Blog of Signaling Pathways

Apolipoprotein E polymorphism impacts white matter injury through microglial phagocytosis after experimental subarachnoid hemorrhage

46 views | Sep 14 2023

The study found that the APOE4 allele significantly worsened white matter injury and impaired microglial phagocytosis after subarachnoid hemorrhage, suggesting that targeting oxidative stress and promoting phagocytosis could be potential therapeutic strategies for managing this condition. [Read the Full Post]

Effects of mitoquinone (MitoQ) supplementation during boar semen cryopreservation on sperm quality, antioxidant status and mitochondrial proteomics

119 views | Sep 14 2023

Supplementation of boar semen extender with 10 μM MitoQ during cryopreservation improves sperm quality by enhancing antioxidant capacity and regulating mitochondrial proteins associated with motility and energy metabolism. [Read the Full Post]

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

37 views | Sep 14 2023

This review discusses the development of selective CDK9 inhibitors and PROTAC degraders for the treatment of cancer, highlighting their structures, inhibitory effects, and the need for further research to explore their efficacy in specific tumor genotypes and combination regimens. [Read the Full Post]

Diverse Mechanisms of Resistance against Osimertinib, a Third-Generation EGFR-TKI, in Lung Adenocarcinoma Cells with an EGFR-Activating Mutation

47 views | Sep 14 2023

The study identified multiple mechanisms of osimertinib resistance in EGFR-mutant NSCLC cells, including wild-type EGFR amplification, KRAS amplification and mutation, dependence on EGFR and IGF1R signaling, Bid cleavage for apoptosis induction, and a SHP2/T507K mutation activating the ERK1/2 pathway, suggesting potential therapeutic strategies for overcoming resistance. [Read the Full Post]

Unique osteogenic profile of bone marrow stem cells stimulated in perfusion bioreactor is Rho-ROCK-mediated contractility dependent

29 views | Sep 14 2023

This study demonstrates that fluid shear stress in a 3D dynamic culture system induces increased actomyosin contractility, upregulation of mechanoreceptors and focal adhesions, and promotes a unique osteogenic profile in bone marrow mesenchymal stem/stromal cells (BMSC), highlighting the importance of mechanical cues in regulating BMSC behavior for potential clinical applications in bone regeneration. [Read the Full Post]

Anti-Klebsiella pneumoniae activity of secondary metabolism of Achromobacter from the intestine of Periplaneta americana

77 views | Sep 13 2023

This study identifies a strain of Achromobacter from the intestinal tract of Periplaneta americana that exhibits strong antibacterial activity against Klebsiella pneumoniae, highlighting the potential for the development of novel antimicrobial compounds from insect intestinal microorganisms. [Read the Full Post]

Hepatocytic AP-1 and STAT3 contribute to chemotaxis in alphanaphthylisothiocyanate-induced cholestatic liver injury

80 views | Sep 13 2023

The study demonstrated that the AP-1 signaling pathway is more crucial than STAT3 in mediating the inflammatory cascade of ANIT-induced CLI, and hepatocytes, rather than Kupffer cells, release chemotactic factors involved in chemotaxis during CLI. [Read the Full Post]

Estimation of Intangible Costs for Factors Associated with Oral Antiviral Drugs for COVID-19 Treatment: A Conjoint Analysis in Japan

24 views | Sep 13 2023

This study conducted a conjoint analysis to estimate the intangible costs associated with factors of oral antiviral drugs for COVID-19 in Japan, revealing preferences such as a higher intangible cost for drugs developed by foreign companies and a lower cost for smaller sizes and tablets compared to larger sizes and capsules, respectively. [Read the Full Post]

Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage

38 views | Sep 13 2023

Increased NOX2 expression in astrocytes after subarachnoid hemorrhage leads to eNOS uncoupling, exacerbating acute vasoconstriction and cerebral ischemia. [Read the Full Post]

The role of E3 ubiquitin ligase in multiple myeloma: potential for cereblon E3 ligase modulators in the treatment of relapsed/refractory disease

40 views | Sep 13 2023

The emerging field of targeted protein degradation, particularly through the redirection of the ubiquitin-proteasome system, offers promising prospects for novel therapeutic approaches in multiple myeloma and other diseases. [Read the Full Post]

