The White Matter Integrity and Functional Connection Differences of Fornix (Cres)/Stria Terminalis in Individuals with Mild Cognitive Impairment Induced by Occupational Aluminum Exposure.

Long-term aluminum (Al) exposure increases the risk of mild cognitive impairment (MCI). The aim of the present study was to investigate the neural mechanisms of Al-induced MCI. In our study, a total of 52 individuals with occupational Al exposure >10 years were enrolled and divided into two groups: MCI (Al-MCI) and healthy controls (Al-HC). Plasma Al concentrations and Montreal Cognitive Assessment (MoCA) score were collected for all participants. And diffusion tensor imaging and resting-state functional magnetic resonance imaging were used to examine changes of white matter (WM) and functional connectivity (FC). There was a negative correlation between MoCA score and plasma Al concentration. Compared with the Al-HC, fractional anisotropy value for the right fornix (cres)/stria terminalis (FX/ST) was higher in the Al-MCI. Furthermore, there was a difference in FC between participants with and without MCI under Al exposure. We defined the regions with differing FC as a "pathway," specifically the connectivity from the right temporal pole to the right FX/ST, then to the right sagittal stratum, and further to the right anterior cingulate and paracingulate gyri and right inferior frontal gyrus, orbital part. In summary, we believe that the observed differences in WM integrity and FC in the right FX/ST between participants with and without MCI under long-term Al exposure may represent the neural mechanisms underlying MCI induced by Al exposure.

A Bayesian network for estimating hypertension risk due to occupational aluminum exposure.

Background: The correlation between metals and hypertension, such as sodium, zinc, potassium, and magnesium, has been confirmed, while the relationship between aluminum and hypertension is not very clear. This study aimed to evaluate the correlation between plasma aluminum and hypertension in electrolytic aluminum workers by the Bayesian networks (BN). Methods: In 2019, 476 male workers in an aluminum factory were investigated. The plasma aluminum concentration of workers was measured by inductively coupled plasma mass spectrometry. The influencing factors on the prevalence of hypertension were analyzed by the BN. Results: The prevalence of hypertension was 23.9% in 476 male workers. The risk of hypertension from plasma aluminum in the Q2, Q3, and Q4 groups was 5.20 (1.90-14.25), 6.92 (2.51-19.08), and 7.33 (2.69-20.01), respectively, compared with that in the Q1 group. The risk of hypertension from the duration of exposure to aluminum of >10 years was 2.23 (1.09-4.57), compared without aluminum exposure. Area under the curve was 0.80 of plasma aluminum and the duration of exposure to aluminum was based on covariates, indicating that aluminum exposure had important predictive value in the prevalence of hypertension in the occupational population. The results of the study using the BN model showed that if the plasma aluminum of all participants was higher than Q4 (≥47.86 µg/L) and the participants were drinking, smoking, diabetes, central obesity, dyslipidemia, and aged >50 years, the proportion of hypertension was 71.2%. Conclusions: The prevalence of hypertension increased significantly with the increase of plasma aluminum level.

Decoupling of gray and white matter functional networks in cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.

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.

Interaction between aluminum exposure and ApoEε4 gene on cognitive function of in-service workers.

The occurrence and development of cognitive impairment, the early stage of AD, may be affected both by factors of environmental (aluminum exposure) and genetic (ApoEε4 gene). But whether there is an interaction between the two factors on cognitive function is still unknown. To explore the interaction between the two factors on cognitive function of in-service workers. A total of 1121 in-service workers in a large aluminum factory were investigated in Shanxi Province. Cognitive function was assessed by the Mini-mental State Examination (MMSE), the clock-drawing test (CDT), the Digit Span Test (DST, including DSFT and DSBT), the fuld object memory evaluation (FOM), and the verbal fluency task (VFT). The plasma-Al (p-Al) concentrations were measured by inductively coupled plasma-mass spectrometry (ICP-MS) as an internal exposure indicator, and the participants were divided into four Al exposure groups according to the quartile of p-Al concentrations, namely Q1, Q2, Q3, and Q4. ApoE genotype was determined by Ligase Detection Reaction (LDR). The multiplicative model was fitted using non-conditional logistic regression and additive model was fitted using crossover analysis to analyze the interaction between p-Al concentrations and the ApoEε4 gene. Finally, a dose-response relationship between p-Al concentrations and cognitive impairment was observed, with the p-Al concentrations increased, cognitive function performance gradually becomes worse (Ptrend＜0.05), and the risk of cognitive impairment gradually increases (Ptrend＜0.05), mainly in executive/visuospatial impairment, auditory memory impairment (particularly the working memory impairment). And ApoEε4 gene may be a risk factor for cognitive impairment, while no association between the ApoEε2 gene and cognitive impairment is observed. Additionally, an additive but no multiplicative interaction between p-Al concentrations and ApoEε4 gene is observed, and when the two factors work together, the risk of cognitive impairment further increased, of which 44.2% can be attributed to the interaction effect.

