Gene therapy can be defined as the transfer of genetic materials to specific cells in order to exert a therapeutic effect. It is a promising approach to the treatment of a wide range of diseases by compensating for defective genes or producing beneficial proteins.1) Gene vectors have much important roles in gene therapy. Recently, nonviral vectors have been increasingly proposed as safer alternatives to viral vectors because of their potential advantages such as ease of synthesis, cell/tissue targeting, low immune response, and unrestricted plasmid size.2) Among nonviral systems, cationic polymers have attracted increasing attention because they can easily form self-assembling polyelectrolyte complexes between plasmid DNA and cationic polymers, and mediate transfection via condensing DNA into nanoparticles, protecting DNA from enzymatic degradation, and facilitating the cell uptake and endolysosomal escape.3) Among cationic polymers, polyethylenimine (PEI) and chitosan are widely used as nonviral vectors for gene delivery. They have the same ability to enter cells by binding to proteoglycans on cell surfaces and undergoing endocytosis.4-6) However, after uptake, they have quite different transfection efficiency. PEI is considered to be the most effective cationic polymer for gene delivery.7) Its high proton-buffering capacity results in rapid osmolysis of the endosomes, and the PEI-DNA complexes escape into the cytosol and are subsequently transported into the nucleus. 8)However, PEI is also associated with dose-dependent toxicity, especially at high molecular weight, which probably explains why it has not yet been used in human studies.9) On the other hand, chitosan does not have high proton-buffering capacity, making it unable to escape from the endosomes in time. Chitosan is degraded in the endosome and the material is then released into the cytoplasm after hyperosmotic rupture of the cell membrane caused by the accumulation of degradation products. The material is then transported to the nucleus.5) Therefore chitosan is generally considered less effective in gene delivery systems than PEI in vitro and in vivo. But it is well known as a biocompatible, biodegradable, and relatively non toxic material with high cationic potential. 10)Therefore to design a complex that has both the advantages of PEI and chitosan, in other words, both high transfection efficiency and low toxicity, would be promising.Several groups have reported the pilot research in this area. Kim et al. 11) demonstrated that when PEI (10k) was combined with a water-soluble chitosan (WSC)/DNA complex, the transfection efficiency was enhanced via the proton sponge effect, and cell survival was not markedly decreased. Another group designed a chitosan-graft-PEI (CHI-g-PEI) copolymer using an imine reaction between periodateoxidized chitosan and low molecular weight PEI and obtained good results.12) However, the influence of the N/P ratio (the ratios of moles of the amine groups of cationic polymers to those of the phosphate ones of DNA), which mi...
Artemisia has long been used in traditional medicine and as a food source for different functions in eastern Asia. Artemisia vulgaris L. (AV) is a species of the genus Artemisia. Essential oils (EOs) were extracted from AV by subcritical butane extraction. EO contents were detected by electronic nose and headspace solid-phase microextraction coupled with gas chromatography (HS-SPME-GC-MS). To investigate the hepatoprotective effects, mice subjected to liver injury were treated intragastrically with EOs or eucalyptol for 3 days. Acetaminophen (APAP) alone caused severe liver injury characterized by significantly increased serum AST and ALT levels, ROS and hepatic malondialdehyde (MDA), as well as liver superoxide dismutase (SOD) and catalase (CAT) depletions. EOs significantly attenuated APAP-induced liver damages. Further study confirmed that eucalyptol is an inhibitor of Keap1, the affinity K D of eucalyptol and Keap1 was 1.42 × 10 −5 , which increased the Nrf2 translocation from the cytoplasm into the mitochondria. The activated Nrf2 increased the mRNA expression of uridine diphosphate glucuronosyltransferases (UGTs) and sulfotransferases (SULTs), also inhibiting CYP2E1 activities. Thus, the activated Nrf2 suppressed toxic intermediate formation, promoting APAP hepatic non-toxicity, whereby APAP was metabolized into APAP-gluc and APAP-sulf. Collectively, APAP non-toxic metabolism was accelerated by eucalyptol in protecting the liver against APAP-induced injury, indicating eucalyptol or EOs from AV potentials as a natural source of hepatoprotective agent.
Colon adenocarcinoma (COAD) is one of the most common malignant tumors with high morbidity and mortality rates worldwide. Due to the poor clinical outcomes, it is indispensable to investigate novel biomarkers for the diagnosis and prognosis of COAD. The aim of this study is to explore key genes as potential biomarkers for the diagnosis and prognosis of COAD for clinical utility. Gene expression profiles (GSE44076 and GSE44861) and gene methylation profile (GSE29490) were analyzed to identify the aberrantly methylated-differentially expressed genes by R language and Perl software. Function enrichments were performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Moreover, hub genes were identified through protein-protein interaction (PPI) network. Besides, key genes were found by the module analysis and The Cancer Genome Atlas (TCGA) survival analysis. Finally, TCGA data and quantitative real-time polymerase chain reaction (RT-qPCR) was used to validate the key genes involved in COAD. Our study found two hypomethylation-high-expression genes (CXCL3 and CXCL8) in COAD tissues compared with the adjacent normal tissues. These results were also confirmed by RT-qPCR with 25 pairs of COAD and adjacent normal tissues. Meanwhile, low expression of the two genes was associated with poor survival in patients with COAD. CXCL3 and CXCL8 may serve as key genes in the diagnosis and prognosis for COAD. K E Y W O R D Sbioinformatics, colon adenocarcinoma, CXCL3, CXCL8, key genes
Phototherapy and immunotherapy in combination is regarded as the ideal therapeutic modality to treat both primary and metastatic tumors. Immunotherapy uses different immunological approaches to stimulate the immune system to identify tumor cells for targeted elimination. Phototherapy destroys the primary tumors by light irradiation, which induces a series of immune responses through triggering immunogenic cancer cell death. Therefore, when integrating immunotherapy with phototherapy, a novel anti-cancer strategy called photoimmunotherapy (PIT) is emerging. This synergistic treatment modality can not only enhance the effectiveness of both therapies but also overcome their inherent limitations, opening a new era for the current anti-cancer therapy. Recently, the advancement of nanomaterials affords a platform for PIT. From all these nanomaterials, inorganic nanomaterials stand out as ideal mediators in PIT due to their unique physiochemical properties. Inorganic nanomaterials can not only serve as carriers to transport immunomodulatory agents in immunotherapy owing to their excellent drug-loading capacity but also function as photothermal agents or photosensitizers in phototherapy because of their great optical characteristics. In this review, the recent advances of multifunctional inorganic nanomaterial-mediated drug delivery and their contributions to cancer PIT will be highlighted.
The encapsulation of therapeutic agents into nano-based drug delivery system for cancer treatment has received considerable attention in recent years. Advancements in nanotechnology provide an opportunity for efficient delivery of anticancer drugs. The unique properties of nanoparticles not only allow cancer-specific drug delivery by inherent passive targeting phenomena and adopting active targeting strategies, but also improve the pharmacokinetics and bioavailability of the loaded drugs, leading to enhanced therapeutic efficacy and safety compared to conventional treatment modalities. Small molecule drugs are the most widely used anticancer agents at present, while biological macromolecules, such as therapeutic antibodies, peptides and genes, have gained increasing attention. Therefore, this review focuses on the recent achievements of novel nano-encapsulation in targeted drug delivery. A comprehensive introduction of intelligent delivery strategies based on various nanocarriers to encapsulate small molecule chemotherapeutic drugs and biological macromolecule drugs in cancer treatment will also be highlighted.
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