Journal: Journal of Nanobiotechnology

Article Title: Bidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c

doi: 10.1186/s12951-025-03943-5

Figure Lengend Snippet: Combination of apo-hIGFBP4 with electropositive AAC2 nanofibers enhances glucose uptake and attenuates the proinflammatory effects of MGO. ( a ) Schematic representation of hIGFBP4 structure highlighting domains susceptible to interaction with charged, hydrophobic, and oxidant molecules. ( b ) AAC structure: a dilysine backbone modified with a hydrophobic coumarin side group, enabling self-assembly into positively charged nanofibers. ( c ) Schematic of methylglyoxal (MGO) production under hyperglycemic stress, showing its role as a precursor of electronegative AGEs and driver of diabetic inflammation. ( d ) FD-glucose uptake in human subcutaneous SVF preadipocytes isolated from obese patients ( n = 6) with and without diabetes. Confluent cells were glucose- and serum-deprived (starved) for 40 min and treated with vehicle (Veh, PBS) or designated concentrations of insulin (Ins), leptin (Lep), and hIGFBP4. Statistical analysis was performed using unpaired t-test. * P = 0.05–0.01; ** P = 0.01–0.001; *** P < 0.001. ( e ) Dose-dependent FD-glucose uptake in 3T3-L1 preadipocytes ( n = 4) starved for 50 min and treated for 90 min with hIGFBP4 alone or with AAC2 (0.1 µM). ( f ) IL-11 reporter activity in HEK293 cells ( n = 4) after 24 h stimulation with recombinant human IL-11 (1 ng/mL), MGO (10 µM), or their combination. Data is expressed as a percentage relative to unstimulated control. ( g ) HEK293 cells ( n = 4) were stimulated for 24 h with IL-11 and MGO (as in panel f) in the presence or absence of AAC2 (1 µM), hIGFBP4 (50 ng/mL), or their combination

Article Snippet: HEK293 IL-11 reporter cells (Invivogen, hkb-hil11rv2) were cultured in T-150 flasks using complete growth medium consisting of high-glucose DMEM (Gibco) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Gibco, A5268-01), 1% penicillin-streptomycin, and 5 mM L-glutamine.

Techniques: Modification, Isolation, Activity Assay, Recombinant, Control

Journal: Journal of Nanobiotechnology

Article Title: Bidirectional regulation of liver sinusoidal clearance by amino acid nanofibers and IGFBP4 complex: effects on HbA1c

doi: 10.1186/s12951-025-03943-5

Figure Lengend Snippet: Expression of Cluster II genes in LSECs and Cluster I genes in other hepatic cell populations supports the scavenging input hypothesis underlying AAC2 and AAC2–hIGFBP4 regulation of capillarized and fenestrated LSEC phenotypes. ( a–g ) Correlation and mechanistic modeling support the scavenging input hypothesis underlying AAC2 and AAC2–hIGFBP4 regulation of LSEC phenotypes. ( a–b ) Cluster II genes expressed in LSECs significantly correlate with Cluster I genes expressed in other hepatic cell populations ( n = 12, R² > 0.33, P < 0.05; Pearson correlation). Specifically, Oit3 correlates positively with Klf9 ( a ), while Klf9 shows an inverse correlation with genes expressed in the hepatocyte-associated Cluster I ( b ). ( c ) Eng expression correlates with receptors of the TGFβ pathway and with Tgfb1 . ( d ) Fcgr2b expression is positively correlated with Adgrf5 . ( e ) Eng correlates with Smad family transcription factors. ( f ) Cdh5 expression is positively associated with Tgfb1 . ( g ) The proposed scavenging input hypothesis suggests that TGFβ production is stimulated by AGE uptake via stabilin 2 ( Stab2 ), which activates the canonical ALK5 pathway underlying the capillarized LSEC phenotype and induces transcription of Eng and other Cluster II genes. Translation of Eng mRNA to protein endoglin defines the transition to ALK1 signaling, which, in conjunction with Cluster II proteins, promotes the fenestrated LSEC phenotype. Endoglin mediates endocytosis that terminates the ALK1 state. This physiological cycle is sustained by renewed scavenger activity, leptin receptor ( Lepr ), and VEGFR2/VE-cadherin signaling, which reinforce TGFβ production adapted for amount of waste in circulation. Binding of positively charged AGEs with AAC2 may reduce scavenger receptor input and suppress the fenestrated LSEC state, whereas the AAC2–hIGFBP4 complex promotes the transition toward a fenestrated phenotype. Inflammatory conditions disrupt this physiological TGFβ cycle in LSEC through cytokines (e.g., IL-11), accumulation of toxic waste, or TGFβ derived from damaged or immune cells that drive a pathological process toward fibrosis

Article Snippet: HEK293 IL-11 reporter cells (Invivogen, hkb-hil11rv2) were cultured in T-150 flasks using complete growth medium consisting of high-glucose DMEM (Gibco) supplemented with 10% heat-inactivated fetal bovine serum (FBS; Gibco, A5268-01), 1% penicillin-streptomycin, and 5 mM L-glutamine.

