Evaluation of the default mode network using nonnegative matrix factorization in patients with cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is an important environmental pathogenic factor for neurodegenerative diseases, especially mild cognitive impairment (MCI). The aim of this study was to evaluate the gray matter volume of structural covariance network alterations in patients with Al-induced MCI. Male subjects who had been exposed to Al for >10 years were included in the present study. The plasma Al concentration, Montreal cognitive assessment (MoCA) score, and verbal memory assessed by the Rey auditory verbal learning test (AVLT) score were collected from each participant. Nonnegative matrix factorization was used to identify the structural covariance network. The neural structural basis for patients with Al-induced MCI was investigated using correlation analysis and group comparison. Plasma Al concentration was inversely related to MoCA scores, particularly AVLT scores. In patients with Al-induced MCI, the gray matter volume of the default mode network (DMN) was considerably lower than that in controls. Positive correlations were discovered between the DMN and MoCA scores as well as between the DMN and AVLT scores. In sum, long-term occupational Al exposure has a negative impact on cognition, primarily by affecting delayed recognition. The reduced gray matter volume of the DMN may be the neural mechanism of Al-induced MCI.

miR-128-3p is involved in aluminum-induced cognitive impairment by regulating the Sirt1-Keap1/Nrf2 pathway.

Aluminum (Al) is a common neurotoxicant in the environment, but the molecular mechanism of its toxic effects is still unclear. Studies have shown that aluminum exposure causes an increase in neuronal apoptosis. The aim of this study was to investigate the mechanism and signaling pathway of neuronal apoptosis induced by aluminum exposure. The rat model was established by intraperitoneal injection of maltol aluminum for 90 days. The results showed that the escape latency of the three groups exposed to maltol aluminum was higher than that of the control group on the 3rd, 4th and 5th days of the positioning cruise experiment (P < 0.05). On the 6th day of the space exploration experiment, compared with the control group(6.00 ± 0.71,15.33 ± 1.08) and the low-dose group(5.08 ± 1.69,13.67 ± 1.09), the number of times that the high-dose group crossed the platform(2.25 ± 0.76) and the platform quadrant(7.58 ± 1.43) was significantly reduced (P < 0.01). The relative expression levels of Sirt1 and Nrf2 in hippocampal tissues of all groups decreased gradually with increasing maltol aluminum exposure dose the relative expression levels of Sirt1 and Nrf2 in high-dose group (0.261 ± 0.094,0.325 ± 0.108) were significantly lower than those in control group (1.018 ± 0.222,1.009 ± 0.156)(P < 0.05). The relative expression level of Keap1 increased gradually with increasing maltol aluminum exposure dose (P < 0.05). The relative expression level of miR-128-3p in the high-dose group(1.520 ± 0.280) was significantly higher than that in the control group(1.000 ± 0.420) (P < 0.05). The content of GSH-Px in the hippocampus of rats decreased with increasing dose. ROS levels gradually increased. We speculated that subchronic aluminum exposure may lead to the activation of miR-128-3p in rat hippocampus of rats, thereby inhibiting the Sirt1-Keap1/Nrf2 pathway so that the Sirt1-Keap1/Nrf2 pathway could not be activated to exert antioxidant capacity, resulting in an imbalance in the antioxidant system of rats and the apoptosis of neurons, which caused reduced cognitive impairment in rats.

Role of the RIP3-PGAM5-Drp1 pathway in aluminum-induced PC12 cells necroptosis.

Epidemiological studies from diverse global regions suggest a correlation between the accumulation of aluminum in the brain and the onset of various neurodegenerative diseases, including Alzheimer's disease, of which, neuronal cells death happen. Our previous research has found the potential of aluminum to induce neuronal cell death. A comprehensive exploration of the regulatory pathways influenced by aluminum in neuronal cell death could contribute to the development of strategies aimed at preventing the detrimental impact of aluminum on neuronal cells. This study is dedicated to exploring the impact of aluminum on mitochondrial homeostasis through the RIP3-PGAM5-Drp1 pathway, with a specific focus on its potential role in necroptosis. We observed that the inhibition of RIP3 function and the reduction in PGAM5 protein expression both mitigate aluminum-induced necroptosis in PC12 cells and enhance mitochondrial function. However, the inhibition of PGAM5 protein expression does not exert an impact on the expression of RIP3 and MLKL proteins. In summary, our study posits that aluminum can induce necroptosis in PC12 cells through the RIP3-PGAM5-Drp1 pathway.

