Characterization and Cytotoxicity Assessment of Synthesized Palladium (II) Complex-Encapsulated Zinc Oxide Nanoparticles for Cancer Treatment.

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%. A drug release experiment conducted at pH 7 showed a steady-state release pattern after 16 h, with a cumulative release of 44.3%. The cytotoxic effects of the Pd(II) complex and its encapsulated form in ZnONPs on the MCF-7 cell line were assessed via MTT test. The Pd(II) complex encapsulated within ZnONPs exhibited decreased toxicity relative to the unencapsulated drug, as evidenced by a higher IC50 value of 418.5 µg/ml. This suggests that the encapsulation facilitates a sustained release, which allows for targeted accumulation within cells. The elevated IC50 value indicates that the drug delivery system may be engineered to modulate the release of the drug in a more controlled manner, potentially resulting in a prolonged release profile rather than an immediate therapeutic impact.

Enhanced Biocompatibility by Evaluating the Cytotoxic and Genotoxic Effects of Magnetic Iron Oxide Nanoparticles and Chitosan on Hepatocellular Carcinoma Cells (HCC).

Hepatocellular carcinoma (HCC), the fifth most prevalent cancer worldwide, is influenced by a myriad of clinic-pathological factors, including viral infections and genetic abnormalities. This study delineates the synthesis, characterization, and the biological efficacy of iron oxide nanoparticles (Fe3O4) and chitosan-coated iron oxide nanoparticles (Fe3O4-CS) against HCC. Analytical methods confirmed the successful synthesis of both nanoparticles, with Fe3O4-CS demonstrating a smaller, uniform spherical morphology and distinct surface and magnetic properties attributable to its chitosan coating. The prepared materials were analyzed using various techniques, and their potential cytotoxic effects on HepG2 cancer cells line for HCC were investigated. In biological evaluations against HepG2 cells, a notable distinction in cytotoxicity was observed. Fe3O4 showed modest anticancer activity with an IC50 of 383.71 ± 23.9 µg/mL, whereas Fe3O4 exhibited a significantly enhanced cytotoxic effect, with a much lower IC50 of 39.15 ± 39.2 µg/mL. The Comet assay further evidenced Fe3O4-CS potent DNA damaging effect, showcasing its superior ability to induce apoptosis through extensive DNA fragmentation. Biochemical analyses integrated into our results reveal that Fe3O4-CS not only induces significant DNA damage but also markedly alters oxidative stress markers. Compared to control and Fe3O4-treated cells, Fe3O4-CS exposure significantly elevated levels of oxidative stress markers: superoxide dismutase (SOD) increased to 192.07 U/ml, catalase (CAT) decreased to 0.03 U/L, glutathione peroxidase (GPx) rose dramatically to 18.76 U/gT, and malondialdehyde (MDA) levels heightened to 30.33 nmol/gT. These results underscore the potential of Fe3O4-CS nanoparticles not only in inducing significant DNA damage conducive to cancer cell apoptosis but also in altering enzymatic activities and oxidative stress markers, suggesting a dual mechanism of action that may underpin their therapeutic advantage in cancer treatment. Our findings advocate for the further exploration of Fe3O4-CS nanoparticles in the development of anticancer drugs, emphasizing their capability to trigger oxidative stress and enhance antioxidant defense mechanisms.

Cerebrolysin potentiates the antidepressant effect of lithium in a rat model of depression.

RATIONALE: Depression is the most prevalent psychiatric disorder worldwide. Although numerous antidepressant treatments are available, there is a serious clinical concern due to their severe side effects and the fact that some depressed patients are resistant to them. Lithium is the drug of choice for bipolar depression and has been used as adjunct therapy with other groups of antidepressants. OBJECTIVES: The present study aims to investigate the effect of lithium augmentation with cerebrolysin on the neurochemical, behavioral and histopathological alterations induced in the reserpine model of depression. METHODS: The animals were divided into control and reserpine-induced model of depression. The model animals were further divided into rat model of depression, rat model treated with lithium, rat model treated with cerebrolysin and rat model treated with a combination of lithium and cerebrolysin. RESULTS: Treatment with lithium, cerebrolysin, or their combination alleviated most of the changes in behavior, oxidative stress parameters, acetylcholinesterase and monoamines in the cortex and hippocampus of the reserpine-induced model of depression. It also improved the alterations in brain-derived neurotrophic factor (BDNF) and histopathology induced by reserpine. CONCLUSIONS: The augmentation of lithium with cerebrolysin showed a clear beneficial effect in the present model of depression suggesting the use of cerebrolysin as an adjuvant in antidepressant treatment.

