ANTI-CANCER DRUGS
·
2021
·Vol. 33
·期 1
·e145
·
IF 2.248
Liu Dan,Wang Yaya,Li Haiming,Peng Sida,Tan Huo,Huang Zhenqian
Multiple myeloma is a frequent hematologic malignancy. Bortezomib is the first-line drug for multiple myeloma chemotherapy. The present study aimed to investigate the potential role and mechanism of circular RNA chaperonin containing TCP1 subunit 3 (circ-CCT3) in bortezomib resistance of multiple myeloma . The levels of circ-CCT3, microRNA-223-3p ( miR-223-3p ), and bromodomain-containing 4 (BRD4) were detected by quantitative real-time PCR or western blot. Cell Counting Kit-8 (CCK-8) method was used to measure the half-inhibitory concentration of bortezomib and cell viability. Cell cycle distribution, apoptosis, proliferation and migration were determined by flow cytometry, 5-ethynyl-2′-deoxyuridine, and wound healing assay. The levels of relevant proteins were checked via western blot. The binding association between miR-223-3p and circ-CCT3/BRD4 was validated via a dual-luciferase reporter assay. Circ-CCT3 and BRD4 were upregulated, while miR-223-3p was downregulated in bortezomib -resistant multiple myeloma patients and cells. Silencing of circ-CCT3 enhanced the sensitivity of bortezomib -resistant multiple myeloma cells to bortezomib . Circ-CCT3 knockdown weakened bortezomib resistance via modulating miR-223-3p . Moreover, miR-223-3p increased bortezomib sensitivity by inhibiting BRD4. Downregulation of circ-CCT3 attenuated bortezomib resistance of multiple myeloma via regulating miR-223-3p /BRD4 pathway, which provided a new potential target for multiple myeloma chemoresistance.
研究领域:
肿瘤学
·
分子生物学
·
血液学
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DOI
PubMed
高影响因子
CHEMICAL PAPERS
·
2022
·Vol. 76
·期 5
·2875-2882
·
IF 2.146
He Xiao-Ling,Huang Fu-Hui,Zhang Chun-Ming,Dong Zhen,Wang Bin-Quan
The larynx is an important organ of human speech, and patients with laryngeal cancer may face great pain of losing their functions. For the prevention and therapy of laryngeal carcinoma, two new Zn(II)/Cd(II) coordination polymers, namely [Zn 3 (L) 2 (4,4′-bipy)] n ·2n(DMF) ( 1 ) and [Cd 3 (L) 2 (bpp 2 ) n ·2n(H 2 O)·2n(DMF) ( 2 ) (H 3 L = 4,4′,4′′-ticarboxytriphenylamine, 4,4′-bipy = 4,4′-bipyridine, bpp = 1,3-bis(4-pyridyl)propane, DMF = N,N-dimethylformamide), were prepared. The treatment and protection activity of the new compounds against the laryngeal carcinoma was evaluated in this research, and the corresponding mechanism was explored at the same time. Firstly, CCK-8 assay was conducted to measure the inhibitory activity of compounds on the viability of laryngeal carcinoma cells. Additionally, the expression of miR-223-3P in MSC exosomes was also measured by real time RT-PCR assay.
研究领域:
肿瘤学
·
药理学
·
生物化学
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DOI
高影响因子
International Journal of Pharmaceutics-X
·
2026
·
IF 7.9
Yuanli Wang,Wenyi Zhang,Feifan Cheng,Jianghao Wang,Kai Xiao,Danxia Wang,Xueqin Zhao,Ruitao Zou,Qingqing Yao
Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with neovascular AMD (nAMD) driven by choroidal neovascularization (CNV), persistent inflammation, and oxidative stress. Although combinatorial strategies targeting these pathological factors hold therapeutic promise, their clinical translation is constrained by the lack of effective delivery systems. In this study, we designed a mannose-functionalized poly(aspartic acid)-based nanocarrier bearing quaternary ammonium and boronic acid groups (MDA/QPABA) for the targeted delivery of microRNA-223 (miR-223). The system exploits charge-driven self-assembly to form stable nanoparticles with high loading efficiency, favorable colloidal stability, and tunable surface properties. The mannose moieties enable specific recognition by mannose receptors on target cells, facilitating cellular uptake and subsequent lysosomal escape. The resulting MDA/QPABA/miR-223 nanoparticles demonstrated pronounced anti-inflammatory, antioxidant, and anti-angiogenic activities in vitro . In a laser-induced CNV mouse model, they effectively reduced inflammatory and angiogenic cytokines, suppressed pathological neovascularization, restored retinal and choroidal structure, and preserved photoreceptor function, with an excellent biosafety. These findings highlight the potential of rationally engineered poly(aspartic acid)-based nanoarchitectures with tailored surface chemistry and biointerfacial properties for multifunctional nucleic acid delivery in nAMD therapy.
