Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: Exploring associations and mediation effects.

Phenols have been shown to influence the cellular proliferation and function of thyroid in experimental models. However, few human studies have investigated the association between phenol exposure and thyroid cancer, and the underlying mechanisms are also poorly understood. We conducted a case-control study by age- and sex-matching 143 thyroid cancer and 224 controls to investigate the associations between phenol exposures and the risk of thyroid cancer, and further to explore the mediating role of oxidative stress. We found that elevated urinary triclosan (TCS), bisphenol A (BPA) and bisphenol S (BPS) levels were associated with increased risk of thyroid cancer (all P for trends < 0.05), and the adjusted odds ratios (ORs) comparing the extreme exposure groups were 3.52 (95% confidence interval (CI): 2.08, 5.95), 2.06 (95% CI: 1.06, 3.97) and 7.15 (95% CI: 3.12, 16.40), respectively. Positive associations were also observed between urinary TCS, BPA and BPS and three oxidative stress biomarkers measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), as well as between urinary 8-isoPGF2α and HNE-MA and the risk of thyroid cancer. Mediation analysis showed that urinary 8-isoPGF2α mediated 28.95%, 47.06% and 31.08% of the associations between TCS, BPA and BPS exposures and the risk of thyroid cancer, respectively (all P < 0.05). Our results suggest that exposure to TCS, BPA and BPS may be associated with increased risk of thyroid cancer and lipid peroxidation may be an intermediate mechanism. Further studies are warranted to confirm the findings.

Factors associated with psychological distress among patients with breast cancer during the COVID-19 pandemic: a cross-sectional study in Wuhan, China.

PURPOSE: This study aimed to examine the prevalence of psychological distress and the corresponding risk factors among patients with breast cancer affected by the outbreak of coronavirus disease 2019 (COVID-19). METHODS: This cross-sectional, survey-based, region-stratified study was conducted from March 14 to March 21, 2020. An online survey was used to collect the basic characteristics of patients with breast cancer. The degree of depression, anxiety, and insomnia symptoms were assessed using the Patient Health Questionnaire (PHQ-9), the Generalized Anxiety Disorder (GAD-7), and the Insomnia Severity Index (ISI) questionnaires, respectively. Multivariate logistic analysis was performed to identify factors associated with psychological distress outcomes. RESULTS: Among the 834 patients with breast cancer included in the study, the prevalence of depression, anxiety, and insomnia was 21.6%, 15.5%, and 14.7%, respectively. No statistically significant difference in the prevalence of these symptoms was observed between patients in Wuhan and those outside Wuhan. Multivariate logistic regression analyses revealed that comorbidity, living alone, deterioration of breast cancer, and affected treatment plan were risk factors for psychological distress including depression, anxiety, and insomnia. When stratified by location, living alone was associated with depression and insomnia only among patients in Wuhan, but not those outside Wuhan. CONCLUSIONS: This study shows an elevated prevalence of depression, anxiety, and insomnia among patients with breast cancer during part of the COVID-19 pandemic. Patients with comorbidity, living alone, deterioration of breast cancer, and whose treatment plan was affected should be paid more attention to prevent mental disorders.

Urinary biomarker of late pregnancy exposure to drinking water disinfection by-products and ultrasound measures of fetal growth in Wuhan, China.

BACKGROUND: Disinfection by-products (DBPs) have been shown to be reproductive and developmental toxicity. However, few studies examine the effect of prenatal exposure to DBPs on fetal growth via ultrasound measures. OBJECTIVE: To investigate the associations between maternal exposure to DBPs during late pregnancy and ultrasound measures of fetal growth. METHODS: We included 332 pregnant women who presented to a hospital to wait for delivery in Wuhan, China. Ultrasound parameters of fetal growth including femur length (FL), head circumference (HC), abdominal circumference (AC) and biparietal diameter (BPD) were assessed. We measured maternal TCAA concentrations in first morning urine collected from late pregnancy as a biomarker of in utero DBP exposure levels. Multivariable linear regression models were used to examine the associations between maternal urinary TCAA concentrations during late pregnancy and ultrasound parameters of fetal growth. RESULTS: We found that elevated maternal creatinine (Cr)-adjusted urinary TCAA levels had negative associations with BPD, HC and FL in boys but not in girls (P interaction = 0.04, 0.05 and 0.08, respectively). Male fetal BPD, HC and FL had decreases of 0.21 cm (95% CI: -0.35, -0.07; P for trend = 0.003), 0.46 cm (95% CI: -0.81, -0.10; P for trend = 0.01) and 0.17 cm (95% CI: -0.30, -0.04; P for trend = 0.01) for the highest vs. lowest tertile of Cr-adjusted urinary TCAA, respectively. These negative associations persisted for maternal Cr-adjusted urinary TCAA concentrations modeled as continuous variables. CONCLUSION: The results from our study suggest that maternal exposure to TCAA during late pregnancy may have adverse effects on male fetal growth.

Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-ß-induced epithelial-mesenchymal transition and metastasis by controlling TIF1γ in non-small cell lung cancer.

BACKGROUND: TGF-ß promotes tumor invasion and metastasis through inducing epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Circular RNAs (circRNAs) are recognized as functional non-coding RNAs involved in human cancers. However, whether and how circRNAs contribute to TGF-ß-induced EMT and metastasis in NSCLC remain vague. Here, we investigated the regulation and function of Circular RNA hsa_circ_0008305 (circPTK2) in TGF-ß-induced EMT and tumor metastasis, as well as a link between circPTK2 and transcriptional intermediary factor 1 γ (TIF1γ) in NSCLC. METHODS: Circular RNAs were determined by human circRNA Array analysis, real-time quantitative reverse transcriptase PCR and northern blot. Luciferase reporter, RNA-binding protein immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization (FISH) assays were employed to test the interaction between circPTK2 and miR-429/miR-200b-3p. Ectopic overexpression and siRNA-mediated knockdown of circPTK2, TGF-ß-induced EMT, Transwell migration and invasion in vitro, and in vivo experiment of metastasis were used to evaluate the function of circPTK2. Transcription and prognosis analyses were done in public databases. RESULTS: CircPTK2 and TIF1γ were significantly down-regulated in NSCLC cells undergoing EMT induced by TGF-ß. CircPTK2 overexpression augmented TIF1γ expression, inhibited TGF-ß-induced EMT and NSCLC cell invasion, whereas circPTK2 knockdown had the opposite effects. CircPTK2 functions as a sponge of miR-429/miR-200b-3p, and miR-429/miR-200b-3p promote TGF-ß-induced EMT and NSCLC cell invasion by targeting TIF1γ. CircPTK2 overexpression inhibited the invasion-promoting phenotype of endogenous miR-429/miR-200b-3p in NSCLC cells in response to TGF-ß. CircPTK2 overexpression significantly decreased the expression of Snail, an important downstream transcriptional activator of TGF-ß/Smad signaling. In an in vivo experiment of metastasis, circPTK2 overexpression suppressed NSCLC cell metastasis. Moreover, circPTK2 expression was dramatically down-regulated and positively correlated with TIF1γ expression in human NSCLC tissues. Especially, circPTK2 was significantly lower in metastatic NSCLC tissues than non-metastatic counterparts. CONCLUSION: Our findings show that circPTK2 (hsa_circ_0008305) inhibits TGF-ß-induced EMT and metastasis by controlling TIF1γ in NSCLC, revealing a novel mechanism by which circRNA regulates TGF-ß-induced EMT and tumor metastasis, and suggesting that circPTK2 overexpression could provide a therapeutic strategy for advanced NSCLC.

USP3 stabilizes p53 protein through its deubiquitinase activity.

p53 is the guardian of the genome integrity and the degradation of p53 protein is mediated by MDM2. Here we report that USP3 interacts with p53 and regulates p53 stability. Depletion of USP3 lead to accelerated degradation of p53 in normal cells thereby enhanced cell proliferation and transformation. Reconstitution of wildtype USP3, but not the USP3 C168S mutant, restored the stability of p53 protein and inhibited cell proliferation and transformation. These findings suggest that USP3 is an important regulator of p53 and regulates normal cell transformation.

