Trimester-specific effect of maternal co-exposure to organophosphate esters and phthalates on preschooler cognitive development: The moderating role of gestational vitamin D status.

Organophosphate esters (OPEs) and phthalate acid esters (PAEs) are prevalent endocrine-disrupting chemicals (EDCs). Humans are often exposed to OPEs and PAEs simultaneously through multiple routes. Given that fetal stage is a critical period for neurodevelopment, it is necessary to know whether gestational co-exposure to OPEs and PAEs affects fetal neurodevelopment. However, accessible epidemiological studies are limited. The present study included 2, 120 pregnant women from the Ma'anshan Birth Cohort (MABC) study. The concentrations of tris (2-chloroethyl) phosphate (TCEP), 6 OPE metabolites and 7 PAE metabolites were measured in the first, second and third trimester using ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS). Cognitive development of preschooler was assessed based on the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV) of the Chinese version. Generalized estimating equations (GEEs), restricted cubic spline (RCS) and generalized additive models (GAMs) were employed to explore the associations between individual OPE exposure and preschooler cognitive development. The quantile-based g-computation (QGC) method was used to estimate the joint effect of PAEs and OPEs exposure on cognitive development. GEEs revealed significant adverse associations between diphenyl phosphate (DPHP) (ß: -0.58, 95% CI: -1.14, -0.01), bis (2-butoxyethyl) phosphate(BBOEP) (ß: -0.44, 95% CI: -0.85, -0.02), bis(1-chloro-2-propyl) phosphate (BCIPP) (ß: -0.81, 95%CI: -1.43, -0.20) and full-scale intelligence quotient (FSIQ) in the first trimester; additionally, TCEP and bis(2-ethylhexyl) phosphate (BEHP) in the second trimester, as well as DPHP in the third trimester, were negatively associated with cognitive development. Through the QGC analyses, mixture exposure in the first trimester was negatively associated with FSIQ scores (ß: -1.70, 95% CI: -3.06, -0.34), mono-butyl phthalate (MBP), BCIPP, and DPHP might be the dominant contributors after controlling for other OPEs and PAEs congeners. Additionally, the effect of OPEs and PAEs mixture on cognitive development might be driven by vitamin D deficiency.

Maternal prednisone exposure during pregnancy elevates susceptibility to osteoporosis in female offspring: The role of mitophagy/FNDC5 alteration in skeletal muscle.

Maternal exposure to glucocorticoids has been associated with adverse outcomes in offspring. However, the consequences and mechanisms of gestational exposure to prednisone on susceptibility to osteoporosis in the offspring remain unclear. Here, we found that gestational prednisone exposure enhanced susceptibility to osteoporosis in adult mouse offspring. In a further exploration of myogenic mechanisms, results showed that gestational prednisone exposure down-regulated FNDC5/irisin protein expression and activation of OPTN-dependent mitophagy in skeletal muscle of adult offspring. Additional experiments elucidated that activated mitophagy significantly inhibited the expression of FNDC5/irisin in skeletal muscle cells. Likewise, we observed delayed fetal bone development, downregulated FNDC5/irisin expression, and activated mitophagy in fetal skeletal muscle upon gestational prednisone exposure. In addition, an elevated total m6A level was observed in fetal skeletal muscle after gestational prednisone exposure. Finally, gestational supplementation with S-adenosylhomocysteine (SAH), an inhibitor of m6A activity, attenuated mitophagy and restored FNDC5/irisin expression in fetal skeletal muscle, which in turn reversed fetal bone development. Overall, these data indicate that gestational prednisone exposure increases m6A modification, activates mitophagy, and decreases FNDC5/irisin expression in skeletal muscle, thus elevating osteoporosis susceptibility in adult offspring. Our results provide a new perspective on the earlier prevention and treatment of fetal-derived osteoporosis.

Subchronic exposure to di-(2-ethylhexyl) phthalate (DEHP) elicits blood-brain barrier dysfunction and neuroinflammation in male C57BL/6J mice.

