RESUMEN
BACKGROUND: Stroke is the second leading cause of death for all human beings and poses a serious threat to human health. Environmental exposure to a mixture of metals may be associated with the occurrence and development of stroke, but the evidence in the Chinese population is not yet conclusive. OBJECTIVES: This study evaluated the association between stroke risk and 13 metals METHODS: Metal concentrations in whole blood samples from 100 stroke cases and 100 controls were measured by ICP-MS. The cumulative impact of mixed metal on stroke risk was investigated by using three statistical models, BKMR, WQS and QGC. RESULTS: The case group had higher concentrations of Mg, Mn, Zn, Se, Sn, and Pb than the control group (p<0.05). BKMR model indicated a correlation between the risk of stroke and exposure to mixed metals. WQS model showed that Mg (27.2â¯%), Se (25.1â¯%) and Sn (14.8â¯%) were positively correlated with stroke risk (OR=1.53; 95â¯%Cl: 1.03-2.37, p=0.013). The QGC model showed that Mg (49.2â¯%) was positively correlated with stroke risk, while Ti (31.7â¯%) was negatively correlated with stroke risk. CONCLUSIONS: Mg may be the largest contributor to the cumulative effect of mixed metal exposure on stroke risk, and the interaction between metals requires more attention. These findings could provide scientific basis for effectively preventing stroke by managing metals in the environment.
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Exposición a Riesgos Ambientales , Accidente Cerebrovascular , Humanos , Estudios de Casos y Controles , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/inducido químicamente , Exposición a Riesgos Ambientales/estadística & datos numéricos , China/epidemiología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Contaminantes Ambientales/sangre , Metales/sangre , Metales/análisis , Metales Pesados/sangre , Factores de Riesgo , Adulto , Plomo/sangreRESUMEN
Atmospheric particulate matter (PM) exacerbates the risk factor for Alzheimer's and Parkinson's diseases (PD) by promoting the alpha-synuclein (α-syn) pathology in the brain. However, the molecular mechanisms of astrocytes involvement in α-syn pathology underlying the process remain unclear. This study investigated PM with particle size <200 nm (PM0.2) exposure-induced α-syn pathology in ICR mice and primary astrocytes, then assessed the effects of mammalian target of rapamycin inhibitor (PP242) in vitro studies. We observed the α-syn pathology in the brains of exposed mice. Meanwhile, PM0.2-exposed mice also exhibited the activation of glial cell and the inhibition of autophagy. In vitro study, PM0.2 (3, 10 and 30 µg/mL) induced inflammatory response and the disorders of α-syn degradation in primary astrocytes, and lysosomal-associated membrane protein 2 (LAMP2)-mediated autophagy underlies α-syn pathology. The abnormal function of autophagy-lysosome was specifically manifested as the expression of microtubule-associated protein light chain 3 (LC3II), cathepsin B (CTSB) and lysosomal abundance increased first and then decreased, which might both be a compensatory mechanism to toxic α-syn accumulation induced by PM0.2. Moreover, with the transcription factor EB (TFEB) subcellular localization and the increase in LC3II, LAMP2, CTSB, and cathepsin D proteins were identified, leading to the restoration of the degradation of α-syn after the intervention of PP242. Our results identified that PM0.2 exposure could promote the α-syn pathological dysregulation in astrocytes, providing mechanistic insights into how PM0.2 increases the risk of developing PD and highlighting TFEB/LAMP2 as a promising therapeutic target for antagonizing PM0.2 toxicity.
