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BMC Public Health Feb 2024Recent studies suggested inconclusive associations between bisphenols exposure and hyperuricemia risk. Our objective was to assess the potential association of bisphenol...
Bisphenol A and its alternatives bisphenol S and F exposure with serum uric acid levels, hyperuricemia, and gout prevalence among US adults: a nationally representative cross-sectional study.
BACKGROUND
Recent studies suggested inconclusive associations between bisphenols exposure and hyperuricemia risk. Our objective was to assess the potential association of bisphenol A (BPA) and its substitutes bisphenol S and F (BPS and BPF) exposure with serum uric acid (SUA) levels, hyperuricemia, and gout prevalence among US adults within the NHANES 2013-2016 datasets.
METHODS
Multivariable linear and logistic regression models were used to explore the associations of urinary bisphenols concentrations with SUA levels, hyperuricemia, and gout prevalence, in total population and different sex groups. The restricted cubic spline (RCS) model was used to explore the dose-response relationship.
RESULTS
In total population, doubling of urinary BPS and ∑BPs concentrations showed associations with an increase of 2.64 μmol/L (95% CI: 0.54, 4.74) and 3.29 μmol/L (95% CI: 0.59, 5.99) in SUA levels, respectively. The RCS model indicated a significantly "J"-shaped dose-response relationship between BPS exposure and SUA levels. Compared to the reference group of urinary BPS, males in the highest quartile displayed a 13.06 μmol/L (95% CI: 0.75, 25.37) rise in SUA levels. For females, doubling of urinary BPS concentrations was associated with a 3.30 μmol/L (95% CI: 0.53, 6.07) increase in SUA levels, with a significant linear dose-response relationship. In total population, doubling of urinary BPA concentrations showed a 1.05-fold (95% CI: 0.97, 1.14) adjusted risk of having hyperuricemia, with an inverted "U" curve. Doubling of urinary ∑BPs concentrations was associated with a 1.05-fold (95% CI: 0.96, 1.14) adjusted risk of hyperuricemia in total population, with a significant monotonic dose-response relationship. In females, doubling of urinary BPS concentrations was associated with a 1.45-fold (95% CI: 1.01, 2.08) adjusted increased risk of having gout, with a "J" shaped relationship.
CONCLUSIONS
BPA and BPS exposure to some extent were associated with elevated SUA levels and increased risk of hyperuricemia, with different dose-response relationships and sex differences.
Topics: Adult; Humans; Male; Female; Hyperuricemia; Uric Acid; Cross-Sectional Studies; Prevalence; Nutrition Surveys; Gout; Benzhydryl Compounds; Phenols; Sulfones
PubMed: 38317153
DOI: 10.1186/s12889-024-17883-6 -
Electrophoresis Aug 2023In order to accelerate Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), here we propose an optimized version of the technique enabled by...
In order to accelerate Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), here we propose an optimized version of the technique enabled by experimental tuning reinforced by theoretical description. In the resulting system, the gel buffer was diluted twofold and supplemented with glycine at a low concentration, whereas a higher voltage was applied. This approach reduced runtime from 90 to 18 min. It is important to emphasize that, despite the high voltage applied to the gel, the resolution of the bands did not decrease compared to the original Laemmli method. The proposed acceleration approach can be used in other variants of SDS-PAGE.
Topics: Proteins; Sodium Dodecyl Sulfate; Electrophoresis, Polyacrylamide Gel; Glycine
PubMed: 37075472
DOI: 10.1002/elps.202300011 -
Life Sciences Nov 2023The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF).
AIMS
The purpose of this study was to evaluate the role of the NLRP3-inflammasome in heart failure with preserved ejection fraction (HFpEF).
MAIN METHODS
Serum inflammatory cytokines were detected in patients with heart failure. Correlation analysis was performed to investigate the relationship between serum inflammatory cytokines and left ventricular diastolic function. A 'two-hit' (metabolic stress and mechanical stress) mouse model of HFpEF was established. Furthermore, MCC950 was used to determine the role of NLRP3-inflammasome inhibition in cardiac and pulmonary artery remodelling in HFpEF mice.
