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The region encoding the N-terminal of human β2-adrenergic receptor gene ( ADRB2 ) shows several polymorphisms. To this end, we studied change in susceptibility and/or response to therapy in 175 asthmatic children and adolescents by the two most common variants of the ADRB2 gene namely, rs1042713 (Gly16Arg) and rs1042714 (Gln27Glu). Although, the variants did not correlate with risk of development nor with the severity of the asthma, Gly16/Glu27 haplotype in homozygous individuals conferred protection against development of asthma and was associated with a lower frequency of dyspnea and sputum production. In contrast, the Arg16/Gln27 haplotype was associated with a better response to treatment. These findings show that the risk of development of asthma or response to treatment can be, respectively, deciphered by the detection of both rs1042713 and rs1042714 variants in ADRB2 gene.

Glioblastoma (GB) represents the most common malignant brain tumor, which, despite extensive research, remains of poor prognosis. The focus of recent studies of GB pathogenesis has shifted to the study of the role of noncoding RNAs (ncRNAs). In this study, we examined the expression levels of the microRNA miR-326 and the long ncRNA H19 (on which a miR-326 putative binding site was found by in-silico analysis) in brain tumor tissue from GB patients as compared to cancer-free brain tissue. Relative expression levels of miR-326 were not found to be significantly altered in GB patients. By comparison, H19 was consistently over-expressed in all GB patients ( p < 0.001), and correlated with poorer overall survival (OS) and progression-free survival (PFS) ( p = 0.026 and p = 0.045, respectively). At a cutoff value of 5.27, H19 up-regulation could predict OS in GB patients, with a 71.4% sensitivity and 59.6% specificity ( p = 0.026). The current GB patients were clustered by the multivariate analysis into 4 groups based on miR-326 and H19 expression profiles, age at diagnosis, and PFS. Our data suggest a role for H19 in the pathogenesis of GB and could be a potential prognostic biomarker for GB.

Interleukin-17 (IL-17) is a critical cytokine involved in inflammation-associated cancers. Single nucleotide polymorphisms (SNPs) might promote carcinogenesis. In this current meta-analysis, we investigated the association of IL-17A and IL-17F gene polymorphisms with gastric cancer (GC) risk. Eligible genetic association studies were retrieved from PubMed, Web of Science and Scopus database sources. Two reviewers independently assessed methodological quality and extracted data from eligible articles. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Quantitative data synthesis was conducted using comprehensive meta-analysis v2. Subgroup analysis and heterogeneity analysis were performed. Begg's funnel plot and Egger's regression tests were used to judge publication bias. In silico data analysis was executed to analyze the functional and structural impact of the SNPs. A total of 21 case-control studies for rs2275913 c.-197G > A (7660 patients and 9409 controls), 9 studies for rs3748067 c.*1249C > T (3378 patients and 4120 controls), and 14 studies for rs763780 c.482A > G (4481 patients and 5354 controls) were included. The pooled estimate revealed an association between IL-17A rs2275913 polymorphism and the risk of GC under all genetic models (A vs. G, OR 1.187, 95% CI 1.086-1.297, P < 0.001; GA vs. GG, OR 1.108, 95% CI 1.008-1.218, P = 0.033; AA vs. GG, OR 1.484, 95% CI 1.236-1.781, P < 0.001), while no evidence of association was found with IL-17A rs3748067 or IL-17F rs763780 polymorphisms. Our results showed that IL-17A promoter rs2275913 variant might represent a potential risk factor for gastric cancer susceptibility.

Spirulina platensis (SP) is a traditionally used microalga for a wide range of pharmacological activities, including amelioration of heavy metals and pesticides toxicity. This study evaluated the antioxidant and organoprotective effects of SP against diazinon (DZN)-induced subacute toxicity on the blood, heart, liver, and kidneys of male Wistar albino rats. Diazinon (20 mg/kg, subcutaneous) was administered to animals either alone or along with an oral pure SP powder at doses of 500 and 1000 mg/kg. Alterations in hematological and serum biochemical parameters, as well as oxidative stress markers in the hepatic, renal, and cardiac tissues were evaluated, using colorimetric spectrophotometric techniques. The obtained results revealed that in comparison to the control group, DZN-treated rats exhibited significantly lower (p < 0.05) red blood cells and platelets counts, hemoglobin and hematocrit values, and activities of serum acetylcholinesterase and tissue antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase). Meanwhile, biochemical analysis showed significantly higher (p < 0.05) white blood cells count, serum concentrations of tumor necrosis factor-α and cardiac [creatine kinase (CK) and CK-muscle/brain fraction], hepatic [transaminases and alkaline phosphatase], and renal [uric acid, urea and creatinine] injury markers, and tissue levels of malondialdehyde (a marker of lipid peroxidation) in the DZN-intoxicated group, compared to normal controls. Interestingly, the administration of SP significantly ameliorated the previous hemato-biochemical alterations and mitigated DZN-induced organ injuries and oxidative stress. In conclusion, the natural antioxidant microalga (SP) effectively alleviated the DZN-induced hematologic alterations and organ injuries, probably through its antioxidant and anti-inflammatory activities.

