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Chem Impex International manganese ii chloride tetrahydrate
Manganese Ii Chloride Tetrahydrate, supplied by Chem Impex International, used in various techniques. Bioz Stars score: 95/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
https://www.bioz.com/product/01496/Manganese(II)+chloride+tetrahydrate/pm33595555-42-26-29
Average 95 stars, based on 1 article reviews

manganese ii chloride tetrahydrate - by Bioz Stars, 2026-09

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Article Title: Highly selective simultaneous determination of Cu(ii), Co(ii), Ni(ii), Hg(ii), and Mn(ii) in water samples using microfluidic paper-based analytical devices.
Article Snippet: A new paper-based analytical device design was fabricated by a wax printing method for simultaneous determination of Cu(II), Co(II), Ni(II), Hg(II), and Mn(II).. Colorimetry was used to quantify these heavy metal ions using bathocuproine (Bc), dimethylglyoxime (DMG), dithizone (DTZ), and 4-(2-pyridylazo) resorcinol (PAR) as complexing agents.. The affinity of complexing agents to heavy metal ions is dependent on the formation constant (Kf ).

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( A ) Focal NMO model: stereotaxic infusion into mouse striatum of AQP4-IgG or control IgG (Ctrl-IgG) with or without CHI3L1 (200 ng). ( B ) Confocal images showing striatal demyelinating lesions; myelin basic protein (MBP) loss areas (white dashed lines) quantified across groups. Scale bar: 500 μm; n = 5 mice per group (3 sections per mouse). ( C ) Ex vivo model: organotypic cerebellar slices (P7, 7 days in vitro) treated 48 hours with AQP4-IgG or Ctrl-IgG with or without CHI3L1 (100 ng/mL); immunostaining for NMO markers and immunoblot validation of CHI3L1 induction ( n = 3 biological replicates per group). ( D ) Ex vivo demyelination quantified by MBP signal (normalized to Ctrl-IgG + vehicle = 1.0); neurofilament-heavy (NFH) used to assess axonal process integrity. Scale bar: 300 μm; n = 5 slices per group (3 sections per slice). ( E ) Ex vivo microglial activation quantified as Iba1 + total and Iba1 + CD68 + activated microglia. Scale bar: 100 μm; n = 5 slices per group. ( F ) Ex vivo complement activation: C3d levels and membrane attack complex (C5b-9), normalized to Ctrl-IgG + vehicle = 1.0. Scale bar: 100 μm; n = 5 mice per group (3 sections per mouse). ( G ) Systemic NMO model in vivo: blood-brain/blood-spinal barrier disruption with CFA (s.c.) and pertussis toxin (PTX) (i.p.), followed by daily i.p. AQP4-IgG or Ctrl-IgG; CHI3L1 (1 μg/mouse) or vehicle given i.v. at indicated times. ( H ) Lumbar spinal cord (L4) demyelination quantified by MBP intensity normalized to Ctrl-IgG + vehicle. Scale bar: 100 μm; n = 5 mice per group (3 sections per mouse). ( I ) Motor deficits: gait (stride length) and rotarod latency in systemic model ( n = 8 mice per group). Statistics: Mean ± SEM. Student’s t test ( C ); 2-way ANOVA for rotarod latency ( I ); all other comparisons by 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) Focal NMO model: stereotaxic infusion into mouse striatum of AQP4-IgG or control IgG (Ctrl-IgG) with or without CHI3L1 (200 ng). ( B ) Confocal images showing striatal demyelinating lesions; myelin basic protein (MBP) loss areas (white dashed lines) quantified across groups. Scale bar: 500 μm; n = 5 mice per group (3 sections per mouse). ( C ) Ex vivo model: organotypic cerebellar slices (P7, 7 days in vitro) treated 48 hours with AQP4-IgG or Ctrl-IgG with or without CHI3L1 (100 ng/mL); immunostaining for NMO markers and immunoblot validation of CHI3L1 induction ( n = 3 biological replicates per group). ( D ) Ex vivo demyelination quantified by MBP signal (normalized to Ctrl-IgG + vehicle = 1.0); neurofilament-heavy (NFH) used to assess axonal process integrity. Scale bar: 300 μm; n = 5 slices per group (3 sections per slice). ( E ) Ex vivo microglial activation quantified as Iba1 + total and Iba1 + CD68 + activated microglia. Scale bar: 100 μm; n = 5 slices per group. ( F ) Ex vivo complement activation: C3d levels and membrane attack complex (C5b-9), normalized to Ctrl-IgG + vehicle = 1.0. Scale bar: 100 μm; n = 5 mice per group (3 sections per mouse). ( G ) Systemic NMO model in vivo: blood-brain/blood-spinal barrier disruption with CFA (s.c.) and pertussis toxin (PTX) (i.p.), followed by daily i.p. AQP4-IgG or Ctrl-IgG; CHI3L1 (1 μg/mouse) or vehicle given i.v. at indicated times. ( H ) Lumbar spinal cord (L4) demyelination quantified by MBP intensity normalized to Ctrl-IgG + vehicle. Scale bar: 100 μm; n = 5 mice per group (3 sections per mouse). ( I ) Motor deficits: gait (stride length) and rotarod latency in systemic model ( n = 8 mice per group). Statistics: Mean ± SEM. Student’s t test ( C ); 2-way ANOVA for rotarod latency ( I ); all other comparisons by 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Article Snippet: Strains were ALDH1L1-CreERT2 (031008, The Jackson Laboratory), STAT3 fl/fl (016923, The Jackson Laboratory), RAGE fl/fl ( Ager fl/fl ; NM-CKO-2116109, Shanghai Model Organisms), and Chil1 fl/fl (RDDC/Cyagen; exons 3–5 floxed).

