Effects of Urban Particulate Matter on the Olfactory System in a Mouse Model

2021 ◽  
pp. 194589242110264
Author(s):  
Boo-Young Kim ◽  
Ju Y. Park ◽  
Kwang J. Cho ◽  
Jung H. Bae

Background Exposure to urban particulate matter (UPM) is linked to the aggravation of various health problems. Although the nasal cavity is the first barrier to encounter UPM, there is a lack of studies on the impact of UPM on the olfactory area. The purpose of this study was to investigate the cytotoxic effects of UPM on mouse olfactory epithelium, the underlying pathophysiology involved, and changes in cytokine levels. Methods Mice were divided into 4 groups: control, 400UPM (administered 400 µg UPM daily; standard reference material 1649b; average particle diameter 10.5 μm) 1week, 400UPM 2weeks, and recovery 1week after 400UPM 2weeks (n = 10, 6, 6, and 6, respectively). Olfactory function was evaluated by conducting a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. Results Compared to those in the control group, olfactory marker protein, olfactory receptor 1507, adenylyl cyclase 3, and GNAL mRNA levels were lower and S-100, 2′,3′-cyclic nucleotide 30-phosphodiesterase, nerve growth factor receptor-associated protein, brain-derived neurotrophic factor, and tachykinin receptor mRNA levels were higher in the 400UPM group olfactory neuroepithelium. There were no significant differences in neuroepithelial inflammatory marker levels between the 400UPM and saline group. Conclusions UPM decreased olfactory function and might have cytotoxic effects on the olfactory epithelium. Olfactory ensheathing cells and trigeminal nerve might be related to the regeneration of the olfactory epithelium after olfactory destruction associated with UPM.

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
B.-Y. Kim ◽  
J.Y. Park ◽  
K.J. Cho ◽  
J.H. Bae

Background: Urban particulate matter (UPM) in ambient air is implicated in a variety of human health issues worldwide, however, few studies exist on the effect of UPM on the olfactory system. This study aimed to identify the factors affecting the destruction of the olfactory system in a mouse model following UPM exposure. Methods: Mice were divided into: control and four UPM-exposed groups (200 µg UPM at 1 and 2 weeks, and 400 µg UPM at 1 and 2 weeks [standard reference material 1649b; average particle diameter 10.5 μm]). The olfactory neuroepithelium was harvested for histologic examination, gene ontology, quantitative real-time polymerase chain reaction, and western blotting. Results: Compared to the control group, olfactory marker protein, Olfr1507, ADCY3, and GNAL mRNA levels were lower, and S-100, CNPase, NGFRAP1, BDNF, and TACR3 mRNA levels were higher in the olfactory neuroepithelium of the UPM groups. Moderately positive correlation was present between the 1- and 2-week groups. After analyzing the 200 and 400 UPM groups separately, the strength of the association between the 200 UPM 1- and 2-week groups was moderately positive. No differences was present in the neuroepithelial inflammatory marker levels between the UPM and control groups. Conclusions: UPM could have cytotoxic effects on the olfactory epithelium. The exposure time and particular concentration of UPM exposure could affect the degree of destruction of the olfactory neuroepithelium. The olfactory regeneration mechanism could be related to the neurotrophic factors, olfactory ensheathing cell stimulation, and trigeminal nerve support.


2020 ◽  
Vol 21 (17) ◽  
pp. 6079
Author(s):  
Yu Ri Woo ◽  
Seo-Yeon Park ◽  
Keonwoo Choi ◽  
Eun Sun Hong ◽  
Sungjoo Kim ◽  
...  

