Serum selenium status in Egyptians patients who had Graves' disease with and without ophthalmopathy.

Selenium is efficient in reducing the progression of active Graves' orbitopathy and improving life quality. The impact of mending relative deficiency of selenium on improving Graves' orbitopathy is not known, due to the lack of previous measurement of baseline levels of selenium. The study object was to determine whether serum selenium levels are lower in patients with Graves' ophthalmopathy (GO) disease in comparison with those without ophthalmopathy. This prospective case control study was conducted between 2019 and 2021 at the endocrine and ophthalmology clinics, Ain Shams University, Cairo. The study included a total of 75 subjects, 50 patients with Graves' disease (GD) and 25 subjects as a control group. Of the GD patients, 25 had Graves' orbitopathy. Serum selenium concentrations were measured in each group. The mean level of serum selenium was significantly lower in patients with Graves' orbitopathy (16.6 ± 7.5 ng/ml) than in patients with Graves' disease (42.9 ± 8.2 ng/ml) (p < 0.001). Mean selenium levels were reduced with increasing severity of GO, as selenium level was 30-55 ng/ml in GD, 21-28 ng/ml in mild GO, 18-22 ng/ml in moderate GO and 5-16 ng/ml in severe GO (p < 0.001). In conclusion, serum selenium levels were lower in GO patients compared with GD patients in an Egyptian population. Low selenium levels may be a risk factor for ophthalmopathy in Graves' disease patients.

Circulating miR-199a and long noncoding-RNA ANRIL as Promising Diagnostic Biomarkers for Inflammatory Bowel Disease.

BACKGROUND & AIMS: Inflammatory bowel disease (IBD), involving both Crohn's disease (CD) and ulcerative colitis (UC), represents a chronic, immune-mediated inflammatory disease due to an uncontrolled, ongoing inflammatory response to intestinal bacteria in those with genetic susceptibility. MicroRNA (miRNA) extrusion from relevant remote organs or tissues is reflected in the expression of miRNAs in serum and plasma. Both UC and CD patients had higher blood levels of expressed miR-199a. Long noncoding RNA (lncRNA) ANRIL is a proinflammatory gene that mediates nuclear factor κB to play a role in inflammatory diseases, such as IBD. The aim of the current study is to investigate the potential role of both miR-199a and ANRIL in diagnosing IBD in adult patients. METHODS: Sixty-seven IBD patients diagnosed clinically, radiologically, endoscopically, and histologically were included in this prospective cohort study. Participants were classified into 3 groups: the UC group (n = 35), the CD group (n = 32), and the control group (n = 30). Demographics, history taking, laboratory characteristics, and treatments were recorded. Tumor necrosis factor α , miR-199a, and ANRIL were measured. RESULTS: The findings suggested that miR-199a and ANRIL might be associated with the occurrence or progression of IBD because both genes were substantially expressed in the peripheral blood of patients with this condition. Receiver-operating characteristic curve analysis indicated that the detection of miR-199a and ANRIL had a predictive sensitivity of 62.9% and 88.6% and a specificity of 70.7% and 96.7% for the occurrence of UC cases, respectively, and a predictive sensitivity of 72.4% and 46.9% and a specificity of 96.7% and 34.7% for the occurrence of CD cases, respectively. CONCLUSIONS: Both miR-199a and ANRIL are abundant in the sera of IBD adult Egyptian patients (UC and CD). Both can represent a noninvasive marker for early disease diagnosis.

This study investigated the relation between tumor necrosis factor α, ANRIL, and miR-199a in inflammatory bowel disease patients to determine the probability of using them as prognostic and diagnostic biomarkers, as well as distinguishing between Crohn's disease and ulcerative colitis patients. Our findings showed that ANRIL and miR-199a can represent noninvasive biomarkers for early disease diagnosis.

Association of long non-coding RNAs NEAT1, and MALAT1 expression and pathogenesis of Behçet's disease among Egyptian patients.

