Diagnostic Performance of Epithelial Cell Adhesion Molecule for Early Detection of Hepatocellular Carcinoma Among HCV High-Risk Patients.

OBJECTIVE: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. Circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with routine laboratory tests for accurate detection of HCC. MATERIAL & METHODS: Epithelial cell adhesion molecule (EpCAM), α-fetoprotein, albumin, and platelets count were assayed in HCC patients (98), liver cirrhosis patients (77). Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. RESULTS: A novel score named EpCAM-HCC = AFP (U/L) × 0.11 - Albumin (g/dl) × 1.5 + EpCAM % × 2.9 - Platelets count (×109)/L× 0.75 - 93. EpCAM-HCC score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 1.7 (i.e., less than 1.7 the case is considered cirrhotic, whereas above 1.7 it is considered HCC. CONCLUSION: EpCAM-HCC score could replace AFP during screening of HCV patients and early detection of HCC.

Diagnostic Performance of Circulating Tumor Cells for Predicting of Hepatocellular Carcinoma in Hepatitis C Virus-High Risk Patients: Role of Liquid Biopsy.

PURPOSE: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver and a global health problem. It is often diagnosed at advanced stage where hopeless for effective therapies. Identification of more reliable biomarkers for early detection of HCC is urgently needed. circulating tumor cells (CTCs) represent a unique liquid biopsy carrying comprehensive biological information of the primary tumor. Herein, we sought to develop a novel score based on the combination of the most significant CTCs biomarkers with and routine laboratory tests for accurate detection of HCC. METHODS: Cytokeratin 18 (CK18), Cytokeratin 19 (CK19), albumin, platelets count, and α-fetoprotein were assayed in HCC patients (42), liver cirrhosis patients (83) and healthy control (20). RESULTS: Areas under receiving operating curve (AUCs) were calculated and used for construction on novel score. A novel score named HCC-CTCs = AFP (U/L) × 0.08 - Albumin (g/dl) × 84 + CK 18 % × 2.9 + CK19 × 3.1- Platelets count (×109)/L× 0.75- 510. HCC-CTCs score produce AUC of 1 for differentiate patients with HCC from those with liver cirrhosis with sensitivity and specificity of a cut-off 0. CONCLUSIONS: HCC-CTCs score could replace AFP during screening of HCV patients and early detection of HCC.

Evaluation of reproductive hormones in Egyptian workers occupationally exposed to di-2-ethylhexyl phthalate (DEHP): a cross-sectional study.

OBJECTIVES: Di-2-ethylhexyl phthalate (DEHP) is ubiquitous, known as an endocrine disruptor. DEHP is a widespread prevalence in general and occupational populations which raised great public concerns due to its potentially harmful health effects on the male reproductive system. We aimed to assess occupational levels of DEHP on gonadotropin and gonadal hormones including luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone (TT), and sex hormone binding globulin (SHBG) and evaluate its potential effects on Asp327Asn polymorphisms SHBG gene. METHODS: We measured the levels of DEHP of 90 male workers in one of polyvinyl chloride (PVC) industry plant using enzyme-linked immunosorbent assay. Sex hormones were examined and Asp327Asn polymorphisms SHBG gene were detected by PCR-RFLP in all participants. RESULTS: The workers were divided into low- and high- DEHP exposed groups based on the geometric mean (GM) levels (183.86 U/L) in serum. TT and TT: LH ratio were negatively correlated to DEHP levels (r=-0.213, p=0.038), (r=-0.225, p=0.027), respectively. The linear regression analysis revealed that a 10-fold increase of serum DEHP was found to be associated with 2.07 fold decreased in TT and a 2.26 fold decreased in TT/LH ratio. CONCLUSIONS: Serum testosterone is negatively associated with DEHP exposure in occupational workers.

Impact of Bisphenol A on Gonadotropic Hormone Levels in Children with Autism Spectrum Disorders.

