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.

Artemisinin ameliorates cognitive decline by inhibiting hippocampal neuronal ferroptosis via Nrf2 activation in T2DM mice.

BACKGROUND: Neuronal ferroptosis plays a critical role in the pathogenesis of cognitive deficits. The present study explored whether artemisinin protected type 2 diabetes mellitus (T2DM) mice from cognitive impairments by attenuating neuronal ferroptosis in the hippocampal CA1 region. METHODS: STZ-induced T2DM mice were treated with artemisinin (40 mg/kg, i.p.), or cotreated with artemisinin and Nrf2 inhibitor MEL385 or ferroptosis inducer erastin for 4 weeks. Cognitive performance was determined by the Morris water maze and Y maze tests. Hippocampal ROS, MDA, GSH, and Fe2+ contents were detected by assay kits. Nrf2, p-Nrf2, HO-1, and GPX4 proteins in hippocampal CA1 were assessed by Western blotting. Hippocampal neuron injury and mitochondrial morphology were observed using H&E staining and a transmission electron microscope, respectively. RESULTS: Artemisinin reversed diabetic cognitive impairments, decreased the concentrations of ROS, MDA and Fe2+, and increased the levels of p-Nr2, HO-1, GPX4 and GSH. Moreover, artemisinin alleviated neuronal loss and ferroptosis in the hippocampal CA1 region. However, these neuroprotective effects of artemisinin were abolished by Nrf2 inhibitor ML385 and ferroptosis inducer erastin. CONCLUSION: Artemisinin effectively ameliorates neuropathological changes and learning and memory decline in T2DM mice; the underlying mechanism involves the activation of Nrf2 to inhibit neuronal ferroptosis in the hippocampus.

Impact of PM2.5 and ozone on incidence of influenza in Shijiazhuang, China: a time-series study.

Most of the studies are focused on influenza and meteorological factors for influenza. There are still few studies focused on the relationship between pollution factors and influenza, and the results are not consistent. This study conducted distributed lag nonlinear model and attributable risk on the relationship between influenza and pollution factors, aiming to quantify the association and provide a basis for the prevention of influenza and the formulation of relevant policies. Environmental data in Shijiazhuang from 2014 to 2019, as well as the data on hospital-confirmed influenza, were collected. When the concentration of PM2.5 was the highest (621 µg/m3), the relative risk was the highest (RR: 2.39, 95% CI: 1.10-5.17). For extremely high concentration PM2.5 (348 µg/m3), analysis of cumulative lag effect showed statistical significance from cumulative lag0-1 to lag0-6 day, and the minimum cumulative lag effect appeared in lag0-2 (RR: 0.760, 95% CI: 0.655-0.882). In terms of ozone, the RR value was 2.28(1.19,4.38), when O3 concentration was 310 µg/m3, and the RR was 1.65(1.26,2.15), when O3 concentration was 0 µg/m3. The RR of this lag effect increased with the increase of lag days, and reached the maximum at lag0-7 days, RR and 95% CI of slightly low concentration and extremely high concentration were 1.217(1.108,1.337) and 1.440(1.012,2.047), respectively. Stratified analysis showed that there was little difference in gender, but in different age groups, the cumulative lag effect of these two pollutants on influenza was significantly different. Our study found a non-linear relationship between two pollutants and influenza; slightly low concentrations were more associated with contaminant-related influenza. Health workers should encourage patients to get the influenza vaccine and wear masks when going out during flu seasons.

The association between air pollution, meteorological factors, and daily outpatient visits for urticaria in Shijiazhuang, Hebei Province, China: a time series analysis.

The associations of air pollution and meteorological factors with the outpatient visits of urticaria remain poorly studied. This study aimed to assess the association between air pollution, meteorological factors, and daily outpatient visits for urticaria in Shijiazhuang, China, during 2014-2019. Daily recordings of air pollutant concentrations, meteorological data, and outpatient visits data for urticaria were collected during the 6 years. Descriptive research methods were used to describe the distribution characteristics and demographic features of urticaria. A combination of the generalized linear regression model (GLM) and distribution lag nonlinear model (DLNM) was used to evaluate the lag association between environmental factors and daily outpatient visits for urticaria. Stratified analyses by gender (male; female) and age (< 18 years; 18-39 years; > 39 years) were further conducted. The dose-response relationship between daily urticaria visits and CO, NO2, O3, temperature, and relative humidity was nonlinear. High concentrations of CO, NO2, O3, and high temperatures increased the risk of urticaria outpatient visits. The maximum cumulative association of high concentrations of CO, NO2, and O3 was lag 0-14 days (CO: RR = 1.10, 95%CI: 1.06, 1.31; NO2: RR = 1.09, 95%CI: 1.01, 1.08; O3: RR = 1.16, 95%CI: 1.08, 1.25), and high temperatures was lag 0-7 days (RR = 1.27, 95%CI: 1.14, 1.41). Low concentrations of NO2, O3, and high humidity, on the other hand, act as protective factors for urticaria outpatient. The maximum cumulative association of low concentrations of NO2 was the 0-day lag (RR = 0.97, 95%CI: 0.95, 0.99), O3 was lag 0-5 days (RR = 0.94, 95%CI: 0.88, 0.99), and high humidity was lag 0-10 days (RR = 0.93, 95%CI: 0.89, 0.98). Stratified analyses showed that the risk of urticaria outpatient visits was higher for the males and in the < 18 years age group. In conclusion, we found that the development of urticaria in Shijiazhuang has a distinct seasonal and cyclical nature. Air pollutants and meteorological factors had varying degrees of influence on the risk of urticaria outpatient visits. This study provides indirect evidence for a link between air pollution, meteorological factors, and urticaria outpatient visits.

