Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: Inflammation and pyroptosis were increased in CP mice. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. The animals were sacrificed at 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A-C ) Representative photos and quantitative of F4/80 and CD11b staining; ( D ) Serum IL-6 level; ( E ) Serum TNF-α level; ( F & G ) Western blot analysis and quantitative of the expression of NLRP3 in the pancreas; ( H ) Serum IL-18 level; ( I ) Serum IL-1β level; ( J ) Correlation analysis of serum IL-18 and Masson positive aera; ( K ) Correlation analysis of serum IL-1β and Masson positive aera; ( L ) Correlation analysis of serum CIRP and F4/80 positive cells; ( M ) Correlation analysis of serum CIRP and CD11b positive cells; ( N ) Correlation analysis of serum CIRP and F4/80 positive cells; ( O ) Correlation analysis of serum CIRP and CD11b positive cells; ( R ) Correlation analysis of serum CIRP and IL-18; ( S ) Correlation analysis of serum CIRP and IL-1β; ( T ) Correlation analysis of serum CIRP and serum IL-18 in CP patients; ( U ) Correlation analysis of serum CIRP and serum IL-1β in CP patients; ( V ) Correlation analysis of serum CIRP and serum HMGB1 in CP patients. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Statistical significance was determined by t-test or one-way ANOVA with Tukey’s post-hoc test. Correlations were assessed using Spearman’s rank correlation coefficient. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; L-arg, L-arginine; Cer, Cerulein; IL-6, interleukin 6; TNF-α, tumor necrosis factor-α; NLRP3, Nod-like receptor family protein 3; IL-18, interleukin 18; IL-1β, HMGB1, high mobility group protein B1; interleukin 1β

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Staining, Western Blot, Expressing, RNA Binding Assay

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: CIRP deficiency alleviates inflammation and pyroptosis in CP model mice. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. 8 mg/kg C23 was administered 2 h after the last L-arginine or cerulein injection each time. To determine the role of TLR4 in CIRP’s effect in CP, TAK-242, a specific TLR4 receptor inhibitor, were administered through intraperitoneal injection at 1 h after the last injection of L-arginine or cerulein each time. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A & B ) Western blot analysis and quantitative of the expression of NLRP3, Cleaved Caspase-1 and Cleaved Gasdermin D in the pancreas; ( C-E ) Representative photos and quantitative of F4/80 and CD11b staining; ( F ) Serum IL-1β level; ( G ) Serum IL-18 level; ( H-J ) Western blot analysis and quantitative of the expression of NLRP3 and Cleaved Gasdermin D in the pancreas; ( K & L ) Representative photos and quantitative of F4/80 staining. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; KO, knockout; L-arg, L-arginine; NLRP3, Nod-like receptor family protein 3; TLR4, Toll-like receptor 4; IL-18, interleukin 18; IL-1β, interleukin 1β; Cer, Cerulein

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Western Blot, Expressing, Staining, RNA Binding Assay, Knock-Out

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: NLRP3 inhibitor alleviates inflammation and pancreatic fibrosis in Experimental CP. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. At 2 h after the last injection of L-arginine or cerulein each time, normal saline (vehicle) or 5, 20, 100 mg/kg NLRP3 inhibitor was administered by intraperitoneal injection. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A ) Western blot analysis of the expression of CIRP, NLRP3, Cleaved Caspase-1 and Cleaved Gasdermin D in the pancreas; ( B ) Serum IL-1β level; ( C ) Serum IL-6 level; ( D-G ) Representative photos and quantitative of H&E, Sirius red and F4/80 staining; ( H ) Serum HMGB1 level. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; NLRP3, Nod-like receptor family protein 3; IL-6, interleukin 6; IL-1β, interleukin 1β; HMGB1, high mobility group protein B1; Cer, Cerulein; L-arg, L-arginine

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Saline, Western Blot, Expressing, Staining, RNA Binding Assay

