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--- | ||
figid: PMC10313363__jci-133-162479-g168 | ||
pmcid: PMC10313363 | ||
image_filename: PMC10313363__jci-133-162479-g168.jpg | ||
figure_link: /pmc/articles/PMC10313363/figure/F1/ | ||
number: Figure 1 | ||
figure_title: Improved whole-body metabolism in Cdk4R/R mice | ||
caption: '(A) Glucose tolerance and (B) insulin sensitivity in Cdk4R/R mice compared | ||
with those in Cdk4WT mice. (C) Body weight, (D) fat mass, (E) lean mass, (F) fasting | ||
and fed blood glucose levels, (G) glucose tolerance, and (H) insulin sensitivity | ||
in Cdk4R/R mice and Cdk4WT mice in response to 60% HFD. (I) Histology of white adipose | ||
(WAT) (top) and liver tissues (bottom) from HFD-fed Cdk4R/R mice and similarly fed | ||
Cdk4WT mice. Scale bars: 100 μm. (J) Whole-body and (K) skeletal muscle glucose | ||
uptake during hyperinsulinemic-euglycemic clamp assay in regular chow–fed Cdk4R/R | ||
mice compared with Cdk4WT mice. (L) Phosphorylation levels of insulin signaling | ||
pathway intermediatory proteins, IRS-1 and Akt, in Cdk4R/R muscle in comparison | ||
to Cdk4WT muscle. Total IRS-1,Akt, and α-tubulin proteins are shown as controls. | ||
(M) Energy expenditure, (N) ambulatory activity, (O) RER, and (P) muscle exercise | ||
work in Cdk4R/R mice and Cdk4WT mice (n = 9–11 mice each group). Between 6 and 8 | ||
mice per group fed regular chow were used in each experiment, unless mentioned otherwise. | ||
Data are shown as the mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001 by 2-tailed | ||
Student’s t test' | ||
article_title: CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and | ||
function to affect myogenesis and metabolism | ||
citation: Young Jae Bahn, et al. J Clin Invest. 2023 Jul 3;133(13). | ||
year: '2023' | ||
pub_date: 2023-7-3 | ||
epub_date: 2023-7-3 | ||
doi: 10.1172/JCI162479 | ||
journal_title: The Journal of Clinical Investigation | ||
journa_nlm_ta: J Clin Invest | ||
publisher_name: American Society for Clinical Investigation | ||
keywords: | ||
- Metabolism | ||
- Muscle Biology | ||
- Mitochondria | ||
- Skeletal muscle | ||
--- |
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figid: PMC10313365__jci-133-169993-g001 | ||
pmcid: PMC10313365 | ||
image_filename: PMC10313365__jci-133-169993-g001.jpg | ||
figure_link: /pmc/articles/PMC10313365/figure/F1/ | ||
number: Figure 1 | ||
figure_title: Genome-wide Screen Identifies Purine and Pyrimidine Synthesis Pathways | ||
as Essential for viability in MLL3/4-KO mESCs | ||
caption: (A) Flowchart showing CRISPR KO-based dropout screening in WT and KO cells. | ||
(B) GO biological process pathway analysis (using MAGeCK) of the top 300 negatively | ||
selected genes in MLL3/4-KO cells. (C) Rank plot showing the distribution of negative | ||
RRA score with the scores of the 12 genes involved in purine/pyrimidine synthesis | ||
that were identified as essential in MLL3/4 KO. (D) β scores of gene essentiality | ||
were calculated for WT and KO cells. The 12 screen-identified genes involved in | ||
purine/pyrimidine synthesis are shown in the 9-square view. Orange, genes selectively | ||
essential in KO not WT; light purple, genes selectively essential in WT not KO; | ||
green, genes depletion of which enhanced survival in KO not WT; dark purple, genes | ||
depletion of which enhanced survival in WT not KO. (E) Distribution of sgRNA read | ||
counts (normalized) of the 2 representative genes Ppat and Mthfd1 in WT and KO cells | ||
at different time points. The four colors represent the four distinct sgRNAs in | ||
the Brie CRISPR library | ||
article_title: Therapeutic targeting of metabolic vulnerabilities in cancers with | ||
MLL3/4-COMPASS epigenetic regulator mutations | ||
citation: Zibo Zhao, et al. J Clin Invest. 2023 Jul 3;133(13). | ||
