Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 51
Filtrar
1.
Chemosphere ; 286(Pt 3): 131963, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34426263

RESUMO

BACKGROUND: Exposure to air pollution has been linked with altered immune function in adults, but little is known about its effects on early life. This study aimed to investigate the effects of exposure to air pollution during prenatal and postnatal windows on cell-mediated immune function in preschoolers. METHODS: Pre-school aged children (2.9 ± 0.5 y old, n = 391) were recruited from a mother-child cohort study in Wuhan, China. We used a spatial-temporal land use regression (LUR) model to estimate exposures of particulate matter with aerodynamic diameters ≤2.5 µm (PM2.5) and ≤10 µm (PM10), and nitrogen dioxide (NO2) during the specific trimesters of pregnancy and the first two postnatal years. We measured peripheral blood T lymphocyte subsets and plasma cytokines as indicators of cellular immune function. We used multiple informant models to examine the associations of prenatal and postnatal exposures to air pollution with cell-mediated immune function. RESULTS: Prenatal exposures to PM2.5, PM10, and NO2 during early pregnancy were negatively associated with %CD3+ and %CD3+CD8+ cells, and during late pregnancy were positively associated with %CD3+ cells. Postnatal exposures to these air pollutants during 1-y or 2-y childhood were positively associated with IL-4, IL-5, IL-6, and TNF-α. We also observed that the associations of prenatal or postnatal air pollution exposures with cellular immune responses varied by child's sex. CONCLUSIONS: Our results suggest that exposure to air pollution during different critical windows of early life may differentially alter cellular immune responses, and these effects appear to be sex-specific.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Criança , Pré-Escolar , Estudos de Coortes , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Imunidade Celular , Masculino , Dióxido de Nitrogênio/análise , Dióxido de Nitrogênio/toxicidade , Material Particulado/análise , Material Particulado/toxicidade , Gravidez
2.
J Hazard Mater ; 421: 126683, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34315024

RESUMO

Experimental studies have demonstrated that disinfection byproducts (DBPs) can cause ovarian toxicity including inhibition of antral follicle growth and disruption of steroidogenesis, but there is a paucity of human evidence. We aimed to investigate whether urinary biomarkers of exposure to drinking water DBPs were associated with ovarian reserve. The present study included 956 women attending an infertility clinic in Wuhan, China from December 2018 to January 2020. Antral follicle count (AFC), ovarian volume (OV), anti-Mullerian hormone (AMH), and follicle-stimulating hormone (FSH) were measured as indicators of ovarian reserve. Urinary dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) were assessed as potential biomarkers of drinking water DBP exposures. Multivariate linear and Poisson regression models were applied to estimate the associations of urinary DCAA and TCAA concentrations with indicators of ovarian reserve. Elevated urinary DCAA and TCAA levels were monotonically associated with reduced total AFC (- 5.98%; 95% CI: - 10.30%, - 1.44% in DCAA and - 12.98%; 95% CI: - 17.00%, - 8.76% in TCAA comparing the extreme tertiles; both P for trends ≤ 0.01), and the former was only observed in right AFC but not in left AFC, whereas the latter was estimated for both right and left AFC. Moreover, elevated urinary TCAA levels were monotonically associated with decreased AMH (- 14.09%; 95% CI: - 24.79%, - 1.86% comparing the extreme tertiles; P for trend = 0.03). These negative associations were still observed for the exposure biomarkers modeled as continuous variables. Our findings suggest that exposure to drinking water DBPs may be associated with decreased ovarian reserve.


Assuntos
Água Potável , Reserva Ovariana , Biomarcadores , Estudos Transversais , Desinfecção , Feminino , Humanos
4.
Chemosphere ; 288(Pt 1): 132464, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34619260

