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Increased cardiometabolic risk is associated with abnormalities in blood biomarkers profile and adiposity measurements. Some substances found in the food matrix and the environment, called endocrine-disrupting chemicals, may impair cardiometabolic health in the early and later stages of life. Bisphenol A (BPA) is a food contaminant that migrates from food contact materials and may act as an endocrine disruptor, negatively affecting human health. The present work aims to longitudinally assess the association between BPA exposure and cardiometabolic outcomes, considering data from Portuguese population-based birth cohort Generation XXI. Blood insulin (0.06stdβ; 95 %CI:0.03,0.09) and insulin resistance (0.05stdβ; 95 %CI:0.02,0.08) presented a significant longitudinal association with BPA daily exposure after adjustment for important variables and energy. The same findings were observed for fat mass (0.03stdβ; 95 %CI 0.01,0.06) and waist circumference (0.06stdβ; 95 %CI:0.04,0.08). For z-BMI, a significant cross-sectional (0.03stdβ; 95 %CI:0.01,0.04) and longitudinal (0.02stdβ; 95 %CI:0.00,0.04) association was found. This was the first study assessing the association between BPA exposure and health outcomes from childhood to adolescence. We found an association between BPA exposure and increased blood insulin level, insulin resistance, fat mass percentage, waist circumference and z-BMI. Our results point to the need to reduce exposure to BPA in the early stages of life., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The liver toxicity of alkylphenols (APs) has been demonstrated in animal studies. However, relevant epidemiological evidence is still lacking in humans, especially during pregnancy. We obtained the levels of biochemical indicators of liver function in early (<13 weeks, mean gestation=9.80±1.96 weeks) and late (≥32 weeks, mean gestation = 37.23±2.45 weeks) pregnancies from 219 pregnant women in the Guangxi Zhuang birth cohort from 2015-2017. We also examined the serum levels of APs in these pregnant women in early pregnancy. The present study aimed to investigate the correlations between the exposure of pregnant women to APs and their serum liver function indices. The results of the generalized linear model (GLM) in this study revealed that nonylphenol (NP) was positively correlated with total bilirubin (TBIL) (P=0.04) in early pregnancy, and 4-n-nonylphenol (4-N-NP) was negatively correlated with glutamyl transferase (GGT) (P=0.012). In late pregnancy, NP was positively associated with TBIL (P=0.002), and 4-tert-octylphenol (4-T-OP) was positively correlated with alanine aminotransferase (ALT) (P=0.02). Restricted cubic spline (RCS) results revealed doseresponse relationships between NP and TBIL (Poverall=0.011) and between 4-N-NP and GGT (Poverall=0.007) in early pregnancy. In late pregnancy, there were doseresponse relationships between NP and TBIL (Poverall=0.001) and between 4-T-OP and ALT (Poverall=0.033). There was also a doseresponse relationship between NP volume and GGT with an inverted 'U' shape (Poverall=0.041, Pnonlinear=0.012). Bayesian kernel machine regression modeling (BKMR) revealed that TBIL increased significantly (P<0.05) with increasing levels of coexposure to APs in both early and late pregnancy. Overall, exposure to APs during pregnancy affects maternal liver function to varying degrees. The present study provides new epidemiological evidence that exposure to alkylphenols in pregnant women interferes with liver function., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Endocrine-disrupting environmental chemicals are a public health concern, particularly fetal exposure to Bisphenol derivatives. This study aimed to assess fetal exposure to Bisphenol derivatives (BPA, BPF, and BPS) by measuring their levels in cord blood and investigating their association with plastic material used in daily life as well as cord blood TSH and free L-thyroxine (fT 4 ) levels. In this descriptive study, a questionnaire with a face-to-face interview was administered before birth, and cord blood samples were taken immediately after delivery. The mean levels of BPA, BPF, TSH, and fT 4 were measured as 10.69 ± 2.39 ng/ml, 3.80 ± 0.58 ng/ml; 2.36 ± 0.23 µIU/ml, and 14.18 ± 0.53 pg/ml, respectively, in a total of 104 cord blood samples. All BPS levels remained below the detection limit. Linear regression analysis revealed a positive association between birth weight and cord blood BPA concentration (β = 0.26; p  = 0.02). Further research on maternal exposure during the fetal and neonatal period is critical for public health.

Polycystic Ovary Syndrome (PCOS) is a multifaceted condition influenced by genetic, hormonal, and environmental factors. Among environmental factors, Bisphenol A (BPA)-a recognized endocrine disruptor-has been implicated in the development of PCOS. The study aimed to compare BPA levels in women diagnosed with PCOS with those in healthy controls, using the high-performance liquid chromatography (HPLC) technique. The study involved 80 women diagnosed with PCOS and 50 healthy control participants. Demographic and biochemical parameters were recorded, including age, Body Mass Index (BMI), and levels of testosterone, estradiol, Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), Prolactin (PRL), Dehydroepiandrosterone Sulfate (DHEA-S), Thyroid Stimulating Hormone (TSH), and Insulin Resistance as measured by the Homeostatic Model Assessment (HOMA-IR). Furthermore, BPA levels were measured using the HPLC technique. Women with PCOS exhibited significantly higher mean age and BMI compared to healthy controls (p = 0.01, p < 0.0001, respectively). Additionally, higher levels of testosterone (p = 0.04), LH (p = 0.03) and BPA (p < 0.0001) were observed in women with PCOS. However, estradiol, FSH, PRL, LH/FSH ratio, DHEA-S, and TSH levels were not significantly different between the two groups. HOMA-IR levels were not recorded for the control group. A notable positive relationship emerged between Bisphenol A and luteinizing hormone (LH) levels (r = 0.23, p = 0.03), also significant negative correlation appeared between Bisphenol A and thyroid-stimulating hormone (TSH) levels. This study found that women with PCOS have elevated BPA levels compared with healthy controls, showing a need for further research on the relationship between BPA exposure and the development of PCOS., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The increasing global prevalence of gestational diabetes mellitus (GDM) has been hypothesized to be associated with maternal exposure to environmental chemicals. Here, among 420 women participating in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort study, we examined associations between GDM and second trimester blood or urine concentrations of endocrine disrupting chemicals (EDCs): bisphenol-A (BPA), bisphenol-S (BPS), twelve phthalate metabolites, eight perfluoroalkyl acids (PFAAs), and eleven trace elements. Fifteen (3.57%) of the women were diagnosed with GDM, and associations between the environmental chemical exposures and GDM diagnosis were examined using multiple logistic and LASSO regression analyses in single- and multi-chemical exposure models, respectively. In single chemical exposure models, BPA and mercury were associated with increased odds of GDM, while a significant inverse association was observed for zinc. Double-LASSO regression analysis selected mercury (AOR: 1.51, CI: 1.12-2.02), zinc (AOR: 0.017, CI: 0.0005-0.56), and perfluoroundecanoic acid (PFUnA), a PFAAs, (AOR: 0.43, CI: 0.19-0.94) as the best predictors of GDM. The combined data for this Canadian cohort suggest that second trimester blood mercury was a robust predictor of GDM diagnosis, whereas blood zinc and PFUnA were protective factors. Research into mechanisms that underlie the associations between mercury, zinc, PFUnA, and the development of GDM is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aims to investigate the associations of bisphenols with sex and thyroid hormones in cord blood among newborns. Four bisphenols, three hormones related to gonadal function, and four parameters related to thyroid function were measured in umbilical cord blood in 378 mother-newborn pairs. Multivariable linear regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression were used. In the multivariable linear regression, bisphenol A (BPA) was associated with increased testosterone (TT) (regression coefficient, β = 0.049, 95% confidence interval, CI: 0.013,0.085; p = 0.007) and free tri-iodothyronine (FT3) levels (β = 0.019, 95% CI: 0.003, 0.035; p = 0.023), and decreased thyroid peroxidase antibody (TPOAb) (β = -0.053, 95% CI: 0.098, -0.008; p = 0.021). Consistently associations were observed in males, except TT, which was observed in females, and bisphenol AF (BPAF) was associated with decreased follicle-stimulating hormone (FSH) in females. These associations were also observed in a mixture of bisphenols. Moreover, we observed maternal prepregnancy body mass index (BMI) and delivery mode disparity in the relationship between bisphenols and sex and thyroid hormones. This study suggests that bisphenols may exert effects on sex and thyroid hormones in newborns, the effect may vary with sex differences, maternal prepregnancy BMI, and delivery mode., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: In this study, we aimed to evaluate BPA levels in the maternal serum and amniotic fluid of patients diagnosed with NTD. In addition, we wanted to investigate the relationship between neurodevelopmental defects, such as neural tube defects (NTD), and BPA levels., Study Design: This prospective observational study was carried out at Bursa Yüksek İhtisas Training and Research Hospital between April 15, 2021, and April 15, 2022. The study consisted of 92 patients between the ages of 18-45 who had an amniocentesis at 15-22 weeks of gestation. The patients were divided into two groups according to the indications of amniocentesis. Group 1 contained the patients with abnormal maternal serum screening results or cell-free DNA results and abnormal ultrasonography findings (45 patients). Group 2 contained the patients with a pre-diagnosis of NTD (47 patients). The first 5 cc fluids and maternal serum samples taken during the amniocentesis procedure of all patients were delivered to the biochemistry laboratory. The BPA values between groups were compared., Results: A statistically significant difference was found between the two groups in terms of amniotic fluid BPA levels (36.66 (19.00:82.00) and 39.62 (19.02-73.87)) and maternal blood BPA levels (22.26 (12.60-228) and 47.81 (12.89-228.39)). In cases with NTD, amniotic fluid BPA levels and maternal blood BPA levels were significantly higher than the control group. When AUC values were compared, the AFP numerical value was higher than the amniotic fluid and maternal blood BPA levels., Conclusion: Plastic, which is indispensable for modern life, may negatively affect fetal development in intrauterine life. The data in this study says that high maternal blood BPA may be associated with NTD., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Steroid hormone imbalance is believed to increase the odds of developing PE. Bisphenol A (BPA) and its substitutes (e.g., bisphenol S (BPS) and bisphenol F (BPF)) have estrogen-like effects, and its exposure may be related to the development of preeclampsia (PE). To explore the effects of bisphenol exposure on maternal serum steroid hormones and the potential mediating role of steroid hormones in the association between bisphenol exposure and developing PE, concentrations of bisphenols and steroid hormones in serum samples of 383 pregnant women were examined before delivery (including 160 PE cases and 223 control cases). Multivariable logistic and linear models were used to explore the associations of maternal serum bisphenols concentrations with both maternal steroid hormones and PE risk. Mediation modeling was employed to evaluate the mediating role of steroid hormones in the association between bisphenols and PE. Results showed that maternal serum BPS concentrations were positively associated with testosterone (T) concentrations. The mediation analyses suggested that approximately 10.17 % of the associations between BPS concentrations and the development of PE might be mediated by maternal T. In conclusion, maternal exposure to BPS during pregnancy is linked to higher maternal T concentrations, which might increase the odds of developing PE. T might mediate the association between BPS exposure and the development of PE., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Competing Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Studies have shown that bisphenol S (BPS) is mainly present as its conjugated metabolites in human blood. However, the distribution of conjugated BPS metabolites in different human blood matrices has not been characterized. In this study, paired human serum and whole blood samples (n = 79) were collected from Chinese participants, and were measured for the occurrence of BPS and 4 BPS metabolites. BPS was detectable in 49% of human serum (

