Blog of Signaling Pathways

Cantharidin induces senescence via inhibition of AMP-activated protein kinase and activation of NLRP3 inflammasome in H9c2 cardiomyocytes

13 views | Dec 07 2023

Cantharidin induces cardiomyocyte senescence and senescence-associated secretory phenotype (SASP) through activation of the NLRP3 inflammasome and inhibition of AMPK phosphorylation, providing novel insights into its cardiotoxic effects. [Read the Full Post]

The Crystal Structure of Engineered Nitroreductase NTR 2.0 and Impact of F70A and F108Y Substitutions on Substrate Specificity

25 views | Dec 07 2023

A newly engineered nitroreductase enzyme, NTR 2.0, with enhanced reduction capabilities for the prodrug metronidazole, has been characterized through X-ray crystallography and substrate analysis, enabling faster cell ablation kinetics, cleaner interrogations of cell function, ablation of previously recalcitrant cell types, and extended ablation paradigms valuable for modeling chronic diseases and exploring applications such as alternative ablation prodrugs and environmental remediation. [Read the Full Post]

Putative nucleotide-based second messengers in archaea

16 views | Dec 06 2023

Nucleotide-based second messengers in archaea, including cyclic di-AMP and cyclic oligoadenylates, have been identified with specific roles in osmoregulation and Type III CRISPR-Cas defense, while other putative second messengers await further characterization, highlighting the complexity of cellular signaling in these organisms. [Read the Full Post]

Dnmt3a is downregulated by Stat5a and mediates G0/G1 arrest by suppressing the miR-17-5p/Cdkn1a axis in Jak2V617F cells

39 views | Dec 06 2023

**In Jak2V617F positive classical myeloproliferative neoplasms, aberrant activation of Stat5a downregulates Dnmt3a through binding to its promoter, leading to dysregulation of the miR-17-5p/Cdkn1a axis and G0/G1 cell cycle arrest, providing a potential therapeutic target.** [Read the Full Post]

Selective inhibition of indoleamine and tryptophan 2,3-dioxygenases: Comparative study on kynurenine pathway in cell lines via LC-MS/MS-based targeted metabolomics

17 views | Dec 06 2023

This paper presents a validated LC-MS/MS method to quantify multiple metabolites in the kynurenine pathway, enabling the characterization of cell secretome, insights into disease scenarios, evaluation of enzyme inhibitors, and multivariate analysis, thereby advancing our understanding of cancer immunotherapy and preclinical drug research. [Read the Full Post]

Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta

15 views | Dec 06 2023

Theophylline-induced endothelium-dependent vasodilation in isolated rat thoracic aortas is mediated by increased endothelial nitric oxide release, guanylate cyclase activation, elevated cGMP levels, and enhanced endothelial nitric oxide synthase phosphorylation. [Read the Full Post]

Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells

26 views | Dec 06 2023

The experimental study demonstrates that Pyrintegrin (Ptn) promotes robust adipogenesis both in vitro and in vivo, suggesting its potential therapeutic application in soft tissue reconstruction and augmentation by inducing the formation of adipose tissue from transplanted and endogenous cells. [Read the Full Post]

Effect of feed enriched by products formulated from coconut water, palm sap sugar, and mushroom on the chemical composition of feed and carcass, growth performance, body indices, and gut micromorphology of giant gourami, Osphronemus goramy (Lacepède, 1801), juveniles

19 views | Dec 05 2023

The study found that the formulation KP3, incorporating palm sap sugar, coconut water, and specific microorganisms, significantly improved the nutrition, growth, and body composition of giant gourami juveniles, making it a promising option for aquaculture in Indonesia. [Read the Full Post]

UMI-77 Modulates the Complement Cascade Pathway and Inhibits Inflammatory Factor Storm in Sepsis Based on TMT Proteomics and Inflammation Array Glass Chip

27 views | Dec 05 2023

UMI-77, administered at 7.0 mg/kg, significantly improves the survival rate of septic mice by suppressing inflammatory storm-related cytokines and modulating the complement cascade pathway, revealing its potential as a treatment for sepsis. [Read the Full Post]

Natto extract inhibits infection caused by the Aujeszky

23 views | Dec 05 2023

The discovery that Fraction No. 10 from natto, a traditional Japanese fermented food, can functionally impair Aujeszky's disease virus (ADV) infection through serine protease inhibition, providing a potential avenue for developing natural antiviral treatments in the swine industry, holds significant promise for mitigating economic losses and promoting animal welfare. [Read the Full Post]

