Exploring The Effects Of Genetic Variation On Gene Regulation In Cancer In The Context Of 3D Genome Structure

Background Numerous genome-wide association studies (GWAS) conducted to date revealed genetic variants associated with various diseases, including breast and prostate cancers. Despite the availability of these large-scale data, relatively few variants have been functionally characterized, mainly because the majority of single-nucleotide polymorphisms (SNPs) map to the non-coding regions of the human genome. The functional characterization of these non-coding variants and the identification of their target genes remain challenging. Results In this communication, we explore the potential functional mechanisms of non-coding SNPs by integrating GWAS with the high-resolution chromosome conformation capture (Hi-C) data for breast and prostate cancers. We show that more genetic variants map to regulatory elements through the 3D genome structure than the 1D linear genome lacking physical chromatin interactions. Importantly, the association of enhancers, transcription factors, and their target genes with breast and prostate cancers tends to be higher when these regulatory elements are mapped to high-risk SNPs through spatial interactions compared to simply using a linear proximity. Finally, we demonstrate that topologically associating domains (TADs) carrying high-risk SNPs also contain gene regulatory elements whose association with cancer is generally higher than those belonging to control TADs containing no high-risk variants. Conclusions Our results suggest that many SNPs may contribute to the cancer development by affecting the expression of certain tumor-related genes through long-range chromatin interactions with gene regulatory elements. Integrating large-scale genetic datasets with the 3D genome structure offers an attractive and unique approach to systematically investigate the functional mechanisms of genetic variants in disease risk and progression

Start-up delay Estimation at Signalized Intersections: Impact of Left-Turn Phasing Sequences

This paper aims to investigate the start-up delay at signalized intersections in Abu Dhabi (AD) city, UAE. Impact of external factors that may affect the start-up delay is examined including left turn phasing sequences (split/lead/lag), movement turning (through/left), intersection location (CBD/non-CBD) and day time (peak/off-peak). A new technique of data collection was applied based on the automate records of license plate of vehicles and a comparison with the traditional video recorded technique was carried out. Data covered 66 approaches of 36 signalized intersections. The analysis showed that overall estimated mean value of the start-up delay is 2.201 sec. with a standard deviation of 1.823 sec. The t-test shows significant statistical difference in start-up delay between observations at through and left movements, at CDB and non-CDB area and at split and lead/lag phasing. However, no significant differences were found between peak and off-peak periods and between split and lead phasing. In general, lead/lag phasing sequences not only improved the overall delay at signalized intersection but also improved the start-up delay.nbsp nbs

The potential gonadoprotective effects of grape seed extract against the histopathological alterations elicited in an animal model of cadmium-induced testicular toxicity

Background: Grape seed extract (GSE) is a powerful antioxidant containing high levels of bioflavonoids, vitamin C and vitamin E. The aim of the work is to study the possible protective and ameliorative effects of grape seed extract in an animal model of cadmium (Cd)-induced testicular toxicity in rats.Materials and methods: A thirty-day oral gavage study in adult male albino rats was performed using 32 animals, randomly divided into four equal groups; negative control, Cd (5 mg/k/day), GSE (100 mg/k/day), and Cd + GSE. Testicular weights were measured. Haematoxylin and eosin (H&E) staining and proliferating nuclear cell antigen (PCNA) immunohistochemistry, as a marker for proliferation were done. Morphometric parameters were assessed and subjected to statistical analysis.Results: The H&E results showed atrophy and distortion of the seminiferous tubules (STs) with sloughing of the spermatogenic epithelium in cadmium group. The interstitial spaces were widened and showed oedema and mononuclear cell infiltrations. No remarkable changes were observed in the GSE-only group when compared to the control group. In Cd + GSE group, maintaining of the STs and their lining cells was evident. The immunohistochemical results showed marked positive PCNA immunoreactivity in both control and GSE groups, while negative immunoreaction was noticed in Cd group. Limited positive PCNA immunoreactivity was ameliorated in Cd + GSE group.Conclusions: Grape seed extract protected against cadmium-induced testicular toxicity in rats, reducing induced histopathological changes, and maintaining testicular histoarchitecture

