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Background: Diabetes mellitus is a known risk factor for stroke and may be linked to poorer post-stroke outcomes. However, the underlying molecular mechanisms remain to be fully identified. In this study we assessed the association of the lncRNA Nuclear enriched abundant transcript 1 ( NEAT1 )'s expression and its target miRNA-124 with acute ischemic stroke (AIS) in type II diabetic patients (T2DM). Methods and Results: Diabetic patients with stroke, non-diabetics with stroke, diabetics without stroke, and controls were recruited. NEAT1 and miR-124 expression levels in plasma samples from the participants were investigated using real-time reverse transcription-polymerase chain reaction (RT-qPCR). C reactive protein (CRP) and tumor necrosis factor alpha (TNF-α) were measured using an enzyme linked immunosorbent assay (ELISA) technique. In the DM+AIS group, NEAT1 expression was considerably higher, compared with AIS group and with control group. In comparison to the AIS-only patients, DM patients and controls, miR-124 expression was considerably lower in the DM+AIS group. NEAT1 was shown to have good predictive value for AIS risk in diabetics, based on Receiver Operating Characteristic (ROC) curve analysis. In both the DM+AIS and the AIS group, NEAT1 levels was strongly linked with the National Institutes of Health Stroke Scale (NIHSS) score. Also, a significant positive correlation was observed between NEAT1 expression and the inflammatory markers CRP and TNF-α and significant negative association with miRNA-124 in patient groups. Conclusion: In diabetic patients, the lncRNA NEAT1 may influence the incidence, severity, inflammation, and prognosis of AIS. NEAT1 expression levels could be used as a diagnostic marker of stroke in diabetic patients.

Computer aided diagnosis (CAD) of biomedical images assists physicians for a fast facilitated tissue characterization. A scheme based on combining fuzzy logic (FL) and deep learning (DL) for automatic semantic segmentation (SS) of tumors in breast ultrasound (BUS) images is proposed. The proposed scheme consists of two steps: the first is a FL based preprocessing, and the second is a Convolutional neural network (CNN) based SS. Eight well-known CNN based SS models have been utilized in the study. Studying the scheme was by a dataset of 400 cancerous BUS images and their corresponding 400 ground truth images. SS process has been applied in two modes: batch and one by one image processing. Three quantitative performance evaluation metrics have been utilized: global accuracy (GA), mean Jaccard Index (mean intersection over union (IoU)), and mean BF (Boundary F1) Score. In the batch processing mode: quantitative metrics' average results over the eight utilized CNNs based SS models over the 400 cancerous BUS images were: 95.45% GA instead of 86.08% without applying fuzzy preprocessing step, 78.70% mean IoU instead of 49.61%, and 68.08% mean BF score instead of 42.63%. Moreover, the resulted segmented images could show tumors' regions more accurate than with only CNN based SS. While, in one by one image processing mode: there has been no enhancement neither qualitatively nor quantitatively. So, only when a batch processing is needed, utilizing the proposed scheme may be helpful in enhancing automatic ss of tumors in BUS images. Otherwise applying the proposed approach on a one-by-one image mode will disrupt segmentation's efficiency. The proposed batch processing scheme may be generalized for an enhanced CNN based SS of a targeted region of interest (ROI) in any batch of digital images. A modified small dataset is available: https://www.kaggle.com/mohammedtgadallah/mt-small-dataset (S1 Data)., Competing Interests: The authors have declared that no competing interests exist.

Background: MicroRNAs (miRNAs) contribute to the development and progression of systemic lupus erythematosus (SLE) by affecting a wide range of targeted genes and facilitating the development of lupus nephritis (LN). The present study aimed to analyze the serum expression of miR-181a and miR-223 in SLE patients and to assess whether they could serve as novel biomarkers for SLE diagnosis and to distinguish LN., Methods: The study included 70 control subjects and 116 patients with SLE (67 non-LN and 49 LN groups). Circulating miR-181a and miR-223 expression levels were analyzed among the Egyptian population using a real-time polymerase chain reaction., Results: Up-regulation of miR-181a was detected among SLE patients compared to healthy controls and higher values were reported among the LN group compared to the non-LN group. Down-regulation of miR-223 was reported among SLE patients compared to controls and lower values were reported among the LN group compared to the non-LN group. The higher miR-181a expression and the lower miR-223 expression were associated with higher stages of LN. SLE disease activity index, proteinuria and serum creatinine were independently correlated with miR-181a and miR-223 among SLE patients by linear regression analysis. Receiver-operating characteristic curve analysis revealed that combined miR-181a and miR-223 expression increased the sensitivity and specificity for the diagnosis of SLE and further distinguished LN from non-LN patients., Conclusions: miR-181a and miR-223 could play a role in evaluating SLE disease progression and prognosis. Combined miR-181a and miR-223 expression analysis could serve as novel serum-based biomarkers in the diagnosis of SLE and predicting LN among Egyptians., (© 2021 John Wiley & Sons, Ltd.)

