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Cupric oxide nanoparticles (CuO NPs) were phytofabricated utilizing leaf extract of Simarouba glauca and aerial extract of Celastrus paniculatus and are considered to hold excellent anticancer capability. Synthesized CuO NPs were characterized for their morphology, crystallinity, and structure. The presence of functional groups of phytochemicals on synthesized nanoparticles was validated by Fourier transform infrared spectroscopy (FTIR) analysis. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) examination reveal the uniform distribution of particles and the average particle size is 35 nm. The anticancer activities on MCF-7 and HT-29 cell lines revealed that CuO NPs synthesized using leaf extract of S. glauca (CuO-SG) induced cell death with half-maximal inhibitory concentration (IC50) value of 107.56 µg/mL and 208.57 µg/mL, while CuO NPs synthesized using the aerial extract of C. paniculatus (CuO-CP) indicated IC50 values of 97.39 µg/mL and 205.11 µg/mL, respectively. To be more precise for anti-cancerous effect, the molecular mechanism was examined in MCF-7 cell line treated with CuO-CP NPs by cell cycle analysis that depicted 75.28% of cell arrest in Sub G0/G1 phase and 71.29% of cells were gated in the late apoptotic phase of Annexin V and propidium iodide (PI) compared to control cells. The present work reports in vivo antitumor studies of CuO-CP NPs against Ehrlich ascites carcinoma (EAC) bearing C57 mice for the first time and was examined by variations in growth parameters, biochemical assays, hematological profile, and histopathological analysis. CuO-CP NPs could eliminate oxidants like lactoperoxidase and myeloperoxidase, stimulate reduced glutathione, restore the hematological profile and increase the life span of tumor-bearing mice treated by them in comparison with control.

This work highlights how the treatment of ZSM-5 (parent Zeolite Socony Mobil&ndash, 5, Si/Al = 23) with different surfactant templates and alkaline solution, improved the catalytic performance in the Friedel-Crafts acylation of anisole with a propionic anhydride to obtain p-methoxypropiophenone. The modified microporous to mesoporous zeolite catalysts were characterized using different analytical techniques, including X-ray diffraction (XRD), nitrogen porosimetry, Fourier-transform infrared spectroscopy (FT-IR), temperature-programmed desorption (ammonia-TPD) and field emission scanning electron microscopy (FE-SEM) to analyze the crystallographic structure, surface acidity, surface area, porosity, morphology, and particle size. The results showed that the formed mesoporous zeolite by NaOH solution had smaller mesopores (ca. 3.7 nm) as compared to the mesoporous zeolites obtained by surfactant templates, such as, CTAB (ca. 14.9 nm), TPAOH (ca. 11.1 nm) and mixture of CTAB/TPAOH (ca. 15.2 nm). The catalytic acylation reaction was conducted in a batch glass reactor at various temperatures and the products were analyzed using off-line gas chromatography&ndash, mass spectrometry (GC-MS). It was found that the activity of treated ZSM-5 with mixed surfactant templates (CTAB/TPAOH) exhibited enhanced selectivity towards the main product (p-methoxypropiophenone) by a factor 1.7 or higher than unmodified ZSM-5 due to its increased surface area by 1.5 times and enhanced acid sites.

Introduction: Monosodium glutamate (MSG) is worldwide used food flavoring agent. Its safety as food additive is controversial. Vitamin C is a water soluble vitamin with antioxidant activities Aim of the study: The aim of this study was to evaluate the possible toxic effect of MSG on the heart and to evaluate the potential protective effect of concomitant administration of vitamin C together with MSG on the heart of adult male albino rats. Material and methods: The current study was conducted on 60 adult male albino rats. Rats were divided into six equal groups. The first group was used as control group. Group II was treated with vitamin C (100mg/kg/day). Group III was treated with MSG (100mg/kg/day). Group IV was treated with MSG (4g/kg/day). Group V was treated with MSG (100mg/kg/day) together with vitamin C (100mg/kg/day). Group VI was treated with MSG (4g/kg/day) together with vitamin C (100mg/kg/day). All drugs were given orally for 45 days. The weight of the heart was recorded. The level of cardiac troponin I (cTnI) enzyme and the activity of creatine kinase MB (CK- MB) enzyme in serum were assessed. Histopathological examination of heart tissue was carried out. Results: Administration of MSG led to significant increase in the heart weight with significant elevation in the serum cTnI levels and serum CK-MB activity. Sections from low dose MSG treated rats revealed cloudy swelling, while sections form high dose MSG treated rats revealed extensive cloudy swelling with fiber separation and vascular congestion. Concomitant administration of vitamin C together with MSG significantly protected against all these changes Conclusion: It was concluded that MSG is cardiotoxic and that concomitant administration of vitamin C is protective against MSG cardiotoxicity. Recommendations: The current study recommends that the use of MSG should be restricted to very small amounts and should be under supervision of health authorities. The use of vitamin C as a natural and cheap dietary supplement is highly recommended especially in persons who consume diets reach in flavoring agents such as MSG.

