膀胱移行细胞癌E2F3、miR-17-5p、miR-20a的表达及相关性分析

目的检测E2F3、miR-17-5p、miR-20a在膀胱癌中的表达情况,分析E2F3与miR-17-5p、miR-20a之间是否存在关联性。方法荧光定量RT-PCR法检测不同病理分级膀胱移行细胞癌组织和细胞系5637、T24中miR-17-5p、miR-20a和E2F3基因的表达,Western blot检测E2F3蛋白的表达。结果与正常膀胱黏膜比较,膀胱移行细胞癌组织及5637、T24细胞系中E2F3、miR-17-5p和miR-20a均高表达（P〈0.05）。E2F3表达随着病理分级的升高逐步增多,miR-20a表达随病理分级的升高有降低趋势。5637细胞系相对T24细胞系高表达E2F3（P〈0.05）。结论膀胱移行细胞癌中miR-17-5p、miR-20a和E2F3均高表达,miR-20a和miR-17-5p的表达与E2F3的增高密切相关。     

Serum leptin in systemic lupus erythematosus patients: Its correlation with disease activity and some disease parameters

Aim of the work

To evaluate serum leptin levels in systemic lupus erythematosus (SLE) patients and correlate these levels with clinical and laboratory parameters as well as disease activity using systemic lupus disease activity index (SLEDAI).

Clinical significance of vitamin D deficiency and receptor gene polymorphism in systemic lupus erythematosus patients

Introduction

The vitamin D receptor (VDR) gene is a candidate for susceptibility to autoimmune disorders.

Role of syndecan-1 (CD138) in Egyptian systemic lupus erythematosus patients with lupus nephritis: Relation to disease activity

BackgroundSyndecan-1, a transmemebrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is readily shed and released under certain pathologic conditions and remains biologically active to plasma cells behaviour.Aim of the workTo assess the level of syndecan-1 in relation to lupus nephritis (LN) and systemic lupus erythematosus (SLE) activity.Patients and methodsThe study included 60 SLE patients subgrouped according to the presence of LN and activity. SLE disease activity index (SLEDAI) was assessed. Serum syndecan-1 level was measured.ResultsThe patients mean age was 25.9 ± 8.6 years, they were 54 females and 6 males with a disease duration of 3.8 ± 3.4 years. There was a significant difference in the level of syndecan-1 between healthy control (46.3 ± 12.2 ng/ml) and SLE patients whether they were with active LN (150.2 ± 31.1 ng/ml) (p < 0.001), extrarenal flare (86.9 ± 16.7 ng/ml) (p < 0.001) or inactive (79.1 ± 19.8 ng/ml) (p < 0.003). Syndecan-1 was significantly higher in patients with active LN compared to those with extrarenal flare and inactive disease (p < 0.001 and p < 0.001 respectively). Serum syndecan-1 level was significantly higher in patients with arthralgia, arthritis, pleurisy and pericarditis) (all p < 0.001). There was a significant correlation between syndecan-1 level and 24 h urinary proteins (r = 0.8, p < 0.0001), and inversely with the complement (C3: r = −0.54, p < 0.0001 and C4: r = −0.48, p < 0.0001). There was a significant correlation between syndecan-1 and SLEDAI (r = 0.68, p < 0.001).ConclusionSerum syndecan-1 is significantly high in active LN patients and can be a useful tool for diagnosis of active nephritis. It correlates with disease activity, consumed complement and proteinuria. It was significantly related to the presence of musculoskeletal manifestations and serositis.     

miR-106b-25/miR-17-92 clusters: Polycistrons with oncogenic roles in hepatocellular carcinoma

