The treatment of cancer often leads to a range of adverse effects. Encapsulating drugs can mitigate these effects and enhance drug efficacy by enabling a controlled release at the site of interest. This study details the successful synthesis of zinc oxide nanoparticles (ZnONPs) through the precipitation of Zn(NO3)2·6H2O with KOH. A Pd(II) complex drug was synthesized from a Schiff base ligand derived from 2-hydroxybenzohydrazide and (E)-1-(2-(p-tolyl)hydrazono)propan-2-one using potassium tetrachloropalladate(II). This complex was subsequently incorporated into ZnONPs. Characterization of the resulting compounds was performed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta Potential, Fourier Transform Infrared (FTIR) Spectroscopy, and UV-visible spectroscopy. TEM imaging revealed particle sizes of 160.69 ± 4.74 nm for ZnONPs and 185.28 ± 2.3 nm for the Pd(II) complex-encapsulated ZnONPs. The Zeta potential values were 6.53 mV for ZnONPs and 7.36 mV for Pd(II) complex-encapsulated ZnONPs. UV-visible spectroscopy showed an absorption peak at 360 nm for ZnONPs, while the Pd(II) complex-encapsulated ZnONPs exhibited a peak at 410 nm. FTIR analysis indicated the presence of the Pd(II) complex within the ZnONPs, as evidenced by a consistent Zn-O vibrational band at 832 cm−1 and a shift in another peak from 460 to 413 cm−1. Additionally, the detection of a C = N stretching vibration at 1548 cm-1 and a carbonyl stretch at 1626 cm−1 was observed. The Encapsulation Efficiency (E.E.) of the Pd(II) complex was 97.2

Metallic antitumor drugs with heterocyclic ligands, such as novel AMI (amino methyl imidazole) complexes [Pd(AMI)Cl 2 ](1), [Cu(AMI)L 1 ](2), and [Cu(AMI)L 2 ·2H 2 O](3) where L 1 = oxalate and L 2 = malonate, were synthesized and characterized. Assessments included elemental analyses, mass spectrometry, Fourier transform-infrared spectroscopy, ultraviolet–visible spectroscopy, and thermal analysis. The cytotoxicity of AMI complexes compared to cisplatin was assessed using MTT (3-[4,5-dimethylthiazol-2-yl] 2,5diphenyl tetrazolium bromide) assay with breast (MCF-7) and cervical (HeLa) cancer cell lines. After treating these cells with the AMI complexes' IC 50 values for 48 h, malondialdehyde levels and catalase activity were used to assess oxidative stress, antioxidant activity was evaluated with DPPH radical scavenging method, comet assays assessed DNA damage, and DNA fragmentation was evaluated using the gel electrophoresis. In vitro, antimicrobial activity was assessed using a disc diffusion method. The anticancer activity results showed that IC 50 (half-maximal inhibitory concentration) values of complex one, two, and three against MCF-7 and HeLa cancer cells are 0.156 ± 0.0006, 0.125 ± 0.001, 0.277 ± 0.002 μM respectively for MCF-7 cells and 0.222 ± 0.0005, 0.126 ± 0.0009, 0.152 ± 0.001 μM respectively for HeLa cells. Complex two demonstrated strong anticancer activity against MCF-7 and Hela cells. The study of oxidative stress parameters revealed that Malondialdehyde levels increased in cancer cell lines treated with complexes compared to untreated cells. Catalase activity decreased in cells treated with palladium chelate. The DPPH radical scavenging assay results identified that complex one was a more potent antioxidant in MCF-7 and Hela cells than other complexes with SC 50 values of 227.5 ± 0.28 and 361 ± 1.2 μL/mL, respectively. The comet assay results showed that complex two caused significant DNA damage in MCF-7 and HeLa cancer cells treated. Antimicrobial assays identified complex three as the most effective. Copper complexes give better antifungal activity against A. flavus than the palladium complex. We conclude that complex two is the most active in both cell types and might be assessed as a clinically useful drug for breast cancer treatment. The significance of the current study is the synthesis of antitumor drugs containing heterocyclic ligands, such as novel AMI complexes, and the study of their biological activities.

