Background: Sevoflurane inhalation initiated cognitive deficits implicated in mitochondrial dysfunction, synaptogenesis impairment and neuroinflammation. Egr2 plays a crucial role in maintaining cognitive function. Therefore, we attempted to clarify the potential correlation regarding Egr2 expression and cognitive deficits induced by sevoflurane administration. Methods: Animals received sevoflurane anesthesia, and the behavioral tests including Morris water maze, novel object recognition test and trace fear conditioning were performed. Then, the Golgi-Cox staining and Nissl staining were employed to detect the effect of sevoflurane inhalation in hippocampal neurons. Meanwhile, bioinformatics analysis was implemented, and western blot (WB) and bisulfite sequencing PCR (BSP) technique were utilized to validate this hypothesis. Moreover, the level of lipid peroxidation, mitochondrial membrane potential, morphology and membrane permeability, and cytoplasm calcium levels were investigated after Egr2 interference by using JC-1 probe, MitoTracker staining, Mitochondrial permeability transition pore (mPTP) assay, and Fluo calcium indicators, respectively. Additionally, Prussian blue staining was used to evaluate the iron content.Results: The behavioral tests indicated that the cognitive function was significantly attenuated after sevoflurane administration. The Golgi-Cox staining displayed that the dendritic length, density and nodes were significantly reduced, and the typical neuropathological changes including neuron loss, nucleus shrinkaged and disappearance of Nissl bodies were observed by Nissl staining. Moreover, bioinformatics analysis showed that the Egr2 expression was significantly upregulated, and WB and BSP confirmed this result. Additionally, the results suggested that sevoflurane administration elevated the cytoplasm calcium levels, reduced the mitochondrial membrane potential and triggered the opening of mPTP. Prussian blue staining showed that the iron deposition was apparently increased. However, Egr2 level downregulation partly reversed these above changes.Conclusion: These findings demonstrated that sevoflurane administration elicited mitochondrial dysfunction and iron dyshomeostasis, and eventually resulted in cognitive impairments, whereas suppressing Egr2 expression partly improved this pathological process.

1.1 Aim: Fibrosarcoma is a rare malignant tumor of subcutaneous tissue characterized by slow infiltrative growth and a high rate of local recurrence. The participation of microRNAs (miRNAs/miRs) in the pathogenesis of human diseases and the vital role of miR-145 in different types of cancer. However, the role of miR-145 in fibrosarcoma remains unclear. The present study aimed to investigate the effect of miR-145 in the progression of fibrosarcoma and its potential application as a new therapeutic target. 1.2. Methods: The present study screened out a differential gene named high mobility group protein A2 (HMGA2) via bioinformatics analysis. In the present study, the gene expression profiles of fibrosarcoma cells and normal cells were downloaded from GEO Datasets GSE10021 and GSE1774. The human fibrosarcoma cell line HT1080 were transfected with miR-145 mimics, mimic negative control (NC), pCMV6 vector, overexpression plasmid vector of HMGA2, (si)RNA-HMGA2 or siRNA-NC. Reverse transcription-quantitative PCR and western blot analysis were performed to examine the mRNA (miR-145) and protein (HMGA2, N-cadherin, Vimentin and E-cadherin) expression levels in HT1080 cells. Cell Counting Kit-8, wound healing and Transwell assays were used to examine the TH1080 cell viability, proliferation and migratory capacities, respectively. Bioinformatics prediction and luciferase reporter assay were performed to investigate the relationship between miR145 and its potential target gene (HMGA2). 1.3. Results: The results demonstrated that overexpression of HMGA2 promoted cell proliferation, migration and invasion of HT1080 fibrosarcoma cells, whereas HMGA2 knockdown had no effect on the proliferation of HT1080 fibrosarcoma cells. However, overexpression of miR-145 reversed the facilitating effects of HMGA2 in tumor progression via epithelial-to-mesenchymal transition (EMT) modulation. Mechanistically, miR-145 exerted its inhibitory role in fibrosarcoma by directly binding to the 3’-untranslated region of HMGA2. 1.4. Conclusion: miR-145 plays an inhibitory role in fibrosarcoma progression by directly suppressing HGMA2 expression and EMT progression. Thus, miR-145 may act as a potential therapeutic target for malignant fibrosarcoma therapy