Interaction of 2-APB,dantrolene, and TDMT with IP3R and RyR modulates ER stress-induced programmed cell death I and II in neuron-like PC12 cells: an experimental and computational investigation

Ca²⁺ is an essential second messenger, playing a fundamental role in maintaining cell viability and neuronal activity. Two specific endoplasmic reticulum calcium channels, ryanodine receptors (RyRs) and inositol 1,4,5-trisphosphate receptors (IP₃Rs) play an important role in Ca²⁺ regulation. In the present study, we provided a 3D structure of RyR and IP3R by homology modeling, and we predicted their interactions with a known neuroprotective compound, 3-thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine (TDMT), as well as two inhibitors, dantrolene and 2-aminoethoxydiphenyl borate (2-APB). Interestingly, we found that dantrolene and 2-APB can bind to the IP3-binding domain of IP3R and RyR, while TDMT may directly block both channels by interacting with the putative resident domains in the pore. Cell culture experiments showed that these compounds could protect PC12 cells against H₂O₂-induced apoptosis and activate autophagic pathways. Collectively, our computational (in silico) and cell culture studies suggest that RyR and IP3R are novel and promising targets to be used against neurodegenerative diseases.     

Design of a liquid nano-sized drug delivery system with enhanced solubility of rivaroxaban for venous thromboembolism management in paediatric patients and emergency cases

Abstract

The increasing incidence of venous thromboembolism (VTE) in paediatric population has stimulated the development of liquid anticoagulant formulations. Thus our goal is to formulate a liquid formulation of poorly-water soluble anticoagulant, rivaroxaban (RIVA), for paediatric use and to assess the possibility of its intravenous administration in emergencies. Self-nanoemulsifying drug delivery systems (SNEDDSs) were developed and characterized. SNEDDS constituents were estimated from the saturated solubility study followed by plotting the corresponding ternary phase diagrams to determine the best self-emulsified systems. Thermodynamic stability, emulsification, dispersibility, robustness to dilution tests, in vitro dissolution, particle size, and zeta potential were executed to optimize the formulations. The optimized formulation, that composed of Capryol 90:Tween 20:PEG 300 (5:45:50), increased RIVA solubility (285.7-fold than water), it formed nanoemulsion with a particle size of 16.15?nm, PDI of 0.25 and zeta potential of ?21.8. It released 100.83?±?2.78% of RIVA after 5?min. SNEDDS was robust to dilution with oral and parenteral fluids and showed safety to human RBCs. SNEDDS showed enhanced bioavailability after oral and intravenous administration than the oral drug suspension (by 1.25 and 1.26-fold, respectively). Moreover, it exhibited enhanced anticoagulant efficacy in the prevention and treatment of carrageenan-induced thrombosis rat model.     

Efficiency of certain miscible oils and chlorpyriphos methyl insecticide against the soft scale insect,Kilifia acuminata Signoret (Homoptera: Coccidae) and their toxicities on rats

Abstract

The toxicity and efficacy of using three miscible oils; cabl-2, citrole and bio-dux and a chemical insecticide (chlorpyrifos-methyl) were studied against a soft scale insect, Kilifia acuminata (Signoret) infesting mango trees. The sub-chronic toxicity of tested chemicals on white albino rats was also studied. Considering the general mean number of K. acuminata stages after 3 months post spraying, chlorpyrifos methyl and capl-2 were the most efficient compounds followed by citrol and bio-dux in descending order. Chlorpyrifos-methyl was the most effective treatment for all months after spraying, the mean reduction percentage being 94.10, 91.63 and 92.00% while it gave the highest toxic effect after three months; 90.27, 87.84 and 89.73% reduction in infestation on pre-adult, adult and gravid female stages, respectively. Results also indicate that the general mean percent reduction in K. acuminata infestation were 82.62, 86.67, 78.87 and 89.28% in treated trees by citrole, cabl-2, bio-dux and chlorpyrifos-methyl, respectively. Citrole, bio-dux, cabl-2 and chlorpyrifos-methyl caused significant increase in WBCs counts, ALT and AST activities of treated rats after 15 and 30 days from treatment comparison with control. Changes occurring in the creatinine concentration showed a significant increase in rats treated with the tested chemicals 30 days from treatment, except in the case of bio-dux oil, while there were no significant changes after 15 days in rats treated with tested oils. On the contrary, tested chemicals caused a significant decrease in RBCs count and hemogobin values after 15 and 30 days form treatment, except in rats treated with bio-dux oil. Hemoglobin content showed no significant changes over the same periods.     