BACKGROUND:Schiff base metal complexes are considered promising chemotherapeutic agents due to their potential application in cancer therapy. METHODS:The current work sought to synthesize a brand-new Schiff base ligand obtained from 2-hydroxybenzohydrazide and (E)- 1-(2-(p-tolyl)hydrazono)propan-2-one with metal ions which included Pd(II) and Zn(II) ions. Elemental analyses, FT-IR, mass spectra, 1H NMR, UV-Vis spectrometer, and computational analysis characterized the compound's structure. In vitro, the breast cancer cell line (MCF-7) was tested for its sensitivity to Schiff base (HL) and its Pd(II) and Zn(II) complexes. The half-maximal inhibitory concentration IC50 of the compounds was determined and used to perform the comet assay, which was carried out to reveal the photo-induced DNA damaging ability of the compounds of individual cells. Moreover, the compounds' effects on antioxidant defense systems of enzymes in cells: superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and oxidant Malondialdehyde (MDA) were examined in MCF-7 cells. RESULTS:The Pd(II) complex displayed approximately the same IC50 as Cisplatin, while Zn(II) complex had better activity than Cisplatin with very low IC50, 1.40 μg/ml. Significant alterations in SOD, CAT, GPx, and MDA production were discovered, inducing oxidative stress, enlarging ROS production, and reducing the antioxidant amount. This change was approximately similar in most compounds. Consequently, it promoted apoptosis, particularly the Zn(II) complex, which demonstrated an improved impact because of its ability to influence the antioxidant defense systems of enzymes, mostly SOD and GPx, besides increasing MDA levels. CONCLUSION:It can be concluded that Zn(II) complex is the most effective anticancer drug since it induced a very similar genotoxic effect as Cisplatin and has a very low IC50 value.

Background Oral insulin administration has recently become one of the most exciting research subjects. Different approaches have been carried out to get an effective oral insulin delivery system using nanotechnology. The development of a delivery system that overcomes the difficulties of oral insulin administration, achieving high stability and minimal side effects, is still an urgent need. Therefore, this study is considered one of the efforts to design a new prospective drug delivery nano-composite (silica-coated chitosan-dextran sulfate nanoparticles). Methods Chitosan-dextran sulfate nanoparticles (CS-DS NPs) were prepared via a complex coacervation method and then coated with silica. Uncoated and silica-coated CS-DS NPs were physically characterized via different techniques. Transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis, and atomic force microscopy (AFM) have been used to investigate the chemical elements, size, morphology, and surface properties of the prepared formulations. Differential scanning calorimetry (DSC) to assess the thermal properties of formed nano-formulations. Fourier transform infrared (FT-IR) spectroscopy investigated the silica coat and chitosan interaction. The encapsulation efficiency was evaluated using high-performance liquid chromatography (HPLC) analysis. The insulin release profile of nano-formulations was performed with and without silica coat at two different pHs (5.5,7), nearly simulating the environment of the gastrointestinal tract (GIT). Results The silica-coated CS-DS NPs revealed interesting physicochemical properties exemplified by suitable core particle size obtained by TEM images (145.31 ± 33.15 nm), hydrodynamic diameter (210 ± 21 nm), high stability indicated by their zeta potential value (-32 ± 3.2 mV), and adequate surface roughness assessed by AFM. The encapsulation efficiency of insulin-loaded chitosan nanoparticles (ICN) was (66.5%) higher than that of insulin-chitosan complex nanoparticles (ICCN). The silica-coated ICN demonstrated a controlled insulin release profile at pHs (5.5 and 7) compared with uncoated ICN. Conclusion The silica-coated ICN can be an efficient candidate as a desired oral delivery system, overcoming the common obstacles of peptides and proteins delivery and achieving high stability and controlled release for further applications.

The effect of electroporation on the physical characteristics of 1,2-dipalmitoyl-Sn-glycerol-3-phosphocholine (DPPC) liposome loading diclofenac sodium, ascorbic acid and Rhodamine B was studied. Group one liposomes were incubated with diclofenac sodium, group two liposomes were incubated with ascorbic acid and group three: liposomes were incubated with Rhodamine B. The three groups were subjected to electroporation protocol. Samples were exposed to different field strengths at pulses 30, 60 and 90 pulses respectively with pulse duration 4 milliseconds. After electroporation, liposomes were separated from unentrapped drugs and form the dye through centrifugation. Physical characteristics of liposomes were examined using Transmission electron microscope (TEM), Confocal laser scanning microscopy (CLSM) and particle size analysis. Liposomes are entrapping ascorbic acid with high efficiency at the values of 900 V/0.2 cm with 60 pulses, 800 and 1000 V/0.2 cm at 90 pulses. Diclofenac sodium was entrapped at 800 V/0.2 cm and 90 pulses. Rhodamine B was entrapped at 500 and 1000 V/0.2 cm at 30 pulses. Based on the present results, entrapping of diclofenac sodium and ascorbic acid into liposomes can be controlled efficiently by electroporation technique. Optimum entrapping occurred at 800 V/0.2 cm and 90 pulses for ascorbic acid and DS at 900 V/0.2 cm and 30 pulses for Rh-B.

