Hepatitis C virus infection and gene expression of hepatocellular carcinoma in Egyptian patients

Introduction: Gene expression profiling of hepatocellular carcinoma (HCC)is promising for refining the diagnosis and prognosis as well as identifyingpotential therapeutic targets.Aim of the Study: Our study aimed to study the gene expression in 40 HCC patients infected with hepatitis C virus (HCV) using RT-PCR technique on surgical liver sample. Gene expression changes in HCV-positive group were compared with gene expression in HCV-negative group. Four genes were included in this study, AFP gene, CD10 gene, HGF gene and GRB2 gene. The expression of the four genes were slightly higher in HCV positive group than in HCV negative group, however, the difference between the two groups wasnon-significant. HGF gene was expressed in only 20% of HCC patients andGRB2 gene was expressed in 95% of HCC patients. AFP gene and CD10 gene were expressed in all patients.Conclusion: AFP gene, CD10 gene and GRB2 gene play an important role as diagnostic markers of HCC.Key Words: Hepatocellular carcinoma, hepatitis C virus, AFP gene, CD10 gene, HGF gene and GRB2 gene

Oxidative Stress -a Phenotypic Hallmark of Fanconi Anemia and Down Syndrome: The Effect of Antioxidants

Background: Oxidative stress plays a major role in the pathogenesis of leukemia.prone diseases such as Fanconi anemia (FA) and Down syndrome (DS). Aim: To explore the oxidative stress state in children with DS and FA by estimating the levels of antioxidants (e.g., malondialdehyde [MDA], total antioxidant capacity, and superoxide dismutase [SOD] activity) and DNA damage, and to evaluate of the effect of antioxidant treatment on these patients.Subjects and Methods: The study included 32 children clinically diagnosed with (15 patients) and FA (17 patients) in addition to 17 controls matched for age and sex. MDA, total antioxidant capacity, SOD activity, and DNA damage were measured. Antioxidants including Vitamin A, E, and C were given to the patients according to the recommended daily allowance for 6 months. Clinical follow.up and re.evaluation were conducted for all patients. Laboratory tests including complete blood count, karyotyping, DNA  damage, and oxidative stress were re.evaluated. Statistical analysis was performed using statistical computer program Statistical Package for the Social Sciences version 14.0. Results: Children with FA and DS had elevated levels of oxidative stress and more DNA damage than controls. Oxidative stress parameters and DNA damage improved in FA and DS patients after antioxidant administration. Conclusion: Early administration of antioxidants to FA and DS patients is recommended for slowing of the disease course with symptoms   amelioration and improvement of general health.Keywords: Down syndrome, Oxidative DNA damage, Oxidative stres

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

Predictive Value Of Biochemical Markers In Pregnancy Induced Hypertension

Hypertensive disorders of pregnancy complicate 10% of all pregnancies. They include gestational hypertension, preeclampsia, eclampsia, and chronic hypertension. The aim of this study was to identify predictive markers for early diagnosis of women who are at risk of gestational hypertension or preeclampsia. This study was conducted on a total of 64 cases. Twenty nine were pregnant females who developed pregnancy induced hypertension and 35 females were normotensive throughout pregnancy with normal pregnancy outcome taken as controls. Subjects were recruited from the Prenatal Diagnosis Clinic, at the National Research Center. Maternal blood samples were taken as part of the department\'s routine second trimester biochemical screening program at 14- 20 weeks gestation. All cases were subjected to the estimation of human chorionic gonadotropin (hCG), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), nitric oxide (NO) and the lipid peroxidation product malondialdehyde (MDA), in addition to the estimation of lipid profiles {cholesterol (Ch), high density lipoprotein cholesterol (HDLc), low density lipoprotein cholesterol (LDLc) and triglycerides (TG)}, urea and creatinine. The study showed significant increase of β-hCG, TNF-α, CRP, MDA, urea, creatinine, TG, Ch and LDLc in women who developed PIH compared with normotensive pregnant women, while NO was significantly decreased in women who developed PIH compared with normotensive pregnant women. It could be concluded that the elevated levels of TNF-α, β-hCG, CRP and MDA, in addition to decreased levels of NO and abnormal lipid profiles were implicated in subsequent risk for PIH. Furthermore TNF-α and MDA may be considered as important predictive markers for early detection of PIH. Keywords: PIH, TNF-α, MDA, CRP, hCG, biochemical markers Egyptian Journal of Biochemistry and Molecular Biology Vol. 26 (2) 2008: pp. 49-6

Putative adjunct therapies to target mitochondrial dysfunction and oxidative stress in phenylketonuria, lysosomal storage disorders and peroxisomal disorders

Introduction: Oxidative stress (OS) and mitochondrial dysfunction are implicated in the pathogenesis of a number of metabolic diseases. OS occurs when there is an imbalance between the pro-oxidant/antioxidant homeostasis, leading to an increased generation of reactive oxidant species (ROS) with resultant cellular dysfunction. It is becoming apparent that increased ROS generation may be attributable to secondary mitochondrial dysfunction as a consequence of disease pathophysiology. Mitochondrial dysfunction occurs as a result of oxidative damage from enhanced ROS generation as well as the accumulation of toxic metabolites in some metabolic diseases. Areas covered: The present review will discuss evidence of OS and mitochondrial dysfunction in phenylketonuria (PKU), lysosomal storage disorders (LSDs), and peroxisomal disorders. In addition, potential adjunct therapies which have the potential to enhance mitochondrial functioning and mitigate OS will be explored. The databases utilized for this review were Pubmed and the Wed of science, with inclusive dates, 1988–2020. Expert opinion: There is an un-unified approach in the treatment of metabolic diseases. Agents including augmenters of mitochondrial function, antioxidants, and activators of mitochondrial biogenesis, may be beneficial. However, although successful in some cases, these adjunct therapies have yet to be incorporated into the clinical-management of metabolic diseases

Bone Health in Classic Galactosemia:Systematic Review and Meta-Analysis

Previous studies have reported an association between classic galactosemia (CG) and decreased bone mass. The primary objective of this systematic review with meta-analysis was to determine the extent of bone mineral density (BMD) Z-score reduction. Low BMD was defined as a Z-score ≤-2 standard deviations (SD). The secondary objective was to evaluate other indicators of bone status through a descriptive analysis. Systematic search strategies were developed by an experienced clinical librarian. Selection of relevant manuscripts, risk of bias assessment, and data extraction were performed independently by two investigators. Four studies were included in the meta-analysis. BMD Z-scores in children and adults with CG measured at the lumbar spine (LBMD; 4 studies; n  = 112), total hip (HBMD; 2 studies; n = 58), and femoral neck (FBMD; 2 studies; n = 73) were assessed. Mean BMD Z-scores in the CG population were LBMD -0.70 (95% CI: -0.88, -0.52); HBMD -0.89 (95% CI: -1.14, -0.64); and FBMD -0.63 (95% CI -1.29, 0.02). Results from studies included in the descriptive analysis (n = 7) show that vitamin D levels were frequently in the low reference range, whereas serum calcium levels were within reference range. The mean BMD Z-score in the CG population is -0.7, which is lower than in the general population, though still within two SD of the reference mean of zero. This indicates that bone health is mildly affected in CG and that more patients, compared to the general population, are at risk for a BMD Z-score ≤-2 SD. In conclusion, clinicians should ensure appropriate preventive and therapeutic measures for CG patient