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DOI
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高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2026
·Vol. 30
·期 17
·e71359
·
IF 4.7
Xuesong Xu,Shichong Qiao
Apoptosis and functional loss of articular chondrocytes serve as initiating events in temporomandibular joint osteoarthritis (TMJOA), and FoxO3 represents a critical molecule for sustaining chondrocyte homeostasis. This study investigates the regulatory mechanism of the lncRNA‐OIP5‐AS1/hsa‐miRNA‐223‐3p/FoxO3 axis in TMJOA, aiming to identify potential therapeutic targets for this disease. Single‐cell database analysis first revealed markedly reduced FoxO3 expression in TMJOA‐derived chondrocytes. A rat TMJOA model was then constructed and assigned to control, model, and FoxO3 overexpression groups; micro‐CT and histological staining, including HE and Safranin O‐fast green staining, were applied to assess articular cartilage injury, while immunohistochemistry was used to detect cartilage‐associated proteins Col2a1, MMP‐13, Aggrecan, and ADAMTS‐5. Further in vitro experiments validated the chondroprotective function of FoxO3 as well as the binding interaction between FoxO3 and rno‐miRNA‐223‐3p. Database screening confirmed significant down‐regulation of FoxO3 in TMJOA cartilage. Animal experiments demonstrated that FoxO3 overexpression mitigated chondrocyte injury in rat TMJOA lesions, increased Col2a1 and Aggrecan levels, and suppressed MMP‐13 and ADAMTS‐5 expression. Cellular assays showed that FoxO3 overexpression enhanced chondrocyte proliferation and matrix synthesis and preserved chondrocyte function. Sequencing and cellular evidence indicated that rno‐miRNA‐223‐3p directly targets FoxO3 mRNA to repress its transcription and negatively modulate FoxO3 abundance, consequently aggravating chondrocyte apoptosis. Collectively, rno‐miRNA‐223‐3p suppresses FoxO3 activity to facilitate TMJOA pathogenesis, and the lncRNA‐OIP5‐AS1/rno‐miRNA‐223‐3p/FoxO3 regulatory cascade may act as a promising molecular target for TMJOA clinical intervention.
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DOI
PubMed
高影响因子
International Heart Journal
·
2026
·Vol. 67
·期 1
·87-97
·
IF 1.3
Zhuyuan Liu,Yanru He,Chunshu Hao
Myocardial ischemia-reperfusion injury (MI/RI) refers to the deterioration of cardiac function after restoring ischemic myocardium perfusion. Stem cell exosomes have produced unique advantages in treating MI/RI. However, the roles of exosomal microRNA-223-3p (miR-223-3p) from adipose-derived stem cells (ADSCs) on MI/RI are still unclear. This study aimed to investigate the effects of exosomal miR-223-3p from ADSCs on hypoxia/reoxygenation (H/R)-induced H9c2 cell injuries. Our findings indicated that the separated ADSC-derived exosomes (ADSC-Exo) were spherical, with a complete cell membrane, an average diameter of 110 nm, and CD9 and CD63 expression. ADSC-Exo increased the cell viability, proliferation, glutathione (GSH) level, and glutathione peroxidase 4 (GPX4) and miR-223-3p expression and decreased the apoptosis, reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+ levels and acyl-CoA synthetase long chain family member 4 (ACSL4) and transferrin receptor (TFRC) expression of H9c2 cells. Overexpressing exosomal miR-223-3p from ADSCs further strengthened the effects of ADSC-Exo on H9c2 cells. Overexpressing TFRC in H9c2 cells effectively reversed the effects of miR-223-3p overexpressed ADSC-Exo on H9c2 cells. In addition, miR-223-3p targeted and negatively regulated TFRC. This study confirmed that exosomal miR-223-3p from ADSCs alleviated H/R-induced ferroptosis of H9c2 cells by inhibiting TFRC, providing a novel target and pathway for the clinical treatment of MI/RI.
