Whole-exome sequencing reveals the major genetic factors contributing to neuromyelitis optica spectrum disorder in Chinese patients with aquaporin 4-IgG seropositivity.

BACKGROUND AND OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)-IgG seropositivity. METHODS: Whole-exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4-IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen (HLA) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted. RESULTS: A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1. HLA sequencing confirmed that the most significant allele was HLA-DQB1*05:02 (p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA-DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model (p < 0.05). The proportion of haplotype "HLA-DQB1*05:02-DRB1*15:01" was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively (p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss-of-function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1-G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls (p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes. CONCLUSIONS: Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1-G390R play important roles in disease susceptibility.

Helios but not CD226, TIGIT and Foxp3 is a Potential Marker for CD4+ Treg Cells in Patients with Rheumatoid Arthritis.

BACKGROUND/AIMS: Rheumatoid arthritis (RA) is a progressive, chronic, even disabling systemic autoimmune disease. Imbalance between pathogenic immune cells and immunosuppressive cells is associated with the pathogenesis and development of RA and other autoimmune diseases. As Foxp3 is also expressed on activated CD4+ cells in the presence of inflammation, the identification of Treg cells in patients with RA remains a challenge. METHODS: Comprehensive analyses were carried out by Flow cytometry. Expression of Helios, CD226, T cell immunoreceptor with Ig and ITIM domains clinical samples and healthy controls. RESULTS: We have systemically examined three potential markers, Helios, CD226 and TIGIT, that are possibly related to Treg identification, and found that Helios expression on CD4+Foxp3+cells was decreased and negatively correlated with the disease activity of RA patients, while CD226 and TIGIT both showed elevated expression levels in CD4+Foxp3+cells in RA patients and they were not associated with disease activity of RA patients. CONCLUSION: Taken together, our findings indicate that CD4+CD25hiCD127low/-Foxp3+Helios+ may represent the real Treg cell population in patients with RA.

Purification and bioactivities of phycocyanin.

Phycocyanin is an important light-harvesting pigment antenna protein in cyanobacteria, rhodophyta, cryptophyta, and glaucophyta, with a variety of bioactivities. The introduction of purification and bioactivities of phycocyanin contributes to a significant improvement in developing it into final processed products. In fact, the knowledge of phycocyanin has experienced a rapid increase in the past 20 years, and has promoted the relevant technological revolution with a decisive contribution to final application. The purpose of this review is to critically introduce the present knowledge of purification and bioactivities of phycocyanin, and to illustrate main problems and prospects.

Physicochemical properties and protective effects on UVA-induced photoaging in Hs68 cells of Pleurotus ostreatus polysaccharides by fractional precipitation.

The development of natural ingredients protecting skin from UVA-induced photoaging is widely expected. The present study investigated the physicochemical properties, antioxidant, moisturizing, collagenase and elastase inhibitory activities, and protective effect on UVA-induced photoaging in Hs68 cells of Pleurotus ostreatus polysaccharides (POPs). POP-40, POP-60, and POP-80 were extracted by gradient precipitation of 40 %, 60 %, and 80 % ethanol, which could be prepared in large quantities. The results showed that POPs had good DPPH and ABTS radical scavenging abilities, water retention capacity, and collagenase and elastase inhibition effects. POP-80 had the best efficacy. Further determined the anti-inflammatory and antisenescence activities of POPs in Hs68 cells. The results indicated that after UVA irradiation, the contents of ROS, senescent cells, NF-κB activity, and proinflammatory cytokines increased in Hs68 cells. However, cells pretreated with 50 µg/mL POPs significantly decreased the contents of ROS and the number of senescent cells, reduced NF-κB activity, and inhibited IL-6 and TNF-α production. There was no significant difference in reducing the accumulation of ROS and senescent cells between POP-80 and the common anti-inflammatory substance quercetin. The results suggested that POP-80 may be potential cosmeceutical ingredients as it can protect Hs68 cells from photodamage.

Anti-Inflammatory and Anti-Oxidative Effects of Polysaccharides Extracted from Unripe Carica papaya L. Fruit.

