Serum,synovial and mRNA expression of interleukin-33 in juvenile idiopathic arthritis patients: Potential role as a marker of disease activity and relation to musculoskeletal ultrasound

Aim of the workTo measure interleukin-33 (IL-33) serum and synovial fluid (SF) levels as well as its relative expression in peripheral blood mononuclear cells (PBMC) of juvenile idiopathic arthritis (JIA) patients and to study their relation to clinical, laboratory and musculoskeletal ultrasound characteristics, disease activity and functional status.Patients and methodsThe study included 60 JIA patients and 60 healthy controls and SF levels were measured in 20. Juvenile arthritis disease activity score (JADAS27) and Juvenile Arthritis Multidimensional Assessment Report (JAMAR) were assessed; Ten-joint grey scale (GS) and power Doppler (PD) MSUS score was performed. Rheumatoid factor (RF) titer and C-reactive protein (CRP) levels were measured.ResultsIn JIA patients, serum IL-33 levels (median 12.6; 7.4–23.8 ng/l) and its relative mRNA expression (median 3.3; 2.5–3.7) were significantly higher than their levels in the controls (median 1.7; 0.8–2.4 ng/l and median 1 ng/ml; p < 0.001). Polyarticular subtype (n = 20) had higher IL-33 serum levels compared to oligoarticular (n = 28, p < 0.001) and systemic-onset (n = 12, p = 0.006) subtypes. In JIA patients, the serum and SF levels of IL-33 significantly correlated with JADAS27 (p < 0.001 and 0.002 respectively), CRP (p < 0.001 and 0.007 respectively), GS (p < 0.001 and 0.001 respectively) and PD (p < 0.001 and 0.005 respectively). Serum IL-33 correlated with RF (p = 0.039) while, SF IL-33 correlated with physical function (p = 0.02).ConclusionsJIA patients have significantly elevated IL-33 serum concentrations and mRNA expression that considerably correlated with different inflammatory parameters, RF and physical function suggesting that it could be a valuable marker of JIA disease activity and implies a possible prognostic role.     

单羧酸转运蛋白1促进胰腺导管癌细胞浸润转移的机制研究

背景与目的：单羧酸转运蛋白1（monocarboxylate transporter 1，MCT1）是细胞转运乳酸、丙酮酸等代谢产物及能量物质的一种重要蛋白质，其在胰腺导管癌中的作用及机制鲜有研究报道。该研究旨在探讨MCT1在胰腺导管癌中的表达及临床病理学意义。方法：纳入78例胰腺导管癌患者的癌组织及癌旁正常组织，运用免疫组织化学技术检测MCT1在癌组织和癌旁正常组织中的表达水平并分析其临床病理学意义。在体外细胞系水平上，我们运用胰腺癌细胞系PANC-1和Capan-1，运用细胞克隆形成实验、细胞划痕和Transwell实验分析沉默MCT1后胰腺癌细胞增殖、迁移和浸润的改变。为明确MCT1的相关作用机制，我们通过生物信息学分析，预测miR-124-3p是MCT1的潜在调控微小RNA；为了进一步验证，我们运用双荧光素酶报告实验分析miR-124-3p对MCT1的调控效果；运用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）分别检测51对新鲜胰腺癌组织中MCT1和miR-124-3p的基因表达并分析两者的相关性。结果：MCT1的阳性表达主要位于细胞膜和细胞质。相比癌旁正常组织，MCT1在胰腺导管癌组织中显著高表达，其表达水平与胰腺导管癌的分化程度、临床分期、淋巴结转移和不良预后具有显著相关性。在体外细胞系水平上，沉默MCT1能够显著抑制胰腺癌细胞系PANC-1和Capan-1的增殖、迁移和浸润；miR-124-3p在胰腺癌组织中显著低表达，并且与MCT1 mRNA的表达具有显著负相关性，能够负调控MCT1的蛋白表达。结论：MCT1是胰腺导管腺癌的致癌基因，miR-124-3p能够负调控MCT1的表达。     

Time Dependent Release of Interleukin-8 and Tumor Necrosis Factor-α in Platelet Concentrate

Contaminating white blood cells in stored platelet concentrate (PC) are the source of many pro-inflammatory cytokines. These are implicated in transfusion reactions. To study the release of interleukin (IL)-8 and tumor necrosis factor alpha (TNF-α) at different time interval in PC prepared by-platelet rich plasma (PRP) and buffy coat (BC) using different principles. Fifteen PCs were prepared by both the methods. The supernatants of PCs prepared by PRP and BC methods were collected aseptically after 1, 18, 65 and 112 h of preparation. pH, platelet and WBC counts were done. The supernatants were frozen in aliquots at −56 °C for measurement of IL-8 and TNF-α concentration using ELISA. The Mean ± SD value of WBC in PRP-PC was 7.4 ± 3.75 × 10⁷ and in BC-PC 3.9 ± 2.2 × 10⁷. The mean platelet counts were 6.05 ± 1.94 × 10¹⁰ and 6.54 ± 2.18 × 10¹⁰ respectively. The highest level of IL-8 in one hour was up to 30 pg/ml in both the type of PC. It increased up to 986 pg/ml in PRP-PC and 481 pg/ml in BC-PC at 112 h. IL-8 increased significantly during storage period of 5 days in both types of PCs (P0.000 and P0.01). TNF-α level remained low up to 18 h. The highest level was 72 pg/ml in PRP-PC and 57 pg/ml in BC-PC at 65 h. IL-8 levels significantly increased after one hour of storage and TNF-α. levels were low up to 18 h and then showed increase. The BC-PC had significantly low levels of IL-8 compared to PRP-PC (P0.0001).