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a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b <t>p-p38</t> expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of <t>p38</t> <t>MAPK-related</t> genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.
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a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b <t>p-p38</t> expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of <t>p38</t> <t>MAPK-related</t> genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.
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a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b <t>p-p38</t> expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of <t>p38</t> <t>MAPK-related</t> genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.
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Effects of PVN infusion of HA or vehicle on the expressions of <t>p-p38</t> <t>MAPK</t> in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.
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Effects of PVN infusion of HA or vehicle on the expressions of <t>p-p38</t> <t>MAPK</t> in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.
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Image Search Results


a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Intrinsic temperature increase drives lipid metabolism towards ferroptosis evasion and chemotherapy resistance in pancreatic cancer

doi: 10.1038/s41467-024-52978-z

Figure Lengend Snippet: a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Article Snippet: Slides were incubated with primary antibody to phospho-p38 MAPK (Thr180/Tyr182) (1:200; Cell Signaling, #4511), followed by a horseradish peroxidase (HRP)-labeled secondary antibody for 30 min each.

Techniques: Expressing, Immunohistochemistry, Activation Assay, RNA Sequencing Assay, Cell Culture

a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Intrinsic temperature increase drives lipid metabolism towards ferroptosis evasion and chemotherapy resistance in pancreatic cancer

doi: 10.1038/s41467-024-52978-z

Figure Lengend Snippet: a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Article Snippet: Equal amounts of protein were loaded onto precast gels (NuPAGE, ThermoFisher), transferred to nitrocellulose membranes, and incubated with antibodies against phospho-p38 MAPK (1/1000 dilution) (Cell Signaling, #4511) and p38 MAPK (1/1000 dilution) (Cell Signaling, #8690).

Techniques: Expressing, Immunohistochemistry, Activation Assay, RNA Sequencing Assay, Cell Culture

a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Intrinsic temperature increase drives lipid metabolism towards ferroptosis evasion and chemotherapy resistance in pancreatic cancer

doi: 10.1038/s41467-024-52978-z

Figure Lengend Snippet: a Cell death of PANC-1 or BxPC3 cells treated with RSL3 and Doramapimod for 24 h ( n = 4 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. b p-p38 expression in wild-type or MAPK14 KO PANC-1 and BxPC3 cells. c Cell death of wild-type or MAPK14 KO PANC-1 ( n = 4 different wells, one representative experiment of 2 independent experiments is shown) and BxPC3 ( n = 3; n = 6 different wells, respectively) cells treated with vehicle or RSL3 for 24 h. One-way ANOVA with Šídák’s multiple comparisons test. d Overall survival of patients with PDAC with either high ( n = 47 patients) or low ( n = 48 patients) p-p38 expression. Log-rank (Mantel–Cox) test. e Representative image of IHC staining for p-p38 in human PDAC ( f ) p38 activation status in patients with PDAC with either high ( n = 55 patients, Ferroptosis Low) or low ( n = 53 patients, Ferroptosis High) expression of ferroptosis suppressor genes. Unpaired two-sided Student’s t -test. g Expression of p38 MAPK-related genes as measured by RNA-Seq in BxPC3 cells treated for 240 h with vehicle or gemcitabine ( n = 4 different wells). h Protein expression of p-p38 and p38 in PANC-1 cells treated with vehicle or GEM, cultured at 37 °C or 38 °C for 10 days. i Time-course confluence of PANC-1 ( n = 4 different wells, one representative experiment of 3 independent experiments is shown) or BxPC3 ( n = 6; n = 3; n = 6 different wells, respectively, one representative experiment of 3 independent experiments is shown) cells treated with GEM and supplemented with SB203580 or cultured at 38 °C. j Time-course confluence of wild-type or MAPK14 KO PANC-1 ( n = 6 different wells, one representative experiment of 2 independent experiments is shown) or BxPC3 ( n = 6; n = 12 different wells, respectively, one representative experiment of 2 independent experiments is shown) cells treated with vehicle or GEM. k Relative confluence of PANC-1 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C for 400 h ( n = 12 different wells, one representative experiment of 2 independent experiments is shown). One-way ANOVA with Šídák’s multiple comparisons test. l Time-course confluence of BxPC3 cells treated with GEM and supplemented with Doramapimod and ePLs or cultured at 38 °C ( n = 6 different wells, one representative experiment of 2 independent experiments is shown). m Survival of PANC-1 xenograft bearing NMRInu/nu mice treated with vehicle ( n = 3 mice) or GEM ( n = 8 mice), supplemented with the p38 inhibitor SB203580 ( n = 9 mice). Log-rank (Mantel–Cox) test. n Tumor volumes of individual PANC-1 xenograft bearing NMRInu/nu mice following treatment with gemcitabine (GEM, n = 10 mice) supplemented with SB203580 ( n = 10 mice). Error bars represent s.e.m. from mean. Source data are provided as a Source Data file.