Air pollution reportedly contributes to the development and exacerbation of atopic dermatitis (AD). However, the exact mechanism underlying this remains unclear. To examine the relationship between air pollution and AD, a clinical, histological, and genetic analysis was performed on particulate matter (PM)-exposed mice. Five-week-old BALB/c mice were randomly divided into four groups (control group, ovalbumin (OVA) group, PM group, OVA + PM group; n = 6) and treated with OVA or PM10, alone or together. Cutaneous exposure to OVA and PM10 alone resulted in a significant increase in skin severity scores, trans-epidermal water loss (TEWL) and epidermal thickness compared to the control group at Week 6. The findings were further accentuated in the OVA + PM group showing statistical significance over the OVA group. A total of 635, 501, and 2149 genes were found to be differentially expressed following OVA, PM10, and OVA + PM10 exposure, respectively. Strongly upregulated genes included RNASE2A, S100A9, SPRR2D, THRSP, SPRR2A1 (OVA vs. control), SPRR2D, S100A9, STFA3, CHIL1, DBP, IL1B (PM vs. control) and S100A9, SPRR2D, SPRR2B, S100A8, SPRR2A3 (OVA + PM vs. control). In comparing the groups OVA + PM with OVA, 818 genes were differentially expressed with S100A9, SPRR2B, SAA3, S100A8, SPRR2D being the most highly upregulated in the OVA + PM group. Taken together, our study demonstrates that PM10 exposure induces/aggravates skin inflammation via the differential expression of genes controlling skin barrier integrity and immune response. We provide evidence on the importance of public awareness in PM-associated skin inflammation. Vigilant attention should be paid to all individuals, especially to those with AD.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Maria Lerche Mace ◽  
Eva Gravesen ◽  
Anders Nordholm ◽  
Soeren Egstrand ◽  
Marya Morevati ◽  
...  

Abstract Background and Aims Several studies report an association between low BMD and vascular calcification (VC) in the general population and in CKD patients. Development of VC in CKD is a cell regulated process where the vascular smooth muscle cell alters phenotype to a bone-like secretory cell. Our group has previously demonstrated the expression of Wnt inhibitors in VC and so we ask if the presence of VC affects bone metabolism. Method A novel model of isogenic aorta transplantation (ATx) was developed and used in the study. Severe uremic vascular calcifications were induced in inbred Dark Aguti (DA) rats by 5/6 nephrectomy, high phosphate diet and calcitriol treatment. After 14 weeks the calcified abdominal aorta of the uremic rat was transplanted into a normal DA rat (uremic ATx, n=16). A normal aorta was transplanted into a normal DA rat as sham group (normal ATx, n=9) and age-matched normal rats were used as one more control group (control, n=6). Rats were sacrificed 4 weeks after ATx and plasma biochemistry, bone and vessels were analyzed. Data are presented as mean±SEM or median [range]. Statistical significance *p<0.5,**p<0.01,*** p<0.001. Results The uremic donor rat suffered from severe kidney disease with disturbed mineral balance and its aorta had a high calcium content of 15.7±0.8 µg Ca/mg vs. none in the normal aorta. Uremic ATx, normal ATx and control rats had same plasma levels of creatinine, Ca2+, phosphate, PTH, FGF23 and sclerostin. The uremic ATx had significant lower bone mineral density (BMD) compared to normal ATx and control rats (1576±5 vs. 1592±5* & 1613±6* mg/cc). The impact on bone mineralization was also detected in the bone histomorphometry analysis, where the uremic ATx had less osteoid compared to normal ATx (median 3% [0,3%;8%] vs. 5% [2%;8%]*). Moreover, the uremic ATx had fewer osteoblasts and more osteoclasts. The effect on bone was supported by substantial gene analysis of several genes related to bone remodeling, mineralization and Wnt signaling. The uremic ATx rats had significant changes in mRNA levels of several genes in bone compared to normal ATX and control rats such as increased alkaline phosphatase (3.26±0.29 vs. 1.56±0.32*** & 0.86±0.12***), decreased osteoblast marker osteocalcin (0.54±0.06 vs. 0.92±0.14* & 1.19±0.06***) and increased osteoclast marker cathepsin K (2.36±0.24 vs. 1.19±0.23** & 1.01±0.07***). In addition, we found upregulation of the bone mineralization inhibitors osteopontin (1.46±0.18 vs. 0.69±0.17** & 0.49±0.06**) and progressive ankylosis protein homolog (8.10±0.60 vs. 3.21±0.74** & 2.39±0.48**) as well as collagen I (9.30 [2.73;14.81] vs. 2.30 [0.31;19.33]* & 2.78 [1.63;7.52]***). The inhibitor of bone formation sclerostin was significant increased (2.90 [1.54;13,29] vs. 1,23 [0.32;3.20]** & 0.93 [0.39;2,19]**) along with a slight downregulation of bone stimulator BMP2 (3.18±0.15 vs. 4.06±0.30* & 3.98±0.44*. Finally, the Wnt signaling pathway was affected by upregulation of β-catenin (3.15±0.25 vs. 1.28±0.26*** & 1.03±0.13***) and the downstream gene Snail1 (3.73±0.33 vs. 1.54±0.45*** & 1.04±0.12***). Conclusion These novel findings indicate the existence of a tissue crosstalk between vessels and bone. The presence of vascular calcification lowers BMD, decreases the amount of osteoid and affects several pathways in bone.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Okumura ◽  
M Arai ◽  
N Otsuka ◽  
K Nagashima ◽  
R Watanabe ◽  
...  