Cognitive status and its risk factors in patients with hypertension and diabetes in a low-income rural area of China: A cross-sectional study.

OBJECTIVES: The proportion of older people with dementia in China is gradually increasing with the increase in the aging population over recent years. Hypertension and diabetes are common non-communicable diseases among rural populations in China. However, it remains unclear whether these conditions affect the occurrence and development of cognitive impairment as there is limited research on cognitive status and its risk factors among residents of rural areas. METHODS: A multi-stage stratified cluster random sampling method was used to select 5400 participants from rural permanent residents. A self-designed structured questionnaire was used to investigate demographic data of the participants. Cognitive function was assessed using the Montreal Cognitive Function Assessment Scale (MoCA). The results were analyzed using chi-square test, ANOVA and multiple linear regression analysis. RESULTS: A total of 5028 participants returned the survey, giving a response rate of 93.1%. Higher education (odds ratio (OR) = 3.2, 95% confidence interval (CI) 2.87-3.54, p < 0.001), higher income (OR = 1.61, 95% CI 1.16-2.07, p < 0.001), and dietary control (OR = 0.66, 95%CI 0.34-0.98, p < 0.001) were protective factors. A visual representation of the relationship between annual income and MoCA score showed an inverted U-curve, the group with an annual income of 6000-7999 RMB had a maximum OR of 1.93 (95%CI 0.12-2.74, p < 0.001). While difficulty in maintaining sleep were risk factors for cognitive impairment (OR = -2.28, 95% CI-4.18-0.39, p = 0.018). CONCLUSIONS: Participants with middle incomes had better cognitive status than those with the highest incomes. Higher education, proper diet control and good sleep are beneficial to the cognitive status of residents in rural areas.

Lnc001209 Participates in aluminium-induced apoptosis of PC12 cells by regulating PI3K-AKT-mTOR signalling pathway.

Aluminium (Al) is a common environmental neurotoxin, but the molecular mechanism underlying its toxic effects remains unclear. Many studies have shown that aluminium exposure leads to increased neuronal apoptosis. This study aimed to investigate the mechanisms and signalling pathways involved in aluminium exposure-induced neuronal apoptosis. The results showed a decrease in the number of PC12 cells and changes in cell morphology in the aluminium maltol exposure group. The viability of PC12 cells decreased gradually with increasing of exposure doses, and the apoptosis rate increased. The expression of Lnc001209 decreased gradually with an increase in the aluminium exposure dose. After transfection of Lnc001209 siRNA in aluminium-exposed PC12 cells, the protein expression levels of p-Akt Ser473, p-Akt Thr308, p-P85 Tyr467, p-mTOR Ser2448 and CD36 were increased. RNA pull-down MS showed that Lnc001209 interacts with the CD36 protein. Expression of the CD36 protein was increased in PC12 cells exposed to aluminium. The results of the CD36 intervention experiment showed that the protein expression levels of p-Akt Ser473, p-Akt Thr308, p-P85 Tyr467, and p-mTOR Ser2448 likely increased after CD36 overexpression. In addition, the phosphorylation level of AKT had the most significant increase. The enhancement of p-Akt activity promotes neuronal apoptosis.

Simultaneous effects of aluminum exposure on the homeostasis of essential metal content in rat brain and perturbation of gut microbiota.

