Blog of Signaling Pathways

C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway

35 views | Dec 30 2023

High levels of C5a accelerate vascular smooth muscle cell calcification via C5aR1, activating the PERK-eIF2α-ATF4-CREB3L1 pathway, highlighting C5 or C5aR1 as potential therapeutic targets for vascular calcification. [Read the Full Post]

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

0 views | Dec 30 2023

Research into selective CDK9 inhibitors and PROTAC degraders shows promise in targeting specific tumor genotypes, with VIP152 demonstrating efficacy in advanced high-grade lymphoma and solid tumors, highlighting the potential for precision cancer therapy. [Read the Full Post]

A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides

26 views | Dec 30 2023

This study developed gallium-labeled radiopeptides, notably [67Ga]Ga-HBED-CC-DX600, showing selective ACE2 targeting and promising tissue distribution, offering a potential noninvasive imaging tool to assess (patho)physiological ACE2 expression levels post-SARS-CoV-2 infection. [Read the Full Post]

CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis

58 views | Dec 30 2023

The study's findings suggest that CCT251545 in combination with chemotherapy demonstrates a potent synergistic effect by enhancing drug uptake through Rac1-dependent macropinocytosis and elevating NAD levels, providing a promising avenue for managing multidrug-resistant cancers. [Read the Full Post]

Prenatal Nicotine Exposure Raises Male Blood Pressure via FTO-Mediated NOX2/ROS Signaling

30 views | Dec 30 2023

Nicotine exposure during pregnancy appears to increase the risk of hypertension in male offspring by influencing the epigenetic regulation of vascular NOX2 via the m6A demethylase FTO, revealing a potential target for preventing developmental hypertension programming. [Read the Full Post]

Identification of upregulated genes in glioblastoma and glioblastoma cancer stem cells using bioinformatics analysis

76 views | Dec 29 2023

This comprehensive study uncovered potential therapeutic targets for glioblastoma by identifying highly coexpressed genes in cancer stem cells, highlighting DUSP6 and SOX2 as prognostically relevant hub genes and proposing (E/Z)-BCI and BCI compounds as promising anti-cancer agents via strong binding interactions with DUSP6's ERK2 binding domain. [Read the Full Post]

Treating Autoimmune Diseases With LANCL2 Therapeutics: A Novel Immunoregulatory Mechanism for Patients With Ulcerative Colitis and Crohn's Disease

18 views | Dec 29 2023

Activation of LANCL2 through therapeutics like Omilancor shows promise in addressing autoimmune diseases by enhancing regulatory T cell responses and suppressing inflammatory reactions in the gut, presenting a potential breakthrough in treating conditions like ulcerative colitis and Crohn's disease. [Read the Full Post]

Translating in vitro CFTR rescue into small molecule correctors for cystic fibrosis using the Library of Integrated Network-based Cellular Signatures drug discovery platform

40 views | Dec 29 2023

Research employing transcriptomic signatures from CF expression data and LINCS in silico screening identified XL147, among other compounds, as a promising candidate for partially restoring ΔF508-CFTR function, showing efficacy in primary CF airway epithelia and demonstrating potential for improved CF corrector therapies. [Read the Full Post]

Effects of combined exposure to ethanol and delta-9-tetrahydrocannabinol during adolescence on synaptic plasticity in the prefrontal cortex of Long Evans rats

53 views | Dec 29 2023

Exposure to ethanol, THC, or their combination during adolescence in rats resulted in reduced body weight gain, altered substance intake, and disrupted long-term depression in the medial prefrontal cortex, potentially implicating lasting changes in GABA and GSK3β signaling pathways. [Read the Full Post]

Increased palmitoylation improves estrogen receptor alpha-dependent hippocampal synaptic deficits in a mouse model of synucleinopathy

31 views | Dec 29 2023

The study highlights how the modulation of estrogen receptor alpha (ERα) through palmitoylation plays a pivotal role in mitigating synaptic abnormalities and α-synuclein pathology, offering potential therapeutic insights for Parkinson's disease. [Read the Full Post]

A Degron Blocking Strategy Towards Improved CRL4CRBN Recruiting PROTAC Selectivity