We study the synthesis and electrochemical performance of molecular precursor-derived ceramic (PDC)/carbon nanotube-embedded graphene self-supporting composite papers as Li-ion battery and supercapacitor electrodes. The composite papers are prepared using vacuum filtration of PDC-graphene oxide (GO) dispersion, followed by thermal reduction at 500 °C. Tested as a Li-ion battery electrode, the composite papers deliver a reversible capacity as high as 300 mA h g−1 (normalized with respect to total mass of the electrode) with negligible capacity loss after 1000 charge/discharge cycles. Boron-doped silicon carbon nitride (Si(B)CN) outperforms its undoped counterpart (SiCN) in terms of rate capability, cyclic stability, and coulombic efficiency. Among the PDC materials analyzed, Si(B)CN–CNT–rGO demonstrates the lowest ohmic resistance and highest specific capacitance of approximately 269.52 F g−1 at a current density of 5 A g−1, making it a promising electrode material for electrochemical energy storage applications.

Lamprophyre dykes within the granitoid and charnockite are reported for the first time from the Western Bastar Craton, Chandrapur district, Maharashtra. It shows porphyritic–panidiomorphic texture under a microscope, characterised by the predominance of biotite phenocrysts with less abundance of amphibole and clinopyroxene microphenocryst. The groundmass is composed more of K-feldspars over plagioclase, amphiboles, clinopyroxene, biotite, chlorite, apatite, sphene and magnetite. The mineral chemistry of biotite and magnesio-hornblende is indicative of minette variety of calc-alkaline lamprophyre (CAL), which is further supported by preliminary major oxides and trace element geochemistry. This unique association of CAL with granitoid provides an opportunity to study the spatio-temporal evolution of the lamprophyric magma in relation to the geodynamic perspective of the Bastar Craton.

Introduction: Atrazine (ATR), a worldwide triazine herbicide, induces oxidative stress and DNA damage. It was found that oxidative stress is closely linked to apoptosis. Curcumin has strong antioxidant, antimicrobial, anticancer and anti-inflammatory actions. Aim of the study: The aim of this study was to assess the possible ameliorative effect of curcumin on ATR- induced oxidative stress, oxidative DNA damage, mitochondrial dysfunction, and apoptosis in the kidney of adult male albino rats. Material and methods: The current study was conducted on 40 adult male albino rats. Rats were divided into four equal groups. The first group was control. Group II was treated with curcumin (100mg/kg/day). Group III was treated with ATR (400mg/kg/day). Group IV was treated with both ATR (400mg/kg/day) and curcumin (100mg/kg/day). All were given orally for 21days. Body and kidney weights, blood urea and creatinine as well as 24 hours urinary protein levels were measured. Levels of malondialdehyde (MDA), reduced glutathione (GSH), and 8-Hydroxy-2′-deoxyguanosine (8- OHdG) as well as activities of catalase (CAT), heme oxygenase-1 (HO-1) and complex-1 were assessed. Histopathological and immunohistochemical examination of renal tissue were carried out. Results: ATR treated group was significantly decreased in body and kidney weights, GSH level and HO-1 as well as complex 1 activities while there was significant increase in blood urea, creatinine, 24 hours urinary protein, MDA and 8-OHdG levels as well as CAT activity. Renal cloudy swelling was observed in H&E sections. Caspase 3 immunohistochemistry revealed high rate of apoptosis. Curcumin administration along with ATR significantly improved these observations. Conclusion: It was concluded that administration of curcumin along with ATR ameliorated oxidative stress, DNA damage, mitochondrial dysfunction and apoptosis induced by ATR. Recommendations: The current study recommend further studies to clarify issues related to human exposure to ATR and the ameliorative effect of curcumin in Egypt and elsewhere around the world.