Techniques: Control, Ex Vivo, In Vitro, Immunostaining, Western Blot, Biomarker Discovery, Activation Assay, Membrane, In Vivo, Disruption

( A ) Systemic NMO model: BBB/blood–spinal cord barrier disruption with CFA (s.c.) and PTX (i.p.), followed by daily i.p. AQP4-IgG or Ctrl-IgG; anti-CHI3L1 (10 μg, i.v.) or control IgG (msCtrl-IgG) administered at indicated times. ms, mouse. ( B ) L4 spinal cord confocal images showing that anti-CHI3L1 reduces AQP4-IgG–induced CHI3L1 upregulation and astrocyte activation (GFAP). Quantified GFAP and CHI3L1 signals normalized to Ctrl-IgG + vehicle = 1.0. Scale bar: 20 μm; n = 4 mice per group (3 sections per mouse). ( C ) Anti-CHI3L1 mitigates demyelination and gliosis: MBP intensity and densities of GFAP + astrocytes and Iba1 + microglia in L4 sections. n = 5 mice per group (3 sections per mouse). ( D ) Motor function: anti-CHI3L1 improves stride length and rotarod latency in systemic NMO mice. n = 8 per group. ( E ) Quantitative PCR (qPCR) heatmap of NF-κB–regulated cytokines (TNF-α, IL-1β, IL-6, IL-1α, CCL5, CCL7, C3) in lumbar cord after CHI3L1 neutralization, normalized to Ctrl-IgG + vehicle. n = 3 per group. ( F ) ELISA of secreted cytokines in lumbar cord lysates with anti-CHI3L1 versus msCtrl-IgG. n = 3 per group. ( G ) Electron microscopy of L4 white matter showing preservation of myelin with anti-CHI3L1. Scale bar: 2 μm; n = 3 animals per group. Quantified myelinated-axon density (normalized to Ctrl-IgG + msCtrl-IgG = 1.0) and g-ratio; 150 axons per group from 3 animals. ( H ) Conditional astrocyte-specific CHI3L1 knockout (Chil1 cKO): Chil1 fl/fl × ALDH1L1-CreERT2, tamoxifen-induced; subjected to systemic NMO paradigm, followed by behavioral testing and histopathology. ( I ) Chil1 cKO improves gait and rotarod performance versus floxed controls under AQP4-IgG. n = 8 per group. ( J ) Chil1 cKO reduces demyelination and gliosis: MBP intensity and GFAP + Iba1 + cell densities in L4 sections. n = 5 per group (3 sections per mouse). Statistics: Mean ± SEM. Rotarod latency analyzed by 2-way ANOVA ( D and I ). All other bar graphs: 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) Systemic NMO model: BBB/blood–spinal cord barrier disruption with CFA (s.c.) and PTX (i.p.), followed by daily i.p. AQP4-IgG or Ctrl-IgG; anti-CHI3L1 (10 μg, i.v.) or control IgG (msCtrl-IgG) administered at indicated times. ms, mouse. ( B ) L4 spinal cord confocal images showing that anti-CHI3L1 reduces AQP4-IgG–induced CHI3L1 upregulation and astrocyte activation (GFAP). Quantified GFAP and CHI3L1 signals normalized to Ctrl-IgG + vehicle = 1.0. Scale bar: 20 μm; n = 4 mice per group (3 sections per mouse). ( C ) Anti-CHI3L1 mitigates demyelination and gliosis: MBP intensity and densities of GFAP + astrocytes and Iba1 + microglia in L4 sections. n = 5 mice per group (3 sections per mouse). ( D ) Motor function: anti-CHI3L1 improves stride length and rotarod latency in systemic NMO mice. n = 8 per group. ( E ) Quantitative PCR (qPCR) heatmap of NF-κB–regulated cytokines (TNF-α, IL-1β, IL-6, IL-1α, CCL5, CCL7, C3) in lumbar cord after CHI3L1 neutralization, normalized to Ctrl-IgG + vehicle. n = 3 per group. ( F ) ELISA of secreted cytokines in lumbar cord lysates with anti-CHI3L1 versus msCtrl-IgG. n = 3 per group. ( G ) Electron microscopy of L4 white matter showing preservation of myelin with anti-CHI3L1. Scale bar: 2 μm; n = 3 animals per group. Quantified myelinated-axon density (normalized to Ctrl-IgG + msCtrl-IgG = 1.0) and g-ratio; 150 axons per group from 3 animals. ( H ) Conditional astrocyte-specific CHI3L1 knockout (Chil1 cKO): Chil1 fl/fl × ALDH1L1-CreERT2, tamoxifen-induced; subjected to systemic NMO paradigm, followed by behavioral testing and histopathology. ( I ) Chil1 cKO improves gait and rotarod performance versus floxed controls under AQP4-IgG. n = 8 per group. ( J ) Chil1 cKO reduces demyelination and gliosis: MBP intensity and GFAP + Iba1 + cell densities in L4 sections. n = 5 per group (3 sections per mouse). Statistics: Mean ± SEM. Rotarod latency analyzed by 2-way ANOVA ( D and I ). All other bar graphs: 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: Disruption, Control, Activation Assay, Real-time Polymerase Chain Reaction, Neutralization, Enzyme-linked Immunosorbent Assay, Electron Microscopy, Preserving, Knock-Out, Histopathology

