Proteomic characteristics of the treatment trajectory of patients with COVID-19.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 has prompted global concern due to its profound impact on public health and the economy. Effective treatment of COVID-19 patients in the acute phase or of those with long COVID is a major challenge. Using data-independent acquisition (DIA) technology, we performed proteomic profiling on plasma samples from 22 COVID-19 patients and six healthy controls at Dazhou Central Hospital. Random forest and least absolute shrinkage and selection operator algorithms were used for analysis at various COVID-19 treatment stages. We identified 79 proteins that were differentially expressed between COVID-19 patients and healthy controls, mainly involving pathways associated with cell processes and binding. Across different treatment stages of COVID-19, five proteins-PI16, GPLD1, IGFBP3, KRT19, and VCAM1-were identified as potential molecular markers for dynamic disease monitoring. Furthermore, the proteins BTD, APOM, IGKV2-28, VWF, C4BPA, and C7 were identified as candidate biomarkers for distinguishing between SARS-CoV-2 positivity and negativity. Analysis of protein change profiles between the follow-up and healthy control groups highlighted cardiovascular changes as a concern for patients recovering from COVID-19. Our study revealed the infection profiles of SARS-CoV-2 at the protein expression level comparing different phases of COVID-19. DIA mass spectrometry analysis of plasma samples from COVID-19 patients undergoing treatment identified key proteins involved in signaling pathways that might be used as markers of the recovery phase. These findings provide insight for the development of therapy options and suggest potential blood biomarkers for COVID-19.

[Ca(2+)-dependent potassium channels play important roles in regulatory volume decrease in human nasopharyngeal carcinoma cells].

It has been shown that cell volume regulation mechanisms play important roles in various cell functions. We demonstrated previously that volume-activated chloride channels were involved in cell volume regulation. The present study aimed to clarify the roles of various types of potassium channels in regulatory volume decrease (RVD) induced by hypotonic challenges in human nasopharyngeal carcinoma cells (CNE-2Z cells). The whole-cell patch clamp technique was used to record hypotonic challenge-induced potassium currents. During current recordings, cells were held at 0 mV and stepped to +/-46 and +/-92 mV, repeatedly. The cell volume was computed from cell diameters. The changes of cell volume were monitored and analyzed by the time-lapse imaging technique. The results showed that the exposure to 160 mOsm/L hypotonic solution caused the cells to swell by (144.5+/-4.2)%, activated a potassium current (59.2 pA/pF+/-13.3 pA/pF at 92 mV), and induced RVD. Cell volume was recovered from hypotonic challenge-induced swelling by (48.9+/-4.6)% after 20 min. The potassium current (at 92 mV) and RVD were inhibited by the calcium-dependent potassium channel blocker, clotrimazole (100 mumol/L), by (98.5+/-2.8)% and (89.3+/-4.9)%, respectively. Depletion of extracellular calcium prevented the activation of the hypotonic challenge-induced potassium current and inhibited the process of RVD. The voltage-gated potassium channel blocker, 4-AP (5 mmol/L), partially inhibited the hypotonic challenge-activated potassium currents by (66.6+/-5.3)% (at 92 mV). These results suggest that the Ca(2+)-dependent potassium channel is the main component of volume-activated potassium channels and plays an important role in volume regulation of CNE-2Z cells. The voltage-gated potassium channels may also contribute in part to the formation of the volume-activated potassium current.

[Changes of fast and slow components of brainstem auditory evoked potentials in the rat pups with hyperbilirubinemia].

OBJECTIVE: To probe the changes of fast component of brainstem auditory evoked potentials (FC-BAEP), slow component of brainstem auditory evoked potentials (SC-BAEP) and the mitochondrial ultrastructures of the neurons in the brainstem in the rat pups with hyperbilirubinemia. METHODS: 7 days old SD rat pups were randomly divided into control group (C, 17 rat pups) and two test groups (T1, 17 rat pups and T2, 17 rat pups). Bilirubin solutions (2 g/L) were injected into the abdominal cavity of the rat pups in the group T1 and T2 at the postnatal day 7 and 10. Six hours after the second injection, seven rat pups of each group were randomly selected to test serum bilirubin concentration via a micro-gauge. FC-BAEP and SC-BAEP were examined with an evoked potential recorder in the rest rat pups of each group at postnatal day 17 and 20. At the postnatal day 20, the endocardial perfusion was performed in these rat pups for the fixation of the brain, and then the brains were taken out. The cochlear nuclei were used for observation via electron microscope. RESULTS: Six hours after the injection of bilirubin solution at the postnatal day 10, the serum bilirubin concentrations of the rat pups in group T1 and T2 were increased significantly. Except for II-IV inter-peak latency(IPL), all the peak latency(PL) and IPL of FC-BAEP evoked via three sound stimulating rates (10/s, 40/s,80/s) at the postnatal day 17 prolonged significantly in the rat pups of group T1 and T2, and the PL in group T2 were much longer than that in group T1. Except for II-IV IPL of FC-BAEP evoked via sound stimulating rates of 10/s and 40/s, all the PL and IPL at the postnatal day 20 prolonged significantly in the rat pups of group T1 and T2. The PL of SC-BAEP evoked via sound stimulating rate of 10/s at the postnatal day 17 and 20 in the rat pups of group T1 and T2 prolonged significantly, and the PL at the postnatal day 17 in group T2 were much longer than that of group T1. The changes of mitochondria of the neurons in the cochlear nuclei at the postnatal day 20 in the rat pups of group T1 and T2 were characterized by swell, the slurred membranes, the broken crista and so on. CONCLUSION: There were the abnormal changes of FC-BAEP, SC-BAEP and the mitochondrial ultrastructures of the neurons in the brainstem in the rat pups with hyperbilirubinemia. The PL and IPL of FC-BAEP and SC-BAEP could be taken as the objective and sensitive indexes for early monitoring the bilirubin-induced hearing loss and brain injury.

[Effects of hyperthermia on brainstem auditory evoked potentials and middle latency response in rats].

AIM: To study the effects of hyperthermia on brainstem auditory evoked potentials (BAEP) and middle latency response (MLR) in rats. METHODS: BAEP and MLR were recorded at the skull surface of rats. The body temperature of anesthetized rats increased gradually with a physical method and was detected by a digital thermometer inserted into the rectum. The peak latency (PL), interpeak latency (IPL), wave amplitude and the critical body temperature at which BAEP and MLR completely lost had been observed. RESULTS: All PL and I - II, I - III and I -IV IPL of BAEP shortened more and more as the body temperature increased step by step from 37 degrees C to 41.5 degrees C. But all PL and I - II and I -IV IPL did not shortened further and prolonged a little contrary as the body temperature at 42 degrees C and over 42 degrees C. All PL and P1-P3 and P2-P3 IPL of MLR also shortened as the body temperature increased from 37 degrees C to 43 degrees C. The wave amplitudes of BAEP and MLR decreased as the body temperature increased, especially as the body temperature over 42 degrees C. BAEP and MLR lost completely and synchronously at the body temperature (43.1 +/- 0.5) degrees C, which was not reversed as the body temperature returning to normal by cooling. CONCLUSION: There were obvious effects of hyperthermia on both BAEP and MLR in rats, and irreversible impairments appeared at a critical body temperature.