scholarly journals The Cytotoxicity of PM2.5 and its Effect on the Secretome of Normal Human Bronchial Epithelial Cells

Author(s):  
Zhigang Sui ◽  
Xiaoyao Song ◽  
Yujie Wu ◽  
Rui Hou ◽  
Jianhui Liu ◽  
...  

Abstract Exposure to airborne fine particulate matter (PM2.5) induced various adverse health effects, such as metabolic syndrome, systemic inflammation and respiratory infection. Many works have studied the influence of PM2.5 exposure to intracellular proteome and the underlying mechanism. But the extracellular proteome changes under PM2.5 exposure, and the correlation between secretome changes and PM2.5-induced cytotoxicity remains confusing. Herein, the cytotoxicity of PM2.5 on normal human bronchial epithelia cells (BEAS-2B) was evaluated and the secretome profile of BEAS-2B cells before and after PM2.5 exposure was investigated. The secretion of 83 proteins (58 up-regulated and 25 down-regulated) was differentially expressed upon PM2.5 treatment. In addition to apoptosis, extracellular matrix (ECM) organization, complement activation and RNA splicing were also found to be involved in PM2.5 mediated cytotoxicity. These results provide an insight into the underlying mechanism of respiratory injury caused by PM2.5.

2006 ◽  
Vol 17 (2) ◽  
pp. 566-575 ◽  
Author(s):  
Sita Aggarwal ◽  
Seung-Wook Kim ◽  
Kyounga Cheon ◽  
Fazal H. Tabassam ◽  
Joo-Heon Yoon ◽  
...  

Vitamin A (retinol) is essential for normal regulation of cell growth and differentiation. We have shown that the retinol metabolite retinoic acid (RA) induces mucous cell differentiation of normal human tracheobronchial epithelial (NHTBE) cells. However, early biological effects of RA in the differentiation of bronchial epithelia are largely unknown. Here, we showed that RA rapidly activated cAMP response element-binding protein (CREB). However, RA did not use the conventional retinoic acid receptor (RAR)/retinoid X receptor (RXR) to activate CREB. RA activated CREB in NHTBE and H1734 cells in which RARs/RXR were silenced with small interfering RNA (siRNA) targeting RAR/RXR expression or deactivated by antagonist. Inhibition of protein kinase C (PKC) or extracellular regulated kinase (ERK1/2) blocked the RA-mediated activation of CREB. In addition, depletion of p90 ribosomal S6 kinase (RSK) via siRSK1/2 completely abolished the activation, suggesting that PKC, ERK, and RSK are required for the activation. Altogether, this study provides the first evidence that RA rapidly activates CREB transcription factor via PKC, ERK, and RSK in a retinoid receptor-independent manner in normal bronchial epithelial cells. This noncanonical RA signaling pathway may play an important role in mediating early biological effects in the mucociliary differentiation of bronchial epithelia.


1994 ◽  
Vol 71 (01) ◽  
pp. 091-094 ◽  
Author(s):  
M Cattaneo ◽  
B Akkawat ◽  
R L Kinlough-Rathbone ◽  
M A Packham ◽  
C Cimminiello ◽  
...  

SummaryNormal human platelets aggregated by thrombin undergo the release reaction and are not readily deaggregated by the combination of inhibitors hirudin, prostaglandin E1 (PGE1) and chymotrypsin. Released adenosine diphosphate (ADP) plays an important role in the stabilization of thrombin-induced human platelet aggregates. Since ticlopidine inhibits the platelet responses to ADP, we studied thrombin-induced aggregation and deaggregation of 14C-serotonin-labeled platelets from 12 patients with cardiovascular disease before and 7 days after the oral administration of ticlopidine, 250 mg b.i.d. Before and after ticlopidine, platelets stimulated with 1 U/ml thrombin aggregated, released about 80–90% 14C-serotinin and did not deaggregate spontaneously within 5 min from stimulation. Before ticlopidine, hirudin (5× the activity of thrombin) and PGE1 (10 μmol/1) plus chymotrypsin (10 U/ml) or plasmin (0.06 U/ml), added at the peak of platelet aggregation, caused slight or no platelet deaggregation. After ticlopidine, the extent of platelet deaggregation caused by the same inhibitors was significantly greater than before ticlopidine. The addition of ADP (10 μmol/1) to platelet suspensions 5 s after thrombin did not prevent the deaggregation of ticlopidine-treated platelets. Thus, ticlopidine facilitates the deaggregation of thrombin-induced human platelet aggregates, most probably because it inhibits the effects of ADP on platelets.


Author(s):  
Jill Hahn ◽  
Diane R. Gold ◽  
Brent A. Coull ◽  
Marie C. McCormick ◽  
Patricia W. Finn ◽  
...  

