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Article ; Online: Transcriptomic analysis of World Trade Center particulate Matter-induced pulmonary inflammation and drug treatments

Yun-Ti Chen / Jinhui Li / Jen-Ning Chang / Yong-Chun Luo / Wuyue Yu / Lung-Chi Chen / Jinn-Moon Yang

Environment International, Vol 177, Iss , Pp 108027- (2023)

2023

Abstract: Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause ... ...

Abstract	Over 400,000 people are estimated to have been exposed to World Trade Center particulate matter (WTCPM) since the attack on the Twin Towers in Lower Manhattan on September 11, 2001. Epidemiological studies have found that exposure to dust may cause respiratory ailments and cardiovascular diseases. However, limited studies have performed a systematic analysis of transcriptomic data to elucidate the biological responses to WTCPM exposure and the therapeutic options. Here, we developed an in vivo mouse exposure model of WTCPM and administered two drugs (i.e., rosoxacin and dexamethasone) to generate transcriptomic data from lung samples. WTCPM exposure increased the inflammation index, and this index was significantly reduced by both drugs. We analyzed the transcriptomics derived omics data using a hierarchical systems biology model (HiSBiM) with four levels, including system, subsystem, pathway, and gene analyses. Based on the selected differentially expressed genes (DEGs) from each group, WTCPM and the two drugs commonly affected the inflammatory responses, consistent with the inflammation index. Among these DEGs, the expression of 31 genes was affected by WTCPM exposure and consistently reversed by the two drugs, and these genes included Psme2, Cldn18, and Prkcd, which are involved in immune- and endocrine-related subsystems and pathways such as thyroid hormone synthesis, antigen processing and presentation, and leukocyte transendothelial migration. Furthermore, the two drugs reduced the inflammatory effects of WTCPM through distinct pathways, e.g., vascular-associated signaling by rosoxacin, whereas mTOR-dependent inflammatory signaling was found to be regulated by dexamethasone. To the best of our knowledge, this study constitutes the first investigation of transcriptomics data of WTCPM and an exploration of potential therapies. We believe that these findings provide strategies for the development of promising optional interventions and therapies for airborne particle exposure.
Keywords	World Trade Center dust ; Pulmonary inflammation ; Hierarchical Systems Biology Model ; Rosoxacin ; Dexamethasone ; Environmental sciences ; GE1-350
Subject code	610
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Ambient fine particulate matter exposure disrupts placental autophagy and fetal development in gestational mice

Ran Li / Jing Peng / Wenhui Zhang / Yunlu Wu / Renjie Hu / Rucheng Chen / Weijia Gu / Lu Zhang / Li Qin / Mianhua Zhong / Lung-Chi Chen / Qinghua Sun / Cuiqing Liu

Ecotoxicology and Environmental Safety, Vol 239, Iss , Pp 113680- (2022)

2022

Abstract: Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM2.5). However, potential mechanism remains to be elucidated. ...

Abstract	Recent studies have shown that some adverse pregnancy outcomes, especially intrauterine growth restriction (IUGR), are associated with gestational exposure to ambient fine particulate matter (PM2.5). However, potential mechanism remains to be elucidated. In the present study, pregnant C57BL/6 mice were randomly assigned to be exposed to either filtered air or ambient PM2.5 in the gestation period via a concentrated whole-body exposure system. We found that gestational PM2.5 exposure exerted no effect on implantation, preterm delivery, as well as fetal resorption and death. However, in utero fetal exposure to PM2.5 showed a significant reduction in body weight and crown-rump length on GD13 and GD18. Meanwhile, maternal blood sinusoid in placenta was markedly reduced along with abnormal expression of placental nutrient transporters and growth hormone in dams exposed to PM2.5. Additional tests showed gestational PM2.5 exposure decreased autophagy-related protein levels and inhibited autophagy flux mainly on GD15. Correspondingly, AMPK/mTOR signaling pathway, a critical negative regulator of autophagy, was activated in placenta on GD15 by PM2.5 exposure as well. These findings provide evidences that placental developmental disorder caused by autophagy inhibition might be an important mechanism for the growth restriction caused by PM2.5 exposure.
Keywords	Fine particulate matter ; Inhalation ; Gestational exposure ; Fetal growth restriction ; Placenta development ; Autophagy ; Environmental pollution ; TD172-193.5 ; Environmental sciences ; GE1-350
Language	English
Publishing date	2022-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Analysis of Acrolein Exposure Induced Pulmonary Response in Seven Inbred Mouse Strains and Human Primary Bronchial Epithelial Cells Cultured at Air-Liquid Interface

