Amphiphilic hydroxyethyl starch-based nanoparticles carrying linoleic acid modified berberine inhibit the expression of krasv12 oncogene in zebrafish.

Cancer is one of the most lethal diseases all over the world. Despite that many drugs have been developed for cancer therapy, they still suffer from various limitations including poor treating efficacy, toxicity to normal human cells, and the emergence of multidrug resistance. In this study, the amphiphilic LHES polymers were prepared using hydroxyethyl starch (HES) and linoleic acid as starting materials. The content and substitution degree of linoleic acid groups in LHES polymers were analyzed. The LHES polymers were used for fabricating LHES-B nanoparticles carrying a linoleic acid modified berberine derivative (L-BBR). The LHES-B nanoparticles showed high drug loading efficiency (29%) and could quickly release L-BBR under acidic pH condition (pH = 4.5). Biological investigations revealed that LHES-B nanoparticles significantly inhibited the proliferation of HepG2 cells and exhibited higher cytotoxicity than L-BBR. In a transgenic Tg(fabp10:rtTA2s-M2; TRE2:EGFP-krasv12) zebrafish model, LHES-B nanoparticles obviously inhibited the expression of krasv12 oncogene. These results indicated that LHES carriers could improve the anticancer activity of L-BBR, and the synthesized LHES-B nanoparticles showed great potential as anticancer drug.

Fabrication of yeast ß-glucan/sodium alginate/γ-polyglutamic acid composite particles for hemostasis and wound healing.

Particles with a porous structure can lead to quick hemostasis and provide a good matrix for cell proliferation during wound healing. Recently, many particle-based wound healing materials have been clinically applied. However, these products show good hemostatic ability but with poor wound healing ability. To solve this problem, this study fabricated APGG composite particles using yeast ß-glucan (obtained from Saccharomyces cerevisiae), sodium alginate, and γ-polyglutamic acid as the starting materials. The structure of yeast ß-glucan was modified with many carboxymethyl groups to obtain carboxymethylated ß-glucan, which could coordinate with Ca2+ ions to form a crosslinked structure. A morphology study indicated that the APGG particles showed an irregular spheroidal structure with a low density (<0.1 g cm-3) and high porosity (>40%). An in vitro study revealed that the particles exhibited a low BCI value, low hemolysis ratio, and good cytocompatibility against L929 cells. The APGG particles could quickly stop bleeding in a mouse liver injury model and exhibited better hemostatic ability than the commercially available product Celox. Furthermore, the APGG particles could accelerate the healing of non-infected wounds, and the expression levels of CD31, α-SMA, and VEGF related to angiogenesis were significantly enhanced.

The alleviative effect of C-phycocyanin peptides against TNBS-induced inflammatory bowel disease in zebrafish via the MAPK/Nrf2 signaling pathways.

INTRODUCTION: Ulcerative colitis (UC) is an incurable and highly complex chronic inflammatory bowel disease (IBD) affecting millions of people worldwide. C-phycocyanin (C-PC) has been reported to possess outstanding anti-inflammatory activities and can effectively inhibit various inflammation-related diseases. Whether C-PC-derived bioactive peptides can inhibit intestinal inflammation is worth research and consideration. METHODS: The inhibition activities of three anti-neuroinflammatory peptides were evaluated using 2-4-6-trinitrobenzen sulfonic acid (TNBS)-induced zebrafish colitis model. Subsequently, the abilities of peptides to promote gastrointestinal motility were also examined. The changes in the intestinal pathological symptoms and ultrastructure of intestinal, reactive oxygen species (ROS) levels, and antioxidant enzymes were then determined after co-treatment with peptides and TNBS. Transcriptome analysis was used to investigate the underlying ameliorating TNBS-induced colitis effects molecular mechanisms of better activity peptide. Furthermore, quantitative reverse-transcription polymerase chain reaction and molecular docking techniques verified the mRNA sequencing results. RESULTS: Three peptides, MHLWAAK, MAQAAEYYR and MDYYFEER, which significantly inhibit macrophage migration, were synthesized. The results showed that these peptides could effectively alleviate the inflammatory responses in the TNBS-induced zebrafish model of colitis. In addition, co-treatment with TNBS and C-PC peptides could decrease ROS production and increase antioxidant enzyme activities in zebrafish larvae. Moreover, MHLWAAK had the most significantly therapeutic effects on colitis in zebrafish. The transcriptome analysis suggests that the effect of MHLWAAK on TNBS-induced colitis may be associated with the modulation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and mitogen-activated protein kinase (MAPK) signaling pathway associated genes. In addition, molecular docking was conducted to study the prospective interaction between peptides and the key proteins that streamline the Nrf2 and MAPK signaling pathways. IL-6, JNK3, TNF-α, KEAP1-NRF2 complex and MAPK may be the core targets of MHLWAAK in treating colitis. CONCLUSION: The results suggested that the three C-PC-derived peptides could ameliorate TNBS-induced colitis in zebrafish, and these peptides might be a promising therapeutic candidate for UC treatment.