Techniques: Expressing, Activity Assay, Binding Assay, Derivative Assay

Journal: Nature communications

Article Title: Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

doi: 10.1038/s41467-022-35306-1

Figure Lengend Snippet: Fig. 1 | Autocrine IL11 activity initiates a pro-inflammatory and mesenchymal program in tubular epithelial cells via activation of both STAT3 and ERK. a Representative immunofluorescence (IF) images (scale bars: 100 µm) of EGFP and E-Cadherin expression in the kidneys of Il11EGFP/+ mice following folic acid (FA) injection (kidneys were collected atday 3, day21, and day 28, representative dataset from n = 3/group. b Representative IF images of IL11RA staining of primary human renal TECs (scale bars: 100 µm; representative dataset from n = 3/group). c ELISA of IL11 secretion from TGFβ1-stimulated TECs (24 h, n = 4/group). d Western blots of STAT3, MEK, ERK, p90RSK, and GSK3β activation and expression levels of SNAI1 and E-Cadherin in IL11-stimulated TECs over a time course (representative dataset from n = 4/group). e, f Data for RNA sequencing (RNA-seq) experiments on TEC stimulated with IL11 for 0 (Bsl), 1, 6, and 24 h. e Principal component analysis (PCA) of RNA-seq across the time-series. PC1 and PC2 account for 59% and 18% variance of gene expression, respectively. f Volcano plot displaying the adjusted p-value (−log10(p-adj)) and fold change (log2(Fold change)) of genes between IL11-

Article Snippet: For replication, and to exclude potential off-target effects, we repeated the preemptive treatment experiment with a second, commercially available, neutralizing IL11 antibody (MAB218, R&D Systems) and compared its effects to X203 (Fig. 3d).

Techniques: Activity Assay, Activation Assay, Expressing, Injection, Staining, Enzyme-linked Immunosorbent Assay, Western Blot, RNA Sequencing, Gene Expression

Journal: Nature communications

Article Title: Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

doi: 10.1038/s41467-022-35306-1

Figure Lengend Snippet: Fig. 5 | Therapeutic targeting of IL11 protects mice from UUO-induced renal tubule damage, inflammation, and fibrosis. a Representative immuno- fluorescence images (scale bars: 100 µm) of EGFP and E-Cadherin expression in UUO and control kidneys of Il11EGFP/+ mice (representative dataset from n = 3/group) and b Western blots of IL11 protein expression in control and UUO kidneys (representative dataset from n = 5/group). Kidneys were collected at day 10 and contralateral kidneys were used as controls. c Schematic of X203 therapeutic dosing of mice subjected to left unilateral ureteral obstruction for experiments shown in (d–h). IgG/X203 (10 mg/kg) was administered on day 4 and day 8 post UUO and kidneys were collected on day 10; contralateral (right) kidneys from the IgG group were used as controls. d Western blots of pERK, ERK, pp90RSK, p90RSK, pGSK3β, GSK3β, SNAI1, ZEB, E-Cadherin, Cyclin D1, αSMA, FN1, and GAPDH

Article Snippet: For replication, and to exclude potential off-target effects, we repeated the preemptive treatment experiment with a second, commercially available, neutralizing IL11 antibody (MAB218, R&D Systems) and compared its effects to X203 (Fig. 3d).

Techniques: Expressing, Control, Western Blot

Journal: Nature communications

Article Title: Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease.

doi: 10.1038/s41467-022-35306-1

Figure Lengend Snippet: Fig. 9 | Anti-IL11 promotes kidney regeneration and reverses renal dysfunction in chronic kidney disease. a Schematic of X203 therapeutic dosing regimen for CKD reversal experiments shown in (b–l): X203 or IgG (IP, 10 mg/kg) was admi- nistered 2X/week for 12 weeks from day 21 (week 3) after FA injury, when CKD is established and sustained. Blood and kidneys were collected every 3 weeks; full course serum and kidney phenotyping study were performed at the study end- point (week 15: 12 weeks after the start of X203 therapy); blood and kidneys from control mice i.e., those receiving IP injection of vehicle control (0.3 M NaHCO3) were collected at week 3 and 15. b Representative kidney gross anatomy, c kidney weights (NaHCO3 (W3), FA (W3) (n = 11/group), FA + IgG (W6, W9), FA + X203 (W6, W12) (n = 4/group), FA + X203 (W9), FA + IgG (W12), NaHCO3 (W15) (n = 5/group), FA + IgG/X203 (W15) n = 13/group)), d renal collagen content by hydroxyproline assay, e representative Masson’s Trichrome images of whole kidney cross section (scale bars: 500 µm, representative dataset from n = 4/group for kidneys collected at week 6, 9, 12 or from n = 5/group for week 3 and 15), f Western blots showing renal ERK and p90RSK activation, GSK3β inactivation, and SNAI1, ZEB, E- Cadherin, Cyclin D1, αSMA, FN1, GAPDH expression (representative dataset from

Article Snippet: For replication, and to exclude potential off-target effects, we repeated the preemptive treatment experiment with a second, commercially available, neutralizing IL11 antibody (MAB218, R&D Systems) and compared its effects to X203 (Fig. 3d).