Epidemiological characteristics of fractures of spine, hip, proximal humerus and forearm during the haze epidemic period.

BACKGROUND: Air pollutants have an impact on the occurrence of spine fractures, hip fractures, proximal humerus fractures and forearm fractures. This study aimed at evaluating the short-term impact of particulate matter with aerodynamic diameters of less than 2.5 µm (PM2.5) on the occurrence of those fractures in Shijiazhuang, Hebei, China. METHODS: The daily meteorological, pollution, and fracture data of Shijiazhuang from 2014 to 2019 were collected. Distribution characteristics of fractures were described using descriptive epidemiological methods. The distributed lag nonlinear model (DLNM) was used to reveal the description of those fractures in the exposed and lag dimensions at the same time. Based on gender and age (<18 years old, 18-69 years old and >69 years old), stratified analysis was performed. Sensitivity analysis was performed to ascertain the robustness of the results. RESULTS: Between 2014 and 2019, fracture incidences in Shijiazhuang exhibited an overall increasing trend, with an obvious seasonality. PM2.5 was positively related to daily fracture cases and the effects were more obvious in women, adolescents and people of working age. When PM2.5 concentrations increased by one interquartile range (IQR) (70 µg/m3), RR exhibited a unimodal distribution. Its peak appeared on the 16th day of lag (RR=1.005987, 95% CI:1.002472,1.009652), and the RRs were also statistically significant from the 10th to 22nd day of lag. Similarly, cumulative effects of each increase in the concentration of PM2.5 IQR also showed a unimodal distribution. The largest cumulative effect occurred on the 28th day of lag (RR=1.084457, 95% CI:1.012207,1.161864), and the cumulative RRs were also statistically significant from the 19th day to 30nd days. In the dose-response relationship, as PM2.5 concentrations increased, RR increased. CONCLUSION: Year by year, fractures in Shijiazhuang City exhibited an increasing trend. PM2.5 can affect the occurrence of those fractures. The impact on women, adolescents and people of working age is even greater. The supervision of PM2.5 should be strengthened while large-scale emissions should be limited.

The association between maternal perfluoroalkyl substances exposure and early attention deficit hyperactivity disorder in children: a systematic review and meta-analysis.

Some studies have shown that maternal exposure to perfluoroalkyl substances (PFASs) may be associated with early attention deficit hyperactivity disorder (ADHD) in children. The purpose of this systematic review and meta-analysis is to verify this association by reviewing existing studies and to provide a strong basis for preventing ADHD. The researchers searched electronic databases such as PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase for all studies published before October 2020. Finally, we included nine articles for analysis. Our meta-analysis showed that maternal exposure to PFASs was not significantly associated with the prevalence rate of early childhood ADHD (perfluorooctanoic acid (PFOA), odds ratio (OR) = 1.00, 95% confidence interval (95% CI) = 0.75-1.25; perfluorooctane sulfonate (PFOS), OR = 1.01, 95% CI = 0.88-1.14; perfluorohexane sulfonate (PFHxS), OR = 1.08, 95% CI = 0.80-1.09; perfluorononanoic acid (PFNA), OR = 1.13, 95% CI = 0.99-1.28; perfluorodecanoic acid (PFDA), OR = 1.23, 95% CI = 0.15-2.32). Due to significant heterogeneity, we subsequently performed subgroup analysis and sensitivity analysis. Through subgroup analysis, we found that PFOS concentration of children's blood and the prevalence rate of early childhood ADHD were statistically positively correlated, and there was also a positive correlation between PFOS exposure and the prevalence rate of early childhood ADHD in the America. Moreover, there was also a statistically positive correlation between PFNA concentration in maternal blood and the prevalence rate of early childhood ADHD. Sensitivity analysis showed that the final results did not change much, the sensitivity was low, and the results were relatively stable. In conclusion, a causal relationship between maternal PFASs exposure and ADHD in children was unlikely. Among them, PFOS, PFNA, and ADHD might have positive associations worthy of further investigation.

