and anti-apoptotic effects on LPS-elicited primary spinal cord neurons. miR-34a was identified as a target of OIP5-AS1. Upregulated miR-34a partly abated the protective functions of TMPZ and AGS-IV in primary spinal cord neurons. Additionally, miR-34a targeted and repressed Sirt1, thus activating the NF-κB pathway and inflammatory reactions. Sirt1 inhibition reduced the protective effects mediated by OIP5-AS1. Conclusion TMPZ and AGS-IV ameliorate SCI-elicited NP via the OIP5-AS1/miR-34a/Sirt1/NF-κB pathway.
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Materials Today Bio
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2023
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IF 8.2
Zhaowei Yin,Chaoren Qin,Shaowei Pan,Chen Shi,Guanfu Wu,Yan Feng,Jing Zhang,Ziyi Yu,Bin Liang,Jianchao Gui
Exosomes (Exos) secreted by adipose-derived stem cells (ADSCs) have shown potential in alleviating osteoarthritis (OA). Previous studies indicated that infrapatellar fat pad (IPFP) derived stem cells (IPFSCs) may be more suitable for the treatment of OA than subcutaneous adipose tissue (ScAT) derived stem cells (ScASCs). However, it remains unclear which type of Exos offers superior therapeutic benefit for OA. This study first compared the differences between Exos derived from IPFP stem cells (Exos IPFP ) and ScAT stem cells (Exos ScAT ) in OA treatment. Results suggested that Exos IPFP significantly inhibit the degradation of cartilage extracellular matrix (ECM) than Exos ScAT , following this, the differences in microRNA (miRNA) expression between the two types of Exos using small RNA sequencing were performed. Subsequently, miR-99 b-3p was chosen and over-expressed in Exos ScAT (Exos ScAT−99b−3p ), both in vivo and in vitro experiments demonstrated its efficacy in inhibiting the expression of ADAMTS4, promoting the repair of the ECM in OA. Finally, microfluidic technology was performed to fabricate a hyaluronan-based hydrogel microparticles (HMPs) for encapsulating Exos (HMPs@exos), the injectability, sustained release of Exos and long-term therapeutic effect on OA were validated. In summary, these results suggest miR-99 b-3p regulates the degradation of cartilage ECM by targeting ADAMTS4, the upregulation of miR-99 b-3p in Exos ScAT would enable them to exhibit comparable or even superior effectiveness to Exos IPFP for OA treatment, making it a promising approach for OA treatment. Considering the abundant resources of ScAT and the limited availability of IPFP, ScAT harvested through liposuction could be genetically engineered to yield Exos for OA treatment. Furthermore, the encapsulation of Exos in HMPs provides an injectable sustained local drug release system, which could potentially enhance the efficacy of Exos and hold potential as future therapeutic strategies.
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EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2023
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IF 2
Jing Guo,Chang-Yong Tong,Jian-Guang Shi,Xin-Jian Li,Xue-Qin Chen
Lung cancer is prone to bone metastasis, and osteopontin (OPN) has an important significance in maintaining bone homeostasis. The goal of this study was to explore the impact of OPN level on bone metabolism and the molecular mechanism of inhibiting bone metastasis in non-small cell lung cancer (NSCLC). The expression of OPN in NSCLC was ascertained by Western blot and immunohistochemistry, and the correlation between the expression level of OPN and survival of patients was analyzed. Then the shRNA technology was applied to reduce the expression of OPN in NSCLC cells, and CCK-8 assay was carried out to investigate the effect of low expression of OPN on the proliferation of NSCLC cells. In addition, the effects of low expression of OPN on osteoclast differentiation, osteoblast generation and mineralization were studied using osteoclast precursor RAW264.7 and human osteoblast SaOS-2 cells, and whether OPN could regulate miR-34c/ Notch pathway to affect bone metabolism was further explored. The findings showed that the high level of OPN in NSCLC was closely related to the poor prognosis of patients and the abnormal proliferation of NSCLC cell lines. The suppression of OPN was beneficial to inhibit the differentiation of osteoclasts and promote the mineralization of osteoblasts. Besides, this study confirmed that the deletion of OPN can regulate bone metabolism through the regulation of miR-34c/Notch1 pathway, which will contribute to inhibiting the occurrence of osteolytic bone metastasis in NSCLC.
