Background: Biogenic silver nanoparticles (AgNPs) have wider range of biomedical applications. The present work synthesized Tp-AgNPs using mycelial extract of endophytic fungus Talaromyces purpureogenus (MEEF), characterized, and analyzed for antibacterial, anti-proliferation and cell wounding healing activities. Methods: The synthesized Tp-AgNPs were characterized by UV-visible spectrophotometer (UV-Vis), field emission transmission electron microscopy (FETEM) with energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), particle size analysis (PSA) and X-ray diffraction (XRD). Further, antibacterial activity was determined by Kirby–Bauer test and anti-proliferation activity was tested in human lung carcinoma A549 by water-soluble tetrazolium and flow cytometer assay. In addition, cell wounding healing activity was determined by scratch assay. Results: UV-Vis results displayed a strong absorption peak from 390 nm to 420 nm, which indicated the successful synthesis of Tp-AgNPs. FETEM-EDS results indicated the round and triangle shaped Tp-AgNPs with the average size of 25 nm in accordance with PSA. FTIR analysis indicated the involvement of various functional molecules from MEEF in the synthesis of Tp-AgNPs. XRD result proved nature of Tp-AgNPs as a high-quality crystal. The Tp-AgNPs significantly inhibited the growth of bacterial pathogens at the minimal inhibitory concentration of 16.12 μg.mL^−1, for Gram,⁺ and 13.98 μg.mL^−1, for Gram^−, bacteria. Further, Tp-AgNPs (2 μg.mL^−1,) showed a strong anti-proliferation effect in A549. Interestingly, Tp-AgNPs was not cytotoxic to normal NIH3T3 cells. In addition, the NPs exhibited a strong cell wounding healing activity. Conclusion: This work biosynthesized AgNPs with strong antibacterial, anticancer and cell wound healing properties using endophytic fungus T. purpureogenus.

This work tested antioxidant, anti-lung cancer, and antibacterial activities by in vitro, in vivo, and computational experiments for the metabolites extracted from the bark, seed, and stem of Toxicodendron vernicifluum. The results showed that all the extracts significantly scavenged 1,2-diphenyl-1-picrylhydrazyl (DPPH) in a dose-dependent manner. But, the total phenol content (TPC) ranged from 2.12 to 89.25% and total flavonoids content (TFC) ranged from 1.02 to 15.62% in the extracts. The methanolic bark extract (MBE) exhibited higher DPPH scavenging activity than the other extracts, probably due to the higher content of the TPC and TFC present in it. Among the extracts, only the MBE showed anti-lung cancer activity at an acceptable level with a therapeutic index value (22.26) against human lung carcinoma. This was due to the cancer cell death in A549 induced by MBE through reactive oxygen species (ROS) generation, apoptosis, and cell arrest in G1 phase and inhibition of anti-pro-apoptotic protein survivin. Among the extracts, MBE showed significantly higher antibacterial activity as evident through the higher zone of inhibition 13 ± 0.5 mm against methycilin resistant strain of Staphylococcus aureus (MRSA), Salmonila enteria subp. enterica, and P. aeruginosa, 11 ± 0.3 mm against E. coli and 10 ± 0.2 mm against B. cereus. The MBE also showed an excellent antibacterial activity with lower minimal inhibitory concentration (MIC). Particularly, the MBE showed more significant antibacterial activity in MRSA. The in vivo antibacterial activity of the MBE was further tested in C. elegans model. The treatment of the MRSA induced cell disruption, damage and increased mortality of C. elegans as compared to the untreated and MBE treated C. elegans with normal OP50 diet. Moreover, the MBE treatment enhanced the survival of the MRSA infected C. elegans. The compounds, such as 2,3,3-trimethyl-Octane and benzoic from the MBE, metabolized the novel bacterial topoisomerases inhibitor (NBTI) and MRSA related protein (PBP2a). Overall the T. vernicifluum is potentially bioactive as evident by antioxidant, anti-lung cancer, and antibacterial assays. Further studies were targeted on the purification of the novel compounds for the clinical evaluation.

Disruption of the intestinal epithelial barrier, driven by imbalances in gut mucosal immunity and microbial homeostasis, is central to the onset and progression of inflammatory bowel disease (IBD). This study introduces a CO‐releasing polyoxometalates (POMs) nanozyme (PMC), synthesized by coordinating pentacarbonyl manganese bromide with molybdenum‐based POM nanoclusters. PMC demonstrates targeted accumulation at IBD‐affected sites, efficient scavenging of reactive oxygen species (ROS), and responsive CO release, resulting in multiple therapeutic effects. Extensive in vitro and in vivo studies have validated the exceptional capacity of PMC to repair intestinal barrier, attributed to their potent antioxidant and anti‐inflammatory properties, thereby achieving significant therapeutic efficacy in ulcerative colitis treatment. 16S rRNA sequencing indicated that PMC efficiently remodeled the gut microbiota composition. Single‐cell RNA sequencing indicates a reduction in pro‐inflammatory M1 macrophages, alongside suppressed ROS and inflammatory signaling pathways. Concurrently, an increase in reparative M2 macrophages and intestinal stem cells is observed, in addition to significant activation of the VEGF signaling pathway in macrophages and the NOTCH pathway in stem cells, underscoring the potential of PMC to restore immune balance and promote tissue repair. This study positions PMC as a promising, multifunctional therapeutic agent for IBD treatment owing to its robust intestinal barrier‐restoring capability.

Intestinal barrier disruption, driven by oxidative stress, ferroptosis, immune imbalance, and gut microbiota dysbiosis, plays a crucial role in inflammatory bowel disease (IBD) pathogenesis. Current treatments are often ineffective and cause side effects, emphasizing the need for novel therapies. Here, we have developed an engineered probiotic-derived outer membrane vesicle (OMV), GDO@CM, combining antioxidant gallic acid (GA) and anti-inflammatory H₂S for targeted intestinal barrier repair. Constructed from Escherichia coli Nissle 1917 (EcN)-derived OMVs, GA and diallyl trisulfide (DATS) are incorporated into the hydrophilic inner cavity and lipid bilayer, respectively, while mannose-decorated chitosan (CM) is electrostatically attached to the OMVs surface, enhancing stability and enabling targeted delivery to damaged colonic lesions. GDO@CM efficiently enters activated immune cells and epithelial cells, where GA scavenges reactive oxygen species and inhibits ferroptosis, while H₂S amplifies anti-inflammatory effects. OMVs further synergize with GA and DATS to suppress pathogenic bacteria. These combined actions facilitate effective barrier repair and alleviate IBD symptoms. Single-cell RNA sequencing reveals that GDO@CM reduces inflammation, increases the proportion of reparative M2 macrophages and intestinal stem cells, and promotes epithelial cell proliferation via the APP/CD74 axis. Our findings establish GDO@CM as a promising multi-target therapeutic for IBD, offering a novel strategy for intestinal barrier restoration.