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Nutrients Mar 2017Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has... (Review)
Review
Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arthritis; Biological Availability; Cartilage; Dietary Supplements; Dimethyl Sulfoxide; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Hypersensitivity; Inflammation; Myalgia; Neoplasms; Oxidative Stress; Risk Factors; Sulfones
PubMed: 28300758
DOI: 10.3390/nu9030290 -
Nature Medicine Mar 2015The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is...
The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndrome (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis. We describe the development of MCC950, a potent, selective, small-molecule inhibitor of NLRP3. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced interleukin-1β (IL-1β) production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis. Furthermore, MCC950 treatment rescued neonatal lethality in a mouse model of CAPS and was active in ex vivo samples from individuals with Muckle-Wells syndrome. MCC950 is thus a potential therapeutic for NLRP3-associated syndromes, including autoinflammatory and autoimmune diseases, and a tool for further study of the NLRP3 inflammasome in human health and disease.
Topics: Animals; Carrier Proteins; Cryopyrin-Associated Periodic Syndromes; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Furans; Heterocyclic Compounds, 4 or More Rings; Humans; Indenes; Inflammasomes; Inflammation; Interleukin-1beta; Mice; Multiple Sclerosis; NLR Family, Pyrin Domain-Containing 3 Protein; Sulfonamides; Sulfones
PubMed: 25686105
DOI: 10.1038/nm.3806 -
Environmental Health Perspectives Jul 2015Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer... (Review)
Review
BACKGROUND
Increasing concern over bisphenol A (BPA) as an endocrine-disrupting chemical and its possible effects on human health have prompted the removal of BPA from consumer products, often labeled "BPA-free." Some of the chemical replacements, however, are also bisphenols and may have similar physiological effects in organisms. Bisphenol S (BPS) and bisphenol F (BPF) are two such BPA substitutes.
OBJECTIVES
This review was carried out to evaluate the physiological effects and endocrine activities of the BPA substitutes BPS and BPF. Further, we compared the hormonal potency of BPS and BPF to that of BPA.
METHODS
We conducted a systematic review based on the Office of Health Assessment and Translation (OHAT) protocol.
RESULTS
We identified the body of literature to date, consisting of 32 studies (25 in vitro only, and 7 in vivo). The majority of these studies examined the hormonal activities of BPS and BPF and found their potency to be in the same order of magnitude and of similar action as BPA (estrogenic, antiestrogenic, androgenic, and antiandrogenic) in vitro and in vivo. BPS also has potencies similar to that of estradiol in membrane-mediated pathways, which are important for cellular actions such as proliferation, differentiation, and death. BPS and BPF also showed other effects in vitro and in vivo, such as altered organ weights, reproductive end points, and enzyme expression.
CONCLUSIONS
Based on the current literature, BPS and BPF are as hormonally active as BPA, and they have endocrine-disrupting effects.
CITATION
Rochester JR, Bolden AL. 2015. Bisphenol S and F: a systematic review and comparison of the hormonal activity of bisphenol A substitutes.
Topics: Animals; Benzhydryl Compounds; Endocrine Disruptors; Humans; Phenols; Sulfones
PubMed: 25775505
DOI: 10.1289/ehp.1408989 -
Journal of Neuroinflammation Jun 2021Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative...
BACKGROUND
Chronic neuropathic pain is a frequent sequel to peripheral nerve injury and maladaptive nervous system function. Divanillyl sulfone (DS), a novel structural derivative of 4,4'-dihydroxydibenzyl sulfoxide from a traditional Chinese medicine Gastrodia elata with anti-nociceptive effects, significantly alleviated neuropathic pain following intrathecal injection. Here, we aimed to investigate the underlying mechanisms of DS against neuropathic pain.
