Corrigendum to "System Analysis of ROS-Related Genes in the Prognosis, Immune Infiltration, and Drug Sensitivity in Hepatocellular Carcinoma".

[This corrects the article DOI: 10.1155/2021/6485871.].

System Analysis of ROS-Related Genes in the Prognosis, Immune Infiltration, and Drug Sensitivity in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is an aggressive malignant tumor with a poor prognosis. Reactive oxygen species (ROS) play an important role in tumors; however, the role of ROS-related genes is still unclear in HCC. Therefore, we analyzed the role of ROS-related genes in HCC via bioinformatics methods. Firstly, a prognosis model was constructed using LASSO Cox regression and multivariate analyses. We also investigated the potential function of the ROS-related genes and the correlation with immune infiltration, tumor stemness, and drug sensitivity. ICGC database was used for validation. Secondly, we further analyzed the role of 11 ROS-related genes in HCC. As a member of ROS gene family, the role of STK25 has remained unclear in HCC. We explored the biological function of STK25 using in vitro experiments. The present study was the first to construct a ROS-related prognostic model in HCC. The correlation of ROS-related genes with immune infiltration, tumor stemness, and drug sensitivity was dissected. Furthermore, we demonstrated that STK25 knockdown could increase the proliferation, migration, and invasion capacity of HCC cells.

ADAM15 correlates with prognosis, immune infiltration and apoptosis in hepatocellular carcinoma.

ADAM15 is highly expressed in malignant tumors and is correlated with tumor progression. However, the role of ADAM15 in hepatocellular carcinoma (HCC) remains unclear. In the study, our results indicated that ADAM15 was highly expressed in HCC tissues and cells compared with corresponding tissues and liver cells. Overexpression of ADAM15 was linked to poor prognosis, and was an independent risk factor for HCC prognosis. Besides, analysis of immune infiltration indicated that ADAM15 expression was related to tumor infiltrating lymphocytes based on the TIMER, TISIDB and GEPIA databases. Many immune checkpoint gene expression was associated with ADAM15 expression. Functional enrichment analyses indicated that apoptosis, cell adhesion was enriched. ADAM15 knockdown promoted apoptosis and suppressed proliferation, migration and invasion of liver cancer cells. The findings of western blot showed that ADAM15 knockdown reduced the expression of Bcl-2, Vimentin, N-Cadherin and Snail, and elevated the expression of Bax, E-cadherin and ZO-1. However, overexpression of ADAM15 had the opposite results. Collectively, our findings demonstrated that ADAM15 was connected with poor prognosis of HCC patients, and could be considered as a potential biomarker for the diagnosis and treatment of HCC.

Depuration of Cadmium from Blue Mussel (Mytilus edulis) by Protein Hydrolysate-Fe2+ Complex: The Role of Metallothionein.

Metallothionein (MT) plays a major role in the detoxification of toxic metal ions in mussel. This study served to investigate the effects of prepared protein hydrolysate-Fe2+ (PH-Fe2+ ) on depuration of cadmium salt (Cd2+ ) from blue mussel (Mytilus edulis). The results indicated that Cd2+ concentrations in control ranged from 46.1 to 47.1 µg/g during 15 d of depuration. While, 40 mg/L PH-Fe2+ feed mussels exhibited obvious changes in Cd2+ concentration variables, which decreased by 22.8 µg/g after 15 d of depuration, making them significantly lower than the values of the control. Our assumption was that Cd2+ could be dissociated effectively from the complex of MT-Cd2+ in mussels affected by the incorporation of PH-Fe2+ during the feeding period. Further results of homology modeling and molecular dynamics (MD) confirmed that the combined power between MT and Cd2+ weakened significantly by PH-Fe2+ . This condition affected the charge density and/or the loop flexibility of MT and decreased the interaction energy within MT-Cd2+ complex and resulted in the release of Cd2+ from the complex, thereby exhibiting excretion detoxification. Finally, by comparing the experimental results to MD results, significant positive correlations were observed between PH-Fe2+ and the depuration of Cd2+ from MT-Cd2+ complex. Overall, the findings of this study may help better understand the depuration mechanisms of Cd2+ combined with MT, and the PH-Fe2+ can be recommended as a depuration agent to decrease Cd2+ concentrations in mussels. PRACTICAL APPLICATION: Metallothionein (MT) is a low-molecular-weight protein with high metal-ion affinity. If the intracellular concentrations of metals are too high or if toxic metals are present within the cell, then the synthesis of MTs is induced and generated. In our previous work, it was found that the prepared hydrolysate-metal element complex showed obvious depuration activity of heavy metals (Cd2+ ) from blue mussel (Mytilus edulis). This study provided further the depuration mechanisms of Cd2+ from mussel (M. edulis), in particular to the role of MT and its chelate during the depuration process.