( A ) In vitro paradigm: primary mouse astrocytes exposed to recombinant human CHI3L1 at graded doses to assess cell-intrinsic signaling. ( B ) CHI3L1 (10–200 ng/mL, 4 hours) selectively increases NF-κB p65 phosphorylation without activating ERK, AKT, or β-catenin; immunoblot densitometry shown as phospho/total ratios ( n = 3 experiments). ( C ) CHI3L1 dose-dependently induces NF-κB target transcripts (TNF-α, IL-1β, IL-6, IL-1α, CCL5, CCL7, C3) at 24 hours; heatmap normalized to vehicle (0 ng/mL) ( n = 3). ( D ) Corresponding cytokine secretion (TNF-α, IL-1β, IL-6, C3) measured by ELISA from conditioned media after 24 hours of CHI3L1 (10–200 ng/mL) ( n = 3). ( E ) Costimulation design: astrocytes treated with Ctrl-IgG or AQP4-IgG (100 ng/mL) with or without CHI3L1 (100 ng/mL) to test pathway convergence. ( F ) AQP4-IgG and CHI3L1 each increase p65 phosphorylation at 6 hours; combined treatment further augments p65 activation (immunoblot phospho/total p65; n = 3). ( G ) Immunofluorescence at 24 hours shows increased nuclear p65, GFAP upregulation, and AQP4 internalization in response to AQP4-IgG; these effects are enhanced by CHI3L1 cotreatment. Scale bars: 20 μm; n = 5 slides (6 fields per slide). ( H ) qPCR confirms amplification of NF-κB–regulated cytokine mRNAs by CHI3L1 in the AQP4-IgG condition; heatmap normalized to Ctrl-IgG + vehicle ( n = 3). ( I ) ELISA detects higher secreted TNF-α, IL-1β, IL-6, and C3 with AQP4-IgG + CHI3L1 versus either alone (24 hours; n = 3). Statistics: Data are mean ± SEM. Bar graph comparisons used 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) In vitro paradigm: primary mouse astrocytes exposed to recombinant human CHI3L1 at graded doses to assess cell-intrinsic signaling. ( B ) CHI3L1 (10–200 ng/mL, 4 hours) selectively increases NF-κB p65 phosphorylation without activating ERK, AKT, or β-catenin; immunoblot densitometry shown as phospho/total ratios ( n = 3 experiments). ( C ) CHI3L1 dose-dependently induces NF-κB target transcripts (TNF-α, IL-1β, IL-6, IL-1α, CCL5, CCL7, C3) at 24 hours; heatmap normalized to vehicle (0 ng/mL) ( n = 3). ( D ) Corresponding cytokine secretion (TNF-α, IL-1β, IL-6, C3) measured by ELISA from conditioned media after 24 hours of CHI3L1 (10–200 ng/mL) ( n = 3). ( E ) Costimulation design: astrocytes treated with Ctrl-IgG or AQP4-IgG (100 ng/mL) with or without CHI3L1 (100 ng/mL) to test pathway convergence. ( F ) AQP4-IgG and CHI3L1 each increase p65 phosphorylation at 6 hours; combined treatment further augments p65 activation (immunoblot phospho/total p65; n = 3). ( G ) Immunofluorescence at 24 hours shows increased nuclear p65, GFAP upregulation, and AQP4 internalization in response to AQP4-IgG; these effects are enhanced by CHI3L1 cotreatment. Scale bars: 20 μm; n = 5 slides (6 fields per slide). ( H ) qPCR confirms amplification of NF-κB–regulated cytokine mRNAs by CHI3L1 in the AQP4-IgG condition; heatmap normalized to Ctrl-IgG + vehicle ( n = 3). ( I ) ELISA detects higher secreted TNF-α, IL-1β, IL-6, and C3 with AQP4-IgG + CHI3L1 versus either alone (24 hours; n = 3). Statistics: Data are mean ± SEM. Bar graph comparisons used 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: In Vitro, Recombinant, Phospho-proteomics, Western Blot, Enzyme-linked Immunosorbent Assay, Activation Assay, Immunofluorescence, Amplification

$( A ) Candidate CHI3L1 receptors on astrocytes (IL-13Rα2, TMEM219, Gal-3, CD44, CRTH2, RAGE) and shRNA screen design: primary astrocytes transduced with lentivirus encoding GFP plus non-targeting shRNA (shNC) or receptor-targeting shRNA (>90% transduction). ( B ) RAGE is expressed in spinal astrocytes: colocalization of RAGE with GFAP in L4 sections from control mice. Scale bar: 20 μm. ( C ) Receptor knockdown screen identifies RAGE as required for CHI3L1-induced NF-κB: astrocytes expressing shNC or receptor shRNAs were treated with or without CHI3L1 (100 ng/mL, 6 hours); nuclear/cytoplasmic p65 quantified by immunoblot (histone H3 and β-actin as fraction controls) ( n = 3). ( D ) Conditional astrocyte-specific RAGE knockout (RAGE cKO): RAGE fl/fl × ALDH1L1-CreERT2 with tamoxifen induction, followed by systemic NMO paradigm (AQP4-IgG or Ctrl-IgG), behavioral testing, and spinal histopathology. ( E ) RAGE cKO improves motor function: gait (stride length) and rotarod latency in RAGE fl/fl + Ctrl-IgG, RAGE fl/fl + AQP4-IgG, and RAGE cKO + AQP4-IgG groups ( n = 8 per group). ( F ) RAGE cKO reduces demyelination and glial activation and preserves neurons: MBP intensity, GFAP + and Iba1 + cell densities, and NeuN + counts in L4 sections ( n = 5 per group; 3 sections per mouse). ( G ) Proinflammatory transcript suppression in RAGE cKO: qPCR heatmap for NF-κB targets (Tnf, Il1b, Il6, Il1a, Ccl5, Ccl7, C3) in lumbar cord, normalized to RAGE fl/fl + Ctrl-IgG ( n = 3 per group). ( H ) Reduced cytokine proteins in RAGE cKO: ELISA for TNF-α, IL-1β, IL-6, and C3 in lumbar cord lysates ( n = 3 per group). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.$

