Oncolytic virus which arms the therapeutic gene to enhance anti-tumor activity is a prevalent strategy to improve oncovirotherapy of cancer. Newcastle disease virus (NDV) is a naturally oncolytic virus used for cancer therapy. Previously, we generated a mouse-human chimeric HAb18 antibody (cHAb18) against tumor-associated antigen CD147 and demonstrated the inhibition of invasion and migration of hepatocellular carcinoma (HCC) cells. Here, we constructed a recombinant NDV carrying intact cHAb18 gene (rNDV-18HL) based on Italien strain using a reverse genetics system. Recombinant rNDV-18HL was generated using reverse genetics technology. The characteristics of virally expressed cHAb18 antibody were identified by western blot, enzyme-linked immunosorbent assay, transwell invasion assay, and surface plasmon resonance technology. The biodistribution of recombinant rNDV-18HL using orthotopic xenograft mouse model was assessed with living imaging and immunohistochemistry. Kaplan-Meier survival curves and the log-rank test were performed to analyze the anti-tumor activity of rNDV-18HL. The cHAb18 was produced in rNDV-18HL-infected cells followed by releasing into the supernatant by cytolysis. The rNDV-18HL-encoded cHAb18 antibody kept affinity for CD147 and showed inhibiting the migration and invasion of HCC cells. Viral replication and virulence were not attenuated by the incorporation of cHAb18 gene which significantly enhanced the suppression of relict tumor cell migration. The rNDV-18HL selectively replicated in orthotopic HCC xenografts leading to cHAb18 expression in situ, which induced the tumor necrosis, reduced the intrahepatic metastasis, and prolonged the survival in mice. This study provides a new strategy of arming oncolytic NDV with therapeutic antibody to enhance anti-tumor efficacy of cancer therapy.

The Wuzhishan miniature pig originates from Hainan Island, P. R. China, and is considered useful for medical and veterinary research due to its small size; a mature adult weights less than 25 kg. To reveal the genetic characteristics of this breed, the genetic polymorphism in 4 inbred strains was estimated using 30 microsatellite genes, multiplex polymerase chain reaction, and gene scanning. The average number of alleles at the 30 marker loci was 8.300, 4.533, 6.700, and 7.433, respectively. The polymorphism information content was 0.632, 0.507, 0.653, and 0.691, respectively. The average homozygosity in these strains was 0.537, 0.546, 0.549, and 0.520, respectively. These results indicate a relatively high degree of heterozygosity, perhaps becaquse these strains were inbred for 3 generations. Therefore, a long-term inbred breeding program should be conducted for Wuzhishan pigs to establish an experimental model.

Polygonati Rhizoma has been reported to exhibit the ability to retard skin aging. However, the precise molecular mechanisms underlying remain largely elusive. In this study, we screened 9 active compounds in Polygonati Rhizoma using the TCMSP and SwissADME databases. Subsequently, 285 potential targets were identified via Swiss Target Prediction Database. Concurrently, 800 genes related to skin aging were retrieved from GeneCards, OMIM, and TTD databases. By intersecting these datasets with the potential targets of Polygonati Rhizoma, we pinpointed 17 overlapping genes. These genes were further subjected to GO function annotation and KEGG pathway analysis using DAVID database. A compound-target-pathway network was then constructed using Cytoscape software, highlighting two compounds (4',5-dihydroxyflavone and baicalein) and six targets (MAPK1, MAPK10, MMP9, PTGS2, PDGFRB, and CYP1B1). Molecular docking revealed that the binding energy between 4',5-dihydroxyflavone and baicalein with the six targets was less than - 5 kcal/mol, particularly for MMP9, PTGS2, and CYP1B1, indicating a stable interaction. The molecular dynamic simulations demonstrate that both ligands form stable complexes with MMP9 and PTGS2. Finally, the antioxidant capacity of 4'5-dihydroxyflavone and baicalein was evaluated in vitro, confirming significant antioxidant activity. Collectively, our findings provide a systematic foundation for elucidating the molecular mechanisms underlying the anti-aging effects of Polygonati Rhizoma and offer valuable insights into the development of anti-skin aging cosmetics.