EMBO/soda-nel huggingface dataset:
Iron loss triggers mitophagy through induction of mitochondrial ferritin (2020)
Figure 7

Figure 7. Induction of mitochondrial ferritin (FTMT) by deferiprone in vivo and FTMT is required for suppression of hepatocellular carcinoma.

(A) Immunoblots for FTMT, frataxin, mitoferrin, HSP60, FTH1 and TfR using the hepatic mitochondrial fraction lysate and whole liver lysate in control (C57BL/6J) mice and STAM mice treated with DFP (0, 0.0375, or 0.075 mg/g body weight) (n=6). The expression of FTMT, frataxin, mitoferrin, FTH1, and TfR were normalized to HSP60 or β-actin, respectively. The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01.

(B) The mean number of mitophagosome-like structures/100 μm2 from four randomly selected areas in the livers of DFP (0.075 mg/g body weight)-administered mice were compared between control and FTMT siRNA-treated groups for STAM mice (n=6) and DMBA + HFD mice (n=6). The central horizontal bar and the error bards indicate mean ± SD. Two sample t test was used for statistical analysis. NC: negative control siRNA, *: P<0.05.

(C) Frozen liver sections of DFP (0.075 mg/g body weight)-administered mice (STAM mice and DMBA + HFD) with or without FTMT knockdown were stained with dihydroethidium. Red fluorescence indicates the ROS production. Scale bar: 100 μm. siNC: negative control siRNA.

(D, E) STAM mice (D) were fed a high-fat diet without DFP treatment or orally administered with 0.075 mg/g body weight of DFP from the age of 4 weeks, injected with FTMT siRNA (10 μl/g body weight) or negative control siRNA through the tail vein every 2 weeks for 8 weeks prior to sacrifice, and followed until 16 weeks of age (n=6). DMBA + HFD mice (E) were fed a high-fat diet, treated with DFP and siRNA in the same manner with STAM mice, and followed until 30 weeks of age (n=6). The number and maximum size of liver tumors were compared among the three groups (control without DFP, negative control siRNA, and FTMT siRNA with DFP). The central horizontal bar and the error bards indicate mean ± SD. The Tukey's honestly significant test was used for statistical analysis. *: P<0.05, **: P<0.01. Representative liver images are shown in the upper panel. Scale bar: 1 cm.
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 1

Figure 1. Knocking down Nipped-A lengthens the period of fly locomotor rhythms.

A Double-plotted representative actograms of the indicated genotypes. Flies are monitored in LD for 4 days and then DD for 7 days. Dicer2 (dcr2) is co-expressed to enhance the effects of RNAi. White boxes indicate the light phase and black boxes indicate the dark phase. Gray shades indicate DD.

B-D The period of DD locomotor rhythms of flies with Nipped-A knocked down and controls.

E, F Using temperature-sensitive GAL80 system to control Nipped-A RNAi expression. (E) The period of DD locomotor rhythms of flies raised at 18ºC and tested at 29ºC. (F) The period of DD locomotor rhythms of flies raised at 29ºC and tested at 18ºC.

G, H The period of DD locomotor rhythms of flies treated with RU486 to activate the pdfG4-geneswitch (pdf-GS) driver (G) or vehicle control (H).

Data information: (B-H) Error bars represent standard error of the mean (SEM). Digits on the bars are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using One-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###P<0.001, * compared with the GAL4 controls; # compared with the UAS controls. White bar indicates UAS or GAL4 controls. Gray bar indicates flies with Nipped-A knocked down. G4, GAL4; U, UAS.
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 2

Figure 2. NIPPED-A acts to increase the mRNA and protein levels of core clock gene tim and Pdp1ε.

A Plots of relative mRNA abundance vs circadian time (CT) for clock genes determined by qRT-PCR in whole head extracts of Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1/+) and control (timG4/+;Udcr2/+) collected on DD1 (tim/cry, n=5; Pdp1ε/per/clk/cyc, n=3; vri, n=6). For each time series, the value of the lowest time point was set to 1.