This study investigated the association of blood and semen Bisphenol A (BPA) levels of the male partner on the reproductive outcome in intracytoplasmic sperm injection (ICSI) treatment cycles. For this prospective study (ClinicalTrials.gov identifier: NCT02703584), blood and semen samples of the male partner of the 75 women who had ICSI were analyzed. The study group consisted of men who had ICSI for male factor infertility other than azoospermia, while men with normal spermiogram whose partners underwent ICSI due to tubal factor infertility were taken as the study group. Habitual consumption of drinking water from plastic carboys/bottles (PBW) at home was also questioned in both groups as it was considered as chronic BPA exposure. The association of ICSI outcome with blood BPA (bBPA) and semen BPA (sBPA) levels was analyzed in both groups. No significant correlation was found between sperm parameters and bBPA levels in both groups. A negative correlation was found between sBPA levels and total sperm count and progressive sperm motility in men who consumed PBW. Embryo development arrest was found to be significantly higher in patients who have high sBPA levels. Although sBPA levels were not different in PBW consumers, bBPA levels were found to be significantly lower in those who consumed tap water (TW) than those who used PBW. Elevated bBPA were associated with a significant decrease in clinical pregnancy rate. Considering the widespread human exposure to BPA, the effect of BPA on the male reproductive system needs to be further examined., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Recent evidence has revealed associations between endocrine-disrupting chemicals (EDCs) and placental insufficiency due to altered placental growth, syncytialization, and trophoblast invasion. However, no epidemiologic study has reported associations between exposure to EDCs and asymmetric fetal growth restriction (FGR) caused by placenta insufficiency. The aim of this study was to evaluate the association between EDC exposure and asymmetric FGR. This was a prospective cohort study including women admitted for delivery to the Maternal Fetal Center at Seoul St. Mary's Hospital between October 2021 and October 2022. Maternal urine and cord blood samples were collected, and the levels of bisphenol-A (BPA), monoethyl phthalates, and perfluorooctanoic acid in each specimen were analyzed. We investigated linear and non-linear associations between the levels of EDCs and fetal growth parameters, including the head circumference (HC)/abdominal circumference (AC) ratio as an asymmetric parameter. The levels of EDCs were compared between fetuses with and without asymmetric FGR. Of the EDCs, only the fetal levels of BPA showed a linear association with the HC/AC ratio after adjusting for confounding variables ( β  = 0.003, p  < 0.05). When comparing the normal growth and asymmetric FGR groups, the asymmetric FGR group showed significantly higher maternal and fetal BPA levels compared to the normal growth group (maternal urine BPA, 3.99 μg/g creatinine vs. 1.71 μg/g creatinine [ p  < 0.05]; cord blood BPA, 1.96 μg/L vs. -0.86 μg/L [ p  < 0.05]). In conclusion, fetal exposure levels of BPA show linear associations with asymmetric fetal growth patterns. High maternal and fetal exposure to BPA might be associated with asymmetric FGR., Competing Interests: MY and HWK were employed by the company Goodbeing Center Co. Ltd., Republic of Korea. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hong, Kang, Kim, Won, Kim, Wie, Shin, Choi, Jo, Kim, Yang, Kang, Lee, Park, Park and Ko.)

Background: Bisphenol A (BPA) is an oil-derived, large-market volume chemical with endocrine disrupting properties and reproductive toxicity. Moreover, BPA is frequently used in food contact materials, has been extensively researched recently, and widespread exposure in the general population has been reported worldwide. However, national information on BPA levels in general Chinese people is lacking., Methods: This study collected and analyzed 145 (104 in urine and 41 in serum) research articles published between 2004 and 2021 to reflect the BPA internal exposure levels in Chinese populations. The Monte Carlo simulation method is employed to analyze and estimate the data in order to rectify the deviation caused by a skewed distribution., Results: Data on BPA concentrations in urine and serum were collected from 2006 to 2019 and 2004 to 2019, respectively. Urinary BPA concentrations did not vary significantly until 2017, with the highest concentration occurring from 2018 to 2019 (2.90 ng/mL). The serum BPA concentration decreased to the nadir of 1.07 ng/mL in 2011 and gradually increased to 2.54 ng/mL. Nationally, 18 provinces were studied, with Guangdong (3.50 ng/mL), Zhejiang (2.57 ng/mL), and Fujian (2.15 ng/mL) having the highest urine BPA levels. Serum BPA was investigated in 15 provinces; Jiangsu (9.14 ng/mL) and Shandong (5.80 ng/mL) were relatively high. The results also indicated that males' urine and serum BPA levels were higher than females, while the BPA levels in children were also higher than in adults ( p  < 0.001). Furthermore, the volume of garbage disposal ( r  = 0.39, p  < 0.05), household sewage ( r  = 0.34, p  < 0.05), and waste incineration content ( r  = 0.35, p  < 0.05) exhibited a strong positive connection with urine BPA levels in Chinese individuals., Conclusion: Despite using a data consolidation approach, our study found that the Chinese population was exposed to significant amounts of BPA, and males having a higher level than females. Besides, the levels of BPA exposure are influenced by the volume of garbage disposal, household sewage, and waste incineration content., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Li, Wang, Zhang, Zhang, Ji and Lu.)

