Blog of Signaling Pathways

SIRT3 ameliorates polycystic ovary syndrome through FOXO1/PGC-1α signaling pathway

23 views | Aug 09 2023

The study demonstrates that SIRT3 regulates the FOXO1/PGC-1α signaling pathway, mitigating mitochondrial dysfunction and improving polycystic ovary syndrome (PCOS). [Read the Full Post]

Design of Novel IRAK4 Inhibitors Using Molecular Docking, Dynamics Simulation and 3D-QSAR Studies

61 views | Aug 09 2023

This research focused on the development of small molecule inhibitors targeting IRAK4 through molecular modeling, dynamics simulations, binding free energy calculations, and 3D-QSAR studies, leading to the design of more potent compounds for the treatment of cancer and autoimmune diseases. [Read the Full Post]

Binding Energy Partition of Promising IRAK-4 Inhibitor (Zimlovisertib) for the Treatment of COVID-19 Pneumonia

24 views | Aug 09 2023

This study utilized Fragment-Based Drug Design (FBDD) and Interacting Quantum Atoms (IQA) energy partitioning to quantitatively analyze the interactions of ligand fragments with the IRAK-4 protein target, aiding in the rational design of Zimlovisertib for the treatment of COVID-19 pneumonia. [Read the Full Post]

Glutathione-Scavenging Nanoparticle-Mediated PROTACs Delivery for Targeted Protein Degradation and Amplified Antitumor Effects

38 views | Aug 09 2023

The development of Nano-PROTACs, which involve encapsulating PROTACs in GSH-responsive polymeric nanoparticles, demonstrates improved bioavailability, enhanced protein degradation, and superior anti-tumor efficacy, showing promise for the targeted treatment of diseases. [Read the Full Post]

Downregulated XBP-1 Rescues Cerebral Ischemia/Reperfusion Injury-Induced Pyroptosis via the NLRP3/Caspase-1/GSDMD Axis

73 views | Aug 08 2023

Downregulation of XBP-1 inhibits pyroptosis through the NLRP3/Caspase-1/GSDMD pathway, providing neuronal protection in the context of cerebral ischemia/reperfusion injury. [Read the Full Post]

C-C motif chemokine receptor 2 inhibition reduces liver fibrosis by restoring the immune cell landscape

41 views | Aug 08 2023

Cenicriviroc (CVC) treatment and CCR2 deletion alleviate liver fibrosis by restoring the immune cell landscape, inhibiting the hepatic accumulation of inflammatory macrophages and neutrophils, and suppressing profibrotic gene transcription through inactivation of the CCR2-STAT1/NFκB/ERK signaling pathways. [Read the Full Post]

Tropifexor plus cenicriviroc combination versus monotherapy in non-alcoholic steatohepatitis: Results from the Phase 2b TANDEM study

61 views | Aug 08 2023

The combination therapy of tropifexor (TXR) and cenicriviroc (CVC) did not show significant additional efficacy compared to respective monotherapies in terms of alanine aminotransferase (ALT) levels, body weight, or histological endpoints in the treatment of non-alcoholic steatohepatitis (NASH) in a phase 2b study. [Read the Full Post]

Complement dependent TNFα production in neutrophil-like HL60 cells

80 views | Aug 08 2023

This study demonstrates that complement C3 activation mediates TNFα production in neutrophil-like HL60 cells, which is enhanced by intracellular calcium elevation and negatively regulated by interactions with fibrinogen or fibronectin. [Read the Full Post]

A phase II trial of GSK2256098 and trametinib in patients with advanced pancreatic ductal adenocarcinoma

75 views | Aug 08 2023

The combination of GSK2256098 and trametinib did not show significant clinical benefit in advanced pancreatic ductal adenocarcinoma (PDAC) patients, with short median progression-free survival and overall survival observed in the study. [Read the Full Post]

HDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice

52 views | Aug 07 2023

The study reveals that HDAC9 induction in renal tubular epithelial cells mediates G2/M cell cycle arrest, leading to tubulointerstitial fibrosis, and suggests HDAC9 as a potential therapeutic target for treating kidney fibrosis. [Read the Full Post]

A phase Ib/II study of BLU-554, a fibroblast growth factor receptor 4 inhibitor in combination with CS1001, an anti-PD-L1, in patients with locally advanced or metastatic hepatocellular carcinoma