Background: Obesity and insulin resistance are common features accompanying polycystic ovary syndrome (PCOS). Aim: To analyze the impact of obesity on the expression of the visfatin and sterol regulatory element-binding protein ( SREBP )-1c genes among a group of Egyptian women with PCOS, and to assess their suitability as PCOS biomarkers. Subject and methods: Seventy healthy women (control group) (35 nonobese and 35 obese) and 140 women with PCOS (70 nonobese and 70 obese) were enrolled in this study. The visfatin and SREBP-1c genes' expression analyses were performed via real-time polymerase chain reaction. Serum visfatin and SREBP-1c protein levels were measured with ELISA kits. Results: Among PCOS patients, upregulation of visfatin and SREBP-1c expression was observed. We did not identify significant differences between the obese and nonobese PCOS patients nor between obese and non-obese controls. The mRNA expression levels of both genes were significantly positively correlated with their serum protein levels, as well as with fasting serum insulin levels, homeostatic model assessments of insulin resistance (HOMA-IR), luteinizing hormone (LH) ratios, LH/follicular stimulating hormone ratios, total testosterone, and free androgens. We observed significant negative correlations between visfatin and SREBP-1c expression levels and sex hormone binding globulin levels in all studied groups. Receiver operating characteristic curve analyses revealed that combining the visfatin and SREBP-1c expression data increased the sensitivity (95.92%) and specificity (93.2%) for PCOS diagnoses. Conclusion: Upregulation of visfatin and SREBP-1c was observed among PCOS patients. These genes may play a role in the pathogenesis of PCOS independent of obesity. Combined visfatin and SREBP-1c analyses could be used as a noninvasive biomarker for PCOS.

Background: Previous studies have suggested a strong genetic effect on sepsis pathogenesis. The present study aimed to investigate the role of miRNA-146-a expression in pediatric sepsis., Methods: The study included 55 pediatric sepsis patients and 60 control children of the same age and sex. Serum miRNA-146-a expression was measured using a quantitative real-time polymerase chain reaction. C-reactive protein, interleukin-6, tumor necrosis factor-α and procalcitonin levels were measured by an enzyme-linked immunosorbent assay. The outcome of the pediatric sepsis group was determined at 28 days of follow up., Results: The results obtained revealed that serum miRNA-146-a levels were significantly decreased in sepsis group compared to the control group. Serum level of miRNA-146a correlated with sepsis severity, with the pediatric septic shock group having the lowest level, followed by the severe sepsis and sepsis groups. The miRNA-146-a level could indicate sepsis (area under curve = 0.803). Serum miRNA-146-a expression was negatively associated with C-reactive protein, pro-calcitonin, interleukin-6 and tumor necrosis factor-α. Patients with miRNA-146-a at a level lower than 0.4 had an increased mortality rate., Conclusions: miRNA-146-a is of significant diagnostic and prognostic value in pediatric sepsis and could be used for planning therapeutic strategies., (© 2019 John Wiley & Sons, Ltd.)

Many tumor-suppressor genes contain CpG islands in their promoter regions which raised the necessity of investigating the role of methylation in silencing these genes. We examined p16 methylation as a potential biomarker in the peripheral blood of colorectal cancer (CRC) patients. Using methylation-specific polymerase chain reaction method, the methylation status of p16 was investigated in the tumor tissue and blood of 65 CRC patients and blood samples from 70 healthy control individuals. Also, the relationship between p16 methylation level and the clinical-pathological findings in CRC was evaluated. The frequency of blood p16 methylation in CRC cases was significantly higher than in control (P = 0.0001). The sensitivity and specificity of p16 methylation in diagnosing CRC was 55.38% and 98.5%, respectively, with 77.7% diagnostic accuracy. There was significant association between p16 methylation and age, sex, Dukes staging, lymph node involvement, and carcinoembryonic antigen levels. Our study revealed that p16 promoter methylation could be considered as both potential diagnostic and prognostic biomarker of CRC., (© 2018 Wiley Periodicals, Inc.)