B Western blots of proteins from whole head extracts of Nipped-A RNAi and control flies collected on DD1 and probed with TIM, PDP1ε and PER antibodies.

C Quantification of TIM (n=5), PDP1ε (n=3) and PER (n=3) protein levels of blots in (B). TIM, PDP1ε and PER protein levels were normalized to that of HSP70. For each time series, the value of the control at the peak time point was set to 1.

D Brains from Udcr2/+;cryG4-16/+ and Udcr2/+;cryG4-16/UNipped-ARNAi flies collected at CT0, 4, 8, 12, 16, 20 on DD1 were immunostained with TIM (green) , PDP1ε (red), PER (green) and PDF (red or green) antisera. The scale bar represents 10µm.

E Quantification of TIM, PDP1ε and PER protein levels in the s-LNvs of images in (D) (TIM: CT8: Udcr2/+;cryG4-16/+, n=89; Udcr2/+;cryG4-16/UNipped-ARNAi, n=58; CT20: Udcr2/+;cryG4-16/+, n=130; Udcr2/+;cryG4-16/UNipped-ARNAi, n=80; PDP1ε: CT4: Udcr2/+;cryG4-16/+, n=46; Udcr2/+;cryG4-16/UNipped- RNAi, n=26; CT16: Udcr2/+;cryG4-16/+, n=65; Udcr2/+;cryG4-16/UNipped-ARNAi, n=41; PER: CT0: Udcr2/+;cryG4-16/+, n=90; Udcr2/+;cryG4-16/UNipped-ARNAi, n=58; CT12: Udcr2/+;cryG4-16/+, n=86; Udcr2/+;cryG4-16/UNipped-ARNAi, n=64).

Data information: Error bars represent SEM. Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. G4, GAL4; U, UAS.
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 3

Figure 3. Nipped-A synergistically interacts with tim, Pdp1ε and per to determine period length.

A, B The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing tim (A) or carrying heterozygous tim01 mutation (B). Ptim is a tim cDNA construct driven by tim promoter.

C, D The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing Pdp1ε (C) or carrying heterozygous Pdp1ε3135 mutation (D).

E, F The period of DD locomotor rhythm of Nipped-A RNAi flies over-expressing per (E) or carrying perL mutation (F).

Data information: Error bars represent SEM. Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, *P<0.05, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the over-expression or mutant flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated core clock gene. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated core clock gene and Nipped-A knocked down. G4, GAL4; U, UAS.
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 4

Figure 4. NIPPED-A is physically associated with tim and Pdp1ε loci.

A Plots of relative mRNA abundance of Nipped-A in whole head extracts of w1118 flies in LD and DD1 determined by qRT-PCR (n=3).

B Left panel: Western blots of proteins from whole heads of w1118 and Nipped-A RNAi flies collected during LD or DD1 and probed with NIPPED-A antibody. Right panel: quantification of NIPPED-A protein levels of blots in the left panel (LD, n=3; DD1, n=5).

C Chromatin immunoprecipitation (ChIP) assays to detect NIPPED-A binding at E-box, transcription start site (TSS) and gene body of tim, Pdp1ε and per using w1118 flies (n=3).

Data information: Error bars represent SEM. Two-way ANOVA, significant effect between NIPPED-A and IgG were found for tim E-box (P<0.001), Pdp1ε E-box (P<0.001), per E-box (P<0.001), tim TSS (P<0.001), Pdp1ε TSS (P<0.001), per TSS (P<0.001), tim gene body (P<0.001), Pdp1ε gene body and per gene body (P<0.001). Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. G4, GAL4; U, UAS.
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 5

Figure 5. NIPPED-A promotes the transcription of tim and Pdp1ε and facilitates H2B deubiquitination.

A Plots of relative pre-mRNA abundance of tim (n=5) and Pdp1ε (n=3) determined by qRT-PCR in the whole head extracts of Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1) and control (timG4/+;Udcr2/+) flies during DD1.

