Role of STAT3 activated NLRP3 inflammasomes in BV2 cell inflammatory response induced by maltol aluminum / 环境与职业医学

Background Aluminum activates signal transducer and activator of transcription 3 (STAT3), causing microglial nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) inflammasome activation and inflammatory responses and producing neurotoxicity. Objective To explore the role of STAT3 regulated NLRP3 inflammasomes in the inflammatory response of mouse microglia cell line (BV2) cells induced by maltol aluminum [Al(mal)3]. Methods BV2 cells were assigned to five groups: one control group, three Al(mal)3 exposure groups (low, medium, and high doses at 40, 80, and 160 μmol·L−1 Al(mal)3 respectively), and one C188-9 (STAT3 antagonist) intervention group [10 μmol·L−1 C188-9 +160 μmol·L−1 Al(mal)3]. Cell viability was detected by CCK8. The expression of M1/M2 type markers, i.e. CD68/CD206, STAT3, p-STAT3, NLRP3, cleaved-casepase-1, and apoptosis-associated speck-like protein (ASC) in BV2 cells were detected by Western blotting, and proinflammatory cytokines interleukin (IL)-1β and IL-18, and anti-inflammatory cytokine IL-10 were determined by ELISA. Results The results of cell viability assay showed that cell viability gradually decreased with the increase of Al(mal)3 dose. Compared with the control group, the cell viability of the Al(mal)3 high-dose group was decreased by 18% (P<0.05); compared with the Al(mal)3 high-dose group, the cell viability of the C188-9 intervention group was significantly elevated by 14% (P<0.05). Compared with the control group, the expression levels of CD68 in the Al(mal)3 low-, medium-, and high-dose groups were elevated by 19%, 20%, and 21%, respectively (P<0.05); the expression level of CD206 in the Al(mal)3 high-dose group was decreased by 25% (P<0.05). Compared with the Al(mal)3 high-dose group, the expression level of CD68 in the C188-9 intervention group was reduced by 9% (P<0.05), whereas the expression level of CD206 was elevated by 22% (P<0.05). Compared with the control group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the Al(mal)3 high-dose group increased by 129% and 127%, respectively (P<0.05). Compared with the Al(mal)3 high-dose group, the p-STAT3 protein expression and the p-STAT3/STAT3 ratio in the C188-9 intervention group were decreased by 55% and 54%, respectively (P>0.05). Compared with the control group, the expression level of NLRP3 protein increased by 75% in the Al(mal)3 high-dose group (P<0.05), the expression levels of cleaved-casepase-1 protein increased by 28% and 35% in the Al(mal)3 medium- and high-dose groups (P<0.05), and the expression levels of ASC increased by 22%, 25%, and 53% in the Al(mal)3 low-, medium- and high-dose groups (P<0.05), respectively. Compared with the Al(mal)3 high-dose group, the expression levels of NLRP3, cleaved-casepase-1, and ASC proteins in the C188-9 intervention group decreased by 30%, 19%, and 32%, respectively (P<0.05). Compared with the control group, the levels of IL-1β in the Al(mal)3 medium- and high-dose groups increased by 18% and 21%, respectively (P<0.05), and the level of IL-18 in the Al(mal)3 high-dose group increased by 10% (P<0.05). Compared with the Al(mal)3 high-dose group, the IL-18 levels were reduced by 23% in the C188-9 intervention group (P<0.05). The content of anti-inflammatory factor IL-10 did not differ significantly between groups (P>0.05). Conclusion Aluminum can induce inflammatory responses in BV2 microglia and is predominantly pro-inflammatory, and the mechanism may involve STAT3 regulation of NLRP3 inflammasome secretion of inflammatory factors.