Fipronil (FPN) is a phenylpyrazole insecticide, widely used for agricultural and veterinary activities. Early reports indicated that FIP organ toxicity is primarily mediated by the induction of oxidative stress. Both thymoquinone (TQ) and diallyl sulfide (DAS) are natural antioxidants with established health benefits. This study investigated the potential ameliorative effects of DAS and TQ against FPN-induced toxicity in rats. Thirty-two male Wistar rats (150-180 g) were randomized into four treatment groups, receiving (I) saline, (II) FPN (10 mg/kg bw), (III) FPN with DAS (200 mg/kg bw), and (IV) FPN with TQ (10 mg/kg bw). All treatments were administered once daily for 28 days. The results showed that compared to the control rats, FPN-treated rats had significantly increased (p < 0.05) serum levels of uric acid, urea, creatinine, cholesterol, aspartate transferase, alanine transferase, alkaline phosphatase, lactate dehydrogenase, and γ-glutamyl transferase. Moreover, FPN significantly reduced (p < 0.05) the serum levels of total proteins, albumin, and triglycerides. In addition, compared with the control group, FPN-treated rats had significantly elevated (p < 0.05) malondialdehyde and nitric oxide levels, as well as significantly reduced glutathione concentration and activities of glutathione peroxidase, superoxide dismutase, and catalase enzymes in the hepatic, renal, and brain tissues. Cotreatment with DAS or TQ significantly ameliorated (p < 0.05) the FPN-induced alterations in all the previously mentioned parameters with more frequent restoration of normal control ranges in the TQ group. In conclusion, both DAS and TQ alleviated the oxidative injury of FPN, probably by enhancing tissue antioxidant defenses.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality worldwide. The oncogenic function of the long non-coding RNA; metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in HCC remains unclear. We aimed to evaluate MALAT1 serum expression profile in HCC and explore its relation to the clinicopathological features. Quantitative Real Time-Polymerase Chain Reaction was applied in 70 cohorts (30 HCC, 20 HCV, 20 controls). Further meta-analysis of clinical studies and in vitro validated experiments was employed. Serum MALAT1 showed area under the curve of 0.79 and 0.70 to distinguish patients with cancer from normal and cirrhotic individuals at fold change of 1.0 and 1.26, respectively. Expression level was significantly higher in males (P <0.001) and patients with massive ascites (P = 0.005). Correlation analysis showed positive correlation of MALAT1 with total bilirubin (r = 0.456, P <0.001) and AST (r = 0.280, P = 0.019), and negative correlation with the hemoglobin level (r = 0.312, P = 0.009). Meta-analysis showed that the over-expressed MALAT1 was linked to tumor number [Cohen's d = 0.450, 95% CI (0.21 to 0.68)], clinical stage [Cohen's d = 0.048, 95% CI (-0.83 to 0.74)], and AFP level [Cohen's d = 0.354, 95% CI (0.1 to 0.57)]. In silico data analysis and systematic review confirmed MALAT1 oncogenic function in cancer development and progression. In conclusion, circulatory MALAT1 might represent a putative non-invasive prognostic biomarker indicating worse liver failure score in HCV-related HCC patients with traditional markers. Large-scale verification is warranted in future studies., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Prolongation of QT interval is possible with fluoroquinolones, yet the underlying contributing factors have not been elucidated. Two widely used fluoroquinolone drugs were at the focus of this study in rats with/without acute myocardial dysfunction (AMI) induced by isoproterenol. The effects of levofloxacin and ciprofloxacin on the cardiac mRNA expression of rat Kv4.3, Kv1.2 and Nav1.5 mRNAs were determined. Administration of the two antibiotics produced dose-dependent changes in ECG parameters that were more prominent in rats with AMI than healthy rats; this was accompanied by elevations in serum lactate dehydrogenase and creatine kinase-MB. Histopathological examination indicated some loss of striations, edema and fibrotic changes in rats with AMI; however the two antibiotics did not further exacerbate the cardiac histopathology. mRNA expression of the ion channels was altered in rats with AMI and healthy rats. In conclusion, long-term administration of levofloxacin and ciprofloxacin produced deleterious effects on the ECG pattern of rats with/without AMI. The effect was generally baseline-dependent and therefore, rats with AMI showed greater ECG disturbances and increases in cardiac enzymes. Taken together, these data make it advisable to monitor patients with a history of acute AMI requiring treatment with these antibiotics until data from human studies are available., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: MicroRNAs (miRNAs) have been linked to cancer development and progression. The molecular mechanisms underlying the genetic associations of the miRNA single nucleotide polymorphism with cancer vary by cancer site. As there are no previous studies on the miR-196a2 variant or expression in any type of cancer among our population, we aimed to determine the expression profile of mature miR-196a2 in various types of solid tumors and to analyze the impact of its polymorphism (rs11614913; C/T) on the expression levels., Materials and Methods: The study included 230 cancer patients (including 17 types of cancer), 26 patients with pre-cancer lesions, and 100 unrelated controls. Archived formalin-fixed, paraffin-embedded specimens (n = 197) were available for both miRNA expression analysis and single nucleotide polymorphism identification. Venous blood was collected from 59 histologically confirmed sporadic cancer patients and the study controls for single nucleotide polymorphism identification. Real-time polymerase chain reaction analysis was performed for allelic discrimination and relative quantification of miR-196a2 in the study samples. In silico target gene prediction and network analysis was performed., Results: We found that individuals with the T variant were associated with cancer risk under all genetic association models, especially in colorectal, esophageal, skin, lung, thyroid, and renal cancer. Overall and stratified analysis showed miR-196a2 over-expression in most of the current malignant tumor samples relative to their corresponding cancer-free tissues. Carriers of the C allele had significantly higher expression levels of miR-196a2. Correlation with the clinicopathological features of cancer showed organ-specific effects. Gene enrichment analysis of predicted and validated targets speculated the putative role of miR-196a2 in cancer-associated biology., Conclusions: We highlighted cancer-type specific expression profiles of miR-196a2, which was correlated with the clinicopathological features in various types of cancer. Taken together, our results suggest that the miRNA signature could have promising diagnostic and prognostic significance.