RESUMO

Studies indicate that phthalates can disrupt spermatogenesis and lead to the reduction of semen quality. However, the underlying mechanisms remain unclear. This study aimed to examine the associations of phthalate exposures as individual chemicals and mixtures with spermatogenesis-related miRNA106a. We detected eight phthalate metabolites in repeated urine samples and a single seminal plasma specimen among 111 men from an infertility clinic in Wuhan, China. Spermatogenesis-related miRNA106a was measured in seminal plasma. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) models to separately evaluate the associations of phthalate metabolites as individual chemicals and mixtures with spermatogenesis-related miRNA106a. Elevated tertiles of urinary mono (2-ethylhexyl) phthalate (MEHP) was associated with decreased miRNA106a (-61.71%; 95%CI: 81.92, -18.93% for the highest vs. lowest tertile; P for trend = 0.01). Similarly, an inverse exposure-response relationship between seminal plasma MEHP concentrations and miRNA106a was also observed (-59.44%; 95%CI: 79.19, -20.95% for the highest vs. lowest tertile; P for trend = 0.01). The BKMR models showed that the mixtures of seminal plasma phthalate metabolites were associated with decreased miRNA106a when the chemical mixtures were ≥35th percentile compared to their medians. Nonlinear associations with miRNA106a were estimated for urinary and seminal plasma MEHP while fixing other phthalate metabolites at their medians. Our findings suggest that mixtures of phthalate metabolites in seminal plasma were negatively associated with spermatogenesis-related miRNA106a, and individual MEHP was the major contributor to the adverse effects.

5.
Org Lett ; 23(19): 7618-7623, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34546759

RESUMO

We report that structurally complex guanidinium heterocycles can be prepared in one step by regio- and stereoselective [4 + 2]-cycloadditions of N-amidinyliminium ions with indoles or benzothiophene. In contrast to reactions of these heterodienes with alkenes, density functional theory (DFT) calculations show that these cycloadditions take place in a concerted asynchronous fashion. The [4 + 2]-cycloaddition of N-amidinyliminium ions (1,3-diaza-1,3-dienes) with indoles and benzothiophene are distinctive, as related [4 + 2]-cycloadditions of N-acyliminium ions (1-oxa-3-aza-1,3-dienes) are apparently unknown.

6.
Clin Proteomics ; 18(1): 22, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34418970

RESUMO

BACKGROUND: Preeclampsia and gestational hypertension can cause vascular function impairment in offspring. In our previous work, we described the protein expression profiles of umbilical artery tissues from patients with preeclampsia. METHODS: To gain insights into the mechanisms of vascular dysfunction in adult rats born to preeclamptic dams, we analyzed thoracic aorta tissues by using iTRAQ isobaric tags and 2D nano LC-MS/MS. RESULTS: By using the iTRAQ method, we analyzed 1825 proteins, of which 106 showed significantly different expression in the thoracic aortic. Ingenuity pathway analysis (IPA) showed that the majority of differentially expressed proteins (DEPs) were associated with cardiovascular function. Further analysis indicated that glucose-6-phosphate dehydrogenase (G6PD), which is inhibited by miR-423-5p and activated by TP53, had the strongest effect on cardiovascular function. The expression of G6PD was upregulated in thoracic aorta tissues, as confirmed by Western blotting. The expression of two other vascular function-related proteins, cysteine- and glycine-rich protein 2 (CSRP2) and tubulin alpha-4 A (TUBA4A), was upregulated, as demonstrated by mass spectrometry (MS). CONCLUSIONS: Although the results require further functional validation, these data provide novel findings related to vascular function impairment in the adult offspring of preeclamptic mothers.

7.
Environ Pollut ; 286: 117386, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34051689

RESUMO

Studies have documented that exposure to organochlorine pesticides (OCPs) is linked with breast cancer, but the underlying biological mechanisms are still unknown. This study included 313 women diagnosed with breast cancer and 313 controls in Wuhan, China, and measured 18 OCPs in serum and 3 oxidative stress biomarkers in urine. Multivariable adjusted regression models were used to evaluate the associations among OCPs, oxidative stress biomarkers, and breast cancer. The mediating effect of oxidative stress was assessed by mediation analysis. We observed that most OCPs were positively associated with risk of breast cancer (all FDR-P values < 0.05 or 0.10). Moreover, we found that p,p'-DDT, p,p'-DDD, dieldrin, heptachlor, and heptachlor epoxide were positively associated with 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA) and 8-iso-prostaglandin F2α (8-isoPGF2α), which in turn were positively associated with risk of breast cancer. Mediation analysis indicated that HNE-MA and 8-isoPGF2ɑ mediated the positive associations between these OCPs and risk of breast cancer, with mediating proportion ranging from 6.23% to 19.9%. Our results suggest that lipid peroxidation may mediate the positive associations between OCP exposures and risk of breast cancer.


