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Cordia dichotoma Forst. (F. Boraginaceae) has been traditionally used for the management of a variety of human ailments. In our earlier work, the antidiabetic activity of methanolic bark extract of C. dichotoma (MECD) has been reported. In this paper, two flavonoid molecules were isolated (by column chromatography) and identified (by IR, NMR and Mass spectroscopy/spectrometry) from the MECD with an aim to investigate their antidiabetic effectiveness. Molecular docking and ADMET studies were carried out using AutoDock Vina software and Swiss ADME online tool, respectively. The isolated flavonoids were identified as 3,5,7,3’,4’-tetrahydroxy-4-methoxyflavanone-3-O-L-rhamnopyranoside and 5,7,3’-trihydroxy-4-methoxyflavanone-7-O-L-rhamnopyranoside (quercitrin). Docking and ADMET studies revealed the promising binding affinity of flavonoid molecules for human lysosomal alpha-glucosidase and human pancreatic alpha-amylase with acceptable ADMET properties. Based on computational studies, our study reports the antidiabetic potential of the isolated flavonoids with predictive pharmacokinetics profile.

Background: E110 is one of the food colorants which is widely used in dairy products, fast foods, jam and dry beverage powders, aqueous drug solutions, tablets, capsules, toothpastes mouthwashes, hair care products and cosmetics. Doubts have accumulated in recent years that food additives might cause allergic reactions in humans or increase these ailments. In this study, side effects of Sunset yellow FCF (E110) on the embryonic development of chicken spleen were evaluated by means of histological, histomorphometrical and enzyme histochemical methods. Methods: In the study, 250 fertilized broiler eggs obtained from a commercial broodstock were used. Eggs were divided into 5 groups each having 50 eggs. Control eggs were either nontreated or distilled water injected via air sac. The eggs in the experimental groups were injected with 100ng/egg, 500ng/egg and 1.000ng/egg E110 prior to incubation. Blood and spleen samples were taken from randomly selected 10 eggs of each group at 11th, 15th, 18th and 21st days of incubation. Leukocyte formula, alpha-naphtyl acetate esterase-positive and acid phosphatase-positive lymphocyte percentages were determined in the blood samples and embriyonic development of the spleen was assessed in the tissue sections. Results: In the 500ng/egg and 1.000ng/egg E110 injected experimental groups, embryonic development of the spleen retarded, alpha-naphtyl acetate esterase-positive and acid phosphatase-positive lymphocyte rates were significantly depressed. Conclusions: Significant disturbances in the immune system functions of the affected animals might occure at post-natal period of their life.

Malignancies constitute a global health concern and chemotherapy remains the main mode of treatment. The present study was designed to evaluate the cytotoxicity of 8 compounds from Desbordesia glaucescens namely lanosta-7,24-dien-3-one (1), friedelanone (2), friedelanol (3), 3,3'-di-O-methylellagic acid (4), 3,3',4'-tri-0-methylellagic acid (5), ellagic acid (6), 3',4'-di-0-methylellagic acid 4-0-beta-o-glucopyranoside (7) and 3,3'-di-0-methylellagic acid 4'-0-beta-c-xylopyranoside (8) against 4 human carcinoma cell lines and normal CRL2120 fibroblasts. The neutral red uptake (NRU) assay was used for cytotoxicity testing. Caspase-Glo assay, cell cycle analysis, measurements of mitochondrial membrane potential (MMP) and levels of reactive oxygen species (ROS) were used to evaluate apoptosis induction. Compounds 4 and 6 as well as doxorubicin had IC50 values below 45 pM in the four tested cancer cell lines meanwhile other compounds displayed selective activity. The IC50 values ranged from 11.23 mu M (towards breast adenocarcinoma MCF-7 cells) to 44.65 mu M (colon carcinoma Caco-2 cells) for 4, from 14.07 mu M (towards MCF-7 cells) to 77.73 mu M (Caco-2 cells) for 6 and from 0.07 mu M (towards SPC212 cells) to 1.01 mu M (A549 cells) for doxorubicin. Compound 4 induced apoptosis in MCF-7 cells mediated by MMP loss. The constituents of Desbordesia glaucescens and especially ellagic acid (6) and its derivative 4 are potential cytotoxic compounds that deserve more investigations towards developing novel antiproliferative drugs against human carcinoma. (C) 2017 SAAB. Published by Elsevier B.V. All rights reserved.

