Role of NLRP3 and NLRP1 inflammasomes signaling pathways in pathogenesis of rheumatoid arthritis.

OBJECTIVES: To investigate the role of NLRP3 and NLRP1 inflammasomes signaling pathways in rheumatoid arthritis (RA). METHODS: A total of 36 patients with RA were selected, peripheral blood mononuclear cell (PBMC) and granulocyte were separated from venous blood. RT-qPCR method was used to detect the expression level and diversity of NLRP3 and NLRP1 in PBMC and granulocyte mRNA in patients with RA, and detect the mRNA expression of downstream factor IL-1α. The correlation between RA and the expression of NLRP3 and NLRP1 was analyzed. Normal 30 cases were set as control group. RESULTS: Expression levels of NLRP1, and caspase-1 mRNA in PBMC of RA group were significantly lower than those of control group (P<0.05), while there was no significant difference in expression levels of NLRP3, ASC, IL-1α mRNA between these two groups (P>0.05); NLRP3, caspase-1, and ASC mRNA expression in granulocyte of RA patients were significantly lower than those in control group (P<0.05). There was no correlation between rheumatoid factor and expression levels of NLRP3, ASC, caspase-1 mRNA in RA group (P>0.05); NLRP1, IL-1α mRNA expression level had a negative correlation with anti-rheumatoid factor antibody (P=0.033 2, 0.034 0). CONCLUSIONS: NLRP3 and NLRP1 inflammasomes signaling pathways are involved in RA inflammatory reaction process as protective factors, and play an important role in RA inflammatory mechanisms.

Lung injury following lower extremity blast trauma in rats.

BACKGROUND: Lower extremity blast trauma is a common injury during armed conflict and after terrorist attacks with a high mortality, which is likely associated with distant vital organ injury. The current study aimed to investigate the underlying mechanisms of remote lung injury after blast lower extremity trauma. METHODS: Sprague-Dawley rats were randomly divided into two groups: sham and blast. The blast group underwent blast trauma to the left hind limb using chartaceous electricity detonators, which was then subdivided into the time at which they were sacrificed: 0.5, 1, 3, and 6 hours. The sham group was also subdivided into the baseline control and time course groups. The baseline group was sacrificed 0.5 hours after artery cannulation and the time course at 6 hours after sham blast. The lungs were harvested for histologic analysis and water content measurement. Blood samples were harvested at each end of experiment and analyzed for cytokines, myeloperoxidase, malondialdehyde, and superoxide dismutase and cystathionine γ-lyase activity and hydrogen sulfide. RESULTS: Blast hind limb trauma induced alveolar injury and cell infiltration, together with an increase in lung water content, in a time-dependent manner. Plasma and lung levels of proinflammatory cytokines, tumor necrosis factor-α and interleukin 6, and malondialdehyde, were found to be significantly increased in conjunction with a rise in myeloperoxidase and a concurrent fall in superoxide dismutase, cystathionine γ-lyase, and hydrogen sulfide. CONCLUSION: Our data demonstrated that blast limb trauma causes remote lung injury, which is likely associated with remarkable inflammatory response, oxidative stress, and depletion of protective mechanisms.

[The clinical significance of serum leptin level in IgA nephropathy patients].

AIM: To explore the change of serum leptin level and its clinical significance in the patients with IgA nephropathy. METHODS: A total of 40 IgA nephropathy patients were divided into group A (unnecessary for hemodialysis regimen) and B group (requisite for hemodialysis regimen). Other 20 healthy people for health examination homeochronously in our hospital were used as the control group (C group). The radioimmunoassay(RIA) was performed to detect the serum leptin contents of all the individuals and to analyze its clinical significance. RESULTS: The mean serum concentrations (MSCs) of A, B and C group were (4.98 ± 0.78) µg/L, (6.45 ± 0.76) µg/L and (3.96 ± 0.56) µg/L, respectively. And the MSCs before and after dialysis of group B patients were (6.50 ± 0.86) µg/L and (5.21 ± 0.66) µg/L, respectively. Statistical analysis indicated that the MSCs of group A and B were significantly higher than that of group C, and group B was obviously higher than that of group A (P<0.05). The MSC before dialysis was statistically higher than that after dialysis in group B (P<0.05). CONCLUSION: The serum leptin was significantly increased in IgA nephropathy patients, which may be significant in the progression of IgA nephropathy.

Low- and high-dose hydrogen peroxide regulation of transcription factor NF-E2-related factor 2.

BACKGROUND: Reactive oxygen species (ROS) may play both physiological and pathophysiological roles. Transcription factor NF-E2-related factor 2 (Nrf2) regulates antioxidant response element (ARE)-mediated genes expression and coordinates induction of chemoprotective proteins in response to physical and chemical stresses. The exact role of Nrf2 in cellular responses to different levels of oxidative stresses remains unknown. METHODS: Rat pulmonary microvascular endothelial cells were cultured and treated with 0 mmol/L, 0.125 mmol/L, 0.25 mmol/L, 0.5 mmol/L, 1.0 mmol/L and 2.0 mmol/L hydrogen peroxide solution for 2 hours. Nrf2 gene expression was assayed by reverse transcription-PCR, Nrf2-ARE binding activity was assayed with electrophoretic mobility shift assay (EMSA), and localization of Nrf2 was detected with immunohistochemistry. RESULTS: Low and moderate (0.125 mmol/L, 0.25 mmol/L and 0.5 mmol/L) doses hydrogen peroxide exposure of rat pulmonary microvascular endothelial cells led to the nuclear accumulation of Nrf2, increased activity of transcription regulation and up-regulation of ARE-medicated gene expression. In contrast, high doses of hydrogen peroxide (1 mmol/L, 2 mmol/L) exposure of the cells led to the nuclear exclusion of Nrf2, decreased activity transcription regulation and down-regulation of ARE-mediated gene expression. CONCLUSION: Low and moderate doses of hydrogen peroxide play protective roles by increasing transcription activity of Nrf2, whereas high- dose hydrogen peroxide plays a deleterious role by decreasing transcription activity of Nrf2.