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BACKGROUND: The inconsistent relationship between chemical exposure and estimated glomerular filtration rate (eGFR) has been examined in only a few studies. We investigated the association between paraben exposure and indicators of renal function in a total of 361 individuals recruiting from a representative study. METHOD: The levels of urinary parabens, including methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP), were measured using UPLC-MS/MS. The association between paraben exposure and indices of renal function was assessed using multiple logistic regression and Bayesian Kernel Machine Regression (BKMR). RESULTS: The median levels of urinary parabens in the adult group were significantly higher than those in the minor group, that is, 397 vs. 148â¯ng/mL for MeP, 38.8 vs. 13.6â¯ng/mL for EtP, 117 vs. 57.7â¯ng/mL for PrP, and 6.61 vs. 2.79â¯ng/mL for BuP (all P < 0.001). In the adult group, multivariate regression models confirmed a positive association between the albumin-to-creatinine ratio and urinary MeP (ß = 0.580) and a positive association of BUN (ß = 0.061) and a negative association of eGFR (ß = -0.051) with urinary EtP (all P < 0.001). In the adult group, compared with the lowest tertile group, the adjusted odds ratio in the third tertile (T3) of urinary EtP levels indicated a 3.08 times increased risk of eGFR abnormalities, followed by the second tertile (T2) with a 2.63 times increased risk. The generalized additive model (GAM) and BKMR models showed a non-linear correlation between urinary EtP levels and early CKD, as well as reduced eGFR. We observed a significant positive cumulative effect of urinary paraben on eGFR, and a significant positive single exposure effect of urinary EtP with eGFR abnormality. CONCLUSION: We found a significant association between exposure to EtP and an increased risk of high BUN levels and decreased eGFR.
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Introduction: Ever since the use of bisphenol A (BPA) has been restricted, concerns have been raised regarding the use of its substitutes, such as bisphenol S (BPS) and bisphenol F (BPF). Meanwhile, the EU European Food Safety Authority (EFSA) issued the new tolerable daily intake (TDI) after the latest re-risk assessment for BPA, which enforced the need for cumulative risk assessment in the population. This study was conducted to identify BPA and its substitute's exposure characteristics of the general Taiwanese population and estimate the cumulative risk of bisphenol exposure. Methods: Urine samples (N = 366 [adult, 271; minor, 95]) were collected from individuals who participated in the Taiwan Environmental Survey for Toxicants 2013. The samples were analyzed for BPA, BPS, and BPF through ultraperformance liquid chromatography-tandem mass spectrometry. Daily intake (DI) levels were calculated for each bisphenol. Hazard quotients (HQs) were calculated with the consideration of tolerable DI and a reference dose. Additionally, hazard index (HI; sum of HQs for each bisphenol) values were calculated. Results: Our study found that the median level of BPA was significantly higher in adults (9.63 µg/g creatinine) than in minors (6.63 µg/g creatinine) (p < 0.001). The DI of BPS was higher in female (0.69 ng/kg/day) than in male (0.49 ng/kg/day); however, the DIs of BPF and BPS were higher in boys (1.15 and 0.26 ng/kg/day, respectively) than in girls (0.57 and 0.20 ng/kg/day, respectively). Most HI values exceeded 1 (99% of the participants) after EFSA re-establish the TDI of BPA. Discussion: Our study revealed that the exposure profiles and risk of BPA and its substitute in Taiwanese varied by age and sex. Additionally, the exposure risk of BPA was deemed unacceptable in Taiwan according to new EFSA regulations, and food contamination could be the possible source of exposure. We suggest that the risk of exposure to BPA and its substitutes in most human biomonitoring studies should be reassessed based on new scientific evidence.
Subject(s)
Benzhydryl Compounds , Environmental Exposure , Phenols , Sulfones , Humans , Phenols/urine , Phenols/analysis , Phenols/toxicity , Benzhydryl Compounds/urine , Benzhydryl Compounds/toxicity , Female , Male , Taiwan , Adult , Risk Assessment , Environmental Exposure/analysis , Environmental Exposure/statistics & numerical data , Child , Middle Aged , Adolescent , Sulfones/analysis , Young Adult , Aged , Child, Preschool , Tandem Mass Spectrometry , Environmental Monitoring , Surveys and Questionnaires , Environmental Pollutants/analysisABSTRACT
Background/purpose: Vertical root fracture (VRF) is a prevalent reason for tooth extraction following root canal treatment and even after crown placement. Predicting fractures is challenging due to multifactorial nature. The current study aimed to predict the likelihood of fracture following root canal treatment and crown placement by developing a deep learning (DL) model. Materials and methods: DL techniques were employed to analyze a dataset comprising 145 clinical cases consisting of 97 fractured teeth and 48 non-fractured teeth. This dataset spanned a five-year period and encompassed cases involving root canal therapy and crown installation. The analysis identified several root fracture-related parameters, which were incorporated into the DL system. The dataset consisted of 17 features presented in a mixed-type tabular format. Results: The deep neural network (DNN) model surpassed the support vector machine (SVM) model with a higher accuracy (80.7 % vs. 71.7 %) and F1-score value (0.857 vs. 0.817) for predicting root fracture. Furthermore, in determining root fracture occurrence, it was observed that 17 significant characteristics in the DNN model outperformed the 7 features by 11.7 % in accuracy and 10 % in F1-score. Conclusion: DL shows promise in predicting root fracture post root canal therapy and prosthesis, and it may have the potential to aid clinicians in assessing fracture risk and improving decision-making.
