{"title":"Role of SIRT1 in Potentially Toxic Trace Elements (Lead, Fluoride, Aluminum and Cadmium) Associated Neurodevelopmental Toxicity.","authors":"Aqsa Fathima, Newly Bagang, Nitesh Kumar, Somasish Ghosh Dastidar, Smita Shenoy","doi":"10.1007/s12011-024-04116-5","DOIUrl":"10.1007/s12011-024-04116-5","url":null,"abstract":"<p><p>The formation of the central nervous system is a meticulously planned and intricate process. Any modification to this process has the potential to disrupt the structure and operation of the brain, which could result in deficiencies in neurological growth. When neurotoxic substances are present during the early stages of development, they can be exceptionally dangerous. Prenatally, the immature brain is extremely vulnerable and is therefore at high risk in pregnant women associated with occupational exposures. Lead, fluoride, aluminum, and cadmium are examples of possibly toxic trace elements that have been identified as an environmental concern in the aetiology of a number of neurological and neurodegenerative illnesses. SIRT1, a member of the sirtuin family has received most attention for its potential neuroprotective properties. SIRT1 is an intriguing therapeutic target since it demonstrates important functions to increase neurogenesis and cellular lifespan by modulating multiple pathways. It promotes axonal extension, neurite growth, and dendritic branching during the development of neurons. Additionally, it contributes to neurogenesis, synaptic plasticity, memory development, and neuroprotection. This review summarizes the possible role of SIRT1 signalling pathway in potentially toxic trace elements -induced neurodevelopmental toxicity, highlighting some molecular pathways such as mitochondrial biogenesis, CREB/BDNF and PGC-1α/NRF1/TFAM.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139982295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cyto and Genoprotective Potential of Tannic Acid Against Cadmium and Nickel Co-exposure Induced Hepato-Renal Toxicity in BALB/c Mice.","authors":"Madhu Sharma, Pooja Devi, Surbhi Kaushal, Aitizaz Ul-Ahsan, Sweety Mehra, Muskan Budhwar, Mani Chopra","doi":"10.1007/s12011-024-04117-4","DOIUrl":"10.1007/s12011-024-04117-4","url":null,"abstract":"<p><p>Tannic acid (TA) is a metal chelating polyphenol that plays a crucial role in metal detoxification, but its modulatory role in co-exposure of these heavy metals' exposure needs to be explored. Cadmium (Cd) and nickel (Ni) are inorganic hazardous chemicals in the environment. Humans are prone to be exposed to the co-exposure of Cd and Ni, but the toxicological interactions of these metals are poorly defined. Present study was undertaken to study the preventive role of TA in Cd-Ni co-exposure-evoked hepato-renal toxicity in BALB/c mice. In the current investigation, increased oxidative stress in metal intoxicated groups was confirmed by elevated peroxidation of the lipids and significant lowering of endogenous antioxidant enzymes. Altered hepato-renal serum markers, DNA fragmentation, and histological alterations were also detected in the metal-treated groups. Present study revealed that Cd is a stronger toxicant than Ni and when co-exposure was administered, additive, sub-additive, and detrimental effects were observed. Prophylactic treatment with TA significantly reinstated the levels of lipid peroxidation (LPO), non-enzymatic, and enzymatic antioxidants. Moreover, it also restored the serum biomarker levels, DNA damage, and histoarchitecture of the given tissues. TA due to its metal chelating and anti-oxidative properties exhibited cyto- and genoprotective potential against Cd-Ni co-exposure-induced hepatic and renal injury.