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产品关联
DOI
PubMed
高影响因子
Nanoscale Advances
·
2023
·
IF 4.7
Chunying Cui,Shuang Zhang,Dandan Li,Danni Liu,Yaoqi Wang,Qi Sun,Ran Sun,Jie Zhang,Xiaoxuan Hong,Ran Huo
Atherosclerosis is a chronic inflammatory disease, characterized by a lipid accumulated plaque. Anti-oxidative and anti-inflammation as well as lipid metabolism promoting therapeutic strategies have been applied for atherosclerosis treatment. However, the therapeutic effect by a single therapeutic method is limited. Combination of the two strategies could for one thing prevent lipid accumulation cause by inflammation and oxidative stress, for another thing promote lipid efflux from atherosclerotic plaque, to normalize arteries maximumly. Hence, a multifunctional liposome co-encapsulating an antioxidant and anti-inflammatory drug epigallocatechin-3-gallate(EGCG) as well as a lipid-efflux promoting gene miR-223 was established. The system (lip@EGCG/miR-223) could encapsulate miR-223 in core areas of the liposomes to provide an effective protective effect for gene drugs. Moreover, lip@EGCG/miR-223 was smaller in size (91.28±2.28 nm characterized by DLS), making it easier to target to AS lesions which had a smaller vascular endothelial spaces. After internalized into cellular efficiently, lip@EGCG/miR-223 exhibited excellent antioxidant and anti-inflammatory effects in vitro by eliminating overproduced ROS and decreasing the level of inflammatory cytokines (TNF-α, IL-1β and MCP-1), which is due to the effect of EGCG. Besides, the lipid-efflux promoting protein ABCA1 was up-regulated when treated with lip@EGCG/miR-223. By the two therapies mentioned, lip@EGCG/miR-223 could effectively inhibit the formation of foam cells, which is a main component of atherosclerotic plaques. In AS model mice, after intravenous (i.v.) administration, lip@EGCG/miR-223 was effectively accumulated in atherosclerotic plaques, and the distribution of drugs in heart and aorta to that in kidney was significantly increased when compared with free drugs (the ratio was 6.27% for free miR-223 treated group, and was increased to 66.10% for lip@EGCG/miR-223 treated group.). By decreasing inflammation level and lipid accumulation, the arterial vessels in AS were normalized with less macrophages and micro-angiogenesis when treated with lip@EGCG/miR-223. Overall, this study demonstrates lip@EGCG/miR-223 can be developed as a potential system for atherosclerosis treatment by a combined treatment of antioxidant, anti-inflammatory and lipid-efflux promoting effects, which provides a novel strategy for safe and efficient management of atherosclerosis.
研究领域:
药理学
·
心血管疾病
·
纳米技术
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ni Ding,Gangjian Luo,Huiting Li,Chengyuan Xing,Yuanji Gao,Wenjie Xi,Weijie Wu,Dan Wang,Lei Zheng,Yang Kang,Xinjin Chi
The mortality rate of sepsis remains high despite improvements in the diagnosis and treatment of sepsis using symptomatic and supportive therapies, such as anti-infection therapy and fluid resuscitation. Nucleic acid-based drugs have therapeutic potential, although their poor stability and low delivery efficiency have hindered their widespread use. Herein, it is confirmed that miR-223 can polarize proinflammation M1 macrophages to anti-inflammation M2 macrophages. A pH-sensitive nano-drug delivery system comprising β-cyclodextrin-poly(2-(diisopropylamino)ethyl methacrylate)/distearoyl phosphoethanolamine-polyethylene glycol (β-CD-PDPA/DSPE-PEG) is synthesized and developed to target M1 macrophages and miR-223 is encapsulated into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 demonstrated in vitro pH responsiveness with favorable biosafety, stability, and high delivery efficiency. In vivo studies demonstrate that NPs/miR-223 are preferentially accumulated and retained in the inflammation site, thereby reducing inflammation and improving the survival rate of mice with sepsis while exhibiting ideal biosafety. Mechanically, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway, thereby achieving an anti-inflammatory effect. Collectively, it is demonstrated that the miRNA delivery vector described here provides a new approach for sepsis treatment and accelerates the advancement of nucleic acid drug therapy.
研究领域:
药学
·
生物医学工程
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免疫学
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纳米技术
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治疗学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2022
·
IF 11.467
Keke Huang,Zhiqing Lin,Yuanyuan Ge,Xuhao Chen,Yining Pan,Ziru Lv,Xiaoting Sun,Hao Yu,Jiangfan Chen,Qingqing Yao
Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization . However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid–chitosan (FA–CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA–CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA–CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS , IL-1β , and IL-6 . Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA–CS/PMSN/miR-223 nanoparticles (1 μg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA–CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.
研究领域:
眼科学
·
纳米技术
·
分子生物学
·
炎症
·
治疗学
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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）