The Positive Influence of Polyphenols Extracted From Pueraria lobata Root on the Gut Microbiota and Its Antioxidant Capability.

Pueraria lobata, an edible food and medicinal plant, is a rich source of bioactive components. In this study, a polyphenol-rich extract was isolated from P. lobata. Puerarin was identified, and the high antioxidant bioactivity of the P. lobata extract was evaluated using the methods of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS), and hydroxyl free radical scavenging ratio. Additionally, the IC50 values of DPPH, ABTS, and hydroxyl radical scavenging activities were 50.8, 13.9, and 100.4 µg/ml, respectively. Then, the P. lobata extract was administered to C57Bl/6J mice and confirmed to have a superior effect on enhancing the antioxidant status including improving superoxide dismutase activity, glutathione peroxidase peroxide activity, total antioxidant capacity activity, and malondialdehyde contents in vivo. Furthermore, the P. lobata extract had beneficial and prebiotic effects on the composition and structure of gut microbiota. Results showed that the P. lobata extract significantly increased the abundance of beneficial bacteria, involving Lactobacillaceae and Bacteroidetes, and decreased the abundance of Ruminococcaceae, Prevotellaceae, and Burkholderiaceae. Overall, our results provided a basis for using the P. lobata extract as a promising and potential functional ingredient for the food industry.

Establishment of drug screening in human embryonic stem cells based on a high-content screening system.

High-content screening (HCS) systems can be used for high-throughput screening of drugs in human embryonic stem cells (hESCs). However, hESCs require immunofluorescence staining with stemness markers (e.g., Oct-4) prior to HCS, which can be time consuming and labor intensive. In this study, we employed transgenic hESCs with enhanced green fluorescent protein driven by stemness gene Oct-4 promoter (Oct-4-EGFP-H9), in which the colony area and relative green fluorescence area inferred a state of hESC proliferation and stemness, respectively. The Oct-4-EGFP-H9 transgenic hESCs were cultured in mTeSR medium with different concentrations of 5-Fluorouracil (5-FU), vitamin C (VC), or retinoic acid (RA) for 5-7 days, followed by repeated imaging using the HCS system. Finally, the hESC colony area and green fluorescence area were calculated. Results showed that 5-FU treatment markedly reduced colony area in a dose-dependent manner, whereas VC and RA treatments did not. MTT assay and flow cytometry indicated that 5-FU inhibited the proliferation of hESCs significantly, verifying reliability of the data from the HCS system based on colony area analysis. The green fluorescence to total colony area ratio decreased with RA treatment, suggesting that RA significantly promoted differentiation, whereas 5-FU and VC had almost no effect, as verified by quantitative real-time polymerase chain reaction and western blot analysis. In conclusion, our study established a rapid and efficient drug screening system without the requirement of staining based on HCS.

Biodegradable nanotheranostics with hyperthermia-induced bubble ability for ultrasound imaging-guided chemo-photothermal therapy.

BACKGROUND: Theranostics, elaborately integrating both therapeutic and diagnostic functions into a nanoplatform holds great potential for precision cancer medicine. METHODS: Herein, a biodegradable theranostic nanoplatform with hyperthermia-induced bubble ability for highly efficient ultrasound (US) imaging-guided chemo-photothermal therapy of breast tumors was developed. The prepared nanoparticles consisted of polydopamine (PDA)-modified hollow mesoporous organosilica nanoparticles (HMONs) with approximately 75 nm in diameter for doxorubicin (DOX) loading and perfluoropentane (PFP) filling. In addition, the pH-sensitive PDA coating served as both gatekeeper controlling DOX release and photothermal agent for inducing hyperthermia. RESULTS: Such nanoplatform (PDA@HMONs-DOX/PFP, PHDP) provides efficient loading (328 mg/g) and controllable stimuli-responsive release of DOX for chemotherapy. The incorporated disulfide bonds in the framework of HMONs endowed nanoparticles with intrinsic glutathione-responsive biodegradability and improved biocompatibility. Benefiting from the hyperthermia upon an 808-nm laser irradiation of PDA, the liquid-gas phase transition of the loaded PFP was induced, resulting in the generation of the nanobubbles, followed by the coalescence into microbubbles. This conversation could enhance the tumor cell uptake of nanoparticles, as well as intensify the US imaging signals. In addition, a synergistic therapeutic effect of our fabricated nanoplatform on cells/tumor growth effect has been systematically evaluated both in vitro and in vivo. CONCLUSION: Therefore, such "all-in-one" PHDP nanoparticles with satisfactory biocompatibility and biodegradability, hyperthermia-induced bubble ability and simultaneous US imaging performance hold great potential for cancer nanotheranostics.