Terbinafine hydrochloride loaded liposome film formulation for treatment of onychomycosis: in vitro and in vivo evaluation

Onychomycosis is a fungal infection of nail unit that is caused by dermatophytes. Oral Terbinafine hydrochloride (TBF-HCl) is being used for the treatment of onychomycosis since 24 years. The side effects caused by the systemic application and limitations of topical administration of this drug regarding the diffusion through nail lead to the development of a new formulation based on, TBF-HCl-loaded liposome. The newly obtained film formulations were prepared and characterized via several parameters, such as physical appearance, drug content, thickness, bioadhesive properties and tensile strength. In vitro and ex vivo permeation studies were performed to select an optimum film formulation for antifungal activity to show the efficiency of formulations regarding the treatment of onychomycosis. The in vitro release percentages of drug were found 71.6?±?3.28, 54.4?±?4.26, 56.1?±?7.48 and 46.0?±?2.43 for liposome loaded pullulan films (LI-P, LII-P) and liposome loaded Eudragit films (LI-E, LII-E), respectively. The accumulated drug in the nail plates were found 31.16?±?4.22, 24.81?±?5.35, 8.17?±?1.81 and 8.92?±?3.37 for LI-P, LII-P, LI-E and LII-E, respectively, which within therapeutic range for all film formulations. The accumulated drug in the nail plate was found within therapeutic range for all film formulations. The efficacy of the selected TBF-HCl-loaded liposome film formulation was compared with TBF-HCl-loaded liposome, ethosome, liposome poloxamer gel and ethosome chitosan gel formulations. It was found that TBF-HCl-loaded liposome film formulation had better antifungal activity on fungal nails which make this liposome film formulation promising for ungual therapy of fungal nail infection.     

Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach

The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life-threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain-2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti-malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand-protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross-correlation matrix showed positive outcomes for the protein-ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.     

Thermoluminescence in pumice stone collected from the Mediterranean coast

Pumice is a low-density, light-coloured volcanic rock (igneous rock) formed when the magma from a volcanic eruption is suddenly cooled. It has a porous structure and can be different colours and have different densities. Pumice stone, unlike other rock, does not sink in water because it has a low density. In the present study, the thermoluminescent (TL) dosimetric characteristics, such as the dose–response, TL signal fading as a function of storage time, heating rate, and reusability of pumice collected on the Mediterranean coast were investigated. From this study, it was concluded that the pumice stone showed TL properties with a TL glow curve including an obviously wide peak at ∼200°C. A wide linear dose–response region up to 144 Gy, low fading of the TL signal when it was kept in a dark room for a long time, and poor reusability properties were observed for dosimetry use.     

Intracerebral connections after administration of kainate into the caudal part of ventral sections of the medulla oblongata]

It was found that 1 day after unilateral destruction with kainate of neurons in the caudal ventral medulla unanesthetized animals showed disorders of arterial pressure control with a prevalence of hypertensive response. In 7 days after operation there was a decrease in the rate of neuronal uptake of serotonin and an increase in choline-, dopamine-, noradrenaline-, and glycinergic mediation in the basal hypothalamus and rostral ventral medulla, which characterize the functional state of synaptic formations in the brain stem structures connected to neurons in the caudal ventral medulla and involved in cardiovascular regulation.     

BRCA-1 depletion impairs pro-inflammatory polarization and activation of RAW 264.7 macrophages in a NF-κB-dependent mechanism

Molecular and Cellular Biochemistry - Inadequate migration and invasion of the trophoblast cells during embryo implantation is one of the reasons for pregnancy-related complications such as...     