BACKGROUND: Exposure to di-(2-ethylhexyl) phthalate (DEHP) can cause neurotoxicity but the mechanism is not clear. Blood brain barrier (BBB) is one of the most important tissues to protect the brain. However, whether DEHP can disrupt the BBB or not remains unclear. The objective of this study is to investigate the potential effects of subchronic DEHP exposure on BBB integrity and discuss the role of BBB in DEHP inducible neurotoxicity with an emphasis on neuroinflammatory responses. Male adult C57BL/6J mice were orally administered with vehicle or 200 or 750 mg/kg/day DEHP for 90 days. Subchronic exposure to high-dose DEHP increased water intake but decreased body weight and brain weight. The concentrations of DEHP metabolites increased in serum from all DEHP-exposed groups while increased in brain only from the high-dose group. DEHP induced neurobehavioural alterations and damaged hippocampal neurons. DEHP increased BBB permeability by Evans blue (EB) extravasation and decreased tight junction proteins (ZO-1, occludin, and claudin-5) while presenting a neuroinflammatory feature characterized by the upregulated inflammatory mediators TNF-α and the NLRP3/caspase-1/IL-1ß inflammasome pathway. Our data provide new insights into neurotoxicity caused by subchronic DEHP exposure, which is probably involved in BBB dysfunction and neuroinflammatory responses.

Identification and prediction model of placenta-brain axis genes associated with neurodevelopmental delay in moderate and late preterm children.

BACKGROUND: Moderate and late preterm (MLPT) birth accounts for the vast majority of preterm births, which is a global public health problem. The association between MLPT and neurobehavioral developmental delays in children and the underlying biological mechanisms need to be further revealed. The "placenta-brain axis" (PBA) provides a new perspective for gene regulation and risk prediction of neurodevelopmental delays in MLPT children. METHODS: The authors performed multivariate logistic regression models between MLPT and children's neurodevelopmental outcomes, using data from 129 MLPT infants and 3136 full-term controls from the Ma'anshan Birth Cohort (MABC). Furthermore, the authors identified the abnormally regulated PBA-related genes in MLPT placenta by bioinformatics analysis of RNA-seq data and RT-qPCR verification on independent samples. Finally, the authors established the prediction model of neurodevelopmental delay in children with MLPT using multiple machine learning models. RESULTS: The authors found an increased risk of neurodevelopmental delay in children with MLPT at 6 months, 18 months, and 48 months, especially in boys. Further verification showed that APOE and CST3 genes were significantly correlated with the developmental levels of gross-motor domain, fine-motor domain, and personal social domain in 6-month-old male MLPT children. CONCLUSIONS: These findings suggested that there was a sex-specific association between MLPT and neurodevelopmental delays. Moreover, APOE and CST3 were identified as placental biomarkers. The results provided guidance for the etiology investigation, risk prediction, and early intervention of neurodevelopmental delays in children with MLPT.

Identification of novel cell-free RNAs in maternal plasma as preterm biomarkers in combination with placental RNA profiles.

BACKGROUND: Preterm birth (PTB) is the main driver of newborn deaths. The identification of pregnancies at risk of PTB remains challenging, as the incomplete understanding of molecular mechanisms associated with PTB. Although several transcriptome studies have been done on the placenta and plasma from PTB women, a comprehensive description of the RNA profiles from plasma and placenta associated with PTB remains lacking. METHODS: Candidate markers with consistent trends in the placenta and plasma were identified by implementing differential expression analysis using placental tissue and maternal plasma RNA-seq datasets, and then validated by RT-qPCR in an independent cohort. In combination with bioinformatics analysis tools, we set up two protein-protein interaction networks of the significant PTB-related modules. The support vector machine (SVM) model was used to verify the prediction potential of cell free RNAs (cfRNAs) in plasma for PTB and late PTB. RESULTS: We identified 15 genes with consistent regulatory trends in placenta and plasma of PTB while the full term birth (FTB) acts as a control. Subsequently, we verified seven cfRNAs in an independent cohort by RT-qPCR in maternal plasma. The cfRNA ARHGEF28 showed consistence in the experimental validation and performed excellently in prediction of PTB in the model. The AUC achieved 0.990 for whole PTB and 0.986 for late PTB. CONCLUSIONS: In a comparison of PTB versus FTB, the combined investigation of placental and plasma RNA profiles has shown a further understanding of the mechanism of PTB. Then, the cfRNA identified has the capacity of predicting whole PTB and late PTB.

Urinary antibiotic exposure and low grip strength risk in community-dwelling elderly Chinese by gender and age.