B ChIP assays to detect ub-H2B binding at E-box, TSS and gene body of tim, Pdp1ε, per and clk in Nipped-A RNAi (timG4/+;Udcr2/UNipped-ARNAi-1) and control (timG4/+;Udcr2/+) (n≥3).

Data information: Student's t-test, *P < 0.05. Two-way ANOVA, significant effect between ub-H2B and IgG were found for all genomic regions tested (P<0.001). Significant effect of genotypes were found for tim E-box (P<0.05), Pdp1ε E-box (P<0.01), tim TSS (P<0.01) and Pdp1ε TSS (P<0.001).
Nipped-A Regulates the Drosophila Circadian Clock via Histone Deubiquitination (2019)
Figure 6

Figure 6. Nipped-A synergistically interacts with not to determine period length. A, B The period (A) and power (B) of DD locomotor rhythms of flies with not knocked down and controls.

C Plots of relative mRNA abundance vs CT for clock genes determined by qRT-PCR in whole head extracts of not RNAi (timG4/+;Udcr2/UnotRNAi) and control (timG4/+;Udcr2/+) collected on DD1 (n=5).

D ChIP assays to detect ub-H2B binding at E-box, TSS and gene body of tim and Pdp1ε in not RNAi (timG4/+;Udcr2/UnotRNAi) and control (timG4/+;Udcr2/+) (n=3).

E, F The period of DD locomotor rhythm of flies when knocking down Nipped-A and over-expressing not.

G The period of DD locomotor rhythm of flies co-expressing Nipped-A RNAi and not RNAi.

Data information: Error bars represent SEM. (A, B, E-G) Digits on the bar are the number of flies tested. Percentage of rhythmicity is indicated above the bars. Statistical difference is measured using one-way ANOVA, P<0.001, Tukey's multiple comparison test, **P<0.01, ***/###/+++/$$$P<0.001, * compared with the G4 control, # compared with the UAS control, + compared with the Nipped-A RNAi flies, $ compared with the not overexpression flies. White bar indicates UAS or GAL4 controls. Dashed bar indicates flies with genetically manipulated not. Gray bar indicates flies with Nipped-A knocked down. Checked bar indicates flies with both genetically manipulated not and Nipped-A knocked down. (C, D) Student's t-test, *P < 0.05, **P < 0.01, ***P < 0.001. Statistical difference is measured using two-way ANOVA, P<0.001, significant effect of genotypes were found for tim E-box (P<0.01), Pdp1ε E-box (P<0.05), tim TSS (P<0.05) and Pdp1ε TSS (P<0.001) and tim gene body (P<0.01). G4, GAL4; U, UAS.
PROTECTIVE ANTIGENIC SITES IDENTIFIED IN RESPIRATORY SYNCYTIAL VIRUS FUSION PROTEIN REVEALS IMPORTANCE OF p27 DOMAIN (2021)
Figure 6

Figure 6. CD4/CD8 T-cells in the airways and distal alveoli of mouse lungs following viral challenge and ADCC activity of post-immunization serum.

(A) Lung tissues from individual mice (n=5) at day 5 post-RSV challenge (or uninfected control) were used to evaluate CD4/CD8 T cells separately for airway and distal lungs. Lung slides were fixed and stained with DAPI to visualize nuclei (blue) and either anti-CD4 (green) or anti-CD8 (red) T cells. The number of CD4/CD8 T cells were determined in each lung airway and distal region. Individual CD4+/CD8+ T cells data are presented as number of positive cells per 174 x 174 µm of lung tissue for each mice. Results are presented as box and whisker plots, where boxes extends from 25th to 75th percentile, whiskers show minimum to maximum value and central band represents the median value for the group.

