Functional analysis of Syndecan-1, a novel target of miR-10b, in breast cancer progression

Der heparan Sulfat proteoglycan syndecan-1 (sdc-1) ist hoch, bezogen auf die Oberfläche von Epithelzellen. Es hat sich immer deutlicher, dass es spielt eine entscheidende Rolle bei der Regulierung der zellulären Wachstum. Sdc-1 ist Co-Rezeptor für die Hepatozyten Wachstumsfaktor (HGF)-Rezeptor c-Met in multiplem Myelom. Das Ziel unserer Studie war es, eine mögliche Rolle der sdc-1 in Brustkrebs Progression. Wir beschäftigen siRNA-Technologie zur niederschlagen Ausdruck der sdc-1 in den hoch aggressiven MDA-MB231 Brustkrebs Zelllinie. Down Regulierung der sdc-1 sank HGF-induzierte nachgeschalteten Signal der Rezeptor-Tyrosin-Kinase c-Met, und sein Signal-Strecken, die, die in die Regulierung von Krebs Zellproliferation und Invasivität. Knockdown der Sdc-1 erbrachten die Zellen invasive unabhängig von HGF Induktion, was auf weitere HGF-unabhängige Effekte der sdc-1 auf Brustkrebs Zelle Invasivität. Unsere Ergebnisse deuten darauf hin, eine Rolle für sdc-1 als funktionelle Co-Rezeptor für HGF, dass fördert die Signalisierung durch die c-Met-Rezeptor in MDA-MB231 Zellen

New Fused Pyrimidines of Potential Biosignificant Interest. Syntheses and Molecular Modelling Studies

Abstract New derivatives of thieno [3,2-d]pyrimidine and thieno [2,3-b]pyrrole 5a,b and 6a,b, respectively, were obtained from the corresponding thiophene-2-carboxamides 4a,b. On the basis of compounds 5b, 6a and 6b, two novel series of tricyclic-and tetracyclic-condensed pyrimidines 8-15 and 16-19, respectively, were synthesized by the application of the cyclization reactions of 5b and 6a,b with a variety of commercially available reactants. Geometry optimization of selected structures, using the AM1 semiemperical method, revealed a smaller ionization potential and a lower degree of conformational freedom for the tetracyclic pyrimidine derivatives relative to their tricyclic counterparts. Interestingly, computation of the solvation free energies of the lowest energy conformers at physiological conditions indicated that the series is highly soluble under these conditions. The trend in solubility as implied by the relative magnitudes of the solvation free energies is suggestive of a greater contribution of higher moments of charge distribution in modulating the interaction of the structures with the biological environment which could be detrimental for the binding modes of these structures to their putative receptor sites

Multiproxy analyses of paleoenvironmental and paleoceanographic changes during the Danian-Selandian in East Central Sinai: An integrated stable isotope and planktic foraminiferal data

Forty-three planktic foraminifera samples from the Themed section (East Central Sinai; Egypt) spanning the Zone Parvularugoglobigerina eugubina (Pα) to the Subzone Acarinina subsphaerica (P4b) have been studied. Data from δ13C, δ18O, and planktic foraminifera-based species diversity, depth habitat, preference for warm and cool surface waters, and nutrients (oligotrophic, mesotrophic, and eutrophic conditions) are used to infer paleoenvironmental changes throughout the Danian‒Selandian duration. Based on quantitative multivariate analyses (hierarchical cluster and principal component), three distinct intervals were recognized, Interval 1 (Pα‒P1b), Interval 2 (P1c‒P3a), and Interval 3 (P3a‒P4b). Interval 2 is further subdivided into three subintervals, 2a (part P1c), 2b (part P1c), and 2c (P2‒P3a). Two δ13C events are identified, Dan-C2 and Latest Danian Event (LDE) and elaborated concerning paleoenvironmental changes. During the earliest Danian planktic foraminiferal Pα Zone, moderately shallow and eutrophic conditions prevailed with cool surface waters and a shallow thermocline. Comparable conditions were still prevailing during P1a‒P1b, but with slightly deeper and mesotrophic conditions and a somewhat deeper thermocline and reduced stratification. P1b‒P1c exhibits a major shift from Eoglobigerina to Subbotina‒ Parasubbotina with cooler surface waters and moderate mesotrophic conditions. For Subzone P1c (upper part), slightly mesotrophic conditions were inferred, whereas for P2‒P3a (lower part), surface water warming and thermocline shallowing events have inferred with increased oligotrophic conditions. The Latest Danian Event (mid-P3a) is marked by a dramatic negative δ13C excursion, warm waters, increased mesotrophic conditions, and enhanced stratification. The dominance of Morozovella, Acarinina, and Igorina specify warm and oligotrophic conditions for subzones P3b‒P4b

Chemical Profiling of Significant Antioxidant and Phytotoxic Microwave-Extracted Essential Oil from Araucaria heterophylla Resin

