Recent updates on pyroptosis in tumors of the digestive tract.

Pyroptosis is an inflammasome-dependent form of programmed cell death that is mediated by caspases-1, -4, -5, and -11, and the gasdermin protein family. It is characterized by the rupture of cell membrane and the subsequent release of cell contents and interleukins, leading to inflammatory reaction and activation of the immune system. Recent studies have suggested that pyroptosis plays a role in the development of gastrointestinal tumors, impeding tumor generation and progression as well as providing a favorable microenvironment for tumor growth. In this review we outlined the current knowledge regarding the implications of pyroptosis in gastrointestinal cancers.

Significant correlation between HSPA4 and prognosis and immune regulation in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is an inflammation-associated tumor involved in immune tolerance and evasion in the immune microenvironment. Heat shock proteins (HSPs) are involved in the occurrence, progression, and immune regulation of tumors. Therefore, HSPs have been considered potential therapeutic targets. Here, we aimed to elucidate the value of HSP family A (Hsp70) member 4 (HSPA4) in the diagnosis and predicting prognosis of HCC, and its relationship with immune cell infiltration, immune cell biomarkers, and immune checkpoints. Gene mutation, DNA methylation, and the pathway involved in HCC were also analyzed. METHODS: The gene expression omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to compare HSPA4 expression, and the results were confirmed by immunohistochemical staining of clinical samples. R package was used to analyze the correlation between HSPA4 and cancer stage, and to establish receiver operating characteristic (ROC) curve of diagnosis, time-dependent survival ROC curve, and a nomogram model. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation, and their effect on prognosis. The Tumor Immune Estimation Resource (TIMER) was used to analyze immune cell infiltration, immune cell biomarkers, and immune checkpoints. The STRING database was used to analyze protein-protein interaction network information. Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functions of HSPA4 and its functional partner genes. RESULTS: Overexpression of HSPA4 was identified in 25 cancers. Overexpression of HSPA4 considerably correlated with cancer stage and alpha-fetoprotein (AFP) level in HCC. Patients with higher HSPA4 expression showed poorer prognosis. HSPA4 expression can accurately identify tumor from normal tissue (AUC = 0.957). The area under 1-, 3-, and 5-year survival ROCs were above 0.6. The HSPA4 genetic alteration rate was 1.3%. Among the 14 DNA methylation CpG sites, seven were related to the prognosis of HCC. HSPA4 was positively related to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. The KEGG pathway enrichment analysis revealed HSPA4 enrichment in antigen processing and presentation together with HSPA8 and HSP90AA1. We verified the value of HSPA4 in the diagnosis and predicting prognosis of HCC. HSPA4 may not only participate in the occurrence and progression but also the immune regulation of HCC. Therefore, HSPA4 can be a potential diagnostic and prognostic biomarker and a therapeutic target for HCC.

An immunomagnetic separation and bifunctional Au nanoparticle probe-based multiamplification electrochemical strategy.

A novel electrochemical magnetoimmunosensor for the rapid and sensitive detection of carcinoembryonic antigen (CEA) was fabricated based on a combination of high-efficiency immunomagnetic separation, bifunctional Au-nanoparticle (bi-AuNP) probes, and enzyme catalytic amplification. The reaction carrier magnetic beads (MBs) effectively reduced the toxicity of the complex sample to the working electrode, and the signal carrier bi-AuNP probes loaded a large amount of signal molecules, both of which enhanced the signal-to-noise ratio and further improved the detection sensitivity. A detection limit as low as 0.11 pg/mL was achieved for CEA detection based on the immunomagnetic separation and bi-AuNP probe-based multiamplification strategy, and the strategy was further successfully applied in human serum samples. The transducer was regenerated via a simple washing procedure, which enabled the detection of all samples on a single electrode with high reproducibility. The proposed strategy, which has the merits of high sensitivity, selectivity, and reproducibility exhibits great potential for detection in complex samples.

Synthesis of a new chitosan derivative and assay of Escherichia coli adsorption.

A new chitosan derivative is prepared using chitosan. Ethyl cholorocarbonate was first introduced to the hydroxyl group of phthaloylchitosan through a nucleophilic reaction. Hydrazine was then added to recover the amino groups of chitosan, and promote cross-linking. The structure of this new chitosan derivative was characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy, and its physical properties were determined by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The thermal and chemical stabilities of the new derivative were improved compared with those of native chitosan. Assay of Escherichia coli adhesion on a film based on this chitosan derivative showed good adsorption and biofilm formation.