Biomaterials Science
·
2022
·Vol. 10
·期 13
·3637-3646
·
IF 7.59
Qingyan Zhang,Ying Huang,Ruoxi Yang,Junmei Mu,Zhanwei Zhou,Minjie Sun
Despite the great progress in the control of primary tumor growth, metastasis remains the major challenge of breast cancer therapy in clinics, which is highly related to the upregulation of reactive oxygen species (ROS) and overexpression of its relevant pro-survival miR-155 gene. Therefore, we fabricated a poly-antioxidant (FTP) to deliver anti-miR-155 for synergistic treatment of metastatic breast cancer by ROS scavenging and miR-155 inhibition. FTP was synthesized by the polymerization of fluorated-polyethyleneimine (FPEI) and antioxidants (TEMPOL), using a glutathione (GSH) responsive linker for controlled drug release. Notably, the poly-drug strategy could not only promote the tumoral accumulation of small molecular antioxidants but also enhance the transfection efficiency of anti-miR-155 owing to the hydrophobic property of TEMPOL. After synergistic treatment, the NF-κB pathway was significantly blocked, thereby generating strong anti-metastatic ability both in vitro and in vivo. The poly-antioxidant could be a new type of nanoplatform for highly efficient and safe miRNA delivery, which also provides a promising strategy for the synergistic treatment of metastatic breast cancer.
研究领域:
肿瘤学
·
药学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
·
2025
·Vol. 113
·期 5
·e37923
·
IF 3.9
Linsen Li,Di An,Jinhu Zhao,Yue Yu,Yating Zeng,Xiayan Yang,Qifeng Yu,Ke Kang,Yao Wu,Qiangying Yi
Medical implants serve as pivotal therapeutic interventions for cardiovascular diseases. Nevertheless, challenges including endothelial injury, excessive smooth muscle cell migration, and inflammatory responses associated with implantation hinder their long-term adoption in vivo. In this work, a versatile coating of cardiovascular implants was constructed by the remarkable adhesive properties of dopamine and the precision and efficiency of click chemistry. The functional coating was obtained through programmed assembly of heparin, miR-155 inhibitor, and endothelial cell affinity peptide. Cellular experiments have demonstrated that this coating could modulate macrophage phenotype through anti-miR155 inhibitors, thereby inhibiting the release of inflammatory factors and improving the inflammatory environment on the surface. Furthermore, this coating could also promote the adhesion and proliferation of endothelial cells while inhibiting the excessive proliferation of smooth muscle cells, thereby ensuring the endothelialization of the implant surface. Additionally, animal experiments have revealed the coating's exceptional anticoagulant properties, significantly reducing the formation of thrombus. With its simple and efficient preparation process and excellent performance, this coating emerges as a promising candidate for promoting early endothelialization and improving the performance of cardiovascular implants.
研究领域:
医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Zhibin Yan,Dan Wang,Chunmei An,Hongjiao Xu,Qian Zhao,Ying Shi,Nazi Song,Bochuan Deng,Xiaomin Guo,Jing Rao,Lu Cheng,Bangzhi Zhang,Lingyun Mou,Wenle Yang,Xianxing Jiang,Junqiu Xie
The antimicrobial peptide APKGVQGPNG (named YD), a natural peptide originating from Bacillus amyloliquefaciens CBSYD1, exhibited excellent antibacterial and antioxidant properties in vitro . These characteristics are closely related to inflammatory responses which is the central trigger for liver fibrosis. However, the therapeutic effects of YD against hepatic fibrosis and the underlying mechanisms are rarely studied. In this study, we show that YD improved liver function and inhibited the progression of liver fibrosis by measuring the serum transaminase activity and the expression of α -smooth muscle actin and collagen I in carbon tetrachloride-induced mice. Then we found that YD inhibited the level of miR-155, which plays an important role in inflammation and liver fibrosis. Bioinformatics analysis and luciferase reporter assay indicate that Casp12 is a new target of miR-155. We demonstrate that YD significantly decreases the contents of inflammatory cytokines and suppresses the NF- κ B signaling pathway. Further studies show that transfection of the miR-155 mimic in RAW264.7 cells partially reversed the YD-mediated CASP12 upregulation, the downregulated levels of inflammatory cytokines, and the inactivation of the NF- κ B pathways. Collectively, our study indicates that YD reduces inflammation through the miR-155– Casp12 –NF- κ B axis during liver fibrosis and provides a promising therapeutic candidate for hepatic fibrosis.
