Mg-6Zn alloy was studied as candidate biodegradable metallic implants for the common bile duct (CBD) in terms of its in vitro corrosion and in vivo corrosion. Electrochemical measurements, immersion tests and hydrogen evolution were performed in the bile and Hanks' solution to evaluate the in vitro degradation behavior of Mg-6Zn alloy. The results showed that the degradation rate and hydrogen evolution were higher when Mg-6Zn alloy immersed in the bile than in the Hanks' solution. The polarization resistance of the samples in the Hanks' solution was about 1.5 times to that in the bile. In the in vivo experiment, Mg-6Zn alloy stents were inserted in CBD of 42 rabbits, and CT scans, the value of total bilirubin (TB) and in vivo corrosion rate were determined. From the results of CT images and the fluctuations of TB values, it can be seen that the stent was degraded gradually in CBD. After 1 week post-implantation, the majority of the Mg-6Zn alloy sample remained in the CBD. Usually the required support time for CBD stent was approximately 7-10 days, thus the Mg-6Zn alloy stent was very close to the clinical requirement for CBD support materials. After three weeks, the residual weight of the Mg-6Zn alloy was only 9% of the original weight. The in vivo corrosion rate of Mg-6Zn alloy was ~0.107 mm·year(-1), which was much lower than that calculated in vitro (~0.72 mm·year(-1) by electrochemical test). Based on our research, there is promising for the Mg-6Zn alloy in CBD applications.
Skin injury in adult mammals brings about a series of events and inflammation in the wounded area is initiated first and provides lots of inflammatory factors, which is critical for the final scar formation. While the postinjured skin of fetus and nude mice heals scarlessly owing to the absence of inflammation or immunodeficient, we designed a feasible acid-responsive ibuprofen-loaded poly(L-lactide) (PLLA) fibrous scaffolds via doping sodium bicarbonate to prevent excessive inflammation and achieve scarless healing finally. The morphological results of in vivo experiments revealed that animals treated with acid-responsive ibuprofen-loaded PLLA fibrous scaffolds exhibited alleviative inflammation, accelerated healing process, and regulated collagen deposition via interference in the collagen distribution, the ?-smooth muscle actin (?-SMA), and the basic fibroblast growth factor (bFGF) expression. The lower ratios of collagen I/collagen III and TGF-?1/TGF-?3 and higher ratio of matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) in acid-responsive ibuprofen-loaded PLLA fibrous scaffolds group were confirmed by real-time qPCR as well. These results suggest that inhibiting the excessive inflammation will result in regular collagen distribution and appropriate ratio between the factors, which promote or suppress the scar formation, then decrease the scar area, and finally achieve the scarless healing.
Drug-loaded electrospun PLLA membranes are not conducive to adhesion between materials and tissues due to the strong hydrophobicity of PLLA, which possibly attenuate the drugs' effect loaded on the materials. In the present work, we developed a facile method to improve the hydrophilicity of doxorubicin (DOX)-loaded electrospun PLLA fibrous membranes, which could enhance the anti-tumor effect at the early stage after implantation. A mussel protein, polydopamine (PDA), could be easily grafted on the surface of hydrophobic DOX-loaded electrospun PLLA membranes (PLLA-DOX/pDA) in water solution. The morphology analysis of PLLA-DOX/pDA fibers displayed that though the fiber diameter was slightly swollen, they still maintained a 3D fibrous structure, and the XPS analysis certified that pDA had successfully been grafted onto the surface of the fibers. The results of surface wettability analysis showed that the contact angle decreased from 136.7° to 0° after grafting. In vitro MTT assay showed that the cytotoxicity of PLLA-DOX/pDA fibers was the strongest, and the stereologic cell counting assay demonstrated that the adhesiveness of PLLA/pDA fiber was significantly better than PLLA fiber. In vivo tumor-bearing mice displayed that, after one week of implantation, the tumor apoptosis and necrosis of PLLA-DOX/pDA fibers were the most obvious from histopathology and TUNEL assay. The caspase-3 activity of PLLA-DOX/pDA group was the highest using biochemical techniques, and the Bax: Bcl-2 ratio increased significantly in PLLA-DOX/pDA group through qRT-PCR analysis. All the results demonstrated that pDA can improve the affinity of the electrospun PLLA membranes and enhance the drug effect on tumors.