Efficacy of flattening filter-free beams with the acuros XB algorithm in thoracic spine stereotactic body radiation therapy.

This study aimed to determine the dosimetric value of flattening filter-free (FFF) beams compared to flattening filter (FF) beams using different algorithms in the treatment planning of thoracic spine stereotactic body radiation therapy (SBRT). A total of 120 plans were created for 15 patients using the Anisotropic Analytical Algorithm (AAA) and the Acuros External Beam (AXB) algorithm with FF and FFF beams at 6 MV and 10 MV energies. Various dosimetric parameters were evaluated, including target coverage, dose spillage, and organs-at-risk sparing of the spinal cord and esophagus. Treatment delivery parameters, such as the monitor units (MUs), modulation factors (MFs), beam-on time (BOT), and dose calculation time (DCT), were also collected. Significant differences were observed in the dosimetric parameters when AXB was used for all energies (P < 0.05). 6 XFFF energy was the best option for target coverage, dose spillage, and organs-at-risk sparing. In contrast, dosimetric parameters had no significant difference when using the AAA. The AAA and AXB calculations showed that the 6 XFFF beam had the shortest DCT. The treatment delivery parameters indicated that 10 XFF beam required the fewest MUs and MFs. In addition, the 10 XFFF beam demonstrated the shortest BOT. For effective treatment of the thoracic spine using SBRT, it is recommended to use the 10 XFFF beam because of the short BOT. Moreover, the AXB algorithm should be used because of its accurate dose calculation in regions with tissue heterogeneity.

Ameliorative effect of zinc oxide-chitosan conjugates on the anticancer activity of cisplatin: Approach for breast cancer treatment.

Breast cancer is the second most prevalent cancer affecting both males and females, comprising nearly 30 % of all cancer cases. While chemotherapeutic agents, such as cisplatin (Cis), have proven successful in cancer treatment, concerns persist regarding their efficacy and the potentially dangerous side effects. Consequently, there is a crucial and ongoing need to develop approaches that minimize side effects associated with chemotherapy. In the present work, various types of nanoparticles (NPs) were synthesized and loaded with Cis. Cis was conjugated with nanocarriers such as zinc oxide (ZnO), ZnO modified with mandelic acid and graphene oxide (GO), chitosan (CS), and CS modified with ZnO and GO to enhance the selectivity of Cis towards cancer cells. Zeta potentials and particles size were assessed using electrophoretic light scattering and dynamic light scattering. NPs were characterized using transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction. The impact of standalone Cis as well as its nanoconjugated form on the behavior of MCF-7 cell line was investigated using WST-1 cell proliferation and apoptosis/necrosis assays. Experimental findings revealed that among the various NPs tested, ZnO, and CS NPs exhibited the highest loading percentage of Cis, surpassing the loading percentages achieved with other NPs. Cytotoxicity assay showed the enhanced effect of Cis when conjugated with ZnO and CS NPs. Flow cytometry-based assays and confocal microscopy confirmed that ZnO/Cis and CS/Cis induced apoptosis. The cisplatin-nanocomplex exhibited a descending order of early apoptosis and late apoptosis in the following order: ZnO, Cis, CS, ZnO-M, CS-GO, ZnO-GO, CS-ZnO, and CS-ZnO, Cis, CS, CS-GO, ZnO-M, ZnO, ZnO-GO, respectively. None of the nanoparticle complexes displayed a significant percentage of necrotic cells, with the highest percentage reaching 4.65 % in the case of CS-GO/Cis.