Assuntos
Neoplasias da Mama , Hidrocarbonetos Clorados , Praguicidas , Biomarcadores , Neoplasias da Mama/induzido quimicamente , Feminino , Humanos , Hidrocarbonetos Clorados/análise , Estresse Oxidativo , Praguicidas/análise
8.
Sci Total Environ ; 784: 147184, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-33901963

RESUMO

BACKGROUND: Exposure to bisphenol A (BPA) has been associated with various adverse health outcomes. Recently, an increasing concern on its alternatives such as bisphenol S (BPS) and bisphenol F (BPF) has been aroused due to the restriction use of BPA. Few studies have identified predictors of exposure to BPA alternatives and assessed their health risks. OBJECTIVE: The aim of this study was to identify predictors of BPA and its alternatives and to assess their health risks among pregnant women. METHODS: We detected first morning urinary concentrations of BPA and its alternatives (BPS and BPF) among 1097 pregnant women from an established Chinese cohort. A questionnaire was conducted to obtain demographic characteristics, dietary habits, and lifestyles. We examined the predictors of creatinine-adjusted urinary BPA and its alternatives concentrations using multivariable linear regression. Risk assessment of exposure to BPA and its alternatives was calculated based on the estimated of daily intake (EDI). RESULTS: Geometric means of creatinine-adjusted urinary BPA, BPF, and BPS were 0.92, 0.12, and 0.08 µg/g creatinine, respectively. Pregnant women from Wuhan had lower concentrations of BPA, BPF, and ∑BPs (sum of BPA, BPF, and BPS) than those from Xiaogan. Intake of fried food was related to higher concentrations of BPA, and intake of pickled food was associated with higher concentrations of BPF and ∑BPs. The maximum EDI values for exposure to BPA, BPF, BPS, and ∑BPs ranged from 5.6428 to 13.3356 nmol/kg body weight/day, which were below the tolerable daily intake (TDI) for BPA defined by the European Food Safety Authority (EFSA) (18 nmol/kg body weight/day). The maximum hazard index (HI) value was 0.7409. CONCLUSION: Several predictors identified in this study may inform public recommendations to reduce exposure to BPA and its alternatives.


Assuntos
Compostos Benzidrílicos , Gestantes , Estudos de Coortes , Feminino , Humanos , Fenóis , Gravidez , Medição de Risco
9.
J Org Chem ; 86(8): 5792-5804, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33769821

RESUMO

We examine the theoretical underpinnings of the seminal discoveries by Reiner Sustmann about the ambiphilic nature of Huisgen's phenyl azide cycloadditions. Density functional calculations with ωB97X-D and B2PLYP-D3 reproduce the experimental data and provide insights into ambiphilic control of reactivity. Distortion/interaction-activation strain and energy decomposition analyses show why Sustmann's use of dipolarophile ionization potential is such a powerful predictor of reactivity. We add to Sustmann's data set several modern distortion-accelerated dipolarophiles used in bioorthogonal chemistry to show how these fit into the orbital energy criteria that are often used to understand cycloaddition reactivity. We show why such a simple indicator of reactivity is a powerful predictor of reaction rates that are actually controlled by a combination of distortion energies, charge transfer, closed-shell repulsion, polarization, and electrostatic effects.


Assuntos
Azidas , Reação de Cicloadição , Fenômenos Físicos , Eletricidade Estática
10.
J Psychopharmacol ; 35(5): 591-605, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33749357