MicroRNAs are small endogenously expressed RNA molecules which are involved in the process of silencing gene expression through translational regulation. The polycistronic miR-17-92 cluster is the first microRNA cluster shown to play a role in tumorigenesis. It has two other paralogs in the human genome, the miR-106b-25 cluster and the miR-106a-363 cluster. Collectively, the microRNAs encoded by these clusters can be further grouped based on the seed sequences into four families, namely the miR-17, the miR-92, the miR-18 and the miR-19 families. Over-expression of the miR-106b-25 and miR-17-92 clusters has been reported not only during the development of cirrhosis but also subsequently during the development of hepatocellular carcinoma. Members of these clusters have also been shown to affect the replication of hepatitis B and hepatitis C viruses. Various targets of these microRNAs have been identified, and these targets are involved in tumor growth, cell survival and metastasis. In this review, we first describe the regulation of these clusters by c-Myc and E2F1, and how the members of these clusters in turn regulate E2F1 expression forming an auto-regulatory loop. In addition, the roles of the various members of the clusters in affecting relevant target gene expression in the pathogenesis of hepatocellular carcinoma will also be discussed.     

Role of glutathione S-transferases polymorphisms and monocyte CD64 expression in Egyptian patients with systemic lupus erythematosus

Aim of work

To study the genetic variants of glutathione S-transferases and monocyte CD64 expression in systemic lupus erythematosus patients and to evaluate their role in disease susceptibility, activity and damage.

Clinical characteristics and health related quality of life (HRQoL) in Egyptian patients with systemic lupus erythematosus

Aim of the work

To study the clinical characteristics and health related quality of life (HRQoL) in systemic lupus erythematosus patients.

Quantitative clinical assessment of disease activity in systemic lupus erythematosus: progress report and research agenda

Summary No single test allows an adequate measure of disease activity in multisystem diseases such as systemic lupus erythematosus (SLE). In order to evaluate the spectrum of manifestations of disease activity in SLE, investigators have developed numerous ad hoc scales which have not been tested for their validity or reliability. Three instruments have been extensively studied: the British Isles Lupus Activity Group instrument (BILAG), the SLE Disease Activity Index (SLEDAI), and the Systemic Lupus Activity Measure (SLAM). All three have been demonstrated to have convergent and construct validity when compared to the clinician's judgement. The summation of the number of criteria of the American Rheumatism Association (ARA) SLE criteria has been shown to be an inadequate measure of disease activity. Standardized measures of disease activity for SLE should enhance our ability to compare results from different centers in finer distinctions than dead or alive.     

Lymphopenia and systemic lupus erythematosus,a preliminary study: Correlation with clinical manifestations,disease activity and damage indices

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production against ‘self’ antigens and immunocomplex formation, resulting in frequent widespread inflammatory damage to target multiple organ systems.Aim of workTo determine the association of lymphopenia with the clinical manifestations, serologic abnormalities, disease activity and disease damage as well as drug intake in SLE patients.Patients and methodsThe present study was carried out on forty-five SLE female patients fulfilling the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE. They were divided into two groups according to the lymphocytes’ count: Group-I: thirty patients with lymphopenia (<1500/mm³) and group-II: fifteen patients without lymphopenia (⩾1500/mm³). Ten healthy age matched females (group-III) taken as a control group. Patients and control groups were recruited from the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University Hospitals. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Disease damage was assessed with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index.ResultsLymphopenia in patients with SLE was found to be associated with lupus nephritis (p = 0.023), leucopenia (p = 0.004), increased disease activity index (p = 0.03) and increased organ damage index (p = 0.02), and was not associated with other clinical lupus manifestations, serological abnormalities or with the drug intake (p > 0.05).ConclusionLymphopenia in SLE was associated with lupus nephritis, leucopenia and increased both disease activity and organ damage indices.     

IL-17 is a key cytokine correlating with disease activity and clinical presentation of systemic lupus erythematosus