Clinical and genetic risk factors for cystic fibrosis-related liver disease in Egyptian CF children: A single-center experience.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disease. It affects multiple organ systems, including the liver, leading to CF-related liver disease (CFLD). It was noted that CFLD in Egyptian children with CF is more common than in non-Egyptian people with CF (pwCF). This study aimed to determine the incidence of CFLD and the potential risk factors for developing CFLD in Egyptian children. The correlation between CFLD and the various genotypes prevalent in Egyptian CF children will be discussed. In addition, comparison of CFLD in Egyptian and non-Egyptian CF patients will be presented. METHODS: This cross-sectional study included 50 pwCF from Ain Sham University's Pediatric Pulmonology Clinic in Children's Hospital, Cairo, Egypt. The sweat chloride test and genetic studies were done at the time of diagnosis. Additionally, all subjects underwent detailed history taking, laboratory investigations, clinical assessment, and pelvic abdominal ultrasound for evaluation of hepatic involvement. RESULTS: One-third of the Egyptian children with CF were found to have liver disease. The following independent risk factors for developing CFLD were identified as: male sex, severe genetic mutation (class I and II), long duration of CF disease, early onset of the CF, pancreatic insufficiency, as well as history of meconium ileus. In addition, diabetes mellitus and severe lung disease were proven to significantly increase the risk of developing CFLD. CONCLUSION: CFLD is common in Egyptian pwCF. CFLD's risk factors are similar to other reported research from other countries in the region.

Evaluation of the Therapeutic Effect of Curcumin-Conjugated Zinc Oxide Nanoparticles on Reserpine-Induced Depression in Wistar Rats.

Depression, a devastating brain illness, necessitates the exploration of novel antidepressant treatments. We evaluated the antidepressant effects of free curcumin, zinc oxide nanoparticles (ZnO NPs), and curcumin-conjugated zinc oxide nanoparticles (Zn(cur)O NPs). The nanoformulations were extensively characterized using advanced techniques. An acute toxicity study ensured the safety of Zn(cur)O NPs. Rats were assigned to one of five groups: control, reserpine-induced depression model, treatment with ZnO NPs, free curcumin, or Zn(cur)O NPs. Behavioral assessments (forced swimming test [FST] and open-field test [OFT]) and neurochemical analyses were conducted. Zn(cur)O NPs exhibited superior efficacy in ameliorating reserpine-induced behavioral and neurochemical effects compared to free curcumin and ZnO NPs. The reserpine-induced model displayed reduced motor activity, swimming time, and increased immobility time in the FST and OFT. Treatment with Zn(cur)O NPs 45 mg/kg significantly improved motor activity and reduced immobility time. Furthermore, Zn(cur)O NPs decreased malondialdehyde (MDA) levels while increasing reduced glutathione (GSH) and catalase (CAT) levels. Additionally, concentrations of serotonin (5-HT) and norepinephrine (NE) increased. In conclusion, curcumin-conjugated zinc oxide nanoparticles demonstrate potent antidepressant effects, alleviating depressive-like behavior in rats. These findings support Zn(cur)O NPs as a promising therapeutic strategy for depression management, warranting further investigation and clinical validation.

Study of novel bidentate heterocyclic amine-based metal complexes and their biological activities: cytotoxicity and antimicrobial activity evaluation.

Metallic antitumor drugs with heterocyclic ligands, such as novel AMI (amino methyl imidazole) complexes [Pd(AMI)Cl2](1), [Cu(AMI)L1](2), and [Cu(AMI)L2·2H2O](3) where L1 = oxalate and L2 = 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' IC50 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 IC50 (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 SC50 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.

Novel palladium(II) and Zinc(II) Schiff base complexes: Synthesis, biophysical studies, and anticancer activity investigation.

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.

Controlled release of silica-coated insulin-loaded chitosan nanoparticles as a promising oral administration system.

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.

Evaluation of the therapeutic potential of cerebrolysin and/or lithium in the male Wistar rat model of Parkinson's disease induced by reserpine.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and represents a challenge for clinicians. The present study aims to investigate the effects of cerebrolysin and/or lithium on the behavioral, neurochemical and histopathological alterations induced by reserpine as a model of PD. The rats were divided into control and reserpine-induced PD model groups. The model animals were further divided into four subgroups: rat PD model, rat PD model treated with cerebrolysin, rat PD model treated with lithium and rat PD model treated with a combination of cerebrolysin and lithium. Treatment with cerebrolysin and/or lithium ameliorated most of the alterations in oxidative stress parameters, acetylcholinesterase and monoamines in the striatum and midbrain of reserpine-induced PD model. It also ameliorated the changes in nuclear factor-kappa and improved the histopathological picture induced by reserpine. It could be suggested that cerebrolysin and/or lithium showed promising therapeutic potential against the variations induced in the reserpine model of PD. However, the ameliorating effects of lithium on the neurochemical, histopathological and behavioral alterations induced by reserpine were more prominent than those of cerebrolysin alone or combined with lithium. It can be concluded that the antioxidant and anti-inflammatory effects of both drugs played a significant role in their therapeutic potency.

