RESUMEN
Though RNAi and RNA-splicing machineries are involved in regulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication, their precise roles in coronavirus disease 2019 (COVID-19) pathogenesis remain unclear. Herein, we show that decreased RNAi component (Dicer and XPO5) and splicing factor (SRSF3 and hnRNPA3) expression correlate with increased COVID-19 severity. SARS-CoV-2 N protein induces the autophagic degradation of Dicer, XPO5, SRSF3, and hnRNPA3, inhibiting miRNA biogenesis and RNA splicing and triggering DNA damage, proteotoxic stress, and pneumonia. Dicer, XPO5, SRSF3, and hnRNPA3 knockdown increases, while their overexpression decreases, N protein-induced pneumonia's severity. Older mice show lower expression of Dicer, XPO5, SRSF3, and hnRNPA3 in their lung tissues and exhibit more severe N protein-induced pneumonia than younger mice. PJ34, a poly(ADP-ribose) polymerase inhibitor, or anastrozole, an aromatase inhibitor, ameliorates N protein- or SARS-CoV-2-induced pneumonia by restoring Dicer, XPO5, SRSF3, and hnRNPA3 expression. These findings will aid in developing improved treatments for SARS-CoV-2-associated pneumonia.
Asunto(s)
COVID-19 , Carioferinas , Ribonucleasa III , SARS-CoV-2 , Factores de Empalme Serina-Arginina , Animales , Factores de Empalme Serina-Arginina/metabolismo , Factores de Empalme Serina-Arginina/genética , Humanos , Ribonucleasa III/metabolismo , Ribonucleasa III/genética , SARS-CoV-2/genética , COVID-19/metabolismo , COVID-19/virología , COVID-19/genética , Ratones , Carioferinas/metabolismo , Carioferinas/genética , ARN Helicasas DEAD-box/metabolismo , ARN Helicasas DEAD-box/genética , Regulación hacia Abajo , Pulmón/metabolismo , Pulmón/patología , Pulmón/virología , Masculino , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Empalme del ARN , Autofagia/genética , Daño del ADN , Ribonucleoproteína Heterogénea-Nuclear Grupo A-BRESUMEN
This study investigated the impact of Human Papillomavirus (HPV) on inflammation and growth in oral epithelial cells, with a focus on the role of Interleukin-37 (IL37). Oral epithelial cells, including HOEC and HSC-3 cells, were employed in the research. The results revealed that HPV significantly induced inflammation in both types of oral epithelial cells, concurrently promoting cell growth and inhibiting apoptosis. IL37, a cytokine, was found to mitigate HPV-induced inflammation in oral epithelial cells. Moreover, IL37 counteracted HPV's effects on apoptosis and cell viability in oral epithelial cells. The study also identified a reduction in autophagy in HPV-infected oral epithelial cells, a phenomenon alleviated by IL37. Furthermore, chemical inhibition of autophagy was observed to attenuate HPV-induced inflammation and growth in oral epithelial cells. These findings contribute valuable insights into the pathogenesis of inflammation in oral epithelial cells associated with HPV and oral cancers, offering potential avenues for novel therapeutic strategies.
RESUMEN
This work proposes a highly sensitive sandwich heterostructure multimode optical fiber microbend sensor for heart rate (HR), respiratory rate (RR), and ballistocardiography (BCG) monitoring, which is fabricated by combining a sandwich heterostructure multimode fiber Mach-Zehnder interferometer (SHMF-MZI) with a microbend deformer. The parameters of the SHMF-MZI sensor and the microbend deformer were analyzed and optimized in detail, and then the new encapsulated method of the wearable device was put forward. The proposed wearable sensor could greatly enhance the response to the HR signal. The performances for HR, RR, and BCG monitoring were as good as those of the medically approved commercial monitors. The sensor has the advantages of high sensitivity, easy fabrication, and good stability, providing the potential for application in the field of daily supervision and health monitoring.
