Genotoxic drugs constitute a major treatment modality for human cancers; however, cancer cells' intrinsic DNA repair capability often increases the threshold of lethality and renders these drugs ineffective. The emerging roles of HDACs in DNA repair provide new opportunities for improving traditional genotoxic drugs. Here, we report the development and characterization of CY190602, a novel bend...

Although the prognosis for clinically localized prostate cancer is now favorable, there are still no curative treatments for castration-resistant prostate cancer (CRPC) and, therefore, it remains fatal. In this study, we investigate a new therapeutic approach for treatment of CRPC, which involves dual targeting of a major signaling pathway that is frequently deregulated in the disease. We found...

objective(s): p-glycoprotein (p-gp) is an efflux protein, the overexpression of which has been associated with multidrug resistance in various cancers. although sirna delivery to reverse p-gp expression may be promising for sensitizing of tumor cells to cytotoxic drugs, the therapeutic use of sirna requires effective carriers that can deliver sirna intracellularly with minimal toxicity on targe...

We have demonstrated that stimulation of somatic afferents during electroacupuncture (EA) inhibits sympathoexcitatory cardiovascular rostral ventrolateral medulla (rVLM) neurons and reflex responses. Furthermore, EA at P5-P6 acupoints over the median nerve on the forelimb activate serotonin (5-HT)-containing neurons in the nucleus raphe pallidus (NRP). The present study, therefore, examined the...

Background: Semaphorin has been found as a neuronal guidance molecule, but recently called “immune semaphorin”, their critical role in immune cell activation, differentiation and migration revealed. In particular, class 4 semaphorin shown to contribute lymphocyte activation homeostasis. Objectives: This study was aimed investigate the expression of neuropilin-1 (NRP-1), receptor semaphorin, mur...

The Neuropilins (Nrps) are a family of essential cell surface receptors involved in multiple fundamental cellular signaling cascades. Nrp family members have key functions in VEGF-dependent angiogenesis and semaphorin-dependent axon guidance, controlling signaling and cross-talk between these fundamental physiological processes. More recently, Nrp function has been found in diverse signaling an...

After internalization, transmembrane receptors (TMRs) are typically recycled back to the cell surface or targeted for degradation. Efficient TMR trafficking is critical for regulation of several processes, including signal transduction pathways, development, and disease. Here, we determined that trafficking of the angiogenic receptor neuropilin-1 (NRP-1) is abrogated by the liver kinase B1 (LKB...

The aim of this work was to investigate possible differences in peripheral blood concentrations of 13, 14 dihydro 15 keto PGF alpha (PGFM) and 6 keto PGF1 alpha (PGIM), between dairy cows retaining (RP) and not retaining (NRP) their placenta. Blood samples were collected 5, 30, and 60 minutes postpartum from 8 RP and 17 NRP cows. PGFM concentrations were significantly lower in RP cows than in N...