67 views | Aug 07 2023

The preliminary trial results indicate that combining BLU-554 and CS1001 is a safe and effective treatment option for patients with locally advanced or metastatic hepatocellular carcinoma (HCC), with a 50% objective response rate and 100% disease control rate observed. [Read the Full Post]

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC

92 views | Aug 07 2023

The study revealed that elevated expression of E74-like factor 4 (ELF4) in colorectal cancer is associated with increased metastasis and poor prognosis, and targeting the ELF4-related positive feedback circuit may offer a novel therapeutic approach. [Read the Full Post]

Educational level-dependent melanoma awareness in a high-risk population in Switzerland

88 views | Aug 07 2023

The study revealed that melanoma patients had a higher tendency to use a higher sun protection factor (SPF) compared to at-risk patients, emphasizing the significance of UV protection in melanoma prevention. [Read the Full Post]

Senescent Human Pancreatic Stellate Cells Secrete CXCR2 Agonist CXCLs to Promote Proliferation and Migration of Human Pancreatic Cancer AsPC-1 and MIAPaCa-2 Cell Lines

60 views | Aug 07 2023

Senescent pancreatic stellate cells (PSCs) and their secreted chemokines, such as CXCLs, play a significant role in promoting the proliferation and migration of pancreatic cancer cells, suggesting their potential as therapeutic targets for pancreatic cancer treatment. [Read the Full Post]

Cellular senescence in the response of HR+ breast cancer to radiotherapy and CDK4/6 inhibitors

77 views | Aug 06 2023

The study findings suggest that the inferiority of CDK4/6 inhibition followed by radiation therapy (P→RT) compared to radiation therapy followed by CDK4/6 inhibition (RT→P) in preclinical models of HR+ breast cancer may be partially attributed to the differential accumulation of senescent cells in the tumor microenvironment. [Read the Full Post]

Inhibition of the MAPK/c-Jun-EGR1 Pathway Decreases Photoreceptor Cell Death in the rd1 Mouse Model for Inherited Retinal Degeneration

46 views | Aug 06 2023

This study demonstrated that early growth response-1 (EGR1) promotes photoreceptor cell death in a mouse model of retinitis pigmentosa (RP), and inhibiting the MAPK/c-Jun pathway reduces EGR1 and poly (ADP-ribose) polymerase-1 (PARP1) expression, offering a potential therapeutic avenue for RP. [Read the Full Post]

Discovery of the c-Jun N-Terminal Kinase Inhibitor CC-90001

59 views | Aug 06 2023

This manuscript describes the synthesis and optimization of JNK inhibitors, resulting in the identification of CC-90001, a promising candidate currently in Phase II clinical trials for idiopathic pulmonary fibrosis. [Read the Full Post]

Inhibition of EED activity enhances cell survival of female germline stem cell and improves the oocytes production during oogenesis in vitro

18 views | Aug 06 2023

The study demonstrated that EED226 treatment increased the survival of female germline stem cells (FGSCs), promoted their differentiation into oocytes, and suggested an effective culture strategy for in vitro oogenesis. [Read the Full Post]

A PDX model combined with CD-DST assay to evaluate the antitumor properties of KRpep-2d and oxaliplatin in KRAS (G12D) mutant colorectal cancer

71 views | Aug 06 2023

The combination of patient-derived xenograft (PDX) models and the collagen gel droplet embedded culture drug sensitivity test (CD-DST) offers a comprehensive and feasible approach for evaluating the antitumor properties of compounds, as demonstrated by the significant inhibitory effects of oxaliplatin but lack of effectiveness of KRpep-2d in both tests. [Read the Full Post]

Coupling the immunomodulatory properties of the HDAC6 inhibitor ACY241 with Oxaliplatin promotes robust anti-tumor response in non-small cell lung cancer

0 views | Aug 05 2023

The study demonstrates that the HDAC6 inhibitor ACY241 promotes favorable changes in the tumor immune microenvironment, enhancing T cell function and macrophage activation, and when combined with Oxaliplatin, it leads to significantly improved tumor-associated T cell effector functionality, suggesting its potential as a therapeutic intervention in non-small cell lung cancer (NSCLC). [Read the Full Post]