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BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) <t>(100ug/ml)</t> for <t>TLR3</t> stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .
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BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) <t>(100ug/ml)</t> for <t>TLR3</t> stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .
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BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) <t>(100ug/ml)</t> for <t>TLR3</t> stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .
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BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) <t>(100ug/ml)</t> for <t>TLR3</t> stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .
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Age at diagnosis according to IL10 and <t>TLR3</t> SNPs. Boxplots displaying median and interquartile ranges of ALK-positive ALCL patients age at diagnosis according to the genotype of selected SNPs. rs1800872 is shown in ( A ), rs1800896 in ( B ) and rs3775291 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Mann-Whitney test was used to calculate statistical significance, expressed as p values and *. * p < 0.05, ** p < 0.01
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MedChemExpress tlr3 inhibitor
A Differentially expressed genes (DEGs) in full-thickness bladder tissues from HIC patients and controls identified via RNA sequencing (|log₂FC|≥2; adjusted p < 0.05, two-sided Wald test using DESeq2). Gene Ontology (GO) ( B ) and KEGG ( C ) enrichment analyses of DEGs (two-sided hypergeometric test with FDR correction). D UMAP visualization of single-cell transcriptomic landscape of urothelium, with urothelial cells (UCs) identified by KRT19 and UPK1A expression. GO ( E ) and KEGG ( F ) analyses of upregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). GO ( G ) and KEGG ( H ) analyses of downregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). I , J Gene Set Enrichment Analysis (GSEA) of altered pathways in UCs (two-sided permutation test with 1000 permutations, with multiple testing corrected using the FDR). The exact p value for TLR signaling of UCs in panel I is 0.0009. K Expression of Toll-like receptor (TLR) subtypes in UCs from HIC bladders. mRNA ( L ) and protein ( M ) expression levels of <t>TLR3</t> in isolated urothelium from control and HIC patients ( n = 7 control vs. 10 HIC; data show median (IQR); two-sided Mann–Whitney U test; ns not significant; Bar for panel M: 1 cm). N Immunostaining showing the distribution of TLR3 protein in the urothelium of patients with HIC ( n = 7 control vs. 10 HIC; one section and field per patient; Bar: 100 μm). IHC immunohistochemistry, HL Hunner lesions, U urothelium, LP lamina propria (blue line), M muscularis. Source data are provided as a Source Data file.
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Image Search Results


BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) (100ug/ml) for TLR3 stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .

Journal: bioRxiv

Article Title: Aquamin a marine derived multi mineral attenuates toll like receptor mediated inflammatory responses in macrophages

doi: 10.64898/2026.01.19.700098

Figure Lengend Snippet: BMDMs pretreated with Aquamin (2mg/ml) for 3 h prior to stimulation with the corresponding TLR agonists overnight, LPS (100ng/ml) for TLR4 stimulation, Poly(I:C) (100ug/ml) for TLR3 stimulation and CpG (3μM) for TLR9 stimulation. (a)IL-6 and (b) TNF-alpha cytokine levels in the cell culture supernatants by ELISA. Data are expressed as mean ±sem from 3 independent experiments. **p<0.01, ***p<0.001 vs LPS alone using one way ANOVA statistical test .

Article Snippet: The following toll-like receptor (TLR) agonists were used TLR3 Poly(I:C) HMW (100ug/ml), TLR 9 CpG ODN 1826 (3μM) (both InvivoGen) and TLR4 LPS (100ng/ml) from Escherichia coli O55:B5 (Sigma Aldrich, L6529). hPBMCs or mBMDMs were first treated with Aqaumin (0.5,1,2 mg/ml) for 3h prior to TLR agonist stimulation for a further 4-12h.

Techniques: Cell Culture, Enzyme-linked Immunosorbent Assay

Age at diagnosis according to IL10 and TLR3 SNPs. Boxplots displaying median and interquartile ranges of ALK-positive ALCL patients age at diagnosis according to the genotype of selected SNPs. rs1800872 is shown in ( A ), rs1800896 in ( B ) and rs3775291 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Mann-Whitney test was used to calculate statistical significance, expressed as p values and *. * p < 0.05, ** p < 0.01

Journal: Journal of Translational Medicine

Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

doi: 10.1186/s12967-025-07410-5

Figure Lengend Snippet: Age at diagnosis according to IL10 and TLR3 SNPs. Boxplots displaying median and interquartile ranges of ALK-positive ALCL patients age at diagnosis according to the genotype of selected SNPs. rs1800872 is shown in ( A ), rs1800896 in ( B ) and rs3775291 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Mann-Whitney test was used to calculate statistical significance, expressed as p values and *. * p < 0.05, ** p < 0.01

Article Snippet: TLR3 , rs3775291 , C___1731425_10.