Due to the various hazards of using synthetic chemical compounds in pharmaceutics, agriculture, and industry, scientists and researchers do their best to explore and assess new green natural compounds from natural resources with potent activity. The essential oil (EO) from the resin collected from Araucaria heterophylla Salisb. was extracted by the microwave technique and chemically characterized via GC-MS analysis. Furthermore, the extract EO was assessed for its antioxidant and phytotoxic activities. The EO has 33 compounds, mainly terpenes (98.23%), and the major compounds were α-pinene (62.57%), β-pinene (6.60%), germacrene D (5.88%), and β-caryophyllene (3.56%). The extracted EO showed substantial antioxidant activity, where it showed IC50 values of 142.42 and 118.03 mg L−1 for DPPH and ABTS, respectively. On the other hand, the EO revealed considerable phytotoxicity against the weed Chenopodium murale, where the EO showed IC50 values of 304.0, 230.1, and 147.1 mg L−1, for seed germination, seedling shoot growth, and seedling root growth, respectively. Moreover, the EO showed the same pattern of allelopathic inhibition against the weed Sonchus oleraceus, where it showed IC50 values of 295.7, 224.5, and 106.1 mg L−1, for seed germination, seedling shoot growth, and seedling root growth, respectively. The present study showed that the extraction technique affects the constituents of the EO, particularly the quantitative composition. The EO of A. heterophylla resin also revealed considerable antioxidant and phytotoxic activity against weeds. Therefore, it can be considered a promising natural resource that could be integrated into the weed management approach. However, further study is recommended for deep characterization of their authentic compounds and evaluation of their mode of action(s) on a wide spectrum of weeds

The ligational behavior of a phenolic quinolyl hydrazone towards copper(II)- ions

<p>Abstract</p> <p>Background</p> <p>The heterocyclic hydrazones constitute an important class of biologically active drug molecules. The hydrazones have also been used as herbicides, insecticides, nematocides, redenticides, and plant growth regulators as well as plasticizers and stabilizers for polymers. The importance of the phenolic quinolyl hydrazones arises from incorporating the quinoline ring with the phenolic compound; 2,4-dihydroxy benzaldehyde. Quinoline ring has therapeutic and biological activities whereas, phenols have antiseptic and disinfectants activities and are used in the preparation of dyes, bakelite and drugs. The present study is planned to check the effect of the counter anions on the type and geometry of the isolated copper(II)- complexes as well as the ligational behavior of the phenolic hydrazone; 4-[(2-(4,8-dimethylquinolin-2-yl)hydrazono)methyl] benzene-1,3-diol; (H₂L).</p> <p>Results</p> <p>A phenolic quinolyl hydrazone (H₂L) was allowed to react with various copper(II)- salts (Cl‾, Br‾, NO₃‾, ClO₄‾, AcO‾, SO₄^2-). The reactions afforded dimeric complexes (ClO₄‾, AcO‾ ), a binuclear complex (NO₃‾ ) and mononuclear complexes (the others; Cl‾, Br‾, SO₄^2-). The isolated copper(II)- complexes have octahedral, square pyramid and square planar geometries. Also, they reflect the strong coordinating ability of NO₃‾, Cl‾, Br‾, AcO‾ and SO₄^2-anions. Depending on the type of the anion, the ligand showed three different modes of bonding <it>viz</it>. (NN)⁰for the mononuclear complexes (<b>3, 4, 6</b>), (NO)^-with O- bridging for the dimeric complexes (<b>1, 5</b>) and a mixed mode [(NN)⁰+ (NO)^-with O- bridging] for the binuclear nitrato- complex (<b>2</b>).</p> <p>Conclusion</p> <p>The ligational behavior of the phenolic hydrazone (H₂L) is highly affected by the type of the anion. The isolated copper(II)- complexes reflect the strong coordinating power of the SO₄^2-, AcO‾, Br‾, Cl‾ and NO₃‾ anions. Also, they reflect the structural diversity (octahedral, square pyramid and square planar) depending on the type of the counter anion.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Improvement of renal oxidative stress markers after ozone administration in diabetic nephropathy in rats

<p>Abstract</p> <p>Background</p> <p>Several complications of diabetes mellitus (DM) e.g. nephropathy (DN) have been linked to oxidative stress. Ozone, by means of oxidative preconditioning, may exert its protective effects on DN.</p> <p>Aim</p> <p>The aim of the present work is to study the possible role of ozone therapy in ameliorating oxidative stress and inducing renal antioxidant defence in streptozotocin (STZ)-induced diabetic rats.</p> <p>Methods</p> <p>Six groups (n = 10) of male Sprague Dawley rats were used as follows: Group C: Control group. Group O: Ozone group, in which animals received ozone intraperitoneally (i.p.) (1.1 mg/kg). Group D: Diabetic group, in which DM was induced by single i.p. injections of streptozotocin (STZ). Group DI: Similar to group D but animals also received subcutaneous (SC) insulin (0.75 IU/100 gm BW.). Group DO: In which diabetic rats received the same dose of ozone, 48 h after induction of diabetes. Group DIO, in which diabetic rats received the same doses of insulin and ozone, respectively. All animals received daily treatment for six weeks. At the end of the study period (6 weeks), blood pressure, blood glycosylated hemoglobin (HbA_1c), serum creatinine, blood urea nitrogen (BUN), kidney tissue levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (GPx), aldose reductase (AR) activities and malondialdehyde (MDA) concentration were measured.</p> <p>Results</p> <p>Induction of DM in rats significantly elevated blood pressure, HbA_1c, BUN, creatinine and renal tissue levels of MDA and AR while significantly reducing SOD, CAT and GPx activities. Either Insulin or ozone therapy significantly reversed the effects of DM on all parameters; in combination (DIO group), they caused significant improvements in all parameters in comparison to each alone.</p> <p>Conclusions</p> <p>Ozone administration in conjunction with insulin in DM rats reduces oxidative stress markers and improves renal antioxidant enzyme activity which highlights its potential uses in the regimen for treatment of diabetic patients.</p