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Long noncoding RNAs (lncRNAs) represent promising therapeutic targets associated with hepatocellular carcinoma (HCC). lncRNA VPS9D1 antisense RNA 1 (VPS9D1-AS1) regulates colon and prostate cancer, but its relevance in HCC remains to be clarified. Using microarray data from the NCBI Gene Expression Omnibus (GEO) database (GSE65485) and The Cancer Genome Atlas (TCGA) database, VPS9D1-AS1 expression in HCC and normal liver tissue sample HCC were compared. Relative lncRNA expression was also measured through real-time quantitative PCR (qPCR) in 80 pairs of HCC tumor and paracancerous tissues and in human HCC cell lines. VPS9D1-AS1 knockdown was achieved by transfecting these HCC cells with a specific siRNA construct in vitro, and the proliferation of these cells was quantified through cell proliferation assays and colony formation assays, while flow cytometry was employed to assess their cell cycle progression. The role of the VPS9D1-AS1 lncRNA as a regulator of HCC tumorigenesis was also assessed in vivo by subcutaneously implanting BALB/c nude mice with HepG2 cells stably expressing either sh-VPS9D1-AS1 or a control shRNA construct. Mechanistic analyses were additionally conducted by examining in vitro CDK4 and HuR expression through western blotting and qPCR. VPS9D1-AS1 expression was significantly increased in HCC tissues in the analyzed databases and our independent tissue samples. Elevated VPS9D1-AS1 expression was related to larger tumor size and more advanced tumor, node, metastasis (TNM) stage, and HCC patients expressing higher levels of this lncRNA exhibited poorer survival outcomes. Knocking down VPS9D1-AS1 impaired the proliferative and colony formation activity of HepG2 cells while promoting their apoptotic death. Consistently, VPS9D1-AS1 silencing suppressed HCC tumor growth in vivo. Mechanistically, VPS9D1-AS1 was able to bind to the HuR protein and thereby influence the stability and expression of the CDK4 mRNA, thus impacting HCC cell proliferation. The VPS9D1-AS1/HuR/CDK4 signaling axis regulates HCC tumor cell oncogenic activity, highlighting this pathway as a promising therapeutic target. [ABSTRACT FROM AUTHOR]

The present study was designed to investigate the significance of calpain‐1 in the high‐fat diet (HFD)‐induced liver dysfunction and to explore the possible mechanism. C57 mice and calpain‐1 knockout (KO) mice were fed with standard diet (SD) or HFD, respectively, for 16 weeks. The activities of calpain, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and superoxide dismutase (SOD) in serum and/or liver of mouse were measured. Lipid profiles in the serum and liver were examined. Contents of oxidized low‐density lipoprotein (oxLDL), malondialdehyde (MDA), tumor necrosis factor (TNF‐α), and interleukin‐6 (IL‐6) in serum or/and liver were detected. The results showed that compared with C57 mice fed with SD, HFD‐fed C57 mice showed the increased activities of AST and ALT in the serum, which was decreased in calpain‐1 KO mice fed with HFD. In addition, knockout of calpain‐1 decreased the contents of oxLDL, MDA, TNF‐α, and IL‐6, while increased SOD activity, in serum and/or liver. However, knockout of calpain‐1 had no effects on lipid profiles in both serum and liver. When fed with SD, all these parameters of C57 and calpain‐1 KO mice were comparable except for decreased calpain activity in the liver of calpain‐1 KO mice. The results suggested that knockout of calpain‐1 protects against HFD‐induced liver dysfunction through inhibiting oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]

Aims The present study was to investigate the role of calpain in reactive oxygen species (ROS) production in endothelial cells and endothelium-dependent vascular dysfunction under experimental conditions of diabetes. Methods and results Exposure to high glucose activated calpain, induced apoptosis and reduced nitric oxide (NO) production without changing eNOS protein expression, its phosphorylation and dimers formation in primary human umbilical vein endothelial cells (HUVECs). These effects of high glucose correlated with intracellular ROS production and mitochondrial superoxide generation. Selectively scavenging mitochondrial superoxide increased NO production in high glucose-stimulated HUVECs. Inhibition of calpain using over-expression of calpastatin or pharmacological calpain inhibitor prevented high glucose-induced ROS production, mitochondrial superoxide generation and apoptosis, which were concurrent with an elevation of NO production in HUVECs. In mouse models of streptozotocin-induced type-1 diabetes and OVE26 type-1 diabetic mice, calpain activation correlated with an increase in ROS production and peroxynitrite formation in aortas. Transgenic over-expression of calpastatin reduced ROS production and peroxynitrite formation in diabetic mice. In parallel, diabetesinduced reduction of endothelium-dependent relaxation in aortic ring was reversed by overexpression of calpastatin in mouse models of diabetes. However, the protective effect of calpastatin on endothelium-dependent relaxation was abrogated by eNOS deletion in diabetic mice. Conclusions This study suggests that calpain may play a role in vascular endothelial cell ROS production and endothelium-dependent dysfunction in diabetes. Thus, calpain may be an important therapeutic target to overcome diabetes-induced vascular dysfunction. [ABSTRACT FROM AUTHOR]

Boron Neutron Capture Therapy (BNCT) is a new binary radiation therapy for tumor tissue, which kills tumor cells with neutron capture reaction. Boron neutron capture therapy has become a technical means for glioma, melanoma, and other diseases has been included in the clinical backup program. However, BNCT is faced with the key problem of developing and innovating more efficient boron delivery agents to solve the targeting and selectivity. We constructed a tyrosine kinase inhibitor- L -p-boronophenylalanine (TKI-BPA) molecule, aiming to improve the selectivity of boron delivery agents by conjugating targeted drugs while increasing the molecular solubility by adding hydrophilic groups. It shows excellent selectivity in differential uptake of cells, and its solubility is more than 6 times higher than BPA, leading to the saving of boron delivery agents. This modification method is effective for improving the efficiency of the boron delivery agent and is expected to become a potential alternative with high clinical application value., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Zhang, Miao, Zhang, Tang, Teng and Li.)