Protective Role of Quercetin on Polychlorinated Biphenyls (Aroclor‐1254) Induced Oxidative Stress and Apoptosis in Liver of Adult Male Rats

The present study aims to investigate the protective effect of quercetin against Aroclor‐1254–induced hepatotoxicity in rats. Male Wistar rats were grouped into Group I control received vehicle (corn oil; 1 mL/kg bwt); Group II quercetin alone (50 mg/kg bwt/day orally); Group III Aroclor‐1254 (2 mg/kg bwt/day intraperitoneally); Group IV Aroclor‐1254 + quercetin treated for 30 days. The Aroclor‐1254 treatment caused significant alteration in the biochemical parameters (hydrogen peroxide, lipid peroxidation, reduced glutathione levels, and alkaline phosphatase activity). The expressions of apoptotic and antiapoptotic proteins and the liver histology of Aroclor‐1254–exposed rats showed cytoplasmic degeneration along with infiltration of polymorphonuclear cells. Whereas simultaneous treatment with quercetin normalized all the biochemical parameters, consequently it inhibited apoptosis mediated by Aroclor‐1254 by downregulating aryl hydrocarbon receptor, p53 and apoptotic protein (Bax, caspase‐9, caspase‐3) and upregulating the antiapoptotic protein (Bcl‐2) expression patterns; thereby, quercetin reduces alteration in hepatocellular morphology. Thus quercetin exhibited hepatoprotective effect. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 26:522‐532, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21466     

Evaluation of a novel commercial quaternary ammonium compound for eradication of Mycobacteria,HCV and HBV in Egypt

Endoscopes are a common source of outbreaks of healthcare-associated infections. It is therefore important to identify high-level disinfectants capable of eliminating or killing all vegetative bacteria, mycobacteria, and viruses. Aldehydebased disinfectants are most commonly used in clinical practice but resistance has recently been detected and side effects associated with these disinfectants are well documented. In this study, we evaluated Virusolve+® EDS, a novel quaternary ammonium compound formulation supplied by Amity international, against Mycobacterium bovis (ATCC-27289), hepatitis C virus (HCV)-positive serum and hepatitis B surface antigen-positive serum. We also compared its efficacy against Cidex® (glutaraldehyde 2%), an aldehyde-based disinfectant. M. bovis showed no growth after 10 weeks with either Virusolve+® or Cidex®. Virusolve+® achieved a 10⁴- fold reduction in the initial 10⁶ HCV load under clean conditions (without red blood cells) for 20 min, whereas Cidex® achieved this reduction under clean and dirty conditions (without and with red blood cells, respectively) after both 10 and 20 min. Both Virusolve+® and Cidex® were able to eradicate hepatitis B virus (HBV) infectivity under clean conditions after 10 and 20 min, whereas under dirty conditions they were only able to eradicate virus infectivity after 20 min. Virusolve+® EDS when compared with Cidex® showed equal mycobactericidal activity completely eradicating M. bovis. However, both showed comparable virucidal activity against HBV, which was more effective under clean conditions, emphasizing the importance of the cleaning step in endoscope reprocessing. Cidex® was more effective at eradicating HCV under dirty conditions after a short contact time.     

Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities

Mdm4 is a critical inhibitor of the p53 tumor suppressor. Mdm4 null mice die early during embryogenesis due to increased p53 activity. In this study, we explore the role that Mdm4 plays in the intestinal epithelium by crossing mice carrying the Mdm4 floxed allele to mice with the Villin Cre transgene. Our data show that loss of Mdm4 (Mdm4^intΔ) in this tissue resulted in viable animals with no obvious morphological abnormalities. However, these mutants displayed increased p53 levels and apoptosis exclusively in the proliferative compartment of the intestinal epithelium. This phenotype was completely rescued in a p53 null background. Notably, the observed compartmentalized apoptosis in proliferative intestinal epithelial cells was not due to restricted Mdm4 expression in this region. Thus, in this specific cellular context, p53 is negatively regulated by Mdm4 exclusively in highly proliferative cells.     