Atrazin is currently the most widely used herbicide in agriculture with lots of adverse effects on human health. Curcumin is a polyphenol known for its antioxidant, anti-inflammatory, and anticancer properties. In the present study, the protective effect of curcumin on atrazin-intoxicated rats is evaluated. Toxicity was induced by oral administration of atrazine (400 mg/kg/day) for 3 weeks. Curcumin at a dose of 400 mg/kg/day was given simultaneously by oral route. Redox status, mitochondrial function, 8-hydroxydeoxyguanosine (8-OHdG) level by immunoassay, and caspace-3 expression by immunohistochemistry were evaluated. Curcumin showed significant cardiac protection with improvement of redox status, mitochondrial function, 8-OHdG level, caspase-3 immunoreactivity, and cardiac muscle degeneration. From this current study, it can be concluded that administration of curcumin improved atrazine-induced cardiotoxicity through its modulatory effect on redox status, mitochondrial function, and caspase-3 expression.

Expression of carbonic anhydrase 9 (CA9) is associated with poor prognosis and increased tumor aggressiveness and does not always correlate with HIF-1α expression. Presently, we analyzed the regulation of CA9 expression during hypoxia by HIF-1α, Notch3, and the von Hippel-Lindau (VHL) in breast carcinoma cells. Both HIF-1α and Notch3 were absolutely required for the expression of CA9 mRNA, protein, and reporter. Reciprocal co-immunoprecipitation of HIF-1α, Notch3 intracellular domain (NICD3), and pVHL demonstrated their association. The presence of common consensus prolyl hydroxylation and pVHL binding motifs (L(XY)LAP);LLPLAP(2191) suggested an oxygen-dependent regulation for NICD3. However, unlike the HIF-1α protein, NICD3 protein levels were not modulated with hypoxia or hypoxia-mimetic agents. Surprisingly, mutations of the common prolyl hydroxylation and pVHL binding domain lead to the loss of CA9 mRNA, protein, and reporter activity. Chromatin immunoprecipitation assay demonstrated the association of NICD3, HIF-1α, and pVHL at the CA9 promoter. Further, the NICD3 mutant defective in prolyl hydroxylation and subsequent pVHL binding caused a reduction in cell proliferation of breast carcinoma cells. We show here for the first time that the interaction of HIF-1α with NICD3 is important for the regulation of CA9 expression. These findings suggest that although CA9 is a hypoxia-responsive gene, its expression is modulated by the interaction of HIF-1α, Notch3, and VHL proteins. Targeting the expression of CA9 by targeting upstream regulators could be useful in cancer/stem cell therapy.

A farm of two broiler flocks fed from one day old to 56 days of age a diet naturally contaminated with high level of Aflatoxin (AF), were suffered from caecal coccidiosis at 35 days of age Aflatoxin levels in feed commodities and mixed feed were determined using ELISA test. Results of ELISA showed that the average level of corn, soybean and mixed feeds contamination with aflatoxin were 1915, ppb, 229 ppb and 860 ppb respectively. Diagnosis of caecal coccidiosis was confirmed by clinical signs, post-mortem findings, fecal oocyst excretion per gram, oocyt size, morphological characteristic of eggs, lesion score and schizonts size. The significance of AF as predisposing factor to coccidiosis infection was discussed.

Forty five finished poultry feed samples , collected from different broilers, broiler breeders and layers farms were divided into two parts, for mycological and mycotoxins examination . In counting of molds , dilute plate technique was used, whereas feed parts were used for mycotoxin estimation, they were subjected to four standard kits of Aflatoxin, Ochratoxin, T-2 toxin and Fumonisins. Mold counts were around 10 5 cfu.g -1 sample. Fourteen mold genera were recovered. From the systematic point of view, 2 genera belonged to Zygomycetes (i.e. Mucor, Rhizopus ,), 1 genus belong to Ascomycetes (i.e. Eurotium ); the majority, within so-called mitotic fungi (formerly Deuteromycetes ), encompassed 11 genera (i.e. Acremonium, Alternaria, Aspergillus, Fusarium, Paecilomyces, Penicillium, Scopulariopsis,, Trichothecium, Ulocladium and Aerobasidium ). The most frequent fungi were those from the genus Aspergillus . The concentrations of the four analyzed mycotoxins in the poultry finished feeds, and the percentages of the recovered mycotoxins, revealed that aflatoxins was recovered in 91.1% of the examined samples, with a mean value of 179.1µg/kg. The same percentage was found with Ochratoxins, but with lower mean concentration of 159.4µg/kg. In the third order were Fumonisins mycotoxins were in the third order, and they were recovered in 51.1% of the tested samples with a mean value of 127µg/kg. In the fourth order was T-2 toxin, with a percentage of 2.2% and a value of 50.0µg/kg .

