Our results indicate that artesunate exerts an anti-inflammatory effect in RA FLS and provide the evidence that artesunate may have therapeutic potential for RA.

Tumor hypoxia is a major contributor to resistance to anti-cancer therapies. Given that the results of hypoxia-targeted therapy trials have been disappointing, a more personalized approach may be needed. Here we characterize multi-OMIC molecular features associated with tumor hypoxia and identify molecular alterations that correlate with both drug-resistant and drug-sensitive responses to anti-cancer drugs. Based on a well-established hypoxia gene expression signature, we classify about 10,000 tumor samples into hypoxia score-high and score-low groups across different cancer types from The Cancer Genome Atlas and demonstrate their prognostic associations. We then identify various types of molecular features associated with hypoxia status that correlate with drug resistance but, in some cases, also with drug sensitivity, contrasting the conventional view that hypoxia confers drug resistance. We further show that 110 out of 121 (90.9%) clinically actionable genes can be affected by hypoxia status and experimentally validate the predicted effects of hypoxia on the response to several drugs in cultured cells. Our study provides a comprehensive molecular-level understanding of tumor hypoxia and may have practical implications for clinical cancer therapy.

Our study highlights important roles for APA in human cancer, including reshaping cellular pathways and regulating specific gene expression, exemplifying the complex interplay between APA and other biological processes and yielding new insights into the action mechanism of cancer drugs.

ObjectivesHepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease. In this study, we tried to investigate the effects of saturated and unsaturated fatty acids on hepatoma cell apoptosis.MethodsH4IIE liver cells were treated with palmitic acid, linoleic acid, or both with or without the calcium-specific chelator BAPTA-AM after which the expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels, and calcium flux were measured.ResultsPalmitic or linoleic acid (250 μM) induced H4IIE cell apoptosis, which required calcium flux but not caspase-3. Apoptosis was not observed when cells were co-treated with linoleic acid (125 μM) and palmitic acid (250 μM). Importantly, the release of cytochrome C from mitochondria into cytoplasm during cell apoptosis was specifically detected only when linoleic acid (125 μM), but not palmitic acid (250 μM), was added to the cells. Depletion of intracellular calcium flux by the calcium-specific chelator, BAPTA-AM, abolished linoleic acid-induced apoptosis. Moreover, in the presence of BAPTA-AM, expression of the unfolded protein response (UPR)-associated genes, CHOP, GRP78, and GRP94, was induced by linoleic acid, but not palmitic acid.ConclusionsThe results suggest that linoleic acid promotes cell apoptosis through the release of cytochrome C, only if the intracellular calcium flux is unperturbed and intact. These results confirm that ER stress contributes to fatty acid-induced liver cell apoptosis.

The long noncoding RNA (lncRNA) has previously been identified as a prognostic marker in hepatocellular carcinoma. Here, we performed a comprehensive analysis of lncRNA expression profiles from RNA-Seq data and report that plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. bound and stabilized the YBX1 protein. Silencing of triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this network, p21 played an oncogenic role by promoting cell proliferation and antiapoptosis in lung cancers. played a tumor-suppressive role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer. The lncRNA functions as a tumor suppressor, with potential use a diagnostic/prognostic marker and therapeutic target in lung cancer..