Role of Autophagy and Apoptosis in Aluminum Exposure-Induced Liver Injury in Rats.

Aluminum (Al) exposure can lead to different degrees of damage to various organ systems of the body. It has been previously revealed that Al exposure can damage the liver, causing liver dysfunction. However, the specific mechanism remains unclear. This research aims to uncover the damaging effect of Al exposure on rat liver and to demonstrate the role of autophagy and apoptosis in this effect. Thirty-two Wistar rats were randomly divided into the control group (C group), low-dose Al exposure group (L group), middle-dose Al exposure group (M group), and high-dose Al exposure group (H group) (n = 8). The rats, respectively, received intraperitoneal injections of 0, 5, 10, and 20 mg/kg·day AlCl3 solution for 4 weeks (5 times/week). After the experiment, changes in the ultrastructure and autolysosome in rat liver were observed; the liver function, apoptosis rate, as well as levels of apoptosis-associated proteins and autophagy-associated proteins were detected. The results indicated that Al exposure damaged rat liver function and structure and resulted in an increase in autolysosomes. TUNEL staining revealed an elevated number of apoptotic hepatocytes after Al exposure. Moreover, we found from Western blotting that the levels of autophagy-associated proteins Beclin1 and LC3-II were increased; apoptotic protein Caspase-3 level was elevated and the Bcl-2/Bax ratio was reduced. Our research suggested that Al exposure can lead to high autophagy and apoptosis levels of rat hepatocytes, accompanied by hepatocyte injury and impaired liver function. This study shows that autophagy and apoptosis pathways participate in Al toxication-induced hepatocyte injury.

Diffusion Kurtosis Imaging in Evaluating the Mild Cognitive Impairment of Occupational Aluminum Workers.

RATIONALE AND OBJECTIVES: To investigate whether diffusion kurtosis imaging (DKI) can distinguish mild cognitive impairment (MCI) from normal controls (NC) in aluminum (Al)-exposed workers, and to explore the association of DKI with cognitive performance and plasma Al concentration. MATERIALS AND METHODS: 28 patients with MCI and 25 NC at Al factory were enrolled in this study. All subjects underwent conventional MRI and DKI scans. The mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), mean diffusivity (MD) and fractional anisotropy (FA) parameters of the hippocampus, substantia nigra, red nucleus, thalamus, anterior cingulate gyrus, genu and crus of the corpus callosum, frontal, parietal and temporal lobe were measured. To compare the parameters between the two groups, the Mann-Whitney rank sum test was used. The correlation of parameter values with cognitive performance and plasma Al concentration was analyzed using Spearman correlation analysis. The receiver operating characteristic (ROC) curve and the Z-scores were used to evaluate the diagnostic efficacy of each parameter. RESULTS: Compared with the NC group, the MK, Ka, Kr, and FA values in the MCI group were significantly decreased, and the MD values were significantly increased (p<0.05). For the diagnosis of MCI, MK in the right hippocampus showed the largest AUC (0.924). The MK, Kr, MD and FA values were correlated with the Montreal Cognitive Assessment (MoCA) scores, and MK values in the right hippocampus showed the greatest correlation with MoCA scores (r=0.744, p <0.001). Plasma Al in the MCI group was higher than that in the NC group, although there was no significant difference in plasma Al between the two groups (p=0.057). There was no correlation between DKI parameters and plasma Al. CONCLUSION: The DKI method might be a sensitive imaging biomarker to discriminate MCI from NC, and could preliminarily assess the severity of cognitive impairment in Al-exposed workers. MK in the right hippocampus appeared to be the best independent predictor. The mechanism of cognitive decline is an important content of aluminum exposure research. This study indicates that the DKI technique could provide valuable information for the diagnosis of MCI.