Ten broiler flocks claimed to be suffering from aflatoxicosis in Ninavah governorate were subjected to study the correlation between natural contamination of feed samples with aflatoxin and European production efficiency factor (EPEF). Enzyme-linked immunosorbent assay (ELISA) method was adopted for estimation of AF level in broiler feeds. Growth performance parameters were recorded including final body weight, mortality, feed consumption and conversion ratio. Aflatoxins levels in feeds were ranged from 31 to 2381.8 ppb and EPEF was between 91.55-151.05. There was a highly negative correlation between AF concentration in broiler flock feeds and their EPEF (-0.828).

Three experiments were conducted to elucidate the alleviation effects of Mycofix plus 3.0 on Newcastle antibody formation during aflatoxicosis in broiler chickens. Three levels of Mycofix (0.05%, 0.15%, and 0.25%) and aflatoxin (2.5ppm, 3.5ppm, and 5ppm) were used. Chickens were vaccinated at 8 and 18 days of age. Enzyme-linked immunosorbent assay and Haemagglutination inhibition tests were employed for determination Newcastle antibody titers at 28 days. The results showed that, Mycofix , and only at its high level of addition (0.25%) was effective in ameliorating the negative effect of aflatoxin at the rates 2.5ppm and 3.5 ppm levels of inclusion on antibody production but not at the high level of 5ppm on antibody production, comparing with titers in control groups.

Two hundred and twenty six broilers feed commodities were collected from different broiler flocks in Ninevah governorate(Iraq), through the period from January 2004 toDecember 2005. Enzyme linked immunosorbent assay method was used for T-2 toxin estimation. Results showed that, 81.5% of the total examined feed samples were positive to T-2 toxin contamination. Individually these percentages were as follows; 95% for wheat; 87% for corn; 85% for soybean; 74% for barley; and 70% for mixed feed. The range for T-2 contamination was between 8-1200 ppb. Most of the samples (58.4%) had low T-2 toxin natural contamination levels. Thirty two percent of positive samples had medium contamination level, while only 18.6% experienced high natural contamination levels with T-2 toxin.

One hundred and forty one-day-old-male broiler chicks (Ross), were divided into 7 groups (20 chicks/group) and fed T-2 toxin alone or with five different types of adsorbents; Montmorillonite 0.5%, Vermiculite 0.5%, Pigacine 0.5%, Gezilgure 0.5%; and the resin Perlite 0.5%. Gross and microscopic examinations reveal that all adsorbents used were unable to alleviate the oral lesions induced by T-2 toxin in broiler chickens.

One hundred and fifty eight broiler compound feed samples were delivered from broiler flocks in Ninevah governorates. These flocks were clamed to be affected with field aflatoxicosis. All the examined samples had aflatoxin levels higher than of the permissible limit (20 ppb). The range of AF levels was 22-2263 ppb. The mean value of AF concentration was 592.7ppb. The percentage of AF concentrations from 0-500 ppb was 48.7%, and from 500-1000 ppb was 41.2%, while that from 1000-2500 was 10.2%.

The possible protective effect of Mycofix against the toxic effect of T-2 toxin in growing broiler chickens was investigated in two age stages; the first and second ages, ranged from 1-21 and 22-42 days, respectively. The experiment was consisted of 4 dietary treatments: treatment 1: control; treatment 2: 2.5g Mycofix/kg feed; treatment 3: 8 ppm T-2 toxin alone; treatment 4: 8 ppm T-2 toxin plus Mycofix 2.5g Mycofix /kg feed. T-2 toxin alone significantly (p

Edelfosine is a synthetic alkyl-lysophospholipid that possesses significant antitumor activity in several human tumor models. Here, we investigated the effects of edelfosine combined with androgen deprivation (AD) in LNCaP and VCaP human prostate cancer cells. This treatment regimen greatly decreased cell proliferation compared with single agent or AD alone, resulting in higher levels of apoptosis in LNCaP compared with VCaP cells. Edelfosine caused a dose-dependent decrease in AKT activity, but did not affect the expression of total AKT in either cell line. Furthermore, edelfosine treatment inhibited the expression of androgen receptor (AR) and was associated with an increase in activating transcription factor 3 (ATF3) expression levels, a stress response gene and a negative regulator of AR transactivation. ATF3 binds to AR after edelfosine + AD and represses the transcriptional activation of AR as demonstrated by PSA promoter studies. Knockdown of ATF3 using siRNA-ATF3 reversed the inhibition of PSA promoter activity, suggesting that the growth inhibition effect of edelfosine was ATF3 dependent. Moreover, expression of AR variant 7 (ARv7) and TMPRSS2-ERG fusion gene were greatly inhibited after combined treatment with AD and edelfosine in VCaP cells. In vivo experiments using an orthotopic LNCaP model confirmed the antitumor effects of edelfosine + AD over the individual treatments. A significant decrease in tumor volume and PSA levels was observed when edelfosine and AD were combined, compared with edelfosine alone. Edelfosine shows promise in combination with AD for the treatment of prostate cancer patients. Mol Cancer Ther; 15(6); 1353–63. ©2016 AACR.

