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The benchmark of this study is to evaluate the antioxidant protective efficiency of Diosmin-Hesperidin combination, a natural citrus flavone of hesperidin derivative on heavy metals intoxication and Oxidative stress-induced damage in Wistar albino rats. Oral doses of diosmin-hesperidin in rats (200 and 100 mg/kg body weight, respectively) for a month (every other day) prior to heavy metals intoxication. Evaluation of the protective and antioxidant effects of the combination of diosmin and hesperidin, various Rt-PCR estimations, biochemical estimations, histopathological alterations as well as comet assay and caspase-3 activity for assessment of apoptosis were performed. Results indicated that heavy metals intoxication-induced decline in the levels of liver tissue P53 gene expression and increase of liver tissues of the apoptotic caspase-3 gene, also induced decline in the levels of liver tissue antioxidant parameters (SOD, GPx, and GSH), increased lipid peroxidation (MDA), DNA damage and apoptosis, these parameters were improved by pre-administration of diosmin+hesperidine. Diosmin+hesperidine dose (200 and100 mg/kg body wt. respectively) restored the p53 and caspase-3 genes near-normal values, antioxidant status to near normal and reduced lipid peroxidation, DNA, and tissue damage. These results were confirmed by histopathological examinations, which showed that pre-administration of diosmin+hesperidine protected the liver of albino rats against heavy metals intoxication-induced damage. Hence, it has been illustrated that diosmin+hesperidine might be an effective antioxidant and protector against heavy metals intoxication-induced damage in rats. Moreover, the diosmin+hesperidine alone pretreated group did not show any biochemical alterations, fold change of P53 or caspase-3 genes or DNA damage indicating the protective nature of the drug.

A comparative field study was performed to assess the heavy metals contamination in surficial sediments of highly and less polluted zones at the northern part of the Suez Gulf. In addition, to highlight the relationship among metal contamination and enzyme activity. Seven heavy metals Mn, Fe, Pb, Cd, Zn, Ni, and Cu were analyzed using atomic absorption spectrophotometer. The activity of enzymes (alkaline phosphatase and urease) was estimated in the sediment samples. The statistical results showed that there were high significant differences at p ≤ 0.01 among Cu, Pb, Cd, Ni, Mn and Zn between highly polluted and less polluted sediments. Urease activity had no significant relationship with the tested metals concentrations. Cd, Cu, Mn, Ni, Pb and Zn may inhibit alkaline phosphatase activity. Alkaline phosphatase activity showed high significant difference at p ≤ 0.01 between summer and winter seasons in highly polluted sediment. Moreover, there was significant seasonal difference in Pb concentration at p ≤ 0.01 in the same category. Correlations of the enzymes with each metal showed that alkaline phosphatase activity had significant negative correlation coefficients (r = −0.55, −0.49, −0.27, −0.37, −0.37, and −0.60) with Cu, Cd, Fe, Ni, Zn and Pb respectively in winter, but only with Zn (r = −0.46) in summer season. As a result, ALP activity can possibly be used as a predictor and sensitive indicator of heavy metals bioavailability in marine sediments.

Background Systemic lupus erythematosus (SLE) patients have lower bone mineral density (BMD) compared with healthy individuals because of general, genetic, disease and medication-related factors. The disturbance of the receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio has been reported to be associated with low BMD in many disorders in adults and children alike. Objectives The objectives of this study were (i) to assess serum OPG, RANKL and RANKL/OPG ratio levels in SLE children and controls, (ii) to determine whether the cumulative glucocorticoid (CGCS) dose had any effect on the concentration of serum RANKL, OPG and RANKL/OPG ratio, and (iii) to determine the relation of these parameters to BMD. Methods We evaluated 50 SLE children and 50 age- and sex-matched healthy controls. RANKL and OPG were assessed in serum and compared between patients and controls. For SLE patients, a univariate followed by multivariable analysis were carried out to detect the possible predictors of the changes in RANKL, OPG and RANKL/OPG ratio levels. Lumbar BMD for all patients was assessed by dual-energy X-ray absorptiometry (DXA) scan and then correlated to different probable correlated factors. Results RANKL, OPG and RANKL/OPG ratio were significantly higher in SLE patients ( p ≤ 0.001). Univariate analysis showed significant correlations of RANKL with CGCS ( p ≤ 0.001) and with DXA scan z-score ( p = 0.007): OPG was significantly correlated to Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ( p = 0.001) and anti-double-stranded DNA ( p = 0.001), whereas RANKL/OPG was significantly correlated to duration of illness and DXA z-score ( p = 0.002). The multivariable analysis showed that DXA z-score was an independent predictor of RANKL and RANKL/OPG ratio ( p = 0.019 and 0.008, respectively), whereas SLEDAI score was an independent predictor of OPG levels. BMD was negatively correlated to disease duration ( p = 0.008) and CGCS dose ( p = 0.015), but no significant correlation has been found between BMD and cumulative SLEDAI score ( p = 0.29). Conclusions Serum RANKL/OPG ratio is elevated in Egyptian children with SLE and is considered a risk factor for reduced bone mass in these children. Other risk factors for low BMD include high CGCS dose and disease duration, supporting that osteoporosis in SLE is multifactorial.

