Blog of Signaling Pathways

Challenges in the treatment of melanoma with BRAF and MEK inhibitors in patients with sickle cell disease: case report and review of the literature

72 views | Apr 07 2023

The use of BRAF/MEK inhibitors for melanoma treatment in patients with sickle cell disease may be challenging due to potential inflammatory adverse events, and HU treatment may provide protective effects against inflammation and vaso-occlusion. [Read the Full Post]

MTORC2 is a physiological hydrophobic motif kinase of S6 Kinase 1

17 views | Apr 07 2023

The study identifies mTORC2 as a physiological hydrophobic motif (HM) kinase of S6K1, proposing a novel mechanism for S6K1 regulation where mTORC1 and mTORC2 act in tandem to activate the enzyme. [Read the Full Post]

Prelimbic Cortical Stimulation with L-methionine Enhances Cognition through Hippocampal DNA Methylation and Neuroplasticity Mechanisms

26 views | Apr 07 2023

The study suggests that targeting hippocampal DNA methyltransferase (DNMT) through prelimbic cortical deep brain stimulation (PrL DBS) and L-methionine (MET) co-administration may enhance memory and serve as a potential therapeutic approach for treating dementia. [Read the Full Post]

Design, synthesis and bioevaluation of 1,2,4-thiadiazolidine-3,5-dione derivatives as potential GSK-3β inhibitors for the treatment of Alzheimer's disease

117 views | Apr 07 2023

The development of compound 10a as a potential GSK-3β inhibitor for Alzheimer's disease shows promising results in vitro and in vivo. [Read the Full Post]

The Current Role of Disease-modifying Osteoarthritis Drugs

99 views | Apr 07 2023

The review explores the potential of disease-modifying osteoarthritis drugs (DMOADs) to induce repair and regeneration of articular tissues, but their clinical effectiveness has not yet been demonstrated for managing OA. [Read the Full Post]

In vitro pharmacological profile of KW-6356, a novel adenosine A2A receptor antagonist/inverse agonist

34 views | Apr 06 2023

The study found that KW-6356 is a potent and selective adenosine A2A receptor antagonist/inverse agonist with insurmountable antagonism, while istradefylline exhibits surmountable antagonism, and crystallography explains the differences in their pharmacological properties. [Read the Full Post]

Distinct Protein Kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes

30 views | Apr 06 2023

The study found that distinct PKC isoforms are responsible for the preferential appearance of nestin(+)- or nestin(-)-NNVMs that re-enter the cell cycle in the presence of SB203580. [Read the Full Post]

Lonafarnib improves cardiovascular function and survival in a mouse model of Hutchinson-Gilford progeria syndrome

52 views | Apr 06 2023

This study reports the positive effects of lonafarnib on cardiovascular structure, properties, and function in a mouse model of progeria, leading to 100% survival of treated mice and improved arterial structure and function, while rapamycin did not improve outcomes. [Read the Full Post]

N-palmitoylethanolamide synergizes the antinociception of morphine and gabapentin in the formalin test in mice

51 views | Apr 06 2023

The study investigated the synergistic antinociceptive effect of PEA in combination with MOR or GBP and found that PPARα and opioid receptors are involved in both interactions, suggesting potential use in treating inflammatory pain. [Read the Full Post]

The role of transforming growth factor-β2 in cigarette smoke-induced lung inflammation and injury

111 views | Apr 06 2023

The study found that TGF-β2 attenuated CSE-induced IL-8 production in PBECs and alleviated lung inflammation/injury in CS-exposed mice through the Smad3 signaling pathway. [Read the Full Post]

Methyltransferase K-D-K-E motif influences the intercellular transmission of Newcastle disease virus

177 views | Apr 05 2023

This research demonstrates that mutations in the K-D-K-E methyltransferase motif restrict the cell-to-cell spread of Newcastle disease virus via tunnelling nanotubes. [Read the Full Post]

Extracellularly Detectable Electrochemical Signals of Living Cells Originate from Metabolic Reactions

27 views | Apr 05 2023

This study demonstrates that intracellular metabolic pathways generating ATP contribute to extracellularly detectable electrochemical signals in living cells, which can be amplified with metabolic activator cocktails and used to detect the effects of anticancer drugs and quantify senescence in mesenchymal stem cells. [Read the Full Post]

Pyruvate Dehydrogenase Inhibition Leads to Decreased Glycolysis, Increased Reliance on Gluconeogenesis and Alternative Sources of Acetyl-CoA in Acute Myeloid Leukemia

66 views | Apr 05 2023

AML cells compensate for devimistat-mediated inhibition of PDH and glycolysis by activating alternative metabolic pathways such as gluconeogenesis, fatty acid oxidation, and non-glycolytic sources of acetyl-CoA, highlighting the need to explore strategies targeting these escape pathways to improve the efficacy of devimistat in AML. [Read the Full Post]

Patient-reported outcomes in capmatinib-treated patients with METex14-mutated advanced NSCLC: Results from the GEOMETRY mono-1 study

49 views | Apr 05 2023

Capmatinib showed meaningful improvements in cough and preserved quality of life in patients with METex14-mutated advanced non-small cell lung cancer, as reported by patient-reported outcomes in the GEOMETRY mono-1 study. [Read the Full Post]

Real-world outcomes in non-small-cell lung cancer patients with MET Exon 14 skipping mutation and brain metastases treated with capmatinib

92 views | Apr 05 2023

This retrospective medical record review study demonstrated that capmatinib is effective in treating non-small-cell lung cancer patients with MET exon 14 skipping mutation and brain metastases in a real-world setting, with high response rates and progression-free survival. [Read the Full Post]

The Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Improving Morbidity and Mortality of Heart Failure: A Systematic Review

66 views | Apr 04 2023

SGLT2 inhibitors have shown a beneficial effect in reducing cardiovascular mortality and morbidity in patients with type 2 diabetes mellitus and may have a broader application beyond diabetes. [Read the Full Post]

Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene

43 views | Apr 04 2023

This case report highlights the potential effectiveness of crizotinib, a MET inhibitor, in ALK-positive lung cancer patients with MET amplification who have developed resistance to ALK-TKIs. [Read the Full Post]

Non-canonical NLRC4 inflammasomes in astrocytes contribute to glioma malignancy

71 views | Apr 04 2023

This study demonstrates the pathological role of non-canonical NLRC4 inflammasomes in glioma and proposes therapeutic strategies based on modulating the inflammatory tumor microenvironment. [Read the Full Post]

Structural Biology Insight for the Design of Sub-type Selective Aurora Kinase Inhibitors

0 views | Apr 04 2023

Sub-type selective Aurora kinase inhibitors targeting specific residues unique to either Aurora A or B may have advantages over pan-selective inhibitors and could be useful in the treatment of cancer. [Read the Full Post]

Monitoring paxillin in astrocytes reveals the significance of the adhesion GPCR VLGR1/ADGRV1 for focal adhesion assembly

97 views | Apr 04 2023

VLGR1 is a vital component of focal adhesions and regulates cell migration by controlling focal adhesion turnover during their assembly, and its dysfunctions may contribute to the pathogenesis of Usher syndrome, epilepsy, and other related diseases. [Read the Full Post]