Effect of aluminum-fluoride interactions on overall cognitive function of aluminum plant workers / 环境与职业医学

Background Aluminum and fluoride are neurotoxic, and aluminum exposure alone is closely related to the overall cognitive function of operational workers. It is unclear about the effect of aluminum and fluoride interactions on cognitive function. Objective To evaluate a potential interaction effect of blood aluminum and urinary fluoride on the overall cognitive function of workers working in an aluminum plant. Methods Using cluster sampling, 230 workers in the electrolysis workshop of an aluminum group company in Shanxi Province were selected, and plasma aluminum concentrations were determined by inductively coupled plasma mass spectrometry (ICP-MS) and urinary fluoride by ion-selective electrode. The study participants were divided into a low blood aluminum group and a high blood aluminum group according to the median (M) of blood aluminum concentration, and a low urinary fluoride group and a high urinary fluoride group by a predetermined cutoff point (2.160 mg·L−1). The Montreal Cognitive Assessment-Beijing (MoCA-BJ) was used to assess overall cognitive function of the workers. Logistic regression model was used to analyze the relationship between blood aluminum, urinary fluoride, and mild cognitive impairment (MCI), including multiplicative interaction analysis and correlation analysis; R language was used to fit an additive interaction model of blood aluminum and urinary fluoride on MCI and to calculate synergy index (S), relative excess risk due to interaction (RERI), and attributable proportion due to interaction (API). Results Among the 230 operational workers, the median blood aluminum concentration (P25, P75) was 40.11 (25.16, 58.89) µg·L−1, and there were 104 cases of abnormal urinary fluoride, with an abnormality rate of 45.2%. There was a multiplicative interaction (OR=7.783, 95%CI: 1.377, 43.991) and no additive interaction (RERI=0.030, 95%CI: −0.498, 0.559; API=0.018, 95%CI: −0.279, 0.316; S=1.049, 95%CI: 0.519, 2.118) for the effect between blood aluminum and urinary fluoride on overall cognitive function of the workers. The logistic regression analysis showed that the risk of MCI was 12.105 (95%CI: 2.802, 52.287) times higher in workers with both high blood aluminum and high urinary fluoride than in those with low blood aluminum and low urinary fluoride, after adjusting for selected influencing factors. Conclusion Occupational exposure related high blood aluminum and high urinary fluoride are risk factors for cognitive dysfunction, and the coexistence of both indicators increases the risk of MCI in workers with occupational aluminum exposure, with a multiplicative interaction.

Correlation between aluminum concentration and miR-134-3p expression in peripheral blood in occupational aluminum exposed workers / 环境与职业医学

Background Previous studies show that aluminum exposure could increase the expression of miRNA-134-3p, which is involved in the mechanism of aluminum induced learning and memory impairment. However, it has not been investigated whether the expression level of miRNA-134-3p in the peripheral blood of occupational aluminum exposed workers is related to the blood aluminum concentration yet. Objective To evaluate a potential correlation between aluminum concentration in peripheral blood and miR-134-3p expression in occupational aluminum exposed workers. Methods A total of 184 male aluminum workers in the electrolytic aluminum workshop, aluminum oxide workshop, and thermal power workshop of an aluminum plant in Shanxi were selected by cluster sampling. They were divided into four groups (Q1-Q4) according to the quartiles of blood aluminum concentration, with 46 workers in each group. The basic information of workers was collected by questionnaire survey, and the cognitive function of workers was evaluated by Montreal Cognitive Assessment (MoCA). The plasma of workers was collected, and the relative expression level of miR-134-3p in plasma was detected by real-time quantitative polymerase chain reaction (RT-PCR). The plasma aluminum concentration was detected by inductively coupled plasma mass spectrometry (ICP-MS). The associations among workers' peripheral blood aluminum concentration, plasma miR-134-3p expression level, and total MoCA score were evaluated by generalized linear models. Results The workers' medians (P25, P75) of blood aluminum concentration, plasma relative expression level of miR-134-3p, and MoCA score were 39.31 (25.30, 57.41) μg·L-1, 2.93 (2.29, 3.74), and 22.0 (20.0, 26.0), respectively. The results of the generalized linear model showed that after adjusting for age, body mass index, smoking, and alcohol consumption, compared with the Q1 group, blood aluminum in the Q2, Q3, or Q4 group had an impact on related plasma miR-134-3p expression level and total MoCA score (P<0.05). With increasing blood aluminum concentration, the expression level of miR-134-3p in workers' plasma gradually increased, showing a positive correlation (b>0, Ptrend<0.001), while the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). As the expression level of miR-134-3p in plasma increased, the total score of MoCA gradually decreased, showing a negative correlation (b<0, Ptrend<0.001). There was a linear relationship between peripheral blood aluminum concentration and plasma relative expression level of miR-134-3p of the workers in the middle school and below group and the high school group (Ptrend<0.05), b (95%CI)=1.796 (1.248, 2.344) and 1.192 (0.874, 1.510), and no correlation was found in the workers in the college and above group (Ptrend>0.05). Conclusion Occupational aluminum exposure can lead to an increase in the expression level of miR-134-3p in plasma of workers, which may be related to a decrease in cognitive function of workers.