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Cancer Medicine
·
2023
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IF 4
Jun Ma,Di Zhao,Dahai Yu,Wei Song,Xiaofang Yang,Haitao Yin
Background Ginsenoside Rh2 (G-Rh2) exerts anti-tumor activity in non-small cell lung cancer (NSCLC). microRNAs (miRNAs, miRs) play pivotal roles in NSCLC. We aimed to investigate whether G-Rh2 inhibited NSCLC progression by targeting miRNA. Methods Cell viability, apoptosis and cycle were determined by Cell Counting Kit-8, 6-diamidino-2-phenylindole (DAPI) staining and flow cytometry. The potential target miRNAs of G-Rh2 were screened by real-time quantitative polymerase chain reaction (RT-qPCR). The difference in miR-28-5p expression between lung adenocarcinoma (LUAD) tissues and normal tissues or lung squamous cell carcinoma (LUSC) tissues and normal tissues was retrieved from TCGA-LUAD and TCGA-LUSC, respectively. Kaplan–Meier Plotter was conducted to analyze the survival rate for different serine/threonine-protein kinase 4 (STK4) expressions with different prognostic risks. immunohistochemistry of STK4 expression in non-tumor and tumor tissues was analyzed from the HPA database. RT-qPCR and Western blot were adopted for detecting mRNA and protein expression. TargetScan V7.2, miRanda and PITA were adopted for predicting targets of miR-28-5p, overlapped genes were subjected to GO analysis. The interactions of miR-28-5p-Wnt and miR-28-5p-STK4 were detected by TOP/FOP luciferase reporter assay and dual luciferase reporter assay, respectively. Results Current study observed that G-Rh2 reduced miR-28-5p expression in NSCLC cells dose-dependently. miR-28-5p was upregulated in NSCLC tissues and cells. The target genes of miR-28-5p were enriched in negative regulation of Wnt signaling. miR-28-5p inhibitor inactivated Wnt signaling, inhibited cell viability and cell cycle, while enhanced cell apoptosis of NSCLC cells by targeting STK4. G-Rh2 exerted the similar effects with miR-28-5p inhibitor by reducing miR-28-5p. G-Rh2 and miR-28-5p inhibitor exerted a synergistic effect on inhibiting NSCLC tumor growth. Conclusion In conclusion, G-Rh2 attenuates NSCLC development by affecting miR-28-5p/STK4 axis and inactivating Wnt signaling. Taken together, we project out a novel therapeutic target for NSCLC.
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International Journal of Genomics
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2023
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IF 2.9
Yi Zhu,Xiaofeng Tian,Yan Wang,Chengxiang Wang,Naiquan Yang,Lianghong Ying,Hongyan Niu
Vascular smooth muscle cells (VSMCs) are critical elements of the vascular wall and play a crucial role in the genesis and development of atherosclerosis (AS). Increasingly, studies have indicated that long noncoding RNAs (lncRNAs) regulate VSMC proliferation, apoptosis, and other biological processes. Nevertheless, the role of lncRNA NFIA-AS1 (hereinafter referred to as NFIA-AS1) in VSMCs and AS remains unclear. Quantitative real-time PCR (qRT-PCR) was performed to analyze the messenger RNA (mRNA) levels of NFIA-AS1 and miR-125a-3p. CCK-8 and EdU staining were performed to detect VSMC proliferation. VSMC apoptosis was evaluated by flow cytometry. The expression of various proteins was detected using western blotting. The levels of inflammatory cytokines secreted by VSMCs were measured by enzyme linked immunosorbent assay (ELISA). The binding sites of NFIA-AS1 and miR-125a-3p, as well as miR-125a-3p and AKT1, were analyzed using bioinformatics methods and validated using a luciferase reporter assay. The function of NFIA-AS1/miR-125a-3p/AKT1 in VSMCs was clarified through loss- and gain-of-functional experiments. We confirmed that NFIA-AS1 was highly expressed in AS tissues and VSMCs induced by oxidized low-density lipoprotein (Ox-LDL). Knockdown of NFIA-AS1 restrained the exceptional growth of Ox-LDL-induced VSMCs, promoted their apoptosis, and decreased the secretion of inflammatory factors and expression of adhesion factors. In addition, NFIA-AS1 regulated the proliferation, apoptosis, and inflammatory response of VSMCs through the miR-125a-3p/AKT1 axis, suggesting that NFIA-AS1 may be a potential therapeutic target for AS.
