RESUMEN
Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of any systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genomic instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared the effects of 5-azacytidine (AC), 2'-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair. The most effective inhibitor of TGS was DAC, followed by DZNep, zebularine and AC. We confirmed that all inhibitors induce DNA damage and suggest that this damage is repaired by multiple pathways with a critical role of homologous recombination and of the SMC5/6 complex. A strong positive link between the degree of cytidine analog-induced DNA demethylation and the amount of DNA damage suggests that DNA damage is an integral part of cytidine analog-induced DNA demethylation. This helps us to understand the function of DNA methylation in plants and opens the possibility of using epigenetic inhibitors in biotechnology.
Asunto(s)
Daño del ADN , Epigénesis Genética , Silenciador del Gen , Adenosina/análogos & derivados , Adenosina/farmacología , Arabidopsis/genética , Azacitidina/farmacología , Aberraciones Cromosómicas/efectos de los fármacos , Citidina/análogos & derivados , Citidina/farmacología , Daño del ADN/efectos de los fármacos , Metilación de ADN/efectos de los fármacos , Reparación del ADN/efectos de los fármacos , Decitabina/farmacología , Epigénesis Genética/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Heterocromatina/efectos de los fármacos , Interferencia de ARN/efectos de los fármacos , Secuencias Repetidas en Tándem/efectos de los fármacosRESUMEN
Barotrauma is a commonly reported complication in critically ill patients with ARDS caused by different etiologies, it's rate is reported to be around %10. Pneumothorax/pneumomediastinum in COVID-19 patients seem to be more common and have different clinical characteristics. Here we report 9 patients who had pneumothorax and/or pneumomediastinum during their stay in the ICU. Patients who were admitted to ICU between March 2020 and December 2020, were reviewed for presence of pneumothorax, pneumomediastinum and subcutaneous emphysema during their ICU stay. Demographic characteristics, mechanical ventilation settings, documented ventilation parameters, outcomes were studied. A total of 161 patients were admitted to ICU during the study period, 96 were invasively ventilated. Nine patients had developed pneumothorax, pneumomediastinum and/or subcutaneous emphysema during their admission. Five of them were men and median age was 66.6 years. All patients were intubated and mechanically ventilated. All patients were managed conservatively. One patient was discharged from ICU, the others were lost due to other complications related to COVID-19. Upon detection of pneumothorax and/or mediastinum all patients were managed conservatively by limiting their PEEP and maximum inspiratory pressures and were followed by daily chest X-rays (CXR) for detection of any progress. None of the patients showed increase in size of their pneumothorax and/or pneumomediastinum. Hemodynamically instability due to pneumothorax and/or pneumomediastinum was not observed in any of the patients. Tension pneumothorax was not observed in any of the patients. Most common reason for death was sepsis due to secondary bacterial infections. Acute deterioration with rapid oxygen desaturation or palpation of crepitation over thorax and neck in a COVID-19 patient should prompt a search for pneumothorax or pneumomediastinum. Conservative management may be an option as long as the patients are stable.