Gunnar Johanson / Aishwarya Mishra Dwivedi / Lena Ernstgård / Lena Palmberg / Koustav Ganguly / Lung Chi Chen / Karen Galdanes / Terry Gordon / Swapna Upadhyay

BioMed Research International, Vol

2020 Volume 2020

Abstract: Background. Acrolein is a major component of environmental pollutants, cigarette smoke, and is also formed by heating cooking oil. We evaluated the interstrain variability of response to subchronic inhalation exposure to acrolein among inbred mouse ... ...

Abstract	Background. Acrolein is a major component of environmental pollutants, cigarette smoke, and is also formed by heating cooking oil. We evaluated the interstrain variability of response to subchronic inhalation exposure to acrolein among inbred mouse strains for inflammation, oxidative stress, and tissue injury responses. Furthermore, we studied the response to acrolein vapor in the lung mucosa model using human primary bronchial epithelial cells (PBEC) cultured at an air-liquid interface (ALI) to evaluate the findings of mouse studies. Methods. Female 129S1/SvlmJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ mice were exposed to 1 part per million (ppm) acrolein or filtered air for 11 weeks. Total cell counts and protein concentrations were measured in bronchoalveolar lavage (BAL) fluid to assess airway inflammation and membrane integrity. PBEC-ALI models were exposed to acrolein vapor (0.1 and 0.2 ppm) for 30 minutes. Gene expression of proinflammatory, oxidative stress, and tissue injury-repair markers was assessed (cut off: ≥2 folds; p<0.05) in the lung models. Results. Total BAL cell numbers and protein concentrations remained unchanged following acrolein exposure in all mouse strains. BALB/cByJ, C57BL/6J, and 129S1/SvlmJ strains were the most affected with an increased expression of proinflammatory, oxidative stress, and/or tissue injury markers. DBA/2J, C3H/HeJ, A/J, and FVB/NJ were affected to a lesser extent. Both matrix metalloproteinase 9 (Mmp9) and tissue inhibitor of metalloproteinase 1 (Timp1) were upregulated in the strains DBA/2J, C3H/HeJ, and FVB/NJ indicating altered protease/antiprotease balance. Upregulation of lung interleukin- (IL-) 17b transcript in the susceptible strains led us to investigate the IL-17 pathway genes in the PBEC-ALI model. Acrolein exposure resulted in an increased expression of IL-17A, C, and D; IL-1B; IL-22; and RAR-related orphan receptor A in the PBEC-ALI model. Conclusion. The interstrain differences in response to subchronic acrolein exposure in mouse suggest a genetic predisposition. Altered expression of IL-17 pathway genes following acrolein exposure in the PBEC-ALI models indicates that it has a central role in chemical irritant toxicity. The findings also indicate that genetically determined differences in IL-17 signaling pathway genes in the different mouse strains may explain their susceptibility to different chemical irritants.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Longitudinal impact on rat cardiac tissue transcriptomic profiles due to acute intratracheal inhalation exposures to isoflurane.

Sung-Hyun Park / Yuting Lu / Yongzhao Shao / Colette Prophete / Lori Horton / Maureen Sisco / Hyun-Wook Lee / Thomas Kluz / Hong Sun / Max Costa / Judith Zelikoff / Lung-Chi Chen / Mitchell D Cohen

PLoS ONE, Vol 16, Iss 10, p e

2021 Volume 0257241

Abstract: Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, ... ...

