Insights into the Activation Mechanism of HCA1, HCA2, and HCA3.

Hydroxy-carboxylic acid receptors HCA1, HCA2, and HCA3 can be activated by important intermediates of energy metabolism. Despite the research focusing on HCA2, its clinical application has been limited by adverse effects. Therefore, the role of HCA1 as a promising target for the treatment of lipolysis warrants further exploration.

Vincristine loaded pegylated liposomal drug delivery for efficient treatment of acute lymphoblastic leukaemia.

Vincristine sulfate (VIN) is commonly employed as a cytotoxic agent in the treatment of hematological malignancies, particularly acute lymphoblastic leukaemia (ALL). However, its maximum therapeutic benefits have been hindered due to the dose-dependent neurotoxic effects it can induce, which traditionally manifest as autonomic and peripheral sensory-motor neuropathy. The innovative approach aimed to address VIN's neurotoxic limitations while preserving its therapeutic efficacy in combating hematological malignancies, including ALL.

Structure of human GPR119-G complex binding APD597 and characterization of GPR119 binding agonists.

The rhodopsin-like receptor GPR119 plays a crucial role in glucose homeostasis and is an emerging target for the treatment of type 2 diabetes mellitus. In this study, we analyzed the structure of GPR119 with the agonist APD597 bound and in complex with the downstream G protein trimer by single particle cryo-electron microscopy (cryo-EM). Structural comparison in combination with function assay revealed the conservative and specific effects of different kinds of GPR119 agonists.

Activation and signaling mechanism revealed by GPR119-G complex structures.

Agonists selectively targeting cannabinoid receptor-like G-protein-coupled receptor (GPCR) GPR119 hold promise for treating metabolic disorders while avoiding unwanted side effects. Here we present the cryo-electron microscopy (cryo-EM) structures of the human GPR119-G signaling complexes bound to AR231453 and MBX-2982, two representative agonists reported for GPR119. The structures reveal a one-amino acid shift of the conserved proline residue of TM5 that forms an outward bulge, opening up a hydrophobic cavity between TM4 and TM5 at the middle of the membrane for its endogenous ligands-monounsaturated lipid metabolites.

Up-regulation of plakophilin-2 is correlated with the progression of glioma.

Glioma is the most common type of primary brain tumor in the CNS. Due to its poor prognosis and high mortality rates, it is urgent to find out more effective therapies. Plakophilin-2 (PKP2) is a widespread desmosomal plaque protein.