This study was designed to identify the potential key protein interaction networks, genes, and correlated pathways in early-onset colorectal cancer (CRC) via bioinformatics methods. We selected microarray data GSE4107 consisting 12 patient’s colonic mucosa and 10 healthy control mucosa; initially, the GSE4107 were downloaded and analyzed using limma package to identify differentially expressed genes (DEGs). A total of 131 DEGs consisting of 108 upregulated genes and 23 downregulated genes of patients in early-onset CRC were selected by the criteria of adjusted P values <.01 and |log2 fold change (FC)| ≥ 2. The gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were accomplished to view the biological process, cellular components, molecular function, and the KEGG pathways of DEGs. Finally, protein–protein interactions (PPIs) were constructed, and the hub protein module was identified. Genes such as ACTA2 , ACTG2 , MYH11 , CALD1 , MYL9 , TPM2, and LMOD1 were strongly implicated in CRC. In summary, in this study, we indicated that molecular mechanisms were involved in muscle contraction and vascular smooth muscle contraction signaling pathway, which improve our understanding of CRC and could be used as new therapeutic targets for CRC.

Mindin has a broad spectrum of roles in the innate immune system, including in macrophage migration, antigen phagocytosis and cytokine production. Mindin functions as a pattern‐recognition molecule for microbial pathogens. However, the underlying mechanisms of mindin‐mediated phagocytosis and its exact membrane receptors are not well established. Herein, we generated mindin‐deficient mice using the CRISPR‐Cas9 system and show that peritoneal macrophages from mindin‐deficient mice were severely defective in their ability to phagocytize E  coli . Phagocytosis was enhanced when E  coli or fluorescent particles were pre‐incubated with mindin, indicating that mindin binds directly to bacteria or non‐pathogen particles and promotes phagocytosis. We defined that 131 I‐labelled mindin binds with integrin Mac‐1 (CD11b/CD18), the F‐spondin (FS)‐fragment of mindin binds with the α M ‐I domain of Mac‐1 and that mindin serves as a novel ligand of Mac‐1. Blockade of the α M ‐I domain of Mac‐1 using either a neutralizing antibody or si‐Mac‐1 efficiently blocked mindin‐induced phagocytosis. Furthermore, mindin activated the Syk and MAPK signalling pathways and promoted NF‐κB entry into the nucleus. Our data indicate that mindin binds with the integrin Mac‐1 to promote macrophage phagocytosis through Syk activation and NF‐κB p65 translocation, suggesting that the mindin/Mac‐1 axis plays a critical role during innate immune responses.

Single-biomolecule electronic sensing techniques are of great importance in many fields, from medical diagnosis to disease surveillance. As the physiological changes of single biomolecules can be converted into measurable electrical signals, single-molecule electronic biosensors can realize real-time, highly sensitive, and high-bandwidth detection of individual intra-or inter-molecular interactions. These powerful single-molecule sensing devices have demonstrated key advantages in precisely providing rare and detailed intermediate information along reaction pathways and revealing unique properties hidden in ensemble measurements. This review summarizes significant advances in single-molecule electronic biosensors, emphasizing biomolecule recognition, interaction, and reaction dynamics at the single-molecule level. Sensor configurations, sensing mechanisms, and representative applications are also discussed. Furthermore, a perspective on the use of photoelectric integrated systems for synchronous sensing of the electrical and optical signals of single biomolecules is provided.

Background Primary cutaneous malignant melanoma is a cancer of the pigment cells of the skin, some of which are accompanied by BRAF mutation. Melanoma incidence and mortality rates have been rising around the world. As the current knowledge about pathogenesis, clinical and genetic features of cutaneous melanoma is not very clear, we aim to use bioinformatics to identify the potential key genes involved in the expression and mutation status of BRAF . Methods Firstly, we used UCSC public hub datasets of melanoma (Lin et al., Cancer Res 68(3):664, 2008) to perform weighted genes co-expression network analysis (WGCNA) and differentially expressed genes analysis (DEGs), respectively. Secondly, overlapping genes between significant gene modules and DEGs were screened and validated at transcriptional levels and overall survival in TCGA and GTEx datasets. Lastly, the functional enrichment analysis was accomplished to find biological functions on the web-server database. Results We performed weighted correlation network and differential expression analyses, using gene expression data in melanoma samples. We identified 20 genes whose expression was correlated with the mutation status of BRAF . For further validation, three of these genes ( CYR61 , DUSP1 , and RNASE4 ) were found to have similar expression patterns in skin tumors from TCGA compared with normal skin samples from GTEx. We also found that weak expression of these three genes was associated with worse overall survival in the TCGA data. These three genes were involved in the nucleic acid metabolic process. Conclusion In this study, CYR61 , DUSP1 , and RNASE4 were identified as potential genes of interest for future molecular studies in melanoma, which would improve our understanding of its causes and underlying molecular events. These candidate genes may provide a promising avenue of future research for therapeutic targets in melanoma. Electronic supplementary material The online version of this article (10.1186/s12881-019-0791-1) contains supplementary material, which is available to authorized users.

A previous study by our group indicated that combined treatment with taurine, epigallocatechin gallate (EGCG) and genistein protects against liver fibrosis. The aim of the present study was to elucidate the antifibrotic mechanism of this combination treatment using isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics in an activated rat hepatic stellate cell (HSC) line. In the present study, HSC-T6 cells were incubated with taurine, EGCG and genistein, and cellular proteins were extracted and processed for iTRAQ labeling. Quantification and identification of proteins was performed using two-dimensional liquid chromatography coupled with tandem mass spectrometry. Proteomic analysis indicated that the expression of 166 proteins were significantly altered in response to combination treatment with taurine, EGCG and genistein. A total 76 of these proteins were upregulated and 90 were downregulated. Differentially expressed proteins were grouped according to their association with specific Kyoto Encyclopedia of Genes and Genomes pathways. The results indicated that the differentially expressed proteins hexokinase-2 and lysosome-associated membrane glycoprotein 1 were associated with glycolysis, gluconeogenesis and lysosome signaling pathways. The expression of these proteins was validated using western blot analysis; the expression of hexokinase-2 was significantly decreased and the expression of lysosome-associated membrane glycoprotein 1 was significantly increased in HSC-T6 cells treated with taurine, EGCG and genistein compared with the control, respectively (P<0.05). These results were in accordance with the changes in protein expression identified using the iTRAQ approach. Therefore, the antifibrotic effect of combined therapy with taurine, EGCG and genistein may be associated with the activation of several pathways in HSCs, including glycolysis, gluconeogenesis, and the ribosome and lysosome signaling pathways. The differentially expressed proteins identified in the current study may be useful for treatment of liver fibrosis in the future.