Effect of certain organic materials in controlling Meloidogyne incognita root-knot nematode infesting banana

Efficacy of certain plant wastes as onion bulb envelope, dry leaves of sugar beet, fleabane and jojoba, filter cake or mud as sugar cane industrial residue and nile fertile mineral bio-fertilisers were studied under field conditions for managing Meloidogyne incognita on banana Cv. Williams. All the tested treatments significantly (P ≤ 0.05 and 0.01) proved to be effective in reducing the studied nematode criteria during the growing season of banana. The highest percentage reductions of 87.5 and 85.5% were recorded in the number of second-stage juveniles caused by fleabane at vegetative and harvest stages, respectively. As for galls, the highest percentage reductions of 80.4 and 79.6% were achieved at harvest stage by sugar beet waste and filter cake residue, respectively. Also, sugar beet waste was the best at increasing banana fruit yield per feddan (77.0%), followed by jojoba (53.1%) and fleabane (50.4%). The number of fingers and hands per bunch increased by the different materials at various degrees.     

Severe Hypoglycemia in a Juvenile Diabetic Rat Model: Presence and Severity of Seizures Are Associated with Mortality

It is well accepted that insulin-induced hypoglycemia can result in seizures. However, the effects of the seizures, as well as possible treatment strategies, have yet to be elucidated, particularly in juvenile or insulin-dependent diabetes mellitus (IDDM). Here we establish a model of diabetes in young rats, to examine the consequences of severe hypoglycemia in this age group; particularly seizures and mortality. Diabetes was induced in post-weaned 22-day-old Sprague-Dawley rats by streptozotocin (STZ) administered intraperitoneally (IP). Insulin IP (15 U/kg), in rats fasted (14–16 hours), induced hypoglycemia, defined as <3.5 mM blood glucose (BG), in 68% of diabetic (STZ) and 86% of control rats (CON). Seizures occurred in 86% of STZ and all CON rats that reached hypoglycemic levels with mortality only occurring post-seizure. The fasting BG levels were significantly higher in STZ (12.4±1.3 mM) than in CON rodents (6.3±0.3 mM), resulting in earlier onset of hypoglycemia and seizures in the CON group. However, the BG at seizure onset was statistically similar between STZ (1.8±0.2 mM) and CON animals (1.6±0.1 mM) as well as between those that survived (S+S) and those that died (S+M) post-seizure. Despite this, the S+M group underwent a significantly greater number of seizure events than the S+S group. 25% glucose administered at seizure onset and repeated with recurrent seizures was not sufficient to mitigate these continued convulsions. Combining glucose with diazepam and phenytoin significantly decreased post-treatment seizures, but not mortality. Intracranial electroencephalograms (EEGs) were recorded in 10 CON and 9 STZ animals. Predictive EEG changes were not observed in these animals that underwent seizures. Fluorojade staining revealed damaged cells in non-seizing STZ animals and in STZ and CON animals post-seizure. In summary, this model of hypoglycemia and seizures in juvenile diabetic rats provides a paradigm for further study of underlying mechanisms. Our data demonstrate that severe hypoglycemia (<2.0 mM) is a necessary precondition for seizures, and the increased frequency of these seizures is associated with mortality.     

Potential antidiabetic activity and molecular docking studies of novel synthesized 3.6-dimethyl-5-oxo-pyrido[3,4-f][1,2,4]triazepino[2,3-a]benzimidazole and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole derivatives

Diabetes affects a large population of the globe and is considered as a leading cause of death. Many synthetic and natural inhibitors have been developed for diabetes treatment. Herein, we report the potential antidiabetic activity of two new heterocyclic systems, namely 3.6-dimethyl-5-oxo-pyrido[3,4f][1,2,4]triazepino[2,3-a]benzimidazole (I) and 10-amino-2-methyl-4-oxo pyrimido[1,2-a]benzimidazole (II) against three related enzymes: α-amylase, α-glucosidase and β-galactosidase. Compounds I and II were synthesized by the action of DMF-DMA and dimethyl sulfate in the presence of water on 2-methyl-3H-benzimidazolo[1,2b][1,2,4]triazepin-4(5H)-one, and are characterized by single X-ray diffraction. The binding interaction modes in the active sites of I and II and targeted enzymes (stable complexes ligand-receptor) are emphasized using the molecular docking approach by applying the Lamarckian genetic algorithm method. Furthermore, plausible mechanisms have been proposed explaining their synthesis. Hirshfeld surface analysis reveals the nature of molecular interactions and fingerprint plots provide information about the percentage contribution from each individual molecular contact to the structure surface.

Open image in new window

Graphical abstract Left Molecular packing of 1,4-dimethyl-2-oxo-pyrimido[1,2-a]benzimidazole hydrate. Right Docking active site of α-glucosidase

     

Characterization of Asymmetric Tapered Dipole Nanoantenna for Energy Harvesting Applications

In this paper, systematic study for asymmetric tapered dipole nanoantenna is implemented using finite element frequency domain (FEFD) solver where harvesting efficiency, field confinement, surface current, and input impedance are calculated at wavelength of 500 nm. The proposed nanoantennas achieve a harvesting efficiency of 61.3% and a field enhancement factor of 37.7 over the conventional dipole nanoantenna. This enhancement is attributed to the irregularity of the surface current distribution on the asymmetric designs. Particle swarm optimization technique is used to find the optimum design geometrical parameters through an external link between the optimization algorithm and the FEFD solver. Moreover, the proposed designs offer a resonance impedance of 500 Ω to match that of fabricated rectifiers. Further study of the structure fabrication tolerance is included which shows the robustness of the proposed nanoantennas.     

