Blog of Signaling Pathways

Targeting Echinococcus multilocularis PIM kinase for improving anti-parasitic chemotherapy

116 views | Mar 18 2023

The study identified PIM kinase as a potential target for the development of novel treatments for alveolar echinococcosis, and demonstrated the utility of high-throughput in silico approaches to design small molecule compounds of higher specificity for parasite cells. [Read the Full Post]

High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection

58 views | Mar 18 2023

The study developed a high-throughput screening assay to identify candidate drugs that protect the blood-brain spinal cord barrier function and demonstrated the neuroprotective effect of berberine and mubritinib after spinal cord injury. [Read the Full Post]

Mubritinib enhanced the inhibiting function of cisplatin in lung cancer by interfering with mitochondrial function

45 views | Mar 18 2023

Mubritinib can target mitochondrial electron transport chain complexes and disrupt mitochondrial function, ultimately inducing oxidative stress and increasing ROS levels, leading to its antitumor effect in lung cancer. [Read the Full Post]

Biweekly cetuximab in combination with capecitabine and oxaliplatin (XELOX) or irinotecan (XELIRI) in the first-line and second-line treatment of patients with RAS wild-type metastatic colorectal cancer

76 views | Mar 18 2023

The study found that biweekly cetuximab in combination with XELOX or XELIRI is well-tolerated and effective in patients with RAS wild-type metastatic colorectal cancer, with favorable outcomes observed. [Read the Full Post]

Targeting peripheral immune organs with self-assembling prodrug nanoparticles ameliorates allogeneic heart transplant rejection

73 views | Mar 18 2023

The passage describes the development of a self-assembling nanoparticle, DHA-PP242 nanoparticle (DPNP), which targets immune organs to regulate T cell function and has shown promise in reducing inflammatory response and extending the survival of grafts in an experimental model of heart transplantation. [Read the Full Post]

Sterol O-Acyltransferase Inhibition Ameliorates High-Fat Diet-Induced Renal Fibrosis and Tertiary Lymphoid Tissue Maturation after Ischemic Reperfusion Injury

67 views | Mar 17 2023

High-fat diet-induced renal tertiary lymphoid tissues and sustained inflammation in mice with ischemic reperfusion injury were found to be associated with sterol O-acyltransferase (SOAT) 1-dependent cholesteryl ester accumulation, and SOAT1 inhibition was found to attenuate TLT formation and renal inflammation, suggesting its potential as a therapeutic target for CKD prevention and treatment. [Read the Full Post]

Blocking Cholesterol Metabolism with Tumor-Penetrable Nanovesicles to Improve Photodynamic Cancer Immunotherapy

112 views | Mar 17 2023

Researchers have designed matrix metalloproteinase-2-sensitive tumor-penetrable nanovesicles that can regulate cholesterol metabolism to enhance photodynamic cancer immunotherapy by reinvigorating the functions of CD8+ T cells and suppressing the migration of tumor cells. [Read the Full Post]

Unusually High Affinity of the PLK Inhibitors RO3280 and GSK461364 to HSA and Its Possible Pharmacokinetic Implications

77 views | Mar 17 2023

The study investigated the binding processes of two Polo-like kinase inhibitors, RO3280 and GSK461364, to the human serum albumin (HSA) protein, finding that RO3280 binds to HSA in the charge state +1 prior to a deprotonation pre-equilibrium and has a higher binding affinity for HSA than GSK461364. [Read the Full Post]

Intravenous dabigatran provides adequate anticoagulation for cardiopulmonary bypass using a rabbit model

67 views | Mar 17 2023

The study demonstrated that dabigatran provides acceptable anticoagulation similar to heparin to prevent thrombosis in a rabbit CPB model, providing a potential alternative anticoagulant approach to heparin. [Read the Full Post]

Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of dabigatran etexilate, intermediate metabolite and dabigatran in 50μL rat plasma and its application to pharmacokinetic study

27 views | Mar 17 2023

A simple, rapid, and specific LC-MS/MS method has been developed for the simultaneous determination of dabigatran etexilate and its metabolites in rat plasma, which has been successfully applied to a pharmacokinetic study following a single oral administration of 15mg/kg dabigatran etexilate. [Read the Full Post]