Techniques: Biomarker Discovery, Variant Assay, MANN-WHITNEY

Progression-free survival of ALK-positive ALCL-patients according to selected SNP genotypes. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected SNP genotypes. IFNGR2 rs17882748 is shown in ( A ), TLR3 rs3775291 in ( B ) and CD86 rs1129055 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05. Numbers at the bottom of the figure are number at risk

Journal: Journal of Translational Medicine

Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

doi: 10.1186/s12967-025-07410-5

Figure Lengend Snippet: Progression-free survival of ALK-positive ALCL-patients according to selected SNP genotypes. Kaplan-Meier plots displaying progression-free survival of patients with ALK-positive ALCL after chemotherapy. Patients were categorized according to selected SNP genotypes. IFNGR2 rs17882748 is shown in ( A ), TLR3 rs3775291 in ( B ) and CD86 rs1129055 in ( C ). Dominant or recessive behavior of the variant allele was tested by grouping patients bearing at least one variant or reference allele (middle and right panels). Observations of patients alive without failure were censored at the time of their last follow-up and indicated by a cross on the curve at the censoring time. Log-rank test was used to calculate statistical significance, expressed as p values and *. * p < 0.05. Numbers at the bottom of the figure are number at risk

Article Snippet: TLR3 , rs3775291 , C___1731425_10.

Techniques: Variant Assay

IL10 and TLR3 expression levels according to rs1800872, rs1800896 and rs3775291 genotypes. IL10 and TLR3 mRNA levels in circulating PBMCs of ALK-positive ALCL patients ( n = 85) were assessed using qRT-PCR. Relative expression, as 2^(−ΔCt), is presented according to rs1800872 ( A ), rs1800896 ( B ) or rs3775291 ( C ) genotypes. Statistical significance was calculated using the Student’s t-test with Welch’s correction and expressed as p values and *. * p < 0.05, ** p < 0.01

Journal: Journal of Translational Medicine

Article Title: Association of immune relevant single nucleotide polymorphisms with ALK-positive anaplastic large cell lymphoma presentation and outcome: results of the immuno ALCL study

doi: 10.1186/s12967-025-07410-5

Figure Lengend Snippet: IL10 and TLR3 expression levels according to rs1800872, rs1800896 and rs3775291 genotypes. IL10 and TLR3 mRNA levels in circulating PBMCs of ALK-positive ALCL patients ( n = 85) were assessed using qRT-PCR. Relative expression, as 2^(−ΔCt), is presented according to rs1800872 ( A ), rs1800896 ( B ) or rs3775291 ( C ) genotypes. Statistical significance was calculated using the Student’s t-test with Welch’s correction and expressed as p values and *. * p < 0.05, ** p < 0.01

Article Snippet: TLR3 , rs3775291 , C___1731425_10.

Techniques: Expressing, Quantitative RT-PCR

A Differentially expressed genes (DEGs) in full-thickness bladder tissues from HIC patients and controls identified via RNA sequencing (|log₂FC|≥2; adjusted p < 0.05, two-sided Wald test using DESeq2). Gene Ontology (GO) ( B ) and KEGG ( C ) enrichment analyses of DEGs (two-sided hypergeometric test with FDR correction). D UMAP visualization of single-cell transcriptomic landscape of urothelium, with urothelial cells (UCs) identified by KRT19 and UPK1A expression. GO ( E ) and KEGG ( F ) analyses of upregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). GO ( G ) and KEGG ( H ) analyses of downregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). I , J Gene Set Enrichment Analysis (GSEA) of altered pathways in UCs (two-sided permutation test with 1000 permutations, with multiple testing corrected using the FDR). The exact p value for TLR signaling of UCs in panel I is 0.0009. K Expression of Toll-like receptor (TLR) subtypes in UCs from HIC bladders. mRNA ( L ) and protein ( M ) expression levels of TLR3 in isolated urothelium from control and HIC patients ( n = 7 control vs. 10 HIC; data show median (IQR); two-sided Mann–Whitney U test; ns not significant; Bar for panel M: 1 cm). N Immunostaining showing the distribution of TLR3 protein in the urothelium of patients with HIC ( n = 7 control vs. 10 HIC; one section and field per patient; Bar: 100 μm). IHC immunohistochemistry, HL Hunner lesions, U urothelium, LP lamina propria (blue line), M muscularis. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Multi-omics analysis identifies a microbiota–bile acid–TLR signaling axis driving bladder injury in interstitial cystitis