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International Journal of Nanomedicine
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2023
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IF 8
Xiao Liang,Yudi Wang,Hui Shi,Mengmeng Dong,Haobo Han,Quanshun Li
Background Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.Materials and Methods The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. The therapeutic efficacy and related mechanism of micelles were explored based on the in vitro and in vivo active targeting ability and the suppression of MDR, using hepatocellular carcinoma cell line HepG2 as a model.Results The micelle was demonstrated to possess favorable cellular uptake and tumor penetration ability by specifically recognizing the nucleolin in an AS1411 aptamer-dependent manner. Further, the intracellular accumulation of doxorubicin was significantly improved due to the suppression of ABCG2-mediated drug efflux by miR-519c, resulting in the efficient inhibition of tumor growth.Conclusion The micelle-mediated co-delivery of doxorubicin and miR-519c provided a promising strategy to obtain ideal anti-cancer efficacy through the active targeting function and the reversion of MDR.
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ADVANCED FUNCTIONAL MATERIALS
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2016
·Vol. 26
·期 15
·2532-2544
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IF 11.382
Shengnan Huang,Shaofeng Duan,Jing Wang,Shijin Bao,Xiaojing Qiu,Chunming Li,Ying Liu,Lijuan Yan,Zhenzhong Zhang,Yurong Hu
Therapeutic strategies based on modulation of microRNAs (miRNAs) activity hold much promise for cancer therapy, but for clinical applications, the efficient delivery of miRNAs to tumor cells or tumor tissues remains a great challenge. In this work, microRNA-181b inhibitor (anti-miR-181b) is successfully condensed into polyethyleneimine (PEI)-modified and folate receptor (FR)-targeted PEGylated gold nanocages (AuNCs). This delivery system is designated as anti-miR-181b/PTPAuNCs nanocomplexes (PTPAuNC-NPs), which begin with chemical modification of AuNCs with SH-PEG 5000 -folic acid (SH-PEG 5000 -FA) and SH-PEG 5000 through a gold–sulfur bond, followed by conjugating PEI using lipoic acid as a linker. Finally anti-miR-181b is condensed via electrostatic interactions. In vitro and in vivo experiments show that PTPAuNC-NPs can efficiently deliver anti-miR-181b into target sites to suppress tumor growth, and considerably decrease tumor volumes in SMMC-7721 tumor-bearing nude mice under near-infrared radiation. All these results suggest that PTPAuNC-NP gene delivery system with combination of gene therapy and photothermal therapy will be of great potential use in future cancer therapy.
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Advanced Science
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2024
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IF 14.3
Gaoxiang Yu,Yijie Chen,Ningning Yang,Haojie Zhang,Xuzi Zhang,Yibo Geng,Jiayi Zhao,Zhuliu Chen,Chengji Dong,Lidan Lin,Jianjun Qi,Xuanlong Zhang,Xiaoqiong Jiang,Weiyang Gao,Yuepiao Cai,Xiangyang Wang,Jian Ding,Jian Xiao,Kailiang Zhou
Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.
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BIOCHEMICAL PHARMACOLOGY
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2024
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IF 5.3
Jin Wu,Xiang Li,Hepeng Nie,Yue Shen,Zixiang Guo,Catherine Huihan Chu,Kunzhan Cai,Chunbo Tang
Diabetes-related hyperglycemia inhibits bone marrow mesenchymal stem cell (BMSC) function, thereby disrupting osteoblast capacity and bone regeneration. Dietary supplementation with phytic acid (PA), a natural inositol phosphate, has shown promise in preventing osteoporosis and diabetes-related complications. Emerging evidence has suggested that circular (circ)RNAs implicate in the regulation of bone diseases, but their specific regulatory roles in BMSC osteogenesis in hyperglycemic environments remain elucidated. In this study, in virto experiments demonstrated that PA treatment effectively improved the osteogenic capability of high glucose-mediated BMSCs. Differentially expressed circRNAs in PA-induced BMSCs were identified using circRNA microarray analysis. Here, our findings highlight an upregulation of circEIF4B expression in BMSCs stimulated with PA under a high-glucose microenvironment. Further investigations demonstrated that circEIF4B overexpression promoted high glucose-mediated BMSC osteogenesis . In contrast, circEIF4B knockdown exerted the opposite effect. Mechanistically, circEIF4B sequestered microRNA miR-186-5p and triggered osteogenesis enhancement in BMSCs by targeting FOXO1 directly. Furthermore, circEIF4B inhibited the ubiquitin-mediated degradation of IGF2BP3, thereby stabilizing ITGA5 mRNA and promoting BMSC osteogenic differentiation. In vivo experiments, circEIF4B inhibition attenuated the effectiveness of PA treatment in diabetic rats with cranial defects. Collectively, our study identifies PA as a novel positive regulator of BMSC osteogenic differentiation through the circEIF4B/miR-186-5p/FOXO1 and circEIF4B/IGF2BP3/ITGA5 axes, which offers a new strategy for treating high glucose-mediated BMSC osteogenic dysfunction and delayed bone regeneration in diabetes.