year: '2023' | ||
pub_date: 2023-7-3 | ||
epub_date: 2023-7-3 | ||
doi: 10.1172/JCI169993 | ||
journal_title: The Journal of Clinical Investigation | ||
journa_nlm_ta: J Clin Invest | ||
publisher_name: American Society for Clinical Investigation | ||
keywords: | ||
- Genetics | ||
- Metabolism | ||
- Colorectal cancer | ||
- Epigenetics | ||
--- |
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figid: PMC10313365__jci-133-169993-g003 | ||
pmcid: PMC10313365 | ||
image_filename: PMC10313365__jci-133-169993-g003.jpg | ||
figure_link: /pmc/articles/PMC10313365/figure/F3/ | ||
number: Figure 3 | ||
figure_title: MLL3/4-KO mESCs display enhanced sensitivity to purine synthesis inhibition | ||
caption: |- | ||
(A) WT and MLL3/4-KO cells were treated with 0–2.5 μM LTX with a 2-fold dilution in the presence or absence of 50 μM HPX for 48 hours. A CellTiter-Glo luminescent cell viability assay was performed to determine the percentage of cell growth inhibition under these conditions. WT, n = 3; MLL3/4 KO, n = 3. (B) WT and KO cells were treated with 0.3 μM LTX ± 50 μM HPX for 48 hours, and cells were harvested for RNA-Seq (n = 2 for each condition). Differential gene expression analyses were performed with the indicated comparisons. (C) PC analysis of RNA-Seq in B. The 500 most variable genes among all the conditions were included by default. (D) Hierarchical clustering heatmap showing differentially expressed genes in KO cells compared with WT cells. Differentially expressed genes with Benjamini-Hochburg Padj | ||
< 0.01 were selected. (E) Venn diagram showing the overlap of genes downregulated upon LTX treatment in WT or KO cells. (F) Pathway enrichment analysis of the genes downregulated upon LTX treatment in both WT and KO cells. (G) Pathway enrichment analysis of the genes uniquely downregulated upon LTX treatment in WT cells. (H) Pathway enrichment analysis of the genes uniquely downregulated upon LTX treatment in MLL3/4-KO cells | ||
article_title: Therapeutic targeting of metabolic vulnerabilities in cancers with | ||
MLL3/4-COMPASS epigenetic regulator mutations | ||
citation: Zibo Zhao, et al. J Clin Invest. 2023 Jul 3;133(13). | ||
year: '2023' | ||
pub_date: 2023-7-3 | ||
epub_date: 2023-7-3 | ||
doi: 10.1172/JCI169993 | ||
journal_title: The Journal of Clinical Investigation | ||
journa_nlm_ta: J Clin Invest | ||
publisher_name: American Society for Clinical Investigation | ||
keywords: | ||
- Genetics | ||
- Metabolism | ||
- Colorectal cancer | ||
- Epigenetics | ||
--- |
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figid: PMC10313365__jci-133-169993-g008 | ||
pmcid: PMC10313365 | ||
image_filename: PMC10313365__jci-133-169993-g008.jpg | ||
figure_link: /pmc/articles/PMC10313365/figure/F8/ | ||
number: Figure 8 | ||
figure_title: The roadmap of molecular changes and cellular phenotypes when cells | ||
lose MLL3/4-COMPASS | ||
caption: To identify targetable cellular vulnerabilities that arise when MLL3/4 are | ||
compromised, a variety of multiomics approaches were utilized including a synthetic | ||
lethality screen and metabolic, transcriptomic, and proteomic profiling. In addition | ||
to the downregulation of MLL3/4 target genes, the loss of MLL3/4 also leads to the | ||
activation of MLL1/COMPASS, which drives the upregulated expression of de novo purine | ||
metabolism genes. This upregulation was found to be reversible by the specific inhibition | ||
of interaction between MLL1 and the cofactor WDR5. These findings led to the therapeutic | ||
evaluation of the de novo purine nucleotide synthesis pathway targeting in MLL4 | ||
mutant colorectal cancer using lometrexol, a specific inhibitor of the purine synthesis | ||
enzyme GART. This promising approach may offer new hope for patients with MLL4 mutant | ||
