Blog of Signaling Pathways

A network meta-analysis of the efficacy of hypoxia-inducible factor prolyl-hydroxylase inhibitors in dialysis chronic kidney disease

25 views | Jul 20 2023

In conclusion, roxadustat demonstrated the highest efficacy in increasing hemoglobin levels but was associated with an increased risk of hypertension and thrombosis, while molidustat and ESAs may be preferable options for patients at risk of hypertension and thrombosis. [Read the Full Post]

Extracellular Release of Citrullinated Vimentin Directly Acts on Osteoclasts to Promote Bone Resorption in a Mouse Model of Periodontitis

48 views | Jul 20 2023

The release of citrullinated vimentin (CV) promotes osteoclastogenesis and bone resorption in periodontitis, suggesting a potential shared pathogenesis with rheumatoid arthritis. [Read the Full Post]

The tumor stroma influences immune cell distribution and recruitment in a PDAC-on-a-chip model

135 views | Jul 20 2023

This study utilized a 3D PDAC model to investigate the interaction between tumor stroma and immune cells, revealing that stromal cells create a physical and biochemical barrier that hinders immune cell infiltration, and targeting the stroma can increase immune cell infiltration, offering potential therapeutic strategies for PDAC. [Read the Full Post]

Divergent splanchnic sympathetic efferent nerve pathways regulate interleukin-10 and tumour necrosis factor-α responses to endotoxaemia

81 views | Jul 19 2023

This study demonstrates that the splanchnic sympathetic nerves mediate an endogenous neural reflex that enhances interleukin-10 levels and suppresses tumor necrosis factor-α levels in response to systemic immune challenge, with distinct pathways regulating these cytokine responses. [Read the Full Post]

How We Manage Patients with Indolent B-Cell Malignancies on Bruton's Tyrosine Kinase Inhibitors: Practical Considerations for Nurses and Pharmacists

35 views | Jul 19 2023

This paper provides Canadian nurses and pharmacists with a comprehensive reference guide on dosing, co-administration, and adverse event management strategies for patients with indolent B-cell NHL or CLL being treated with Bruton's tyrosine kinase (BTK) inhibitors. [Read the Full Post]

BET inhibition targets ABC-DLBCL constitutive B-cell receptor signaling through PAX5

25 views | Jul 19 2023

The study demonstrates that combining the BET inhibitor AZD5153 with the Bruton tyrosine kinase inhibitor acalabrutinib enhances efficacy in ABC-DLBCL by targeting PAX5 and BCR signaling pathways, offering potential for improved treatment outcomes in relapsed or refractory patients. [Read the Full Post]

Effects of the Combined Treatment with a G-Quadruplex-Stabilizing Ligand and Photon Beams on Glioblastoma Stem-like Cells: A Magnetic Resonance Study

66 views | Jul 19 2023

The study found that while the GSC line #1 showed significant metabolic changes and sensitivity to the treatments, the GSC line #83 did not exhibit distinct metabolic responses, and there were no synergistic effects observed from the combination of ligand #190 and photon beam radiation in either GSC line. [Read the Full Post]

5-FU mediated depletion of myeloid suppressor cells enhances T-cell infiltration and anti-tumor response in immunotherapy-resistant lung tumor

137 views | Jul 19 2023

Depletion of MDSCs using low-dose 5-fluorouracil (5-FU) chemotherapy showed significant anti-tumor effects by increasing the infiltration of CD8+ cytotoxic T-cells in a cold tumor model of Lewis Lung Carcinoma (LLC). [Read the Full Post]

Mortality trends of aortic stenosis in high-income countries from 2000 to 2020

50 views | Jul 18 2023

This study investigates recent mortality trends from aortic stenosis among eight high-income countries, revealing an increase in crude mortality rates but shifts towards decreasing trends in age-standardized rates in three countries and among individuals aged ≥80 years. [Read the Full Post]

Efficacy and safety of sotagliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease

