Study of the Effects of Total Flavonoids of Astragalus on Atherosclerosis Formation and Potential Mechanisms

Astragalus mongholicus Bunge has long been used to treat cardiovascular disease in Chinese traditional medicine. However, its mechanisms are not fully understood. In this study, we explored potential mechanisms and protective effects of total flavonoids of Astragalus (TFA) on cardiovascular disease using in vitro experiments and diet-induced atherosclerotic rabbits. We identified six components and their proportion in TFA. The animal experiments showed that TFA significantly reduced plasma levels of total cholesterol and LDL cholesterol (P < 0.05 to 0.01), increased HDL cholesterol levels (P < 0.01), and reduced the aortic fatty streak area by 43.6 to 63.6% (P < 0.01). We also found that TFA scavenged superoxide and hydroxyl radicals and this effect increased with higher TFA concentration. In in vivo experiments, TFA effectively inhibited the free radical spectrum in the ischemia-reperfusion module. In conclusion, TFA was the active component of Astragalus mongholicus Bunge, which benefits cardiovascular disease attributing to the potent antioxidant activity to improve the atherosclerosis profile

Temporal profiling of the cortical synaptic mitochondrial proteome identifies ageing associated regulators of stability

Synapses are particularly susceptible to the effects of advancing age, and mitochondria have long been implicated as organelles contributing to this compartmental vulnerability. Despite this, the mitochondrial molecular cascades promoting age-dependent synaptic demise remain to be elucidated. Here, we sought to examine how the synaptic mitochondrial proteome (including strongly mitochondrial associated proteins) was dynamically and temporally regulated throughout ageing to determine whether alterations in the expression of individual candidates can influence synaptic stability/morphology. Proteomic profiling of wild-type mouse cortical synaptic and non-synaptic mitochondria across the lifespan revealed significant age-dependent heterogeneity between mitochondrial subpopulations, with aged organelles exhibiting unique protein expression profiles. Recapitulation of aged synaptic mitochondrial protein expression at the Drosophila neuromuscular junction has the propensity to perturb the synaptic architecture, demonstrating that temporal regulation of the mitochondrial proteome may directly modulate the stability of the synapse in vivo

IL-4Rα Blockade by Dupilumab Decreases Staphylococcus aureus Colonization and Increases Microbial Diversity in Atopic Dermatitis.

Dupilumab is a fully human antibody to interleukin-4 receptor α that improves the signs and symptoms of moderate to severe atopic dermatitis (AD). To determine the effects of dupilumab on Staphylococcus aureus colonization and microbial diversity on the skin, bacterial DNA was analyzed from swabs collected from lesional and nonlesional skin in a double-blind, placebo-controlled study of 54 patients with moderate to severe AD randomized (1:1) and treated with either dupilumab (200 mg weekly) or placebo for 16 weeks. Microbial diversity and relative abundance of Staphylococcus were assessed by DNA sequencing of 16S ribosomal RNA, and absolute S.&nbsp;aureus abundance was measured by quantitative PCR. Before treatment, lesional skin had lower microbial diversity and higher overall abundance of S.&nbsp;aureus than nonlesional skin. During dupilumab treatment, microbial diversity increased and the abundance of S.&nbsp;aureus decreased. Pronounced changes were seen in nonlesional and lesional skin. Decreased S.&nbsp;aureus abundance during dupilumab treatment correlated with clinical improvement of AD and biomarkers of type 2 immunity. We conclude that clinical improvement of AD that is mediated by interleukin-4 receptor α inhibition and the subsequent suppression of type 2 inflammation is correlated with increased microbial diversity and reduced abundance of S.&nbsp;aureus

Hard rock landforms generate 130 km ice shelf channels through water focusing in basal corrugations

This work is licensed under a Creative Commons Attribution 4.0 International License.Satellite imagery reveals flowstripes on Foundation Ice Stream parallel to ice flow, and meandering features on the ice-shelf that cross-cut ice flow and are thought to be formed by water exiting a well-organised subglacial system. Here, ice-penetrating radar data show flow-parallel hard-bed landforms beneath the grounded ice, and channels incised upwards into the ice shelf beneath meandering surface channels. As the ice transitions to flotation, the ice shelf incorporates a corrugation resulting from the landforms. Radar reveals the presence of subglacial water alongside the landforms, indicating a well-organised drainage system in which water exits the ice sheet as a point source, mixes with cavity water and incises upwards into a corrugation peak, accentuating the corrugation downstream. Hard-bedded landforms influence both subglacial hydrology and ice-shelf structure and, as they are known to be widespread on formerly glaciated terrain, their influence on the ice-sheet-shelf transition could be more widespread than thought previously.NASA grant # NNX10AT68GANT # NT-0424589University of KansasUK NERC AFI grant NE/G013071/

Impacts of ambient air quality on acute asthma hospital admissions during the COVID-19 pandemic in Oxford City, UK:a time-series study

