The ameliorating role of sofosbuvir and daclatasvir on thioacetamide-induced kidney injury in adult albino rats.

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

Carotid plaques in adult rheumatoid arthritis patients; association with paroxonase 1 enzymatic activity and Q192R paroxonase 1 gene polymorphism.

Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case-control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml.

Circulating Cell Free Nuclear DNA, Mitochondrial DNA and Global DNA Methylation: Potential Noninvasive Biomarkers for Breast Cancer Diagnosis.

Eighty seven women with benign breast lesion, 120 patients with breast cancer (BC) and one hundred controls were included in the study. Quantification of mtDNA and nDNA was done by qPCR. Global DNA methylation was measured using ELISA. Circulating cell-free nDNA and mtDNA were significantly elevated in BC and benign breast lesions patients. Global methylation was significantly low in BC patients. Combining the studied parameters in one panel, nDNA/mtDNA/hypomethylation, improved their sensitivity in detecting BC to reach 92.5%. Circulating cell-free nDNA, mtDNA and global DNA hypomethylation can be used as diagnostic and prognostic markers for BC.

Circulating methylated RUNX3 and SFRP1 genes as a noninvasive panel for early detection of colorectal cancer.

OBJECTIVE: This study was conducted to assess the methylation status of runt-related transcription factor 3 (RUNX3) and secreted frizzled-related protein 1 (SFRP1) genes in paired tissue and serum samples of colorectal cancer (CRC), adenomatous, and control subjects and elucidate the association between methylation status on RUNX3 and SFRP1 mRNA expression. METHODS: Methylation status of RUNX3 and SFRP1 in paired tissue and serum samples and RUNX3 and SFRP1 mRNA expression in tissue from 85 patients with CRC, 40 with adenoma, and 40 healthy controls were determined using methylation-specific PCR and reverse transcription PCR. RESULTS: The frequency RUNX3 and SFRP1 genes methylation was significantly higher in both tissues and serum of CRC patients and was significantly associated with absence of its corresponding mRNA expression. The concordance between tissue and serum methylation status was 94.4% for RUNX3 and 94.3% for SFRP1. Tissue RUNX3 methylation status detected CRC with 63.53% sensitivity and 80.00% specificity, while serum RUNX3 methylation status detected CRC with 60.00% sensitivity and 82.50% specificity. Tissue SFRP1 methylation status showed a sensitivity of 82.35% and specificity of 65.00%, while serum SFRP1 methylation status showed a sensitivity of 77.65% and specificity of 70.00% in detection of CRC. RUNX3/SFRP1/carcinoembryonic antigen (CEA) panel identified CRC with sensitivity of 89.41% in tissue and 84.71% in serum. CONCLUSION: Our results verified the reliability of using serum RUNX3 and SFRP1 methylation status as a noninvasive biomarker for diagnosis of CRC and that combined detection of RUNX3/SFRP1/CEA panel might be a promising strategy for early detection of CRC.

Genetic and epigenetic modifications of adiponectin gene: Potential association with breast cancer risk.

BACKGROUND: Adipokines produced by adipose tissue are directly linked to obesity and may contribute to the pathogenesis of cancer. We hypothesized that genetic and epigenetic modifications in the adiponectin (ADIPOQ) gene and their impact on serum ADIPOQ levels may participate in increasing breast cancer (BC) risk. The present study aimed to investigate ADIPOQ +45 T/G gene polymorphism, methylation status at CpG sites -74 nucleotides (nt) and -283 nt of the ADIPOQ gene, and ADIPOQ serum levels in BC obese women. METHODS: Serum ADIPOQ was measured by an enzyme-linked immunosorbent assay. ADIPOQ +45 T/G gene polymorphism and ADIPOQ promoter methylation status were determined using a polymerase chain reaction (PCR) and a methylation-specific PCR, respectively, in 120 obese women with BC and 120 age-matched controls. RESULTS: ADIPOQ +45 GG genotype carriers had a significant increased risk of developing BC (odds ratio = 6.2, 95% confidence interval = 1.3-29.6, p = 0.02). ADIPOQ gene methylation at site -74 nt resulted in a 1.7-fold increased BC risk. Methylation at site -283 nt resulted in a 1.9-fold increased BC risk. Moreover serum levels of ADIPOQ were significantly decreased in BC patients and down-regulated in the presence of methylation in both examined sites. By contrast, no association between ADIPOQ gene polymorphism and serum ADIPOQ level was detected. Using both methylated sites in one panel detected cancer breast with 76.67% sensitivity and 62.18% accuracy. CONCLUSIONS: ADIPOQ +45 T/G polymorphism and ADIPOQ promoter methylation were found to be associated with BC risk in obese Egyptian women.

miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients.