Abstract Background Metabolic syndrome is a cluster of conditions including obesity, insulin resistance, hypertension, and abnormal cholesterol, which increases the cardiovascular risk. Metabolic syndrome or obesity has been reported to provide systemic inflammation and oxidative stress. Increased epicardial fat volume is a manifestation of obesity or metabolic syndrome. Those systemic and local conditions related to obesity or metabolic syndrome have been linking to the risk of atrial fibrillation (AF). The underlying mechanisms of obesity linking epicardial fat to AF progression have not been fully examined. Purpose To investigate the impact of obesity linked to epicardial fat on electrophysiologic and anatomical AF substrates. Methods Twenty dogs aged 3 years were divided into four groups (n=5 per each): normal diet for over 20 weeks (control group [median body weight: 12.0 kg]), rapid atrial pacing (RAP) for last 4–15 (median 8) weeks during a normal diet for the same period (RAP group [10.5 kg]), high-fat diet (HFD) maintained for over 20 weeks without RAP (MetS group [16.0 kg]), and RAP for last 4–12 (median 6) weeks during HFD maintained for 24 weeks (MetS-RAP group [17.0 kg]), respectively. Activation/voltage maps of the atria during sinus rhythm were created with Ensite NavX mapping system. The effective refractory period (ERP) at 5 left atrial (LA) and pulmonary vein (PV) sites (LA appendage [LAA], LA body, right and left superior PVs, and inferior PV), and AF inducibility by burst LAA pacing were determined. At study completion, hearts were excised for histopathological and gene expression analyses. Results The LA pressure was more significantly increased in MetS than the MetS-RAP, RAP, and control groups (22.5 [17–28.8] mmHg vs. 14.0 [10.5–16.3] mmHg, 10.5 [7.4–17.2] mmHg and 10.7 [9.6–13.5] mmHg, respectively, P<0.05). The LA/PV ERP at a basic cycle length of 400 ms was shorter in the MetS-RAP and RAP than MetS and control groups (118±39 ms and 122±44 ms vs. 136±18 ms and 155±39 ms, respectively, P<0.05). Short duration AF was more induced in the MetS and MetS-RAP than RAP and control groups (3 [0–5.5] sec and 2 [0.5–3.5] sec vs. 0 [0–4.5] sec and 0 [0–0] sec, P<0.05). Histological examinations showed the fatty infiltration extending from epicardial fat increased more in the Mets and Mets-RAP than RAP and control groups (Figure). The Fibronectin 1 and collagen I/III mRNA levels increased more in the MetS-RAP and AF than MetS and control groups. Conclusions AF vulnerability was associated with increased LA pressures and fibrofatty infiltration from epicardial fat in the MetS group, and with fibrofatty infiltration from epicardial fat with subtle fibrosis in the MetS-RAP group. This suggested that fibrofatty infiltration and epicardial fat plays an important role in AF pathogenesis in obese patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Scientific Research (KAKENHI)


2021 ◽  
Vol 22 (2) ◽  
pp. 818
Author(s):  
Narjes Nasiri-Ansari ◽  
Chrysa Nikolopoulou ◽  
Katerina Papoutsi ◽  
Ioannis Kyrou ◽  
Christos S. Mantzoros ◽  
...  

