Blog of Signaling Pathways

Inhibition of IL-1 Receptor-Associated Kinase 1 Decreases Murine Acute Graft-versus-Host Disease While Preserving the Graft-versus-Lymphoma Effect

17 views | Nov 21 2023

The selective IRAK1 inhibitor Jh-X-119-01 demonstrates promise as a therapeutic intervention for acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic cell transplantation, effectively mitigating aGVHD severity while preserving the graft-versus-tumor response and hematopoietic recovery. [Read the Full Post]

Identification of circRNA-miRNA-mRNA network regulated by Hsp90 in human melanoma A375 cells

50 views | Nov 21 2023

The study reveals that targeting the ECM-receptor interaction pathway, specifically the integrin (ITG) and collagen (COL) network, following Hsp90 inhibition by SNX-2112, offers a promising and novel therapeutic approach for melanoma treatment. [Read the Full Post]

Reducing the Invasiveness of Low- and High-Grade Endometrial Cancers in Both Primary Human Cancer Biopsies and Cell Lines by the Inhibition of Aquaporin-1 Channels

25 views | Nov 21 2023

Inhibition of AQP1 ion channels using specific inhibitors AqB011 and PMFC demonstrates significant reduction in invasiveness of both low- and high-grade endometrial cancer cells, indicating a promising therapeutic strategy to impede tumor progression and enhance patient outcomes. [Read the Full Post]

Assessing the venous system: Correlation of mean systemic filling pressure with the venous excess ultrasound grading system in cardiac surgery

22 views | Nov 20 2023

The study demonstrates a strong positive correlation between the venous excess ultrasound (VExUS) grading system and mean systemic filling pressure (Pmsf) in the early postoperative period after cardiac surgery, highlighting the critical role of systemic venous congestion in patient outcomes. [Read the Full Post]

Myeloid-derived growth factor suppresses VSMC dedifferentiation and attenuates postinjury neointimal formation in rats by activating S1PR2 and its downstream signaling

15 views | Nov 20 2023

The study demonstrates that Myeloid-derived growth factor (MYDGF) alleviates neointimal formation in rat carotid arteries post balloon injury by inhibiting vascular smooth muscle cell dedifferentiation through the S1PR2-RhoA-G/F-actin-MRTF-A signaling pathway, suggesting its potential as a therapeutic target for preventing restenosis after angioplasty. [Read the Full Post]

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity

24 views | Nov 20 2023

Using advanced molecular dynamics simulations, researchers identified masitinib's stable hydrogen bond interactions with the Mpro enzyme, pinpointing the crucial role of His163, leading to the design of effective derivatives M3 and M4 with increased inhibitory efficiency against SARS-CoV-2. [Read the Full Post]

Reconstructing the immunosenescence core pathway reveals global characteristics in pan-cancer

26 views | Nov 20 2023

Your study systematically analyzed multi-omics data from 12,836 tumor samples, revealing disordered immunosenescence pathways across cancer types, emphasizing the pan-cancer activation of immunosenescence pathways, and identifying the MTOR gene as a potential sex-specific immunosenescence biomarker in head and neck squamous carcinoma, suggesting OSI-027 as a promising sex-specific drug. [Read the Full Post]

Lysin (K)-specific demethylase 1 inhibition enhances proteasome inhibitor response and overcomes drug resistance in multiple myeloma

36 views | Nov 20 2023

The study demonstrates that inhibiting lysine-specific demethylase 1 (LSD1) synergizes with proteasome inhibitors, such as carfilzomib, overcoming drug resistance in multiple myeloma and other B-cell malignancies, offering a promising therapeutic strategy. [Read the Full Post]

A sequential scheme including PTT and 2'3'-cGAMP/CQ-LP reveals the antitumor immune function of PTT through the type I interferon pathway

16 views | Nov 19 2023

The study elucidates the mechanisms underlying Photothermal Therapy (PTT) by demonstrating STING-dependent and STING-independent type I interferon production, and proposes a synergistic approach using a novel liposome co-loaded with the STING agonist cGAMP and chloroquine, which, when combined with PTT, induces significant tumor cell apoptosis and modulates the tumor microenvironment, providing crucial insights for the rational design of potent antitumor combination treatments. [Read the Full Post]

Spinal cannabinoid receptor 2 activation alleviates neuropathic pain by regulating microglia and suppressing P2X7 receptor

