Evaluation of methylation pattern in promoter region of E-cadherin gene and its relation to tumor grade and stage in breast cancer

The epithelial cadherin gene (CDH1) has been identified as a tumor suppressor gene located within the 16q22.1 region. The CDH1 gene encodes a transmembrane glycoprotein involved in cell to cell adhesion and loss of CDH1 expression contributes to increased proliferation, invasion and metastasis in breast carcinoma. No mutation in CDH1 have been identified in invasive ductal carcinoma (IDC), suggesting that, other inactivation mechanisms are responsible for IDC oncogenesis. In order to analyze the role of promoter methylation in CDH1 gene inactivation in breast cancer, the CpG methylation status of Ecadherin promoter region by bisulfite sequencing PCR (BSP) was investigated. 10 CpG sites [nucleotide (nt) 863, 865, 873, 879, 887, 892, 901, 918, 920 and 940] in the promoter region were screened for methylation. The CDH1 methylation was detected in 94% (47 to 50) of breast tumors which was associated with higher tumor grade (p = 0.035), tumor stage (p = 0.000) and tumor metastasis (p = 0.000). There was also a significant correlation between tumor stage, grade and metastatic status with sites of methylation (p = 0.000). The data indicate that CDH1 promoter methylation might be a potential mechanism for epigenetic silencing of CDH1 in primary breast cancer suggesting a valuable molecular marker for detection of breast cancer progression.Key words: Breast cancer, E-cadherin, methylation pattern, tumor stage, tumor grade

Database and Data Mining in Social Networking

Today’s data driven world exploiting the latest trends of database and its allied technologies like Data Warehouse and Data Mining. Data Mining in recent years emerged as one of the most efficient database technique proved to be very reliable almost in every organisation enabling to find previously unknown hidden data patterns for the benefit of organisation. At the same time it is imposing serious problems concerned to data privacy and its potential misuse

Prediabetes and diabetes prevalence and risk factors comparison between ethnic groups in the United Arab Emirates

The economic growth has paralleled the rise of diabetes and its complications in multiethnic population of United Arab Emirates (UAE). Previous studies have shown that characteristics of diabetes is variable across different ethnicities. The objective of this study was to compare diabetes prevalence and risk factors between UAE nationals and different expatriate's ethnic groups in UAE using data from UAE National Diabetes and Lifestyle Study (UAEDIAB). The UAE nationals made one-fourth (n = 797, 25%) of total cohort and the remaining 75% belonged to immigrants. Across different ethnicities, adjusted prevalence of prediabetes ranged from 8% to 17%, while adjusted prevalence of newly diagnosed diabetes ranged from 3% to 13%. UAE nationals, Arabs non-nationals and Asians had the highest number of pre-diabetic as well as newly diagnosed diabetic patients. Adjusted prevalence of diabetes was highest in UAE nationals (male 21% and female 23%) as well as Asian non-Arabs (male 23% and female 20%), where 40% of both groups fell under the range of either prediabetes or diabetes conditions. Multivariate factors of diabetes versus non-diabetes included older age, ethnicities of Asian non-Arabs and local UAE nationals, family history of diabetes, obesity, snoring, decreased level of high density lipoprotein, elevated levels of triglycerides and blood pressure. In conclusion, diabetes prevalence and risk factors vary across the different ethnic groups in UAE, and hence interventions towards identification and prevention of diabetes should not treat all patients alike

Enhanced Expression of Autoantigens During SARS-CoV-2 Viral Infection

Immune homeostasis is disturbed during severe viral infections, which can lead to loss of tolerance to self-peptides and result in short- or long-term autoimmunity. Using publicly available transcriptomic datasets, we conducted an in-silico analyses to evaluate the expression levels of 52 autoantigens, known to be associated with 24 autoimmune diseases, during SAR-CoV-2 infection. Seven autoantigens (MPO, PRTN3, PADI4, IFIH1, TRIM21, PTPRN2, and TSHR) were upregulated in whole blood samples. MPO and TSHR were overexpressed in both lung autopsies and whole blood tissue and were associated with more severe COVID-19. Neutrophil activation derived autoantigens (MPO, PRTN3, and PADI4) were prominently increased in blood of both SARS-CoV-1 and SARS-CoV-2 viral infections, while TSHR and PTPRN2 autoantigens were specifically increased in SARS-CoV-2. Using single-cell dataset from peripheral blood mononuclear cells (PBMCs), we observed an upregulation of MPO, PRTN3, and PADI4 autoantigens within the low-density neutrophil subset. To validate our in-silico analysis, we measured plasma protein levels of two autoantigens, MPO and PRTN3, in severe and asymptomatic COVID-19. The protein levels of these two autoantigens were significantly upregulated in more severe COVID-19 infections. In conclusion, the immunopathology and severity of COVID-19 could result in transient autoimmune activation. Longitudinal follow-up studies of confirmed cases of COVID-19 could determine the enduring effects of viral infection including development of autoimmune disease