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Several studies have suggested that some endocrine disruptors such as synthetic phenols, parabens and phthalates may disrupt thyroid hormone signaling and associated negative feed-backs with the central hypothalamic-pituitary-thyroid (HPT) axis. Therefore, we investigated urinary paraben and blood thyroid hormone levels in the Taiwanese population. Our sample comprised 264 adults (aged 18-97 years) and 75 minors (aged 7-17 years) from Taiwan Environmental Survey for Toxicants 2013. Urinary levels of methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and butylparaben (BuP) were assessed. Hormones of particular interest include: thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4). We sought integrated parameters to describe the transfer of thyroid hormones in homeostatic models. The geometric mean urinary paraben levels of the adults were higher than those of the minors (adults vs. minors; MeP: 383 vs. 62.4 ng/mL; PrP: 109 vs. 8.00 ng/mL; EtP: 39.5 vs. 2.38 ng/mL, and BuP: 6.36 vs. 2.13 ng/mL). In the male adults, we discovered that 0.253% (p = 0.032), 0.256% (p = 0.041) and 0.257% (p = 0.037) decreases in the TSH, TSH/T4 and TSH/FreeT4 ratio was associated with 1% EtP increases, respectively. In the female minors, 0.093% (p = 0.044), 0.072% (p = 0.047) and 0.156 (p = 0.004) increases in the TSH ratios were associated with a 1% MeP, EtP and BuP increase, respectively. Moreover, 0.151% (p = 0.008) and 0.177% (p = 0.001) increases in TSH/T4 and TSH/free T4 ratios were associated with a BuP 1% increase, respectively. Finally, EtP was positively associated with SPINA-GT (ß: 15.66, p = 0.036) in the male adults. By contrast, EtP were positively associated with Jostel's TSH index and sTSHI (ß: 0.072, p = 0.049; ß: 0.107, p = 0.049) in the female minors. The Taiwanese population is commonly exposed to parabens, which can potentially lead to alteration of thyroid hormone homeostasis.
Subject(s)
Parabens , Thyroid Gland , Male , Humans , Female , Thyroid Gland/chemistry , Parabens/analysis , Taiwan , Thyroid Hormones , Thyrotropin , Hazardous Substances , Homeostasis , Environmental Exposure/analysisABSTRACT
BACKGROUND: B cells are essential for providing humoral protection against acute influenza A virus (IAV) infection. FcγRIIB, a regulator of antibody (Ab) production, influences immune responses during pathogen infections, but its specific impact on humoral protection and B cell-mediated responses against IAV remains unclear. METHODS: To investigate FcγRIIB's role in host defense and B cell function during acute IAV infection, we generated mice with systemic FcγRIIB deficiency, functional impairment, and B cell-specific FcγRIIB deletion. We infected these mice with PR8 (H1N1) or Hkx31 (H3N2) IAVs and evaluated body weight preservation, survival rates, Ab production, viral neutralization, Ab affinity maturation, and germinal center B cell development. RESULTS: Mice lacking FcγRIIB or with impaired function showed improved protection, preserved body weight, and increased survival rates during IAV infection. Notably, mice with haploinsufficient FcγRIIB function displayed protective effects. Selective deficiency of FcγRIIB in B cells led to enhanced Ab production, resulting in elevated IAV-specific Abs in the serum with superior viral neutralizing potency. However, the impact on the affinity maturation index of virus-specific Abs was modest. Accordingly, FcγRIIB-deficient B cells maintained normal germinal center B cell development during IAV infection, whereas wild-type mice exhibited delayed differentiation. CONCLUSION: Our research underscores the pivotal role of FcγRIIB in host defense and B cell-mediated immunity during acute IAV infection. Additionally, our discoveries hold implications for antiviral treatments, particularly during the initial stages of IAV infection, aimed at enhancing the host's humoral immune response.
Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A virus , Influenza, Human , Orthomyxoviridae Infections , Animals , Humans , Mice , Body Weight , Germinal Center , Influenza A Virus, H3N2 SubtypeABSTRACT
School-age children living near large petrochemical factories may be at high risk of exposure to benzene released during manufacturing processes. We aimed to investigate the urinary concentrations of trans, trans-muconic acid (t,t-MA) in school-age children living near a petrochemical complex and to estimate their cumulative risk of benzene exposure. We examined an established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-age children (aged 6-13 years) who lived near large petrochemical factories in central Taiwan between October 2013 and September 2014. The cohort comprised 297 children from five elementary schools, namely S.-C. Branch (n = 63, school A, ~0.9 km), F.-A. (n = 51, school B, ~2.7 km), C.-T. (n = 63, school C, ~5.5 km), M.-L. (n = 54, school D, ~6.9 km), and L.-F. (n = 66, school E, ~8.6 km). We analyzed the urinary t,t-MA levels of each participant and estimated their daily intake of benzene. We also performed multiple regression analysis to investigate potential risk factors for a high urinary t,t-MA level in the study cohort. The median urinary t,t-MA levels and median estimated benzene daily intake of the children from each school were as follows: school A, 64.07 ng/mL, 11.13 µg/kg/day; school B, 61.01 ng/mL, 15.32 µg/kg/day; school C, 59.38 ng/mL, 14.81 µg/kg/day; school D, 42.35 ng/mL, 11.67 µg/kg/day; school E, undetected, 0.14 µg/kg/day. The distance between a school and a petrochemical complex (greater distance: ß = -0.26, 95% confidence interval [CI] = -0.52 to 0.00, p = 0.053), and the age of the children (older age: ß = -3.44, 95% CI = -5.90 to -1.46, p < 0.001) were identified as potential risk factors. After confounders were adjusted for, the creatinine adjusted urinary t,t-MA levels of the school-age children tended to be lower when the distance between their school and a petrochemical complex was greater.
Subject(s)
Benzene , Humans , Child , Taiwan/epidemiology , Risk Assessment , Risk FactorsABSTRACT
Human biomonitoring (HBM) provides information to identify chemicals that need to be assessed regarding potential health risks to human populations. We established a population-representative sample in Taiwan, namely the Taiwan Environmental Survey for Toxicants (TESTs) in 2013-2016. In total, 1871 participants (aged 7-97 years) were recruited from throughout Taiwan. A questionnaire survey was applied to obtain individuals' demographic characteristics, and urine samples were obtained to assess metal concentrations. Inductively coupled plasma-mass spectrometry was used to determine concentrations of urinary As (total), Cd, Co, Cr, Cu, Fe, Ga, In, Mn, Ni, Pb, Se, Sr, Tl, and Zn. The purpose of this study was to establish the human urinary reference levels (RVs) for metals in the general population of Taiwan. We found that median concentrations of urinary Cu, Fe, Pb, and Zn in males were statistically significant (p < 0.05) higher than in females (Cu: 11.48 vs. 10.00 µg/L; Fe: 11.48 vs. 10.46 µg/L; Pb: 0.87 vs. 0.76 µg/L; and Zn: 448.93 vs. 348.35 µg/L). On the contrary, Cd and Co were significantly lower in males than in females (Cd: 0.61 vs. 0.64 µg/L; and Co: 0.27 vs. 0.40 µg/L). Urinary Cd levels in the ≥18-year-old group (0.69 µg/L) were significantly higher than those in the 7-17-year-old group (0.49 µg/L, p < 0.001). Among the investigated metals, most were significantly higher in the 7-17-year-old group than in the ≥18-year-old group, except for Cd, Ga, and Pb. Participants who lived in central Taiwan had higher median levels of urinary Cd, Cu, Ga, Ni, and Zn than those in other regions. Median levels of urinary As, Cd, Pb, and Se were significantly higher in participants who lived in harbor (94.12 µg/L), suburban (0.68 µg/L), industrial (0.92 µg/L), and rural (50.29 µg/L) areas, respectively, than the others who lived in other areas. RV95 percentiles of urinary metals (ng/mL) for 7-17/≥18-year-old groups were As (346.9/370.0), Cd (1.41/2.21), Co (2.30/1.73), Cr (0.88/0.88), Cu (28.02/22.78), Fe (42.27/42.36), Ga (0.13/0.12), In (0.05/0.04), Mn (3.83/2.91), Ni (8.09/6.17), Pb (8.09/5.75), Se (122.4/101.9), Sr (556.5/451.3), Tl (0.57/0.49), and Zn (1314.6/1058.8). In this study, we have highlighted the importance of As, Cd, Pb, and Mn exposure in the general population of Taiwan. The established RV95 of urinary metals in Taiwanese would be fundamental information to promote the reduction of metal exposure or policy intervention. We concluded that urinary levels of exposure to certain metals in the general Taiwanese population varied by sex, age, region, and urbanization level. References of metal exposure in Taiwan were established in the current study.
