Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction

Preeclampsia, a severe unpredictable complication of pregnancy, occurs in 6% of pregnancies, usually in the second or third trimester. The specific etiology of preeclampsia remains unclear, although the pathophysiological hallmark of this condition appears to be an inadequate blood supply to the placenta. As a result of the impaired placental blood flow, intrauterine growth restriction (IUGR) and consequential fetal oxidative stress may occur. Consistent with this view, pregnancies complicated by preeclampsia and IUGR are characterized by up-regulation of key transcriptional regulators of the hypoxic response including, hif1α and as well as p53 and its target genes. Recently, the presence of circulating cell-free fetal RNA has been documented in maternal plasma. We speculated that pregnancies complicated by preeclampsia and IUGR, will be associated with an abnormal expression of p53 and/or hif1α related genes in the maternal plasma. Maternal plasma from 113 singleton pregnancies (72 normal and 41 complicated pregnancies) and 19 twins (9 normal and 10 complicated pregnancies) were collected and cell free RNA was extracted. The expression of 18 genes was measured by one step real-time RT-PCR and was analyzed for prevalence of positive/negative expression levels. Results indicate that, among the genes examined, cell free plasma expressions of p21 and hif1α were more prevalent in pregnancies complicated by hypoxia and/or IUGR (p<0.001). To conclude, we present in this manuscript data to support the association between two possible surrogate markers of hypoxia and common complications of pregnancy. More work is needed in order to implement these findings in clinical practice

Study of mannose-binding lectin in smokers with and without COPD

Background: Deficiency of mannose-binding lectin (MBL) was claimed to increase susceptibility to and chronicity of microbial infections in different body systems. Tobacco smoking was also claimed to be associated with reduced blood levels of MBL in blood and defective efferocytosis in the airways. Both effects of smoking may be responsible for development of COPD in smokers and for frequent exacerbations in patients who get COPD. Aim: The aim of this study was to evaluate MBL in blood of smokers with and without COPD. Methods: The study included 70 subjects, classified into two groups; 35 smokers without COPD (group I: divided into 2 subgroups; 17 subjects mild to moderates smokers – group IA, and 18 heavy smoker subjects – group IB). 35 smokers with COPD (group II) also divided into 2 subgroups: 17 subjects with mild to moderate disease (group IIA) and 18 subjects severe to very severe disease (group IIB) according to GOLD (2013) [7] criteria. 20 healthy nonsmoker subjects were also included as a control group (group III). Blood levels of MBL (measured by ELISA) were recorded. Results: Levels of MBL were significantly higher in nonsmoker than smoker groups and in smokers without COPD than in those with it. Also a significant inverse relation was found between smoking index and MBL levels and a direct relation between it and FEV1%. These results indicate that smoking reduces levels of MBL and its deficiency might contribute to development of COPD in smokers. Conclusion: Levels of MBL decrease in smokers with and without COPD and this might play a role in the pathogenesis of lung inflammation in smokers with and without COPD

Matrix Metalloproteinase-2, Squamous Cell Carcinoma Antigen, and Tissue Polypeptide-Specific Antigen Expression in Egyptian Patients with Cervical Carcinoma: Relationship with Prognosis

Matrix metalloproteinases (MMPs), a family of proteolytic enzymes produced by both stromal and tumor cells, appear to have a key role in the events leading to local invasion and metastasis by malignant neoplasms. In the present study, we evaluated the role of MMP-2, squamous cell carcinoma antigen (SCCA), and tissue polypeptide – specific antigen (TPS) in cervical neoplasia. Using Western blotting and enzyme immunoassay (EIA), we analyzed 50 patients with cervical carcinoma (CC) and 25 normal controls for expression of MMP-2 in tissue cell lysates. We also quantified SCCA and TPS with microparticle immunoassay and EIA, respectively. The results were correlated with human papilloma virus (HPV) infection, clinicopathological findings, and disease outcome. The cutoff point for each marker was estimated from receiver operating characteristic curves. Logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for each marker. MMP-2, SCCA, and TPS protein expression were significantly higher in patients with CC than in normal controls. While TPS was the best marker for discriminating between patients and controls, MMP-2 was associated with an advanced tumor stage (OR, 13.9 [95% CI, 1.4-133.9]) and poor histological grade (OR, 10.2 [95% CI, 1.7-60.5]). Moreover, independent of the effect of an advanced CC stage and grade, the patients' age, and the presence of HPV infection, MMP-2 was considered a strong predictor for CC recurrence (OR, 8.1 [95% CI, 1.3- 49.1]). Tissue markers may be used to select high-risk patients for early detection of and adjuvant therapy for recurrence. Our MMP-2 findings are particularly relevant to the development of protease inhibitors as a new cancer therapy approach

CRISPR/Cas9 mediated knock-out of VPREB1 gene induces a cytotoxic effect in myeloma cells.

