[Changes and clinical significance of NLRP3 inflammasomes and related factors in patients with spinal fracture complicated with acute spinal cord injury].

OBJECTIVE: To investigate the changes and clinical significance of NOD like receptor protein 3 (NLRP3) inflammasomes and related factors in patients with spinal fractures complicated with acute spinal cord injury (SCI). METHODS: Eighty-six spinal fracture patients complicated with acute SCI admitted to hospital from June 2019 to March 2022 were selected as SCI group, There were 48 males and 38 females, with an average age of (43.48±6.58) years old. And 100 healthy volunteers who underwent physical examination during the same time were selected as control group, including 56 males patients and 44 females patients, with an average age of (45.13±6.43) years old. Peripheral blood mononuclear cell (PBMC) were collected, and the mRNA expressions of NLRP3 and Caspase-1 were detected. Serum was collected and the levels of interleukin (IL)- 1ß, IL-18 were detected. According to Frankel's grade, the SCI group was divided into complete injury patients and incomplete injury patients, and according to the Japanese Orthopedic Society (JOA) grade, the SCI group was divided into good prognosis group and poor prognosis group. The difference of NLRP3, Caspase-1, IL-1ß, IL-18 among groups were compared, the influencing factors for poor prognosis in SCI patients was analyzed by Logistic regression. RESULTS: The mRNA expression levels of NLRP3 (1.41±0.33) and Caspase-1 (1.44±0.35) in PBMC and the levels of IL-1ß(45.34±13.22) pg·ml-1, IL-18(40.95±8.77) pg·ml-1 in serum of SCI group were higher than those of the control group[(1.00±0.19), (1.00±0.16), (16.58±4.24) pg·ml-1, (12.57±3.68) pg·ml-1] (P<0.05). The mRNA expression levels of NLRP3(1.63±0.34) and Caspase-1 (1.67±0.27) in PBMC and the levels of IL-1ß(51.09±11.10) pg·ml-1, IL-18 (47.65±7.93) pg·ml-1 in serum of patients with complete injury in the SCI group were higher than those of patients with incomplete injury [(1.31±0.27), (1.34±0.33), (42.85±13.36) pg·ml-1, (38.05±7.48) pg·ml-1](P<0.05). The mRNA expression levels of NLRP3 (1.66±0.31) and Caspase-1 (1.72±0.31)in PBMC and the levels of IL-1ß(51.21±11.31) pg·ml-1, IL-18 (45.70±7.25) pg·ml-1 in serum, the proportion of complete injury(21 patients), and the proportion of spinal cord edema or bleeding of patients(15 patients) with poor prognosis in the SCI group were higher than those of patients with good prognosis[(1.28±0.26), (1.37±0.36), (42.79±13.25) pg·ml-1、(38.90±8.63) pg·ml-1, 5、20 cases](P<0.05). Complete injury and the mRNA expression of NLRP3 in PBMC were the influencing factors for poor prognosis in the SCI group (P<0.05). CONCLUSION: The activation of NLRP3 inflammasomes in patients with spinal fractures complicated with acute SCI is associated with worsening injury and poor prognosis, and NLRP3 expression can serve as a marker for evaluating prognosis.

Brief Pain Inventory (BPI) Pain Survey Versus Cysteine Protease Caspase-1 (Casp1) Blood Levels Following Midline Laparotomy: A Prospective Randomized Study of Patients With Benign Disease and Patients With Cancer.

BACKGROUND/AIM: There is lack of studies assessing the correlation between pain scales and acute phase immune response (APR) following surgery. The purpose of this work was to assess the correlation between cysteine protease caspase-1 (Casp1) blood levels and two pain scales in a cohort of 56 midline laparotomy (MLa) patients and to assess their link with other cytokines (CYTs). PATIENTS AND METHODS: Blood levels of Casp1 and other CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-8, IL-10, IL-1ß) were measured before operation and following surgery in patients with MLa. Pain levels were assessed using the Numerical Rating Scale (NRS) and Brief Pain Inventory (BPI) scale, both preoperatively and postoperatively. RESULTS: Casp1 blood levels showed an increasing trend at postoperative day 1 (POP1) and this increase was almost significant in a linear mixed effect model (LME) analysis (p=0.06). Additionally, Casp1 blood levels were higher in patients with cancer than those with benign disease and correlated with IL-18 blood levels (r=0.24, p=0.007). Furthermore, Casp1 blood levels correlated with BPIsev (severity) score values in MLa patients (r=-0.49, p=0.048). A significant correlation was also observed between Casp1 blood levels and NRS scores in patients with MLa. CONCLUSION: This is the first report to evaluate two pain surveys (NRS and BPI) in MLa patients in relation to blood levels of Casp1 and eight CYTs. This analysis is important in confirming the significant correlation between NRS and BPI pain scales and Casp1 blood levels. Our study is also the first to demonstrate that adequate postoperative analgesia in patients with MLa provides better functional ability and improved patient satisfaction.

