HY-13582R Search Results


bay2416964  (MedChemExpress)
93
MedChemExpress bay2416964
<t>BAY2416964</t> inhibits kynurenine-induced AHR activity in PyMT mouse mammary cancer cells. Kynurenine increased Cyp1a1 (A) , Cyp1b1 (B) and Parp7 (C) mRNA levels in a dose-response manner in PyMT cells as measured by RT-qPCR. Relative mRNA levels of Cyp1a1 (D) and Cyp1b1 (E) after dose-response treatment with BAY2416964. Cyp1a1 (F) and Cyp1b1 (G) mRNA levels after treatment with increasing doses of GNF351. Relative Cyp1a1 and Cyp1b1 mRNA levels after treatment with increasing amounts of BAY2416964 (H, I) or GNF351 (J, K) in the presence of 100 µM kynurenine. RT-qPCR results are generated by samples treated 6 h with test compounds and presented as mean ± S.E.M n=3. (L) Western blot of PyMT cells treated for 6 h with kynurenine, BAY2416964 or GNF351 at the concentrations indicated. Representative image n=3. (M) Quantification of western blot. (N) AHR protein in cytoplasmic and nuclear fractions after 6 h treatment with BAY2416964 or GNF351. Representative image n=3. (O) Protein quantification of cytoplasmic AHR relative to loading control (Tubulin). (P) Protein quantification of nuclear AHR relative to loading control (Lamin A/C). *p<0.05 compared with control (DMSO).
Bay2416964, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/bay2416964/product/MedChemExpress
Average 93 stars, based on 1 article reviews
bay2416964 - by Bioz Stars, 2026-02
93/100 stars
  Buy from Supplier
ta1  (MedChemExpress)
93
MedChemExpress ta1
<t>TA1</t> enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice
Ta1, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/ta1/product/MedChemExpress
Average 93 stars, based on 1 article reviews
ta1 - by Bioz Stars, 2026-02
93/100 stars
  Buy from Supplier
roginolisib  (MedChemExpress)
93
MedChemExpress roginolisib
<t>TA1</t> enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice
Roginolisib, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/roginolisib/product/MedChemExpress
Average 93 stars, based on 1 article reviews
roginolisib - by Bioz Stars, 2026-02
93/100 stars
  Buy from Supplier
carbendazim  (MedChemExpress)
92
MedChemExpress carbendazim
<t>TA1</t> enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice
Carbendazim, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 92/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/carbendazim/product/MedChemExpress
Average 92 stars, based on 1 article reviews
carbendazim - by Bioz Stars, 2026-02
92/100 stars
  Buy from Supplier
necroptosis  (MedChemExpress)
90
MedChemExpress necroptosis
<t>TA1</t> enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice
Necroptosis, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 90/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/result/necroptosis/product/MedChemExpress
Average 90 stars, based on 1 article reviews
necroptosis - by Bioz Stars, 2026-02
90/100 stars
  Buy from Supplier

Image Search Results


BAY2416964 inhibits kynurenine-induced AHR activity in PyMT mouse mammary cancer cells. Kynurenine increased Cyp1a1 (A) , Cyp1b1 (B) and Parp7 (C) mRNA levels in a dose-response manner in PyMT cells as measured by RT-qPCR. Relative mRNA levels of Cyp1a1 (D) and Cyp1b1 (E) after dose-response treatment with BAY2416964. Cyp1a1 (F) and Cyp1b1 (G) mRNA levels after treatment with increasing doses of GNF351. Relative Cyp1a1 and Cyp1b1 mRNA levels after treatment with increasing amounts of BAY2416964 (H, I) or GNF351 (J, K) in the presence of 100 µM kynurenine. RT-qPCR results are generated by samples treated 6 h with test compounds and presented as mean ± S.E.M n=3. (L) Western blot of PyMT cells treated for 6 h with kynurenine, BAY2416964 or GNF351 at the concentrations indicated. Representative image n=3. (M) Quantification of western blot. (N) AHR protein in cytoplasmic and nuclear fractions after 6 h treatment with BAY2416964 or GNF351. Representative image n=3. (O) Protein quantification of cytoplasmic AHR relative to loading control (Tubulin). (P) Protein quantification of nuclear AHR relative to loading control (Lamin A/C). *p<0.05 compared with control (DMSO).