Deregulated immunity is one of the most important factors implicated in recurrent pregnancy loss (RPL). The possible role of interleukin-33 (IL-33) and forkhead/winged helix transcription factor (Foxp3) in RPL have not been fully investigated. We aimed to evaluate IL-33 rs1929992 and Foxp3 rs2232365 single nucleotide polymorphisms (SNPs) and their serum levels in Egyptian RPL females. Blood samples were collected from 142 RPL patients and 123 women as healthy controls. IL-33 rs1929992 SNP was determined by polymerase chain reaction restriction fragment length polymorphism and Foxp3 rs2232365 SNP was determined using allele specific polymerase chain reaction. The serum IL-33 and Foxp3 levels were measured by enzyme linked immunosorbent assay. Foxp3 rs2232365 SNP showed statistically significant association with RPL. The risk of RPL was significantly higher in women carrying Foxp3 G allele than those carrying A allele. Lower serum levels of Foxp3 and IL-33 were observed in RPL patients than controls (P < 0.001). Foxp3 serum levels were much lower in carriers of G allele than those carrying A allele in all studied groups. Foxp3 rs2232365 SNP could be considered as a risk factor for RPL. The lowered serum levels of IL-33 and Foxp3 in RPL patients suggested that they might have an important role in the pathogenesis of the disease. Therefore, we hypothesized that Foxp3 polymorphisms may be important in RPL pathogenesis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Prostate cancer (PCa) is considered the most common malignancy in men. The aim of this study is to assess the role of serum miR-15a and miR-16-1 expression in PCa development, diagnosis and prognosis aiming to find a specific noninvasive biomarker. This study comprised 70 patients with PCa, 70 patients complaining of benign prostatic hyperplasia (BPH), 30 patients with chronic prostatitis and 70 controls. Circulating miR-15a and miR-16-1 expression was detected by real-time polymerase chain reaction. Prostate specific antigen levels were measured by enzyme-linked immunosorbent assay. The expression levels of serum miR-15a were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.43 ± 0.12, 1.7 ± 0.76, 1.56 ± 0.34 and 1.53 ± 0.65, respectively). The expression levels of serum miR-16-1 were decreased in PCa patients compared with controls, chronic prostatitis and BPH patients (0.55 ± 0.23, 2.15 ± 0.87, 2.08 ± 0.54 and 1.96 ±0.61, respectively). Downregulation of miR-15a and miR-16-1 correlated with higher Gleason score (P = 0.002 and P = 0.006, respectively), higher tumor stage (P = 0.001 and P = 0.01, respectively), PCa metastasis (P = 0.002 and P = 0.025, respectively) and lymph node involvement (P = 0.02 and P = 0.007, respectively). Moreover, Receiver operating characteristic curve analysis revealed that combined miR-15a/miR-16-1 and PSA increased the sensitivity and specificity for the diagnosis of PCa (97.1% and 94.3%, respectively) more than prostate specific antigen alone (82.9% sensitivity and 75.7% specificity). Combined serum miR-15a/miR-16-1 expression and PSA level can be used as promising specific noninvasive biomarkers in the diagnosis and prognosis of PCa better than prostate specific antigen alone. © 2018 IUBMB Life, 70(5):437-444, 2018., (© 2018 International Union of Biochemistry and Molecular Biology.)

