Potential mechanistic roles of Interleukin-33 in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that occurs mainly in synovial joints, causing synovial inflammation and joint injury. If diagnosed and treated in time, the disease can be well controlled. However, in clinical practice, patients often fail to get timely and effective treatment due to misdiagnosis, missed diagnosis, and other reasons, resulting in deterioration of the condition and poor prognosis, seriously affecting the patient's quality of life. So far, the pathogenesis of RA is still unclear. In recent years, it has been found that the imbalance of cytokines plays a vital role in the occurrence and development of RA. Most RA-related cytokines are produced by immune cells, which bind to the specific receptors of effector cells through paracrine and autocrine pathways. The effect of cytokines on inflammation can be divided into pro-inflammatory and anti-inflammatory factors. When the impact of pro-inflammatory factors is more significant than anti-inflammatory factors, the condition of RA will be aggravated, resulting in more inflammatory severe reactions and immune disorders. Interleukin-33 (IL-33) is a new member of the interleukin-1(IL-1) family, and its receptor is suppression of tumorigenicity 2 (ST2). IL-33 plays a vital role in immune diseases such as RA by promoting a series of biochemical reactions in macrophages, mast cells, granulocytes, and other cells. This article aims to summarize the research progress of IL-33 in the pathogenesis of RA in recent years, discuss its role in the pathogenesis of RA, and provide new ideas for the prevention and treatment of RA in the future.

Ataxin-10 Inhibits TNF-α-Induced Endothelial Inflammation via Suppressing Interferon Regulatory Factor-1.

Endothelial inflammation is a crucial event in the initiation of atherosclerosis. Here, we identify Ataxin-10 protein as a novel negative modulator of endothelial activation by suppressing IRF-1 transcription activity. The protein level of Ataxin-10 is relatively higher in human vascular endothelial cells, which can be significantly suppressed by TNF-α in both HUVECs and HLMECs. Overexpression of Ataxin-10 markedly inhibited the mRNA expressions of VCAM-1 and several cytokines including MCP-1, CXCL-1, CCL-5, and TNF-α; thus, it can also suppress monocyte adhesion to endothelial cells. Accordingly, Ataxin-10 silencing promoted endothelial inflammation. However, Ataxin-10 did not affect the MAPK/NF-κB signaling pathway stimulated by TNF-α in HUVECs. Using the yeast two-hybrid assay, we found that Ataxin-10 can directly bind to interferon regulatory factor-1 (IRF-1). Upon TNF-α stimulation, Ataxin-10 promoted the cytoplasmic localization of IRF-1, which inhibited the transcription of VCAM-1. Moreover, knockdown of IRF-1 can eliminate the effect of Ataxin-10 on the expression of VCAM-1 in HUVECs induced by TNF-α. Taken together, these results indicate that Ataxin-10 inhibits endothelial cell activation and may serve as a promising therapeutic target for some vascular inflammatory-related diseases such as atherosclerosis.

Serum adiponectin levels are reduced in autism spectrum disorder and association with severity of symptoms.

Recent evidence highlights the role of adiponectin in the pathophysiology of autism spectrum disorder (ASD), yielding conflicting results. The aims of this study were (1) To assess the adiponectin levels of children with ASD and typical developing (TP); (2) To investigate the relationship between adiponectin levels and symptom severity of children with ASD. This is a single-center cross-sectional study from China. From December 2017 to November 2019, first-diagnosis and drug-naïve children with ASD were included. Same TP children who were matched with clinical groups by gender and age were included as the control group. The enzyme-linked immunosorbent assay (ELISA) kit was used to determine serum concentrations of adiponectin. We recorded 176 children (88 were ASD and 88 were TP children) and 77.3% (n = 136) were boys and the mean age was 4.3 years (standard deviations [S.D.]: 1.2). The mean (S.D.) levels of adiponectin were 9.01(2.19) and 11.55(2.32) µg/ml for those with ASD and TP subjects. The difference between those two groups was significant (t = 7.169, p < 0.001). There was a negative correlation between serum levels of adiponectin and Childhood Autism Rating Scale [CARS] score (r = -0.498, p < 0.001). At admission, 39 ASD (54.5%) had a minor autism (CARS<37). In these children, the mean (S.D.) adiponectin level was higher than that observed in children with moderate-to-severe clinical severity (10.09[2.32] vs.8.15[1.64] µg/ml, P < 0.001). This study shows that serum adiponectin. Levels are decreased in ASD when compared with in healthy children. The findings also indicate an inverse association between serum adiponectin levels and severity of symptoms in ASD.

Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with autism spectrum disorders.

OBJECTIVE: The compositions of the gut microbiota and its metabolites were altered in individuals with Autism Spectrum Disorder (ASD). The aim of this study was to assess whether plasma levels of gut-derived metabolite trimethylamine N-oxide (TMAO) were associated with ASD and the degree of symptom severity. METHODS: From September 2017 to January 2019, a total of three hundred and twenty-eight Chinese children (164 with ASD and 164 their age-sex matched control subjects) aged 3-8 years were included. TMAO levels in plasma were determined using high-performance liquid chromatography tandem mass spectrometry (LC/MS/MS). Logistic regression analysis was used to examine the TMAO-ASD association. RESULTS: In the study, the median age of the ASD group was 5 years (interquartile range [IQR], 4-6 years) and 129 (78.7%) were boys. The median plasma levels of TMAO in children with ASD and typically-developing (TD) children at admission were 4.2 (IQR, 3.0-5.6) µmol/l and 3.0 (2.0-4.4) µmol/l, respectively (P < 0.001). For each 1 µmol/l increase of plasma TMAO, the unadjusted and adjusted risk of ASD would be increased by 54% (with the odds ratios [OR] of 1.54; 95% confidence intervals [CI]: 1.32-1.78; P < 0.001) and 27% (1.27 [1.10-1.45], P < 0.001), respectively. Symptom severity was classified as mild-to-moderate (CARS < 37) for 66 children with ASD (40.2%). In these children, the plasma levels of TMAO were lower than in the 98 children with ASD (59.8%) whose symptoms were classified as severe (CARS > 36) (3.5[2.5-4.9] µmol/l vs. 4.5(3.7-6.0) µmol/l; P < 0.001). For each 1 µmol/l increase of plasma TMAO, the unadjusted and adjusted risk of severe autism would be increased by 61% (with the OR of 1.61 [95% CI 1.28-2.01], P < 0.001) and 31% (1.31 [1.08-1.49], P < 0.001), respectively. CONCLUSIONS: Elevated plasma levels of TMAO were associated with ASD and symptom severity.

VEGF Gene Polymorphisms Affect Serum Protein Levels and Alter Disease Activity and Synovial Lesions in Rheumatoid Arthritis.

BACKGROUND: Our study investigated 2 common single-nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) for their influences on serum VEGF levels, disease activity, and synovial lesions in rheumatoid arthritis (RA). MATERIAL/METHODS: Clinical information and venous blood samples were collected from 98 RA patients and 100 healthy controls. Genotyping on samples from the subjects was performed using matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). Serum VEGF levels were determined using the enzyme-linked immunosorbent assay (ELISA). The synovial thickness and joint effusion of 28 joints were measured in RA patients, and total sharp score (TSS) and disease activity score (DAS) of 28 joints were recorded. RESULTS: The genotype and allele frequencies of VEGF rs833070 (G>A) and rs3025030 (G>C) were significantly different between RA group and control group (all P<0.05). VEGF rs833070 and rs3025030 polymorphisms were associated with increasing VEGF serum levels in the RA group (all P<0.01). Statistically significant difference was observed in DAS28 between the different genotypes of VEGF rs833070 in RA patients (P<0.05). Importantly, significant differences in synovial thickening, joint effusion and synovial angiogenesis were observed between the different genotypes of VEGF rs833070 and rs3025030 polymorphisms (all P<0.05). CONCLUSIONS: Our study provides evidence that VEGF polymorphisms might be important indicators of disease activity and synovial lesions, and prognostic factors in evaluating the treatment effectiveness in RA.