The Gondpipri mafic-ultramafic complex consists of several tectonically dismembered gabbro-websterite-troctolite peridotite bodies disposed intermittently in a 10 km long NE-SW trending linear belt within tonalite- trondhjemite-granodiorite (TTG) and charnockite-enderbite, Western Bastar Craton (WBC), Central India. Ni-Co sulphide associated PGE mineralization is recorded in gabbro variants viz. norite gabbro-anorthositic gabbro-gabbro at Heti. The mineralized gabbroic body extends for 500 m strike length with 40 m width and dips 45° to 55° southerly following regional structural trends. The host rocks contain total Cu + Ni up to 5000 ppm with a Cu: Ni ratio

Ninety eight samples of feed commodities (wheat, soybean and corn ) were collected during the period 2000–2004 from various broiler farms showed clinical signs of ochratoxicosis. Feed samples were divided into two equal parts, one for mycological study, for detection of feed commodities contamination with A. ochracous, and the other part for ochratoxin analysis using Enzyme-linked immunosorbent assay. Mycological results showed that wheat samples show the higher percentage of contamination with A. ochraceus (73%) with log 10 CFU/gm of 2.77. Toxicological analysis shows that wheat samples had the highest rate of ochratoxin contamination (86%) followed by soybean (76%) and then corn samples (70%). Ochratoxin levels in all feed samples were ranged from < 100 ppb to 400 ppb. The importance of ochratoxin in poultry health was discussed. اركولاا مومسب محللا جورف فلاعأ تانوكم ضعبل يعيبطلا ثولتلا

Quantification of total and individual amino acids in biological fluids such as plasma, urine and cerebrospinal fluid has an important diagnostic implication in laboratory medicine. The present paper describes protocols for the assay of total amino acids by modified method based on dinitrophenyl and HPLC profile involving pre-column derivatization with o-pthalaldehyde (OPA) derivatization, respectively. The method, based on the alkylation of-SH groups prior to OPA derivatization of amino acids followed by reverse phase high performance liquid chromatography, provide a comprehensive profile of more than twenty amino acids (including-SH group containing) in a single run lasting about 45 minutes. The present study, apart from establishing the normal profile of amino acids in plasma of Indian sub population, also presents HPLC profile for some of the rare amino acidopathies.

The adsorption of lead (Pb II) ion on different types of synthesized zeolite was investigated. The BET surface area, total pore volume & average pore size distribution of these synthesized zeolites were determined by adsorption isotherms for N2, the surface area & total pore volume of their sources were found by adsorption isothermN2.The adsorption equilibrium was measured after 24h at room temperature (RT) & concentration 10mg.L-1 of Pb (II) was used. The adsorption of heavy metal Pb (II) on four different prepared zeolites (LTA from Montmorillonite clay, FAU(Y)-B.H (G2) from Barley husk, Mordenite (G1) from Chert rock, FAU(X)-S.C (G3) from shale clay & modified Shale clay by oxalic acid (N1) & sodium hydroxide (N2)), were compared with the adsorption of their sources by using static batch experimental method. The major factors affecting the heavy metal ion sorption on different synthesized zeolites & their sources were investigated. The adsorption equilibrium capacity (Qm) of Pb (II) ion for different synthesized zeolites ordered from (N1>N2>LTA>G3>G2>G1&for their sources ordered Shale clay >Montmorilonite> Barley husk>Chert rock. The atomic absorption spectrometry was used for analysis of lead heavy metal ion, the obtained results in this study showed that the different synthesized zeolites were efficient ion exchanges for removing heavy metal, in particular, the modified zeolite from shale clay by oxalic acid.