Background Micro-RNAs (miRNAs) are evolving as biological markers for multiple sclerosis (MS) both in activity and remission. miR-96 is associated with remission, however, the exact mechanism through which it contributes to the anti-inflammatory pathway is not clear. Objective To study the expression of miR-96 and IL-10 (anti-inflammatory mediator) in relapsing remitting (RR) MS. Subjects and methods A case control study including 32 RRMS patients from Kasr Al-Ainy MS clinic, Cairo University, Egypt, and 26 healthy controls (HC). Assessment of serum IL-10 by ELISA, and miR-96 via real time PCR was done during relapse and remission in patients, and in HC. Results IL-10 was higher in RRMS patients during remission and in HC compared with relapse (P ˂ 0.001). miR-96 expression was higher in RRMS patients during remission compared with relapse and HC, and was higher in HC than in relapse (P ˂ 0.001). IL-10 level in remission correlated positively with disease duration (r = 0.41; P = 0.02). Otherwise, no correlation was found between IL-10 and relapse number or EDSS (P>0.05). miR-96 in relapse negatively correlated with EDSS in relapse (r=−0.47; P=0.007), but no correlation was found with disease duration or relapse number, whereas, miR-96 in remission did not correlate with any clinical parameters (P>0.05). No correlation was found between IL-10 and miR-96 either in relapse or remission (P>0.05). Conclusion IL-10 and miR-96 are associated with MS quiescence, however, the lack of a significant correlation between them implicates that the influence of miR-96 may be exhibited through some pathway other than IL-10.

Bladder urothelial carcinoma (BUC) is a chronic relapsing urological malignancy, which poses a serious threat to human life. Non-resolving chronic-inflammation at the neoplastic site is associated consistently with inducing tumor-progression and poor patient outcomes. Interleukin 23 receptor (IL-23R) is a key element in T-helper 17 cell-mediated inflammatory process, that plays a critical role in orchestrating tumor-promoting inflammation. Therefore, we hypothesized that potentially functional genetic variant rs1884444 G/T of IL-23R may modify BUC risk. To validate this hypothesis, our findings demonstrated that the rs1884444 G/T variant was significantly associated with a reduced risk of BUC compared to controls observed under allelic (T vs. G) and dominant (GT + TT vs. GG) models (P 0.05). In addition, the frequency of the T-allele has dropped to very low values in the case of high-grades and invasive-tumors (P 0.05). Thus, T-allele has emerged as a reliable genetic marker for good prognosis of BUC. In tumorgenesis, the binding-affinity of the receptor seemed to be distorted by the effect of the non-conservative G/T variation, which in turn caused the IL-23/IL-17 pathway to be disabled. This was recognized by low levels of IL-23 and IL-17 in the serum of patients, under the influence of all the tested genetic models (P 0.01). Results also indicated that the level of the receptor-bearing immune cells could be altered in response to the G/T protective effect. For example, the median counts of T-helper CD4

The involvement of micro RNAs (miRNAs) in multiple sclerosis (MS) has been recently explored. Up-regulated miRNAs may play critical roles in MS pathogenesis and may be used as a signature for MS. Besides, the role of inflammatory cytokines has been long established with recent focus on interleukin-17 (IL-17).To evaluate the level of expression miR-18b in relation to IL-17A in relapsing remitting (RR) MS patients during relapse and remission SUBJECTS AND METHODS: Twenty-eight RRMS patients and 26 age and sex matched control subjects were included. Serum miR-18b was assessed by quantitative real-time PCR, and serum level of IL-17A was measured by ELISA.Serum miR-18b expression was higher in relapse compared with remission and with controls (24.8 ± 21.91 vs 2.49 ± 0.97 vs 1 ± 0.36 respectively; P 0.001). Serum IL-17Awas higher in MS patients during relapse than during remission and controls (8.49 ± 1.26 vs 5.78 ± 2.27 vs 4.18 ± 2.13, respectively; P 0.001). No correlations existed between miR-18 and IL-17 in MS patients during relapse (r = 0.35; P = 0.22) or remission (r = 0.340; P = 0.234).Upregulation of miR-18 during relapse in patients with RRMS points to a possible contribution to the pathogenesis of the inflammatory process in MS. The lack of a significant correlation between upregulated miR-18 and IL-17A implicates that the influence of miR-18 may be exhibited via another inflammatory pathway.

