Acute effects of ambient nitrogen dioxide exposure on serum biomarkers of nervous system damage in healthy older adults.

Ambient nitrogen dioxide (NO2)-induced adverse health effects have been studied, but documented evidence on neural systems is limited. This study aimed to determine the acute effect of NO2 exposure on nervous system damage biomarker levels in healthy older adults. Five rounds of follow-up among 34 healthy retired people were scheduled from December 2018 to April 2019 in Xinxiang, China. The real-time NO2 concentrations were measured using a fixed site monitor. Serum samples were acquired during each round to measure nervous system damage biomarker levels: brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calcium-binding protein B (S100B). A linear mixed-effect model was incorporated to analyze the association between short-term NO2 exposure and serum concentrations of the above-mentioned biomarkers. Stratification analysis based on sex, educational attainment, glutathione S-transferase theta 1 gene (GSTT1) polymorphism, and physical activity intensity was conducted to explore their potential modification effect. The NO2 concentration ranged from 34.7 to 59.0 µg/m3 during the study period. Acute exposure to ambient NO2 was significantly associated with elevated serum levels of NfL, PGP9.5, and BDNF. In response to a 10 µg/m3 increase in NO2 concentration, NfL and PGP9.5 levels increased by 76 % (95 % confidence interval [CI]: 12-140 %) and 54 % (95 % CI: 1-107 %) on the lag0 day, respectively, while BDNF levels increased by 49 % (95 % CI: 2-96 %) at lag4 day. The estimated effect of NO2 on NSE levels in GSTT1-sufficient participants was significantly higher than that in GSTT1-null participants. Intriguingly, the estimation of NO2 on PGP9.5 levels in females was significantly higher than that in males. Most two-pollutant models showed robust results, except for O3, which might have had confounding effects on NO2-induced BDNF stimulation. In summary, acute exposure to NO2 was associated with increased levels of serum nervous system damage biomarker levels including NFL, PGP9.5, and BDNF. The present study provided insights into NO2 exposure-induced adverse neural effects.

Associations of Short-Term Exposure to Fine Particulate Matter with Neural Damage Biomarkers: A Panel Study of Healthy Retired Adults.

Exposure to fine particulate matter (PM2.5) is associated with various adverse health effects, such as respiratory and cardiovascular diseases. This study aimed to evaluate the association of PM2.5 with neural damage biomarkers. A total of 34 healthy retirees were recruited from Xinxiang Medical University from December 2018 to April 2019. Concentrations of PM2.5 constituents including 24 metals and nonmetallic elements and 6 ions, and 5 biomarkers of neural damage including brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calcium-binding protein B (S100B) in serum were measured. A linear mixed-effect model was employed to estimate the association of PM2.5 and its constituents with neural damage biomarkers. Modification effects of glutathione S-transferase theta 1 gene (GSTT1) polymorphism, sex, education, and physical activity on PM2.5 exposure with neural damage were explored. PM2.5 and its key constituents were significantly associated with neural damage biomarkers. A 10 µg/m3 increase in PM2.5 concentration was associated with 2.09% (95% CI, 39.3-76.5%), 100% (95% CI, 1.73-198%), and 122% (95% CI, 20.7-222%) increments in BDNF, NfL, and PGP9.5, respectively. Several constituents such as Cu, Zn, Ni, Mn, Sn, V, Rb, Pb, Al, Be, Cs, Co, Th, U, Cl-, and F- were significantly associated with NfL. The estimated association of PM2.5 with NSE in GSTT1-sufficient volunteers was significantly higher than that in GSTT1-null volunteers. Therefore, short-term PM2.5 exposure was associated with neural damage, and GSTT1 expression levels modified the PM2.5-induced adverse neural effects.

Short-term ozone exposure and serum neural damage biomarkers in healthy elderly adults: Evidence from a panel study.

