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Nature Communications Sep 2020Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Mimicry of this homopolymer self-assembly using...
Natural biomolecules such as peptides and DNA can dynamically self-organize into diverse hierarchical structures. Mimicry of this homopolymer self-assembly using synthetic systems has remained limited but would be advantageous for the design of adaptive bio/nanomaterials. Here, we report both experiments and simulations on the dynamic network self-assembly and subsequent collapse of the synthetic homopolymer poly(propylene sulfone). The assembly is directed by dynamic noncovalent sulfone-sulfone bonds that are susceptible to solvent polarity. The hydration history, specified by the stepwise increase in water ratio within lower polarity water-miscible solvents like dimethylsulfoxide, controls the homopolymer assembly into crystalline frameworks or uniform nanostructured hydrogels of spherical, vesicular, or cylindrical morphologies. These electrostatic hydrogels have a high affinity for a wide range of organic solutes, achieving >95% encapsulation efficiency for hydrophilic small molecules and biologics. This system validates sulfone-sulfone bonding for dynamic self-assembly, presenting a robust platform for controllable gelation, nanofabrication, and molecular encapsulation.
Topics: Alkenes; Hydrogels; Hydrophobic and Hydrophilic Interactions; Polypropylenes; Static Electricity; Sulfones
PubMed: 32994414
DOI: 10.1038/s41467-020-18657-5 -
Cell Biology and Toxicology Apr 2021Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal...
BACKGROUND
Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders. It was also suggested that MSM might play a beneficial role in cancer treatment.
PURPOSE
So far, the MSM might have a potentially beneficial effect in endometrial cancer (EC) treatment.
STUDY DESIGN
This study evaluated the effect and usefulness of MSM in combinatory therapy with known drug doxorubicin (DOX).
METHODS
The effect of combinational treatment of MSM and DOX on the induction of apoptosis was evaluated in EC cell lines (ISHIKAWA, MFE-296, MFE-280).
RESULTS
We observed that MSM itself induces apoptosis in EC cell lines, and pre-treatment with MSM for 24 h increases the sensitivity of EC cells to DOX-induced apoptosis and DNA damage and that effect might be regulated by p42/44 (Erk1/2) MAPK and Akt (protein kinase B).
CONCLUSION
These results for the first time show that MSM might act as a sensitizer of EC cells to known drugs, for which EC cells quickly acquire resistance. Graphical abstract.
Topics: Apoptosis; Cell Line, Tumor; Cell Survival; Dimethyl Sulfoxide; Doxorubicin; Endometrial Neoplasms; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mitogen-Activated Protein Kinase 3; Poly(ADP-ribose) Polymerases; Proto-Oncogene Proteins c-akt; Sulfones; Superoxide Dismutase
PubMed: 32562081
DOI: 10.1007/s10565-020-09542-4 -
Frontiers in Public Health 2024To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices.
OBJECTIVE
To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices.
METHODS
Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism.
RESULTS
The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend ( < 0.001), whereas insulin levels demonstrated a downward linear trend ( = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: = 0.059, < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin = -0.194, < 0.001, HOMA-IR = -0.132, = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin = 0.191, = 0.018, HOMA-IR = 0.220, = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS.
CONCLUSION
Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.
Topics: Humans; Middle Aged; Environmental Pollutants; Nutrition Surveys; Bayes Theorem; Fluorocarbons; Alkanesulfonates; Glucose; Insulins; Caprylates; Fatty Acids; Sulfonic Acids
PubMed: 38633237
DOI: 10.3389/fpubh.2024.1370971 -
Chemosphere Sep 2007Polychlorinated biphenyls (PCBs) were commercially produced between 1959 and 1984 in eastern Slovakia. Improper handling led to a highly contaminated local environment...