Increased serum caspase-1 in adult-onset Still's disease.

BACKGROUND: Caspase-1 is a crucial component in the inflammasome activation cascade. This study evaluated the potential of serum caspase-1 level as an inflammatory biomarker in patients with adult-onset Still's disease (AOSD). METHODS: The study included 51 consecutive patients diagnosed with AOSD based on the Yamaguchi criteria, 66 patients with rheumatoid arthritis (RA) as disease control, and 36 healthy controls (HCs). Serum caspase-1 concentrations were measured using enzyme-linked immunosorbent assay. The serum 69 cytokine levels were analyzed using a multisuspension cytokine array in patients with AOSD, and a cluster analysis of each cytokine was performed to determine specific molecular networks. RESULTS: Patients with AOSD had significantly increased serum caspase-1 levels versus patients with RA (p < 0.001) and HCs (p < 0.001). Additionally, serum caspase-1 demonstrated significant positive correlations with AOSD disease activity score (Pouchot score, r = 0.59, p < 0.001) and serum ferritin (r = 0.54, p < 0.001). Furthermore, among patients with AOSD, significant correlations existed between serum caspase-1 and inflammatory cytokines, including interleukin-18. Immunoblot analysis detected the cleaved form of caspase-1 (p20) in the serum of untreated patients with AOSD, not in those from patients with inactive AOSD receiving immunosuppressive treatments. CONCLUSIONS: Caspase-1 is a useful biomarker for AOSD diagnosis and monitoring. Caspase-1 activation could be correlated with the inflammatory component of AOSD, specifically through proinflammatory cytokine induction via inflammasome activation cascades.

Correlation Between Blood Levels of Cysteine Protease Caspase-1 (Casp1) and Pain Scores (NRS) Post-surgery: A Prospective Randomized Study of Patients With Cholelithiasis.

BACKGROUND/AIM: Cysteine protease caspase-1 (Casp1) plays a crucial role in the conversion of pro-cytokines to active cytokines (CYTs). The purpose of this work was to determine Casp1 blood levels in a cohort of 114 cholecystectomy patients and assess their association with other CYTs and numeric rating scale (NRS) pain scores, postoperatively. PATIENTS AND METHODS: Blood levels of Casp1 and seven CYTs (IL-18, IL-18BP, IL-1ra, IL-6, IL-10, IL-1ß, and IL-8) were measured at three time points; before operation, immediately after operation, and six hours after operation in 114 patients with cholelithiasis (Chole). RESULTS: Casp1 blood levels correlated with NRS pain scores at 24 h following surgery (p=0.016). In addition, Casp1 blood levels correlated significantly to IL-18 blood levels (p<0.001). CONCLUSION: This is the first report to evaluate Casp1 blood levels in Chole patients in correlation with other CYTs. The findings confirm a significant correlation between Casp1 blood levels and NRS pain scores. Moreover, this study provides initial evidence suggesting that inhibition of the activity of Casp1 may reduce postsurgical acute phase immune response possibly through the Casp1/pro-Il-18 pathway.

Evaluation of inflammasomes as biomarker following non-surgical periodontal treatment.

OBJECTIVE: The purpose of this study was to investigate interleukin (IL)-1ß, IL-18, nod-like receptor pyrin domain-containing protein 3 (NLRP3), apoptosis-related speck-like protein containing a caspase activation and recruitment domain (ASC), and caspase-1 levels in saliva and serum in different periodontal diseases and to evaluate the changes after non-surgical periodontal treatment (NSPT). DESIGN: A total of 45 participants, 15 healthy, 15 gingivitis, and 15 stage III grade C (SIIIGC) periodontitis patients, were included in the study. Periodontal parameters were assessed, and salivary and serum samples were collected at baseline in all groups and one and three months after NSPT in gingivitis and periodontitis groups. An enzyme-linked immunosorbent assay was used to analyse IL-1ß, IL-18, NLRP3, ASC, and caspase-1 levels. RESULTS: After NSPT, improvement was observed in all clinical parameters, along with periodontal inflamed surface area (PISA) in gingivitis and periodontitis groups. PISA scores were positively correlated with IL-1ß, NLRP3, and caspase-1 at baseline (p < 0.05). Salivary and serum IL-1ß, NLRP3 levels were higher in periodontitis compared to healthy controls at baseline and reduced after treatment (p < 0.05). Receiver operating characteristic analysis revealed that salivary IL-1ß, NLRP3, and caspase-1 had the ability to discriminate SIIIGC periodontitis patients from healthy subjects (p < 0.05). CONCLUSION: In conclusion, salivary IL-1ß, NLRP3, and caspase-1 are at aberrantly high levels in SIIIGC periodontitis and are remarkably decreased following NSPT; these inflammasome biomarkers may show potential utility in diagnosing and monitoring periodontitis.