Abstract	Isoflurane (ISO) is a widely used inhalation anesthetic in experiments with rodents and humans during surgery. Though ISO has not been reported to impart long-lasting side effects, it is unknown if ISO can influence gene regulation in certain tissues, including the heart. Such changes could have important implications for use of this anesthetic in patients susceptible to heart failure/other cardiac abnormalities. To test if ISO could alter gene regulation/expression in heart tissues, and if such changes were reversible, prolonged, or late onset with time, SHR (spontaneously hypertensive) rats were exposed by intratracheal inhalation to a 97.5% air/2.5% ISO mixture on two consecutive days (2 hr/d). Control rats breathed filtered air only. On Days 1, 30, 240, and 360 post-exposure, rat hearts were collected and total RNA was extracted from the left ventricle for global gene expression analysis. The data revealed differentially-expressed genes (DEG) in response to ISO (compared to naïve control) at all post-exposure timepoints. The data showed acute ISO exposures led to DEG associated with wounding, local immune function, inflammation, and circadian rhythm regulation at Days 1 and 30; these effects dissipated by Day 240. There were other significantly-increased DEG induced by ISO at Day 360; these included changes in expression of genes associated with cell signaling, differentiation, and migration, extracellular matrix organization, cell-substrate adhesion, heart development, and blood pressure regulation. Examination of consistent DEG at Days 240 and 360 indicated late onset DEG reflecting potential long-lasting effects from ISO; these included DEG associated with oxidative phosphorylation, ribosome, angiogenesis, mitochondrial translation elongation, and focal adhesion. Together, the data show acute repeated ISO exposures could impart variable effects on gene expression/regulation in the heart. While some alterations self-resolved, others appeared to be long-lasting or late onset. Whether such changes occur in ...
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Longitudinal Impact of WTC Dust Inhalation on Rat Cardiac Tissue Transcriptomic Profiles

Sung-Hyun Park / Yuting Lu / Yongzhao Shao / Colette Prophete / Lori Horton / Maureen Sisco / Hyun-Wook Lee / Thomas Kluz / Hong Sun / Max Costa / Judith Zelikoff / Lung-Chi Chen / Matthew W. Gorr / Loren E. Wold / Mitchell D. Cohen

International Journal of Environmental Research and Public Health, Vol 19, Iss 919, p

2022 Volume 919

Abstract: First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative ... ...

Abstract	First responders (FR) exposed to the World Trade Center (WTC) Ground Zero air over the first week after the 9/11 disaster have an increased heart disease incidence compared to unexposed FR and the general population. To test if WTC dusts were causative agents, rats were exposed to WTC dusts (under isoflurane [ISO] anesthesia) 2 h/day on 2 consecutive days; controls received air/ISO or air only. Hearts were collected 1, 30, 240, and 360 d post-exposure, left ventricle total RNA was extracted, and transcription profiles were obtained. The data showed that differentially expressed genes (DEG) for WTC vs. ISO rats did not reach any significance with a false discovery rate (FDR) < 0.05 at days 1, 30, and 240, indicating that the dusts did not impart effects beyond any from ISO. However, at day 360, 14 DEG with a low FDR were identified, reflecting potential long-term effects from WTC dust alone, and the majority of these DEG have been implicated as having an impact on heart functions. Furthermore, the functional gene set enrichment analysis (GSEA) data at day 360 showed that WTC dust could potentially impact the myocardial energy metabolism via PPAR signaling and heart valve development. This is the first study showing that WTC dust could significantly affect some genes that are associated with the heart/CV system, in the long term. Even > 20 years after the 9/11 disaster, this has potentially important implications for those FR exposed repeatedly at Ground Zero over the first week after the buildings collapsed.
Keywords	WTC dust ; rat cardiac tissue ; transcriptomic profiles ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mapping urban air quality using mobile sampling with low-cost sensors and machine learning in Seoul, South Korea

Chris C. Lim / Ho Kim / M.J. Ruzmyn Vilcassim / George D. Thurston / Terry Gordon / Lung-Chi Chen / Kiyoung Lee / Michael Heimbinder / Sun-Young Kim

Environment International, Vol 131, Iss , Pp - (2019)

2019

Abstract: Recent studies have demonstrated that mobile sampling can improve the spatial granularity of land use regression (LUR) models. Mobile sampling campaigns deploying low-cost (<$300) air quality sensors could potentially offer an inexpensive and practical ... ...