Behçet's disease (BD) is a chronic inflammatory disease. Immunological defects have been shown to play a significant role in the progression of BD. The serum levels of two long non-coding RNAs (lncRNAs), NEAT1 and MALAT1, were examined in patients with BD to identify their role in the disease pathogenesis. Both lncRNAs were mentioned as essential regulators of innate immune responses and have a crucial role in inflammatory diseases. Fifty patients with BD and a similar number of control individuals were involved in our study. At enrollment, data was collected from patients and controls, and the disease severity in active cases was determined using the Behçet's Disease Current Activity Form (BDCAF). Levels of the two studied biomarkers in the serum, NEAT1 and MALAT1, were investigated by quantitative RT-PCR (qRT-PCR). NEAT1 levels were significantly turned down in BD patients (fold changes = 0.77, p = 0.0001) and correlated negatively with the BDCAF (r = -0.41; p = 0.003). On the other hand, the MALAT1 levels were significantly up-regulated in BD patients (fold changes = 2.65, p = 0.003). Serum levels of NEAT1 were significantly decreased in patients with active states than in stationary cases (0.387 versus 1.99, respectively; p = 0.01) and compared with controls (p = 0.001). Also, NEAT1 levels were significantly increased in patients with stationary states compared to controls (p = 0.03). There was a positive association between NEAT1 and MALAT1 levels among BD patients (r = 0.29, p = 0.04). Our findings demonstrate a possible role of NEAT1 and MALAT1 in the pathogenesis of BD.

Long Non-Coding RNA PVT1 and Its Target miRNA-146a as Potential Prognostic Biomarkers in Rheumatoid Arthritis Patients.

OBJECTIVE: Long non-coding RNAs (lncRNAs) and their target microRNAs were documented in multiple studies to have a significant role in different joint disorders such as rheumatoid arthritis (RA) and osteoarthritis (OA). The current work aimed to determine the potential role of lnc-PVT1 and miR-146a as promising biomarkers to distinguish between RA, OA patients, and healthy individuals. METHODS: The expression levels of lnc-PVT1 and its target miR-146a in the serum were measured for three different groups, including patients with RA (40), OA patients (40), and healthy controls (HCs) (40). Participating individuals were subjected to a full history investigation and clinical examination. Blood samples were tested for ESR, RF, CBC, as well as liver and renal functions. Serum was used to detect the relative expression levels of lnc-PVT1 and miR-146a and we correlated the levels with RA and OA activity and severity signs. RESULTS: Lnc-PVT1 expression level was greater among patients with RA compared to that of OA patients, with a fold change median of 2.62 and 0.22, respectively (p = 0.001). The miR-146a fold change was significantly demonstrated between the RA, OA, and HCs groups. There was no correlation between both biomarkers with the disease activity scales (DAS28) of RA, the Knee injury Osteoarthritis Outcome Score (KOOS), or any sign of detection of the disease severity of OA. CONCLUSIONS: lnc-PVT1 and miR-146a could be considered as promising biomarkers for the diagnosis of RA and OA and may have an important role as therapeutic targets in the future.

Association between CD4+, CD25+, FOXP3+ Regulatory T-cells and Cardiovascular Complications in Diabetic Patients Type 1.

T regulatory cells (Tregs) are a cornerstone regulator for immune responses and inflammatory reactions. Abnormal number or function of Tregs causes deranged immune response that increases the autoimmune disorders and inflammatory conditions. Type 1 diabetes mellitus is an autoimmune disease associated with many complications, of which, Cardiovascular complications are fundamental and responsible for profound morbidity and mortality. Understanding the immunopathogenesis of these disorders allows early diagnosis and better management by innovating new therapeutic targets. In this study, we aimed to detect the association between CD4+CD8+FOX3+ Tregs, T1DM, and associated cardiovascular complications. The study included 144 individuals divided into three groups, group 1 included 48 patients suffering from T1DM without cardiovascular complications, group II: included 48 type T1DM patients with cardiovascular complications. Group III: included 48 healthy control subjects. For all participants, markers for inflammation, and cardiovascular involvement were assessed. The percentage of CD4+ CD25+ FOXP3+ Regulatory T- cells (Tregs) was measured by flow cytometry using peripheral blood samples. The level of Treg was lowest in group II and highest in group III, the difference was highly significant P < 0.001. Treg in group I significantly correlated with age (r= 0.58, P=0.004), CK-mb (r= 0.61, P=0.04) and LDL (r= -.61, P=0.4). While in group II, it correlated with triglyceride level, (r= 0.65 and a P =- 0.02). In conclusion, Lower levels of Tregs are associated with cardiovascular complications in TIDM patients.