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Astrocitos , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Proteína 2 de la Membrana Asociada a los Lisosomas , Lisosomas , Ratones Endogámicos ICR , Material Particulado , alfa-Sinucleína , Animales , Astrocitos/efectos de los fármacos , alfa-Sinucleína/metabolismo , Autofagia/efectos de los fármacos , Ratones , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Material Particulado/toxicidad , Contaminantes Atmosféricos/toxicidadRESUMEN
BACKGROUND: Single nucleotide polymorphisms (SNPs) in N6AMT1 and AS3MT are associated with arsenic (As) metabolism, and efficient As methylation capacity has been associated with diabetes. However, little is known about the gene-As interaction on gestational diabetes mellitus (GDM). OBJECTIVE: This study aimed to explore the individual and combined effects of N6AMT1 and AS3MT SNPs with As metabolism on GDM. METHODS: A cross-sectional study was performed among 385 Chinese pregnant women (86 GDM and 299 Non-GDM). Four SNPs in N6AMT1 (rs1997605 and rs1003671) and AS3MT (rs1046778 and rs11191453) were genotyped. Urinary inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were determined, and the percentages of As species (iAs%, MMA%, and DMA%) were calculated to assess the efficiency of As metabolism. RESULTS: Pregnant women with N6AMT1 rs1997605 AA genotype had lower iAs% (B: 2.11; 95% CI: 4.08, -0.13) and MMA% (B: 0.21; 95% CI: 0.39, -0.04) than pregnant women with GG genotype. The AS3MT rs1046778 and rs11191453 C alleles were negatively associated with iAs% and MMA% but positively associated with DMA%. Higher urinary MMA% was significantly associated with a lower risk of GDM (OR: 0.54; 95% CI: 0.30, 0.97). The A allele in N6AMT1 rs1997605 (OR: 0.46; 95% CI: 0.26, 0.79) was associated with a decreased risk of GDM. The additive interactions between N6AMT1 rs1997605 GG genotypes and lower iAs% (AP: 0.50; 95% CI: 0.01, 0.99) or higher DMA% (AP: 0.52; 95% CI: 0.04, 0.99) were statistically significant. Similar additive interactions were also found between N6AMT1 rs1003671 GG genotypes and lower iAs% or higher DMA%. CONCLUSIONS: Genetic variants in N6AMT1 and efficient As metabolism (indicated by lower iAs% and higher DMA%) can interact to influence GDM occurrence synergistically in Chinese pregnant women.
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Arsénico , Diabetes Gestacional , Humanos , Femenino , Embarazo , Arsénico/metabolismo , Polimorfismo de Nucleótido Simple , Diabetes Gestacional/genética , Mujeres Embarazadas , Metiltransferasas/genética , Metiltransferasas/metabolismo , Estudios Transversales , Pueblos del Este de Asia , Ácido Cacodílico , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/genética , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/metabolismoRESUMEN
As one of the most important coal-producing provinces of China, Shanxi Province has been concerned about soil potentially toxic elements (PTEs) contamination in recent years. The study aimed to determine the status and sources of PTEs contamination and evaluate the quality of the soil ecology. This study investigated the degree of 13 PTEs contamination. The sources and contributions of PTEs were traced by the absolute principal component score followed by a multiple linear regression model (APCS-MLR). And the status of the soil ecosystem was verified by evaluating the soil nematode community around the coal mining areas in Jinzhong. The results showed that the mean PTEs concentration of 5 trace elements were higher than the background values of Shanxi, and safe to considerable was indicated by the pollution and ecological risk values. Soil Hg was the most contaminated element, followed by Cd. The distribution of PTEs was determined by coal mining activities (44.72%) followed by agricultural practice (32.37%) and coal transportation (21.37%). The nematode genera Acrobeloides (4.01%), Aphelenchus (20.30%), Meloidogyne (11.95%) and Aporcelaimus (2.74%) could be regarded as bioindicators of soil PTEs contamination by their tolerance. Concentrations of soil Cr, Mn, Ti and Cd showed remarkable influences on the total nematode abundance, maturity index, enrichment index, structural index, Shannon-Wiener diversity index and Pielou index of soil nematode. It is an appropriate method to evaluate the status of soil PTEs contamination combining the response of a single nematode genus and the nematode community evaluation index.
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Metales Pesados , Nematodos , Contaminantes del Suelo , Animales , Suelo/química , Metales Pesados/toxicidad , Metales Pesados/análisis , Ecosistema , Granjas , Cadmio , Monitoreo del Ambiente/métodos , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Medición de Riesgo/métodos , China , Carbón MineralRESUMEN
Arsenic poses a profound health risk including male reproductive dysfunction upon prolonged exposure. Histone methylation is an important epigenetic driver; however, its role in arsenic- induced steroidogenic pathogenesis remains obscure. In current study, we investigated the effect of histone H3K9 tri-methylation (H3K9me3) on expression pattern of steroidogenic genes in rat testis after long-term arsenic exposure. Our results revealed that arsenic exposure down-regulated the mRNA expressions of all studied steroidogenic genes (Lhr, Star, P450scc, Hsd3b, Cyp17a1, Hsd17b and Arom). Moreover, arsenic significantly increased the H3K9me3 level in rat testis. The plausible explanation of increased H3K9me3 was attributable to the up-regulation of histone H3K9me3 methyltransferase, Suv39h1 and down-regulation of demethylase, Jmjd2a. Since H3K9me3 activation leads to gene repression, we further investigated whether the down-regulation of steroidogenic genes was ascribed to the increased H3K9me3 level. To elucidate this, we determined the H3K9me3 levels in steroidogenic gene promoters, which also showed significant increase of H3K9me3 in the investigated regions after arsenic exposure. In conclusion, arsenic exposure suppressed the steroidogenic gene expression by activating H3K9me3 status, which contributed to steroidogenic inhibition in rat testis.