colorectal cancer | ||
article_title: Therapeutic targeting of metabolic vulnerabilities in cancers with | ||
MLL3/4-COMPASS epigenetic regulator mutations | ||
citation: Zibo Zhao, et al. J Clin Invest. 2023 Jul 3;133(13). | ||
year: '2023' | ||
pub_date: 2023-7-3 | ||
epub_date: 2023-7-3 | ||
doi: 10.1172/JCI169993 | ||
journal_title: The Journal of Clinical Investigation | ||
journa_nlm_ta: J Clin Invest | ||
publisher_name: American Society for Clinical Investigation | ||
keywords: | ||
- Genetics | ||
- Metabolism | ||
- Colorectal cancer | ||
- Epigenetics | ||
--- |
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--- | ||
figid: PMC10340012__animals-13-02223-g001a | ||
pmcid: PMC10340012 | ||
image_filename: PMC10340012__animals-13-02223-g001a.jpg | ||
figure_link: /pmc/articles/PMC10340012/figure/F1/ | ||
number: Figure 1 | ||
figure_title: Effect of interference with DGAT gene on differentiation of bovine proadipocytes. | ||
caption: 'Effect of interference with DGAT gene on differentiation of bovine proadipocytes. | ||
(A) mRNA expression of DGAT post siRNA infection. (B) Oil red O staining (Scale | ||
bars: 200 µm). (C) Concentration of triglycerides and adiponectin. (D) Expression | ||
of genes associated with triglyceride synthesis pathway. (E) Expression of genes | ||
associated with lipid metabolism. Data are presented as the mean ± SEM (n = 3). | ||
The different letters (a–d) represent significant differences (p < 0.05) in gene | ||
expression' | ||
article_title: Interference with DGAT Gene Inhibited TAG Accumulation and Lipid Droplet | ||
Synthesis in Bovine Preadipocytes | ||
citation: Panpan Guo, et al. Animals (Basel). 2023 Jul;13(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-06 | ||
doi: 10.3390/ani13132223 | ||
journal_title: 'Animals : an Open Access Journal from MDPI' | ||
journa_nlm_ta: Animals (Basel) | ||
publisher_name: MDPI | ||
keywords: | ||
- tiacylglycerol | ||
- DGAT | ||
- preadipocyte | ||
- interference | ||
- transcriptome | ||
--- |
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--- | ||
figid: PMC10340012__animals-13-02223-g005 | ||
pmcid: PMC10340012 | ||
image_filename: PMC10340012__animals-13-02223-g005.jpg | ||
figure_link: /pmc/articles/PMC10340012/figure/F5/ | ||
number: Figure 5 | ||
figure_title: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially | ||
expressed genes (DEGs) in the sh-NC vs. | ||
caption: Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially | ||
expressed genes (DEGs) in the sh-NC vs. sh-1 groups (A), sh-NC vs. sh-2 groups (B) | ||
and sh-NC vs. sh-1 + 2 groups (C) | ||
article_title: Interference with DGAT Gene Inhibited TAG Accumulation and Lipid Droplet | ||
Synthesis in Bovine Preadipocytes | ||
citation: Panpan Guo, et al. Animals (Basel). 2023 Jul;13(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-06 | ||
doi: 10.3390/ani13132223 | ||
journal_title: 'Animals : an Open Access Journal from MDPI' | ||
journa_nlm_ta: Animals (Basel) | ||
publisher_name: MDPI | ||
keywords: | ||
- tiacylglycerol | ||
- DGAT | ||
- preadipocyte | ||
- interference | ||
- transcriptome | ||
--- |
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--- | ||
figid: PMC10340012__animals-13-02223-g006a | ||
pmcid: PMC10340012 | ||
image_filename: PMC10340012__animals-13-02223-g006a.jpg | ||
figure_link: /pmc/articles/PMC10340012/figure/F6/ | ||
number: Figure 6 | ||
figure_title: DEGs were enriched in PPAR, WNT, and AMPK signaling pathways (A–C). | ||
caption: DEGs were enriched in PPAR, WNT, and AMPK signaling pathways (A–C). A total | ||
of 12 differential genes were screened and verified using real-time quantitative | ||
PCR (A–C) | ||
article_title: Interference with DGAT Gene Inhibited TAG Accumulation and Lipid Droplet | ||
Synthesis in Bovine Preadipocytes | ||