(B) RSV-specific antibody-dependent cellular cytotoxicity (ADCC) activity of post-second immunization serum was evaluated using RSV-infected A549 cells or mock A549 cells that served as target cells. After incubation with serum, Jurkat/NFAT-luc+ FcγRIV that expresses a luciferase reporter were added as the effector cells. The amount of luciferase was then measured as relative luciferase units (RLU). The RLU readings of ADCC induction from serum of each group were normalized to assay control (no serum) background. The RSV specific ADCC activity (RLU measured) fold-change induced is shown as the ratio of normalized RLU from RSV infected target cells to normalized RLU from un-infected target cells. The experiments were performed twice and variation between the two independent experiments (two biological replicates) was <12%. Results are presented as box and whisker plots, where boxes extends from 25th to 75th percentile, whiskers show minimum to maximum value and central band represents the median value for the group.

Data information: Statistical significances were performed by one-way ANOVA in GraphPad Prism; **** p<0.0001, *** p<0.001, ** p<0.01, * p<0.05.
Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington’s disease mice (2015)
Figure 2

Figure 2. g7-NPs reach different brain cells and release cholesterol in R6/2 mice. (A-B) Representative confocal images of liver (A) and brain (B) slices from R6/2 mice ip injected with C-NPs (left) or with g7-NPs (right) and sacrificed after 4 hrs. (C) Quantification of g7-NPs localized in the liver, striatum, and cortex of WT (n=3) and R6/2 mice (n=3). Data represent mean (µg) ± SEM. (D-E) g7-NPs in brain slices from R6/2 mice administered with a single ip injection and sacrificed after 24 hrs (D, left) or 2 weeks (D, right) and after multiple ip injections within 1 week (E). (F-I) Representative confocal images of immunostaining against IBA1 (F), GFAP (G), calbindin (H), and DARPP-32 (I) on coronal sections of brains isolated from R6/2 mice ip injected with g7-NPs and sacrificed at the indicated time points. White arrowheads indicate intracellular g7-NPs. DAPI (A,B,D) or Hoechst 33258 (Ho) (F-I) were used to counterstain nuclei. Scale bars: 20m (A); 10 m (B-D-E); 5m (F-I). Data in (C) are expressed as the number of g7-NPs for 100 m2 sem. Statistics: *P<0,05 determined by Student’s t-test (C).
Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington’s disease mice (2015)
Figure 6

Figure 6. Systemic injections of g7-NPs-Chol positively influence synaptic protein network but not neuropathology. (A-B) protein levels (A) and relative densitometry quantification (B) of several synaptic proteins in triton-insoluble (synaptic enriched) fractions purified from total brains. Levels of PSD95 and NMDA receptor subunits GluN1 and GluN2B are rescued in R6/2 mice by cholesterol supplementation. (C-D-E) mRNA levels for Bdnf (C), Snap25 (D) in cortex and hippocampus; Complexin II (E) in cortex, hippocampus and striatum from a subset of WT (n=4), R6/2-untreated (n=7) and R6/2-chol animals (n=3). As no differences were found between R6/2 mice treated with saline or treated with empty g7-NPs, data were pooled. (F-G) Representative images of Nissl Staining (F) and ventricle volume revealed by Neurolucida Analysis at 12 weeks of age in WT (n= 7), R6/2 (n=7), R6/2-emp (n=6), R6/2-Chol (n=8). Data in (B-E, F) represent mean ± SEM. *#P<0.05, **##P<0.01, ***###P<0.01 were determined by one-way ANOVA followed by Newmann-Keuls multiple comparison tests (in B-E) and by Student’s t-test between R6/2-untreated and R6/2-Chol (in C-D). Source Data are available online for Figure 6A.
Cholesterol-loaded nanoparticles ameliorate synaptic and cognitive function in Huntington’s disease mice (2015)
Figure 7