AimsTo determine the role of IL-17 cytokine in systemic lupus erythematosus (SLE) patients and its association with clinical presentation of the disease and disease activity.Methods72 SLE patients and 70 healthy age and sex matched controls were included in the study. SLE disease activity was assessed in all patients with SLE disease activity index (SLEDAI-2K) scores. Plasma levels of IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay and correlated their levels with clinical manifestations of the disease and SLEDAI-2K.ResultsPlasma levels of IL-6 and IL-17 were significantly elevated in SLE patients than in control subjects (13.98 ± 6.95 versus 7.47 ± 1.23 pg/mL) and (19.47 ± 10.21 versus 9.93 ± 1.89 pg/mL), respectively. IL-6 and IL-17 were positively correlated with SLEDAI-2K scores (r = 0.684 at P < 0.001, r = 0.322 at P = 0.006), and lupus nephritis (r = 0.364 at P = 0.002, r = 0.474 at P < 0.001) respectively; similarly, the IL-17/IL-6 ratio was positively correlated with SLEDAI-2K (r = 0.243 at P = 0.039). Also, the level of both cytokines was positively correlated to each other during periods of disease activity (r = 0.755, P < 0.001) as well as during remission (r = 0.384, P = 0.040).ConclusionOver-expression of IL-17 correlates with disease activity of SLE. A longitudinal study in a larger cohort of SLE patients can help validate the results.     

结肠癌SW480细胞中miR-142-3p靶基因的确定及意义

目的 确定结肠癌SW480细胞中miR-142-3p的靶基因,探讨miR-142-3p与其靶基因的相互作用.方法 通过miRNA数据库预测可能与miR-142-3p相互作用的靶基因,构建miR-142-3p及阴性对照序列;将miR-142-3p、对照序列、TCF7的3'非翻译区(3'UTR)以及突变的TCF7 3'UTR分别克隆到表达载体上,共转染SW480细胞,36 h后检测绿色荧光蛋白的表达水平;Trizol抽提RNA,RT-PCR检测TCF7 mRNA表达水平;Western blot检测TCF7蛋白表达水平.结果 生物信息学方法预测TCF7可能为miR-142-3p的靶基因,进一步双荧光素酶报告实验验证了miR-142-3p可以与TCF7的3'UTR结合,阻断TCF7蛋白翻译过程,从而下调TCF7的蛋白水平.结论 TCF7可能为miR-142-3p的靶基因,miR-142-3p通过转录后负调控靶基因TCF7蛋白的表达.     

非酒精性脂肪性肝病合并2型糖尿病患者外周血miR-17、miR-20a和miR-20b变化及其临床意义*

目的 探讨非酒精性脂肪性肝病(NAFLD)合并2型糖尿病(T2DM)患者外周血miR-17、miR-20a和miR-20b变化及其临床意义。方法 2018年12月～2020年6月我院收治的T2DM患者46例和NAFLD合并T2DM患者50例(轻度19例、中度17例和重度14例)。采用实时荧光定量RT-PCR法检测血清miR-17、miR-20a和miR-20b mRNA水平。采用多因素Logistic回归分析NAFLD合并T2DM发生的独立危险因素,应用受试者工作特征曲线(ROC)下面积(AUC)分析各指标诊断严重NAFLD的效能。结果 NAFLD合并T2DM患者外周血miR-17、miR-20a和miR-20b mRNA水平分别为(5.6±1.3)、(3.8±0.9)和(1.8±0.5),显著高于T2DM患者【分别为(4.4±1.1)、(3.1±0.6)和(1.4±0.4),P<0.05】;重度NAFLD组血清miR-17、miR-20a和miR-20b mRNA水平分别为(6.0±1.1)、(4.0±0.8)和(1.9±0.5),显著高于中度患者【分别为(4.4±1.0)、(3.4±0.6)和(1.5±0.4),P<0.05】或轻度患者【分别为(4.1±0.6)、(2.8±0.8)和(1.2±0.3),P<0.05】;多因素Logistic回归分析显示,BMI、血清LDL-C、miR-17、miR-20a和miR-20b是NAFLD合并T2DM发生的独立危险因素(P<0.05);ROC分析结果显示,血清miR-17、miR-20a和miR-20b诊断严重NAFLD的AUC分别为0.75、0.74和0.70。结论 NAFLD合并T2DM患者外周血miR-17、miR-20a和miR-20b水平显著升高,可能参与了NAFLD的发病过程,对判断NAFLD的严重程度具有一定的意义。     

Potential role of high sensitivity cardiac troponin T in subclinical coronary atherosclerosis in systemic lupus erythematosus patients