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genome-Wide Screens Identify Genes Responsible for Intrinsic Boric Acid Resistance in Escherichia coli.","authors":"Bekir Çöl, Merve Sezer Kürkçü, Esra Di Bek","doi":"10.1007/s12011-024-04129-0","DOIUrl":"10.1007/s12011-024-04129-0","url":null,"abstract":"<p><p>Boric acid (BA) has antimicrobial properties and is used to combat bacterial infections, including Enterobacteria. However, the molecular mechanisms and cellular responses to BA are still unknown. This genomics study aims to provide new information on the genes and molecular mechanisms related to the antimicrobial effect of BA in Escherichia coli. The Keio collection of E. coli was used to screen 3985 single-gene knockout strains in order to identify mutant strains that were sensitive or hypersensitive to BA at certain concentrations. The mutant strains were exposed to different concentrations of BA ranging from 0 to 120 mM in LB media. Through genome-wide screens, 92 mutants were identified that were relatively sensitive to BA at least at one concentration tested. The related biological processes in the particular cellular system were listed. This study demonstrates that intrinsic BA resistance is the result of various mechanisms acting together. Additionally, we identified eighteen out of ninety-two mutant strains (Delta_aceF, aroK, cheZ, dinJ, galS, garP, glxK, nohA, talB, torR, trmU, trpR, yddE, yfeS, ygaV, ylaC, yoaC, yohN) that exhibited sensitivity using other methods. To increase sensitivity to BA, we constructed double and triple knockout mutants of the selected sensitive mutants. In certain instances, engineered double and triple mutants exhibited significantly amplified effects. Overall, our analysis of these findings offers further understanding of the mechanisms behind BA toxicity and intrinsic resistance in E. coli.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140100992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mahdi Banaee, Amir Zeidi, Nikola Mikušková, Caterina Faggio
{"title":"Assessing Metal Toxicity on Crustaceans in Aquatic Ecosystems: A Comprehensive Review.","authors":"Mahdi Banaee, Amir Zeidi, Nikola Mikušková, Caterina Faggio","doi":"10.1007/s12011-024-04122-7","DOIUrl":"10.1007/s12011-024-04122-7","url":null,"abstract":"<p><p>Residual concentrations of some trace elements and lightweight metals, including cadmium, copper, lead, mercury, silver, zinc, nickel, chromium, arsenic, gallium, indium, gold, cobalt, polonium, and thallium, are widely detected in aquatic ecosystems globally. Although their origin may be natural, human activities significantly elevate their environmental concentrations. Metals, renowned pollutants, threaten various organisms, particularly crustaceans. Due to their feeding habits and habitat, crustaceans are highly exposed to contaminants and are considered a crucial link in xenobiotic transfer through the food chain. Moreover, crustaceans absorb metals via their gills, crucial pathways for metal uptake in water. This review summarises the adverse effects of well-studied metals (Cd, Cu, Pb, Hg, Zn, Ni, Cr, As, Co) and synthesizes knowledge on the toxicity of less-studied metals (Ag, Ga, In, Au, Pl, Tl), their presence in waters, and impact on crustaceans. Bibliometric analysis underscores the significance of this topic. In general, the toxic effects of the examined metals can decrease survival rates by inducing oxidative stress, disrupting biochemical balance, causing histological damage, interfering with endocrine gland function, and inducing cytotoxicity. Metal exposure can also result in genotoxicity, reduced reproduction, and mortality. Despite current toxicity knowledge, there remains a research gap in this field, particularly concerning the toxicity of rare earth metals, presenting a potential future challenge.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
James T F Wise, Haiyan Lu, Idoia Meaza, Sandra S Wise, Aggie R Williams, Jamie Young Wise, Michael D Mason, John Pierce Wise
{"title":"Prolonged Particulate Hexavalent Chromium Exposure Induces DNA Double-Strand Breaks and Inhibits Homologous Recombination Repair in Primary Rodent Lung Cells.","authors":"James T F Wise, Haiyan Lu, Idoia Meaza, Sandra S Wise, Aggie R Williams, Jamie Young Wise, Michael D Mason, John Pierce Wise","doi":"10.1007/s12011-024-04136-1","DOIUrl":"10.1007/s12011-024-04136-1","url":null,"abstract":"<p><p>Hexavalent chromium [Cr(VI)] is a known lung carcinogen and a driving mechanism in human lung cells for Cr(VI)-induced lung cancer is chromosome instability, caused by prolonged Cr(VI) exposure inducing DNA double-strand breaks, while simultaneously inhibiting the repair of these breaks. In North Atlantic right whales, Cr(VI) induces