Article Snippet: Equal amounts of protein were loaded onto precast gels (NuPAGE, ThermoFisher), transferred to nitrocellulose membranes, and incubated with antibodies against phospho-p38 MAPK (1/1000 dilution) (Cell Signaling, #4511) and p38 MAPK (1/1000 dilution) (Cell Signaling, #8690).

Techniques: Expressing, Immunohistochemistry, Activation Assay, RNA Sequencing Assay, Cell Culture

Effects of PVN infusion of HA or vehicle on the expressions of p-p38 MAPK in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.

Journal: Journal of Cardiovascular Pharmacology

Article Title: The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt–Induced Hypertension

doi: 10.1097/FJC.0000000000001622

Figure Lengend Snippet: Effects of PVN infusion of HA or vehicle on the expressions of p-p38 MAPK in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.

Article Snippet: The concentrations of the primary antibodies are as follows: CBS (1:1000, bs-4193R, Bioss), p-p38 MAPK (1:1000, AF5887, Beyotime), p38 MAPK (1:1000, AF7668, Beyotime), p-ERK (1:1000, sc-136521, Santa Cruz), ERK (1:3000, AF1051, Beyotime), p-JNK (1:1000, AF1762, Beyotime), and JNK (1:1000, AJ518, Beyotime).

Techniques: Staining, Western Blot, Expressing, Control

Effects of PVN infusion of HA or vehicle on the expressions of p-p38 MAPK in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.

Journal: Journal of Cardiovascular Pharmacology

Article Title: The Impact of Hydrogen Sulfide in the Paraventricular Nucleus on the MAPK Pathway in High Salt–Induced Hypertension

doi: 10.1097/FJC.0000000000001622

Figure Lengend Snippet: Effects of PVN infusion of HA or vehicle on the expressions of p-p38 MAPK in the PVN. The expressions of PVN p-p38 MAPK were higher in the HS groups than in the NS groups and increased significantly in the HS + HA group ( P < 0.01). A, Representative IF staining of p-p38 MAPK. B, Densitometric analysis of IF intensity of p-p38 MAPK in the PVN (n = 4). C, Representative western blot of p-p38 MAPK in the PVN. D, Densitometric analysis of protein expression of p-p38 MAPK in the PVN (p-p38 MAPK/t-p38 MAPK, n = 6). * P < 0.01 versus control (the NS groups); # P < 0.01 HS + PVN HA versus HS + PVN vehicle.

Article Snippet: The concentrations of the primary antibodies are as follows: CBS (1:1000, bs-4193R, Bioss), p-p38 MAPK (1:1000, AF5887, Beyotime), p38 MAPK (1:1000, AF7668, Beyotime), p-ERK (1:1000, sc-136521, Santa Cruz), ERK (1:3000, AF1051, Beyotime), p-JNK (1:1000, AF1762, Beyotime), and JNK (1:1000, AJ518, Beyotime).

Techniques: Staining, Western Blot, Expressing, Control