Enzyme-mediated hydrogel encapsulation of single cells for high-throughput screening and directed evolution of oxidoreductases

Directed evolution of oxidoreductases to improve their catalytic properties is being ardently pursued in the industrial, biotechnological, and biopharma sectors. Hampering this pursuit are current enzyme screening methods that are limited in terms of throughput, cost, time, and complexity. We present a directed evolution strategy that allows for large-scale one-pot screening of glucose oxidase (GOx) enzyme libraries in well-mixed homogeneous solution. We used GOx variants displayed on the outer cell wall of yeasts to initiate a cascade reaction with horseradish peroxidase (HRP), resulting in peroxidase-mediated phenol cross-coupling and encapsulation of individual cells in well-defined fluorescent alginate hydrogel shells within ~10 min in mixed cell suspensions. Following application of denaturing stress to whole-cell GOx libraries, only cells displaying GOx variants with enhanced stability or catalytic activity were able to carry out the hydrogel encapsulation reaction. Fluorescence-activated cell sorting was then used to isolate the enhanced variants. We characterized three of the newly evolved Aspergillus niger GOx enzyme sequences and found up to ~5-fold higher specific activity, enhanced thermal stability, and differentiable glycosylation patterns. By coupling intracellular gene expression with the rapid formation of an extracellular hydrogel capsule, our system improves high-throughput screening for directed evolution of H ₂O ₂-producing enzymes many folds.     

Water salinity effects on embryogenesis of the lesser sandeel,Ammodytes tobianus (Linnaeus, 1758)

Effects of water salinity (3.0–9.0 PSU) on the duration and outcome of embryogenesis in the lesser sandeel (Ammodytes tobianus (L.) as well as on survival, size, and malformation rate of the newly hatched larvae were followed, based on observations involving equipment consisting of a microscope and still and digital cameras. The images obtained and measurements of egg and larval dimensions were analyzed using the NIS elements Br. computer software package. The lowest salinity tested (3.0 PSU), similar to that in the inshore Baltic Sea waters native for the species studied, produced a lower fertilization rate and resulted in extended embryogenesis, reduced embryo survival, changes in the hatch size, and increased larval malformation rate. The high-end salinity (7.5–9.0 PSU), higher than that prevailing in the species’s spawning grounds in the Baltic Sea, resulted — similarly to the low-end salinity — in disturbed development and growth of the embryos.     

Cold acclimation of SnRK2.2 kinases mutant Chlamydomonas reinhardtii

In Chlamydomonas reinhardtii, plant‐specific serine/threonine kinases (SnRK2 kinases) play a central role in sulfur metabolism. However, their role in environmental stress has not been clearly understood. Cold stress is one of the most important factors that limit the growth, productivity, and development of photosynthetic organisms. In this report, the effect of cold stress on some physiological parameters were investigated in SnRK2.2 mutant and wild type C. reinhardtii culture. Our results showed that cold stress had significantly enhanced lipid peroxidation rate in wild type, while no significant change was observed in SnRK2.2 mutant culture. Our data also indicated a decline in Rubisco protein amount of wild type culture under low temperature exposure. Low temperature reduced glutathione reductase (GR) activity in the wild type, while GR activity was enhanced in SnRK2.2 mutant. This result indicated the potential of SnRK2 kinase in cold acclimation process.     

Mislocalization of the exitatory amino-acid transporters (EAATs) in human astrocytoma and non-astrocytoma cancer cells: effect of the cell confluence

Background  

Astrocytomas are cancers of the brain in which high levels of extracellular glutamate plays a critical role in tumor growth and resistance to conventional treatments. This is due for part to a decrease in the activity of the glutamate transporters, i.e. the Excitatory Amino Acid Transporters or EAATs, in relation to their nuclear mislocalization in astrocytoma cells. Although non-astrocytoma cancers express EAATs, the localization of EAATs and the handling of L-glutamate in that case have not been investigated.     

The in situ localization of folic acid.

A histochemical azo-coupling method for localizing folic acid in situ is described. Cat and rat liver, kidney, bone marrow and brain were found to be rich in folic acid; stomach, intestine, salivary glands, and blood contained less. Folic acid was localized in the cytoplasm of tissues having a very active metabolism, but in the nucleus of highly specialized cells such as neurons.