Impaired cell-cell communication and axon guidance because of pulmonary hypoperfusion during postnatal alveolar development.

BACKGROUND: Pulmonary hypoperfusion is common in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH) and causes adult pulmonary dysplasia. Systematic reviews have shown that some children with CHDs or PH have mitigated clinical outcomes with COVID-19. Understanding the effects of pulmonary hypoperfusion on postnatal alveolar development may aid in the development of methods to improve the pulmonary function of children with CHDs or PH and improve their care during the COVID-19 pandemic, which is characterized by cytokine storm and persistent inflammation. METHODS AND RESULTS: We created a neonatal pulmonary hypoperfusion model through pulmonary artery banding (PAB) surgery at postnatal day 1 (P1). Alveolar dysplasia was confirmed by gross and histological examination at P21. Transcriptomic analysis of pulmonary tissues at P7(alveolar stage 2) and P14(alveolar stage 4) revealed that the postnatal alveolar development track had been changed due to pulmonary hypoperfusion. Under the condition of pulmonary hypoperfusion, the cell-cell communication and axon guidance, which both determine the final number of alveoli, were lost; instead, there was hyperactive cell cycle activity. The transcriptomic results were further confirmed by the examination of axon guidance and cell cycle markers. Because axon guidance controls inflammation and immune cell activation, the loss of axon guidance may explain the lack of severe COVID-19 cases among children with CHDs or PH accompanied by pulmonary hypoperfusion. CONCLUSIONS: This study suggested that promoting cell-cell communication or supplementation with guidance molecules may treat pulmonary hypoperfusion-induced alveolar dysplasia, and that COVID-19 is less likely to cause a cytokine storm in children with CHD or PH accompanied by pulmonary hypoperfusion.

[Characteristics, Ozone Formation Potential, and Source Apportionment of VOCs During the COVID-19 Epidemic in Xiong'an].

Many restrictive measures were implemented in China from January-February 2020 to control the rapid spread of COVID-19. Many studies reported that the COVID-19 lockdown impacted PM2.5, SO2, volatile organic compounds (VOCs), etc. VOCs play important roles in the production of ozone and PM2.5. Ambient VOCs in Xiong'an were measured from December 25, 2019 to January 24, 2020 (prior to epidemic prevention, P1) and from January 25, 2020 to February 24, 2020 (during epidemic prevention, P2) through a VOCs online instrument. In the study, VOCs characteristics and ozone generation potential (OFP) of ambient VOCs were analyzed, and source apportionment of VOCs were analyzed by using Positive Matrix Factorization (PMF). The results showed that φ(TVOCs) during epidemic prevention and control was 45.1×10-9, which was approximately half of that before epidemic prevention and control (90.5×10-9). The chemical composition of VOCs showed significant changes after epidemic prevention and control, the contribution rate of alkanes increased from 37.6% to 53.8%, and the contribution rate of aromatic hydrocarbons and halogenated hydrocarbons decreased from 13.3% and 12.0% to 7.5% and 7.8%, respectively. Aromatic hydrocarbons, halogenated hydrocarbons, and OVOCs decreased by more than 60%. Seven types of the top ten species were the same before and during the epidemic prevention and control, mainly low-carbon alkanes, olefins, aldehydes, and ketones. Dichloromethane, trichloromethane, and BTEXs decreased significantly. The OPP was 566 µg·m-3 and 231 µg·m-3 in P1 and P2, respectively. The OPP of VOCs decreased by more than 30%. The proportion of OFP contribution of aromatic hydrocarbons decreased significantly after the epidemic prevention and control, and the proportion of OFP contribution of alkanes and alkynes increased significantly. Positive matrix factorization (PMF) was then applied for VOCs sources apportionment. Six sources were identified, including background sources, oil-gas volatile sources, combustion sources, industrial sources, solvent use sources, and vehicle exhaust sources. The results showed that after the epidemic prevention and control, the contribution rate of solvent use sources to TVOCs decreased from 24% to 9%. The contribution rates of background sources, oil-gas volatile sources, and combustion sources increased from 13%, 34%, and 24% to 6%, 14%, and 13%, respectively. The relative contributions of vehicle exhaust sources before and after epidemic prevention and control were 21% and 18%, respectively. The observation points were affected by the emission of VOCs from paroxysmal industrial sources before the epidemic prevention and control. The emission was stopped after the epidemic prevention and control, and its contribution rate was reduced from 22% before the epidemic prevention and control to 1%. The concentrations of industrial sources, solvent sources, motor vehicle tail gas sources, and combustion sources decreased by 97%, 82%, 61%, and 15%, respectively, after the epidemic prevention and control. The concentration of background sources remained stable, and the concentration of oil and gas volatile sources increased by 7%. The control of production and traffic activities cannot reduce the emission of VOCs from oil and gas volatile sources, which is the focus of VOCs control in Xiong'an.

