Gas chromatography/mass spectrometry-based metabolite profiling of chia and quinoa seeds in comparison with wheat and oat.

INTRODUCTION: With an increasing interest in healthy and affordable cereal intake, efforts are made toward exploiting underutilized cereals with high nutritional values. OBJECTIVES: The current study aims to explore the metabolome diversity in 14 cultivars of chia and quinoa collected from Germany, Austria, and Egypt, compared with wheat and oat as major cereals. MATERIAL AND METHODS: The samples were analyzed using gas chromatography-mass spectrometry (GC-MS). Multivariate data analysis (MVA) was employed for sample classification and markers characterization. RESULTS: A total of 114 metabolites were quantified (sugars, alcohols, organic and amino acids/nitrogenous compounds, fatty acids/esters), but the inorganic and phenolic acids were only identified. Fatty acids were the major class followed by amino acids in quinoa and chia. Chia and oats were richer in sucrose. Quinoa encompassed higher amino acids. Quinoa and chia were rich in essential amino acids. Higher levels of unsaturated fatty acids especially omega 6 and omega 9 were detected in quinoa versus omega 3 in chia compared with oat and wheat, whereas ω6/ω3 fatty acid ratio of chia was the lowest. To the best of our knowledge, this is the first comprehensive metabolite profiling of these pseudo cereals. CONCLUSION: Quinoa and chia, especially red chia, are more nutritionally valuable compared with oat and wheat because of their compositional profile of free amino acids, organic acids, and essential fatty acids, besides their low ω6/ω3 fatty acid ratio. Such results pose them as inexpensive alternative to animal proteins and encourage their inclusion in infant formulas.

Assessment of the Effect of Surface Modification of Metal Oxides on Silver Nanoparticles: Optical Properties and Potential Toxicity.

Silver nanoparticles (AgNPs) have garnered significant interest due to their distinctive properties and potential applications. Traditional fabrication methods for nanoparticles often involve high-energy physical conditions and the use of toxic solvents. Various green synthesis approaches have been developed to circumvent these issues and produce environmentally benign nanoparticles. Our study focuses on the green synthesis of AgNPs using L-ascorbic acid and explores the modification of their properties to enhance antibacterial and anticancer effects. This is achieved by coating the nanoparticles with Zinc oxide (ZnO) and Silica oxide (SiO2), which alters their optical properties in the visible spectrum. The synthesized formulations-AgNPs, zinc oxide-silver nanoparticles (Ag@ZnO), and silica oxide-silver nanoparticles (Ag@SiO2) core/shell nanoparticles-were characterized using a suite of physicochemical techniques, including Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta potential measurement, UV-Vis spectroscopy, Refractive Index Measurements, and Optical Anisotropy Assessment. TEM imaging revealed particle sizes of 11 nm for AgNPs, 8 nm for Ag@ZnO, and 400 nm for Ag@SiO2. The Zeta potential values for Ag@ZnO and Ag@SiO2 were measured at -17.0 ± 5 mV and -65.0 ± 8 mV, respectively. UV-Vis absorption spectra were recorded for all formulations in the 320 nm to 600 nm wavelength range. The refractive index of AgNPs at 404.7 nm was 1.34572, with slight shifts observed for Ag@ZnO and Ag@SiO2 to 1.34326 and 1.37378, respectively. The cytotoxicity of the nanocomposites against breast cancer cell lines (MCF-7) was assessed using the MTT assay. The results indicated that AgNPs and Ag@ZnO exhibited potent therapeutic effects, with IC50 values of 494.00 µg/mL and 430.00 µg/mL, respectively, compared to 4247.20 µg/mL for Ag@SiO2. Additionally, the antibacterial efficacy of AgNPs was significantly enhanced under visible light irradiation. Ag@ZnO demonstrated substantial antibacterial activity both with and without light exposure, while the Ag@SiO2 nanocomposites significantly reduced the inherent antibacterial activity of silver. Conversely, the Ag@ZnO nanocomposites displayed pronounced antibacterial and anticancer activities. The findings suggest that silver-based nanocomposites, particularly Ag@ZnO, could be practical tools in water treatment and the pharmaceutical industry due to their enhanced therapeutic properties.

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.

Evaluation of chlorophyll-loaded mesoporous silica nanoparticles for photodynamic therapy on cancer cell lines.