Early developmental exposures to endocrine disruptors including bisphenol A (BPA) may affects the body's endocrine system producing adverse neurologic, reproductive, cardiovascular, metabolic, and immune effects in humans. Many studies show the effect of BPA on human reproduction at lower concentrations than that of the safety limit recommendations. However, limited studies have been associated between environmental exposure of BPA and gonadotropic hormone levels in children with autism spectrum disorders (ASDs). This study was done to evaluate association between the serum levels of hormones; follicle-stimulating (FSH), inhibin B (INHB), and estradiol (E2) and BPA in 49 ASD children compared with 40 healthy control children. Serum levels of FSH, INHB, and E2 were lower in ASD group than that of control. Correlations between BPA and FSH, INHB, and E2 within autistic children were not significant. The observed results revealed that BPA may cause endocrine dysfunction in ASD children.

Upregulation of MC4R and PPAR-α expression mediates the anti-obesity activity of Moringa oleifera Lam. in high-fat diet-induced obesity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: various extracts of Moringa oleifera Lam. leaves, were reported to possess antiobesity effect in experimental animals models, yet its active doses and mechanism of action are still unclear. MATERIALS AND METHODS: The metabolic profiling of 70% ethanol extract of M. oleifera (MO) leaves was performed using HPLC-MS/MS analysis. The antiobesity activity of MO was tested in high fat diet induced obesity in rats at 200 and 400 mg/kg body weight orally for 1 month. Total cholesterol (TC), high density lipoproteins (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides (TGs), insulin resistance, insulin sensitivity, and adipose tissue index were monitored. In addition, fatty acid synthase (FAS) and HMG-CoA reductase mRNA from liver tissue, Peroxisome Proliferator-Activated Receptor alpha (PPARα) and Melanocortin-4 receptor (MC4R) RNA from adipose tissue were quantified using qRT-PCR. MO hard gelatin capsules (400 mg/capsule) were formulated and standardized using HPLC-RP analysis and tested on fifteen female participants, aged 45-55 with a BMI of 29-34 kg/m2. RESULTS: Thirteen metabolites were tentatively identified using HPLC-MS/MS analysis including flavonols, flavones and a phenolic acid. MO 400 showed a prominent effect on reducing the rats' final weights, % weight increase and adiposity index (P < 0.05). Glucose, insulin and HOMA-IR were significantly reduced and R-QUICKI was significantly increased by MO 400 (P < 0.001). Mean tissue level of leptin and vaspin were significantly reduced, adiponectin, omentin and GLUT-4 expression were increased significantly by MO 400 (P < 0.01). MO 400 significantly suppressed FAS and HMG-CoA reductase and increased mRNA expression of MC4R and PPAR-α (P < 0.01). Eight weeks administration of MO hard gelatin capsules to obese patients showed significant reduction of the average BMI, TC and LDL compared to the baseline values (p < 0.05). CONCLUSION: Our results presented a scientific evidence for the traditional use of M. oleifera leaves as antiobesity herbal medicine.

Study of the Effect of Bisphenol A on Oxidative Stress in Children with Autism Spectrum Disorders.

The role of bisphenol A (BPA) in autism was investigated in 49 children (mean age = 5.950 ± 1.911 years) with autism spectrum disorders (ASDs) and 40 comparable age and sex matched children used as controls (mean age = 5.333 ± 2.279 years). In addition, 8-Hydroxydeoxyguanosine (8-oxodG) was also studied as a biomarker of oxidative stress in the same set of two selected groups. The results showed that both BPA and 8-oxodG were significantly higher in children with autism than those of control children (p values = 0.025 and 0.0001, respectively). There were positive correlations between both BPA and 8-oxodG with ASDs severity (r = 0.400 and 0.805, respectively), these correlations were highly significant (p values = 0.004 and 0.001, respectively). There was a significance positive correlation between BMI and BPA, but the correlation between BMI and 8-oxodG was not significant in children with autism. The observed results revealed that BPA may increase oxidative stress resulting in mitochondrial dysfunction that affecting the behavior and functioning of ASDs children.

Down-regulation of circulating microRNA let-7a in Egyptian smokers.

Altered miRNAs were associated with cigarette smoking. The study aimed to examine the gene expression level of plasma let-7a among healthy smokers and compared it with the non-smokers. Forty subjects were recruited for the present study and classified into 21 smokers and 19 non-smokers, age, and sex were matched. The software that used to design functional primers was MIRprimer. Quantitative real-time PCR was employed to compare the relative expression of plasma let-7a. Results showed that the level of let-7a was down-regulated in smokers to 0.34fold (p = 0.006) that of the non-smokers. Plasma let-7a showed an area under curve (AUC) of 0.749 with sensitivity 43% and specificity 100%. In conclusion, plasma let-7a was significantly down-regulated in the smokers, and it might be considered a candidate biomarker to discriminate between smokers and non-smokers.

