First responders increasing use of drones to save lives

Firefighters, EMS providers and police are using the technology to increase their visibility, making their job easier

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Boy uses CPR to save mother's life

The woman was trying to get her son out of a van when she hit her head on the door and became unconscious

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Phenotypic expressions of hereditary Transthyretin Ala97Ser related Amyloidosis (ATTR) in Taiwanese

The disease course and early signs specific to ATTR Ala97Ser, the most common endemic mutation in Taiwan, have not been well described. Since new medications can slow down the rate of disease progression, the ...

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Caught in a no-win situation: discussions about CCSVI between persons with multiple sclerosis and their neurologists – a qualitative study

In recent years, shared decision making (SDM) has been promoted as a model to guide interactions between persons with MS and their neurologists to reach mutually satisfying decisions about disease management –...

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Aggregation-prone GFAP mutation in Alexander disease validated using a zebrafish model

Alexander disease (AxD) is an astrogliopathy that predominantly affects the white matter of the central nervous system (CNS), and is caused by a mutation in the gene encoding the glial fibrillary acidic protei...

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The hemorrhagic transformation index score: a prediction tool in middle cerebral artery ischemic stroke

We aimed to develop a tool, the hemorrhagic transformation (HT) index (HTI), to predict any HT within 14 days after middle cerebral artery (MCA) stroke onset regardless of the intravenous recombinant tissue pl...

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A multifunctional nanocarrier for efficient TRAIL-based gene therapy against hepatocellular carcinoma with desmoplasia

Abstract

The anti-cancer efficacy of TNF-related apoptosis-inducing ligand (TRAIL)-based therapy is limited due to systemic toxicity, poor bioavailability, and the development of TRAIL-resistance. We developed a tumor-targeted LCPP (Lipid/Calcium/Phosphate/Protamine) nanoparticle (NP) to deliver TRAIL plasmid DNA (pDNA) into hepatocellular carcinoma (HCC) cells. TRAIL pDNA was encapsulated in a pH stimuli-responsive calcium phosphate (CaP) core, and protamine was added to facilitate nuclear delivery of pDNA. In addition, the intracellular release of Ca²⁺ from the CaP core overcame TRAIL resistance via calcium influx-dependent DR5 upregulation. TRAIL expression also attenuated fibrosis in the liver tissues surrounding HCCs by reverting activated hepatic stellate cells (HSCs) to a quiescent state or by directly inducing apoptosis in activated HSCs. Conclusion: TRAIL pDNA delivered by HCC-targeted LCPP NPs in combination with conventional sorafenib treatment attenuated HCC progression as well as liver fibrosis. Overall, our study presents an effective TRAIL-based cancer therapy that could be developed for clinical applications. This article is protected by copyright. All rights reserved.

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