Association between plasma and dietary trace elements and obesity in a rural Chinese population.

Trace elements may play an important role in obesity. This study aimed to assess the plasma and dietary intake levels of four trace elements, Mn, Cu, Zn and Se in a rural Chinese population, and analyse the relationship between trace elements and obesity. A cross-sectional study involving 2587 participants was conducted. Logistic regression models were used to analyse the association between trace elements and obesity; restricted cubic spline (RCS) models were used to assess the dose-response relationship between trace elements and obesity; the weighted quantile sum (WQS) model was used to examine the potential interaction of four plasma trace elements on obesity. Logistic regression analysis showed that plasma Se concentrations in the fourth quartile (Q4) exhibited a lower risk of developing obesity than the first quartile (Q1) (central obesity: OR = 0·634, P = 0·002; general obesity: OR = 0·525, P = 0·005). Plasma Zn concentration in the third quartile (Q3) showed a lower risk of developing obesity in general obesity compared with the first quartile (Q1) (OR = 0·625, P = 0·036). In general obesity, the risk of morbidity was 1·727 and 1·923 times higher for the second and third (Q2, Q3) quartiles of dietary Mn intake than for Q1, respectively. RCS indicated an inverse U-shaped correlation between plasma Se and obesity. WQS revealed the combined effects of four trace elements were negatively associated with central obesity. Plasma Zn and Se were negatively associated with obesity, and dietary Mn was positively associated with obesity. The combined action of the four plasma trace elements had a negative effect on obesity.

Association between multiple-heavy-metal exposures and systemic immune inflammation in a middle-aged and elderly Chinese general population.

BACKGROUND: Exposure to heavy metals alone or in combination can promote systemic inflammation. The aim of this study was to investigate potential associations between multiple plasma heavy metals and markers of systemic immune inflammation. METHODS: Using a cross-sectional study, routine blood tests were performed on 3355 participants in Guangxi, China. Eight heavy metal elements in plasma were determined by inductively coupled plasma mass spectrometry. Immunoinflammatory markers were calculated based on peripheral blood WBC and its subtype counts. A generalised linear regression model was used to analyse the association of each metal with the immunoinflammatory markers, and the association of the metal mixtures with the immunoinflammatory markers was further assessed using weighted quantile sum (WQS) regression. RESULTS: In the single-metal model, plasma metal Fe (log10) was significantly negatively correlated with the levels of immune-inflammatory markers SII, NLR and PLR, and plasma metal Cu (log10) was significantly positively correlated with the levels of immune-inflammatory markers SII and PLR. In addition, plasma metal Mn (log10 conversion) was positively correlated with the levels of immune inflammatory markers NLR and PLR. The above associations remained after multiple corrections. In the mixed-metal model, after WQS regression analysis, plasma metal Cu was found to have the greatest weight in the positive effects of metal mixtures on SII and PLR, while plasma metals Mn and Fe had the greatest weight in the positive effects of metal mixtures on NLR and LMR, respectively. In addition, blood Fe had the greatest weight in the negative effects of the metal mixtures for SII, PLR and NLR. CONCLUSION: Plasma metals Cu and Mn were positively correlated with immunoinflammatory markers SII, NLR and PLR. While plasma metal Fe was negatively correlated with immunoinflammatory markers SII, NLR, and PLR.

Association between combined exposure to plasma heavy metals and dyslipidemia in a chinese population.