Figure 7. Exogenous cholesterol or g7-NPs per se do not influence endogenous cholesterol synthesis or induce inflammatory response. (A-B) Lathosterol and 24OHC measured by mass spectrometry in the brain of WT (n=6), R6/2-untreated (n=7) and R6/2-Chol (n=5) mice. Data represent mean ± SEM. (C-D) mRNA levels of hmgcr and fdft1 in liver and lung of WT (n=7), R6/2-untreated (n=8) and R6/2-Chol (n=4) mice. As no differences were found between R6/2 mice treated with saline or treated with empty g7-NPs, data were pooled. (E-F) mRNA levels of inflammatory genes in liver and lung of the of WT (n=7), R6/2 (n=4), R6/2-emp (n=4) and R6/2-Chol (n=5) mice. Data in (A-F) represent mean ± SEM. *P<0.05, **P<0.01, ***P<0.01 was determined by one-way ANOVA followed by Newmann-Keuls multiple comparison tests.
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 1

Figure 1. Nontargeted TLR7 agonist (TLR7-54) and folate-targeted TLR7 agonist (FA-TLR7-54) downregulate profibrotic macrophage markers.

(A-C) Human monocytic (THP-1) cells were induced to acquire an M2-like phenotype (see Methods) and treated with different concentrations of TLR7-54 or FA-TLR7-54 for either 48h (A-B) or 2h (C). In the latter case, after the 2h incubation, culture medium was replaced with drug-free medium and incubation was continued for 46h. All treatment groups were then analyzed by qPCR for gene expression and cell supernatants were analyzed for secreted cytokines by ELISA. (A) Changes in mRNA levels of indicated profibrotic macrophage markers by induced by different concentrations of TLR7-54 and FA-TLR7-54 (n=3, technical replicates). (B-C) Changes in CCL18 and IL-1β in the culture media induced upon treatment with TLR7-54 and FA-TLR7-54 for the treatment regimens (n=3, technical replicates).

Data information: Mean ± SD. Statistical significance between TLR7-54 or FA-TLR7-54 treated groups versus M2-untreated group compared using Dunnett's multiple comparison test (#P<0.05, ##P<0.01 ###P<0.001, ####P<0.0001).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 2

Figure 2. Both targeted and nontargeted TLR7 agonists reprogram human monocyte-derived profibrotic macrophages to an anti-fibrotic phenotype.

(A-F) M2-induced human monocyte-derived macrophages were treated with 100 nM of the indicated drug either continuously for 48h, or initially for 2h in the presence or absence of FA-glucosamine (competition) followed by 46h in the absence of drug (2+46h), as described in Fig 1. mRNA levels of profibrotic markers, Arg1 (A), CD206 (B) and CD163 (C), and protein levels of secreted profibrotic CCL18 (D) and antifibrotic cytokines, CXCL10 (E) and IL-6 (F) (n=3, technical replicates) were then determined. Changes in both sets of cytokines were inhibited by blockade of unoccupied folate receptors with excess FA-glucosamine (2+46h, competition).

Data information: Mean ± SD. Statistical significance between groups was determined using unpaired two-tailed t-test (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 3

Figure 3. Evaluation of folate-dye conjugate targeting to FRβ+ macrophages in lungs of mice with pulmonary fibrosis.

(A) Healthy mice or BLM-induced mice were tail vein injected on day 10 with 10 nmol OTL38 in the absence or presence of 200-fold excess FA-glucosamine to block all folate receptors. After 2h, mice were euthanized, resected and imaged for fluorescence intensity (n=5).

(B) Alternatively, lungs from mice injected with 100 nmol OTL38 in the present or absence of 200-fold excess FA-glucosamine were collagenase digested and stained with 7AAD plus antibodies to CD11b and F4/80 prior to FACS analysis (n=3). Representative plots showing the gating strategy yielding live macrophages (7AAD- CD11b+ F4/80+) and OTL38 positive macrophages are shown.

(C) Percentages of live macrophages in BLM-induced mice (n=3).

(D) Percentages of lung macrophages that accumulated OTL38 in vivo (n=3).

Data information: Mean ± SD. Statistical significance between groups were compared using unpaired two-tailed t-test (***P<0.001, ****P<0.0001).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 4

Figure 4. Effect of a single dose of targeted or nontargeted TLR7-54 on phenotypic markers of pulmonary fibrosis macrophages in vivo.

