Bowleswilliam0995

The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype. In recent years, autophagy has become a research hotspot in the field of pancreatic adenocarcinoma (PAAD) due to its ambiguous roles in pancreatic tumor progression. Hence, it is necessary to assess its clinical significance in a larger cohort of patients with PAAD. Here, we identified autophagy-related genes with prognostic value in PAAD and constructed a risk model based on these genes. We found that patients in high-risk group were significantly associated with poor prognosis. Genome mutation analysis suggested that KRAS and TP53 mutations were significantly higher in high-risk groups. In addition, functional enrichment analysis showed that high-risk groups were associated with immune cell infiltration and tumor-associated signaling pathways. We further performed CIBERSORT analysis and observed increased macrophage infiltration in high-risk group, but decreased B and T cell counts compared to that in low-risk group. Gene set enrichment analysis indicated that the Hippo pathway was enriched in the high-risk group. Further, using weighted gene co-expression network analysis, Yes-associated protein 1 (YAP1) was identified as a critical hub gene. Interestingly, we found that the autophagy status and YAP1 expression status could influence each other, thus creating a positive feedback loop. In conclusion, in this study, we highlighted the clinical significance of autophagy in pancreatic cancer, constructed an autophagy-related prognostic predictive system, and identified a promising target for autophagy regulation in pancreatic cancer. Cisplatin (CP) is a chemotherapeutic drug used to treat cancerous solid tumors, but it causes serious side effects, including ototoxicity. The major cause of CP-induced ototoxicity is increased levels of mitochondrial reactive oxygen species (ROS). In this study, we examined the effect of 2-Isopropyl-3H-naphtho(1,2-d)imidazole-4,5-dione (KL1333), a β-lapachone derivative, on CP-induced ototoxicity using ex vivo organotypic culture system of cochlea. Hair cell damages in CP-treated cochlear explants with or without KL1333 were compared by immunohistochemistry. CP-induced oxidative stress and the preventive effect of KL1333 were analyzed by measuring intracellular ROS levels and depolarization of mitochondrial membrane potential. Activation of apoptosis signaling pathway was detected using TUNEL assay and immunostaining of cleaved caspase-3. As the results, it was found that KL1333 pretreatment significantly decreased stereocilia degeneration and hair cell loss, and prevented an increase in mitochondrial ROS levels in response to CP. Immunohistochemical examinations of cochlear explants revealed greater caspase-3 immunopositivity in the CP group than in controls, while the KL1333 + CP group showed significantly less immunopositivity than the CP group (P less then 0.05). Thus, it appeared that KL1333 protected hair cells in the organ of Corti from CP-induced apoptosis by decreasing mitochondrial damages due to the production of mitochondrial ROS. This study is the first report showed the preventive effect of KL1333 against CP-induced ototoxicity. Although further studies should be performed to determine if KL1333 could maintain anticancer effect of CP, our data cautiously suggests that the antioxidant KL1333 can be used as an effective anti-apoptotic agent to prevent ototoxicity caused by CP-induced oxidative stress, and may prove useful in preventing hearing loss caused by CP. Many different types of pathologies can arise in the central nervous system (CNS), such as neurodegeneration. The incidence of neurodegenerative diseases continues to increase, yet the pathogenesis underlying most neurodegenerative diseases, notably in amyotrophic lateral sclerosis (ALS), remains elusive. Neuronal support cells, or glia, are known to play a crucial role in ALS. Microglia are the resident immune cells of the CNS and also have neurotrophic support functions. These cells have a disease-modifying function in ALS, yet this role is not well understood. FINO2 A likely reason for this is that the intact CNS is particularly challenging to access for investigation in patients and in most animal models, which has impeded research in this field. The zebrafish is emerging as a robust model system to investigate cells in vivo, and offer distinct advantages over other vertebrate models for investigating neurodegenerative diseases. Live imaging in vivo is a powerful technique to characterize the role of dynamic cells such as microglia during neurodegeneration, and zebrafish provide a convenient means for live imaging. Here, we discuss the zebrafish as a model for live imaging, provide a brief overview of available high resolution imaging platforms that accommodate zebrafish, and describe our own in vivo studies on the role of microglia during motor neuron degeneration. Live in vivo imaging is anticipated to provide invaluable advancements to defining the pathogenesis underlying neurodegenerative diseases, which may in turn allow for more specifically targeted therapeutics. BACKGROUND The planning behaviors of children with autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) during writing remain overlooked. Targeted examination of planning behaviors may help to better understand their heterogeneous writing skills. AIMS This study examined overt planning behaviors of three groups of school-age children (ASD, ADHD, and typically developing [TD]) during the planning stage of a standardized narrative writing assessment. Aims explored group differences in time spent planning, between- and within-group differences in overt planning behaviors, and relationships between planning behaviors and writing performance as well as age, cognitive skills, and diagnostic symptom severity. METHODS AND PROCEDURES This study included 121 9-17-year-old children (60 ASD, 32 ADHD, and 29 TD). Video recordings captured overt planning behaviors during a two-minute prewriting planning stage. OUTCOMES AND RESULTS Not all participants planned, but group membership overwhelmingly did not influence planning likelihood.