Dose-enhancement of MCF 7 cell line radiotherapy using silica-iron oxide nanocomposite.

Cancer radiotherapy is one of the most effective regimens of cancer treatments, but cancer cell radioresistance remains a concern. Radiosensitizers can selectively improve the efficacy of radiotherapy and reduce inherent damage. The purpose of this work is to evaluate the effect of silica-coated iron oxide magnetic nanoparticles (SIONPs) as a radiosensitizer and compare their therapeutic effect with that of Iron oxide magnetic nanoparticles (IONPs). IONPs and SIONPs were characterized using several physical techniques such as a transmission electron microscope (TEM) and Vibrating sample magnetometer (VSM). MTT and DNA double-strand breaks (Comet) assays have been used to detect the cytotoxicity, cell viability, and DNA damage of MCF-7 cells, which were treated with different concentrations of prepared nanoparticles and exposed to an X-ray beam. In this study, an efficient radiosensitizer, SIONPs, was successfully prepared and characterized. With 0.5 Gy dose, dose enhancement factor (DEF) values of cells treated with 5 and 10 µg/ml of IONPs were 1 and 1.09, respectively, while those treated with SIONPs at these concentrations had DEF of 1.21 and 1.32, respectively. Results demonstrated that SIONPs provide a potential for improving the radiosensitivity of breast cancer.

Novel lipid-coated mesoporous silica nanoparticles loaded with thymoquinone formulation to increase its bioavailability in the brain and organs of Wistar rats.

AIMS: The Blood-Brain Barrier (BBB) is a filter for most medications and blocks their passage into the brain. More effective drug delivery strategies are urgently needed to transport medications into the brain. This study investigated the biodistribution of thymoquinone (TQ) and the effect on enzymatic and non-enzymatic oxidative stress indicators in different brain regions, either in free form or incorporated into nanocarriers as mesoporous silica nanoparticles (MSNs). Lipid bilayer-coated MSNs. MATERIALS AND METHODS: MSNs and LB-MSNs were synthesized and characterized using a transmission electron microscope and dynamic light scattering to determine the particle size and zeta potential. TQ encapsulation efficiency and TQ's release profile from LB-MSNs were also examined. The impact of loading LB-MSNs with TQ-on-TQ delivery to different brain areas was examined using chromatographic measurement. Furthermore, nitric oxide, malondialdehyde (MDA), reduced glutathione, and catalase were evaluated as oxidant and antioxidant stress biomarkers. KEY FINDINGS: The LB-MSNs formulation successfully transported TQ to several areas of the brain, liver, and kidney, revealing a considerable increase in TQ delivery in the thalamus (81.74%) compared with that in the free TQ group and a considerable reduction in the cortex (-44%). The LB-MSNs formulation had no significant effect on TQ delivery in the cerebellum, striatum, liver, and kidney. SIGNIFICANCE: TQ was redistributed in different brain areas after being encapsulated in LB-MSNs, indicating that LB-MSNs have the potential to be developed as a drug delivery system for selective clinical application of specific brain regions. CONCLUSIONS: LB-MSNs are capable nanoplatforms that can be used to target medications precisely to specific brain regions.

Evaluation of the therapeutic effect of mesoporous silica nanoparticles loaded with Gallic acid on reserpine-induced depression in Wistar rats.