BACKGROUND: Although converging lines of research have pointed to the adverse neural effects of air pollution, evidence linking ozone (O3) and neural damage remains limited. OBJECTIVES: To investigate the subclinical neural effects of short-term ozone (O3) exposure in elderly adults. METHODS: A panel of healthy elderly individuals was recruited, and five repeated measurements were conducted from December 2018 to April 2019 in Xinxiang, China. Serum neural damage biomarkers, including brain-derived neurotrophic factor (BDNF), neurofilament light chain (NfL), neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), and S100 calcium-binding protein B (S100B) were measured at each follow-up session. Personal O3 exposure levels were calculated based on outdoor monitoring and sampling times. A linear mixed-effects model was adopted to quantify the acute effect of O3 on serum neural damage biomarkers. Stratification analysis based on sex, education level, physical activity, and glutathione S-transferases (GST) gene polymorphism analysis was performed to explore their potential modifying effects. RESULTS: A total of 34 healthy volunteers aged 63.7 ± 5.7 y were enlisted and completed the study. The concentration of the daily maximum 8-h average O3 (O3-8h) ranged from 19.5 to 160.5 µg/m3 during the study period. Regression analysis showed that short-term O3 exposure was associated positively with serum concentrations of neural damage biomarkers. A 10 µg/m3 increase in O3-8h exposure was associated with an increment of 74 % (95 % CI:1 %-146 %) and 197 % (95 % CI:39 %-356 %) in BDNF (lag 2 d) and NfL (lag 1 d), respectively. The stratification results suggest that males, people with lower education levels, lower physical activity, and GST theta 1 (GSTT1)-sufficient genotype might be marginally more vulnerable. CONCLUSIONS: This study provides new evidence for the neural damage risk posed by O3 exposure, even at relatively low concentrations, which, therefore, requires that stringent air quality standards be developed and implemented.

Function and molecular mechanism analysis of CaLasSDE460 effector involved in the pathogenesis of "Candidatus Liberibacter asiaticus" in citrus.

Citrus Huanglongbing (HLB), caused by Candidatus Liberibacter asiaticus (CaLas), is the most serious disease worldwide. CaLasSDE460 was previously characterized as a potential virulence factor of CaLas. However, the function and mechanism of CaLasSDE460 involved in CaLas against citrus is still elusive. Here, we showed that transgenic expression of CaLasSDE460 in Wanjincheng oranges (C. sinensis Osbeck) contributed to the early growth of CaLas and the development of symptoms. When the temperature increased from 25 °C to 32 °C, CaLas growth and symptom development in transgenic plants were slower than those in WT controls. RNA-seq analysis of transgenic plants showed that CaLasSDE460 affected multiple biological processes. At 25 °C, transcription activities of the "Protein processing in endoplasmic reticulum" and "Cyanoamino acid metabolism" pathways increased while transcription activities of many pathways decreased at 32 °C. 124 and 53 genes, separately annotated to plant-pathogen interaction and MAPK signaling pathways, showed decreased expression at 32 °C, compared with these (38 for plant-pathogen interaction and 17 for MAPK signaling) at 25 °C. Several important genes (MAPKKK14, HSP70b, NCED3 and WRKY33), remarkably affected by CaLasSDE460, were identified. Totally, our data suggested that CaLasSDE460 participated in the pathogenesis of CaLas through interfering transcription activities of citrus defense response and this interfering was temperature-dependent.

Microglial Activation and Oxidative Stress in PM2.5-Induced Neurodegenerative Disorders.

Fine particulate matter (PM2.5) pollution remains a prominent environmental problem worldwide, posing great threats to human health. The adverse effects of PM2.5 on the respiratory and cardiovascular systems have been extensively studied, while its detrimental effects on the central nervous system (CNS), specifically neurodegenerative disorders, are less investigated. Neurodegenerative disorders are characterized by reduced neurogenesis, activated microglia, and neuroinflammation. A variety of studies involving postmortem examinations, epidemiological investigations, animal experiments, and in vitro cell models have shown that PM2.5 exposure results in neuroinflammation, oxidative stress, mitochondrial dysfunction, neuronal apoptosis, and ultimately neurodegenerative disorders, which are strongly associated with the activation of microglia. Microglia are the major innate immune cells of the brain, surveilling and maintaining the homeostasis of CNS. Upon activation by environmental and endogenous insults, such as PM exposure, microglia can enter an overactivated state that is featured by amoeboid morphology, the over-production of reactive oxygen species, and pro-inflammatory mediators. This review summarizes the evidence of microglial activation and oxidative stress and neurodegenerative disorders following PM2.5 exposure. Moreover, the possible mechanisms underlying PM2.5-induced microglial activation and neurodegenerative disorders are discussed. This knowledge provides certain clues for the development of therapies that may slow or halt the progression of neurodegenerative disorders induced by ambient PM.