Mediating role of brain functional connectivity in cognitive decline induced by occupational aluminum exposure in workers / 环境与职业医学

Background Occupational aluminum exposure may associate with cognitive impairment in workers. At present, brain functional imaging data are not available for evaluating cognitive dysfunction in workers with occupational exposure to aluminum. The role of brain functional connectivity in cognitive decline associated with occupational aluminum exposure is not clear yet. Objective To explore potential mediating effect of brain functional connectivity value on cognitive decline induced by occupational aluminum exposure, to assess the relationship between cognitive impairment and brain functional connectivity, and to identify appropriate imaging evidence of early cognitive changes induced by occupational aluminum exposure. Methods This study used a subset data from a previous cross-sectional survey. Based on the data of aluminum-exposed workers, over 40 years old, aluminum-exposed working years >1 year, Montreal International Cognitive Assessment (MoCA) (Beijing version) score <26 points, 20 workers were selected as the case group, and 40 healthy workers with the same basic conditions (age, smoking, drinking, etc.) in non-aluminum production were selected as the control group with a 1∶2 matching ratio. The basic information of the subjects was collected, plasma aluminum level and cognitive function level were evaluated, and different brain functional connectivity values of default mode network (DMN) were measured by magnetic resonance imaging. The mediating effect analysis was conducted to examine the role of brain functional connectivity in the relationship between aluminum exposure and cognitive function. Results The plasma aluminum concentration of the case group was 1.76 times higher than that of the control group [(33.04±12.02) µg·L−1 vs (18.74±8.95) µg·L−1, P<0.05]; the MoCA score was 9.5 points lower [(18.35±2.64) vs (27.85±0.92), P<0.05]. The mean functional connection values of DMN1 and DMN2 in the case group were lower than those in the control group (P<0.05). The mean functional connection values of the left precuneus, left middle cingulate cortex, left superior medial gyrus, left precentral gyrus, and left cerebellum also decreased in the case group compared with the control group (P<0.05). Plasma aluminum concentration was negatively correlated with DMN1 functional connectivity value and MoCA scores (b=−0.004, 95%CI: −0.008–−0.001; b=−0.15, 95%CI: −0.233–−0.067; P<0.05). The mean functional connection values of DMN1 and DMN2 were positively correlated with MoCA scores (b=10.945, 95%CI: 5.574–16.316; b=10.107, 95%CI: 2.457–17.758; P<0.05). With the increase of plasma aluminum concentration, MoCA score decreased, but when the plasma aluminum concentration exceeded 19.50 µg·L−1, MoCA score decreased slowly. With the increase of the mean functional connectivity value of DMN1, MoCA score increased, but when the mean functional connectivity value of DMN1 exceeded 1.05 and continued to increase, the increase of MoCA score slowed down. The results of mediating effect analysis showed that the functional connectivity value of DMN1 partially mediated the relationship between plasma aluminum concentration and MoCA score, and the mediating effect was 25.80%. Conclusion Cognitive impairment in occupational aluminum-exposed workers is closely related to brain resting-state functional connectivity. There is a dose-response relationship of plasma aluminum concentration with DMN1 functional connectivity value and MoCA scores, and DMN1 functional connectivity value partially mediates the relationship between plasma aluminum concentration and MoCA scores. The brain functional connectivity value can be used as meaningful imaging data to study the cognitive decline induced by chronic aluminum exposure.

