Multi-drug-resistant bacterial infections, which have become a global threat, lack effective treatments. The discoveries of non-antibiotics with different modes of antibacterial action, such as ...methylsulfonylmethane (MSM), are a promising new treatment for multi-drug-resistant pathogens.
We constructed a mouse peritonitis infection model to evaluate the effects of MSM against methicillin-resistant Staphylococcus aureus (MRSA) infection. The time-kill kinetics of MSM against MRSA and the effect of MSM on the integrity of bacterial cell membrane were measured. Viability effects of MSM on THP1 cells were performed by CCK-8 cytotoxicity assay. Systematic inflammatory factor levels of mice were detected using ELISA. The immune response of peritoneal macrophages during MRSA-infection was evaluated using RNA sequencing. Gene Ontology function, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, and correlation analyses were applied to analysis RNA sequencing data. RT-qPCR, western blotting and flow cytometry were performed to analysis the gene and protein expression levels of macrophages.
In in vitro experiments, MSM did not show significant killing effects on the growth of MRSA directly and did not destroy bacterial membrane integrity. MSM also displayed no significant effects on the proliferative capacity of THP1 cells. However, MSM treatment protected mice against a lethal dose MRSA-infection and decreased systemic inflammation. MSM upregulated metabolic pathway in peritoneal macrophages, especial glycolysis, during MRSA infection. MSM increased the expression of M2 markers (such as Arg1), promoted phosphorylation of STAT3 (which regulates M2 polarization), and decreased the expression of M1 markers in peritoneal macrophages. Additionally, MSM treatment increased the expression of H3K18 lactylation specific target genes, including Arg1. GNE-140, the LDHA-specific inhibitor of glycolysis, blocked the MSM-induced Arg1 expression in this disease model.
MSM protects against MRSA infection through immunomodulation. MSM promotes the expression of Arg1 by lactate-H3K18la pathway to control macrophage to M2 polarization; it firstly provides therapeutic potential for drug-resistant infections and sepsis.
•MSM relieves inflammation and improves mice survival rate after MRSA infection.•MSM promotes M2 polarization of peritoneal macrophages via H3K18la-Arg1 pathway.•MSM could be a potential therapeutic agent against lethal MRSA-induced sepsis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Methylsulfonylmethane (MSM) is a naturally occurring anti-inflammatory compound that effectively treats multiple degenerative diseases such as osteoarthritis and acute pancreatitis. Our previous ...studies have demonstrated the ability of MSM to differentiate stem cells from human exfoliated deciduous (SHED) teeth into osteoblast-like cells. This study examined the systemic effect of MSM in 36-week-old aging C57BL/6 female mice
by injecting MSM for 13 weeks. Serum analyses showed an increase in expression levels of bone formation markers osteocalcin (OCN) and procollagen type 1 intact N-terminal propeptide (P1NP) and a reduction in bone resorption markers tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collag (CTX-I) in MSM-injected animals. Micro-computed tomographic images demonstrated an increase in trabecular bone density in mandibles. The trabecular bone density tended to be higher in the femur, although the increase was not significantly different between the MSM- and phosphate-buffered saline (PBS)-injected mice. In mandibles, an increase in bone density with a corresponding decrease in the marrow cavity was observed in the MSM-injected mice. Furthermore, immunohistochemical analyses of the mandibles for the osteoblast-specific marker - OCN, and the mesenchymal stem cell-specific marker - CD105 showed a significant increase and decrease in OCN and CD105 positive cells, respectively. Areas of bone loss were observed in the inter-radicular region of mandibles in control mice. However, this loss was considerably decreased due to stimulation of bone formation in response to MSM injection. In conclusion, our study has demonstrated the ability of MSM to induce osteoblast formation and function
, resulting in increased bone formation in the mandible. Hence, the application of MSM and stem cells of interest may be the right combination in alveolar bone regeneration under periodontal or other related diseases that demonstrate bone loss.
Metabolism-associated fatty liver disease (MAFLD) is a global health concern because of its association with obesity, insulin resistance, and other metabolic abnormalities. Methylsulfonylmethane ...(MSM), an organic sulfur compound found in various plants and animals, exerts antioxidant and anti-inflammatory effects. Here, we aimed to assess the anti-obesity activity and autophagy-related mechanisms of Methylsulfonylmethane.
Human hepatoma (HepG2) cells treated with palmitic acid (PA) were used to examine the effects of MSM on autophagic clearance. To evaluate the anti-obesity effect of MSM, male C57/BL6 mice were fed a high-fat diet (HFD; 60% calories) and administered an oral dose of MSM (200 or 400 mg/kg/day). Moreover, we investigated the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin complex 1 (mTORC1)/UNC-51-like autophagy-activating kinase 1 (ULK1) signaling pathway to further determine the underlying action mechanism of MSM.
