Recent advances in ginsenosides against respiratory diseases: Therapeutic targets and potential mechanisms.

BACKGROUND: Respiratory diseases mainly include asthma, influenza, pneumonia, chronic obstructive pulmonary disease, pulmonary hypertension, lung fibrosis, and lung cancer. Given their high prevalence and poor prognosis, the prevention and treatment of respiratory diseases are increasingly essential. In particular, the development for the novel strategies of drug treatment has been a hot topic in the research field. Ginsenosides are the major component of Panax ginseng C. A. Meyer (ginseng), a food homology and well-known medicinal herb. In this review, we summarize the current therapeutic effects and molecular mechanisms of ginsenosides in respiratory diseases. METHODS: The reviewed studies were retrieved via a thorough analysis of numerous articles using electronic search tools including Sci-Finder, ScienceDirect, PubMed, and Web of Science. The following keywords were used for the online search: ginsenosides, asthma, influenza, pneumonia, chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung fibrosis, lung cancer, and clinical trials. We summarized the findings and the conclusions from 176 manuscripts on ginsenosides, including research articles and reviews. RESULTS: Ginsenosides Rb1, Rg1, Rg3, Rh2, and CK, which are the most commonly reported ginsenosides for treating of respiratory diseases, and other ginsenosides such as Rh1, Rk1, Rg5, Rd and Re, all primarily reduce pneumonia, fibrosis, and inhibit tumor progression by targeting NF-κB, TGF-ß/Smad, PI3K/AKT/mTOR, and JNK pathways, thereby ameliorating respiratory diseases. CONCLUSION: This review provides novel ideas and important aspects for the future research of ginsenosides for treating respiratory diseases.

Upregulation of PD-L1 by SARS-CoV-2 promotes immune evasion.

Patients with severe COVID-19 often suffer from lymphopenia, which is linked to T-cell sequestration, cytokine storm, and mortality. However, it remains largely unknown how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces lymphopenia. Here, we studied the transcriptomic profile and epigenomic alterations involved in cytokine production by SARS-CoV-2-infected cells. We adopted a reverse time-order gene coexpression network approach to analyze time-series RNA-sequencing data, revealing epigenetic modifications at the late stage of viral egress. Furthermore, we identified SARS-CoV-2-activated nuclear factor-κB (NF-κB) and interferon regulatory factor 1 (IRF1) pathways contributing to viral infection and COVID-19 severity through epigenetic analysis of H3K4me3 chromatin immunoprecipitation sequencing. Cross-referencing our transcriptomic and epigenomic data sets revealed that coupling NF-κB and IRF1 pathways mediate programmed death ligand-1 (PD-L1) immunosuppressive programs. Interestingly, we observed higher PD-L1 expression in Omicron-infected cells than SARS-CoV-2 infected cells. Blocking PD-L1 at an early stage of virally-infected AAV-hACE2 mice significantly recovered lymphocyte counts and lowered inflammatory cytokine levels. Our findings indicate that targeting the SARS-CoV-2-mediated NF-κB and IRF1-PD-L1 axis may represent an alternative strategy to reduce COVID-19 severity.

Application of Remote Fetal Heart Rate Monitoring Based on Internet in Late Pregnancy During the COVID-19 Pandemic (preprint)

Objective：To evaluate the consistency of pregnancy outcomes and related clinical monitoring indicators in high and low risk group under two different monitoring methods during COVID-19 pandemic.Methods：760 cases of late pregnant women admitted to our hospital from March 2020 to February 2021 were selected for this study. They were randomly divided into control group (n = 380) and observation group (n = 380). Observation group the fetus was monitored remotely at home，while the control group went to the hospital for fetal heart monitoring.To evaluate the consistency of pregnancy outcomes and related clinical monitoring indicators in different groups under two different monitoring .Results:It was found that there was no statistically significant difference between the two groups in terms of pregnancy outcome (including mode of delivery, postpartum hemorrhage, etc.) and neonatal outcome (including preterm birth rate, neonatal weight, neonatal Apgar score, etc.) (p>0.05). It should also be noted that the difference in EPDS score results between the two groups was statistically significant (p<0.05) . Meanwhile, there was a statistically significant difference in the total cost of labor and delivery between two groups (p<0.05) and total time spent on labor and delivery between the two groups(p<0.05).Conclusions:Remote Fetal Heart Rate Monitoring Based on Internet is an innovative, acceptable, and effective reduced-frequency prenatal examination model. Compared to routine prenatal examination, Remote Fetal Heart Rate Monitoring Based on Internet resulted in higher patient satisfaction and lower prenatal stress. Besides, Remote Fetal Heart Rate Monitoring Based on Internet compared with the traditional fetal heart monitoring does not affect the pregnancy outcomes of pregnant women with different risk factors, maternal accept degree is high, and to reduce the medical resources pressure. It is an effective and feasible way for self-monitoring of pregnancies in late pregnancy during the pandemic of COVID-19 and is worthy of clinical application.