The ameliorative effect of graded levels of dietary sodium bentonite (0.2, 0.4 and 0.6 per cent wt/wt of feed) on in vitro-impaired phagocytosis and suppressed immune response to Newcastle disease vaccine during aflatoxicosis (AF) in broiler chicks was investigated. Both percentage and mean of phagocytic activities were decreased significantly (P0.05) in chicks fed 2.5 mg aflatoxin per kg feed. The addition of sodium bentonite was significantly effective in ameliorating the negative effect of AF on the percentage and mean of phagocytosis. The presence of AF alone in the diet depressed the immune response of chicks as measured by haemagglutination inhibition (HI) test. Sodium bentonite was also effective in ameliorating the suppressive effect of AF on the HI -titre in chicks vaccinated against Newcastle disease. The best results obtained when sodium bentonite was added at the rate of 0.4 per cent wt/wt of feed to the AF-containing diets.

The BclXL apoptotic repressor bears the propensity to associate into megadalton oligomers in solution, particularly under acidic pH. Herein, using various biophysical methods, we analyze the effect of temperature on the oligomerization of BclXL. Our data show that BclXL undergoes irreversible aggregation and assembles into highly-ordered rope-like homogeneous fibrils with length in the order of mm and a diameter in the μm-range under elevated temperatures. Remarkably, the formation of such fibrils correlates with the decay of a largely α-helical fold into a predominantly β-sheet architecture of BclXL in a manner akin to the formation of amyloid fibrils. Further interrogation reveals that while BclXL fibrils formed under elevated temperatures show no observable affinity toward BH3 ligands, they appear to be optimally primed for insertion into cardiolipin bicelles. This salient observation strongly argues that BclXL fibrils likely represent an on-pathway intermediate for insertion into mitochondrial outer membrane during the onset of apoptosis. Collectively, our study sheds light on the propensity of BclXL to form amyloid-like fibrils with important consequences on its mechanism of action in gauging the apoptotic fate of cells in health and disease.

Adsorption characteristics and catalytic photodegradation of carbendazim (methyl benzimidazol-2-ylcarbamate) have been investigated in Kurdistan natural soil and different natural waters (drinking, river, lake and ground water). Physico-chemical properties of the natural soil and water were determined. The equilibrium adsorption of carbendazim onto studied soil samples described by Freundlich adsorption model. The catalytic photodegradation processes were studied in aqueous Titanium dioxide (TiO 2 ) suspensions under UV radiation. The kinetic study was done by monitoring the concentration during the degradation process, using High performance Liquid Chromatography (HPLC), coupled with UV-visible spectrophotometer. It was found that the photocatalytic degradation process in this work exhibited pseudo first-order kinetics. The rates of catalytic photodegradation of carbendazim in natural water were lower than that in distilled water.

Schistosoma mansoni (S. mansoni) eggs trapped in the host liver elicit a chain of oxidative processes that may be, at least in part, responsible for the pathology and progression of fibrosis associated with schistosomal hepatitis. This study was designed to assess the protective effect of the antioxidant coenzyme-Q10 (Co-Q10) against experimental S. mansoni-induced oxidative stress in the liver, and its potential role as an adjuvant to praziquantel (PZQ) therapy. The oxidative stress and overall liver function were improved under Co-Q10 therapy as evidenced by significant reduction in oxidative stress markers and preservation of antioxidant factors. Liver fibrosis was also reduced with a positive impact on liver function. Moreover, addition of Co-Q10 to PZQ therapy caused: significant reduction of liver egg load, significant improvement of the redox status, and lastly decreased liver fibrosis.

Agriculture in northern Iraq (Kurdistan) relies on the widespread use of pesticides to promote crop performance. Over-application of many pesticides is commonplace, however, and may compromise soil and water quality, and ultimately human health, within the region. The aim of this study was to investigate the sorption–desorption kinetics and equilibrium partitioning of two selected pesticides in agricultural soils from northern Iraq. This was achieved by fitting a dual-rate sorption–desorption model to time-dependent data obtained from batch experiments. 2,4-D and carbaryl were selected for scrutiny since both are in common use in the region. Six agricultural soils, sampled around the city of Erbil, were investigated. These were low in organic carbon (OC) compared with many agricultural soils from more temperate regions. However, there was still a clear trend of increasing sorption of both 2,4-D and carbaryl with increasing % OC. In the case of both compounds, fast and slow adsorption rate coefficients and 48 h experimental K d values were positively correlated with % OC. It was assumed that K OC would provide a simple and reliable predictor of K d . However, while this assumption holds true for short-term (48 h) experimental data, longer-term sorption in some soils (as indicated by theoretical K d values estimated from kinetic parameters in our study) appears to be under-predicted by K OC alone. The data presented here provide a useful starting point for further site-specific investigations of pesticide impacts in the Kurdistan region of Iraq.