Emerging studies have shown that environmental contaminants were related to decreased handgrip strength. Nevertheless, no prior research has investigated the relationship of exposure to environmental antibiotics with grip strength. Thus, we explored the relationship between urinary antibiotic burden and grip strength among the elderly in China. This study consisted of 451 men and 539 women from the baseline survey of a cohort study. Commonly used antibiotics for humans and animals were detected in 990 urine samples through a biomonitoring method. Grip strength was measured by an electronic dynamometer. We examined the associations of antibiotic exposure with low grip strength (LGS), grip strength, and grip strength index, respectively. Results suggested that 34.9% of participants developed LGS, and 93.0% of individuals were exposed to 1-10 antibiotics. Among women, oxytetracycline (Quartile 2: odds ratio: 2.97, 95% confidence interval: 1.36-6.50), florfenicol (Quartile 3: 2.60 [1.28-5.27]), fluoroquinolones (Quartile 4: 1.88 [1.07-3.30]), and chloramphenicols (Quartile 3: 2.73 [1.35-5.51]) could enhance LGS risk. Among men, ofloxacin (Quartile 2: 3.32 [1.45-7.59]) increased LGS risk, whereas tetracycline (Quartile 2: 0.31 [0.11-0.88]) was implicated in reduced LGS risk. In participants < 70 years, ofloxacin (Quartile 2: 3.00 [1.40-6.42]) could increase LGS risk. For participants who were 70 years of age or older, veterinary antibiotics (Quartile 3: 1.73 [1.02-2.94]) were linked to a 73% increased risk of LGS. Our findings suggested that antibiotics mainly pertained to LGS, and there were gender and age disparities in associations between antibiotic exposure and muscle strength indicators in the elderly Chinese population.

Association Between the Ratios of Selenium to Several Elements and Mild Cognitive Impairment in the Elderly.

To investigate the relationship between the correlation ratios of selenium (Se) and other elements and mild cognitive impairment (MCI) among older adults. A total of 1000 individuals participated in our research analysis. The concentrations of elements in whole blood were determined using inductively coupled plasma mass spectrometry to reflect their exposure levels. Participants' cognitive function was assessed using the Mini-Mental State Examination. Logistic regression analysis was used to evaluate the relationship between elemental ratios and MCI. Se concentration was positively correlated with red blood cell count (r = 0.219, p < 0.001), haemoglobin level (r = 0.355, p < 0.001), haematocrit (r = 0.215, p < 0.001), mean corpuscular haemoglobin (r = 0.294, p < 0.001) and mean corpuscular haemoglobin concentration (r = 0.428, p < 0.001) and negatively correlated with red cell volume distribution width-standard deviation (r = -0.232, p < 0.001) and platelet distribution width (r = -0.382, p < 0.001). Compared with the normal group, the ratios of Se/vanadium (V), Se/lead (Pb) and Se/cadmium (Cd) in the whole blood of the MCI group were significantly lower (all p < 0.001), while the ratios of manganese (Mn)/Se and iron (Fe)/Se were higher (all p < 0.001). The increase in the ratios of Se/V, Se/Pb and Se/Cd is related to a decreased risk of MCI among older adults; contrarily, an increase in the ratios of Mn/Se and Fe/Se may be a risk factor for MCI.

Combined effects of prenatal phthalate exposure on cardiometabolic risk score among 4- to 7-year-old children: MABC study.

There is currently no consensus about the impact of prenatal phthalate exposure on blood pressure and glycolipids in children. Few studies consider the health effects as an integrated indicator. The combined effect of multiple phthalate exposures is often ignored. Based on the Ma'anshan Birth Cohort, 2298 woman-child pairs were included in this study. Maternal urine was collected in each trimester to analyze 6 phthalate metabolites. The overall cardiometabolic risk (CMR) score was calculated based on serum glycolipids and blood pressure for children aged 4-7 years. A higher score represents a less favorable CMR profile. The restricted cubic spline model was used to explore the relationship between prenatal phthalate exposure and childhood CMR score. In addition, the quantile g-computation and the Bayesian kernel machine regression were used to evaluate the combined effect. The MBP exposure in the 1st trimester (MBP-1st) and the MEP-2nd were non-linearly associated with the CMR score (Fnonlinear = 3.28 and 5.60, Pnonlinear = 0.0378 and 0.0038, respectively). The MBP-3rd (Flinear = 5.31, Plinear = 0.0012) and the ∑LMWP-3rd (Flinear = 4.37, Plinear = 0.0045) were negatively associated with the score in a linear manner. The phthalate mixture in the 2nd trimester increased the score (psil = 0.1747, 95% CI = 0.0077-0.3416), with the MEP being the most common [weights = 0.5290; posterior inclusion probability (PIP) = 0.40]. The phthalate mixture in the 3rd trimester decreased the score (psil = -0.2024, 95% CI = -0.4097－0.0048), with the MEHP (weights = -0.5101; PIP = 0.14) and the MBP (weights = -0.3993, PIP = 1.00) being the greatest contributors. In conclusion, the MBP-1st and the MEP-2nd are non-linearly associated with the cardiometabolic risk in children. The MBP-3rd and the ∑LMWP-3rd decrease the childhood risk. The combined exposure to phthalate mixture in the second and third trimester elevates and decreases the risk of childhood cardiometabolism, respectively.

