Purpose: The prognosis for colorectal cancer (CRC) patients is drastically impacted by the presence of lymph node or liver metastases at diagnosis or resection. On this basis it is sought to identify novel proteins as biomarkers and determinants of CRC metastasis. Experimental Design: Proteomic analyses are undertaken using primary tissues from ten Chinese CRC patients presenting with or without liver metastases and immunohistochemistry used to validate selected proteins in an independent patient cohort. Results: Comparing CRC against paired normal adjacent tissues identifies 1559 differentially expressed proteins (DEPs) with 974 upregulated and 585 downregulated proteins, respectively. The highest number of DEPs is selectively associated with metastatic tumors (519 upregulated and 267 downregulated proteins, respectively) with a smaller number of unique DEPs identified only in non-metastatic CRC cases (116 upregulated and 29 downregulated proteins, respectively). The remaining DEPs are commonly expressed in both non-metastatic and metastatic tumors. The upregulation of three representative DEPs (S100A11, S100P, and RBM25) is confirmed using immunohistochemistry against 154 CRC tissues embedded in a tissue microarray. Conclusions and Clinical Relevance: The data reveal both previously identified CRC biomarkers along with novel candidates which provide a ready resource of DEPs in CRC for further investigation.
Interleukin-22 (IL-22) is a potential therapeutic agent for diseases driven by epithelial injury. To characterize the IL-22 expressed by rhesus macaques, animals that are irreplaceable for human disease research, rhesus macaque IL-22 (rhIL-22) was cloned and expressed, and its biological activity and in vivo distribution were examined. It was found that the rhIL-22 gene consists of five introns and six exons, including a short non-coding exon starting 22 bp downstream of a putative TATA box. The amino acid sequence of rhIL-22 showed 95·5% identity to that of humans, and it shared two conserved disulphide bonds, three N-glycosylation sites and all the critical residues for binding to IL-22R1. High levels of IL-22 mRNA were observed in the liver, pancreas, lymphoid tissues and especially in the outer-body barriers such as the intestinal tract of rhesus macaques. Functionally, purified rhIL-22 has a similar but a little earlier effect on signal transducer and activator of transcription 3 phosphorylation at Tyr705 compared with that of commercial human IL-22. The expression of the antibacterial proteins β-defensin-2, S100A8, S100A9, RegIIIα and Muc1 by HT-29 cells was largely upregulated after stimulation with rhIL-22. Recombinant rhIL-22 could also significantly promote the proliferation of human intestinal epithelial cells without affecting cell apoptosis. These data indicate that rhesus macaque IL-22 is highly similar to that of humans in both structure and function, and tests of therapeutic effects of human IL-22 on human diseases in rhesus macaques are warranted.
Rhesus macaques ( Macaca mulatta ) and cynomolgus macaques ( Macaca fascicularis ) are frequently used in establishing animal models for human diseases. To determine the differences in gut microbiota between these species, rectal swabs from 20 rhesus macaques and 21 cynomolgus macaques were collected, and the microbial composition was examined by deep sequencing of the 16S rRNA gene. We found that the rectal microbiota of cynomolgus macaques exhibited significantly higher alpha diversity than that of rhesus macaques, although the observed number of operational taxonomic units (OTUs) was almost the same. The dominant taxa at both the phylum and genus levels were similar between the two species, although the relative abundances of these dominant taxa were significantly different between them. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) showed significant differences in the functional components between the microbiota of the two species, in particular the lipopolysaccharide (LPS) synthesis proteins. The above data indicated significant differences in microbial composition and function between these two closely related macaque species, which should be taken into consideration in the future selection of these animals for disease models.
No abstract
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.