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Image Search Results
Journal: bioRxiv
Article Title: Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons
doi: 10.1101/2023.12.22.572877
Figure Lengend Snippet: (A) MGO stimulates the integrated stress response (ISR) and promotes the phosphorylation of eIF2α. DRF is a prodrug and is metabolized to MMF which activates the Nrf2 antioxidant response neutralizing MGO. (B) Male (n=8 per condition) and female (n=8 per condition) mice were treated with DRF (60 or 100 mg/kg) for five days. MGO (20 ng) was administered in an intraplantar injection on the third day, 1-hour after oral DRF administration for the day. Mechanical and cold sensitivity was assessed using von Frey and acetone tests, respectively. Acetone test was performed an hour after von Frey testing was complete. We observed that male (C) and female (D) mice had reduced von Frey thresholds in response to MGO injection on day 3. Daily treatment with DRF prevented MGO-induced mechanical hypersensitivity following MGO injection on day 3. (E, F) Using area under the curve of von Frey thresholds, we determined that DRF at a dose of 100 mg/kg were effective at preventing MGO-induced tactile hypersensitivity in males while both 60 mg/kg and 100 mg/kg doses were effective in females. MGO produced cold hypersensitivity in male (G) and female (H) mice which was abrogated in DRF treated mice at both doses. For (C, D, G, H) significance was calculated with repeated measures two-way ANOVA with Tukey’s multiple comparison test. *, &, # p<0.05; **, ## p<0.01; ***, &&& p<0.001; **** p<0.0001. * indicates comparison to veh-only, & indicates comparison to MGO+DRF-60, # indicates comparison to MGO+DRF-100. For (E, F) signficance was caluclated with a one-way ANOVA with Brown-Forsythe correction. * p<0.05; ** p<0.01.
Article Snippet: Antibodies used in this study were:
Techniques: Phospho-proteomics, Injection, Produced, Comparison
Journal: bioRxiv
Article Title: Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons
doi: 10.1101/2023.12.22.572877
Figure Lengend Snippet: (A-C) Representative images of immunohistochemistry of mouse DRG neurons cultured for 24 hours and subsequently treated with vehicle-only, MGO (1µM), or MGO (1µM) plus MMF (10, 20, 50 µM). (D) We observed a significant increase in the levels of p-eIF2α when cells were treated with MGO as compared to vehicle-treated cells. MMF treatment with MGO prevented elevation of p-eIF2a particularly at 20 µM and 50 µM concentrations. Neurons were identified by their expression of beta3 tubulin. Vehicle-only (n=18), MGO (n=37), MGO+10µM MMF (n=20), MGO+20µM MMF (n=16), MGO+50µM MMF (n=32). A one-way ANOVA was used to calculate significance. *p<0.05, **p<0.01.
Article Snippet: Antibodies used in this study were:
Techniques: Immunohistochemistry, Cell Culture, Expressing
Journal: bioRxiv
Article Title: Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decreases ISR activation in DRG neurons
doi: 10.1101/2023.12.22.572877
Figure Lengend Snippet: (A-C) Representative images of human DRG neurons obtained from organ donors treated with vehicle, MGO (1µM), and MGO plus MMF. (D) MGO (1µM) increases p-eIF2α in human DRG neurons which is prevented with 20 µM and 50 µM MMF cotreatment. Vehicle-only (n=170), MGO (n=152), MGO+10µM MMF (n=125), MGO+20µM MMF (n=176), MGO+50µM MMF (n=111). A one-way ANOVA was used to calculate statistical significance. *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.
Article Snippet: Antibodies used in this study were:
Techniques: