Blog of Signaling Pathways

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition

26 views | Dec 11 2023

The study reveals that CDK6 inhibition using BSJ disrupts the primordial-to-primary follicle transition, emphasizing the crucial role of precise cell cycle regulation in ovarian follicle development and suggesting potential implications for fertility-related interventions. [Read the Full Post]

MLN4924 inhibits hedgehog signaling pathway and activates autophagy to alleviate mouse laser-induced choroidal neovascularization lesion

0 views | Dec 11 2023

MLN4924, a selective inhibitor of NEDD8-activating enzyme, mitigates neovascular age-related macular degeneration by inhibiting choroidal neovascularization through the upregulation of hedgehog pathway-regulated autophagy in choroidal endothelial cells under hypoxia conditions. [Read the Full Post]

Straightforward Access to a New Class of Dual DYRK1A/CLK1 Inhibitors Possessing a Simple Dihydroquinoline Core

17 views | Dec 10 2023

In this study, a novel class of dihydroquinolines was developed, exhibiting potent inhibitory activities in the nanomolar range against DYRK1A and CLK1, two kinases implicated in Alzheimer's disease and Down syndrome, with the most potent inhibitor also demonstrating antioxidant and radical scavenging properties. [Read the Full Post]

Supervised screening of Tecovirimat-like compounds as potential inhibitors for the monkeypox virus E8L protein

33 views | Dec 10 2023

The study utilized computational methods and machine learning-guided screening to identify five promising drugs, ABX-1431, Alflutinib, Avacopan, Caspitant, and Darapalib, which effectively engage the MPXV E8L surface binding protein with higher affinity than Tecovirimat, potentially offering new avenues for the development of personalized treatments for Monkeypox virus infections. [Read the Full Post]

PI3K pathway mutation predicts an activated immune microenvironment and better immunotherapeutic efficacy in head and neck squamous cell carcinoma

16 views | Dec 10 2023

*PI3K pathway mutations in head and neck squamous cell carcinoma patients are associated with significantly extended overall survival and enhanced immunotherapeutic responses, indicating their potential as a valuable biomarker for clinical prognosis and treatment outcomes.* [Read the Full Post]

Retinoic acid delays murine palatal shelf elevation by inhibiting Wnt5a-mediated noncanonical Wnt signaling and downstream Cdc-42/F-actin remodeling in mesenchymal cells

41 views | Dec 10 2023

This study elucidates the mechanism by which retinoic acid disrupts palate development, causing cleft palate in mice, revealing the crucial role of Wnt5a-mediated noncanonical Wnt signaling downstream of Rho GTPase Cdc42 in regulating cytoskeletal remodeling and cell migration during the process. [Read the Full Post]

The Multikinase Inhibitor AD80 Induces Mitotic Catastrophe and Autophagy in Pancreatic Cancer Cells

44 views | Dec 10 2023

The study reveals that AD80, a multikinase inhibitor, exerts potent antineoplastic effects in pancreatic cancer cells by inducing mitotic aberrations, DNA damage, autophagy, and apoptosis, providing crucial insights into potential targeted therapeutic strategies for this deadly disease. [Read the Full Post]

Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies

21 views | Dec 09 2023

The recent approval of topical agents like Roflumilast and Tapinarof, along with ongoing research into various targeted therapies and optimized formulations, represents a promising shift in the management of pediatric psoriasis, offering diverse and potentially more effective treatment options for young patients. [Read the Full Post]

Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition

32 views | Dec 09 2023

**LPS-induced inhibition of autophagy leads to trigeminal ganglion neurite loss, highlighting a potential therapeutic target for corneal nerve damage.** [Read the Full Post]

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems

20 views | Dec 09 2023

Harnessing live-cell bright-field imaging and machine learning, this study enables real-time recognition of diverse cell types, predictive assessment of differentiation efficiency, and iterative optimization of pluripotent stem cell differentiation, ensuring consistent high efficiency across cell lines and batches for biomedical applications. [Read the Full Post]

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia

33 views | Dec 09 2023

Microgravity-induced shortening of primary cilia triggers overexpression and hyperactivity of TRPV4 channels, leading to intracellular Ca2+ overload, oxidative stress, and loss of osteogenic potential in osteoblasts, a process preventable by protecting primary cilia. [Read the Full Post]

Increased recombinant adeno-associated virus production by HEK293 cells using small molecule chemical additives