Subject(s)
Cadmium , Metals, Heavy , Male , Female , Humans , Adolescent , Child , Cadmium/urine , Biological Monitoring , Taiwan , Lead/analysis , Reference Values , Environmental Monitoring/methods , Hazardous Substances , Surveys and Questionnaires , Metals, Heavy/analysisABSTRACT
BACKGROUND: School-aged children living near plastics-producing factories may have higher risk of exposure to phthalates released during the manufacturing processes. OBJECTIVES: We aimed to investigate the urinary concentrations of phthalate metabolites in school-aged children living near a petrochemical complex and estimate the cumulative risk of phthalate exposure. METHODS: We used a well-established cohort (Taiwan Petrochemical Complex Cohort for Children, TPE3C) of school-aged children (6-13 years old) living near polyvinyl chloride (PVC) and vinyl chloride monomer (VCM) factories in central Taiwan from October 2013 to September 2014. A total of 257 children were included from five elementary schools: Syu-Cuo Branch (n = 58, school A, ~0.9 km), Feng-An (n = 40, school B, ~2.7 km), Ciao-Tou (n = 58, school C, ~5.5 km), Mai-Liao (n = 37, school D, ~6.9 km), and Lung-Feng (n = 57, school E, ~8.6 km). We analyzed 11 metabolites of seven phthalates (including di-2-ethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP)) in urine. Daily intakes (DIs) were compared with acceptable intake levels to calculate the hazard quotient (HQ) for individual phthalates, and the cumulative risk for each child was assessed using a hazard index (HI), which was the sum of the the individual HQs. RESULTS: The geometric mean and proportion of participants with HIs exceeding one for hepatic (HIhep) and reproductive (HIrep) effects were 0.33 (13.2%) and 0.24 (7.8%), respectively. The major contributors to phthalate exposure risk were DEHP, di-iso-butyl phthalate (DiBP) and DnBP in all children. Moreover, we observed a U shaped distribution of DEHP exposure by school distance from the PVC and VCM factories (school A: 7.48 µg/kg/day and school E: 80.44 µg/kg/day). This may be due to emissions (closest) and and being located downwind of PVC scrap incineration (farthest). CONCLUSIONS: Our findings suggest that children living near a petrochemical complex were at a greater risk of phthalate exposure than normal school-aged children and that phthalate exposure was mainly attributed to DEHP, DiBP and DnBP. In addition, inhalation may have been a risk factor for people living near to PVC and VCM factories.
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OBJECTIVE: Oxidative stress biomarkers (OSBs) may be strongly associated with disease progression and recurrent pregnancy loss (RPL). However, the research on associations of most OSBs (e.g., 8-nitroguanine [8-NO2Gua] and 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA]) with RPL is limited. Therefore, we aimed to investigate the effect of OSBs exposure on RPL risk by performing a case-control study. MATERIAL AND METHODS: We use our established dataset, Taiwan Recurrent Pregnancy Loss and Environmental Study (TREPLES), which included 514 Taiwanese reproductive age women (aged 20-50 years; 397 cases and 117 controls) from National Cheng Kung University Hospital. RPL is clinically defined by a history of two or more consecutive miscarriages, where a miscarriage is defined as the termination of pregnancy before 20 weeks of gestation. The urinary levels of several OSBs (e.g., 8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-NO2Gua, 8-isoprostaglandin F2α [8-isoPGF2α], and HNE-MA) and malondialdehyde (MDA) were measured using isotope dilution liquid chromatography-tandem mass spectrometry and thiobarbituric acid reactive substances, respectively. RESULTS: The median levels of 8-NO2Gua (6.15 vs. 3.76 ng/mL) and HNE-MA (30.12 and 21.54 ng/mL) were significantly higher in the RPL group than in the control group. By categorizing the OSBs data into tertiles, after we adjusted for age and urine creatinine levels discovered that the RPL risk associated with 8-NO2Gua and HNE-MA levels in the third tertile were approximately 2 times higher than those in the first tertile (8-NO2Gua, adjusted OR = 3.27, 95 % CI = 1.66-6.43; HNE-MA, adjusted OR = 1.96, 95 % CI = 1.05-3.64; p < 0.05). These findings suggest that the oxidative stress biomarkers of 8-NO2Gua and HNE-MA are risk factors for RPL. CONCLUSION: Our findings indicate that specific OSBs are associated with an increased RPL risk, suggesting that reducing OSB levels can improve RPL risk. Nevertheless, more studies on preventive medicine are required to understand the exposure sources and adverse outcome pathways of OSBs associated with RPL.
