The Combined Use of Dickkopf-1 and Soluble Axl Improves Hepatocellular Carcinoma Diagnostic Efficacy in Hepatitis C Patients.

BACKGROUND: Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases. METHODS: A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants. RESULTS: HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages. CONCLUSIONS: combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.

The Potential Impact of MYH9 (rs3752462) and ELMO1 (rs741301) Genetic Variants on the Risk of Nephrotic Syndrome Incidence.

The kidney lost a lot of protein in the urine when you have nephrotic syndrome (NS). Clinical manifestations mostly common in NS include massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Idiopathic nephrotic syndrome is currently classified into steroid-dependent (SDNS) and steroid-resistant (SRNS) based on the initial response to corticosteroid therapy at presentation. Several reports examined the association of the MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs741301 G > A) variant as risk factors for Nephrotic Syndrome. This study aimed to determine the potential effect of the MYH9 gene (rs3752462, C > T) and ELMO1 gene (rs741301) variant on the risk of (NS) among Egyptian Children. This study included two hundred participants involving 100 nephrotic syndrome (NS) cases and 100 healthy controls free from nephrotic syndrome (NS). The MYH9 gene (rs3752462, C > T) variant and ELMO1 gene (rs G > A741301) variant were analyzed by ARMS-PCR technique. Nephrotic syndrome cases include 74% SRNS and 26% SDNS. Higher frequencies of the heterozygous carrier (CT) and homozygous variant (TT) genotypes of the MYH9 (rs3752462, C > T) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the MYH9 (rs3752462, C > T variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.85, p < 0.001), dominant (OR 3.97, p < 0.001) models, and the recessive model OR 5.94, p < 0.001). Higher frequencies of the heterozygous carrier (GA) and homozygous variant (AA) genotypes of ELMO1gene (rs G > A741301) variant were observed in NS patients compared to the controls with p-value < 0.001. The frequencies of the ELMO1 (rs G > A741301) variant indicated a statistically significant elevated risk of NS under various genetic models, including allelic model (OR 2.15, p < 0.001), dominant models (OR 2.8, p < 0.001), and the recessive model (OR 4.17, p = 0.001). Both MYH9 and ELMO1 gene variants are significantly different in NS in comparison with the control group (p < 0.001). The MYH9 gene (rs3752462, C > T) and ELMO1gene (rs G > A741301) variants were considered independent risk factors for NS among Egyptian Children.

Association of HOTAIR gene rs920778 (C > T) and rs4759314 (A > G) polymorphism with breast cancer in Egyptian women.

BACKGROUND: Hox transcript antisense RNA (HOTAIR) is considered an oncogene associated with the initiation and progression of many malignancies. Previous studies have examined the connection between HOTAIR SNPs rs4759314 and rs920778 for breast cancer (BC), getting variable results in multiple ethnicities. Therefore, this study was designed to evaluate the connection between these two SNPs and disease vulnerability, clinic-laboratory, and hormonal parameters, featuring status associations with the BC risk in an Egyptian woman sample. METHODS AND RESULTS: In this case-control study, DNA was taken from the blood of 100 BC patients and 100 unrelated healthy Egyptian females. The characterization of rs4759314 was genotyped using the T-ARMS-PCR method and rs920778 using the SNP-RFLP technique for all participants. The frequency of the rs4759314 A > G variation revealed a statistically significant increase in BC risk with dominant (p = 0.013, OR = 1.592, 95% Cl = 1.105-2.293), co-dominant (p = 0.006, OR = 2.314, 95%Cl = 1.278-4.191) and overdominant (p = 0.002, OR = 2.571, 95% Cl = 1.430-4.624) genetic models. On the other hand, the rs920778 C > T polymorphism was not significantly associated with BC. ER/PR positivity with HER2 negativity was significantly associated with the AA genotype compared to the AG genotype. Otherwise, no significant associations between the two SNPs and clinical stage or hormonal features could be found. In conclusion, the rs4759314 A > G SNP in the HOTAIR gene is strongly associated with BC, which might warrant its determination among affected families for prevention and early treatment.