Serum fetuin-B level is an independent marker for nonalcoholic fatty liver disease in patients with type 2 diabetes.

OBJECTIVE: Previous studies have assessed serum fetuin-B and its relation to nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) and as a link between them through inducing insulin resistance (IR). Therefore, we examined the potential of serum fetuin-B to be an independent marker for NAFLD in patients with T2DM. PATIENTS AND METHODS: The study group consisted of 270 patients with T2DM. Clinical and laboratory features were evaluated. The NAFLD severity was graded by ultrasound into three subgroups: grade 0 (no fatty liver), grade 1 (mild fatty liver), and grade 2-3 (medium to severe fatty liver). Fetuin-B, retinol-binding protein-4, and adiponectin were measured. RESULTS: Patients with grade 2-3 NAFLD had high fetuin-B levels in comparison with non-NAFLD group. Age and sex adjusted fetuin-B demonstrated positive correlations with triglycerides, γ-glutamyl transferase, fasting plasma glucose, 2-h postprandial plasma glucose, homeostasis model assessment of IR, fasting insulin, glycated hemoglobin, high-sensitivity C-reactive protein, and estimated glomerular filtration rate, but it had a negative correlation with serum creatinine. Adiponectin level was decreased with increasing NAFLD severity, but no difference was found in retinol-binding protein-4. The estimated odds ratio (OR) for the occurrence of grade 2-3 NAFLD was increased significantly with increasing levels of fetuin-B (OR: 3.92; 95% confidence interval: 2.14-8.32 vs. OR: 8.91; 95% confidence interval: 4.22-18.41). The OR of fetuin-B in the uppermost tertile group was still significant after controlling for homeostasis model assessment of IR, glycated hemoglobin, waist circumference, BMI, hepatic enzymes, high-density lipoprotein cholesterol, triglycerides, and high-sensitivity C-reactive protein. CONCLUSIONS: Our study demonstrated that serum fetuin-B had an independent association with NAFLD in patients with T2DM.

Serum endostatin level as a marker for coronary artery calcification in type 2 diabetic patients.

OBJECTIVE: To assess the relationship between serum endostatin (ES) and coronary artery calcification (CAC) in type 2 diabetic (T2DM) patients. METHODS: The study included 110 participants with coronary artery disease (CAD); 55 with T2DM, for serum ES levels by enzyme-linked immunosorbent assay and CAC by contrast-enhanced spiral computed tomography (CT). RESULTS: Mean serum ES value was 66.54 ng/mL [95% confidence interval (CI), 61.77-71.32 ng/mL]. Serum ES levels positively correlated with Agatston score index [ASI; r = 0.701, p < 0.001; high sensitive C-reactive protein (hs-CRP) r = 0.783, p < 0.001]. On multiple regression analysis, the highest three ES quartiles (2, 3, and 4) were related to ASI in diabetic patients, adjusted ES level was an independent predictor of CAD [odds ratio (OR) = 1.065; 95% CI, 1.008-1.126; p = 0.026] and for the number of coronary vessels affected (OR = 1.089; 95% CI, 1.018-1.164; p = 0.013) in T2DM patients. Receiver operating characteristics (ROC) analysis showed serum ES at a cutoff value of 86.5 ng/mL can predict the risk of CAC in T2DM, with a sensitivity of 74.1%, specificity of 71.4%, p < 0.001 and area under curve (AUC) of 0.776. CONCLUSION: Measurement of serum ES levels can improve diagnosis of CAC and could be useful as a high sensitive marker for the presence and progression of atherosclerosis in T2DM patients.

Serum cathelicidin as a marker for diabetic nephropathy in patients with type 1 diabetes.

