streptozotocin (stz) solution  (Beijing Solarbio Science)

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 2. Pathological changes in STZ-induced diabetic mice. (A) Changes in blood glucose and body weight of WT (WT-STZ) and LCN2−/−(LCN2−/−-STZ) mice induced by intraperitoneal injections of STZ. The control group received sodium citrate solution (WT-SC and LCN2−/−-SC). The observation period spanned 12 weeks after STZ injection. ns (blue), compared to the WT-SC; ns (green), compared to the WT-STZ. ****P < 0.0001 compared to the WT-SC (n = 24). (B) Representative images of lenses in four groups of mice. Scale bar: 1 mm. (C) Representative fluorescence signal images of flatmounted retinas after injection of Evans blue dye. Scale bar: 100 μm (n = 4). (D) Representative images of retinal OCT in four groups of mice (n = 3). (E) Representative retinal H&E staining images for the four groups. Scale bar: 50 μm (n = 3).(F, G) Quantitative analysis of total retinal and inner plexiform layer thickness (n = 3). *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Control, Injection, Fluorescence, Staining

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 3. Quality control of untargeted metabolomics data. In each image of Fig. 3, A–D represent the LCN2−/−-STZ group, WT-STZ group, LCN2−/−-SC group, and WT-SC group of the lenses and E–H represent the LCN2−/−-STZ group, WT-STZ group, LCN2−/−-SC group, and WT-SC group of the retinas. (A) Principal component analysis of the lens and retinal groups in cationic mode. (B) Principal component analysis of lens and retinal groups in anion mode. (C, D) Score plots and permutation analysis plot of OPLS-DA among the four lens groups from STZ-induced WT mice and LCN2−/−mice in cationic mode. (E, F) Score plots and permutation analysis plot of OPLS-DA among the four retina groups from STZ-induced WT mice and LCN2−/−mice in cationic mode.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Control

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 4. Metabolic changes in mice lenses by STZ induction. In each image of Fig. 4, (B) and (D) represent the WT-STZ group (n = 9) and WT-SC group (n = 8) of the lenses. (A) Volcano plot of 136 differential metabolites. Compared to the WT-SC group, metabolites that were significantly upregulated in the WT-STZ group are marked in red, with VIP > 1, P < 0.05, and fold change (FC) > 1.5. Metabolites that were remarkedly downregulated in the WT-STZ group are marked in blue. Metabolites with VIP > 1, P < 0.05, and FC < 1.5 are indicated in yellow. Non-significant metabolites are represented in gray. The size of the dots corresponds to the magnitude of the VIP values. (B) Heatmap of 136 differential metabolites. Red represents significantly upregulated metabolites in the WT-STZ group compared to the WT-SC group, and blue represents downregulated metabolites. (C) Classification of 136 differential metabolites. (D) The top 20 differential abundance score with P < 0.05 based on KEGG enrichment analysis. DA-score = (number of upregulated metabolites −number of downregulated metabolites)/(total number of differential metabolites in the pathway). (E) Chord plots of the top 10 KEGG enrichment terms with P < 0.05. (F) Circle plots of the top 10 KEGG enrichment terms with P < 0.05. Red represents metabolites with elevated expression, and blue represents metabolites with decreased expression.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Expressing

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 5. Metabolic alterations in lenses of STZ-induced WT and LCN2−/−mice. In each image of Fig. 5, A and B represent the LCN2−/−- STZ group (n = 8) and WT-STZ group (n = 9) of the lenses. (A) Volcano plot of 54 differential metabolites. Compared to the WT-STZ group, metabolites that were significantly upregulated in the LCN2−/−-STZ group are marked in red, with VIP > 1, P < 0.05, and FC > 1.5. Metabolites that were remarkedly downregulated in the LCN2−/−-STZ group are marked in blue. Metabolites with VIP > 1, P < 0.05, and FC < 1.5 are indicated in yellow. Non-significant metabolites are shown in gray. The size of the dots corresponds to the magnitude of the VIP values. (B) Heatmap of 54 differential metabolites. Red represents significantly upregulated metabolites in the LCN2−/−-STZ group compared to the WT-STZ group, and blue represents downregulated metabolites. (C) Chord plots of the top 10 KEGG enrichment terms with P < 0.05. (D) The top 20 differential abundance score with P < 0.05 based on KEGG enrichment analysis. (E) The relative expression levels of differential metabolites in the top three KEGG pathways between the two groups. *P < 0.05, **P < 0.01, ****P < 0.0001.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Expressing