METHODS
A chronic constrictive injury (CCI) mouse model of neuropathic pain induced by sciatic nerve ligation was performed to evaluate the effect of DS by measuring the limb withdrawal using Von Frey filament test. Immunofluorescence staining was used to assess the cell localizations and expressions of Iba-1, ASC, NLRP3, and ROS, the formation of autolysosome. The levels of NLRP3-related proteins (caspase-1, NLRP3, and IL-1β), mitophagy-related proteins (LC3, Beclin-1, and p62), and apoptosis-related proteins (Bcl-XL and Bax) were detected by Western blotting. The apoptosis of BV-2 cell and caspase activity were evaluated by flow cytometry.
RESULTS
DS significantly alleviated the neuropathic pain by increasing the mechanical withdrawal threshold and inhibiting the activation of NLRP3 in CCI-induced model mice. Our findings indicated that DS promoted the mitophagy by increasing the LC3II and Beclin 1 and decreasing the levels of p62 protein in BV-2 cell. This is accompanied by the inhibition of NLRP3 activation, which was shown as inhibited the expression of NLRP3 in lysates as well as the secretion of mature caspase-1 p10 and IL-1β p17 in supernatants in cultured BV-2 microglia. In addition, DS could promote mitophagy-induced improvement of dysfunctional mitochondria by clearing intracellular ROS and restoring mitochondrial membrane potential.
CONCLUSION
Together, our findings demonstrated that DS ameliorate chronic neuropathic pain in mice by suppressing NLRP3 inflammasome activation induced by mitophagy in microglia. DS may be a promising therapeutic agent for chronic neuropathic pain.
Topics: Animals; Apoptosis; Caspase 1; Cell Line; Disease Models, Animal; Inflammasomes; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Microglia; Mitochondria; Mitophagy; NLR Family, Pyrin Domain-Containing 3 Protein; Neuralgia; Sciatic Nerve; Sulfones
PubMed: 34162415
DOI: 10.1186/s12974-021-02178-z -
International Journal For Vitamin and... Jul 2022: Methylsulfonylmethane (MSM) is an organosulfur compound with known benefits for joint health, sports nutrition, immune function, and anti-aging formulations and is...
: Methylsulfonylmethane (MSM) is an organosulfur compound with known benefits for joint health, sports nutrition, immune function, and anti-aging formulations and is gaining popularity as a nutritional supplement for the support of hair, skin and nails. : The study was conducted in two steps; in Part I (pilot study) a panel of 20 participants ingested either 3 g a day of MSM or placebo capsules for 16 weeks. Visual and subject self assessment of wrinkles and skin texture as the predominant sign of ageing was observed. In Part II (dose-response study), 63 participants ingested either 1 g or 3 g per day of MSM for 16 weeks. Expert clinical grading, instrumental measurements and consumer perception was used to evaluate skin conditions like lines and wrinkles. Additionally, instrumentational analysis was conducted using corneometer and cutometer for investigation of skin hydration, firmness and elasticity. : Part I of the study clearly indicates that oral ingestion of MSM (3 g/d) reduces signs of ageing like facial wrinkles ( < 0.05) and skin roughness ( < 0.05) as compared to placebo. Detailed analysis in Part II instrumentation assessments showed a significant ( < 0.05) improvement from baseline in the severity of facial wrinkles, as well as improved skin firmness, elasticity and hydration with MSM. Some of these parameters exhibited a good dose-response indicating that the higher (3 g/d) of the supplement was more effective than the lower dose of 1 g/d, but generally the lower dose of 1 g/d appeared to be sufficiently effective in reducing the facial signs of ageing. : This study indicated that MSM is effective in reducing visual signs of skin ageing even at a low dose of 1 g/d.
Topics: Administration, Oral; Beauty; Dimethyl Sulfoxide; Humans; Pilot Projects; Skin Aging; Sulfones; Sulfur
PubMed: 32083522
DOI: 10.1024/0300-9831/a000643 -
Environmental Health Perspectives May 2023Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined.
Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis.
BACKGROUND
Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined.
OBJECTIVES
This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture.
METHODS
From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners.
RESULTS
After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, , ), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [ (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, , and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women.
CONCLUSIONS
In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, , and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.
