Association between SIRT1 Gene Polymorphisms and Breast Cancer in Egyptians.

Breast cancer is reported to cause the highest mortality among female cancer patients. Previous studies have explored the association of silent mating-type information regulator 2 homolog 1 (SIRT1) gene expression with prognosis in breast cancer. However, no studies exist, so far, on the role of SIRT1 gene polymorphism in breast cancer risk or prognosis. The present study aimed to assess the association between SIRT1 gene polymorphisms and breast cancer in Egyptians.The study comprised 980 Egyptian females divided into a breast cancer group (541 patients) and a healthy control group (439 subjects). SIRT1 gene single nucleotide polymorphisms (SNPs) rs3758391, rs3740051 and rs12778366 were genotyped using real-time polymerase chain reaction (RT-PCR). Allelic and genotypic frequencies were determined in both groups and association with breast cancer and clinicopathological characteristics was assessed.Breast cancer patients exhibited elevated serum SIRT1 levels which varied among different tumor grades. SIRT1 rs3758391 and rs12778366 TT genotypes were more frequent, exhibited higher SIRT1 levels than CC and CT genotypes and were associated with histologic grade and lymph node status. SIRT1 rs12778366 TT genotype also correlated with negative estrogen receptor (ER) and progesterone receptor (PR) statuses. The T allele frequency for both SNPs was higher in breast cancer patients than in normal subjects. Combined GG and AG genotypes of rs3740051 were more frequent, showed higher serum SIRT1 levels than the AA genotype, and were associated with ER and PR expression. Furthermore, inheritance of the G allele was associated with breast cancer.Our findings reveal that rs3758391 and rs12778366 polymorphisms of SIRT1 gene are associated with breast cancer risk and prognosis in the Egyptian population

A novel role for SIRT-1 in L-arginine protection against STZ induced myocardial fibrosis in rats.

BACKGROUND: L-arginine (L-ARG) effectively protects against diabetic impediments. In addition, silent information regulator (SIRT-1) activators are emerging as a new clinical concept in treating diabetic complications. Accordingly, this study aimed at delineating a role for SIRT-1 in mediating L-ARG protection against streptozotocin (STZ) induced myocardial fibrosis. METHODS: Male Wistar rats were allocated into five groups; (i) normal control rats received 0.1 M sodium citrate buffer (pH 4.5); (ii) STZ at the dose of 60 mg/kg dissolved in 0.1 M sodium citrate buffer (pH 4.5); (iii) STZ + sirtinol (Stnl; specific inhibitor of SIRT-1; 2 mg/Kg, i.p.); (iv) STZ + L-ARG given in drinking water (2.25%) or (v) STZ + L-ARG + Stnl. RESULTS: L-ARG increased myocardial SIRT-1 expression as well as its protein content. The former finding was paralleled by L-ARG induced reduction in myocardial fibrotic area compared to STZ animals evidenced histopathologically. The reduction in the fibrotic area was accompanied by a decline in fibrotic markers as evident by a decrease in expression of collagen-1 along with reductions in myocardial TGF-β, fibronectin, CTGF and BNP expression together with a decrease in TGF-β and hydroxyproline contents. Moreover, L-ARG increased MMP-2 expression in addition to its protein content while decreasing expression of PAI-1. Finally, L-ARG protected against myocardial cellular death by reduction in NFκ-B mRNA as well as TNF-α level in association with decline in Casp-3 and FAS expressions andCasp-3protein content in addition to reduction of FAS positive cells. However, co-administration of L-ARG and Stnl diminished the protective effect of L-ARG against STZ induced myocardial fibrosis. CONCLUSION: Collectively, these findings associate a role for SIRT-1 in L-ARG defense against diabetic cardiac fibrosis via equilibrating the balance between profibrotic and antifibrotic mediators

Nutrition of medieval town populations according to archaeozoological evidence

Through a through exploration of available literature, this dissertation presents an overview of the explanatory capacity of Czech archeozoology and archeobotany regarding dietary practices of medival urban communities. The first section offers a summary of published information obtained through archeological research of medieval towns. Subsequently, the paper attempts a more detailed insight into the issue through the use of two case studies of selected urban locations. In the final section, it then contemplates the possibilities and limitations of comparative approaches and assesses the potential of environmental studies in documenting various forms of supply structures of medieval cities. Key words Archaeobotany, zooarchaeology, High Middle Ages, medieval towns, diet, Most, Chrudi

Therapeutic Potential of Date Palm Pollen for Testicular Dysfunction Induced by Thyroid Disorders in Male Rats.