The theory of the brain-gut axis has confirmed that gut microbiota and metabolites are involved in the progression of neurodegenerative diseases through multiple pathways. However, few studies have highlighted the role of gut microbiota in cognitive impairment induced by aluminum (Al) exposure and its correlations with the homeostasis of essential metal content in the brain. To explore the relationship between alterations in the content of essential metals in the brain and relative abundance changes in gut microbiota induced by Al exposure, the Al, zinc (Zn), copper (Cu), iron (Fe), chromium (Cr), manganese (Mn), and cobalt (Co) content level in the hippocampus, olfactory bulb, and midbrain tissue were measured by inductively coupled plasma mass spectrometry (ICP-MS) methods after Al maltolate was intraperitoneally injected every other day for exposed groups. Then the unsupervised principal coordinates analysis (PCoA) and linear discriminant analysis effect size (LEfSe) were used to analyze the relative abundance of the gut microbiota community and the structure of the gut microbiome. Finally, the correlations between gut microbiota composition and essential metal content in the different exposure groups were explored by using the Pearson correlation coefficient method. Based on the results, we indicated that the content of Al in the hippocampus, olfactory bulb, and midbrain tissue was increased and then decreased with the increasing exposure duration, with peaks occurring between 14 and 30 days. Concomitantly, Al-exposure decreased the Zn, Fe, and Mn levels in these tissues. 16 S rRNA gene sequencing results indicated that significant differences in the intestinal microbial community structure at the phylum, family, and genus levels were found in the Day 90 exposed group compared with the Day 7 exposed group. Ten enriched species in the exposed group were identified as markers at the three levels. Furthermore, ten bacteria at the genus level were identified to have a significantly strong correlation (r = 0.70-0.90) with Fe, Zn, Mn, and Co.

Effect of the Reelin-Dab1 signaling pathway on the abnormal metabolism of Aß protein induced by aluminum.

Aluminum (Al) is a common neurotoxic element that can exacerbate intracellular ß-amyloid (Aß) deposition. Reelin is a highly conserved extracellular glycoprotein that is involved in intracellular Aß deposition. However, the action of Reelin on aluminum-induced Aß deposition is not fully understood. Here, we investigated the effects of the Reelin-Dab1 signaling pathway on Aß deposition in aluminum maltol (Al(mal)3) exposure in rat pheochromocytoma-derived cells (PC12). Our results showed that Al(mal)3 exposure decreased activity of PC12, increased expression of Aß42, and decreased expression of Aß40. Moreover, Al(mal)3 exposure in PC12 induced Reelin-Dab1 signaling pathway-associated proteins changed, decreased expression of Reelin and Dab1, and increased expression of pdab1. Moreover, the expression of Reelin, Dab1, and Aß40 was found to be elevated in PC12 exposed to Al(mal)3 and corticosterone compared to those exposed to Al(mal)3. Also, the expression of Reelin, Dab1, and Aß40 was found to be depressed in PC12 exposed to Al(mal)3 and streptozotocin compared with cells exposed to Al(mal)3 alone. These results suggested that Al(mal)3 inhibits the expression of the Reelin-Dab1 signaling pathway, promoting Aß deposition. Thus, our findings provided important evidence to better understand how the Reelin-Dab1 signaling pathway may be a potential mechanism of Aß deposition induced by aluminum.

Aluminum Induced Necroptosis of PC12 Cells via TNFR1-RIP1/RIP3 Signalling Pathway.

In addition to apoptosis, it has also been reported that aluminum (Al) causes necroptosis, a new form of programmed necrosis, which has recently been discovered, in nerve cells, but its molecular mechanism is not elucidated. In order to explore the answer, in this study, we apply for this method that after PC12 cells were exposed to maltol aluminum [200 µM Al(mal)3], siRNA were used as interference technique to explore the role of Tumour necrosis factor receptor 1 (TNFR1), receptor interaction proteins 1 (RIP1) and receptor interaction proteins 3 (RIP3) in necroptosis caused by Al(mal)3. After the end of this research, we demonstrated that, initially, Al(mal)3 could trigger apoptosis and necroptosis in PC12 cells and up-regulate both mRNA and protein expressions of TNFR1, RIP1 and RIP3, also, up-regulate the phosphorylated mixed lineage kinase domain-like protein (MLKL) protein expression. Additionally, in PC12 cells treated with Al(mal)3, suppression of TNFR1 was found to enhance apoptosis and attenuate the expression of RIP1/RIP3 and phosphorylated MLKL. At last, deficiency of RIP1/RIP3 reduced the extent of necroptosis. Briefly, our results verify that the TNFR1-RIP1/RIP3 pathway could be involved in Al(mal)3 induced necroptosis.

Prenatal benzo[a]pyrene exposure impairs hippocampal synaptic plasticity and cognitive function in SD rat offspring during adolescence and adulthood via HDAC2-mediated histone deacetylation.