breaks but does not inhibit repair. It is unclear if this repair inhibition is specific to human lung cells or occurs in other species, as it has only been considered in humans and North Atlantic right whales. We evaluated these outcomes in rodent cells, as rodents are an experimental model for metal-induced lung carcinogenesis. We used a guinea pig lung fibroblast cell line, JH4 Clone 1, and rat lung fibroblasts. Cells were exposed to two different particulate Cr(VI) compounds, ranging from 0 to 0.5 ug/cm<sup>2</sup>, for 24 or 120 h and assessed for cytotoxicity, DNA double-strand breaks, and DNA double-strand break repair. Both particulate Cr(VI) compounds induced a concentration-dependent increase in cytotoxicity and DNA double-strand breaks after acute and prolonged exposures. Notably, while the repair of Cr(VI)-induced DNA double-strand breaks increased after acute exposure, the repair of these breaks was inhibited after prolonged exposure. These results are consistent with outcomes in human lung cells indicating rodent cells respond like human cells, while whale cells have a markedly different response.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11408706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140157545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quercetin Alleviates Perimenopausal Depression Induced by Ovariectomy Combined with Chronic Unpredictable Mild Stress Through Regulating Serum Elements and Inhibiting Ferroptosis in Prefrontal Cortex of Rats.","authors":"Dan Wang, Jing Wang, Ziran Yu, Ranqi Yao, Jingnan Zhang, Xiujuan Zhao","doi":"10.1007/s12011-024-04106-7","DOIUrl":"10.1007/s12011-024-04106-7","url":null,"abstract":"<p><p>This study investigated the effects of quercetin on the alterations of serum elements in perimenopausal depression rat model induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS) and possible mechanisms. According to the results of the sucrose preference test, the rats were randomly assigned to four groups: sham, OVX-CUMS, OVX-CUMS + 17β-estradiol (17β-estradiol: 0.27 mg/kg.bw), and OVX-CUMS + Quercetin (Quercetin: 50 mg/kg.bw). At the end of experiment, serum and prefrontal cortex of rats were collected. The inductively coupled plasma mass spectrometry (ICP-MS) analysis showed that levels of calcium (Ca), magnesium (Mg), selenium (Se), cobalt (Co) and zinc (Zn) decreased, and levels of iron (Fe) and copper (Cu) increased in serum and prefrontal cortex of OVX-CUMS rats compared with sham group (p < 0.01). Meanwhile, the levels of the above elements in prefrontal cortex had correlation with behavioral characteristics in OVX-CUMS rats (p < 0.05 or p < 0.01). The abnormal elements in serum may cross blood-brain-barrier into the brain and induce oxidative stress, leading to ferroptosis. Furtherly, the expressions of ferroptosis-related protein including GPX4 and SLC7A11 were decreased in prefrontal cortex of OVX-CUMS rats (p < 0.01), which confirmed the above results. Quercetin treatment restored the above abnormal indicators (p < 0.05 or p < 0.01) induced by OVX-CUMS in rats. Our study suggested that quercetin regulated variation of elements in serum and prefrontal cortex, further inhibiting ferroptosis in prefrontal cortex through alleviating oxidative stress in OVX-CUMS rats.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139929898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos E Franco, Emma L Rients, Fabian E Diaz, Stephanie L Hansen, Jodi L McGill
{"title":"Dietary Zinc Supplementation in Steers Modulates Labile Zinc Concentration and Zinc Transporter Gene Expression in Circulating Immune Cells.","authors":"Carlos E Franco, Emma L Rients, Fabian E Diaz, Stephanie L Hansen, Jodi L McGill","doi":"10.1007/s12011-024-04123-6","DOIUrl":"10.1007/s12011-024-04123-6","url":null,"abstract":"<p><p>Zinc (Zn) is critical for immune function, and marginal Zn deficiency in calves can lead to suboptimal growth and increased disease susceptibility. However, in contrast to other trace minerals such as copper, tissue concentrations of Zn do not change readily in conditions of supplementation or marginal deficiency. Therefore, the evaluation of Zn status remains challenging. Zinc transporters