Status of TWEAK DNA methylation and mRNA expression in systemic lupus erythematosus.

OBJECTIVE: Draw upon research into the serum concentration, mRNA expression, and DNA methylation of TNF-like weak inducer of apoptosis (TWEAK) in the peripheral blood of systemic lupus erythematosus patients and healthy controls in an attempt to investigate the epigenetics associated with TWEAK in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: A total of 178 SLE patients (SLE group) and 131 sex-age matched healthy controls (HC group) were recruited. Enzyme-linked immunosorbent assays (ELISA) was used to detect serum protein concentration of TWEAK. TWEAK mRNA expression was analyzed by Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Methylation levels of the promotor of TWEAK were measured using quantitative DNA methylation analysis on the MassARRAY spectrometry. RESULTS: Serum TWEAK concentrations were not statistically significant in SLE patients and HCs. Nevertheless, serum TWEAK concentrations were significantly lower in patients with renal involvement when compared to those without it. Serum TWEAK concentrations were reduced in clinically active patients (SLEDAI ≥ 10) compared with clinically stable patients (SLEDAI < 10). It was also significantly associated with SLEDAI. Compared with the HC group, the TWEAK mRNA expression in the SLE group was significantly lower. The global DNA methylation levels of TWEAK in the SLE group were observed to be significantly higher than the HC group. SLE patients with renal involvement, and the clinically active patients had higher TWEAK global methylation as well as exhibited variation in certain CpG island methylation. Furthermore, TWEAK methylation negatively correlated with TWEAK mRNA expression. CONCLUSION: This study suggests that TWEAK DNA methylation is a valuable as a focus for epigenetic studies because of it potentially influencing TWEAK gene expression in SLE patients. Aberrant DNA methylation of TWEAK may be involved in the initiation and development of SLE.

Dynamic changes of amplitude of low-frequency in systemic lupus erythematosus patients with cognitive impairment.

Background: Cognitive dysfunction (CI) is frequently reported in patients with systemic lupus erythematosus (SLE), but the identification and assessment of SLE-related CI remain challenging. Previous studies have focused on changes in static brain activity, and no studies have investigated the characteristics of dynamic brain activity in SLE patients with CI. Objects: We calculated the dynamic amplitude of low-frequency fluctuation (dALFF) by combining the ALFF with a sliding window method to assess the temporal variability of brain functional activity in SLE patients with and without CI. Methods: Thirty-eight SLE with CI, thirty-eight SLE without CI, and thirty-eight healthy controls (HCs) were recruited. By comparing static ALFF (sALFF) and dALFF among the three groups, changes in brain activity intensity and its temporal variability were assessed in patients with SLE with or without CI. Spearman correlation coefficients were calculated between the brain function indicator and Mini-mental State Examination (MMSE) scores of SLE with CI. Results: Subjects among the three groups exhibited significant sALFF differences in the right parahippocampal gyrus, left caudate nucleus, right putamen, and left cuneus. Compared to the SLE without CI, the right parahippocampal gyrus exhibited higher sALFF in the SLE with CI group. Compared to the HCs, the left caudate nucleus exhibited increased sALFF in the SLE with CI group. Participants in the three groups exhibited significant dALFF variability in the right parahippocampal gyrus, right lingual gyrus, and bilateral inferior occipital gyrus. Compared to the HCs, the right lingual gyrus exhibited reduced dALFF in the SLE without CI group. Compared to the HCs, the right parahippocampal gyrus exhibited increased dALFF, left calcarine fissure, and the surrounding cortex exhibited reduced dALFF in the SLE with CI group. There was no significant correlation between the MMSE score, sALFF, and dALFF in the SLE with CI group. Conclusion: SLE patients with CI have abnormal brain activity intensity and stability. By analyzing the dynamics of intrinsic brain activity, it provides a new idea for evaluating SLE-related CI. However, more research and validation with multiple metrics are needed to determine the link between the severity of cognitive impairment (CI) and brain activity in patients with SLE.

Increasing of Blood Brain Barrier Permeability and the Association With Depression and Anxiety in Systemic Lupus Erythematosus Patients.