doi: 10.1038/s41467-025-68060-1

Figure Lengend Snippet: A Differentially expressed genes (DEGs) in full-thickness bladder tissues from HIC patients and controls identified via RNA sequencing (|log₂FC|≥2; adjusted p < 0.05, two-sided Wald test using DESeq2). Gene Ontology (GO) ( B ) and KEGG ( C ) enrichment analyses of DEGs (two-sided hypergeometric test with FDR correction). D UMAP visualization of single-cell transcriptomic landscape of urothelium, with urothelial cells (UCs) identified by KRT19 and UPK1A expression. GO ( E ) and KEGG ( F ) analyses of upregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). GO ( G ) and KEGG ( H ) analyses of downregulated DEGs in UCs (two-sided hypergeometric test with FDR correction). I , J Gene Set Enrichment Analysis (GSEA) of altered pathways in UCs (two-sided permutation test with 1000 permutations, with multiple testing corrected using the FDR). The exact p value for TLR signaling of UCs in panel I is 0.0009. K Expression of Toll-like receptor (TLR) subtypes in UCs from HIC bladders. mRNA ( L ) and protein ( M ) expression levels of TLR3 in isolated urothelium from control and HIC patients ( n = 7 control vs. 10 HIC; data show median (IQR); two-sided Mann–Whitney U test; ns not significant; Bar for panel M: 1 cm). N Immunostaining showing the distribution of TLR3 protein in the urothelium of patients with HIC ( n = 7 control vs. 10 HIC; one section and field per patient; Bar: 100 μm). IHC immunohistochemistry, HL Hunner lesions, U urothelium, LP lamina propria (blue line), M muscularis. Source data are provided as a Source Data file.

Article Snippet: TLR3 inhibitor group: Same intravesical TCDCA instillation as above, followed by intraperitoneal injection of a TLR3 inhibitor (CU-CPT 4a, MCE, Cat. HY-108473) at 1 mg/kg , twice per week for 2 weeks.

Techniques: RNA Sequencing, Expressing, Isolation, Control, MANN-WHITNEY, Immunostaining, Immunohistochemistry

A Experimental workflow of E. avium colonization in antibiotic-pretreated mice (Abx-mice, n = 6 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . B Increased abundance of E. avium confirmed by metagenomic sequencing ( n = 6 per group). C Evaluation of voiding behavior following E. avium transplantation ( n = 6 per group; one measurement per mouse). D Measurement of mechanical pain threshold post-transplantation ( n = 6 per group). E Representative histological analysis of bladder tissues after E. avium transplantation ( n = 6 per group; one section and field per mouse). F , G Quantification of blood and urinary bile acids using comprehensive targeted bile acid profiling ( n = 6 per group). H Cell viability of human urothelial cells (HUCs) following TCDCA or TUDCA treatment ( n = 3 independent experiments). I Expression of ZO-1, TNF-α, and TLR3 following TCDCA (200 µM) exposure ( n = 3 independent experiments). J Experimental workflow of intravesical instillation of TCDCA in rats ( n = 5 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . K Evaluation of voiding function after TCDCA instillation ( n = 5 per group; each rate measured once). L Assessment of mechanical pain threshold following TCDCA exposure ( n = 5 per group). M Representative histology of bladder tissues post-instillation ( n = 5 per group; one section per rat, one field quantified per section). For panels ( B – H , K , L ): data are presented as median (IQR). Statistical analysis was performed using the two-sided Mann–Whitney U test. IHC immunohistochemistry, Red arrow: urothelial thinning, detachment, and exposure, Blue line: LP lamina propria, U urothelium, M muscularis. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Multi-omics analysis identifies a microbiota–bile acid–TLR signaling axis driving bladder injury in interstitial cystitis

