Triptonoterpene, a Natural Product from <i>Celastrus orbiculatus</i> Thunb, Has Biological Activity against the Metastasis of Gastric Cancer Cells

Cancer is one of the greatest threats to human health. Gastric cancer (GC) is the fifth most common malignant tumor in the world. Invasion and metastasis are the major difficulties in the treatment of GC. Herbal medicines and their extracts have a lengthy history of being used to treat tumors in China. The anti-tumoral effects of the natural products derived from herbs have received a great deal of attention. Our previous studies have shown that the traditional Chinese herb Celastrus orbiculatus Thunb extract (COE) can inhibit the invasion and metastasis of GC cells, but the specific anti-cancer components of COE are still unclear. Dozens of natural products from COE have been isolated and identified by HPLC spectroscopy in our previous experiments. Triptonoterpene is one of the active ingredients in COE. In this study, we focused on revealing whether Triptonoterpene has an excellent anti-GC effect and can be used as an effective component of Celastrus orbiculatus Thunb in the treatment of tumors. We first observed that Triptonoterpene reduces GC cell proliferation through CCK-8 assays and colony formation experiments. The cell adhesion assays have shown that Triptonoterpene inhibits adhesion between cells and the cell matrix during tumor invasion. In addition, the cell migration assay has shown that Triptonoterpene inhibits the invasion and migration of GC cells. The high-connotation cell dynamic tracking experiment has also shown the same results. The effects of Triptonoterpene on epidermal mesenchymal transition (EMT)-related and matrix metalloproteinases (MMPs)-related proteins in gastric cancer cells were detected by Western blots. We found that Triptonoterpene could significantly inhibit the changes in EMT-related and invasion and metastasis-related proteins. Altogether, these results suggest that Triptonoterpene is capable of inhibiting the migration and invasion of GC cells. Triptonoterpene, as a natural product from Celastrus orbiculatus Thunb, has significant anti-gastric cancer effects, and is likely to be one of the major equivalent components of Celastrus orbiculatus Thunb

Mitochondrial Membrane Potential Independent Near-Infrared Mitochondrial Viscosity Probes for Real-Time Tracking Mitophagy

Mitophagy is a vital cellular process playing vital roles in regulating cellular metabolism and mitochondrial quality control. Mitochondrial viscosity is a key microenvironmental index, closely associated with mitochondrial status. To monitor mitophagy and mitochondrial viscosity, three molecular rotors (Mito-1, Mito-2, and Mito-3) were developed. All probes contain a cationic quinolinium unit and a C12 chain so that they can tightly bind mitochondria and are not affected by the mitochondrial membrane potential. Optical studies showed that all probes are sensitive to viscosity changes with an off–on fluorescence response, and Mito-3 shows the best fluorescence enhancement. Bioimaging studies showed that all these probes can not only tightly locate and visualize mitochondria with near-infrared fluorescence but also effectively monitor the mitochondrial viscosity changes in cells. Moreover, Mito-3 was successfully applied to visualize the mitophagy process induced by starvation, and mitochondrial viscosity was found to show an increase during mitophagy. We expect Mito-3 to become a useful imaging tool for studying mitochondrial viscosity and mitophagy

Selection of Aptamers for Hydrophobic Drug Docetaxel To Improve Its Solubility

With the development of combinatorial chemistry and high-throughput screening, the number of hydrophobic drug candidates continues to increase. However, the low solubility of hydrophobic drugs could induce erratic absorption patterns and affect the drug efficacy. Aptamers are artificially selected highly water-soluble oligonucleotides that bind to ions, small molecules, proteins, living cells, and even tissues. Herein, to increase the solubility of hydrophobic drug, we screened the aptamer by exploiting DNA library immobilization selection strategy and microfluidic technology. The highly water-soluble aptamer might influence the dissolving capacity of its target. To demonstrate the concept, docetaxel (DOC), a second-generation taxoid cytotoxic with significant antitumor agent activity, was chosen as the model. It is generally known that the clinical application of docetaxel is limited greatly owing to its poor water solubility and serious side effects. After seven rounds of selection, two docetaxel-specific aptamers DOC6–5 and DOC7–38, were successfully obtained, and their apparent dissociation constants (<i>K</i>_d) were at nanomolar level. Then these two 100 mer ssDNA aptamers against docetaxel were truncated to 22 mer ones by utilizing the recognition domain. Moreover, the shorter aptamer exhibited higher binding affinity than 100 mer ssDNA aptamers. By adding the optimized aptamer, the solubility of docetaxel was increased from ∼14 μM to ∼145 μM, and the cytotoxicity of docetaxel did not reduce in the presence of aptamer. Therefore, the aptamer was used as a solubilizer to improve the solubility of hydrophobic drug (docetaxel) in aqueous phase. This strategy may also be extended to other hydrophobic drugs. Meanwhile, this work could also provide a useful tool for tumor targeting therapy by combining with cell target ligands

Realizing a Brain-Like Transistor Memory with Triple Data-Storage Modes by One Single Smart Molecular Dopant in the Dielectric Layer

Human brain simultaneously gains sensory memory, short-term memory, and long-term memory, which allows information from the outside world to be sensed in the form of chemical and physical stimuli and enables highly efficient information storage, exchange, and processing. Such intelligent memory behavior guarantees human beings to not only solve the most complicated tasks but also rapidly respond to external environments. Developing brain-like memory with versatile data-storage modes plays an increasingly important role in modern information technologies. However, traditional memory devices generally only show one single mode of memory and suffer from poor tunability. To this end, here we develop a brain-like transistor memory with triple operation modes (i.e., sensory, short-term, and long-term memory) by doping the dielectric layer with multistimuli responsive donor–acceptor Stenhouse adducts. When been written with humidity, the transistor behaves like a “sensory memory” as the data fade immediately upon humidity removal. When been written with light, the transistor exhibits a volatile memory and could be erased by heating, analogous to the “short-term memory.” Further, when the transistor is programmed by heat or electrical field, a long-term memory is created. This work opens a new door to design intelligent memories for advanced applications