To study the best planning techniques for post operative breast radiotherapy either F-IMRT or I-IMRT and VMAT .Another strategy is to check the dosimetric difference between using 6 or 10 MV energies for both I-IMRT and VMAT .: In the present study, four different inverse plans and one forward plan of randomly selected twenty left breast cancer patients were compared dosimetrically.Plans were done on Monaco (5.1) treatment planning system and data analyses were accomplished using one-way Anova test using IBM SPSS (20) data editor software.Inverse planning achieve superior target coverage over forward planning (p value =0.001 ,0.07) and conformity index (p value < 0.05) maintaining adequate homogeneity index (p value = 0.461, 0.138) .Left lung and heart high dose levels decreased using I-IMRT, VMAT ( p value <0.05) at the cost of increasing volume irradiated by low doses (p value < 0.05 ).For contralateral lung VMAT increased absorbed dose over F-IMRT ( p< 0.05) but I-IMRT showed non significant increase of V5 GY ( p value = 0.14) .For contralateral breast both I-IMRT and VMAT increased absorbed dose over F-IMRT (P < 0.05 ) .It may be concluded that with inverse planning achieved better target coverage that increases tumor control .Inverse planning also achieved lower volume of high doses that reduces acute radiation effect and increased irradiated volume by low doses significantly that increases the probability of late radiation effect.

Aims: The aim of the present study was to evaluate the toxicity of magnetic iron oxide nanoparticles (MIONs) which were synthesized using carob leaf extract on various brain areas of Wistar rats. Main methods: Carob leaf synthesized-MIONs were characterized using different techniques: Dynamic Light Scattering (DLS), Transmission Electron Microscope (TEM), UV-vis spectrophotometer, Fourier Transform infrared (FTIR), X-Ray Diffraction (XRD) and Atomic Force Microscope (AFM). The toxicity of MIONs in vivo was evaluated by: monitoring rat's body weight, measuring iron content in different brain areas, evaluating some oxidative stress parameters, estimating acetylcholinesterase (AChE) in addition to histopathological investigations. Key findings: The present study demonstrated no body weight changes of MIONs- treated rats. According to the conditions of the present study, the hippocampus and striatum were the most affected areas and demonstrated neuronal degeneration due to MIONs exposure. MIONs treatment of Wistar rats, also affected the iron homeostasis in both striatum and midbrain by decreasing iron content in these areas. The least affected areas were thalamus and cerebellum. The histopathological examination of brain areas demonstrated moderate neuronal degeneration in hippocampus and striatum, mild neuronal degeneration in cortex and slight degeneration in hypothalamus and pons-medulla areas were detected. Significance: The results suggested that MIONs have a toxic impact on different brain areas and the effect varies according to the brain area.

This work investigates the effects of electroporation parameters on the transdermal delivery of insulin. Electroporation (EP) is known to induce temporal pores in the membrane, which are expected to enhance the diffusion of insulin through rabbits' skin. For such purpose, 5 different formulations of insulin and enhancers are applied to rabbit groups (5 rabbits each) with induced hyperglycemia in the presence of electroporative pulses. The blood sugar level (BSL) is followed up to 5-hour duration starting from the administration of the hyperglycemia-inducing factor. The effect of different electroporation parameters on BSL of rabbits is examined and compared with control groups. Results show that the increase in the number of pulses (from 15 up to 60 successive pulses) at an insulin concentration of 50 IU/mL, the increase in insulin concentration (from 50 to 70 IU/mL), and the decrease in applied field strength (from 200 to 100 V/cm) result in a significant decrease in BSL compared with control. Among all of the investigated formulations, the best performance is recorded for the insulin solution + EP (without enhancers) in almost all of the studied experimental conditions.

Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats ("EAE" group). 2- "N. sativa + EAE" group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- "EAE + N. sativa" group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE.

Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of multiple sclerosis. This study aimed to investigate the protective and therapeutic effects of Nigella sativa (N. sativa) seeds (2.8g/kg body weight) in EAE-induced rats. EAE-induced animals were divided into: (1) EAE-induced animals (“EAE” group). (2) “N. sativa+EAE” group received a daily oral administration of N. sativa 2weeks prior to EAE induction until the end of the experiment. (3) “EAE+N. sativa” group received a daily oral administration of N. sativa after the appearance of the first clinical signs until the end of the experiment. All animals were sacrificed at the 28th day post EAE-induction. Disease pathogenesis was monitored using a daily clinical scoring, body weight, open field test, histopathological and ultrastructural examination and determination of some oxidative stress parameters in the cortex and hippocampus. N. sativa ameliorated the clinical signs and suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the hippocampus. However, protection of rats with N. sativa administered 2weeks prior to EAE induction and its continuation until the end of the experiment resulted in a significant increase in the cortical lipid peroxide level with reference to control and “EAE” rats. In conclusion, N. sativa seeds could be used as a protective agent or an adjunct treatment for EAE even when the treatment started after the appearance of the first clinical signs. However, the dose and duration of N. sativa must be taken into consideration to avoid its probable pro-oxidant effect.

NS3 serine protease is considered as one of the most important non-structure proteins for hepatitis C virus (HCV) replication. The significance of NS3 protease function is the conversion of polypeptides to functional proteins to produce new mature HCV. Knowing that the currently available treatment is expensive and effective in only 50-60% of treated patients. It is thus crucially important to exert maximum effort in the design of new formulations aiming to achieve better treatment performance.

Electrical activity recording from the brains of awake animals is a corner stone in the study of the neurophysiological basis of behavior.To meet this need, a microelectrode driver suitable for the animal of interest has to be developed.In the present study a miniature microdrive was developed specifically for the leopard toad, Bufo regularis, however, it can be used for other small animals.The microdrive was designed to meet the following requirements: small size, light weight, simple and easy way of attaching and removing, advancing and withdrawing of microelectrode in the animal brain without rotation, can be reused and made from inexpensive materials.To assess the performance of the developed microdrive, we recorded auditory evoked potentials from different auditory centers in the toad's brain.The potentials were obtained from mesencephalic, diencephalic and telencephalic auditory sensitive areas in response to simple and complex acoustic stimuli.The synthetic acoustical tones introduced to the toad were carrying the dominant frequencies of their mating calls.

NS3 protease is considered as important antiviral target. By using NS5A/NS5B junction sequences for Egyptian genotype 4a (Glu-Asp-Val-Val-Cys-Cys), a new NS3 protease inhibitors were designed with two groups. The first group has hexapeptide binding to cellulose monomer at position 2, 3 or 6 while the second group has hexapeptide binding to cellulose dimmer at position 2, 3, 6, 2', 3' or 6'. QSAR descriptors of introduced compounds will be calculated at PM3 method and compared with that of natural substrate. The represented results indicate that the second group compounds especially at position 2, 2' and 6' are more hydrophilic and soluble in polar solutions and may increase the interaction of this class of compounds with the NS3 protease active site.

Two novel groups of hexapeptide inhibitors for NS3 serine protease of the hepatitis C virus (HCV) are designed. The hexapeptide is an amino acid sequence of NS5A/NS5B substrate (Glu-Asp-Val-Val-Cys-Cys). In the first group, the hexapeptide binds to a cellulose monomer at the positions 2, 3 or 6 while in the second group, the hexapeptide binds to a cellulose dimmer at the positions 2, 3, 6, 2', 3' or 6'. Molecular modeling semiemprical PM3 calculations are used to optimize the geometry and calculate the electronic properties of the suggested inhibitors compared to that of natural substrate. Computational results show that the second group has the maximum stability and reactivity indicating that it would be considered as a promising HCV NS3 protease inhibitor.

A Fullerene based system is modified in order to increase its solubility and enhance its ability to carry a protein-like structure. The modified structure, which is proposed to act as HIV-1 protease inhibitor, is [C₆₀-C2H4N-(2,4- XCOCH₂OH)C₆H₄], where the X atom is either O, S or Se. The geometry optimization, vibrational spectra and thermodynamics were performed using semiempirical quantum mechanical PM3 method in order to study the proposed compounds. Furthermore, the quantitative structure activity relationship (QSAR) properties of the compounds are calculated at the same level of theory. Results indicate a possible use of the investigated structures as HIV-1 protease inhibitors. The compounds containing oxygen is more stable as compared to the other two compounds.