doi: 10.1038/s41467-025-68060-1

Figure Lengend Snippet: A Experimental workflow of E. avium colonization in antibiotic-pretreated mice (Abx-mice, n = 6 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . B Increased abundance of E. avium confirmed by metagenomic sequencing ( n = 6 per group). C Evaluation of voiding behavior following E. avium transplantation ( n = 6 per group; one measurement per mouse). D Measurement of mechanical pain threshold post-transplantation ( n = 6 per group). E Representative histological analysis of bladder tissues after E. avium transplantation ( n = 6 per group; one section and field per mouse). F , G Quantification of blood and urinary bile acids using comprehensive targeted bile acid profiling ( n = 6 per group). H Cell viability of human urothelial cells (HUCs) following TCDCA or TUDCA treatment ( n = 3 independent experiments). I Expression of ZO-1, TNF-α, and TLR3 following TCDCA (200 µM) exposure ( n = 3 independent experiments). J Experimental workflow of intravesical instillation of TCDCA in rats ( n = 5 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . K Evaluation of voiding function after TCDCA instillation ( n = 5 per group; each rate measured once). L Assessment of mechanical pain threshold following TCDCA exposure ( n = 5 per group). M Representative histology of bladder tissues post-instillation ( n = 5 per group; one section per rat, one field quantified per section). For panels ( B – H , K , L ): data are presented as median (IQR). Statistical analysis was performed using the two-sided Mann–Whitney U test. IHC immunohistochemistry, Red arrow: urothelial thinning, detachment, and exposure, Blue line: LP lamina propria, U urothelium, M muscularis. Source data are provided as a Source Data file.

Article Snippet: TLR3 inhibitor group: Same intravesical TCDCA instillation as above, followed by intraperitoneal injection of a TLR3 inhibitor (CU-CPT 4a, MCE, Cat. HY-108473) at 1 mg/kg , twice per week for 2 weeks.

Techniques: Sequencing, Transplantation Assay, Expressing, MANN-WHITNEY, Immunohistochemistry

A , B Expression of tight junction protein ZO-1 and inflammatory marker TNF-α after TLR3 intervention in TCDCA-pretreated human urothelial cells (HUCs) ( n = 3 independent experiments). C Transepithelial resistance (TER) changes following TLR3 intervention in TCDCA-pretreated HUCs ( n = 3 independent experiments). D , E Expression of ZO-1 and TNF-α after pentosan polysulfate sodium (PPS) administration in TCDCA-pretreated HUCs ( n = 3 independent experiments). F TER changes following PPS intervention in TCDCA-pretreated HUCs ( n = 3 independent experiments). G Experimental workflow showing TLR3 inhibitor and PPS administration to rats following intravesical TCDCA instillation ( n = 5 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . H Assessment of voiding function (one measurement per rat) and pain threshold after TLR3 inhibition ( n = 5 per group). I Representative histological images of bladder tissues post-TLR3 inhibition ( n = 5 per group; one section and field per rat). For panels ( B , C , E , F , H ): data are presented as median (IQR). Statistical analysis was performed using the Kruskal–Wallis test. ns not significant, IHC immunohistochemistry, Red arrow: urothelial thinning, detachment, and exposure, Blue line: LP lamina propria, U urothelium, M muscularis. Source data are provided as a Source Data file.

Journal: Nature Communications

Article Title: Multi-omics analysis identifies a microbiota–bile acid–TLR signaling axis driving bladder injury in interstitial cystitis

doi: 10.1038/s41467-025-68060-1

Figure Lengend Snippet: A , B Expression of tight junction protein ZO-1 and inflammatory marker TNF-α after TLR3 intervention in TCDCA-pretreated human urothelial cells (HUCs) ( n = 3 independent experiments). C Transepithelial resistance (TER) changes following TLR3 intervention in TCDCA-pretreated HUCs ( n = 3 independent experiments). D , E Expression of ZO-1 and TNF-α after pentosan polysulfate sodium (PPS) administration in TCDCA-pretreated HUCs ( n = 3 independent experiments). F TER changes following PPS intervention in TCDCA-pretreated HUCs ( n = 3 independent experiments). G Experimental workflow showing TLR3 inhibitor and PPS administration to rats following intravesical TCDCA instillation ( n = 5 per group). Created in BioRender. Chen, J. (2025) https://BioRender.com/3lccwo1 . H Assessment of voiding function (one measurement per rat) and pain threshold after TLR3 inhibition ( n = 5 per group). I Representative histological images of bladder tissues post-TLR3 inhibition ( n = 5 per group; one section and field per rat). For panels ( B , C , E , F , H ): data are presented as median (IQR). Statistical analysis was performed using the Kruskal–Wallis test. ns not significant, IHC immunohistochemistry, Red arrow: urothelial thinning, detachment, and exposure, Blue line: LP lamina propria, U urothelium, M muscularis. Source data are provided as a Source Data file.

Article Snippet: TLR3 inhibitor group: Same intravesical TCDCA instillation as above, followed by intraperitoneal injection of a TLR3 inhibitor (CU-CPT 4a, MCE, Cat. HY-108473) at 1 mg/kg , twice per week for 2 weeks.

Techniques: Expressing, Marker, Inhibition, Immunohistochemistry