Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1α-VEGF signaling pathway.

Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1α-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no = 35), adenomas (no = 51), and neoplasm free controls (no = 101). Serum levels of VEGF and HIF-1α was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1α was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p < 0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-α. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p < 0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1α VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.

Exposure to pesticide components causes recurrent pregnancy loss by increasing placental oxidative stress and apoptosis: a case-control study.

We investigated the plasma levels of pesticides components namely polychlorinated biphenyls (PCBs), dieldrin, dichlorodiphenyldichloroethylene (DDE), ethion, malathion, and chlorpyrifos in recurrent pregnancy loss (RPL) cases, and tested their associations with placental oxidative stress (OS) biomarkers [nitric oxide (NO.), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), and superoxide dismutase (SOD)] and with placental apoptotic/antiapoptotic indices (Bcl-2 and caspase-3), and evaluated their possible cut-off points to distinguish RPL cases. The study recruited 101 pregnant women divided into; G1 [n = 49, control, normal 1st-trimester pregnancy, normal obstetric history with at least one previous normal live birth], G2 [n = 26, cases with missed abortion (< 3 abortions) before 24 weeks of gestation], and G3 [n = 26, cases with missed abortion (≥ 3 abortions) before 24 weeks of gestation]. The plasma pesticide levels were analyzed by gas chromatography-mass spectrometry. Plasma human chorionic gonadotrophin (HCG), placental OS, Bcl-2, and caspase-3, were analyzed by their corresponding methods and kits. Plasma PCBs, DDE, dieldrin, and ethion levels were significantly higher in RPL cases than in normal pregnancies (p ≤ 0.001). These levels correlated positively with placental OS and apoptosis and negatively with plasma HCG levels. Also, these levels were reliable markers of risk to RPL. Malathion and chlorpyrifos were not detected in any of the study's participants. Pesticides may be risk factors in cases of spontaneous RPL cases. They are associated with an increasing placental OS and placental apoptosis. Specific measures should be taken to decrease maternal exposure to these pollutants' sources, especially in underdeveloped and developing countries.

Prognostic value of serum soluble FMS-like tyrosine kinase (sFlt-1) levels in pre-eclampsia and eclampsia; a prospective cohort study.

OBJECTIVE: To evaluate the levels of circulating sFlt-1 in pre-eclampsia (PE) and eclampsia patients and to assess its prognostic value in detection of PE complications. METHODS: The present study was a prospective cohort study conducted in tertiary hospital between January and December 2016. Included patients were divided into two groups; (Group I) severe PE group and (Group II) eclampsia group. Age-, parity-, and gestational age-matched women had approached to participate in the study as a control group (Group III). Serum sFlt-1 levels were measured at inclusion and 2 days later with all basic investigations. Patients were followed up until delivery to record any complications. Correlation analysis was performed between the serum sFlt-1 levels and clinical, laboratory investigations. Receiver operating characteristic analysis was constructed for the evaluation of the area under curve (AUC) as well as the sensitivity and specificity regarding the cutoff point of sFlt-1 level that predict occurrence of complications. RESULTS: The study included 84 women. Women with complicated severe PE showed higher sFlt-1 levels than in non-complicated cases (120.2 ± 19.6 versus 72.2 ± 19.6, p < 0.001). Similarly, the mean serum level of sFlt-1 in complicated eclampsia was higher than in non-complicated cases (298.3 ± 75.2 versus 128.1 ± 36.5, p < 0.001) (OR = 1.119, 95% CI: 10.057-1.184, p < 0.001). SFlt-1 levels were strongly correlated with systolic blood pressure (r = 0.641) and diastolic blood pressure (r = 0.540) (p < 0.001 and p < 0.001, respectively). At cutoff point 102.60 ng/ml of sFlt-1 levels, the sensitivity was 90% and specificity was 80% with AUC = 0.923, 95% CI: 0.871-0.975. CONCLUSIONS: Serum sFlt-1 can be used as a prognostic marker to predict the occurrence of complications of preeclampsia.

The effect of follicullar fluid pesticides and polychlorinated biphenyls concentrations on intracytoplasmic sperm injection (ICSI) embryological and clinical outcome.