Polychlorinated biphenyls (PCBs) were commercially produced between 1959 and 1984 in eastern Slovakia. Improper handling led to a highly contaminated local environment and high levels of PCBs in humans and wildlife in the Michalovce area. The aim of this study was to analyse serum for methylsulfonyl metabolites of PCB (MeSO(2)-PCBs) and DDE (3-MeSO(2)-DDE) in serum samples from pregnant women and in a selected number of paired cord blood samples to assess maternal sulfone levels and patterns, and transplacental transfer of these metabolites. The donating women were from two districts in eastern Slovakia. A liquid-liquid extraction method together with separation of substance groups and further clean-up on silica gel columns were applied prior to analysis by gas chromatography/mass spectrometry. 3-MeSO(2)-DDE was the major methyl sulfone in most of the samples followed by a yet not identified MeSO(2)-hexaCB, 4'-MeSO(2)-CB101, 4'-MeSO(2)-CB87 and 4-MeSO(2)-CB149. The women from the contaminated area had three times higher concentrations of the MeSO(2)-PCBs than women from the reference area. This is the first report on methyl sulfone metabolites of PCB and DDE in human cord serum. It is shown that these metabolites are transported through the placenta. The levels of MeSO(2)-PCBs in the maternal serum were about 1.5 times higher than in the corresponding cord serum on a lipid weight basis. For 3-MeSO(2)-DDE, the levels were about the same in maternal and cord serum. The difference in the maternal:cord ratio, comparing MeSO(2)-PCBs with 3-MeSO(2)-DDE might be due to differences in transport through the placenta caused by their different affinities for lipoproteins and plasma proteins.
Topics: Cohort Studies; Dimethyl Sulfoxide; Female; Fetal Blood; Gas Chromatography-Mass Spectrometry; Humans; Polychlorinated Biphenyls; Pregnancy; Slovakia; Sulfones
PubMed: 17574648
DOI: 10.1016/j.chemosphere.2007.04.081 -
The Science of the Total Environment May 2024No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims...
BACKGROUND
No study has examined the association between per- and polyfluoroalkyl substances (PFAS) exposure and chronic obstructive pulmonary disease (COPD) risk. This study aims to explore this relationship.
METHODS
This study enrolled 4541 individuals who had available data on PFAS, COPD, and covariates from NHANES 2007-2018. Serum PFAS including perfluorohexane sulfonate (PFHxS), perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) were analyzed, because of high detective rates. Considering the skew distribution of PFAS levels, the natural logarithm-transformed PFAS (Ln-PFAS) was used. Logistic regression analysis, restricted cubic spline (RCS), and weighted quantile sum (WQS) regression were performed to explore the single, nonlinear, and mixed effects. A mediating analysis was used to evaluate the mediated effects of albumin.
RESULTS
Individuals with COPD had higher levels of PFHxS, PFNA, PFOA, and PFOS compared to those without COPD. Ln-PFNA (OR : 1.92, 95 % CI:1.31 to 2.80, P: <0.001; OR : 1.07, 95 % CI: 0.81 to 1.40, P: 0.636) and ln-PFOA (OR : 2.17, 95 % CI:1.38 to 3.41, P: <0.001; OR : 1.49, 95 % CI: 1.08 to 2.05, P: 0.016) were associated with COPD risk especially in males. The interaction between PFNA exposure and sex on COPD risk was significant (P : <0.001). The RCS curve demonstrated the nonlinear relationship between the ln-PFOA (P :0.001), ln-PFNA (P :0.045), and COPD risk in males. WQS analysis showed mixed PFAS exposure was correlated with COPD risk in males (OR: 1.44, 95 % CI:1.18 to 1.75, P: <0.001). Albumin mediated the relationship between PFOA and COPD (mediated proportion: -17.94 %).
CONCLUSION
This study concludes PFOA and PFNA are linked to a higher COPD risk in males, and serum albumin plays a mediating role in the relationship between PFOA and COPD. Thess findings are beneficial for the prevention of COPD. Further studies are required to explore potential mechanisms.
Topics: Male; Female; Humans; Nutrition Surveys; Environmental Pollutants; Serum Albumin; Prevalence; Alkanesulfonic Acids; Fluorocarbons; Alkanesulfonates; Pulmonary Disease, Chronic Obstructive; Caprylates; Fatty Acids
PubMed: 38494022
DOI: 10.1016/j.scitotenv.2024.171742 -
Environment International Jul 2020Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional...
BACKGROUND
Exposure to per-/polyfluoroalkyl substances (PFASs) can disrupt endocrine hormones in humans. Prior studies have focused on the harmful effects of the two traditional per-/polyfluoroalkyl substances (PFASs), perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Other PFASs, used as the replacements of PFOS and PFOA, are widely and increasingly detected in humans. Whether these replacements influence glucocorticoids and progestogens in newborns remains unknown.
OBJECTIVE
To investigate the associations between exposures of PFOS, PFOA and their replacements and glucocorticoids and progestogens in newborns.
METHODS
We measured the concentrations of 13 PFASs, 3 glucocorticoids (11-deoxycortisol, cortisol and cortisone) and 2 progestogens [progesterone, 17-hydroxyprogesterone (17OHP)] in the cord sera of 374 neonates in a birth cohort from Wuhan, China, between 2013 and 2014. We evaluated the associations of each PFAS with glucocorticoids and progestogens using multiple linear regression models, and multiple comparisons were additionally corrected via false discovery rates (FDR).