61 views | Jul 18 2023

The study found that sotagliflozin, at a dose of 400 mg but not 200 mg, significantly reduced HbA1c levels compared to placebo after 26 weeks in adults with type 2 diabetes and stage 3 chronic kidney disease, while both doses showed reductions in urine albumin-creatinine ratio at week 26, but not sustained at week 52, and the safety profile was similar to previous reports. [Read the Full Post]

Adenosine A2A Receptors Shut Down Adenosine A1 Receptor-Mediated Presynaptic Inhibition to Promote Implementation of Hippocampal Long-Term Potentiation

82 views | Jul 18 2023

Activation of A2A receptors dampens the inhibitory effects of A1 receptors, enabling the implementation of hippocampal long-term potentiation (LTP) during high-frequency induction. [Read the Full Post]

TP53 mutations and RNA-binding protein MUSASHI-2 drive resistance to PRMT5-targeted therapy in B-cell lymphoma

61 views | Jul 18 2023

The proposed therapeutic strategy in lymphoma combines PRMT5 inhibition with either MSI2 or BCL-2 inhibition, leveraging the synergistic effects observed to potentially enhance therapeutic efficacy. [Read the Full Post]

Prmt1 upregulated by Hdc deficiency aggravates acute myocardial infarction via NETosis

29 views | Jul 18 2023

The study reveals that histidine decarboxylase deficiency in mice leads to disorderly recruitment of neutrophils, enhanced migration and ROS/NETs production, promoting cardiac damage, but treatment with histamine or PRMT1 inhibitors attenuates these effects, suggesting potential therapeutic strategies for cardiovascular disease. [Read the Full Post]

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes

52 views | Jul 17 2023

This study demonstrates that centromere transcription in growing oocytes, associated with DNA repair proteins, plays a role in maintaining centromere stability and kinetochore assembly, providing insights into the accurate segregation of chromosomes during oocyte maturation. [Read the Full Post]

Icaritin inhibits CDK2 expression and activity to interfere with tumor progression

35 views | Jul 17 2023

Icaritin directly targets CDK2 in tumor cells, leading to downregulation of CDK2 activity, inhibition of cell cycle progression, and promotion of apoptosis, suggesting its potential as a therapeutic agent for cancer treatment. [Read the Full Post]

Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

79 views | Jul 17 2023

The development of p97 inhibitors as UPS-targeting cancer therapies represents a promising approach for addressing protein homeostasis deficiencies underlying various cancers and neurodegenerative diseases. [Read the Full Post]

Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR

41 views | Jul 17 2023

Shikonin, a recently identified inhibitor of the DNA damage response (DDR), has been found to suppress DDR activation by targeting ATM and ATRIP, leading to enhanced anti-cancer effects of chemotherapy, making it a potential candidate for chemotherapy sensitization. [Read the Full Post]

Hexavalent chromium disrupts the skin barrier by targeting ROS-mediated mitochondrial pathway apoptosis in keratinocytes

53 views | Jul 17 2023

This study demonstrates that hexavalent chromium (Cr(VI)) exposure leads to skin deterioration, hemorrhaging, collagen fiber layer thinning, impaired membrane integrity, and apoptosis primarily targeting keratinocytes, highlighting the importance of apoptosis and ROS-mediated mitochondrial pathway in Cr(VI)-induced skin barrier injury. [Read the Full Post]

Targeting FLT3 Mutation in Acute Myeloid Leukemia: Current Strategies and Future Directions

28 views | Jul 16 2023

FLT3 inhibitors have improved clinical outcomes for acute myeloid leukemia patients with FLT3 mutations, but the emergence of resistance and the need for novel therapeutic strategies remain ongoing challenges. [Read the Full Post]

Biomarker-Based Prediction of Recurrent Ischemic Events in Patients With Acute Coronary Syndromes

65 views | Jul 16 2023

This study developed and validated an 8-item biomarker-based prediction score, named ABC-ACS ischemia, for assessing the 1-year risk of cardiovascular death or myocardial infarction in patients with acute coronary syndrome undergoing percutaneous coronary intervention. [Read the Full Post]