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Environmental Research Dec 2022Exposure to phenols and phthalates has been separately linked to increased risks of infertility in women of reproductive age. However, the combined effect of phenols and...
BACKGROUND
Exposure to phenols and phthalates has been separately linked to increased risks of infertility in women of reproductive age. However, the combined effect of phenols and phthalates exposure on infertility has not been explored.
METHODS
Data from the National Health and Nutrition Examination Surveys (NHANES) were used. A total of 857 women of reproductive age (18-45 years) with available information on urinary phenol and phthalate metabolites, reproductive questionnaires, and covariates were included in the present study. The definition of infertility was based on self-reports. Multivariable logistic regression, principal component analysis (PCA), and Bayesian kernel machine regression (BKMR) with stratified variable selection were applied to determine what associations were found between combined exposure to these mixtures and risk of infertility among women of reproductive age.
RESULTS
After adjusting for potential confounders, bisphenol A (BPA), mono(3-carboxypropyl) phthalate (MCPP) and four di(2-ethylhexyl) phthalate (DEHP) metabolites [mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)] were positively associated with infertility. PCA revealed that the DEHP-BPA factor's PC score was significantly positively related to the likelihood of infertility [adjusted odds ratio (aOR) = 1.45; 1.08, 1.82]. The DEHP-BPA component consistently had the highest group posterior inclusion probability (PIP) in BKMR models. The BKMR model also found that MEOHP, MEHHP, and BPA were positively associated with infertility risk when the remaining combination concentrations were held at their median values. In addition, we observed that the probability of infertility increased dramatically as the quantiles of total mixture concentration increased.
CONCLUSION
Our findings indicate that a combination of phenol and phthalate metabolites is linked to infertility among reproductive-age women. BPA and DEHP, in particular, are significantly related to the risk of infertility.
Topics: Adolescent; Adult; Bayes Theorem; Benzhydryl Compounds; Diethylhexyl Phthalate; Environmental Exposure; Environmental Pollutants; Female; Humans; Infertility; Middle Aged; Nutrition Surveys; Phenol; Phenols; Phthalic Acids; Young Adult
PubMed: 36058272
DOI: 10.1016/j.envres.2022.114244 -
Frontiers in Endocrinology 2022In standard 52-week phase III clinical trials, once weekly lonapegsomatropin, somatrogon and somapacitan have been found to yield non-inferior height velocities and... (Review)
Review
In standard 52-week phase III clinical trials, once weekly lonapegsomatropin, somatrogon and somapacitan have been found to yield non-inferior height velocities and similar safety profiles to daily GH (DGH) in children with pediatric growth hormone deficiency (PGHD). Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration (FDA) in August 2021 for the treatment of PGHD and has also been approved in other regions of the world. Somatrogon was approved for the treatment of PGHD beginning in some regions beginning in late 2021. Somapacitan was approved by the FDA for the treatment of Adult GHD in August 2020. The phase III clinical trial of somapacitan for the treatment of PGHD has been completed and demonstrated non-inferiority of somapacitan to DGH. New LAGH products may improve patient adherence, quality of life and clinical outcomes, particularly in patients with poor adherence to daily GH injections in the future. With the availability of new LAGH products, clinicians will need to identify the best candidates for LAGH therapy and understand how to monitor and adjust therapy. Long-term surveillance studies are needed to demonstrate adherence, efficacy, cost-effectiveness and safety of LAGH preparations and to understand how the non-physiological pharmacokinetic and pharmacodynamic profiles following administration of each LAGH product relate to short- and long-term safety and efficacy of LAGH therapy.
Topics: Adult; Child; Dwarfism, Pituitary; Growth Hormone; Histidine; Human Growth Hormone; Humans; Mannitol; Phenol; Quality of Life; United States
PubMed: 36072938
DOI: 10.3389/fendo.2022.980979 -
Signal Transduction and Targeted Therapy May 2020Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases,...
Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.
Topics: Animals; Bibenzyls; Calcium; Calcium Signaling; Calmodulin; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dendrobium; Female; Ferroptosis; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Proteins; Phenol; Plant Extracts
PubMed: 32382060
DOI: 10.1038/s41392-020-0149-3 -
The American Journal of Clinical... Jun 2023Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Evidence suggests that the intake of blueberry (poly)phenols is associated with improvements in vascular function and cognitive performance. Whether these cognitive effects are linked to increases in cerebral and vascular blood flow or changes in the gut microbiota is currently unknown.