Ginsenoside-Rg1 mitigates cardiac arrest-induced cognitive damage by modulating neuroinflammation and hippocampal plasticity.

Ginsenoside-Rg1 can effectively ameliorate mental disorders, but whether ginsenoside-Rg1 plays a neuroprotective role in cardiac arrest and cardiopulmonary resuscitation (CA/CPR)-induced cognitive impairment remains unclear. In this study, a 5-min asphyxia-based CA/CPR rat model was established to explore the mechanisms underlying the effects of ginsenoside-Rg1 (40 mg·kg-1·d-1, ip, 14 days) on its cognitive alterations. These CA/CPR rats displayed spatial learning and memory impairment in the Morris water maze, as reflected in the compromised basal synaptic transmission and long-term potentiation (LTP) at the Schaffer collateral of hippocampal CA1 area in vivo electrophysiology, whereas the ginsenoside-Rg1 remarkably mitigated these alterations. Next, we found that ginsenoside-Rg1 inhibited hippocampal neuroinflammation by alleviating the CA/CPR-induced hippocampal activation of microglia and astrocytes and the overexpression of related proinflammatory cytokines interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α). In addition, ginsenoside-Rg1 improved CA/CPR-induced hippocampal neuronal apoptosis, dendritic spines and synaptic ultrastructure defects as associated with the upregulation of the key synaptic regulatory proteins. Furthermore, ginsenoside-Rg1 could ameliorate CA/CPR-induced aberrant expression of the key regulators of hippocampal glutamate signaling pathways, excitatory amino acid transporter 2 (EAAT2), excitatory amino acid transporter 1 (EAAT1), Glutamine Synthetase (GS), GluN2B, and glutamate. In conclusion, ginsenoside-Rg1 exerts its neuroprotective effects by ameliorating hippocampus-dependent neuroglia activation-mediated neuroinflammation and neuroplasticity deficits, shedding new light on the therapeutic intervention of CA/CPR-related cognitive disorders.

Associations Between Mild Cognitive Impairment and Whole Blood Zinc and Selenium in the Elderly Cohort.

Some studies have shown that an imbalance in trace element homeostasis can lead to cognitive dysfunction, but data are lacking. The purpose of this study was to investigate the association between whole blood zinc (Zn), selenium (Se), copper-zinc ratio (Cu/Zn), copper-selenium ratio (Cu/Se), and zinc-selenium ratio (Zn/Se) and mild cognitive impairment (MCI) in elderly Chinese individuals. The study was based on the Elderly Health and Controlled Environmental Factors Cohort in Lu'an, Anhui Province, China, from June to September 2016. The cognitive function of the elderly was determined by the Mini-Mental State Examination (MMSE) and activities of daily living (ADL) scales. The concentrations of Zn, Cu, and Se in the whole blood were measured by inductively coupled plasma-mass spectrometry (ICP-MS). Binary logistic regression was used to analyze the associations between trace elements and MCI. A total of 1006 participants with an average age of 71.70 years old were included in this study. Compared with healthy people, MCI patients had higher whole blood Zn levels and lower Se levels, and Cu/Zn, Cu/Se, and Zn/Se were also significantly different. Binary logistic regression analysis showed that Zn, Cu/Se, and Zn/Se exposure in the third tertile was associated with an increased risk of MCI, while Se exposure in the third tertile was associated with a reduced risk of MCI. After adjustment for sex, age, marital status, BMI, and living status, whole blood Zn, Se, Cu/Zn, Cu/Se, and Zn/Se were significantly associated with MCI risk, especially in elderly women.