On random coincidence points and random best approximation in p-normed spaces

In this paper random coincidence point results are proved for pair of commuting mapping defined on weakly compact separable subset of complete p-normed space. And then , use them to study the random best approximation in p-normed space with separablity condition.Keywords : p-normed space ,random coincidence point ,random best approximation

Astrophysical and electromagnetic emissivity properties of black holes surrounded by a quintessence type exotic fluid in the Scalar-Vector-Tensor Modified Gravity

The astrophysical consequences of the presence of a quintessence scalar field on the evolution of the horizon and on the accretion disk surrounding a static black hole, in the Scalar-Vector-Tensor version of Modified Gravity (MOG), are investigated. The positions of the stable circular orbits of the massive test particles, moving around the central object, are obtained from the extremum of the effective potential. Detailed calculations are also presented to investigate the light deflection, shadow and Shapiro effect for such a black hole. The electromagnetic properties of the accretion disks that form around such black holes are considered in detail. The energy flux and efficiency parameter are estimated analytically and numerically. A comparison with the disk properties in Schwarzschild geometry is also performed. The quantum properties of the black hole are also considered, and the Hawking temperature and the mass loss rate due to the Hawking radiation are considered. The obtained results may lead to the possibility of direct astrophysical tests of black hole type objects in modified gravity theories.Comment: 30 pages, including diagrams and table

Cardiovascular medications and regulation of COVID-19 receptors expression

INTRODUCTION: Emerging epidemiological studies suggested that Renin–Angiotensin–Aldosterone system (RAAS) inhibitors may increase infectivity and severity of COVID-19 by modulating the expression of ACE2. METHODS: In silico analysis was conducted to compare the blood expression levels of SARS-CoV-2 entry genes between age and gender matched cohort of hypertensive patients versus control, and to determine the effect of common cardiovascular medications on the expression of COVID-19 receptors in vitro using primary human hepatocytes. RESULTS: The transcriptomic analysis revealed a significant increase of ACE2 and TMPRSS2 in the blood of patients with hypertension. Treatment of primary human hepatocytes with captopril, but not enalapril, significantly increased ACE2 expression. A similar pattern of ACE2 expression was found following the in vitro treatments of rat primary cells with captopril and enalapril. Telmisartan, a second class RAAS inhibitors, did not affect ACE2 levels. We have also tested other cardiovascular medications that may be used alone, or in combination with RAAS inhibitors. Some of these medications increased TMPRSS2, while others, like furosemide, significantly reduced COVID-19 receptors. CONCLUSIONS: The increase in ACE2 expression levels could be due to chronic use of RAAS inhibitors or alternatively caused by other hypertension-related factors or presence of other comorbidities. Treatment of common co-morbidities often require chronic use of multiple medications, which may result in an additive increase in the expression of ACE2 and TMPRSS2. Our data suggest that more research is needed to determine the effect of different medications, as well as medication combinations, on COVID-19 receptors

Whole genome amplification: Use of advanced isothermal method

Laboratory method for amplifying genomic deoxyribonucleic acid (DNA) samples aiming to generate more amounts and sufficient quantity DNA for subsequent specific analysis is named whole genome amplification (WGA). This method is only way to increase input material from few cells and limited DNA contents. While PCR-based WGA methods have been under continuous development for over a decade, shortcomings of these methods enforced many researchers to switch to the use of non-PCR-based linear amplification techniques. Moreover, application of high fidelity and high possessive DNA polymerases enabled development of an isothermal WGA technique named multiple displacement amplification (MDA). MDA is not based on PCR and doses not require thermal cycling. It should be noted that, while MDA-based techniques proposed aiming to overcome the drawbacks of PCR-based methods however, MDA is still facing some challenges. It seems that PCR-based WGA methods alsohave some merits. One of the problems which encountered both MDA and PCR-based methods is in the amplification of degraded DNA templates. WGA methods such as T7-based linear amplification of DNA(TLAD), balanced-PCR amplification and restriction and circularization-aided rolling circle amplification (RCA-RCA) have been suggested to aim at amplification of such DNA templates.Keywords: Whole genome amplification, multiple displacement amplification (MDA), non PCR-based method