Techniques: Control, Injection, Hydroxyproline Assay, Western Blot, Activation Assay, Expressing

Journal: Bioactive Materials

Article Title: Ameliorating post-infarction myocardial fibrosis and cardiac function via ROS-responsive hydrogel-mediated IL-11 antibody delivery

doi: 10.1016/j.bioactmat.2026.01.041

Figure Lengend Snippet: The expression of interleukin-11 (IL-11) is increased in myocardial fibrosis in vitro and in vivo. A. Western blot analysis of IL-11 and vimentin expression in angiotensin II (AngII, 100 nM) or TGF-β (10 ng/mL)-treated cardiac fibroblasts. B. Quantification of (A). C. TUNEL staining and (D) its quantitative analysis in treated cells. E. CCK-8 viability assays (n = 3). F. Circulating IL-11 levels in mouse blood measured by ELISA (n = 3). ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: Following separation by SDS-PAGE and transfer to PVDF membranes, blots were probed overnight with primary antibodies targeting IL-11 (Santa Cruz, sc-133063), Vimentin (Abcam, ab92547), p-ERK1/2 (Sigma-Aldrich, M − 9692), ERK1/2 (Cell Signaling, 4696), and PCNA (Cell Signaling, 2586)

Techniques: Expressing, In Vitro, In Vivo, Western Blot, TUNEL Assay, Staining, CCK-8 Assay, Enzyme-linked Immunosorbent Assay

Journal: Bioactive Materials

Article Title: Ameliorating post-infarction myocardial fibrosis and cardiac function via ROS-responsive hydrogel-mediated IL-11 antibody delivery

doi: 10.1016/j.bioactmat.2026.01.041

Figure Lengend Snippet: Assessment of intrapericardial MAB delivery and P-T@MAB combination therapy in mice. A. Experimental timeline of animal studies. B. In vivo cardiac IVIS imaging following intrapericardial injection of free MAB or P-T@MAB at indicated time points (0 h, 24 h, 2 d, 4 d; n = 3). C. Quantification of cardiac MAB fluorescence. D–I. Serum levels of IL-11, TIMP-1, MMP-2, MMP-9, CCL8, and CXCL2 measured by ELISA (n = 3). n.s., not significant; ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: Following separation by SDS-PAGE and transfer to PVDF membranes, blots were probed overnight with primary antibodies targeting IL-11 (Santa Cruz, sc-133063), Vimentin (Abcam, ab92547), p-ERK1/2 (Sigma-Aldrich, M − 9692), ERK1/2 (Cell Signaling, 4696), and PCNA (Cell Signaling, 2586)

Techniques: In Vivo, Imaging, Injection, Fluorescence, Enzyme-linked Immunosorbent Assay

Journal: Bioactive Materials

Article Title: Ameliorating post-infarction myocardial fibrosis and cardiac function via ROS-responsive hydrogel-mediated IL-11 antibody delivery

doi: 10.1016/j.bioactmat.2026.01.041

Figure Lengend Snippet: Western blot and immunofluorescence analysis of myocardial fibrosis markers in myocardial infarction ( MI) mice. A. Western blot analysis for interleukin-11 (IL-11) and vimentin expression in heart tissue of MI mice after treatment with phosphate buffered saline, Gel, MAB, and P-T@MAB and sham group. B-C. Statistical evaluation of IL-11 and vimentin expression. D. Western blot of phosphorylated extracellular signal-regulated kinase (ERK) in heart tissues from MI mice. E.Quantification of (D) (n = 3). F–G. Immunofluorescence staining of α-SMA, collagen Ⅰ, and collagen Ⅲ in scar tissue (H) with corresponding quantitative analysis. Scale bar: 100 μm (n = 5). n.s., not significant; ∗ p < 0.05, ∗∗ p < 0.01, ∗∗∗ p < 0.001, ∗∗∗∗ p < 0.0001.

Article Snippet: Following separation by SDS-PAGE and transfer to PVDF membranes, blots were probed overnight with primary antibodies targeting IL-11 (Santa Cruz, sc-133063), Vimentin (Abcam, ab92547), p-ERK1/2 (Sigma-Aldrich, M − 9692), ERK1/2 (Cell Signaling, 4696), and PCNA (Cell Signaling, 2586)

Techniques: Western Blot, Immunofluorescence, Expressing, Saline, Staining