are essential for maintaining intracellular Zn homeostasis, and their expression may indicate changes in Zn status in the animal. Here, we investigated the effects of dietary Zn supplementation on labile Zn concentration and Zn transporter gene expression in circulating immune cells isolated from feedlot steers. Eighteen Angus crossbred steers (261 ± 14 kg) were blocked by body weight and randomly assigned to two dietary treatments: a control diet (58 mg Zn/kg DM, no supplemental Zn) or control plus 150 mg Zn/kg DM (HiZn; 207 mg Zn/kg DM total). After 33 days, Zn supplementation increased labile Zn concentrations (as FluoZin-3 fluorescence) in monocytes, granulocytes, and CD4 T cells (P < 0.05) but had the opposite effect on CD8 and γδ T cells (P < 0.05). Zn transporter gene expression was analyzed on purified immune cell populations collected on days 27 or 28. ZIP11 and ZnT1 gene expression was lower (P < 0.05) in CD4 T cells from HiZn compared to controls. Expression of ZIP6 in CD8 T cells (P = 0.02) and ZnT7 in B cells (P = 0.01) was upregulated in HiZn, while ZnT9 tended (P = 0.06) to increase in B cells from HiZn. These results suggest dietary Zn concentration affects both circulating immune cell Zn concentrations and Zn transporter gene expression in healthy steers.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11502596/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140027319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of Various Heavy Metal Exposures on Insulin Resistance in Non-diabetic Populations: Interpretability Analysis from Machine Learning Modeling Perspective.","authors":"Jun Liu, Xingyu Li, Peng Zhu","doi":"10.1007/s12011-024-04126-3","DOIUrl":"10.1007/s12011-024-04126-3","url":null,"abstract":"<p><p>Increasing and compelling evidence has been proved that heavy metal exposure is involved in the development of insulin resistance (IR). We trained an interpretable predictive machine learning (ML) model for IR in the non-diabetic populations based on levels of heavy metal exposure. A total of 4354 participants from the NHANES (2003-2020) with complete information were randomly divided into a training set and a test set. Twelve ML algorithms, including random forest (RF), XGBoost (XGB), logistic regression (LR), GaussianNB (GNB), ridge regression (RR), support vector machine (SVM), multilayer perceptron (MLP), decision tree (DT), AdaBoost (AB), Gradient Boosting Decision Tree (GBDT), Voting Classifier (VC), and K-Nearest Neighbour (KNN), were constructed for IR prediction using the training set. Among these models, the RF algorithm had the best predictive performance, showing an accuracy of 80.14%, an AUC of 0.856, and an F1 score of 0.74 in the test set. We embedded three interpretable methods, the permutation feature importance analysis, partial dependence plot (PDP), and Shapley additive explanations (SHAP) in RF model for model interpretation. Urinary Ba, urinary Mo, blood Pb, and blood Cd levels were identified as the main influencers of IR. Within a specific range, urinary Ba (0.56-3.56 µg/L) and urinary Mo (1.06-20.25 µg/L) levels exhibited the most pronounced upwards trend with the risk of IR, while blood Pb (0.05-2.81 µg/dL) and blood Cd (0.24-0.65 µg/L) levels showed a declining trend with IR. The findings on the synergistic effects demonstrated that controlling urinary Ba levels might be more crucial for the management of IR. The SHAP decision plot offered personalized care for IR based on heavy metal control. In conclusion, by utilizing interpretable ML approaches, we emphasize the predictive value of heavy metals for IR, especially Ba, Mo, Pb, and Cd.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Chen, Lu Sun, Hengyu Shi, Guanghua Mao, Ting Zhao, Weiwei Feng, Liuqing Yang, Xiangyang Wu
