Attenuated T cell activation and rearrangement of T cell receptor ß repertoire in silica nanoparticle-induced pulmonary fibrosis of mice.

Silica nanoparticles (SiNPs) cause pulmonary fibrosis through a complex immune response, but the underlying mechanisms by which SiNPs interact with T cells and affect their functions remain unclear. The T cell receptor (TCR) repertoire is closely related to T cell activation and proliferation and mediates innate and adaptive immunity. High-throughput sequencing of the TCR enables comprehensive monitoring of the immune microenvironment. Here, the role of the TCRß repertoire was explored using a mouse model of SiNP-induced pulmonary fibrosis and a co-culture of RAW264.7 and CD4+ T cells. Our results demonstrated increased TCRß expression and decreased CD25 and CD69 expression in CD4+ T cells from peripheral blood and lung collected 14 days after the induction of pulmonary fibrosis by SiNPs. Simultaneously, SiNPs significantly decreased CD25 and CD69 expression in CD4+ T cells in vitro via RAW264.7 cell presentation. Mechanistically, pLCK and pZap70 expression, involved in mediating T cell activation, were also decreased in the lung of mice with SiNP-induced pulmonary fibrosis. Furthermore, the profile of the TCRß repertoire in mice with SiNP-induced pulmonary fibrosis showed that SiNPs markedly altered the usage of V genes, VJ gene combinations, and CDR3 amino acids in lung tissue. Collectively, our data suggested that SiNPs could interfere with T cell activation by macrophage presentation via the LCK/Zap70 pathway and rearrange the TCRß repertoire for adaptive immunity and the pulmonary microenvironment.

Vascular benefits of vitamin C supplementation against fine particulate air pollution in healthy adults: A double-blind randomised crossover trial.

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 µg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

Simultaneous Determination of Six Immunosuppressants in Human Whole Blood by HPLC-MS/MS Using a Modified QuEChERS Method.

A high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of mycophenolic acid, mycophenolate mofetil, tacrolimus, rapamycin, everolimus and pimecrolimus in human whole blood by optimizing the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) preparation method. Whole blood was extracted into ethyl acetate, salted out with anhydrous magnesium sulfate, and purified with ethylenediamine-N-propyl silane adsorbent. The supernatant was evaporated under nitrogen until dry and finally reconstituted in methanol. Chromatographic separation was performed on an Agilent Poroshell 120 EC-C18 column in methanol (mobile phase A)-water (optimized for 0.1% acetic acid and 10 mM ammonium acetate, mobile phase B) at a 0.3 mL·min−1 flow rate. Electrospray ionization and positive ion multiple reaction monitoring were used for detection. The time for of analysis was 13 min. The calibration curves range of tacrolimus, rapamycin, everolimus and pimecrolimus were in the range of 1−100 ng·mL−1, mycophenolate mofetil in the range of 0.1−10 ng·mL−1 and mycophenolic acid at 10−1000 ng·mL−1. All correlation coefficients were >0.993. The coefficients of variation (CV, %) for inter-day and intra-day precision were less than 10%, while the spiked recoveries were in the range of 92.1% to 116%. Our method was rapid, sensitive, specific, and reproducible for the simultaneous determination of six immunosuppressants in human whole blood. Importantly, our approach can be used to monitor drug concentrations in the blood to facilitate disease treatment.

Effects of low-concentration glyphosate and aminomethyl phosphonic acid on zebrafish embryo development.

Glyphosate (GLY) is the most widely used broad-spectrum, non-selective herbicide in the world, whose main degradation product is aminomethyl phosphonic acid (AMPA). Because of long-term and large-scale use, residual GLY and AMPA in the environment pose great environmental and human health threats. The purpose of this study is to evaluate the effects and mechanism of residual low-concentrations of GLY and AMPA in the environment on the development of zebrafish embryos. Zebrafish embryos were exposed to 0, 1, 10, 100, and 700 ng·mL-1 GLY and AMPA for 72 h (from 2 to 74 h post-fertilization). With increasing exposure dose, heart rates of both embryos and larvae showed a rising trend and obvious arrhythmia appeared. Defects in cardiac development and function of zebrafish juveniles may be related to altered transcription levels of cardiac development genes (TBX5, NKX2.5, BMP4) and apoptosis genes (Bcl-2, Bax). In addition, pericardial edema and bone deformation of zebrafish embryos may be caused by inhibition of Na+/K+-ATPase and Ca2+-ATPase after exposure to GLY and AMPA. The present results demonstrated that at typical environmental residual concentrations of GLY and AMPA had similar developmental toxicity in zebrafish embryos.

Multiple techniques to evaluate the relationship between carotid artery plaque and acute stroke.