Aims/hypothesis: SGLT-2 inhibitors (SGLT-2i) have been studied as potential treatments against NAFLD, showing varying beneficial effects. The molecular mechanisms mediating these effects have not been fully clarified. Herein, we investigated the impact of empagliflozin on NAFLD, focusing particularly on ER stress, autophagy and apoptosis. Methods: Five-week old ApoE(-/-) mice were switched from normal to a high-fat diet (HFD). After five weeks, mice were randomly allocated into a control group (HFD + vehicle) and Empa group (HFD + empagliflozin 10 mg/kg/day) for five weeks. At the end of treatment, histomorphometric analysis was performed in liver, mRNA levels of Fasn, Screbp-1, Scd-1, Ppar-γ, Pck-1, Mcp-1, Tnf-α, Il-6, F4/80, Atf4, Elf2α, Chop, Grp78, Grp94, Χbp1, Ire1α, Atf6, mTor, Lc3b, Beclin-1, P62, Bcl-2 and Bax were measured by qRT-PCR, and protein levels of p-EIF2α, EIF2a, CHOP, LC3II, P62, BECLIN-1 and cleaved CASPASE-8 were assessed by immunoblotting. Results: Empagliflozin-treated mice exhibited reduced fasting glucose, total cholesterol and triglyceride serum levels, as well as decreased NAFLD activity score, decreased expression of lipogenic enzymes (Fasn, Screbp-1c and Pck-1) and inflammatory molecules (Mcp-1 and F4/80), compared to the Control group. Empagliflozin significantly decreased the expression of ER stress molecules Grp78, Ire1α, Xbp1, Elf2α, Atf4, Atf6, Chop, P62(Sqstm1) and Grp94; whilst activating autophagy via increased AMPK phosphorylation, decreased mTOR and increased LC3B expression. Finally, empagliflozin increased the Bcl2/Bax ratio and inhibited CASPASE-8 cleavage, reducing liver cell apoptosis. Immunoblotting analysis confirmed the qPCR results. Conclusion: These novel findings indicate that empagliflozin treatment for five weeks attenuates NAFLD progression in ApoE(-/-) mice by promoting autophagy, reducing ER stress and inhibiting hepatic apoptosis.


2021 ◽  
pp. 3834-3841
Author(s):  
Shaimaa H. Al–Dulaimi ◽  
Adel M. Rabee

The impact of exposure to different sizes of particulate matter (PM1, PM2.5, PM7, and PM10) was evaluated in  Babylon concrete plant workers who had been exposed to concrete dust for at least 10 years.  The effects of  these particles on the hematological parameters, malondialdehyde (MDA) levels, and  antioxidant enzymes (catalase and glutathione peroxidase ) were examined. The results exhibited that the levels of PM2.5 and PM10 were higher than the acceptable limits approved by the National Ambient Air Quality Standards (NAAQS). The blood parameters, namely white blood cells (WBC), red blood cell (RBC) and platelets counts, demonstrated non-significant differences between workers exposed to the PM as compared to the control group. However, differentiated white blood cells count revealed a significant increase of  polymorphonuclear leukocytes (PMN)  in exposed workers in comparison with the control group. However, both  MDA and glutathione peroxidase showed a highly significant increase in the workers ass compared to the control group. Thus, we may conclude that the concrete plant workers are exposed to a higher risk of oxidative stress that could lead to alterations in hematological parameters, enzymatic activities, and MDA level.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Nanan Nur’aeny ◽  
Dida Akhmad Gurnida ◽  
Oki Suwarsa ◽  
Irna Sufiawati