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Arsénico/toxicidad , Metilación de ADN/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Histonas/metabolismo , Esteroides/biosíntesis , Testículo/efectos de los fármacos , Animales , Arsénico/metabolismo , Regulación hacia Abajo , Histona Demetilasas/metabolismo , Masculino , Ratas , Ratas Sprague-Dawley , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testículo/metabolismo , Testosterona/biosíntesisRESUMEN
OBJECTIVE: Monitoring infants' exposure to 10 phthalates by measuring their urinary metabolites using a modified high performance liquid chromatography tandemelectrospray ionization mass spectrometry( HPLC-ESI-MS/MS) method. METHODS: A total of 50 infants at 0-6 month-old were recruited and their urine samples were collected by commercial available gel diapers. After the urine expression, phthalates were hydrolyzed by ß-glucuronidase, cleaned up by HLB cartridge, then these metabolites were measured by HPLC-ESI-MS/MS equipped with a Hypersil Gold Phenyl column. The target compounds were quantified by the stable isotope dilution technique. RESULTS: The limit of detection( LOD) was 0. 06-0. 16 µg/L with linear ranged 0. 2-500 µg/L. 8 of 10 phthalate metabolites could be detected with > 98% frequencies, from the high to low levels( geometric mean, µg/L) they were Mi BP( 10. 35), MECPP( 5. 13), MBP( 4. 53), MEP( 1. 98), MMP( 1. 69), MEHP( 1. 22), MEHHP( 1. 18) and MEOHP( 0. 99). MBz P and MCHP could be detected in very low frequencies of 28% and 2%, respectively. Formula feeding might be one of the major routes of infant exposure to DEHP( parent compound of MEHP, MEOHP, MEHHP and MECPP) and BBz P( parent compound of MBz P). CONCLUSION: The modified HLB-HPLC-MS/MS method can be used for determination of PAEs metabolites in infant urine effectively, and it is valuable for monitoring the infant'exposure risk to PAEs.
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Cromatografía Líquida de Alta Presión/métodos , Exposición a Riesgos Ambientales/análisis , Contaminantes Ambientales/metabolismo , Ácidos Ftálicos/metabolismo , Espectrometría de Masas en Tándem/métodos , Contaminantes Ambientales/orina , Humanos , Lactante , Recién Nacido , Ácidos Ftálicos/orinaRESUMEN
The general population is exposed to phthalates through various sources and routes. Integration of omics data and epidemiological data is a key step toward directly linking phthalate biomonitoring data with biological response. Urine metabolomics is a powerful tool to identify exposure biomarkers and delineate the modes of action of environmental stressors. The objectives of this study are to investigate the association between low-level environmental phthalate exposure and urine metabolome alteration in male population, and to unveil the metabolic pathways involved in the mechanisms of phthalate toxicity. In this retrospective cross-sectional study, we studied the urine metabolomic profiles of 364 male subjects exposed to low-level environmental phthalates. Di(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are the most widely used phthalates. ∑DEHP and MBP (the major metabolite of DBP) were associated with significant alteration of global urine metabolome in the male population. We observed significant increase in the levels of acetylneuraminic acid, carnitine C8:1, carnitine C18:0, cystine, phenylglycine, phenylpyruvic acid and glutamylphenylalanine; and meanwhile, decrease in the levels of carnitine C16:2, diacetylspermine, alanine, taurine, tryptophan, ornithine, methylglutaconic acid, hydroxyl-PEG2 and keto-PGE2 in high exposure group. The observations indicated that low-level environmental phthalate exposure associated with increased oxidative stress and fatty acid oxidation and decreased prostaglandin metabolism. Urea cycle, tryptophan and phenylalanine metabolism disruption was also observed. The urine metabolome disruption effects associated with ∑DEHP and MBP were similar, but not identical. The multibiomarker models presented AUC values of 0.845 and 0.834 for ∑DEHP and MBP, respectively. The predictive accuracy rates of established models were 81% for ΣDEHP and 73% for MBP. Our results suggest that low-level environmental phthalate exposure associates with urine metabolome disruption in male population, providing new insight into the early molecular events of phthalate exposure.
