Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Environmentally Friendly and Broad-Spectrum Antibacterial Poly(hexamethylene guanidine)-Modified Polypropylene and Its Antifouling Application.

Biological fouling is one of the main reasons that limits the application of traditional polypropylene (PP) fishing nets in aquaculture. Here, a new environmentally friendly and broad-spectrum antibacterial agent called cationic poly(hexamethylene guanidine) (PHMG) was grafted onto PP molecular chains via permanent chemical bonding to inhibit the biological fouling. The antibacterial monofilaments were obtained by blending different contents of PP-g-PHMG with PP by melt spinning. FTIR results found PHMG to be stably present in the mixed monofilaments after high-temperature melt spinning molding. The crystallinity, relaxation behavior, mechanical properties, water absorptivity, and antibacterial and antifouling efficiencies of the PP-g-PHMG/PP blends were strongly dependent on PP-g-PHMG. The crystallinity increased with increasing PP-g-PHMG content. Adding PP-g-PHMG improved the breaking strength, knotting strength, and elongation at the break for all ratios of PP-g-PHMG/PP blends. However, the water absorption caused by PHMG is low, ranging between 2.48% and 3.45% for the PP-g-PHMG/PP monofilaments. The monofilaments showed excellent nonleaching antimicrobial activities against Staphylococcus aureus and Escherichia coli. The electrostatic adsorption of the negatively charged bacteria and the destruction of their cell membrane allowed the growth inhibition to reach 99.69% with a PP-g-PHMG content of 40%. The marine fish farming experiment also showed a long-term antifouling effect.

Development of a recombinant adenovirus-vectored vaccine against both infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in rainbow trout (Oncorhynchus mykiss).

Infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV) are typical pathogens of rainbow trout Oncorhynchus mykiss, and the concurrent infection of the two viruses is very common among modern trout hatcheries, which has caused huge economic losses to the rainbow trout farming industry. To prevent and control the spread of IHNV and IPNV in juvenile trout simultaneously, in this study a bivalent recombinant adenovirus vaccine with IHNV Glycoprotein (G) and IPNV VP2 genes was developed. After immunizing juvenile trout with this bivalent vaccine via the immersion route, the expression levels of IHNV G and IPNV VP2 and the representative immune genes in vaccinated and control rainbow trout were tested to evaluate the correlation of immune responses with the expression of viral genes. The neutralizing antibody level induced by this bivalent vaccine as well as the protection efficacy of the vaccine against IHNV and IPNV was also evaluated. The results showed that IHNV G and IPNV VP2 were successfully expressed in juvenile trout, and all the innate and adaptive immune genes were up-regulated. This indicated that the level of the innate and adaptive immune responses were significantly increased, which might be induced by the high expression of the two viral proteins. Compared with the controls, high levels of neutralizing antibodies against IHNV and IPNV were induced in the vaccinated trout. Besides, the bivalent recombinant adenovirus vaccine showed high protection rate against IHNV, with the relative percent survival (RPS) of 81.25%, as well as against IPNV, with the RPS of 78.95%. Taken together, our findings clearly demonstrated that replication-defective adenovirus can be developed as a qualified vector for fish vaccines and IHNV G and IPNV VP2 were two suitable antigenic genes that could induce effective immune protection against these two pathogens. This study provided new insights into developing bivalent vectored vaccines and controlling the spread of IHNV and IPNV simultaneously in juvenile trout.

Histological and Comparative Transcriptome Analyses Provide Insights into Small Intestine Health in Diarrheal Piglets after Infection with Clostridium Perfringens Type C.

C. perfringens type C can induce enteritis accompanied by diarrhea and annually causes significant economic losses to the global pig industry. The pathogenic mechanisms of C. perfringens type C in pigs are still largely unknown. To investigate this, we challenged seven-day-old piglets with C. perfringens type C to cause diarrhea. We performed hematoxylin & eosin (H&E) staining of the small intestine (including duodenum, jejunum, and ileum) and assessed gene expression in the ileal tissue. H&E staining of the duodenum, jejunum, and ileum demonstrated inflammation and edema of the lamina propria and submucosa. A total of 2181 differentially expressed genes (DEGs) were obtained in ileal tissues. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of DEGs indicated that the main pathways were enriched in the T cell receptor signaling pathway, NF-kappa B signaling pathway, and (tumor necrosis factor) TNF signaling pathway. These results provide insights into the pathogenicity of C. perfringens type C and improve our understanding of host-bacteria interactions.

Development of a live vector vaccine against infectious hematopoietic necrosis virus in rainbow trout.

Infectious hematopoietic necrosis virus (IHNV) leads to serious disease and economic losses in the salmonid aquaculture industry. The present study aimed to develop an effective and efficient vaccine to protect rainbow trout (Oncorhynchus mykiss) against IHNV infection. Administered via the immersion route, a live vector vaccine containing the regions of the IHNV glycoprotein (G) induced immune responses in rainbow trout. Use of the immersion route induced more-efficient mucosal immunity than intramuscular injection vaccination. IHNV G gene expression was detected in the spleens of rainbow trout at 3, 7 and 15 days post-vaccination (dpv). The G gene expression continuously decreased between 3 and 15 dpv. In addition, the expression of TLR-3, TLR-7 and TLR-8 was upregulated after vaccination, and the highest expression levels of IFN-1, Mx-1, Mx-3, Vig-1 and Vig-2 were observed at 3 dpv. Four markers of the adaptive immune response (CD4, CD8, IgM and IgT) gradually increased. When experimental fish were challenged with IHNV by immersion, significant differences in cumulative percentage mortality were observed in the vaccinated fish and the unvaccinated (empty-plasmid-vaccinated) fish. The relative survival rate was 92% and 6% in the vaccinated group and empty-plasmid group, respectively. Serum antibody levels gradually increased in the vaccinated fish, unlike in the unvaccinated fish, after 7 dpv. Our results suggest there was a significant increase in fish immune responses and resistance to infection with IHNV following administration of the live vector vaccine. Therefore, this live vector vaccine is a promising vaccine that may be utilized to protect rainbow trout against IHNV.