Decreased DIO3OS Expression Predicts Poor Prognosis in Hepatocellular Carcinoma and is Associated with Immune Infiltration.

Hepatocellular carcinoma has become one of the most shared cancers in the whole world because of its high morbidity, poor survival rate, and low recovery rate. LncRNA DIO3 opposite strand upstream RNA (DIO3OS) has been reported to be obviously important in several human cancers, while its biological function in hepatocellular carcinoma (HCC) remains unclear. Here, DIO3OS gene expression data and clinical information of HCC patients were extracted from the Cancer Genome Atlas (TCGA) database and the university of California Santa Cruz (UCSC) Xena database. In our study, the Wilcoxon rank sum test was used to compare DIO3OS expression between healthy individuals and HCC patients. It was found that patients with HCC had significantly lower DIO3OS expression than healthy individuals. Furthermore, Kaplan-Meier curves and Cox regression analysis showed that high DIO3OS expression tended to predict better prognosis and higher survival rate in HCC patients. In addition, the gene set enrichment analysis (GSEA) assay was used to annotate the biological function of DIO3OS. It was found that DIO3OS was significantly correlated with immune invasion in HCC. This was also aided by the subsequent ESTIMATE assay. Our study provides a novel biomarker and therapeutic strategy for patients with hepatocellular carcinoma.

3,4­Dihydroxyacetophenone attenuates oxidative stress­induced damage to HUVECs via regulation of the Nrf2/HO­1 pathway.

It has been reported that oxidative stress plays a prominent role in diabetic macrovascular diseases. 3,4­Dihydroxyacetophenone (3,4­DHAP) has been found to have a variety of biological activities. However, few studies have assessed the antioxidant capacity of 3,4­DHAP and the underlying mechanisms. Thus, the aim of the present study was to explore the effects of 3,4­DHAP on oxidative stress in human umbilical vein endothelial cells (HUVECs). HUVECs were pre­treated with 3,4­DHAP and then exposed to high glucose conditions. Cell viability and cytotoxicity were measured using an MTT assay. Reactive oxygen species (ROS) levels were measured using an inverted fluorescence microscope and a fluorescent enzyme labeling instrument. Protein expression levels of nuclear factor E2­related factor 2 (Nrf2), heme oxygenase­1 (HO­1), microtubule­associated protein 1A/1B­light chain 3 (LC3) and poly ADP­ribose polymerase­1 (PARP­1) were measured using western blotting, and mRNA expression of Nrf2 and HO­1 were measured through reverse transcription­quantitative PCR (RT­qPCR). Nrf2 nuclear translocation was evaluated using immunofluorescence analysis and autophagosomes were observed using transmission electron microscope (TEM). The results of the present study demonstrated that compared with the control group, cell viability of the high glucose group was reduced and cell cytotoxicity of the high glucose group was increased. ROS production in the high glucose group was clearly enhanced. In addition, high glucose upregulated Nrf2 and HO­1 protein and mRNA expression levels. Nuclear translocation of Nrf2 in the high glucose group was also increased. The formation of autophagosomes in the high glucose group was also higher than that in the control group. Furthermore, LC3­II/LC3­I and PARP­1 protein expression levels were increased after treatment with high glucose. However, compared to the high glucose group, 3,4­DHAP (10 µmol/l) significantly enhanced cell viability. 3,4­DHAP markedly decreased the production of ROS, increased Nrf2 and HO­1 protein and mRNA expression levels, and promoted nuclear translocation of Nrf2 in HUVECs. In addition, 3,4­DHAP promoted the formation of autophagosomes, and notably increased the protein expression levels of LC3­II/LC3­I and PARP­1. Moreover, it was determined that compared to the 3,4­DHAP group, treatment with 3,4­DHAP and ML385 enhanced cell viability, and decreased ROS production, Nrf2 and HO­1 protein and mRNA expression levels, nuclear translocation of Nrf2, and LC3­II/LC3­I and PARP­1 protein expression levels. Collectively, the results of the present study showed that 3,4­DHAP protected HUVECs against oxidative stress via regulation of the Nrf2/HO­1 pathway, by increasing autophagy and promoting DNA damage repair.

S-nitrosoglutathione functionalized polydopamine nanoparticles incorporated into chitosan/gelatin hydrogel films with NIR-controlled photothermal/NO-releasing therapy for enhanced wound healing.

Nitric oxide (NO) has aroused wide interest in the treating infected wounds due to its characteristic functionalities. However, its utilization is limited due to its volatile properties, high reactivity, direct potential toxicity, and byproducts of NO donors limited its application. Herein, endogenously NO donor S-nitrosoglutathione (GSNO) was connected covalently to polydopamine nanoparticles (PDA-GSNO NPs) to minimize the loss of NO in aqueous medium. Meanwhile, near-infrared (NIR)-controlled NO release and photothermal therapy (PTT) was obtained through the photothermal conversion by PDA. Then chitosan (CS)/gelatin (GE) biocomposite hydrogel films with preferable biocompatibility, surface hydrophilicity, hydroabsorptivity, and mechanical adhesive properties were constructed. By embedding PDA-GSNO NPs into the films, a multifunctional wound dressing was fabricated. Under NIR light irradiation, the combination of PTT, NO-releasing, and CS antibacterial agents can strengthen the in vitro antimicrobial efficacy and in vivo wound healing activities. Meanwhile, the obtained wound dressing presented good biocompatibility. This work outlines an approach for combating bacterial infections and demonstrating the possibility for synergistic NO-releasing wound healing.