Summary Background Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m 2 (on days 1–14) and intravenous cisplatin 80 mg/m 2 (on day 1), with or without weekly cetuximab (400 mg/m 2 initial infusion on day 1 followed by 250 mg/m 2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2–5·5) compared with 5·6 months (5·1–5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92–1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3–4 adverse events, including grade 3–4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3–4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3–4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding Merck KGaA.

Effects of six tillage practices on some soil microbiological properties and crop yields were evaluated for a clay soil (Typic Haploxererts) under semi-arid Mediterranean conditions in a three year study (2006-2009). The experiment was designed as a completely randomized-block with three replications. Treatments were: conventional tillage with residue incorporated (CT1), conventional tillage with residue burned (CT2), reduced tillage with heavy tandem disc harrow (RT1), reduced tillage with rotary tiller (RT2), reduced tillage with heavy tandem disc harrow for the first crop + no-tillage for the second crop (RNT), and no tillage (NT). The study was conducted in wheat-corn, wheat-soybean and wheat crop rotations. Dehydrogenase activity, soil respiration, mycorrhizal spore number, total organic carbon (TOC), and total N were determined at three depths (0-10, 10-20 and 20-30 cm). The mycorrhizal spore number responded quite early to tillage practices. Significant tillage effects on TOC and total N were observed only at 0-10 cm depth. The TOC content was increased by NT, RT2, RNT and RT1 practices compared to the initial values at the same depth as 74%, 62%, 56%, and 50%, respectively. Dehydrogenase activity (DHA) and soil respiration were higher on the surface and decreased with depth. Reduced and no-tillage practices significantly increased the mycorrhizal spore number, dehydrogenase activity and soil respiration at all depths (P

Physical, chemical and biological attributes of soil surface are significantly affected by tillage practices and crop rotation. The objective of this study was to determine the short-term (2006-2009) effects of conventional and conservational tillage practices on selected soil physical properties of a heavy clay soil under two wheat-corn and wheat-legume rotation in a semi-arid Mediterranean Region. Treatments included conventional tillage with residue incorporated in soil (CT1), conventional tillage with burned residue (CT2), reduced tillage with heavy tandem disc-harrow (RT1), reduced tillage with rotary tiller (RT2), reduced tillage with heavy tandem disc harrow fallowed by no-tillage (RNT) and no tillage (NT). Disturbed and undisturbed soil samples were collected to determine saturated hydraulic conductivity (HC), bulk density (BD), mean weight diameter (MWD), available water content (AWC) and total porosity at 0-10, 10-20 and 20-30 cm depths. The highest HC values of 0-10 cm and 10-20 cm depths were obtained with CT1 (9.70x10(-6) m s(-1), 8.74x10(-6) m s(-1)) and CT2 (9.39x10(-6) m s(-1), 8.58x10(-6) m s(-1)) applications. CT2 treatment destructed the soil aggregates and resulted in greater bulk density and low total porosity at 0-10 cm depth. The available water content at 0-10 cm depth was significantly reduced with the CT1 (P

