ROS-mediated heme degradation and cytotoxicity induced by iron nanoparticles: hemoglobin and lymphocyte cells as targets

Nanoparticles (NPs) due to their small size and high surface area induce remarkable adverse effects on the biological systems. However, the exact mechanism by which NPs interacted with biological system and induce their adverse effects is still an enigma. Herein, the interaction of zero valent iron NPs (ZVFe NPs) with human hemoglobin (Hb) was evaluated using a variety of techniques including circular dichroism, fluorescence, and UV–visible (UV–vis) spectroscopy methods. Also, the cytotoxicity of ZVFe NPs on the human lymphocyte cell line as a model of blood system cell line was investigated by reactive oxygen species (ROS), caspase-9, and caspase-3 activities assays. It was revealed that ZVFe NP interaction resulted in heme displacement and degradation and induction of protein cabonylation. It was also shown that ZVFe NPs impaired the complexity of lymphocyte cells through ROS generation and apoptotic pathway. Together, these data suggest that NPs influence the biological system and induce adverse effects through ROS generation.     

Modification of wool surface by liposomes for dyeing with weld

In this research work, wool surface has been modified by liposome to investigate its effects on dyeing with weld, a yellow natural dye. To do this, samples were first treated with aluminium sulphate and afterward with different concentrations of liposomes at various temperatures for 30?minutes and, finally, dyed with weld at 75, 85, and 95°C for 30, 45, and 60?minutes. K/S values of fabric samples were calculated and washing, light and rub fastness properties of the samples were indicated. The results proposed that the sample treated with 1% liposomes and dyed at 75°C for 60?min has the highest K/S value. The central composite design (CCD) used for the experimental plan with three variables on the results of color strength and statistical analysis confirms the optimum conditions obtained by the experimental results. It was also found that washing, light, wet, and dry rub fastness properties of samples dyed with weld, including liposomes, have not significantly changed. The results of water drop absorption indicated that the hydrophobicity is higher for the samples pretreated with liposomes. The SEM picture of wool sample treated with mordant and liposomes and finally dyed with weld shows a coated layer on the fiber surface.     

Endogenous auxins in plant growth-promoting Cyanobacteria—Anabaena vaginicola and Nostoc calcicola

Three isolates of heterocystous cyanobacteria, belonging to the genera Anabaena and Nostoc, gathered from Iranian terrestrial and aquatic ecosystems exhibited considerable growth promotion effect on several vegetables and herbaceous plants. To study the ability of these three isolates to produce auxins, three endogenous auxins, including indole-3-acetic acid (IAA), and two of its main homologues, indole-3-propionic acid and indole-3-butyric acid, were extracted and analyzed with high-performance liquid chromatography equipped with diode array detector and fluorescence detector, and the results were further confirmed with liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the negative-ion mode. The dominant auxin observed in all isolates was indole-3-butyric acid (IBA) in the range of 140.10–2146.96 ng g^?1 fresh weight (FW), and only small amounts of IAA (2.19–9.93 ng g^?1 FW) were detected. The predominance of IBA in these strains is reported for the first time which is different from the previously reported auxin profiles in microalgae and algae with the predominance of IAA.     

Cyclic electron transport around photosystem I and its relationship to non-photochemical quenching in the unicellular green alga Dunaliella salina under nitrogen deficiency

Electron transport in photosystem II (PSII) and photosystem I (PSI) was estimated in terms of chlorophyll fluorescence and changes in P700 redox, respectively, in the unicellular green alga Dunaliella salina in the presence or absence of a nitrogen source in the culture medium. In a nitrogen-containing medium, the quantum yield of PSII (Φ_II) and that in PSI (Φ_I) were at the same level in low light, but cyclic electron transport around photosystem I (CET-PSI) was induced under high light as estimated from an increase in Φ_I/Φ_II. High light might further enhance the rate of electron transport in PSI by inducing the state 2 transition, in which the distribution of light energy is shifted to PSI at the expense of PSII. Nitrogen deficiency resulted in a decrease in Φ_II and an increase in Φ_I. As a consequence, the rate of CET-PSI was expected to increase. The high CET-PSI under N deficiency was probably associated with a high level of energy quenching (qE) formation in PSII.     