Glial progenitors from the brain of normal adult Sprague-Dawley rats were compared to their initiated and malignant counterparts that were isolated from apparently normal brains of animals exposed to methylnitrosourea (MNU). Fibroblast growth factor-2 (FGF-2) or platelet-derived growth factor (PDGF)-A or -B induced differentiation of normal progenitors to a pro-astrocytic or oligodendrocytic morphology, respectively, whereas the combination of these factors resulted in their terminal differentiation to oligodendrocytes and senescence. In contrast, initiated progenitors did not exit the cell cycle when stimulated with PDGF and/or FGF-2. cDNA oligoarray analysis and RT-PCR verification showed an early upregulation/ induction of growth factor/receptors, PDGF-A, PDGFR-beta, IGFR-1, IGF-1 and -2, IL-6, MEGF-5, FRAG-1, IRS-2, HSPG, and FGFR-1, followed by a late increase in the expression IGFBP-6, PDGF-alpha, FGFR-4A, c/ERB-A, and FGFR-4, 2, and 1 during the tumorigenic progression. Western blot analyses demonstrated that MNU exposure caused progressive reduction of p21 protein levels, an increase of Rb phosphorylation, activation of AKT and CDK2, and upregulation of FGF receptors. Double immunofluorescence labeling showed progressive increase in nuclear colocalization of FGFR1, 2, and 4, which peaked in malignant lines. It is postulated that transition of normal rat glial progenitors to an initiated state is driven by IGF-1 and 2, IL-6, and the upregulation of the receptors PDGFR-beta and FGFR-1, 2, and 4. Deregulation of the cell cycle in this state involves reduction of p21 protein, concomitant upregulation of CDC2, and an increase in Rb phosphorylation that favors expression and nuclear translocation of FGFR-4 and FRAG-1 and 2. These events are associated with progressive activation of AKT and RAS. Malignant transformation is enhanced by near elimination of p21 and PC3, induction of AP-1 (upregulation of JUN-B, c-JUN, FRA-1), activation of the NF-kB pro-survival pathway, and inhibition of the TGF-beta pro-apoptotic pathway possibly in response to changes in the expression of nerve growth factor (NGF) I-A and NGFI-B. These data demonstrate that the events leading to malignancy in the rat brain in response to MNU treatment are to a great extent similar to those described for secondary glial malignancies in humans.

Methionine deprivation imposes a metabolic stress, termed methionine stress, that inhibits mitosis and induces cell cycle arrest and apoptosis. The methionine-dependent central nervous system tumor cell lines DAOY (medulloblastoma), SWB61 (anaplastic oligodendroglioma), SWB40 (anaplastic astrocytoma), and SWB39 (glioblastoma multiforme) were compared with methionine-stress resistant SWB77 (glioblastoma multiforme). The cDNA-oligoarray analysis and reverse transcription-PCR verification indicated common changes in gene expression in methionine-dependent cell lines to include up-regulation/induction of cyclin D1, mitotic arrest deficient (MAD)1, p21, growth arrest and DNA-damage-inducible (GADD)45 alpha, GADD45 gamma, GADD34, breast cancer (BRCA)1, 14-3-3sigma, B-cell CLL/lymphoma (BCL)1, transforming growth factor (TGF)-beta, TGF-beta-induced early response (TIEG), SMAD5, SMAD7, SMAD2, insulin-like growth factor binding protein (IGFBP7), IGF-R2, vascular endothelial growth factor (VEGF), TNF-related apoptosis-inducing ligand (TRAIL), TNF-alpha converting enzyme (TACE), TRAIL receptor (TRAIL-R)2, TNFR-related death receptor (DR)6, TRAF interacting protein (I-TRAF), IL-6, MDA7, IL-1B convertase (ICE)-gamma, delta and epsilon, IRF1, IRF5, IRF7, interferon (IFN)-gamma and receptor components, ISG15, p65-NF-kappaB, JUN-B, positive cofactor (PC)4, C/ERB-beta, inositol triphosphate receptor I, and methionine adenosyltransferase II. On the other hand, cyclins A1, A2, B1 and B2, cell division cycle (CDC)2 and its kinase, CDC25 A and B, budding uninhibited by benzimidazoles (BUB)1 and 3, MAD2, CDC28 protein kinase (CKS)1 and 2, neuroepithelial cell transforming gene (NET)1, activator of S-phase kinase (ASK), CDC14B phosphatase, BCL2, TGF-beta activated kinase (TAK)1, TAB1, c-FOS, DNA topoisomerase II, DNA polymerase alpha, dihydrofolate reductase, thymidine kinase, stathmin, and MAP4 were down-regulated. In the methionine stress-resistant SWB77, only 20% of the above genes were affected, and then only to a lesser extent. In addition, some of the changes observed in SWB77 were opposite to those seen in methionine-dependent tumors, including expression of p21, TRAIL-R2, and TIEG. Despite similarities, differences between methionine-dependent tumors were substantial, especially in regard to regulation of cytokine expression. Western blot analysis confirmed that methionine stress caused the following: (a) a marked increase of GADD45alpha and gamma in the wt-p53 cell lines SWB61 and 40; (b) an increase in GADD34 and p21 protein in all of the methionine-dependent lines; and (c) the induction of MDA7 and phospho-p38 in DAOY and SWB39, consistent with marked transcriptional activation of the former under methionine stress. It was additionally shown that methionine stress down-regulated the highly active phosphatidylinositol 3'-kinase pathway by reducing AKT phosphorylation, especially in DAOY and SWB77, and also reduced the levels of retinoblastoma (Rb) and pRb (P-ser780, P-ser795, and P-ser807/811), resulting in a shift in favor of unphosphorylated species in all of the methionine-dependent lines. Immunohistochemical analysis showed marked inhibition of nuclear translocation of nuclear factor kappaB under methionine stress in methionine-dependent lines. In this study we show for the first time that methionine stress mobilizes several defined cell cycle checkpoints and proapoptotic pathways while coordinately inhibiting prosurvival mechanisms in central nervous system tumors. It is clear that methionine stress-induced cytotoxicity is not restricted by the p53 mutational status.