Laboratory and semi-field evaluation of three entomopathogenic nematode species on two non-target insect predators,Coccinella septumpunctata (Coleoptera: Coccinellidae) and Chrysoperla carnea (Neuroptera: Chrysopidae)

Abstract

Biocontrol potential of the entomopathogenic nematodes (EPNs) on the second-instar larvae of the non-target insect predators, Coccinella septumpunctata and Chrysoperla carnea as compared to Spodoptera littoralis (Boisd.) was evaluated. The pathogenicity of EPNs, namely, Heterorhabditis bacteriophora, Steinernema feltiae and Steinernema carpocapsae at concentrations 100, 200, 400, 800 and 1600 IJs/cup) were tested at 2, 4 and 6 days’ post-inoculation. Laboratory results showed significant differences among the mortality rates of different tested larvae, for each concentration at different time intervals. H. bacteriophora induced the highest mortality followed by S. carpocapsae treatment. However, S. feltiae was found to be more safety on predators as it causes less mortality at 6 days of treatment. The values of half lethal concentrations (LC₅₀) were 614.06, 3797.43 and 676.47 IJs/cup for C. Carnea and 390.60, 1209.88 and 503.65 IJs/cup for C. septumpunctata treated by H. bacteriophora, S. feltiae and S. carpocapsae, respectively. In semi-field experiments, there were non-significant differences among mortality of each predator indicated at concentrations of the different EPNs after 2 days or 6 days’ post-inoculation. The study revealed a lethal pathogenic effect of EPNs against insect pests but caused low mortality on the non-target ones.     

Impact of some insecticides and their mixtures on the population of tomato borers,Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) and Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) in tomato crop at Upper Egypt

Impact of some insecticides and their mixtures (Emamectin benzoate, Imidaclopride, Chlorfenapyr, Indoxacarb, Profenofos, Pyridalyl, Methomyl and Teflubenzuron) were evaluated against the tomato borers, Tuta absoluta (Meyrick) and Helicoverpa armigera (Hübner) population in tomato crop at Upper Egypt. Results of LC₅₀ values indicated that Emamectin benzoate was the most toxic compound (LC₅₀ 0.461%) against T. absoluta, larvae. The carbamate insecticide, Methomyl, followed this descending order, showing almost similar toxicity, while Teflubenzuron and Chlorfenapyr were less effective (LC₅₀ 1.054 and 3.165%, respectively). Pyridalyl was found to be the most effective insecticide against larval stage of H. armigera. (LC₅₀ 0.513%). The corresponding toxicities of the other tested insecticides, arranged according to their LC₅₀ values in descending order were as follow: Methomyl, Emamectin benzoate, Profenofos, Imidaclopride, Teflubenzuron, Indoxacarb and Chlorfenapyr. Their LC₅₀ values were ranged between (0.513 and 0.872%). While, their toxicity indexes were ranged between (92.432 and 58.830%, respectively). On the other hand, there were no differences occurred among the treatments. Mean of percent infestation was decreased six weeks after six sprayings, and the per cent reduction in infestation was 79.73, 80.22, 78.41, 80.88, 80.50, 78.30, 79.64 and 78.25% using Emamectin benzoate, Methomyl, Imidaclopride, Pyridalyl, Profenofos, Indoxacarb, Teflubenzuron and Chlorfenapyr, respectively. The efficiency of the tested insecticides was increased with increasing the number of sprays from two to six causing reduction in insect borer infestation ranged between 68.02 and 80.88%, respectively. Generally, the tested insecticides and their mixtures achieved a considerable reduction in T. absoluta and H. armigera population.     