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Contaminantes Ambientales/metabolismo , Metaboloma , Estudios Transversales , Dietilhexil Ftalato/metabolismo , Exposición a Riesgos Ambientales , Humanos , Masculino , Ácidos Ftálicos/orina , Estudios RetrospectivosRESUMEN
Di (2-ethylhexyl) phthalate (DEHP) is extensively distributed in marine environments. However, limited research on the toxicological and molecular effects of DEHP on marine organisms has been conducted. Our study investigated the accumulation, elimination, and endocrine-disruptive effects of DEHP on embryonic marine medaka (Oryzias melastigma). The medaka embryos were continuously exposed to DEHP (0.01, 0.1, and 1 mg/L) or 17ß-estradiol (E2, 0.01 mg/L) until hatching, and the newly hatched larvae were then transferred to clean sea water for 12 days of depuration. DEHP and E2 appeared to have no significant effects on the mortality and hatching rates of medaka embryos, but E2 exposure significantly delayed the hatching. Significantly higher DEHP embryonic burdens were detected in the group treated with higher DEHP (0.1 and 1 mg/L) at 10 dpf (days post fertilization). The recovered larvae showed an elimination tendency of DEHP during the recovery period. DEHP had no significant effects on the transcriptional responses of endocrine-disrupting biomarker genes in the 3-dpf embryos. Treatment with 0.1 and 1 mg/L DEHP elicited a significant induction of transcriptional responses of ER, PPAR, and the CYP19 genes in a concentration-dependent manner at 10 dpf, indicating endocrine disruption may be due to bioaccumulation of DEHP. With the elimination of DEHP during the depuration period, all of the effects on these genes showed no significant effects. However, 0.1 mg/L E2 significantly affected the expression of ER, PPAR, and the CYP19 genes in the exposed embryos at both 3 and 10 dpf and recovered larvae. Therefore, these results demonstrate that accumulation of DEHP caused endocrine disruption in medaka embryos and that recovery in clean sea water may weaken the endocrine-disrupting effects.
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Disruptores Endocrinos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Aromatasa/metabolismo , Dietilhexil Ftalato/toxicidad , Embrión no Mamífero/efectos de los fármacos , Embrión no Mamífero/metabolismo , Estradiol/toxicidad , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Oryzias/crecimiento & desarrollo , Oryzias/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores de Estrógenos/metabolismo , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismoRESUMEN
Recently, the number of women suffering from gestational diabetes mellitus (GDM) has risen dramatically. GDM attracts increasing attention due to its potential harm to the heath of both the fetus and the mother. We designed this case-control study to investigate the metabolome response of newborn meconium and urine to maternal GDM. GDM mothers (n = 142) and healthy controls (n = 197) were recruited during June-July 2012 in Xiamen, China. The newborns' metabolic profiles were acquired using liquid chromatography coupled to mass spectrometry. The data showed that meconium and urine metabolome patterns clearly discriminated GDM cases from controls. Fourteen meconium metabolic biomarkers and three urinary metabolic biomarkers were tentatively identified for GDM. Altered levels of various endogenous biomarkers revealed that GDM may induce disruptions in lipid metabolism, amino acid metabolism, and purine metabolism. An unbalanced lipid pattern is suspected to be a GDM-specific feature. Furthermore, the relationships between the potential biomarkers and GDM risk were evaluated by binary logistic regression and receiver operating characteristic analysis. A combined model of nine meconium biomarkers showed a great potential in diagnosing GDM-induced disorders.
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Biomarcadores/metabolismo , Diabetes Gestacional/metabolismo , Regulación de la Expresión Génica/fisiología , Meconio/fisiología , Metaboloma/genética , Orina/fisiología , Biomarcadores/orina , Estudios de Casos y Controles , China , Femenino , Humanos , Recién Nacido , Modelos Logísticos , Metaboloma/fisiología , Embarazo , Curva ROCRESUMEN
BACKGROUND: Environmental pollutant exposure may play certain roles in the pathogenesis and progression of diabetes mellitus including gestational diabetes mellitus (GDM). We hypothesize that heavy metal exposure may trigger GDM during pregnancy. The objective of this study was to investigate the possible associations between selected heavy metal exposure and GDM risk. METHODS: This investigation is a retrospective case-control study nested within a cohort of 1359 pregnant women. These participants were recruited in Xiamen Maternity and Child Care Hospital, China, during June to July, 2012. All their newborns' meconium samples were collected. By reviewing the antenatal care records, 166 GDM mothers were screened out from the 1359 participants; 137 of 166 GDM mothers offered their newborns' meconium samples for the metal analysis. Those 137 mothers were set as the case group. Similarly, 294 healthy mothers without any gestational complication were initially screened out from the rest 1193 non-GDM mothers. 190 of the 294 healthy mothers offered their newborns' meconium samples for the metal analysis. Those 190 mothers were set as the control group. Arsenic (As), mercury (Hg), lead (Pb), cadmium (Cd), and chromium (Cr) levels in these case-control meconium samples were measured by inductively coupled plasma mass spectrometry. The possible association between the metal levels and maternal GDM risk of studied subjects was assessed by binary logistic regression. RESULTS: GDM prevalence of 12.21% was observed in the investigated 1359 participants. The concentrations of As, Hg, Cr and Cd in studied cases were significantly higher (p < 0.05) than those of controls. After adjustments for maternal age, pre-pregnant body mass index, gravidity, parity, hepatitis B virus infection, and newborn sex, As, Cd and Cr were found to be positively associated with GDM prevalence in dose-dependent manners. Among them, As was detected in all samples and its levels associated the maternal GDM with the adjusted odds ratios of 3.28 [95% CI 1.24, 8.71], 3.35 [95% CI 1.28, 8.75] and 5.25 [95% CI 1.99, 13.86] for the 2(nd), 3(rd) and 4(th) quartiles, respectively. CONCLUSIONS: The present work implies that exposure to some of the selected metals (noticeably As) may contribute to maternal GDM risk during pregnancy.
