RESUMEN
To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC50) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL-1, respectively; 50% inhibitory concentration (IC50) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL-1 with safety index (SI) of 4.64 and 21.99, respectively; IC50 of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.
RESUMEN
<p><b>OBJECTIVE</b>To understand the influence of different sleep stages on respiratory regulation in normal people.</p><p><b>METHODS</b>We measured ventilation (VE) and occlusion pressure (P0.1) responses to hyperoxia hypercapnia (deltaVE/deltaPaCO2, deltaP0.1/deltaPaCO2) and isocapnic hypoxia (deltaVE/deltaSaO2 and deltaP0.1/deltaSaO2) in eleven non-snoring healthy people during wakefulness and during non-rapid eye movement (NREM) I + II, NREM III+IV, and rapid eye movement (REM) sleep stages.</p><p><b>RESULTS</b>During NREM I + II and NREM III+IV, the normal subjects showed no significant decrease in P0.1, deltaP0.1/deltaSaO2 and deltaP0.1/deltaPaCO2 (P > 0.05), but deltaVE/ deltaSaO2 and deltaVE/ deltaPaCO2 decreased significantly (P < 0.05). During REM sleep, P0.1 maintained the level during wakefulness, but both hypoxic and hypercapnic responses decreased significantly (P < 0.05).</p><p><b>CONCLUSIONS</b>Sleep has significant influence on respiratory regulation in normal people. The respiratory drive (P0.1) in both NREM and REM sleep stages could maintain the awake level due to an effective compensation to the increase of upper airway resistance. The P0.1 responses to both hypoxia and hypercapnia decrease only in REM sleep stage, which is in consistent with the clinical phenomenon that sleep disordered breathing occurs in REM in normal people.</p>