Background IL-23 is a pro-inflammatory cytokine belonging to the IL-12 cytokine family. IL-23 is essential for the differentiation of Th17 lymphocytes, a subtype of T lymphocyte implicated in chronic inflammatory/autoimmune mediated diseases. Experimental models of arthritis and clinical indications have highlighted an important role for Th17 lymphocytes in the pathogenesis of RA. However the role and mechanism of action of IL-23 in the pathogenesis of RA are still not fully understood. Objective This study was conducted to assess the level of IL-23 in patients with RA as well as the relationship between the IL-23 level and disease activity. Methods The study includes 77 patients with RA fulfilling the American College of Rheumatology (ACR) revised criteria for diagnosis of RA as well as 25 age and sex matched healthy subjects as controls. Patients were divided according to disease activity into four groups: DAS 28 score (˂ 2.6), 10 patients in remission, DAS 28 score between 2.6–3.2, 10 patients with low disease activity, DAS 28 score ranges between (3.2–5.1), 30 patients with moderate disease activity and DAS 28 score (˂ 5.1), 27 patients with High disease activity. Disease activity were determined by the 28-joint disease activity score (DAS 28). Anti-citrullinated protein antibodies (ACPA) was done. The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA). Results Serum level of IL-23 was significantly elevated in RA patients (78.92 ± 52.47) compared to control group (33.34 ± 3.99) (P and other patients characteristics . Conclusion Our results imply that IL-23 may potentially play a role in the pathogenesis of RA and may be a useful biomarker for the diagnosis of this disease. Targeting the IL-23 cytokine may provide a new therapeutic approach in the treatment of RA.

BackgroundThe incidence of metabolic syndrome (MetS) increases in rheumatoid arthritis (RA) patients which increases the risk of cardiovascular disease (CVD). Angiopoietin-2 levels increase in RA and were reported to predict CVD.Aim of the workTo assess the level of angiopoietin-2 in RA patients and study its relation to disease activity and its role in those with MetS.Patients and methodsThe study included 80 RA patients (67 females and 13 males) and 20 healthy age and sex matched controls. The patients were divided into Group 1 (n=40) with MetS and Group 2 (n=40) without. Data were collected throughout history, basic clinical examination and investigation. Disease activity score (DAS-28) was assessed in all patients. Enzyme linked immunosorbent assay was used for the estimation of angiopoietin-2.ResultsThe age and disease duration of those with MetS (40.7±7.23years and 9.63±6.73years respectively) and those without (38.6±9.2 and 8.65±5.52years respectively) were comparable (p=0.26 and p=0.48 respectively). The disease activity (DAS-28) was also similar in both groups (5.12±0.77 and 5.01±0.96 respectively; p=0.56). There was a significant increase in the angiopoietin-2 levels in RA patients with MetS (5.31±0.56ng/ml) than those without (4.93±0.44ng/ml) (p

Background Cytokines are major contributors in the immune disruption in multiple sclerosis (MS). Objective Evaluating the proinflammatory (IL-17A) and anti-inflammatory (IL-10) cytokines in relapsing-remitting (RR) MS patients at time of relapse and during remission. Subjects and method A case-control study including 30 RRMS patients and 15 controls. Patients were recruited from the Kasr Al-Ainy MS research unit (KAMSU), Cairo University, Egypt. Levels of IL-17A and IL-10 were assessed in patients' sera, during relapse and 30 days after IV methylprednisolone, and in control subjects using enzyme linked immunosorbent assays (ELISA). Results IL-17 was higher in patients during relapse and remission phases when compared with controls (P = 0.001), whereas, IL-10 was higher in patients during remission but normal during relapse (P = 0.01; 0.86 respectively). IL-17 increased during relapses (P = 0.001) while IL-10 increased during remissions (P = 0.028). No significant correlations were found between both interleukins and age at onset; disease duration, number of relapses; or EDSS. Conclusion RRMS patients can have a regulatory imbalance between both pro-and antiinflammatory cytokines, which could be a target for treatment strategies rather than focusing on a single cytokine.