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Arsénico/toxicidad , Diabetes Gestacional/epidemiología , Exposición Materna , Meconio/química , Metales Pesados/toxicidad , Adulto , Estudios de Casos y Controles , China/epidemiología , Diabetes Gestacional/inducido químicamente , Femenino , Humanos , Masculino , Embarazo , Estudios Retrospectivos , Medición de Riesgo , Adulto JovenRESUMEN
In this study, a novel method for the analysis of perfluorinated compounds in whole blood has been developed and validated. The method was developed by using a conventional reversed-phase C18 column as a trapping column for the elimination of background contamination and high-performance liquid chromatography with tandem mass spectrometry for the target compounds analysis. The trapping column provided fast online separation of the background contamination of perfluorinated compounds. In this developed method, the limits of detection for different perfluorinated compounds ranged from 0.06 to 0.14 ng/mL. It is notable that the limit of detection (0.07 ng/mL) for perfluorooctanoic acid was improved significantly after the elimination of background contamination. The method was also validated in terms of sensitivity, accuracy, and precision. The recoveries ranged from 66.8 to 111.9%, with relative standard deviations from 2.1 to 15.3%. Our preliminary data suggest that the novel method based on trapping column cleanup followed by high-performance liquid chromatography with tandem mass spectrometry could be applied in studies on the human exposure to perfluorinated compounds.
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Cromatografía Líquida de Alta Presión/métodos , Fluorocarburos/sangre , Espectrometría de Masas en Tándem/métodos , Humanos , Límite de Detección , Control de Calidad , Reproducibilidad de los ResultadosRESUMEN
Normozoospermic infertility has become a common and important health problem worldwide. We designed this metabolomic case-control study to investigate the possible mechanism and urinary biomarkers of normozoospermic infertility. Normozoospermic infertile cases (n = 71) and fertile controls (n = 47) were recruited. A urinary metabolome pattern could discriminate normozoospermic infertile cases from fertile controls. A total of 37 potential biomarkers were identified; these have functionally important roles in energy production, antioxidation, and hormone regulation in spermatogenesis. This gave rise to a combined biomarker pattern of leukotriene E4, 3-hydroxypalmitoylcarnitine, aspartate, xanthosine, and methoxytryptophan pointing to a diagnostic capability (AUC = 0.901, sensitivity = 85.7%, and specificity = 86.8%) in a ROC model; these markers may highlight keynote events of normozoospermic infertility. Stalled medium- and long-chain fatty acid metabolism with improved ketone body metabolism, plus decreased levels of malate and aspartate could result in citrate cycle alterations via a malate-aspartate shuttle in ATP generation in spermatogenesis. Inhibitory alterations in the normal hormone-secreting activity in spermatogenesis were suggested in normozoospermic infertility. Folate deficiency and oxidative stress may jointly impact infertile patients. The disruption of eicosanoid metabolism and xanthine oxidase system, which were tightly associated with energy metabolism and oxidative stress, was also a potential underlying mechanism. In addition, depression might be associated with normozoospermic infertility via neural activity-related metabolites. This study suggests that the urinary metabolome can be used to differentiate normozoospermic infertile men from fertile individuals. Potential metabolic biomarkers derived from these analyses might be used to diagnose what remains a somewhat idiopathic condition and provide functional insights into its pathogenesis.