METHODS
A double-blind, parallel randomized controlled trial was conducted in 61 healthy older individuals aged 65-80 y. Participants received either 26 g of freeze-dried wild blueberry (WBB) powder (302 mg anthocyanins) or a matched placebo (0 mg anthocyanins). Endothelial function measured by flow-mediated dilation (FMD), cognitive function, arterial stiffness, blood pressure (BP), cerebral blood flow (CBF), gut microbiome, and blood parameters were measured at baseline and 12 wk following daily consumption. Plasma and urinary (poly)phenol metabolites were analyzed using microelution solid-phase extraction coupled with liquid chromatography-mass spectrometry.
RESULTS
A significant increase in FMD and reduction in 24 h ambulatory systolic BP were found in the WBB group compared with the placebo group (0.86%; 95% CI: 0.56, 1.17, P < 0.001; -3.59 mmHg; 95% CI: -6.95, -0.23, P = 0.037; respectively). Enhanced immediate recall on the auditory verbal learning task, alongside better accuracy on a task-switch task was also found following WBB treatment compared with placebo (P < 0.05). Total 24 h urinary (poly)phenol excretion increased significantly in the WBB group compared with placebo. No changes in the CBF or gut microbiota composition were found.
CONCLUSIONS
Daily intake of WBB powder, equivalent to 178 g fresh weight, improves vascular and cognitive function and decreases 24 h ambulatory systolic BP in healthy older individuals. This suggests that WBB (poly)phenols may reduce future CVD risk in an older population and may improve episodic memory processes and executive functioning in older adults at risk for cognitive decline. Clinical Trial Registration number in clinicaltrials.gov: NCT04084457.
Topics: Humans; Aged; Anthocyanins; Blueberry Plants; Phenols; Phenol; Powders; Fruit; Cognition; Memory, Short-Term; Double-Blind Method
PubMed: 36972800
DOI: 10.1016/j.ajcnut.2023.03.017 -
Redox Biology Nov 2023Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are enzymes that generate superoxide anion (O•) and hydrogen peroxide (HO), and that are widely... (Review)
Review
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOXs) are enzymes that generate superoxide anion (O•) and hydrogen peroxide (HO), and that are widely distributed in mammalian tissues. Many bioactives, especially plant (poly)phenols are being studied for their capacity to regulate NOXs. The modulation of these enzymes are of central relevance to maintain redox homeostasis and regulate cell signaling. In in vitro and ex vivo assays, and in experimental animal models, different (poly)phenols are able to modulate NOX-dependent generation of O• and HO. Mechanistically, most of the known effects of (poly)phenols and of their metabolites on NOX1, NOX2, and NOX4, include the modulation of: i) the expression of the different constituent subunits, and/or ii) posttranslational modifications involved in the assembly and translocation of the protein complexes. Very limited evidence is available on a direct action of (poly)phenols on NOX active site (electron-transferring protein). Moreover, it is suggested that the regulation by (poly)phenols of systemic events, e.g. inflammation, is frequently associated with their capacity to regulate NOX activation. Although of physiological significance, more studies are needed to understand the specific targets/mechanisms of NOX regulation by (poly)phenols, and the (poly)phenol chemical structures and moieties directly involved in the observed effects. It should be kept in mind the difficulties of NOX's studies associated with the complexity of NOXs biochemistry and the methodological limitations of O• and HO the determinations. Studies relating human ingestion of specific (poly)phenols, with NOX activity and disease conditions, are guaranteed to better understand the health importance of (poly)phenol consumption and the involvement of NOXs as biological targets.
Topics: Animals; Humans; Reactive Oxygen Species; Phenols; Hydrogen Peroxide; Phenol; NADPH Oxidases; NADPH Oxidase 1; Mammals
PubMed: 37857000
DOI: 10.1016/j.redox.2023.102927 -
Current Pain and Headache Reports Mar 2021This review aims to provide relevant, aggregate information about a variety of disinfectants and antiseptics, along with potential utility and limitations. While not... (Review)
Review
PURPOSE OF REVIEW
This review aims to provide relevant, aggregate information about a variety of disinfectants and antiseptics, along with potential utility and limitations. While not exhaustive, this review's goal is to add to the body of literature available on this topic and give interventional providers and practitioners an additional resource to consider when performing procedures.
