Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: FXR and TGR5 modulate the inflammatory response induced by SARS-CoV-2 in THP-1 cells. ( a – f ) THP-1 cells were stimulated by SARS-CoV-2 and treated with 20 μM GW4064 or INT-777 for 24 h. The intracellular mRNA expression levels of IL-1β ( a ), IL-8 ( b ), and CXCL5 ( c ) were measured by RT–qPCR. The supernatant protein concentrations of IL-1β ( d ), IL-8 ( e ), and TNF-α ( f ) were measured by CBA. These samples derived from the same experiment. ( g – i ) A total of 3 μM SBI-115 was administered 2 h prior to the 24 h treatment with CDCA and GCDCA to block TGR5 signaling in the context of SARS-CoV-2 stimulation. The intracellular mRNA expression levels of IL-1β ( g ), IL-8 ( h ), and CXCL5 ( i ) were measured by RT–qPCR. These samples derived from the same experiment. ( j , k ) A total of 5 μM Guggulsterone was administered 2 h prior to the 24 h treatment with CDCA and GCDCA to block FXR signaling in the context of SARS-CoV-2 stimulation. The intracellular mRNA expression level of IL-8 ( j ) was measured by RT–qPCR. The supernatant protein concentration of IL-6 ( k ) was measured by CBA. These samples derived from the same experiment. Multiple comparisons were performed except for the blank control ( a – f ); n = 5 biologically independent samples. Multiple comparisons were performed among virus, V+CDCA/GCDCA, and V+CDCA/GCDCA+antagonist ( g – k ), respectively; n = 5 biologically independent samples. Data are presented as mean ± s.d. The two-sided p values were examined using one-way ANOVA followed by Tukey’s multiple-comparison test for comparison of continuous variables among multiple groups ( a – k ).

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques: Expressing, Quantitative RT-PCR, Derivative Assay, Blocking Assay, Protein Concentration, Control, Virus, Comparison

Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: The treatment of CDCA, GCDCA, and TGR5 agonist INT-777 exhibit the mechanistic parallels in modulating the inflammatory response induced by SARS-CoV-2 in THP-1 cells through the NOD-like receptor signaling pathway. ( a , b ) RNA sequencing of THP-1 cell line stimulated by SARS-CoV-2 treated with 2.5 μM CDCA, 20 μM GCDCA, 20 μM GW4064, or 20 μM INT-777 for 24 h. PCA ( a ) and sample correlation analysis ( b ) of DEGs among the treatment of four compounds. ( c ) KEGG enrichment of TOP 10 upregulated and downregulated pathways induced by SARS-CoV-2 stimulation. ( d – h ) GSEA of NOD-like receptor signaling pathway in THP-1 cells stimulated by SARS-CoV-2 ( e ) and treated with CDCA ( f ), GCDCA ( g ), INT-777 ( h ), and GW4064 ( d ). The enrichment plot has three components. (Top) Enrichment score profile showing the maximum deviation from zero. The green curve represents the running enrichment score. (Middle) The bars indicate gene set member positions in the ranked gene list, while the core enrichment genes are highlighted in red. (Bottom) Red/blue gradient indicates high/low expression of leading-edge genes within the pathway. Gray area plot displays Signal2Noise values across all genes (ranked left-to-right). The heatmap plot indicates variations of the Transcript per Kilobase per Million mapped reads (TPM) between each sample of the two groups.

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques: RNA Sequencing, Expressing

Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: A schematic presentation of the treatment of CDCA, GCDCA, and INT-777 modulating the inflammatory response induced by SARS-CoV-2 in THP-1 cells through the NOD-like receptor signaling pathway.

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques:

Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: FXR and TGR5 modulate the inflammatory response induced by SARS-CoV-2 in THP-1 cells. ( a – f ) THP-1 cells were stimulated by SARS-CoV-2 and treated with 20 μM GW4064 or INT-777 for 24 h. The intracellular mRNA expression levels of IL-1β ( a ), IL-8 ( b ), and CXCL5 ( c ) were measured by RT–qPCR. The supernatant protein concentrations of IL-1β ( d ), IL-8 ( e ), and TNF-α ( f ) were measured by CBA. These samples derived from the same experiment. ( g – i ) A total of 3 μM SBI-115 was administered 2 h prior to the 24 h treatment with CDCA and GCDCA to block TGR5 signaling in the context of SARS-CoV-2 stimulation. The intracellular mRNA expression levels of IL-1β ( g ), IL-8 ( h ), and CXCL5 ( i ) were measured by RT–qPCR. These samples derived from the same experiment. ( j , k ) A total of 5 μM Guggulsterone was administered 2 h prior to the 24 h treatment with CDCA and GCDCA to block FXR signaling in the context of SARS-CoV-2 stimulation. The intracellular mRNA expression level of IL-8 ( j ) was measured by RT–qPCR. The supernatant protein concentration of IL-6 ( k ) was measured by CBA. These samples derived from the same experiment. Multiple comparisons were performed except for the blank control ( a – f ); n = 5 biologically independent samples. Multiple comparisons were performed among virus, V+CDCA/GCDCA, and V+CDCA/GCDCA+antagonist ( g – k ), respectively; n = 5 biologically independent samples. Data are presented as mean ± s.d. The two-sided p values were examined using one-way ANOVA followed by Tukey’s multiple-comparison test for comparison of continuous variables among multiple groups ( a – k ).