Journal: Frontiers in Oncology

Article Title: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

doi: 10.3389/fonc.2024.1466658

Figure Lengend Snippet: BAY2416964 inhibits kynurenine-induced AHR activity in PyMT mouse mammary cancer cells. Kynurenine increased Cyp1a1 (A) , Cyp1b1 (B) and Parp7 (C) mRNA levels in a dose-response manner in PyMT cells as measured by RT-qPCR. Relative mRNA levels of Cyp1a1 (D) and Cyp1b1 (E) after dose-response treatment with BAY2416964. Cyp1a1 (F) and Cyp1b1 (G) mRNA levels after treatment with increasing doses of GNF351. Relative Cyp1a1 and Cyp1b1 mRNA levels after treatment with increasing amounts of BAY2416964 (H, I) or GNF351 (J, K) in the presence of 100 µM kynurenine. RT-qPCR results are generated by samples treated 6 h with test compounds and presented as mean ± S.E.M n=3. (L) Western blot of PyMT cells treated for 6 h with kynurenine, BAY2416964 or GNF351 at the concentrations indicated. Representative image n=3. (M) Quantification of western blot. (N) AHR protein in cytoplasmic and nuclear fractions after 6 h treatment with BAY2416964 or GNF351. Representative image n=3. (O) Protein quantification of cytoplasmic AHR relative to loading control (Tubulin). (P) Protein quantification of nuclear AHR relative to loading control (Lamin A/C). *p<0.05 compared with control (DMSO).

Article Snippet: BAY2416964 and GNF351 were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Activity Assay, Quantitative RT-PCR, Generated, Western Blot, Control

The murine pancreatic cancer cell line CR705 responds to BAY2416964 similarly as PyMT cells. Basel levels of Cyp1a1 (A) and Cyp1b1 (B) mRNA level decreased with 0.1 µM and 1 µM BAY2416964 and increased with 10 µM BAY2416964 in CR705 cells treated for 6 h. RT-qPCR of Cyp1a1 (C) and Cyp1b1 (D) mRNA levels in CR705 cells treated 6 h with kynurenine alone, or in combination with increasing doses of BAY2416964. RT-qPCR data presented as mean ± S.E.M. n=3 p<0.05. (E) Western blot of CR705 cells treated with 50 µM kynurenine or 10 µM BAY2416964. Representative image n=2. (F) Protein quantification of western blot presented in (E) . *p<0.05 compared with control (DMSO).

Journal: Frontiers in Oncology

Article Title: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

doi: 10.3389/fonc.2024.1466658

Figure Lengend Snippet: The murine pancreatic cancer cell line CR705 responds to BAY2416964 similarly as PyMT cells. Basel levels of Cyp1a1 (A) and Cyp1b1 (B) mRNA level decreased with 0.1 µM and 1 µM BAY2416964 and increased with 10 µM BAY2416964 in CR705 cells treated for 6 h. RT-qPCR of Cyp1a1 (C) and Cyp1b1 (D) mRNA levels in CR705 cells treated 6 h with kynurenine alone, or in combination with increasing doses of BAY2416964. RT-qPCR data presented as mean ± S.E.M. n=3 p<0.05. (E) Western blot of CR705 cells treated with 50 µM kynurenine or 10 µM BAY2416964. Representative image n=2. (F) Protein quantification of western blot presented in (E) . *p<0.05 compared with control (DMSO).