National temporal trend for organophosphate pesticide DDT exposure and associations with chronic kidney disease using age-adapted eGFR model.

Whilst certain environmental organochlorine pesticide exposure may still pose significant burden, the associations between dichloro-diphenyl-trichloroethane (DDT) and chronic kidney disease (CKD) remain disputable notwithstanding the potentially inaccurate disease definition between age groups. National DDT exposure burden atlas was depicted from 92,061 participants by measuring their serum concentrations of DDT congeners and major metabolite in the US from 1999 to 2016. Temporal analyses of these toxicant exposure suggested that although serum DDT concentrations exhibited recent decline, the detection rates remain up to 99.8% every year, posing great concern for exposure risk. A total of 3,039 US adults were further included from these participants demonstrating the weighted CKD prevalence of 40.2% using the new age-adapted CKD-EPI40 model compared to 28.0% using the current CKD-EPI method. After adjustment for covariates, logistic regression model results showed individual metabolites and total DDT burden were positively, yet monotonically, associated with risk of CKD incidence (P-trend for all < 0.05), particularly among adults 40 years of age and older. Much heightened renal disease risk was also observed with high DDT exposure (OR, 1.55; 95 % CI, 1.11-2.15) in those who were hypertensive (P for heterogeneity < 0.001) but not with diabetes. The current high DDT exposure risk combined with elevated probability for CKD incidence call for health concerns and management for the environmentally persistent pollutants.

Short-term effects of personal exposure to temperature variability on cardiorespiratory health based on subclinical non-invasive biomarkers.

Growing literatures have explored the cardiorespiratory health effects of the daily temperature, but such effects of temperature variability remain unclear. We investigated the acute associations of personal levels of temperature variability with cardiorespiratory biomarkers. This is a panel study with four repeated measurements among forty eligible college students in Hefei, Anhui Province, China. We collected personal-level temperature data using temperature/humidity data loggers. Temperature variability parameters included diurnal temperature range (DTR), the standard-deviation of temperature (SDT) and temperature variability (TV). Cardiorespiratory health indicators included three BP parameters [systolic BP (SBP), diastolic BP (DBP) and mean article pressure (MAP)], fractional exhaled nitric oxide (FeNO), and four saliva biomarkers [C-reactive protein (CRP), cortisol, alpha-amylase and lysozyme]. Linear mixed-effect models were then used to assess the associations of temperature variability with these cardiorespiratory biomarkers. We found that short-term exposure to the three temperature variability parameters was associated with these cardiorespiratory biomarkers. The magnitude, direction and significance of these associations varied by temperature variability parameters, by biomarkers and by lags of exposure. Specifically, temperature variability parameters were inversely associated with BP and saliva lysozyme; positively associated with airway inflammation biomarkers (FeNO and saliva CRP) and stress response biomarkers (saliva cortisol and alpha-amylase). The results were robust to further control for air pollutants, and these associations were more prominent in females and in subjects with abnormal body mass index. Our findings suggested that acute exposure to temperature variability could significantly alter cardiorespiratory biomarker profiles among healthy young adults in China.

Associations of typical antibiotic residues with elderly blood lipids and dyslipidemia in West Anhui, China.