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques: Expressing, Quantitative RT-PCR, Derivative Assay, Blocking Assay, Protein Concentration, Control, Virus, Comparison

Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: The treatment of CDCA, GCDCA, and TGR5 agonist INT-777 exhibit the mechanistic parallels in modulating the inflammatory response induced by SARS-CoV-2 in THP-1 cells through the NOD-like receptor signaling pathway. ( a , b ) RNA sequencing of THP-1 cell line stimulated by SARS-CoV-2 treated with 2.5 μM CDCA, 20 μM GCDCA, 20 μM GW4064, or 20 μM INT-777 for 24 h. PCA ( a ) and sample correlation analysis ( b ) of DEGs among the treatment of four compounds. ( c ) KEGG enrichment of TOP 10 upregulated and downregulated pathways induced by SARS-CoV-2 stimulation. ( d – h ) GSEA of NOD-like receptor signaling pathway in THP-1 cells stimulated by SARS-CoV-2 ( e ) and treated with CDCA ( f ), GCDCA ( g ), INT-777 ( h ), and GW4064 ( d ). The enrichment plot has three components. (Top) Enrichment score profile showing the maximum deviation from zero. The green curve represents the running enrichment score. (Middle) The bars indicate gene set member positions in the ranked gene list, while the core enrichment genes are highlighted in red. (Bottom) Red/blue gradient indicates high/low expression of leading-edge genes within the pathway. Gray area plot displays Signal2Noise values across all genes (ranked left-to-right). The heatmap plot indicates variations of the Transcript per Kilobase per Million mapped reads (TPM) between each sample of the two groups.

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques: RNA Sequencing, Expressing

Journal: Biomolecules

Article Title: Significant Reduction of Chenodeoxycholic Acid and Glycochenodeoxycholic Acid in the Elderly with Severe COVID-19

doi: 10.3390/biom15070943

Figure Lengend Snippet: A schematic presentation of the treatment of CDCA, GCDCA, and INT-777 modulating the inflammatory response induced by SARS-CoV-2 in THP-1 cells through the NOD-like receptor signaling pathway.

Article Snippet: After virus stimulation, the medium with or without CDCA (MCE, Monmouth Junction, NJ, USA), GCDCA (MCE, Monmouth Junction, NJ, USA), GW4064 (FXR receptor agonist; MCE, Monmouth Junction, NJ, USA), and INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist; MCE, Monmouth Junction, NJ, USA) was added, and the cells were incubated at 37 °C (5% CO 2 ) for 24 h. Guggulsterone (FXR antagonist; MCE, Monmouth Junction, NJ, USA) and SBI-115 (TGR5 antagonist; MCE, Monmouth Junction, NJ, USA) were used to block FXR and TGR5, respectively.

Techniques:

Journal: Frontiers in Immunology

Article Title: Critical role of reproductive tract microbiota and derived metabolites in inflammation, tumor immunity, and tumorigenesis of gynecological cancers: a narrative review

doi: 10.3389/fimmu.2026.1734792

Figure Lengend Snippet: Innate immune sensing mechanisms regulating the threshold of mucosal inflammation and tumorigenesis. Under dysbiotic conditions, mucosal barrier compromise facilitates the translocation of microbe-associated molecular patterns (MAMPs), such as LPS. Engagement of TLR4 by LPS triggers the NF-κB signaling cascade in innate immune cells, orchestrating the release of pro-inflammatory cytokines and chemokines. This inflammatory loop drives oxidative stress, DNA damage, and myeloid cell recruitment, promoting neoplastic transformation. Conversely, secondary bile acids (SBAs) produced via microbial biotransformation activate the metabolic sensors TGR5 and FXR. This signaling pathway acts as an innate immune "brake" by suppressing NLRP3 inflammasome assembly and NF-κB activity, thereby dampening inflammation and maintaining tissue integrity.

Article Snippet: SBAs, produced via microbial biotransformation, act as specific ligands for the Takeda G protein-coupled receptor 5 (TGR5) and FXR expressed on macrophages and monocytes.

Techniques: Translocation Assay, Transformation Assay, Produced, Activity Assay