RESUMO

BACKGROUND: Long-term morphine use is associated with serious side effects, such as morphine-induced hyperalgesia and analgesic tolerance. Previous investigations have documented the association between dopamine (DA) neurons in the ventral tegmental area (VTA) and pain. However, whether VTA DA neurons are implicated in morphine-induced hyperalgesia and analgesic tolerance remains elusive. METHODS: Initially, we observed behavioural effects of lidocaine administration into VTA or ablation of VTA DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance. Subsequently, c-Fos expression in nucleus accumbens (NAc) shell-projecting and medial prefrontal cortex (mPFC)-projecting VTA DA neurons after chronic morphine treatment was respectively investigated. Afterwards, the effects of chemogenetic manipulation of NAc shell-projecting or mPFC-projecting DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance were observed. Additionally, effects of chemogenetic manipulation of VTA GABA neurons on c-Fos expression in VTA DA neurons were investigated. RESULTS: Lidocaine injection into VTA relieved established hyperalgesia and anti-nociceptive tolerance whereas ablation of VTA DA neurons prevented the development of morphine-induced hyperalgesia and anti-nociceptive tolerance. Chronic morphine treatment increased c-Fos expression in NAc shell-projecting DA neurons, rather than in mPFC-projecting DA neurons. Chemogenetic manipulation of NAc shell-projecting DA neurons had influence on morphine-induced hyperalgesia and tolerance. However, chemogenetic manipulation of mPFC-projecting DA neurons had no significant effects on morphine-induced hyperalgesia and anti-nociceptive tolerance. Chemogenetic manipulation of VTA GABA neurons affected the c-Fos expression in VTA DA neurons. CONCLUSIONS: These findings revealed the involvement of NAc shell-projecting VTA DA neurons in morphine-induced hyperalgesia and anti-nociceptive tolerance, and may shed new light on the clinical management of morphine-induced hyperalgesia and analgesic tolerance. PERSPECTIVE: This study demonstrated that NAc shell-projecting DA neurons rather than mPFC-projecting DA neurons in the VTA were implicated in morphine-induced hyperalgesia and anti-nociceptive tolerance. Our findings may pave the way for the discovery of novel therapies for morphine-induced hyperalgesia and analgesic tolerance.

11.
Zhongguo Zhong Yao Za Zhi ; 46(3): 599-604, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33645025

RESUMO

Protein kinase C(PKC) is a type of protein kinase widely involved in cell proliferation and development, but the developmental mechanism in the gonads of androgynous animals is still unclear. In order to explore the role of protein kinase C in the development of Whitmania pigra germ cells, the Wh. pigra PKC(Wp-PKC) gene was cloned, bioinformatics analysis was conducted, and fluorescent quantitative PCR was used to analyze the expression of female and male gonads. The results showed that:(1)The cloned Wp-PKC had a full length of 2 580 bp, a relative molecular weight of 76 555.19, and contains an open reading frame encoding 670 amino acids, Wp-PKC was closely related to Danio rerio PKC-α and rat PKC-γ. The similarity of amino acid sequence was 55% and 58%.(2)The protein encoded by Wp-PKC had no signal peptide and was a hydrophilic protein. The secondary structure is mainly composed of random coils, α-helices, extended chains, folds and folds, with the largest proportion of random coils and α-helices. Wp-PKC protein does not contain a transmembrane domain. Multiple sequence alignment and domain prediction analysis show that Wp-PKC contains 4 conserved domains of classical protein kinase C.(3)Fluorescence quantitative results showed that the expression of Wp-PKC in Wh. pigra gonads was positively correlated with the development of germ cells, and the expression in male gonads was significantly higher than that in female gonads. In summary, Wp-PKC is a classic PKC, and Wp-PKC may promote the development of Wh. pigra, especially the development of male gonads, and provide references for further research on the developmental mechanisms of Wh. pigra.


Assuntos
Sanguessugas , Animais , Clonagem Molecular , Feminino , Gônadas , Sanguessugas/genética , Masculino , Ovário , Proteína Quinase C/genética , Ratos
12.
Acta Pharmacol Sin ; 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33782543

RESUMO

Mifepristone (Mif), an effective synthetic steroidal antiprogesterone drug, is widely used for medical abortion and pregnancy prevention. Due to its anti-glucocorticoid effect, high-dose Mif is also used to treat Cushing's syndrome. Mif was reported to active pregnane X receptor (PXR) in vitro and PXR can induce hepatomegaly via activation and interaction with yes-associated protein (YAP) pathway. High-dose Mif was reported to induce hepatomegaly in rats and mice, but the underlying mechanism remains unclear. Here, the role of PXR was studied in Mif-induced hepatomegaly in C57BL/6 mice and Pxr-knockout mice. The results demonstrated that high-dose Mif (100 mg · kg-1 · d-1, i.p.) treatment for 5 days significantly induced hepatomegaly with enlarged hepatocytes and promoted proliferation, but low dose of Mif (5 mg · kg-1 · d-1, i.p.) cannot induce hepatomegaly. The dual-luciferase reporter gene assays showed that Mif can activate human PXR in a concentration-dependent manner. In addition, Mif could promote nuclear translocation of PXR and YAP, and significantly induced the expression of PXR, YAP, and their target proteins such as CYP3A11, CYP2B10, UGT1A1, ANKRD, and CTGF. However, Mif (100 mg · kg-1 · d-1, i.p.) failed to induce hepatomegaly in Pxr-knockout mice, as well as hepatocyte enlargement and proliferation, further indicating that Mif-induced hepatomegaly is PXR-dependent. In summary, this study demonstrated that PXR-mediated Mif-induced hepatomegaly in mice probably via activation of YAP pathway. This study provides new insights in Mif-induced hepatomegaly, and provides novel evidence on the crucial function of PXR in liver enlargement and regeneration.