Effects of occupational aluminum exposure, types of alcohol consumption, and their interaction on cognitive function of workers / 环境与职业医学

Background Occupational aluminum exposure is closely related to cognitive impairment, and alcohol consumption is also closely related to cognitive dysfunction. Objective To explore the effects of types of alcohol consumption on cognitive function of occupational aluminum exposed workers. Methods A total of 181 workers aged from 23 to 56 years were selected by cluster sampling method in an electrolytic aluminum workshop of an aluminum plant in a region and in a maintenance workshop of another plant in the same region from July to August, 2019. Venous blood was collected, and plasma aluminum concentration was determined by inductively coupled plasma mass spectrometry. The study subjects were divided into low and high exposure groups based on the median blood aluminum level and type of work. Their basic information was collected by occupational health examination. Workers' cognitive function was assessed using the Montreal Cognitive Assessment Scale-Beijing Edition. Logistic regression was used to analyze the association between plasma aluminum concentration and cognitive impairment, and between the types of alcohol consumption (including Baijiu, red wine, and beer) and cognitive impairment, Unconditional logistic regression was used to fit multiplicative interaction model as well as additive interaction model of plasma aluminum concentration and the types of alcohol consumption, and to calculate the relative excess relative risk due to interaction (RERI) and attributable proportion due to interaction (AP). Results The M (P25, P75) concentrations of plasma aluminum were 40.01 (25.05, 60.56) µg·L−1 in the total study subjects, 25.16 (17.13, 34.78) µg·L−1 in the low exposure group and 60.56 (47.40, 68.53) µg·L−1 in the high exposure group. After adjusting the type of alcohol consumption, drinking, age, duration of exposure to aluminum, education, marital status, and smoking, the odds ratios for impairments of attention, language expression, and overall cognitive function in the high exposure group were 4.295 (95%CI: 1.912-9.648), 5.687 (95%CI: 1.355-23.867), and 2.720 (95%CI: 1.225-6.040) times of the low exposure group respectively. Besides, after adjusting blood aluminum concentration, total alcohol consumption, age, duration of exposure to aluminum, education, marital status, and smoking, the risk of attention impairment of the Baijiu drinkers was 2.613 (95%CI: 1.054 to 6.837) times of the non-Baijiu drinkers; the risks of impairment of visuospatial abilities and execution functions, language expression, delayed recall, and overall cognitive function of the beer drinkers were 3.165 (95%CI: 1.285-7.797), 17.898 (95%CI: 1.590-201.480), 3.118 (95%CI: 1.215-8.003), and 3.824 (95%CI: 1.736-8.423) times of the non-beer drinkers. There were both additive [RERI (95%CI): 1.745 (1.394-2.097), AP (95%CI): 0.415 (0.201-0.630)] and multiplicative (OR=3.591, 95%CI: 1.393-9.255) interactions between Baijiu intake and plasma aluminum concentration levels on the attention domain. The cognitive impairment attributed to the interactive effects of drinking Baijiu and plasma aluminum concentration in individuals with attention impairment accounted for 41.5%. There were both additive [RERI (95%CI): 5.955 (0.562-11.328), AP (95%CI): 0.829 (0.577-1.081)] and multiplicative (OR=42.174, 95%CI: 5.469-325.252) interactions between beer drinking and plasma aluminum concentration on the overall cognitive function. Among the individuals with overall cognitive impairment, the cognitive impairment caused by the interaction of beer drinking and plasma aluminum concentration accounted for 82.9%. Conclusion Occupation aluminum exposed workers' attention, language expression, and overall cognitive function are closely related to their plasma aluminum concentration. Plasma aluminum concentrations have interactions with Baijiu and beer consumption on cognitive impairment of workers.