BACKGROUND: Exposure to heavy metals in the environment is widespread, while the relationship between combined exposure to heavy metals and dyslipidemia is unclear. METHODS: A cross-sectional study was performed, and 3544 participants aged 30 years or older were included in the analyses. Heavy metal concentrations in plasma were based on inductively coupled plasma‒mass spectrometry. The relationship between heavy metals and dyslipidemia was estimated by logistic regression. BKMR was used to evaluate metal mixtures and their potential interactions. RESULTS: In logistic regression analysis, participants in the fourth quartile of Fe and Zn (Fe > 1352.38 µg/L; Zn > 4401.42 µg/L) had a relatively higher risk of dyslipidemia (Fe, OR = 1.13, 95% CI: 0.92,1.38; Zn, OR = 1.30, 95% CI: 1.03,1.64). After sex stratification, females in the third quartile of plasma Zn (1062.05-4401.42 µg/L) had a higher relative risk of dyslipidemia (OR = 1.75, 95% CI: 1.28, 2.38). In BKMR analysis, metal mixtures were negatively associated with dyslipidemia in females when all metal concentrations were above the 50th percentile. In the total population (estimated from 0.030 to 0.031), As was positively associated with dyslipidemia when other metals were controlled at the 25th, 50th, or 75th percentile, respectively, and As was below the 75th percentile. In females (estimated from - 0.037 to -0.031), Zn was negatively associated with dyslipidemia when it was above the 50th percentile. CONCLUSION: This study indicated that As was positively associated with dyslipidemia and that Zn may be negatively associated with dyslipidemia in females. Combined metal exposure was negatively associated with dyslipidemia in females. Females with low plasma Zn levels are more likely to develop dyslipidemia and should receive more clinical attention in this population.

Development and validation of a new 18 X-STR typing assay for forensic applications.

With a unique inheritance pattern compared to autosomal short tandem repeats (A-STRs), X chromosomal STRs (X-STRs) have special usage in forensic relationship testing. In this study, we designed a multiplex amplification system (named TYPER-X19 multiplex assay) consisting of 18 STR loci spreading from 7.837 to 149.460 Mb on the X chromosomes (DXS9895, DXS8378, DXS9902, DXS6810, DXS7132, DXS10079, DXS6789, DXS7424, DXS101, DXS6797, DXS7133, DXS6804, GATA165B12, DXS10103, HPRTB, GATA31E08, DXS8377, and DXS7423), and the amelogenin. PCR primers were marked with four kinds of fluorophores including FAM, HEX, TAMRA, and ROX. The multiplex system was optimized and tested for precision, concordance, reproducibility, sensitivity, stability, DNA mixture, and species specificity according to the conventional validation guidelines. The results indicated that the system was accurate, reliable, and sensitive enough, and was suitable for common forensic case-type samples. In the population genetic study, a total of 148 alleles were detected at the 18 X-STR loci in 398 Southern Han Chinese. Relatively high combined power of discrimination in male (PDm ), power of discrimination in female (PDf ), mean paternity exclusion chance in trios (MECtrio ), and mean paternity exclusion chance in duos (MECDuo ) by Desmarais were detected, and HPRTB-DXS10103 was in linkage disequilibrium. The results suggested that the TYPER-X19 multiplex assay was suitable for forensic applications.

Correlation between urinary contents of some metals and fasting plasma glucose levels: A cross-sectional study in China.

Many metals are involved in the pathogenesis of diabetes, but most of existing studies focused on single metals. The study of mixtures represents real-life exposure scenarios and deserves attention. This study aimed to explore the potential relationship of urinary copper (Cu), zinc (Zn), arsenic (As), selenium (Se), and strontium (Sr) contents with fasting plasma glucose (FPG) levels in 2766 participants. The levels of metals in urine were determined by inductively coupled plasma-mass spectrometry. We used linear regression models and the Bayesian kernel machine regression (BKMR) to evaluate the association between metals and FPG levels. In the multiple metals linear regression, Zn (ß = 0.434), Se (ß = 0.172), and Sr (ß = -0.143) showed significant association with FPG levels (all P < 0.05). The BKMR model analysis showed that the results of single metal association were consistent with the multiple metals linear regression. The mixture of five metals had a positive over-all effect on FPG levels, and Zn (PIP = 1.000) contributed the most to the FPG levels. Cu and As were negatively correlated with FPG levels in women. The potential interaction effect between Cu and Sr was observed in participants aged ≥ 60 years old (Pinteraction = 0.035). In summary, our results suggested that multiple metals in urine are associated with FPG levels. Further studies are needed to confirm these findings and clarify the underlying mechanisms.