Bisphenol-A (BPA), an estrogenic endocrine disrupting chemical, significantly impacts numerous diseases and abnormalities in mammals. Estrogens are known to play an important role in the biology of the prostate; however, little is known about the role of bisphenols in the etiology of prostate pathologies, including benign prostate hyperplasia (BPH) and associated lower urinary tract dysfunction (LUTD). Bisphenol-F (BPF) and bisphenol-S (BPS) are analogs often used as substitutes for BPA; they are both reported to have in vitro and in vivo estrogenic effects similar to or more potent than BPA. The objective of this study was to assess the role of these bisphenols in the development of LUTD in adult male mice. In adult mice exposed to BPA, BPS or BPF, we examined urinary tract histopathology and physiological events associated with urinary dysfunction. Mice treated with bisphenols displayed increased bladder (p < 0.005) and prostate (p < 0.0001) mass, and there was an increased number of prostatic ducts in the prostatic urethra (p < 0.05) and decreased size of the urethra lumen (p < 0.05) compared to negative controls. After two months of bisphenol exposure, mice displayed notable differences in cystometric tracings compared to controls, consistent with LUTD. Treatment of male mice with all bisphenols also induced voiding dysfunction manifested by detrusor instability and histologic changes in the prostatic urethra of male rodents, consistent with LUTD. Our results implicate BPA and its replacements in the development and progression LUTD in mice and provide insights into the development and progression of BPH/LUTS in men., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Endocrine-disrupting chemicals (EDCs) might increase the risk of childhood diseases by disrupting hormone-mediated processes that are critical for growth and development during childhood, however, the association among the exposure level of EDCs such as Nonylphenol (NP), Bisphenol A (BPA), Dimethyl phthalate (DMP) in children and environmental risk factors, as well as hepatic function has not been elaborated. This study aimed to discuss this interesting relationship among NP, BPA, DMP concentrations in serum, environmental risk factors, hepatic function of 5- to 14-year-old children in industrial zone, residential zone and suburb in northern district of Guizhou Province, China. In Zunyi city, 1006 children participated in cross-sectional health assessments from July to August 2018, and their parents completed identical questionnaires on the environmental risk factors of EDCs exposure to mothers and children. Serum NP, BPA and DMP concentrations were measured by high performance liquid chromatography (HPLC). Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) were detected with automatic biochemical analyzer. The median concentrations of serum NP, BPA, and DMP in the participants were 45.85 ng/mL, 26.31 ng/mL and 31.62 ng/mL, respectively, which were higher than the environmental concentration limits of the U.S. National Environmental Protection Agency (EPA). Hair gels used during pregnancy, types of domestic drinking water, nail polish and cosmetics used by children were significantly positive correlated with serum NP concentration (P < 0.05). Gender, feeding pattern, plastic water cup used during pregnancy, hair spray and perfume use for children, duration of children birth, materials for baby bottle or cup and ways to plastic products were significantly positively correlated with serum BPA concentration (P < 0.05). Gender, perms used during pregnancy, hair spray and perfume use for children, using plastic lunch box during pregnancy, duration of children birth, exposure to pesticides, parents' occupations were significantly positively correlated with serum DMP concentrations (P < 0.05). Serum NP (β = 0.296, P = 0.036) and DMP (β = 0.316, P = 0.026) concentrations and TBIL level were significantly positively correlated. Serum NP concentration and the levels of IBIL (β = 0.382, P = 0.006) are significantly positively correlated. Cosmetics used during pregnancy significantly increased AST level (β = 2.641, P = 0.021). There was a positive correlation between the frequency of hair spray and perfume use for children and the AST (β = 4.241, P = 0.022). NP, BPA and DMP, which were commonly detected in the serum of children aged 5-14 years old in Zunyi City, Northern Guizhou Province, China, were closely related to the environmental risk factors of exposure environment during pregnancy, infancy and school age. Exposure to NP, BPA and DMP would have negative effects on hepatic function, and these effects showed differences in gender and geographical location. Notably,The relationships were more evident in girls than in boys., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bisphenol A (BPA), also known as 2,2,-bis(4-hydroxyphenyl) propane, is a common component of plastics worldwide. However, it has been shown to act as an endocrine disruptor with some hormonal functions. Furthermore, high levels of BPA have been related to the development of cardiovascular events and the activation of carcinogenesis pathways. Patients with chronic kidney disease (CKD) have higher serum concentrations of BPA due to their impaired renal function. This situation is aggravated in CKD patients requiring dialysis, because the BPA content of dialysis devices (such as, for example, the filters) is added to the lack of excretion. In addition to the development of BPA-free dialysis filters, some techniques can contribute to the reduction of BPA levels in these patients. The aim of this review is to illustrate the impact of BPA on dialysis patients and suggest some strategies to reduce its inherent risks.

Background: Bisphenol A (BPA) is an endocrine disruptor that it is present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident breast and prostate cancer in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: We designed a case-cohort study within the EPIC-Spain cohort. Study population consisted on 4812 participants from 4 EPIC-Spain centers (547 breast cancer cases, 575 prostate cancer cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Borgan II weighted Cox regression was used to estimate hazard ratios., Results: Median follow-up time in our study was 16.9 years. BPA geometric mean serum values of cases and sub-cohort were 1.12 ng/ml vs 1.10 ng/ml respectively for breast cancer and 1.33 ng/ml vs 1.29 ng/ml respectively for prostate cancer. When categorizing BPA into tertiles, a 40% increase in risk of prostate cancer for tertile 1 (p = 0.022), 37% increase for tertile 2 (p = 0.034) and 31% increase for tertile 3 (p = 0.072) was observed with respect to values bellow the limit of detection. No significant association was observed between BPA levels and breast cancer risk., Conclusions: We found a similar percentage of detection of BPA among cases and sub-cohort from our population, and no association with breast cancer risk was observed. However, we found a higher risk of prostate cancer for the increase in serum BPA levels. Further investigation is needed to understand the influence of BPA in prostate cancer risk., (© 2021. The Author(s).)

Human exposure to bisphenols has rarely been reported. The most important challenges in this regard are the sensitivity and accuracy of the analytical methods employed. Dansyl chloride derivatization prior to high-performance liquid chromatography-tandem mass spectrometry has been prevalently employed to improve sensitivity. However, the dose effect of the derivatization reagent on the reaction products is not well understood, especially for reactants with two or more active groups. This study investigated the mass ratio of dansyl chloride to bisphenols and found the mass ratio played a vital role in changing the composition of derivatives; further, the optimal ratio for obtaining di-substituted derivatives was confirmed. Under optimal conditions, solid-phase extraction followed by dansyl chloride derivatization coupled with high-performance liquid chromatography-tandem mass spectrometry was used to detect eight bisphenols in human serum samples. The method detection limits of the eight bisphenols were 0.025-0.28 ng/mL, and the recoveries were 72.9-121.7% by spiking bisphenols (2, 5, and 20 ng/mL) into bovine serum. The detection frequencies of bisphenol A and bisphenol F in 73 serum samples obtained from children from Guangzhou were 41.1% and 71.2%, respectively, while the detection frequencies of other bisphenols were below 20%. The concentrations of bisphenol A and bisphenol F were < 0.28-8.0 ng/mL and < 0.028-7.6 ng/mL, respectively., (© 2021 Wiley-VCH GmbH.)