Subject(s)
Abortion, Habitual , Biomarkers , Guanine/analogs & derivatives , Nitrosative Stress , Oxidative Stress , Humans , Female , Adult , Abortion, Habitual/metabolism , Abortion, Habitual/etiology , Pregnancy , Biomarkers/urine , Taiwan , Case-Control Studies , Middle Aged , Young Adult , Risk Factors , Guanine/urine , Guanine/metabolism , Aldehydes/metabolism , Aldehydes/urine , 8-Hydroxy-2'-Deoxyguanosine/urineABSTRACT
Childhood asthma has become one of the most common chronic diseases in children and adolescents. However, few case-control studies investigating the relationship between phthalate exposure and asthma in children and adolescents have been conducted, especially in Asia. Therefore, we assessed the potential associations between phthalate exposure and asthma among children and adolescents in Taiwan. Because various demographic and environmental variables may influence the incidence and prognosis of asthma, we performed a case-control study with propensity score matching. Out of 615 Childhood Environment and Allergic Diseases Study participants, we conditionally matched 41 children with clinically diagnosed asthma with 111 controls. We then analyzed 11 phthalate metabolites by using liquid chromatography with tandem mass spectrometry. Compared with the control group, the median urinary phthalate levels for most phthalate metabolites in the case group were slightly increased, including monomethyl phthalate, mono-n-butyl phthalate, monobenzyl phthalate, monoethylhexyl phthalate, mono-(2-ethyl-5-hydroxyhexyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethyl-5-carboxypentyl) phthalate, and mono-(2-carboxymethylhexyl) phthalate. Hence, our results suggest that phthalate exposure may be associated with the development of asthma. In addition, prenatal environmental factors, such as active or passive smoking during pregnancy, may increase the risk of asthma.
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Parabens, a group of endocrine disrupting chemicals (EDCs), are well known preservatives in pharmaceuticals and personal care products (PPCPs). However, studies on parabens exposure and their cumulative effects in Asian population are limited. This study aimed to identify the exposure characteristics and estimate the cumulative risk of four parabens in the general Taiwanese. We have collected urine samples including 271 adults (18-97 yrs old) and 95 minors (7-17 yrs old), from Taiwan Environmental Survey for Toxicants 2013, and analyzed for four urinary parabens including methyl (MeP)-, ethyl (EtP)-, propyl (PrP)-, and butylparaben (BuP) by using ultraperformance liquid chromatography-tandem mass spectrometry. The health-based guidance value (HBGV) and the antiandrogenic properties of parabens were used to calculate the hazard index (HI) for cumulative risk. MeP and PrP were most abundant compounds and startlingly higher than those in other countries. Adults had a higher geometric mean level of four parabens than minors (adults: MeP, 381.7; PrP, 108.6; EtP, 39.6 and BuP 6.3 ng/mL; minors: MeP, 65.7; PrP, 7.9, EtP, 2.6 and BuP 2.2 ng/mL). Participants who used a higher number of personal care products had a significantly higher risk with higher concentrations of PrP (above 75th %tile) [adjusted odds ratio (aOR): 1.79, 95 % CI: 1.01-3.15] and BuP [aOR: 1.78, 95 % CI: 1.03-3.07]. The median and 95th %tile HI (the sum of the HQs of each paraben) was as 1.10 and 4.39-fold higher than acceptable cumulative threshold (HI <1) and PrP accounted for 90 % of the HI. Our results indicate omnipresent exposure to parabens among the Taiwanese population, which might cause certain level of concerns. These significant increasing trends of HI with age dependence were observed, which mainly driven by PPCPS used. Routine survey of parabens in PPCPs and continued biomonitoring needs to be urgently addressed.
Subject(s)
Cosmetics , Endocrine Disruptors , Adult , Cosmetics/analysis , Endocrine Disruptors/urine , Environmental Exposure , Humans , Parabens/analysis , Preservatives, Pharmaceutical , Risk AssessmentABSTRACT
Whether low-dose phthalate exposure triggers asthma among children, and its underlying mechanisms, remain debatable. Here, we evaluated the individual and mixed effects of low-dose phthalate exposure on children with asthma and five (oxidative/nitrosative stress/lipid peroxidation) mechanistic biomarkers-8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), 8-isoprostaglandin F2α (8-isoPF2α), and malondialdehyde (MDA)-using a propensity score-matched case-control study (case vs. control = 41 vs. 111). The median monobenzyl phthalate (MBzP) concentrations in the case group were significantly higher than those in the control group (3.94 vs. 2.52 ng/mL, p = 0.02), indicating that dust could be an important source. After adjustment for confounders, the associations of high monomethyl phthalate (MMP) (75th percentile) with 8-NO2Gua (adjusted odds ratio (aOR): 2.66, 95% confidence interval (CI): 1.03-6.92) and 8-isoPF2α (aOR: 4.04, 95% CI: 1.51-10.8) and the associations of mono-iso-butyl phthalate (MiBP) with 8-isoPF2α (aOR: 2.96, 95% CI: 1.13-7.79) were observed. Weighted quantile sum regression revealed that MBzP contributed more than half of the association (56.8%), followed by MiBP (26.6%) and mono-iso-nonyl phthalate (MiNP) (8.77%). Our findings supported the adjuvant effect of phthalates in enhancing the immune system response.
