New glycosyl-(carboxamide)-1,2,3-triazole-N-nucleosides: synthesis and antitumor activity

A series of potential bioactive compounds, 1-glucopyranosyl- 1,2,3-triazole-4,5-dimethylcarboxylate, 1-glucopyranosyl-1,2,3-triazole-4,5-N-dicarboxamide,-dialkyl-dicarboxamide-N-nucleosides and 6-amino-4H-1-(beta-D-glucopyranosyl)-8-hydroxy-1,2.3-triazolo[4,5-e][1,3]-diazepin-4-one, were synthesized. Primary activity screening of the novel nucleosides showed poor or no anticancer activity against breast, lung and CNS tumors.     

Effect of Endoxylanase and Iron Oxide Nanoparticles on Performance and Histopathological Features in Broilers

Biological Trace Element Research - Endoxylanase enzyme is used as poultry feed additive to degrade anti-nutritional factors like non-starch polysaccharides. Moreover, iron is one of the most...     

Review: role of carbon sources for in vitro plant growth and development

In vitro plant cells, tissues and organ cultures are not fully autotrophic establishing a need for carbohydrates in culture media to maintain the osmotic potential, as well as to serve as energy and carbon sources for developmental processes including shoot proliferation, root induction as well as emission, embryogenesis and organogenesis, which are highly energy demanding developmental processes in plant biology. A variety of carbon sources (both reducing and non-reducing) are used in culture media depending upon genotypes and specific stages of growth. However, sucrose is most widely used as a major transport-sugar in the phloem sap of many plants. In micropropagation systems, morphogenetic potential of plant tissues can greatly be manipulated by varying type and concentration of carbon sources. The present article reviews the past and current findings on carbon sources and their sustainable utilization for in vitro plant tissue culture to achieve better growth rate and development.     

Is Time to Reach EDSS 6.0 Faster in Patients with Late-Onset versus Young-Onset Multiple Sclerosis?

MethodsThis cross-sectional cohort study was conducted to identify LOMS and YOMS patients’ with relapsing remitting course at MS diagnosis. Time (years) to reach sustained EDSS 6.0 was compared between LOMS and AOMS patients. Cox proportional hazards model was used to evaluate the demographic and clinical predictors of time to EDSS 6.0 in these cohorts.ResultsLOMS and YOMS cohorts comprised 99 (10.7%) and 804 (89.3%) patients respectively. Spinal cord presentation at MS onset was more common among LOMS patients (46.5% vs. 32.3%). The proportions of LOMS and YOMS patients reaching EDSS 6.0 during the follow-up period were 19.2% and 15.7% respectively. In multivariable Cox proportional hazards model, older age at MS onset (adjusted hazard ratio (aHR) = 3.96; 95% CI: 2.14–7.32; p < 0.001), male gender (aHR = 1.85; 95% CI: 1.22–2.81; p = 0.004) and spinal cord presentation at onset (aHR = 1.47; 95% CI: 0.98–2.21; p = 0.062) were significantly associated with shorter time to EDSS 6.0.ConclusionsLOMS patients attained EDSS 6.0 in a significantly shorter period that was influenced by male gender and spinal cord presentation at MS onset.     

Health implications resulting from the timing of elective cesarean delivery

Background  

The literature is nearly unanimous in recommending elective cesarean delivery at 39 weeks of gestation because of the lower rates of neonatal respiratory complications compared to 38 weeks. However, elective cesarean delivery at 39 weeks or more may have maternal and other fetal consequences compared to delivery at 38 weeks, which are not always addressed in these studies.     

New inhibitors of VEGFR-2 targeting the extracellular domain dimerization process

We are reporting the discovery of small molecule inhibitors for vascular endothelial growth factor receptor type 2 (VEGFR-2) extracellular domain. The VEGFR-2 extracellular domain is responsible for the homo-dimerization process, which has been recently reported as a main step in VEGFR signal transduction cascade. This cascade is essential for the vascularization and survival of most types of cancers. Two main design strategies were used; Molecular docking-based Virtual Screening and Fragment Based Design (FBD). A virtual library of drug like compounds was screened using a cascade of docking techniques in order to discover an inhibitor that binds to this new binding site. Rapid docking methodology was used first to filter the large number of compounds followed by more accurate and slow ones. Fragment based molecular design was adopted afterwards due to unsatisfactory results of screening process. Screening and design process resulted in a group of inhibitors with superior binding energies exceeding that of the natural substrate. Molecular dynamics simulation was used to test the stability of binding of these inhibitors and finally the drug ability of these compounds was assisted using Lipinski rule of five. By this way the designed compounds have shown to possess high pharmacologic potential as novel anticancer agents.     

The Proapoptotic Protein tBid Forms Both Superficially Bound and Membrane-Inserted Oligomers

Bid is a proapopotic activator protein of the Bcl-2 family that plays a pivotal role in controlling mitochondrial outer membrane permeabilization during apoptosis. Here, we characterized the interaction of fluorescently labeled truncated Bid (tBid) with a mitochondria-like supported lipid bilayer at the single-molecule level. The proteins observed at the membrane exhibited a very wide range of mobility. Confocal images of the membrane displayed both diffraction-limited Gaussian spots and horizontal streaks, corresponding to immobile and mobile tBid species, respectively. We observed 1), fast-diffusing proteins corresponding to a loosely, probably electrostatically bound state; 2), slowly diffusing proteins, likely corresponding to a superficially inserted state; and 3), fully immobilized proteins, suggesting a fully inserted state. The stoichiometry of these proteins was determined by normalizing their fluorescence intensity by the brightness of a tBid monomer, measured separately using fluorescence fluctuation techniques. Strikingly, the immobile species were found to be mainly tetramers and higher, whereas the mobile species had on average a significantly lower stoichiometry. Taken together, these results show that as soluble Bid progresses toward a membrane-inserted state, it undergoes an oligomerization process similar to that observed for Bax.