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) Candidate CHI3L1 receptors on astrocytes (IL-13Rα2, TMEM219, Gal-3, CD44, CRTH2, RAGE) and shRNA screen design: primary astrocytes transduced with lentivirus encoding GFP plus non-targeting shRNA (shNC) or receptor-targeting shRNA (>90% transduction). ( B ) RAGE is expressed in spinal astrocytes: colocalization of RAGE with GFAP in L4 sections from control mice. Scale bar: 20 μm. ( C ) Receptor knockdown screen identifies RAGE as required for CHI3L1-induced NF-κB: astrocytes expressing shNC or receptor shRNAs were treated with or without CHI3L1 (100 ng/mL, 6 hours); nuclear/cytoplasmic p65 quantified by immunoblot (histone H3 and β-actin as fraction controls) ( n = 3). ( D ) Conditional astrocyte-specific RAGE knockout (RAGE cKO): RAGE fl/fl × ALDH1L1-CreERT2 with tamoxifen induction, followed by systemic NMO paradigm (AQP4-IgG or Ctrl-IgG), behavioral testing, and spinal histopathology. ( E ) RAGE cKO improves motor function: gait (stride length) and rotarod latency in RAGE fl/fl + Ctrl-IgG, RAGE fl/fl + AQP4-IgG, and RAGE cKO + AQP4-IgG groups ( n = 8 per group). ( F ) RAGE cKO reduces demyelination and glial activation and preserves neurons: MBP intensity, GFAP + and Iba1 + cell densities, and NeuN + counts in L4 sections ( n = 5 per group; 3 sections per mouse). ( G ) Proinflammatory transcript suppression in RAGE cKO: qPCR heatmap for NF-κB targets (Tnf, Il1b, Il6, Il1a, Ccl5, Ccl7, C3) in lumbar cord, normalized to RAGE fl/fl + Ctrl-IgG ( n = 3 per group). ( H ) Reduced cytokine proteins in RAGE cKO: ELISA for TNF-α, IL-1β, IL-6, and C3 in lumbar cord lysates ( n = 3 per group). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: shRNA, Transduction, Control, Knockdown, Expressing, Western Blot, Knock-Out, Histopathology, Activation Assay, Enzyme-linked Immunosorbent Assay

( A ) KEGG pathway analysis of differentially expressed genes from primary astrocytes treated with AQP4-IgG versus Ctrl-IgG identifies JAK/STAT3 among the top pathways activated by AQP4 autoantibody exposure. ( B ) AQP4-IgG activates STAT3 and NF-κB and induces CHI3L1 in primary astrocytes; WP1066 (STAT3 inhibitor) suppresses p-STAT3, p-p65, and CHI3L1 levels. Immunoblot densitometry shown as CHI3L1/β-actin and phospho/total ratios for STAT3 and p65 ( n = 3 experiments). ( C ) Cultures were treated with AQP4-IgG or Ctrl-IgG in the presence of FPS-ZM1 or sRAGE; no exogenous CHI3L1 was added. RAGE blockade (FPS-ZM1 or sRAGE) does not affect AQP4-IgG–evoked p-STAT3 but reduces p-p65, placing STAT3 upstream of CHI3L1/RAGE/NF-κB. Phospho/total immunoblot ratios are shown ( n = 3 per group). ( D ) Model: AQP4-IgG triggers astrocytic STAT3 activation → CHI3L1 expression/secretion → autocrine engagement of RAGE → NF-κB–dependent proinflammatory signaling. ( E ) Conditional astrocyte-specific STAT3 knockout (STAT3 cKO): STAT3 fl/fl × ALDH1L1-CreERT2 with tamoxifen induction, followed by systemic NMO paradigm (AQP4-IgG or Ctrl-IgG), behavioral testing, and spinal histopathology. ( F ) Efficiency of STAT3 depletion in astrocytes confirmed in striatum and L4 spinal cord by IHC (~80% reduction in STAT3 signal in GFAP + cells) in STAT3-cKO versus STAT3 fl/fl controls. Scale bar: 20 μm. ( G ) STAT3 cKO improves motor outcomes: gait (stride length) and rotarod latency across STAT3 fl/fl + Ctrl-IgG, STAT3 fl/fl + AQP4-IgG, STAT3 cKO + Ctrl-IgG, and STAT3 cKO + AQP4-IgG groups ( n = 8 per group). Statistics: Data are mean ± SEM. Bar graph comparisons in B , C , and F used 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Rotarod latency was analyzed by 2-way ANOVA ( G ). Non-significant comparisons are not shown. * P < 0.05; *** P < 0.001; **** P < 0.0001.

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) KEGG pathway analysis of differentially expressed genes from primary astrocytes treated with AQP4-IgG versus Ctrl-IgG identifies JAK/STAT3 among the top pathways activated by AQP4 autoantibody exposure. ( B ) AQP4-IgG activates STAT3 and NF-κB and induces CHI3L1 in primary astrocytes; WP1066 (STAT3 inhibitor) suppresses p-STAT3, p-p65, and CHI3L1 levels. Immunoblot densitometry shown as CHI3L1/β-actin and phospho/total ratios for STAT3 and p65 ( n = 3 experiments). ( C ) Cultures were treated with AQP4-IgG or Ctrl-IgG in the presence of FPS-ZM1 or sRAGE; no exogenous CHI3L1 was added. RAGE blockade (FPS-ZM1 or sRAGE) does not affect AQP4-IgG–evoked p-STAT3 but reduces p-p65, placing STAT3 upstream of CHI3L1/RAGE/NF-κB. Phospho/total immunoblot ratios are shown ( n = 3 per group). ( D ) Model: AQP4-IgG triggers astrocytic STAT3 activation → CHI3L1 expression/secretion → autocrine engagement of RAGE → NF-κB–dependent proinflammatory signaling. ( E ) Conditional astrocyte-specific STAT3 knockout (STAT3 cKO): STAT3 fl/fl × ALDH1L1-CreERT2 with tamoxifen induction, followed by systemic NMO paradigm (AQP4-IgG or Ctrl-IgG), behavioral testing, and spinal histopathology. ( F ) Efficiency of STAT3 depletion in astrocytes confirmed in striatum and L4 spinal cord by IHC (~80% reduction in STAT3 signal in GFAP + cells) in STAT3-cKO versus STAT3 fl/fl controls. Scale bar: 20 μm. ( G ) STAT3 cKO improves motor outcomes: gait (stride length) and rotarod latency across STAT3 fl/fl + Ctrl-IgG, STAT3 fl/fl + AQP4-IgG, STAT3 cKO + Ctrl-IgG, and STAT3 cKO + AQP4-IgG groups ( n = 8 per group). Statistics: Data are mean ± SEM. Bar graph comparisons in B , C , and F used 1-way ANOVA with Tukey’s post hoc test or Welch’s ANOVA with Dunnett’s T3 test for unequal variances. Rotarod latency was analyzed by 2-way ANOVA ( G ). Non-significant comparisons are not shown. * P < 0.05; *** P < 0.001; **** P < 0.0001.