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OBJECTIVE: We aimed to identify the genetic cause of one hydrops fetalis with Noonan syndrome (NS) manifestations including increased nuchal translucency (INT) and ascites through prenatal whole exome sequencing (WES). CASE REPORT: The case is a gestational age (GA) 18 fetus of two healthy parents with a normal child. We proceeded the genomic DNA from both fetus amniotic cells and parents to WES and identified a RIT1 mutation (c.268A>G) as the pathogenic cause of the hydrops fetalis by automatic prioritization algorithm after array-comparative genomic hybridization results showing negative. CONCLUSION: Mutations in RIT1 have been reported as the causes for different fetus structural abnormities in the recent years. This case contributes to the summary delineations of the prenatal NS phenotypes related to RIT1 mutation. In addition, the fast WES application, in this case, has demonstrated its advantage in prenatal disorder diagnosis when conventional karyotyping or chromosomal microarray testing result is negative.
Subject(s)
Noonan Syndrome , Comparative Genomic Hybridization , Female , Humans , Hydrops Fetalis/diagnosis , Hydrops Fetalis/genetics , Mutation , Noonan Syndrome/diagnosis , Noonan Syndrome/genetics , Pregnancy , Exome Sequencing , ras Proteins/geneticsABSTRACT
BACKGROUND: Epidemiological studies concerning whether oxidative stress mediates phthalate exposure-insulin resistance (IR) associations in young adults are limited. Therefore, we investigated this potential mediation by using a cumulative risk approach involving daily intake (DI) and a hazard index (HIRfD). METHODS: The participants were 391 Taiwanese military personnel. This study measured their IR (as homeostatic model assessment of estimated IR [HOMA-IR]), levels of oxidative stress biomarkers (8-hydroxy-2-deoxyguanosine, 8-nitroguanine, 8-iso-prostaglandin F2α, and N-acetyl-S-[tetrahydro-5-hydroxy-2-pentyl-3-furanyl]-L-cysteine [HNE-MA]), the sum of these four biomarkers (ΣOS), and urinary phthalate metabolite concentrations. The HIRfD was estimated on the basis of urinary levels of phthalate metabolite, and the DI of five phthalates was determined: dimethyl phthalate, benzyl butyl phthalate (BBzP), diethyl phthalate, dibutyl phthalate (DBP), and di (2-ethylhexyl) phthalate (DEHP). Logistic regression models were employed to explore associations among DI, HIRfD, oxidative stress biomarkers, and HOMA-IR values. The role played by oxidative stress in the phthalate exposure-HOMA-IR association was determined using mediation analysis. RESULTS: We discovered positive associations between high DI of DBP, BBzP, and DEHP; high HIRfD; and high ΣOS. High ΣOS and HNE-MA were associated with a higher likelihood of a high HOMA-IR value. Mediation analysis indicated that high ΣOS and HNE-MA were significant mediators of the associations between phthalates and IR. CONCLUSION: Oxidative stress may partially mediate the phthalate-IR relationship in young adults.
Subject(s)
Diethylhexyl Phthalate , Environmental Pollutants , Insulin Resistance , Military Personnel , Phthalic Acids , Biomarkers/urine , Dibutyl Phthalate/urine , Diethylhexyl Phthalate/metabolism , Environmental Exposure/analysis , Environmental Pollutants/analysis , Humans , Oxidative Stress , Phthalic Acids/urine , Risk Assessment , Young AdultABSTRACT
Oxidative and nitrosative stress have been linked to thyroid function in both animal and human studies. In the present study, the associations between oxidative and nitrosative stress and thyroid hormones were investigated. Measurements were obtained from 97 Taiwanese pregnant women at the first, second, and third trimesters. Levels of five oxidative and nitrosative stress biomarkers (8-hydroxy-2'-deoxyguanosine [8-OHdG], 8-nitroguanine [8-NO2Gua], 4-hydroxy-2-nonenal-mercapturic acid [HNE-MA], 8-isoprostaglandin F2α [8-isoPGF2α], and malondialdehyde [MDA]) were measured using urine samples, and levels of five thyroid hormones (triiodothyronine [T3], thyroxine [T4], free T4, thyroid-stimulating hormone [TSH], and T4-binding globulin [TBG]) were measured in blood samples. Multiple linear regressions and linear mixed-model regressions were conducted to determine the associations between oxidative or nitrosative stress biomarkers and thyroid hormones in pregnant women. We found that TSH was negatively and significantly associated with 8-NO2Gua (-14%, 95% CI [-26.9% to -1.1%]) and HNE-MA (-23%, 95% CI [-35.9% to -10.0%]) levels. However, T4 (3%, 95% CI [0.2%-5.8%]) and free T4 (4.3%, 95% CI [0.8%-7.8%]) levels were positively and significantly associated with 8-NO2Gua. The T4 to TBG and free T4 to TBG ratios were positively and significantly associated with 8-NO2Gua level (T4/TBG: 3.6%, 95% CI [0.5%-6.7%]; free T4/TBG: 5.6%, 95% CI [0.2%-11.1%]). However, the TSH to T4 ratio was negatively and significantly associated with 8-NO2Gua level (-17.3%, 95% CI [-30.4% to -4.3%]). The T3 to TSH ratio was positively and significantly associated with HNE-MA level (25.2%, 95% CI [11.2%-39.2%]). However, the TSH to T4 and TSH to free T4 ratios were negatively and significantly associated with HNE-MA level (TSH/T4: -21.2%, 95% CI [-34.5% to -7.8%] and TSH/free T4: -24.0%, 95% CI [-38.3% to -9.6%]). Our findings suggest that an imbalance of oxidative and nitrosative stress may alter thyroid hormone homeostasis during pregnancy. Disruption of the maternal thyroid homeostasis during pregnancy would affect embryonic and fetal development.