Benzo[a]pyrene (B[a]P) is a widespread carcinogenic pollutant in the environment. Although previous studies have demonstrated the neurodevelopmental toxicity of B[a]P, the precise mechanisms underlying the neurotoxic effects induced by prenatal B[a]P exposure remain largely unknown. In the present study, pregnant Sprague-Dawley (SD) rats were injected intraperitoneally with 0, 10, 20, or 40 mg/kg-bw of B[a]P for three consecutive days on embryonic days 17-19. The learning and memory abilities of offspring were determined by Morris Water Maze (MWM) test, while the number of dendritic branches and the density of dendritic spines in hippocampal CA1 and DG regions were evaluated by Golgi-Cox staining at PND 45 and PND 75. The mRNA expression of BDNF, PSD-95, and SYP in offspring hippocampus were detected by qRT-PCR, and the protein expression of BDNF, PSD-95, SYP, HDAC2, acH3K9, and acH3K14 were measured by Western blotting or immunohistochemistry. CHIP-PCR was performed to further detect the levels of acH3K9 and acH3K14 in the promoter regions of BDNF and PSD-95 genes. Our results showed that rats prenatally exposed to B[a]P exhibited impaired spatial learning and memory abilities and the number of dendritic branches and the density of dendritic spines in the hippocampal CA1 and DG regions were significantly reduced during adolescence and adulthood. The expression of HDAC2 protein was significantly upregulated, while acH3K9, acH3K14, BDNF, PSD-95, and SYP protein levels were significantly downregulated in the hippocampus of B[a]P- exposed rats. In addition, CHIP results showed that prenatal B[a]P exposure markedly decreased the level of acH3K9 and acH3K14 in the promoter region of BDNF and PSD-95 gene in the hippocampus of PND 45 and PND 75 offspring. All of the results suggest that prenatal B[a]P exposure impairs cognitive function and hippocampal synaptic plasticity of offspring in adolescence and adulthood, and HDAC2-mediated histone deacetylation plays a crucial role in these deficits.

Phosphorylation of p53 by Cdk5 contributes to benzo[a]pyrene-induced neuronal apoptosis.

Benzo[a]pyrene (B[a]P) is a ubiquitous carcinogenic pollutant in the environment, however, the potential neurotoxic effects of B[a]P has not been elucidated clearly. In the present study, we explored the potential involvement of p53 phosphorylation by Cdk5 in B[a]P-induced neuronal apoptosis at both in vitro and in vivo settings. For in vitro studies, primary cortical neurons isolated from the brains of Sprague Dawley (SD) rat pup were exposed to 0, 10, 20, and 40 µM of B[a]P for 12, 24, or 48 h. For in vivo studies, SD rats were injected intraperitoneally with 0, 1.0, 2.5, and 6.25 mg/kg of B[a]P every other day for 1, 2, or 3 months. Our results demonstrated that exposure to B[a]P caused a dose- and a time-dependent increase in neuronal apoptotic ratio in both in vitro and in vivo studies. There was also a dose- and a time-dependent upregulation of p35, p25, Cdk5, and phosphorylated p53 at Ser15 after B[a]P exposure. In order to explore whether B[a]P-induced increased neuronal apoptosis was through Cdk5/p53 pathway, roscovitine, a specific Cdk5 inhibitor, was applied to pretreat neurons prior to B[a]P exposure. The results showed that pretreatment of neurons with roscovitine partially rescued cells from B[a]P-induced apoptosis, and alleviated B[a]P-induced upregulation of phosphorylated p53 at Ser15. Our results suggest that Cdk5/p53 signaling pathway may be involved in B[a]P-induced neuronal apoptosis, which will provide information to further elucidate the molecular mechanisms of B[a]P-induced neurotoxicity.

Deferoxamine ameliorated Al(mal)3-induced neuronal ferroptosis in adult rats by chelating brain iron to attenuate oxidative damage.