A field experiment was conducted to compare the effects of long-term tillage and crop residue management on some physical properties and nitrate leaching of a Typic Haploxerert soil under winter wheat (Triticum vulgare L.)-soybean (Glycine max L.) double-cropping system. The tillage systems consisted of conventional tillage with stubble (CT1), conventional tillage with stubbles burned (CT2), heavy disc harrow reduced tillage (RT1), rototiller reduced tillage (RT2), reduced tillage with heavy tandem disc harrow fallowed by no-tillage (RNT) and no-till (NT). Each tillage method applied at 480 m2 plot and replicated three times in randomly distributed plots. In the experiment, organic matter content (OM), aggregate stability (AS), penetration resistance (PR), porosity, bulk density (BD) in 0-15 cm and 15-30 cm depth and nitrate concentrations at 90 cm depth were determined. Tillage practices significantly affected the measured properties at both soil depths. The BD and PR within the conservational managed plots were higher than under conventional managed plot. Whereas, OM content and AS were significantly greater under conservational managed plots, indicating improved soil quality. Soybean yield was not affected by tillage practices. The concentrations of NO3-N leached had strong variation within sampling dates and significantly different among treatments after the first and the third irrigation (P?0.01). The highest average NO3-N (1440.8b±74.9 mg L-1) in leachate was measured in the CT2 plot while the lowest value (774.8a±56.5 mg L-1) was obtained in the RT1 plot. The results of this study revealed that reduced tillage and no-till treatments could significantly improve soil physical quality and reduce NO3-N leaching of Typic Haploxerert soil in the Çukurova Region. © 2017, Gorgan Univ Agricultural Sciences and Natural Resources. All rights reserved.

OBJECTIVES: We aimed to investigate the effects of weak extremely low frequency electromagnetic fields (ELF-EMFs) on the nucleus size, the silver staining nucleolar organizer regions (AgNORs), the frequency of micro nucleated peripheral blood lymphocytes (MPBLs) and the micro nucleated polychromatic erythrocytes (MPCEs).

The aims of the present study were to evaluate the efficacy and tolerability of ledipasvir/sofosbuvir (LDV/SOF) with or without ribavirin in the treatment of chronic hepatitis C (CHC) in patients with advanced liver disease and to analyse whether the use of LDV/SOF treatment is associated with a new occurrence of hepatocellular carcinoma (HCC) during and after LDV/SOF treatment. The Turkish Early Access Program provided LDV/SOF treatment to a total of 200 eligible CHC patients with advanced liver disease. The median follow-up period was 22 months. All patients were Caucasian, 84% were infected with genotype 1b, and 24% had a liver transplantation before treatment. The sustained virological response (SVR12) was 86.0% with ITT analysis. SVR12 was similar among patients with Child-Pugh classes A, B and C disease and transplant recipients. From baseline to SVR12, serum ALT level and MELD score were significantly improved (P < 0.001). LDV/SOF treatment was generally well tolerated. Only one patient developed a new diagnosed HCC. Seventeen of the 35 patients, who had a history of previous HCC, developed HCC recurrence during the LDV/SOF treatment or by a median follow-up of 6 months after treatment. HCC recurrence was less commonly observed in patients who received curative treatment for HCC compared with those patients who received noncurative treatment (P = 0.007). In conclusion, LDV/SOF with or without ribavirin is an effective and tolerable treatment in CHC patients with advanced liver disease. Eradication is associated with improvements in liver function and a reduced risk of developing a new occurrence of HCC.

Contains fulltext : 118506.pdf (Publisher’s version ) (Closed access) Molecular pathology is an integral part of daily diagnostic pathology and used for classification of tumors, for prediction of prognosis and response to therapy, and to support treatment decisions. For these reasons, analyses in molecular pathology must be highly reliable and hence external quality assessment (EQA) programs are called for. Several EQA programs exist to which laboratories can subscribe, but they vary in scope, number of subscribers, and execution. The guideline presented in this paper has been developed with the purpose to harmonize EQA in molecular pathology. It presents recommendations on how an EQA program should be organized, provides criteria for a reference laboratory, proposes requirements for EQA test samples, and defines the number of samples needed for an EQA program. Furthermore, a system for scoring of the results is proposed as well as measures to be taken for poorly performing laboratories. Proposals are made regarding the content requirements of an EQA report and how its results should be communicated. Finally, the need for an EQA database and a participant manual are elaborated. It is the intention of this guideline to improve EQA for molecular pathology in order to provide more reliable molecular analyses as well as optimal information regarding patient selection for treatment.