Recently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.

Osteopontin and interleukin-17A genes polymorphisms in Egyptian systemic lupus erythematosus patients: A relation to disease activity and severity.

Osteopontin (OPN) is involved in the regulation of the immune response and is accused in the pathogenesis of several autoimmune diseases including systemic lupus erythematosus (SLE). An obvious link between OPN and T cells, particularly T helper 17 cells is reported, where OPN produced by dendritic cells supports interleukin-17 (IL-17) expression, contributing to pathology of autoimmune disorders. The aim of the study was to investigate the association of genotypes and alleles frequencies of OPN 9250 (rs1126616) and IL-17A 197 (rs2275913) genes polymorphisms with their serum levels, susceptibility, disease activity and severity in Egyptian SLE patients. A total of 80 SLE patients and 80 healthy subjects were enrolled. The PCR-RFLP technique was used to detect OPN 9250 C/T and IL-17A 197 G/A genes polymorphisms. Serum OPN and IL- 17 levels were measured by the enzyme-linked immunosorbent assay. OPN TT genotype and T allele were significantly detected in SLE patients more than controls (P = 0.003, P < 0.001 respectively). IL-17A AA genotype showed non-significant higher frequency in SLE patients than in their controls (P = 0.07). While only the A allele of IL-17A polymorphism was significantly elevated in patients (P = 0.048). There was statistical significant association between OPN CT and TT genotypes and both renal and mucocutaneous manifestations. Also IL-17A AG and AA genotypes was significantly associated with renal, mucocutaneous in addition to the hematological manifestations. Serum OPN levels were significantly increased with TT genotype while serum IL-17 levels were significantly increased with AA genotype. Disease activity and severity scores were significantly elevated with both OPN TT and IL-17A AA genotypes. In conclusion, OPN 9250 C/T and IL-17A 197 G/A genes polymorphisms and their serum levels seemed to have a role in pathogenesis of SLE.

RASSF1A and SOCS1 genes methylation status as a noninvasive marker for hepatocellular carcinoma.

BACKGROUND: DNA methylation status is one of the most prevalent molecular alterations in human cancers. Identification of powerful diagnostic and prognostic biomarkers for hepatocellular carcinoma (HCC) without a biopsy is urgently required. OBJECTIVE: The purpose of this study was to determine the methylation status of RASSF1A and SOCS-1genes as a non-invasive biomarker for HCC identification and prognosis. METHODS: Methylation specific-PCR technique was performed to recognize the methylation status of RASSF1A and SOCS-1 genes in 100 patients with HCC, 100 patients with liver cirrhosis (LC) but without HCC were considered as cirrhotic liver control group and 100 healthy control. RESULTS: Methylation of RASSF1A and SOCS-1 genes were detected in 40% and 38% of HCC patients respectively, 14% and 20% of LC patients respectively. Methylation of SOCS-1 gene in peripheral blood of healthy control was 23%. Methylation of RASSF1A gene was associated with age, tumor size, vascular invasion and α fetoprotein (AFP), while SOCS-1 gene methylation was significantly associated with tumor size and AFP. Furthermore, using RASSF1A/ SOCS-1/ AFP panel improve diagnostic sensitivity for HCC 86% and specificity of 75%. CONCLUSION: RASSF1A and SOCS1 genes methylation status may play an important role in the process of hepatocarcinogenesis and may be used as diagnostic and prognostic noninvasive biomarkers for HCC when combined with serum AFP.

Early prediction of acute kidney injury in patients with acute on chronic liver failure by measuring kidney injury Molecule-1 level in Urine at Zagazig University Hospitals

Background and study aim: Some of patients with decompensated cirrhosis will exhibit newly developed acute liver failure. This condition is called acute-on-chronic liver failure (ACLF). Acute kidney injury (AKI) is common with ACLF. Kidney injury Molecule-1 (KIM-1) is an ideal biomarker of AKI. The aim of this study was to evaluate role of KIM-1 in prediction of AKI in ACLF patients. Patients and Methods: Eighty four patients were included in this study. They were selected from hospitalized patients with acute decompensated cirrhosis. They were allocated into two groups; group I: patients with no acute-on-chronic liver failure (ACLF), group II: patients with ACLF. Results: KIM-1 was significantly higher in the ACLF (group II). KLM-1 median was 2.4 in group I vs 7.35 in group II with p value <0.001. We found that at cut off value of ≥0.5 KLM-1 can predict the presence of AKI with sensitivity of 85.7%, specificity 88.1%, positive predictive value 87.8%, negative predictive value 86%, accuracy 86.9% and AUC= 0.867 p <0.001. Conclusion: KLM-1 rises significantly in patients with ACLF. KLM-1 can be reliable in prediction of the presence of acute kidney injury in decompensated cirrhosis

B2 adrenergic receptor gene polymorphism effect on childhood asthma severity and response to treatment.