AIM: To evaluate the important characteristics of the plaque vulnerability using multimodal ultrasound imaging methods (2D, contrast-enhanced ultrasound, and elastography), and to explore the relationship between plaque and acute stroke. METHODS: A total of 244 patients with carotid plaque were enrolled, including 104 patients with acute stroke ipsilateral to the plaque as the case group and 140 patients as the control group. All patients underwent conventional carotid ultrasound, contrast-enhanced ultrasound (CEUS) and elastography (SWE). The results of each examination were compared and analyzed, and the relationship between the results and the occurrence of stroke was discussed. RESULTS: In the acute stroke group, the men, with a history of alcohol consumption the direction of contrast media diffusion was higher than that in the control group, but the plaque gray value (GSM), maximum, average and minimum Young's elastic modulus imaging values (YM) were slightly lower than those in the control group (P < 0.05). Logistic regression analysis showed that waist to body ratio (WHtR), GSM, YM, neovascularization density and contrast diffusion direction were independent risk factors for predicting acute ischemic stroke. The influence degree of each factor from strong to weak was waist to body ratio, neovascularity density, GSM and YM, respectively. The area under the curve (AUC) for the diagnosis of acute ischemic stroke by regression model was 0.746. CONCLUSION: The combination of multiple ultrasound techniques to evaluate the vulnerability of carotid plaque and predict the occurrence of acute stroke provides valuable information for clinical decision making.

The effect of temperature on infectious diarrhea disease: A systematic review.

This study aimed to ascertain the delayed effects of various exposure temperatures on infectious diarrhea. We performed a Bayesian random-effects network meta-analysis to calculate relative risks (RR) with 95 % confidence intervals (95 % CI). The heterogeneity was analyzed by subgroup analysis. There were 25 cross-sectional studies totaling 6858735 patients included in this analysis, with 12 articles each investigating the effects of both hyperthermia and hypothermia. Results revealed that both high temperature (RRsingle = 1.22, 95%CI:1.04-1.44, RRcum = 2.96, 95%CI:1.60-5.48, P < 0.05) and low temperature (RRsingle = 1.17, 95%CI:1.02-1.37, RRcum = 2.19, 95%CI:1.33-3.64, P < 0.05) significantly increased the risk of infectious diarrhea, while high temperature caused greater. As-sociations with strengthening in bacillary dysentery were found for high temperatures (RRcum = 2.03, 95%CI:1.41-3.01, P < 0.05; RRsingle = 1.17, 95%CI:0.90-1.62, P > 0.05), while the statistical significance of low temperatures in lowering bacterial dysentery had vanished. This investigation examined that high temperature and low temperature were the conditions that posed the greatest risk for infectious diarrhea. This research offers fresh perspectives on preventing infectious diarrhea and will hopefully enlighten future studies on the impact of temperature management on infectious diarrhea.

A systematic review and meta-analysis of the association between air pollutants and the incidence of tuberculosis.

Objective: To investigate the association between air pollutants and the incidence of tuberculosis (TB) through a systematic review and meta-analysis, and to provide directions for future research and prevention of TB. Methods: A search was conducted for all literature related to the incidence of TB and air pollution in the database. We screened the retrieved articles and proceeded statistical analyses using random effects models to investigate the relationships between five air pollutants (PM2.5, PM10, SO2, NO2 and O3) and the incidence of TB. Results: The initial search identified 100 pieces of literature and 9 studies met the screening criteria after the screening. The single-day lagged risk ratio (RR) and 95% Confidence Intervals (CIs) for the combined effects estimates are as follows: PM2.5: 1.059 (0.966, 1.160); PM10: 1.000 (0.996, 1.004); SO2: 0.980 (0.954, 1.007); NO2: 1.011 (0.994, 1.027); O3: 0.994 (0.980,1.008). The cumulative lagged results for these five pollutants are listed like this: PM2.5: 1.095 (0.983, 1.219); PM10: 1.035 (1.006, 1.066); SO2: 0.964 (0.830, 1.121); NO2: 1.037 (1.010, 1.065); O3: 0.982 (0.954, 1.010). Conclusion: The single-day lag effects of PM2.5, PM10, SO2, NO2, and O3 are not statistically significantly relevant for the occurrence of TB. However, the cumulative lag results show that both PM10 and NO2 contribute to the prevalence of TB, while the statistical relationship between the cumulative lag effects of PM2.5, SO2, and O3 and the onset of TB remains unknown.

Sesamin Ameliorates Fine Particulate Matter (PM2.5)-Induced Lung Injury via Suppression of Apoptosis and Autophagy in Rats.

Lung damage can be caused by fine particulate matter (PM2.5). Thus, effective prevention strategies for PM2.5-induced lung injury are urgently required. Sesamin (Ses) is a natural polyphenolic compound that has attracted considerable attention of researchers because of its wide range of pharmacological activities. The present study aims to elucidate whether Ses pretreatment could alleviate PM2.5-induced lung damage and identify its possible mechanisms. Sprague-Dawley rats were orally dosed with 0.5% carboxymethylcellulose (CMC) and different concentrations of Ses once a day for 21 days. Then, the rats of the PM2.5 exposure group and Ses-treated group were exposed to PM2.5 by intratracheal instillation every 2 days for 1 week. Biomarkers associated with lung injury were detected in bronchoalveolar lavage fluid (BALF). Lung tissue was collected for histology, inflammation, oxidative stress, immunohistochemistry, and Western blot. Our results showed that PM2.5 exposure could cause pathological changes in lung tissue and increase levels of TP, AKP, and ALB in BALF. Meanwhile, exposure to PM2.5 can cause oxidative stress and inflammation in the lungs. In addition, Ses pretreatment could ameliorate histopathological injury, oxidative stress, and inflammation caused by PM2.5 exposure. It could also inhibit PM2.5-induced apoptosis and upregulation of autophagy-associated proteins. Collectively, our study indicated that Ses pretreatment could ameliorate PM2.5-induced lung damage via inhibiting apoptosis and autophagy in rats.