研究领域:
分子生物学
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药理学
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肝病学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2025
·
IF 3.8
Xiaomin Ye,Peiqu Zhong,Qiongfang Chen,Dongmei Zhou,Jieyu Luo,Youcai Liang,Jiayuan Zhang,Lijian Zhao
The widespread use of perfluorooctanesulfonic acid (PFOS) has raised concerns regarding its potential on pregnant women, particularly in relation to the development of pre-eclampsia (PE). This study investigates the impact of PFOS exposure on the LncRNA/Rnd3 axis in pregnant mice and its association with trophoblast cell functions in PE. Bioinformatics analysis revealed PFOS-related gene alterations in PE, with pathways enriched in apoptotic signaling and cytokine interactions. Experimental findings showed the downregulation of Oip5os1 and Rnd3, along with the upregulation of miR-155, affecting trophoblast behavior. Animal experiments confirmed that PFOS-induced gene expression changes are linked to PE progression. PFOS exposure impairs trophoblast proliferation and migration via the Oip5os1/miR-155/Rnd3 axis, contributing to PE development.
研究领域:
毒理学
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生殖生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Lin Peng,Shasha Chen,Hongjin Lin,Chunyan Wan,Xiang Li,Shiwen Xu,Shu Li
Bisphenol A (BPA) is an endocrine disruptor. Excessive BPA intake can damage the structure and function of the respiratory tract. Dietary selenium (Se) deficiency may also cause immune tissue damage. To investigate the potential mechanism of BPA on tracheal damage in selenium-deficient chickens and the role of microRNAs (miRNAs) in this process, we established in vitro and in vivo Se deficiency and BPA exposure models and screened out miR-155 for follow-up experiments. We further predicted and confirmed the targeting relationship between miR-155 and TRAF3 using TargetScan and dual luciferase assays and found that miR-155 was highly expressed and caused inflammatory damage. Further studies showed that BPA exposure increased airway oxidative stress, activated the NF-κB pathway, and caused inflammation and immune damage in selenium-deficient chickens, but down-regulating miR-155 and NAC treatment could reverse this phenomenon. This suggested that these pathways are regulated by the miR-155/TRAF3/ROS axis. In conclusion, BPA exposure aggravates airway inflammation in selenium-deficient chickens by regulating miR-155/TRAF3/ROS. This study revealed the mechanism of BPA exposure combined with Se deficiency in tracheal inflammatory injury in chickens and enriched the theoretical basis of BPA injury in poultry.
研究领域:
毒理学
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免疫学
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分子生物学
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兽医学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry C
·
2022
·Vol. 10
·期 48
·18258-18263
·
IF 8.067
Li Ping Cao,Yao Wang,Yan Bai,Yong Jian Jiang,Chun Mei Li,Yuan Fang Li,Cheng Zhi Huang,Shu Jun Zhen
Owing to their simple and convenient synthesis, the application of metal–organic gels (MOGs) in fluorescence detection has been increasingly studied. However, most relevant studies are based on the fluorescence changes of MOGs themselves caused by the direct interaction between the target and MOG, resulting in limited universality and insufficient sensitivity and other shortcomings. Thus, we combined a Cu-based metal–organic gel (Cu-MOG) with an entropy-driven circuit (EDC), as an isothermal enzyme-free amplification technique, to detect miR-155 as a proof-of-principle target. The substrate for the EDC was designed as a three-strand duplex (TD) containing an output strand (OS) which was modified with 6-carboxyfluorescein (FAM). In the presence of the target, namely miR-155, the EDC was triggered and OS was released, making the OS transition from the hybrid state to the free state. The fluorescence of the FAM modified free OS strand was then quenched owing to the intramolecular photo-induced electron transfer (PET) of the new ground state complex formed between the OS and MOG with a quenching constant of 1.48 mL μg−1, which is much higher than that (0.08 mL μg−1) of the hybrid state OS. This method provided a dynamic detection range of 1 nM to 5 nM with a detection limit of 0.23 nM for miR-155, demonstrating that the Cu-MOG coupled EDC has promising applications in bioassays, and opens up a new application field of MOGs in EDC development.
研究领域:
分析化学
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生物传感器
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纳米技术
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分子生物学
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产品关联
DOI
高影响因子
BMC Pulmonary Medicine
·
2024
·Vol. 24
·期 1
·1-16
·
IF 2.6
Sun Lili,Liu Lihua,Liang Dongxue,Liu Linlin
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2024
·Vol. 20
·期 8
·1307-1314
·
IF 2.9
Zhu Yunhan,Chen Renshou
Sepsis-induced Acute kidney injury (SA-AKI), a common complication in sepsis, significantly impacts patients’ health and quality of life. M1 macrophages have been demonstrated to release inflammatory mediators that exacerbate kidney injury. MiR-155 has been implicated in promoting
inflammation and damage during sepsis while reducing miR-155 levels alleviates SA-AKI. However, the relationship between miR-155 and M1 macrophage-derived exosomes in regulating autophagy during SA-AKI remains unclear. In this study, we aim to investigate the relationship between M1 macrophage-derived
exosomes and miR-155 in regulating autophagy during SA-AKI. A mouse model of SA-AKI was established by performing cecal ligation and puncture (CLP) surgery. Additionally, the HK-2 cell line was utilized to establish a sepsis cell model by inducing lipopolysaccharide (LPS). We demonstrated
that the mice model of SA-AKI exhibited renal injury along with enhanced autophagy, inflammation response, and macrophage polarization after CLP surgery. M1 macrophages attenuated cell viability and enhanced autophagy in LPS-treated HK-2 cells. Additionally, M1 macrophage-derived exosomes
were observed to enhance autophagy in LPS-treated HK-2 cells. Furthermore, we confirmed an increased expression of miR-155 in M1 macrophage-derived exosomes. Furthermore, exosome-mediated miR-155 enhanced autophagy in LPS-treated HK-2 cells. In conclusion, this study provides the first evidence
that exosomal miR-155 derived from M1 macrophages enhances autophagy in SA-AKI. These findings suggest that targeting exosomal miR-155 could be a promising therapeutic strategy for SA-AKI.