Chlorophyll (Chl) is a promising natural photosensitizer (PS) in photodynamic treatment (PDT). Mesoporous silica nanoparticles (MSNs) were chosen to increase the effectiveness of PDT. This study aimed to evaluate the synergistic efficacy of chlorophyll-loaded mesoporous silica nanoparticles (Chl-MSNs) with photodynamic therapy (PDT) and to investigate their potential toxicity in HepG2, MDA-MB-231, and HSF cell lines. Chl-MSNs were prepared via the physical adsorption method. TEM, DLS, and zeta potential examined morphology, size, and surface characteristics. MSNs and Chl-MSNs were characterized using the same techniques. HPLC was used to assess the encapsulation efficiency. At pH 7.4, an in vitro release experiment of Chl-MSNs was performed. Chl, MSNs, and Chl-MSNs were applied to the three cell lines at different concentrations and subjected to red (650 nm) and blue (450-500 nm) lasers. MSNs and Chl-MSNs' sizes were 90.338 ± 38.49 nm and 123.84 ± 15.67 nm, respectively, as obtained by TEM; the hydrodynamic diameter for MSNs (93.69 ± 20.53 nm) and Chl-MSNs (212.95 ± 19.76 nm); and their zeta potential values are - 16.7 ± 2.19 mV and - 18.84 ± 1.40 mV. The encapsulation efficiency of Chl-MSNs was 70%. Chl-MSNs displayed no toxicity in dark conditions but showed excellent photostability under blue and red light exposure. Furthermore, using Chl over Chl-MSNs has a higher PDT efficiency than the tested cell lines. Chl-MSNs have the potential to be an effective delivery system. PDT proved to be an essential technique for cancer treatment. Blue laser is recommended over red laser with Chl and MSNs for destroying cancer cells.

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.

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.

A new vision of photothermal therapy assisted with gold nanorods for the treatment of mammary cancers in adult female rats.

Over the past decade, the therapeutic landscape has markedly changed for patients with breast cancers (BCs), yet few studies have evaluated the power of the photothermal therapy (PTT) technique. The present study aimed to assess the potency of 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancer treatment with this technique. In total, forty-two adult virgin female Wistar rats were categorized into seven groups, negative control, polyvinylpyrrolidone-capped gold nanorods (PVP-AuNRs) positive control (400 µL per rat ∼ 78 ppm), NIR laser irradiation 808 nm positive control with an intensity of (808 nm NIR CW diode laser, 200 mW cm-2 for 5 min), DMBA-treatment, DMBA-induced mammary cancer group treated with polyvinylpyrrolidone-capped gold nanorods, DMBA-induced mammary cancer group treated with NIR laser irradiation, and DMBA-induced mammary cancer group treated with polyvinylpyrrolidone-capped gold nanorods and NIR laser irradiation. Treatment with polyvinylpyrrolidone-capped gold nanorods and/or NIR laser irradiation was performed after three weeks of DMBA-induced mammary cancer. The mammary tumor lesions in the rat model induced with DMBA are highly invasive. Synthesis and characterization of gold nanorods (AuNRs) with an aspect ratio ranging from 2.8 to 3 were employed to validate the nanostructure and polyvinylpyrrolidone capping and their stability in absorbing near-infrared light. As a result, the therapy strategy, DMBA + PVP-AuNRs + NIR, effectively treated the tumor and halted its growth. The mammary glands were dissected and subjected to biochemical analysis for serum and tissue. Our treatment technique improved the histological aspects of mammary cancer in various forms of mammary cancer detected. Immuno-histochemical localization and TEM images supported these results reflecting the efficacy of this technique. Finally, our findings uncover for the first time the revolutionary effect of the PTT strategy using PVP-capped AuNRs in selectively destroying mammary cancer cells in rats.

Effect of Phenolics from Aeonium arboreum on Alpha Glucosidase, Pancreatic Lipase, and Oxidative Stress; a Bio-Guided Approach.

Metabolic syndrome (MetS) is a global issue affecting over a billion people, raising the risk of diabetes, cardiovascular disorders, and other ailments. It is often characterized by hypertension, dyslipidemia and/or obesity, and hyperglycemia. Chemical investigation of Aeonium arboreum (L.) Webb & Berthel led to the isolation of six compounds, viz. ß-sitosterol, ß-sitosterol glucoside, myricetin galactoside, quercetin rhamnoside, kaempferol rhamnoside, and myricetin glucoside. Interestingly, A. arboreum's dichloromethane (DCM), 100 and 50% MeOH Diaion fractions and the isolated compound (quercetin-3-rhamnoside) revealed potent α-glucosidase inhibitory activity, especially 50% Diaion fraction. In addition, they also showed very potent antioxidant potential, especially the polar fractions, using DPPH, ABTS, FRAP, ORAC, and metal chelation assays. Notably, the 50% Diaion fraction had the highest antioxidant potential using DPPH and ORAC assays, while the 100% Diaion fraction and quercetin-3-rhamnoside showed the highest activity using ABTS, FRAP, and metal chelation assays. Also, quercetin-3-rhamnoside showed a good docking score of -5.82 kcal/mol in comparison to acarbose. In addition, molecular dynamic stimulation studies illustrated high stability of compound binding to pocket of protein. Such potent activities present A. arboreum as a complementary safe approach for the management of diabetes mellitus as well as MetS.