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Infertilidad Masculina/orina , Metaboloma , Adulto , Ácido Aspártico/orina , Biomarcadores/orina , Carnitina/orina , Humanos , Infertilidad Masculina/diagnóstico , Leucotrieno E4/orina , Masculino , Metabolómica , Curva ROC , Ribonucleósidos/orina , Triptófano/análogos & derivados , Triptófano/orina , Xantinas , Adulto JovenRESUMEN
Whether there is a relationship between quality, DNA methylation, and mitochondrial DNA (mtDNA) copy number in human-derived sperm specimens is unknown. A cohort (n = 118) of male partners of couples who were undergoing fertility assessment because of an idiopathic inability to conceive were recruited. Sperm motility parameters were determined by computer-aided sperm analysis (CASA), while sperm quality was assessed using World Health Organization criteria, mtDNA copy number was measured by real-time PCR, and DNA methylation patterns were analyzed employing high-melting resolution PCR and bisulfite sequencing PCR. The mtDNA copy number negatively correlated with semen parameters, including sperm motility, concentration, morphology, progression, and motion characteristics (r for -0.19 to -0.54; P < 0.05 for all). As a surrogate marker for global DNA methylation, LINE-1 negatively correlated with sperm motility (r = -0.25; P = 0.009). Meanwhile, after adjustment for age, length of abstinence, smoking, and alcohol intake, there was a suggested association for increased LINE-1 methylation and mtDNA copy number tertiles versus sperm motility (odd ratios were 1.0, 2.6, and 4.7, and 1.0, 2.5, and 4.9, respectively). Altered mtDNA copy number and DNA methylation may serve as genetic and epigenetic markers to assess human sperm quality together with CASA parameters.
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Metilación de ADN/fisiología , ADN Mitocondrial/genética , Análisis de Semen , Semen/fisiología , Adulto , Humanos , Masculino , Motilidad EspermáticaRESUMEN
Urinary biomonitoring provides the most accurate arsenic exposure assessment; however, to improve the risk assessment, arsenic-related metabolic biomarkers are required to understand the internal processes that may be perturbed, which may, in turn, link the exposure to a specific health outcome. This study aimed to investigate arsenic-related urinary metabolome changes and identify dose-dependent metabolic biomarkers as a proof-of-concept of the information that could be obtained by combining metabolomics and targeted analyses. Urinary arsenic species such as inorganic arsenic, methylarsonic acid, dimethylarsinic acid and arsenobetaine were quantified using high performance liquid chromatography (HPLC)-inductively coupled plasma-mass spectrometry in a Chinese adult male cohort. Urinary metabolomics was conducted using HPLC-quadrupole time-of-flight mass spectrometry. Arsenic-related metabolic biomarkers were investigated by comparing the samples of the first and fifth quintiles of arsenic exposure classifications using a partial least-squares discriminant model. After the adjustments for age, body mass index, smoking, and alcohol consumption, five potential biomarkers related to arsenic exposure (i.e., testosterone, guanine, hippurate, acetyl-N-formyl-5-methoxykynurenamine, and serine) were identified from 61 candidate metabolites; these biomarkers suggested that endocrine disruption and oxidative stress were associated with urinary arsenic levels. Testosterone, guanine, and hippurate showed a high or moderate ability to discriminate the first and fifth quintiles of arsenic exposure with area-under-curve (AUC) values of 0.89, 0.87, and 0.83, respectively; their combination pattern showed an AUC value of 0.91 with a sensitivity of 88% and a specificity of 80%. Arsenic dose-dependent AUC value changes were also observed. This study demonstrated that metabolomics can be used to investigate arsenic-related biomarkers of metabolic changes; the dose-dependent trends of arsenic exposure to these biomarkers may translate into the potential use of metabolic biomarkers in arsenic risk assessment. Since this was a proof-of-concept study, more research is needed to confirm the relationships we observed between arsenic exposure and biochemical changes.
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Arsénico/orina , Metaboloma , Adulto , Arsenicales/orina , Biomarcadores/orina , Ácido Cacodílico/orina , Cromatografía Líquida de Alta Presión , Monitoreo del Ambiente , Guanina/orina , Hipuratos/orina , Humanos , Análisis de los Mínimos Cuadrados , Masculino , Espectrometría de Masas , Metabolómica , Testosterona/orina , Adulto JovenRESUMEN
Infant exposure to endocrine disruptors (EDs) may cause adverse health effects because of their fast growth and development during this life stage. However, collecting urine from infants for exposure assessment using biological monitoring is not an easy task. For this purpose, we evaluated the feasibility of using urine expressed from disposable gel absorbent diapers (GADs) as a matrix for biomonitoring selected phenolic EDs. GADs urine was expressed with the assistance of CaCl(2) and was collected using a device fabricated in our laboratory. The analytes were extracted and concentrated using a liquid-liquid method and their hydroxyl groups were modified by dansyl chloride to enhance their chromatography and detection. Finally, the analytes were measured by high-performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem mass spectrometry (MS/MS). The target chemicals were bisphenol A, triclosan, 17 α-ethynylestradiol, the natural hormone estrone, and 17 ß-estradiol. The ratio of the CaCl(2) to the urine-wetted gel absorbent, variation of the inter-urination volume, and analyte deposition bias in the diaper were assessed. Analyte blank values in the diapers, the sample storage stabilities, and recoveries of the analytes were also evaluated. The results showed that 70-80 % of the urine could be expressed from the diaper with the assistance of CaCl(2) and 70.5-124 % of the spiked analytes can be recovered in the expressed urine. The limits of detections (LODs) were 0.02-0.27 ng/mL, well within the range for detection in human populations. Our pilot data suggest that infants are widely exposed to the selected EDs.