Article Snippet: BAY2416964 and GNF351 were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Quantitative RT-PCR, Western Blot, Control

Loss of AHR prevents increases in kynurenine-induced AHR target genes and reduces proliferation of PyMT cells. (A) Ahr mRNA levels in PyMT Ahr KO cells compared with WT cells as determined by RT-qPCR. Significance was determined with Student’s t-test, n=3 (B) Western blot of WT and Ahr KO cells detected no AHR protein in the PyMT Ahr KO cell line. Representative image of n=3. AHR activity was determined in the PyMT WT and Ahr KO cell lines by treatment with 100 µM kynurenine, 10 µM BAY2416964 or combination for 6 hours. Kynurenine and high concentration of BAY2416964 failed to increase Cyp1a1 (C) , Cyp1b1 (D) and Parp7 (E) expression levels in Ahr KO cells. RT-qPCR results are presented as mean ± S.E.M. of n=3. Significance was determined using Two-Way ANOVA, p<0.05. * Significant from PyMT WT control (DMSO). (F) Ahr KO cells proliferate more slowly than WT cells. (G) BAY2416964 did not affect proliferation of PyMT WT cells. (H) Proliferation of PyMT WT cells treated with increasing doses of GNF351. Treatment with 10 µM GNF351 decreased proliferation of PyMT WT cells. Proliferation of Ahr KO cells treated with increasing concentrations of BAY2416964 (I) or GNF351 (J) . Only 10 µM GNF351 affected proliferation of Ahr KO cells compared to DMSO control. WT was added for comparison. Data are presented as mean ± S.E.M of n=12, measured by IncuCyte. Significance was determined using Area under curve with p<0.05.

Journal: Frontiers in Oncology

Article Title: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

doi: 10.3389/fonc.2024.1466658

Figure Lengend Snippet: Loss of AHR prevents increases in kynurenine-induced AHR target genes and reduces proliferation of PyMT cells. (A) Ahr mRNA levels in PyMT Ahr KO cells compared with WT cells as determined by RT-qPCR. Significance was determined with Student’s t-test, n=3 (B) Western blot of WT and Ahr KO cells detected no AHR protein in the PyMT Ahr KO cell line. Representative image of n=3. AHR activity was determined in the PyMT WT and Ahr KO cell lines by treatment with 100 µM kynurenine, 10 µM BAY2416964 or combination for 6 hours. Kynurenine and high concentration of BAY2416964 failed to increase Cyp1a1 (C) , Cyp1b1 (D) and Parp7 (E) expression levels in Ahr KO cells. RT-qPCR results are presented as mean ± S.E.M. of n=3. Significance was determined using Two-Way ANOVA, p<0.05. * Significant from PyMT WT control (DMSO). (F) Ahr KO cells proliferate more slowly than WT cells. (G) BAY2416964 did not affect proliferation of PyMT WT cells. (H) Proliferation of PyMT WT cells treated with increasing doses of GNF351. Treatment with 10 µM GNF351 decreased proliferation of PyMT WT cells. Proliferation of Ahr KO cells treated with increasing concentrations of BAY2416964 (I) or GNF351 (J) . Only 10 µM GNF351 affected proliferation of Ahr KO cells compared to DMSO control. WT was added for comparison. Data are presented as mean ± S.E.M of n=12, measured by IncuCyte. Significance was determined using Area under curve with p<0.05.

Article Snippet: BAY2416964 and GNF351 were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Quantitative RT-PCR, Western Blot, Activity Assay, Concentration Assay, Expressing, Control, Comparison