Forecasting and analysis of the effect of lifestyle on cognitive dysfunction induced by occupational aluminum exposure based on Bayesian networks.

OBJECTIVES: To evaluate the risk of cognitive impairment in workers with plasma aluminum concentrations and lifestyles using a Bayesian network (BN). METHODS: In 2019, 476 male workers in the Shanxi Aluminum factory were investigated. We measured plasma aluminum concentrations in workers by inductive coupled plasma mass spectrometry (ICPMS) and tested workers' cognitive function by the MoCA scale. We collected the data of lifestyle by the occupational Workers' Health questionnaire and express the influence of lifestyle on cognition by the OR value (95 %CI) of logistic regression. A Bayesian network model was used to predict the risk of cognitive dysfunction. RESULTS: The subjects were divided into a cognitively normal group and cognitively impaired group according to MoCA scores. There were statistically significant differences in age, education level, alcohol consumption, physical exercise, reading, aluminum length of service and blood aluminum concentration between the two groups (P < 0.05). The plasma aluminum concentration in the cognitive impairment group was 1.68 times higher than that in the cognitive normal group. Four groups were established according to the quartile of blood aluminum concentration of the subjects, namely, Group Q1 (<14.95 µg/L), Q2 group (14.95-32.96 µg/L), Q3 group (32.96-56.62 µg/L), and Q4 group (>56.62 µg/L). Binary logistic regression analysis showed that in the adjustment variable Model2, drinking, short sleep, long sleep, and mobile phone use increased the risk of cognitive impairment by 1.505(0.99,2.289), 1.269(0.702,2.295), 1.125(0.711,1.781) and 1.19(0.779,1.82), respectively, compared with their reference values. The risk of cognitive impairment from reading and exercise was 0.7(0.398,1.232) and 0.787(0.51,1.217), respectively, compared with those of no reading and no exercise. The risk of cognitive impairment of blood aluminum concentration in the Q2, Q3, and Q4 groups was 2.103(1.092,4.051), 1.866(0.955,3.644) and 3.679(1.928,7.020), respectively, compared with that in the Q1 group. Compared with age <40 , the risk of cognitive impairment of age ≥40 was 2.515(1.508,4.193) (P < 0.05). Bayesian network model results showed that if all participants had plasma aluminum concentrations higher than Q4, the prevalence of cognitive impairment was 54.5 %. The prevalence of cognitive impairment was 75.0 % if all participants had plasma aluminum levels above Q4, were older than 40, smoked, drank alcohol, used a cell phone for more than 2 h, slept for more than 8 h, did not exercise, and did not read. CONCLUSIONS: Our findings suggest that both poor lifestyle and occupational aluminum exposure may affect cognitive function. Workers must maintain a reasonable lifestyle and reduce aluminum exposure, which can control the occurrence of cognitive impairment.

Aluminum exposure induces nephrotoxicity via fibrosis and apoptosis through the TGF-ß1/Smads pathway in vivo and in vitro.

Aluminum (Al), the most common element in nature, can enter the body through various routes. Unfortunately, excessive accumulation of Al in the body can cause chronic toxicity. In this study, rats were randomly allocated to 4 groups and intraperitoneally injected with AlCl3 solution at 0, 5, 10, and 20 mg/(kg·d), respectively, for 4 weeks. The kidney function of rats and Al contents in the kidney were measured, and the pathological structural changes and apoptosis of the kidney were observed. Meanwhile, the expression of fibrosis- and apoptosis-related proteins was detected with western blot. For the in vitro assay, HK-2 cells were used to construct a model to evaluate the effects of Al exposure on cell viability, cell apoptosis, and the expression of fibrosis- and apoptosis-related proteins. Additionally, the TGF-ß1/Smads pathway was also altered in HK-2 cells, followed by the measurement of changes in apoptosis and fibrosis-related proteins. The results revealed that Al could accumulate in kidney tissues, then leading to histopathological changes and kidney function impairment, promoting renal tubular cell apoptosis and renal collagen fiber deposition, and also elevating the expression of TGF-ß1/Smads pathway-related proteins. In vitro experiments also exhibited that Al exposure increased apoptosis and the expression of fibrosis-related factors in HK-2 cells, accompanied by activation of the TGF-ß1/Smads pathway. Further modulation of the TGF-ß1/Smads pathway manifested that activation of the TGF-ß1/Smads pathway facilitated Al-induced apoptosis and fibrosis-related factor expression, while inhibition of the pathway negated this effect of Al. In conclusion, the findings of the present study illustrate that Al exposure damages kidney function and facilitate apoptosis and kidney fibrosis, which may be achieved through the activation of the TGF-ß1/Smads pathway. This study provides a new theoretical basis for the study of nephrotoxicity induced by excessive Al exposure.