Comparative evaluation of autosomal STRs and X-chromosome STRs as a complement of autosomal STRs in kinship testing in Southern Han Chinese.

Nowadays, kinship testing is very common in forensic caseworks, but the power of autosomal short tandem repeats (A-STRs) may be limited in complex cases. X-Chromosome short tandem repeats (X-STRs), having a unique heritage mode, should be of special use in some deficient cases. To evaluate and compare the potential of A-STR and X-STR as supplement genetic markers in deficient kinship testing, we simulated 10,000 duos for each of 18 kinds of relationships involving full sibling, half-sibling, grandparent-grandchild, and uncle/aunt-nephew/niece. Loci from STRTyper10, PowerPlex 16, and Investigator Argus X-12 were studied in Southern Han Chinese and the distribution of likelihood ratio (LR) values was analysed. With the addition of the X-12 system, the distribution of LR values for the full sisters, paternal half-sisters, paternal grandmother-granddaughters, maternal aunt-nieces, and maternal aunt-nephews separated much more obviously from those of unrelated duos, and the effectiveness was 1.0000, 0.99865, 0.9991, 0.8996 and 0.9634, respectively, which was more efficient than A-STRs. For the individual duos with other relationships, the effects of adding X-STRs and A-STRs were similar. Therefore, for the Southern Han Chinese, X-STRs can be very useful in kinship testing involving full sisters, paternal half-sisters, paternal grandmother-granddaughters, and maternal aunt-nieces/nephews.

Development of a new 25plex STRs typing system for forensic application.

We have developed a novel STR 25-plex florescence multiplex-STR kit (DNATyper25) to genotype 23 autosomal and two sex-linked loci for forensic applications and paternity analysis. Of the 23 autosomal loci, 20 are non-CODIS. The sex-linked markers include a Y-STR locus (DYS391) and the Amelogenin gene. We present developmental validation studies to show that the DNATyper25 kit is reproducible, accurate, sensitive, and robust. Sensitivity testing showed that full profiles were achieved with as low as 125 pg of human DNA. Specificity testing demonstrated a lack of cross reactivity with a variety of commonly encountered non-human DNA contaminants. Stability testing showed that full profiles were obtained with humic acid concentration ≤60 ng/µL and hematin concentration <400 µM. For forensic evaluation, the 23 autosomal STRs followed the Hardy-Weinberg equilibrium. In an analysis of 509 Chinese (CN) Hans, we detected a combined total of 181 alleles at the 23 autosomal STR loci. Since these autosomal STRs are independent from one another, PM was 8.4528 × 10-22 , TDP was 0.999 999 999 999 999 999 999, CEP was 0.999 999 8395. The forensic efficiency parameters demonstrated that these autosomal STRs are highly polymorphic and informative in the Han population of China. We performed population comparisons and showed that the Northern CN Han has a close genetic relationship with the Luzhou Han, Tujia, and Bai populations. We propose that the DNATyper25 kit will be useful for cases where paternity analysis is difficult and for situations where DNA samples are limited in quantity and low in quality.

Allele frequencies of 18 autosomal STR loci in the Uyghur population living in Kashgar Prefecture, Northwest China.

There is currently no large population data-based data set in Kashgar Prefecture Uyghur. The allele frequencies of 18 autosomal short tandem repeat (STR) loci included in the DNATyper™ 19 kit were evaluated in 2600 Uyghur individuals living in Kashgar Prefecture, Northwest China. The values of combined power of discrimination (CPD) and combined probability of exclusion (CPE) of all 18 autosomal STR loci were 0.99999999999999999998235 and 0.99999998670, respectively. Phylogenetic analyses revealed that the Uyghur population has a closer relationship with the Xinjiang-Kazakh, Inner Mongolia-Mongolian, and other three Uyghur populations. In addition, our results are consistent with the hypothesis that Uyghur population is an admixture of Eastern Asian and European populations.

Genetic analysis of 29 Y-STR loci in Han population from Dongfang, Southern China.