citation: Panpan Guo, et al. Animals (Basel). 2023 Jul;13(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-06 | ||
doi: 10.3390/ani13132223 | ||
journal_title: 'Animals : an Open Access Journal from MDPI' | ||
journa_nlm_ta: Animals (Basel) | ||
publisher_name: MDPI | ||
keywords: | ||
- tiacylglycerol | ||
- DGAT | ||
- preadipocyte | ||
- interference | ||
- transcriptome | ||
--- |
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--- | ||
figid: PMC10340072__animals-13-02234-g002 | ||
pmcid: PMC10340072 | ||
image_filename: PMC10340072__animals-13-02234-g002.jpg | ||
figure_link: /pmc/articles/PMC10340072/figure/F2/ | ||
number: Figure 2 | ||
figure_title: Identification and analysis of E75 and E125 differentially expressed | ||
(DE) messenger RNAs (mRNAs). | ||
caption: Identification and analysis of E75 and E125 differentially expressed (DE) | ||
messenger RNAs (mRNAs). (a) Violin plots of gene expression patterns for each sample. | ||
(b) Venn diagram of mRNA distribution across samples, where the overlap represents | ||
consensus mRNA for two sample types. (c) Volcano plots of log2-fold change (FC) | ||
for E75 and E125 mRNA. (d) Cluster analysis heatmap. (e) Gene Ontology (GO) functional | ||
annotations. (f,g) GO functional enrichment and Kyoto Encyclopedia of Genes and | ||
Genomes (KEGG) signalling pathway enrichment. Circle size and colour represent the | ||
degree of enrichment and enrichment significance, respectively | ||
article_title: Effect of Fibroblast Growth Factor 10 and an Interacting Non-Coding | ||
RNA on Secondary Hair Follicle Dermal Papilla Cells in Cashmere Goats’ Follicle | ||
Development Assessed by Whole-Transcriptome Sequencing Technology | ||
citation: Yuan Gao, et al. Animals (Basel). 2023 Jul;13(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-07 | ||
doi: 10.3390/ani13132234 | ||
journal_title: 'Animals : an Open Access Journal from MDPI' | ||
journa_nlm_ta: Animals (Basel) | ||
publisher_name: MDPI | ||
keywords: | ||
- cashmere goats | ||
- hair follicle development | ||
- FGF10 | ||
--- |
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--- | ||
figid: PMC10340072__animals-13-02234-g004 | ||
pmcid: PMC10340072 | ||
image_filename: PMC10340072__animals-13-02234-g004.jpg | ||
figure_link: /pmc/articles/PMC10340072/figure/F4/ | ||
number: Figure 4 | ||
figure_title: Identification and analysis of E75 and E125 DEmiRNAs. | ||
caption: Identification and analysis of E75 and E125 DEmiRNAs. (a) Violin plots of | ||
gene expression patterns for each sample. (b) Venn diagram of miRNA distribution | ||
across samples with the intersecting section representing shared miRNAs of both | ||
samples. (c) Volcano plot of log2 FC (ST/CK) for E75 and E125 miRNAs. (d) Cluster | ||
analysis heatmap. (e,f) GO functional enrichment and Kyoto Encyclopedia of Genes | ||
and Genomes (KEGG) signalling pathway enrichment. The circle size and circle colour | ||
represent enrichment and enrichment significance, respectively | ||
article_title: Effect of Fibroblast Growth Factor 10 and an Interacting Non-Coding | ||
RNA on Secondary Hair Follicle Dermal Papilla Cells in Cashmere Goats’ Follicle | ||
Development Assessed by Whole-Transcriptome Sequencing Technology | ||
citation: Yuan Gao, et al. Animals (Basel). 2023 Jul;13(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-07 | ||
doi: 10.3390/ani13132234 | ||
journal_title: 'Animals : an Open Access Journal from MDPI' | ||
journa_nlm_ta: Animals (Basel) | ||
publisher_name: MDPI | ||
keywords: | ||
- cashmere goats | ||
- hair follicle development | ||
- FGF10 | ||
--- |
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--- | ||
figid: PMC10340602__cells-12-01768-g003 | ||
pmcid: PMC10340602 | ||
image_filename: PMC10340602__cells-12-01768-g003.jpg | ||