Aim of the workTo determine the role of high sensitivity cardiac troponin T (HS cTnT) in subclinical coronary atherosclerosis in SLE patients at an apparent low risk for CVD according to traditional risk factors.Patients and methodsThe presence of subclinical coronary atherosclerosis was assessed by non-contract coronary computerized tomography and calcium score was measured using Agatston score in 30 SLE patients asymptomatic for CVD and 30 age and sex matched apparently healthy controls. SLE disease activity index (SLEDAI) was assessed. Serum HScTnT concentration was measured using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean age of the patients was 33 ± 5.7 years, disease duration of 33.7 ± 22 months and mean SLEDAI 8.1 ± 5.02. The mean HS cTnT level was 12.8 ± 11.3 ng/L (1–36 ng/L). Their Framingham score was 4.8 ± 3.1 (1–12). Framingham score was low in both SLE patients (range 1–12%) and controls (1–9%) (p = 0.12). 11 (36.7%) patients, but none of the controls, had coronary artery calcification (CAC). Serum HScTnT concentration was detectable (>3 ng/L) in 16 (53.3%) patients and 2 (6.7%) control (p < 0.001). Interestingly, it was detectable in all patients with CAC, but in only 26.3% of patients without (p < 0.001). HScTnT significantly correlated with Agatston (r = 0.63, p = 0.04), with erythrocyte sedimentation rate (r = ?0.65, p = 0.03), and with C-reactive protein (r = 0.76, p = 0.03) in SLE patients with CAC.ConclusionSerum HScTnT level is high and associated with CAC in SLE patients who are at an apparently low risk for CVD according to the Framingham risk score. HS cTnT may be a useful biomarker for SLE-associated subclinical atherosclerosis.     

Auditory disorders in patients with systemic lupus erythematosus: Relation to clinical parameters

Aim of the workTo evaluate the hearing disorders in SLE patients with particular regard to their frequency and relationship to disease duration and activity.Patients and methodsTwenty female SLE patients were enrolled in the study. Assessment of disease activity was done using the SLE disease activity index (SLEDAI). Another 20 otologically healthy subjects of matched age and sex served as controls. Auditory assessment was performed and included otoscopic examination, pure tone audiometry (PTA), acoustic immittance testing and speech audiometry.ResultsThe PTA was abnormal in 13 (65%) patients; 4 had tinnitus and 1 vertigo. The PTA results showed a highly significant statistical difference from the control (p < 0.001). Otoscopic examination, acoustic immittance testing and speech audiometry of all patients were normal. A significant difference was found in the age at disease onset between those with and without abnormal PTA (p = 0.023). Moreover, there was a significantly lower hearing level (right ear) at 12,000 Hz in juvenile-onset (N = 6) (20.83 ± 3.76 db) compared to adult-onset cases (32.5 ± 15.66 db) (p = 0.02). No significant difference was present in the audiovestibular manifestations (p = 0.114), clinical, laboratory parameters or disease activity between those with or without hearing loss. However, hearing levels were significantly lower in those with lupus nephritis and those receiving hydroxychloroquine.ConclusionPure tone audiometry revealed SNHL in 65% of SLE patients. Absence of audiovestibular manifestations does not exclude inner ear affection. Age at disease onset is remarkably associated with hearing loss in SLE. Lupus nephritis and hydroxychloroquine use are associated with lower hearing levels and possible early hearing loss.     

系统性红斑狼疮患者循环微小RNAs差异表达的初步分析

目的 检测系统性红斑狼疮(SLE)患者血浆中差异表达的微小RNAs(miRNAs),为寻求一种新的无创性SLE生物标志物奠定基础.方法 采用Agilent human miRNA芯片检测并筛选出SLE患者与健康人血浆中表达丰度有显著变化miRNA,并通过实时荧光定量聚合酶链反应(RT-qPCR)对部分差异表达基因进行验证.2组间的比较用独立样本的t检验.结果 MiRNAs芯片检测发现,SLE患者与健康对照间存在明显差异的循环miRNAs共有51个,其中19个上调,32个下调;RT-qPCR对其中4个上调(miR- 126、miR-21、miR-223和miR-451)和3个下调(miR-125a-3p、miR-146a和miR-155)循环miRNAs的验证结果与芯片数据所示具有较好的一致性.结论 SLE患者和健康人体内循环miRNAs的表达谱存在着明显差异,这些差异的循环miRNAs可作为一种潜在的SLE候选生物标志物.     