KEY FINDINGS
Compared with heart failure patients with reduced ejection fraction, patients with HFpEF have significantly elevated serum inflammatory cytokine levels. Serum NLRP3 and interleukin-1β levels were positively correlated with the diastolic function of HFpEF. In the HFpEF mouse model, the inhibition of the NLRP3-inflammasome by MCC950 improved exercise intolerance, glucose intolerance, and left ventricular diastolic function, but had no significant effect on systolic function. Meanwhile, MCC950 attenuated the release of inflammatory cytokines, cardiomyocyte hypertrophy and cardiac fibrosis. Mechanistically, the potential protective effects of MCC950 are achieved by inhibiting activation of the NLRP3-IL-1β pathway and cascade expansion of downstream inflammatory cytokines. Additionally, the inhibition of NLRP3-inflammasome by MCC950 reduced pulmonary artery pressure and improved pulmonary artery remodelling in HFpEF.
SIGNIFICANCE
The NLRP3-inflammasome plays a considerable role in inflammation and cardiac and pulmonary artery remodelling in HFpEF by activating the cascade reaction of inflammatory cytokines. This study is the first to comprehensively elucidate the role of the NLRP3-inflammasome in HFpEF, and will provide reference for future study.
Topics: Humans; Mice; Animals; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Heart Failure; Sulfones; Stroke Volume; Pulmonary Artery; Sulfonamides; Disease Models, Animal; Cytokines
PubMed: 37858713
DOI: 10.1016/j.lfs.2023.122185 -
Current Problems in Cardiology Nov 2023Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing... (Meta-Analysis)
Meta-Analysis Review
Despite potential advantages of torsemide over furosemide, <10% of the patients with heart failure (HF) are on torsemide in clinical practice. Prior studies comparing furosemide to torsemide in patients with HF have shown conflicting findings, regarding hospitalizations and mortality. We aimed to pool all the studies conducted to date and provide the most updated and comprehensive evidence, regarding the effect of furosemide vs torsemide in reducing mortality and hospitalizations in patients with HF. We conducted a comprehensive literature search of the PubMed/Medline, Cochrane Library and Scopus from inception till June 2023, for randomized and nonrandomized studies comparing furosemide to torsemide in adult patients (>18 years) with acute or chronic HF. Data about all-cause mortality, HF-related hospitalizations and all-cause hospitalizations was extracted, pooled, and analyzed. Forest plots were created based on the random effects model. A total of 17 studies (n = 11,996 patients) were included in our analysis with a median follow-up time of 8 months. Our pooled analysis demonstrated no difference in all-cause mortality between furosemide and torsemide groups in HF patients (OR = 0.98, 95% CI: 0.75-1.29, P = 0.89). However, torsemide was associated with a significantly lesser incidence of HF-related hospitalizations (OR = 0.73, 95% CI: 0.54-0.99, P = 0.04), and all-cause hospitalizations (OR = 0.84, 95% CI: 0.73-0.98, P = 0.03), as compared to furosemide. Torsemide significantly reduces HF-related and all-cause hospitalizations as compared to furosemide, with no difference in mortality. We recommend transitioning from furosemide to torsemide in HF patients who are not attaining symptomatic control.
Topics: Adult; Humans; Furosemide; Torsemide; Sodium Potassium Chloride Symporter Inhibitors; Heart Failure; Hospitalization
PubMed: 37453532
DOI: 10.1016/j.cpcardiol.2023.101927 -
Environment International Nov 2023Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further...
BACKGROUND
Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation.
METHODS
Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice.
RESULTS
The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was -2.47 (95 % CI: -3.89, -1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P < 0.001) in the target quadrant, as observed from morris water maze (MWM) test. The protein expression of brain-derived neurotrophic factor (BDNF) and growth associated protein-43 (GAP-43) levels were decreased, as compared to control (0.367-fold, P < 0.001; 0.366-fold, P < 0.001; respectively). We also observed the upregulation of dopamine transporter (DAT) (2.940-fold, P < 0.001) consistent with the trend of dopamine content (1.313-fold, P < 0.001) in the hippocampus.
CONCLUSION
Early life exposure to F-53B is associated with adverse neurobehavioral changes in developing children and weaning mice which may be modulated by dopamine-dependent synaptic plasticity.
