RESUMO
Hippocampus is a critical component of the central nervous system. SRSF10 is expressed in central nervous system and plays important roles in maintaining normal brain functions. However, its role in hippocampus development is unknown. In this study, using SRSF10 conditional knock-out mice in neural progenitor cells (NPCs), we found that dysfunction of SRSF10 leads to developmental defects in the dentate gyrus of hippocampus, which manifests as the reduced length and wider suprapyramidal blade and infrapyramidal blade.Furthermore, we proved that loss of SRSF10 in NPCs caused inhibition of the differentiation activity and the abnormal migration of NPCs and granule cells, resulting in reduced granule cells and more ectopic granule cells dispersed in the molecular layer and hilus. Finally, we found that the abnormal migration may be caused by the radial glia scaffold and the reduced DISC1 expression in NPCs. Together, our results indicate that SRSF10 is required for the cell migration and formation of dentate gyrus during the development of hippocampus.
Assuntos
Movimento Celular , Giro Denteado , Camundongos Knockout , Células-Tronco Neurais , Fatores de Processamento de Serina-Arginina , Animais , Células-Tronco Neurais/metabolismo , Giro Denteado/metabolismo , Movimento Celular/fisiologia , Fatores de Processamento de Serina-Arginina/metabolismo , Fatores de Processamento de Serina-Arginina/genética , Neurônios/metabolismo , Hipocampo/metabolismo , Camundongos , Neurogênese/fisiologia , Diferenciação Celular/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: This research was designed to elucidate the anti-inflammatory impacts of liquiritin on lipopolysaccharide (LPS)-activated human corneal epithelial cells (HCECs). METHODS: The Cell Counting kit-8 (CCK-8) assay was adopted to assess cell viability. The enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α. Transcriptome analysis was conducted to identify the genes that exhibited differential expression between different treatment. The model group included cells treated with LPS (10 µg/mL), the treatment group comprised cells treated with liquiritin (80 µM) and LPS (10 µg/mL), and the control group consisted of untreated cells. To further validate the expression levels of the selected genes, including CSF2, CXCL1, CXCL2, CXCL8, IL1A, IL1B, IL24, IL6, and LTB, quantitative real-time PCR was performed. The expression of proteins related to the Akt/NF-κB signaling pathway was assessed through western blot analysis. NF-κB nuclear translocation was evaluated through immunofluorescence staining. RESULTS: The secretion of IL-6, IL-8, and TNF-α in LPS-induced HCECs was significantly downregulated by liquiritin. Based on the transcriptome analysis, the mRNA expression of pro-inflammatory cytokines, namely IL-6, IL-8, IL-1ß, IL-24, TNF-α, and IL-1α was overproduced by LPS stimulation, and suppressed after liquiritin treatment. Furthermore, the Western blot results revealed a remarkable reduction in the phosphorylation degrees of NF-κB p65, IκB, and Akt upon treatment with liquiritin. Additionally, immunofluorescence analysis confirmed liquiritin's inhibition of LPS-induced p65 nuclear translocation. CONCLUSIONS: Collectively, these findings imply that liquiritin suppresses the expression of proinflammatory cytokines, and the anti-inflammatory impacts of liquiritin may be caused by its repression of the Akt/NF-κB signaling pathway in LPS-induced HCECs. These data indicate that liquiritin could provide a potential therapeutic application for inflammation-associated corneal diseases.
Assuntos
Sobrevivência Celular , Citocinas , Ensaio de Imunoadsorção Enzimática , Epitélio Corneano , Flavanonas , Glucosídeos , Lipopolissacarídeos , Humanos , Lipopolissacarídeos/toxicidade , Flavanonas/farmacologia , Epitélio Corneano/metabolismo , Epitélio Corneano/efeitos dos fármacos , Epitélio Corneano/patologia , Glucosídeos/farmacologia , Citocinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Reação em Cadeia da Polimerase em Tempo Real , Western Blotting , Transdução de Sinais , Inflamação/metabolismo , NF-kappa B/metabolismo , Regulação da Expressão GênicaRESUMO
Both thermoelectric and mechanical properties are important to the practical applications of thermoelectric materials. Herein, we develop a strategy for alloying KCu7S4 to improve the dimensionless figure of merit (zT), compressive strength, and Vickers hardness of polycrystalline SnSe. Through chemical synthesis and particle mixing in solutions, powders with SnSe nanoparticles and KCu7S4 nanowires are produced, and the subsequent spark plasma sintering triggers the reaction between the two chalcogenides, resulting in the formation of Cu2SnSe3 nanoparticles and substitution of Cu and S in the SnSe matrix. The composition tuning and secondary phase formation effectively enhance the power factor and diminish the lattice thermal conductivity, leading to a maximum zT of 1.13 at 823 K for the optimal sample, which is improved by 135% over that of SnSe. Simultaneously, the compressive strength and hardness are also enhanced, as exemplified by a high compressive strength of 135 MPa that is enhanced by â¼81% compared to that of SnSe. The current study demonstrates effective composite and composition design toward enhanced thermoelectric and mechanical performance in polycrystalline SnSe.