In the present study, blood samples of 984 unrelated Han individuals were collected from Dongfang, Southern China, after informed consent. A total of 29 Y-chromosomal short tandem repeat (Y-STR) were analyzed, including DYF387S1, DYS19, DYS385ab, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS444, DYS447, DYS448, DYS449, DYS456, DYS458, DYS460, DYS481, DYS508, DYS518, DYS533, DYS576, DYS635, DYS643 and GATAH4. A total of 749 different haplotypes were found among 984 individuals, of which 645 were unique. The haplotype diversity was 0.9988 and the discrimination capacity was 0.7612, while the match probability was 0.0025. The smallest genetic distance (RST = 0.0155) was found between the Dongfang Han population and Guizhou Han population, while the largest genetic distance (RST = 0.1284) was observed with Gansu Tibetan.

Nrf2 attenuates inflammatory response in COPD/emphysema: Crosstalk with Wnt3a/ß-catenin and AMPK pathways.

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/ß-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/ß-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2-/- mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2 and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/ß-catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, ß-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/ß-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.

Activation of Wnt/ß-catenin signalling is required for TGF-ß/Smad2/3 signalling during myofibroblast proliferation.

Fibrosis in animal models and human diseases is associated with aberrant activation of the Wnt/ß-catenin pathway. Despite extensive research efforts, effective therapies are still not available. Myofibroblasts are major effectors, responsible for extracellular matrix deposition. Inhibiting the proliferation of the myofibroblast is crucial for treatment of fibrosis. Proliferation of myofibroblasts can have many triggering effects that result in fibrosis. In recent years, the Wnt pathway has been studied as an underlying factor as a primary contributor to fibrotic diseases. These efforts notwithstanding, the specific mechanisms by which Wnt-mediated promotes fibrosis reaction remain obscure. The central role of the transforming growth factor-ß (TGF-ß) and myofibroblast activity in the pathogenesis of fibrosis has become generally accepted. The details of interaction between these two processes are not obvious. The present investigation was conducted to evaluate the level of sustained expression of fibrosis iconic proteins (vimentin, α-SMA and collagen I) and the TGF-ß signalling pathway that include smad2/3 and its phosphorylated form p-smad2/3. Detailed analysis of the possible molecular mechanisms mediated by ß-catenin revealed epithelial-mesenchymal transition and additionally demonstrated transitions of fibroblasts to myofibroblast cell forms, along with increased activity of ß-catenin in regulation of the signalling network, which acts to counteract autocrine TGF-ß/smad2/3 signalling. A major outcome of this study is improved insight into the mechanisms by which epithelial and mesenchymal cells activated by TGFß1-smad2/3 signalling through Wnt/ß-catenin contribute to lung fibrosis.

High-Mobility Group Box 1 Mediates Epithelial-to-Mesenchymal Transition in Pulmonary Fibrosis Involving Transforming Growth Factor-ß1/Smad2/3 Signaling.

Epithelial-to-mesenchymal transition (EMT) is a crucial event in the cellular origin of myofibroblasts that secrete extracellular matrix in the progression of pulmonary fibrosis (PF). High-mobility group box 1 (HMGB1) is a novel mediator of EMT. However, whether this process involves the recognized transforming growth factor-ß1 (TGF-ß1)/Smad signaling that also contributes to EMT in PF has not yet been elucidated. Here, we developed a model of PF induced by bleomycin (BLM) in rats and conducted several simulation experiments in A549 (human) and RLE-6TN (rat) alveolar epithelial cell (AEC) lines to unravel the role of TGF-ß1/Smad2/3 signaling in HMGB1-mediated EMT. We found that the levels of serum HMGB1 and lung hydroxyproline were severely elevated after BLM administration. Moreover, the protein expression of HMGB1, TGF-ß1, phosphorylated Smad2/3 (p-Smad2/3), and mesenchymal markers including α-smooth muscle actin, vimentin, and type I collagen were significantly increased with the reduced protein expression of an epithelial marker (E-cadherin) in the rat model by Western blot or immunohistochemical analysis. In addition, the uptake of both exogenous TGF-ß1 and HMGB1 by AECs could induce EMT; meanwhile, HMGB1 dramatically enhanced TGF-ß1 expression and triggered Smad2/3 phosphorylation. In contrast, TGF-ß1 deficiency evidently ameliorated HMGB1-mediated EMT with reduced p-Smad2/3 in A549 cells. It provides new insights that HMGB1 release from injured lungs promotes AEC damage through induction of the EMT process, in which TGF-ß1/Smad2/3 signaling is activated and contributes to PF. These results suggest that HMGB1 may constitute a therapeutic target for developing antifibrotic agents for abnormal lung remodeling.