Aluminum (Al), a neurotoxic element, can induce Alzheimer's disease-like (AD-like) changes by triggering neuronal death. Iron homeostasis disturbance has also been implicated in Alzheimer's disease (AD), and excess iron exacerbates oxidative damage and cognitive defects. Ferroptosis is a nonapoptotic form of cell death dependent upon intracellular iron. However, the involvement of neuronal death induced by aluminum maltolate (Al(mal)3) in the pathogenesis of AD remains elusive. In this study, the results of three different behavioral experiments suggested that the learning and memory ability deteriorated and autonomous activity declined of these rats that exposed Al(mal)3 were alleviated by deferoxamine (DFO). Transmission electron microscope observations showed that the membrane was ruptured, and the membrane density increased and ridge disappearance (the most prominent characteristic of ferroptosis) in the perinuclear and cytoplasmic compartments of the hippocampal neurons were perceived in the exposure group, while the DFO group and 18 µM/kg Al(mal)3+DFO group were alleviated compared with 18 µM/kg Al(mal)3. In addition, DFO prevented oxidative stress, such as increased glutathione (GSH) and decreased malondialdehyde (MDA) and reactive oxygen species (ROS), while the latter two indexes had the same changing tendency as the total iron of brain tissue. These data indicated that Al(mal)3 could cause ferroptosis in Sprague-Dawley (SD) rat neurons, which was inhibited by DFO via reducing the content of iron and increasing the ability of cells to resist oxidative damage.

miR-29a and the PTEN-GSK3ß axis are involved in aluminum-induced damage to primary hippocampal neuronal networks.

We previously reported that aluminum (Al) can cause a range of neurotoxic injuries including progressive irreversible synaptic structural damage and synaptic dysfunction, and eventually neuronal deaths. Mechanism of Al-induced electrophysiological and neuronal connectivity changes in neurons may indicate damage to the neuronal network. Here, mouse primary hippocampal neurons were cultured on micro-electrode array (MEA)- and high-content analysis (HCA)-related plates, showing that Al exposure significantly inhibited hippocampal neuronal electrical spike activity and neurite outgrowth characterized by a reduction in neurite branching and a decrease in the average total neurite length in relation to both Al dose and time of incubation. In recent years, miR-29a/ phosphatase and tensin homolog (PTEN) have been found to play pivotal roles in the morphogenesis of neurons, it has been confirmed in vitro and in vivo that the PTEN-Glycogen synthase kinase-3ß (GSK-3ß) axis regulates neurite outgrowth. The present study demonstrated that increases in Al exposure and dose gradually reduce miR-29a expression. Up-regulation of miR-29a in the hippocampal neurons by lentivirus transfection reversed the decrease in electrical spike activity and the reduction in both neurite branching and length induced by Al. Moreover, miR-29a suppressed the expression of PTEN and increased the level of phosphorylated Protein Kinase B (p-AKT) and p-GSK-3ß which were inhibited by the Al treatment. This suggests that miR-29a is critically involved in the functional and structural neuronal damage induced by Al and is a potential target for Al neurotoxicity. Moreover, the reduction of neurite length and branching induced by Al exposure was regulated by miR-29a and its target neuronal PTEN-GSK3ß signaling pathway, which also represents a possible mechanism of Al-induced the inhibition of the electrical activity. Collectively, Al-induced damage to the neuronal network occurred through miR-29a-mediated alterations of the PTEN-GSK3ß signaling pathway.

Increased aluminum and lithium and decreased zinc levels in plasma is related to cognitive impairment in workers at an aluminum factory in China: A cross-sectional study.

BACKGROUND: Previous studies have shown that multiple imbalances of metal ions in the brain are closely associated with the neurodegenerative disorders. Our studies have shown that long-term working exposure to aluminum induces increased plasma aluminum levels and causes cognitive impairment in workers at aluminum factories. OBJECTIVE: To explore the levels of nine metals in plasma and the effect on cognitive function among in-service workers. METHODS: In this cross-sectional study, cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), which included seven subitems: executive/visuospatial abilities; naming; attention and calculation; language; abstract; recall; and orientation. The plasma levels of nine kinds of metals were measured by inductively coupled plasma-mass spectrometry (ICP-MS). A multivariate generalized linear regression model and Bayesian kernel machine regression (BKMR) were selected to estimate the relationship between metal plasma level and MoCA scores with adjustment for confounders. RESULTS: One hundred and eighty-seven workers participated in this study. In the multivariable generalized linear model, among these nine metals studied, five were related to the MoCA score: aluminum, lithium, cobalt, zinc and chromium. In the BKMR model, a significantly negative correlation between the plasma aluminum, lithium and the total MoCA score was observed. Moreover, for subitems on the MoCA scale, the plasma levels of lithium, aluminum, and zinc had a significant correlation with the executive/visuospatial abilities, naming, and orientation abilities, respectively. The log-transformation concentrations of plasma aluminum and lithium were negatively correlated with the executive/visuospatial abilities and naming abilities, respectively. The log-transformation plasma zinc concentration was positively correlated with orientation abilities. CONCLUSION: Based on the results, we determined that increased aluminum and lithium and decreased zinc levels in plasma were associated with the incidence of mild cognitive impairment (MCI) in workers at a Chinese aluminum plant.