Decreased expression of EZH2 reactivates RASSF2A by reversal of promoter methylation in breast cancer cells.

EZH2, the catalytic subunit of polycomb repressor complex 2, has oncogenic properties, whereas RASSF2A, a Ras association domain family protein, has a tumor suppressor role in many types of human cancer. However, the interrelationship between these two genes remains unclear. Here, we showed that the downregulation of EZH2 reduces CpG island methylation of the RASSF2A promoter, thereby leading to increased RASSF2A expression. Our findings also showed that knockdown of EZH2 increased RASSF2A expression in the human breast cancer cell line MCF-7 in cooperation with DNMT1. This was similar to the effect of 5-Aza-CdR, a DNA methylation inhibitor that reactivates tumor suppressor genes and activated RASSF2A expression in our study. The EZH2 inhibitor DZNep markedly suppressed the proliferation, migration, and invasion of MCF-7 cells treated with ADR and TAM. EZH2 inhibits the expression of tumor suppressor gene RASSF2A via promoter hypermethylation. Thus, it plays an important role in tumorigenesis and is a potential therapeutic target for the treatment of breast cancer.

MiR-142-3p represses TGF-ß-induced growth inhibition through repression of TGFßR1 in non-small cell lung cancer.

TGFßR1 plays an important role in TGF-ß signaling transduction and serves as a tumor suppressor. Our previous studies show that reduced expression of TGFßR1 is common in non-small cell lung cancer (NSCLC) and TGFßR1 variants confer risk of NSCLC. However, the epigenetic mechanisms underlying the role of TGFßR1 in NSCLC carcinogenesis are still elusive. We investigated the function and regulation of TGF-ß signaling-based miRNAs in NSCLC. Computational algorithms predicted that the 3'-untranslated region (3'-UTR) of TGFßR1 is a target of miR-142-3p. Here a luciferase reporter assay confirmed that miR-142-3p can directly bind to 3'-UTR of TGFßR1. Overexpression of miR-142-3p in NSCLC A549 cells suppressed expression of TGFßR1 mRNA and protein, while knockdown of endogenous miR-142-3p led to increased expression of TGFßR1. On TGF-ß1 stimulation, stable overexpression of miR-142-3p attenuated phosphorylation of SMAD3, an indispensable downstream effector in canonical TGF-ß/Smad signaling, via repression of TGFßR1 in A549 cells. Furthermore, miR-142-3p-mediated down-regulation of TGFßR1 weakened TGF-ß-induced growth inhibition effect, and this effect was reversed by stable knockdown of endogenous miR-142-3p in A549 cells. In NSCLC tissues, miR-142-3p expression was increased and inversely correlated with TGFßR1 expression. These data demonstrate that miR-142-3p influences the proliferation of NSCLC cells through repression of TGFßR1.

One pot, two phases: individual orthorhombic and face-centered cubic ZnSnO3 obtained synchronously in one solution.

Many modern technologies rely on the functional materials that are subject to their phase purity. The topic of obtaining pure crystals from the concomitant allotropes is ever before the eyes of numerous researchers. Here we adopt a template-inducing route and obtain the isolated allotropes located in the appointed regions in the same reaction system. As a typical example, well-defined individual face-centered cubic and orthorhombic ZnSnO3 crystals were successfully synthesized assisted by a ZnO inducing template or without it in an identical solution, respectively. And the different growing mechanisms of the ZnSnO3 allotropes were also proposed, which takes a pivotal step toward the realization of allotropes dividing. Moreover, the two individual pure-phased ZnSnO3 allotropes obtained in one reaction system exhibit porous microspherical morphologies constructed by the tiny nanograins, resulting in their high sensitivities to ethanol with fast response and recovery and good selectivity and stability.

Effects of Notch-1 down-regulation on malignant behaviors of breast cancer stem cells.