Tamarindus indica ameliorates behavioral and cytoarchitectural changes in the cerebellar cortex following prenatal aluminum chloride exposure in Wistar rats.

Aluminium exposure has been linked with developmental neurotoxicity in humans and experimental animals. The study aimed to evaluate the ameliorative effect of Tamarindus indica on the developing cerebellar cortex, neurobehavior, and immunohistochemistry of the cerebellar cortex following prenatal aluminum chloride (AlCl3) exposure. Pregnant timed Wistar rats were divided into 5 groups (n=4). Group I (negative control) was given distilled water, group II was treated with 200 mg/kg of AlCl3, group III were given 200 mg/kg of AlCl3 and 400 mg/kg of ethyl acetate leaf fraction of Tamarindus indica (EATI), group IV were given 200 mg/kg of AlCl3 and 800 mg/kg of EATI, and group V were treated with 200 mg/kg of AlCl3 s/c and 300 mg/kg of vitamin E for 14 days (prenatal day 7-21) via the oral route. Male pups (n=6) were randomly selected and taken for neurobehavioral studies, and humanely sacrificed via intraperitoneal injection of thiopental sodium. The cerebellum was removed, fixed and tissue processed for histological and immunohistochemical studies. The results revealed that prenatal AlCl3 exposure impacted neurodevelopment and neurobehaviour among exposed pups. Prenatal AlCl3 exposure was marked with delayed cytoarchitectural development of the cerebellar cortex and increased GFAP expression in the cerebellar cortex. On the other hand, treatment with EATI and vitamin E were marked with significant improvements. The present study therefore concluded treatment with EATI shows an ameliorative effect to prenatal AlCl3 exposure.

Blood glucose mediated the effects of cognitive function impairment related to aluminum exposure in Chinese aluminum smelting workers.

OBJECT: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum. METHOD: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis. RESULT: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al. CONCLUSION: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function.

Resveratrol alleviates aluminum-induced intestinal barrier dysfunction in mice.

BACKGROUND: Aluminum is mainly exposed to the general population through food and water, and is absorbed into the systemic circulation through intestine, which in turn damages the intestinal barrier. METHODS: The mice model of subchronic exposure to aluminum chloride (AlCl3 ) was established via oral. Tail suspension test was used to detect depressive behavior. H&E staining was performed to assess pathological intestinal injury. Intestinal permeability was estimated by exogenous Evans blue content. The level of inflammatory cytokines and tight junction protein were assessed via ELISA and western blotting. Simultaneously, resveratrol (Rsv, an agonist of Sirt1) was evaluated the protective role against intestinal barrier injuries caused by aluminum exposure. RESULTS: Our results showed that AlCl3 induced depressive-like behavior, intestinal pathological damage and intestinal barrier permeability, resulting in intestinal barrier dysfunction. Besides, aluminum induced the expression of inflammatory cytokines, which further triggered IRF8-MMP9-mediated downregulation of tight junction proteins including CLD1, OCLD and ZO-1. After Rsv treatment, SIRT1 expression was increased, depressive symptom was improved, pathological injury was reduced, inflammatory reaction was alleviated, and intestinal barrier function restored. CONCLUSION: Our findings revealed that aluminum exposure induced intestinal barrier dysfunction by IRF8-MMP9 signaling pathway. Rsv alleviated these injuries via activating SIRT1.

Molecular Mechanism of Aluminum-Induced Oxidative Damage and Apoptosis in Rat Cardiomyocytes.