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The development of a rapid analytical approach for determining levels of antibacterial agents, plasticizers, and ultraviolet filters in biosamples is crucial for individual exposure assessment. We developed an analytical method to determine the levels of four parabens-bisphenols A (BPA) and its analogs, triclosan (TCS), triclocarban, and benzophenone-3 (BP-3)-in human urine. We further measured the levels of these chemicals in children and adolescents. We used a supported liquid extraction (SLE) technique coupled with an isotope-dilution ultraperformance liquid chromatography-tandem mass spectrometry (ID-UPLC-MS/MS) method to assess the detection performance for these chemicals. Forty-one urine samples from 13 children and 28 adolescents were assessed to demonstrate the capability and feasibility of our method. An acceptable recovery (75.6-102.4%) and matrix effect (precision < 14.2%) in the three-level spiked artificial urine samples were achieved, and good performance of the validated ID-UPLC-MS/MS method regarding linearity, limits of detection, and quantitation was achieved. The within-run and between-run accuracy and precision also demonstrated the sensitivity and stability of this analytical method, applied after SLE. We concluded that the ID-UPLC-MS/MS method with SLE pretreatment is a valuable analytical method for the investigation of urinary antibacterial agents, plasticizers, and ultraviolet filters in humans, useful for human biomonitoring.
ABSTRACT
Cartilage injury is the main cause of disability in the United States, and it has been projected that cartilage injury caused by osteoarthritis will affect 30% of the entire United States population by the year 2030. In this study, we modified hyaluronic acid (HA) with γ-poly(glutamic) acid (γ-PGA), both of which are common biomaterials used in cartilage engineering, in an attempt to evaluate them for their potential in promoting cartilage regeneration. As seen from the results, γ-PGA-GMA and HA, with glycidyl methacrylate (GMA) as the photo-crosslinker, could be successfully fabricated while retaining the structural characteristics of γ-PGA and HA. In addition, the storage moduli and loss moduli of the hydrogels were consistent throughout the curing durations. However, it was noted that the modification enhanced the mechanical properties, the swelling equilibrium rate, and cellular proliferation, and significantly improved secretion of cartilage regeneration-related proteins such as glycosaminoglycan (GAG) and type II collagen (Col II). The cartilage tissue proof with Alcian blue further demonstrated that the modification of γ-PGA with HA exhibited suitability for cartilage tissue regeneration and displayed potential for future cartilage tissue engineering applications. This study built on the previous works involving HA and further showed that there are unlimited ways to modify various biomaterials in order to further bring cartilage tissue engineering to the next level.
ABSTRACT
BACKGROUND: The regulation of thyroid hormones in the early stages of gestation plays a crucial role in the outcome of a pregnancy. Furthermore, thyroid hormones are fundamental for the fetal development of all organs, including endocrine hormone changes in uterus. Endocrine disrupting chemicals have been shown to have an effect on thyroid hormone homeostasis in newborns, which affects their later development. Few studies have proposed how phthalates could alter thyroid function through several mechanisms and the possible effects on thyroid hormone homeostasis of phthalates on pregnant women. However, the effects of cord blood phthalates and prenatal phthalate exposure on thyroid hormones in newborns remain unclear. OBJECTIVES: We aim to follow up on our previous established subjects and determine the correlation between phthalate exposure and thyroid hormones in pregnant women and newborns. MATERIALS AND METHODS: We recruited 61 pregnant women from the Obstetrics and Gynecology Department of a medical hospital in southern Taiwan and followed up. High performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was used to analyze urine samples for five phthalate metabolites. Serum levels of thyroid hormones were analyzed using electrochemoluminescence immunoassay (ECLIA) method. We used Spearman and Pearson correlation coefficients to evaluate the correlation between each phthalate metabolites in serum and the thyroid hormone levels in fetus and parturient. Finally, multiple logistic regression was used to explore the relationship between hormones and their corresponding phthalate metabolites in cord blood. RESULTS: High MBP in cord blood was correlated with negative cord serum TSH in newborns (r = -0.25, p < 0.06). By using multiple linear regression after adjusting for potential confounders (gestational and maternal age), cord serum MBP levels showed a negative association with cord serum TSH (ß = 0.217, p < 0.05), cord serum T4 (ß = 1.71, p < 0.05) and cord serum T4 × TSH (ß = 42.8, p < 0.05), respectively. CONCLUSION: We found that levels of cord serum TSH and T4 in newborns was significantly negatively associated with cord serum MBP levels after adjusting for significant covariate. The fall in TSH in newborns may potentially be delaying their development.