Total glycosides of Yupingfeng protects against bleomycin-induced pulmonary fibrosis in rats associated with reduced high mobility group box 1 activation and epithelial-mesenchymal transition.

BACKGROUND: Pulmonary fibrosis (PF) is a fatal inflammatory disease with limited effective strategies. Epithelial-mesenchymal transition (EMT) is a pivotal origin of myofibroblasts that secrete extracellular matrix (ECM) in the development of PF. High mobility group box 1 (HMGB1), one of the mediators of inflammation, has been proved abnormal activation in the pathogenesis of PF. AIM: The present study was aimed to investigate the potential effects of total glycoside of Yupingfeng (YPF-G), the natural compound extracted from Yupingfeng san, on HMGB1 activation and EMT in bleomycin-induced PF, which was a serious disease of respiratory system. METHODS: The Sprague-Dawley (SD) rat model of PF was duplicated by intratracheal instillation of bleomycin (5 mg kg(-1)). After that, YPF-G (5, 10 mg kg(-1)) and prednisone (5 mg kg(-1)) were separately administered intragastrically, and then the rats were killed at days 14 and 28, respectively. Hematoxylin and eosin and Masson's trichrome staining were performed to assess the histopathologic level of lung tissues, western blotting and the common kits were utilized to investigate the hallmarks molecule expression of ECM and EMT, and the level of HMGB1 in lung tissues and serum. RESULTS: We found that both dose of YPF-G markedly reduced bleomycin-induced alveolitis and PF in rats. Besides, the levels of HMGB1, laminin, hyaluronic acid, and hydroxyproline were effectively reduced. Meanwhile, the increased protein expression of HMGB1 and the mesenchymal markers including vimentin and alpha-smooth muscle actin, and the decreased protein expression of epithelial marker E-cadherin were dramatically inhibited after YPF-G treatment. CONCLUSION: Our results demonstrated that YPF-G could ameliorate bleomycin-induced PF by reducing HMGB1 activation and reversing EMT.

Genetic overlap and causal inferences between diet-derived antioxidants and small-cell lung cancer.

Several studies have reported that antioxidants exert both preventive and inhibitory effects against tumors. However, their causal effects on small-cell lung cancer (SCLC) remain controversial. Herein, we explored the causal effects of 6 antioxidants on SCLC by combining a genome-wide association study database and the Mendelian randomization (MR) approach. We obtained antioxidant genetic variance data for 6 exposure factors: carotene, vitamin A (retinol), selenium, zinc, vitamin C, and vitamin E, from the genome-wide association study database. The instrumental variables for exposure factors and SCLC outcomes were integrated by screening instrumental variables and merging data. Two-sample MR was used to analyze the causal relationship between exposure and outcomes. Finally, we examined the heterogeneity and horizontal pleiotropy of the MR analysis by performing multiple sensitivity analyses. We found a causal relationship between carotene and SCLC using two-sample MR analysis and sensitivity analysis (P = .02; odds ratio = 0.73; 95% confidence interval: 0.55-0.95). In contrast, there was no causal relationship between other examined antioxidants and SCLC. We found that diet-derived circulating antioxidants could afford protection against SCLC, and carotene is the causal protective factor against SCLC.