Growing evidence has indicated the association of clinical antibiotic use with abnormal blood lipid levels; however, no epidemiological study has examined the relationship of antibiotic exposure, probably derived from food chains, with blood lipid levels. This study investigated the relationships of urinary antibiotic levels with blood lipid levels and dyslipidemias in the older population. Baseline data of 960 participants from the Cohort of Elderly Health and Environment Controllable Factors were used in the present study. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was performed to detect antibiotic residues in the urine samples of the participants. Our findings revealed that each 1 µg/g increase in enrofloxacin and ciprofloxacin levels was associated with an increase of 0.084 (95 % confidence interval (CI): 0.030, 0.139) and 0.049 (95 % CI: 0.012, 0.086) in triglyceride levels, respectively. Enrofloxacin was associated with an increased risk of hypertriglyceridemia. Each 1 µg/g increase in the enrofloxacin level corresponded to an increase of 0.052 (95 % CI: 0.006, 0.098) in the low-density lipoprotein cholesterol level. Furthermore, florfenicol exposure increased the risks of both hyperbetalipoproteinemia and hypoalphalipoproteinemia. By contrast, each 1 µg/g increase in sulfaclozine and doxycycline levels was associated with a - 0.062 (95 % CI: -0.111, -0.020), and - 0.083 (95 % CI: -0.160, -0.007) decrease in total cholesterol levels, respectively. Sulfaclozine was closely related to a decreased risk of hypercholesterolemia. Stratification analysis revealed specific differences in the correlation between antibiotic exposure and lipid levels based on the waist circumference (WC) values of the participants. Except for sulfaclozine and doxycycline, other antibiotics exerted adverse effects on lipid levels and increased dyslipidemia prevalence. The older participants with higher WC values were vulnerable to antibiotic exposure. Therefore, an appropriate understanding of the epidemiological attributes of antibiotic residues is indispensable to prevent abdominal obesity in the older population.

Relationship of individual and mixed prenatal phthalate exposure with placental structure and efficiency in the prospective Ma'anshan Birth Cohort Study.

BACKGROUND: Few studies have investigated the associations between prenatal phthalate exposure and placental structure and function with inconsistent conclusions. METHODS: Nested on the Ma'anshan Birth Cohort study, 2723 women provided spot urine samples during the first, second and third trimesters of pregnancy to analyze six phthalate metabolites. The outcomes of interest were placental weight, efficiency (birth weight/placental weight), chorionic disc area and disc eccentricity. The relationships of prenatal exposure to a single phthalate with placental measures were analyzed. The associations between prenatal phthalate mixture exposure and placental measures were also evaluated. RESULTS: Most phthalate metabolites were significantly associated with placental weight, efficiency and chorionic disc area during the whole gestation and in each trimester of pregnancy, with different directions of relationships. Sensitivity analyses revealed similar findings, indicating the robustness of the statistical results. Furthermore, inverted U-shaped nonlinear relationships of prenatal exposure to some phthalate metabolites with placental weight, efficiency and chorionic plate area were observed. However, quantile g-computation mixture models did not reveal any association between maternal combined exposure to the total phthalate metabolites and placental measures. CONCLUSIONS: Maternal exposure to most phthalates and their metabolites was associated with placental weight, efficiency and chorionic plate area in both a linear manner and an inverted U-shaped nonlinear manner. However, the mixture of multiple phthalate metabolites was not observed to be associated with any placental measure.

Antibiotics in elderly Chinese population and their relations with hypertension and pulse pressure.

Although antibiotic exposure in the general population has been well documented by a biomonitoring approach, epidemiologic data on the relationships between urinary antibiotic burden in the elderly with blood pressure (BP) are still lacking. The current study revealed thirty-four antibiotics in urine specimens from 990 elderly patients in Lu'an City, China, with detection frequencies ranging from 0.2 to 35.5%. Among the elderly, the prevalence of hypertension was 72.0%, and 12 antibiotics were detected in more than 10% of individuals with hypertension. The elderly with hypertension had the maximum daily exposure (5450.45 µg/kg/day) to fluoroquinolones (FQs). Multiple linear regression analyses revealed significant associations of BP and pulse pressure (PP) with exposure to specific antibiotics. The estimated ß values (95% confidence interval) of associations with systolic blood pressure (SBP) in the right arm were 4.42 (1.15, 7.69) for FQs, 4.26 (0.52, 8.01) for the preferred as human antibiotics (PHAs), and 3.48 (0.20, 6.77) for the mixtures (FQs + tetracyclines [TCs] (tertile 3 vs. tertile 1)), respectively. Increased concentrations of TCs were associated with decreased diastolic BP (DBP; tertile 3: -1.75 [-3.39, -0.12]) for the right arm. Higher levels of FQs (tertile 3: 4.28 [1.02, 7.54]), PHAs (tertile 3: 4.25 [0.49, 8.01]), and FQs + TCs (tertile 3: 3.99 [0.71, 7.26]) were associated with increased SBP, and an increase in DBP for FQs (tertile 3: 1.82 [0.22, 3.42]) was shown in the left arm. Also, higher urinary concentrations of FQs (tertile 3: 3.18 [0.53, 5.82]), PHAs (tertile 3: 3.42 [0.40, 6.45]), and FQs + TCs (tertile 3: 3.06 [0.40, 5.72]) were related to increased PP, whereas a decline in PP for TCs (tertile 2: -2.93 [-5.60, -0.25]) in the right arm. And increased concentrations of penicillin V (tertile 3: 5.31 [1.53, 9.10]) and FQs + TCs (tertile 3: 2.84 [0.19, 5.49]) were related to higher PP in the left arm. By utilizing restricted cubic splines, our current study revealed a potential nonlinear dose-response association between FQ exposure and hypertension risk. In conclusion, this investigation is the first to present antibiotic exposure using a biomonitoring approach, and informs understanding of impacts of antibiotic residues, as emerging hazardous pollutants, on the hypertension risk in the elderly.