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 6. Metabolic changes in mice retinas by STZ induction. In each image of Fig. 6, F and H represent the WT-STZ group (n = 8) and WT-SC group (n = 8) of the retinas. (A) Volcano plot of 218 differential metabolites. Compared to the WT-SC group, metabolites that were significantly upregulated in the WT-STZ group are marked in red, with VIP > 1, P < 0.05, and FC > 1.5. Metabolites that were remarkedly downregulated in the WT-STZ group are indicated in blue. Metabolites with VIP > 1, P < 0.05, and FC < 1.5 are indicated in yellow. Non-significant metabolites are represented in gray. The size of the dots corresponds to the magnitude of the VIP values. (B) Heatmap of 218 differential metabolites. Red represents significantly upregulated metabolites in the WT-STZ group compared to the WT-SC group, and blue represents downregulated metabolites. (C) Classification of 218 differential metabolites. (D) The top 20 DA-scores with P < 0.05 based on KEGG enrichment analysis. (E) Chord plots of the top 10 KEGG enrichment terms with P < 0.05. (F) Circle plots of the top 10 KEGG enrichment terms with P < 0.05. Red represents metabolites with elevated expression, and blue represents metabolites with decreased expression.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Expressing

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 7. Metabolic alterations in retinas of STZ-induced WT and LCN2−/−mice. In each image of Fig. 7, E and F represent the LCN2−/−- STZ group (n = 8) and WT-STZ group (n = 9) of the retinas. (A) Volcano plot of 35 differential metabolites. Compared with the WT-STZ group, metabolites that were significantly upregulated in the LCN2−/−-STZ group are marked in red, with VIP > 1, P < 0.05, and FC > 1.5. Metabolites that were remarkedly downregulated in the LCN2−/−-STZ group are marked in blue. Metabolites with VIP > 1, P < 0.05, and FC < 1.5 are indicated in yellow. Non-significant metabolites are represented in gray. The size of the dots corresponds to the magnitude of the VIP values. (B) Heatmap of 35 differential metabolites. Red represents significantly upregulated metabolites in the LCN2−/−-STZ group compared to the WT-STZ group, and blue represents downregulated metabolites. (C) Chord plots of the top 10 KEGG enrichment terms with P < 0.05. (D) The top 20 differential abundance score with P < 0.05 based on KEGG enrichment analysis. (E) Metabolites involving multiple enriched metabolic pathways. *P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques:

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 8. Lens and retinas change metabolites in STZ-induced WT mice. In each image of Fig. 8, B and D represent the WT-STZ (n = 9) group and WT-SC group (n = 8) of the lenses, and F and H represent the WT-STZ group (n = 8) and WT-SC group (n = 8) of the retinas. (A) Overlap of differential metabolites in different groups. (B) Relative expression of differential metabolites in different groups. *P < 0.05, **P < 0.01, ***P < 0.001,****P < 0.0001, #P < 0.05, ##P < 0.01, ###P < 0.001, ####P < 0.0001.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Expressing

Journal: Investigative ophthalmology & visual science

Article Title: Untargeted Metabolomics Reveals the Role of Lipocalin-2 in the Pathological Changes of Lens and Retina in Diabetic Mice.

doi: 10.1167/iovs.65.14.19

Figure Lengend Snippet: FIGURE 9. Lens and retinas change metabolites in STZ-induced WT mice compared with LCN2−/−mice. In each image of Fig. 9, A and B represent the LCN2−/−-STZ group (n = 8) and WT-STZ group (n = 9) of the lenses, and E and F represent the LCN2−/−-STZ group (n = 8) and WT-STZ group (n = 9) of the retinas. (A) Overlap of differential metabolites in different groups. (B) Relative expression of differential metabolites in different groups. *P < 0.05, **P < 0.01, ##P < 0.01, ###P < 0.001.

Article Snippet: Mice in the STZ groups were intraperitoneally injected with STZ solution (50 mg/kg for 5 days, MP Biomedicals, Santa Ana, CA, USA).

