TXNIP activates NLRP3/IL-1ß and participate in inflammatory response and oxidative stress to promote deep venous thrombosis.

Increasing evidence indicates that deep venous thrombosis (DVT) is a common peripheral vascular disease. This study aims to investigate the mechanisms of thioredoxin-interacting protein (TXNIP) and nod-like receptor protein 3 (NLRP3) inflammasome in deep venous thrombosis (DVT). A total of 66 Sprague-Dawley (SD) rats were employed to conduct DVT model. DVT rat was treated with silenced TXNIP (si-TXNIP) lentivirus and MCC950 (a NLRP3 inhibitor). The thrombosis weight and weight/length ratio, tissue factor, inflammatory factors, superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were measured. Hematoxylin-eosin (H&E) staining was used to investigate the pathological change. Western blotting was used to determine the protein expression level. The expression level of thioredoxin (TRx) was suppressed, whereas TXNIP and NLRP3 were elevated in DVT rat. Si-TXNIP or MCC950 could reduce the thrombosis weight and weight/length ratio, ameliorate the pathological change, and decrease inflammatory reaction. Mechanistically, si-TXNIP or MCC950 inhibited the expression levels of TXNIP, NLRP3, and interleukin (IL)-1ß while elevating the TRx level, thereby suppressing the DVT. Our study indicated that si-TXNIP or MCC950 injection rescued the injury of vein induced by DVT. The possible mechanisms connected with the inhibition of TXNIP and NLRP3. TXNIP is a possible therapeutic target for DVT.

Resveratrol Ameliorates Deep Vein Thrombosis-Induced Inflammatory Response Through Inhibiting HIF-1α/NLRP3 Pathway.

Deep vein thrombosis (DVT) has become a prevalent and increasingly serious problem globally and resveratrol (Res) is a natural antitoxin that inhibits arterial thrombosis. To investigate the effect of Res on DVT and further explore its mechanism, thrombosis was monitored at different time points and the pathological changes occurring in the inferior vena cava (IVC) and lung tissue were observed in Sprague-Dawley rats. The protein expression of HIF-1α and NLRP3 in the IVC and lung tissue and the concentrations of D-dimer (D2D), prothrombin fragment 1 + 2 (F1 + 2), interleukin-1ß (IL-1ß), caspase-1, and tissue factor (TF) in the plasma were determined. After setting different doses of Res groups and using low-molecular-weight heparin (LMWH) as a positive control to determine the effective experimental dose of Res, rats were further divided into sham, DVT, HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. The above indicators were tested repeatedly. The DVT was formed on the 1st day of modeling. With the extension of time, DVT was gradually institutionalized and finally recanalized. Lesions in the IVC and lung tissue were effectively ameliorated, and thrombosis was significantly decreased in the LMWH or 60 mg/kg Res-treated groups. The levels of D2D, F1 + 2, IL-1ß, caspase-1, TF, and the expression of HIF-1α and NLRP3 were significantly reduced in the HIF-1α inhibitor, Res, and HIF-1α inhibitor + Res groups. Res can ameliorate DVT in rats by inhibiting HIF-1α/NLRP3 pathway, which provides a novel therapeutic strategy for DVT treatment.

Sleep-disordered breathing and risk of lung cancer: a meta-analysis longitudinal follow-up studies.

Consensus remains lack regarding whether sleep-disordered breathing (SDB) is an independent risk factor for lung cancer. We therefore conducted a meta-analysis to clarify the relationship of SDB and lung cancer. Longitudinal follow-up studies investigating the association between SDB and incidence of lung cancer were included by search of electronic databases including PubMed, Embase, and Cochrane's Library. A random-effects model was adopted to combine the results. Seven studies were included. Pooled results showed that presence of SDB was independently associated with higher incidence of lung cancer [adjusted risk ratio (RR): 1.28; 95% confidence interval (CI), 1.11-1.47; P < 0.001; I2 = 37%]. Sensitivity analysis limited to studies with adjustment of smoking showed consistent results (three studies, RR: 1.34; 95% CI, 1.22-1.48; P < 0.001; I2 = 8%). Subgroup analysis suggested that the association between SDB and higher risk of lung cancer was not significantly affected by study characteristics such as study design, source of population, sample size, evaluation methods for SDB, follow-up duration, methods for validation of lung cancer, or score of study quality (P values for subgroup difference all >0.05). No significant publication bias was observed (P for Egger's regression test = 0.258). These results suggested that SDB may be an independent risk factor of lung cancer in adult population. Intensive screening and prevention of lung cancer in subjects with SDB should be considered.

Predictive Role of Tumor-Stroma Ratio for Survival of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis.

Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and meta-analysis was conducted to summarize current evidence for the role of TSR in NSCLC. Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and meta-regression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the meta-analysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = -0.012, p = 0.03) and OS (Coefficient = -0.013, p = 0.04), respectively. Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.