The abnormal contribution of long non-coding RNA (lncRNAs) expression to human tumorigenesis is still a matter of debate. Breast cancer is the most common cancer in females; it represents a terrible problem in our country. The aim of this research was to assess the role of MALAT1, as one of lncRNAs, as a potential biomarker in breast cancer. This study comprised 80 patients with breast cancer and 80 controls. MALAT1 expression was measured by RT-quantitative polymerase chain reaction (qPCR). CA15-3 was estimated using chemiluminescence immunoassay (CLIA). MALAT1 expression was significantly elevated in breast cancer cases compared to controls (P < 0.0001). By performing the ROC curve analysis, we assumed that the diagnostic sensitivity and specificity for breast cancer were 83.7% and 81.2%, respectively for MALAT1 expression and 77.5% and 82.5% respectively for CA15-3 level. Moreover, combination analysis of the 2 parameters improved the diagnostic sensitivity of CA15-3 in breast cancer. In conclusion, MALAT1 expression level was positively correlated with lymph node status, estrogen receptor (ER), tumor stage and histological grade indicating its possible prognostic value. MALAT1 expression can be used as an accurate marker for diagnosis of breast cancer, in addition it possesses a prognostic value of such disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Incretins have opened a new era in type 2 diabetes mellitus (T2DM) pathogenesis. The present study aimed to assess whether there is an association between GIPR rs2302382, GIPR rs1800437 and GLP-1R rs367543060 polymorphisms with T2DM or not and also to determine the effect of these polymorphisms on gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) levels., Methods: One hundred and fifty T2DM patients and 150 healthy controls were included in the study. Polymorphisms of GIPR rs1800437, GIPR rs2302382 and GLP-1R rs367543060 were genotyped using restriction fragment length polymorphism (RFLP)-polymerase chain reaction (PCR), multiplex allele-specific PCR and RFLP-PCR respectively. GIP and GLP levels were measured by an enzyme-linked immunosorbent assay., Results: We found a significant association of both the homozygous AA and the minor allele A of GIPR rs2302382 with T2DM. The frequency of haplotype C(rs2302382) G(rs1800437) was significantly higher in controls than in diabetics; odds ratio (95% confidence interval): 1.99 (1.44-2.75) (p < 0.001), whereas the haplotype A(rs2302382) C(rs1800437) was significantly higher in patients than controls. We did not find any association of GLP-1R rs367543060 polymorphism with T2DM. We found a significant increase in serum total GIP and a significant decrease of GLP-1 levels in T2DM patients., Conclusions: We reveal for the first time an association between the GIPR rs2302382 polymorphism and T2DM in Egyptians. Yet, there was no significant association of GIPR rs1800437 or GLP-1R rs367543060 with T2DM risk. The haplotype A (rs2302382) C (rs1800437) was associated with an increased risk of T2DM. Furthermore, there was a significant increase of GIP and a significant decrease of GLP-1 levels when diabetic patients were compared with controls. An important finding was that there was a relationship between both GIPR rs2302382 and rs1800437 variants and their cognate ligand levels., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Hepatocellular carcinoma (HCC) is the 6th most common cancer and the 3rd leading cause of cancer causing death allover the world. The aim of this research to explore the clinical relevance of blood angiopoietin-like protein-3 (ANGPTL3) and ANGPTL4 expression and their proteins levels as non invasive biomarkers in cirrhotic and HCC patients and their influence on the clinicopathological features of HCC., Material and Methods: This work comprised 200 patients with chronic hepatitis (120 cases complicated with cirrhosis, 80 patients with primary HCC) and 100 controls. circulating ANGPTL3 and ANGPTL4 expression was estimated by real-time polymerase chain reaction (RT-PCR). ANGPTL3 and ANGPTL4 protein levels were determined by enzyme-linked immunosorbent assay (ELISA)., Results: The circulating ANGPTL3 and ANGPTL 4 expression was significantly elevated in HCC cases compared to chronic hepatitis patients and controls. There were much more serum ANGPTL3 and ANGPTL4 values in HCC and chronic hepatitis patients as compared to controls, but we couldn't detect this significance between chronic hepatitis and HCC cases as regards ANGPTL4. By Multiple stepwise linear regression analysis, an increased ANGPTL3 expression, alpha-fetoprotein (AFP), serum ANGPTL 3 levels, Child-Pugh grade were significantly assosciatedassociated with increased risk of HCC. Logistic regression analysis revealed that ANGPTL 3 expression and AFP levels were the only pridectorspredictors of HCC (odd's ratio (OR)=8.9; 8.6 respectively, P=0.003). Receiver operator characteristic (ROC) demonsterated that serum ANGPTL3 and ANGPTL4 levels were usufuluseful biomarkers discriminating chronic hepatitis cases from controls (AUC=0.820,0.887, respectively P<0.001). However, they fail to discriminate HCC patients from chronic hepatitis patients (P=0.27,0.12 respectively). Moreover, ANGPTL3 and ANGPTL 4 expression were promising biomarkers discriminating chronic hepatitis cases from controls and those HCC cases from chronic hepatitis patients (P<0.001). Combined ANGPTL3 expression and serum level wasn't useful in discriminating HCC patient from chronic hepatitis (P=0.09). In contrast, combined ANGPTL4 expression and serum level was an useful biomarker discriminating HCC cases from chronic hepatitis., Conclusion: ANGPTL3 and ANGPTL 4 expression and serum levels can be promising non invasive biomarkers in diagnosis of chronic hepatitis and HCC especially their expression could be useful in discriminating HCC from chronic hepatitis patients., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.

Aims: To investigate the effect of the insulin-like growth factor-1 (IGF-1) gene's rs6214 and rs5742632 polymorphisms on IGF-1 expression levels and their association with different types of myopia in Egyptian patients., Methods: A case-control format was used that included 272 patients with myopia and 136 controls. The IGF-1 gene rs6214 and rs5742632 polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses. IGF-1 levels were measured by an enzyme-linked immunosorbent assay., Results: In patients with high-grade myopia, the frequencies of the IGF-1 rs6214 GA and AA genotypes, and the A allele were significantly increased compared to the control group: 41.9% vs. 33.8%, 17.7% vs. 8.9%, and 38.9% vs. 25.7%, respectively. Subjects with the GA and AA genotypes and carriers of A allele were significantly more likely to have high-grade myopia: odds ratios (OR) = 1.75, 95% confidence interval (CI) = 1.03-2.9, and p = 0.03; OR = 2.8, 95% CI = 1.3-6.0, and p = 0.003; and OR = 1.8, 95% CI = 1.25-2.61, and p = 0.001, respectively. A nonsignificant association of the IGF-1 gene rs5742632 polymorphism with the two myopia groups was also observed. The IGF-1 levels were significantly increased in patients with high-grade myopia and simple myopia compared to the control group (p < 0.05). In addition, our results showed a nonsignificant association of the IGF-1 (rs6214-rs5742632) haplotype with either simple myopia or high-grade myopia., Conclusions: We found a significant association of the IGF-1 gene rs6214 polymorphism in Egyptian patients with simple myopia and high-grade myopia. IGF-1 levels were significantly increased in relation to the IGF-1 rs6214 genotypes, while a nonsignificant association was found between IGF-1 level and the IGF-1 (rs5742632) genotypes.