RESULTS
Out of the 13 PFASs, 9 were detected in over 95% of cord sera. The Chinese specific PFOS replacement - 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA, trade name F-53B) was positively associated with 13.13% change in cortisol in girls (95% CI = 4.47%, 22.52%, for each IQR increase in 6:2 Cl-PFESA). Seven PFASs had positive associations with the precursor of cortisol, namely 11-deoxycortisol (percent change ranged from 6.41% to 11.24%, for each IQR increase in PFASs). Perfluorobutane sulfonate (PFBS) in cord sera was positively associated with progesterone in the linear model, whereas PFOS and perfluorohexane sulfonate (PFHxS) levels were associated with progesterone in the quartile models. No PFASs were related to 17OHP or cortisone.
CONCLUSIONS
In this study, PFOS, PFOA and/or their replacements were positively associated with progesterone, cortisol and 11-deoxycortisol in newborns. These results suggested that not only PFOS and PFOA, but also other PFASs have potential impacts on glucocorticoids and progestogens in newborns.
Topics: Alkanesulfonates; Alkanesulfonic Acids; Caprylates; China; Environmental Pollutants; Ethers; Female; Fluorocarbons; Glucocorticoids; Humans; Infant, Newborn; Progestins
PubMed: 32474218
DOI: 10.1016/j.envint.2020.105636 -
Xenobiotica; the Fate of Foreign... Feb 2021We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of...
We investigated the plasma toxicokinetic behavior of free (parent) and total (parent and conjugated forms) of bisphenol S (BPS) and bisphenol AF (BPAF) in plasma of adult male rats and mice following exposure via feed for 7 days to BPS (338, 1125, and 3375 ppm) or BPAF (338, 1125, and 3750 ppm). In rats, the exposure concentration-normalized maximum concentration [C/D (ng/mL)/(ppm)] and area under the concentration time curve [AUC/D (h × ng/mL)/(ppm)] for free was higher for BPS (C/D: 0.476-1.02; AUC/D: 3.58-8.26) than for BPAF (C/D: 0.017-0.037; AUC/D:0.196-0.436). In mice, the difference in systemic exposure parameters between free BPS (C/D: 0.376-0.459; AUC/D: 1.52-2.54) and free BPAF (C/D: 0.111-0.165; AUC/D:0.846-1.09) was marginal. Elimination half-lives for free analytes (4.41-10.4 h) were comparable between species and analogues. When systemic exposure to free analyte was compared between species, in rats, BPS exposure was slightly higher but BPAF exposure was much lower than in mice. BPS and BPAF were highly conjugated; total BPS AUC values (rats ≥18-fold, mice ≥17-fold) and BPAF (rats ≥127-fold, mice ≥16-fold) were higher than corresponding free values. Data demonstrated that there are analogue and species differences in the kinetics of BPS and BPAF.
Topics: Animals; Benzhydryl Compounds; Hazardous Substances; Kinetics; Male; Mice; Phenols; Rats; Sulfones; Toxicity Tests; Toxicokinetics
PubMed: 32985913
DOI: 10.1080/00498254.2020.1829171 -
Environment International Jul 2023Perfluorohexyl sulfonate (PFHxS) is the third most abundant per- and polyfluoroalkyl substances and its developmental toxicity remains very poorly understood. Here,...
Perfluorohexyl sulfonate (PFHxS) is the third most abundant per- and polyfluoroalkyl substances and its developmental toxicity remains very poorly understood. Here, pregnant mice exposed to PFHxS at human relevant dose showed increased fetal death incidence in the high-dose PFHxS-H group (P < 0.01). Body distribution analyses suggested that PFHxS crossed the placental barrier reaching the fetus in a dose-dependent manner. Histopathological data demonstrated impairment in the placenta with reduced blood sinus volume, placental labyrinth area as well as thickness of labyrinthine layer. Further lipidomic and transcriptomic data together showed that PFHxS exposure caused significant disruption in placental lipid homeostasis, including total lipid accumulation in the placenta, and dysregulation in phospholipid and glycerol lipid metabolism. Gene expression analyses uncovered elevation in key placental fatty acid transporters including fabp2, whereas protein expression showed transporter specific disruptions following exposure. Together, gestational exposure to human relevant level of PFHxS may increase the incidence of fetal deaths and caused placental dysplasia via disruption in lipid metabolism homeostasis. These findings raise the concern regarding the highly prevalent and persistent chemical towards early sensitive developing stages and provide basis for further understanding of its effects on lipid metabolism and underlying mechanisms.
