SwS: a solvation web service for nucleic acids

SwS, based on a statistical analysis of crystallographic structures deposited in the NDB, is designed to provide an exhaustive overview of the solvation of nucleic acid structural elements through the generation of 3D solvent density maps. A first version (v1.0) of this web service focuses on the interaction of DNA, RNA and hybrid base pairs linked by two or three hydrogen bonds with water, cations and/or anions. Data provided by SwS are updated on a weekly basis and can be used by: (i) those involved in molecular dynamics simulation studies for validation purposes; (ii) crystallographers for help in the interpretation of solvent density maps; and all those involved in (iii) drug design and, more generally, in (iv) nucleic acid structural studies. SwS provides also statistical data related to the frequency of occurrence of different types of base pairs in crystallographic structures and the conformation of the involved nucleotides. This web service has been designed to allow a maximum of flexibility in terms of queries and has also been developed with didactic considerations in mind. AVAILABILITY: http://www-ibmc.u-strasbg.fr/arn/sws.html     

ELABELA (ELA) Peptide Exerts Cardioprotection Against Myocardial Infarction by Targeting Oxidative Stress and the Improvement of Heart Function

International Journal of Peptide Research and Therapeutics - Emerging evidence has shown that ELA peptide plays a pivotal role in cardiac development and modulation of vascular and cardiac...     

Antimicrobial Pyridazines: Synthesis,Characterization, Cytotoxicity,Substrate Promiscuity,and Molecular Docking

A facile and convenient synthesis of new pyridazines suitable for use as antimicrobial agents was reported. The hydrazide intermediate was coupled with various benzaldehydes and/or acetophenones and cyclized instantaneously to afford target pyridazine derivatives. The structures of new pyridazines were confirmed by IR, ¹H‐ and ¹³C‐NMR, elemental analysis in addition to representative LC/MS. Antimicrobial activity was screened against 10 bacterial and fungal strains. The new pyridazines showed strong to very strong antibacterial activity against Gram‐negative (GNB) bacteria, while none of them showed significant antifungal activity at the same concentration range. Chloro derivatives exhibited the highest antibacterial activity with MICs (0.892–3.744 μg/mL) lower than that of chloramphenicol (2.019–8.078 μg/mL) against E. coli, P. aeruginosa, and S. marcescens. Prediction of ADME parameters, pharmacokinetics, and substrate promiscuity revealed that these new pyridazines could be promising drug candidates. Cytotoxic studies on rat hepatocytes showed how much safe these new pyridazines on living organisms (IC₅₀>64 μg/mL). MOE docking studies showed a good overlay of these new pyridazines with co‐crystallized ligand within an E. coli DNA gyrase subunit B active sites (4KFG).     

Circular RNA-associated ceRNA network involved in HIF-1 signalling in triple-negative breast cancer: circ_0047303 as a potential key regulator

The aggressive and highly metastatic nature of triple-negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF-1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non-coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA-associated ceRNA network involved in HIF-1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303-mediated ceRNA regulatory axes have been extracted and validated across TNBC samples. We show that circ_0047303 has the highest degree in the circRNA-associated ceRNA network and shows a significant up-expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis-related genes, including HIF-1, EIF4E2 and VEGFA in TNBC through sponging the tumour-suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC.     

siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468)

Molecular Biology Reports - CD44, as a superficial cellular glycoprotein, is an essential factor in cell–cell and cell–matrix interaction. The CD44 expression level has been...     

Production of green biocellulose nanofibers by Gluconacetobacter xylinus through utilizing the renewable resources of agriculture residues

The present study demonstrates the ability to produce green biocellulose nanofibers using the renewable resources of agriculture residues. Locally grown wheat straws (WS) were hydrolyzed under different conditions. Their hydrolysates were utilized to produce the nanofibers in separate hydrolysis fermentation process by Gluconacetobacter xylinus strain bacterium. Highest biocellulose production of ~10.6 g/L was achieved with samples that were enzymatically hydrolyzed. Moreover, acidic hydrolyzed WS produced up to 9.7 g/L, with total sugar concentrations in culture media of 43 g/L. Generally, enzymatic hydrolysis of WS resulted in more total sugar concentration than the acidic hydrolysis (i.e., 52.12 g/L), while water hydrolysis produced the least. This can be related to utilizing Xylanase in addition to Cellulase and Beta-glucosidase that helps to hydrolyse WS dry basis of cellulose and hemicelluloses. Sugar mixtures produced under all hydrolysis conditions were mainly composed of glucose and xylose with average percentages of 56 and 28 %, respectively. Acidic hydrolysis at higher acid concentration, as well as soaking WS in the acidic solution for longer time, improved the total sugar concentration in the culture media by 18 %. Conducting thermal treatment at more intense conditions of higher temperature or heating time improved the total sugar produced with acidic hydrolysis. These conditions, however, resulted in further production of furfural, which considerably affected bacterial cells proliferation. This resulted in lowest sugar consumption in the range of 62–64 % that affected final BC production.     

Interplay between Ca2+ cycling and mitochondrial permeability transition pores promotes reperfusion-induced injury of cardiac myocytes

Uncontrolled release of Ca(2+) from the sarcoplasmic reticulum (SR) contributes to the reperfusion-induced cardiomyocyte injury, e.g. hypercontracture and necrosis. To find out the underlying cellular mechanisms of this phenomenon, we investigated whether the opening of mitochondrial permeability transition pores (MPTP), resulting in ATP depletion and reactive oxygen species (ROS) formation, may be involved. For this purpose, isolated cardiac myocytes from adult rats were subjected to simulated ischemia and reperfusion. MPTP opening was detected by calcein release and by monitoring the ΔΨ(m). Fura-2 was used to monitor cytosolic [Ca(2+)](i) or mitochondrial calcium [Ca(2+)](m), after quenching the cytosolic compartment with MnCl(2). Mitochondrial ROS [ROS](m) production was detected with MitoSOX Red and mag-fura-2 was used to monitor Mg(2+) concentration, which reflects changes in cellular ATP. Necrosis was determined by propidium iodide staining. Reperfusion led to a calcein release from mitochondria, ΔΨ(m) collapse and disturbance of ATP recovery. Simultaneously, Ca(2+) oscillations occurred, [Ca(2+)](m) and [ROS](m) increased, cells developed hypercontracture and underwent necrosis. Inhibition of the SR-driven Ca(2+) cycling with thapsigargine or ryanodine prevented mitochondrial dysfunction, ROS formation and MPTP opening. Suppression of the mitochondrial Ca(2+) uptake (Ru360) or MPTP (cyclosporine A) significantly attenuated Ca(2+) cycling, hypercontracture and necrosis. ROS scavengers (2-mercaptopropionyl glycine or N-acetylcysteine) had no effect on these parameters, but reduced [ROS](m). In conclusion, MPTP opening occurs early during reperfusion and is due to the Ca(2+) oscillations originating primarily from the SR and supported by MPTP. The interplay between Ca(2+) cycling and MPTP promotes the reperfusion-induced cardiomyocyte hypercontracture and necrosis. Mitochondrial ROS formation is a result rather than a cause of MPTP opening.