13.
Zhongguo Zhong Yao Za Zhi ; 46(6): 1374-1378, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33787134

RESUMO

Protein kinase C(PKC) is a kind of kinase which is widely involved in cell proliferation and development. PKC(Wp-PKC) in Whitmania pigra body belongs to classic PKC. In order to investigate the effect of Wp-PKC on the development of Wh. pigra germ cells, 17ß-estradiol(17ß-E2)(100 ng·mL~(-1)) and methyltestosterone(MT)(150 µg·L~(-1)), 150 µg·L~(-1)(MT)+0.5 mg·L~(-1) PKC, 0.5 mg·L~(-1) PKC inhibitor were added to Wh. pigra culture water, and no addition group(control group) was added, and the effects on the development of Wh. pigra germ cells and the expression of Wp-PKC were observed. The results showed that: Wp-PKC in male gonads was always higher than that in female gonads; MT promoted the development of male gonads in Wh. pigra, while the expression of Wp-PKC was significantly higher than that in the control; 17ß-E2 promoted the development of female gonads in Wh. pigra and Wp-PKC expression significantly lower than that of the control; while the development of the female and male gonads in the PKC inhibitor group was inhibited, the expression of Wp-PKC was significantly lower than that of the control. In summary, Wp-PKC may promote the development of Wh. pigra, especially the development of male gonads.


Assuntos
Gônadas , Sanguessugas , Animais , Estradiol , Feminino , Masculino , Metiltestosterona , Ovário
14.
Phytomedicine ; 84: 153520, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662920

RESUMO

BACKGROUND: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown. PURPOSE: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly. METHODS: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence. RESULTS: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice. CONCLUSION: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ciclo-Octanos/toxicidade , Dioxóis/toxicidade , Hepatomegalia/induzido quimicamente , Lignanas/toxicidade , Receptor de Pregnano X/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatomegalia/metabolismo , Hepatomegalia/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Receptor de Pregnano X/genética , Schisandra/química , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética
15.
Acta Pharmacol Sin ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33758356

RESUMO

Ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI) in clinic. The activation of NLRP3 inflammasome is associated with inflammation and renal injury in I/R-induced AKI. In the current study we explored the molecular and cellular mechanisms for NLRP3 inflammasome activation following renal I/R. Mice were subjected to I/R renal injury by clamping bilateral renal pedicles. We showed that I/R injury markedly increased caspase-11 expression and the cleavage of pannexin 1 (panx1) in the kidneys accompanied by NLRP3 inflammasome activation evidenced by the activation of caspase-1 and interlukin-1ß (IL-1ß) maturation. In Casp-11-/- mice, I/R-induced panx1 cleavage, NLRP3 inflammasome activation as well as renal functional deterioration and tubular morphological changes were significantly attenuated. In cultured primary tubular cells (PTCs) and NRK-52E cells, hypoxia/reoxygenation (H/R) markedly increased caspase-11 expression, NLRP3 inflammasome activation, IL-1ß maturation and panx1 cleavage. Knockdown of caspase-11 attenuated all those changes; similar effects were observed in PTCs isolated from Casp-11-/- mice. In NRK-52E cells, overexpression of caspase-11 promoted panx1 cleavage; pretreatment with panx1 inhibitor carbenoxolone or knockdown of panx1 significantly attenuated H/R-induced intracellular ATP reduction, extracellular ATP elevation and NLRP3 inflammasome activation without apparent influence on H/R-induced caspase-11 increase; pretreatment with P2X7 receptor inhibitor AZD9056 also attenuated NLRP3 inflammasome activation. The above results demonstrate that the cleavage of panx1 by upregulated caspase-11 is involved in facilitating ATP release and then NLRP3 inflammasome activation in I/R-induced AKI. This study provides new insight into the molecular mechanism of NLRP3 inflammasome activation in AKI.