Aluminum exposure can mediate either acute toxicity or chronic toxicity. Aluminum exerts toxic effects on the cardiovascular system, but there are few studies on its related mechanisms. In this study, we investigated the molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Thirty-two male Wistar rats were randomly divided into four groups, including the control group (GC), low-dose group of aluminum exposure (GL), medium-dose group (GM), and high-dose group (GH), with eight rats in each group. The GL, GM, and GH groups were given 5, 10, and 20 mg/(kg·d) of AlCl3 solution by intraperitoneal injection, and the GC group received intraperitoneal injection of the same volume of normal saline (2 ml/rat/day), 5 times a week for 28 days. At the end of the experiment, the levels of aluminum, malondialdehyde (MDA), plasma lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB), and alpha-hydroxybutyrate dehydrogenase (HBDH) were measured. The pathological changes of myocardium were observed by H&E staining. The apoptosis of cardiomyocytes was detected by TUNEL staining, and the expression of apoptosis-related proteins was determined by western blot. The results showed that the levels of CKMB and HBDH in the GM and GH groups were significantly higher than those in the GC group (P < 0.05). The content of aluminum in the myocardium and serum of the aluminum exposure groups was significantly higher than that of the GC group (P < 0.05). The level of MDA in the GM and GH groups was significantly higher than that in the GC group (P < 0.05). The pathological results showed that vacuolated and hypertrophied cardiomyocytes were found in aluminum exposure groups, especially in the GM and GH groups. The TUNEL staining showed that the apoptosis rate of the aluminum exposure groups was considerably higher than that of the GC group (P < 0.05). Western blot showed that the expression of Bcl-2, an anti-apoptotic protein, in cardiomyocytes of aluminum exposure groups was lower than that of the GC group (P < 0.05), while the levels of Bax and caspase-3 in the cardiomyocytes of the GM and GH groups were higher than those of the GC group (P < 0.05). The experimental results showed that aluminum could accumulate in myocardial tissues and cause damage to cardiomyocytes. It could induce oxidative stress damage by increasing the content of MDA in cardiomyocytes and trigger cardiomyocyte apoptosis by activating the pro-apoptotic proteins caspase-3 and Bax and reducing the anti-apoptotic protein Bcl-2.

Aluminum induced intestinal dysfunction via mechanical, immune, chemical and biological barriers.

Aluminum is the most abundant metal element in the Earth's crust, which exists naturally in the form of aluminum compounds. Aluminum is mainly absorbed through the gastrointestinal tract, which varies with different aluminum compounds. During this process, aluminum could induce the disruption of intestinal mucosa barrier. However, its underlying mechanism has not been elucidated yet. Previous studies have reported that aluminum can firstly promote the apoptosis of intestinal epithelial cells, destroy the structure of tight-junction proteins, and increase the intestinal permeability, injuring the mechanical barrier of gut. Also, it can induce the activation of immune cells to secrete inflammatory factors, and trigger immune responses, interfering with immune barrier. Moreover, aluminum treatment can regulate intestinal composition and bio-enzyme activity, impairing the function of chemical barrier. In addition, aluminum accumulation can induce an imbalance of the intestinal flora, inhibit the growth of beneficial bacteria, and promote the proliferation of harmful bacteria, which ultimately disrupting biological barrier. Collectively, aluminum may do extensive damage to intestinal barrier function covering mechanical barrier, immune barrier, chemical barrier and biological barrier.

Aluminum impairs cognitive function by activating DDX3X-NLRP3-mediated pyroptosis signaling pathway.