Effect of occupational aluminum exposure on the visuospatialconstruction ability / 预防医学

Objective@#To examine the correlation between visuospatial construction ability and occupational aluminum exposure among aluminum workers, so as to provide the evidence for early protection of occupational injury among aluminum workers.@*Methods@#A total of 442 workers in an aluminum factory in Shanxi Province were selected using a cluster sampling method, and participants' demographic features and occupational history were collected. The blood aluminum concentration was measured using inductively coupled plasma mass spectrometry (ICP-MS), and the visuospatial construction ability was evaluated with the Cube Copying Test (CCT) of the Chinese version of the Montreal Cognitive Assessment (MoCA). The correlation between the visuospatial construction ability and blood aluminum concentration was examined using a multivariable logistic regression model.@*Results@#A total of 442 aluminum workers were enrolled, and all participants were male, with a mean age of (43.40±7.31) years, labor service duration of (23.64±8.35) years and a mean blood aluminum concentration of 33.87 µg/L. Of all participants, there were 206 workers with impaired visuospatial construction ability (46.61%), including 127 workers with blood aluminum concentrations of >33.87 µg/L (61.65%); 190 workers with educational duration of 6 to 9 years (92.23%), 118 electrolytic aluminum workers (57.28%), 114 workers with work shifts (55.34%), and 123 workers with a very good sleep quality (59.71%). Multivariable logistic regression analysis revealed that blood aluminum concentrations of >33.87 µg/L (OR=2.490, 95%CI: 1.531-4.052), educational duration of 6 years or more (OR: 0.075-0.246, 95%CI: 0.015-0.622), work type as a non-electrolytic aluminum worker (OR=0.838, 95%CI: 0.425-0.987), work shift (OR=1.179, 95%CI: 1.078-1.435) and a very good sleep quality (OR=0.104, 95%CI: 0.012-0.896) significantly correlated with impaired visuospatial construction ability among aluminum worker.@*Conclusion@#Impaired visuospatial construction ability correlates with occupational aluminum exposure among aluminum workers.

Association between metabolic syndrome and colorectal carcinoma based on a case-control study / 国际肿瘤学杂志

Objective To evaluate the association between metabolic syndrome and colorectal carcino-ma. Methods A total of 900 patients with colorectal carcinoma from 2013 to 2016 in Qianfoshan Hospital Af-filiated to Shandong University were selected as the case group and 1774 non-colorectal carcinoma participants from health management center as the control group. Logistic regression model was used to identify the relation-ship between metabolic syndrome and colorectal carcinoma. Results Compared with the controls (27. 0％), metabolic syndrome was more prevalent among cases (35. 4％). The difference was statistically significant (χ2 = 20. 33,P < 0. 01). Multivariate logistic regression analyses showed that metabolic syndrome as an entity increased colorectal carcinoma risk (OR = 1. 38,95％ CI:1. 08-1. 75,χ2 = 17. 68,P < 0. 01). Subjects with 2 and 3 or more components of the metabolic syndrome had an increased risk of colorectal carcinoma,and the ORs of colorectal carcinoma were 1. 37 and 1. 60,respectively. Gender-specific patterns were also observed in the association between metabolic syndrome,component and colorectal carcinoma (χ2 = 5. 40,P = 0. 02;χ2 =8. 66,P < 0. 01). Conclusion Metabolic syndrome is associated with the occurrence of colorectal carcinoma. An increasing trend in risk of colorectal carcinoma with the number of metabolic syndrome components is observed.

Influence of aluminum on microRNA29 and β-site amyloid precursor protein cleaving enzyme 1 in the brain of rats / 中华劳动卫生职业病杂志