BackgroundAlterations of B2 adrenergic receptor (ß2AR) can modulate the severity of asthma and the response to treatment. Therefore, we aimed to evaluate ß2AR gene polymorphism at codons 16 and 27 and their effect on asthma severity and response to treatment in asthmatic children.MethodsCase-control study was conducted on 156 children; 104 of them had bronchial asthma and 52 were healthy children (control group). Subjects of the study underwent history taking, clinical examination, pulmonary function tests, serum IgE level assessment, and identification of ß2AR-16 A46G and ß2AR-27 C79G polymorphism using PCR-Restriction Fragment length polymorphisms (RFLP) test.ResultsThere was a higher frequency of Arg-Gly genotypes (odds ratio (OR)=6.57; confidence interval (CI): 2.42-18.81, P<0.001) and lower frequency of Arg-Arg (OR=4.7; CI: 2.05-10.95, P<0.001) among asthmatic children compared with that among controls at codon 16. The presence or absence of Gly16 or Glu27 either homozygous or heterozygous for both correlated with the grade of asthma severity. The presence of heterozygous Arg-Gly and Gln-Glu gives a better response to drug therapy than the presence of Gly-Gly and Glu-Glu genotypes at codons 16 and 27.ConclusionPolymorphism of ß2AR at codons 16 and 27 correlates with asthma severity and response to treatment in asthmatic children.

Molecular effect of human umbilical cord blood CD34-positive and CD34-negative stem cells and their conjugate in azoospermic mice.

Currently, azoospermia is one of the most common diseases of male infertility. Stem cell research is the new hope for novel therapy with a higher degree of safety and lower cost. This study aimed to investigate the effect of umbilical cord blood-derived stem cells (" and mesenchymal "UCB-MSCs") and mono-cell layer implanted into the induced azoospermic mice testis. Stem cells were isolated from umbilical cord blood and CD34+ve cells were separated from negative one by Mini MACs column. At 5th week after single injection of busulfan, stained mesenchymal (CD34-ve), hematopoietic stem cells (CD34+ve) and their conjugate (mono-cell layer) were injected locally into testis. At the end of the study, MSCs group showed that mRNA levels of genes related to meiosis (Vasa, SCP3, and PgK2) were increased with significant decrease of FSH and LH levels, compared to control group. Histologically, most of the tubules restored normal architecture. In contrast, HSCs and mono-cell layer groups showed statically insignificant change of FSH, LH, and gene expression, compared to control group. Histologically, distorted seminiferous tubules, with reduction in sperm content, and interstitial mononuclear cellular infiltration were seen. There was significant increase in the optical density of PCNA immune reaction in MSCs group than azoospermia, HSCs, and mono-cell layer, while there was non-significant difference between MSCs and control group. The present study suggested that injection of MSCs into chemotherapeutic-induced azoospermia in mice improved testicular failure; histologically and functionally, by restoration of spermatogenic gene expression while HSC and mono-cell layer showed no effect on spermatogenesis added to that mono-cell layer may induce testicular tissue damage.

Therapeutic effect of spermatogonial stem cell on testicular damage caused by lead in rats.

OBJECTIVE: To investigate the possible therapeutic effect of spermatogonial stem cells (SSCs) on lead-induced apoptosis and consequently infertility in adult male rats. MATERIALS AND METHODS: Sixty-six Sprague Dawley adult male rats were divided into three groups: control group, lead (Pb) acetate exposed group received (20mg Pb/kg) for 3weeks, and SSCs treated group. Each group included twenty-two rats. Serum testosterone level, 3 beta-hydroxysteroid dehydrogenase (3ß-HSD), 17 beta-hydroxysteroid dehydrogenase (17ß-HSD), proliferating cell nuclear antigen (PCNA) genes expression by RT-PCR, caspase 3 expression by immunohistochemistry and testicular histological findings were tested. RESULTS: Pb acetate exposed rats showed a significant decrease in the epididymal sperm count, motility, viability, serum testosterone level and testicular expression of 3ß-HSD, 17ß-HSD and PCNA compared to the control group, while treatment with SSCs attenuated Pb acetate induced decrease for these variables. Moreover, the increasing apoptosis of germinal cells as well as the high expression of caspase-3 induced by Pb acetate was reduced by SSCs treatment. CONCLUSION: SSCs exhibited therapeutic effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and severity of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.

