Background Prostate cancer (PCa), a prevalent malignancy worldwide, is frequently identified in advanced stages due to the absence of distinctive early symptoms, thereby culminating in the development of chemotherapy-induced drug resistance. Exploring novel resistance mechanisms and identifying new therapeutic agents can facilitate the advancement of more efficacious strategies for PCa treatment. Methods Bioinformatics analysis was employed to investigate the expression of FOXG1 in PCa tissues. Subsequently, qRT-PCR was utilized to validate FOXG1 mRNA expression levels in corresponding PCa cell lines. FOXG1 knockdown was performed, and cell proliferation was assessed using CCK-8 assays, while cell migration and invasion capabilities were evaluated through wound healing and Transwell assays. Western blot and Seahorse analyzer were used to measure oxidative phosphorylation (OXPHOS) levels. Additionally, to explore potential approaches to alleviate PCa drug resistance, this study assessed the impact of biologically active saikosaponin-d (SSd) on PCa malignant progression and resistance by regulating FOXG1 expression. Results FOXG1 exhibited high expression in PCa tissues and cell lines. Knockdown of FOXG1 inhibited the proliferation, migration, and invasion of PCa cells, while FOXG1 overexpression had the opposite effect and promoted OXPHOS levels. The addition of an OXPHOS inhibitor prevented this outcome. Finally, SSd was shown to suppress FOXG1 expression and reverse docetaxel resistance in PCa cells through the OXPHOS pathway. Conclusion This work demonstrated that SSd mediated FOXG1 to reverse malignant progression and docetaxel resistance in PCa through OXPHOS.
Background Cyanidin (CY) is one of the most abundant anthocyanidins found in red-purple diet sources such as grapes, blueberries and purple corns . CY has been proven to exhibit a wide range of biological functions including antioxidant, antiviral, anticarcinogenic and anti-inflammatory properties. Purpose This study investigated the anti-depressive activity of CY and its related mechanism. Methods In the behavioral tests, CY-related effects on depressive symptoms were evaluated. Then the changes in PI3K/AKT/FOXG1/FGF-2 signaling and adult neurogenesis including doublecortin (DCX+) cell number, dendritic length, secondary and third dendrites number in the hippocampus were investigated by Immunofluorescence and Western blot analyses. PI3K antagonist LY 294,002 was used to verify the unique impact of PI3K/AKT/FoxG1/FGF-2 signaling on CY-related antidepressant efficacy. Results CY grossly reversed CUMS-induced behavioral defects, The DCX+ cell number and protein levels increased in CUMS mice receiving CY administration. LY 294,002 successfully blocked CY-induced improvements in depressive behaviors, neurogenesis, and protein levels in CUMS mice. Conclusion The findings demonstrated that CY was efficacious in alleviating depression-like symptoms, which was dependent on PI3K/AKT/FoxG1/FGF-2 signaling-modulated neurogenesis enhancement.
Striatal dysfunction is a feature of autism spectrum disorder (ASD); however, the molecular mechanisms underlying its development remain unclear. Mutations in the transcription factor FOXG1 lead to FOXG1 syndrome, which shares core clinical features with ASD. In the present study, we conditionally deleted Foxg1 in the striatal direct pathway spiny projection neurons (dSPNs) to create Foxg1 conditional knockout (cKO) mice, which we found recapitulated classic ASD-like symptoms, including social deficits, communication impairments, and restricted repetitive behaviors. Loss of FOXG1 further resulted in simplified dendritic arborization and reduced dendritic spine density. We found that FOXG1 drives a set of ASD risk genes, including synaptic receptors and scaffolding proteins, to coordinate the development and function of dSPNs. Further, FOXG1 directly regulated the transcription of GABA B receptor subunit 2 to control the activity of dSPNs. Pharmacological enhancement of the GABA B receptor activity effectively restored the excitation/inhibition balance and ameliorated behavioral abnormalities in Foxg1 cKO mice. Our findings reveal a novel role for FOXG1 in dSPNs, provide new insights into the pathogenesis of ASD and FOXG1 syndrome, and indicate that targeting GABA B receptor activation may serve as a potential therapeutic strategy for ASD.
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