Stem cell therapy is considered as a promising approach in the treatment of myocardial infarction (MI). This study was designed as a comparison of human umbilical cord blood (HUCB)-derived CD34+ and HUCB-derived MSCs for the repair of cardiac tissue by induction of the angiogenesis. Forty-eight male rats were randomized into four groups: sham-operated group, MI group, MSCs-treated group, and CD34+ cells-treated group. After 4 weeks, the rats were sacrificed. All sections from left ventricles of all groups were subjected to hematoxylin & eosin, Masson's trichrome, and immunohistochemical stains (CD133, CD44, and α-smooth muscle actin). RNA was extracted for gene expression of the angiogenic markers. A significant reduction of the infarct size and the amplitude of T-wave in the CD34+ cells-treated group when compared with the MSCs-treated group were determined. Histologically, the MI group showed scar tissue, congested blood capillaries around the infarcted area, some necrotic cells, and inflammatory cells. Administration of either MSCs or CD34+ cells had a therapeutic potential to induce regenerative changes in the myocardium with better results in CD34+cells-treated group. Quantitative RT-PCR analysis revealed a significant increase in the expression of vascular endothelial growth factor (VEGF), VEGFR-2, Ang-1, and Tie-2 and a significant decreased expression of Ang-2 in stem cells transplanted groups when compared with the noncell transplanted hearts. A significant increase of VEGF, VEGFR-2, Ang-1, and Tie-2 expression in the group receiving CD34+ cells than those receiving MSCs was found. Finally, there was an upregulation of both human VEGF and human hypoxia-inducible factor 1α in the infarcted hearts treated by CD34+ cells than that treated by MSCs. We first revealed a superior efficacy of CD34+ cells when compared with MSCs in induction of regenerative changes in the MI model. Both cell therapies may repair the damaged heart tissue primarily by secretion of proangiogenic factors that induce the angiogenesis and activate the angiogenesis signaling pathway. © 2016 IUBMB Life, 68(5):343-354, 2016., (© 2016 International Union of Biochemistry and Molecular Biology.)

Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders; however, its pathophysiology is still unclear. Certain polymorphisms of luteinizing hormone beta-subunit (LHβ) and LH/choriogonadotrophin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. We aimed to investigate possible associations between polymorphisms in the LHβ and LHCGR genes and PCOS among Egyptian women. We also aimed to shed light on the impact of these polymorphisms on LH level, hormonal, and metabolic features of PCOS. A case-control study included unrelated 210 patients with PCOS and 200 healthy controls, and they were stratified according to their body mass index into two subgroups: lean and obese. Polymorphisms of LHβ G1502A and LHCGR [G935A, and ins18LQ] genes were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Our results revealed that LHβ G1052A GA genotype and A allele, LHCGR G935A GA, AA genotypes, or A allele were significantly associated with PCOS risk, while the LHCGR ins18LQ polymorphism was not. Additionally, there is a synergism between LHβ G1052A minor A and minor A allele of LHCGR G935A or minor ins allele of LHCGR ins18LQ and susceptibility to PCOS. When we stratified PCOS women or controls into obese and lean subjects, we found that LHβ G1502A GA genotype and A allele being more frequent in the obese group when compared with lean patients with PCOS [The odds ratio and 95% confidence interval were 5.6 (1.30-24.56) and 5.15 (1.21-21.90), respectively, P = 0.01, for each group.] These results suggested that LHβ G1052A and LHCGR G935A genes polymorphisms are associated with increased risk of PCOS in Egyptian women especially in obese cases. There was a synergism between LHβ G1052A minor A allele and of LHCGR G935A minor A or minor ins alleles of LHCGR ins18LQ and PCOS risk. © 2015 IUBMB Life, 68(1):23-36, 2016., (© 2015 International Union of Biochemistry and Molecular Biology.)

