RESUMO
Colorectal cancer (CRC) is a formidable threat to human well-being, characterized by a largely enigmatic occurrence and progression mechanism. A growing body of literature has underscored the potential influence of propofol, a frequently administered anesthetic, on clinical outcomes in malignant tumor patients. However, the precise molecular mechanisms underlying the impact of propofol on the progression of CRC have yet to be fully elucidated. This study reveals a notable upregulation of LINC01133 expression in CRC cells subsequent to propofol treatment, which is mediated by FOXO1. Subsequently, a series of experiments were conducted to elucidate the role and mechanisms underlying propofol-induced LINC01133 in CRC development. Our study uncovers that the upregulation of LINC01133 exerts a substantial inhibitory effect on the proliferation, migration, and invasion of CRC cells. Further investigation revealed that LINC01133 can attenuate the proliferation, invasion, and migration of CRC cell lines through the miR-186-5p/NR3C2 axis. Results from in vivo experiments unequivocally demonstrated a significant reduction in the growth rate of subcutaneous implant tumors upon LINC01133 overexpression in CRC cells. These findings posit that propofol induces LINC01133 expression, leading to the inhibition of CRC progression. This revelation offers a novel perspective on propofol's antitumor properties and underscores the potential of LINC01133 as a promising therapeutic target for CRC.
Assuntos
Neoplasias Colorretais , MicroRNAs , Propofol , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Propofol/farmacologia , Neoplasias Colorretais/metabolismo , Regulação para Cima , Linhagem Celular , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Receptores de Mineralocorticoides/metabolismoRESUMO
Exposure to sevoflurane leads to serious neurological side effects, including neuronal apoptosis and cognitive impairment. In the mouse model, cyclin dependent kinase 9 (CDK9) was significantly downregulated after exposure to sevoflurane, but the effect of CDK9 on neuronal apoptosis and cognitive impairment after sevoflurane exposure has not been elucidated. Here, we found that the upregulation of P300 by sevoflurane in vitro and in vivo inhibited the expression of CDK9 and induced neuron apoptosis. The effect of sevoflurane on CDK9 expression is based on inhibition of its transcription process. P300 inhibited the binding of Sp1 to DNA by affecting the level of Sp1 acetylation, thereby inhibiting the expression of CDK9, cell-cycle arrest and increasing neuron apoptosis. After the use of P300 inhibitor, the acetylation level of Sp1 decreased, thereby increasing binding in the CDK9 promoter region and exerting anti-apoptosis effects. Mice exposed to sevoflurane using P300 inhibitor also showed decreased levels of apoptosis of cortical cells and a decrease in recent cognitive impairment. In summary, sevoflurane-induced P300 inhibited activity of Sp1 by increasing Sp1 acetylation modification, down-modulates CDK9 expression and promotes the occurrence of neuronal apoptosis.
Assuntos
Quinase 9 Dependente de Ciclina , Neurônios , Camundongos , Animais , Sevoflurano/farmacologia , Quinase 9 Dependente de Ciclina/metabolismo , Regulação para Cima , Neurônios/metabolismoRESUMO
An increasing number of studies have reported that lncRNAs are responsible for the development of neuropathic pain. In our current study, chronic constriction injury (CCI) rat models were established and we observed that lncRNA XIST was greatly increased. Knockdown of XIST can relieve pain characteristics including both mechanical and thermal hyperalgesia in CCI rats. Meanwhile, XIST down-regulation could inhibit neuro-inflammation by reducing expression of inflammatory cytokines including tumor necrosis factor (TNF)-α, IL-1ß, and IL-6 and in CCI rats. By performing bioinformatics technology, miR-544 was predicted to have interactions with XIST and dual-luciferase reporter assays validated the correlation between them. A negative correlation between miR-544 and XIST was observed by carrying out XIST loss or gain of function tests. miR-544 markedly alleviated neuropathic pain development in CCI rats via targeting inflammatory cytokines, which was reversed by XIST over-expression. Moreover, STAT3 was manifested to be a target gene of miR-544 by bioinformatics predictions and it was activated in CCI rats. Over-expression of STAT3 was able to induce neuropathic pain and miR-544 inhibited this process in vivo. Furthermore, XIST increased STAT3 expression by sponging miR-544 in neuropathic pain development. To conclude, our present study indicated that XIST can contribute to neuropathic pain progression in rats through down-regulating miR-544 and up-regulating STAT3. Our results suggested that XIST/miR-544/STAT3 axis can serve as a novel therapeutic target in neuropathic pain development.