Circulating microRNAs - a new horizon in molecular diagnosis of breast cancer.

BACKGROUND: The potential use of microRNAs (miRNAs) as ideal tumor markers has been the focus of recent research. OBJECTIVE: Our hypothesis was that circulating miRNAs are differentially expressed in pretherapeutic sera of breast cancer patients compared to controls. MATERIALS AND METHODS: Using real-time quantitative polymerase chain reaction (qPCR) analysis, levels of 5 candidate miRNAs (miR10b, miR34a, miR155, miR195 and miR16) were quantified in sera of breast cancer patients and control individuals. RESULTS: Levels of preoperative sera showed significant upregulation of 3.36 fold rise in miR10b (p<0.001), a 2.07 fold rise in miR155 (p =0.005) and remarkable over expression of 11.9 fold rise in miR195 (p<0.001) of cases than controls. There was significant down regulation of miR34a (0.032, p<0.001). The comparison with the clinicopathological data of the breast cancer patients revealed significant high serum level of miR155 (p =0.004) and miR195 (p =0.002) in patients with lymph node metastasis and higher levels of miR10b (p =0.001) and miR155 (p <0.001) with distant metastasis (M1) than without metastasis (M0), in addition to significant decrease in miR34a (p <0.001) level in M1 than M0 cases. CONCLUSIONS: These findings suggest that systemic circulating miRNAs have potential use as novel biomarkers for breast cancer.

Vitamin D Profile: can it affect the response to standard Hepatitis C treatment in Egyptian patients?

Background and study aim : Vitamin D is a potent immunomodulator. It is reported to be related to the severity of fibrosis and responsiveness to interferon-based therapy in genotype 1 chronic hepatitis C (CHC), so we aimed to evaluate if there is an association between vitamin D metabolism related genes and vitamin D level with the degree of liver damage and the response to treatment of CHC in our locality. Patients and methods : Two hundred and forty five Egyptian patients (123 patients with sustained virological response and 122 patients with treatment failure) were included. They were subjected to routine investigation needed for treatment, in addition to estimation of 25-OH vitamin D level in serum by ELISA and CYP27B1-1260 gene polymorphism by PCR-RFLP method. Results: We found that serum levels of vitamin D showed statistically significant increase in responders in comparison with non responders. The distribution of CYP27B1-1260 AC and CC genotypes were significantly presented in the non responders in comparison with the responders. CYP27B1-1260 AC and CC genotypes carriers had a high risk for treatment failure, (OR= 14.7, 95% CI= 2.3-20.1, P<0.001; OR = 20.4, 95% CI= 2.9-21.3, P<0.005 respectively). Serum levels of vitamin D showed statistically significant negative correlations with the activity and fibrosis of the liver in both responders and non responders. Also, there was negative correlation between vitamin D level and viral load in non responder patients (r= -.232, P=0.01). As regard the value of serum vitamin D level in discriminating responders from non responders; area under the ROC curve was 0.708 (95% CI 0.643-0.774). At a cutoff value of 19 ng/dL of serum vitamin D yielded sensitivity 79%, specificity 58%, positive predictive value (PPV) 65%, and negative predictive value (NPV) 73%. Conclusion: Vitamin D serum level and CYB27B1 -1260 genotype could be used as a predictor to anti HCV treatment response in our locality

Estrogen receptor alpha (ERα) promoter methylation status in tumor and serum DNA in Egyptian breast cancer patients.

BACKGROUND: Status of DNA methylation is one of the most common molecular alterations in human neoplasia. Because it is possible to detect these epigenetic alterations in the bloodstream of patients, we investigated the aberrant DNA methylation status of estrogen receptor alpha (ERα) in patient pretherapeutic sera and tissue. MATERIALS AND METHODS: In this case control study the patient series consisted of 120 sporadic primary breast cancer cases and 100 patients with benign breast lesion. ER3, ER4, and ER5 primers were used for methylation-specific polymerase chain reaction (MSP) to analyze the CpG methylation of promoter region of ERα gene. Correlation between ER3, ER4, and ER5 methylation and clinicopathological characteristics of the patients was investigated. RESULT: The methylation status of ER3, ER4 and ER5 was 65%, 26.7% and 61.7% in tissue respectively and 57.5%, 21.7% and 55.8% in serum respectively. The concordance between tumor and serum DNA methylation was 80%, 72% and 92% for ER3, ER4 and ER5 respectively. CONCLUSIONS: This study demonstrated the potential utility of serum DNA methylation of ERα gene promoter as a non-invasive diagnostic and/or prognostic marker in patients with breast cancer.