系统性红斑狼疮细胞与其病情活动性的相关性研究

目的 观察系统性红斑狼疮（SLE）患者外周血狼疮细胞（LEC）形态的变化，探讨其与SLE疾病活动性的关系。方法 采用经典改良血块法观察了50例SLE疾病活动期和30例SLE非活动期患者外周血LEC形态，同时与血清自身抗体、补体及SLE疾病活动指数（SLEDAI）对比研究。结果 特殊形态的LEC与自身抗体的抗dsDNA抗体和抗核小体抗体（AnuA）（r=0．588，P=0．056；r=0．759，P=0．135），补体C3和C4（r=-0．648，P=0．058；r=-0．589，P=0．057）及SLEDAI（r=0．686．P〈0．05）具有明显相关性。SLE活动期组特殊型LEC、自身抗体和补体与SLE非活动期组差异有统计学意义（P〈0．01）。当自身抗体和补体与SLEDAI无相关性时，特殊型LEC仍具有良好的相关性（r=0．786，P〈0．05）。结论 特殊型LEC与自身抗体、补体及SLEDAI有明显的相关性，可作为判断SLE疾病活动性的独特指标。     

Utero-placental and cerebrovascular indices in pregnant women with systemic lupus erythematosus: Relation to disease activity and pregnancy outcome

Aim of the workTo assess maternal and fetal vascular indices in SLE patients during pregnancy, and the impact of disease activity on these vascular indices.Patients and methods30 pregnant SLE patients and 30 age -matched healthy females with uncomplicated pregnancies were assessed during the third trimester using ultrasonography (US) and Doppler study to detect fetal biometry, the uterine, umbilical (UA) and fetal middle cerebral (MCA) arterial resistance (RI) and pulsatility (PI) indices, as well as cerebro-placental ratio (CPR). Disease activity was determined using the SLE Disease Activity Index (SLEDAI).ResultsThe mean uterine artery PI, RI and the UA-PI in SLE group were significantly higher than controls (p value < 0.001), but no significant difference as regards UA-RI (p = 0.68) between both groups. There was unilateral uterine artery notch in 20% and bilateral in 6.7% while it was absent in 73.3%. The MCA-PI was significantly lower in SLE group (p = 0.003), Where the MCA-RI showed higher values than control (p < 0.001). The CPR showed a lower significant values for SLE group compared to controls (p < 0.001), while the PR interval was significantly higher in SLE group (p = 0.006). Fetal biometry showed no significant difference between two groups apart from higher abdominal circumference (AC) values in controls (p = 0.01). There was no significant correlation between abnormal vascular indices or biometric parameters and SLEDAI score (p > 0.05).ConclusionPregnancies in SLE are associated with abnormal maternal and fetal vascular indices. Doppler US can identify at-risk pregnancies and optimize the time of delivery; confirming a good pregnancy outcome.     

Echocardiographic findings, lipids and lipoprotein(a) in patients with systemic lupus erythematosus

Summary Cardiac involvement, evaluated by echo-doppler-cardiography, occurred in 41 of 50 (82%) patients with systemic lupus erythematosus (SLE). Valvular pathology with aortic cusp sclerosis was the most prevalent finding irrespective of age. This finding, suggestive of atherosclerotic heart disease, was supported by increased levels of cholesterol and triglycerides in these patients. There was no significant increase in Lp(a) in the whole patient group, but Lp(a) was raised in patients with proteinuria. Forty percent of the SLE patients had pericarditis. Twelve patients with hypertension and/or mitral regurgitation had increased dimensions of left ventricle, left atrium or interventricular septum while 15 of 50 patients had isolated increase of these parameters. Localized hypokinesia was found in nine patients. Reduced cardiac index was found in five patients with SLE. There was no association between valvular disease, increased pulmonary artery pressure, and anticardiolipin antibodies.