Evaluation of Glycogen Synthase Kinase Pathway for Assessing the Antidepressant-like Effect of Glucosamine as a Radioprotector in Rats: Behavioral and Biochemical Studies.

Radiotherapy is a very important tool in the treatment of cancer; nevertheless, its side effects are a hindrance to its use. The present study is designed to evaluate glucosamine effects against radiation-induced brain oxidative stress and depression-like effect in rats. Four groups of female Wister rats were used as control, irradiated (4 × 2 Gy), glucosamine (1 g/kg P.O), and glucosamine + irradiated group. The behavioral responses are estimated. The brain hippocampi of the rats are separated to evaluate oxidative stress biochemical parameters and glycogen synthase kinase pathway in addition to the biogenic amines. Irradiation exposure led to disturbances in the behavioral assessments (forced swimming test, light-dark box, and open field test) and a significant decrease in brain GSH, neurotransmitters (serotonin, norepinephrine, and dopamine), phosphatidylinositol 3 kinase (PI3K), and phosphorylated protein kinase-B (p-AKT) levels. Additionally, MDA and ROS levels increased significantly post-irradiation along with the phosphorylated glycogen synthase kinase (p-GSK3). Glucosamine administration before irradiation caused improvement in the behavioral valuations and the biochemical parameters in the brain as well. Glucosamine might be used as a radioprotector to improve brain function and as an antidepressant drug. It could be promising as a future therapy in managing depression occurring during radiotherapy.

Potential impact of mesenchymal stem cells on nephrotoxicity induced by gamma irradiation and antiepileptic drugs cotherapy in rats.

The goal of this study was to assess the influence of bone marrow-derived mesenchymal stem cells (BM-MSCs) on the nephrotoxicity induced by fractionated doses of gamma irradiation (Rad) and the cotherapy of levetiracetam and oxcarbazepine in male rats. Adult rats were randomly divided into four groups. Group I: Control, Group II: antiepileptic drugs (AEDs), Group III: AEDs +Rad and Group IV: AEDs + Rad + MSCs. Rats treated with AEDs and exposed to fractionated doses of γ-irradiation displayed a discernible increase in serum urea, creatinine, kidney injury marker, kidney malondialdehyde, transforming growth factor beta (TGF-ß) and the relative expression of Smad3 along with a decrease in the relative expression of Smad7 and glutathione level. Alternatively, groups treated with BM-MSCs with AEDs and Rad showed a substantial modification in the majority of the evaluated parameters and looked to be successful in reducing the hazards of the combination therapy of AEDs and radiation. The reno-histopathological study supports the biochemical analysis. In conclusion, BM-MSCs exhibited therapeutic potential against nephrotoxicity induced by fractionated doses of γ-irradiation and AEDs. The outcome was brought about by the downregulation of the TGF-ß/Smad pathway. BM-MSCs might be suggested as a valuable therapeutic strategy to overcome kidney injury induced by gamma irradiation during AEDs cotherapy.

Role of TLR4 signaling pathway in the mitigation of damaged lung by low-dose gamma irradiation.