30 views | Dec 28 2023

Your work addressing selectivity challenges in PROTAC design by leveraging structural insights and computational modeling offers valuable principles and tools crucial for advancing targeted protein degradation strategies. [Read the Full Post]

Blockade of CCR1 induces a phenotypic shift in macrophages and triggers a favorable antilymphoma activity

33 views | Dec 28 2023

Inhibiting CCR1 in B-cell lymphoma's microenvironment reprograms protumor macrophages, diminishes immunosuppression, and presents a promising therapeutic avenue for reshaping the tumor milieu and improving patient outcomes. [Read the Full Post]

Role of parthenolide in paclitaxel-induced oxidative stress injury and impaired reproductive function in rat testicular tissue

111 views | Dec 28 2023

Parthenolide treatment in rats demonstrated a dose-dependent mitigation of oxidative stress-induced testicular damage caused by paclitaxel, showing promise as a potential therapeutic avenue for addressing testicular toxicity and supporting reproductive function. [Read the Full Post]

Identification of a cancer-associated fibroblast classifier for predicting prognosis and therapeutic response in lung squamous cell carcinoma

29 views | Dec 28 2023

This comprehensive study unveils a robust molecular classifier for high-risk cancer-associated fibroblasts (CAFs)-related lung squamous cell carcinoma (LUSC) patients, suggesting potential therapeutic targets within the PI3K-Akt signaling pathway and identifying promising compounds for more effective personalized treatments. [Read the Full Post]

LncRNA HOTAIR Enhances Epithelial-to-mesenchymal Transition to Promote the Migration and Invasion of Liver Cancer by Regulating NUAK1 via Epigenetic Inhibition miR-145-5p Expression

16 views | Dec 28 2023

The HOTAIR/miR-145-5p/NUAK1 axis, identified through its intricate epigenetic regulation and influence on the EMT process in liver cancer cells, holds promise as both a prognostic biomarker and a potential therapeutic target. [Read the Full Post]

Adaptive c-Met-PLXDC2 Signaling Axis Mediates Cancer Stem Cell Plasticity to Confer Radioresistance-associated Aggressiveness in Head and Neck Cancer

60 views | Dec 27 2023

The identification of c-Met phosphorylation as a pivotal mechanism driving radioresistance-associated aggressiveness in HNSCC cells offers a promising therapeutic strategy by targeting this pathway with inhibitors like SU11274 to enhance the efficacy of radiotherapy. [Read the Full Post]

Vascular smooth muscle cell mechanotransduction through serum and glucocorticoid inducible kinase-1 promotes interleukin-6 production and macrophage accumulation in murine hypertension

35 views | Dec 27 2023

The investigation demonstrated that mechanical activation of serum and glucocorticoid-inducible kinase-1 (SGK-1) in aortic vascular smooth muscle cells (VSMCs), both in vivo in hypertensive mice and in vitro through cyclic stretch, promotes inflammatory signaling and macrophage accumulation, suggesting SGK-1 as a potential pharmacotherapeutic target for hypertensive vascular pathology. [Read the Full Post]

Dysregulation of the Progranulin-driven Autophagy-lysosomal Pathway Mediates Secretion of the Nuclear Protein TDP-43

42 views | Dec 27 2023

Dysregulation of the progranulin-driven autophagy-lysosomal pathway promotes the secretion of TDP-43, potentially fueling its cell-to-cell spread in neurodegenerative diseases like amyotrophic lateral sclerosis and frontotemporal lobar degeneration. [Read the Full Post]

Research update and opportunity of non-hormonal male contraception: Histone demethylase KDM5B-based targeting

16 views | Dec 27 2023

In exploring non-hormonal male contraceptives, leveraging in-silico studies of tissue-specific targets and small-molecule candidates presents a promising avenue, albeit with hurdles, toward potentially transformative developments in contraceptive options. [Read the Full Post]

PM2.5 induces cardiac malformations via PI3K/akt2/mTORC1 signaling pathway in zebrafish larvae

85 views | Dec 27 2023

Exposure to PM2.5 triggers a complex cascade involving PI3K/akt2/mTORC1 signaling through AHR/ROS-induced PTEN suppression, leading to mitochondrial-mediated intrinsic apoptosis, Wnt signaling suppression, and ultimately contributing to cardiac defects in zebrafish larvae. [Read the Full Post]