BACKGROUND: The current study evaluates the free gallic acid (GA) and GA-loaded mesoporous silica nanoparticles (MSNs) antidepressant efficacy in a rat model of depression caused by reserpine. METHODS: By using a scanning electron microscope (SEM), dynamic light scattering (DLS), and zeta potential, MSNs and GA-loaded MSNs were characterized. The efficiency of encapsulation and the release of GA-loaded MSNs were also investigated. The effect of GA, either in its free form or loaded on (MSNs) on oxidative stress biomarkers and monoamine neurotransmitters levels (serotonin (5-HT), norepinephrine (NEP), and dopamine (DA)), were evaluated in these areas (cortex, hippocampus, striatum, and hypothalamus) of control, a depression model of rat, a depression model of rat treated with either free GA, MSNs or GA loaded MSNs. The forced swimming test (FST) also the open field test (OFT) were carried out to evaluate the behavioral changes in all groups. RESULTS: Reserpine caused a decrease in the time spent in motor and swimming activity besides increasing the time of immobility, as demonstrated by OFT and FST. Significantly reductions in 5-HT, NEP, and DA were obtained in the cortex, hippocampus, hypothalamus, and striatum of reserpine-treated rats. Free GA was more effective in increasing the serotonin level in the cortex, hippocampus, and hypothalamus, while GA-loaded MSNs were more effective in increasing it in the striatum. GA-loaded MSNs also increased the level of NEP in the four studied brain areas. Free GA increased dopamine levels in the cortex and striatum, whereas GA-loaded MSNs increased DA levels in the hippocampus and hypothalamus compared with the depressed untreated group. CONCLUSIONS: MSNs can be used as a drug delivery system to target GA selectively to specific brain areas.

Surface modifications affect iron oxide nanoparticles' biodistribution after multiple-dose administration in rats.

Iron oxide nanoparticles (IONPs) possess many utilizable physical and chemical properties and have an acceptable level of biocompatibility. Therefore, they are extensively used in different medical applications. Hence, the challenge is to modify the surfaces of prepared iron oxide nanoformulations with a biocompatible coat to enhance their biosafety. In this study, different formulations of IONPs with different capping agents (citrate [Cit-IONPs], curcumin [Cur-IONPs], and chitosan [CS-IONPs]) were prepared and characterized using various physicochemical techniques. The biodistribution of iron and the histopathology of affected tissues were assessed after Cit-IONPs, Cur-IONPs, CS-IONPs, and commercial ferrous sulfate were orally administered to adult female Wistar rats for 10 consecutive days at a dose of 4 mg/kg of body weight/day. The results were compared with a control group injected orally with saline. The iron content in the kidneys, liver, and spleen was measured by atomic absorption spectroscopy. Histopathological alterations were also examined. The biodistribution results demonstrate that iron accumulated mainly in the liver tissue, whereas the lowest liver accumulation was observed after the administration of Cit-IONPs or CS-IONPs, respectively. In contrast, the administration of CS-IONPs displayed the highest spleen iron accumulation. The ferrous sulfate (FeSO4 )-treated group showed the highest kidney iron accumulation as compared with the other groups. The histopathological examination revealed that signs of toxicity were predominant for groups treated with Cit-IONPs or commercial FeSO4 . However, Cur-IONPs and CS-IONPs showed mild toxicity when administered at the same doses. The results obtained in the present study will provide insights into the expected in vivo effects after administration of each nanoformulation.

Biodistribution and toxicity assessment of copper nanoparticles in the rat brain.

AIMS: The increase in the usage of copper nanoparticles (Cu NPs) in the industrial and medical fields has raised concerns about their possible adverse effects. The present study aims to investigate the potential adverse effects of Cu NPs on the brain of adult male Wistar rats through the estimation of some oxidative stress parameters and acetylcholinesterase (AChE) activity. BASIC PROCEDURES: Cu NPs were prepared and characterized using different techniques: Dynamic Light Scattering, X-Ray Diffraction, Transmission and Scanning Electron Microscopy, Fourier transform Infrared Spectroscopy, in addition to Energy Dispersive X-ray Spectroscopy. Rats were divided into two groups: Cu NPs-treated group (IV injected with 15 mg/kg ˷ 13 nm Cu NPs for 2 successive days) and a control group (injected with saline). Rats of the 2 groups were decapitated simultaneously after 48 h of the last injection. The Cu content in different brain areas was analyzed using inductively coupled plasma mass spectrometry. Moreover, the effect of Cu NPs on brain edema was evaluated. The behavior of rats in an open-field was also examined 24 h post the last injection. MAIN FINDINGS: Significant increases of Cu content in the cortex, cerebellum, striatum, thalamus and hippocampus were found. Moreover, Cu NPs lead to the induction of oxidative stress condition in the thalamus, hypothamaus and medulla. In addition, Cu NPs induced significant increases in AChE activity in the medulla, hippocampus, striatum besides midbrain. Cu NPs-injected rats showed also decreased exploratory behaviour. PRINCIPAL CONCLUSION: The results obtained in the present study point to the importance of toxicity assessments in evaluating the efficiency of Cu NPs for the safe implementation in different applications.