figure_link: /pmc/articles/PMC10340602/figure/F3/ | ||
number: Figure 3 | ||
figure_title: Effects of xanol on the AKT signaling pathway in human OSCC cells. | ||
caption: 'Effects of xanol on the AKT signaling pathway in human OSCC cells. (A,B) | ||
Human OSCC cells were treated with xanol for 24 h at 1–10 μM concentrations, and | ||
p-PI3K (Tyr458), PI3K, p-AKT (Ser473), and AKT (A) and p-mTOR (Ser2481), mTOR, p-p70S6K | ||
(Thr421/Ser424), and p70S6K (B) were analyzed by western blotting. (C,D) p-AKT (red | ||
color) levels were observed using an immunofluorescence assay. 4′,6-Diamidino-2-phenylindole | ||
(DAPI, blue color) was used to detect the nuclei of human OSCC cells (C). pAKT intensity | ||
is shown as a bar graph. Red symbol: n number. Dotted line: mean value (D). Data | ||
are representative of three independent experiments. Statistical significance was | ||
set at p < 0.05 * and data were analyzed using GraphPad Prism version 5' | ||
article_title: Xanol Promotes Apoptosis and Autophagy and Inhibits Necroptosis and | ||
Metastasis via the Inhibition of AKT Signaling in Human Oral Squamous Cell Carcinoma | ||
citation: Hyung-Mun Yun, et al. Cells. 2023 Jul;12(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-03 | ||
doi: 10.3390/cells12131768 | ||
journal_title: Cells | ||
journa_nlm_ta: Cells | ||
publisher_name: MDPI | ||
keywords: | ||
- A. keiskei | ||
- apoptosis | ||
- autophagy | ||
- necroptosis | ||
- OSCC | ||
- xanol | ||
--- |
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--- | ||
figid: PMC10340704__cells-12-01777-g004 | ||
pmcid: PMC10340704 | ||
image_filename: PMC10340704__cells-12-01777-g004.jpg | ||
figure_link: /pmc/articles/PMC10340704/figure/F4/ | ||
number: Figure 4 | ||
figure_title: ASIV promotes ALDH2 expression, inhibits autophagy, and activates AKT/mTOR | ||
signaling pathway in vivo. | ||
caption: 'ASIV promotes ALDH2 expression, inhibits autophagy, and activates AKT/mTOR | ||
signaling pathway in vivo. (a) ALDH2 mRNA level in the renal tissues using qRT-PCR | ||
for each group. (b) Protein expression of ALDH2 in the renal tissues of each group | ||
using Western blotting. (c) Quantitative analysis of the relative protein expression | ||
of ALDH2 in the renal tissues. (d) Representative images of immunohistochemistry | ||
staining for ALDH2 in the rat kidneys (n = 6, 100 µm scale bar). (e) Relative gene | ||
expressions of Mtor, Map1lc3b, Becn1, and Atg7 in the renal tissues of each group | ||
(n = 6). (f) Protein expressions of p-AKT, t-AKT, p-mTOR, t-mTOR, ATG7, SQSTM1, | ||
Beclin1, and LC3 I/II in the renal tissues of each group using Western blotting. | ||
(g) Quantitative analysis of the phosphorylation levels of AKT and mTOR in the renal | ||
tissues. (h) Quantitative analysis of the relative protein expressions of ATG7, | ||
SQSTM1, Beclin1, and LC3 II/LC3 I in the renal tissues. (i) Representative images | ||
of immunofluorescence staining for LC3 I/II/α-tubulin in the rat kidneys (n = 6, | ||
100 µm scale bar). Data are presented as mean ± SEM. One-way ANOVA was followed | ||
by Dunnett’s multiple comparisons test. ### p < 0.001 vs. the control group, * p | ||
< 0.05, ** p < 0.01, *** p < 0.001 vs. the adenine group' | ||
article_title: Astragaloside IV Blunts Epithelial–Mesenchymal Transition and G2/M | ||
Arrest to Alleviate Renal Fibrosis via Regulating ALDH2-Mediated Autophagy | ||
citation: Dong Li, et al. Cells. 2023 Jul;12(13). | ||
year: '2023' | ||
pub_date: 2023-7- | ||
epub_date: 2023-7-04 | ||
doi: 10.3390/cells12131777 | ||
journal_title: Cells | ||
journa_nlm_ta: Cells | ||
publisher_name: MDPI | ||
keywords: | ||
- renal fibrosis | ||
- astragaloside IV | ||
- ALDH2 | ||
- autophagy | ||
- AKT/mTOR | ||
--- |
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