Prenatal maternal exposure to air pollution may cause adverse health effects in offspring, potentially through altered immune responses. Maternal psychosocial distress can also alter immune function and may increase gestational vulnerability to air pollution exposure. We investigated whether prenatal exposure to air pollution is associated with altered immune responses in cord blood mononuclear cells (CBMCs) and potential modification by maternal depression in 463 women recruited in early pregnancy (1999–2001) into the Project Viva longitudinal cohort. We estimated black carbon (BC), fine particulate matter (PM2.5), residential proximity to major roadways, and near-residence traffic density, averaged over pregnancy. Women reported depressive symptoms in mid-pregnancy (Edinburgh Postnatal Depression Scale) and depression history by questionnaire. Immune responses were assayed by concentrations of three cytokines (IL-6, IL-10, and TNF-α), in unstimulated or stimulated (phytohemagglutinin (PHA), cockroach extract (Bla g 2), house dust mite extract (Der f 1)) CBMCs. Using multivariable linear or Tobit regression analyses, we found that CBMCs production of IL-6, TNF-a, and IL-10 were all lower in mothers exposed to higher levels of PM2.5 during pregnancy. A suggestive but not statistically significant pattern of lower cord blood cytokine concentrations from ever (versus never) depressed women exposed to PM2.5, BC, or traffic was also observed and warrants further study.


Sensors ◽  
2021 ◽  
Vol 21 (14) ◽  
pp. 4698
Author(s):  
Xian Yue ◽  
Yaliang Yang ◽  
Fei Xiao ◽  
Hao Dai ◽  
Chao Geng ◽  
...  

Virtual Shack–Hartmann wavefront sensing (vSHWS) can flexibly adjust parameters to meet different requirements without changing the system, and it is a promising means for aberration measurement. However, how to optimize its parameters to achieve the best performance is rarely discussed. In this work, the data processing procedure and methods of vSHWS were demonstrated by using a set of normal human ocular aberrations as an example. The shapes (round and square) of a virtual lenslet, the zero-padding of the sub-aperture electric field, sub-aperture number, as well as the sequences (before and after diffraction calculation), algorithms, and interval of data interpolation, were analyzed to find the optimal configuration. The effect of the above optimizations on its anti-noise performance was also studied. The Zernike coefficient errors and the root mean square of the wavefront error between the reconstructed and preset wavefronts were used for performance evaluation. The performance of the optimized vSHWS could be significantly improved compared to that of a non-optimized one, which was also verified with 20 sets of clinical human ocular aberrations. This work makes the vSHWS’s implementation clearer, and the optimization methods and the obtained results are of great significance for its applications.


Author(s):  
Bing Song ◽  
Xiao-Yong Yan ◽  
Suoyi Tan ◽  
Bin Sai ◽  
Shengjie Lai ◽  
...  

Understanding the spatial interactions of human mobility is crucial for urban planning, traffic engineering, as well as for the prevention and control of infectious diseases. Although many models have been developed to model human mobility, it is not clear whether such models could also capture the traveling mechanisms across different time periods (e.g. workdays, weekends or holidays). With one-year long nationwide location-based service (LBS) data in China, we investigate the spatiotemporal characteristics of population movements during different time periods, and make thorough comparisons for the applicability of five state-of-the-art human mobility models. We find that population flows show significant periodicity and strong inequality across temporal and spatial distribution. A strong “backflow” effect is found for cross-city movements before and after holidays. Parameter fitting of gravity models reveals that travels in different type of days consider the attractiveness of destinations and cost of distance differently. Surprisingly, the comparison indicates that the parameter-free opportunity priority selection (OPS) model outperforms other models and is the best to characterize human mobility in China across all six different types of days. However, there is still an urgent need for development of more dedicated models for human mobility on weekends and different types of holidays.


2019 ◽  
Author(s):  
Xuebin Tian ◽  
Qiongdan Wang ◽  
Xiangkuo Zheng ◽  
Yajie Zhao ◽  
Renchi Fang ◽  
...  

Abstract The emergence of carbapenem-resistant Kelbsiella pneumoniae (CRKP) posed threats to human health. Although there are numerous studies regarding porin alteration in association with the production of ESBLs and/or AmpC β-lactamase, a systematic research about the treatment-emergence of porins alteration in antibiotic resistance does not exist yet. The aim of this study was to investigate the underlying mechanism and evolution of resistance of K. pneumoniae during carbapenem treatment. Here, we reported three strains (FK-2624, FK-2723 and FK-2820) isolated from one patient before and after imipenem treatment during hospitalization. Antibiotic susceptibility testing indicated that FK-2624 was susceptible to almost antimicrobials but fosfomycin; FK-2723 and FK-2820 were MDR. After imipenem therapy, FK-2820 was evolved to carbapenem-resistant. PCR and Whole-Genome sequencing ( WGS) indicated that resistance genes bla SHV , oqxA and fosA5 were detected in FK-2624, in addition, FK-2723 and FK-2820 harbored bla DHA , qnrB , aac (6’)-Ib . Virulence factors K57, ybtA, mrkD, entB and iroN were detected simultaneously in all of three strains. The results of pairwise comparisons , multi-locus sequencing typing (MLST) and pulsed-field gel electrophoresis (PFGE) revealed high homology among the isolates. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results showed that isolate FK-2820 lacked OmpK 36 as there was a premature stop codon of the outer membrane porin encoding gene ompk36 confirmed by sequencing. Real-time RT-PCR revealed that the expression of ompK36 in FK-2820 was 0.093 times the control isolate ATCC 13883. Our study highlighted that the alteration of outer membrane porins due to the 14-day use of imipenem clinically play a potential role in leading to the carbapenems-resistance of FK-2820.


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