This study examined the effect of Notch-1 signaling on malignant behaviors of breast cancer cells by regulating breast cancer stem cells (BCSCs). BCSCs were enriched by using serum-free medium and knocked out of Notch-1 by using a lentiviral vector. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to detect the Notch-1 expression levels in breast cancer cell lines and BCSCs, and flow cytometry to detect the proportion of BCSCs in BCSC spheres. The BCSC self-renewal, migration, invasion, and tumorigenicity were examined by the tumor microsphere-forming assay and transwell assay and after xenotransplantation. The results showed that the Notch-1 silencing reduced the number of BCSC spheres, the proportion of BCSCs, and the number of cells penetrating through the transwell membrane. It also decreased the size of tumors that were implanted in the nude mice. These results suggest that Notch-1 signaling is intimately linked to the behaviors of BCSCs. Blocking Notch-1 signaling can inhibit the malignant behaviors of BCSCs, which may provide a promising therapeutical approach for breast cancer.

Th17 cell plays a role in the pathogenesis of Hashimoto's thyroiditis in patients.

Hashimoto's thyroiditis (HT) has long been epidemiologically associated with excess iodine levels. However, the underlying immunological mechanisms still remain largely unexplored. Th17 cells are commonly recognized as playing vital roles in various autoimmune diseases. Here we show that intra-thyroid infiltrating Th17 cells and serum IL-17 levels were significantly increased in HT patients. However, the concentration of serum IL-17 was inversely correlated with patients' residual thyroid function while the heterogeneously expressed thyroid IL-17 was directly correlated with local fibrosis. Administration of moderate high levels of iodine was found to facilitate the polarization of murine splenic naïve T cells into Th17 cells, whereas extreme high levels of iodine favored Th1 polarization and inhibited Treg development. These findings suggest that both Th1 and Th17 cells may be involved in the pathogenesis of HT and high levels of iodine may play a critical role in this process by modulating T cell differentiation.

Clinicopathological features of breast cancer with different molecular subtypes in Chinese women.

A retrospective study was performed to explore the relationship between molecular subtypes and clinicopathological features of breast cancer in Chinese women. Six hundred and twenty-eight Chinese women with breast cancer were classified into four molecular subtypes according to their estrogen receptor (ER), progesterone receptor (PR) and Her-2 status. The prevalence rate of each molecular subtype was analyzed. Relationship between the subtypes and clinicopathologic features was determined. The distribution of molecular subtypes was as follows: luminal A 46.5%, luminal B 17.0%, basal 21.5%, HER2/neu 15.0%. The subtypes had no significant difference under different menopausal status. However, in the age-specific groups, the age group of ≤35 years was more likely to get basal cell-like cancer (36.9%). Statistically significant differences were found among molecular subtypes by age, nuclear grade, tumor size, lymph node (LN) metastasis, tumor stage by American Joint Committee on Cancer (AJCC), radiotherapy but not by chemotherapy, types of surgery. After adjusting for several relative confounding factors, the basal subtype more likely had lower nodal involvement in both the incidence of LN metastasis (≥1 positive LN) and incidence of high-volume LN metastasis (≥4 positive LN). The HER2/neu subtype had higher nodal involvement in the incidence of high-volume LN metastases. After adjusting for relative confounding factors, the HER2/neu subtype more likely had higher AJCC tumor stages. It was suggested that there existed close relationship between molecular subtypes and clinicopathological features of breast cancer. In addition, the breast cancer subtypes have been proven to be an independent predictor of LN involvement and AJCC tumor stage. These findings are very important for understanding the occurrence, development, prognosis and treatment of breast cancer in Chinese population.

Corrigendum: Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry.

[This corrects the article DOI: 10.3389/fendo.2022.1018608.].

Oxidative stress mediates the associations between phthalate exposures and thyroid cancer/benign nodule risk.

