Jinhua Qinggan granules attenuates acute lung injury by promotion of neutrophil apoptosis and inhibition of TLR4/MyD88/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute lung injury (ALI) is one of the fatal complications of respiratory virus infections such as influenza virus and coronavirus, which has high clinical morbidity and mortality. Jinhua Qinggan granules (JHQG) has been approved by China Food and Drug Administration in the treatment of H1N1 influenza and mild or moderate novel coronavirus disease 2019 (COVID-19), which is an herbal formula developed based on Maxingshigan decoction and Yinqiao powder that have been used to respiratory diseases in China for thousands of years. However, the underlying mechanism of JHQG in treating infectious diseases remains unclear. AIM OF THE STUDY: This study investigated the effects of JHQG on neutrophil apoptosis and key signaling pathways in lipopolysaccharide (LPS) -induced ALI mice in order to explore its mechanism of anti-inflammation. MATERIALS AND METHODS: The effect of JHQG on survival rate was observed in septic mouse model by intraperitoneal injection of LPS (20 mg/kg). To better pharmacological evaluation, the mice received an intratracheal injection of 5 mg/kg LPS. Lung histopathological changes, wet-to-dry ratio of the lungs, and MPO activity in the lungs and total protein concentration, total cells number, TNF-α, IL-1ß, IL-6, and MIP-2 levels in BALF were assessed. Neutrophil apoptosis rate was detected by Ly6G-APC/Annexin V-FITC staining. Key proteins associated with apoptosis including caspase 3/7 activity, Bcl-xL and Mcl-1 were measured by flow cytometry and confocal microscope, respectively. TLR4 receptor and its downstream signaling were analyzed by Western blot assay and immunofluorescence, respectively. RESULTS: JHQG treatment at either 6 or 12 g/kg/day resulted in 20% increase of survival in 20 mg/kg LPS-induced mice. In the model of 5 mg/kg LPS-induced mice, JHQG obviously decreased the total protein concentration in BALF, wet-to-dry ratio of the lungs, and lung histological damage. It also attenuated the MPO activity and the proportion of Ly6G staining positive neutrophils in the lungs, as well as the MIP-2 levels in BALF were reduced. JHQG inhibited the expression of Mcl-1 and Bcl-xL and enhanced caspase-3/7 activity, indicating that JHQG partially acted in promoting neutrophil apoptosis via intrinsic mitochondrial apoptotic pathway. The levels of TNF-α, IL-1ß, and IL-6 were significantly declined in LPS-induced mice treated with JHQG. Furthermore, JHQG reduced the protein expression of TLR4, MyD88, p-p65 and the proportion of nuclei p65, suggesting that JHQG treatment inhibited TLR4/MyD88/NF-κB pathway. CONCLUSION: JHQG reduced pulmonary inflammation and protected mice from LPS-induced ALI by promoting neutrophil apoptosis and inhibition of TLR4/MyD88/NF-κB pathway, suggesting that JHQG may be a promising drug for treatment of ALI.

Effect of COVID-19 lockdown on the characterization and mixing state of carbonaceous particles in the urban atmosphere of Liaocheng, the North China Plain

To investigate the effect of COVID-19 control measures on aerosol chemistry, the chemical compositions, mixing states, and formation mechanisms of carbonaceous particles in the urban atmosphere of Liaocheng in the North China Plain (NCP) were compared before and during the pandemic using a single particle aerosol mass spectrometry (SPAMS). The results showed that the concentrations of five air pollutants including PM2.5, PM10, SO2, NO2, and CO decreased by 41.2%–71.5% during the pandemic compared to those before the pandemic, whereas O3 increased by 1.3 times during the pandemic because of the depressed titration of O3 and more favorable meteorological conditions. The count and percentage contribution of carbonaceous particles in the total detected particles were lower during the pandemic than those before the pandemic. The carbonaceous particles were dominated by elemental and organic carbon (ECOC, 35.9%), followed by elemental carbon-aged (EC-aged, 19.6%) and organic carbon-fresh (OC-fresh, 13.5%) before the pandemic, while EC-aged (25.3%), ECOC (17.9%), and secondary ions-rich (SEC, 17.8%) became the predominant species during the pandemic. The carbonaceous particle sizes during the pandemic showed a broader distribution than that before the pandemic, due to the condensation and coagulation of carbonaceous particles in the aging processes. The relative aerosol acidity (Rra) was smaller before the pandemic than that during the pandemic, indicating the more acidic particle aerosol during the pandemic closely related to the secondary species and relative humidity (RH). More than 95.0% and 86.0% of carbonaceous particles in the whole period were internally mixed with nitrate and sulfate, implying that most of the carbonaceous particles were associated with secondary oxidation during their formation processes. The diurnal variations of oxalate particles and correlation analyses suggested that oxalate particles before the pandemic were derived from aqueous oxidation driven by RH and liquid water content (LWC), while oxalate particles during the pandemic were originated from O3-dominated photochemical oxidation.

Structure genomics of SARS-CoV-2 and its Omicron variant: drug design templates for COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has brought an unprecedented public health crisis and persistently threatens to humanity. With tireless efforts from scientists around the world, understanding of the biology of coronavirus has been greatly enhanced over the past 2 years. Structural biology has demonstrated its powerful impact on uncovering structures and functions for the vast majority of SARS-CoV-2 proteins and guided the development of drugs and vaccines against COVID-19. In this review, we summarize current progress in the structural biology of SARS-CoV-2 and discuss important biological issues that remain to be addressed. We present the examples of structure-based design of Pfizer's novel anti-SARS-CoV-2 drug PF-07321332 (Paxlovid), Merck's nucleotide inhibitor molnupiravir (Lagevrio), and VV116, an oral drug candidate for COVID-19. These examples highlight the importance of structure in drug discovery to combat COVID-19. We also discussed the recent variants of Omicron and its implication in immunity escape from existing vaccines and antibody therapies.

Influence of COVID-19 lockdown overlapping Chinese Spring Festival on household PM2.5 in rural Chinese homes.

During the 2019 novel coronavirus (COVID-19) pandemic, many countries took strong lockdown policy to reduce disease spreading, resulting in mitigating the ambient air pollution due to less traffic and industrial emissions. However, limited studies focused on the household air pollution especially in rural area, the potential risk induced by indoor air pollution exposure was unknown during this period. This field study continuously measured real-time PM2.5 levels in kitchen, living room, and outdoor in the normal days (Period-1) and the days of COVID-19 lockdown overlapping the Chinese Spring Festival (Period-2) in rural homes in China. The average daily PM2.5 concentrations increased by 17.4 and 5.1 µg/m3 in kitchen and living room during Period-2, respectively, which may be due to more fuel consumption for cooking and heating caused by larger family sizes than those during the normal days. The ambient PM2.5 concentration in rural areas in Period-2 decreased by 6.7 µg/m3 compared to the Period-1, less than the drop in urban areas (26.8 µg/m3). An increase of mass fraction of very fine particles in ambient air was observed during lockdown overlapping annual festival days, which could be explained by the residential solid fuel burning. Due to higher indoor air pollution level and longer time spent in indoor environments, daily personal exposure to PM2.5 was 134 ± 40 µg/m3 in Period-2, which was significantly higher than that during in Period-1 (126 ± 27 µg/m3, p < 0.05). The increase of personal PM2.5 exposure during Period-2 could potentially have negative impact on human health, indicating further investigations should be performed to estimate the health impact of global COVID-19 lockdown on community, especially in rural homes using solid fuels as the routine fuels.