Blog of Signaling Pathways

Promoting TFEB nuclear localization with curcumin analog C1 attenuates sensory hair cell injury and delays age-related hearing loss in C57BL/6 mice

14 views | Nov 25 2023

The study reveals that the curcumin analog C1 promotes nuclear localization of TFEB, restores impaired autophagy, alleviates hair cell injury, and delays age-related hearing loss, highlighting TFEB as a promising therapeutic target for AHL. [Read the Full Post]

Proxalutamide reduces SARS-CoV-2 infection and associated inflammatory response

9 views | Nov 25 2023

The study suggests that proxalutamide, an androgen receptor antagonist, has the potential to prevent SARS-CoV-2 infection, inhibit multiple variants, protect against cytokine-induced lung damage, and may yield promising clinical outcomes pending ongoing phase 3 trials. [Read the Full Post]

Phase 1 Results of Bromodomain and Extraterminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies

25 views | Nov 25 2023

In a phase I trial, the combination therapy of PLX51107 (a bromodomain and extra-terminal domain inhibitor) and azacitidine demonstrated a 22% overall response rate and significant changes in gene and protein expressions, providing modest clinical benefit in heavily pre-treated patients with relapsed/refractory high-risk myelodysplastic syndrome and acute myeloid leukemia. [Read the Full Post]

Repeated Mild Traumatic Brain Injury and JZL184 Produce Sex-Specific Increases in Anxiety-Like Behavior and Alcohol Consumption in Wistar Rats

18 views | Nov 24 2023

Repeated mild traumatic brain injury (rmTBI) increased alcohol consumption in female rats, had varying effects on anxiety-like behavior in males and females, and systemic treatment with JZL184 did not consistently mitigate these behavioral changes, revealing robust sex differences in rmTBI effects. [Read the Full Post]

Pharmacological Inhibition of PTEN Rescues Dopaminergic Neurons by Attenuating Apoptotic and Neuroinflammatory Signaling Events

20 views | Nov 24 2023

The discovery that PTEN serves as a critical early stress sensor, modulating Fyn kinase activation, mitochondrial dysfunction, and neuroinflammation, establishes it as a promising pharmacological target for the development of novel therapeutic strategies in Parkinson's disease. [Read the Full Post]

Topical non-aqueous nanoemulsion of Alpinia galanga extract for effective treatment in psoriasis: In vitro and in vivo evaluation

13 views | Nov 24 2023

A non-aqueous nanoemulsion of Alpinia galanga extract, optimized using a Box-Behnken design, exhibited a 10-fold increase in skin permeation compared to the extract alone, confirming its efficacy in ameliorating psoriasis in an IMQ-induced mouse model via trans-follicular transport mechanism. [Read the Full Post]

DOCK2 is involved in the host genetics and biology of severe COVID-19

37 views | Nov 24 2023

A genome-wide association study in a Japanese population identified a specific genetic variant (rs60200309-A) near the DOCK2 gene on chromosome 5, linked to decreased DOCK2 expression in immune cells, revealing its crucial role in the host immune response to SARS-CoV-2 infection and suggesting its potential as a biomarker and therapeutic target for severe COVID-19. [Read the Full Post]

Retinal transcriptome profiling identifies novel candidate genes associated with visual impairment in a mouse model of multiple sclerosis

11 views | Nov 24 2023

This study identifies immune-related gene expression changes in the retinas of mice with experimental autoimmune encephalomyelitis (EAE), providing molecular insights into the visual impairments observed in EAE and implicating potential targets for understanding and treating similar conditions in multiple sclerosis. [Read the Full Post]

HDAC11 mediates the ubiquitin-dependent degradation of p53 and inhibits the anti-leukemia effect of PD0166285

35 views | Nov 23 2023

The study demonstrates the potential of the WEE1 inhibitor PD0166285 as a promising chemotherapeutic drug for acute myeloid leukemia, highlighting the negative correlation between HDAC11 expression and AML patient survival, and revealing HDAC11's impact on p53 stability and MAPK pathway phosphorylation levels. [Read the Full Post]

