Synergistic effects of quercetin-loaded CoFe2O4@Liposomes regulate DNA damage and apoptosis in MCF-7 cancer cells: based on biophysical magnetic hyperthermia.

INTRODUCTION: Breast cancer (BC) is the most common malignancy in women globally. Significant progress has been made in developing structural nanoparticles (NPs) and formulations for targeted smart drug delivery (SDD) of pharmaceuticals, improving the precision of tumor cell targeting in therapy.Significance: Magnetic hyperthermia (MHT) treatment using magneto-liposomes (MLs) has emerged as a promising adjuvant cancer therapy. METHODS: CoFe2O4 magnetic NPs (MNPs) were conjugated with nanoliposomes to form MLs, and the anticancer drug quercetin (Que) was loaded into MLs, forming Que-MLs composites for antitumor approach. The aim was to prepare Que-MLs for DD systems (DDS) under an alternating magnetic field (AMF), termed chemotherapy/hyperthermia (chemo-HT) techniques. The encapsulation efficiency (EE), drug loading capacity (DL), and drug release (DR) of Que and Que-MLs were evaluated. RESULTS: The results confirmed successful Que-loading on the surface of MLs, with an average diameter of 38nm and efficient encapsulation into MLs (69%). In vitro, experimental results on MCF-7 breast cells using MHT showed high cytotoxic effects of novel Que-MLs on MCF-7 cells. Various analyses, including cytotoxicity, apoptosis, cell migration, western blotting, fluorescence imaging, and cell membrane internalization, were conducted. The Acridine Orange-ethidium bromide double fluorescence test identified 35% early and 55% late apoptosis resulting from Que-MLs under the chemo-HT group. TEM results indicated MCF-7 cell membrane internalization and digestion of Que-MLs, suggesting the presence of early endosome-like vesicles on the cytoplasmic periphery. CONCLUSIONS: Que-MLs exhibited multi-modal chemo-HT effects, displaying high toxicity against MCF-7 BC cells and showing promise as a potent cytotoxic agent for BC chemotherapy.

Synthesis and characterization of magnetic Ag-Fe3O4@polymer hybrid nanocomposite systems with promising antibacterial application.

INTRODUCTION: Bacterial infections caused by different strains of bacteria still one of the most important disorders affecting humans worldwide. Polymers nanocomposite systems could be considered as an alternative to conventional antibiotics to eradicate bacterial infections. SIGNIFICANCE: In an attempt to enhance the antibacterial performance of silver and iron oxide nanoparticles, decrease their aggregation and toxicity, a polymeric hybrid nanocomposite system combining both nanoparticles is produced. METHODS: Magnetic Ag-Fe3O4@polymer hybrid nanocomposites prepared using different polymers, namely polyethylene glycol 4000, ethyl cellulose, and chitosan were synthesized via wet impregnation and ball-milling techniques. The produced nanocomposites were tested for their physical properties and antibacterial activities. RESULTS: XRD, FT-IR, VSM, and TEM results confirmed the successful preparation of hybrid nanocomposites. Hybrid nanocomposites have average crystallite sizes in the following order Ag-Fe3O4@CS (8.9 nm) < Ag-Fe3O4@EC (9.0 nm) < Ag-Fe3O4@PEG4000 (9.4 nm) and active surface area of this trend Ag-Fe3O4@CS (130.4 m2g-1) > Ag-Fe3O4@EC (128.9 m2g-1) > Ag-Fe3O4@PEG4000 (123.4 m2g-1). In addition, they have a saturation magnetization in this order: Ag-Fe3O4@PEG4000 (44.82 emu/g) > Ag-Fe3O4@EC (40.14 emu/g) > Ag-Fe3O4@CS (22.90 emu/g). Hybrid nanocomposites have a pronounced antibacterial action against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus intermedius compared to iron oxide nanoparticles and positive antibacterial drug. In addition, both Ag-Fe3O4@EC and Ag-Fe3O4@CS have a lower MIC values compared to Ag-Fe3O4@PEG and positive control. CONCLUSION: Magnetic Ag-Fe3O4 hybrid nanocomposites could be promising antibacterial nanomaterials and could pave the way for the development of new materials with even more unique properties and applications.

The Mechanical Properties of Aluminum Metal Matrix Composites Processed by High-Pressure Torsion and Powder Metallurgy.