Topics: Humans; Pregnancy; Child; Female; Animals; Mice; Alkanesulfonates; Alkanesulfonic Acids; Dopamine; Weaning; Zebrafish; Water Pollutants, Chemical; Fluorocarbons; Placenta
PubMed: 37890264
DOI: 10.1016/j.envint.2023.108272 -
Environment International Jan 2024Micro/nanoplastics (MNP) are ubiquitous in the environment and multiple living organisms. The toxicity of some common types of MNP, e.g., polyethersulfone (PES) MNP,... (Comparative Study)
Comparative Study
Micro/nanoplastics (MNP) are ubiquitous in the environment and multiple living organisms. The toxicity of some common types of MNP, e.g., polyethersulfone (PES) MNP, remains poorly understood. Multi-omics approaches were used in this study to determine the effects of foodborne and airborne PES MNP on liver and lung, respectively. Foodborne MNP were capable of inducing gut microbial dysbiosis, gut and serum metabolic disruption, and liver transcriptomic dysregulation, and affecting serum antioxidant activity and liver function, resulting in liver injury. As for the airborne MNP, they were found to induce nasal and lung microbial dysbiosis, serum and lung metabolic disruption, and liver transcriptome disturbance, and cause disrupted serum antioxidant activity and lung injury. Foodborne and airborne PES NP were found to respectively induce greater liver and lung toxicity than MP, which could be associated with the differences between NP and MP exposures. The relevant results suggest that foodborne PES MNP could disrupt the "gut microbiota-gut-liver" axis and induce hepatic injury, while airborne PES MNP could affect the "airborne microbiota-lung" axis and cause lung injury. The findings could benefit the diagnoses of liver and lung injury respectively induced by foodborne and airborne PES MNP, as well as the proper use of PES in human living environment.
Topics: Animals; Humans; Mice; Antioxidants; Dysbiosis; Liver; Lung Injury; Microplastics; Plastics; Polymers; Sulfones
PubMed: 38043322
DOI: 10.1016/j.envint.2023.108350 -
Environmental Research Aug 2023Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health...
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) are ubiquitous, environmentally persistent chemicals, and prenatal exposures have been associated with adverse child health outcomes. Prenatal PFAS exposure may lead to epigenetic age acceleration (EAA), defined as the discrepancy between an individual's chronologic and epigenetic or biological age.
OBJECTIVES
We estimated associations of maternal serum PFAS concentrations with EAA in umbilical cord blood DNA methylation using linear regression, and a multivariable exposure-response function of the PFAS mixture using Bayesian kernel machine regression.
METHODS
Five PFAS were quantified in maternal serum (median: 27 weeks of gestation) among 577 mother-infant dyads from a prospective cohort. Cord blood DNA methylation data were assessed with the Illumina HumanMethylation450 array. EAA was calculated as the residuals from regressing gestational age on epigenetic age, calculated using a cord-blood specific epigenetic clock. Linear regression tested for associations between each maternal PFAS concentration with EAA. Bayesian kernel machine regression with hierarchical selection estimated an exposure-response function for the PFAS mixture.
RESULTS
In single pollutant models we observed an inverse relationship between perfluorodecanoate (PFDA) and EAA (-0.148 weeks per log-unit increase, 95% CI: -0.283, -0.013). Mixture analysis with hierarchical selection between perfluoroalkyl carboxylates and sulfonates indicated the carboxylates had the highest group posterior inclusion probability (PIP), or relative importance. Within this group, PFDA had the highest conditional PIP. Univariate predictor-response functions indicated PFDA and perfluorononanoate were inversely associated with EAA, while perfluorohexane sulfonate had a positive association with EAA.
CONCLUSIONS
Maternal mid-pregnancy serum concentrations of PFDA were negatively associated with EAA in cord blood, suggesting a pathway by which prenatal PFAS exposures may affect infant development. No significant associations were observed with other PFAS. Mixture models suggested opposite directions of association between perfluoroalkyl sulfonates and carboxylates. Future studies are needed to determine the importance of neonatal EAA for later child health outcomes.