Randomized double-blinded pilot clinical study of the antidiabetic activity of Balanites aegyptiaca and UPLC-ESI-MS/MS identification of its metabolites.

CONTEXT: Balanites aegyptiaca Del. (Zygophyllaceae) fruits are traditionally known for the treatment of hyperglycaemia. Several in vitro and in vivo studies proposed some mechanisms of action. However, clinical trials in human beings were never reported to date. OBJECTIVES: To investigate the antidiabetic efficacy of the 70% ethanol extract of the pericarps of B. aegyptiaca (BE) within a nutritional intervention in elderly people. MATERIALS AND METHODS: Ultra-performance electrospray ionization-mass spectroscopy (UPLC-ESI-MS/MS) analysis was used for metabolic profiling of BE which was incorporated in hard gelatine capsules (400 mg/day) and tested on 30 type 2 diabetes (T2D) Egyptian patients for 8 weeks. According to sex, age and body mass index participants were divided into two equivalent groups, placebo and treatment. RESULTS: Thirteen compounds were identified in BE using UPLC-ESI-MS/MS analysis among which five steroidal saponins, seven phenolic compounds and a sterol glucoside. At the end of the 8-week treatment, the treated group showed 26.88% decrease in 2 h postprandial plasma glucose relative to 2.6% increase in the placebo group, while fasting plasma glucose was reduced to 10.3%. Treatment with BE capsules for 8 weeks produced significant reduction in the plasma triglyceride, total cholesterol and low-density lipoprotein cholesterol by 9.0, 12.76 and 21.35%, respectively, with 29.8% increase in the high-density lipoprotein cholesterol. Plasma alanine transaminase and aspartate transaminase were reduced by 42.6 and 43.3%, respectively. DISCUSSION AND CONCLUSION: Administration of the BE capsules to T2D resulted in significant improvements in the glycaemic markers and the lipid profile, without adverse effects or hypoglycaemia.

Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of Alzheimer's disease.

The current study was undertaken to elucidate a possible neuroprotective role of dehydroepiandrosterone (DHEA) against the development of Alzheimer's disease in experimental rat model. Alzheimer's disease was produced in young female ovariectomized rats by intraperitoneal administration of AlCl(3) (4.2 mg/kg body weight) daily for 12 weeks. Half of these animals also received orally DHEA (250 mg/kg body weight, three times weekly) for 18 weeks. Control groups of animals received either DHAE alone, or no DHEA, or were not ovariectomized. After such treatment the animals were analyzed for oxidative stress biomarkers such as hydrogen peroxide, nitric oxide and malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activities, antiapoptotic marker Bcl-2 and brain derived neurotrophic factor. Also brain cholinergic markers (acetylcholinesterase and acetylcholine) were determined. The results revealed significant increase in oxidative stress parameters associated with significant decrease in the antioxidant enzyme activities in Al-intoxicated ovariectomized rats. Significant depletion in brain Bcl-2 and brain-derived neurotrophic factor levels were also detected. Moreover, significant elevations in brain acetylcholinesterase activity accompanied with significant reduction in acetylcholine level were recorded. Significant amelioration in all investigated parameters was detected as a result of treatment of Al-intoxicated ovariectomized rats with DHEA. These results were confirmed by histological examination of brain sections. These results clearly indicate a neuroprotective effect of DHEA against Alzheimer's disease.

Effect of aluminium on the levels of some essential elements in occupationally exposed workers.

The mechanism of aluminium-induced cytotoxicity has not yet been defined. This study investigated possible changes in essential elements in workers occupationally exposed to Al fumes. It included 60 exposed workers and a matching control group of 60 employees not occupationally exposed to Al. Mean serum copper, calcium, zinc and iron were significantly lower in the exposed group than in controls. In addition, mean plasma and urine levels of Al were significantly higher in the exposed employees than in the controls. A statistically significant negative correlation was found between plasma and urinary Al and the studied essential elements. These findings corroborate the hypothesis that Al exposure has an adverse effect on essential elements in humans, with subsequent impact on the cellular enzymatic and metabolic processes.