Assuntos
MicroRNAs/biossíntese , Neuralgia/genética , RNA Longo não Codificante/metabolismo , Fator de Transcrição STAT3/biossíntese , Animais , Linhagem Celular , Regulação para Baixo , Feminino , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Inflamação/genética , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Modelos Animais , Neuralgia/patologia , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/biossínteseRESUMO
In order to solve the problem of CT reconstruction imaging, this paper presents a study on the clinical application of preanesthesia in patients with tracheal stenosis. Patients with tracheal stenosis and multislice spiral CT virtual endoscopy (CTVE) were diagnosed, and their application effects were analyzed. Methods. 60 patients with tracheal stenosis were selected for clinical observation. The patients were given tracheal stenosis examination and multislice spiral CT virtual endoscopy. The examination results of the two groups were compared and analyzed by statistical methods. Results. There was no significant difference in the detection rate, sensitivity, accuracy, and specificity between the two groups (P > 0.05). Conclusion. Multislice spiral CT virtual endoscopy combined with a fiberoptic bronchoscope for clinical diagnosis of tracheal stenosis can complement each other. Combined use can effectively improve the detection consistency, and is safe and reliable. It can be used as an effective means for the diagnosis of tracheal stenosis.
Assuntos
Anestesia , Estenose Traqueal , Humanos , Tomografia Computadorizada Espiral/métodos , Estenose Traqueal/diagnóstico por imagem , Estenose Traqueal/cirurgiaRESUMO
The study focused on the application value of ultrasound images processed by restoration algorithm in evaluating the effect of dexmedetomidine in preventing neurological disorder in patients undergoing sevoflurane anesthesia. 90 patients undergoing tonsillectomy anesthesia were randomly divided into normal saline group, propofol group, and dexmedetomidine group. The ultrasound images were processed by restoration algorithm, and during the postoperative recovery period, ultrasound images were used to evaluate. The results showed that the original ultrasonic image was fuzzy and contained interference noise, and that the image optimized by restoration algorithm was clear, without excess noise, and the image quality was significantly improved. In the dexmedetomidine group, the extubation time was 10.6 ± 2.3 minutes, the recovery time was 8.4 ± 2.2 minutes, the average pain score during the recovery period was 2.6 ± 0.7, and the average agitation score was 7.2 ± 2.4. Of 30 patients, there were 13 cases with vertigo and 1 case with nausea and vomiting. The vascular ultrasound imaging showed that, in the dexmedetomidine group, the peak systolic velocities (PSV) of the bilateral vertebral arteries during the recovery period were 67.7 ± 14.3 and 67.9 ± 15.2 cm/s, respectively; the end-diastolic velocities (EDV) of the bilateral vertebral arteries were 27.8 ± 6.7 and 24.69 ± 5.9 cm/s, respectively; the PSV in bilateral internal carotid artery systolic peak velocities were 67.2 ± 13.9 and 67.8 ± 12.7 cm/s, respectively; the EDV in bilateral internal carotid arteries were 27.7 ± 5.3 and 26.9 ± 4.9 cm/s, respectively; bilateral vertebral artery resistance indexes (RIs) were 0.6 ± 0.02 and 0.71 ± 0.08, respectively; the bilateral internal carotid artery RIs were 0.57 ± 0.04 and 0.58 ± 0.06, respectively, all better than the normal saline group (12.1 ± 2.5 minutes, 10.1 ± 2.3 minutes, 3.9 ± 0.6, 10.6 ± 3.7, 15 cases, 11 cases, 81.5 ± 13.6, 80.7 ± 11.6 cm/s, 29.3 ± 6.8, 28.9 ± 6.7 cm/s, 74.3 ± 10.2, 73.9 ± 12.5 cm/s, 29.1 ± 4.3, 29 ± 4.5 cm/s, 0.84 ± 0.06, 0.83 ± 0.05, 0.8 ± 0.04, and 0.81 ± 0.05) and the propofol group (11.4 ± 2.1 minutes, 9.0 ± 2.1 minutes, 3.4 ± 0.8, 8.5 ± 2.3, 12 cases, 9 cases, 72.5 ± 12.9, 73.4 ± 11.8 cm/s, 28.6 ± 5.4, 26.5 ± 5.1 cm/s, 72.1 ± 11.4, 73.5 ± 10.6 cm/s, 28.8 ± 5.6, 27.3 ± 4.7 cm/s, 0.78 ± 0.07, 0.82 ± 0.06, 0.76 ± 0.03, and 0.78 ± 0.05), and the differences were statistically significant (P < 0.05). In conclusion, ultrasound images processed by restoration algorithm have high image quality and high resolution. The dexmedetomidine can prevent neurological disorder in patients with sevoflurane anesthesia and is suggested in postoperative rehabilitation.