RESUMEN
Fluoroquinolone (FQ) antibiotics, one of the leading environmental pollutants, have ecotoxic effects that can accumulate through ecosystems and harm human health. The determination of FQs is still difficult due to the complex matrix, many interfering factors, and low concentration. Hence, a magnetic microporous organic network (MON) composite denoted as Fe3O4@MON-NH2@CM-ß-CD with excellent FQ adsorption performance was prepared by ß-CD covalent modification of a MON. Based on the existence of π-π packing, hydrophobic interaction, and hydrogen bonding between Fe3O4@MON-NH2@CM-ß-CD and FQs, a new magnetic solid phase extraction (MSPE) method for the enrichment of FQs was developed. Under optimized MSPE conditions, five FQs were detected by HPLC-UV with good linearity (R2 ≥ 0.9989) in the range of 0.02-1 µg mL-1, and detection limits (S/N = 3) in the range of 0.0014-0.0023 µg mL-1. The satisfactory recoveries ranged from 93.1 to 116.2% with RSDs lower than 8.39% when applied to actual environmental water samples. These results revealed that Fe3O4@MON-NH2@CM-ß-CD as an adsorbent for MSPE had excellent performance for FQ extraction from real samples, and the MON material types were expanded through the functionalization of MONs, which would have great potential for further application in various analytical methods.
Asunto(s)
Antibacterianos , Fluoroquinolonas , Extracción en Fase Sólida , Contaminantes Químicos del Agua , beta-Ciclodextrinas , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Fluoroquinolonas/análisis , Fluoroquinolonas/química , Fluoroquinolonas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Antibacterianos/análisis , Antibacterianos/química , beta-Ciclodextrinas/química , Porosidad , Adsorción , Cromatografía Líquida de Alta Presión/métodos , Límite de DetecciónRESUMEN
Per- and polyfluoroalkyl substances (PFAS) can pass through the placental barrier and pose health risks to fetuses. However, exposure and transplacental transfer patterns of emerging PFAS remain unclear. Here, 24 PFAS were measured in paired maternal whole blood (n = 228), umbilical cord whole blood (n = 119) and serum (n = 120). Orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to differentiate PFAS between different matrices. The transplacental transfer (TPT) of PFAS was calculated using cord to maternal whole blood concentration ratios. PFOS and PFOA were still the dominant PFAS in maternal samples. The emerging PFAS had higher TPT than PFOS and PFOA. Moreover, PFAS with the same chain length but different functional groups and C-F bonds showed different TPT, such as PFOS and PFOSA (C8, median: 0.090 vs. 0.305, p < 0.05) and PFHxS and 4:2 FTS (C6, median: 0.220 vs. 1.190, p < 0.05). A significant sex difference in 4:2 FTS (median: boys 1.250, girls 1.010, p < 0.05) were found. Furthermore, we observed a significant U-shaped trend for the TPT of carboxylates with increasing carbon chain length. PFAS showed a compound-specific transfer through placental barrier and a compound-specific distribution between different matrices in this study.