Biodegradable common bile duct (CBD) stents are in high clinical demand. Animal experiments concerning the surgical placement of biliary stents made of new materials are being performed more frequently than ever before. However, these animal experiments only use large animals. In this study, a central venous catheterization set was used as a modified stent introducer system in rabbits. A biodegradable Mg-6Zn alloy CBD stent was passed through the duodenal papilla using this stent introducer system. Computed tomography (CT) scanning of the CBD stent in vivo and levels of serum lipase (LPS) were investigated. Twelve rabbits underwent CBD stent insertion and one animal died due to an anesthetic accident. After 3 weeks, when the remaining 11 rabbits were sacrificed, no jaundice or bile leakage was observed. CT scanning of the 11 rabbits suggested that the biodegradable Mg-6Zn stent was successfully placed into the CBD. When the preoperative and postoperative levels of LPS were compared, no statistically significant differences were observed. This new method appears to be feasible and safe for the placement of stents into the CBDs of small animals. This new method can increase the animal number of CBD stent experiment, and improve the quality of experiments.
microRNAs (miRNAs) are involved in the pathogenesis of diverse human cancers through its target genes, including papillary thyroid cancer (PTC). However, there are few studies regarding associations between clinicopathological features of PTC with the expression of specific miRNAs and its potential target genes. In the present study, analysis of miRNA was integrated with mRNA expression profiles in aggressive PTC. miRNA and gene expression arrays were used to identify a subset of differentially expressed miRNAs and mRNAs between aggressive and non-aggressive PTCs. These miRNAs and mRNAs were further validated by qPCR in a cohort of 20 PTCs with extrathyroidal invasion and/or distant metastases, and 20 PTCs with no extrathyroidal invasion. The target of these miRNAs was determined by luciferase reporter and bioinformatic analysis. The miRNA arrays identified 14 upregulated miRNAs and 10 downregulated miRNAs in aggressive compared with non-aggressive PTCs. Significant miRNA deregulation was confirmed in the validation cohort, with upregulation of miR-146b-5p and miR-221/222 and downregulation of miR-16 and miR-613 in aggressive PTCs. The gene arrays identified 2000 differentially expressed genes, in which TIMP3, ZNFR3, FN1 and ITGA2 were observed to be target genes inversely correlated with miR-221/222, miR-146b-5p, miR-613 and miR-16, respectively. The results of the present study indicated the potential importance of miR-221/222, miR-146b-5p, miR-16 and miR-613 in determining the aggressive properties of PTC by targeting TIMP3, ZNFR3, FN1 and ITGA2, respectively. Additional studies should be conducted to confirm the results.
Breast cancer is a common malignant neoplasm that is a leading cause of cancer death in women despite recent advances in treatment and research. The role of lymphangiogenesis in breast cancer development remains a source of controversy in current research.
Thrombolytics inevitably led to the risk of hemorrhagic complications due to their non-specific plasminogen activation in treatment of thrombosis. The aim of this study was to determine whether a kind of superparamagnetic mesoporous silica nanoparticle with expanded pore size could achieve effectively targeted thrombolysis. The magnetic mesoporous silica nanoparticles (M-MSNs) with the pore size of 6 nm were prepared by method of the surfactant templating on nano magnetic particles. We investigated the feasibility and efficacy of target thrombolysis with the resultant spheres through fibrin agarose plate assay (FAPA) and a dynamic flow system in vitro. It displayed a 30-fold enhancement of urokinase (UK) loading capacity over the particles without mesoporous layer or the magnetic spheres with mesopores of 3.7 nm. A sustained release behavior was observed due to its larger pore size, higher surface area and narrow mesopore channals contrast to non-mesoporous and small mesopore of 3.7 nm controls. Meanwhile, fibrin agarose plate assay revealed that UK/M-MSNs exhibited a more rapid growth rate of thrombolysis even lasting for 3 days. Additionally, flow model test in vitro suggested this kind of nanoparticle complex enhanced the thrombolysis efficacy by 3.5 fold over the same amount of native UK in 30 min. When compared to non-mesoporous and small mesopore controls, it also represented an extremely higher lysis efficiency (ANOVA, P < 0.01) and a shorter reperfusion time (ANOVA, P < 0.001). Such a magnetic mesoporous silica nanoparticle carrier was expected to be further studied for targeted thrombolytic therapy.
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