Organisms frequently suffer negative effects from large doses of ionizing radiation. However, radiation is not as hazardous at lower doses as was once believed. The current study aims to evaluate the possible radio-adaptive effect induced by low-dose radiation (LDR) in modulating high-dose radiation (HDR) and N-nitrosodiethylamine (NDEA)-induced lung injury in male albino rats. Sixty-four male rats were randomly divided into four groups: Group 1 (control): normal rats; Group 2 (D): rats given NDEA in drinking water; Group 3 (DR): rats administered with NDEA then exposed to fractionated HDR; and Group 4 (DRL): rats administered with NDEA then exposed to LDR + HDR. In the next stage, malondialdehyde (MDA), glutathione reduced (GSH), catalase (CAT), and superoxide dismutase (SOD) levels in the lung tissues were measured. Furthermore, the enzyme-linked immunoassay analysis technique was performed to assess the Toll-like receptor 4 (TLR4), interleukin-1 receptor-associated kinase 4 (IRAK4), and mitogen-activated protein kinases (MAPK) expression levels. Histopathological and DNA fragmentation analyses in lung tissue, in addition to hematological and apoptosis analyses of the blood samples, were also conducted. Results demonstrated a significant increase in antioxidant defense and a reduction in MDA levels were observed in LDR-treated animals compared to the D and DR groups. Additionally, exposure to LDR decreased TLR4, IRAK4, and MAPK levels, decreased apoptosis, and restored all the alterations in the histopathological, hematological parameters, and DNA fragmentation, indicating its protective effects on the lung when compared with untreated rats. Taken together, LDR shows protective action against the negative effects of subsequent HDR and NDEA. This impact may be attributable to the adaptive response induced by LDR, which decreases DNA damage in lung tissue and activates the antioxidative, antiapoptotic, and anti-inflammatory systems in the affected animals, enabling them to withstand the following HDR exposure.

Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.

Serum and cervico-vaginal glycodelin concentrations as predictors of successful implantation after embryo transfer.

OBJECTIVE: Evaluation of glycodelin (Gd) concentrations in serum and cervico-vaginal secretions as a predictor for implantation after ICSI. MATERIALS AND METHODS: Prospective study on 50 women undergoing ICSI where long protocol ovarian stimulation was used. Serum and cervico-vaginal lavage Gd concentrations were measured then rates of biochemical and clinical pregnancy were detected and predictive value was evaluated using logistic regression analysis. RESULTS: Using cut-off values of 2.2 ng/ml and 1.9 ng/ml for serum and cervico-vaginal Gd concentrations respectively for biochemical pregnancy and values of 2.7 ng/ml and 1.3 ng/ml respectively for clinical pregnancy, there was no significant difference regarding sensitivity (72% & 56%, and 72% & 89%, respectively and respectively). Specificity was statistically similar for biochemical pregnancy (72% and 89%, respectively) while specificity was significantly higher for clinical pregnancy using cervico-vaginal Gd concentration of 1.3 ng/ml (88%) compared to serum Gd concentration of 1.9 ng/ml (53%). CONCLUSION: Glycodelin appears to be a promising marker for implantation after IVF/ICSI.

Iron-Nickel Alloy with Starfish-like Shape and Its Unique Magnetic Properties: Effect of Reaction Volume and Metal Concentration on the Synthesized Alloy.

Iron-nickel alloy is an example of bimetallic nanostructures magnetic alloy, which receives intensive and significant attention in recent years due to its desirable superior ferromagnetic and mechanical characteristics. In this work, a unique starfish-like shape of an iron-nickel alloy with unique magnetic properties was presented using a simple, effective, high purity, and low-cost chemical reduction. There is no report on the synthesis of such novel shape without complex precursors and/or surfactants that increase production costs and introduce impurities, so far. The synthesis of five magnetic iron-nickel alloys with varying iron to nickel molar ratios (10-50% Fe) was undertaken by simultaneously reducing Fe(II) and Ni(II) solution using hydrazine hydrate as a reducing agent in strong alkaline media for 15 min at 95-98 °C. The effect of reaction volume and total metal concentration on the properties of the synthesized alloys was studied. Alloy morphology, chemical composition, crystal structure, thermal stability, and magnetic properties of synthesized iron-nickel alloys were characterized by means of SEM, TEM, EDX, XRD, DSC and VSM. ImageJ software was used to calculate the size of the synthesized alloys. A deviation from Vegard's law was recorded for iron molar ration higher than 30%., in which superstructure phase of FeNi3 was formed and the presence of defects in it, as well as the dimensional effects of nanocrystals. The saturation magnetization (Ms), coercivity (Hc), retentivity (Mr), and squareness are strongly affected by the molar ratio of iron and nickel and reaction volume as well as the total metal concentration.

