RESUMO
Acute carbon monoxide poisoning (CO-poisoning) causes neurotoxicity by inducing necrosis, apoptosis, lipid peroxidation, and oxidative stress. DL-3-n-butylphthalide (NBP) is a synthetic compound originally extracted from the seeds of Chinese celery and based on pure l-3-n-butylphthalide. In ischemia/reperfusion, it exerts neuroprotective effects through its anti-apoptotic, anti-necrotic and antioxidant properties, and activation of pro-survival pathways. Our study performed bioinformatic analysis to identify the differential expression genes. CO-poisoning patients' blood was collected to confirm the findings. Male rats were exposed to CO 3000 ppm for 40 min, and NBP (100 mg/kg/day) was continuously injected intraperitoneally immediately after poisoning and for the next 15 days. After NBP treatment, the rats were evaluated by Morris water maze test. At the end of experiments, blood and brain tissues of the rats were collected to evaluate the expression levels of IL-2, AKT and BCL-2. We found that IL-2 was elevated in CO-poisoning patients and animal models. Brain tissue damage in CO-poisoning rats was significantly alleviated after NBP treatment. Furthermore, NBP increased the expression of IL-2, AKT and BCL-2 in rat CO-poisoning model. NBP showed neuroprotective action by increasing IL-2, AKT, and BCL-2 expressions.
Assuntos
Intoxicação por Monóxido de Carbono , Masculino , Animais , Ratos , Intoxicação por Monóxido de Carbono/tratamento farmacológico , Interleucina-2 , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2/genética , NecroseRESUMO
OBJECTIVE: Papillary thyroid cancer (PTC) is one of the most serious diseases of the endocrine system. In view of the limited therapeutic effects of current medical methods, this study starts from the molecular level and looks for potential treatments. The interaction between HAGLROS/miR-206/HMGA2 was studied using multi-omics methods, which provided new ideas and methods for future treatments. METHOD: Microarray analysis and R language were used for differential analysis to screening experimental targets of lncRNA, miRNA, and mRNA. qRT-PCR was used to detect RNA expression in tissues and cells. Double luciferase reporter assays analyzed and validated binding relationships between different RNAs. Colony formation, flow cytometry, and transwell assays were used to measure the effect of them on cell proliferation, apoptosis, and migration. RESULT: Microarray analysis identified lncRNAs, miRNAs, and mRNAs differentially expressed in PTC and normal cells, and selected lncRNA HAGLROS, miR-206, and mRNA HMGA2 as study subjects. LncRNA HAGLROS and mRNA HMGA2 were highly expressed in PTC cells while miR-206 was lowly expressed in PTC cells. LncRNA HAGLROS/HMGA2 can inhibit apoptosis of PTC cells, promote proliferation and migration, and miR-206 promotes the above process. HAGLROS and HMGA2 were negatively correlated with miR-206. shHAGLROS promoted miR-206 expression, inhibited HMGA2 expression and repressed PTC tumor growth in mice. CONCLUSIONS: HAGLROS promotes the growth of PTC by competitively binding to miR-206 to promote HMGA2 expression.