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Chronic kidney disease is a common disease closely related to renal tubular inflammation and oxidative stress, and no effective treatment is available. Activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is an important factor in renal inflammation, but the mechanism remains unclear. Micheliolide (MCL), which is derived from parthenolide, is a new compound with antioxidative and anti-inflammatory effects and has multiple roles in tumors and inflammatory diseases. In this study, we investigated the effect of MCL on lipopolysaccharide- (LPS-) induced inflammation in renal tubular cells and the related mechanism. We found that MCL significantly suppressed the LPS-induced NF-κB signaling and inflammatory expression of cytokines, such as tumor necrosis factor-α and monocyte chemoattractant protein-1 in a rat renal proximal tubular cell line (NRK-52E). MCL also prevented LPS- and adenosine triphosphate-induced NLRP3 inflammasome activation in vitro, as evidenced by the inhibition of NLRP3 expression, caspase-1 cleavage, and interleukin-1β and interleukin-18 maturation and secretion. Additionally, MCL inhibited the reduction of mitochondrial membrane potential and decreases the release of reactive oxygen species (ROS). Moreover, MCL can prevent NLRP3 inflammasome activation induced by rotenone, a well-known mitochondrial ROS (mROS) agonist, indicating that the mechanism of MCL’s anti-inflammatory effect may be closely related to the mROS. In conclusion, our study indicates that MCL can inhibit LPS-induced renal inflammation through suppressing the mROS/NF-κB/NLRP3 axis in tubular epithelial cells.

Objective. The aim of this study is to construct a computational model of blood D-dimer, cystatin C, and CRP levels and to predict the risk of intracranial aneurysms and their rupture. Methods. A total of 69 intracranial aneurysms patients were selected as the case group, including 28 cases in the ruptured group and 41 cases in the unruptured group. Another 64 non-intracranial aneurysm patients were selected as the control group. The detection results of serum D-dimer, cystatin C, and CRP were collected. The logistic regression computational model was used to analyze the occurrence and risk factors of intracranial aneurysms. The receiver operating curves (ROC) of serum D-dimer, cystatin C, and C reactive protein (CRP) levels for predicting intracranial aneurysms and their rupture were drawn, and the area under the curve (AUC), sensitivity, and specificity were calculated. Results. The serum levels of D-dimer, cystatin C, and CRP in patients with intracranial aneurysms were significantly higher than those in the control group and the differences were statistically significant P < 0.05 . The serum levels of D-dimer, cystatin C, and CRP in patients with ruptured intracranial aneurysms were higher than those in patients with unruptured intracranial aneurysms, and the differences were also statistically significant P < 0.05 . The combined detection of serum D-dimer, cystatin C, and CRP levels has a higher AUC (0.9014) for predicting intracranial aneurysms and higher AUC (0.9412) for predicting ruptured intracranial aneurysms than D-dimer (0.7118 and 0.8750, respectively), cystatin C (0.6489 and 0.6180, respectively), and CRP (0.7764 and 0.6551, respectively) independent detection; the combined detection had a sensitivity of 93.75% and 87.80 for predicting the occurrence and rupture of intracranial aneurysms, and the specificity was 68.12% and 92.86%, respectively. Conclusion. The combined detection of serum D-dimer, cystatin C, and CRP levels is a very valuable indicator for predicting the occurrence and rupture of intracranial aneurysms, and combined detection can provide scientific evidence-based guidance for clinical prediction of the occurrence and rupture of intracranial aneurysms. [ABSTRACT FROM AUTHOR]

Glioma is the most commonly occurring primary neuroepithelial neoplasm. Long noncoding RNAs (lncRNAs) are emerging as pivotal modulators of gene expression in the immune system and play critical roles in the growth, progression, and immune response of carcinomas. In this study, we performed univariate Cox regression analysis on survival data from TCGA and identified 20 prognostic lncRNAs. Moreover, we revealed that these prognosis-related lncRNAs (PRLnc) were dysregulated in glioma. Furthermore, we constructed a signature based on the expression levels of these prognosis-related lncRNAs based on 13 prognostic lncRNAs, including AGAP2-AS1, CYTOR, MIR155HG, LINC00634, HOTAIRM1, SNHG18, LINC01841, LINC01842, LINC01426, MIR9-3HG, TMEM220-AS1, LINC00641, LINC01270, and LINC01503. The Kaplan–Meier curves show that high-risk patients had a shorter survival time. Finally, the glioma samples were classified into 2 subgroups based on the median expression of prognosis-related lncRNAs in each sample. In summary, these findings suggest that PRLnc is associated with tumor-infiltrating immune cells in glioma and that subtype 2 patients may respond more positively to immunotherapy. [ABSTRACT FROM AUTHOR]

Background. Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. Methods. From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74 , 2.74 < NLR ≤ 3.96 , and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. Results. During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39 , 95 % CI = 1.01 ‐ 1.93 , P = 0.046) and CVD mortality (HR = 1.81 , 95 % CI = 1.22 ‐ 2.69 , P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95 % CI = 1.26 − 3.23 , P = 0.003) and CVD mortality was 2.98 (95 % CI = 1.58 − 5.62 , P = 0.001) in the younger group (age < 60 years). Conclusions. NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old. [ABSTRACT FROM AUTHOR]