16.
Environ Int ; 146: 106305, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33395947

RESUMO

BACKGROUND: Bisphenol A (BPA) can cause detrimental effects on fetal growth. However, the effects of BPA alternatives, such as bisphenol F (BPF) and bisphenol S (BPS), on fetal growth are less known. OBJECTIVE: To investigate the relationships of prenatal BPA, BPF, and BPS exposures with fetal growth parameters and gestational age. METHODS: Urinary BPA, BPF, and BPS were measured in 1,197 pregnant women before delivery in a Chinese cohort. The associations of prenatal exposure to BPA, BPF, and BPS with fetal growth parameters and gestational age were examined, and associations stratified by fetal sex were also conducted. We used a restricted cubic splines (RCS) model to examine the dose-response associations between exposures and outcomes. RESULTS: Maternal urinary BPA and BPF were negatively related to birth length (-0.30 cm, 95% CI: -0.44, -0.15 and -0.21 cm, 95% CI: -0.36, -0.07 comparing the extreme exposure groups, respectively, both p for trends < 0.01). These associations were more pronounced in girls with inverted U-shaped dose-response relationships. Maternal urinary BPA and BPF were positively related to ponderal index (0.05 g/cm3 × 100, 95% CI: 0.01, 0.09 and 0.04 g/cm3 × 100, 95% CI: 0.01, 0.08 comparing the extreme exposure groups, respectively, both p for trends = 0.02), and maternal urinary BPS was associated with shorter gestational age (-0.20 weeks, 95% CI: -0.37, -0.03 comparing the extreme exposure groups, p for trend = 0.02). These associations were only observed in girls and exhibited a linear dose-response relationship. CONCLUSIONS: Prenatal BPA, BPF, and BPS exposures were associated with detrimental effects on fetal growth parameters, and stronger effects were noted in female infants.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Compostos Benzidrílicos/toxicidade , Estudos de Coortes , Feminino , Desenvolvimento Fetal , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Masculino , Fenóis , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
17.
Ecotoxicol Environ Saf ; 208: 111694, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396025

RESUMO

Experimental studies have shown that nonradioactive strontium (Sr), in the form of Sr2+, have a positive effect on semen quality, but human evidence is lacking. This study aimed to examine the associations between nonradioactive Sr exposure and semen quality in Chinese men (n = 394). We recruited men who presented at an infertility clinic in Wuhan, China to seek for semen parameter analyses. Urinary Sr concentration as an exposure biomarker was measured using inductively coupled plasma mass spectrometer. We estimated the associations between urinary Sr concentrations and semen parameters using multivariable logistic and linear regression models. In multivariable linear regressions models, positive dose-response associations were estimated for sperm concentration, motility, and count across increasing urinary Sr quartiles (all p for trends<0.05), and the consistent positive associations were also observed for urinary Sr concentration modeled as a continuous exposure. In multivariable logistic models, decreased risks of below-reference sperm concentration, motility, and count were also estimated across increasing urinary Sr quartiles (all p for trends<0.05). Our results suggest that nonradioactive Sr exposure may have a beneficial effect on semen quality, but more investigations are warranted to confirm the results.


Assuntos
Exposição Ambiental/análise , Análise do Sêmen , Estrôncio/urina , Adulto , Biomarcadores/urina , China , Clínicas de Fertilização , Humanos , Masculino , Contagem de Espermatozoides , Motilidade Espermática , Espermatozoides/citologia
18.
Environ Pollut ; 272: 116416, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33433341

RESUMO

Prior human studies have explored effects of phthalate exposures on thyroid function, but the underlying biological mechanisms remain poorly unclear. We aimed to explore the associations between phthalate exposures and thyroid function among a potentially susceptible population such as patients with thyroid nodules, and further to assess the mediating role of oxidative stress. We measured eight phthalate metabolites, three oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in urine and three thyroid function biomarkers [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4)] in serum among 214 patients with thyroid nodules. Multivariate regression models were applied to assess the associations among urinary phthalate metabolites, oxidative stress and thyroid function biomarkers. The potential mediating role of oxidative stress was explored by mediation analysis. We observed that multiple urinary phthalate metabolites were associated with altered FT4 and increased oxidative stress biomarkers (all FDR-adjusted P ≤ 0.05). Meanwhile, we found that 8-isoPGF2α was negatively associated with FT3/FT4 among patients with benign thyroid nodules (FDR-adjusted P = 0.08). The mediation analysis indicated that 8-isoPGF2α mediated the associations of urinary MEHHP and %MEHP with FT3/FT4, with 55.6% and 32.6% proportion of the mediating effects, respectively. Our data suggest that lipid peroxidation may be an intermediate mechanism involved in the effects of certain phthalate exposures on altered thyroid function among patients with benign thyroid nodules.


