Chelerythrine ameliorates acute cardiac allograft rejection in mice

The improvement in graft survival over the past decade has been mainly due to calcineurin inhibitors, which interfere with the calcium-mediated pathway. Recently, other pathways such as those mediated by protein kinase C (PKC) are coming into view. The purpose of this study was to assess the immunosuppressive properties of chelerythrine, a specific PKC inhibitor, in preventing acute rejection in murine heterotopic heart transplantation. Mice were randomly divided into control and chelerythrine treated group. The control group received PBS while the chelerythrine treated group was given intraperitoneal injection doses (1, 5, 10 mg/kg) of chelerythrine from day 0 to day 14 after heart transplantation. Six days after transplantation, cardiac allografts were harvested for further tests. The mean survival time (MST) of the cardiac allograft in untreated animals was 8 days while graft MSTs observed in chelerythrine treated group was 13 and 23 days at 5 and 10 mg/kg treatment doses, respectively (P < 0.05). Histologic assessment of the allograft in chelerythrine group showed a significant decline in histologic rejection score, as well as CD4 + and CD8 + T cell infiltration and ICAM-1 + endothelial cell activation. Down-regulation of Th1/Th2 cytokine expression was observed in chelerythrine treatment group. Meanwhile, chelerythrine was also found to inhibit the dephosphorylation of phosphorylated nuclear factor of activated T cells (NFAT) protein 1 and 4.     

Pancreatic ductal adenocarcinoma: Emerging therapeutic strategies

The seventh leading cause of cancer-related death globally, pancreatic ductal adenocarcinoma (PDAC) involves the exocrine pancreas and constitutes greater than 90% of all pancreatic cancers. Surgical resection in combination with systemic chemotherapy with or without radiation remains the mainstay of treatment and the only potentially curative treatment option. While there has been improvement in systemic chemotherapy, long-term survival among patients with PDAC remains poor. Improvement in the understanding of tumorigenesis, genetic mutations, the tumor microenvironment (TME), immunotherapies, as well as targeted therapies continued to drive advances in PDAC treatment. We herein review the TME, genetic landscape, as well as various metabolic pathways associated with PDAC tumorigenesis relative to emerging therapies.