Human Bcl2 blocking peptide

Current chemoimmunotherapy is unable to cure up to 40% of patients diagnosed with diffuse large B-cell lymphoma (DLBCL). Targeting the mechanisms by which DLBCL evades apoptosis is crucial to overcoming treatment failure in this heterogeneous disease as both current and novel treatments depend on the apoptosis of malignant cells. Despite the common overexpression of BCL-2, venetoclax is ineffective in DLBCL due to MCL-1 co-expression. This is driven by pro-growth PI3-kinase signaling, which is promoted in turn by PIM kinases. In this study, the novel dual-kinase inhibitor, IBL-202, was combined with venetoclax against a panel of DLBCL cell lines that have variable expression of pro-survival proteins. The results support the efficacy of simultaneously targeting inter-related molecules to overcome apoptotic escape in this biologically heterogeneous disease. As venetoclax, pan-PIM-kinase and pan-PI3-kinase inhibitors have, or are currently being studied in clinical trials, it may be rational to consider these drugs in combination for the treatment of DLBCL.

Huangqi Jianzhong Tang (HQJZT) is a traditional Chinese herbal formula consisting of seven different herbs: Radix Astragali, Radix Paeoniae Alba, Ramulus Cinnamomi, Fructus Jujubae, Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle, Rhizoma Zingiberis Recens, and Saccharum Granorum. The present study aims to evaluate the possible effects of HQJZT on cardiac function in acute myocardial infarction (AMI) and related mechanism. AMI model was established by ligation of the left anterior descending coronary artery followed by one-week HQJZT treatment. Survival rate was calculated. Rat heart function was assessed by heart performance analysis system. 5-Triphenyltetrazolium chloride (TTC) staining was used to observe myocardial infarct size. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and western blot were applied to evaluate tissue apoptotic level. Treatment with high dose of HQJZT improved cardiac function, reduced infarct size, number of apoptotic cells and expression of apoptotic proteins, Bax (a proapoptotic protein), and increased expression of antiapoptotic protein, Bcl2. However, enalapril (an angiotensin-converting enzyme inhibitor) treatment did not show marked improvement of these parameters. Our present data suggest that HQJZT has potential therapeutic effects to improve cardiac function by regulation of apoptotic signaling pathway.