Characterization of Ahr KO and long-term BAY2416964 treated PyMT cells. (A) Western blot of PyMT WT, PyMT Ahr KO and PyMT LT-BAY cells show AHR protein levels are not changed in PyMT LT-BAY cells compared to WT cells. Representative image of n=3. (B) Quantification of western blot from figure (A) , presented as mean ± S.E.M of n=3. Relative Cyp1a1 (C) and Cyp1b1 (D) mRNA levels in PyMT WT, Ahr KO and LT-BAY cells after exposure to 100 µM kynurenine for 6 hours, measured by RT-qPCR. Data are presented as mean ± S.E.M of n=3. *p<0.05 relative to WT DMSO, and # p<0.05 between Ahr KO and LT-BAY determined by one-way ANOVA for DMSO samples only. $ p<0.05 compared with WT DMSO and a p<0.05 significance between indicated comparisons determined by two-way ANOVA. (E) Proliferation of PyMT WT, Ahr KO and LT-BAY cells measured by IncuCyte. Data are presented as mean ± S.E.M. of n=16. (F) Migration of WT, Ahr KO and LT-BAY cells in a transwell assay measured by xCELLigence. Data are presented as mean ± S.E.M. of n=8. Significance was determined by area under curve, p<0.05.

Journal: Frontiers in Oncology

Article Title: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

doi: 10.3389/fonc.2024.1466658

Figure Lengend Snippet: Characterization of Ahr KO and long-term BAY2416964 treated PyMT cells. (A) Western blot of PyMT WT, PyMT Ahr KO and PyMT LT-BAY cells show AHR protein levels are not changed in PyMT LT-BAY cells compared to WT cells. Representative image of n=3. (B) Quantification of western blot from figure (A) , presented as mean ± S.E.M of n=3. Relative Cyp1a1 (C) and Cyp1b1 (D) mRNA levels in PyMT WT, Ahr KO and LT-BAY cells after exposure to 100 µM kynurenine for 6 hours, measured by RT-qPCR. Data are presented as mean ± S.E.M of n=3. *p<0.05 relative to WT DMSO, and # p<0.05 between Ahr KO and LT-BAY determined by one-way ANOVA for DMSO samples only. $ p<0.05 compared with WT DMSO and a p<0.05 significance between indicated comparisons determined by two-way ANOVA. (E) Proliferation of PyMT WT, Ahr KO and LT-BAY cells measured by IncuCyte. Data are presented as mean ± S.E.M. of n=16. (F) Migration of WT, Ahr KO and LT-BAY cells in a transwell assay measured by xCELLigence. Data are presented as mean ± S.E.M. of n=8. Significance was determined by area under curve, p<0.05.

Article Snippet: BAY2416964 and GNF351 were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: Western Blot, Quantitative RT-PCR, Migration, Transwell Assay

RNA sequencing revealing expressional effects of AHR inhibition. mRNA from PyMT WT, Ahr KO and LT-BAY cells was sequenced and analyzed of n=4, p<0.01. (A) Principal component analysis (PCA) plot of the 4 replicates. (B) Heatmap illustrating the relative gene expression profiles of overlapping differentially expressed genes in Ahr KO and LT-BAY cells relative to WT for each replicate. There is close homogeneity among the replicates, in addition to a greater effect of the genetic loss of Ahr , compared to pharmacological inhibition with BAY2416964. (C) Venn diagram of significantly changed genes in Ahr KO or LT-BAY cells compared with WT. Top up- and downregulated genes in Ahr KO (D) and in LT-BAY (E) compared with WT. Upregulated genes are marked in red, and downregulated genes in blue, with the size of the dot indicating the level of significance. (F) Presentation of AHR target genes that are significantly different in Ahr KO compared to WT, and in LT-BAY compared to WT. (G) Comparison of the top 12 commonly regulated pathways in Ahr KO or LT-BAY vs WT identified by ingenuity pathway analysis. Significantly changed pathways are defined by a Z-score >2 or <-2.

