Journal: The Korean Journal of Pain

Article Title: cGAS–STING signaling in the anterior cingulate cortex modulates electroacupuncture analgesia in a rat neuropathic pain model

doi: 10.3344/kjp.26061

Figure Lengend Snippet: Antagonism of cGAS or STING in the ACC reversed the hyperalgesia caused by CCI. (A) Experimental flow chart. (B) Verification of the ACC catheterization with methylene blue. (C) RU.521 and C-176 (Selleck) significantly increased MT as compared with DMSO (n = 7, ANOVA, *** P < 0.001; ### P < 0.001). (D) RU.521 and C-176 significantly decreased ATS compared with DMSO (n = 7, ANOVA, *** P < 0.001; ### P < 0.001). Data are presented as mean ± standard error of the mean. CCI: chronic constriction injury, MT: mechanical threshold, DMSO: dimethyl sulfoxide, ATS: acetone test score, cGAS: GMP–AMP synthase, STING: stimulator of interferon genes, ACC: anterior cingulate cortex, ANOVA: analysis of variance.

Article Snippet: The cGAS inhibitor RU.521 (Selleck) and the STING inhibitor C-176 (Selleck) were dissolved in 10% dimethyl sulfoxide (DMSO) at a concentration of 20 μg/μL, based on previous reports and the authors’ pilot experiments [ , , ].

Techniques: Analysis

Journal: Science signaling

Article Title: HRAS promotes mutant NRAS-driven transformation with codon and allele specificity

doi: 10.1126/scisignal.aej6209

Figure Lengend Snippet: ( A ) Heatmaps of cell viability and excess over Bliss (EOB) in the indicated NRAS-mutated cancer cell lines left untreated or treated with increasing (semi-log) doses of the pan-RAS(ON) inhibitor (RASi-ON) RMC-7977 (10 −10.5 –10 −7 M) with or without the FTI tipifarnib (HRASi; 10 −10 –10 −6.5 M) for 72 hours under 3D culture conditions. Data are the average (heatmaps) or individual values and mean ± S.D. (SUM EOB) from N = 3 independent experiments, each with n = 3 technical replicates. Significance was assessed by one sample t and Wilcoxon test, * P < 0.05, ** P < 0.01 compared to Bliss Independence (additive drug effect, EOB = 0); and by ANOVA with Tukey’s correction for multiple comparisons, ^ P < 0.05, ^^ P < 0.01 compared to G12D-mutated TALL-1 and KE-37 cells. ( B ) Unifying schematic model depicting the contribution of WT RAS proteins to mutant NRAS signaling depending on the specific codon mutation. In cells harboring “cycling” G12X mutants, WT RAS augments RTK-stimulated mutant RAS signaling to enhance transformation. In cells harboring “GTP-locked” Q61X mutants, RTK-stimulated WT RAS signaling serves as an obligate partner to promote downstream effector signaling and transforming potential. The differential requirements for WT RAS revealed from genetic depletion and DepMap analysis suggest non-overlapping therapeutic strategies: inhibiting proximal RTK pathway (SOS1i) synergizes with inhibitors of cycling G12X mutants, whereas inhibiting WT HRAS using tipifarnib creates a synthetic vulnerability when combined with a pan-RAS(ON) inhibitor in GTP-locked Q61X-mutated cells.

Article Snippet: TALL-1 and KE-37 were purchased from DSMZ.

Techniques: Mutagenesis, Transformation Assay, Analysis