(A-C) Healthy mice or BLM-induced mice were injected intravenously on day 10 with either vehicle (3% DMSO in PBS), or 10 nmol TLR7-54 or FA-TLR7-54 dissolved in vehicle, and 1 or 4h later sacrificed to collect both lungs and bronchioalveolar lavage fluid (BALF). (A) Lungs were digested and macrophages were isolated by flow cytometry prior to analysis for expression of the indicated mRNAs by qPCR (n=3). (B) BALF cells were pelleted and similarly analyzed for the indicated mRNAs (n=3). (C) BALF supernatant was also collected and analyzed by ELISA for IL-6, IFNα and TNFα (n=3).

Data information: Mean ± SD. Statistical significance between groups were compared using unpaired two-tailed t-test (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001). Statistical significance between groups at 1h or 4h time point were compared using Dunnett's multiple comparison test (#P<0.05, ##P<0.01, ####P<0.0001).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 5

Figure 5. Effect of alternate day dosing with FA-TLR7-54 on fibrotic markers in BLM-induced mice.

(A) BLM-induced mice were treated every other day beginning on day 10 with 10 nmol/dose FA-TLR7-54 or TLR7-54.

(B) Survival analysis of the treatment groups (Healthy, n=5; others, n=10).

(C-H) BALF was collected on day 21 and centrifuged to isolate cell pellets. Cells (primarily macrophages) were analyzed by qPCR for Arg1 (C), MMP9 (D), TIMP3 (E), CD86 (F) and IRAK4 (G) (n=5). BALF supernatant was analyzed by ELISA for IFNγ (H) (n=5).

(I-K) (I) Lungs were resected and subjected to hematoxylin-eosin (H&E), trichome (collagen) and α-SMA IHC staining (scale bars, 200 μm), (J) or hydrolyzed and analyzed for hydroxyproline content as a measure of collagen content (Healthy, n=5; others, n=10), (K) Ashcroft score quantitation of fibrosis (n=5).

Data information: Mean ± SD. Statistical significance between groups was compared using unpaired two-tailed t-test (*P<0.05, **P<0.01, ***P<0.001).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 6

Figure 6. Concentration dependence of FA-TLR7-54 suppression of BLM-induced fibrosis.

Healthy control (filled circles) or BLM-induced mice were treated with vehicle (filled squares), 1 nmol (empty circles), 3 nmol (empty squares), or 10 nmol (filled triangles) FA-TLR7-54 and then sacrificed on day 21 for analysis.

(A) Analysis of body weight change versus time (n=10).

(B) Analysis of the number of cells per milliliter of BALF (n=5).

(C) Quantitation of total hydroxyproline content per right lung (Healthy control, n=5; others, n=7-9).

(D) H&E staining and trichrome staining of lung tissue (scale bars, 200 μm).

Data information: Mean ± SD. Statistical significance between groups was determined using unpaired two-tailed t-test (*P<0.05, **P<0.01).
Reprogramming of Profibrotic Macrophages for Treatment of Bleomycin-Induced Pulmonary Fibrosis (2020)
Figure 7

Figure 7. Comparison of plasma cytokine levels in healthy mice following treatment with nontargeted versus folate-targeted TLR7-54.

Healthy mice were tail vein injected with 10 nmol TLR7-54 (circles) or FA-TLR7-54 (squares), and peripheral blood was collected at indicated time points after drug injection.

(A-C) Measurement of plasma IL-6 (A), IFNα (B) and TNFα (C) (n=3).

(D-F) Effect of drug concentration on plasma levels of IL-6 (D), IFNα (E), and TNFα (F) at 1.5h, 1h, or 1h after treatment, respectively (n=2).

(G) Change in body weight as a measure of systemic toxicity during alternate day dosing (n=2).

Data information: Mean ± SD. Statistical significance between groups was compared using unpaired two-tailed t-test (*P<0.05, **P<0.01, ***P<0.001).