Techniques: Western Blot, Activation Assay, Expressing, Knock-Out, Histopathology

( A ) Ex vivo paradigm: organotypic cerebellar slices treated 48 hours with AQP4-IgG or Ctrl-IgG with or without WP1066 (100 ng/mL), followed by immunostaining for myelination and glial activation. ( B ) WP1066 reduces AQP4-IgG–induced demyelination; MBP fluorescence normalized to Ctrl-IgG + vehicle = 1.0. NFH marks axonal process integrity. n = 5 slices per group (3 sections per slice). ( C ) WP1066 attenuates microgliosis and complement activation; Iba1 + total and Iba1 + CD68 + activated microglia densities, C3d levels, and MAC (C5b-9) quantified relative to Ctrl-IgG + vehicle. n = 5 slices per group. ( D ) In vivo design: systemic NMO model with WP1066 (10 μg/mouse) or vehicle. Groups: Ctrl-IgG + vehicle, AQP4-IgG + vehicle, AQP4-IgG + WP1066. ( E ) WP1066 suppresses STAT3 activation and CHI3L1 induction in lumbar spinal cord; immunoblot densitometry shown as p-STAT3/STAT3 and CHI3L1/β-actin ( n = 3). ( F ) WP1066 improves motor function in systemic NMO mice; gait (stride length) and rotarod latency ( n = 8 per group). ( G ) WP1066 mitigates spinal demyelination and glial activation and preserves neurons; MBP intensity, GFAP + Iba1 + cell densities, and NeuN + counts in L4 sections. Scale bars: 100 μm; n = 5 mice per group (3 sections per mouse). Statistics: Mean ± SEM. Bar graphs analyzed by 1-way ANOVA with Tukey’s post hoc test; rotarod latency by 2-way ANOVA ( F ). Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Journal: The Journal of Clinical Investigation

Article Title: Astrocyte-intrinsic signaling of chitinase-like protein CHI3L1 drives inflammation and amplifies demyelination in neuromyelitis optica

doi: 10.1172/JCI195506

Figure Lengend Snippet: ( A ) Ex vivo paradigm: organotypic cerebellar slices treated 48 hours with AQP4-IgG or Ctrl-IgG with or without WP1066 (100 ng/mL), followed by immunostaining for myelination and glial activation. ( B ) WP1066 reduces AQP4-IgG–induced demyelination; MBP fluorescence normalized to Ctrl-IgG + vehicle = 1.0. NFH marks axonal process integrity. n = 5 slices per group (3 sections per slice). ( C ) WP1066 attenuates microgliosis and complement activation; Iba1 + total and Iba1 + CD68 + activated microglia densities, C3d levels, and MAC (C5b-9) quantified relative to Ctrl-IgG + vehicle. n = 5 slices per group. ( D ) In vivo design: systemic NMO model with WP1066 (10 μg/mouse) or vehicle. Groups: Ctrl-IgG + vehicle, AQP4-IgG + vehicle, AQP4-IgG + WP1066. ( E ) WP1066 suppresses STAT3 activation and CHI3L1 induction in lumbar spinal cord; immunoblot densitometry shown as p-STAT3/STAT3 and CHI3L1/β-actin ( n = 3). ( F ) WP1066 improves motor function in systemic NMO mice; gait (stride length) and rotarod latency ( n = 8 per group). ( G ) WP1066 mitigates spinal demyelination and glial activation and preserves neurons; MBP intensity, GFAP + Iba1 + cell densities, and NeuN + counts in L4 sections. Scale bars: 100 μm; n = 5 mice per group (3 sections per mouse). Statistics: Mean ± SEM. Bar graphs analyzed by 1-way ANOVA with Tukey’s post hoc test; rotarod latency by 2-way ANOVA ( F ). Non-significant comparisons are not shown. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001.

Techniques: Ex Vivo, Immunostaining, Activation Assay, Fluorescence, In Vivo, Western Blot

( A ) Stereotaxic infusion of fibrillary Aβ 42 (1 mM) or vehicle into the DG of 8-week-old wild-type mice ( n = 7 per group) induced astrocyte activation. Two weeks later, GFAP and CHI3L1 immunofluorescence—normalized to vehicle levels (set to 1.0)—was both elevated and colocalized with GFAP (scale bars, 300 μm; inset, 100 μm). ( B ) Human iAstro treated with Aβ 42 for 48 hours ( n = 4) displayed hypertrophic morphology and increased GFAP and CHI3L1 expression compared to vehicle (scale bar, 100 μm). ( C ) Dose-dependent CHI3L1 secretion from Aβ 42 -exposed iAstro was quantified by immunoprecipitation of conditioned media and normalized to cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ( n = 3). ( D ) iNPC proliferation, assessed by EdU incorporation after 72 hours of CHI3L1 treatment ( n = 3), decreased in a CHI3L1 concentration–dependent manner (scale bars, 100 μm). ( E ) PAX6 + iNPCs underwent neuronal differentiation for 72 hours in the presence of Aβ 42 (1 μM), CHI3L1 (500 ng/ml), or both ( n = 4). DCX immunostaining revealed that each treatment suppressed immature neuron numbers, with the combination exerting additive inhibition (scale bar, 100 μm). Data are means ± SEM. * P < 0.05 and **** P < 0.0001 by unpaired two-tailed t test [(A) and (B)] or one-way ANOVA with Tukey’s post hoc test [(C) to (E)].