研究领域:
免疫学
·
肾病学
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分子生物学
·
重症医学
✓ 已验证
DOI
高影响因子
Acta Pharmaceutica Sinica B
·
2020
·
IF 7.097
Chao Teng,Chenshi Lin,Feifei Huang,Xuyang Xing,Shenyu Chen,Ling Ye,Helena S. Azevedo,Chenjie Xu,Zhengfeng Wu,Zhongjian Chen,Wei He
Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo . In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
研究领域:
药理学
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纳米技术
·
心血管疾病
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分子生物学
·
炎症
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2018
·
IF 4.37
Yang Li,Yanhong Duo,Jiangang Bi,Xiaowei Zeng,Lin Mei,Shiyun Bao,Lisheng He,Aijun Shan,Yue Zhang,Xiaofang Yu
Introduction MicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics. Methods In this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC. Results Results showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy. Conclusion Thus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.
研究领域:
肿瘤学
·
纳米技术
·
分子生物学
·
癌症治疗
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 2
·1-11
·
IF 2.447
Jingli Zhang,Lingling Zhu,Hong Shi,Huizhe Zheng
Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate the role of miR‑155‑5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon‑γ (IFN‑γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription‑quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual‑luciferase reporter assay was performed to verify the interaction between miR‑155‑5p and arrestin β2 (ARRB2). The protein levels in the NF‑κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treatment with IFN‑γ increased miR‑155‑5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR‑155‑5p promoted IFN‑γ‑induced apoptosis and inflammation in SGECs. Overexpression of miR‑155‑5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin‑6 and tumor necrosis factor‑α, and decreased Bcl‑2 protein expression in IFN‑γ‑treated SGECs. By contrast, all of the effects aforementioned were reversed following miR‑155‑5p knockdown. These results demonstrated that miR‑155‑5p activated the NF‑κB signaling pathway, where treatment with the NF‑κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR‑155‑5p overexpression on the inflammatory factors in IFN‑γ‑induced SGECs. miR‑155‑5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR‑155‑5p overexpression on the inflammatory response, apoptosis and the NF‑κB signaling pathway in IFN‑γ‑treated SGECs. Collectively, results from the present study suggest that miR‑155‑5p may activate the NF‑κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR‑155‑5p may serve to be a potential target for the treatment of SS.
研究领域:
免疫学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG AND CHEMICAL TOXICOLOGY
·
2025
·
IF 1.9
Aicun Tang,Luying Wei,Jiayi Gao,Zheng Zhang,Bingyu Xia,Xin Li,Qiuyu Lu
To analyze tadehaginoside (TA) for its effect on liver fibrosis and the associated mechanism. Mice with CCl4-mediated liver fibrosis were administered TA treatment for 6 weeks. Histopathological alterations in liver tissues were evaluated, and serum markers of hepatic injury, as well as the hepatic profibrotic gene and protein levels were detected. Transforming growth factor-β1 (TGF-β1) was adopted for inducing LX-2 cells. Following a 24-h TA intervention, we assessed pro-fibrotic gene and protein activation, proliferation and levels of TGF-β1-activated LX-2 cells. miR-155 and FOXO3 expressions were quantified in mice liver tissues and cells. The targeting relation of miR-155 with FOXO3 was verified. After regulating miR-155 and FOXO3 expression, the function of TA in cell activation, proliferation, and collagen accumulation was evaluated. The results indicated that TA treatment markedly alleviated CCl4-mediated mouse liver injury, inhibited collagen fiber deposition, and downregulated the hepatic pro-fibrotic gene and protein levels. Additionally, TA treatment suppressed TGF-β1-induced cell activation and proliferation, thus significantly reducing pro-fibrotic marker levels within cells. Furthermore, treatment with TA down-regulated miR-155 and up-regulated FOXO3 within CCl4-induced liver tissues as well as TGF-β1-induced cells. However, miR-155 overexpression or FOXO3 silencing partially mitigated the inhibition of TA against TGF-β1-mediated activation, proliferation, and fibrosis in cells. In conclusion, TA inhibits the activation of hepatic stellate cell (HSC) via miR-155/FOXO3 axis, thereby exerting its anti-hepatic fibrosis effect.
研究领域:
药理学
·
分子生物学
·
肝脏病学
·
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）