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Phosphodiesterase 10A Inhibitor Modulates Right Ventricular Outflow Tract Electrophysiological Activities and Calcium Homeostasis via the cGMP/PKG Pathway.
J Cell Mol Med
March 2025
Fu Jen Catholic University, School of Medicine, New Taipei City, Taiwan.
Phosphodiesterase inhibitors regulate intracellular Ca of cardiomyocytes through enhancing second messenger signalling. This study aimed to investigate whether TP-10, a selective phosphodiesterase10A inhibitor, modulates Ca cycling, attenuating arrhythmogenesis in the right ventricular outflow tract (RVOT). Right ventricular tissues from New Zealand white rabbits were harvested, and electromechanical analyses of ventricular tissues were conducted.
View Article and Find Full Text PDFPGRMC2 is a pressure-volume regulator critical for myocardial responses to stress in mice.
Nat Commun
March 2025
Department of Biomedical and Pharmaceutical Sciences, Chapman University, Irvine, CA, USA.
Progesterone receptors are classified into nuclear and membrane-bound receptor families. Previous unbiased proteomic studies indicate a potential association between cardiac diseases and the progesterone receptor membrane-bound component-2 (PGRMC2); however, the role of PGRMC2 in the heart remains unknown. In this study, we use a heart-specific knockout (KO) mouse model (MyH6•Pgrmc2) in which the Pgrmc2 gene was selectively deleted in cardiomyocytes.
View Article and Find Full Text PDFGLP-1 as a regulator of sepsis outcomes: Insights into cellular metabolism, inflammation, and therapeutic potential.
Int Immunopharmacol
March 2025
Department of Emergency and Critical Care Medicine, The Second Hospital of Jilin University, NO.218 Ziqiang Street, Changchun, 130041, People's Republic of China. Electronic address:
Glucagon-like peptide-1 (GLP-1) has been widely studied in the context of treating obesity and various forms of metabolic disease. Sepsis is a life-threatening medical emergency characterized by the widespread dysregulation of energy metabolism within cells. The potential for GLP-1 to improve sepsis patient outcomes through improvements in energy metabolism and inflammation has been a focus of growing research interest, with many studies of GLP-1 itself and related compounds, including GLP-1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, having explored the impact on sepsis in cells and organs.
View Article and Find Full Text PDFDual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy.
Proc Natl Acad Sci U S A
March 2025
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immunotherapy combinations. Traditional approaches combining conventional immune checkpoint inhibitors with neoantigen vaccines have shown some promise in treating PDAC but are often compromised by intratumoral T lymphocyte exhaustion and systemic toxicity. Hence, novel approaches are needed to address these challenges.
View Article and Find Full Text PDFEnhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt.
Proc Natl Acad Sci U S A
March 2025
Department of Biomedical Sciences, University of Padova, Padova 35131, Italy.
Regulation of mitochondrial Ca uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca handling, including mitochondrial uptake mechanisms, have been implicated in pathological heart hypertrophy. Enhancing mitochondrial Ca uniporter (MCU) expression has been suggested to interfere with maladaptive development of heart failure.
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