Topics: Infant; Infant, Newborn; Pregnancy; Child; Female; Humans; Fetal Blood; Prenatal Exposure Delayed Effects; Prospective Studies; Bayes Theorem; Environmental Pollutants; Fluorocarbons; Alkanesulfonates; Mothers; Carboxylic Acids; Epigenesis, Genetic; Alkanesulfonic Acids
PubMed: 37224946
DOI: 10.1016/j.envres.2023.116215 -
Legal Medicine (Tokyo, Japan) Nov 2023Fenthion (MPP) is a popular organophosphorus pesticide that acts via inhibition of the enzyme cholinesterase. It is well known that fenthion is metabolized by plants,...
Fenthion (MPP) is a popular organophosphorus pesticide that acts via inhibition of the enzyme cholinesterase. It is well known that fenthion is metabolized by plants, animals and soil microorganisms to sulfone and sulfoxide by oxidation of thioether and is further metabolized by conversion of P = S to P = O (oxon). Although human fenthion poisonings sometimes occur, details of the distribution of fenthion and its metabolites within the bodies of victims are unclear. In this study, we developed and validated an approach that uses liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify the concentrations of fenthion and its five metabolites (MPP-sulfoxide, MPP-sulfone, MPP-oxon, MPP-oxon sulfoxide and MPP-oxon sulfone) in the fluids [blood, cerebral spinal fluid (CSF) and urine] of a human cadaver. The calibration curves were linear in the concentration range 5-200 ng/mL. Our method allowed for repeatable and accurate quantification with intra- and inter-assay coefficients of variation smaller than 8.6% and 11.0%, respectively, for each target compound. We used the developed method to measure the fenthion concentration in the blood of a dead victim of fenthion poisoning and found the concentration to be in the comatose-fatal range. In addition, we detected for the first time fenthion and all five fenthion metabolites in the cadaveric blood and CSF. The concentrations of the oxidized forms of fenthion, including MPP-sulfone and MPP-sulfoxide, were higher in CSF than in the blood.
Topics: Animals; Humans; Fenthion; Pesticides; Organophosphorus Compounds; Sulfoxides; Sulfones
PubMed: 37742496
DOI: 10.1016/j.legalmed.2023.102323 -
Investigative Ophthalmology & Visual... Nov 2023The proliferative and neurogenic potential of retinal Müller glia after injury varies widely across species. To identify the endogenous mechanisms regulating the...
PURPOSE
The proliferative and neurogenic potential of retinal Müller glia after injury varies widely across species. To identify the endogenous mechanisms regulating the proliferative response of mammalian Müller glia, we comparatively analyzed the expression and function of nestin, an intermediate filament protein established as a neural stem cell marker, in the mouse and rat retinas after injury.
METHODS
Nestin expression in the retinas of C57BL/6 mice and Wistar rats after methyl methanesulfonate (MMS)-induced photoreceptor injury was examined by immunofluorescence and Western blotting. Adeno-associated virus (AAV)-delivered control and nestin short hairpin RNA (shRNA) were intravitreally injected to rats and Müller glia proliferation after MMS-induced injury was analyzed by BrdU incorporation and immunofluorescence. Photoreceptor removal and microglia/macrophage infiltration were also analyzed by immunofluorescence.
RESULTS
Rat Müller glia re-entered the cell cycle and robustly upregulated nestin after injury whereas Müller glia proliferation and nestin upregulation were not observed in mice. In vivo knockdown of nestin in the rat retinas inhibited Müller glia proliferation while transiently stimulating microglia/macrophage infiltration and phagocytic removal of dead photoreceptors.
CONCLUSIONS
Our findings suggest a critical role for nestin in the regulation of Müller glia proliferation after retinal injury and highlight the importance of cross species analysis to identify the molecular mechanisms regulating the injury responses of the mammalian retina.
Topics: Animals; Mice; Rats; Cell Proliferation; Eye Injuries; Methyl Methanesulfonate; Mice, Inbred C57BL; Nestin; Rats, Wistar; Neuroglia
PubMed: 37934159
DOI: 10.1167/iovs.64.14.8 -
High Altitude Medicine & Biology Mar 2024Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. .... (Review)
Review
Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. . 25:16-25, 2024. High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.
Topics: Humans; Sildenafil Citrate; Altitude; Altitude Sickness; Hypoxia; Hypertension, Pulmonary
PubMed: 37751174
DOI: 10.1089/ham.2022.0043