Al-Al2O3 and SiC metal matrix composites (MMCs) samples with different volume fractions up to 20% were produced by high-pressure torsion (HPT) using 10 GPa for 30 revolutions of Al-Al2O3, and SiC and powder metallurgy (PM). The effect of the processing method of micro-size Al MMCs on the density, microstructure evolution, mechanical properties, and tensile fracture mode was thoroughly investigated. HPT processing produces fully dense samples relative to those produced using powder metallurgy (PM). The HPT of the Al MMCs reduces the Al matrix grain size and fragmentation of the reinforcement particles. The Al matrix average grain size decreased to 0.39, 0.23, and 0.2 µm after the HPT processing of Al, Al-20% Al2O3, and SiC samples. Moreover, Al2O3 and SiC particle sizes decreased from 31.7 and 25.5 µm to 0.15 and 0.13 µm with a 99.5% decrease. The production of ultrafine grain (UFG) composite samples effectively improves the microhardness and tensile strength of the Al and Al MMCs by 31-88% and 10-110% over those of the PM-processed samples. The good bonding between the Al matrix and reinforcement particles noted in the HPTed Al MMCs increases the strength relative to the PM samples. The tensile fracture surface morphology results confirm the tensile properties results.

Influence of Parallel Tubular Channel Angular Pressing (PTCAP) Processing on the Microstructure Evolution and Wear Characteristics of Copper and Brass Tubes.

The influence of the number of passes and the tube materials on the microstructural evolution, mechanical properties, and wear behavior of Cu and brass tubes after parallel tubular channel angular pressing (PTCAP) was investigated. The grain size decreased to final grain sizes of 138.6 nm and 142.7 nm, after PTCAP of the Cu and brass tubes was conducted in up to 4 and 2 passes, respectively. PTCAP contributes to obtaining an ultra-fine grain (UFG) microstructure, with a mixture of different grain sizes that conferred high hardness. The present results indicate the superior wear resistance of Cu and brass PTCAP tubes, relative to Cu and brass samples that were previously deformed by different severe plastic deformation (SPD) processes. The wear mechanism of the Cu tubes changed from delamination and cracks with a high degree of adhesive wear before PTCAP into a combination of adhesive and abrasive wear, with a decrease in the presence of oxygen content after the PTCAP procedure. The wear mechanism also changed from a combination of adhesive and abrasive mechanisms into abrasive ones with the absence of oxygen after the PTCAP of brass tubes.

Parallel Tubular Channel Angular Pressing (PTCAP) Processing of the Cu-20.7Zn-2Al Tube.

Commercial Al-brass tube was successfully processed by Parallel Tubular Channel Angular Pressing (PTCAP) in 2 passes under an imposed strain of 1.49 per pass. The effect of the number of PTCAP passes on the microstructure and the mechanical properties (hardness, tensile, and wear mass loss) of the Al-brass tubes was fully investigated. The average grain size of the as-received tube decreased to 1.28 µm after up to two passes of PTCAP with a mixture of ultrafine grain (UFG) and coarse grain (CG). The annealed tubes' tensile strength and Vickers hardness increased by 237.65% and 175.6%, respectively, after two passes. In addition, a ductile fracture occurred with a clear necking. The fracture surface morphology indicated an apparent decrease in dimple size after PTCAP processing, combined with a decrease in ductility. Moreover, the wear mass loss decreased with increasing number of PTCAP passes due to the decrease in the grain size, and the increase of the hardness of the tubes was enhanced after PTCAP processing.

Novel synthesis of antibacterial pyrone derivatives using kinetics and mechanism of oxidation of azithromycin by alkaline permanganate.

Dimethylamino-2H-5-dihydropyrane-6-methyl-4-one (DADHP) is a novel antibacterial pyrones derivatives and potential pharmaceutical that was quantitatively synthesized by oxidizing azithromycin (AZ) antibiotic with potassium permanganate in an alkaline medium (pH > 12). The oxidation reaction was kinetically studied using spectrophotometric technique at ionic strength equal to 0.02 mol dm-3. The redox reaction was discovered to have two separate stages that could be measured. The first stage was relatively fast and corresponding to the formation of coordination intermediate complexes involving blue hypomanganate (V) and/or green manganate (VI) transient species. Variable parameters like as the concentration of permanganate ion and AZ substrate, as well as pH and ionic strength, have been studied to see how they affect oxidation rates. The experimental results showed a first-order dependency in [MnO4-] and fractional first-order kinetics in each of [AZ] and alkali concentration under pseudo-first-order reaction conditions of [AZ] ≫ 10 [MnO4-]. The oxidation process was base-catalyzed, and the oxidation rates increased as the alkali concentration increased. The product was confirmed by Fourier Transform Infrared spectroscopy (FTIR), elemental analysis, condensation tests with 2,4-dinitrophenyl haydrazine and hydroxyl amine, and GC-Mass. The oxidation product obtained can be employed as interesting class of organic compounds with diverse chemical and pharmacological applications.

Nebulized Magnesium Sulfate for Treatment of Persistent Pulmonary Hypertension of Newborn: A Pilot Randomized Controlled Trial.