BackgroundMultiple Myeloma (MM) is a heterogeneous, hematological neoplasm that accounts 2% of all cancers. Although, autologous stem cell transplantation and chemotherapy are currently the most effective therapy, it carries a notable hazards, in addition for being non curative. Recently, the Clustered Regular Interspaced Short Palindromic Repeats (CRISPR-cas9) has been successfully tried at the experimental level, for the treatment of several hematological malignancies.ObjectivesWe aimed to investigate the in-vitro effect of CRISPR-cas9-mediated knock-out of V-set pre B-cell surrogate light chain 1"VPREB1" gene on the malignant proliferation of primary cultured myeloma cells.MethodsBioinformatics' analysis was performed to explore the gene expression profile of MM, and the VPREB1 gene was selected as a target gene for this study. We knocked-out the VPREB1 gene in primary cultured myeloma cells using CRISPR-cas9, the VPREB1 gene editing efficacy was verified by determining VPREB1 gene expression at both the mRNA and protein levels by qPCR and immunofluorescence, respectively. Furthermore, the cytotoxic effect on primary myeloma cells proliferation was evaluated using cytotoxicity assay.ResultsThere was a statistically significant reduction of both VPREB1 mRNA and protein expression levels (pConclusionCRISPR-cas9-mediated knock-out of VPREB1 gene is effective for inhibiting the proliferation of primary myeloma cells. This would provide a basis for a promising therapeutic strategy for patients with multiple myeloma

Diagnostic performance of transthoracic ultrasound in patients with pulmonary embolism

Background Pulmonary embolism (PE) is an acute, significant, and life-threatening condition. Transthoracic ultrasound (TUS) is one of the noninvasive diagnostic modalities that has been presented for detection of numerous chest disorders as well as PE. Objectives The goal of this work was to estimate the accuracy, sensitivity, and specificity of bedside TUS in PE detection. Patients and methods Fifty patients with moderate-to-high clinical suspicion of PE were examined by TUS. Diagnosis of PE depended on clinical suspicion and was confirmed by computed tomography pulmonary angiography. Results Most of the lesions related to PE and detected by US examination were on the right side (60%) and posterior lower lobe (70%) with predominance of A profile. Sensitivity, specificity, accuracy, negative, and positive predictive values of TUS in diagnosis of PE were 93.3, 65, 82, 86.7, and 80%, respectively. Conclusion TUS is an important diagnostic tool as a noninvasive bedside test in detecting PE principally for critically ill or unmoving patients with high sensitivity and moderate specificity

Study of anti nuclear and anti smooth muscle antibodies in patients with chronic obstructive pulmonary disease

Background/aim: Autoimmunity is a disease in which the immune system mistakenly attacks the body’s own cells and tissues. Sometimes the whole body is attacked, and sometimes only one organ. The aim of the work: The aim of this study was to evaluate antinuclear and anti smooth muscle antibodies, two common markers of autoimmunity, in COPD and their relation with different components of the disease and disease severity. Methods: The study included 50 clinically stable COPD patients classified into two groups mild to moderate (group A) and severe to very severe (group B) according to GOLD (2009) [13] criteria plus 30 healthy control subjects (15 smokers and 15 non smokers). Blood levels of ANA and ASMA (measured by ELISA) were recorded. Results: Levels of both ANA and ASMA were significantly higher in patients than in controls as a whole group but smoker controls showed significantly higher levels of both antibodies than mild to moderate COPD group (group A) indicating that not only smoking is responsible for COPD but other factors also play a role. Also high levels of these antibodies in smoker controls than in non smokers indicate a role of smoking in their development which is augmented by the direct relation with smoking index both in patients and controls. Conclusion: Both ANA and ASMA levels are elevated in COPD patients compared to controls (smokers and non smokers) and levels elevated in healthy smokers compared to group A COPD patients. Autoimmunity plays a role in the pathogenesis of COPD

Evaluation of Primary Health Care service participation in the National Tuberculosis Control Program in Qalyubia Governorate, Egypt

Objective: The aim of this work was to evaluate the Primary Health Care service performance in National Tuberculosis Control Program in Qalyubia Governorate. Methods: The studied area (Qalyubia Governorate) includes 8 health territories (each contains 5 primary care units/centers). A questionnaire based on 6 parameters was used to evaluate the PHC system performance: I – Physicians with basic knowledge about TB (causative agent, methods of spread, clinical picture, essential steps in investigations: X-ray and sputum smear), II – Facilities for primary investigation (sputum examination and chest X-ray), III – Communication with the central health authorities or a TB specialist, IV – Proper recording systems needed for proper patient management and follow up, V – Follow up schedules are available for the detected patients, VI – Have a role in community education about the disease. The data obtained were tabulated and statistically analyzed. Results: Studied area included 8 health territories and 40 primary care units (35% were urban and 65% rural) with one physician in each unit. The mean percent of the correct answers of the basic knowledge score was 48.2% (range = 18%–100%), higher in urban units physicians than rural units physicians, with lack of proper laboratory (for sputum analysis) or X-ray apparatus. Communication with central health authorities in urban areas was higher than rural areas (65.4% versus 57.1%). Case recording was lower in urban than rural areas (42.9% versus 46.2%). Patient follow up after referral to central health units was higher in rural than urban areas (11.5% versus 7.1%). Participation of community education was 78.6% in urban units and 76.9% in rural units. Conclusion: In Qalyubia Governorate, PHC physicians lack proper knowledge about TB and their units lack proper equipments (Lab and CXR). The PHC system needs to be empowered by the health care authorities through training and equipments for better performance in NTP