3D printing is a promising technology used in the fabrication of complex oral dosage delivery pharmaceuticals.This study first reports an innovative color jet 3D printing(CJ-3DP)technology to produce colorful cartoon ...3D printing is a promising technology used in the fabrication of complex oral dosage delivery pharmaceuticals.This study first reports an innovative color jet 3D printing(CJ-3DP)technology to produce colorful cartoon levetiracetam pediatric preparations with high accuracy and reproducibility.For this study,the ideal printing ink consisted of 40%(v/v)isopropanol aqueous solution containing 0.05%(w/w)polyvinylpyrrolidone and 4%(w/w)glycerin,which was satisfied with scale-up of the production.The external and internal spatial structures of the tablets were designed to control the appearance and release,and cartoon tablets with admirable appearances and immediate release characteristics were printed.The dosage model showed a good linear relationship between the model volume and the tablet strength(r>0.999),which proved the potential of personalized administration.The surface roughness indicated that the appearance of the CJ-3DP tablets was significantly better than the first listed 3D printed drug(Spritam R).Moreover,the scanning electron microscopy and porosity results further showed that the tablets have a structure of loose interior and tight exterior,which could ensure good mechanical properties and rapid dispersion characteristics simultaneously.In conclusion,the innovative CJ-3DP technology can be used to fabricate personalized pediatric preparations for improved compliance.Due to the stable formulation and fabrication process,this technology has the potential in scale-up production.展开更多
Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanism...Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.展开更多
基金This work was supported by the National Natural Science Foundation of China(No.82073793)the National Major Science and Technology Projects of China(No.2018ZX09721003-007/No.2018ZX09J18107).
文摘3D printing is a promising technology used in the fabrication of complex oral dosage delivery pharmaceuticals.This study first reports an innovative color jet 3D printing(CJ-3DP)technology to produce colorful cartoon levetiracetam pediatric preparations with high accuracy and reproducibility.For this study,the ideal printing ink consisted of 40%(v/v)isopropanol aqueous solution containing 0.05%(w/w)polyvinylpyrrolidone and 4%(w/w)glycerin,which was satisfied with scale-up of the production.The external and internal spatial structures of the tablets were designed to control the appearance and release,and cartoon tablets with admirable appearances and immediate release characteristics were printed.The dosage model showed a good linear relationship between the model volume and the tablet strength(r>0.999),which proved the potential of personalized administration.The surface roughness indicated that the appearance of the CJ-3DP tablets was significantly better than the first listed 3D printed drug(Spritam R).Moreover,the scanning electron microscopy and porosity results further showed that the tablets have a structure of loose interior and tight exterior,which could ensure good mechanical properties and rapid dispersion characteristics simultaneously.In conclusion,the innovative CJ-3DP technology can be used to fabricate personalized pediatric preparations for improved compliance.Due to the stable formulation and fabrication process,this technology has the potential in scale-up production.
基金supported by the National Key Research and Development Project of China(No.2018YFA0800404)the National Natural Science Foundation of China(Nos.82100255 and 81970736)the China Postdoctoral Science Foundation(Nos.2021M691459 and 2022T150299).
文摘Cardiac fibrosis is a cause of morbidity and mortality in people with heart disease.Anti-fibrosis treatment is a significant therapy for heart disease,but there is still no thorough understanding of fibrotic mechanisms.This study was carried out to ascertain the functions of cytokine receptor-like factor 1(CRLF1)in cardiac fibrosis and clarify its regulatory mechanisms.We found that CRLF1 was expressed predominantly in cardiac fibroblasts.Its expression was up-regulated not only in a mouse heart fibrotic model induced by myocardial infarction,but also in mouse and human cardiac fibroblasts provoked by transforming growth factor-β1(TGF-β1).Gain-and loss-of-function experiments of CRLF1 were carried out in neonatal mice cardiac fibroblasts(NMCFs)with or without TGF-β1 stimulation.CRLF1 overexpression increased cell viability,collagen production,cell proliferation capacity,and myofibroblast transformation of NMCFs with or without TGF-β1 stimulation,while silencing of CRLF1 had the opposite effects.An inhibitor of the extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway and different inhibitors of TGF-β1 signaling cascades,comprising mothers against decapentaplegic homolog(SMAD)-dependent and SMAD-independent pathways,were applied to investigate the mechanisms involved.CRLF1 exerted its functions by activating the ERK1/2 signaling pathway.Furthermore,the SMAD-dependent pathway,not the SMAD-independent pathway,was responsible for CRLF1 up-regulation in NMCFs treated with TGF-β1.In summary,activation of the TGF-β1/SMAD signaling pathway in cardiac fibrosis increased CRLF1 expression.CRLF1 then aggravated cardiac fibrosis by activating the ERK1/2 signaling pathway.CRLF1 could become a novel potential target for intervention and remedy of cardiac fibrosis.