Journal: Science Advances

Article Title: CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer’s disease

doi: 10.1126/sciadv.adv1492

Figure Lengend Snippet: ( A ) Stereotaxic infusion of fibrillary Aβ 42 (1 mM) or vehicle into the DG of 8-week-old wild-type mice ( n = 7 per group) induced astrocyte activation. Two weeks later, GFAP and CHI3L1 immunofluorescence—normalized to vehicle levels (set to 1.0)—was both elevated and colocalized with GFAP (scale bars, 300 μm; inset, 100 μm). ( B ) Human iAstro treated with Aβ 42 for 48 hours ( n = 4) displayed hypertrophic morphology and increased GFAP and CHI3L1 expression compared to vehicle (scale bar, 100 μm). ( C ) Dose-dependent CHI3L1 secretion from Aβ 42 -exposed iAstro was quantified by immunoprecipitation of conditioned media and normalized to cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ( n = 3). ( D ) iNPC proliferation, assessed by EdU incorporation after 72 hours of CHI3L1 treatment ( n = 3), decreased in a CHI3L1 concentration–dependent manner (scale bars, 100 μm). ( E ) PAX6 + iNPCs underwent neuronal differentiation for 72 hours in the presence of Aβ 42 (1 μM), CHI3L1 (500 ng/ml), or both ( n = 4). DCX immunostaining revealed that each treatment suppressed immature neuron numbers, with the combination exerting additive inhibition (scale bar, 100 μm). Data are means ± SEM. * P < 0.05 and **** P < 0.0001 by unpaired two-tailed t test [(A) and (B)] or one-way ANOVA with Tukey’s post hoc test [(C) to (E)].

Article Snippet: The conditional CHI3L1 knockout mouse strain, Chil1 -f/f (with exon 5 of the mouse Chil1 gene floxed), was developed by Cyagen Biosciences (NCBI: 12654).

Techniques: Activation Assay, Immunofluorescence, Expressing, Immunoprecipitation, Concentration Assay, Immunostaining, Inhibition, Two Tailed Test

$( A ) Schematic for the iNPC/iAstro coculture system. iAstro were transduced with control (shCtrl) or CHI3L1 shRNA (shCHI3L1), exposed to fibrillar Aβ 42 (1 μM, 48 hours) or vehicle, washed, and cocultured with iNPCs for 3 days. Four independent experiments were analyzed (three to five fields each). ( B ) iNPC proliferation. EdU incorporation showed that Aβ-treated shCtrl iAstro reduce iNPC proliferation (EdU + /DAPI + /GFP − ) relative to vehicle controls; this decline is rescued when CHI3L1 is silenced in the astrocytes. ( C ) iNPC neuronal differentiation. DCX staining revealed parallel effects on neuronal output: Aβ-stimulated shCtrl iAstro lowered the DCX + /DAPI + /GFP − ratio, whereas CHI3L1 knockdown restored differentiation. ( D ) Schematic of the ACM assay. iAstro were treated for 3 days with Aβ 42 (Aβ ACM) or vehicle (Ctrl ACM). CHI3L1 was depleted with anti-CHI3L1 antibody (+αCHI3L1) or left intact (+Ctrl-IgG); IgG was removed and the ACM applied to iNPCs for proliferation and differentiation tests (four independent experiments, three to five images each). ( E ) iNPC proliferation in ACM. EdU + /Nestin + /DAPI + cells were expressed as a fraction of the total Nestin + /DAPI + iNPC population. Aβ ACM containing CHI3L1 (+Ctrl-IgG) markedly reduced EdU + /Nestin + iNPCs versus vehicle or control ACM; CHI3L1 clearance (+αCHI3L1) restored proliferation to baseline. ( F ) iNPC neuronal differentiation in ACM. The same Aβ ACM suppressed neuronal differentiation (fold change of DCX + /DAPI + , vehicle = 1.0), an effect fully reversed by CHI3L1 removal, pinpointing CHI3L1 as the key inhibitory factor released from Aβ-activated astrocytes. Scale bars, 100 μm. Data are means ± SEM; ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA with Tukey’s post hoc test.$

Journal: Science Advances

Article Title: CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer’s disease