LORNOXICAM-LOADED NANOSPONGES FOR CONTROLLED ANTI-INFLAMMATORY EFFECT: IN VITRO/IN VIVO ASSESSMENT

Objective: To design a controlled topical delivery system of lornoxicam (LX) in order to enhance skin permeation and treatment efficacy. Nanosponges were selected as a novel carrier for this purpose. Methods: Nanosponges were formulated via the emulsion solvent evaporation method using ethyl cellulose (polymer) and polyvinyl alcohol (surfactant). Nanosponge dispersions were characterized for colloidal properties, entrapment efficiency and in vitro release study. The nanosponge formulation (LS1) was then incorporated into carboxymethyl cellulose sodium hydrogels and evaluated for pH, viscosity and in vitro drug release. Skin irritation was evaluated, and anti-inflammatory activity was assessed via rat hind paw edema method. Results: Nanosponges were in the nano-sized range and attained a uniform round shape with a spongy structure. LS1exhibited the highest LX release after 6 h, so it was incorporated as hydrogel. Formulated hydrogels showed acceptable physicochemical parameters (pH, drug content and rheological properties). Skin irritation testing proved LX-loaded nanosponge hydrogel formulation (G1) to be non-irritant. In vivo study revealed an enhanced anti-inflammatory activity of G1 for 6 h (p<0.001). Conclusion: The developed nanosponge hydrogel is an efficient nanocarrier for improved and controlled topical delivery of LX

Stem cells and metformin synergistically promote healing in experimentally induced cutaneous wound injury in diabetic rats

Introduction. Diabetes mellitus (DM) is a serious, chronic metabolic disorder commonly complicated by diabetic foot ulcers with delayed healing. Metformin was found to have a wound healing effect through several mechanisms. The current study investigated the effect of both bone marrow-derived mesenchymal stem cells (BM-MSCs) and metformin, considered alone or combined, on the healing of an experimentally induced cutaneous wound injury in streptozotocin-induced diabetic rats.Material and methods. Forty adult male albino rats were used. Diabetes was induced by single intravenous (IV) injection of streptozotocin (STZ). Next, two circular full thickness skin wounds were created on the back of the animals, then randomly assigned into 4 groups, ten rats each. BM-MSCs were isolated from albino rats, 8 weeks of age and labeled by PKH26 before intradermal injection into rats of Group III and IV. Groups I (diabetic positive control), II (metformin-treated, 250 mg/kg/d), III (treated with 2×106 BM-MSCs), and IV (wounded rats treated both with metformin and BM-MSCs cells). Healing was assessed 3, 7, 14, and 21 days post wound induction through frequent measuring of wound diameters. Skin biopsies were obtained at the end of the experiment.Results. Gross evaluation of the physical healing of the wounds was done. Skin biopsies from the wound areas were processed for hematoxylin and eosin (H&E), Masson’s trichrome staining and immunohistochemical staining for CD31. The results showed better wound healing in the combined therapy group (IV) as compared to monotherapy groups.Conclusions. Although both metformin and BM-MSCs were effective in the healing of experimentally induced skin wounds in diabetic rats, the combination of both agents appears to be a better synergistic option for the treatment of diabetic wound injuries

Serum Leptin and Bone Mineral Density in Hemodialysis Patients with or without Liver Diseases

Introduction: Leptin is a hormone secreted by adipocytes that plays an important role in regulating appetite and energy expenditure. Our aim was to evaluate serum leptin level in hemodialysis (HD) patients with or without chronic liver disease (CLD) and study the relationship between serum leptin level and bone mineral density in these groups of patients. Methods: we recruited 20 healthy volunteers as controls (group I), 20 patients on regular HD with normal liver function (group II), 20 CLD patients with normal kidney function (group III) and 20 patients on regular HD with CLD (group IV). We measured serum calcium, phosphorus, parathyroid hormone (PTH), total alkaline phosphatase (ALP), serum leptin, 24-hours urinary hydroxyproline and bone mineral density (BMD) of the lumber spine and femoral neck by DEXA scan. Results: Serum leptin level was significantly higher (P <0.001) in HD patients and CLD patients compared to controls. Its level was also significantly elevated in HD patients without liver disease (group II) compared to patients with CLD who had no renal failure (group III). Urinary hydroxyproline level was increased in both HD patients and CLD patients. We detected a positive correlation between serum leptin level and urinary hydroxyproline in all patient groups. There was a significant decrease in BMD in HD and CLD patients. BMD was significantly lower in HD patients without CLD compared to HD patients with CLD. There was a significant negative correlation between serum leptin level and BMD in CLD patients without renal disease but not in other groups (r = - 0.6, P = 0.01). Conclusion: Serum leptin is elevated in HD patients with or without liver disease and in CLD patients. Serum leptin level is inversely correlated with BMD in CLD patients without renal disease.Keywords: Bone Mineral Density; Cirrhosis; Chronic Liver Disease; Hemodialysis; Lepti

