Dendritic targeted mRNA expression via a cis-acting RNA UTR element.

Local translation in neurites is considered as an important mechanism to modulate synaptic plasticity of neurons. However, it is hard to specifically express a protein-coding gene in neurites. Recently, the 5'-UTR of Tick-borne encephalitis virus (TBEV) is reported to be able to drive its RNA to the dendrites of infected neurons, as a cis-acting RNA element. To construct a neurite specific gene expression system, present study tested the ability of 5'-UTR of TBEV to bring a mRNA (mCherry CDS) to the neurites for targeted expression. We showed that both the 5'-UTR of TBEV and the 3'-UTR of Actb gene could bring the protein coding mRNA to neurites, and the TBEV 5'-UTR bearing mRNA was more robust targeted into neurites. About the safety of the TBEV 5'-UTR, there was no obvious cytotoxicity to the neurons when adding either cis-acting RNA element to the protein-expressing plasmid vectors. Given the short length and high efficiency of the TBEV 5'-UTR, the 5'-UTR of TBEV were assemble into an AAV plasmid to produce virus particles for expressing protein-coding gene in vivo. After two weeks infection, the TBEV 5'-UTR infected neurons expressed more mCherry protein in their neurites. In conclusion, as a short while high efficient cis-acting RNA element, TBEV 5'-UTR could be useful in neural system research and locally express synaptic proteins more precisely.

Platelet membrane-based biochemotactic-targeting nanoplatform combining PDT with EGFR inhibition therapy for the treatment of breast cancer.

Presently, the commonly used anti-tumor drugs lack targeting ability, resulting in a limited therapeutic efficacy and significant side effects. In this view, platelet membranes (PMs) not only exhibit specific binding of its P-selectin protein with CD44, which is highly expressed on breast cancer cells, to promote tumor-active targeting by PM biomimetic nanoplatforms, but also respond to vascular damage, thus inducing biochemotactic targeting to further facilitate the aggregation of these nanoplatforms. Therefore, in this study, a PM was applied to construct a biochemotactic-targeting nanotherapeutic platform based on dendritic large pore mesoporous silica nanoparticles (DLMSNs) co-loaded with chlorin e6 (Ce6) and lapatinib (LAP) to achieve the combination of photodynamic therapy (PDT) and EGFR inhibition therapy for breast cancer. Under laser irradiation, PM@DLMSN/Ce6/Lap could not only effectively kill breast tumor cells by the PDT, but also damage blood vessels. By combining the EGFR inhibition of LAP, PM@DLMSN/Ce6/Lap could better inhibit the migration and movement of tumor cells. In vitro and in vivo results showed that PM@DLMSN/Ce6/Lap could achieve active-targeting drug delivery to breast tumors and further recruit more nanoparticles to accumulate at tumor sites after the PDT-induced damage of blood vessels through biochemotactic targeting, achieving continuous EGFR inhibition to prevent tumor proliferation and metastasis. In conclusion, this study not only provides a new strategy for the clinical treatment of breast cancer, but also provides a design idea for improving the targeted delivery of anti-tumor drugs.

Treatment of lung cancer by acupuncture combined with medicine based on pathophysiological mechanism: A review.

Lung cancer is one of the most frequently diagnosed cancers in the world. There are an estimated 2.2 million new cases and 1.79 million deaths each year. Over the past 2 decades, our understanding of disease biology, the use of predictive biomarkers, and improvements in therapeutic approaches have made significant progress and transformed the outcomes of many patients. Treatment is determined by the subtype and stage of the cancer; however, the effect of personalized treatment remains unsatisfactory. The use of Chinese medicines has attracted increasing attention worldwide. Chinese medicine treatment of lung cancer has few side effects, which can effectively prolong the survival expectation of patients and improve their quality of life, and has attracted increasing attention. Based on the pathophysiological mechanism of lung cancer reported in modern medical research, this article explores the efficacy and safety of acupuncture combined with medicine in the treatment of lung cancer.