Functional characterization and FTIR-based 3D modeling of full length and truncated forms of Scorpio maurus venom phospholipase A2

Background

Heterodimeric phospholipase A₂ from venom glands of Tunisian scorpion Scorpio maurus (Sm-PLGV) had been purified. It contains long and short chains linked by a disulfide bridge. Sm-PLGV exhibits hemolytic activity towards human erythrocytes and interacts with phospholipid monolayers at high surface pressure. The investigation of structure-function relationships should provide new clues to understand its activity.

T-DM1-resistant cells gain high invasive activity via EGFR and integrin cooperated pathways

Ado-trastuzumab emtansine (Kadcyla®; T-DM1) is an antibody-drug conjugate developed to treat trastuzumab-resistant disease. Despite initial favorable outcomes, most patients eventually cease to respond due to developing acquired resistance to T-DM1. Currently, there is no targeted therapy to treat T-DM1-resistant disease. To explore novel therapeutic targets to improve therapeutic efficacy of T-DM1, we generated T-DM1-resistant cells using trastuzumab-resistant JIMT1 cells. We found that the loss of human epidermal growth factor receptor 2 confers T-DM1 resistance, which in turn activates a compensatory mechanism that increases epidermal growth factor receptor (EGFR) expression. Upregulation of EGFR increases the protein levels of α5β1 and αVβ3 integrins, resulting in enhanced motility and invasion of T-DM1-resistant cells. This study delineates previously unappreciated relationships between α5β1 and αVβ3 and suggests that specific integrins should be carefully selected as therapeutic targets to treat T-DM1-resistant disease. Specifically, silencing β1 integrin expression by siRNA in T-DM1-resistant cells destabilizes α5, but increases expression of αV, a critical integrin mediating the invasion and metastases in many different cancers. As a consequence, T-DM1-resistant cells gain metastatic potential and become more invasive. This finding is underscored by the fact that β1 integrin blockage induced by an inhibitory antibody, MAB 13, significantly increases invasion of T-DM1-resistant cells. However, the increased cell invasion induced by β1 integrin blockage can be significantly reduced by either EGFR inhibitor or specific siRNA against αV integrin. The discovery of functional cooperation between EGFR and αV integrin in regulating cell growth and invasion provides an opportunity to develop novel therapeutic strategy by dual-targeting EGFR and specific integrin to overcome T-DM1 resistance.     

Activated Kupffer cells attenuate the liver response to the peroxisome proliferator perfluorooctanoic acid

It has been suggested that peroxisome proliferators stimulate Kupffer cells, an effect which may be involved in their mechanism of action. To evaluate this hypothesis, this study was designed to investigate the effect of stimulating Kupffer cells on basal as well as induced peroxisomal enzyme activity. Twenty four hours following treatment of male Sprague-Dawley rats with the peroxisome proliferating agent perfluorooctanoic acid (PFOA), in corn oil or with corn oil alone, hepatic peroxisomal -oxidation was 4.6 ± 0.2 and 1.8 ± 0.1 U/g liver, respectively. As expected, PFOA did not influence the catalase activity. Stimulating Kupffer cells in vivo by zymosan A (25 mg/kg, iv) prior to treatment with corn oil or PFOA diminished basal as well as PFOA-induced peroxisomal b-oxidation by 20-35%. Activation of Kupffer cells by zymosan A also diminished catalase activity by over 60%. Furthermore, PFOA reduced blood colloidal carbon clearance by 35% within 2 h of its administration. The data suggest that activation of Kupffer cells exerts a negative effect on basal as well as PFOA-induced peroxisomal enzyme activities. Data also suggest that PFOA inhibits Kupffer cells. Activated Kupffer cells may indeed produce factors which interfere with normal hepatic peroxisomal functions and responses.     

Imiquimod‐induced apoptosis of melanoma cells is mediated by ER stress‐dependent Noxa induction and enhanced by NF‐κB inhibition

Melanoma is characterized by dysregulated intracellular signalling pathways including an impairment of the cell death machinery, ultimately resulting in melanoma resistance, survival and progression. This explains the tumour's extraordinary resistance to the standard treatment. Imiquimod is a topical immune response modifier (imidazoquinoline) with both antiviral and antitumour activities. The mechanism by which imiquimod triggers the apoptosis of melanoma cells has now been carefully elucidated. Imiquimod‐induced apoptosis is associated with the activation of apoptosis signalling regulating kinase1/c‐Jun‐N‐terminal kinase/p38 pathways and the induction of endoplasmic stress characterized by the activation of the protein kinase RNA‐like endoplasmic reticulum kinase signalling pathway, increase in intracellular Ca²⁺ release, degradation of calpain and subsequent cleavage of caspase‐4. Moreover, imiquimod triggers the activation of NF‐κB and the expression of the inhibitor of apoptosis proteins (IAPs) such as, X‐linked IAP (XIAP) together with the accumulation of reactive oxygen species (ROS). Also, imiquimod triggers mitochondrial dysregulation characterized by the loss of mitochondrial membrane potential (Δψm), the increase in cytochrome c release, and cleavage of caspase‐9, caspase‐3 and poly(ADP‐ribose) polymerase (PARP). Inhibitors of specific pathways, permit the elucidation of possible mechanisms of imiquimod‐induced apoptosis. They demonstrate that inhibition of NF‐kB by the inhibitor of nuclear factor kappa‐B kinase (IKK) inhibitor Bay 11‐782 or knockdown of XIAP induces melanoma apoptosis in cells exposed to imiquimod. These findings support the use of either IKK inhibitors or IAP antagonists as adjuvant therapies to improve the effectiveness topical imiquimod in the treatment of melanoma.