OBJECTIVES: To investigate the effectiveness of nebulized magnesium sulfate in treating persistent pulmonary hypertension of newborn (PPHN). METHODS: Twenty-eight mechanically ventilated term neonates with severe PPHN were randomized into two groups: NebMag group (n = 14), who receiving nebulized isotonic magnesium (1024 mg/h), and IVMag group (n = 14), who received intravenous magnesium (200 mg/kg over 30 min, followed by 50 mg/kg/h). The study time frame was 24 h. Outcome measures were the changes in oxygenation index (OI), mean arterial blood pressure (MABP), vasoactive inotropic score (VIS), and serum magnesium level. RESULTS: Baseline demographic, ventilatory, and hemodynamic characteristics were comparable between the two groups. At the end of the study, the OI decreased by 44.3% in the NebMag group compared with 35.3% in the IVMag group (mean difference -3.14; 95%CI -5.08, -1.19; p 0.003). The NebMag group had a higher MABP (mean difference 2.29 mmHg; 95% CI 1.80, 2.77; p 0.000) and lower VIS (mean difference -14.64; 95% CI -16.52, -12.77; p 0.000) at the 24-h study time point. The increase in serum magnesium level, measured at 12-h study time point, was lower in the NebMag group (mean difference -2.26 mmol/L; 95% CI -2.58, -1.96; p 0.000). CONCLUSION: Nebulized magnesium sulfate may be an effective therapeutic modality for neonates with severe PPHN on mechanical ventilation, but this should be confirmed by larger studies. Retrospectively registered at www.clinicaltrials.gov (identifier: NCT04328636).

Mechanical and biological behavior of ultrafine-grained Ti alloy aneurysm clip processed using high-pressure torsion.

Severe plastic deformation (SPD) has recently been advanced as the main process for fabricating bulk ultrafine grained or nanocrystalline metallic materials, which present much higher strength and better bio-compatibility than coarse-grained counterparts. Medical devices, such as aneurysm clips and dental implants, require high mechanical and biological performance (e.g., stiffness, yield strength, fatigue resistance, and bio-compatibility). These requirements match well the characteristics of SPD-processed materials. Typical aneurysm clips are made of a commercial Ti-6Al-4V alloy, which has higher yield strength than Ti. In this work, Ti and Ti-6Al-4V workpieces were processed by high-pressure torsion (HPT) to enhance their mechanical properties. Tensile tests and hardness tests were performed to evaluate their mechanical properties, and their microstructure was investigated. The hardness and yield stress of the HPT-processed Ti are comparable to those of the initial Ti-6Al-4V due to significantly refined microstructure. Finite element analyses for evaluating the opening performance of a specific geometry of the YASARGIL aneurysm clip were carried out using mechanical properties of the initial and HPT-processed Ti and Ti-6Al-4V. These results indicate that SPD-processed Ti could be a good candidate to substitute for Ti-6Al-4V in aneurysm clips.

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency.

Beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase (T2) deficiency) is an inherited disease of isoleucine catabolism and ketone body utilization caused by ACAT1 mutations. We identified ten Indian patients who manifested with ketoacidotic episodes of variable severity. The patients showed increased urinary excretion of isoleucine-catabolic intermediates: 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate, and tiglylglycine. Six patients had a favorable outcome, one died, and three developed neurodevelopmental sequela. Mutational analysis revealed a common (p.Met193Arg) and four novel (p.Ile323Thr, p.Ala215Asn, c.1012_1015dup, and c.730+1G>A) ACAT1 mutations. Transient expression analyses of wild-type and mutant cDNA were performed at 30, 37, and 40°C. A p.Ile323Thr mutant T2 was detected with relative enzyme activity and protein amount of 20% and 25%, respectively, compared with wild type at 37°C; it was more prevalent at 30°C but ablated at 40°C. These findings showed that p.Ile323Thr had a significant residual T2 activity with temperature-sensitive instability. Neither residual enzymatic activity nor mutant T2 protein was identified in p.Met193Arg, p.Ala215Asn, and c.1012_1015dup mutations using supernatants; however, these mutant T2 proteins were detected in insoluble pellets by immunoblot analysis. Expression analyses confirmed pathogenicity of these mutations. T2 deficiency has a likely high incidence in India and p.Met193Arg may be a common mutation in the Indian population.

Molecular spectroscopic analyses of gelatin.

The molecular structure of gelatin was studied using Fourier transform infrared spectroscopy FTIR. The spectrum is subjected to deconvolution in order to elucidate the constituents of the molecular structure. B3LYP/6-31g** was used to study 13 amino acids then the scaled spectrum was compared to those of protein in order to describe the contribution of each amino acid into protein structure. A special interest was paid to the NH and C=O region. The reactivity of each amino acid was studied in terms of some important physical parameters like total dipole moment and HOMO/LUMO which describe the interaction of amino acid with their surrounding molecules. Results indicated that B3LYP/6-31g** model is a suitable and precise method for studying molecular structure of protein.