Methylsulfonylmethane treatment significantly mitigated PA-induced protein aggregation in human hepatoma HepG2 cells. Additionally, Methylsulfonylmethane treatment reversed the PA-induced impairment of autophagic flux. Methylsulfonylmethane also enhanced the insulin sensitivity and significantly suppressed the HFD-induced obesity and hepatic steatosis in mice. Western blotting revealed that Methylsulfonylmethane improved ubiquitinated protein clearance in HFD-induced fatty liver. Remarkably, Methylsulfonylmethane promoted the activation of AMPK and ULK1 and inhibited mTOR activity.
Our study suggests that MSM ameliorates hepatic steatosis by enhancing the autophagic flux via an AMPK/mTOR/ULK1-dependent signaling pathway. These findings highlight the therapeutic potential of MSM for obesity-related MAFLD treatment.
This study was conducted to determine the effect of methylsulfonylmethane (MSM) on growth performance, immune function, antioxidant capacity, and meat quality in Pekin ducks. A total of 960 female ...1-day-old Pekin ducklings (53.3 ± 0.4 g) were randomly allotted to 3 treatments with 8 replicates of 40 birds, based on their body weight (BW). The experiment lasted 6 wks, and dietary treatments included a corn–soybean meal–based diet supplemented with 0%, 0.15%, and 0.3% MSM, that is, CON, MSM1, and MSM2, respectively. Growth performance, serum profiles, and meat quality were determined. During the period of days 22–42, BW gain (BWG) in MSM2 treatment was higher (P < 0.05) and feed-to-gain ratio (F/G) was lower (P < 0.05) than those of CON and MSM1 treatments. BW gain and final BW in MSM2 treatment were increased (P < 0.05) compared with CON and MSM1 treatments during the period of days 1–42. Serum activities of superoxide dismutase and glutathione peroxidase, total antioxidative capacity, and concentrations of interleukin-2 and interleukin-6 were higher (P < 0.05) in MSM2 than in CON treatment. Ducks in the MSM2 treatment group had lower (P < 0.05) serum malondialdehyde, interferon gamma, and tumor necrosis factor-α levels than those in the CON treatment group. The supplementation of MSM increased (P < 0.05) water-holding capacity and redness (a*) and decreased (P < 0.05) values for 2-thiobarbituric acid and drip loss on day 5. Ducks in the MSM2 treatment group had higher (P < 0.05) pH24h than those in the CON treatment group. Taken together, the inclusion of MSM (0.3%) increased final BW and BWG during periods of days 22–42 and days 1–42, reduced feed-to-gain ratio during the period of days 22–42, and resulted in positive effects on immunity, antioxidant capacity, and meat quality.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The purpose of this study was to compare clinical outcomes obtained with the use of glucosamine, chondroitin sulfate, and methylsulfonylmethane (GCM) supplementation after arthrocentesis plus ...intraarticular hyaluronic acid (HA) injection.
A randomized clinical trial was implemented with adult participants with TMJ-OA who were referred to the author’s clinic between February 2014 and May 2015. The sample was entirely composed of patients with TMJ-OA who were treated randomly with a one-session arthrocentesis plus intraarticular HA injection only (control group), or an initial one-session arthrocentesis plus intraarticular HA injection followed by 3 months of GCM supplementation (study group). The predictor variable was management (treatment) technique. The outcome variables were visual analog scale evaluations (masticatory efficiency, pain complaint, joint sound) and mandibular mobility (maximal interincisal opening MIO, and lateral and protrusive motions of the mandible). The outcome variables were recorded preoperatively and 12 months postoperatively.
Thirty-one participants were enrolled in the study. Five were lost during follow-up. The final study sample consisted of 26 participants (age 28.35 ± 10.85 y): 14 in the control group (age 28.71 ± 10.94 y); and 12 in the study group (age 27.92 ± 11.20 y). Pain complaints (p < 0.001) and joint sounds (p = 0.030 for the control group; p = 0.023 for the study group) showed statistically significant decreases. Masticatory efficiency (p < 0.001 for the control group; p = 0.040 for the study group) and lateral mandibular motion (p = 0.040 for the control group; p = 0.004 for study group) showed statistically significant increases in both groups, whereas MIO and protrusive mandibular motion showed no significant changes in either group (p > 0.05). After estimating the differences between the follow-up and baseline outcomes, the mean changes in the primary outcome variables (VAS scores, MIO, and mandibular motion) showed no statistically significant differences between the two groups (p > 0.05).
Progressions (reparative remodeling) of hard-tissue TMJ structures were observed on CBCT scans of some participants in both groups.