Stem cell transcriptional signature activation is an essential event in the development of cancer. This study aimed to investigate the differential expression profile of three pluripotency-associated genes ( OCT4 , NANOG , and SOX2 ), G-protein-coupled chemokine receptor 4 ( CXCR4 ) and the ligand ( CXCL2 ), and alpha feto-protein ( AFP ) in hepatogenic differentiated stem cells and in sera of hepatitis C virus (HCV) and HCV-induced hepatocellular carcinoma (HCC) patients. Mesenchymal stem cells derived from umbilical cord blood were differentiated using hepatogenic differentiation media. Serum specimens were collected from 96 patients (32 cirrhotic HCV, 32 early HCC, and 32 late HCC) and 96 controls. Real-time quantitative reverse transcription polymerase chain reaction was performed for relative quantification of the 6 target genes using LIVAC method. In silico network analysis was also executed to explore the pluripotency and tumorigenic regulatory circuits in liver cancer. The expression levels of all genes declined gradually during the stages of stem cell differentiation. On univariate and multivariate analyses, NANOG , CXCR4 and AFP were significantly up-regulated in HCC patients with late clinical stage. In contrast, SOX2 and CXCL2 were markedly over-expressed in cirrhotic patients and could be used for clear demarcation between cirrhotic and HCC patients in our cases. In conclusion, our data highlight the potential role of SOX2 stem cell marker and CXCL2 chemokine in liver cell degeneration and fibrogenesis in HCV-induced hepatic cirrhosis in our sample of the Egyptian population. In addition, the significant association of NANOG and CXCR4 high-expression with late HCC, could contribute to the acquisition of stem cell-like properties in hepatic cancer and dissemination in late stages, respectively. Taken together, our results could have a potential application in HCC prognosis and treatment.