Evaluation of serum kallistatin level as a predictor of esophageal varices in cirrhotic patients

Introduction: The Baveno VI consensus recommended the use of noninvasive predictors to identify patients at high risk of esophageal varices (EV) in whom endoscopic evaluation is most needed. Kallistatin is a protein molecule synthesized by the liver, and its level declines with the deterioration of liver functions. We aim to explore the role of kallistatin as a predictor of esophageal varices. Methods: This case–control study included 70 cirrhotic patients (35 patients with EV and 35 patients without EV). The laboratory investigations and upper GI endoscopy were performed, and the serum kallistatin level was measured in all patients. Results: The mean level of serum kallistatin was significantly lower in patients with varices (12.2 ± 5.6 vs 16.9 ± 4.8 μg/ml, p = 0.009). It also shows a significant decline in patients with large varices. Kallistatin can predict the presence of EV and large EV at cut off values of 15.8 and 8.9 μg/ml, respectively, with sensitivity and specificity of 71.4% and 54.3% for EV and 50% and 94.8% for large EV. Discussion: Kallistatin is a promising marker that can be used to predict the presence of esophageal varices especially when they are large and risky

Photo-identification of Dugongs in Marsa Alam and Wadi El Gemal National Park, Egypt

1351-1358Using photo-identification techniques, 30 dugongs were recorded at the southern Egyptian Red Sea coast between December 2015 and October 2017, 16 at Marsa Alam and 14 at Wadi El Gemal National Park (WGNP). Males were recorded seven times more frequently than females and calves were also recorded. A Photo ID catalogue was prepared for the dugongs with records of their occurrence among sites. We confirmed the presence of particular dugong specific sites. Long- and short-distance movements within the study sites were recorded for eight different dugongs. This is the first study to document the number of dugongs in inshore areas of the Egyptian Red Sea coast. Further studies are recommended for offshore sites in WGNP for better documentation of this group of animals

YAG Laser in the Treatment of Nail Psoriasis: Clinical and Dermoscopic Assessment

Background: The Nd:YAG laser has emerged as a promising modality for the management of nail psoriasis owing to its ability for deep penetration of the skin surface, which has the advantage of destroying deep vessels. Objective: To assess the efficacy and safety of Nd:YAG laser in treating nail psoriasis. Methods: The present study was a randomized controlled study, conducted on 20 patients of both sexes (age older than 12 years) with mild to moderate psoriasis with nail involvement. We utilized facial telangiectasia parameters of Nd:YAG laser and beam diameter of 2.5 mm. Laser energy started with 110 J/cm2 in the first session and 130 J/cm2 in the rest of the sessions. Sessions were performed once monthly for up to 6 sessions. Results: We found no statistically significant difference in total Nail Psoriasis Severity Index (NAPSI) and nail bed scores before and after treatment among the treated group. However, there was statistically significant improvement in nail matrix score after treatment. On the other hand, the control group did not show any statistically significant changes for all scores throughout the study, except for the nail matrix score mean difference (0.35 ± 1.23 vs -1.00 ± 1.86 in the treated group). The degree of dermoscopic improvement was evident in the treated group (45% vs 25% in the control group). However, it was not statistically significant because of small sample size. The patients' satisfaction and the external investigator's assessment showed statistically significant negative correlation with total NAPSI mean difference in the treated group. Conclusion: The role of Nd:YAG laser in nail psoriasis is still controversial

Photo-identification of Dugongs in Marsa Alam and Wadi El Gemal National Park, Egypt

1351-1358Using photo-identification techniques, 30 dugongs were recorded at the southern Egyptian Red Sea coast between December 2015 and October 2017, 16 at Marsa Alam and 14 at Wadi El Gemal National Park (WGNP). Males were recorded seven times more frequently than females and calves were also recorded. A Photo ID catalogue was prepared for the dugongs with records of their occurrence among sites. We confirmed the presence of particular dugong specific sites. Long- and short-distance movements within the study sites were recorded for eight different dugongs. This is the first study to document the number of dugongs in inshore areas of the Egyptian Red Sea coast. Further studies are recommended for offshore sites in WGNP for better documentation of this group of animals