Typical antibiotic exposure and dysglycemia risk in an elderly Chinese population.

Studies examined the connection between antibiotic exposure in urine and dysglycemia risk (including prediabetes and diabetes) in the elderly were limited. Multiple linear regression, binary logistic regression, restricted cubic splines (RCS), and stratified analysis were applied to analyze the relationship between antibiotic exposure and dysglycemia risk. We observed that sulfaclozine exposure 0.07 (95% confidence interval [CI]: 0.01-0.23) significantly increased fasting blood glucose (FBG) level. By mechanism, usage, and antimicrobial action, sulfonamides 0.08 (95% CI: 0.06-0.36), veterinary antibiotics (VA) 0.07 (95% CI: 0.01-0.30), or bacteriostatic antibiotics 0.07 (95% CI: 0.02-0.29) significantly increased FBG level. Additionally, sulfaclozine exposure 1.54 (95% CI: 1.02-2.33) resulted in a higher dysglycemia risk, while doxycycline exposure 0.53 (95% CI: 0.30-0.95) resulted in a lower dysglycemia risk. By mechanism, usage, and antimicrobial action, sulfonamides 1.44 (95% CI: 1.02-2.04), VA 1.68 (95% CI: 1.21-2.35), or bacteriostatic antibiotics 1.40 (95% CI: 1.02-1.93) exposure had a higher dysglycemia risk. Taken together, exposure to sulfonamides, VA, especially sulfaclozine, was correlated with a higher dysglycemia risk in the elderly. Exposure to bacteriostatic antibiotics was associated with a higher dysglycemia risk in the female.

Maternal exposure to bis(2-ethylhexyl) phthalate during the thyroid hormone-dependent stage induces persistent emotional and cognitive impairment in middle-aged offspring mice.

Prenatal DEHP exposure can cause offspring neurodevelopmental toxicity, but the persistent effects of such exposure window are unclear. This study aimed to investigate the lasting neurobehavioral impact of DEHP on offspring following early exposure from GD9.5 (fetal neural tube closure) to GD16.5 (fetal thyroxin, TH, synthesis). Data showed maternal exposure to DEHP during the thyroid hormone-dependent stage induced a range of neurobehavioral phenotypic changes in adult and middle-aged mice, including anxiety, depression and cognitive impairment. Significant reductions in free TH, TH transporters, and TH metabolic enzyme deiodinase II (D2) were observed in the fetal brain, whereas D3 was elevated, indicating that TH signaling disruption was caused by in utero exposure. Gene expression analyses suggested the expression levels of the TH receptors Trα1, Trß1 and their downstream target, brain-derived neurotrophic factor, were significantly attenuated, which may partially explain the mechanisms of neurodevelopmental impairment. This study provides new evidence of the persistent effects of sex-specific neurodevelopmental impairment due to in utero DEHP exposure, possibly through damage to the fetal brain TH signaling systems that causes lifelong brain damage. These results further suggest a profound neurobehavioral toxicity of DEHP that may be programmed during early developmental stage exposure and manifested later in life.

Chronic inflammation as a potential mediator between phthalate exposure and depressive symptoms.

