Rhein kills Actinobacillus pleuropneumoniae, reduces biofilm formation, and effectively treats bacterial lung infections in mice.

Background. Actinobacillus pleuropneumoniae, a member of the Pasteurellaceae family, is known for its highly infectious nature and is the primary causative agent of infectious pleuropneumonia in pigs. This disease poses a considerable threat to the global pig industry and leads to substantial economic losses due to reduced productivity, increased mortality rates, and the need for extensive veterinary care and treatment. Due to the emergence of multi-drug-resistant strains, Chinese herbal medicine is considered one of the best alternatives to antibiotics due to its unique mechanism of action and other properties. As a type of Chinese herbal medicine, Rhein has the advantages of a wide antibacterial spectrum and is less likely to develop drug resistance, which can perfectly solve the limitations of current antibacterial treatments.Methods. The killing effect of Rhein on A. pleuropneumoniae was detected by fluorescence quantification of differential expression changes of key genes, and scanning electron microscopy was used to observe the changes in A. pleuropneumoniae status after Rhein treatment. Establishing a mouse model to observe the treatment of Rhein after A. pleuropneumoniae infection.Results. Here, in this study, we found that Rhein had a good killing effect on A. pleuropneumoniae and that the MIC was 25 µg ml-1. After 3 h of action, Rhein (4×MIC) completely kills A. pleuropneumoniae and Rhein has good stability. In addition, the treatment with Rhein (1×MIC) significantly reduced the formation of bacterial biofilms. Therapeutic evaluation in a murine model showed that Rhein protects mice from A. pleuropneumoniae and relieves lung inflammation. Quantitative RT-PCR (Quantitative reverse transcription polymerase chain reaction is a molecular biology technique that combines both reverse transcription and polymerase chain reaction methods to quantitatively detect the amount of a specific RNA molecule) results showed that Rhein treatment significantly downregulated the expression of the IL-18 (Interleukin refers to a class of cytokines produced by white blood cells), TNF-α, p65 and p38 genes. Along with the downregulation of genes such as IL-18, it means that Rhein has an inhibitory effect on the expression of these genes, thereby reducing the activation of inflammatory cells and the production of inflammatory mediators. This helps reduce inflammation and protects tissue from further damage.Conclusions. This study reports the activity of Rhein against A. pleuropneumoniae and its mechanism, and reveals the ability of Rhein to treat A. pleuropneumoniae infection in mice, laying the foundation for the development of new drugs for bacterial infections.

Self-cleaning and regenerable nano zero-valent iron modified PCN-224 heterojunction for photo-enhanced radioactive waste reduction.

The expansion of large-scale nuclear power causes a substantial volume of radioactive wastewater containing uranium to be released into the environment. Because of uranium's toxicity and bioaccumulation, it is critical to develop the efficient and sustainable materials for selective removal of uranium (VI). Herein, a regenerable anti-biofouling nano zero-valent iron doped porphyrinic zirconium metal-organic framework (NZVI@PCN-224) heterojunction system was successfully fabricated. Due to the Schottky-junction effect at the NZVI/MOF interface, the NZVI nanomaterial immobilized on PCN-224 could improve interfacial electron transfer and separation efficiency, and enhance entire reduction of highly soluble U(VI) to less soluble U(IV), involving photocatalytic reduction and chemical reduction. Meanwhile, the photocatalytic effect also prompts the NZVI@PCN-224 to produce more biotoxic reactive oxygen species (ROS), resulting in high anti-microbial and anti-algae activities. Under dark conditions, NZVI@PCN-224 with a large specific surface area could provide sufficient oxo atoms as the uranium binding sites and show the highest uranium-adsorbing capability of 57.94 mg/g at pH 4.0. After eight adsorption-desorption cycles, NZVI@PCN-224 still retained a high uranium adsorption capacity of 47.98 mg/g and elimination efficiency (91.72%). This sorption/reduction/anti-biofouling synergistic strategy of combining chelation, chemical reduction and photocatalytic performance inspires new insights for highly efficient treatment of liquid radioactive waste.

A Cascade-Targeting Nanocapsule for Enhanced Photothermal Tumor Therapy with Aid of Autophagy Inhibition.

Autophagy is a homeostatic lysosome-dependent metabolic process to eliminate damaged or dysfunctional cellular organelles, which is closely associated with tumor progression. Indocyanine green (ICG) can convert NIR light energy to localized heat for cancer cell and tissue ablation. However, the effect of autophagy modulation on ICG-mediated photothermal therapy remains unknown. In this study, it is found that primaquine (PQ) suppresses autophagy flux at a late stage through the impeding fusion of the autophagosome with the lysosome to form an autophagolysosome, leading to cell apoptosis or necrosis. This autophagosome-lysosome fusion inhibitory effect and the autophagosome accumulation are more evident in the photothermal therapy combined with autophagy inhibition. Motivated by this notable effect, a cascade-targeting nanocapsule (HCP) is constructed using an organic solvent-free strategy to coencapsulate PQ and ICG. By targeting the cluster designation 44 molecule and sequentially enhancing the cell-penetrating peptide-mediated endocytosis, the codelivery of PQ/ICG by HCP achieves selective recognition and reinforces the internalization by MCF-7 cells to exert a synergistic therapeutic effect on MCF-7 cells both in vitro and in vivo. The HCP system for the photothermal and autophagy inhibition combination therapy represents a novel strategy for the treatment of breast cancer.