A spectrophotometric method based on dinitrophenol (DNP) derivatization of proteolytic products was developed for monitoring the increase in NH(2)-groups as a function of protease activity. DNP derivatization of amino acids and proteolytic products was carried out at an alkaline pH of 8.8, in presence of 2,4-dinitrofluorobenzene (DNFB), followed by the stabilization of products by adjusting the pH to approximately 2.5. Using casein as substrate, under the defined assay conditions for proteases, trichloroacetic acid soluble proteolytic products were derivatized with DNFB reagent. Though alkaline pH favored the DNP derivatization of primary amino compounds, the products formed were found to be unstable. However, upon adjusting the pH to 2.5+/-0.1, DNP derivatives of amino acids and proteolytic products were found to be stable with identical lambda(max) of 395 nm. The utility of the method was evaluated by assaying the proteolytic activities of trypsin and calcium activated neutral protease (CANP). Proteolytic activity was quantified by employing the molar extinction coefficient of DNP derivatives of an equimolar concentration of glutamate and glycine. By employing this method, CANP activity in different regions of rat brain was determined. The proposed method to monitor the increase in NH(2)-end groups as a function of proteolytic activity could be employed to assay the activity of proteases.

Although arsenic is toxic and a proven carcinogen, the mechanism underlying carcinogenesis is unknown. Until recently the metabolism of arsenic was thought to be a detoxification process. MMAIII is a toxic intermediate of arsenic metabolism. Recent studies show that MMAIII is more cytotoxic and genotoxic than AsIII or AsV. Our aim was to develop an animal model to study the role of MMAIII in arsenic carcinogenesis and in particular to study the development of skin cancer, the predominant presenting feature in humans.Female C57BL/6J mice were given drinking water containing 0 mg/L and 500 mg/L arsenic as MMAIII ad libitum for 2 years. Five animals from each group were sacrificed at various times up to 24 months for arsenic and biomarker measurements. HPLCnICPMS was used to assess excretion of As species. DMAV was the major metabolite which showed a significant dose-dependent increase over 2 years of exposure.An excess of tumors were observed in the MMAIII-treated animals around 18 months. MMAIII treatment resulted in firstly, dermatitis which progressed to trichoepithelioma. There was also an excess of liver cancer. Genome-wide expression profiling of the liver tumors induced by MMAIII by Affymetrix (Mouse genome 430 2.0Array) system for 45,000 probe sets, indicated the disruption of signaling pathways. The components mediating the outcome were different in treatment modalities with the same end result of increase in the expression of Bcl2 a prosurvival gene.Our results show MMAIII is carcinogenic in female C57BL/6J mice and supports the contention that methylation is a toxic process, not a detoxification pathway. MMAIII derived metabolically from inorganic arsenic is likely to be the proximal carcinogen.