Abstract	Recent studies have demonstrated that mobile sampling can improve the spatial granularity of land use regression (LUR) models. Mobile sampling campaigns deploying low-cost (<$300) air quality sensors could potentially offer an inexpensive and practical approach to measure and model air pollution concentration levels. In this study, we developed LUR models for street-level fine particulate matter (PM2.5) concentration levels in Seoul, South Korea. 169 h of data were collected from an approximately three week long campaign across five routes by ten volunteers sharing seven AirBeams, a low-cost ($250 per unit), smartphone-based particle counter, while geospatial data were extracted from OpenStreetMap, an open-source and crowd-generated geographical dataset. We applied and compared three statistical approaches in constructing the LUR models – linear regression (LR), random forest (RF), and stacked ensemble (SE) combining multiple machine learning algorithms – which resulted in cross-validation R2 values of 0.63, 0.73, and 0.80, respectively, and identification of several pollution ‘hotspots.’ The high R2 values suggest that study designs employing mobile sampling in conjunction with multiple low-cost air quality monitors could be applied to characterize urban street-level air quality with high spatial resolution, and that machine learning models could further improve model performance. Given this study design's cost-effectiveness and ease of implementation, similar approaches may be especially suitable for citizen science and community-based endeavors, or in regions bereft of air quality data and preexisting air monitoring networks, such as developing countries.
Keywords	Environmental sciences ; GE1-350
Subject code	333
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Five-year lung cancer mortality risk analysis and topography in Xuan Wei

Jinhui Li / Wenbo Guo / Jinjun Ran / Robert Tang / Hualiang Lin / Xiao Chen / Bofu Ning / Jihua Li / Yongchun Zhou / Lung-Chi Chen / Linwei Tian / Yunchao Huang

BMC Public Health, Vol 19, Iss 1, Pp 1-

a spatiotemporal correlation analysis

2019 Volume 14

Abstract: Abstract Background In Xuan Wei, China, the lung cancer mortality rate is rising significantly more than that of the nation overall. However, it remains unclear 1) if improved diagnosis can just partially explain this observation and how other local risk ...

Abstract	Abstract Background In Xuan Wei, China, the lung cancer mortality rate is rising significantly more than that of the nation overall. However, it remains unclear 1) if improved diagnosis can just partially explain this observation and how other local risk factors may be correlated with the lung cancer mortality rate and 2) how the lung cancer mortality rates differ within Xuan Wei and how these spatiotemporal patterns are linked with local risk factors. To increase etiological knowledge, this study evaluated the spatial and temporal distributions of the health effects (the lung cancer mortality rates) from 2011 to 2015. Methods Four steps of spatial analysis were applied, as follows: 1) hotspot analysis to determine the geographical patterns of lung cancer mortality, 2) spatially-weighted sum to identify areas with higher health risks, 3) bivariate statistical analysis to assess the overall correlation between coal mines and lung cancer mortality, and 4) geographically-weighted regression to test for correlations among different towns within Xuan Wei. Results Women had higher lung cancer mortality rates than those in men, with an increasing trend in both sexes over time. The incidence rates in Laibin Town were the highest in Xuan Wei every year. Over the 5-year study period, the lung cancer mortality was increasingly concentrated in Laibin, Shuanglong, and Longchang, where the smoky coal mines are most concentrated. The population-level health risks from the coal mine in Xuan Wei were mapped and divided into five types of risk areas (Type I – Type IV). Correlation analysis revealed that there was no significant correlation between lung cancer mortality as a whole and coal mine distribution during the 5-year study period. However, the geographically-weighted regression revealed a stronger correlation in medium (Type III) and second-lowest (Type IV) health risks. Conclusions Xuan Wei lung cancer mortality has increased continuously since the third national retrospective surveys on the causes of death by the ...
Keywords	Xuan Wei ; Lung cancer ; Mortality risk ; Coal mine ; Spatiotemporal correlation ; Public aspects of medicine ; RA1-1270
Subject code	610 ; 310
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Electronic cigarettes and insulin resistance in animals and humans

Olusola A Orimoloye / S M Iftekhar Uddin / Lung-Chi Chen / Albert D Osei / Mohammadhassan Mirbolouk / Marina V Malovichko / Israel D Sithu / Omar Dzaye / Daniel J Conklin / Sanjay Srivastava / Michael J Blaha

PLoS ONE, Vol 14, Iss 12, p e

Results of a controlled animal study and the National Health and Nutrition Examination Survey (NHANES 2013-2016).

2019 Volume 0226744

Abstract: BACKGROUND:The popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of ... ...