Bisphenol A (BPA) is a compound that is especially widespread in most commonly used objects due to its multiple uses in the plastic industry. However, several data support the need to restrict its use. In recent years, new implications of BPA on the renal system have been discovered, which denotes the need to expand studies in patients. To this end, a systematic review and a meta-analysis was performed to explore existing literature that examines the BPA-kidney disease paradigm and to determine what and how future studies will need to be carried out. Our systematic review revealed that only few relevant publications have focused on the problem. However, the subsequent meta-analysis revealed that high blood concentrations of BPA could be a factor in developing kidney disease, at least in people with previous pathologies such as diabetes or hypertension. Furthermore, BPA could also represent a risk factor in healthy people whose urinary excretion is higher. Finally, the data analyzed from the NHANES 03-16 cohort provided new evidence on the possible involvement of BPA in kidney disease. Therefore, our results underline the need to carry out a thorough and methodologically homogeneous study, delving into the relationship between urinary and blood BPA, glomerular filtration rate, and urine albumin-to-creatinine ratio, preferably in population groups at risk, and subsequently in the general population, to solve this relevant conundrum with critical potential implications in Public Health.

Oxidative stress and inflammation have been considered the main factors in the liver injury of clofibrate (CF). To obtain a novel antihyperlipidemic agent with antioxidant, anti-inflammation and hepatoprotection, the combination of sesamol and clofibric acid moieties was performed and achieved sesamol-clofibrate (CF-Sesamol). CF-Sesamol showed significant hypolipidemia effects in hyperlipidemia mice induced by Triton WR 1339, reducing TG by 38.8% (P < 0.01) and TC by 35.1% (P < 0.01). CF-Sesamol also displayed an alleviating effect on hepatotoxicity. The hepatic weight and hepatic coefficient were decreased. The amelioration of liver function was observed, such as aspartate and lactate transaminases (AST and ALT), alkaline phosphatase (ALP) and total proteins (TP) levels. Liver histopathological examination showed that hepatocyte necrosis, cytoplasmic loosening, nuclear degeneration and inflammatory cell infiltration reduced obviously by treatment with CF-Sesamol. Related molecular mechanisms on hepatoprotection showed that CF-Sesamol up-regulated Nrf2 and HO-1 expression and down-regulated p-NF-κB p65 expression in hepatic tissues. CF-Sesamol has significant antioxidant and anti-inflammatory effects. Plasma antioxidant enzymes such as SOD and CAT increased, anti-lipid peroxidation product MDA decreased. The expression of TNF-α and IL-6 inflammatory cytokines in liver was significantly lower than that in the CF group. The results indicated that CF-Sesamol exerted more potent antihyperlipidemic effects and definite hepatoprotective activity partly through the Nrf2/NF-κB-mediated signaling pathway., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: to explore the association of plasma concentrations of bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF) with unilateral cryptorchidism. In addition, to analyze selected demographic and intraoperative characteristics., Design: Retrospective analysis to determine plasma concentrations of total BPA, BPS and BPF using gas chromatography - mass spectrometry (GC-MS) among prepubertal boys with cryptorchidism and prebupertal male control subjects. During operation, the size, turgor and location of the cryptorchid testes were assessed., Main Outcome Measure: Plasma concentrations of total BPA, BPS and BPF., Results: In children with cryptorchidism, plasma levels of BPA, BPS and BPF were significantly higher compared to the control subjects. For BPA, it was: median value: 9.95 ng/mL vs . 5.54 ng/mL, p<0.05. For BPS, it was: median value: 3.93 ng/mL vs . 1.45 ng/mL, p<0.001. For BPF, it was: median value: 3.56 ng/mL vs . 1.83 ng/mL, p<0.05. In cryptorchid group, BPA was detected in 61.4% samples, BPS in 19.3% and BPF in 19.3%. All the three bisphenols were detected in plasma samples of both the healthy subjects and the study cohort. In the latter group, we found significant higher levels of BPA in boys from urban areas. We found a weak positive correlation between the levels of BPS and BPF and reduced turgor of the testes. Furthermore, results showed weak positive correlations between BPA and BPS levels and the age of the children as well as between BPS and BPF concentrations and the place of residence., Conclusions: Results provide a first characterization of prepubertal boys suffering from cryptorchidism and exposed to different kind of bisphenols. Our study suggests that cryptorchid boys are widely exposed to BPA and, to a lesser extent, also to its alternatives, such as BPS and BPF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Komarowska, Grubczak, Czerniecki, Hermanowicz, Hermanowicz, Debek and Matuszczak.)

Research Question: Do bisphenol A (BPA) levels in maternal urine, serum and follicular fluid affect embryo quality and intracytoplasmic sperm hinjection (ICSI) cycle outcomes in women with unexplained infertility?, Design: Prospective study conducted between 1 April 2019 and 30 September 2019. The study cohort consisted of 82 women aged between 23 and 33 years who underwent intracytoplasmic sperm injection owing to unexplained infertility and provided urine, blood and follicular fluid samples on the day of oocyte retrieval. Consumption of drinking water from plastic carboys or bottles at home were considered as chronic BPA exposure. Demographic features and IVF outcomes of the patients were collected., Results: Among the 82 women with unexplained infertility, clinical pregnancy was achieved in 22 (26.8%) patients after the IVF and embryo transfer cycle. The patients who consumed tap water had statistically significantly lower BPA values in three body fluids compared with patients who consumed plastic bottled water (all P < 0.001). Women who had grade 1 embryos transferred had lower serum BPA values than women who had grade 2 embryos transferred (10.8 ± 5.2 versus 26.9 ± 22 ng/ml, P = 0.003). Serum and follicular fluid BPA levels were statistically significantly higher in women who failed to achieve clinical pregnancy (P < 0.001, P = 0.006, respectively) and obtain a live birth (both P = 0.007)., Conclusions: A negative relationship was found between serum and follicular fluid BPA levels and embryo quality, clinical pregnancy and live birth in these women. In addition, the BPA levels of women who consume tap water at home were lower than those who use plastic bottled water., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine disruptors, short-chain fatty acids, tryptophan and cytokines were measured. Bacterial-DNA and serum endotoxin levels were also evaluated. Gene expression of ER-α, ER-β and GPER was measured in PBMCs. All patients were genotyped for NOD2 and ATG16L1 polymorphisms. A series of 200 CD patients (140 in remission, 60 with active disease) was included in the study. Bisphenol A was significantly higher in patients with active disease versus remission and in colonic versus ileal disease. GPER was significantly increased in active patients and correlated with BPA levels. BPA was significantly increased in patients with bacterial-DNA and correlated with serum endotoxin levels, (r = 0.417; P = .003). Serum butyrate and tryptophan levels were significantly lower in patients with bacterial-DNA and an inverse relationship was present between them and BPA levels (r = -0.491; P = .001) (r = -0.611; P = .001). Serum BPA levels correlated with IL-23 (r = 0.807; P = .001) and IL-17A (r = 0.743; P = .001). The multivariate analysis revealed an independent significant contribution of BPA and bacterial-DNA to serum levels of IL-23 and IL-17A. In conclusion, bisphenol A significantly affects systemic inflammatory response in CD patients with gut barrier disruption and dysbiotic microbiota secretory products in blood. These results provide evidence of an endocrine disruptor playing an actual pathogenic role on CD., (© 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Sensitive analysis of very low-molecular weight metabolites using liquid chromatography with quadrupole-time-of-flight mass spectrometry is challenging due to the high losses of ions in a time-of-flight analyzer. Improvement in sensitivity for these analytes via the optimization of advanced parameters, including quadrupole profile, ion guide parameters, and duty cycle, has been achieved. The optimization of the method was carried out using a large spectrum of structurally different compounds including (iso)flavonoids and their known metabolites. These compounds can be categorized into two major groups, that is, compounds with (iso)flavonoid core and low-molecular weight phenolics. The optimization of the duty cycle enabled up to a 15-fold increase in analyte responses while the contribution of tuning ion optics and quadrupole profile was negligible. The limits of quantifications of our new method were assessed using both standard solutions and rat plasma. They were decreased at least 10 times for several low-molecular weight phenolics enabling measurement of their concentrations in a range of 1-50 ng/mL in rat plasma after protein precipitation. Concurrently, the limits of quantifications for compounds with (iso)flavonoid core did not increase distinctly allowing their detection in a range of 0.5-10 ng/mL. The new method was used for the targeting of phenolics in biological samples from pharmacokinetics experiments., (© 2021 Wiley-VCH GmbH.)