There is emerging evidence to support the role of microRNAs in allergic airway diseases and inflammation. Genetic variants in microRNA genes might affect microRNA-mediated cell regulation. This preliminary study was designed to investigate the association of the microRNA-196a2 rs11614913 (C/T) polymorphism with susceptibility to asthma and clinical outcomes in children and adolescents. Genotyping of rs11614913 polymorphism was determined in 96 patients with bronchial asthma (6-18 years of age) and 96 unrelated controls, using real-time polymerase chain reaction technology. In-silico target prediction and network core analyses were performed. The asthmatics did not show significant differences in genotype distribution (p = 0.609) and allele frequencies (p = 0.428) compared with the controls. There were also no associations with disease duration, age at onset, asthma phenotype, asthma control, therapeutic level, airway hyper-responsiveness, or biochemical parameters in the blood. However, the CC genotype was associated with a more severe degree of asthma (p = 0. 023) and higher frequency of nocturnal asthma (p = 0.002). Carriers for CC were 17 times more likely to develop nocturnal asthma, and had a more than 2.5-fold increased risk for poor disease outcome compared with CT and TT individuals. In conclusion, microRNA-196a2 rs11614913 polymorphism might be associated with asthma severity in our sample of the Egyptian population. Further investigations in studies with a larger sample size and functional tests are needed to validate our findings and to explore the detailed biological mechanisms.

NAD + -dependent Isocitrate Dehydrogenase (NAD + -IDH) could be one of the cell phone radiation targets. Enzyme activity alteration may lead to decline in sperm motility during radio-frequency electromagnetic waves (RF-EMW) exposure. The current case control study aimed to investigate the possible relationship between mitochondrial NAD + -IDH activity in human seminal plasma and sperm motility among asthenozoospermic cellular phone users. A total number of ninety idiopathic infertile males referred from the Department of Dermatology and Andrology, were enrolled in this study. NAD + -IDH activity was measured in human seminal plasma by spectrophotometer. Computer-aided sperm analysis (CASA) following WHO criteria has been used for semen analyses. The results showed that IDH activity was increased in patients with prolonged cell phone daily use ≥4 h/day. Its level, correlated negatively with either the motility ratio percentages (r = -0.46, p  < 0.001) or the progressive motility percentages (r = -0.50, p  < 0.001) in the study groups. The current study suggests that NAD + -IDH in human seminal plasma could be one of seminal plasma biomarkers reflecting the mitochondrial function of spermatozoa. Alteration of its level could reflect the defective motility of sperms among some cases of cellular phone users.

Introduction: Rheumatoid arthritis (RA) has a complex component induced by several genes that interact together with environmental and hormonal factors. We aimed to investigate the association of miR-196a2 rs11614913 (C/T) and miR-499a rs3746444 (A/G) polymorphisms and their combination with RA susceptibility and disease activity in an Egyptian population, and to evaluate their impact on methotrexate drug response and toxicity., Materials and Methods: Bioinformatics databases were searched to select potential micro RNA (miRNA)-messenger RNA (mRNA) interactions involved in RA pathogenesis. Ninety-five RA patients diagnosed according to the American College of Rheumatology and 200 healthy controls were genotyped using real-time polymerase chain reaction technology., Results: In overall and stratified analysis, miR-499a, but not miR-196a2, was associated with RA risk. Heterozygote carriers with rs3746444*A/G displayed protection against developing RA (p = 0.005) with an odds ratio of 0.2 (95 % confidence interval 0.17-0.62). The carriage of the combinations (miR499a*AG + miR196a2*CC) and (miR499a*AA + miR196a2*TT) were 3 and 7.5 times more likely to develop RA, respectively, while the combinations (miR499a*GG + miR196a2*CC), (miR499a*AG + miR196a2*TT) and (miR499a*AA + miR196a2*CT) show less susceptibility to have RA disease (all p < 0.05). rs3746444*AA genotype had a higher disease activity score (DAS28) [p = 0.023], tender joint count (TJC) (p = 0.007), and methotrexate-induced gastrointestinal toxicity (p = 0.043) compared with both AG/GG genotypes. rs11614913*C carriers were associated with higher DAS28 activity (p = 0.021). Homozygote male patients (CC and TT) had higher TJC (p = 0.046) and higher rheumatoid factor levels (p = 0.026), whereas, TT homozygote females had higher levels of ALT (p = 0.022)., Conclusions: Different genotypes of miR-499a rs3746444 single nucleotide polymorphisms (SNPs) are associated with RA risk, disease activity, and methotrexate toxicity in our population. In combination with specific miR-196a2 rs11614913 genotypes, this risk could increase or decrease according to the type of combination. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.