BACKGROUND: The aim of the study was to evaluate the relationship between serum cathelicidin level and diabetic nephropathy (DN) in patients with type 1 diabetes mellitus (T1DM). METHODS: The study group consisted of 76 patients with T1DM (47 men), aged 36 ± 7 years, and with duration of T1DM 14 (7-18) years. Serum cathelicidin was measured by ELISA test in healthy controls (n = 20) and in 76 T1DM patients grouped as follows: G1 = patients with normal urinary albumin excretion (n = 20), G2 = patients with microalbumin excretion (n = 19), G3 = patients with macroalbumin excretion but normal serum creatinine level (n = 19), and G4 = patients with macroalbumin excretion with increased serum creatinine (n = 18). RESULTS: There was no significant difference in serum cathelicidin levels between healthy controls and G1 diabetic patients, but serum levels were progressively increased from the stage of microalbuminuria to frank nephropathy (P < .001). Positive correlation between serum cathelicidin level and the presence of DN, thyroid-stimulating hormone, total cholesterol, and negative with male sex and fasting plasma glucose, was found. In multiple regression analysis, serum cathelicidin level was associated with the presence of DN after adjustment of sex, waist-to-hip ratio, total cholesterol, and thyroid-stimulating hormone. CONCLUSIONS: Patients with T1DM and DN are characterized by increased serum cathelicidin level. There was an independent relationship between serum cathelicidin level and DN. Serum cathelicidin level can be used as an early marker for the presence and progression of DN in T1DM patients.

Apelin, Nitric Oxide and Vascular Affection in Adolescent Type 1 Diabetic Patients.

AIM: To evaluate the relationship of apelin and nitric oxide (NO) to endothelial dysfunction in type 1 diabetics. PATIENTS AND METHODS: Sixty two type 1 diabetics and 30 healthy age and sex matched controls were included. Blood samples for apelin, NO, glycosylated hemoglobin (HbA1c), and lipid profile were collected. Albumin/creatinine ratio was assessed in urine. Flow mediated dilatation (FMD) via ultrasound was done. RESULTS: The mean age of diabetics were 16.3 ± 1.5 yrs (14.0 - 19.0 yrs), and duration of disease, were 9.4 ± 2.9 yrs (5.0 - 16.5 yrs). FMD and FMD/nitrate mediated dilatation (NMD) ratio were lower in diabetics. NO was decreased, while apelin and albumin/creatinine ratio were increased significantly in diabetics. There was a positive correlation between apelin and HbA1c. On the contrary, NO had a negative correlation with HbA1c, albumin/creatinine ratio, LDL-c and OxLDL. CONCLUSION: Diabetic patients had endothelial dysfunction and high apelin level, with no related to each other. High level of apelin is associated with bad glycemic control. Obesity had no role to increase in apelin level. NO is related to diabetic nephropathy and atherosclerosis. We recommend a further large study to evaluate the relationship of apelin with endothelial dysfunction.

A long-term study of bone mineral density in patients with phenylketonuria under diet therapy.

INTRODUCTION: Dietary control of classic phenylketonuria (PKU) needs restriction of natural proteins; adequate protein intake is achieved by adding low phenylalanine (phe) formulae. The adequacy of this diet for normal bone mineralization had not been sufficiently evaluated. Our aim was to evaluate and follow up bone mineral density (BMD) in children and adolescents with PKU within a 2-year time interval to assess the adequacy of a phenylalanine restricted diet for bone mineralization and to search for a possible relationship between BMD, dietary control and blood phenylalanine (phe) concentrations. MATERIAL AND METHODS: Thirty-two patients with classic PKU (3-19 years) were evaluated for their bone mineral status using dual energy X-ray absorptiometry (DEXA) both at the beginning (baseline) and the end (follow-up) of the study. RESULTS: Low BMD was detected in 31.25% at the start and in 6.25% of patients after 2 years follows-up. No relationship was found between BMD and the duration of diet compliance and phe level as well. CONCLUSIONS: In this study the low BMD detected in our patients was both at baseline and follow-up independent of diet restriction. A yearly DEXA would be highly beneficial for early detection and treatment, thus preventing osteoporosis and decreasing the risk of fractures. We also suggest the importance of searching for new emerging therapies such as enzyme substitution or gene therapy as low protein diet compliance was not enough to maintain normal bone mineral density.