doi: 10.1126/sciadv.adv1492

Figure Lengend Snippet: ( A ) Schematic for the iNPC/iAstro coculture system. iAstro were transduced with control (shCtrl) or CHI3L1 shRNA (shCHI3L1), exposed to fibrillar Aβ 42 (1 μM, 48 hours) or vehicle, washed, and cocultured with iNPCs for 3 days. Four independent experiments were analyzed (three to five fields each). ( B ) iNPC proliferation. EdU incorporation showed that Aβ-treated shCtrl iAstro reduce iNPC proliferation (EdU + /DAPI + /GFP − ) relative to vehicle controls; this decline is rescued when CHI3L1 is silenced in the astrocytes. ( C ) iNPC neuronal differentiation. DCX staining revealed parallel effects on neuronal output: Aβ-stimulated shCtrl iAstro lowered the DCX + /DAPI + /GFP − ratio, whereas CHI3L1 knockdown restored differentiation. ( D ) Schematic of the ACM assay. iAstro were treated for 3 days with Aβ 42 (Aβ ACM) or vehicle (Ctrl ACM). CHI3L1 was depleted with anti-CHI3L1 antibody (+αCHI3L1) or left intact (+Ctrl-IgG); IgG was removed and the ACM applied to iNPCs for proliferation and differentiation tests (four independent experiments, three to five images each). ( E ) iNPC proliferation in ACM. EdU + /Nestin + /DAPI + cells were expressed as a fraction of the total Nestin + /DAPI + iNPC population. Aβ ACM containing CHI3L1 (+Ctrl-IgG) markedly reduced EdU + /Nestin + iNPCs versus vehicle or control ACM; CHI3L1 clearance (+αCHI3L1) restored proliferation to baseline. ( F ) iNPC neuronal differentiation in ACM. The same Aβ ACM suppressed neuronal differentiation (fold change of DCX + /DAPI + , vehicle = 1.0), an effect fully reversed by CHI3L1 removal, pinpointing CHI3L1 as the key inhibitory factor released from Aβ-activated astrocytes. Scale bars, 100 μm. Data are means ± SEM; ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA with Tukey’s post hoc test.

Article Snippet: The conditional CHI3L1 knockout mouse strain, Chil1 -f/f (with exon 5 of the mouse Chil1 gene floxed), was developed by Cyagen Biosciences (NCBI: 12654).

Techniques: Transduction, Control, shRNA, Staining, Knockdown

( A ) Immunoblots of 17 candidate mediators after 10-min CHI3L1 exposure (0 to 500 ng/ml). Phospho/total signals were densitometrically normalized to the no-CHI3L1 control (1.0); n = 3 to 4. ( B ) Dose-response blots for p-S6K1 and p-S6 (10 min). Values are phospho/total, expressed relative to untreated cells (1.0); n = 4. ( C ) Dose-response blots for p-IKKβ with the same quantification as in (B); n = 3. ( D ) BMS345541 (10 μM, 30 min) was added 10 min before CHI3L1 (500 ng/ml). p-S6 was quantified as in (B); n = 4. ( E ) iNPCs transfected with CRTH2 siRNA (siCRTH2) or control siRNA (siNC) were exposed to CHI3L1 (500 ng/ml, 48 hours). Proliferation = EdU + /DAPI + cells (% of total DAPI + ); n = 4. ( F ) After the same transfection, cells were differentiated for 3 days under CHI3L1 incubation. Neuronal differentiation output = DCX + /DAPI + (%), expressed as fold change over siNC+Ctrl (1.0); n = 4. Statistics: one-way ANOVA with Tukey’s post hoc for [(A) to (C)] and (E); unpaired t test for (D). * P < 0.05; ** P < 0.005, *** P < 0.001; **** P < 0.0001. n.s., not significant.

Journal: Science Advances

Article Title: CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer’s disease

doi: 10.1126/sciadv.adv1492

Figure Lengend Snippet: ( A ) Immunoblots of 17 candidate mediators after 10-min CHI3L1 exposure (0 to 500 ng/ml). Phospho/total signals were densitometrically normalized to the no-CHI3L1 control (1.0); n = 3 to 4. ( B ) Dose-response blots for p-S6K1 and p-S6 (10 min). Values are phospho/total, expressed relative to untreated cells (1.0); n = 4. ( C ) Dose-response blots for p-IKKβ with the same quantification as in (B); n = 3. ( D ) BMS345541 (10 μM, 30 min) was added 10 min before CHI3L1 (500 ng/ml). p-S6 was quantified as in (B); n = 4. ( E ) iNPCs transfected with CRTH2 siRNA (siCRTH2) or control siRNA (siNC) were exposed to CHI3L1 (500 ng/ml, 48 hours). Proliferation = EdU + /DAPI + cells (% of total DAPI + ); n = 4. ( F ) After the same transfection, cells were differentiated for 3 days under CHI3L1 incubation. Neuronal differentiation output = DCX + /DAPI + (%), expressed as fold change over siNC+Ctrl (1.0); n = 4. Statistics: one-way ANOVA with Tukey’s post hoc for [(A) to (C)] and (E); unpaired t test for (D). * P < 0.05; ** P < 0.005, *** P < 0.001; **** P < 0.0001. n.s., not significant.

Article Snippet: The conditional CHI3L1 knockout mouse strain, Chil1 -f/f (with exon 5 of the mouse Chil1 gene floxed), was developed by Cyagen Biosciences (NCBI: 12654).

Techniques: Western Blot, Control, Transfection, Incubation

( A ) Experimental timeline. Tamoxifen-induced Aldh1l1-CreERT2 Chil1 -f/f mice ( Chil1 -cKO) or littermate controls ( Chil1 -f/f) received DG injections of fibrillar Aβ 42 or vehicle, yielding four groups. Two weeks later mice were tested in the OFT and MWM; EdU and BrdU pulses marked NSC proliferation and neuron birth. ( B ) Immunofluorescence confirmed >90% CHI3L1 loss in cKO astrocytes and showed attenuated Aβ-evoked gliosis (GFAP); n = 4. ( C ) EdU+ proliferating NSCs (radial glia: EdU/Sox2/GFAP; progenitors: EdU/Sox2) were reduced by Aβ in Chil1 -f/f but rescued in Chil1 -cKO; n = 5. ( D ) BrdU labeling 4 weeks later revealed fewer new DCX+ immature and NeuN+ mature neurons after Aβ in Chil1 -f/f; both indices were restored by CHI3L1 deletion; n = 5. ( E ) OFT: Total distance and center entries were unchanged by genotype under vehicle but fell after Aβ in Chil1 -f/f; cKO mice were protected; n = 10. ( F ) MWM: All groups learned during acquisition (escape latency, top). In probe trials (platform removed), Aβ-treated Chi l1-f/f mice showed fewer crossings and less time in the target quadrant; cKO mice again matched vehicle controls. Representative swim paths are shown; n = 10. Scale bars, 100 μm. ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA [(B) to (E), acquisition] or two-way ANOVA (probe) with Tukey’s post hoc.