Objective. To investigate the DNA methylation using pyrosequencing and its effects on the upregulation of IL6 mRNA in patients with recurrent aphthous stomatitis (RAS) in connection with hematinic deficiency and atopy. Material and Methods. This cross-sectional study was conducted at Dr. Hasan Sadikin Hospital, Bandung, from January–March 2019 and was approved by the Health Research Ethics Committee of Universitas Padjadjaran (Ethics No. 990/UN6.KEP/EC/2018). Furthermore, the subjects had RAS ulcers with a history of at least twice a year along with atopy and dietary imbalance with no history of recurrent intraoral herpes or any systemic diseases. This study was performed on 23 RAS patients and 21 healthy subjects, and the sampling was carried out consecutively. The blood samples were collected from all the subjects, and then, the DNA and RNA were extracted from the peripheral blood mononuclear cells (PBMCs). Consequently, the bisulfite-modified DNA was used to confirm the methylation status of the IL6 gene promoter through the pyrosequencing method. The methylation levels of the IL6 promoter were assessed by a reverse transcriptase-polymerase chain reaction technique. The gene expression of RAS and the control group was analyzed by the 2−ΔΔCT method. The statistical analysis using the Mann–Whitney U test was conducted to evaluate IL6 mRNA levels and DNA methylation with p value <0.05 considered to be statistically significant. Result. The IL6 mRNA levels were approximately 1.88-fold in RAS patients, and there was a significant relationship between the expression of the IL6 gene and the increased risk of RAS p < 0.001 . It was reported that four out of six sites in the cytosine phosphate guanine (CpG) island IL6 promoter had a lower degree of methylation, and two other sites in patients with RAS had greater methylation compared with control, but not statistically significant. Conclusion. This study showed the upregulation of IL6 mRNA levels in RAS patients compared to control. DNA methylation in the present study is at sites 566–658, whereas the location of the IL6 promoter is at sites 1–1684. Thus, it would be necessary conducting some research at other CpG sites of IL6 promoter islands to determine the status of DNA methylation.


2012 ◽  
Vol 43 (4) ◽  
pp. 222-231 ◽  
Author(s):  
Nina Hansen ◽  
Tom Postmes ◽  
Nikita van der Vinne ◽  
Wendy van Thiel

This paper studies whether and how information and communication technology (ICT) changes self-construal and cultural values in a developing country. Ethiopian children were given laptops in the context of an ICT for development scheme. We compared children who used laptops (n = 69) with a control group without laptops (n = 76) and a second control group of children whose laptop had broken down (n = 24). Results confirmed that after 1 year of laptop usage, the children’s self-concept had become more independent and children endorsed individualist values more strongly. Interestingly, the impact of laptop usage on cultural values was mediated by self-construal (moderated mediation). Importantly, modernization did not “crowd out” traditional culture: ICT usage was not associated with a reduction in traditional expressions (interdependent self-construal, collectivist values). Theoretical and practical implications are discussed.


Author(s):  
Florian Arendt

A test was done to see if reading a newspaper which consistently overrepresents foreigners as criminals strengthens the automatic association between foreign country and criminal in memory (i.e., implicit cultivation). Further, an investigation was done to find out if reading articles from the same newspaper produces a short-term effect on the same measure and if (1) emotionalization of the newspaper texts, (2) emotional reactions of the reader (indicated by arousal), and (3) attributed text credibility moderate the short-term treatment effect. Eighty-five participants were assigned to one of three experimental conditions. Participants in the control group received short factual crime texts, where the nationality of the offender was not mentioned. Participants in the factual treatment group received the same texts, but the foreign nationality was mentioned. Participants in the emotionalized treatment group received emotionalized articles (i.e., texts which are high in vividness and frequency) covering the same crimes, with the foreign nationality mentioned. Supporting empirical evidence for implicit cultivation and a short-term effect was found. However, only emotionalized articles produced a short-term effect on the strength of the automatic association, indicating that newspaper texts must have a minimum of stimulus intensity to overcome an effect threshold. There were no moderating effects of arousal or credibility pertaining to the impact on the implicit measure. However, credibility moderated the short-term effect on a first-order judgment (i.e., estimated frequency of foreigners of all criminals). This indicates that a newspaper’s effect on the strength of automatic associations is relatively independent from processes of propositional reasoning.


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