Aluminum maltolate triggers ferroptosis in neurons: mechanism of action.

Aluminum (Al), a neurotoxic element, can induce Alzheimer's disease (AD) via triggering neuronal death. Ferroptosis is a new type of programmed cell death related to neurological diseases. Unfortunately, its role in aluminum-induced neuronal death remains completely unclear. This study aimed to investigate whether ferroptosis is involved in neuronal death in response to aluminum exposure as well as its underlying mechanism. In this study, rat adrenal pheochromocytoma (PC12) cells were treated with 200 µM aluminum maltolate (Al(mal)3) for 24 h, and related biochemical indicators were assessed to determine whether ferroptosis was induced by aluminum in neurons. Then, the potential mechanism was explored by detecting of these genes and proteins associated with ferroptosis after adding ferroptosis-specific agonist Erastin (5 µM) and antagonist Ferrostatin-1 (Fer-1) (5 µM). The experimental results demonstrated that aluminum exposure significantly increased the death of PC12 cells and caused specific mitochondrial pathological changes of ferroptosis in PC12 cells. Further research confirmed that ferroptosis was triggered by aluminum in PC12 cells by means of activating the oxidative damage signaling pathway, which was displayed as inhibition of the cysteine/glutamate antiporter system (system Xc-), causing the depletion of cellular glutathione (GSH) and inactivation of glutathione peroxidase (GSH-PX) eventually lead to accumulation of reactive oxygen species (ROS). Taken together, ferroptosis was a means of neuronal death induced by aluminum and oxidative damage may be its underlying mechanism, which also provided some new clues to potential target for the intervention and therapy of AD.

[Regulatory role of Ca MK-â ¡ and PP2A on hyperphosphorylated tau induced by Al Cl_3 in SH-SY5Y cells].

OBJECTIVE: To explore the role of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK-Ⅱ) and protein phosphatase-2 A(PP2 A) on hyperphosphorylation of tau induced by AlCl_3 in SH-SY5 Y cell. METHODS: SH-SY5 Y cells were assigned to the control group, AlCl_3 low, middle, high exposed groups(200, 400800 µmol/L Al~(3+)), KN93 intervention group(800 µmol/L Al~(3+)+0. 5 µmol/L KN93) and sphingosine intervention group(800 µmol/L Al~(3+)+5 nmol/L sphingosine). After 48 h of exposure and intervention, the viabilities of cells were measured by CCK-8 assay, the contents of CaMK-Ⅱ and PP2 A were determined by ELISA, and the expression of tau5 and phosphorylation of Thr-181, Thr-231, Ser-262 and Ser-396 were detected by Western-Blot. RESULTS: The viabilities of cells in AlCl_3 middle and high exposed groups were significantly lower than that of the control group(P<0. 05). Compared with the AlCl_3 high exposed group, the viabilities of cells in KN93 intervention group and sphingosine intervention group were significantly increased(P<0. 05), as well as the difference of the cell viability between sphingosine intervention group and the control group was not statistically significant. Compared with the control group, the contents of CaMK-Ⅱin AlCl_3 low, middle, high exposed groups were significantly increased(P<0. 05), while the contents of PP2 A in those groups were significantly decreased(P<0. 05). Compared with AlCl_3 high exposed group, the contents of CaMK-Ⅱ in KN93 intervention group and sphingosine intervention group were significantly decreased(P<0. 05), and PP2 A in those groups were significantly increased(P<0. 05). The expression of tau5 and phosphorylation of Thr-181, Thr-231, Ser-396 in AlCl_3 low, middle, high exposed group showed significantly higher than those of the control group(P<0. 05), while the phosphorylation of Ser-262 in AlCl_3 high exposed group showed significantly higher than that of the control group(P<0. 05). After intervention with KN93 and sphingosine, the expression of tau5, and phosphorylation of Thr-181, Thr-231, Ser-262, Ser-396 in KN93 intervention group and sphingosine intervention group were significantly lower than those of AlCl_3 high exposed group( P<0. 05), as well as compared with the control group, the phosphorylation of Ser-262 in KN93 intervention group and Thr-181, Thr-231 and Ser-396 in sphingosine intervention group were not statistical difference. CONCLUSION: AlCl_3 could increase the phosphorylation of Thr-181, Thr-231, Ser-262 and Ser396 in SH-SY5 Y cells, which mechanism may relate to the changes of CaMK-Ⅱand PP2 A. CaMK-Ⅱ mainly regulates the phosphorylation of Ser-262 induced by AlCl_3, while PP2 A mainly regulates the phosphorylation of Thr-181, Thr-231 and Ser-396 induced by AlCl_3. It is suggested that hyperphosphorylated tau protein induced by AlCl_3 is closely related to PP2 A.