Oridonin Synergistically Enhances the Pro-Apoptotic Effect of Venetoclax on Acute Myeloid Leukemia Cells by Inhibiting AKT Signaling

32 views | Nov 23 2023

**Synergistic inhibition of AKT signaling by oridonin enhances the apoptotic effects of venetoclax, offering a promising combination therapy to overcome resistance and improve outcomes in acute myeloid leukemia.** [Read the Full Post]

Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors

68 views | Nov 23 2023

The study developed a differentiation method using a unique combination of four differentiation-inducing factors to transform bone marrow-derived stem cells into mature insulin-producing cells, offering a potential novel approach for cell-based therapy in diabetes mellitus. [Read the Full Post]

Carnosic acid and rosemary extract reversed the lipid accumulation induced by bisphenol A in the 3T3-L1 preadipocytes and C57BL/6J mice via SIRT1/FoxO1 pathway

33 views | Nov 23 2023

Carnosic acid (CA) and rosemary extract counteracted Bisphenol A (BPA)-induced adipogenesis and lipid accumulation by downregulating adipogenic proteins, upregulating lipolytic proteins, and activating the SIRT1/FoxO1 pathway in both 3T3-L1 preadipocytes and C57BL/6 J mice. [Read the Full Post]

A nanocellulose molecularly imprinted membrane: Preparation, characterization and application in targeted separation of taxane 10-deacetylbaccatin III

6 views | Nov 23 2023

The study introduces a nanocellulose-based molecular imprinted membrane (NC-MIM) with high specificity and stability, enabling the efficient and selective separation of 10-deacetylbaccatin III (10-DAB), a crucial phytochemical in paclitaxel synthesis, offering a promising and green approach for natural medicine applications. [Read the Full Post]

Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity

44 views | Nov 22 2023

The study reveals that TTK inhibitors, particularly those inducing a shift in the glycine-rich loop by binding to the catalytic lysine at position 553, disrupt the catalytic machinery, leading to potent anti-proliferative effects, offering promising avenues for cancer treatment. [Read the Full Post]

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers

47 views | Nov 22 2023

BOS172722 is a potent spindle assembly checkpoint kinase MPS1 inhibitor that, in combination with paclitaxel, demonstrates significant synergistic effects, inducing chromosomal segregation defects and robust tumor regressions in preclinical models of triple-negative breast cancer, indicating its potential as a promising therapeutic approach for this patient population. [Read the Full Post]

Ubiquitin-specific protease 20 in human disease: Emerging role and therapeutic implications

17 views | Nov 22 2023

The discovery of USP20's diverse physiological roles, including its involvement in metabolic disorders and neurological diseases, alongside the development of specific inhibitors like GSK2643943A, highlights its potential as a valuable therapeutic target for a wide array of diseases. [Read the Full Post]

Ginkgolic acid inhibits the replication of pseudorabies virus in vitro and in vivo by suppressing the transcription of viral late genes

37 views | Nov 22 2023

Ginkgolic acid has been identified as a potent inhibitor of pseudorabies virus (PRV) replication by specifically suppressing the transcription of PRV late genes, offering a promising therapeutic avenue for combating PRV infections in the swine industry. [Read the Full Post]

FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation

28 views | Nov 22 2023

FABP4 regulates crucial processes such as cell migration, endoplasmic reticulum stress, and autophagy in sheep endometrial cells during early pregnancy, emphasizing its significance in orchestrating the establishment of pregnancy in ruminants. [Read the Full Post]

Identifying promising GSK3β inhibitors for cancer management: a computational pipeline combining virtual screening and molecular dynamics simulations

46 views | Nov 21 2023

The computational screening study identified BMS-754807 and GSK429286A as promising GSK3β inhibitors with high binding affinities, suggesting their potential as novel anticancer drugs pending experimental validation. [Read the Full Post]

Doxorubicin resistance in breast cancer is mediated via the activation of FABP5/PPARγ and CaMKII signaling pathway

17 views | Nov 21 2023

The study identifies FABP5 as a pivotal mediator of Doxorubicin resistance in breast cancer, demonstrating its potential as a targetable biomarker for therapeutic interventions aimed at overcoming chemoresistance. [Read the Full Post]