Background: Low dose of NP exposure can alter adipose tissue formation, and the intake of high-fat diet (HFD) can also lead to the fatty liver disease. We investigated the combined effect of NP and HFD on the first offspring of rats, and whether this effect can be passed to the next generation and the possible mechanisms involved., Methods: Pregnant rats had access to be treated with 5 μg/kg/day NP and normal diet. The first generation rats were given normal diet and HFD on postnatal day 21, respectively. Then the second generation rats started to only receive normal diet without NP or HFD. Body weight, organ coefficient of liver tissues, lipid profile, biochemical indexes and the expression of genes involved in lipid metabolism, as well as liver histopathology were investigated in male offspring of rats., Results: NP and HFD interaction had significant effect on the birth weight, body weight and liver tissue organ coefficient of first generation male rats. And HFD aggravated abnormal lipid metabolism, even abnormal liver function and liver histopathological damage of first generation male rats produced by the NP. And this effect can be passed on to the second generation rats. HFD also accelerated the mRNA level of fatty acid synthesis genes such as Lpl, Fas, Srebp-1 and Ppar-γ of first generation rats induced by perinatal exposure to NP, even passed on to the second generation of male rats. NP and HFD resulted in synergistical decrease of the protein expression level of ERα in liver tissue in F2 male rats., Conclusion: HFD and NP synergistically accelerated synthesis of fatty acids in liver of male offspring rats through reducing the expression of ERα, which induced abnormal lipid metabolism, abnormal liver function and hepatic steatosis. Moreover, all of these damage passed on to the next generation rats.

Exposure to Bisphenol A (BPA) during early development particularly in- utero has been linked to a wide range of pathology. The aim of this study was to examine the relationship of BPA and its naturally occurring metabolite BPA-glucuronide (BPA-g) with sex steroid hormone levels in South African mother-child pairs. Third-trimester serum maternal samples and matching cord blood samples were analyzed for BPA, BPA-g and nine sex steroid hormones using liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixty maternal and child pairs were analyzed. Rank correlation demonstrated a significant positive relationship between cord blood estradiol and cord blood BPA (p = 0.002) and maternal BPA levels (p = 0.02) respectively. Cord blood testosterone from male infants showed a negative Spearman's correlation (r=-0.5, p = 0.02) with maternal BPA-g. There was no statistical difference in total testosterone levels in cord blood from male and female infants. The findings of the current study indicate a significant relationship between some key sex steroid hormones namely testosterone, dihydrotestosterone and estradiol and fetal exposure BPA., (Copyright © 2021. Published by Elsevier Inc.)

Aim: Bisphenol-A (BPA) is an endocrine disrupting compound and may exacerbate or induce allergic diseases. To the best of our knowledge, there is little evidence regarding the effects of BPA exposure on allergic rhinitis (AR) in children. In the present study, we sought to examine whether exposure to BPA in children is associated with AR., Methods: This study was designed as a case controlled clinical study. 140 children diagnosed as allergic rhinitis and 140 healthy children as control group were recruited. BPA, interleukin-4, interleukin-13, total IgE and interferon-gamma levels were determined. Skin prick tests were performed in patient group. Total nasal symptom score and ARIA classification were used to predict disease severity., Results: Serum IL-4, IgE and BPA levels of children with allergic rhinitis were found to be significantly higher than the control group. BPA and IL-4 levels were significantly higher in moderate to severe-persistent group. There was a positive correlation between total nasal symptom scores and Bisphenol A levels in children with allergic rhinitis., Conclusions: The present study is the first to observe statistically significant relationship between BPA concentrations and allergic rhinitis in children. Also increased levels of BPA are associated with disease severity.

Bisphenol A (BPA) is a chemical used to manufacture bisphenol A glycidyl methacrylate (BisGMA). BisGMA has been used for decades in dental composite restoratives, sealants, and adhesives. Based on published studies, exposure to low concentrations of BPA are possible from dental and orthodontic devices. The serum BPA concentrations arising from such devices and oral doses were predicted using a PBPK model in children and adult females based on 1) published extraction data for cured and uncured 3M ESPE Filtek Supreme Ultra Flowable, 3M ESPE Filtek Bulk Fill Restorative, and 3M ESPE Clinpro Sealant and 2) published 20% ethanol/water and water rinsate data following orthodontic application with 3M ESPE Transbond MIP Primer and 3M ESPE Transbond XT Adhesive. Predicted oral exposure to BPA arising from these dental and orthodontic devices is low (median <10 ng/treatment) and predicted serum BPA concentrations were also low (<10 -4  nM). Even the maximum predicted exposure in this study (533.2 ng/treatment) yields a margin of exposure of 7.5 relative to the EFSA t-TDI (4 μg/kg-day) and is only 2.8% of the daily BPA exposure for the US population in a 58-kg woman (15,660 ng/day). Therefore, the exposure to BPA arising from the 3M ESPE dental and orthodontic devices evaluated in this study is negligible relative to daily BPA exposure in the general population and these potential BPA sources do not constitute a risk to patients., (Copyright © 2021 Elsevier Inc., 3M Company. Published by Elsevier Inc. All rights reserved.)

Objectives: Bisphenol A (BPA) has been mentioned as a possible factor contributing to feline hyperthyroidism. Nevertheless, there are no previous studies reporting on the concentration of BPA in feline serum and its association with thyroid function. The objectives of this study were to measure serum BPA concentration in cats aged ⩾7 years, considered as healthy by their owners, and to compare the results with clinicopathological findings., Methods: Sixty-nine cats aged ⩾7 years considered as healthy by their owners were enrolled in the study. The concentration of BPA in feline serum was measured using liquid chromatography-tandem mass spectrometry. In all cats, signalment, living environment, diet history, and the results of haematological and biochemical analysis, including thyroxine levels, were available., Results: The mean serum BPA concentration in feline serum was 1.06 ± 0.908 ng/ml. Significant correlation was found between BPA concentration and haemoglobin ( r  = 0.3397; P  = 0.0043), haematocrit ( r  = 0.3245; P  = 0.0065) and the number of red blood cells ( r  = 0.2916; P  = 0.0151), concentration of total protein ( r  = 0.2383; P  = 0.0486), concentration of calcium ( r  = 0.3915; P  = 0.0009) and level of bilirubin ( r  = 0.3848; P  = 0.0011). No other significant correlations were found. Significant differences ( P <0.01) were found between mature (1.28 ± 0.994 ng/ml) and geriatric cats (0.420 ± 0.240 ng/ml), between strictly indoor cats (1.27 ± 0.992 ng/ml) and cats with outdoor access (0.660 ± 0.529 ng/ml), and between cats fed canned food (1.23 ± 0.935 ng/ml) and cats fed non-canned food (0.774 ± 0.795 ng/ml)., Conclusions and Relevance: Measurable serum BPA levels were found in all examined samples. The age of the cats was revealed as a significant factor affecting BPA concentration and mature cats had the highest levels. A significantly higher concentration of BPA was found in cats living strictly indoors and in cats fed canned food. No association was found between BPA and thyroid function. Further studies are needed that focus on hyperthyroid cats for better evaluation of this relationship.

