Citrullinated Antigens with Multiple Citrulline Similar Motif in the Diagnosis of Rheumatoid Arthritis: A Preliminary Single-Center Study.

The presence of anti-citrullinated protein antibodies (ACPAs) in the serum is one of the immunological features of rheumatoid arthritis (RA). Anti-cyclic citrullinated peptide (CCP) assay has been widely used in clinic for the diagnosis of RA. However, up to 40% of RA patients are anti-CCP negative and the diagnostic sensitivity in this population needs to be improved for better clinical management. In this study, peptides with Multiple Citrulline Similar Motif (MCSM) were synthesized and a new ELISA system, which we called RA_CP, was developed to detect citrullinated antigens with MCSM present in the serum. 106 RA,48 other arthritis patients and 41 sex- and age-matched healthy controls (HCs) were included in this study. Patients with RA have a significantly higher amount of citrullinated antigens with MCSM than other arthritis patients and HCs. RA patients with positive anti-CCP are also MCSM positive, whereas 75% anti-CCP negative patients are positive for MCSM. The diagnostic sensitivity for anti-CCP and MCSM was 81.1% and 95.3%, while the specificity was 100% and 94.4%, respectively. ROC curve analyses showed that the area under the curve (AUC) values were 0.906 (95% CI: 0.860-0.951) for anti-CCP and 0.948 (95% CI: 0.912-0.985) for MCSM while the combination of MCSM and anti-CCP test has the highest AUC (0.971, 95% CI: 0.946-0.996). Our results suggest that detection of citrullinated antigens with MCSM has improved sensitivity compared with anti-CCP assay and could serve as a biomarker in diagnosis of RA patients.

Innate lymphoid cells in inflammatory arthritis.

Aberrant activation and dysregulation of immune system is a common feature of many forms of inflammatory arthritis. Since their identification as a distinctive population of leukocytes, innate lymphoid cells (ILCs) have been considered crucial in maintaining tissue homeostasis and bridges between innate and adaptive immune system. Altered ILCs' subset distribution and function have been observed in a variety of autoimmune and chronic inflammatory diseases and suggest a subset-specific role of ILCs in the pathogenesis of immune-mediated inflammation. In this review, we focus on the current knowledge of ILC subset and their role in inflammatory arthritis, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), enteropathic arthritis, and other seronegative spondyloarthritis. By better understanding the biology and function of ILC subset in different disease settings, new therapeutic interventions can be anticipated by modulating dysregulated ILC responses toward promoting resolution of inflammation.

A case report of acute renal failure caused by Amanita neoovoidea poisoning in Anhui Province, eastern China.

Amanita neoovoidea (genus Amanita Pers.) poisoning leads to acute renal failure. Here, we present seven case reports of acute renal failure with acute hepatic failure due to ingestion of A. neoovoidea. Clinical manifestations included gastrointestinal symptoms 1-72 h after ingestion; elevation of renal parameters and blood uric acid, blood urea nitrogen, and creatinine levels; a few abnormal hepatic parameters, primarily albumin decrease and alanine aminotransferase increase; and elevation of zymogram parameters such as cholinesterase and lactate dehydrogenase. To determine whether the hepatic/renal lesions were caused by amanitins, we analyzed the blood and urine samples of patients and specimens of poisonous mushrooms. Morphological and molecular biological analyses indicated that the mushroom was A. neoovoidea. However, no amatoxins and phallotoxins were detected in its basidiomata.

Di-(2-ethylhexyl)-phthalate induces apoptosis via the PPARγ/PTEN/AKT pathway in differentiated human embryonic stem cells.

[OBJECTIVE]: Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, may act as an endocrine disruptor and cause developmental toxicity. Differentiated human embryonic stem cells (hESCs) were used to investigate the underlying mechanism of the embryotoxicity induced by DEHP. [Materials and Methods] H9-hESCs were treated with DEHP at different concentrations for 10 days, and the cytotoxicity of DEHP on cell proliferation was determined using a cell-microelectronic sensing technique (Real-Time Cellular Analysis: RTCA). Based on the 50% inhibitory proliferation concentration (IC50), differentiated H9-hESCs were treated with DEHP at 0, 50, 100, and 200 µg/ml for 120 h, followed by measurement of its toxic effects on the transcriptome by mRNA microarray and QuantiGene Plex (QGP). Proteins were detected by the iTRAQ-based proteomics method and the proteins related to the PPARγ/PTEN/Akt pathways were measured by western blotting. The progression of the cell cycle and apoptosis were characterized using flow cytometry (FCM). In other experiments, hESCs were pre-treated with GW9662 (20 µM), a specific PPARγ inhibitor, for 30 min, followed by exposure to GW9662 (20 µM) and DEHP (200 µg/ml) for 120 h to observe the underlying mechanism of DEHP's embryotoxicity. [RESULTS]: DEHP inhibited H9-hESC cell proliferation in a dose-dependent manner, with an IC50 of 165.78 µg/ml. FCM results showed that DEHP could markedly induce cell cycle arrest and increase apoptosis. Gene microarray and QPG array analyses indicated that the peroxisome proliferator-activated receptor γ (PPARγ) was an apparent target for DEHP. We further demonstrated that DEHP could activate the PPARγ and upregulate the expression of PTEN downstream genes, and then play a negative role in the AKT signaling pathway. Cells pretreated with PPARγ inhibitor, GW9662, were shown to restore the effect of DEHP on the PPARγ/PTEN/AKT signaling pathway, and induce the recovery of cell cycle arrest and apoptosis. [CONCLUSION]: DEHP inhibited cell proliferation, promoted cell cycle arrest, and induced apoptosis through the PPARγ/PTEN/AKT signaling pathway in differentiated human embryonic stem cells. It suggested that DEHP exposure possibly cause reproductive or developmental toxicity in humans through the PPARγ signaling pathway.