Subclinical cardiovascular outcomes of acute exposure to fine particulate matter and its constituents: A glutathione S-transferase polymorphism-based longitudinal study.

To explore the acute subclinical cardiovascular effects of fine particulate matter (PM2.5) and its constituents, a longitudinal study with 61 healthy young volunteers was conducted in Xinxiang, China. Linear mixed-effect models were used to analyze the association of PM2.5 and its constituents with cardiovascular outcomes, respectively, including blood pressure (BP), heart rate (HR), serum levels of high-sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG), tissue-type plasminogen activator (t-PA), and platelet-monocyte aggregation (PMA). Additionally, the modifying effects of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) polymorphisms were examined. A 10 µg/m3 increase in PM2.5 was associated with -1.04 (95 % CI: -1.86 to -0.22) mmHg and -0.90 (95 % CI: -1.69 to -0.11) mmHg decreases in diastolic BP (DBP) and mean arterial BP (MABP) along with 1.83 % (95 % CI: 0.59-3.08 %), 5.93 % (95 % CI: 0.70-11.16 %) increases in 8-OHdG and hs-CRP, respectively. Ni content was positively associated with the 8-OHdG levels whereas several other metals presented negative association with 8-OHdG and HR. Intriguingly, GSTT1+/GSTTM1+ subjects showed higher susceptibility to PM2.5-induced alterations of DBP and PMA, and GSTT1-/GSTM1+ subjects showed higher alteration on t-PA. Taken together, our findings indicated that short-term PM2.5 exposure induced oxidative stress, systemic inflammation, autonomic alterations, and fibrinolysis in healthy young subjects. Among multiple examined metal components Ni appeared to positively associated with systematic oxidative stress. In addition, GST-sufficient subjects might be more prone to PM2.5-induced autonomic alterations.

Overexpression of a "Candidatus Liberibacter Asiaticus" Effector Gene CaLasSDE115 Contributes to Early Colonization in Citrus sinensis.

Huanglongbing (HLB), caused by "Candidatus liberibacter asiaticus" (CaLas), is one of the most devastating diseases in citrus but its pathogenesis remains poorly understood. Here, we reported the role of the CaLasSDE115 (CLIBASIA_05115) effector, encoded by CaLas, during pathogen-host interactions. Bioinformatics analyses showed that CaLasSDE115 was 100% conserved in all reported CaLas strains but had sequence differences compared with orthologs from other "Candidatus liberibacter." Prediction of protein structures suggested that the crystal structure of CaLasSDE115 was very close to that of the invasion-related protein B (IalB), a virulence factor from Bartonella henselae. Alkaline phosphatase (PhoA) assay in E. coli further confirmed that CaLasSDE115 was a Sec-dependent secretory protein while subcellular localization analyses in tobacco showed that the mature protein of SDE115 (mSDE115), without its putative Sec-dependent signal peptide, was distributed in the cytoplasm and the nucleus. Expression levels of CaLasSDE115 in CaLas-infected Asian citrus psyllid (ACP) were much higher (∼45-fold) than those in CaLas-infected Wanjincheng oranges, with the expression in symptomatic leaves being significantly higher than that in asymptomatic ones. Additionally, the overexpression of mSDE115 favored CaLas proliferation during the early stages (2 months) of infection while promoting the development of symptoms. Hormone content and gene expression analysis of transgenic plants also suggested that overexpressing mSDE115 modulated the transcriptional regulation of genes involved in systemic acquired resistance (SAR) response. Overall, our data indicated that CaLasSDE115 effector contributed to the early colonization of citrus by the pathogen and worsened the occurrence of Huanglongbing symptoms, thereby providing a theoretical basis for further exploring the pathogenic mechanisms of Huanglongbing disease in citrus.