Associations of Dietary and Plasma Copper Levels with Liver Function in a Chinese Population.

The potential mechanisms underlying the association between copper (Cu) exposure and impaired liver function are unclear. This study aimed to investigate the potential associations of dietary Cu intake and plasma Cu levels with liver function biomarkers. A cross-sectional study was performed to assess liver function biomarkers-namely, levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), alanine transaminase (ALT), and aspartate transaminase (AST)-in 2376 subjects in Guangxi, China. Dietary Cu intake was determined from a food frequency questionnaire containing 109 common foods. Plasma Cu concentrations were determined by inductively coupled plasma‒mass spectrometry. Multiple linear regression and multivariate restricted cubic splines (RCS) were used to evaluate the correlations of plasma Cu levels and dietary Cu levels with liver function biomarkers. The covariate-adjusted results of the linear regression analysis showed that plasma Cu levels were significantly negatively correlated with serum IBIL (ß = - 0.37), DBIL (ß = - 0.22), and TBIL levels (ß = - 0.32) (all p < 0.05), and dietary Cu was negatively correlated with serum AST levels (ß = - 0.12, p < 0.05). The RCS analysis further indicated a negative linear relationship between dietary Cu levels and AST levels. In summary, our results suggested that the plasma Cu level is associated with serum bilirubin levels and that dietary Cu intake is associated with serum AST levels. Further studies are needed to validate these associations and elucidate the underlying mechanisms.

Association of Dietary and Plasma Magnesium with Glycaemic Markers in a Chinese Population.

Certain metals play a role in the pathogenesis of diabetes. This study aimed to investigate the potential association of plasma magnesium (Mg) and dietary intake of Mg with glycaemic markers. A cross-sectional study was conducted on 2373 subjects in Guangxi, China. Dietary Mg was obtained through a food frequency questionnaire containing 109 common foods. Plasma Mg concentration was determined by inductively coupled plasma mass spectrometry. Multiple linear regression combined with multivariable restricted cubic spline (RCS) functions was applied to evaluate the association of plasma Mg and dietary Mg with haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG). In linear regression, dietary Mg was significantly associated with FPG in the overall population (ß = - 0.087, P < 0.05) and in women (ß = - 0.098, P < 0.05). Plasma Mg was significantly associated with FPG in the overall population (ß = - 0.096, P < 0.05) and in men (ß = - 0.110, P < 0.05) and women (ß = - 0.088, P < 0.05). In the RCS model, no non-linear association was found between dietary and plasma Mg and HbA1c levels. Dietary and plasma Mg are significantly negatively associated with fasting glucose.

Sex-Specific Associations of Urinary Metals with Renal Function: a Cross-sectional Study in China.

BACKGROUND: Extensive studies have revealed the link between heavy metals and CKD. Compared to single meta-elements, mixture of metals reflect real-life metals exposure scenarios and are of interest. However, the mechanism of action of metal mixture on renal function is unclear. METHODS: This study aimed to explore the potential relationship between urinary arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and chromium (Cr) contents with estimated glomerular filtration rate (eGFR) levels in 2775 participants. The levels of metals in urine were determined by inductively coupled plasma-mass spectrometry. We used linear regression models and the Bayesian kernel machine regression (BKMR) to evaluate the association between metals and eGFR levels. RESULTS: In linear regression analysis, urinary As (ß = 2.723, 95%CI: 0.29, 5.157) and Pb (ß = 3.081, 95%CI: 1.725, 4.438) were positively associated with eGFR in the total population. In the BKMR model, a mixture of the five metals had a positive joint effect on eGFR levels, while Pb (PIP = 0.996) contributed the most to eGFR levels. Pb was positively associated with eGFR levels in the total participants and women. As was positively correlated with eGFR levels in women. Pb and eGFR levels were positively correlated when the other metals were set at 25th, 50th, and 75th percentiles. CONCLUSIONS: To the best of our knowledge, all five metals mixed exposure was positively associated with eGFR. Pb showed more important effects than the other four metals in the mixture, especially in women.