RECENT FINDINGS
In the current SARS-CoV2 epidemiological environment, infection control and costs associated with healthcare-associated infections (HAIs) are of paramount importance. Even before the onset of SARS-CoV2, HAIs affected nearly 2million patients a year in the USA and resulted in nearly 90,000 deaths, all of which resulted in a cost to hospitals ranging from US$28 billion to 45 billion. The onset SARS-CoV2, though not spread by an airborne route, has heightened infection control protocols in hospitals and, as such, cast a renewed focus on disinfectants and their utility across different settings and organisms. The aim of this review is to provide a comprehensive overview of disinfectants used in the inpatient setting.
Topics: Chlorine Compounds; Cross Infection; Disinfectants; Ethanol; Formaldehyde; Glutaral; Humans; Hydrogen Peroxide; Iodophors; Oxides; Peracetic Acid; Phenol; Povidone-Iodine; Quaternary Ammonium Compounds; Sodium Hypochlorite; Triazines
PubMed: 33693989
DOI: 10.1007/s11916-021-00938-3 -
Advances in Nutrition (Bethesda, Md.) Sep 2023Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as a cellular... (Review)
Review
Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as a cellular defense mechanism from acquiring potentially harmful genetic faults. However, recent studies highlight that senescent cells might also alter the local tissue environment and concur to chronic inflammation and cancer risk by secreting inflammatory and matrix remodeling factors, acquiring a senescence-associated secretory phenotype (SASP). Indeed, during aging and age-related diseases, senescent cells amass in mammalian tissues, likely contributing to the inevitable loss of tissue function as we age. Cellular senescence has thus become one potential target to tackle age-associated diseases as well as cancer development. One important aspect characterizing senescent cells is their telomere length. Telomeres shorten as a consequence of multiple cellular replications, gradually leading to permanent cell cycle arrest, known as replicative senescence. Interestingly, in the large majority of cancer cells, a senescence escape strategy is used and telomere length is maintained by telomerase, thus favoring cancer initiation and tumor survival. There is growing evidence showing how (poly)phenols can impact telomere maintenance through different molecular mechanisms depending on dose and cell phenotypes. Although normally, (poly)phenols maintain telomere length and support telomerase activity, in cancer cells this activity is negatively modulated, thus accelerating telomere attrition and promoting cancer cell death. Some (poly)phenols have also been shown to exert senolytic activity, thus suggesting both antiaging (directly eliminating senescent cells) and anticancer (indirectly, via SASP inhibition) potentials. In this review, we analyze selective (poly)phenol mechanisms in senescent and cancer cells to discriminate between in vitro and in vivo evidence and human applications considering (poly)phenol bioavailability, the influence of the gut microbiota, and their dose-response effects.
Topics: Animals; Humans; Telomerase; Phenols; Cell Survival; Phenol; Aging; Neoplasms; Cell Proliferation; Mammals
PubMed: 37271484
DOI: 10.1016/j.advnut.2023.05.014 -
Environment International Nov 2022Pregnant women are simultaneously exposed to several non-persistent endocrine-disrupting chemicals, which may influence the risk of childhood obesity and cardiovascular...
BACKGROUND
Pregnant women are simultaneously exposed to several non-persistent endocrine-disrupting chemicals, which may influence the risk of childhood obesity and cardiovascular diseases later in life. Previous prospective studies have mostly examined single-chemical effects, with inconsistent findings. We assessed the association between prenatal exposure to phthalates and phenols, individually and as a mixture, and body mass index (BMI) and blood pressure (BP) in preadolescents.
METHODS
We used data from the Spanish INMA birth cohort study (n = 1,015), where the 1st and 3rd- trimester maternal urinary concentrations of eight phthalate metabolites and six phenols were quantified. At 11 years of age, we calculated BMI z-scores and measured systolic and diastolic BP. We estimated individual chemical effects with linear mixed models and joint effects of the chemical mixture with hierarchical Bayesian kernel machine regression (BKMR). Analyses were stratified by sex and by puberty status.