Techniques: Expressing

Journal: Microbiome

Article Title: BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21

doi: 10.1186/s40168-024-01872-3

Figure Lengend Snippet: Elevated BCAA derive from reduced BCAA degradation ability of the gut microbiota in T1D mice. a Flow diagram of FMT experiment: After 1 week of acclimation, mice were injected with streptozocin (STZ) for 5 days to develop type 1 diabetic (T1D) mice and then administered with a 5-day antibiotic (Abx) treatment after 8 weeks. Subsequently, faecal material from control (Ctrl) mice was transferred to Abx-treated T1Dmice (FMT) for 2 weeks. Finally, mice were subjected to cardiac function test with echocardiography and sample analysis ( n = 5 mice per group). b NMDS analysis showing the beta diversity of the gut microbiota in Ctrl, T1D and FMT mice. Volcano plot analysis based on the gut microbiota at the species level ( c ) between Ctrl and T1D mice and d between T1D and FMT mice. e Venn diagram showing 69 gut microbes that were significantly altered in T1D mice relative to Ctrl mice and then also varied after FMT. f Heatmap showing changes in 69 gut microbes identified from volcano plot. g BCAAs biosynthesis (Ko00290) and h BCAAs degradation (Ko00280) of the gut microbiota in Ctrl, T1D and FMT mice. i The levels of key enzymes in BCAA degradation of the gut microbiota among Ctrl, T1D and FMT mice. The levels of ( j , m ) leucine, ( k , n ) isoleucine and l , o valine in the feces and serum of Ctrl, T1D and FMT mice. The differences among three groups were analyzed by using one-way ANOVA with Bonferroni’s multiple comparisons test, and different lowercase codes represent a statistically significant difference ( p < 0.05)

Article Snippet: To develop a mouse model of type 1 diabetes (T1D), mice after a 12-h fasting were treated with intraperitoneal injection of STZ (Sigma-Aldrich) solution in citrate buffer (pH = 4.5) at a dose of 50 mg/kg body weight for 5 consecutive days.

Techniques: Injection, Control

Journal: Microbiome

Article Title: BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21

doi: 10.1186/s40168-024-01872-3

Figure Lengend Snippet: FGF21 inhibits LAT1 and improves cardiac dysfunction in T1D mice. a Flow diagram of experiment: After 1 week of acclimation, mice were injected with streptozocin (STZ) for 5 days to induce type 1 diabetic (T1D) mice and then treated with FGF21 or JPH203 as a positive control for 8 weeks. After 8 weeks, mice were subjected to cardiac function test with echocardiography and sample analysis ( n = 5–7 mice per group). b Representative histological images of LAT1 staining (bar = 100 μm) and c the corresponding quantitative data to show the level of LAT1 in the heart of normal control (Ctrl), T1D, FGF21-treated and JPH203-treated mice. The levels of d leucine, e isoleucine and f valine in the heart of Ctrl, T1D, FGF21-treated and JPH203-treated mice. g Representative images of M-mode echocardiographs, wheat germ agglutinin (WGA) and Masson staining (bar = 100 μm) in Ctrl, T1D, FGF21-treated and JPH203-treated mice. h Left ventricular ejection fraction (%EF), i left ventricular fractional shortening (%FS), j left ventricular internal dimension at systole (LVIDs), k cardiomyocyte size and l degree of fibrosis in Ctrl, T1D, FGF21-treated and JPH203-treated mice. m Western blotting showing the expression levels of LAT1, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), mTOR and p-mTOR in Ctrl, T1D,FGF21-treated and JPH203-treated mice and n the corresponding quantitative data. The differences among four groups were analyzed by using one-way ANOVA with Bonferroni’s multiple comparisons test, and different lowercase codes represent a statistically significant difference ( p < 0.05)

Article Snippet: To develop a mouse model of type 1 diabetes (T1D), mice after a 12-h fasting were treated with intraperitoneal injection of STZ (Sigma-Aldrich) solution in citrate buffer (pH = 4.5) at a dose of 50 mg/kg body weight for 5 consecutive days.