INTRODUCTION: Aluminum is a kind of chemical contaminants in food which can induce neurotoxicity. Aluminum exposure is closely related to neurodegenerative diseases (ND), in which neuroinflammation might involve. However, the molecular mechanism of aluminum-induced neuroinflammation through pyroptosis is not fully clarified yet. MATERIAL AND METHODS: The mice model of subacute exposure to aluminum chloride (AlCl3) was established. BV2 microglia cells was treated with AlCl3 in vitro. Resveratrol (Rsv) was adopted as intervention agent. RESULTS: Our results showed that aluminum induced cognitive impairment, destroying blood brain barrier (BBB), and causing nerve injury in mice. Meanwhile, aluminum could stimulate nucleotide oligomerization domain-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome assembly and activate caspase-1 (CASP1), inducing gasdermin D (GSDMD)-mediated pyroptosis signaling, releasing cytokines IL-1ß and IL-18, further promoting the activation of glial cells to magnify neuroinflammatory response. Moreover, DEAD-box helicase 3 X-linked (DDX3X) and stress granule RasGAP SH3-domain-binding protein 1 (G3BP1) both participated in neuroinflammation induced by aluminum. When co-treated with Rsv, these injuries were alleviated to some extent. CONCLUSION: Aluminum exposure could induce nerve cell pyroptosis and neuroinflammation by DDX3X-NLRP3 inflammasome signaling pathway, which could be rescued via Rsv activating sirtuin 1 (SIRT1).

High-Dose Aluminum Exposure Further Alerts Immune Phenotype in Aplastic Anemia Patients.

This study explored the relationship between immunological status and clinical characteristics of aplastic anemia (AA) patients to plasma aluminum levels, which were increased after constant exposure to high levels of this metal. Sixty-two AA patients (33 cases with high and 29 cases with low or no exposure to aluminum) and 30 healthy controls were selected for this study. Aluminum in human albumin solution was measured by inductivity coupled plasma mass spectrometry. IL-10, IL-12, IL-17, and INF-γ levels were measured by enzyme-linked immunosorbent assay. The distribution of lymphocyte subsets were determined by flow cytometry. The expression levels of immunoglobulins and complement C3 and C4 were also measured. Exposure to high aluminum raised the levels of serum aluminum in AA patients (P < 0.01). The levels of hemoglobin and complement C4 were lower in AA patients with high aluminum exposure (P < 0.05 and < 0.01, respectively). The percentage of CD4+ T cells and the ratio of CD4+/ CD8+T cells in peripheral blood in AA patients with high aluminum exposure were higher compared with control AA patients (P < 0.05 in both cases), while the percentage of CD8+ T cells was significantly lower than that in non-aluminum-exposed AA patients (P < 0.05). Compared with non-aluminum-exposed AA patients, the level of IL-10 in the high aluminum-exposed AA group was significantly higher (P < 0.05 in both cases). The immunological and clinical characteristics of AA patients from regions of high aluminum exposure are different to those in from non-aluminum areas. These results suggest that high aluminum exposure alters the immune system in patients suffering from AA.

Aluminum-Induced Cognitive Impairment and PI3K/Akt/mTOR Signaling Pathway Involvement in Occupational Aluminum Workers.

Epidemiological studies indicate that long-term occupational exposure to aluminum (Al) causes neurotoxicity and cognitive impairment. While the molecular underpinnings associated with workers' cognitive impairment is unclear, one mechanism may involve Al-induced PI3K/Akt/mTOR activation and neuronal cell death, which impairs learning and memory in rats. Here, we sought to determine whether PI3K/Akt/mTOR is also associated with cognitive impairment in Al-exposed occupational workers. Cognitive function was screened by Mini-Mental State Examination (MMSE) and Clock-Drawing Test (CDT), and serum Al and PI3K/Akt/mTOR-associated gene expression was quantified. A negative correlation between serum Al and scores of MMSE and CDT was found, which might relate with downregulation of PI3K/Akt/mTOR. To determine the role of the PI3K/Akt/mTOR pathway cognitive function, we treated zebrafish with Al and observed a profound impairment in learning and memory. Increased brain Al levels was associated with decreased expression of PI3K/Akt/mTOR in Al-exposed zebrafish. Finally, rapamycin, an mTOR inhibitor, was added to isolate the role of mTOR specifically in the Al exposed zebrafish. The results suggested that Al induces learning and memory deficits by downregulating PI3K, Akt, and mTOR1 expression and inducing neuronal cell death like rapamycin group. This study indicates that aluminum exposure can cause cognitive impairment through PI3K/Akt/mTOR pathway, with mTOR activity being a critical player involved in this mechanism. Future studies are necessary to further characterize the role of PI3K/Akt/mTOR1 signaling in Al-induced neurocognitive decline among Al occupational workers. These findings draw attention to Al risk exposure among occupational workers and the need to implement novel safety and protective measures to mitigate neurocognitive health risks in the Al industrial workspace.