Aim: Early detection of latent tuberculosis infection (LTBI) will prevent development of active TB among health care providers. The aim of the study was to assess the prevalence of LTBI among health care providers and compare the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and Tuberculin skin test in efforts to detect LTBI and to investigate possible associated risk factors of infection., Methods: A cross sectional study was carried out during the period of 6 months in the Chest Hospital in Zagazig city and the Nephrology Unit at Zagazig University Hospitals in 132 randomly selected health care providers who were examined for LTBI by QFT-GIT and Tuberculin skin test and for the associated risk factors as well., Results: The prevalence of LTBI identified by QFT-GIT and by Tuberculin skin test was 28.8% and 59.1%, respectively. Poor agreement was observed between the two tests (kappa=0.10). Working more than 10 years, being nurse, diabetic and smoker were risk factors significantly associated with LTBI (p<0.05)., Conclusions: QFT-GIT is considered a useful tool in detecting LTBI cases, especially in a country where BCG vaccination is a national policy (as in Egypt). Duration of work, profession, diabetes and smoking are the risk factors for LTBI. Active surveillance and infection control measures are recommended to reduce the risk of LTBI., (Copyright© by the National Institute of Public Health, Prague 2015.)

The pathophysiology of COX-2 expression in endometriosis is a matter of debate. The aim was to investigate the role of DNA methylation of the NF-IL6 site within the promoter of COX-2 gene in the pathogenesis of endometriosis. The endometrial tissues (ectopic and eutopic) were collected from 60 women with endometriosis and 30 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation-specific PCR. Quantitative real-time PCR (RT-PCR) was performed to measure COX-2 mRNA levels in endometrial tissues. We found significantly higher levels of COX-2 in ectopic endometriotic tissue compared with eutopic tissue. Also, we found that the frequencies of methylation status of the NF-IL6 site within the COX-2 promoter in the eutopic and ectopic endometrial tissues of endometriosis groups were significantly decreased in comparison to controls (P=0.002, P=0.000 respectively). Our study demonstrated that DNA hypomethylation of the NF-IL6 site within the promoter of COX-2 gene could be a key mechanism for its elevated expression in the eutopic and ectopic tissues of endometriosis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Recurrent pregnancy loss (RPL) is a common problem during early gestation. The aim of our study was to investigate the association of IL-17 F( rs763780), IL-17 A (rs2275913), and leptin (2548 G/A) gene polymorphisms with RPL in obese and lean Egyptian females, and to find out whether these gene polymorphisms affect the women’s serum levels. One hundred and twenty patients with RPL and 120 fertile volunteers with no history of pregnancy loss were genotyped for leptin (2548 G/A), IL-17 A (rs2275913), and IL-17 F (rs763780) polymorphisms by RFLP. The serum level of IL-17 was measured by ELISA, while serum leptin level was measured by HPLC. We found that IL-17 F (rs763780) polymorphism was associated with a decreased risk of RPL in Egyptian females, and we also found that IL-17 A (rs2275913) and LEP (2548 G/A) SNP were associated with an increased risk of RPL. We also demonstrated that both the IL-17 and leptin levels were elevated in the women with RPL and in an obese subgroup within RPL in comparison to a lean one.

Objective: To assess the relation of blood MT-2A expression, serum zinc, copper, Cu/Zn ratio, total antioxidant status (TAS), total oxidant status (TOS) and oxidant status index (OSI) with benign and malignant breast tumors, also, their relation to different clinical stages and grades of breast cancer., Material and Methods: Unrelated 199 female patients with breast tumor and 120 healthy controls were enrolled in this study. Metallothionein-2A (MT-2A) expression was assessed by quantitative real-time polymerase chain reaction (RT-PCR). Serum MT-2A levels were measured by ELISA. Serum copper (Cu) and Zinc (Zn) concentrations were determined by atomic absorption spectrophotometry. Serum TOS and TAS levels were measured colorimetrically., Results: Our study demonstrated that blood metallothionein-2A mRNA level, serum MT-2A, copper, Cu/Zn ratio, total oxidant status and oxidant status index were significantly increased, while, serum zinc level and total antioxidant status were significantly decreased in patients with breast cancer and benign breast disease as compared to controls and in breast cancer group as compared to the benign one., Conclusions: Blood metallothionein-2A expression and serum MT-2A levels could be important prognostic indices of less differentiated, more aggressive breast cancer phenotype. Disturbance of copper, zinc and oxidative stress status might contribute to the pathogenesis of breast tumor and could be useful biomarkers for diagnosing and monitoring such disease., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD) is an important public health problem. Patients with end-stage renal disease have a significant renalase deficiency, which could be one of the mechanisms explaining high prevalence of hypertension in these patients. The aim of this study was to investigate the possible association of renalase gene (rs2296545) polymorphism with normotensive and hypertensive CKD in sampled Egyptian patients and to determine the effect of such polymorphism on epinephrine level. Renalase gene (rs2296545) polymorphism was genotyped in 178 patients with CKD (83 normotensive and 95 hypertensive nephrosclerosis) and 178 normal healthy adults using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Epinephrine level was measured by HPLC method. We found an association of renalase (rs2296545) CC genotype and C allele with CKD. Also, the epinephrine level was significantly increased in normotensive and hypertensive nephrosclerosis patients as compared to controls. CKD patients with CC genotype showed significant high epinephrine level as compared to CG and GG genotypes.