OBJECTIVES: The study aims to investigate the short-term associations between exposure to ambient air pollution (nitrogen dioxide (NO2), particulate matter pollution-particles with diameter&lt;2.5 µm (PM2.5) and PM10) and incidence of asthma hospital admissions among adults, in Oxford, UK.DESIGN: Retrospective time-series study.SETTING: Oxford City (postcode areas OX1-OX4), UK.PARTICIPANTS: Adult population living within the postcode areas OX1-OX4 in Oxford, UK from 1 January 2015 to 31 December 2021.PRIMARY AND SECONDARY OUTCOME MEASURES: Hourly NO2, PM2.5 and PM10 concentrations and meteorological data for the period 1 January 2015 to 31 December 2020 were analysed and used as exposures. We used Poisson linear regression analysis to identify independent associations between air pollutant concentrations and asthma admissions rate among the adult study population, using both single (NO2, PM2.5, PM10) and multipollutant (NO2 and PM2.5, NO2 and PM10) models, where they adjustment for temperature and relative humidity.RESULTS: The overall 5-year average asthma admissions rate was 78 per 100 000 population during the study period. The annual average rate decreased to 46 per 100 000 population during 2020 (incidence rate ratio 0.58, 95% CI 0.42 to 0.81, p&lt;0.001) compared to the prepandemic years (2015-2019). In single-pollutant analysis, we observed a significantly increased risk of asthma admission associated with each 1 μg/m3 increase in monthly concentrations of NO2 4% (95% CI 1.009% to 1.072%), PM2.5 3% (95% CI 1.006% to 1.052%) and PM10 1.8% (95% CI 0.999% to 1.038%). However, in the multipollutant regression model, the effect of each individual pollutant was attenuated.CONCLUSIONS: Ambient NO2 and PM2.5 air pollution exposure increased the risk of asthma admissions in this urban setting. Improvements in air quality during COVID-19 lockdown periods may have contributed to a substantially reduced acute asthma disease burden. Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas.</p

Impacts of ambient air quality on acute asthma hospital admissions during the COVID-19 pandemic in Oxford City, UK: a time-series study

Objectives: The study aims to investigate the short-term associations between exposure to ambient air pollution (nitrogen dioxide (NO2), particulate matter pollution—particles with diameter<2.5 µm (PM2.5) and PM10) and incidence of asthma hospital admissions among adults, in Oxford, UK. Design: Retrospective time-series study. Setting: Oxford City (postcode areas OX1–OX4), UK. Participants: Adult population living within the postcode areas OX1–OX4 in Oxford, UK from 1 January 2015 to 31 December 2021. Primary and secondary outcome measures: Hourly NO2, PM2.5 and PM10 concentrations and meteorological data for the period 1 January 2015 to 31 December 2020 were analysed and used as exposures. We used Poisson linear regression analysis to identify independent associations between air pollutant concentrations and asthma admissions rate among the adult study population, using both single (NO2, PM2.5, PM10) and multipollutant (NO2 and PM2.5, NO2 and PM10) models, where they adjustment for temperature and relative humidity. Results: The overall 5-year average asthma admissions rate was 78 per 100 000 population during the study period. The annual average rate decreased to 46 per 100 000 population during 2020 (incidence rate ratio 0.58, 95% CI 0.42 to 0.81, p<0.001) compared to the prepandemic years (2015–2019). In single-pollutant analysis, we observed a significantly increased risk of asthma admission associated with each 1 μg/m3 increase in monthly concentrations of NO2 4% (95% CI 1.009% to 1.072%), PM2.5 3% (95% CI 1.006% to 1.052%) and PM10 1.8% (95% CI 0.999% to 1.038%). However, in the multipollutant regression model, the effect of each individual pollutant was attenuated. Conclusions: Ambient NO2 and PM2.5 air pollution exposure increased the risk of asthma admissions in this urban setting. Improvements in air quality during COVID-19 lockdown periods may have contributed to a substantially reduced acute asthma disease burden. Large-scale measures to improve air quality have potential to protect vulnerable people living with chronic asthma in urban areas

CD8 T Cell Recognition of Endogenously Expressed Epstein-Barr Virus Nuclear Antigen 1

The Epstein-Barr virus (EBV) nuclear antigen (EBNA)1 contains a glycine-alanine repeat (GAr) domain that appears to protect the antigen from proteasomal breakdown and, as measured in cytotoxicity assays, from major histocompatibility complex (MHC) class I–restricted presentation to CD8+ T cells. This led to the concept of EBNA1 as an immunologically silent protein that although unique in being expressed in all EBV malignancies, could not be exploited as a CD8 target. Here, using CD8+ T cell clones to native EBNA1 epitopes upstream and downstream of the GAr domain and assaying recognition by interferon γ release, we show that the EBNA1 naturally expressed in EBV-transformed lymphoblastoid cell lines (LCLs) is in fact presented to CD8+ T cells via a proteasome/peptide transporter–dependent pathway. Furthermore, LCL recognition by such CD8+ T cells, although slightly lower than seen with paired lines expressing a GAr-deleted EBNA1 protein, leads to strong and specific inhibition of LCL outgrowth in vitro. Endogenously expressed EBNA1 is therefore accessible to the MHC class I pathway despite GAr-mediated stabilization of the mature protein. We infer that EBNA1-specific CD8+ T cells do play a role in control of EBV infection in vivo and might be exploitable in the control of EBV+ malignancies