Hyper- or hypothyroidism can impair testicular function leading to infertility. The present study was designed to examine the protective effect of date palm pollen (DPP) extract on thyroid disorder-induced testicular dysfunction. Rats were divided into six groups. Group I was normal control. Group II received oral DPP extract (150 mg kg(-1)), group III (hyperthyroid group) received intraperitoneal injection of L-thyroxine (L-T4, 300 μg kg(-1); i.p.), group IV received L-T4 plus DPP extract, group V (hypothyroid group) received propylthiouracil (PTU, 10 mg kg(-1); i.p.) and group VI received PTU plus DPP extract. All treatments were given every day for 56 days. L-T4 or PTU lowered genital sex organs weight, sperm count and motility, serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone (T), testicular function markers and activities of testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). Moreover, L-T4 or PTU increased estradiol (E2) serum level, testicular oxidative stress, DNA damage and apoptotic markers. Morphometric and histopathologic studies backed these observations. Treatment with DPP extract prevented LT4- or PTU induced changes. In addition, supplementation of DPP extract to normal rats augmented sperm count and motility, serum levels of LH, T and E2 paralleled with increased activities of 3β-HSD and 17β-HSD as well as testicular antioxidant status. These results provide evidence that DPP extract may have potential protective effects on testicular dysfunction induced by altered thyroid hormones

Hardy-Weinberg equilibrium for SIRT1 rs3758391, rs3740051 and rs12778366 in control subjects and breast cancer patients.

<p>Hardy-Weinberg equilibrium for SIRT1 rs3758391, rs3740051 and rs12778366 in control subjects and breast cancer patients.</p

Demographic, laboratory and clinical data in control and breast cancer groups.

<p>Data are expressed as mean ± S.E., or number and percentage, n (%). ALT, alanine transaminase; AST, aspartate transaminase, ALP, alkaline phosphatase; T. Bil, total bilirubin; † Tumors were graded according to the modified Bloom–Richardson system; T size of the tumor, T1 (< 2 cm), T2 (≥ 2–5 cm), T3 (≥ 5 cm), T4 (infiltration of the chest wall/skin), N regional lymph node involvement, N1 cancer has spread to 1 to 3 axillary lymph node(s), and/or tiny amounts of cancer are found in internal mammary lymph nodes on lymph node biopsy, N2 cancer has spread to 4 to 9 axillary lymph nodes, or cancer has enlarged the internal mammary lymph nodes, N3 cancer has spread to axillary lymph nodes, the internal mammary lymph nodes and/or infraclavicular and supraclavicular lymph nodes; ER, estrogen receptor; PR, progesterone receptor.</p

Effect of STZ alone or in combination with Stnl, L-ARG or Stnl+ L-ARG on incidence of fibrosis depicted histopathologically (A) and (B) % of fibrotic area in left ventricle (LV) as well as (C) LV hydroxylproline content.

<p>Data represent the means of six experiments ±SEM; *, ^#, ^ω and ^δ P<0.05 compared with CONT, STZ, STZ + Stnl and STZ + Stnl + L-ARG, respectively, using one-way ANOVA followed by Tukey's Multiple Comparison Test.</p

Effect of STZalone, or in combination with Stnl, L-ARG or L-ARG + Stnl on Fasting serum glucose (FSG), insulin and HbA1c%.

<p>Data represent the means of sixexperiments ±SEM.</p><p>*^{, #} and ^ωP<0.05 compared with CONT; STZ and STZ+ Stnl, respectively, using one-way ANOVA followed by Tukey's Multiple Comparison Test.</p><p>Effect of STZalone, or in combination with Stnl, L-ARG or L-ARG + Stnl on Fasting serum glucose (FSG), insulin and HbA1c%.</p

MicroRNAs as predictor markers for response to interferon treatment of chronic hepatitis C genotype-4 in Egyptian patients.

Hepatitis C virus genotype 4 (HCV-4) infection is common in the Middle East and Africa, with an extraordinarily high prevalence in Egypt. MicroRNAs (miRNAs) play an important role in various diseases, including HCV infection. The aim of the present study was to assess serum miR-122, miR-221 and miR-21 expression profiles in HCV-4 patients prior to treatment with HCV-4 combination therapy (pegylated alpha interferon and ribavirin) and to determine whether the miRNAs were associated with the drug response.RNA was extracted from pretreatment serum samples, and miR-122, miR-221 and miR-21 levels were measured by quantitative PCR. The results were compared among patients with sustained virological responses (SVR) and non-responders (NR).The expression levels of miR-21 and miR-122 were significantly different between the SVR and NR groups. Receiver operator characteristic (ROC) analysis revealed that the sensitivity, specificity and positive predictive values of miR-21 were 82.2%, 77.3% and 88.1%, respectively, with a cut-off value of 1.7. The sensitivity, specificity and positive predictive values of miR-122 were 68.9%, 59.1% and 77.5%, respectively, with a cut-off value of 3.5.miR-21 and miR-122 might be useful predictors for SVR in HCV-4 patients prior to the administration of combination therapy. A higher predictive response power was obtained for miR-21 than for miR-122. These results should reduce ineffective treatments

Effect of STZ alone or in combination with L-ARG or L-ARG + Stnl on metalloproteinase (MMP)-2 mRNA expression (A) and protein content (B).

<p>Data represent the means of six experiments ±SEM; *, ^#, ^ω and ^δP<0.05 compared with CONT, STZ, STZ+ Stnl and STZ+ Stnl + L-ARG, respectively, using one-way ANOVA followed by Tukey's Multiple Comparison Test.</p