Abstract	BACKGROUND:The popularity of electronic cigarettes (E-cigarettes) has risen considerably. Several studies have suggested that nicotine may affect insulin resistance, however, the impact of E-cigarette exposure on insulin resistance, an early measure of cardiometabolic risk, is not known. METHODS AND RESULTS:Using experimental animals and human data obtained from 3,989 participants of the United States National Health and Nutrition Examination Survey (NHANES), respectively, we assessed the association between E-cigarette and conventional cigarette exposures and insulin resistance, as modelled using the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose tolerance tests (GTT). C57BL6/J mice (on standard chow diet) exposed to E-cigarette aerosol or mainstream cigarette smoke (MCS) for 12 weeks showed HOMA-IR and GTT levels comparable with filtered air-exposed controls. In the NHANES cohort, there was no significant association between defined tobacco product use categories (non-users; sole E-cigarette users; cigarette smokers and dual users) and insulin resistance. Compared with non-users of e-cigarettes/conventional cigarettes, sole E-cigarette users showed no significant difference in HOMA-IR or GTT levels following adjustment for age, sex, race, physical activity, alcohol use and BMI. CONCLUSION:E-cigarettes do not appear to be linked with insulin resistance. Our findings may inform future studies assessing potential cardiometabolic harms associated with E-cigarette use.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Spanning forests on the Sierpinski gasket

Shu-Chiuan Chang / Lung-Chi Chen

Discrete Mathematics & Theoretical Computer Science, Vol 10, Iss

2008 Volume 2

Abstract: We present the numbers of spanning forests on the Sierpinski gasket $SG_d(n)$ at stage $n$ with dimension $d$ equal to two, three and four, and determine the asymptotic behaviors. The corresponding results on the generalized Sierpinski gasket $SG_{d,b}(n) ...

Abstract	We present the numbers of spanning forests on the Sierpinski gasket $SG_d(n)$ at stage $n$ with dimension $d$ equal to two, three and four, and determine the asymptotic behaviors. The corresponding results on the generalized Sierpinski gasket $SG_{d,b}(n)$ with $d=2$ and $b=3,4$ are obtained. We also derive the upper bounds of the asymptotic growth constants for both $SG_d$ and $SG_{2,b}$.
Keywords	Electronic computers. Computer science ; QA75.5-76.95 ; Instruments and machines ; QA71-90 ; Mathematics ; QA1-939 ; Science ; Q ; DOAJ:Computer Science ; DOAJ:Technology and Engineering ; DOAJ:Mathematics ; DOAJ:Mathematics and Statistics
Language	English
Publishing date	2008-04-01T00:00:00Z
Publisher	Discrete Mathematics & Theoretical Computer Science
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Complementary biobank of rodent tissue samples to study the effect of World Trade Center exposure on cancer development

Wil Lieberman-Cribbin / Stephanie Tuminello / Christina Gillezeau / Maaike van Gerwen / Rachel Brody / David J. Mulholland / Lori Horton / Maureen Sisco / Colette Prophete / Judith Zelikoff / Hyun-Wook Lee / Sung-Hyun Park / Lung-Chi Chen / Mitchell D. Cohen / Emanuela Taioli

Journal of Translational Medicine, Vol 17, Iss 1, Pp 1-

2019 Volume 8

Abstract: Abstract World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological ... ...

Abstract	Abstract World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort. Here we describe the implementation of a tissue bank system for the rodents experimentally exposed to WTC dust. NYU samples were experimentally exposed to WTC dust via intratracheal inhalation that mimicked conditions in the immediate aftermath of the disaster. Tissue from Mount Sinai was derived from genetically modified mice exposed to WTC dust via nasal instillation. All processed tissues include annotations of the experimental design, WTC dust concentration/dose, exposure route and duration, genetic background of the rodent, and method of tissue isolation/storage. A biobank of tissue from rodents exposed to WTC dust has been compiled representing an important resource for the scientific community. The biobank remains available as a scientific resource for future research through established mechanisms for samples request and utilization. Studies using the WTC tissue bank would benefit from confirming their findings in corresponding tissues from organs of animals experimentally exposed to WTC dust. Studies on rodent tissues will advance the understanding of the biology of the tumors developed by WTC responders and ultimately impact the modalities of treatment, and the probability of success and survival of WTC cancer patients.
Keywords	Rodents ; World Trade Center Dust ; Biorepository ; Medicine ; R
Subject code	616
Language	English
Publishing date	2019-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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