In the present study, the alteration in the sleep EEG in rats due to chronic exposure to low-level non-thermal electromagnetic radiation was investigated. Two types of radiation fields were used; 900 MHz unmodulated wave and 900 MHz modulated at 8 and 16 Hz waves. Animals has exposed to radiation fields for 1 month (1 h/day). EEG power spectral analyses of exposed and control animals during slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) revealed that the REM sleep is more susceptible to modulated radiofrequency radiation fields (RFR) than the SWS. The latency of REM sleep increased due to radiation exposure indicating a change in the ultradian rhythm of normal sleep cycles. The cumulative and irreversible effect of radiation exposure was proposed and the interaction of the extremely low frequency radiation with the similar EEG frequencies was suggested.

Cationic polymers have been used to condense DNA by electrostatic interaction into small particles (polyplexes), for protecting the DNA from degradation and enhancing its uptake via endocytosis. Polyethylenimine (PEI) is one of the most advanced delivery systems that can condense DNA efficiently forming PEI/DNA complexes. The effect of PEI molecular weight (2k, 5k and 25k) on the physicochemical and biological properties of the polyplexes was investigated. As the molecular weight of PEI increased, the condensation ability, surface charge increased while complexes size decreased. PEI 25k has the lowest buffer capacity compared to 2k and 5k PEI. Transfection efficiency of examined polyplexes was higher in MCF7 cells than in HeLa cells. 25k PEI formed smaller polyplexes and achieved higher transfection efficiencies (into two cell lines HeLa and MCF7) than 2k PEI and 5k PEI. Attachment of different hydrophobic amino acid residues and suitable targeting ligands onto the surface of 25k PEI will increase its transfection efficiency.

PURPOSE The evaluation of the diagnostic capability of easy to measure x-ray scattering profile characterization parameters for the detection of breast cancer in excised samples. The selected parameters are the full width at half maximum (FWHM) and area under the x-ray scattering profile of breast tissue in addition to the ratio of scattering intensities (I2/I1%) at 1.6 nm(-1) to that at 1.1 nm(-1) (corresponding to scattering from soft and adipose tissues, respectively). METHODS A histopathologist is asked to classify 36 excised breast tissue samples into healthy or malignant. A conventional x-ray diffractometer is used to acquire the scattering profiles of the investigated samples. The values of three profile characterization parameters are calculated and the diagnostic capability of each is evaluated by determining the optimal cutoffs of scatter diagrams, calculating the diagnostic indices, and plotting the receiver operating characteristic (ROC) curves. RESULTS At the calculated optimal cutoff for each of the examined parameters, the sensitivity ranged from 78% (for area under curve) up to 94% (for FWHM), the specificity ranged from 94% [for I2/I1% and area under curve] up to 100% (for FWHM), and the diagnostic accuracy ranged from 86% (for area under curve) up to 97% (for FWHM). The area under the ROC curves is greater than 0.95 for all of the investigated parameters, reflecting a highly accurate diagnostic performance. CONCLUSIONS The discussed tests offered a means to quantitatively evaluate the performance of the suggested breast tissue x-ray scattering characterization parameters. The performance results are promising, indicating that the evaluated parameters would be considered a tool for fast, on spot probing of breast cancer in excised tissue samples.

Wide-angle X-ray scattering (WAXS) from lyophilized protein is characterized by the presence of two relatively broad scattering peaks that are linked to protein structure. This work is concerned with the possibility of utilizing these peaks in the probing of the unfolding and breakdown of insulin. Native insulin is subject to thermal denaturation in the presence and in the absence of thiol catalysts. Denatured products are acid-trapped, lyophilized and monitored using WAXS in addition to Fourier transform infrared spectroscopy (FTIR), gel filtration chromatography and Transmission Electron Microscopy (TEM) as supportive techniques. Results show that the WAXS peak at a d-spacing about 10 A is sensitive towards the alpha-helix content of insulin. A reduction in the intensity of such peak is proven to be directly linked to the reduction of native insulin having normal alpha-helix content. The supportive techniques confirmed the decrease in the alpha-helix content of insulin which accompanied the different denaturation treatments.

According to the emerging biological applications of fullerene based systems, we try to utilize C-60 after modifying its surface with polar group to enhance its solubility. Furthermore, we add hydroxymethylcarbonyl to form [C-60-C2H4N-(2,4-XCOCH2OH)C6H4] where the X atom is O, S or Se. After that we perform geometry optimization and vibrational spectra using PM3 quantum mechanical method. Results show possible interaction between our structure and two aspartic acids units through hydrogen bonding This indicates the ability of our structure to further interact with the two aspartic acids of the HIV-1 protease active site through the Hydroxymethylcarbonyl groups; accordingly, could be introduced as HIV-1 Protease Inhibitors