ApoE gene polymorphisms and metals and their interactions with cognitive function.

OBJECTIVE: To analyze the relationship between plasma metal elements, ApoE gene polymorphisms and the interaction between the two and impaired cognitive function in elderly population. METHOD: A stratified sample was drawn according to the age of the study population, and 911 subjects were included. Baseline information and health indicators were obtained, and cognitive function status was assessed by health examination, a general questionnaire and Mini-Mental Status Examination. Plasma metal elements were measured, and SNP typing was performed. Binary logistic regression was used to analyze the factors influencing cognitive function status and the association between the SNP genetic pattern of the ApoE gene and cognitive function. RESULTS: The differences in gene frequencies and genotype frequencies of the ApoE rs7412 and rs7259620 genotype frequencies were statistically different between the cognitive impairment group and the control group (P < 0.05). statistically differences were found for the codominant model in rs7412-TT compared with the CC genotype (OR = 3.112 (1.159-8.359), P = 0.024) and rs7259620-AA compared with the GG genotype (OR = 1.588 (1.007-2.504), P = 0.047). Statistically differences were found in the recessive models rs7412-TT compared with (CC + CT) (OR = 2.979 (1.112-7.978), P = 0.030), rs7259620-AA compared with (GG + GA), and rs405509-GG compared with (TT + TG) (OR = 1.548(1.022-2.344), P = 0.039) all of which increased the risk of developing cognitive impairment. The differences in plasma Fe, Cu, and Rb concentrations between the case and control groups were significant (P < 0.05). The regression results showed that the plasma Cd concentrations in the Q1 range was a protective factor for cognitive function compared with Q4 (0.510 (0.291-0.892), P = 0.018). Furthermore, there was a multiplicative interaction between the codominant and recessive models for the Q2 concentrations of Cd and the rs7259620 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (codominant model OR = 3.577 (1.496-8.555), P = 0.004, recessive model OR = 3.505 (1.479-8.307), P = 0.004). There was also a multiplicative interaction between Cd and the recessive model at the rs405509 loci, and the difference was significant, indicating increased risk of developing cognitive impairment (OR = 3.169 (1.400-7.175), P = 0.006). CONCLUSION: The ApoE rs7412, rs7259620 and rs405509 loci were associated with cognitive impairment in the elderly population, and there was an interaction between plasma metalloid Cd and the rs7259620 and rs405509 loci that increased the risk of cognitive impairment in the elderly population.

JAK2/STAT3 Signaling Pathway and Klotho Gene in Cadmium-induced Neurotoxicity In Vitro and In Vivo.

Cadmium (Cd), a common heavy metal in the environment, is associated with cognitive impairment. In the present study, we carried out a preliminary inquiry to explore whether Cd causes neurotoxicity by regulating the JAK2/STAT3 signaling pathway and affecting the expression of klotho genes in vivo and in vitro, providing clues for the mechanism of Cd-induced cognitive dysfunction. The rat samples were injected with Cd chloride solution for 14 weeks, and the memory function of the rats was detected. Different concentrations of Cd and JAK2/STAT3 signaling pathway inhibitors were used to treat PC12 cells and thus detect the apoptosis rate. The protein expression levels of JAK2, p-JAK2, STAT3, p-STAT3, and klotho in rat and PC12 cell were detected by ELISA and Western blot, respectively. With the increase in exposure dose, the memory function of rats was severely impaired. The expression of p-JAK2 and p-STAT3 proteins was significantly up-regulated, whereas that of klotho was significantly down-regulated both in vivo and in vitro (p < 0.05). In comparison with the high-dose Cd exposure group, after adding tyrphostin AG490 (AG490), the apoptosis rate of PC12 cells increased, whereas the phosphorylation levels of JAK2 and STAT3 in the cells decreased significantly (p < 0.05). Cd exposure may cause neurotoxicity by regulating the JAK2/STAT3 signaling pathway and down-regulating klotho protein expression, leading to cognitive dysfunction.