Design of SERENA-6, a phase III switching trial of camizestrant in ESR1-mutant breast cancer during first-line treatment

66 views | Sep 12 2023

The SERENA-6 study is a phase III trial evaluating the efficacy and safety of switching from an aromatase inhibitor to camizestrant, while maintaining the same CDK4/6 inhibitor treatment, in HR+/HER2- advanced breast cancer patients with ESR1 mutations, with the primary endpoint being progression-free survival. [Read the Full Post]

Detection of Ras nanoclustering-dependent homo-FRET using fluorescence anisotropy measurements

67 views | Sep 12 2023

Fluorescence anisotropy-based homo-FRET measurements using Ras-derived constructs labeled with a single fluorescent protein provide a sensitive and advantageous approach to investigate Ras nanoclustering and assess modulators of functional Ras membrane organization. [Read the Full Post]

PPARδ inhibition blocks the induction and function of tumor-induced IL-10+ regulatory B cells and enhances cancer immunotherapy

31 views | Sep 12 2023

This study demonstrates that PPARδ is crucial for the development and function of IL-10+ Bregs, and targeting PPARδ shows promise in improving antitumor immunotherapy outcomes. [Read the Full Post]

Effects of Apocynin, a NADPH Oxidase Inhibitor, in the Protection of the Heart from Ischemia/Reperfusion Injury

25 views | Sep 12 2023

The study found that infusion of apocynin before ischemia or at reperfusion protected the heart by improving cardiac hemodynamics, reducing infarct size, decreasing pro-inflammatory cytokine levels, increasing anti-inflammatory cytokine and antioxidant levels, and involving CD38, nitric oxide, and acidic stores. [Read the Full Post]

Ursolic acid-downregulated long noncoding RNA ASMTL-AS1 inhibits renal cell carcinoma growth via binding to HuR and reducing vascular endothelial growth factor expression

45 views | Sep 12 2023

The study found that ursolic acid (UA) inhibits renal cell carcinoma (RCC) growth and tumorigenesis by downregulating ASMTL-AS1, which destabilizes VEGF mRNA and suppresses RCC cell migration, invasion, and angiogenesis. [Read the Full Post]

Granulocyte-macrophage colony-stimulating factor suppresses induction of type I interferon in infants with severe pneumonia

89 views | Sep 11 2023

The study suggests that the inhibition of type I interferon production in dendritic cells through the GM-CSF-dependent non-canonical NF-κB pathway is a crucial mechanism contributing to the development of severe infantile bronchopneumonia. [Read the Full Post]

Norepinephrine as the Intrinsic Contributor to Contact Lens-Induced Pseudomonas aeruginosa Keratitis

75 views | Sep 11 2023

This study reveals that norepinephrine, acting through the β2-adrenergic receptor, promotes Pseudomonas aeruginosa keratitis during contact lens wear, suggesting potential therapeutic targets for treating the condition. [Read the Full Post]

Development of a High-Throughput Urosepsis Mouse Model

76 views | Sep 11 2023

This study developed a reproducible murine model of slow-paced, monomicrobial urosepsis originating from the urinary tract, allowing for the investigation of prolonged urosepsis and providing insights into associated biomarkers and immune responses. [Read the Full Post]

Inhibition-of-BUB1-Kinase-by-BAY-1816032-Sensitizes-Tumor-Cells-toward-Taxanes-ATR-and-PARP-Inhibitors-In-Vitro-and-In-Vivo

59 views | Sep 11 2023

The study revealed that overexpression of BUB1 in osteosarcoma is associated with poor clinical outcomes and that inhibiting BUB1 significantly suppresses tumor growth and metastasis while inducing apoptosis, highlighting its potential as a therapeutic target. [Read the Full Post]

Evaluation of mitochondrial oxidative toxicity in mammalian cardiomyocytes by determining the highly reproducible and reliable increase in mitochondrial superoxides after exposure to therapeutic drugs

0 views | Sep 11 2023

The study demonstrated that increased MitoSOX™ red fluorescence following drug exposure is a reliable biomarker for evaluating mitochondrial-specific oxidative toxicity in cardiomyocytes, offering potential applications in new drug development. [Read the Full Post]