Journal: Inflammation

Article Title: Targeting Cold-Inducible RNA-Binding Protein Attenuates Pancreatic Fibrosis by Suppressing Pyroptosis in Chronic Pancreatitis

doi: 10.1007/s10753-026-02490-x

Figure Lengend Snippet: Gasdermin D inhibitor alleviates inflammation and pancreatic fibrosis in Experimental CP. Cerulein-CP was induced by 6 IP injections of cerulein (50 µg/kg/body weight) twice a week for 10 weeks. L-arginine-CP was induced by 2 hourly IP injections of 4.0 g/kg L-arginine twice a week for 10 weeks. At 2 h after the last injection of L-arginine or cerulein each time, normal saline (vehicle) or 5, 20, 50 mg/kg Disulfiram, a potent gasdermin D inhibitor, was administered by intraperitoneal injection. The animals were sacrificed 10 weeks after the first injection of L-arginine or cerulein. Blood and tissue samples were collected. ( A-D ) Representative photos and quantitative of H&E, Sirius red and F4/80 staining; ( E ) Western blot analysis of the expression of CIRP, NLRP3 and Cleaved Gasdermin D in the pancreas; ( F ) Serum IL-18 level. Data are presented as mean ± SD ( n = 6 per group). Statistical analyses were performed using GraphPad Prism 8.0. Data were analyzed by one-way ANOVA with Tukey’s post-hoc test. * P < 0.05 indicates a statistically significant difference. CP, chronic pancreatitis; CIRP, Cold-inducible RNA-binding protein; NLRP3, Nod-like receptor family protein 3; IL-18, interleukin 18

Article Snippet: In the other groups of experimental CP, normal saline (vehicle) or 5, 20 or 100 mg/kg NLRP3 inhibitor [ ] (S3680, Selleck, Inc. CN) was administered by intraperitoneal injection 2 h after the last injection of L-arginine or cerulein.

Techniques: Injection, Saline, Staining, Western Blot, Expressing, RNA Binding Assay

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 1 Dynamics of esophageal ulcer healing and induction of stricture during ulcer healing. An esophageal ulcer was induced by applying 100% acetic acid to the serosa of the lower esophagus. (a, b) Time course of changes in esophageal ulcers during the ulcer healing process. (a) Represen- tative macroscopic images of esophageal ulcers. (b) Ulcer area (mm2) measured using a computerized image-analysis system. n = 8. (c) Fluoroscopic images of esophageal strictures following ulcer healing by esophagography on day 9. (d–f) Time course of representative histological changes deter- mined by hematoxylin/eosin staining of esophageal ulcers during the ulcer healing process. EP, epithelium; SM, submucosal layer; MP, muscularis propria; GT, granulation tissue. The arrow indicates the epithelial cell migration. (g–l) Time courses of changes in mRNA expression of (g) interleukin (IL)-1β, (h) NLRP3, (i) caspase-1, (j) IL-18, (k) transforming growth factor (TGF)-β1, and (l) collagen type I alpha 1 chain (COL1A1) were determined using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of mRNA are expressed as a percentage of the mean values of the non-treated control rats. n = 8; *P < 0.05, **P < 0.01.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Staining, Migration, Expressing, Reverse Transcription, Polymerase Chain Reaction, Quantitative RT-PCR, Control

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 3 PFD suppresses the activation of the NLRP3 inflammasome components and the expression of fibrosis-related molecules. Pirfenidone (500 mg/kg) or vehicle was intraperitoneally administered to rats once daily from 3 days after ulcer induction. (A-F) Comparison of expressions of mRNA of (a) IL-1β, (b) NLRP3, (c) caspase-1, (d) IL-18, (e) TGF-β1, and (f) COL1A1 determined using qRT-PCR between the vehicle-treated and PFD-treated rats on day 6. The mRNA levels are expressed as a percentage of the mean values of non-treated control rats. n = 8. (g) Representative images of western blots of NLRP3, pro-caspase 1, cleaved caspase-1, pro-IL-1β, mature IL-1β, TGF-β1, and COL1A1 on day 6. GAPDH was used as an internal control. n = 6; *P < 0.05, **P < 0.01.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Activation Assay, Expressing, Comparison, Quantitative RT-PCR, Control, Western Blot

Journal: Journal of gastroenterology and hepatology

Article Title: Pirfenidone prevents esophageal stricture by inhibiting nucleotide binding oligomerization domain like receptor protein 3 inflammasome activation.

doi: 10.1111/jgh.15861

Figure Lengend Snippet: Figure 7 Proposed mechanism underlying the protective effects of PFD on esophageal strictures after ulcer healing. ASC, apoptosis-associated speck-like protein containing a CARD; NLRP3, nucleotide-binding and oligomerization domain-like receptor pyrin do- main containing 3.