Highly double selective nitration of nitrostilbenes over zeolite.

A feasible zeolite-assisted ortho C-H nitration of nitrostilbenes has been developed for the first time, which can be used in situ. It uses acetyl nitrate as a mild, easily handled and commercially available nitrating reagent, leading to the synthesis of polynitrostilbenes with double selectivities and in good yields.

Expression and significance of MMP2 and HIF-1α in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a serious threat to human health. HCC is a malignant tumor and its invasion and metastasis are the result of multigene interactions. Matrix metalloproteinase-2 (MMP-2) is capable of degrading the majority of components of the extracellular matrix and is regarded to closely correlate with tumor invasion and metastasis. Furthermore, the hypoxia-inducible factor 1α (HIF-1α) is an important transcription factor, which is closely associated with the process of tumor growth. The aim of the present study was to investigate the expression of MMP2 and HIF-1α) in HCC, and the relationship between MMP2/HIF-1α protein expression and the clinical/pathological characteristics of HCC. The mRNA levels of MMP2 and HIF-1α were detected in 32 cases of HCC and the corresponding normal adjacent tissues with fluorescence-based quantitative polymerase chain reaction (qPCR). The protein expression of MMP2 and HIF-1α was assessed in 45 HCC cases and 33 cases of corresponding normal adjacent tissue, using immunohistochemical methods. The association between MMP2/HIF-1α and pathological features of HCC, and the correlation between MMP2 and HIF-1α were analyzed. The Kaplan-Meier method was used to assess the impact of MMP2 and HIF-1α expression on survival. The fluorescence-based qPCR demonstrated that MMP2 and HIF-1α mRNA expression levels in the HCC tissues were 0.84±0.17 and 0.87±0.11, respectively, which were significantly higher than those in the adjacent normal tissues (0.70±0.13 and 0.68±0.13, respectively; P<0.05). Immunohistochemical analysis revealed that MMP2 and HIF-1α protein expression in the HCC tissues was 63.1 and 70.8%, respectively, which was also higher than that in the adjacent normal tissues (34.2 and 36.8%, respectively). There was no significant correlation between the expression of MMP2 or HIF-1α protein and the age or gender of patients with HCC (P>0.05). However, there was significant correlation between MMP2 or HIF-1α protein expression and tumor size, metastasis, presence of a capsule and clinical TNM staging of HCC. Their expression also had a significant effect on patient survival time. In conclusion, MMP2 and HIF-1α are overexpressed in HCC, and the MMP2 signaling pathway may promote the development of HCC together with HIF-1α.

[Effects of silver ion of silver nanoparticles on gap junctional intercellular communication of human skin cells].