Purpose: To analyze the association of polymorphisms of the endothelial nitric oxide synthase (NOS3) gene and nitric oxide (NO) levels with high-tension primary open-angle glaucoma (POAG) in an Egyptian population., Methods: This case-control study included 160 patients who had high-tension POAG (76 men and 84 women; age range 41-75 years) and 110 controls (56 men and 54 women; age range 55-78 years). Genotyping of T-786C (rs2070744), Glu298Asp (rs1799983), and the 27-bp insertional variable number tandem repeat (VNTR) in intron 4 of the NOS3 gene was performed with an amplification refractory mutation system PCR assay. The NO level was determined by measuring the total nitrate/nitrite (NOX) plasma level., Results: The CC genotype of the T-786C polymorphism was significantly associated with POAG (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.26-5.13, p = 0.007). The C allele was significantly associated with POAG (OR = 1.86, 95% CI = 1.29-2.69, p<0.001). After stratification by sex, the CC genotype and the C allele were significantly associated with POAG in women only (OR = 3.06, 95% CI = 1.07-8.74, p = 0.03 for the CC genotype, and OR = 2.09, 95% CI = 1.24-3.53, p = 0.005 for the C allele). The genotype and allele frequencies of Glu298Asp and intron 4 were not significant between the patients with POAG and the controls, and after stratification by sex. The mean NOX plasma level was significantly lower in patients with POAG than in the controls (p = 0.01) and low in the (TC+CC) genotype compared to the TT genotype of T-786C in the patients and controls (p<0.001)., Conclusions: The results suggest that the CC genotype of T-786C NOS3 may be associated with an increased risk of developing high-tension POAG in Egyptians, particularly women. In addition, decreased NO levels may play a role in the development of POAG.

Cytokines are involved in the pathogenesis of community acquired pneumonia (CAP). The aim of this study is to investigate the association of IL6-174 G/C gene polymorphism with CAP in Egyptian children, to assess its effect on CAP outcome and to determine its effect on the serum IL6 levels in these children. IL6-174 G/C gene polymorphism was genotyped in 210 Egyptian children (100 patients with CAP and 110 healthy controls) using PCR-RFLP, while the serum IL6 levels were measured by ELISA method. We found a significant association between the GG genotype, G allele of IL6-174 G/C SNP and susceptibility to CAP (P=0.02, 0.01 respectively). However, GG genotype and G allele were protective against severe sepsis (p=0.004), acute respiratory failure (p<0.001) and hospital mortality (p<0.001). Serum IL6 levels were significantly increased in these children while there was no relation between GG genotype and serum IL6. In conclusion, IL6-174 G/C gene polymorphism may contribute to susceptibility to CAP in Egyptian children., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Several cytokines were assumed to play an essential role in the induction and the pathogenesis of psoriasis. The aim of this work was to investigate the role of TNF-α-308 and IL-10-1082 polymorphisms and their serum levels in the pathogenesis of psoriasis and determine their relation to disease severity. 110 Psoriasis patients and 120 healthy volunteers were genotyped for TNF-α-308 and IL-10-1082 polymorphism by polymerase chain reaction. Serum level of TNF-α and IL-10 were measured by ELISA. Our study demonstrated an association of IL-10-1082 polymorphism and psoriasis and between TNF α-308 polymorphism and psoriasis disease and severity. Serum TNF α increased in patients, while serum IL-10 decreased in patients with significant correlation between serum TNF-α and psoriasis severity. These results indicated that TNF-α-308 and IL-10-1082 polymorphisms imparted significant risk towards the development of psoriasis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Identification of the genetic basis of systemic lupus erythematosus (SLE) may contribute to the discovery of effective drugs before renal involvement. Our aim of this study was to estimate the association between Fc gamma receptor (FcγR) polymorphisms and SLE and renal involvement in Egyptian patients. FcγRIIB and FcγRIIA R131H gene polymorphisms were genotyped in 180 Egyptian adults. Genotyping for FcγRIIA R131H was performed using allele-specific PCR and FcγRIIB-Ile232 Thr polymorphism was genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The study showed that the homozygous genotype (Thr/Thr) of FcγRIIB significantly increased in all SLE patients (90 patients) and in SLE patients complicated with nephritis (61 patients). The Thr allele was significantly associated with an increased risk of the disease in all the patients and in patients complicated with nephritis. Our study demonstrated an association of FcγRIIB polymorphisms with SLE and lupus nephritis and a lack of association of FcγRIIA polymorphisms with SLE in the Egyptian patients.