Objective@#To investigate the influence of aluminum on microRNA29 (miR29) subtypes miR29a, miR29a*, miR29b1, miR29b2, miR29c1, and miR29c2 and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in the brain of rats.@*Methods@#A total of 40 Sprague-Dawley rats were randomly divided into control group and 15, 30, and 45 μmol/kg groups according to the body weight, with 10 rats in each group. The rats were exposed to aluminum (at a dose of 0.1 ml/100 g body weight) by intraperitoneal injection for 8 weeks. The rats in control group were given 0.9% normal saline, and those in exposure groups were given aluminum-maltolate (equivalent volumesof maltolate and aluminum solution were mixed before exposure) . The cerebral cortex and hippocampus were isolated after exposure ended; Western blotting was used to measure the change in BACE1 expression, and real-time reverse transcription polymerase chain reaction was used to measure the mRNA expression of miR29 subtypes in the cerebral cortex and hippocampus.@*Results@#Compared with the control group, the 45 μmol/kg group had a significant increase in BACE1 expression in the cerebral cortex, and the 30 and 45 μmol/kg groups had significant increases in BACE1 expression in the hippocampus (all P<0.05) . Compared with the control group, the 15, 30, and 45 μmol/kg groups had significant reductions in the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 in the cerebral cortex and hippocampus (all P<0.01) , and the 45 μmol/kg group had significant reductions in the mRNA expression of miR29a and miR29b1 in the cerebral cortex and hippocampus (all P<0.05) . The results of correlation analysis showed that there was no correlation between the mRNA expression of miR29a*, miR29b2, miR29c1, and miR29c2 and BACE1 expression in the cerebral cortex and hippocampus (all P>0.05) , while the mRNA expression of miR29a and miR29b1 was negatively correlated with BACE1 expression (cerebral cortex: r=-0.987 and -0.981, P<0.05; hippocampus: r=-0.992 and -0.991, P<0.05) .@*Conclusion@#Aluminum can reduce the expression of miR29 subtypes and increase BACE1 expression in the brain, and the expression of miR29a and miR29b1 is negatively correlated with BACE1 expression.

Analysis of Allergic Adverse Reaction Caused by Non-ionic Iodinated Contrast Media in 52 Patients With Coronary Angiography / 中国循环杂志

Objective: To analyze the current status of allergic adverse reactions caused by non-ionic iodinated contrast media in patients with coronary angiography (CAG). Methods: A total of 1 225 patients who received non-ionic iodinated contrast media for CAG in our hospital from 2011-02 to 2013-09 were retrospectively studied. There were 52 patients suffered from allergic adverse reactions including 47 (90.38%) male and 5 (9.62%) female. The allergic reaction to iodixanol, iohexol, iopamidol and iopromide were in 34, 3, 3 and 12 patients respectively. The clinical symptoms and outcomes of allergic reaction in 4 iodinated contrast media were analyzed. Results: There were 40/52 (76.92%) patients with mild allergic reaction, 11(21.15%) with moderate and 1 (1.92%) with severe reaction. 13 patients had the reaction within 1 hour of contrast media injection and 39 had the reaction between 1 hour to 3 days of contrast media injection. There 34 patients were cured by symptomatic and anti-allergic treatment, 1 patient was rescued from allergic shock and no death occurred. Conclusion: Application of non-ionic iodinated contrast media in CAG is safe, while closely observe the allergic adverse reaction with the in time and symptomatic treatment is very important in clinical practice.

Fabrication of New GH-CS/Fc-NH2/Cytc Modified Electrode and Its Application in Detection of Nitrite / 分析化学

Highly conjugated linear molecular wires are one of the basic elements for constructing molecular electronic devices. Among these conjugated compounds, ferrocene-terminated compounds as well as their derivatives have been widely studied because of their ideal electrochemical activity. Based on these, a new ferrocene-terminated phenylethynyaniline ( Fc-NH2 ) was synthesized by Sonogashira cross coupling reaction. The structure of the target compound was identified by infrared ( IR) , nuclear magnetic resonance ( NMR) , mass spectra ( MS) and cyclic voltammetry ( CV) . Combined the graphene-chitosan ( GH-CS) and Fc-NH2 , a new composite of GH-CS/Fc-NH2 was prepared and then used for immobilization of Cytc to prepare the GH-CS/Fc-NH2/Cytc/GCE. It was found from the CV result that a pair of peaks near-0. 2 V appeared which can be attributed to Cytc. The GH-CS/Fc-NH2/Cytc modified GCE showed good catalysis towards NaNO2 , and good linear relationship was found in the range of 1 ×10-7-1. 5 ×10-4 mol/L,and the determination limit was bellow 4×10-8 mol/L. Therefore, cytochrome c (Cytc) can be immobilized on the GH-CS/Fc-NH2 and the direct electron transfer can be realized between the electrode and solution and shows good prospect for detection of NaNO2 .