Epidemiological studies have suggested that phthalate exposures are associated with increased risks of thyroid cancer and benign nodule, while the underlying mechanisms are largely unknown. Here, we explored the mediation effects of oxidative stress (OS) biomarkers in the associations between phthalate exposures and the risks of thyroid cancer and benign nodule. Urine samples collected from 143 thyroid cancer, 136 nodule patients, and 141 healthy controls were analyzed for 8 phthalate metabolites and 3 OS biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), and 8-iso-prostaglandin F2α (8-isoPGF2α)]. Multivariable linear or logistic regression models were used to explore the associations of OS biomarkers with phthalate metabolite concentrations and the risks of thyroid cancer and nodule. The mediation role of OS biomarkers was also investigated. Urinary monoethyl phthalate (MEP), monomethyl phthalate (MMP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), mono (2-ethylhexyl) phthalate (MEHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) were positively associated with at least 2 OS biomarkers (all P-values<0.01), and part of these positive associations varied in different subgroups. All 3 OS biomarkers were positively associated with the risks of thyroid nodule and cancer (P-values<0.001). The mediation analysis showed that OS biomarkers significantly mediated the associations between urinary MEHOP concentration and nodule, as well as between urinary MMP, MEHP, and MEHHP concentrations and cancer and nodule, with the estimated proportions of mediation ranging from 15.8% to 85.6%. Our results suggest that OS is a potential mediating mechanism through which phthalate exposures induce thyroid carcinogenesis and nodular formation.

One-pot hydrothermal synthesis of heterostructured ZnO/ZnS nanorod arrays with high ethanol-sensing properties.

ZnO/ZnS heterostructured nanorod arrays with uniform diameter and length were synthesized from zinc substrates in a one-pot procedure by using a simple hydrothermal method. Structural characterization by HRTEM indicated that the heterostructured nanorods were composed of parallel segments of wurtzite-type ZnO and zinc-blende ZnS, with a distinct interface along the axial direction, which revealed the epitaxial relationship, ZnO (1010) and ZnS (111). The as-prepared ZnO/ZnS nanorods showed only two green emissions at around 523 nm and 576 nm. We also found that the nanorods exhibited high sensitivity to ethanol at relatively low temperatures, owing to their smaller size and structure.

Stalled replication fork protection limits cGAS-STING and P-body-dependent innate immune signalling.

Protection of stalled replication forks is crucial for cells to respond to replication stress and maintain genome stability. Genome instability and replication stress have been linked to immune activation. Here we show that Abro1 and FANCD2 protect replication forks, which is linked with the restriction of innate immune responses. We reveal that stalled replication fork degradation induced by Abro1 or FANCD2 deficiency leads to accumulation of cytosolic single-stranded DNA and activation of a cGAS-STING-dependent innate immune response that is dependent on DNA2 nuclease. We further show that the increased cytosolic single-stranded DNA contains ribosomal DNA that can bind to cGAS. In addition, Abro1 and FANCD2 limit the formation of replication stress-induced P-bodies, and P-bodies are capable of modulating activation of the innate immune response after prolonged replication stress. Our study demonstrates a connection between replication stress and activation of the innate immune response that may be targeted for therapeutic purpose.

Depiction of immune heterogeneity of peripheral blood from patients with type II diabetic nephropathy based on mass cytometry.

Diabetic nephropathy (DN) is the most prominent cause of chronic kidney disease and end-stage renal failure. However, the pathophysiology of DN, especially the risk factors for early onset remains elusive. Increasing evidence has revealed the role of the innate immune system in developing DN, but relatively little is known about early immunological change that proceeds from overt DN. Herein, this work aims to investigate the immune-driven pathogenesis of DN using mass cytometry (CyTOF). The peripheral blood mononuclear lymphocytes (PBMC) from 6 patients with early-stage nephropathy and 7 type II diabetes patients without nephropathy were employed in the CyTOF test. A panel that contains 38 lineage markers was designed to monitor immune protein levels in PBMC. The unsupervised clustering analysis was performed to profile the proportion of individual cells. t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the differences in DN patients' immune phenotypes. Comprehensive immune profiling revealed substantial immune system alterations in the early onset of DN, including the significant decline of B cells and the marked increase of monocytes. The level of CXCR3 was dramatically reduced in the different immune cellular subsets. The CyTOF data classified the fine-grained differential immune cell subsets in the early stage of DN. Innovatively, we identified several significant changed T cells, B cell, and monocyte subgroups in the early-stage DN associated with several potential biomarkers for developing DN, such as CTLA-4, CXCR3, PD-1, CD39, CCR4, and HLA-DR. Correlation analysis further demonstrated the robust relationship between above immune cell biomarkers and clinical parameters in the DN patients. Therefore, we provided a convincible view of understanding the immune-driven early pathogenesis of DN. Our findings exhibited that patients with DN are more susceptible to immune system disorders. The classification of fine-grained immune cell subsets in this present research might provide novel targets for the immunotherapy of DN.