Journal: Science Advances

Article Title: CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer’s disease

doi: 10.1126/sciadv.adv1492

Figure Lengend Snippet: ( A ) Experimental timeline. Tamoxifen-induced Aldh1l1-CreERT2 Chil1 -f/f mice ( Chil1 -cKO) or littermate controls ( Chil1 -f/f) received DG injections of fibrillar Aβ 42 or vehicle, yielding four groups. Two weeks later mice were tested in the OFT and MWM; EdU and BrdU pulses marked NSC proliferation and neuron birth. ( B ) Immunofluorescence confirmed >90% CHI3L1 loss in cKO astrocytes and showed attenuated Aβ-evoked gliosis (GFAP); n = 4. ( C ) EdU+ proliferating NSCs (radial glia: EdU/Sox2/GFAP; progenitors: EdU/Sox2) were reduced by Aβ in Chil1 -f/f but rescued in Chil1 -cKO; n = 5. ( D ) BrdU labeling 4 weeks later revealed fewer new DCX+ immature and NeuN+ mature neurons after Aβ in Chil1 -f/f; both indices were restored by CHI3L1 deletion; n = 5. ( E ) OFT: Total distance and center entries were unchanged by genotype under vehicle but fell after Aβ in Chil1 -f/f; cKO mice were protected; n = 10. ( F ) MWM: All groups learned during acquisition (escape latency, top). In probe trials (platform removed), Aβ-treated Chi l1-f/f mice showed fewer crossings and less time in the target quadrant; cKO mice again matched vehicle controls. Representative swim paths are shown; n = 10. Scale bars, 100 μm. ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA [(B) to (E), acquisition] or two-way ANOVA (probe) with Tukey’s post hoc.

Article Snippet: The conditional CHI3L1 knockout mouse strain, Chil1 -f/f (with exon 5 of the mouse Chil1 gene floxed), was developed by Cyagen Biosciences (NCBI: 12654).

Techniques: Immunofluorescence, Labeling

( A ) Design and timeline. Lentiviruses expressing shCRTH2-eGFP or shCtrl-eGFP were injected bilaterally into the DG of 6-month-old wild-type (WT) and 5XFAD mice (shCtrl in one side and shCRTH2 in the other). BrdU was given immediately, EdU 24 hours before euthanasia 4 weeks later. Groups: WT + shCtrl, 5XFAD + shCtrl, and 5XFAD + shCRTH2 ( n = 5). ( B ) Thioflavin-S/Aβ 42 staining showed hippocampal plaques in 5XFAD but not WT; CRTH2 knockdown did not change plaque size or density. ( C ) GFAP and CHI3L1 Immunolabeling indicated comparable astrocytosis and CHI3L1 induction in 5XFAD hemispheres with or without shCRTH2. ( D ) SGZ proliferation. EdU+ GFP+ cells were classified as radial NSCs (GFAP+) or amplifying progenitors (GFAP−). Proliferation was reduced in 5XFAD + shCtrl versus WT but significantly restored by shCRTH2. ( E ) Neuronal output. GFP+ BrdU+ cells coexpressing DCX (immature) or NeuN (mature) were decreased in 5XFAD + shCtrl and rescued by CRTH2 knockdown. Scale bars, 100 μm. ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA with Tukey’s post hoc (comparisons versus WT + shCtrl and 5XFAD + shCtrl).

Journal: Science Advances

Article Title: CHI3L1/YKL-40 signaling inhibits neurogenesis in models of Alzheimer’s disease

doi: 10.1126/sciadv.adv1492

Figure Lengend Snippet: ( A ) Design and timeline. Lentiviruses expressing shCRTH2-eGFP or shCtrl-eGFP were injected bilaterally into the DG of 6-month-old wild-type (WT) and 5XFAD mice (shCtrl in one side and shCRTH2 in the other). BrdU was given immediately, EdU 24 hours before euthanasia 4 weeks later. Groups: WT + shCtrl, 5XFAD + shCtrl, and 5XFAD + shCRTH2 ( n = 5). ( B ) Thioflavin-S/Aβ 42 staining showed hippocampal plaques in 5XFAD but not WT; CRTH2 knockdown did not change plaque size or density. ( C ) GFAP and CHI3L1 Immunolabeling indicated comparable astrocytosis and CHI3L1 induction in 5XFAD hemispheres with or without shCRTH2. ( D ) SGZ proliferation. EdU+ GFP+ cells were classified as radial NSCs (GFAP+) or amplifying progenitors (GFAP−). Proliferation was reduced in 5XFAD + shCtrl versus WT but significantly restored by shCRTH2. ( E ) Neuronal output. GFP+ BrdU+ cells coexpressing DCX (immature) or NeuN (mature) were decreased in 5XFAD + shCtrl and rescued by CRTH2 knockdown. Scale bars, 100 μm. ** P < 0.005, *** P < 0.001, and **** P < 0.0001 by one-way ANOVA with Tukey’s post hoc (comparisons versus WT + shCtrl and 5XFAD + shCtrl).

Article Snippet: The conditional CHI3L1 knockout mouse strain, Chil1 -f/f (with exon 5 of the mouse Chil1 gene floxed), was developed by Cyagen Biosciences (NCBI: 12654).

Techniques: Expressing, Injection, Staining, Knockdown, Immunolabeling

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