Prenatal polycyclic aromatic hydrocarbons metabolites, cord blood telomere length, and neonatal neurobehavioral development.

BACKGROUND: Prenatal exposure to polycyclic aromatic hydrocarbon (PAH) is a potential risk factor for child neurobehavioral development. Telomere length (TL) has important implications for health over the life course. OBJECTIVE: In this study, we aimed to investigate whether prenatal urinary PAH metabolites were associated with adverse neonatal neurobehavioral development and altered cord blood TL and to explore whether the change of TL was a predictor of neonatal neurobehavioral development. METHOD: We enrolled 283 nonsmoking pregnant women in Taiyuan city. Eleven PAH metabolites were measured in maternal urine samples. TL in cord blood was measured by real time quantitative polymerase chain reaction. Neonatal behavioral neurological assessment (NBNA) tests were conducted when the infants were three days old. Multiple linear regression models were used to analyze the associations of maternal urinary PAH metabolites with NBNA scores and cord blood TL, and restricted cubic spline models were further used to examine the shapes of dose-response relationships. A mediation analysis was also conducted. RESULT: We observed dose-response associations of maternal urinary 2-hydroxyfluorene (2-OHFlu) and 2-hydroxyphenanthrene (2-OH Phe) with decreased active tone scores, sum of NBNA scores, and cord blood TL (P for trend<0.05). Each 1 unit increase in urinary levels of Ln (2-OH Flu) or Ln (2-OH Phe) was associated with a 0.092 or 0.135 decrease in the active tone scores and a 0.174 or 0.199 decrease in the sum of NBNA scores. Mediation analysis showed TL could explained 21.74% of the effect of sum of NBNA scores change related to prenatal exposure to 2-OH Phe (P for mediator = 0.047). CONCLUSION: Our data indicates maternal urinary specific PAH metabolites are inversely associated with neonatal neurobehavioral development and cord blood TL. TL mediates the associations of 2-OH Phe with neonatal neurobehavioral development and partly explains the effect of 2-OH Phe on neonatal neurobehavioral development.

Maternal urinary 2-hydroxynaphthalene and birth outcomes in Taiyuan, China.

BACKGROUND: Naphthalene is the simplest polycyclic aromatic hydrocarbon (PAH). It is easily emitted into the atmosphere, posing a significant risk to human health. However, limited studies have described the impact of naphthalene exposure on birth outcomes. In this study, we investigated the association between the maternal urinary metabolites of naphthalene, 2-hydroxynaphthalene (2-OH NAP), and birth outcomes. METHOD: In the present study, four urinary PAH metabolites were measured in 263 pregnant women during late pregnancy. Multiple linear regression analysis was used to analyze the relationship between the concentrations of 2-OH NAP and birth outcomes, and restricted cubic spline models were further used to examine the shapes of the dose-response association. RESULT: General linear models showed that prenatal urinary 2-OH NAP was associated with lower birth weight (BW) (- 4.38% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.049) and higher cephalization index (CI) (4.30% for the high vs. low exposure group of 2-OH NAP; p for trend = 0.038). These associations were linear and significant when 2-OH NAP was modeled as a continuous variable in restricted cubic spline models (P linear = 0.0293 for 2-OH NAP and BW; P linear = 0.0326 for 2-OH NAP and CI). Multiple linear regression data indicated that each 1 ln-unit increase in 2-OH NAP was significantly associated with a 2.09 g/cm increase in the CI. The associations among 2-OH NAP, BW, and CI were also observed in a subset of participants residing close to arterial traffic. CONCLUSION: Our data indicated that prenatal exposure to naphthalene had an adverse effect on fetal birth outcomes, especially the brain development index. Reduced exposure to naphthalene may improve newborn health outcomes. In Taiyuan, naphthalene may result from traffic pollution.

