Association between atherosclerosis and primary Sjogren's syndrome: A cross-sectional study.

Background and Aims: Atherosclerosis (AS) risk increases in patients with systemic autoimmune diseases. The association and mechanism between primary Sjogren's syndrome (pSS) and AS haven't been explained for now. We did this cross-sectional study to clarify the prevalence and risk factors of AS in patients with pSS, and to further explore how immune cells and inflammatory cytokines work in the process. Methods: Patients with pSS were enrolled. General information, AS events, immune cells, inflammatory cytokines, and related clinical data were recorded. Prevalence of AS events was calculated. Correlation analysis between immune factors and AS quantitative parameters were conducted by SPSS v20.0. Results: A total of 155 pSS patients were included with a median Framingham 10-year risk of 7%. Sixty-four AS events were recorded, with a prevalence of 41.3%. Carotid intima-media thickness was positively correlated to immunoglobulin (Ig) A (r = 0.245, p = 0.030) and negatively correlated to IgM (r = -0.227, p = 0.045). Left ankle-brachial pulse wave velocity (baPWV) was positively correlated to the course of disease (r = 0.352, p = 0.004), B cells (r = 0.410, p = 0.001), and T helper (Th) cells (r = 0.284, p = 0.029), while negatively correlated to IgM (r = -0.257, p = 0.042). Right baPWV was positively correlated to the course of pSS (r = 0.319, p = 0.010), B cells (r = 0.453, p < 0.001), Th cells (r = 0.302, p = 0.020), and C-reactive protein (CRP) (r = 0.286, p = 0.042). Use of hydroxychloroquine, cyclophosphamide, and glucocorticoids had no impact on AS events. Conclusion: The prevalence of AS in patients with pSS is reported to be 41.3%. Several risk factors have been associated with AS in these patients, including the duration of the disease, levels of Th cells, B lymphocytes, and CRP. Interestingly, IgM appears to have a protective effect against AS. It is worth noting that traditional therapy for pSS does not seem to have any effect in preventing AS events.

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.

Elevated serum neurofilament levels in young first-episode and medication-naïve major depressive disorder patients with alterative white matter integrity.

The mechanism of white matter (WM) microstructure alteration in major depressive disorder (MDD) is unknown. Serum neurofilament (NF) levels have been identified as promising biomarkers for axonal damage and degeneration in neurological disorders. Furthermore, elevated plasma NF levels were also reported in depressive patients with treatment resistance. The current study investigated the serum NF levels of first-episode, medication-naïve patients with different severities of MDD and assessed their relationships with WM integrity. Diffusion tensor images and serum NF levels of 82 MDD patients and 72 age- and sex-matched healthy controls (HCs) were taken. We found that serum NF levels were significantly higher in patients with MDD than those in HCs. Fractional anisotropy (FA) of six brain WM tracts (the body and genu of the corpus callosum, left superior and posterior corona radiata, and bilateral anterior corona radiata) in patients with MDD were lower than those in the HCs after family-wise error-correction for multiple comparisons. Negative correlations between serum NF levels in the severe group of MDD and the decreased FA of the left anterior corona radiata were found in MDD, which might contribute to an understanding of the pathophysiological mechanism of MDD.

lncRNA TP73-AS1 Regulates miR-21/PTEN Axis to Affect Cell Proliferation in Acute Myeloid Leukemia.

Objective: TP73-AS1 has been reported as an overexpressed oncogenic lncRNA in several types of cancer. However, these analyses of The Cancer Genome Atlas data set revealed downregulation of TP73-AS1 in acute myeloid leukemia (AML). In this study, we aimed to study the molecular mechanism between TP73-AS1 and cell proliferation in AML. Methods: Bone marrow (BM) samples were obtained from 50 AML patients and 50 healthy controls. Cell transient transfections were performed to analyze gene interactions. Dual-luciferase reporter assay, quantitative polymerase chain reaction and Western blot were used to study the gene expressions. Cell proliferation was analyzed by CCK-8 method. Results: TP73-AS1 was confirmed to be downregulated in AML. TP73-AS1 was predicted to interact with miR-21, while overexpression of TP73-AS1 and miR-21 did not affect the expression of each other. Instead, overexpression of TP73-AS1 led to the upregulation of phosphatase and tensin homologue (PTEN), a downstream target of miR-21. Cell proliferation analysis showed that overexpression of TP73-AS1 and PTEN led to a decreased proliferation rate of AML cells. Overexpression of miR-21 played an opposite role and reduced the effects of overexpressing TP73-AS1 and PTEN. Conclusion: TP73-AS1 may regulate the miR-21/PTEN axis to affect cell proliferation in AML.

Association between abnormal serum myelin-specific protein levels and white matter integrity in first-episode and drug-naïve patients with major depressive disorder.

BACKGROUND: Although the structural abnormalities of white matter (WM) have been described in patients with major depressive disorder (MDD), the neuropathological changes remain unclear. The current study aimed to investigate the myelin oligodendrocyte glycoprotein (MOG) and myelin-associated glycoprotein (MAG) levels and their correlations with WM integrity in first-episode, drug-naïve MDD patients. METHODS: We obtained diffusion tensor images of 102 first-episode, drug-naïve MDD patients and 81 age- and sex-matched controls. Serum MOG and MAG levels of all participants were measured and compared between the two groups. The correlations between WM integrity and MOG and MAG levels were examined. RESULTS: MOG and MAG serum levels were significantly higher in MDD patients than in controls. Patients with MDD also showed decreased fractional anisotropy (FA) and axial diffusivity in the WM of the bilateral thalamus, right hippocampus, right temporal lobe, and left pulvinar. At the whole-brain level, no regions showed any correlations of diffusivity parameters with MOG or MAG levels in healthy subjects. However, we observed two-way correlations between the MOG and MAG levels and the FA and mean diffusivity values in the WM of the left middle frontal lobe, right inferior parietal lobe, and right supplementary motor area in MDD patients. LIMITATIONS: Further investigation with a larger sample size and longitudinal studies are required to better understand the neuropathology of WM integrity in MDD. CONCLUSIONS: Our findings represent the first evidence of a relationship between abnormal serum myelin-specific protein levels and impaired WM integrity, which may help to better understand the neurobiological mechanisms of MDD.