Impending HCC diagnosis in patients with cirrhosis after HCV cure features a natural killer cell signature.

BACKGROUND AND AIMS: The risk of developing HCC in chronically infected patients with AQ2 HCV with liver cirrhosis is significantly elevated. This risk remains high even after a sustained virological response with direct-acting antivirals. To date, disease-associated signatures of NK cells indicating HCC development are unclear. APPROACH AND RESULTS: This study investigated NK cell signatures and functions in 8 cohorts covering the time span of HCC development, diagnosis, and onset. In-depth analysis of NK cell profiles from patients with cirrhosis who developed HCC (HCV-HCC) after sustained virological response compared with those who remained tumor-free (HCV-noHCC) revealed increasingly dissimilar NK cell signatures over time. We identified expression patterns with persistently high frequencies of TIM-3 and CD38 on NK cells that were largely absent in healthy controls and were associated with a high probability of HCC development. Functional assays revealed that the NK cells had potent cytotoxic features. In contrast to HCV-HCC, the signature of HCV-noHCC converged with the signature found in healthy controls over time. Regarding tissue distribution, single-cell sequencing showed high frequencies of these cells in liver tissue and the invasive margin but markedly lower frequencies in tumors. CONCLUSIONS: We show that HCV-related HCC development has profound effects on the imprint of NK cells. Persistent co-expression of TIM-3hi and CD38 + on NK cells is an early indicator for HCV-related HCC development. We propose that the profiling of NK cells may be a rapid and valuable tool to assess the risk of HCC development in a timely manner in patients with cirrhosis after HCV cure.

Time-of-flight secondary ion mass spectrometry analysis of chitosan-treated viscose fibres.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was employed to analyse cellulose viscose fibres treated with different chitosan-based solutions. The analysis reports several new features in the TOF-SIMS spectra for systems with various forms of chitosan-treated surfaces. The characteristic positive ion TOF-SIMS signals for chitosan are reported at m/z 147.90, 207.07, and 221.09, and characteristic signals for trimethyl chitosan are present at m/z 58.03 and 102.09. Furthermore, new fragments were suggested to characterise acetylated chitosan molecules. The relative surface concentrations of different species were obtained based on the specific signal ratios (originating from a specific fragment and cellulose). SIMS imaging was then performed in order to investigate the surface distribution of chitosan, trimethyl chitosan, and Na-containing nanoparticles. In order to perform TOF-SIMS imaging, the above-mentioned characteristic signals were employed and m/z 22.99 was used for Na nanoparticles.

Interaction and enrichment of protein on cationic polysaccharide surfaces.

In this study, the interaction of fluorescein isothiocyanate functionalized bovine serum albumin (FITC-BSA) with cellulose surfaces decorated with trimethyl chitosan (TMC) is investigated. Two types of TMC, one exhibiting a lower and one with a higher degree of cationization are used for protein adsorption. The adsorption is carried out at different pH values and concentrations of the protein solution. The amount, morphology and wettability of FITC-BSA coating on TMC/cellulose films are determined using quartz crystal microbalance with dissipation (QCM-D), atomic force microscopy, fluorescence microscopy and contact angle measurements. A lower pH and higher concentration of protein solution resulted in a greater amount of irreversibly adsorbed material owing to the reduced solubility and minimized electrostatic repulsion. A maximum adsorption of protein is observed on cellulose surfaces functionalized with TMC carrying a higher degree of cationization compared to TMC with a lower degree of cationization and pure cellulose surfaces at all applied concentrations and pH values. BSA is a commonly used model protein and is applied in this study to better understand its interaction with cationically rendered cellulose surfaces. Such knowledge is essential for creation of multifunctional polysaccharide-based biomaterials.

Cationically rendered biopolymer surfaces for high protein affinity support matrices.

The use of cationic biopolymer surfaces for high protein binding affinity matrices is described. As model proteins, fluorescently labeled bovine serum albumins (FITC-BSA, TRITC-BSA) have been employed. The amount of proteins on such cationically rendered surfaces was quantified by QCM-D. In addition, flexible, transparent, patterned COP slides have been prepared and loaded with proteins ranging from 15 pM to 15 µM TRITC-BSA.