Hepatic arterial infusion chemotherapy with or without lenvatinib for unresectable cholangiocarcinoma: a single-center retrospective study

43 views | Dec 05 2023

**Combining FOLFOX hepatic arterial infusion chemotherapy with lenvatinib significantly prolongs overall and progression-free survival, making it a promising and safe treatment option for patients with unresectable cholangiocarcinoma.** [Read the Full Post]

Development of a Once-Daily Modified-Release Formulation for the Short Half-Life RIPK1 Inhibitor GSK2982772 using DiffCORE Technology

23 views | Dec 05 2023

The study confirmed the efficacy of GSK proprietary DiffCORE™ technology in creating a stable once-daily pharmacokinetic profile for GSK2982772, overcoming susceptibility to food effects observed in the previous matrix monolithic formulation and leading to the selection of the MR-16 h formulation for further clinical development. [Read the Full Post]

Next-Generation Sequencing-Optimal Sequencing of Therapies in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)

0 views | Dec 04 2023

**This research paper provides a comprehensive overview of evidence-based sequencing of therapies in relapsed/refractory chronic lymphocytic leukemia (CLL) in the era of targeted drugs, emphasizing the importance of personalized treatment strategies and highlighting promising developments, such as noncovalent BTK inhibitors, while underscoring the urgent need for solutions in the challenging subgroup of patients previously exposed to both BTK and BCL2 inhibitors.** [Read the Full Post]

Transarterial chemoembolization with or without multikinase inhibitors for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis of randomized controlled trials

19 views | Dec 04 2023

The systematic review and meta-analysis demonstrate that transarterial chemoembolization (TACE) combined with multikinase inhibitors (MKIs) significantly prolongs time to progression and improves objective response rates, but does not significantly impact overall or progression-free survival in patients with unresectable hepatocellular carcinoma, highlighting the importance of managing MKI-related toxicities in future clinical applications. [Read the Full Post]

Daprodustat: A potential game-changer in renal anemia therapy-A perspective

30 views | Dec 04 2023

As of my last update in September 2021, I cannot confirm the recent FDA approval of daprodustat (DPD) for anemia due to chronic kidney disease in dialysis patients or its potential applications in non-dialysis patients and those with coexisting renal anemia and heart failure; for the latest information, please refer to official sources. [Read the Full Post]

Dual action of Dooku1 on PIEZO1 channel in human red blood cells

20 views | Dec 04 2023

In the context of Red Blood Cells (RBCs), Dooku1, previously considered a PIEZO1 antagonist, was found to behave as a lower-potency agonist, triggering calcium entry and activating PIEZO1 channels, highlighting the complex pharmacological interactions specific to RBC membranes. [Read the Full Post]

Unlocking the potential of approved drugs for the allosteric inhibition of tropomyosin-receptor kinase A using molecular docking and molecular dynamics studies

20 views | Dec 04 2023

The study identified delanzomib and tibalosin as potential allosteric inhibitors of TrkA through molecular docking and dynamics simulations, offering promising candidates for experimental evaluation in cancer therapy due to their stable interactions and high binding affinities. [Read the Full Post]

Allelopathic Effect of Aqueous Extracts of Grass Genotypes on Eruca Sativa L

18 views | Dec 03 2023

The study investigates the allelopathic activity of fifty grass genotypes and identifies phenolic compounds, particularly caffeic acid, in Festulolium genotypes, demonstrating their potent inhibitory effect on the growth of Eruca sativa L., highlighting their potential for sustainable weed control in agriculture. [Read the Full Post]

ARHGEF37 overexpression promotes extravasation and metastasis of hepatocellular carcinoma via directly activating Cdc42

14 views | Dec 03 2023

The study reveals that ARHGEF37 upregulation in hepatocellular carcinoma promotes pulmonary metastasis by enhancing tumor cell adhesion to endothelial cells and trans-endothelial migration via direct activation of Cdc42, and targeted inhibition of this pathway using ZCL278 presents a potential therapeutic approach for preventing and treating HCC lung metastasis. [Read the Full Post]

Conditional lethality profiling reveals anticancer mechanisms of action and drug-nutrient interactions

13 views | Dec 03 2023

The study screened anticancer and non-oncology compounds in conventional and Human Plasma-Like Medium, revealing a dual mechanism of action for brivudine in folate metabolism and identifying conditional phenotypes for various drugs, offering insights into exploiting conditional lethality for therapeutic candidate discovery. [Read the Full Post]