The CRISPR-Cas toolbox for analytical and diagnostic assay development.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) systems have revolutionized biological and biomedical sciences in many ways. The last few years have also seen tremendous interest in deploying the CRISPR-Cas toolbox for analytical and diagnostic assay development because CRISPR-Cas is one of the most powerful classes of molecular machineries for the recognition and manipulation of nucleic acids. In the short period of development, many CRISPR-enabled assays have already established critical roles in clinical diagnostics, biosensing, and bioimaging. We describe in this review the recent advances and design principles of CRISPR mediated analytical tools with an emphasis on the functional roles of CRISPR-Cas machineries as highly efficient binders and molecular scissors. We highlight the diverse engineering approaches for molecularly modifying CRISPR-Cas machineries and for devising better readout platforms. We discuss the potential roles of these new approaches and platforms in enhancing assay sensitivity, specificity, multiplexity, and clinical outcomes. By illustrating the biochemical and analytical processes, we hope this review will help guide the best use of the CRISPR-Cas toolbox in detecting, quantifying and imaging biologically and clinically important molecules and inspire new ideas, technological advances and engineering strategies for addressing real-world challenges such as the on-going COVID-19 pandemic.

Advances in the research of recombinase polymerase amplification technology

The outbreak of coronavirus disease 2019 has made nucleic acid detection widely known. Fluorescent quantitative polymerase chain reaction (PCR) technique is the most commonly used nucleic acid detection method in this epidemic control. However, its requirements on operators, instruments and sites limited its application in some scenarios with lower resources or outside laboratories. Isothermal amplification technology, especially recombinase polymerase amplification (RPA) technology, has the advantages of mild reaction conditions, high sensitivity, excellent specificity and short reaction time, which let it has a good application prospect in the rapid detection of a variety of pathogenic microorganisms. In this paper, the development and application of RPA technology are reviewed and summarized to provide a reference for the further research and promotion of this technology.

Global Pandemic Trends of COVID-19 in 2020 (preprint)

Background: The novel coronavirus pneumonia (COVID-19) has been global threaten to public health. This paper provides perspective to the decision-making for public health control of the pandemic or the spread of epidemic.Methods: According to the WHO global reported database, we developed and used the number of cumulative cases, and the number of cumulative deaths to calculate and analyze rates of incidence, mortality, and fatality by country, with respect to the 30 highest outbreak (Top 30) countries.Results： As of December 31, 2020, of the global population of 7.585 billion, the cumulative number of reported cases was 81,475,053, and the cumulative number of deaths was 1,798,050. The incidence rate of COVID-19 was 1074.13 per 100,000 population, the mortality rate was 23.70 per 100,000, and the case fatality rate was 2.21%. Among the Top 30 countries, the five countries with the highest number of reported cumulative cases were, in rank, the United States (19,346,790 cases), India (10,266,674), Brazil (7,563,551), Russia (3,159,297) and France (2,556,708), and the five countries with the highest number of cumulative deaths were the United States (335,789 cases), Brazil (192,681), India (148,738), Mexico (123,845) and Italy (73,604). Globally, the countries with the highest incidence rate were, in rank, Andorra, Luxembourg, Montenegro, San Marino, and Czechia; the countries with the highest mortality rate were, in rank, San Marino, Belgium, Slovenia, Italy, and North Macedonia. The highest fatality rate was found in Yemen, Mexico, Montserrat, Isle of Man, and Ecuador, respectively. In China, 96,673 cases of COVID-19 and 4788 deaths were reported in 2020, ranking the 78th and the 43rd, respectively, in the world. The incidence rate and mortality rate were 6.90/105 and 0.34/105, respectively, ranking 207th and 188th in the world. The case fatality rate was 4.95%, ranking 11th in the world.Conclusions： The COVID-19 prevalence is still on the rise, and the turning points of incidence and mortality are not yet forecasted. Personal protection, anti-epidemic measures and efforts from public health personnel, medical professionals, biotechnology R&D personnel, effectiveness of the vaccination programs and the governments, are the important factors to determine the future prevalence of this coronavirus disease.

Characteristics of Lymphocyte Subsets and Cytokine Profiles of Patients with Coronavirus Disease 2019 (preprint)

Background: To explore the changes in lymphocyte subsets and cytokine profiles in patients with coronavirus disease 2019 (COVID-19) and their relationship with disease severity. Methods: This study included 228 patients with COVID-19 who were treated at Chongqing University Three Gorges Hospital from January 1, 2020 to February 20, 2020. The characteristics of lymphocyte subsets and cytokine profiles of severe and mild COVID-19 patients were compared. Of the 228 patients enrolled, 48 were severe patients and 180 were mild patients. Results: Lymphocyte counts, absolute number of total T lymphocytes, CD4+T cells, CD8+T cells, and total B lymphocytes were significantly lower in severe patients (0.8×109/L, 424.5×106/L, 266×106/L, 145.5×106/L, 109.5×106/L, respectively) than in mild patients (1.2×109/L, 721×106/L, 439.5×106/L, 281.5×106/L, 135×106/L, respectively). A multivariate logistic regression analysis showed that age, C-reactive protein (CRP) and the neutrophil-to-lymphocyte ratio (NLR) were independent risk factors for developing into severe condition. The lymphocyte subsets decreased and cytokine profiles increased more significantly in severe patients than in mild patients. Conclusions: CRP, NLR, and age may serve as powerful factors for early identification of severe patients.