Bisphenols (BPs) are commonly known plastifiers that are widely used in industry. The knowledge about the impact of BPs on thyroid function is scarce. Proper thyroid functioning is especially important for women of reproductive age, as hypothyroidism affects fertility, pregnancy outcomes and the offspring. There are no studies analyzing the influence of BPs on thyroid function and volume in non-pregnant young women. The aim of this cross-sectional study was to evaluate the relationship between bisphenol A and its 10 analogs (BPS, BPC, BPE, BPF, BPG, BPM, BPP, BPZ, BPFL, and BPBP) on thyroid function and volume in women of reproductive age. Inclusion criteria were: female sex, age 18-40 years. Exclusion criteria were history of any thyroid disease, pharmacotherapy influencing thyroid function, pregnancy or puerperium, and diagnosis of autoimmune thyroid disease during this study. Venous blood was drawn for measurement of thyrotropin (TSH), free thyroxine, thyroid peroxidase antibodies, thyroglobulin antibodies, BPs. Urine samples were analyzed for: ioduria and BPs. Ultrasound examination of thyroid gland was performed. One hundred eighty participants were included into the study. A negative correlation was found between urine BPC and the thyroid volume (R = -0.258; p = 0.0005). Patients with detected urine BPC presented smaller thyroid glands than those with not-detected urine BPC (p = 0.0008). A positive correlation was found between TSH and urine BPC (R = 0.228; p = 0.002). Patients with detected urine BPC presented higher concentrations of TSH versus those with not-detected urine BPC (p = 0.003). There were no relationships between any of serum BPs as well as the other urine BPs and thyroid function and its volume. The only BP that demonstrated the relationship between thyroid function and its volume was BPC, probably because of its chemical structure that most resembles thyroxine. Exposure to this BP may result in the development of hypothyroidism that could have a negative impact on pregnancy and the offspring., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Milczarek-Banach, Rachoń, Bednarczuk, Myśliwiec-Czajka, Wasik and Miśkiewicz.)

Due to structural similarity to bisphenol A and lack of safety data, the National Toxicology Program (NTP) is evaluating the potential toxicity of bisphenol AF (BPAF) in rodent models. The current investigation reports the internal exposure data for free (unconjugated BPAF) and total (free and conjugated forms) BPAF during critical stages of development following perinatal dietary exposure in Hsd:Sprague Dawley®SD® rats to 0 (vehicle control), 338, 1125, and 3750 ppm BPAF from gestation day (GD) 6 to postnatal day (PND) 28. Free and total BPAF concentrations in maternal plasma at GD 18, PND 4, and PND 28 increased with the exposure concentration; free BPAF concentrations were ≤ 1.61% those of total BPAF demonstrating extensive first pass metabolism of BPAF following dietary exposure in adults. Free and total BPAF were quantified in GD 18 fetuses and PND 4 pups with free concentrations 11.7-53.4% that of corresponding total concentrations. In addition, free concentrations were higher (130-571%) and total concentrations were lower (1.71-7.23%) than corresponding concentrations in dams, demonstrating either preferential transfer of free BPAF and/or inability of fetuses and pups to conjugate BPAF. Free and total concentrations in PND 28 pups were similar to maternal concentrations demonstrating direct exposure of pups via feed and that conjugating enzymes are developed in PND 28 pups. In conclusion, these data demonstrate considerable gestational and lactational transfer of parent aglycone from the mother to offspring. Since the ontogeny of conjugating enzymes in humans is similar to that of rodents, the data from rodent BPAF studies may be useful in predicting human risk from exposure to BPAF., (Published by Elsevier Inc.)

Bisphenols are important industrial raw materials that are widely used to produce plastic bottles (feeding bottles), infant cups, and food and beverage (milk powder) cans. Because of the estrogen-like effect of bisphenols, even low-dose intake of these compounds by trace migration affects normal hormone levels in the human body. Therefore, it is imperative to develop a rapid, accurate, and highly sensitive method for the determination of bisphenols in serum. In this study, methyl tert -butyl ether (MTBE) was used as the extraction solvent, and the liquid-liquid extraction pretreatment method was used for sample processing. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the simultaneous determination of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) at trace levels in infant serum. The important parameters affecting the extraction efficiency, such as the extraction solvent, extraction time, and extraction solvent volume for the four bisphenol environmental hormones were optimized. Serum samples were extracted by MTBE at 40℃ for 15 min. The target compounds were separated on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) using ultrapure water and methanol solution containing 0.5 mmol/L ammonium acetate as the mobile phases, with gradient elution at a flow rate of 0.2 mL/min. Finally, the analytes were analyzed by HPLC-MS/MS in the negative ion mode. BPA, BPB, and BPS showed good linearity in the range of 0.25-100 μg/L, while BPF showed good linearity in the range of 1-100 μg/L. The correlation coefficients were 0.9929-0.9959, and the limits of detection for BPA, BPB, BPS, and BPF were 0.05, 0.05, 0.05, 0.5 μg/L, respectively. At the three spiked levels (5, 20, 100 μg/L), the average recoveries of BPA, BPB, BPS, and BPF ranged from 84.56% to 104.43%, and the relative standard deviations were less than 10%. The proposed method was successfully applied to the determination of bisphenol contents in 150 infant serum samples. BPA was detected in most serum samples, and the detection rates in the serum of boys and girls were 90.67% and 89.33%, respectively. The detection rates of BPF in the serum of boys and girls were 6.67% and 1.33%, respectively; the corresponding values for BPS were 5.33% and 16.00%. BPB was not detected. The proposed method has the advantages of simple operation, good recovery, and high precision, and it is suitable for the simultaneous determination of the four bisphenol environmental hormones in infant serum.

Acteoside is one of the most widespread phenylethanoid glycosides with pharmacological activities, including antioxidant, neuroprotective property, etc. However, its bioavailability is poor due to the low absorption and P-gp efflux. This study aimed to select food derived P-gp inhibitors for promoting the acteoside absorption and investigate whether the inhibitors could increase the bioavailability and stability of acteoside. Results showed that EGCG and quercetin significantly decreased the BL-to-AP efflux and promoted the AP-to-BL influx of acteoside across Caco-2 monolayers with optimum concentrations of 320 μM EGCG or 240 μM quercetin adding to 320 μM acteoside. EGCG increased the bioavailability of acteoside to 1.43-fold, but quercetin had no such effect. Further study showed that EGCG and quercetin had no effects on the storage and digestion stability of acteoside. This work revealed that EGCG could improve the acteoside absorption across the Caco-2 monolayers and enhance the bioavailability of acteoside in rats., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition., Methods: Sesamol-PLGA (SM-PLGA) nanosuspension was developed  using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections., Results: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed., Conclusion: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition., Competing Interests: The authors report no conflicts of interest for this work., (© 2020 Gourishetti et al.)

Bisphenol S (BPS) is a component of polyether sulfone used in a variety of industrial applications and consumer products. We investigated the plasma toxicokinetic (TK) behavior of free (unconjugated parent) and total (parent and conjugated) BPS in rats and mice following a single gavage administration (34, 110, or 340 mg/kg). In male rats, BPS was rapidly absorbed with free BPS maximum concentration (C max ) reached at ≤2.27 h. Elimination of free BPS in male rats was dose-dependent with estimated half-lives of 5.77-11.9 h. C max and area under the concentration versus time curve (AUC) increased with dose although the increase in AUC was more than dose proportional. In male rats, total BPS C max was reached ≤2.77 h with both C max (≥ 10-fold) and AUC (≥ 15-fold) higher than free BPS demonstrating rapid and extensive conjugation of BPS. In male mice, the increase in C max and AUC of free BPS was dose-proportional; C max was higher and AUC was lower than in male rats. BPS was cleared more rapidly in male mice (half-life 2.86-4.21 h) compared to male rats (half-life 5.77-11.9 h). Similar to rats, total BPS C max (≥ 6-fold) and AUC (≥ 12-fold) were higher than corresponding free BPS. Oral bioavailability of free BPS was low to moderate (rats, ≤ 21%; mice, ≤ 19%). There were some species differences in TK parameters of free and total BPS and limited sex difference in rats and mice. In addition, there were dose-related effects of plasma TK parameters in rats., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Published by Elsevier Inc.)

