ABSTRACT
Scutellariae radix (“Huang-Qin” in Chinese) is a well-known traditional herbal medicine and popular dietary supplement in the world, extensively used in prescriptions of TCMs as adjuvant treatments for coronavirus pneumonia 2019 (COVID-19) patients in China. According to the differences in its appearance, Scutellariae radix can be classified into two kinds: ZiQin (1∼3 year-old Scutellariae baicalensis with hard roots) and KuQin (more than 3 year-old S. baicalensis with withered pithy roots). In accordance with the clinical theory of TCM, KuQin is superior to ZiQin in cooling down the heat in the lung. However, the potential active ingredients and underlying mechanisms of Scutellariae radix for the treatment of COVID-19 remain largely unexplored. It is still not clear whether there is a difference in the curative effect of ZiQin and KuQin for the treatment of COVID-19. In this research, network pharmacology, LC-MS based plant metabolomics, and in vitro bioassays were integrated to explore both the potential active components and mechanism of Scutellariae radix for the treatment of COVID-19. As the results, network pharmacology combined with molecular docking analysis indicated that Scutellariae radix primarily regulates the MAPK and NF-κB signaling pathways via active components such as baicalein and scutellarin, and blocks SARS-CoV-2 spike binding to human ACE2 receptors. In vitro bioassays showed that baicalein and scutellarein exhibited more potent anti-inflammatory and anti-infectious effects than baicalin, the component with the highest content in Scutellariae radix. Moreover, baicalein inhibited SARS-CoV-2’s entry into Vero E6 cells with an IC50 value of 142.50 μM in a plaque formation assay. Taken together, baicalein was considered to be the most crucial active component of Scutellariae radix for the treatment of COVID-19 by integrative analysis. In addition, our bioassay study revealed that KuQin outperforms ZiQin in the treatment of COVID-19. Meanwhile, plant metabolomics revealed that baicalein was the compound with the most significant increase in KuQin compared to ZiQin, implying the primary reason for the superiority of KuQin over ZiQin in the treatment of COVID-19.
ABSTRACT
Drug discovery from plants usually focuses on small molecules rather than such biological macromolecules as RNAs. Although plant transfer RNA (tRNA)-derived fragment (tRF) has been associated with the developmental and defense mechanisms in plants, its regulatory role in mammals remains unclear. By employing a novel reverse small interfering RNA (siRNA) screening strategy, we show that a tRF mimic (antisense derived from the 5′ end of tRNAHis(GUG) of Chinese yew) exhibits comparable anti-cancer activity with that of taxol on ovarian cancer A2780 cells, with a 16-fold lower dosage than that of taxol. A dual-luciferase reporter assay revealed that tRF-T11 directly targets the 3′ UTR of oncogene TRPA1 mRNA. Furthermore, an Argonaute-RNA immunoprecipitation (AGO-RIP) assay demonstrated that tRF-T11 can interact with AGO2 to suppress TRPA1 via an RNAi pathway. This study uncovers a new role of plant-derived tRFs in regulating endogenous genes. This holds great promise for exploiting novel RNA drugs derived from nature and sheds light on the discovery of unknown molecular targets of therapeutics. Graphical
ABSTRACT
Drug discovery from plants usually focuses on small molecules rather than such biological macromolecules as RNAs. Although plant transfer RNA (tRNA)-derived fragment (tRF) has been associated with the developmental and defense mechanisms in plants, its regulatory role in mammals remains unclear. By employing a novel reverse small interfering RNA (siRNA) screening strategy, we show that a tRF mimic (antisense derived from the 5' end of tRNAHis(GUG) of Chinese yew) exhibits comparable anti-cancer activity with that of taxol on ovarian cancer A2780 cells, with a 16-fold lower dosage than that of taxol. A dual-luciferase reporter assay revealed that tRF-T11 directly targets the 3' UTR of oncogene TRPA1 mRNA. Furthermore, an Argonaute-RNA immunoprecipitation (AGO-RIP) assay demonstrated that tRF-T11 can interact with AGO2 to suppress TRPA1 via an RNAi pathway. This study uncovers a new role of plant-derived tRFs in regulating endogenous genes. This holds great promise for exploiting novel RNA drugs derived from nature and sheds light on the discovery of unknown molecular targets of therapeutics.