Journal: Frontiers in Oncology

Article Title: Long-term exposure to BAY2416964 reduces proliferation, migration and recapitulates transcriptional changes induced by AHR loss in PyMT-induced mammary tumor cells

doi: 10.3389/fonc.2024.1466658

Figure Lengend Snippet: RNA sequencing revealing expressional effects of AHR inhibition. mRNA from PyMT WT, Ahr KO and LT-BAY cells was sequenced and analyzed of n=4, p<0.01. (A) Principal component analysis (PCA) plot of the 4 replicates. (B) Heatmap illustrating the relative gene expression profiles of overlapping differentially expressed genes in Ahr KO and LT-BAY cells relative to WT for each replicate. There is close homogeneity among the replicates, in addition to a greater effect of the genetic loss of Ahr , compared to pharmacological inhibition with BAY2416964. (C) Venn diagram of significantly changed genes in Ahr KO or LT-BAY cells compared with WT. Top up- and downregulated genes in Ahr KO (D) and in LT-BAY (E) compared with WT. Upregulated genes are marked in red, and downregulated genes in blue, with the size of the dot indicating the level of significance. (F) Presentation of AHR target genes that are significantly different in Ahr KO compared to WT, and in LT-BAY compared to WT. (G) Comparison of the top 12 commonly regulated pathways in Ahr KO or LT-BAY vs WT identified by ingenuity pathway analysis. Significantly changed pathways are defined by a Z-score >2 or <-2.

Article Snippet: BAY2416964 and GNF351 were purchased from MedChemExpress (Monmouth Junction, NJ, USA).

Techniques: RNA Sequencing Assay, Inhibition, Expressing, Comparison

TA1 enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice

Journal: Journal of Neuroinflammation

Article Title: Intermittent hypoxia therapy ameliorates beta-amyloid pathology via TFEB-mediated autophagy in murine Alzheimer's disease

doi: 10.1186/s12974-023-02931-6

Figure Lengend Snippet: TA1 enhances the autophagic degradation of Aβ and reduces Aβ pathology in APP/PS1 mice. 6-month-old APP/PS1 mice were administered TA1 orally at 10 mg/kg for 3 months. A , B Mice brain sections were probed with anti-Aβ1–16 (6E10) antibodies. Scale bar = 2 mm. The number of hippocampal and cortical plaques was quantified in twelve evenly spaced brain slices from each mouse. n = 8, 6 (Student's t test). C Aβ1–42 in brain tissues was determined using ELISA. n = 6 (Student's t test). D Brain sections were co-stained with anti-TFEB and anti-Iba1 antibodies. Arrows indicate the PAM nuclei. Scale bar = 25 μm. E – H Brain sections were co-stained with anti-LC3, anti-Iba1, and anti-Aβ1–16 (6E10) or anti-LAMP1 antibodies. Scale bar = 10 μm. The colocalization ratio of LC3 with Aβ or LAMP1 in Iba1 + cells were estimated via Manders' colocalization coefficients. n > 30 (Student's t test). I , J Primary microglia were co-treated with oAβ and TA1 for 12 h, followed with bafilomycin A1 treatment for 1 h. Then, cells were probed with anti-LC3 and anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of LC3 with LAMP1 in single cell was quantified using Manders' colocalization coefficients. n > 40 (two-way ANOVA). K Aβ1–42 in the medium were then detected using ELISA. n = 5 (Student’s t test). L – O After co-treated with oAβ and TA1, cells were incubated with Aβ-555 for 30 min, or co-treated with bafilomycin A1 for 30 min and chased. Then, cells were stained with anti-LC3 or anti-LAMP1 antibodies. Scale bar = 5 μm. The colocalization ratio of Aβ-555 with LC3 or LAMP1 was measured via Manders’ colocalization coefficients. n > 50 (two-way ANOVA). * P < 0.05, ** P < 0.01, and *** P < 0.001. TG, APP/PS1 transgenic mice

Article Snippet: TA1 (CAS 39777-61-2) purchased from MedChemExpress (HY-135825, 99.69% purity) was dissolved in DMSO to yield a final concentration of 25 mg/ml.

Techniques: Enzyme-linked Immunosorbent Assay, Staining, Incubation, Transgenic Assay