OBJECTIVE: To further investigate the effects of silver ion (Ag+) dissolved from silver nanoparticles (AgNps) on gap junctional intercellular communication (GJIC) between HaCaT cells. METHODS: In this study, 20 000×g of 1 g/L AgNps suspension were centrifuged at 4 °C for 2 h, then the supernatant was collected as Ag(+) stock solution and measured by inductively coupled plasma mass spectrometry (ICP-MS); GJIC was detected by the scrape loading/dye transfer assay; connexin 43 (Cx43) protein and mRNA level were estimated by Western-blot and RT-PCR, respectively. RESULTS: Different concentrations of Ag(+) (0.01, 0.1 and 1.0 mg/L) did not affect the GJIC significantly. No notable changes were observed in expression of Cx43 protein and mRNA. CONCLUSION: The characteristics of Ag(+) and the effects on gap junctional intercellular communication between HaCaT cells may be different from those of AgNps.

Targeted treatment of choroidal neovascularization using integrin-mediated sterically stabilized liposomes loaded with combretastatin A4.

PURPOSE: The objective of this study was to develop an efficient vasculature-targeted liposomal combretastatin A4 (CA4), by the modification of the sterically stabilized liposomes (SSL) with a ligand of integrins and to explore the possibility of such system for the treatment of choroidal neovascularization (CNV). METHODS: CA4-loaded liposomes were prepared by thin-film dispersion method. The linear arginine-glycine-aspartic acid tripeptide (RGD) with affinity for integrins such as alphavbeta3 expressed on rapidly proliferative vascular endothelial cells was coupled to the distal end of polyethylene glycol (PEG) connected on the surface of SSL. The liposome delivery system was characterized in terms of size and size distribution profiles by dynamic light scattering method, entrapment efficiency, and leakage properties by high-performance liquid chromatography (HPLC). The uptake efficiency by human umbilical vein endothelial cells (HUVECs) was evaluated by confocal microscopy. The therapeutic efficacy was quantitatively assessed by choroidal flat mounts. RESULTS: CA4-loaded RGD-SSL (RGD-SSL-CA4) was obtained with an entrapment efficiency over 70% and an average diameter of approximately 120 nm. The leakage property of RGD-SSL-CA4 was similar with SSL-CA4, both were slower than CA4 ethanol solution. Confocal microscopy studies revealed that RGD-SSL could facilitate the liposomes' uptake into HUVECs. Rats treated with two intravenous injections of 7 mg/kg RGD-SSL-CA4 resulted in a significant reduction in the area of CNV compared with control group (P < 0.05). CONCLUSIONS: RGD-modified SSL loaded with CA4 can be successfully prepared, and the vasculature-targeted liposome system would increase the uptake of HUVECs and improve the therapeutic efficacy of CA4 on CNV compared with the control formulations.

Study on reaction kinetics of synthesis of thioether by a visualization technique.

In this paper, a novel technique combined light-electronic microscopy and computer imaging trace was used to investigate the synthesis of thioether, which is an intermediate for lansoprazole. The reaction kinetics study by a visualization technique was carried out in a minireactor, and the concentration-grayscale standard curves for thioether were obtained by analyzing the grayscales of digital images for the solutions with 20 different concentrations. Based on the concentration-grayscale standard curves, the reactant concentrations at different times were calculated and the reaction kinetic curve as well as the reaction rate equation were obtained. It was found that the total mass-transfer resistance of sodium imidazole was larger than that of bromopyridine. Liquid-liquid interface of synthesizing thioether was observed and its mass transfer mechanism was discussed.

Visualization study on sedimentation of micron iron oxide particles.

In this paper, a novel technique combined light-electronic microscopy and computer imaging trace was used for visualization of the sedimentation of micron iron oxide particles in a customized micro-reactor. Micron iron oxide particles were recovered from the cinder of sulfuric acid production by sedimentation separating and hydraulic rating. Effects of particle size, shape and surface roughness on the sedimentation velocity were investigated. For irregular-shape particles, the sedimentation velocity and the geometric parameters of the particles were measured by the imaging trace technique. A correction coefficient (c) was used to modify the Stokes equation. In this study, the relationship between the correction coefficient and the equivalent diameter (d(p)) was found to be linear: c=0.6272-0.0298d(p), for iron oxide particles with equivalent diameter 4-22 microm.