Corrigendum to "Characteristics of a novel photoinitiator aceanthrenequinone-initiated polymerization and cytocompatibility of its triggered polymer" [Toxicol. Rep. 9 (2022) 191-203].

[This corrects the article DOI: 10.1016/j.toxrep.2022.01.008.].

Characteristics of a novel photoinitiator aceanthrenequinone-initiated polymerization and cytocompatibility of its triggered polymer.

A number of photoinitiators are available in chemical industry, but less of them in biomedicine or clinical therapy due to the limitation of their cytotoxicity and biocompatibility. Thus, it is urgently necessary to find non-toxic or low-toxic photoinitiators to meet clinical demands. Aceanthrenequinone (AATQ) is a novel photosensitizer with high-photoinitiating ability, but no reports contribute, to date, to its cytotoxicity and biocompatibility. Here, primary cells and various cell lines were exposed to different concentrations of AATQ with or without irradiation. AATQ had the similar photoinitiating conversion efficiency to the extensively used bis(2,4,6-trimethylbenzoyl)-phenylphosphine oxide (BAPO) and higher one than 9,10-phenanthrenequinone (PANQ) with the similar extent of polymerization in depth within a certain range, but displayed much lower cytotoxicity than BAPO under non-irradiation or irradiation. The biocompatibility of BisGMA/TEGDMA polymer prepared by AATQ was superior to that of PANQ, but inferior to that of camphorquinone (CQ) although the far lower dose of AATQ is enough to initiate polymerization of monomer than that of CQ. Hence, AATQ offers a valuable alternative in applications of industrial or biomedical areas.

Biocompatibility and cytotoxicity of novel photoinitiator π-conjugated dithienophosphole derivatives and their triggered polymers.

Photoinitiators have widely been applied to industry, and now increasingly to clinical therapy. A novel high-performance photoinitiation system based on π-conjugated dithienophosphole derivatives (DTPs), including Ph-DTP and TPA-DTP, has recently been developed with high extinction coefficients and amazing polymerization initiating abilities at a relatively low dose in both the near-UV and visible light ranges, and TPA-DTP has better absorption characteristics than Ph-TPA. The purpose of this study was to evaluate cytotoxicity of DTPs and cytocompatibility of their initiated polymers by a MTT assay and calcein AM/propidium iodide staining. The cytotoxicity of Ph-DTP or TPA-DTP exposed to non-irradiation or irradiation is lower than bis (2,4,6-trimethylbenzoyl)-phenylphosphine oxide (BAPO) applied widely to industry. No obvious cytotoxicity was observed in the TPA-DTP-treated primary cells and various cell lines, while the activated Ph-DTP inhibited the cell viability and resulted in the massive cellular apoptosis and necrosis. Compared to camphorquinone (CQ) applied widely to clinical dental prosthetic restoration, the cytocompatibility of DTPs-photopolymerized BisGMA/TEGDMA polymers was inferior to CQ although their extracts exhibited low toxicity, indicating that TPA-DTP but not Ph-DTP is more suitable for industrial application. These results provide a novel insight into underlying potential application of DTPs to industrial deep polymerization or clinical tissue engineering rehabilitation.

LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in Hepatocellular Carcinoma.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. METHODS: In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis and chemoresistance in vivo. RESULTS: HANR was demonstrated to be up-regulated in HCC patients and HCC cell lines. Increased HANR expression in HCC predicted short survival of patients. Knock-down of HANR markedly retarded cell proliferation, suppressed HCC xenograft/orthotopic tumor growth, induced apoptosis and enhanced chemosensitivity to doxorubicin, while over-expression of HANR showed the opposite effects. It was found that HANR bind to GSKIP for regulating the phosphorylation of GSK3ß in HCC. CONCLUSION: Our results demonstrate that HANR contributes to the development of HCC and is a promising therapeutic target for chemosensitization of HCC cells to doxorubicin, which may represent a promising therapeutic target in the future.

Precise Regulation of miR-210 Is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cells in Acute Liver Failure Therapy.

Stem cell transplantation is a promising clinical strategy to cure acute liver failure. However, a low cell survival ratio after transplantation significantly impairs its therapeutic efficacy. This is partly due to insufficient resistance of transplanted stem cells to severe oxidative and inflammatory stress at the injury sites. In the current study, we demonstrated that a small molecule zeaxanthin dipalmitate (ZD) could enhance the defensive abilities against adverse stresses of human adipose-derived mesenchymal stem cells (hADMSCs) in vitro and increase their therapeutic outcomes of acute liver failure after transplantation in vivo. Treatment with ZD dramatically improved cell survival and suppressed apoptosis, inflammation, and reactive oxygen species (ROS) production of hADMSCs through the PKC/Raf-1/MAPK/NF-κB pathway to maintain a reasonably high expression level of microRNA-210 (miR-210). The regulation loop between miR-210 and cellular/mitochondrial ROS production was found to be linked by the ROS inhibitor iron-sulfur cluster assembly proteins (ISCU). Pretreatment with ZD and stable knockdown of miR-210 significantly improved and impaired the stem cell transplantation efficacy through the alteration of hepatic cell expansion and injury amelioration, respectively. Vehicle treatment with ZD did not pose any adverse effect on cell homeostasis or healthy animal. In conclusion, elevating endogenous antioxidant level of hADMSCs with ZD significantly enhances their hepatic tissue-repairing capabilities. Maintenance of a physiological level of miR-210 is critical for hADMSC homeostasis.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B.

AIM: To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS: ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). CONCLUSION: ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.