Comparative GC-MS based nutrients profiling of less explored legume seeds of Melilotus, Medicago, Trifolium, and Ononis analysed using chemometric tools.

Exploring novel sources of plant protein for nutrition of both humans and animals is motivated mainly by its growing demand worldwide, besides identifying healthy alternatives for animal protein. The present study evaluates metabolome diversity within 15 legume seed species. The examined samples comprised three Melilotus, four Medicago, four Trifolium, and four Ononis seed species. A holistic approach for metabolites profiling using gas chromatography-mass spectrometry (GC-MS) led to the annotation and quantification of 87 metabolites comprising alcohols, free amino acids, aromatics, fatty acids/esters, nitrogenous compounds, organic acids, sugar alcohols, sugars, terpenes, and steroids. Fatty acids represented the major metabolite class represented by palmitic, stearic, oleic, linoleic, and linolenic acids. Sucrose and pinitol were the major sugars and sugar alcohols among seeds. Ononis seeds (OR, OS and OA) were the most abundant in fatty acids, sugars, sugar alcohols, and free amino acids, whereas Melilotus species (MO and MS) were least enriched in these key nutrients posing Ononis as potential food source for humans and animals. The examined seeds were generally low in sulfur-containing free amino acids and lacking many of the essential free amino acids. Multivariate data analysis aided in the identification of Ononis metabolite markers belonging to various classes i.e., (alcohol) glycerol, (sugar) allofuranose, and (sugar alcohol) pinitol, although the differentiation between Medicago, Melilotus, and Trifolium genera was not attained suggestive for other analytical platforms for its classification.

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.

Omani Frankincense nanoemulsion formulation efficacy and its latent effects on biological aspects of the spiny bollworm Earias insulana (Boisd.).

Our research shed light on the perspective of formulation technology regarding its responsibility to provide phyto-insecticides that are worthy of research into potential novel applications. There has been an increase in interest in using nanoemulsion as a new formulation in a variety of sectors during the last several decades. Boswellia sacra essential oil (Fam: Burseraceae) from the resin of frankincense trees has been recently proposed as a promising ingredient in a new generation of botanical insecticides. Frankincense nanoemulsion was formulated in 5% ratios comprising frankincense oil, surfactants, and water. A frankincense nanoemulsion was prepared using a high-energy ultra-sonication process and characterized by dynamic light scattering transmission electron microscopy surface tension, viscosity, and zeta potential value. Gas chromatography/mass spectrometry (GC/MS) was used to identify the chemical profiles of frankincense essential oil. Furthermore, insecticidal effects against second instar larvae of the spiny bollworm, Earias insulana, as well as their latent effects on the larvae were studied. In the present study, the formulation was a good nanoemulsion. The surface tension was 53.69, the viscosity was 4.76 cPs, the zeta potential was-10 mV, and the size distribution was 41.30 nm. The polydispersity index (PDI) of the nanoemulsion was found to be 0.26, and the morphology of the frankincense nanoemulsion was visualized in a spherical shape. The main constituents identified in frankincense oil were α-pinene (15.52%); monolinolenin (12.92%); and geranylgeranyl acetate (9.99%). The results showed significant insecticidal activity against the larval stage and considerably decreased the pupation percentage with increasing the volume of the frankincense nanoemulsion. On the other hand, the latent effects of the frankincense nanoemulsion on E. insulana resulted in a higher prolongation of larval and pupal durations as well as a significant reduction in the weight of larvae and pupae of E. insulana. Additionally, frankincense nanoemulsion dramatically influenced the adult emergence percentage. It also caused a significantly lower hatchability percentage compared to the untreated control. The concentrations used and the types of mating combination have a significant effect on the fecundity of E. insulana. This novel frankincense nanoemulsion formulation could be used in strategies to control the spiny bollworm on cotton plants.

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.