Topics: Humans; Female; Polycystic Ovary Syndrome; Case-Control Studies; Bayes Theorem; Overweight; Fluorocarbons; Environmental Exposure; Alkanesulfonic Acids; Infertility; Alkanesulfonates; Obesity; Environmental Pollutants
PubMed: 37134253
DOI: 10.1289/EHP11814 -
Chemistry, An Asian Journal Dec 2022Fluorescent indicators that respond to changes in biological membrane potentials provide a powerful complement to existing methods for monitoring neuronal activity....
Fluorescent indicators that respond to changes in biological membrane potentials provide a powerful complement to existing methods for monitoring neuronal activity. Indicators that absorb and emit in the near infrared window are especially attractive, since lower energy wavelengths excite fewer biological molecules and can penetrate more deeply into biological tissues. In this work, we incorporate sulfone rhodamine chromophores into a voltage-sensitive scaffold in order to generate voltage sensitive fluorophores which absorb and emit above 700 nm. These Sulfone Rhodamine Voltage Reporters (SuRhoVRs) partition into cell membranes and display good sensitivity to membrane potential changes. The most sensitive SuRhoVR derivative also displays excellent photostability and can track membrane potential changes in dissociated rat hippocampal neurons.
Topics: Rats; Animals; Rhodamines; Fluorescent Dyes; Diagnostic Imaging; Sulfones
PubMed: 36356288
DOI: 10.1002/asia.202200906 -
Hypertension (Dallas, Tex. : 1979) Jan 2020Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant... (Comparative Study)
Comparative Study Randomized Controlled Trial
Mineralocorticoid receptors (MRs) are implicated in the pathology of hypertension. MR blockers are recommended for the treatment of salt-sensitive or resistant hypertension. However, use of currently available MR blockers is limited by adverse events. This phase 3 multicenter, randomized, double-blind study compared the efficacy and safety of esaxerenone, a new selective nonsteroidal MR blocker, at 2.5 and 5 mg/day and eplerenone 50 mg/day in Japanese patients with essential hypertension. After a 4-week washout period, 1001 eligible adults with hypertension were randomized evenly to esaxerenone 2.5 or 5 mg/day or eplerenone 50 mg/day treatments, taken orally once daily for 12 weeks. Primary end points were changes in sitting systolic or diastolic blood pressure (BP) from baseline at the end of treatment. Esaxerenone 2.5 mg/day was noninferior to eplerenone for reductions in sitting and 24-hour BP. Reductions in BP with esaxerenone 5 mg/day were significantly greater than those with esaxerenone 2.5 mg/day. Changes in diurnal BP showed persistent 24-hour antihypertensive effects in all treatment groups. The proportions of patients achieving target sitting BP (<140/90 mm Hg) were 31.5%, 41.2%, and 27.5% with esaxerenone 2.5 and 5 mg/day and eplerenone 50 mg/day, respectively. Incidences of adverse events (all mild or moderate) were similar across treatment groups. These results indicate that esaxerenone is an effective and well-tolerated MR blocker in Japanese patients with essential hypertension, with BP-lowering activity at least equivalent to eplerenone. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT02890173.