Urinary biomarkers of acute kidney injury in patients with liver cirrhosis.

Acute kidney injury (AKI) is a common complication in cirrhotic patients. Serum creatinine is a poor biomarker for detection of renal impairment in cirrhotic patients. This study aimed to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary interleukin-18 (IL-18) as early biomarkers of acute kidney injury in cirrhotic patients. 160 patients with cirrhosis admitted to the Liver Units at Zagazig University Hospitals were classified into three groups: (I) nonascitic patients, (II) ascitic patients without renal impairment, and (III) ascitic patients with renal impairment. Patients with renal impairment were further divided into four subgroups: [A] prerenal azotemia, [B] chronic kidney disease (CKD), [C] hepatorenal syndrome (HRS), and [D] acute tubular necrosis (ATN). Significant elevation of both urinary NGAL and urinary IL-18 in cirrhotic patients with renal impairment especially in patients with ATN was observed. Urinary NGAL and urinary IL-18 have the ability to differentiate between AKI types in patients with cirrhosis. This could improve risk stratification for patients admitted to the hospital with cirrhosis, perhaps leading to early ICU admission, transplant evaluation, and prompt initiation of HRS therapy and early management of AKI.

CYP1A1 gene polymorphisms and smoking status as modifier factors for lung cancer risk.

OBJECTIVE: Lung cancer remains the most prevalent malignancy worldwide. Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes. Several metabolic enzymes are currently under investigation for their possible role in lung cancer susceptibility, including members of the cytochrome P450 (CYP) superfamily. The aim of this work was to identify the correlation between CYP1A1 m1 and m2 polymorphisms and lung cancer risk and figure its interactions with smoking as genetic modifiers in the etiology of lung cancer in the Egyptian population. MATERIALS AND METHODS: One hundred and ten patients with lung cancer and one hundred and ten controls were enrolled in the study. CYP1A1 m1 and m2 polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism. RESULTS: Subjects carrying TC and CC genotypes of CYP1A1 m1 and AG and GG genotypes of CYP1A1 m2 were significantly more likely to develop lung cancer especially squamous cell carcinoma. The proportion of lung cancer attributable to the interaction of smoking and CYP1A1 m1 and CYP1A1 m2 polymorphisms was 32% and 52% respectively. CONCLUSION: Our results revealed that CYP1A1 m1 and m2 polymorphisms contribute to smoking related lung cancer risk in the Egyptian population.

Methylation status and protein expression of RASSF1A in breast cancer patients.

Recently genetics and epigenetics alterations have been found to be characteristic of malignancy and hence can be used as targets for detection of neoplasia. RAS association domain family protein 1A (RASSF1A) gene hypermethylation has been a subject of interest in recent researches on cancer breast patients. The aim of the present study was to evaluate whether RASSF1A methylation status and RASSF1A protein expression are associated with the major clinico-pathological parameters. One hundred and twenty breast cancer Egyptian patients and 100-control subjects diagnosed with benign lesions of the breast were enrolled in this study. We evaluated RASSF1A methylation status in tissue and serum samples using Methyl specific PCR together with RASSF1A protein expression in tissues by immunohistochemistry. Results were studied in relation to known prognostic clinicopathological features in breast cancer. Frequency of RASSF1A methylation in tissues and serum were 70 and 63.3 % respectively and RASSF1A protein expression showed frequency of 46.7 %. There was an association between RASSF1A methylation in tissues, serum and loss of protein expression in tissues with invasive carcinoma, advanced stage breast cancer, L.N. metastasis, ER/PR and HER2 negativity. RASSF1A methylation in serum showed high degree of concordance with methylation in tissues (Kappa = 0.851, P < 0.001). RASSF1A hypermethylation in tissues and serum and its protein expression may be a valid, reliable and sensitive tool for detection and follow up of breast cancer patients.

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM. MATERIALS AND METHODS: One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA. RESULT: Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P=<0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR=2.3, 95% CI=1.3-4.2, P=0.005; OR=2.2, 95% CI=1.1-4.7, P=0.04; OR=1.8, 95% CI=1.03-3.04, P=0.04; OR=4.03, 95% CI=1.2-13.1, P=0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not. CONCLUSION: Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.