Objective: To study changes in blood brain barrier (BBB) permeability in systemic lupus erythematosus (SLE) patients, and explore the association between the alterations in BBB permeability and depression/anxiety in SLE. Methods: Brain dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) images were collected from 42 SLE patients and 23 healthy controls (HCs). Based on the Patlak pharmacokinetic model, the Ktrans value of each voxel in the whole brain of each subject was calculated. BBB permeability indicator (the Ktrans value) between SLE patients and healthy control group was compared. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to assess the mental health of SLE patients. The difference in BBB permeability was compared on SLE patients with depression/anxiety, SLE patients without depression/anxiety and HCs by ANOVA analysis. Results: The Ktrans value of the right insular region of the SLE group was significantly higher than that of the healthy control group. And the Ktrans value of the right insular region in SLE patients with depression/anxiety was significantly increased compared with SLE patients without depression/anxiety and HCs. Conclusions: SLE patients have increased BBB permeability, mainly in the right insular area. The increased BBB permeability in the right insular region is associated with the depression/anxiety in SLE patients.

Gout Is Not Just Arthritis: Abnormal Cortical Thickness and Structural Covariance Networks in Gout.

Background: Hyperuricemia is the cause of gout. The antioxidant and neuroprotective effects of uric acid seem to benefit some patients with central nervous system injury. However, changes in the brain structure have not been discovered in patients with gout. Object: Clarify the changes in cortical thickness in patients with gout and the alteration of the structural covariance networks (SCNs) based on cortical thickness. Methods: We collected structural MRIs of 23 male gout patients and 23 age-matched healthy controls. After calculating and comparing the difference in cortical thickness between the two groups, we constructed and analyzed the cortical thickness covariance networks of the two groups, and we investigated for any changes in SCNs of gout patients. Results: Gout patients have thicker cortices in the left postcentral, left supramarginal, right medial temporal, and right medial orbitofrontal regions; and thinner cortices were found in the left insula, left superior frontal, right pericalcarine, and right precentral regions. In SCN analysis, between-group differences in global network measures showed that gout patients have a higher global efficiency. In regional network measures, more nodes in gout patients have increased centrality. In network hub analysis, we found that the transfer of the core hub area, rather than the change in number, may be the characteristic of the gout's cortical thickness covariance network. Conclusion: This is the first study on changes in brain cortical thickness and SCN based on graph theory in patients with gout. The present study found that, compared with healthy controls, gout patients show regional cortical thinning or thickening, and variation in the properties of the cortical thickness covariance network also changed. These alterations may be the combined effect of disease damage and physiological compensation. More research is needed to fully understand the complex underlying mechanisms of gout brain variation.

Curculigoside exerts significant anti­arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF­κB signaling pathway.

The present study aimed to investigate the anti­arthritic effects of curculigoside isolated from the rhizome of Curculigo orchioides Gaertn in vivo and in vitro, as well as to determine the potential underlying mechanisms. A rat model of arthritis was induced with type II collagen. Arthritic rats were treated with curculigoside (50 mg/kg) and blood samples were collected to determine serum levels of tumor necrosis factor (TNF)­α, interleukin (IL)­1ß, IL­6, IL­10, IL­12 and IL­17A. Furthermore, indices of the thymus and spleen were determined. The anti­proliferative effects of curculigoside were detected with Cell Counting kit­8 assays in rheumatoid arthritis­derived fibroblast­like synoviocyte MH7A cells. In addition, expression levels of Janus kinase (JAK)1, JAK3, signal transducer and activator of transcription (STAT)3, nuclear factor (NF)­κB p65 and its inhibitor (IκB) were determined by western blotting. The results revealed that curculigoside inhibited paw swelling and arthritis scores in type II collagen­induced arthritic (CIA) rats. Additionally, curculigoside decreased serum levels of TNF­α, IL­1ß, IL­6, IL­10, IL­12 and IL­17A in CIA rats. Curculigoside also significantly inhibited MH7A cell proliferation in a time and concentration­dependent manner. Furthermore, treatment downregulated the expression of JAK1, JAK3 and STAT3, and upregulated cytosolic nuclear factor (NF)­κB p65 and IκB. In conclusion, the results of the present study indicated that curculigoside exhibited significant anti­arthritic effects in vivo and in vitro, and the molecular mechanism may be associated with the JAK/STAT/NF­κB signaling pathway.