Pharmacology eJournal最新文献

Directionalities of Magnetic Fields and Topographic Scaffolds Synergise to Enhance MSC Chondrogenesis 磁场方向和地形支架协同促进间充质干细胞软骨形成

Pharmacology eJournal Pub Date : 2020-10-06 DOI: 10.2139/ssrn.3686389

Cenk Celik, A. Franco-Obregón, E. Lee, J. Hui, Zheng Yang

{"title":"Directionalities of Magnetic Fields and Topographic Scaffolds Synergise to Enhance MSC Chondrogenesis","authors":"Cenk Celik, A. Franco-Obregón, E. Lee, J. Hui, Zheng Yang","doi":"10.2139/ssrn.3686389","DOIUrl":"https://doi.org/10.2139/ssrn.3686389","url":null,"abstract":"Mesenchymal stem cell (MSC) chondrogenesis is modulated by diverse biophysical cues. We have previously shown that brief, low-amplitude pulsed electromagnetic fields (PEMFs) differentially enhance MSC chondrogenesis in scaffold-free pellet cultures versus conventional tissue culture plastic (TCP), indicating an interplay between magnetism and micromechanical environment. Here, we examined the influence of PEMF directionality over the chondrogenic differentiation of MSCs laden on electrospun fibrous scaffolds of either random (RND) or aligned (ALN) orientations. Correlating MSCs' chondrogenic outcome to pFAK activation and YAP localisation, MSCs on the RND scaffolds experienced the least amount of resting mechanical stress and underwent greatest chondrogenic differentiation in response to brief PEMF exposure (10 min at 1 mT) perpendicular to the dominant plane of the scaffolds (Z-directed). By contrast, in MSC-impregnated RND scaffold, greatest mitochondrial respiration resulted from X-directed PEMF exposure (parallel to the scaffold plane) and was associated with curtailed chondrogenesis. MSCs on TCP or the ALN scaffolds exhibited greater resting mechanical stress and accordingly, were unresponsive, or negatively responsive, to PEMF exposure from all directions. The efficacy of PEMF-induced MSC chondrogenesis is hence regulated in a multifaceted manner involving focal adhesion dynamics, as well as mitochondrial responses, culminating in a final cellular response. The combined contributions of micromechanical environment and magnetic field orientation hence will need to be considered when designing magnetic exposure paradigms.","PeriodicalId":346455,"journal":{"name":"Pharmacology eJournal","volume":"156 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115315399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Light-Activatable Precise Synergistic Chemotherapy Through a Dual Prodrug Polymer Guided by Drug-Mediated Computed Tomography Imaging 通过药物介导的计算机断层成像引导双前药聚合物进行光激活精确协同化疗

Pharmacology eJournal Pub Date : 2019-02-06 DOI: 10.2139/ssrn.3330019

Zigui Wang, Gaizhen Kuang, Zhiqiang Yu, Aimin Li, Dongfang Zhou, Yubin Huang

{"title":"Light-Activatable Precise Synergistic Chemotherapy Through a Dual Prodrug Polymer Guided by Drug-Mediated Computed Tomography Imaging","authors":"Zigui Wang, Gaizhen Kuang, Zhiqiang Yu, Aimin Li, Dongfang Zhou, Yubin Huang","doi":"10.2139/ssrn.3330019","DOIUrl":"https://doi.org/10.2139/ssrn.3330019","url":null,"abstract":"The synergistic efficacy and clinical application of light-responsive polymeric co-delivery are severely restricted by the uncertain drug ratio and the potential adverse effects from light-responsive molecules and extra contrast agents. Here, we report the design of a dual prodrug polymer (DPP) for light-activatable precise synergistic chemotherapy guided by drug-mediated computed tomography imaging without the introduction of any extra light-responsive molecule and contrast agent. The self-assembled nanoparticle (DPP NP) was capable of triggering bioactive Pt(II) release by visible light in cancer cells/tumor, further inducing acid hydrolysis of DMC. Notably, the synergistic cancer cell killing ratio of Pt(II) and DMC in DPP NP was fixed at an optimal value even after cellular uptake, resulting in enhanced synergistic antitumor efficacy in vitro and in vivo. Due to the high content of heavy metal Pt in the polymer chain, the spatial/temporal dynamic bio-distribution as well as metabolism of DPP NP in tumor can be monitored via Pt drug-mediated computed tomography (DMCT) imaging to guide the illumination parameters for optimized light-activatable synergistic chemotherapy. Guided by Pt DMCT imaging, DPP NP showed an excellent light-activatable antitumor efficacy and low toxicity with 75% fully cured tumors. The light-activatable dual drug polymer system could be potential for precise theranostic nanomedicine.","PeriodicalId":346455,"journal":{"name":"Pharmacology eJournal","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130934701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

One Year after the Launch of the First U.S. Biosimilar Drug: Lessons for the Future? 美国首个生物仿制药上市一年后:对未来的启示?

Pharmacology eJournal Pub Date : 2017-08-09 DOI: 10.2139/SSRN.3016138

H. Grabowski, Zoya Marriott, P. Kovacheva, A. Elzinga

引用次数: 0

Legalización del uso terapéutico del cannabis (About Legalizing Medical Use of Cannabis) Legalización del uso terapsamutico del cannabis(关于医用大麻合法化)

Pharmacology eJournal Pub Date : 2016-07-01 DOI: 10.2139/ssrn.3451236

Diego Fernando Ramos Flor

引用次数: 0