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Inflammatory bowel disease (IBD) is a persistent, lifelong inflammation of the digestive system. Dextran sulfate sodium is commonly used to induce colitis in experimental animal models, which causes epithelial damage, intestinal inflammation, mucin depletion, and dysbiosis of the gut microbiota. Various prebiotics, polysaccharides, and polypeptides are used for IBD treatment. In this study, we used a murine model utilizing BALB/c mice, with 10 mice per group, to investigate the treatment effect of sea conch peptide hydrolysate (CPH) on DSS-induced colitis mice. Colitis was induced through the administration of 2.5% DSS in drinking water over a seven-days period. Furthermore, on the eighth day of the experiment, sea conch peptide hydrolysate (CPH) at low (100 mg/kg), medium (200 mg/kg), and high (400 mg/kg) doses, which were continued for 14 days, were assessed for medicinal purposes in DSS-induced colitis mice. Our results showed that CPH treatment significantly alleviated the severity and symptoms of colitis. The epithelial integrity and histological damage were improved. Intestinal inflammation and inflammatory cell infiltration were improved. Furthermore, the expression of pro-inflammatory cytokines was reduced, and intestinal barrier integrity was restored by elevating the tight junction proteins. Moreover, 16s RNA sequencing revealed dysbiosis of the gut microbiota was observed upon DSS treatment, which was reinstated after CPH treatment. An increased level of Firmicutes and Lactobacillus was observed in the treatment groups. Finally, our results suggest that CPH would be recommended as a functional food source and also have the potential to be used as a medicinal product for different gastrointestinal disorders. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. Fibromodulin (FMOD) is the main proteoglycan that contributes to extracellular matrix (ECM) remodeling by binding to matrix molecules, thereby playing an essential role in tumor growth and metastasis. There are still no useful drugs that target FMOD for CRC treatment in clinics. Here, we first used public whole-genome expression datasets to analyze the expression level of FMOD in CRC and found that FMOD was upregulated in CRC and associated with poor patient prognosis. We then used the Ph.D.-12 phage display peptide library to obtain a novel FMOD antagonist peptide, named RP4, and tested its anti-cancer effects of RP4 in vitro and in vivo. These results showed that RP4 inhibited CRC cell growth and metastasis, and promoted apoptosis both in vitro and in vivo by binding to FMOD. In addition, RP4 treatment affected the CRC-associated immune microenvironment in a tumor model by promoting cytotoxic CD8+ T and NKT (natural killer T) cells and inhibiting CD25+ Foxp3+ Treg cells. Mechanistically, RP4 exerted anti-tumor effects by blocking the Akt and Wnt/β-catenin signaling pathways. This study implies that FMOD is a potential target for CRC treatment, and the novel FMOD antagonist peptide RP4 can be developed as a clinical drug for CRC treatment. [ABSTRACT FROM AUTHOR]

Abstract: Based on the aptamer-conjugated core–shell near-infrared fluorescent nanoparticles (NIR-Nps) and fluorescence anisotropy measurement, the present study reported proof-of-principle for a rapid homogeneous assay approach that can detect target cancer cells without the need of the complicated separation steps in whole blood samples. Experimental investigation showed that the novel NIR-Nps have negligible background fluorescence and low inner filtration interference in complex biologic systems such as whole blood. The specific recognition characteristic of aptamer in whole blood samples was investigated by using the proposed fluorescence anisotropy method. The results showed that the fluorescent nanoparticle-tagged aptamer probes sequence could achieve specific recognition of the target cancer cells from complex mixtures including whole blood samples. And the reaction conditions for the binding between fluorescent nanoparticle-conjugated aptamer probes and target cancer cells were optimized. The present approach can exhibit sensitive and reproducible fluorescence anisotropy responses to the target cells concentration and the calibration curve showed good linearity when the target cells concentration is in the range from 4.0×103 to 7.0×105 cells/mL. Moreover, the present fluorescence anisotropy assay technique could be practically utilized for the detection of acute leukemia samples with improved capabilities and be comparable to the immunophenotyping methods clinically used. [Copyright &y& Elsevier]

Triple-negative breast cancer (TNBC) is an aggressive cancer that poses a significant threat to women's health. Unfortunately, the lack of clinical targets leads the poor clinical outcomes in TNBC. Many cancers demonstrate overexpression of receptor for advanced glycation end products (RAGE), which can contribute to cancer progression. Despite the potential therapeutic value of blocking RAGE for TNBC treatment, effective peptide drugs have yet to be developed. In our study, we observed that RAGE was highly expressed in TNBC and was associated with poor disease progression. We subsequently investigated the antitumor effects and underlying mechanisms of the RAGE antagonist peptide RP7 in both in vitro and in vivo models of TNBC. Our study revealed that RP7 selectively binds to RAGE-overexpressing TNBC cell lines, including MDA-MB-231 and BT549, and significantly inhibits cell viability, migration, and invasion in both cell lines. Furthermore, RP7-treatment suppressed tumor growth in TNBC xenograft mouse models without inducing detectable toxicity in normal tissues. Mechanistically, RP7 was found to inhibit the phosphorylation of ERK1/2, IKKα/β, IKBα, and p65 to block the NF-κB pathway, prevent the entry of p65 into the nucleus, decrease the protein expression of Bcl-2 and HMGB1, and promote the release of cytochrome C from the mitochondria into the cytoplasm. These effects were observed to activate apoptosis and inhibit epithelial-mesenchymal transition (EMT) in TNBC cells. This study highlights RAGE as a candidate therapeutic target for TNBC treatment and suggests that the RAGE antagonist peptide RP7 is a promising anticancer drug for TNBC. [ABSTRACT FROM AUTHOR]