Overview of the Relationship Between Aluminum Exposure and Health of Human Being.

Aluminum is a type of ubiquitously existing naturally and widely used metal in our world. It is combined with other elements and forms different compounds. In different pH and due to other conditions, it can be released into ions of different valence states. Our century is an "aluminum age"; aluminum is used in many fields of our daily life, such as vaccine adjuvant, antacids, food additives, skin care products, cosmetics, and cooking wares, and may be as elements or contaminants appeared in a lot of foods, including infant formulae, milk products, juice, wine, sea foods, and tea. It also appears in drinking water due to the water treatment process, or naturally coming from weathering rocks and soils, or released from rocks and soils caused by pollution-induced acid rain. Due to good physical and chemical property, aluminum is being tremendously utilized in many industries. In a lot of production and process procedures, aluminum particulates are seriously exposed by workers. Many factors, such as silicon, citrate, iron, calcium, fluoride, etc., can affect absorption of aluminum in human body. Human being ingests aluminum through the respiratory and digestive system and skin. Aluminum can affect our health, especially impair central nervous system. The important damage is cognitive impairment in Al-exposed peoples, Alzheimer's disease and other neurodegenerative disorders have been related with aluminum exposure, and aluminum has been proposed as etiology.

Alumina at 50 and 13 nm nanoparticle sizes have potential genotoxicity.

Although nanomaterials have the potential to improve human life, their sideline effects on human health seem to be inevitable and still are unknown. Some studies have investigated the genotoxicity of alumina nanoparticles (AlNPs); however, this effect is still unclear due to insufficient evaluation and conflicting results. Using a battery of standard genotoxic assays, the present study offers evidence of the genotoxicity associated with aluminum oxide (alumina) at NP sizes of 50 and 13 nm, when compared with bulk alumina (10 µm). The genotoxicity induced by alumina at bulk and NP sizes was evaluated with Ames test, comet test, micronucleus assay and sperm deformity test. The mechanism related to the induction of reactive oxygen species was explored as well. Our results showed that AlNPs (13 and 50 nm) were able to enter cells and induced DNA damage, micronucleus in bone marrow, sperm deformation and reactive oxygen species induction in a time-, dose- and size-dependent manner. Therefore, we conclude that AlNPs (13 and 50 nm), rather than bulk alumina, induce markers of genotoxicity in mice, with oxidative stress as a potential mechanism driving these genotoxic effects. Copyright © 2017 John Wiley & Sons, Ltd.

[Allergens in occupational allergy: risk management.] / Gli allergeni nell'allergia occupazionale: management del rischio.

OBJECTIVES: The first essential aspect for the prevention of occupational allergy is related to the accurate allergen identification and characterization. At present many efforts are made to characterize the potential for a chemical to be a sensitizing agent. METHODS: 'Omics' show great promise to identify key cellular and molecular events relevant to development of an adverse outcome pathway for respiratory sensitizers. One approach that shows promise is based on the measurement of the peptide reactivity of chemicals; the potential to form stable associations with protein/peptide being a key requirement for the induction of sensitization. RESULTS: Sensitization is a dose-related phenomenon, therefore the lower the exposure the lower the risk of sensitization. CONCLUSIONS: In any way, establishing occupational exposure limits for chemical allergens presents numerous difficulties. Therefore it is important using alternative exposure recommendations and risk management practices, including medical surveillance and tertiary prevention, to aid in protecting workers from exposures to allergens.