Introduction: Obesity is a serious medical condition that affects children and adolescents. ATP-binding cassette transporter A1 (ABCA1) protein is known to mediate the transport of intracellular cholesterol and phospholipids across the cell membranes. Thus, we aimed to investigate the association between ABCA1 gene polymorphisms and overweight/obesity risk, and to evaluate their relation to the lipid profile., Materials and Methods: The study included in silico analysis of ABCA1 gene and protein. Two genetic variants in ABCA1 gene-R219K (rs2230806; G/A) and I883M (rs2066714; A/G)-were genotyped in 128 normal weight and 128 overweight/obese subjects using polymerase chain reaction-restriction fragment length polymorphism technology. Anthropometric and biochemical assessments were performed., Results: Our findings suggest that the heterozygote GA genotype of R219K polymorphism increased susceptibility to obesity under the heterozygous model (odds ratio 2.75, 95 % CI 1.01-6.12; p = 0.014) compared with the control group. This susceptibility could be gender-specific, with higher risk among females. In addition, the A variant was associated with a higher degree of obesity (p < 0.001). On the other hand, individuals with the G variant of I883M polymorphism showed lower susceptibility to obesity under all genetic models (allelic, homozygote, heterozygote, dominant, and recessive models; p < 0.05), with no observed association with body mass index or degree of obesity. However, both single nucleotide polymorphisms (SNPs) showed significant differences in lipid levels among patients with different genotypes., Conclusions: The study results suggest that R219K and I883M SNPs of the ABCA1 gene may play a role in susceptibility to obesity in our Egyptian population; the former increases susceptibility and phenotype severity, and the latter is protective. Larger epidemiological studies are needed for validation of the results.

Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance, oxidative stress, and cytokine imbalance. Boswellic acids, a series of pentacyclic triterpene molecules that are produced by plants in the genus Boswellia, has been traditionally used for the treatment of a variety of diseases. This study aimed at evaluating the protective effect of boswellic acids in a model of diet-induced NAFLD in rats in comparison to the standard insulin sensitizer, pioglitazone. Rats were fed with a high-fat diet (HFD) for 12 weeks to induce NAFLD. Starting from week 5, rats received boswellic acids (125 or 250 mg/kg) or pioglitazone parallel to the HFD. Feeding with HFD induced hepatic steatosis and inflammation in rats. In addition, liver index, insulin resistance index, activities of liver enzymes, and serum lipids deviated from normal. Further, serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and cyclooxygenase 2 were elevated; this was associated with an increase in hepatic expression of inducible nitric oxide synthase (iNOS) and formation of 4-hydroxy-2-nonenal (HNE). Rats treated with boswellic acids (125 or 250 mg/kg) or pioglitazone showed improved insulin sensitivity and a reduction in liver index, activities of liver enzymes, serum TNF-α and IL-6 as well as hepatic iNOS expression and HNE formation compared to HFD group. Furthermore, at the cellular level, boswellic acids (250 mg/kg) ameliorated the expression of thermogenesis-related mitochondrial uncoupling protein-1 and carnitine palmitoyl transferase-1 in white adipose tissues. Data from this study indicated that boswellic acids might be a promising therapy in the clinical management of NAFLD if appropriate safety and efficacy data are available.

This study aimed to investigate thrombin-activatable fibrinolysis inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen (Ag) levels in breast cancer (BC) in the Egyptian population to clarify their role in relation to BC. A group of 300 females was recruited in this study; of these 150 unrelated patients with different stages of BC and 150 age-matched healthy controls. Plasma TAFI Ag was measured by ELISA and TAFI Thr325Ile (rs1926447) polymorphism was genotyped using TaqMan single nucleotide polymorphism (SNP) genotyping assay. The results showed the genotypes of the minor allele; Thr/Ile (CT) and Ile/Ile (TT) were significantly more frequent in patients compared to control group (50.0% and 22.0% vs. 42.0% and 13.3%, respectively) and were also associated with BC susceptibility [OR = 1.9 and 2.6; 95% CI: (1.1-3.3) and (1.3-5.5), respectively P = 0.01]. Ile325 allele carriers were more frequent in cases than in controls (47.0% vs. 34.0%) [OR = 1.7, (95% CI = 1.2-2.4), P = 0.001]. However, TAFI Thr325Ile polymorphism was not associated with BC stage or other clincopathological characteristics. TAFI Ag levels were correlated with advanced stages of BC, poor prognosis and risk of recurrence (P = 0.02, P = 0.04 and P  < 0.001, respectively) and Thr325Ile SNP was significantly correlated with TAFI antigen levels with the C/C genotype corresponding to the highest and the T/T genotype to the lowest TAFI antigen levels (P < 0.001) in the study groups. In conclusion, this study showed for the first time that TAFI Thr325Ile polymorphism could have a contribution to BC susceptibility in our population. Furthermore, high TAFI plasma levels may serve as a predictor of poor prognosis in patients with BC.