Red raspberries (RRB) are high in anthocyanin- and ellagitannin- type (poly)phenols. This study aimed to investigate the effect of 4-week RRB supplementation on (poly)phenolic metabolism in adults with prediabetes and insulin-resistance (PreDM-IR); and whether adding fructo-oligosaccharides (FOS), prebiotics, would augment the microbial metabolites of RRB (poly)phenols. In a randomized crossover clinical trial, subjects (n = 35: PreDM-IR, n = 25; healthy Reference group, n = 10) consumed 1 cup RRB (fresh weight equivalence) per day and RRB with 8 g FOS per day each for 4 weeks in random order separated by 4-week washout. Plasma and urinary (poly)phenolic metabolites were characterized after (0-24h) consuming a RRB-based test drink (2 cups RRB) at baseline/week 0 and again after 4-week supplementations. A total of 123 (poly)phenolic metabolites were quantified. After 4-week RRB supplementation, several metabolite groups were significantly increased ( p < 0.05), including urolithins, phenyl-γ-valerolactones, and phenolic acids. Supplementing FOS with RRB for 4 weeks enhanced benzoic acid derivatives compared to the baseline ( p < 0.05). Specific effects of supplementation by metabolic status indicated 4-week RRB supplementation significantly increased microbial metabolites that were lower in PreDM-IR group. Our results suggest alterations in the capacity of PreDM-IR group to metabolize and render bioavailable raspberry-derived (poly)phenols when consumed regularly.

Highly stable symmetric and asymmetric squaraine fluorophores have been synthesized featuring an internal salt bridge between a quaternary ammonium cation and the central oxycyclobutenolate ring of the chromophore. Some of our newly synthesized symmetric and asymmetric compounds display increased molar absorptivity, quantum yield in serum, and thermal/photochemical stability over previously reported squaraine-based dyes. Consequently, both classes show great promise in resurfacing the normal environment-labile squaraine dyes as novel imaging agents and scaffolds for fluorescence sensing. Furthermore, incorporating a covalent attachment point away from the conjugated system allows for biological tagging applications without disturbing the optimum optical characteristics of the newly designed fluorophore.

Background: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood., Objective: To determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots., Methods: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested., Results: There were 179 differentially expressed genes (p adjusted  < 0.05, log 2 -fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways., Conclusion: Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel "signal-on" electrochemical aptasensor was developed for ultrasensitive and specific detection of BPA, using single-walled carbon nanotubes (SWCNT) as the electro-catalytic probe for further signal amplification. The multi-walled carbon nanotubes (MWCNT), amino-functionalized magnetite, and gold nanoparticles (NH 2 -Fe 3 O 4 /Au NPs) were applied first to modify the glassy carbon electrode (GCE) surface and to form a nanomaterial film with satisfactory conductive properties, stability, and biocompatibility. The BPA aptamer was then loaded onto the sensing platform by hybridization with complementary DNA (CDNA). In the presence of BPA it combines with the aptamer and the BPA-aptamer conjugate was released from the electrode;subsequently the added SWCNT and CDNA assembled quickly. Thus, the dual-amplification of the "signal-on" electrochemical aptasensor takes effect. The [Fe (CN) 6 ] 3-/4- redox probe signal (∆I) detected by DPV (differential pulse voltammetry) is proportional to the negative logarithm of BPA concentration between 10 -19  M and 10 -14  M. The detection limit is 0.08 aM. Importantly, the proposed biosensor represents a successful application for determination of BPA in human serum and lake water. Schematic representation of SWCNT-amplified "signal-on" electrochemical aptasensor for the detection of trace level of bisphenol A in human serum and lake water.

Xenometabolites from microbial and plant sources are thought to confer beneficial as well as deleterious effects on host physiology. Studies determining absorption and tissue uptake of xenometabolites are limited. We utilized a conscious catheterized pig model to evaluate interorgan flux of annotated known and suspected xenometabolites, derivatives, and bile acids. Female pigs ( n = 12, 2-3 mo old, 25.6 ± 2.2 kg) had surgically implanted catheters across portal-drained viscera (PDV), splanchnic compartment (SPL), liver, kidney, and hindquarter muscle. Overnight-fasted arterial and venous plasma was collected simultaneously in a conscious state and stored at -80°C. Thawed samples were analyzed by liquid chromatography-mass spectrometry. Plasma flow was determined with para-aminohippuric acid dilution technology and used to calculate net organ balance for each metabolite. Significant organ uptake or release was determined if net balance differed from zero. A total of 48 metabolites were identified in plasma, and 31 of these had at least one tissue with a significant net release or uptake. All bile acids, indole-3-acetic acid, indole-3-arylic acid, and hydrocinnamic acid were released from the intestine and taken up by the liver. Indole-3-carboxaldehyde, p-cresol glucuronide, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylglycine were also released from the intestines. Liver or kidney uptake was noted for indole-3-acetylglycine, p-cresol glucuronide, atrolactic acid, and dodecanedioic acid. Indole-3-carboxaldehyde, atrolactic acid, and dodecanedioic acids showed net release from skeletal muscle. The results confirm gastrointestinal origins for several known xenometabolites in an in vivo overnight-fasted conscious pig model, whereas nongut net release of other putative xenometabolites suggests a more complex metabolism. NEW & NOTEWORTHY Xenometabolites from microbe origins influence host health and disease, but absorption and tissue uptake of these metabolites remain speculative. Results herein are the first to demonstrate in vivo organ uptake and release of these metabolites. We used a conscious catheterized pig model to confirm gastrointestinal origins for several xenometabolites (e.g., indolic compounds, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylgycine). Liver and kidney were major sites for xenometabolite uptake, likely highlighting liver conjugation metabolism and renal excretion.

This study aimed to investigate the metabolic fate of bioactive components in watermelon and explore their effect on endothelial function. Six healthy overweight/obese (BMI: 28.7 ± 1.6 kg/m 2 ) adults received 100 kcal of watermelon flesh (WF), rind (WR), seeds (WS), or control meal. l-Citrulline, arginine, and (poly)phenolic metabolites were characterized in plasma over 24 h using UHPLC-MS. Endothelial function was assessed using a flow mediated dilation (FMD) technique over 7 h. Maximum concentration ( C max ) and area under the curve (AUC 0-8h ) of l-citrulline were significantly higher after WF- and WR-containing test meals compared to control ( p < 0.05). Likewise, several individual phenolic metabolites in plasma had significantly higher C max after WR, WF, or WS intake compared to control. FMD responses were not different among test meals. Our results provide insights on circulating metabolites from watermelon flesh, seed, and rind and lay the foundation for future clinical trials on vascular benefits of watermelon.

Previous studies highlighted bisphenol S (BPS), an industrial chemical responsible for harmful effects comparable to its congener substance bisphenol A (BPA). Accounted for various adversities to biological functions, it could alter the expression of endogenous metabolites in many metabolic processes. The study was aimed to investigate the altered metabolites in hyperglycemic condition triggered by sub-chronic exposure of BPS in serum and urine samples of Wistar rats. Invaded effects of hyperglycemia due to BPS exposure on Wistar rats were investigated by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Metabolomic profiling of serum and urinary metabolites was done by gas chromatography-mass spectrometry (GC-MS) analysis. The metabolomics data were represented by one way ANOVA, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) along with the mapping of perturbed metabolic pathways. The OGTT and ITT showed increased levels of glucose in treated animals with median and high doses, indicating the manifestation of hyperglycemia. The metabolomic profiling of serum and urine revealed BPS could cause consequential metabolomic perturbation mainly of amino acids, sugars, and organic acids. Furthermore, the extrapolation of Kyoto Encyclopedia of Genes and Genomes (KEGG) based systematic analysis helped to monitor the altered pathways, including amino acids, glycolysis, pyruvate metabolism, etc., which were provoked due to BPS exposure. The overview of the perturbed metabolite profiling in rats promisingly showed early diagnostic markers of hyperglycemic condition triggered due to the BPS exposure. Findings from this study will be helpful towards the exploration of mechanistic insights of several disturbed pathways., Competing Interests: Declaration of Competing Interest The authors have nothing to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85-115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex-related pharmacokinetics., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Prenatal exposures to phthalates and bisphenols are associated with impaired brain development in animals. However, epidemiological studies investigating the association between prenatal phthalate or bisphenol exposure and cognition have produced mixed findings and mostly had modest sample sizes and measured the exposure during the third trimester., Objective: We examined the association between pregnancy maternal urinary biomarkers of phthalate or bisphenol exposure and nonverbal intelligence quotient (IQ) in children 6 years of age., Method: The study sample consisted of 1,282 mother-child pairs participating in the Generation R Study, a population-based birth cohort in Rotterdam, Netherlands (enrollment 2002-2006). We measured maternal urinary concentrations of 18 phthalate metabolites and 8 bisphenols at < 18 , 18-25, and > 25  wks of gestation. Child nonverbal IQ was measured at 6 years of age using the Snijders-Oomen Nonverbal Intelligence Test-Revised. Linear regression models were fit for each of the three collection phases separately, the three collection phases jointly, and for the averaged prenatal exposure across pregnancy., Results: Higher urinary concentrations of phthalate metabolites during early pregnancy were associated with lower child nonverbal IQ score [e.g., B per 10-fold increase in summed low-molecular weight phthalates = - 1.7 (95% CI: - 3.1 , - 0.3 )]. This association remained unchanged when adjusted for mid and late pregnancy exposures. We also observed an inverse association between late pregnancy di- n -octyl phthalate (DNOP) exposure and nonverbal IQ. Maternal urinary concentrations of bisphenols were not associated with child nonverbal IQ. There was no effect estimate modification by sex., Conclusions: We did not observe that maternal biomarkers of bisphenol exposure are associated with nonverbal IQ. We found that phthalate exposure in early pregnancy and DNOP exposure in late pregnancy are associated with lower nonverbal IQ scores in children. Our results might suggest that particularly early pregnancy is a sensitive window of phthalate exposure, but future studies are needed to replicate our findings. https://doi.org/10.1289/EHP6047.