RESULTS
In single-exposure models, benzophenone-3 (BP3) was nonmonotonically associated with higher BMI z-score (e.g. Quartile (Q) 3: β = 0.23 [95% CI = 0.03, 0.44] vs Q1) and higher diastolic BP (Q2: β = 1.27 [0.00, 2.53] mmHg vs Q1). Methyl paraben (MEPA) was associated with lower systolic BP (Q4: β = -1.67 [-3.31, -0.04] mmHg vs Q1). No consistent associations were observed for the other compounds. Results from the BKMR confirmed the single-exposure results and showed similar patterns of associations, with BP3 having the highest importance in the mixture models, especially among preadolescents who reached puberty status. No overall mixture effect was found, except for a tendency of higher BMI z-score and lower systolic BP in girls.
CONCLUSIONS
Prenatal exposure to UV-filter BP3 may be associated with higher BMI and diastolic BP during preadolescence, but there is little evidence for an overall phthalate and phenol mixture effect.
Topics: Bayes Theorem; Blood Pressure; Body Mass Index; Child; Cohort Studies; Environmental Pollutants; Female; Humans; Parabens; Pediatric Obesity; Phenol; Phenols; Phthalic Acids; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 36126421
DOI: 10.1016/j.envint.2022.107527 -
FEMS Microbiology Reviews Jul 2014Phenol-soluble modulins (PSMs) are a recently discovered family of amphipathic, alpha-helical peptides that have multiple roles in staphylococcal pathogenesis and... (Review)
Review
Phenol-soluble modulins (PSMs) are a recently discovered family of amphipathic, alpha-helical peptides that have multiple roles in staphylococcal pathogenesis and contribute to a large extent to the pathogenic success of virulent staphylococci, such as Staphylococcus aureus. PSMs may cause lysis of many human cell types including leukocytes and erythrocytes, stimulate inflammatory responses, and contribute to biofilm development. PSMs appear to have an original role in the commensal lifestyle of staphylococci, where they facilitate growth and spreading on epithelial surfaces. Aggressive, cytolytic PSMs seem to have evolved from that original role and are mainly expressed in highly virulent S. aureus. Here, we will review the biochemistry, genetics, and role of PSMs in the commensal and pathogenic lifestyles of staphylococci, discuss how diversification of PSMs defines the aggressiveness of staphylococcal species, and evaluate potential avenues to target PSMs for drug development against staphylococcal infections.
Topics: Bacterial Proteins; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Immunologic Factors; Phenol; Protein Transport; Staphylococcus aureus; Virulence Factors
PubMed: 24372362
DOI: 10.1111/1574-6976.12057 -
Physical Chemistry Chemical Physics :... Nov 2022Halogenated groups are relevant in pharmaceutical applications and potentially useful spectroscopic probes for infrared spectroscopy. In this work, the structural...
Halogenated groups are relevant in pharmaceutical applications and potentially useful spectroscopic probes for infrared spectroscopy. In this work, the structural dynamics and infrared spectroscopy of -fluorophenol (F-PhOH) and phenol (PhOH) is investigated in the gas phase and in water using a combination of experiment and molecular dynamics (MD) simulations. The gas phase and solvent dynamics around F-PhOH and PhOH is characterized from atomistic simulations using empirical energy functions with point charges or multipoles for the electrostatics, Machine Learning (ML) based parametrizations and with full (QM) and mixed Quantum Mechanical/Molecular Mechanics (QM/MM) simulations with a particular focus on the CF- and OH-stretch region. The CF-stretch band is heavily mixed with other modes whereas the OH-stretch in solution displays a characteristic high-frequency peak around 3600 cm most likely associated with the -OH group of PhOH and F-PhOH together with a characteristic progression below 3000 cm due to coupling with water modes which is also reproduced by several of the simulations. Solvent and radial distribution functions indicate that the CF-site is largely hydrophobic except for simulations using point charges which renders them unsuited for correctly describing hydration and dynamics around fluorinated sites. The hydrophobic character of the CF-group is particularly relevant for applications in pharmaceutical chemistry with a focus on local hydration and interaction with the surrounding protein.
Topics: Quantum Theory; Phenols; Spectrophotometry, Infrared; Water; Solvents; Phenol
PubMed: 36268728
DOI: 10.1039/d2cp02857c