Topics: Aged; Antihypertensive Agents; Blood Pressure; Double-Blind Method; Eplerenone; Essential Hypertension; Female; Humans; Male; Middle Aged; Pyrroles; Sulfones; Treatment Outcome
PubMed: 31786983
DOI: 10.1161/HYPERTENSIONAHA.119.13569 -
Advances in Colloid and Interface... Oct 2022Although the anionic surfactant sodium dodecyl sulfate, SDS, has been used for more than half a century as a versatile and efficient protein denaturant for protein... (Review)
Review
Although the anionic surfactant sodium dodecyl sulfate, SDS, has been used for more than half a century as a versatile and efficient protein denaturant for protein separation and size estimation, there is still controversy about its mode of interaction with proteins. The term "rod-like" structures for the complexes that form between SDS and protein, originally introduced by Tanford, is not sufficiently descriptive and does not distinguish between the two current vying models, namely protein-decorated micelles a.k.a. the core-shell model (in which denatured protein covers the surface of micelles) versus beads-on-a-string model (where unfolded proteins are surrounded by surfactant micelles). Thanks to a combination of structural, kinetic and computational work particularly within the last 5-10 years, it is now possible to rule decisively in favor of the core-shell model. This is supported unambiguously by a combination of calorimetric and small-angle X-ray scattering (SAXS) techniques and confirmed by increasingly sophisticated molecular dynamics simulations. Depending on the SDS:protein ratio and the protein molecular mass, the formed structures can range from multiple partly unfolded protein molecules surrounding a single shared micelle to a single polypeptide chain decorating multiple micelles. We also have much new insight into how this species forms. It is preceded by the binding of small numbers of SDS molecules which subsequently grow by accretion. Time-resolved SAXS analysis reveals an asymmetric attack by SDS micelles followed by distribution of the increasingly unfolded protein around the micelle. The compactness of the protein chain continues to evolve at higher SDS concentrations according to single-molecule studies, though the protein remains completely denatured on the tertiary structural level. SDS denaturation can be reversed by addition of nonionic surfactants that absorb SDS forming mixed micelles, leaving the protein free to refold. Refolding can occur in parallel tracks if only a fraction of the protein is initially stripped of SDS. SDS unfolding is nearly always reversible unless carried out at low pH, where charge neutralization can lead to superclusters of protein-surfactant complexes. With the general mechanism of SDS denaturation now firmly established, it largely remains to explore how other ionic surfactants (including biosurfactants) may diverge from this path.
Topics: Micelles; Proteins; Scattering, Small Angle; Sodium Dodecyl Sulfate; Surface-Active Agents; X-Ray Diffraction
PubMed: 36027673
DOI: 10.1016/j.cis.2022.102754 -
Journal of the American Heart... Sep 2023Background Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP)...
Prenatal and Childhood Per- and Polyfluoroalkyl Substance (PFAS) Exposures and Blood Pressure Trajectories From Birth to Late Adolescence in a Prospective US Prebirth Cohort.
Background Evidence is limited regarding the associations of prenatal and childhood per- and polyfluoroalkyl substance (PFAS) exposures with blood pressure (BP) trajectories in children. Methods and Results Participants are from Project Viva, a prospective prebirth cohort in eastern Massachusetts. We measured PFAS in early-pregnancy maternal (median, 9.6 weeks) and midchildhood (median, 7.7 years) plasma samples. We conducted standardized BP measurements at 6 research visits: birth, infancy (median, 6.3 months), early childhood (median, 3.2 years), midchildhood (median, 7.7 years), early adolescence (median, 12.9 years), and late adolescence (median, 17.5 years). We used linear regression to examine associations of individual PFASs with BP at each visit, linear spline mixed-effects regression to model BP trajectories, and a mixture approach to estimate PFAS exposure burden. We included 9036 BP measures from 1506 participants. We observed associations between particular individual prenatal PFASs and child BP at specific time points, for example, prenatal 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) with higher systolic BP at birth; prenatal perfluorooctane sulfonate (PFOS) and EtFOSAA with lower diastolic BP in infancy; and prenatal PFOS, perfluorooctanoate (PFOA), and EtFOSAA with higher systolic BP at midchildhood. No prenatal or childhood PFAS was consistently associated with BP across all visits. Diastolic BP trajectories from 0 to 20 years differed slightly by prenatal PFOA, perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) ( values 0.01-0.09). Diastolic BP trajectories from 6 to 20 years differed slightly by midchildhood PFHxS and MeFOSAA (-values 0.03-0.08). Prenatal or childhood PFAS mixture burden scores were not associated with BP. Conclusions We found associations of prenatal and childhood PFAS exposures with BP at specific time points between birth and late adolescence but no consistent associations across all time points or PFAS types.
Topics: Infant, Newborn; Child; Female; Pregnancy; Humans; Adolescent; Child, Preschool; Blood Pressure; Prospective Studies; Fluorocarbons; Hypotension; Alkanesulfonates
PubMed: 37642023
DOI: 10.1161/JAHA.123.030760