Assuntos
Ácidos Ftálicos , Nódulo da Glândula Tireoide , Biomarcadores , Humanos , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
19.
Acta Pharmacol Sin ; 42(6): 954-963, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32968210

RESUMO

Diabetic nephropathy (DN) is characterized by sterile inflammation with continuous injury and loss of renal inherent parenchyma cells. Podocyte is an essential early injury target in DN. The injury and loss of podocytes are closely associated with proteinuria, the early symptom of renal injury in DN. However, the exact mechanism for podocyte injury and death in DN remains ambiguous. In this study we investigated whether pyroptosis, a newly discovered cell death pathway was involved in DN. Diabetic mice were generated by high-fat diet/STZ injections. We showed that the expression levels of caspase-11 and cleavage of gasdermin D (GSDMD-N) in podocytes were significantly elevated, accompanied by reduced expression of podocyte makers nephrin and podocin, loss and fusion in podocyte foot processes, increased inflammatory cytokines NF-κB, IL-1ß, and IL-18, macrophage infiltration, glomerular matrix expansion and increased urinary albumin to creatinine ratio (UACR). All these changes in diabetic mice were blunted by knockout of caspase-11 or GSDMD. Cultured human and mouse podocytes were treated with high glucose (30 mM), which significantly increased the expression levels of caspase-11 or caspase-4 (the homolog of caspase-11 in human), GSDMD-N, NF-κB, IL-1ß, and IL-18, and decreased the expression of nephrin and podocin. Either caspase-4 or GSDMD knockdown by siRNA significantly blunted these changes. In summary, our results demonstrate that caspase-11/4 and GSDMD-mediated pyroptosis is activated and involved in podocyte loss under hyperglycemia condition and the development of DN.


Assuntos
Caspases Iniciadoras/metabolismo , Nefropatias Diabéticas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Podócitos/metabolismo , Piroptose/fisiologia , Animais , Caspases Iniciadoras/genética , Células Cultivadas , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Dieta Hiperlipídica , Técnicas de Inativação de Genes , Glucose/farmacologia , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Glomérulos Renais/patologia , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Proteínas de Ligação a Fosfato/genética , Podócitos/efeitos dos fármacos , Estreptozocina
20.
Chemosphere ; 268: 128856, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33189401

RESUMO

Toxicological and epidemiologic evidence has suggested that exposure to disinfection by-products (DBPs) impairs semen quality, while the underlying biological mechanisms remain unclear. This study aimed to examine the mediating role of oxidative stress in association between DBP exposure and semen quality. We measured a urinary biomarker of DBP exposure [trichloroacetic acid (TCAA)] and three urinary biomarkers of oxidative stress [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] among men from an infertility clinic (n = 299). The associations of oxidative stress biomarkers with urinary TCAA and semen quality were evaluated using multivariable linear regression models, and the mediating role of oxidative stress biomarkers was assessed by a mediation analysis. Urinary TCAA was positively associated with urinary 8-OHdG and 8-isoPGF2α in a dose-response manner (both P for trend < 0.001). Significantly inverse dose-response associations were observed between urinary 8-isoPGF2α and sperm concentration and between urinary 8-OHdG and sperm motility (both P for trend < 0.05). The mediation analysis indicated a significant indirect effect of urinary 8-isoPGF2α in the association between urinary TCAA and decreased sperm concentration (P = 0.01). Our results suggest that lipid peroxidation may be an intermediate mechanism by which DBP exposure impairs semen quality.


Assuntos
Clínicas de Fertilização , Análise do Sêmen , Biomarcadores , Desinfecção , Exposição Ambiental/análise , Humanos , Masculino , Análise de Mediação , Estresse Oxidativo , Motilidade Espermática
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...