Genetic studies of nephrotic syndrome in Egyptian children.

INTRODUCTION: Nephrotic syndrome (NS) might be caused by a kidney disorder or it can be a secondary disease. Untreated or resistant to treatment, NS stimulates glomerular damage that reduces the kidney function. This reduction leads to the end stage of renal failure. Therefore, it is very important to diagnose NS early, with the aim of inhibiting or lessening its associated morbidity and mortality. METHODS: Gene polymorphism analysis for the three genes eNOS 27 bp VNTR, GSTP1 and IL-10(1082 G/A) were checked in 98 children with NS and 101 control subjects. RESULTS: eNOS 27 bp VNTR genotypes and alleles are significantly different in the group of 98 children with NS compared to the 101 control subjects. The frequencies of ab and bb genotypes are significantly lower in patients than in the control group (ab: 17.2% vs. 22.8%; OR: 0.19; 95% CI: 0.06-0.58; p = 0.0026 & bb: 54.7% vs. 70.3%; OR: 0.19; 95% CI: 0.07-0.5; p = 0.0004). However, neither GSTP1 nor IL-10(1082 G/A) genotypes showed any significant difference in both groups. CONCLUSIONS: eNOS 27 bp VNTR gene might be considered as an independent risk factor in the early prediction of nephrotic syndrome incidence, which may help prevent/reduce the occurrence of other complications associated with the late diagnosis and treatment of the disease.

Genetic and biochemical studies of hepatic carcinoma in the Egyptian population.

BACKGROUND: Hepatocellular carcinoma (HCC), a deadly malignancy of the liver, is considered the third leading reason behind cancer deaths. It is more frequent in men than in women of ages above 50. Liver disease, leading to liver cirrhosis (LC), is mostly caused by alcoholism abuse, reaction diseases of the liver, or viral hepatitis B or C infection. Interleukin-6 (IL-6) is considered an effective pro-inflammatory cytokine, which plays a crucial role in the host defense mechanism. Its level is higher in HCC patients than in LC cases, indicating that tumor cells increase the production of cytokines. The X-ray repair cross-complementing group 1 (XRCC1) gene is a major DNA repair gene. It acts as a scaffold of various activities that are concerned in the repairing method by interacting with components of base excision repair. This study aims to measure the serum concentrations of IL6 and C-reactive protein (CRP) and investigate whether XRCC1 Arg194Trp and Arg399Gln polymorphisms are related to HCC disease. MATERIALS AND METHODS: Whole-blood DNA was extracted from 123 HCC patients and 123 healthy volunteers. Tetra-primer amplification refractory mutation system was performed in the detection of XRCC1 Arg399Gln and Arg194Trp polymorphisms. RESULTS: Serum concentration levels of IL-6 and CRP are significantly higher in patients with HCC than in control subjects. The allelic and genotype frequency distributions of XRCC1 (Arg399Gln and Arg194Trp) are significantly increased in HCC cases compared to healthy volunteers. CONCLUSION: Arg/Gln, Arg/Trp, Gln/Gln, and Trp/Trp genotypes are associated with higher risk HCC than the Arg/Arg genotype.

Gene polymorphism of 3'APO-VNTR in Egyptians with coronary artery disease.

BACKGROUND: Coronary artery diseases (CAD) are big health problem in both developed and developing countries. It is considered one of the main causes of death in the world. Dyslipidemia increases the risk of CAD incidences. It is aimed in this worktop study the impact of 3'APOBVNTRgene on CAD incidences. METHODS: Eighty CAD patients and ninety-three healthy volunteers are enrolled in this study. Lipid parameters were estimated in both groups and PCR technique has been performed to analyze 3'APOB-VNTR gene polymorphism. RESULTS: The genotypes 31/31, 31/37, 37/37 and 31/44 are more predominant in both groups. The frequency of 24/31 in CAD patients is (0.137) while it is completely absent in the control group. Our results show that there is an increase in the frequency of various genotypes (e.g., 17/31 and 21/34 genotypes) in the control group compared to theca patients group. CONCLUSIONS: 3'APOB-VNTR gene could probably be considered a risk factor for CAD incidences and may help to early diagnose them.