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Materials Today Bio
·
2025
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IF 10.2
Xiaofei Zhang,Linzi Ma,Xiaotong Liu,Xingyu Zhou,Ao Wang,Yunhui Lai,Jun Zhang,Ying Li,Shiling Chen
Background Premature ovarian insufficiency (POI) refers to the severe decline or failure of ovarian function in women younger than 40 years of age. It is a serious hazard to women's physical and mental health, but current treatment options are limited. Mesenchymal stem cell-derived exosomes (MSC-Exo) exhibit promising potential as a therapeutic approach for POI. However, their clinical application is hindered by their instability and low long-term retention rate in vivo . Methods and Results In this study, miR-21 was identified as the predominant miRNA with low-expression in follicular fluid exosomes of POI patients and was shown to possess antiapoptotic activity. Next, we loaded miR-21 agomir to MSC-Exo to form Agomir21-Exo, which significantly reversed the apoptosis of granulosa cells in vitro. Moreover, we successfully developed GelMA hydrogel microspheres for encapsulating Agomir21-Exo through microfluidic technology, named GelMA-Ag21Exo, which had good injectability and significantly enhanced the stability and long-term retention of Agomir21-Exo in mice through sustained release. The release of Agomir21-Exo from GelMA-Ag21Exo notably alleviated the apoptosis of ovarian granulosa cells and improved the ovarian reserve and fertility in POI mice. Conclusion Our findings illustrate that activating miR-21 through Agomir21-Exo could improve the function of ovarian granulosa cells. The GelMA-Ag21Exo enhanced the exosome-based therapeutic efficacy of the Agomir21-Exo in vivo . These findings provide a novel and promising treatment strategy for POI patients.
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CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2019
·Vol. 47
·期 1
·85-94
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IF 2.336
Ning Han,Haitao Xu,Na Yu,Yazhen Wu,Li Yu
Proliferative diabetic retinopathy (PDR) is a common complication of diabetes mellitus, characterized by abnormal retinal angiogenesis. MicroRNA-203-3p (miR-203-3p) was found to be down-regulated in a murine model of proliferative retinopathy. This study was performed to explore the role of miR-203a-3p in retinal angiogenesis of PDR. Firstly, a rat OIR model, which was used to mimic PDR, was established and the OIR rats were treated with scrambled control or miR-203a-3p agomir by intravitreal injection. The results showed that the level of miR-203a-3p was decreased in OIR rats, and forced over-expression of miR-203a-3p inhibited OIR-induced retinal angiogenesis as evidenced by reduced blood vessel profiles and CD31 expression. OIR-induced up-regulation of VEGFA, HIF-α, PCNA, and MMPs in the retina was also counteracted by miR-203a-3p. Additionally, high glucose (HG)-induced proliferation, migration and tube formation of human retinal microvascular endothelial cells (HRMECs) were also dampened by the up-regulation of miR-203a-3p. Dual-luciferase reporter assay showed that miR-203a-3p could specifically bind to the 3′UTR of VEGFA and HIF-1α. Over-expression of VEGFA or HIF-1α restored the tube formation activity of HRMECs suppressed by miR-203a-3p. In conclusion, our findings demonstrate that up-regulation of miR-203a-3p might inhibit pathological retinal angiogenesis of PDR by targeting VEGFA and HIF-1α.
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Bioengineered
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2022
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IF 6.832
Chun Chen,Xiaolong Chang,Shifei Zhang,Qi Zhao,Chunyan Lei
Emerging studies show that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. The present study discovered that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in mouse astrocytes (mAS) treated with oxygen glucose deprivation and reperfusion (OGD/R), and similar results were observed in a mouse middle cerebral artery occlusion model. Overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and the inflammatory response induced by OGD/R in vitro. Up-regulation of circCTNNB1 increased SRB1 expression levels to protect mAS cells from OGD/R-induced damage. CircCTNNB1 and SRB1 interacted with miR-96-5p, and the overexpression of miR-96-5p efficiently reversed the function of circCTNNB1 in OGD/R-treated mAS cells. CircCTNNB1 protected against cerebral ischemia-reperfusion injury by up-regulating SRB1 in vivo. In conclusion, our findings suggest that circCTNNB1 acts as a competitive endogenous RNA for miR-96-5p to alleviate cerebral IRI, which provides novel evidence that circCTNNB1 and SRB1 may be biomarkers and therapeutic targets for cerebral IRI.
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