58 views | Nov 19 2023

The study demonstrates that continuous activation of cannabinoid receptor 2 (CB2R) with the specific agonist PM226 promotes a neuroprotective transition in microglia, attenuates neuropathic pain, and reduces proinflammatory P2X7 receptor content, offering a potential therapeutic avenue for managing neuropathic pain with low abuse potential. [Read the Full Post]

Inhibiting SETD7 methyl-transferase activity impairs differentiation, lipid metabolism and lactogenesis in mammary epithelial cells

23 views | Nov 19 2023

Inhibiting SETD7 catalytic activity using (R)-PFI-2 disrupts mammary epithelial cell differentiation by increasing proliferation, downregulating differentiation markers, and altering lipid metabolism. [Read the Full Post]

Dimeric Lectin Chimeras as Novel Candidates for Gb3-Mediated Transcytotic Drug Delivery through Cellular Barriers

24 views | Nov 19 2023

The study presents a novel dimeric LecA chimera, Di-LecA, paired with the host cell glycosphingolipid Gb3, demonstrating efficient transcytosis across Gb3-positive cellular barriers, offering a promising strategy for targeted drug delivery applications. [Read the Full Post]

Androgen Receptor Variants Confer Castration Resistance in Prostate Cancer by Counteracting Antiandrogen-Induced Ferroptosis

24 views | Nov 19 2023

The passage discusses how acute treatment with the antiandrogen enzalutamide induces ferroptosis in prostate cancer cells by decreasing glutathione production, increasing lipid peroxidation, and upregulating the cystine transporter gene SLC7A11 through both full-length and variant forms of the androgen receptor, revealing a potential mechanism for therapeutic resistance and identifying a target for intervention. [Read the Full Post]

Complement C3a receptor antagonist alleviates tau pathology and ameliorates cognitive deficits in P301S mice

20 views | Nov 18 2023

The study reveals that upregulation of C3aR in tauopathy mouse models leads to tau hyperphosphorylation and behavioral deficits, and pharmacological blockade of C3aR not only ameliorates these pathological features but also improves synaptic integrity, suggesting C3aR as a promising therapeutic target for neurodegenerative diseases like Alzheimer's. [Read the Full Post]

Viability of selected microorganisms in parenteral preparations for novel systemic anti-cancer therapy

38 views | Nov 18 2023

**"This study reveals the persistence of viable pathogenic microorganisms in most aseptically prepared parenteral cancer therapy solutions, emphasizing the importance of strict aseptic conditions and careful consideration of antimicrobial activity when determining their shelf life."** [Read the Full Post]

Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia

74 views | Nov 18 2023

Targeting the overexpressed heat shock factor 1 (HSF1) with the inhibitor KRIBB11 inhibits proliferation, induces apoptosis, disrupts essential signaling pathways, and sensitizes adult T-cell leukemia cells to HSP90 inhibition, offering a potential therapeutic approach for ATL. [Read the Full Post]

Drug Repurposing Analysis for Colorectal Cancer through Network Medicine Framework: Novel Candidate Drugs and Small Molecules

35 views | Nov 18 2023

The study identified a novel gene module associated with colorectal cancer and proposed several previously studied (including polyethylene glycol, pantoprazole, trametinib) and novel (such as lornoxicam, suxamethonium, HDAC6 inhibitor ISOX) drug-repurposing candidates based on network biology approaches and differential co-expression analysis. [Read the Full Post]

Use of RIP1 Kinase Small-Molecule Inhibitors in Studying Necroptosis

36 views | Nov 18 2023

The careful selection and application of small-molecule inhibitors, considering parameters such as potency, selectivity, in vivo efficacy, and potential limitations, are essential for unraveling the complex biology of RIP1 kinase and its role in inflammation and disease pathogenesis. [Read the Full Post]

Atypical Acetylcholine Receptors on the Neurons of the Turkish Snail

34 views | Nov 17 2023

The study on Helix lucorum snail neurons demonstrated that their nicotinic acetylcholine receptors (nAChRs) exhibit a complex and atypical pharmacological profile, responding to various nAChR ligands and muscarinic receptor ligands, with α7, muscle-type, and α9 nAChRs playing key roles in mediating acetylcholine-induced depolarization. [Read the Full Post]

Hydrogen Sulfide Improves Outcomes in a Murine Model of Necrotizing Enterocolitis via the Cys440 Residue on Endothelial Nitric Oxide Synthase

82 views | Nov 17 2023

GYY4137 administration improves clinical outcomes, attenuates intestinal and lung injury, and enhances perfusion in a murine model of necrotizing enterocolitis, with these protective effects being contingent upon the presence of the Cys440 residue in endothelial nitric oxide synthase (eNOS). [Read the Full Post]