Purpose: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes., Methods: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol., Results: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002)., Conclusions: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Plant seeds have been found to contain bioactive compounds that have potential nutraceutical benefits. Guava seeds ( Psidium guajava ) are by-products in the beverage and juice industry; however, they can be utilized for a variety of commercial purposes. This study was designed to analyze the phytochemicals of the n -hexane extract of guava seed oil (GSO), to study its free-radical scavenging activity, and to monitor the changes in serum lipids and fatty acid profiles in rats that were fed GSO. The GSO was analyzed for phytochemicals using chromatographic methods. It was also tested for free-radical scavenging activity in hepatoma and neuroblastoma cells, and analyzed in terms of serum lipids and fatty acids. GSO was found to contain phenolic compounds (e.g., chlorogenic acid and its derivatives) and phytosterols (e.g., stimasterol, β-sitosterol and campesterol), and exerted radical-scavenging activity in cell cultures in a concentration-dependent manner. Long-term consumption of GSO did not increase cholesterol and triglyceride levels in rat serum, but it tended to decrease serum fatty acid levels in a concentration-dependent manner. This is the first study to report on the lipid, phytosterol and phenolic compositions, antioxidant activity, and the hepato- and neuro-protection of hydrogen peroxide-induced oxidative stress levels in the GSO extract.

Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

No-wash detection of small molecules in real samples has been attracting attention in the field of sensors including electroanalytical biosensors. Based on the direct electrochemical oxidation of fluorene-9-bisphenol (BHPF) on a CoN nanoarray electrode, we developed a ratiometric molecularly imprinted polymeric electrochemical (MIP-EC) sensor to realize no-wash detection of BHPF in serum and tap water. The CoN nanoarray in situ grown on carbon cloth (CC) served as the working electrode, which could load the electroactive toluidine blue (TB) and be modified by the MIPs. As the MIP concentration on the modified electrode surface was increased, the amount of BHPF exposed on the electrode surface increased and the amount of exposed TB decreased. Thus, the values of ΔI TB and ΔI BHPF decreased and increased, respectively, with an increasing amount of BHPF. Therefore, a ratiometric strategy was established by using the value of ΔI TB /ΔI BHPF as the instruction response to realize detection of BHPF with high sensitivity and reliability. The developed ratiometric MIP-EC sensor showed strong anti-interference ability, good detection reproducibility and stability towards no-wash detection of BHPF as shown from tests with real samples. This work can further provide theoretical and practical guidance for the detection of other familiar small molecules.

In this study, a novel LC-MS/MS method was designed using a simple extraction procedure that was scientifically developed to capture the most relevant bisphenol A (BPA) analogues (BPB, BPF, BPS, and BPAF) and parabens (propylparaben, ethylparaben, butylparaben, and methylparaben) in human plasma. The LC-MS/MS method was validated using US FDA guidelines, and all validation requirements were satisfactory. This is the method that allows for the detection of plasma bisphenols and parabens in one run and is also the fastest BPA analogue and paraben detection technique for human plasma. The method was used to analyze samples from 150 healthy volunteers from Malaysia who enrolled in the study. No BPB was detected in any of the volunteers; however, 99.3% were positive for BPF. Only 24% and 10.7% of volunteers were positive for BPAF and BPS, respectively. A high percentage of volunteers were negative for propylparaben, ethylparaben, butylparaben, and methylparaben (56%, 68%, 86.7%, and 83.3%, respectively). These results suggest that persons in Malaysia are exposed to different BPA analogues and parabens, from both the daily use of products (cosmetic and plastic products) and the environment., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Idha Arfianti Wiraagni et al.)

Atomoxetine is an approved medicine for attention-deficit/hyperactivity disorder and a cytochrome P450 2D6 (CYP2D6) probe substrate. Simple physiologically based pharmacokinetic (PBPK) models and compartment models were set up to account for drug monitoring results of 33 Japanese patients (6-15 years of age) to help establish the correct dosage for the evaluation of clinical outcomes. The steady-state one-point drug monitoring data for the most participants indicated the extensive biotransformation of atomoxetine to 4-hydroxyatomoxetine under individually prescribed doses of atomoxetine. However, 5 participants (with impaired CYP2D6 activity scores based on the CYP2D6 genotypes) showed high plasma concentrations of atomoxetine (0.53-1.5 μM) compared with those of total 4-hydroxyatomoxetine (0.49-1.4 μM). Results from full PBPK models using the in-built Japanese pediatric system of software Simcyp, one-compartment models, and new simple PBPK models (using parameters that reflected the subjects' small body size and normal/reduced CYP2D6-dependent clearance) could overlay one-point measured drug/metabolite plasma concentrations from almost common 28 participants within threefold ranges. Validated one-compartment or simple PBPK models can be used to predict steady-state plasma concentrations of atomoxetine and/or its primary metabolites in Japanese pediatric patients (>6 years) who took a variety of individualized doses in a clinical setting., (Copyright © 2019 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to examine the influence of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides, and their combination on the plasma metabolome of cats (Felis catus), including circulating microbiome-derived postbiotics. After a 14-day lead-in on the control food, cats were randomized to one of four foods (control, with 6.9% MCT, with fish oil [FO; 0.14% eicosapentaenoate, 1.0% docosahexaenoate], or with FO+MCT; n = 16 per group) for 28 days. Analysis of plasma metabolites showed that the addition of FO and MCT led to synergistic effects not seen with either alone across a number of lipid classes, including fatty acids, acylcarnitines, and acylated amines including endocannabinoids. Notably, the FO+MCT group had an increase in ketone body production relative to baseline and beyond that seen with MCT alone. N-acyl taurines, the accumulation of which has been implicated in the onset of type 2 diabetes, were significantly decreased in the FO+MCT group. Significant decreases in the gut microbiome-derived postbiotic classes of indoles/indolic sulfates and phenols/phenolic sulfates were observed only the FO+MCT group. Overall, the combination of MCT and FO led to number of changes in plasma metabolites that were not observed with either oil alone, particularly in postbiotics., Competing Interests: The study was funded by Hill’s Pet Nutrition, where both MIJ and DEJ were employees at the time of the study. The funder was given opportunity to read manuscript prior to publication but played no role in study design; collection, analysis, or interpretation of data; writing of the paper; and/or decision to submit for publication. This does not alter our adherence to PLOS ONE policies on sharing data and materials.