Article Snippet: To evaluate the role of the NLRP3 inflammasome, some rats were intraperitoneally administered the NLRP3 inhibitor glyburide (10 mg/kg; Novus Biologicals, LLC, Centennial, CO), the caspase-1 inhibitor ac-YVAD-cmk (3 mg/kg; Merck K GaA, Darmstadt, Germany), or rat recombinant IL-1β (0.1 μg/kg; R&D Systems, Inc., Minneapolis, MN).

Techniques: Binding Assay

Journal: PLOS Pathogens

Article Title: Env from EIAV vaccine delicately regulates NLRP3 activation via attenuating NLRP3-NEK7 interaction

doi: 10.1371/journal.ppat.1012772

Figure Lengend Snippet: (A) Time-dependent changes in intracellular K + concentrations in macrophages infected with virulent EIAV or vaccine EIAV. Here NC refers to negative control and LPS+Nigericin (Nig) means positive control. (B) Time-dependent changes in intracellular Ca 2+ concentrations in macrophages infected with virulent EIAV or vaccine EIAV. (C) Time-dependent changes in intracellular K + concentrations in macrophages pre-treated with P2X7 (R) -specific siRNA for 6 h, and then infected with virulent EIAV or vaccine EIAV. (D-E) Evaluation IL-1β in supernatants of 293T cells co-transfected with virulent- env or vaccine- env in the presence of increasing doses of the K + efflux inhibitor (Glybenclamide, 50 µM,100 µM) (D) and KCl (50 µM,100 µM) (E) (Tat served as a negative control) (* P < 0.05, ** P < 0.01). All data are mean of 2 independent experiments (n = 2 per group).

Article Snippet: Glybenclamide (Gly) was purchased from Novus Biologicals (NBP2-30141, USA).

Techniques: Infection, Negative Control, Positive Control, Transfection

Journal: Current Research in Pharmacology and Drug Discovery

Article Title: Can NLRP3 inhibitors improve on dexamethasone for the treatment of COVID-19?

doi: 10.1016/j.crphar.2021.100048

Figure Lengend Snippet: Mechanics of NLRP3 inflammasome activation. Upon inflammasome stimulation, the central protein NLRP3, consisting of its pyrin domain (PYD), NACHT domain and leucine-rich repeat (LRR) domain, associates with the adaptor protein ASC through PYD-PYD interactions. ASC, in turn, associates with caspase-1 through caspase activation and recruitment domain (CARD) interactions. NEK7 also binds NLRP3 at several surfaces, which aids oligomerization of NLRP3. These interactions lead to assembly of the inflammasome complex, which is followed by autocatalytic cleavage of the effector protein caspase-1 into the active subunits p10 and p20. These subunits carry out the effector functions of the inflammasome complex, including the cleavage of IL-1β into its active form.

Article Snippet: Rather than recruiting a cohort of ICU patients with severe COVID-19, Olatec has a target of 80 unhospitalized COVID-19 patients, with the hope of demonstrating that its NLRP3 inhibitor can prevent disease progression into severe COVID-19.

Techniques: Activation Assay

Journal: Current Research in Pharmacology and Drug Discovery

Article Title: Can NLRP3 inhibitors improve on dexamethasone for the treatment of COVID-19?

doi: 10.1016/j.crphar.2021.100048

Figure Lengend Snippet: SARS-CoV drives NLRP3 inflammasome activation. Virus-derived dsRNA and ssRNA can be sensed by endosomal TLR3 and TLR7, as well as by the RIG-I-like receptors (RLRs) RIG-I and melanoma differentiation-associated protein 5 (MDA5), which signal through mitochondrial antiviral signaling protein (MAVS) to upregulate proinflammatory gene expression via NF-κB. Pro-IL-1β expression may be upregulated in this manner and is subsequently processed to mature IL-1β by the NLRP3 inflammasome complex. The NLRP3 inflammasome may be activated by specific viral peptides, including open reading frame (ORF) 3a, ORF8B and the envelope (E) protein. IL-1β is released from the cell through the gasdermin D (GSDMD) pore.

Article Snippet: Rather than recruiting a cohort of ICU patients with severe COVID-19, Olatec has a target of 80 unhospitalized COVID-19 patients, with the hope of demonstrating that its NLRP3 inhibitor can prevent disease progression into severe COVID-19.

Techniques: Activation Assay, Virus, Derivative Assay, Gene Expression, Expressing