Techniques: Injection, Positive Control, Staining, Control, Western Blot, Expressing

Journal: Microbiome

Article Title: BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21

doi: 10.1186/s40168-024-01872-3

Figure Lengend Snippet: AAV-mediated LAT1 overexpression abolishes the cardioprotective effect of FGF21 in T1D mice. a Flow diagram of experiment: After 1 week of acclimation, mice were injected with streptozocin (STZ) for 5 days to induce type 1 diabetic (T1D) mice and then treated with AAV9-LAT1 for the specific overexpression of LAT1 in the heart of T1D mice during FGF21 treatment for 8 weeks. After 8 weeks, mice were subjected to cardiac function test with echocardiography and sample analysis ( n = 5–6 mice per group). b Representative M-mode echocardiographs in control (Ctrl) and T1D mice as well as T1D mice treated with FGF21 plus AAV9-NC (empty vector) or AAV9-LAT1. c Left ventricular ejection fraction (%EF), d left ventricular fractional shortening (%FS) and e left ventricular internal dimension at systole (LVIDs) in Ctrl and T1D mice and T1D mice treated with FGF21 plus AAV9-NC or AAV9-LAT1. f Representative histological images of wheat germ agglutinin (WGA) and Masson staining (bar = 100 μm) and the corresponding quantitative data to show the changes of g cardiomyocyte size and h degree of fibrosis in Ctrl and T1D mice and T1D mice treated with FGF21 plus AAV9-NC or AAV9-LAT1. i Western blotting showing the expression levels of LAT1, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), mTOR and p-mTOR in Ctrl and T1D mice and T1D mice treated with FGF21 plus AAV9-NC or AAV9-LAT1 and j the corresponding quantitative data. The levels of k reduced glutathione (GSH) and l malondialdehyde (MDA) in the heart of Ctrl and T1D mice and T1D mice treated with FGF21 plus AAV9-NC or AAV9-LAT1. The levels of m leucine, n isoleucine and o valine in the heart of Ctrl and T1D mice and T1D mice treated with FGF21 plus AAV9-NC or AAV9-LAT1. The differences among four groups were analyzed by using one-way ANOVA with Bonferroni’s multiple comparisons test, and different lowercase codes represent a statistically significant difference ( p < 0.05)

Article Snippet: To develop a mouse model of type 1 diabetes (T1D), mice after a 12-h fasting were treated with intraperitoneal injection of STZ (Sigma-Aldrich) solution in citrate buffer (pH = 4.5) at a dose of 50 mg/kg body weight for 5 consecutive days.

Techniques: Over Expression, Injection, Control, Plasmid Preparation, Staining, Western Blot, Expressing

Journal: Microbiome

Article Title: BCAA mediated microbiota-liver-heart crosstalk regulates diabetic cardiomyopathy via FGF21

doi: 10.1186/s40168-024-01872-3

Figure Lengend Snippet: AAV-mediated FGF21 knockdown suppresses the cardioprotective effect of FMT in T1D mice. a Flow diagram of experiment: After 1 week of acclimation, mice were injected with streptozocin (STZ) for 5 days to induce type 1 diabetic (T1D) mice, treated with AAV8-shFGF21 for the liver-specific knockdown of FGF21 and then carried out FMT for 2 weeks. Subsequently, mice were subjected to cardiac function test with echocardiography and sample analysis ( n = 5–10 mice per group). b Representative M-mode echocardiographs in control (Ctrl) and T1D mice treated with AAV8-NC (empty vector) or AAV8-shFGF21 with and without FMT. c Left ventricular ejection fraction (%EF), d left ventricular fractional shortening (%FS) and e left ventricular internal dimension at systole (LVIDs) in Ctrl and T1D mice treated with AAV8-NC or AAV8-shFGF21 with and without FMT. f Representative histological images of wheat germ agglutinin (WGA) and Masson staining (bar = 100 μm) and the corresponding quantitative data to show the changes of g cardiomyocyte size and h degree of fibrosis in Ctrl and T1D mice treated with AAV8-NC or AAV8-shFGF21 with and without FMT. i Western blotting showing the expression levels of LAT1, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), mTOR and p-mTOR in Ctrl and T1D mice treated with AAV8-NC or AAV8-shFGF21 with and without FMT and j the corresponding quantitative data. The levels of k reduced glutathione (GSH) and l malondialdehyde (MDA) in the heart of Ctrl and T1D mice treated with AAV8-NC or AAV8-shFGF21 with and without FMT. The differences among four groups were analyzed by using one-way ANOVA with Bonferroni’s multiple comparisons test, and different lowercase codes represent a statistically significant difference ( p < 0.05)

Article Snippet: To develop a mouse model of type 1 diabetes (T1D), mice after a 12-h fasting were treated with intraperitoneal injection of STZ (Sigma-Aldrich) solution in citrate buffer (pH = 4.5) at a dose of 50 mg/kg body weight for 5 consecutive days.

Techniques: Knockdown, Injection, Control, Plasmid Preparation, Staining, Western Blot, Expressing