{"title":"Protective Effect of Protocatechuic Acid on Oxidative Damage and Cognitive Impairment in Pb-Induced Rats.","authors":"Yao Chen, Lu Sun, Hengyu Shi, Guanghua Mao, Ting Zhao, Weiwei Feng, Liuqing Yang, Xiangyang Wu","doi":"10.1007/s12011-024-04095-7","DOIUrl":"10.1007/s12011-024-04095-7","url":null,"abstract":"<p><p>Protocatechuic acid (PCA), a class of water-soluble phenolic acid abundant in the human diet, has been shown to be of great nutritional interest and to have medicinal value. However, the protective effects against lead (Pb)-induced body injury have not been elucidated. In this study, we explored the protective effect of PCA on Pb-induced oxidative damage and cognitive impairment in rats. The results showed that PCA could reduce the Pb content in rat bodies (blood, bone, brain, liver, and kidney) after Pb exposure. Moreover, PCA may inhibit Pb-induced oxidative damage by increasing the activity of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreasing the level of malondialdehyde (MDA) in the brain, liver, and kidney. In addition, PCA may alleviate Pb-induced learning and memory impairment by upregulating neurotransmitter levels; maintaining the normal function of N-methyl-D-aspartate receptors (NMDARs); and promoting Ca<sup>2+</sup> influx, thus activating signaling molecules, related protein kinases, and transcription factors in the cAMP-PKA-CREB pathway. In general, PCA could reduce oxidative stress and ameliorate the learning and memory deficits in Pb-treated rats, indicating that PCA may be an effective preventive agent and treatment or plumbism.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139904892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nan Shang, Xianlin Li, Lan Zhang, ShanShan Wang, Chanting He, Ling Zhang, Qiao Niu, Xiaojun Zheng
{"title":"Zinc as a Mediator Through the ROCK1 Pathway of Cognitive Impairment in Aluminum-Exposed Workers: A Clinical and Animal Study.","authors":"Nan Shang, Xianlin Li, Lan Zhang, ShanShan Wang, Chanting He, Ling Zhang, Qiao Niu, Xiaojun Zheng","doi":"10.1007/s12011-024-04119-2","DOIUrl":"10.1007/s12011-024-04119-2","url":null,"abstract":"<p><p>Aluminum (Al) exposure was implicated in neurodegenerative diseases and cognitive impairment, yet the involvement of zinc (Zn) and its mechanism in Al-induced mild cognitive impairment (MCI) remains poorly understood. The objective is to explore the role of Zn in Al-induced cognitive impairment and its potential mechanisms. Montreal cognitive assessment (MoCA) test scores and serum Al, Zn from Al industry workers were collected. A mediation analysis was performed to evaluate the role of serum Zn among serum Al and MoCA test scores. Subsequently, an Al-exposure study was conducted on a rat model categorized into control, low-, medium-, and high-dose groups. After a Morris Water Maze test and detection of Al, Zn content in the hippocampus, integrated transcriptomic and proteomic analyses between the control group and the high-dose group were performed to identify the differentially expressed genes (DEPs), proteins (DEPs), and pathways. To corroborate these findings, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) were selected to identify the gene and protein results. Zn overall mediates the relationship between serum Al and cognitive function (mediation effect 17.82%, effect value = - 0.0351). In the Al-exposed rat model, 734 DEGs, 18 miRNAs, 35 lncRNAs, 64 circRNAs, and 113 DEPs were identified between the high-dose group and the control group. Among them, ROCK1, DMD, and other four DEPs were identified as related to zinc finger proteins (ZNF). Co-enrichment analyses of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) linked these changes to the RHOA/ROCK1 signaling axis. ZNF-related proteins Rock1, DMD, and DHX57 in the high-dose group were downregulated (p = 0.006, 0.003, 0.04), and the expression of Myl9, Rhoa, miR431, and miR182 was also downregulated (p = 0.003, 0.032, 0.032, and 0.046). These findings also show correlations between Al, Zn levels in the hippocampus, water maze performance, and expressions of Myl9, Rhoa, miR431, miR182, DMD, ROCK1, and DHX57, with both negative and positive associations. Based on the results, we determined that Zn was involved in Al-induced MCI in Al workers and Al-exposed rat models. Al exposure and interaction with Zn could trigger the downregulation of ZNF of ROCK1, DMD, and DHX57. miR431, miR182 regulate RHOA/ROCK1 was one of the Zn-involved pathways in Al-induced cognitive impairment.</p>","PeriodicalId":8917,"journal":{"name":"Biological Trace Element Research","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}