A novel one-pot facile economic approach for the mass synthesis of exfoliated multilayered nitrogen-doped graphene-like nanosheets: new insights into the mechanistic study.

The present research focuses on providing a novel facile, cost-effective and eco-friendly method for the mass production of N-doped graphene-like nanosheets (NGLs), in order to industrially benefit the exploitation of N-doped graphene in electronics, which will lead to the remarkable prosperity of graphene-based nanoelectronics. NGLs have been synthesized through a one-pot single-step process involving hydrolysis/hydrothermal treatment of glucose under mild conditions, using cetyltrimethylammonium bromide (CTAB) and ammonia solution (NH4OH) as the structure-directing agents. NGLs of high yield (65 wt%) and fascinating structural features, including low oxidation level, good crystalline structural order, and large laterally sized and well-exfoliated nanosheets, have been produced. The growth mechanism has been deeply investigated. The impressive chemical nature of CTAB has a synergistic effect in controlling the NGL structure. The cationic head of CTAB and anionic OH- ions resulting from NH4OH ionization have formed a passivating layer that played a profound role in hindering the NGL agglomeration and allowing the NGLs to grow into large lateral dimensions. Meanwhile, the polar (mainly H-bonding) and apolar (hydrophobic) interfacial interactions between the passivating layer and the graphitic network can be mainly considered responsible for the mild disturbed structural order inside the sp2 crystals. On the other hand, the excessive decomposition of CTAB that is also accompanied by fair ammonia decomposition during the hydrothermal treatment resulted in plenty of hydrogen and nitrogen gases in the atmosphere. The nitrogen gas N-doped the graphitic structure and the hydrogen gas effectively deoxygenated it. Furthermore, the high evolution rate of gases throughout the synthesis system contributed to the obstruction of NGL agglomeration. These results emphasize the high yield and good quality of the synthesized NGLs, which makes such a strategy promising in trust acquisition for investors in industrial production of N-doped graphene.

Volatile organic compounds of biofluids for detecting lung cancer by an electronic nose based on artificial neural network.

Lung cancer (LC) incidence represents 11.5% of all new cancers, resulting in 1.72 million deaths worldwide in 2015. With the aim to investigate the capability of the electronic nose (e-nose) technology for detecting and differentiating complex mixtures of volatile organic compounds in biofluids ex-vivo, we enrolled 50 patients with suspected LC and 50 matching controls. Tissue biopsy was taken from suspicious lung mass for histopathological evaluation and blood, exhaled breath, and urine samples were collected from all participants and qualitatively processed using e-nose. Odor-print patterns were further analysed using the principal component analysis (PCA) and artificial neural network (ANN) analysis. Adenocarcinoma, non-small cell LC and squamous cell carcinoma were the predominant pathological types among LC patients. PCA cluster-plots showed a clear distinction between LC patients and controls for all biological samples; where the overall success ratios of classification for principal components #1 and #2 were: 95.46, 82.01, and 91.66% for blood, breath and urine samples, respectively. Moreover, ANN showed a better discrimination between LC patients and controls with success ratios of 95.74, 91.67 and 100% for blood, breath and urine samples, respectively. The e-nose is an easy noninvasive tool, capable of identifying LC patients from controls with great precision.

Underexpression of miR-486-5p but not Overexpression of miR-155 is Associated with Lung Cancer Stages.