ABSTRACT
Organic carbon (OC), elemental carbon (EC), and PM2.5 concentration data obtained from Shanxi Super Station in Jiashan County of Jiaxing City, in the winter of 2018 and 2019, were analyzed to determine the variation and potential source areas of carbonaceous aerosols. The results show that OC concentrations in the winter of 2018 and 2019 were 6.90 µg·m-3 and 5.63 µg·m-3, respectively, while EC concentrations were 2.47 µg·m-3 and 1.57 µg·m-3, respectively. The concentrations of OC and EC in the winter of 2019 were lower than those in the winter of 2018, by approximately 18.4% and 36.4%, respectively. In 2018 and 2019, the concentrations of secondary organic carbon (SOC), calculated using the minimum R-squared (MRS) method, were 1.49 µg·m-3 and 1.97 µg·m-3, respectively, and the concentrations of primary organic carbon (POC) were 5.41 µg·m-3 and 3.66 µg·m-3, respectively. The proportion of POC in OC showed a downward trend, from 96.0% in December 2018 to 64.9% in February 2020, indicating a decrease of 31.1 percentage points. SOC showed an upward trend, increasing by 31.1 percentage points from 4.0% in December 2018 to 35.1% in February 2020. It is worth noting that with the increase in PM2.5 concentration, the concentration of OC and EC increased by 474.7% and 408.2%, respectively, although the proportion of OC in PM2.5 decreased from 18.8% to 12.3%. and the percentage of OC decreased from 5.8% to 3.3%. The contribution of POC to PM2.5 did not fluctuate, and only decreased significantly above 150 µg·m-3, while the contribution of SOC to PM2.5 first decreased and then increased. In Jiaxing, the potential sources of OC and EC were mainly southern Jiangsu, southeastern Anhui, local Jiaxing, and northern Zhejiang. In the winter of the contribution concentrations of OC and EC in the main potential source regions were approximately 2 µg·m-3 and 6 µg·m-3 lower, respectively, than in winter 2018. The range of high values in the potential source regions also decreased in 2019. Before the COVID-19 epidemic, it was affected by both motor vehicle exhaust emissions and coal burning. During the Spring Festival and home isolation, due to traffic control and other reasons, motor vehicle emissions were reduced, which leaving coal burning as the main contributor.
Subject(s)
Air Pollutants , COVID-19 , Aerosols/analysis , Air Pollutants/analysis , Environmental Monitoring , Humans , Particulate Matter/analysis , SARS-CoV-2ABSTRACT
INTRODUCTION: The present study investigated hospitalization data of patients receiving radiotherapy at Anhui Cancer Hospital during the COVID-19 epidemic and analyzed the impact of the epidemic on the clinical data of radiotherapy patients to provide references for the feasibility and safety of radiotherapy at other medical institutions. METHODS: The present study performed a retrospective analysis of hospitalization data of patients undergoing radiotherapy at the Radiation Department (from January 5 to March 19, 2020 according to the Chinese lunar calendar), who were defined as the epidemic group. Hospitalization data for patients undergoing radiotherapy during the same period in 2019 were used as the control group for comparison with the epidemic group in terms of sex, age, distribution of various cancer types, hospitalization costs, average length of stay, completion rate of radiotherapy, treatment mode, and purpose of radiotherapy. RESULTS: A total of 79 and 115 patients received radiotherapy in the epidemic group and control group, respectively. The number of patients who received radiotherapy declined 31.3% during the epidemic period. The number of head and neck cancer patients who received radiotherapy was 36 (45.57%) in the epidemic group and 32 (27.83%) in the control group, which was a significant difference (χ2 =6.476, P=0.011). The proportions of patients with other types of cancer decreased, with no significant difference between the two groups (P>0.05). No significant differences between the two groups were found in terms of other hospitalization data (P>0.05). CONCLUSION: The total number of patients who received radiotherapy decreased during the epidemic period, but the proportion of head and neck cancer increased. The epidemic had no significant effect on other hospitalization data. While strengthening prevention and control measures, we should actively perform radiotherapy to ensure that cancer patients receive timely and safe treatment.
ABSTRACT
BACKGROUND: Since the outbreak of coronavirus disease 2019 (COVID-19), many researchers in China have performed related clinical research. However, systematic reviews of the registered clinical trials are still lacking. Therefore, we conducted a systematic review of clinical trials for COVID-19 to summarize their characteristics. METHODS: This study is based on the PRISMA recommendations in the Cochrane handbook. The Chinese Clinical Registration Center and the ClinicalTrials.gov databases were searched to identify registered clinical trials related to COVID-19. The retrieval inception date was February 9, 2020. Two researchers independently selected the literature based on the inclusion and exclusion criteria, extracted data, and evaluated the risk of bias. RESULTS: A total of 75 registered clinical trials (63 interventional studies and 12 observational studies) for COVID-19 were identified. The majority of clinical trials were sponsored by Chinese hospitals. Only 11 trials have begun to recruit patients, and none of the registered clinical trials have been completed; 34 trials were early clinical exploratory trials or in the pre-experiment stage, 13 trials were phase III, and four trials were phase IV. The intervention methods included traditional Chinese medicine in 26 trials, Western medicine in 30 trials, and integrated traditional Chinese medicine and Western medicine in 19 trials. The subjects were primarily non-critical adult patients (≥ 18 years old). The median sample size of the trials was 100 (IQR: 60-200), and the median length of the trial periods was 179 d (IQR: 94-366 d). The main outcomes were clinical observation and examinations. Overall, the methodological quality of both the interventional trials and observational studies was low. CONCLUSIONS: Intensive clinical trials on the treatment of COVID-19 using traditional Chinese medicine and Western medicine are ongoing or will be performed in China. However, based on the uncertain methodological quality, small sample size, and long trial duration, we will not be able to obtain reliable, high-quality clinical evidence regarding the treatment of COVID-19 in the near future. Improving the quality of study design, prioritizing promising drugs, and using different designs and statistical methods are worth advocating and recommending for clinical trials of COVID-19 in the future.