Administration of Insurance Rate Regulatory Laws

microRNAs (miRNAs) are key posttranscriptional regulators of gene expression. In the present study, regulation of tumor-suppressor gene D-glucuronyl C5-epimerase (GLCE) by miRNA-218 was investigated. Significant downregulation of miRNA-218 expression was shown in primary breast tumors. Exogenous miRNA-218/anti-miRNA-218 did not affect GLCE mRNA but regulated GLCE protein level in MCF7 breast carcinoma cells in vitro. Comparative analysis showed a positive correlation between miRNA-218 and GLCE mRNA, and negative correlation between miRNA-218 and GLCE protein levels in breast tissues and primary tumors in vivo, supporting a direct involvement of miRNA-218 in posttranscriptional regulation of GLCE in human breast tissue. A common scheme for the regulation of GLCE expression in normal and tumor breast tissues is suggested.Funding Agencies|Russian Foundation for Basic Research|11-04-90400-Ukr_f_a|Ukranian State Foundation of Fundamental Research|F40/146-2011F46/457-2011|Swedish Institute|2011/00888|UICC International Cancer Technology Transfer Fellowship|ICRETT-09-069|FEBS Short-term Fellowship||Karolinska Institute||Swedish Cancer Society||Swedish Research Council||</p

Antiproliferative effect of D-glucuronyl C5-epimerase in human breast cancer cells

<p>Abstract</p> <p>Background</p> <p>D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in the biosynthesis of heparansulfate proteoglycans. Down-regulation of <it>GLCE </it>expression in human breast tumours suggests a possible involvement of the gene in carcinogenesis. In this study, an effect of <it>GLCE </it>ectopic expression on cell proliferation and viability of breast carcinoma cells MCF7 <it>in vitro </it>and its potential molecular mechanisms were investigated.</p> <p>Results</p> <p><it>D-glucuronyl C5-epimerase </it>expression was significantly decreased in MCF7 cells compared to normal human breast tissue. Re-expression of <it>GLCE </it>inhibited proliferative activity of MCF7 cells according to CyQUANT NF Cell Proliferation Assay, while it did not affect their viability in Colony Formation Test. According to Cancer PathFinder RT Profiler PCR Array, antiproliferative effect of <it>GLCE </it>in <it>vitro </it>could be related to the enhanced expression of tumour suppressor genes р53 (+3.3 fold), E2F1 (+3.00 fold), BRCA1 (+3.5 fold), SYK (+8.1 fold) and apoptosis-related genes BCL2 (+4.2 fold) and NFKB1 (+2.6 fold). Also, <it>GLCE </it>re-expression in MCF7 cells considerably changed the expression of some genes involved in angiogenesis (IL8, +4.6 fold; IFNB1, +3.9 fold; TNF, +4.6 fold and TGFB1, -5.7 fold) and invasion/metastasis (SYK, +8.1 fold; NME1, +3.96 fold; S100A4, -4.6 fold).</p> <p>Conclusions</p> <p>The ability of <it>D-glucuronyl С5-epimerase </it>to suppress proliferation of breast cancer cells MCF7 through the attenuated expression of different key genes involved in cell cycle regulation, angiogenesis and metastasis molecular pathways supports the idea on the involvement of the gene in regulation of breast cancer cell proliferation.</p

miRNA-218 contributes to the regulation of D-glucuronyl C5-epimerase expression in normal and tumor breast tissues

microRNAs (miRNAs) are key posttranscriptional regulators of gene expression. In the present study, regulation of tumor-suppressor gene D-glucuronyl C5-epimerase (GLCE) by miRNA-218 was investigated. Significant downregulation of miRNA-218 expression was shown in primary breast tumors. Exogenous miRNA-218/anti-miRNA-218 did not affect GLCE mRNA but regulated GLCE protein level in MCF7 breast carcinoma cells in vitro. Comparative analysis showed a positive correlation between miRNA-218 and GLCE mRNA, and negative correlation between miRNA-218 and GLCE protein levels in breast tissues and primary tumors in vivo, supporting a direct involvement of miRNA-218 in posttranscriptional regulation of GLCE in human breast tissue. A common scheme for the regulation of GLCE expression in normal and tumor breast tissues is suggested.Funding Agencies|Russian Foundation for Basic Research|11-04-90400-Ukr_f_a|Ukranian State Foundation of Fundamental Research|F40/146-2011F46/457-2011|Swedish Institute|2011/00888|UICC International Cancer Technology Transfer Fellowship|ICRETT-09-069|FEBS Short-term Fellowship||Karolinska Institute||Swedish Cancer Society||Swedish Research Council||</p

GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population

d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A > G) were similar in healthy Siberian women (n = 136) and cancer patients (n = 129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR = 1.76; 95% CI = 1.04–1.90; P(Y) = 0.035 χ2 = 4.44). Heterozygous AG genotype was associated with tumour size (OR = 3.67, P(Y) = 0.004), ER-negative tumours (OR = 3.25, P(Y) = 0.0028), triple-negative tumours (OR = 4.94, P(Y) = 0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER + PR + luminal A breast cancer (OR = 0.25, P(Y) = 0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes

GLCE rs3865014 (Val597Ile) polymorphism is associated with breast cancer susceptibility and triple-negative breast cancer in Siberian population

d-Glucuronyl C5-epimerase (GLCE) is one of key enzymes in heparan sulfate biosynthesis and possesses tumour-suppressor function in breast carcinogenesis. Here, we investigated a potential involvement of GLCE polymorphism(s) in breast cancer development in Siberian women population. Comprehensive analysis of SNP databases revealed GLCE rs3865014 (Val597Ile) missense polymorphism as the main significantly present in human populations. According the TaqMan-based SNP assay, allele distributions for the rs3865014 (A > G) were similar in healthy Siberian women (n = 136) and cancer patients (n = 129) (A0,73:G0,27) and intermediate between the European and Asian populations, while genotype distributions were different, with the increase of AG rate in breast cancer patients (OR = 1.76; 95% CI = 1.04–1.90; P(Y) = 0.035 χ2 = 4.44). Heterozygous AG genotype was associated with tumour size (OR = 3.67, P(Y) = 0.004), ER-negative tumours (OR = 3.25, P(Y) = 0.0028), triple-negative tumours (OR = 4.94, P(Y) = 0.015) but not menopausal status, PR and HER-2 status, local or distant metastasis. Homozygous GLCE genotypes (AA/GG) were more common for ER + PR + luminal A breast cancer (OR = 0.25, P(Y) = 0.031). Loss-of-heterozigosity was identified in 5 of 51 breast tumours and the loss of G allele was associated with the decreased GLCE expression. Epidemiologic data for the GLCE SNP in different racial/ethnic groups demonstrated high AG genotype rates as a risk factor not for breast cancer incidence but for poor prognosis of the disease. The obtained data suggest an involvement of GLCE rs3865014 in breast cancer development. Heterozygous AG genotype might be a risk factor for breast cancer susceptibility in Siberian women and is associated with aggressive ER-negative and triple-negative cancer subtypes

Bio-hybridization of nanobactericides with cellulose films for effective treatment against members of ESKAPE drug resistant pathogens

The rapid expansion of drug-resistant pathogens has created huge global impact and development of novel antimicrobial leads is one of the top priority studies in the current scenario. The present study aims to develop bio-hybridized nanocellulose films which comprise of phytogenic silver nanobactericides. The nanobactericides were synthesized by treating 1 mM silver nitrate with aqueous extract of Chamerion angustifolium which reduced the metal salt to produce polydispersed nanobactericides which were tested against the members of ESKAPE drug-resistant communities. The synthesized silver nanobactericides were subjected to characterization with UV–visible spectra which displayed maximum absorbance at 408 nm. The bio-molecular interaction of phyto-constituents to mediate synthesis and stabilization of nanobactericides was studied with Fourier-transform infrared spectroscopy (FTIR) which depicted functional groups associated with nanobactericides. The crystalline nature was studied with X-ray diffraction (XRD) which showed Bragg’s intensities at 2θ angle which denoted (111), (200), (220), and (311) planes. The morphological characteristics of silver nanobactericides were defined with transmission electron Microscopy (TEM) image which displayed polydispersity of silver nanobactericides with size ranging from 2 to 40 nm. The synthesized nanobactericides showed a significant activity against MRSA strain with 21 mm zone of inhibition. The minimal inhibitory concentration of silver nanobactericides to inhibit the growth of test pathogens was also determined which ranged between 0.625 and 1.25 μg/ml. The silver nanobactericides were bio-hybridized onto nanocellulose films produced by Komagataeibacter xylinus B-12068 culture strain. The films were dried to determine the mechanical properties which showed increased in Young’s modulus and tensile strength in comparison with control bacterial cellulose films. Overall, the results obtained in the present investigation are promising enough to report bactericidal activity of bio-hybridized nanobactericidal films against ESKAPE. These communities are reported to cause severe threats to all forms of lives irrespective to their habitats which can lead to huge economical crisis