Nicotinamide mononucleotide alleviates Aluminum induced bone loss by inhibiting the TXNIP-NLRP3 inflammasome.

Aluminum (Al) recognized as a persistent environmental contaminant is associated with bone diseases. Nicotinamide mononucleotide (NMN) is an intermediate of nicotinamide adenine dinucleotide (NAD+) biosynthesis widely used to replenish NAD+. Increasing evidences demonstrated that replenishment of NAD+ can protect against bone loss. However, the potentially protective effects of NMN against Al-induced bone impairment and the underlying mechanisms remain unknown. In the present study, we sought to investigate the protective effects of NMN on Al-induced bone damages and elucidate the potential mechanisms. We orally exposed AlCl3 (10 mg/L) to Sprague-Dawley rats in drinking water for 12 weeks while NMN (20 mg/kg) were intraperitoneally injected in last 4 weeks. We found that Al could induce bone damages, bone loss and oxidative stress. In addition, we showed that Al triggered inflammatory responses, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. However, NMN treatment significantly alleviated Al-induced bone injuries by decreasing bone loss, suppressing oxidative stress as well as inhibiting Thioredoxin-interacting protein (TXNIP)-NLRP3 inflammasome pathway and pro-inflammatory cytokine production in vivo and in vitro. Meanwhile, treatment with TXNIP siRNA performed the same protective effects as NMN in Al-treated MC3T3-E1 cells. Collectively, our results suggest that NMN may reduce Al-induced bone loss partly by suppression of the TXNIP-NLRP3 inflammasome pathway.

Effect of Aluminum Exposure on Glucose Metabolism and Its Mechanism in Rats.

The effects of aluminum (Al) exposure on glucose metabolism and its mechanism were investigated. A total of 30 healthy Wistar male rats were randomly divided into two groups: control (GC) and experimental (GE). The GC group received intraperitoneal normal saline. The GE was established by intraperitoneal injected AlCl3 solution at 10 mg/kg for 30 days. Fasting blood glucose (FBG) and serum levels of insulin (FINS) were measured. The insulin resistance index (HOMA-IR) and pancreatic ß cell function index (HOMA-ß) were calculated and analyzed with homeostasis model assessment (HOMA). Pancreatic tissue was taken for pathological examination. Glucose transporter 4 (GLUT4) expression in skeletal muscle was detected by quantitative PCR and Western blot. Levels of FBG and HOMA-IR in GE were higher than those in GC at day 10 and 20 (P < 0.05). FINS in GE were higher than those in GC at day 10 and 20, and lower than those in GC at day 30 (P < 0.05). HOMA-ß in GE was lower than that of GC at every time point (P < 0.05). Pathology showed that pancreatic damage changed more profoundly with prolongation of time in GE. Expression levels of GLUT4 mRNA and protein in rat skeletal muscle in GE were significantly lower than those in GC (P < 0.05). The results suggested that Al exposure affected glucose metabolism through pancreatic damage and reduction of GLUT4 expression.

Lactobacillus plantarum CCFM639 Alleviate Trace Element Imbalance-Related Oxidative Stress in Liver and Kidney of Chronic Aluminum Exposure Mice.

Aluminum (Al) has various adverse effects on health of humans and animals. The aim of present study was to demonstrate that Lactobacillus plantarum CCFM639 can alleviate the adverse effects on liver and kidney of mice caused by chronic Al exposure. Animals were assigned into control, CCFM639 only, Al only, Al plus CCFM639, and Al plus deferiprone groups. The strain was given by oral gavage for 14 weeks, and Al was introduced via drinking water for the first 8 weeks. Analyses of Al and trace elements levels in feces, blood, and tissues were performed. The biochemical markers (GSH, GPx, SOD, CAT, and MDA) of oxidative stress in livers and kidneys, as well as the levels of ALT, AST, BUN, and CRE in blood, were determined. Our results showed that L. plantarum CCFM639 can significantly reduce Al accumulation in tissues, regulate imbalance of trace elements, and thereby alleviate oxidative stress and pathological changes in hepatic and renal tissues. Therefore, L. plantarum CCFM639 could alleviate Al-induced hepatic and renal injuries, and the possible mechanisms may involve in regulating the imbalance of trace elements.