BACKGROUND: Evidence is increasing that microRNAs (miR) are particularly important in lung homeostasis and development and have been shown to be involved in many pulmonary diseases such as asthma, chronic obstructive pulmonary disease, sarcoidosis, Lung Cancer (LC) and other smoking-related diseases. OBJECTIVE: The objective of this study was to investigate the expression of miR-155 and miR-486-5p in tissues from LC patients and healthy endobronchial mucosa as prognostic biomarkers for diagnosing LC. METHODS: Bronchoscopic and thoracoscopic tissue biopsies were taken from 50 LC patients and other 50 control subjects without lung mass, who were planned for a clinical bronchoscopy. The expressions of miR-155 and miR-486-5p in both tumor tissue and healthy mucosa were detected by quantitative real-time polymerase chain reaction. RESULTS: Histopathology showed that 72% of LC patients were in advanced stages III and IV, with non-small cell lung carcinoma and adenocarcinoma being the most common diagnosis. miR-155 was significantly overexpressed while, miR-486-5p was underexpressed, in LC patients as compared to controls. Area under receiver operating characteristic curves of miR-155 (<-0.9) and miR-486 (>-0.62) had sensitivity of 92 and 96% and specificity of 80 and 84%, respectively, in discriminating LC patients from controls with benign solitary pulmonary nodules. CONCLUSION: miR-155 was highly overexpressed, yet it did not correlate with stages, while miR-486- 5p was extremely underexpressed and significantly correlated with stages of LC. Thus, their detection represents an excellent diagnostic/prognostic tool to support more established techniques linked to LC spread locally and systemically.

Anti-apoptotic role of spermine against lead and/or gamma irradiation-induced hepatotoxicity in male rats.

Exposure to either lead (Pb) or γ-irradiation (IR) results in oxidative stress in biological systems. Herein, we explored the potential anti-apoptotic effect of spermine (Spm) against lead and/or γ-irradiation-induced hepatotoxicity in male albino rats. Rats were divided into eight experimental groups of ten rats each: groups including negative control, whole body γ-irradiated (6 Gray (Gy)), lead acetate (PbAct) trihydrate orally administered (75 mg/kg bw ≡ 40 mg/kg bw Pb for 14 consecutive days), and Spm intraperitoneally dosed (10 mg/kg bw for 14 consecutive days) rats and groups subjected to combinations of Pb + IR, Spm + IR, Spm + Pb, and Spm + Pb followed by IR on day 14 (Spm + Pb + IR). A significant decrease in arginase activity as well as mRNA and protein levels of Bcl-2 and p21 was observed in rats intoxicated with Pb and/or γ-irradiation compared to controls, whereas Bax mRNA and protein levels were significantly increased. Also, an increased level of nitric oxide (NO) with a reduced arginase activity was observed in liver tissues of intoxicated rats. Spm co-treatment with lead and/or γ-irradiation attenuated the increase in Bax mRNA and protein expression, while it restored those of Bcl-2 and p21 together with NO levels and arginase activity to control values. Altogether, we suggest that Spm may be useful in combating free radical-induced apoptosis in Pb-intoxicated and/or γ-irradiated rats.

Novel liquid chromatographic methods for the determination of varenicline tartrate.

Two simple, sensitive, rapid, and stability-indicating liquid chromatographic (LC) methods have been developed for the determination of varenicline tartrate. They comprised the determination of varenicline (VRC) in the presence of its oxidative degradates and related impurity (N-formyl varenicline) (NFV). The first method was a LC with diode array detection (DAD) at 235 nm using Ristek-Ultra® C18 column (100 mm × 2.1 mm, 5 µm). Isocratic elution of VRC was employed using a mobile phase consisting of buffer mixture (1.2% potassium dihydrogen phosphate and 0.08% octane sulphonic acid): acetonitrile (86:14, v/v), pH (5.0). In the second method; a fluorimetric detection technique was developed, based on precolumn derivatization of VRC using 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl). The fluorescence detector (FLD) was operated at 474 nm for excitation and 539 nm for emission. Isocratic elution was applied with a mobile phase consisting of methanol-distilled water (70:30, v/v). Separation was achieved using Symmetry® Waters C18 column (150 mm × 4.6 mm, 5 µm). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.5-20.0 µg mL(-1) and 0.2-20.0 µg mL(-1) with the first and the second method, respectively. The optimized methods were validated and proved to be specific, simple, and accurate for the quality control of the drug in its pharmaceutical preparation.