Topics: Humans; Pregnancy; Female; Mice; Animals; Placenta; Alkanesulfonates; Fluorocarbons; Fatty Acids; Homeostasis
PubMed: 37315490
DOI: 10.1016/j.envint.2023.108014 -
Molecules (Basel, Switzerland) May 2023Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the...
Sulfonamides are one of the oldest groups of veterinary chemotherapeutic agents. Physico-chemical properties, the concentration and the nature of the environment are the factors responsible for the distribution of sulfonamides in the living organism. Although these drug compounds have been in use for more than half a century, knowledge about their behavior is still limited. Physiological activity is currently attributed to the sulfanyl radical. Our study is devoted to the spectral properties of aqueous solutions of sulfaguanidine, in which the formation of complexes with an H-bond and a protonated form takes place. The nature of the fluorescent state of sulfaguanidine was interpreted using computational chemistry, the electronic absorption method and the luminescence method. The structure of sulfaguanidine includes several active fragments: aniline, sulfonic and guanidine. To reveal the role of fragments in the physiological activity of the studied antibiotic, we calculated and compared the effective charges of the fragments of aniline and sulfaguanidine molecules. Chromophore groups were identified in molecules, which determine the intermolecular interaction between a molecule and a proton-donor solvent. The study also revealed the impact of sulfone and guanidine groups, as well as complexation, on the effective charge of the antibiotic fragment responsible for physiological activity and luminescent ability.
Topics: Sulfaguanidine; Luminescence; Anti-Bacterial Agents; Sulfonamides; Sulfanilamide; Aniline Compounds; Guanidines
PubMed: 37241901
DOI: 10.3390/molecules28104159 -
Environmental Health Perspectives Jul 2023Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.
BACKGROUND
Nontargeted analysis (NTA) methods identify novel exposures; however, few chemicals have been quantified and interrogated with pregnancy complications.
OBJECTIVES
We characterized levels of nine exogenous and endogenous chemicals in maternal and cord blood identified, selected, and confirmed in prior NTA steps, including linear and branched isomers perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), monoethylhexyl phthalate, 4-nitrophenol, tetraethylene glycol, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid. We evaluated relationships between maternal and cord levels and between gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy in a diverse pregnancy cohort in San Francisco.
METHODS
We collected matched maternal and cord serum samples at delivery from 302 pregnant study participants from the Chemicals in Our Bodies cohort in San Francisco. Chemicals were identified via NTA and quantified using targeted approaches. We calculated distributions and Spearman correlation coefficients testing the relationship of chemicals within and between the maternal and cord blood matrices. We used adjusted logistic regression to calculate the odds of GDM and hypertensive disorders of pregnancy associated with an interquartile range increase in maternal chemical exposures.
RESULTS
We detected linear PFOS, PFHxS, octadecanedioic acid, and deoxycholic acid in at least 97% of maternal samples. Correlations ranged between and 0.9. We observed strong correlations between cord and maternal levels of PFHxS, linear PFOS, and branched PFOS (, 0.8, and 0.8, respectively). An interquartile range increase in linear and branched PFOS, tridecanedioic acid, octadecanedioic acid, and deoxycholic acid was associated with increased odds ratio (OR) of GDM [ (95% CI: 0.89, 2.01), 1.24 (95% CI: 0.86, 1.80), 1.26 (95% CI: 0.93, 1.73), 1.24 (95% CI: 0.86, 1.80), and 1.23 (95% CI: 0.87, 1.75), respectively]. Tridecanedioic acid was positively associated with hypertensive disorders of pregnancy [ (95% CI: 0.90, 1.86)].
DISCUSSION
We identified both exogenous and endogenous chemicals seldom quantified in pregnant study participants that were also related to pregnancy complications and demonstrated the utility of NTA to identify chemical exposures of concern. https://doi.org/10.1289/EHP11546.
Topics: Pregnancy; Female; Humans; Cross-Sectional Studies; Cohort Studies; Hypertension, Pregnancy-Induced; Pregnancy Complications; Diabetes, Gestational; Alkanesulfonic Acids; Alkanesulfonates; Fluorocarbons; Deoxycholic Acid; Environmental Pollutants
PubMed: 37466315
DOI: 10.1289/EHP11546