These findings suggested that the use of GCM supplementation after arthrocentesis plus intraarticular HA injection produced no additional clinical benefits or improvements for patients with TMJ-OA compared with arthrocentesis plus intraarticular HA injection alone.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Osteoarthritis (OA) is a degenerative inflammatory condition of the joint cartilage that currently affects approximately 58 million adults in the world. It is characterized by pain, stiffness, and a ...reduced range of motion with regard to the arthritic joints. These symptoms can cause in the long term a greater risk of overweight/obesity, diabetes mellitus, and falls and fractures. Although the current guidelines for the treatment of OA suggest, as the gold standard for this condition, pharmacological treatment characterized by non-steroidal anti-inflammatory drugs (NSAID), opioids, and cyclooxygenase (COX)-2-specific drugs, a great interest has been applied to nutraceutical supplements, which include a heterogeneous class of molecules with great potential to reduce inflammation, oxidative stress, pain, and joint stiffness and improve cartilage formation. The purpose of this review is to describe the potential application of nutraceuticals in OA, highlighting its molecular mechanisms of actions and data of efficacy and safety (when available).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Methylsulfonylmethane (MSM) is a natural sulfur-containing organic substance that has many biological functions, such as antioxidant, anti-inflammatory, skin nourishing, and hair growth-promoting ...effects. This study was conducted to determine the effect of MSM supplementation on growth performance, antioxidant capacity, and hair quality in kittens. A total of 21 Ragdoll kittens were assigned to three diets by initial body weight and gender: basal diet supplemented with 0%, 0.2%, and 0.4% MSM (CON, LMSM, and HMSM groups) for 65 days. During the whole period, the food intake of kittens in the MSM-treated groups tended to be higher (
P
< 0.10) compared with the CON group, and the average daily gain (ADG) had no significant difference when compared to the kittens in the CON group (
P
> 0.05). Antioxidant capacity had no significant difference (
P
> 0.05) among the groups. The scale thickness of hair tended to be smaller in the LMSM group compared to the CON group (
P
< 0.10) and decreased significantly (
P
< 0.05) over time from d 0 to d 65 in the LMSM group, indicating the improvement of hair quality. Besides, supplementation with LMSM increased bacterial diversity. Kittens fed MSM had no significant differences in fecal genus at the end of the study. No significant differences in fecal short-chain fatty acids were observed among groups. Fecal metabolomics analysis further revealed that MSM hardly affected the metabolites. Overall, dietary supplementation with 0.2% MSM can improve the hair quality of kittens. Furthermore, 0.2∼0.4% of MSM had no detrimental effects on serum biochemistry, growth performance, gut microbiota, and metabolome, which supports the safety inclusion of MSM to a certain degree in feline diets. To the best of our knowledge, this is the first study to investigate the effects of MSM supplementation in cats.
PURPOSE:The present study aimed to investigate the effects of transdermal application of methylsulfonylmethane (MSM) on muscle damage and recovery following eccentric exercise in young men.
METHODS: ...Eleven college-aged men without any cardiovascular or orthopedic disorders underwent two sessions consisting of a control session (CS) and an experimental session (ES) in a random order with at least 2 weeks of wash-out between the sessions. The participants performed 30 maximal eccentric exercises involving their non-dominant elbow flexors in each session. Circumference, muscle soreness, range of motion, maximal voluntary isometric contraction (MVIC), and muscular echo intensity (EI) were measured to evaluate the changes in the level of exercise-induced muscle damage (EIMD). All measurements were performed at 24, 48, 72, and 96 hours after exercise and also immediately before and after exercise.
RESULTS:Transdermal application of MSM in ES attenuated muscle swelling and decreased MVIC after eccentric exercise when compared with CS. Muscle soreness and EI tended to increase less rapidly and decrease more rapidly in ES than in CS.
CONCLUSIONS: Transdermal application of MSM may induce relatively positive effects on EIMD and recovery following eccentric exercise when compared with the treatment that has been widely used previously KCI Citation Count: 0
Abstracts PURPOSE The present study aimed to investigate the effects of transdermal application of methylsulfonylmethane (MSM) on muscle damage and recovery following eccentric exercise in young men. ...METHODS Eleven college-aged men without any cardiovascular or orthopedic disorders underwent two sessions consisting of a control session (CS) and an experimental session (ES) in a random order with at least 2 weeks of wash-out between the sessions. The participants performed 30 maximal eccentric exercises involving their non-dominant elbow flexors in each session. Circumference, muscle soreness, range of motion, maximal voluntary isometric contraction (MVIC), and muscular echo intensity (EI) were measured to evaluate the changes in the level of exercise-induced muscle damage (EIMD). All measurements were performed at 24, 48, 72, and 96 hours after exercise and also immediately before and after exercise. RESULTS Transdermal application of MSM in ES attenuated muscle swelling and decreased MVIC after eccentric exercise when compared with CS. Muscle soreness and EI tended to increase less rapidly and decrease more rapidly in ES than in CS. CONCLUSIONS Transdermal application of MSM may induce relatively positive effects on EIMD and recovery following eccentric exercise when compared with the treatment that has been widely used previously.
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