Recently, several reports addressed the associations of adiponectin (ADIPOQ) gene polymorphisms with abnormal adiponectin serum levels, type 2 diabetes mellitus (T2DM), and diabetic nephropathy (DN); however, results are inconsistent. This study aimed to investigate the possible association of ADIPOQ gene polymorphisms with T2DM and/or DN and whether they affect serum adiponectin levels in Egyptian population. Two hundred and ninety-six T2DM patients (100 normoalbuminuric patients, 103 microalbuminuric patients, and 93 macroalbuminuric patients) and 209 controls were enrolled in the present study. Polymorphisms of +45, -11391, and +276 of the ADIPOQ gene were detected using polymerase chain reaction restriction fragment length polymorphism. Serum adiponectin was measured using ELISA. Our results revealed that ADIPOQ +45 TG and GG genotypes and G allele were significantly associated with T2DM, micro/macroalbuminuria, and decreased serum adiponectin level. ADIPOQ -11391 AA genotype frequency was significantly increased in T2DM group. Moreover, GA and AA genotypes and A allele of ADIPOQ -11391 were significantly associated with susceptibility to macroalbuminuria despite increased serum adiponectin concentrations. While, ADIPOQ +276 TT genotype and T allele were protective factors regarding the susceptibility to T2DM and micro/macroalbuminuria, and they were significantly associated with increased adiponectin levels. We observed also that the decrease of the serum Adiponectin level was accompanied by an insulin resistance, albuminuria, as well as an increase of serum creatinine. We concluded that ADIPOQ +45; ADIPOQ -11391 gene polymorphisms are associated with T2DM and/or DN in Egyptian population. While, ADIPOQ +276 gene polymorphism is a protective factor regarding T2DM and/or DN susceptibility.

Objective: To investigate the association of combined MTHFR C677T and A1298C gene polymorphisms with congenital heart diseases (CHD) in Egyptian children and their mothers and to determine their effect on homocysteine level in these children., Material and Methods: MTHFR C677T and A1298C polymorphisms were genotyped in 160 Egyptian children (80 patients with CHD and 80 healthy controls) and their mothers using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while, homocysteine (Hcy) level was measured optically by enzymatic method., Results: We found that MTHFR 677TT genotype, T allele, 1298CC genotype, and C allele were associated with 2.61, 2.0, 2.91 and 1.99 fold increased risk of CHD in Egyptian children respectively. Furthermore, the frequencies of MTHFR 1298AC and CC genotypes and C allele significantly increased in mothers with CHD affected children. The homocysteine levels were significantly increased in MTHFR 677TT and 1298CC genotypes in children with CHD., Conclusions: Our study demonstrated an association of MTHFR A1298C polymorphisms with CHD in Egyptian children and their mothers, while, MTHFR C677T polymorphisms were significantly associated with the risk of CHD in the children only. An association between combined MTHFR A1298C and C677T polymorphisms and CHD was recorded in the children and their mothers. Also, homocysteine levels were significantly increased with both MTHFR 677TT and 1298CC genotypes in Egyptian children with CHD., (© 2013.)

Studying gene-environment interactions may elucidate the complex origins of atopic diseases. The aim of this study was to evaluate the association of CD14 polymorphisms and atopy in Egyptian children and to study whether atopy is influenced by CD14 interaction with tobacco smoke exposure. CD14 -159 C/T and CD14 -550 C/T were genotyped in 500 asthmaic children, 150 allergic rhinitis children and 150 controls. We found that CD14 -159T allele, CD14 -550T allele and CD14 -159T/-550T haplotype were significantly associated with atopic asthma and allergic rhinitis groups. CD14 -159 TT and CD14 -550 TT genotypes associated with elevated IgE levels in children exposed to tobacco smoke. The TT genotype of CD14 -159 C/T and CD14 -550 C/T was associated with higher serum levels of sCD14. The present study indicated that CD14 gene polymorphisms may contribute to susceptibility to atopy in Egyptian children and influenced with tobacco smoke exposure., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Identification of the genetic basis of asthma may contribute to the discovery of effective asthma drugs., Objective: Our aim was to estimate the association between B2 adrenergic receptor (ADRB2) polymorphisms and nocturnal asthma in Egyptian children., Methods: ADRB2 polymorphisms Gly16 and Glu27 were genotyped in 200 Egyptian children (90 with nocturnal asthma and 110 healthy controls) using allele-specific polymerase chain reaction., Results: The homozygous (Gly16) genotype significantly increased the risk of nocturnal asthma (odds ratio [OR], 3.2; 95% CI, 1.3-7.7; P = .003), as did the Gly allele (OR, 1.8: 95% CI, 1.2-2.8)., Conclusions: Our study demonstrated that nocturnal asthma was associated with ADRB2 Arg/Gly polymorphisms but not with ADRB2 Gln/Glu polymorphisms.