Progress in Traditional Chinese Medicine Against Respiratory Viruses: A Review.

Respiratory viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV)-1, SARS-CoV-2, influenza A viruses, and respiratory syncytial virus, pose a serious threat to society. Based on the guiding principles of "holism" and "syndrome differentiation and treatment", traditional Chinese medicine (TCM) has unique advantages in the treatment of respiratory virus diseases owing to the synergistic effect of multiple components and targets, which prevents drug resistance from arising. According to TCM theory, there are two main strategies in antiviral treatments, namely "dispelling evil" and "fu zheng". Dispelling evil corresponds to the direct inhibition of virus growth and fu zheng corresponds to immune regulation, inflammation control, and tissue protection in the host. In this review, current progress in using TCMs against respiratory viruses is summarized according to modern biological theories. The prospects for developing TCMs against respiratory viruses is discussed to provide a reference for the research and development of innovative TCMs with multiple components, multiple targets, and low toxicity.

Identifying potential treatments of COVID-19 from Traditional Chinese Medicine (TCM) by using a data-driven approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) has been widely used as an approach worldwide. Chinese Medicines (CMs) had been used to treat and prevent viral infection pneumonia diseases for thousands of years and had accumulated a large number of clinical experiences and effective prescriptions. AIM OF THE STUDY: This research aimed to systematically excavate the classical prescriptions of Chinese Medicine (CM), which have been used to prevent and treat Pestilence (Wenbing, Wenyi, Shiyi or Yibing) for long history in China, to obtain the potential prescriptions and ingredients to alternatively treat COVID-19. MATERIALS AND METHODS: We developed the screening system based on data mining, molecular docking and network pharmacology. Data mining and association network were used to mine the high-frequency herbs and formulas from ancient prescriptions. Virtual screening for the effective components of high frequency CMs and compatibility Chinese Medicine was explored by a molecular docking approach. Furthermore, network pharmacology method was used to preliminarily uncover the molecule mechanism. RESULTS: 574 prescriptions were obtained from 96,606 classical prescriptions with the key words to treat "Warm diseases (Wenbing)", "Pestilence (Wenyi or Yibing)" or "Epidemic diseases (Shiyi)". Meanwhile, 40 kinds of CMs, 36 CMs-pairs, 6 triple-CMs-groups existed with high frequency among the 574 prescriptions. Additionally, the key targets of SARS-COV-2, namely 3CL hydrolase (Mpro) and angiotensin-converting enzyme 2(ACE2), were used to dock the main ingredients from the 40 kinds by the LigandFitDock method. A total of 66 compounds components with higher frequency were docked with the COVID-19 targets, which were distributed in 26 kinds of CMs, among which Gancao (Glycyrrhizae Radix Et Rhizoma), HuangQin (Scutellariae Radix), Dahuang (Rhei Radix Et Rhizome) and Chaihu (Bupleuri Radix) contain more potential compounds. Network pharmacology results showed that Gancao (Glycyrrhizae Radix Et Rhizoma) and HuangQin (Scutellariae Radix) CMs-pairs could also interact with the targets involving in immune and inflammation diseases. CONCLUSIONS: These results we obtained probably provided potential candidate CMs formulas or active ingredients to overcome COVID-19. Prospectively, animal experiment and rigorous clinic studies are needed to confirm the potential preventive and treat effect of these CMs and compounds.