Polynorepinephrine nanoparticles activate vascular smooth muscle alpha-1 adrenergic receptors.

Biocompatible polymeric nanoparticles (NPs) as carriers for therapeutic agents with multifunctional activities have received unprecedented attention for a variety of bio-pharmaceutical applications. We describe the synthesis, the fluorescence properties, the bio-compatible nature and the alpha-1 adrenergic receptor bio-activity of engineered quantum dot-like polynorepinephrine (PNE) NPs. The spherical PNE NPs, which are internalized in smooth muscle cells a receptor-selective mechanism, activate alpha-1-adrenoceptors in intact mouse aorta and aorta-derived cultured smooth muscle cells, leading to the activation of calcium signaling/contraction and stimulation of mitogen-activated protein kinase (MAPK), thereby displaying receptor-triggering biological activity, possibly acting both extracellularly and intracellularly.

New criteria for preoperative liver function assessment with safety margins to avoid postoperative mortality during liver resection for hilar cholangiocarcinoma.

Background: Despite recent medical advancements, surgery for hilar cholangiocarcinoma is associated with high complication and mortality rates. This may be partly attributed to the absence of established preoperative liver evaluation criteria for safe surgery. This study aimed to propose a reliable indicator for safe and well-planned management of major hepatectomy with extrahepatic bile duct resection.

Safety, pharmacokinetics, and pharmacodynamics of sofnobrutinib, a novel non-covalent BTK inhibitor, in healthy subjects: First-in-human phase I study.

Bruton's tyrosine kinase (BTK) is a potential therapeutic target for allergic and autoimmune diseases. This first-in-human phase I study evaluated safety, pharmacokinetic, and pharmacodynamic profiles of sofnobrutinib (formerly AS-0871), a highly selective, orally available, non-covalent BTK inhibitor, in healthy adult subjects. Single ascending doses (SAD; 5-900 mg) and multiple ascending doses (MAD; 50-300 mg twice daily [b.

Antitumor Effect of Oleoyl-siRNA against Pancreatic Cancer Using a Portal Vein Infusion Liver-Metastatic Mouse Model.

In this study, we developed an oleoyl-siRNA conjugate in which oleic acid was conjugated at the 5'-end of the sense strand of the siRNA. Furthermore, we examined the effects of RNAi in a mouse model of pancreatic cancer with liver metastasis. The mouse model of pancreatic cancer with liver metastasis was developed by implanting Sui67Luc human pancreatic cancer cells into the portal veins of mice.