The relationship between maternal perfluoroalkylated substances exposure and low birth weight of offspring: a systematic review and meta-analysis.

Some studies have shown that maternal perfluoroalkylated substances (PFAS) exposure may be associated with low birth weight (LBW) of offspring. We conducted a meta-analysis to assess the association between maternal PFASs exposure and LBW in offspring. The researchers searched PubMed, Science Direct, Scopus, Google Scholar, Web of Science, and Embase to find all the articles before October 2020. The Newcastle-Ottawa Scale was used to evaluate the quality of the studies. Finally, six articles were included for meta-analysis. Our meta-analysis showed no significant correlation between maternal perfluorooctanoic acid (PFOA) exposure and LBW of offspring: odds ratio (OR) = 0.90, 95% confidence interval (95% CI) = 0.80-1.01, with low heterogeneity (I2 = 18.4%, P = 0.289); there was a significant positive correlation between maternal perfluorooctane sulfonate (PFOS) exposure and LBW of offspring (OR = 1.32, 95% CI = 1.09-1.55) with no heterogeneity (I2 = 0.00%, P = 0.570). The grouping analysis of PFOS showed was a significant positive correlation between maternal PFOS exposure and LBW of offspring in American (OR = 1.44, 95% CI = 1.15-1.72). This study provided a systematic review and meta-analysis evidence for the relationship between maternal PFASs exposure and LBW of offspring through a small number of studies. Researchers should conduct further studies between different regions.

Corticosterone induces neurotoxicity in PC12 cells via disrupting autophagy flux mediated by AMPK/mTOR signaling.

AIMS: Our previous study indicated that chronic stress caused autophagy impairment and subsequent neuron apoptosis in hippocampus. However, the mechanism underlying the stress-induced damage to neurons is unclear. In present work, we investigated whether stress-level glucocorticoids (GCs) GCs promoted PC12 cell damage via AMPK/mTOR signaling-mediated autophagy. METHODS: Chronic stress-induced PC12 cell injury model was built by treatment with high level corticosterone (CORT). Cell injury was evaluated by flow cytometry assay and transmission electron microscopy observation. RESULTS: Autophagy flux was measured based on the changes in LC3-II and P62 protein expressions, and the color alteration of mCherry-GFP-LC3-II transfection. Our results showed that CORT not only increased cell injury and apoptosis, but also dysregulated AMPK/mTOR signaling-mediated autophagy flux, as indicated by the upregulated expression of LC3-II and P62 proteins, and the lowered ration of autolysosomes to autophagosomes. Mechanistically, our results demonstrated that autophagy activation by AMPK activator metformin or mTOR inhibitor rapamycin obviously promotes cell survival and autophagy flux, improved mitochondrial ultrastructure, and reduced expression of Cyt-C and caspase-3 in CORT-induced PC12 cells. CONCLUSION: These results indicate that high CORT triggers PC12 cell damage through disrupting AMPK/mTOR-mediated autophagy flux. Targeting this signaling may be a promising approach to protect against high CORT and chronic stress-induced neuronal impairment.

MicroRNA-219 exerts a tumor suppressive role in glioma via targeting Sal-like protein 4.

MicroRNAs (miRs) serve important roles in the development and progression of various human cancer types, including glioma. Recently, miR-219 has been suggested to function as a tumor suppressor in glioma; however, the underlying mechanism remains largely unknown. The aim of this study was to investigate the regulatory mechanism of miR-219 in the malignant phenotypes of glioma cells. Quantitative polymerase chain reaction (qPCR) and western blotting were conducted to examine the mRNA and protein expression. An MTT assay, wound healing assay and Transwell assay were used to study cell proliferation, migration and invasion. The qPCR data indicated that the expression of miR-219 was significantly decreased in glioma tissues compared with normal brain tissues. In addition, a low expression of miR-219 was identified to be associated with an advanced pathological grade. In vitro experiments demonstrated that miR-219 was also downregulated in several common glioma cell lines, including A172, U87, U251 and U373, when compared with that in normal astrocytes. Ectopic expression of miR-219 caused a significant decrease in U87 cell proliferation, migration and invasion. Luciferase reporter assay data indicated that Sal-like protein 4 (SALL4) was a direct target gene of miR-219, while the protein expression of SALL4 was negatively regulated by miR-219 in U87 cells. Furthermore, SALL4 was significantly upregulated in glioma tissues and cell lines, and upregulation of SALL4 was associated with a higher pathological grade. Furthermore, overexpression of SALL4 significantly attenuated the suppressive effects of miR-219 on U87 cell proliferation, migration and invasion, suggesting that miR-219 serves a suppressive role in glioma growth and metastasis via targeting SALL4. Therefore, the present study highlighted the clinical significance of the miR-219/SALL4 axis in glioma.

