An integrative multi-omics database is needed urgently, because focusing only on analysis of one-dimensional data falls far short of providing an understanding of cancer. Previously, we presented DriverDB, a cancer driver gene database that applies published bioinformatics algorithms to identify driver genes/mutations. The updated DriverDBv3 database (http://ngs.ym.edu.tw/driverdb) is designed to interpret cancer omics’ sophisticated information with concise data visualization. To offer diverse insights into molecular dysregulation/dysfunction events, we incorporated computational tools to define CNV and methylation drivers. Further, four new features, CNV, Methylation, Survival, and miRNA, allow users to explore the relations from two perspectives in the ‘Cancer’ and ‘Gene’ sections. The ‘Survival’ panel offers not only significant survival genes, but gene pairs synergistic effects determine. A fresh function, ‘Survival Analysis’ in ‘Customized-analysis,’ allows users to investigate the co-occurring events in user-defined gene(s) by mutation status or by expression in a specific patient group. Moreover, we redesigned the web interface and provided interactive figures to interpret cancer omics’ sophisticated information, and also constructed a Summary panel in the ‘Cancer’ and ‘Gene’ sections to visualize the features on multi-omics levels concisely. DriverDBv3 seeks to improve the study of integrative cancer omics data by identifying driver genes and contributes to cancer biology.

In recent decades, chemotherapies targeting apoptosis have emerged and demonstrated remarkable achievements. However, emerging evidence has shown that chemoresistance is mediated by impairing or bypassing apoptotic cell death. Several novel types of programmed cell death, such as ferroptosis, necroptosis, and pyroptosis, have recently been reported to play significant roles in the modulation of cancer progression and are considered a promising strategy for cancer treatment. Thus, the switch between apoptosis and pyroptosis is also discussed. Cancer immunotherapy has gained increasing attention due to breakthroughs in immune checkpoint inhibitors; moreover, ferroptosis, necroptosis, and pyroptosis are highly correlated with the modulation of immunity in the tumor microenvironment. Compared with necroptosis and ferroptosis, pyroptosis is the primary mechanism for host defense and is crucial for bridging innate and adaptive immunity. Furthermore, recent evidence has demonstrated that pyroptosis exerts benefits on cancer immunotherapies, including immune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell therapy (CAR-T). Hence, in this review, we elucidate the role of pyroptosis in cancer progression and the modulation of immunity. We also summarize the potential small molecules and nanomaterials that target pyroptotic cell death mechanisms and their therapeutic effects on cancer.

We previously presented DriverDB, a database that incorporates ∼6000 cases of exome-seq data, in addition to annotation databases and published bioinformatics algorithms dedicated to driver gene/mutation identification. The database provides two points of view, ‘Cancer’ and ‘Gene’, to help researchers visualize the relationships between cancers and driver genes/mutations. In the updated DriverDBv2 database (http://ngs.ym.edu.tw/driverdb) presented herein, we incorporated >9500 cancer-related RNA-seq datasets and >7000 more exome-seq datasets from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and published papers. Seven additional computational algorithms (meaning that the updated database contains 15 in total), which were developed for driver gene identification, are incorporated into our analysis pipeline, and the results are provided in the ‘Cancer’ section. Furthermore, there are two main new features, ‘Expression’ and ‘Hotspot’, in the ‘Gene’ section. ‘Expression’ displays two expression profiles of a gene in terms of sample types and mutation types, respectively. ‘Hotspot’ indicates the hotspot mutation regions of a gene according to the results provided by four bioinformatics tools. A new function, ‘Gene Set’, allows users to investigate the relationships among mutations, expression levels and clinical data for a set of genes, a specific dataset and clinical features.

Corylin is a main compound isolated from Psoralea corylifolia L. (Fabaceae). A variety of pharmacological effects such as antioxidant, anti-proliferation, and anti-inflammatory properties of corylin have been reported. Nevertheless, the effect of corylin in microbial infection and sepsis remains unclear. In the present study, we investigated the anti-inflammatory effects of corylin. Our experimental results demonstrated that corylin inhibited the production of TNF-α, IL-6 and NO by both LPS-activated RAW 264.7 cells and LPS-activated murine peritoneal macrophages. Moreover, corylin suppressed the expression levels of iNOS and COX-2, reduced the production of PGE2 and HMGB1, blocked the translocation of HMGB1 from the nucleus to cytosol, and decreased the phosphorylation of MAPKs in LPS-activated RAW 264.7 cells as well as suppressed the activity of NF-κB in LPS-activated J-Blue cells. In addition, the administration of corylin reduced the production of NO and TNF-α, decreased LPS-induced liver damage markers (AST and ALT) and kidney damage markers (BUN and CRE), attenuated infiltration of inflammatory cells and tissue damage of lung, liver and kidney, and enhanced the survival rate of LPS-challenged mice. Taken together, these results show the anti-inflammatory properties of corylin on LPS-induced inflammation and sepsis. Corylin could potentially be a novel anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.

Hepatocellular carcinoma (HCC) is a leading cause of death, resulting in over 700 thousand deaths annually worldwide. Chemotherapy is the primary therapeutic strategy for patients with late-stage HCC. Heteronemin is a marine natural product isolated from Hippospongia sp. that has been found to protect against carcinogenesis in cholangiocarcinoma, prostate cancer, and acute myeloid leukemia. In this study, heteronemin was found to inhibit the proliferation of the HCC cell lines HA22T and HA59T and induce apoptosis via the caspase pathway. Heteronemin treatment also induced the formation of reactive oxygen species (ROS), which are associated with heteronemin-induced cell death, and to trigger ROS removal by mitochondrial SOD2 rather than cytosolic SOD1. The mitogen-activated protein kinase (MAPK) signaling pathway was associated with ROS-induced cell death, and heteronemin downregulated the expression of ERK, a MAPK that is associated with cell proliferation. Inhibitors of JNK and p38, which are MAPKs associated with apoptosis, restored heteronemin-induced cell death. In addition, heteronemin treatment reduced the expression of GPX4, a protein that inhibits ferroptosis, which is a novel form of nonapoptotic programmed cell death. Ferroptosis inhibitor treatment also restored heteronemin-induced cell death. Thus, with appropriate structural modification, heteronemin can act as a potent therapeutic against HCC.