Marjoram and sage oils protect against testicular apoptosis, suppressed Ki-67 expression and cell cycle arrest as a therapy for male infertility in the obese rats.

Alterations in testicular apoptosis, cell cycle progression and proliferation rate in dietary-induced obese male rats and role of oral administration of marjoram (0.16 ml/kg BW) and sage (0.05 ml/kg BW) oils were evaluated. Results showed increased body weight, serum leptin, testicular lipid peroxidation, protein oxidation and nitric oxide, with reduction in serum testosterone, sperm count and endogenous enzymatic and non-enzymatic antioxidants in testis of the obese rats. Flow cytometry results revealed increased number of annexin-V (+ve) cells with activation of apoptotic proteins (Bax, caspase-3) and reduction of anti-apoptotic Bcl-2. Cell cycle arrest at phases S and G2/M with decline in expression of Bcl-2 and germ cell proliferation marker ki-67 was also validated, indicating lowered spermatogenesis in the obese rats. Supplementation of marjoram or sage oils displayed normalized body weight, sperm count, germ cells apoptosis and proliferation, suggesting the two oils as a new therapeutic approach against obesity promoted male infertility. PRACTICAL APPLICATIONS: Obese men have a greater chance of fertility problems compared to those with normal weight. Obesity-associated oxidative stress and free radicals production have shown to adversely affect sperm quality with activation of pro-apoptotic pathways, allowing germ cell death. Marjoram and sage essential oils are now being widely studied due to their antioxidant and radical scavenging properties. Our findings indicated effectiveness of the two oils for combating body weight gain, testicular oxidative stress, and apoptosis, which seemed to aid in increasing sperm count. The outcomes of this study may help scientists to formulate novel medications for improving fertility problems in men.

Association of polymorphisms G(-174)C in IL-6 gene and G(-1082)A in IL-10 gene with traditional cardiovascular risk factors in patients with coronary artery disease.

Interleukin-6 (IL-6) polymorphism has been associated with the genetic susceptibility to coronary artery disease (CAD) and also with the lipid profile in different populations. The present work aimed at studying the association, if any between the IL-6 (174) G/C and IL-10 (1082) G/A genes with hypertension or hyperlipidimia in Egyptian patients with CAD and the association of the IL-6 -174 G/C polymorphism with serum IL-6 levels. 108 Egyptian patients with CAD and 143 unrelated healthy subjects were included in the study. The different genotypes of IL-6 and IL-10 were detected by polymerase chain reaction. Serum levels of lipoprotein(a) [Lp(a)] and IL-6 were estimated in the patients, as well as in the healthy subjects. Increased frequency of G allele, GG and GC genotypes in IL-6, as well as decreased frequency of C allele and CC genotype were found in CAD patients, compared to healthy subjects [P = < 0.0001, OR = 3.95, 95% CI (2.16-7.22) for GG and GC vs CC genotype], [P = < 0.0001, OR = 3.44, 95% CI (2.26-5.23) for G allele]. There was an increased frequency of G allele vs A allele in IL-10 genotype in CAD patients, compared to healthy subjects [P = 0.005, OR = 1.866, 95% CI (1.2-2.9]. Higher levels of both Lp(a) and IL-6 were observed in CAD patients, compared to control subjects (P = 0.0012, P = 0.0346, respectively). Increased frequency of IL-6 -174 G-allele was implicated in a greater cardiovascular risk and the presence of G allele or homozygosity for G allele of IL-10 G/A (1082) was associated with an increased prevalence of CAD. The GC genotype and G allele in IL-6 had significant correlation with hyperlipidimic CAD patients; however, G allele in IL-6 and IL-10 showed significant association with hypertension. Thus, G allele in IL-6 and IL-10 was considered as an independent risk factor in hypertensive CAD patients.