Journal of Materials Chemistry B
·
2014
·Vol. 2
·期 13
·1825-1837
·
IF 0
Changcan Shi,Fanglian Yao,Jiawen Huang,Guoliang Han,Qian Li,Musammir Khan,Yakai Feng,Wencheng Zhang
Herein, we developed a novel biodegradable gene carrier for rapid endothelialization of endothelial cells (ECs) in vitro. Three triblock amphiphilic copolymers, methoxy-poly(ethylene glycol)-block-poly(3(S)-methyl-2,5-morpholinedione-co-glycolide)-graft-polyethyleneimine (mPEG-b-P(MMD-co-GA)-g-PEI) with different 3(S)-methyl-2,5-morpholinedione and glycolide contents were synthesized. Microparticles (MPs) were obtained via self-assembly of these copolymers. The hydrophobic core composed of P(MMD-co-GA) segments provide crosslinking points for numbers of PEG and short PEI chains to form a highly hydrophilic and positively charged corona/shell of MPs. Using these MPs, potential genes (ZNF580) for rapid endothelialization were efficiently transported into EA.hy926 cells. Because of the hydrophilic PEG chains and low molecular weight PEI in the triblock copolymers, the cytotoxicity of these MPs and their complexes with pEGFP–ZNF580 was decreased significantly. The transfection efficacy of MPs/pEGFP–ZNF580 complexes was as high as Lipofectamine™ 2000 reagent to EA.hy926 cells in vitro. The proliferation and migration of EA.hy926 cells were improved greatly by the expression of pEGFP–ZNF580 after 60 hours. Our results indicated that the mPEG-b-P(MMD-co-GA)-g-PEI based MPs could be a suitable non-viral gene carrier for ZNF580 gene to enhance rapid endothelialization.
研究领域:
生物医学工程
·
基因治疗
·
材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
FITOTERAPIA
·
2024
·
IF 2.5
Songqin Yang,Mao Zhao,Yuhan Feng,Xia Zhang,Qiuhong Li,Wenwen Jiang,Daoping Wang
Toddalia asiatica (L.) Lam. (TA) is a traditional folk medicine of ethnic minorities in the southwest of China. It is widely used in the treatment of dispersing blood stasis and activating blood. However, the effective substance and pharmacological mechanism have not been fully elucidated. The zebrafish larvae were treated with Phenylhydrazine (PHZ) to establish a thrombus model, and the staining intensity of zebrafish red blood cells was analyzed. The antithrombotic activity of TA was verified for the first time, and it was found that the inhibition rate of TA on thrombosis was up to 60.85 %. The chemical ingredients of TA were collected by combining UPLC-HRMS analysis and the literature research. Network pharmacology revealed that six key targets were obtained, which including TNF, AKT1, EGFR, PTGS2, PPARG, and IFNG. It showed that the PI3K-Akt pathway was a core signaling pathway. Coagulation factor III(TF), playing an important role in the process of hemostasis and thrombosis, which ranks high in the PPI network. Moreover, the results of molecular docking showed that the active components had a strong binding force with TF, which indicated that TF might be the key target of TA in treating thrombosis. In vitro experiments showed that TA could inhibit TNF-α-induced high expression of TF in EA.hy926 cells. In addition, TA could inhibit TNF-α-activated expression of Akt, IκBα and P65 protein phosphorylation in PI3K-Akt pathway. The results showed that TA had antithrombotic activity and exerted an antithrombotic effect by inhibiting the expression of TF through the PI3K-Akt-NF-κB signaling pathway.
研究领域:
药理学
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分子生物学
·
传统中药
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斑马鱼研究
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2023
·Vol. 18
·期 1
·1-15
·
IF 2.6
Sun Kai,Xue Yuman,Zhang Xin,Li Xiaodong,Zhao Jun,Xu Xilin,Zhang Xiaofeng,Yang Fubiao
Background The impaired blood supply to the bones is an important pathological feature of steroid-induced osteonecrosis of the femoral head (SIONFH). Danshen is a Chinese herb that shows therapeutic effects on SIONFH, but the effects of one of its major bioactive constituents, Tanshinone I (TsI), on SIONFH remain unknown. Here, we evaluated the effects of TsI on SIONFH, particularly focusing on its effects on angiogenesis, in in vivo and in vitro research. Methods SIONFH was induced in Sprague–Dawley rats by an intramuscular injection of methylprednisolone (40 mg/kg) in combination with an intraperitoneal injection of lipopolysaccharide (20 μg/kg). Morphological alterations of the femoral head were observed by dual-energy X-ray absorptiometry and HE staining. Western blot, qRT-PCR, and immunohistochemical/immunofluorescence staining were used to determine gene expression. Results TsI (10 mg/kg) alleviated bone loss and rescued the expression of angiogenesis-related molecules (CD31, VWF, VEGF, and VEGFR2) in the femoral heads of SIONFH rats. Notably, TsI rescued the down-regulated expression of SRY-box transcription factor 11 (SOX11) in CD31 + endothelial cells in the femoral heads of SIONFH rats. In vitro studies showed that TsI preserved the dexamethasone-harmed angiogenic property (migration and tube formation) of human umbilical vein cells (EA.hy926), suppressed dexamethasone-induced cell apoptosis, reduced pro-apoptotic proteins (cytosolic cytochrome C, Bax, and caspase 3/9) and increased anti-apoptotic protein Bcl-2, whereas silencing of SOX11 reversed these beneficial effects. Conclusions This study demonstrates that TsI alleviates SIONFH and promotes angiogenesis by regulating SOX11 expression. Our work would provide new evidence for the application of TsI to treat SIONFH. Graphical Abstract
研究领域:
药理学
·
骨科
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2024
·
IF 18
Wei Zhang,Miao Dai,Ye Zhu,Siyuan Li,Ying Sun,Xiaoya Liu,Xiaojie Li
Zinc (Zn) alloys have demonstrated significant potential in healing critical-sized bone defects. However, the clinical application of Zn alloys implants is still hindered by challenges including excessive release of zinc ions (Zn 2+ ), particularly in the early stage of implantation, and absence of bio-functions related to complex bone repair processes. Herein, a biodegradable aliphatic polycarbonate drug-eluting coating was fabricated on zinc-lithium (Zn–Li) alloys to inhibit Zn 2+ release and enhance the osteogenesis, angiogenesis, and bacteriostasis of Zn alloys. Specifically, the photo-curable aliphatic polycarbonates were co-assembled with simvastatin and deposited onto Zn alloys to produce a drug-loaded coating, which was crosslinked by subsequent UV light irradiation. During the 60 days long-term immersion test, the coating showed distinguished stable drug release and Zn 2+ release inhibition properties. Benefiting from the regulated release of Zn 2+ and simvastatin, the coating facilitated the adhesion, proliferation, and differentiation of MC3T3-E1 cells, as well as the migration and tube formation of EA.hy926 cells. Astonishingly, the coating also showed remarkable antibacterial properties against both S. aureus and E. coli . The in vivo rabbit critical-size femur bone defects model demonstrated that the drug-eluting coating could efficiently promote new bone formation and the expression of platelet endothelial cell adhesion molecule-1 (CD31) and osteocalcin (OCN). The enhancement of osteogenesis, angiogenesis, and bacteriostasis is achieved by precisely controlling of the released Zn 2+ at an appropriate level, as well as the stable release profile of simvastatin. This tailored aliphatic polycarbonate drug-eluting coating provides significant potential for clinical applications of Zn alloys implants.
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
骨科
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）