Critical role of lncEPAT in coupling dysregulated EGFR pathway and histone H2A deubiquitination during glioblastoma tumorigenesis.

Histone 2A (H2A) monoubiquitination is a fundamental epigenetics mechanism of gene expression, which plays a critical role in regulating cell fate. However, it is unknown if H2A ubiquitination is involved in EGFR-driven tumorigenesis. In the current study, we have characterized a previously unidentified oncogenic lncRNA (lncEPAT) that mediates the integration of the dysregulated EGFR pathway with H2A deubiquitination in tumorigenesis. LncEPAT was induced by the EGFR pathway, and high-level lncEPAT expression positively correlated with the glioma grade and predicted poor survival of glioma patients. Mass spectrometry analyses revealed that lncEPAT specifically interacted with deubiquitinase USP16. LncEPAT inhibited USP16's recruitment to chromatin, thereby blocking USP16-mediated H2A deubiquitination and repressing target gene expression, including CDKN1A and CLUSTERIN. Depletion of lncEPAT promoted USP16-induced cell cycle arrest and cellular senescence, and then repressed GBM cell tumorigenesis. Thus, the EGFR-lncEPAT-ubH2A coupling represents a previously unidentified mechanism for epigenetic gene regulation and senescence resistance during GBM tumorigenesis.

[Corrigendum] Ski prevents TGF­ß­induced EMT and cell invasion by repressing SMAD­dependent signaling in non­small cell lung cancer.

Following the publication of the above paper, an interested reader drew to our attention apparent anomalies associated with Figs. 2, 3 and 4; essentially, these three figures contained panels exhibiting overlapping data, such that data purportedly relating to different experiments were apparently drawn from the same original sources. [Specifically, the Ski, +TGF­ß1 data panel in Fig. 2B, the Mock, +TGF­ß1 data panel in Fig. 3A, and the +TGF­ß1, +SIS3 data panel in Fig. 4B in the original figures were chosen incorrectly.] Upon investigating this matter with the authors, the authors have realized that they made errors in the compilation of the affected figures. The errors were made inadvertently, and the authors have been able to identify the correct data for each of the figures concerned. The corrected versions of these figures are shown opposite and on the next page. Note that these errors did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, the authors apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 34: 87-94, 2015; DOI: 10.3892/or.2015.3961].

Urinary phthalate metabolite concentrations, oxidative stress and thyroid function biomarkers among patients with thyroid nodules.

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.

Urinary biomarkers of phthalates exposure and risks of thyroid cancer and benign nodule.

Phthalates have been reported to affect the function and growth of thyroid. However, there is little data on the effect of phthalates on thyroid oncogenesis. Here we explored the associations between phthalates exposure and the risks of thyroid cancer and benign nodule. We sex-matched 144 thyroid cancer, 138 benign nodule patients and 144 healthy adults from Wuhan, China. Eight phthalate metabolites in spot urine samples were quantified using high-performance liquid chromatography and tandem mass spectrometry. The associations of creatinine-corrected urinary phthalate metabolites with the risks of thyroid cancer and benign nodule were assessed using multivariable logistic regression models. We found that urinary monomethyl phthalate (MMP), mono(2-ethyl-5hydroxyhexyl) phthalate (MEHHP) and mono(2-ethylhexyl) phthalate (MEHP) associated with increased risks of thyroid cancer and nodule, with adjusted odds ratios (ORs) ranging from 1.74 to 4.78 comparing the extreme tertiles, and urinary monobutyl phthalate (MBP) was associated with decreased risks of thyroid cancer and benign nodule (all P for trends < 0.05). Male-specific positive associations of urinary monoethyl phthalate (MEP) with thyroid cancer and nodule as well as urinary mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) with thyroid cancer were also observed. Our results suggest that exposure to certain phthalates may contribute to increased risks of thyroid cancer and benign nodule.