The effect of lipid-lowering therapies on the pro-inflammatory and anti-inflammatory properties of vascular endothelial cells

44 views | Mar 16 2023

The study found that both statins, particularly rosuvastatin, had a stronger anti-inflammatory effect than ezetimibe in endothelial cells damaged by 25-hydroxycholesterol. [Read the Full Post]

PARP-1 inhibitor-AG14361 suppresses acute allograft rejection via stabilizing CD4+FoxP3+ regulatory T cells

35 views | Mar 16 2023

The PARP-1 inhibitor AG14361 may be a promising agent to attenuate acute allograft rejection by maintaining the number and function of Treg cells in allografts. [Read the Full Post]

Molecular Cardiotoxic Effects of Proteasome Inhibitors Carfilzomib and Ixazomib and Their Combination with Dexamethasone Involve Mitochondrial Dysregulation

117 views | Mar 16 2023

The study suggests that proteasome inhibitors may cause cardiotoxicity through stress response and mitochondrial dysfunction, which highlights the need for further studies to develop strategies to minimize their side effects. [Read the Full Post]

Targeting fibroblast growth factor receptors causes severe craniofacial malformations in zebrafish larvae

92 views | Mar 16 2023

The study investigated the effects of mutated fgfr2 sa10729 allele in zebrafish on cartilage and bone formation, and found that pharmacological targeting of FGFR1-4 kinase signaling causes severe craniofacial malformations, while abrogation of FGFR2 kinase signaling alone does not induce craniofacial skeletal abnormalities. [Read the Full Post]

Derivation of Limbal Stem Cells from Human Adult Mesenchymal Stem Cells for the Treatment of Limbal Stem Cell Deficiency

90 views | Mar 16 2023

This study presents a protocol for deriving human limbal stem cells from adipose-derived mesenchymal stem cells, which can aid in restoring vision for patients with LSC deficiency. [Read the Full Post]

Paclitaxel and docetaxel resistance in prostate cancer: Molecular mechanisms and possible therapeutic strategies

42 views | Mar 15 2023

This review highlights the mechanisms of paclitaxel and docetaxel resistance in prostate cancer and discusses the potential of phytochemicals and nanostructures for reversing drug resistance. [Read the Full Post]

Significance of Basal Membrane Permeability of Epithelial Cells in Predicting Intestinal Drug Absorption

51 views | Mar 15 2023

The study showed that assessing the permeability of A and B membranes separately and accounting for the intracellular drug concentration can improve the accuracy of predicting drug absorption in the gastrointestinal tract and understanding the role of transporters and enzymes. [Read the Full Post]

Dishevelled 2 regulates cancer cell proliferation and T cell mediated immunity in HER2-positive breast cancer

41 views | Mar 15 2023

The study demonstrated the potential immune regulatory role of DVL2 proteins in HER2+ breast cancer, and suggested further investigation of DVL paralogs as potential therapeutic targets. [Read the Full Post]

Involvement of the tuberomammillary nucleus of the hypothalamus in the modulation of nociception and joint edema in a model of monoarthritis

106 views | Mar 15 2023

The study suggests that histaminergic projections from the TMN to the spinal cord play a role in the modulation of nociception and peripheral edema in a subacute monoarthritis model, and that the hypothalamus may trigger TMN activation via glutamate and orexin. [Read the Full Post]

Mechanistic in vitro studies indicate that the clinical drug-drug interactions between protease inhibitors and rosuvastatin are driven by inhibition of intestinal BCRP and hepatic OATP1B1 with minimal contribution from OATP1B3, NTCP and OAT3

34 views | Mar 15 2023

This passage describes the use of a mechanistic static model to reconcile the disconnect between predicted and clinically observed area under the plasma concentration-time curve ratio (AUCR) of rosuvastatin due to drug-drug interaction (DDI) with atazanavir, by evaluating the inhibitory effects of atazanavir and other protease inhibitors on additional transporters, and integrating a combined hepatic transport component into the model. [Read the Full Post]