Effect of temperature and relative humidity on the rate of development,fecundity and life table parameters of the red spider mite Oligonychus mangiferus (Rahman and Sapra) (Acari: Tetranychidae)

Studies on biology of Oligonychus mangiferus (Rahman and Sapra) at combination of eight constant temperatures and relative humidities (RHs) viz., 7.0°C with 85% RH, 10°C with 80% RH, 15.0°C with 75% RH, 23.0°C with 70% RH, 31.0°C with 65% RH, 34.0°C with 65% RH, 36.0°C with 60% RH and 40.0°C with 55% RH revealed that the optimal condition for the development of these mites are 15.0–31.0°C and 65–75% RH. The highest temperature and the lowest RH accelerated the rate of development and induced more reproduction of O. mangiferus. Its population also multiplied 30.81 times in a generation time of 27.36 days at 31.0°C and 65% RH, while the same population only increased 7.46 times in a generation time of 48.07 days at 15.0°C and 75% RH. Fecundity was highest at 31.0°C and 65% RH with 46.43 eggs per female. The highest intrinsic rate of natural increase was observed at 31.0°C as 0.125 per day.     

Fresh water snails as bioindicator for some heavy metals in the aquatic environment

The aim of this investigation is to study some freshwater snails as bioindicator for heavy metals Cd, Cu and Pb by determining the concentration of these metals in the field water samples and in whole snail tissues. Seven freshwater snails were used in the present study, some of which are considered medically important snails in Egypt, Biomphalaria alexandrina and Bulinus truncatus, the intermediate hosts for schistosomiasis and nontarget snails Bellamya unicolor, Cleopatra bulimoides, Helisoma duryi, Physa acuta and Theodoxus niloticus. Samples of snails were gathered from three Egyptian governorates: Damietta, Giza and Monufia.. The snails were arranged according to their accumulated concentration of the above‐mentioned microelements in descending order as follows: C. bulimoides > H. duryi > B. truncatus > B. alexandrina >P. acuta > B. unicolor > T. niloticus. It is concluded from the analysis of water and the investigated snails that these snails can accumulate Cu, Pb and Cd with high concentrations in their bodies, so they can be used as bioindicators for heavy metals.     

Bee diversity (Hymenoptera: Apoidea) visiting Broad Bean (Vicia faba L.) flowers in Egypt

Different bee flower visitors were observed during the flowering seasons of Broad Bean in Ismailia, eastern Egypt, the Nile Delta and Alexandria, western Egypt. Eight major bee visitors were observed: Andrena ovatula (Kirby, 1802), Andrena sp. (Andrenidae), Chalicodoma siculum (Rossi, 1792) (Megachilidae), Colletes lacunatus Dours, 1872 (Colletidae), Apis mellifera Linnaeus, 1758, Anthophora hispanica (Fabricius, 1787), A. aegyptiaca (Dalla Torre and Friese, 1895) and Xylocopa pubescens (Spinola, 1838) (Apidae). Anthophora hispanica and A. aegyptiaca as well as Chalicodoma siculum had their peak flying period in the middle of the flowering season of the Broad Bean, while Xylocopa pubescens and Andrena sp. had their peak period in the second half of the flowering period.     

Synthesis and antimicrobial activity of new heterocyclic compounds containing thieno[3,2-c]coumarin and pyrazolo[4,3-c]coumarin frameworks

Reaction of 4-chlorocoumarin-3-carbonitrile with ethyl thioglycolate and ethyl glycinate hydrochloride leads to a series of title products. Hydrazinolysis of amino thienocoumarin carboxylate afforded the hydrazino derivative which underwent various reactions to build new heterocyclic rings containing thienocoumarin moiety. Chloro acetylation of aminoester compound afforded the chloro acetyl amino which underwent nucleophilic substitution reactions with various amines. The following treatment with formaldehyde under Mannich conditions afforded the corresponding imidazo derivatives. Reaction of chloroacetylamino with potassium thiocyanate yielded ethylpyrimidothieno coumarin sulfanylacetate which was used as a versatile precursor for synthesis of other heterocycles. On the other hand, reaction of chloro coumarin carbonitrile with hydrazine gave the aminopyrazolocoumaine which reacted with bifunctionally compounds to give the substituted pyrimido derivatives. Diazotization and coupling of aminopyrazole with ethylcyanoacetate yielded ethylaminotriazinopyrazolocoumarine carboxylate. Several of the compounds obtained demonstrated considerable antifungal and antibacterial activity in the in vitro test systems.