Asunto(s)
Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Humanos , Masculino , Embarazo , Femenino , Estudios de Cohortes , Placenta , Sangre Fetal/química , Fluorocarburos/análisis , China , Ácidos Alcanesulfónicos/análisis , Contaminantes Ambientales/análisisRESUMEN
To investigate the hypothesis that general environmental arsenic (As) exposure can impair male fertility, we designed a case-control study examining possible correlations between the concentrations of different As species in urine [controls (n = 151) vs cases (n = 140)], urinary metabolic biomarkers [controls (n = 158) vs cases (n = 135)], and infertility characterized by poor semen quality. Regional participants were recruited sequentially from the affiliated hospitals of Nanjing Medical University. Elevated inorganic arsenate (Asi(V)) exposure was associated with infertility: in comparison with the first quartile, subjects with Asi(V) levels above the median were more likely to exhibit male idiopathic infertility with increasing adjusted odds ratios (AOR) of 4.9 [95% confidence interval (CI), 1.8-13.6] and 13.6 (95% CI, 4.8-38.6) at the third and fourth quartiles (P = 0.000 for trend), respectively. Other As species did not exhibit a significant dose-dependent correlation with infertility risk. Levels of urinary biomarkers correlated with both male infertility and Asi(V) concentrations [controls (n = 145) vs cases (n = 123)]; the latter correlation was independent of disease. These included acylcarnitines, aspartic acid, and hydroxyestrone, which were negatively associated with infertility, and uridine and methylxanthine, which were positively associated. In conclusion, for the first time we show that elevated urinary concentrations of Asi(V) from general As exposure are significantly associated with male infertility, and As species may exert toxicity via oxidative stress and sexual hormone disrupting mechanisms, as indicated by related biomarkers.
Asunto(s)
Arsénico/toxicidad , Biomarcadores/orina , Etnicidad , Infertilidad Masculina/inducido químicamente , Estrés Oxidativo , Adulto , China , Humanos , MasculinoRESUMEN
Perfluorooctane sulfonate (PFOS) is a global pollutant that has been studied because of its health risks. PFOS has been shown to have immune toxicity. However, few studies have focused on the immune responses of fish larvae exposed to PFOS at early embryonic stages. In this study, the larvae of marine medaka (Oryzias melastigma) were evaluated for postnatal immune toxicity after embryonic exposure to PFOS (0, 1, 4 and 16mg/L) from 2 days post fertilization (dpf). The physiological indices, survival rates, PFOS elimination kinetics, liver histology and gene transcription in the fish larvae were examined after depuration. The elimination rate constant (ke) of PFOS in the fish larvae ranged from 0.04±0.00 to 0.07±0.01d(-1). Embryonic exposure to PFOS severely compromised the postnatal survival of fish larvae after depuration. The survival rate and body width decreased in a concentration dependent manner. PFOS impaired the liver structure in the fish larvae by enlarging the cell nuclei and damaging the cell structure. To explore the toxic mechanisms that affect the immune responses, fish larvae at 27 days post hatch (dph) were exposed to lipopolysaccharides (LPS) to elicit an inflammatory response. The inflammatory response and immune-related genes were generally up-regulated in the fish larvae following embryonic exposure to 0mg/L PFOS. In contrast, the genes were all markedly down-regulated in the fish larvae following embryonic exposure to 1 and 4mg/L PFOS. These results suggest that early life exposure to PFOS could alter immunoregulation functions, leading to functional dysfunction or weakness of the immune system in fish larvae. The immunosuppression effects caused by PFOS could reduce the efficiency of immune defense mechanisms and increase the susceptibility to infectious agents, which may contribute to various detrimental health effects in the fish larvae.
Asunto(s)
Embrión no Mamífero/inmunología , Fluorocarburos/toxicidad , Sistema Inmunológico/efectos de los fármacos , Oryzias/inmunología , Contaminantes Químicos del Agua/toxicidad , Animales , Embrión no Mamífero/efectos de los fármacos , Terapia de Inmunosupresión , Larva/efectos de los fármacos , Oryzias/embriologíaRESUMEN
Purpose: Correcting intestinal microecological imbalance has become one of the core strategies to treat chronic diseases. Some traditional microecology-based therapies targeting intestine, such as prebiotic therapy, probiotic therapy and fecal microbiota transplantation therapy, have been used in the prevention and treatment of clinical chronic diseases, which still facing low safety and poor controllability problems. The development of synthetic biology technology has promoted the development of intestinal microecology-based therapeutics for chronic diseases, which exhibiting higher robustness and controllability, and become an important part of the next generation of microecological therapy. The purpose of this review is to summarize the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases. Methods: The available literatures were searched to find out experimental studies and relevant review articles on the application of synthetic biology in intestinal microecology-based therapeutics for chronic diseases from year 1990 to 2023. Results: Evidence proposed that synthetic biology has been applied in the intestinal microecology-based therapeutics for chronic diseases, covering metabolic diseases (e.g. diabetes, obesity, nonalcoholic fatty liver disease and phenylketonuria), digestive diseases (e.g. inflammatory bowel disease and colorectal cancer), and neurodegenerative diseases (e.g. Alzheimer's disease and Parkinson's disease). Conclusion: This review summarizes the application of synthetic biology in intestinal microecology-based therapeutics for major chronic diseases and discusses the opportunities and challenges in the above process, providing clinical possibilities of synthetic biology technology applied in microecological therapies.