OBJECTIVES: The present study evaluated the correlation between the concentrations of polychlorinated biphenyls (PCBs) and pesticides in the follicular fluid (FF) obtained during intracytoplasmic sperm injection (ICSI) with the ovarian response, endometrial thickness, and embryological and clinical outcomes. DESIGN: Cross-sectional observational study. MATERIALS AND METHODS: Women aged 20 to 38 years (300 infertile couples) presenting to a university-affiliated fertility center were approached to participate in the study. Only 150 couples that underwent ICSI for male factor infertility agreed to participate, and 94 of them had retrieved enough FF samples suitable for laboratory testing. The FF sample was obtained, centrifuged, and stored in liquid nitrogen. Two organochlorine pesticides (OCPs), Lindane and DDT;three organophosphates (OPs);chlorpyrifos;Diazinon; malathion; one Chloroacetanilide (Pretilachlor);two pyrethroids(Bioallethrin and ß-cyfluthrin); and the concentrations of four PCBs, 28, 52, 138, 180, were estimated in the obtained FF samples by using gas chromatography/mass spectrometry. SPSS statistical analysis program (version 17) was used for analysis. Multiple regression analysis was used to correlate the PCBs and pesticides with ICSI outcomes. RESULTS: There were significant negative correlations between FF concentrations of the eight examined pesticides and the four PCBs on the endometrial thickness. However, Pretilachlor, chlorpyrifos, ß-cyfluthrin, and Diazinon were the only toxic agents that negatively correlated with the number of the oocytes retrieved. Fertilization and early embryo cleavage rates were negatively correlated with Pretilachlor and ß-cyfluthrin. Moreover, high concentrations of Lindane,DDT, Diazinon,and chlorpyrifos were significantly associated lower implantation rate. PCB 28 and 180 concentration in the FF was associated with a lower number of retrieved oocytes and fertilization rate, respectively. The number of implanted embryos was negatively correlated with PCB 52 FF concentration. However, the clinical pregnancy rate did not reach the level of significance. CONCLUSION: Higher concentrations of any studied PCBs and pesticides are associated with thinner endometrial thickness. The higher the level of Pretilachlor, ß-cyfluthrin, PCB 28 and 180, the lower the retrieval, fertilization, and embryo cleavage rates. High PCB and pesticide concentrations in the FF adversely affected embryological ICSI outcomes. However, more data are needed to evaluate their effect on the clinical outcome.

Oxidative stress, trace elements, and circulating microparticles in patients with Gaucher disease before and after enzyme replacement therapy.

UNLABELLED: We studied the level of lipid peroxide, nitric oxide (NO), trace elements (TEs), and microparticles (MPs) in Gaucher disease (GD) before and after 1 year of enzyme replacement therapy (ERT). A total of 15 children with GD and 15 healthy controls were enrolled in this study. Serum level of lipid peroxide, NO, and TEs was determined. The MPs were detected by flow cytometry. The level of lipid peroxide was significantly higher in the patients than in the controls even after ERT. Although NO level was normalized in the patients after ERT, zinc and copper were still lower in the patients after ERT. The percentages of various MPs were significantly higher in the patients than in the controls both before and after ERT. There were positive correlations between chitotriosidase and both lipid peroxide and total MPs. CONCLUSION: The GD is associated with alteration in oxidant and antioxidant status and high level of circulating MPs.

Environmental factors and apoptotic indices in patients with intrauterine growth retardation: a nested case-control study.

BACKGROUND: Egypt has one of the highest incidences of IUGR. The current study investigates the effect of heavy metals toxicity as risk factors of IUGR and determines the possible role of increased apoptosis in their pathogenesis. METHODS: This study was conducted in Assiut, Egypt, included 60 women diagnosed to have IUGR. We measured lead and cadmium levels in blood besides arsenic and cadmium levels in urine. Neonatal scalp hair sample were analyzed for arsenic content. Quantitative determination of human placental Bcl-2 and caspase-3 were performed. RESULTS: There are significantly higher levels of heavy metals and caspase-3 and lower levels of placental Bcl-2 in the IUGR group. The levels of heavy metals were positively correlated with caspase-3 while negatively correlated (except cadmium) with Bcl-2 levels. CONCLUSIONS: There is an alarming high level of heavy metals toxicity in Egypt that was positively correlated to IUGR. Increased placental apoptosis may be one of the possible mechanisms behind the effect.

Can serum fibrosis markers predict medium/large oesophageal varices in patients with liver cirrhosis?

BACKGROUND AND STUDY AIMS: Non-invasive predictors of medium/large oesophageal varices (LOVs) could reduce the number of screening endoscopies. As portal hypertension is a consequence of liver fibrosis, serum fibrosis markers were evaluated together with other variables as possible non-invasive predictors of medium OV/LOV. PATIENTS AND METHODS: A total of 154 cirrhotic patients with splenomegaly and 30 healthy control subjects were recruited in a prospective study in two gastroenterology centres in Upper Egypt. Clinical parameters assessed included Child-Pugh class, liver size and ascites. Laboratory parameters included complete blood count, liver function tests, and aspartate aminotransferase (AST)/platelet ratio. Transforming growth factor-ß(1) (TGF-ß(1)), alpha(2) macroglobulin (A(2)M) and hyaluronic acid (HA) were assayed. Ultrasonographic examination was done for assessment of liver span, portal vein diameter and detection of minimal ascites. Oesophageal varices were diagnosed and graded by oesophagogastroduodenoscopy. RESULTS: Fifty-four patients (35%) had no or small varices and 100 (65%) patients had medium OV/LOV by endoscopy. On multivariate analysis, the independent predictors of medium OV/LOV were the presence of ascites (ß=0.258, p=0.047) and serum HA (ß=0.449, p=0.009). The receiver operating characteristic curve for HA showed the area under the curve to be 0.916. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of HA at a cut-off value of 207µgl(-1) were 94%, 77.8%, 88.7%, 87.5% and 88.3%, respectively. CONCLUSIONS: The presence of ascites and serum HA level higher than 207µgl(-1) can predict the presence of medium OV/LOV in cirrhotic patients. This would help physicians to identify patients who would most likely benefit from screening endoscopy and thus, reduce costs and discomfort from unnecessary endoscopic procedures.