Thymoquinone-encapsulated chitosan nanoparticles coated with polysorbate 80 as a novel treatment agent in a reserpine-induced depression animal model.

Depression is a mental illness with a high prevalence in humans reaching 21% of the worldwide population.The present study aims to evaluate the antidepressant effect of different formulations of Thymoquinone; free Thymoquinone (TQ), Thymoquinone-loaded Chitosan nanoparticles (TQ-TPP-Cs NPs) and Thymoquinone-loaded Chitosan nanoparticles coated with polysorbate 80 (TQ-TPP-Cs NPs-PSb80) that have been prepared to avoid the low bioavailability of TQ. Rats were randomly separated into control rats, depression control induced by reserpine, rat model treated with TQ, rat model treated with TQ-TPP-Cs NPs and rat model treated with TQ-TPP-Cs NPs-PSb80. The results indicate that TQ-TPP-Cs NPs loaded with polysorbate 80 was more efficient in ameliorating the behavioral and neurochemical changes induced by reserpine than TQ and TQ-TPP-Cs NPs. Formulationswere characterized for size, morphology, encapsulation efficiency and in vitro drug release before their use in treatment. Reserpine induced a reduction in motor activity and swimming time and increased immobility time as indicated from the open field test (OFT) and forced swimming test (FST). In addition, a significant decrease in the monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) was recorded in the cortex, hippocampus and striatum of reserpine-treated rats. The present data suggest that the antidepressant efficacy of TQ could be enhanced by engaging TQ with chitosan nanoparticles as a drug carrier and the formulations were modified by coating with polysorbate 80.

Neurotoxicity of green- synthesized magnetic iron oxide nanoparticles in different brain areas of wistar rats.

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.

Does a diabetic retinopathy educational program raise awareness among elderly diabetic patients?

BACKGROUND AND AIM: Diabetic retinopathy is a serious and common complication of diabetes that causes irreversible blindness. The aim of the present study was to assess the knowledge, attitudes, and practice regarding diabetic retinopathy among patients attending a diabetic clinic and identify the effect of an educational program about diabetic retinopathy. PATIENTS AND METHODS: Two hundred diabetic patients were recruited from the outpatient's diabetic clinic, Assiut University hospitals, Egypt. Quasi-experimental (pretest-posttest) research design was applied using a structured interview questionnaire; including socio-demographic data, assessment of the patients' knowledge, attitude, and practices toward diabetic retinopathy. RESULTS: The mean score of knowledge and attitude showed significant improvement (5.3 and 15.1, respectively in pretest vs 16.7 and 16.8, respectively in posttest) among the diabetic patients (p<0.001). From multivariate linear regression model; the predictors for knowledge score were educational level, family history of diabetes and diabetic retinopathy and hypertension. Likewise, attitude score predictors were age, residence, and smoking. Predictors for practice score were hypertension, blood sugar level, and weight. CONCLUSION: There was a statistically significant relationship between educational level and mean knowledge score. The diabetic education program significantly helped to improve awareness of patients in relation to diabetic retinopathy.

Plasma membrane proteins: A new probe for the characterization of breast cancer.

This work aimed to characterize normal, benign and malignant excised breast tissues through the analysis of the FTIR spectra of their plasma membrane proteins. Tissue characterization parameters such as peak position, peak intensity, area under the peak, relative peak intensity and relative area under peak were evaluated mainly for protein spectral peaks; 1150 cm-1, Amide I, Amide II, Amide III, and Amide A. The sensitivity, specificity and diagnostic accuracy for each parameter were obtained and Receiver Operating Characteristic (ROC) Curves were plotted. Results showed significant spectral differences between normal and benign tissues compared to malignant tissues at 1536 and 1645 cm-1. The three tissues could be distinguished at 2900 cm-1, where the malignant peak uniquely split into two separate peaks. ROC curves showed that the Amide A peak position yielded a higher accuracy compared to all other investigated characterization parameters. The deconvolution of Amide I revealed the conformational changes in plasma proteins characterizing the transformation to malignancy (a decrease in the percentage of alpha helix accompanied by an increase in the percentage of beta sheets). The use of the present structure-based analysis in conjunction with histopathological examination of excised breast tissues would offer an enhanced characterization that might reduce possible personal diagnostic mistakes.