BACKGROUND: A few studies have reported phthalate exposure as a risk factor for depressive symptoms, but the results have been inconsistent. Whether chronic inflammation mediates the relationship between phthalates (PAEs) and depressive symptoms remains unclear. In this study, we establish mediating models of inflammatory factors and explore the mediating role of chronic inflammation in the association between PAEs exposure and depressive symptoms. METHODS: The sample included 989 participants from the Study on Health and Environment of the Elderly in Lu'an City, Anhui Province. Geriatric depression scale (GDS-30) was used to screen depressive symptoms of the elderly. The levels of seven kinds of PAEs in urine samples and four inflammatory factors in serum of the elderly were measured. To establish the mediating effect of inflammatory factors to explore the potential effect of PAEs exposure on the increased odds of depressive symptoms. RESULTS: Adjusted for multiple variables, the highest tertiles of Mono (2-ethylhexyl) phthalate (MEHP) (95%CI = 1.051-2.112), Mono benzyl phthalate (MBzP) (95%CI = 1.016-2.082) and Mono butyl phthalate (MBP) (95%CI = 1.102-2.262) were positively correlated with depressive symptoms. The mediating effect of IL-6 and generalized inflammation factor between MEHP exposure and depressive symptoms were 15.96% (95%CI=0.0288-0.1971) and 14.25% (95%CI = 0.0167-0.1899). CONCLUSIONS: High levels of MEHP, MBzP and MBP increased the odds of depressive symptoms in the elderly, and chronic inflammation had a partial mediating effect on the increased odds of depressive symptoms due to MEHP exposure.

Di (2-ethyl-hexyl) phthalate disrupts placental growth in a dual blocking mode.

Di (2-ethyl-hexyl) phthalate (DEHP) is a widely used plasticizer. Maternal DEHP exposure inhibits cell proliferation and reduces placentas size, which associates with fetal growth restriction and adulthood diseases. However, the mechanism of placental cell proliferation inhibition by DEHP remains elusive. This study investigated the effect of DEHP on placental cell proliferation from cell cycle arrest. Utilizing in vitro and in vivo experiments, we investigated cell cycle arrest, DNA double-strand break (DSB) repair, genotoxic stress response, and micronuclei formation. Most DEHP metabolizes to mono (2-Ethylhexyl) phthalate (MEHP) and distributes to organs quickly, so MEHP and DEHP were used in cultured cell and animal experiments, respectively. Here, a double blocking mode for the proliferation inhibition of the placental cell was revealed. One is that the classical DSB repair pathways were suppressed, which arrested the cell cycle at the G2/M phase. The other is that DEHP stimulated an elevated level of progesterone, which blocked the cell cycle at metaphase by disrupting chromosome arrangement. These two sets of events facilitated micronuclei formation and resulted in cell proliferation inhibition. This findings provide a novel mechanistic understanding for DEHP to inhibit placental cell proliferation.

Rhizoma drynariae total flavonoids inhibit the inflammatory response and matrix degeneration via MAPK pathway in a rat degenerative cervical intervertebral disc model.

Rhizoma drynariae total flavonoids (RDTF) are extracted from Drynaria fortunei J. Sm (D. fortunei), which was a Chinese herb commonly used to treat fractures and bruises. Modern pharmacological studies indicate flavonoids have anti-inflammatory effect in clinical practice. However, its active ingredients and the mechanisms of action are far from clear. The present study aims to determine whether RDTF can protect against intervertebral disc degeneration in a rat cervical intervertebral disc model and investigate the associated molecular mechanisms. Sprague Dawley (SD) rats were randomized into five groups: control group (CG, n = 8), intervertebral disc degeneration group (NG, n = 8), low-dose RDTF-treated group (LG, n = 8), medium-dose RDTF-treated group (MG, n = 8), and high-dose RDTF-treated group (HG, n = 8). Hematoxylin and eosin (HE) staining, immunohistochemistry (IHC), immunofluorescence, ELISA, Western blot and quantitative real time PCR (qRT-PCR) assays were used to investigate inflammatory, catabolic factors and the latent regulatory mechanism of the effects of RDTF on intervertebral disc cells. HE staining showed disc degeneration in all groups except CG, and the function was restored after RDTF treatment. IHC, Western blot, qRT-PCR, immunofluorescence and ELISA results showed that RDTF prevented intervertebral disc degeneration by suppressing mitogen-activated protein kinase (MAPK) pathway, which reduced expression of intracellular matrix metalloproteinases (MMPs), such MMP3, MMP13, and inflammatory factors including interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α). Notably RDTF inhibited extracellular matrix (ECM) degeneration by increasing expression of aggrecan and collagen type II and preventing the upregulation of collagen type I and III. It suggests that RDTF has a potential therapeutic effect on cervical spondylosis.