Oxidized low-density lipoprotein induced mouse hippocampal HT-22 cell damage via promoting the shift from autophagy to apoptosis.

AIMS: Although oxidized low-density lipoprotein (ox-LDL) in the brain induces neuronal death, the mechanism underlying the damage effects remains largely unknown. Given that the ultimate outcome of a cell is depended on the balance between autophagy and apoptosis, this study was performed to explore whether ox-LDL induced HT-22 neuronal cell damage via autophagy impairment and apoptosis enhancement. METHODS: Flow cytometry and transmission electron microscopy (TEM) were used to evaluate changes in cell apoptosis and autophagy, respectively. The protein expression of LC3-II, p62, Bcl-2, and Bax in HT-22 cells was measured by Western bolt analysis. RESULTS: Our study confirmed that 100 µg/mL of ox-LDL not only promoted TH-22 cell apoptosis, characterized by elevated cell apoptosis rate and Bax protein expression, decreased Bcl-2 protein expression, and damaged cellular ultrastructures, but also impaired autophagy as indicated by the decreased LC3-II levels and the increased p62 levels. Importantly, all of these effects of ox-LDL were significantly aggravated by cotreatment with chloroquine (an inhibitor of autophagy flux). In contrast, cotreatment with rapamycin (an inducer of autophagy) remarkably reversed these effects of ox-LDL. CONCLUSIONS: Taken together, our results indicated that ox-LDL-induced shift from autophagy to apoptosis contributes to HT-22 cell damage.

Apelin-13 Protects PC12 Cells from Corticosterone-Induced Apoptosis Through PI3K and ERKs Activation.

It is widely accepted that environmental stress is a risk factor for mental disorders. Glucocorticoid hormones play a vital role in the regulation of physiological response to stress. High concentrations of corticosterone can induce cellular damage in PC12 cells, which possess typical neuronal features. Apelin and its receptor APJ are widely distributed in the central nervous system including limbic structures involved in stress responses. Previous studies have suggested that apelin has a neuroprotective function. However, the effect of apelin on corticosterone-induced neuronal damage remains to be elucidated. In the present study, we explored the potential protective activity of apelin-13 in PC12 cells treated with corticosterone and its underling mechanisms. The viability of the cells, the apoptosis of the cells, the level of phosphorylation of Akt (p-Akt) and extracellular signal-regulated kinases (p-ERKs) and cleaved caspase-3 expression were detected by MTT, Hoechst staining and flow cytometer assays and Western blotting. Results showed that corticosterone induced cells viability loss, cell apoptosis, down-regulation of p-Akt and p-ERKs and up-regulation of cleaved caspase-3. The effects induced by corticosterone were attenuated by apelin-13 pretreatment. Furthermore, apelin-13-mediated anti-viability loss, antiapoptosis and caspase-3 suppression activities were blocked by specific inhibitors of phosphatidylinositol 3-kinase (PI3K) (LY294002) and ERKs (PD98059). The data suggest that apelin-13 protects PC12 cells from corticosterone-induced apoptosis through activating PI3K/Akt and ERKs signaling pathways.

Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS)-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6k) signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p.) significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (Aß1-42) levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.

[Effect of panax notoginseng saponins injection on brain edema in intracerebral hemorrhage rats].

OBJECTIVE: To study the effect of panax notoginseng saponins (PNS) in treating hemorrhagic apoplexy at super-early stage in rats. METHODS: Rat model of hypertension with cerebral hemorrhage was induced by collagenase method. Sixty rats were randomly divided into 5 groups: the sham operated group, model group, PNS high, middle, and low dose group, 12 in each; 4 h after modeling, PNS or normal saline was intraperitoneally injected into the rats every 12 h, the total is 5 times. Contents of water, sodium and potassium ion in brain, and the diameter of hematoma in rats of different groups were measured 24 h and 72 h after modeling. RESULTS: Compared with the model rats, nerve defect symptoms aggravated, the contents of water and sodium ion in ipsilateral cortex and basal ganglia were significantly higher, the content of potassium ion was lower and the hematoma diameter was obviously less in the PNS-treated rats (all P < 0.05). CONCLUSION: PNS may worsen the brain edema and increase the nerve defect score when it was applied at the early stage of cerebral hemorrhage, but could promote the absorption of hematoma, indicating PNS should be used cautiously in treating patients with large amount of cerebral hemorrhage at super-early stage.