24 views | Dec 09 2023

The study demonstrates that the addition of small molecule bioactive chemical additives, nocodazole and M344, significantly enhances rAAV vector production in HEK cells, increasing genome titre up to three-fold and indicating a promising approach for improving the cost-effectiveness of gene therapy production processes. [Read the Full Post]

Targeted Regulation of Osteoblasts and Osteoclasts in Osteosarcoma Patients by CSF3R Receptor Inhibition of Osteolysis Caused by Tumor Inflammation Based on Transcriptional Spectrum Analysis and Drug Library Screening

33 views | Dec 08 2023

**In summary, the study identifies CSF3R as a key regulator in osteosarcoma progression, influencing bone destruction and patient prognosis by modulating the inflammatory response of osteoblasts and osteoclasts, with Leucovorin and Methotrexate identified as potential therapeutic compounds.** [Read the Full Post]

Single-cell RNA sequencing identifies an Il1rn+/Trem1+ macrophage subpopulation as a cellular target for mitigating the progression of thoracic aortic aneurysm and dissection

39 views | Dec 08 2023

The study on thoracic aortic aneurysm and dissection (TAAD) utilizing single-cell RNA sequencing in a mouse model identified the Il1rn+/Trem1+ pro-inflammatory macrophage subpopulation as the predominant source of detrimental molecules, highlighting the potential of targeted therapy, specifically via Trem1 blockade, as a promising medical treatment for TAAD. [Read the Full Post]

Computational insights into the role of structurally diverse plant secondary metabolites as inhibitors against Imidazole Glycerol Phosphate Dehydratase of Mycobacterium tuberculosis

17 views | Dec 08 2023

The study identified Bismahanine, Ashwagandhanolide, and Daurisoline as promising plant secondary metabolites that form stable complexes with Imidazole Glycerol Phosphate Dehydratase (IGPD) in Mycobacterium tuberculosis, demonstrating strong inhibitory potential and suggesting their candidacy for further in vitro and in vivo anti-tuberculosis drug development. [Read the Full Post]

TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation

38 views | Dec 08 2023

The study demonstrates that the TLR4 inflammatory cascade disrupts vascular integrity by downregulating Dock1 and Elmo1 expression, highlighting Dock1 as a critical target in TLR4-mediated inflammatory lung injury and emphasizing its essential role in maintaining endothelial cell junctional integrity. [Read the Full Post]

Transcriptomics-Guided In Silico Drug Repurposing: Identifying New Candidates with Dual-Stage Antiplasmodial Activity

58 views | Dec 08 2023

The research effort identified two promising compounds, HSP-990 and silvestrol aglycone, demonstrating potent inhibitory activity at nanomolar concentrations against the asexual blood stage of Plasmodium falciparum, with silvestrol aglycone showing low cytotoxicity and transmission-blocking potential, indicating their potential as dual-acting antimalarial and transmission-blocking candidates for malaria control. [Read the Full Post]

Tubular Elabela-APJ axis attenuates ischemia-reperfusion induced acute kidney injury and the following AKI-CKD transition by protecting renal microcirculation

8 views | Dec 07 2023

The study demonstrates that the endogenous tubular ELA-APJ axis regulates renal microvascular blood flow, critically influencing ischemia-reperfusion-induced acute kidney injury, and targeting this pathway by inhibiting ARG2 and activating PGE2 prevents injury progression and improves outcomes. [Read the Full Post]

PFKFB3 Increases IL-1 β and TNF- α in Intestinal Epithelial Cells to Promote Tumorigenesis in Colitis-Associated Colorectal Cancer

23 views | Dec 07 2023

Elevated expression of PFKFB3 in colitis-associated colorectal cancer promotes tumorigenesis by inducing phospho-p65 and the expression of pro-inflammatory cytokines IL-1β and TNF-α, highlighting PFKFB3 as a potential therapeutic target. [Read the Full Post]

Anticancer effects of ABTL0812, a clinical stage drug inducer of autophagy-mediated cancer cell death, in glioblastoma models

67 views | Dec 07 2023

The study demonstrates that ABTL0812, an oral anticancer compound, inhibits GBM cell proliferation, reverses proneural to mesenchymal transition, induces cell differentiation, and promotes autophagy-mediated cell death, providing compelling evidence for its potential as a novel therapy, either alone or in combination with standard treatments, for glioblastoma multiforme. [Read the Full Post]