A facile chemo-, regio- and stereoselective synthesis and cholinesterase inhibitory activity of spirooxindole–pyrrolizine–piperidine hybrids

A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC₅₀ values of 3.33 and 3.13 μM, respectively.     

Production of transgenic goats expressing human coagulation factor IX in the mammary glands after nuclear transfer using transfected fetal fibroblast cells

There are growing numbers of recombinant proteins that have been expressed in milk. Thus one can consider the placement of any gene of interest under the control of the regulatory elements of a milk protein gene in a dairy farm animal. Among the transgene introducing techniques, only nuclear transfer (NT) allows 100?% efficiency and bypasses the mosaicism associated with counterpart techniques. In this study, in an attempt to produce a transgenic goat carrying the human coagulation factor IX (hFIX) transgene, goat fetal fibroblasts were electroporated with a linearized marker-free construct in which the transgene was juxtaposed to ??-casein promoter designed to secret the recombinant protein in goat milk. Two different lines of transfected cells were used as donors for NT to enucleated oocytes. Two transgenic goats were liveborn. DNA sequencing of the corresponding transgene locus confirmed authenticity of the cloning procedure and the complementary experiments on the whey demonstrated expression of human factor IX in the milk of transgenic goats. In conclusion, our study has provided the groundwork for a prosperous and promising approach for large-scale production and therapeutic application of hFIX expressed in transgenic goats.     

Phenylimino-2H-chromen-3-carboxamide derivatives as novel small molecule inhibitors of β-secretase (BACE1)

The inhibition of β secretase (BACE1) is potentially important approach to treatment of Alzheimer disease (AD). A novel series of 4-bromophenyl piperazine derivatives coupled to the phenylimino-2H-chromen-3-carboxamide scaffold were investigated as BACE1 inhibitors in this study. Docking study suggested that the phenyl-imino group of the scaffold establishes favorable π–π stacking interaction with side chain of Phe108 of flap pocket. Some of the docking proposed derivatives were synthesized and evaluated for BACE1 inhibitory activity using a FRET-based assay. High BACE1 inhibitory activities were observed from derivatives containing fused heteroaromtic groups attached through the aliphatic linkage to the N4-piperazine moiety, which may be attributed to the engagement of effective interactions with S1–S′1 sub-pocket residues. Of the most potent compounds, 9e displayed an IC₅₀ value for BACE1 of 98 nM. Some of these derivatives demonstrated good inhibitory activity on Aβ production in N2a-APPswe cells at 5 and 10 μM. These compounds might be considered as promising BACE1 inhibitory agents that could lower Aβ production in AD.     

Synthesis and discovery of novel piperidone-grafted mono- and bis-spirooxindole-hexahydropyrrolizines as potent cholinesterase inhibitors

Three-component reaction of a series of 1-acryloyl-3,5-bisbenzylidenepiperidin-4-ones with isatin and l-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a–k), are more active with IC₅₀ ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a–k) or bisspiropyrrolizines (9a–k). The compounds, 8i and 8e with IC₅₀ values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC₅₀ values obtained from in vitro cholinesterase assay.     

Microwave assisted synthesis,cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives

A series of hitherto unreported pyrido-pyrimidine-2-ones/pyrimidine-2-thiones were synthesized under microwave assisted solvent free reaction conditions in excellent yields and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Among the pyridopyrimidine derivatives, 7e and 7l displayed 2.5- and 1.5-fold higher enzyme inhibitory activities against AChE as compared to standard drug, galanthamine, with IC₅₀ of 0.80 and 1.37 μM, respectively. Interestingly, all the compounds except 6k, 7j and 7k displayed higher inhibitory potential against BChE enzyme in comparison to standard with IC₅₀ ranging from 1.18 to 18.90 μM. Molecular modeling simulations of 7e and 7l was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) and human butyrylcholinesterase (hBChE) enzymes to disclose binding interaction and orientation of these molecule into the active site gorge of respective receptors.