Subject(s)
Phthalic Acids , Tandem Mass Spectrometry , Cohort Studies , Female , Humans , Infant, Newborn , Maternal Exposure/adverse effects , Phthalic Acids/toxicity , Pregnancy , Taiwan , Thyroid HormonesABSTRACT
Cancer metastasis is a common cause of failure in cancer therapy. However, over 60% of oral cancer patients present with advanced stage disease, and the five-year survival rates of these patients decrease from 72.6% to 20% as the stage becomes more advanced. In order to manage oral cancer, identification of metastasis biomarker and mechanism is critical. In this study, we use a pair of oral squamous cell carcinoma lines, OC3, and invasive OC3-I5 as a model system to examine invasive mechanism and to identify potential therapeutic targets. We used two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/TOF MS) to examine the global protein expression changes between OC3 and invasive OC3-I5. A proteomic study reveals that invasive properties alter the expression of 101 proteins in OC3-I5 cells comparing to OC3 cells. Further studies have used RNA interference technique to monitor the influence of progesterone receptor membrane component 1 (PGRMC1) protein in invasion and evaluate their potency in regulating invasion and the mechanism it involved. The results demonstrated that expression of epithelial-mesenchymal transition (EMT) markers including Twist, p-Src, Snail1, SIP1, JAM-A, vimentin and vinculin was increased in OC3-I5 compared to OC3 cells, whereas E-cadherin expression was decreased in the OC3-I5 cells. Moreover, in mouse model, PGRMC1 is shown to affect not only migration and invasion but also metastasis in vivo. Taken together, the proteomic approach allows us to identify numerous proteins, including PGRMC1, involved in invasion mechanism. Our results provide useful diagnostic markers and therapeutic candidates for the treatment of oral cancer invasion.
Subject(s)
Cell Proliferation/genetics , Membrane Proteins/genetics , Mouth Neoplasms/genetics , Neoplasm Proteins/genetics , Receptors, Progesterone/genetics , Animals , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Heterografts , Humans , Mice , Mouth Neoplasms/pathology , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Neoplasm Metastasis , ProteomicsABSTRACT
Phthalate exposure was shown to alter thyroid function, however it is unclear, whether oxidative and nitrosative stress explains the intermediate biological mechanism. This study aimed to investigate the associations between phthalate exposure, oxidative/nitrosative stress, and thyroid function in adults, and to examine the mediating role of oxidative/nitrosative stress in the associations between phthalate exposure and thyroid function. Levels of eleven urinary phthalate metabolites, three urinary biomarkers of oxidative/nitrosative stress (malondialdehyde [MDA], 8-OHdG, and 8-NO2Gua) and five serum thyroid hormones (thyroxine [T4], free T4, triiodothyronine, thyroid-stimulating hormone, and thyroxine-binding globulin) were measured in 266 Taiwanese adults. Cross-sectional associations between phthalate metabolites, biomarkers of oxidative/ nitrosative stress and thyroid hormones were analyzed using multivariate regression models. Mediation analysis was conducted to assess the role of oxidative/nitrosative stress in the associations between phthalate metabolites and thyroid hormone levels. Sum of di-(2-ethylhexyl) phthalate (DEHP) metabolites was positively associated with MDA (ßT1-T2 = 0.253, 95%CI [0.060, 0.447]; ß â§ T2 = 0.317, 95% CI [0.098, 0.536]; Ptrend = 0.005) and 8-NO2Gua (ßT1-T2 = -0.010, 95%CI [-0.138, 0.118]; ß â§ T2 = 0.144, 95% CI [-0.001, 0.289]; Ptrend = 0.045). Mono-n-butyl phthalate (MnBP) was positively associated with 8-NO2Gua (ßT1-T2 = 0.201, 95% CI [0.078, -0.324]; ß â§ T2 = 0.161, 95% CI [0.031, -0.292]; Ptrend = 0.018). T4 was negatively associated with MDA (ßT1-T2 = -0.027, 95% CI [-0.088, 0.0034]; ßâ§T2 = -0.094, 95% CI [-0.161, -0.028]; Ptrend = 0.005) and 8-NO2Gua (ßT1-T2 = -0.068, 95% CI [-0.127, -0.010]; ßâ§T2 = -0.125, 95% CI [-0.184, -0.066]; Ptrend < 0.001). Free T4 was positively associated with MDA (Ptrend = 0.047) and with 8-NO2Gua (Ptrend < 0.001). 8-NO2Gua mediated 11% of the association between the sum of DEHP metabolites and T4, and 17% of the association between MnBP and free T4. These results suggest that phthalate exposure may influence thyroid hormone levels through induced oxidative/nitrosative stress.