This study evaluated the antioxidative and anti-inflammatory activities of polysaccharides extracted from unripe Carica papaya L. (papaya) fruit. Three papaya polysaccharide (PP) fractions, namely PP-1, PP-2, and PP-3, with molecular weights of 2252, 2448, and 3741 kDa, containing abundant xylose, galacturonic acid, and mannose constituents, respectively, were obtained using diethylaminoethyl-Sepharose™ anion exchange chromatography. The antioxidant capacity of the PPs, hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay revealed that the PP-3 fraction had the highest antioxidant activity, with an EC50 (the concentration for 50% of the maximal effect) of 0.96 mg/mL, EC50 of 0.10 mg/mL, and Abs700 nm of 1.581 for the hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay, respectively. In addition, PP-3 significantly decreased reactive oxygen species production by 45.3%, NF-κB activation by 32.0%, and tumor necrosis factor-alpha and interleukin-6 generation by 33.5% and 34.4%, respectively, in H2O2-induced human epidermal keratinocytes. PP-3 exerts potent antioxidative and anti-inflammatory effects; thus, it is a potential biofunctional ingredient in the cosmetic industry.

Different Exosomal microRNA Profile in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) are inflammatory demyelinating diseases of the central nervous system. Exosomal microRNAs (miRNAs) are emerging biomarkers for demyelinating diseases. In this study, 52 aquaporin-4 antibody serum-positive NMOSD patients, 18 relapsing-remitting multiple sclerosis (RRMS) patients and 17 healthy controls (HCs) were included for the next-generation sequencing (NGS). To validate the NGS results, the valuable miRNAs were selected for validation by real-time quantitative polymerase chain reaction in another cohort of patients, comprising 31 NMOSD patients and 14 HCs. In addition, these miRNAs were also validated in a longitudinal study. NGS data revealed the exosomal miRNAs profile in NMOSD patients was different from HCs. Among those potential exosomal miRNAs which can distinguish NMOSD status, hsa-miR-122-3p and hsa-miR-200a-5p were the most abundant miRNAs. In addition, hsa-miR-122-3p and hsa-miR-200a-5p were significantly upregulated in the serum exosome of relapsing NMOSD compared with that in remitting NMOSD. Hsa-miR-122-3p and hsa-miR-200a-5p had positive correlations with disease severity in NMOSD patients. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the MAPK, Wnt and Ras signaling pathways were enriched. Further biological function analysis demonstrated that these two miRNAs might be involved in the immunoregulation of NMOSD pathogenesis. Our results indicated that miRNAs delivered by exosomes could be applied as potential biomarkers for NMOSD.

uPAR promotes tumor-like biologic behaviors of fibroblast-like synoviocytes through PI3K/Akt signaling pathway in patients with rheumatoid arthritis.

Urokinase-type plasminogen activator receptor (uPAR), is a multifunctional receptor on cell surface, widely present in endothelial cells, fibroblasts, and a variety of malignant cells. Current studies have suggested that uPAR overexpressed on synovial tissues or in synovial fluid or plasma in patients with rheumatoid arthritis (RA). However, there are limited researches regarding the role of uPAR on fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLSs) and its underlying mechanisms. Here, our studies show that the expression of uPAR protein was significantly higher in fibroblast-like synoviocytes (FLSs) from RA than those from osteoarthritis or traumatic injury patients. uPAR gene silencing significantly inhibited RA-FLSs cell proliferation, restrained cell transformation from the G0/G1 phase to S phase, aggravated cell apoptosis, interfered with RA-FLSs cell migration and invasion, and reduced activation of the PI3K/Akt signaling pathway, which may be associated with ß1-integrin. Cell supernatants from uPAR gene-silenced RA-FLSs markedly inhibited the migration and tubule formation ability of the HUVECs (a human endothelial cell line). Therefore, we demonstrate that uPAR changes the biological characteristics of RA-FLSs, and affects neoangiogenesis of synovial tissues in patients with RA. All of these may be associated with the ß1-integrin/PI3K/Akt signaling pathway. These results imply that targeting uPAR and its downstream signal pathway may provide therapeutic effects in RA.