MicroRNAs (miRNAs), a class of small RNAs, are important molecules that influence several developmental processes and regulate RNA interference (RNAi), and are abundant in animals, plants, and plant tissues that are traditionally consumed in the diet. The survival of plant small RNAs from the diet in animals, however, remains unclear, and the persistence of miRNAs from dietary plants in the animal gastrointestinal (GI) tract is still under debate. In this study, ICR mice were fed plant total RNAs in quantities of 10–50 μg, extracted from Brassica oleracea. Serum, feces, and various tissues were collected from the mice after RNA consumption and analyzed for several miRNAs. Exogenous plant miRNAs were present in the sera, feces, and tissues of animals and these exogenous plant miRNAs were primarily acquired orally. MiR-172, the most highly enriched exogenous plant miRNA in B. oleracea, was found in the stomach, intestine, serum, and feces of mice that were fed plant RNA extracts including miR-172. The amount of miR-172 that survived passage through the GI tract varied among individuals, with a maximum of 4.5% recovered at the stomach of one individual, and had a range of 0.05–4.5% in different organs. Furthermore, miR-172 was detected in the blood, spleen, liver, and kidney of mice.
Multifunctional lanthanide-based upconversion nanoparticles (UCNPs), which feature efficiently convert low-energy photons into high-energy photons, have attracted considerable attention in the domain of materials science and biomedical applications. Due to their unique photophysical properties, including light-emitting stability, excellent upconversion luminescence efficiency, low autofluorescence, and high detection sensitivity, and high penetration depth in samples, UCNPs have been widely applied in biomedical applications, such as biosensing, imaging and theranostics. In this review, we briefly introduced the major components of UCNPs and the luminescence mechanism. Then, we compared several common design synthesis strategies and presented their advantages and disadvantages. Several examples of the functionalization of UCNPs were given. Next, we detailed their biological applications in bioimaging and disease treatment, particularly drug delivery and photodynamic therapy, including antibacterial photodynamic therapy. Finally, the future practical applications in materials science and biomedical fields, as well as the remaining challenges to UCNPs application, were described. This review provides useful practical information and insights for the research on and application of UCNPs in the field of cancer.
The misfolding and aggregation of amyloid beta (Aβ) peptides into amyloid fibrils are key events in the amyloid cascade hypothesis for the etiology of Alzheimer's disease (AD). Using thioflavin-T (ThT) fluorescence assay, atomic force microscopy, circular dichroism, size exclusion chromatography, surface plasmon resonance (SPR), and cytotoxicity tests, we demonstrate that tabersonine, an ingredient extracted from the bean of Voacanga africana, disrupts Aβ(1-42) aggregation and ameliorates Aβ aggregate-induced cytotoxicity. A small amount of tabersonine (e.g., 10 μM) can effectively inhibit the formation of Aβ(1-42) (e.g., 80 μM) fibrils or convert mature fibrils into largely innocuous amorphous aggregates. SPR results indicate that tabersonine binds to Aβ(1-42) oligomers in a dose-dependent way. Molecular dynamics (MD) simulations further confirm that tabersonine can bind to oligomers such as the pentamer of Aβ(1-42). Tabersonine preferentially interact with the β-sheet grooves of Aβ(1-42) containing aromatic and hydrophobic residues. The various binding sites and modes explain the diverse inhibitory effects of tabersonine on Aβ aggregation. Given that tabersonine is a natural product and a precursor for vincristine used in cancer chemotherapy, the biocompatibility and small size essential for permeating the blood-brain barrier make it a potential therapeutic drug candidate for treating AD.
Manipulation of tumor microRNAs (miRNAs) may offer novel avenues for treatment of cancer. However, development of safe, robust, non-viral delivery methods remains a main challenge to obtain the promise of gene therapy. The miR-145 is dysregulated in many cancers, including colon carcer, and further in vitro investigation established antiproliferative and proapoptotic roles of miR-145. Herein, we study a PLGA/PEI (poly (d, l-lactide-co-glycolide)/polyethylenimine)-mediated miRNA vector delivery system; the validation of the method was carried out using a colon cancer xenograft model with miR-145 vector encoding for the expression of miR-145 (pDNA). First, high-molecular-weight PEI (25000 Da) was conjugated with cetyl to formulate reducible cetylated PEI (PEI-cet), and then PEI-cet was introduced to PLGA suspension. Next, PLGA/PEI-cet was crosslinked with hyaluronic acid (HA) to facilitate cellular uptake of miRNA plasmid vector via HA receptor-mediated endocytosis. After local administration of PLGA/PEI/HA complexes, intact miRNA plasmid vectors were delivered into HCT-116 colon cancer cells and xenograft tumor-bearing mice, and significant antitumor effects were achieved. The results show that the HA-based miR-145 nanocarrier could efficiently facilitate cellular uptake and significantly enhance miR-145 expression in HCT-116 cells. Consequently, the increased miR-145 induced G1 cell cycle arrest, reduced tumor proliferation and increased apoptosis, inhibited HCT-116 cell migration and suppressed c-MYC expressions, a regulatory target of miR-145. Of particular importance is the significant decrease in tumor growth in the mice model of colon cancer with the targeting miR-145 delivery system. The results in this work show that miR-145 has been effectively delivered to colon carcinomas through a PLGA/PEI/HA vehicle, indicating a promising miRNA replacement therapy strategy.
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