Salt tolerance of the annual halophyte <Emphasis Type="Italic">Cakile maritima</Emphasis> as affected by the provenance and the developmental stage

Though halophytes are naturally adapted to salinity, their salt-tolerance limits are greatly influenced by their provenance and developmental stage. In the present study, physio-biochemical responses of two Tunisian ecotypes of the oilseed coastal halophyte Cakile maritima (Brassicaceae) to salinity (0–400 mM NaCl) were monitored during germination and vegetative growth stages. Tabarka and Jerba seeds were collected from humid or arid climatic areas, respectively. Plant response to salinity appeared to depend on the ecotype and salinity levels. Increasing salinity inhibited germination process. Jerba seeds were found to be more salt tolerant than the Tabarka ones. At the autotrophic stage of growth and under salt-free conditions, Jerba was less productive than Tabarka (in terms of dry matter accumulation), but plant biomass production and leaf expansion (area and number) of the former ecotype were progressively improved by 100 mM NaCl, as compared to the control. In contrast, at the same salt concentration, these parameters decreased under increasing salinity in Tabarka (salt sensitive). Leaf chlorophyll content was reduced at severe salinity, but this effect was more conspicuous in the sensitive Tabarka plants. Na⁺ contents in the Jerba and Tabarka leaves collected from the 400 mM NaCl-treated plants were 17- and 12-fold higher than in the respective controls. This effect was accompanied by a significant reduction in the leaf K⁺, Mg²⁺ and Ca²⁺ contents, especially in the salt-treated Tabarka. A significant accumulation of proline and soluble carbohydrates in leaves was found during the period of intensive leaf growth. These organic compounds likely play a role in leaf osmotic adjustment and in protection of membrane stability at severe salinity.     

Lead accumulation in the roots of grass pea (Lathyrus sativus L.): a novel plant for phytoremediation systems?

Eleven day-old grass pea plants (Lathyrus sativus L.) were grown hydroponically for 96 h in the presence of 0.5 mM lead nitrate (Pb(NO(3))(2)). The survival rate was 100%. The mean lead content (measured by ICP-OES) in root tissues was 153 mg Pb g(-1) dry matter. Over three quarters of the lead was not labile. Compared with control plants, lead-exposed plants showed a six-fold, two-fold and three and a half-fold reduction in their root calcium, zinc and copper contents, respectively. Together, these results suggested that Lathyrus sativus L. was tolerant to a deficiency in essential nutrients and able to store large amounts of lead in its root tissues. Therefore, it could be used for the development of new rhizofiltration systems.     

Phytochemicals in Morinda citrifolia fruit selectively modulate age-associated immunity and antioxidant enzyme activities through ERK pathway in splenic lymphocytes of male F344 rats

Context/objective: The mechanisms of immunomodulatory effects of Morinda citrifolia (Noni) were examined through intracellular signaling pathways in the splenocytes and their modulation by phytochemicals using bioinformatics tools. Materials and methods: Noni fruit juices without seeds (NSL) and with seeds (NWS) were co-incubated in vitro with splenocytes from young, middle-aged and old F344 male rats and proliferation of lymphocytes, cytokine production, antioxidant enzyme activities and intracellular signaling markers were measured. Results: NSL decreased lymphoproliferation in early middle-aged rats, and IL-2 and IFN-γ production in old rats. In contrast, NWS enhanced lymphoproliferation in young and old rats, IL-2 and IFN-γ production in middle-aged and old rats. The activities of antioxidant enzymes were augmented by NWS and NSL in old rats. NWS reversed age-related increase in lipid peroxidation in all age-groups, while NSL increased lipid peroxidation in old rats. NSL increased p-ERK in old rats and decreased p-CREB in young and middle-aged rats. In contrast, NWS decreased p-ERK in all age groups and increased p-CREB in old rats. Both NSL and NWS increased p-Akt expression in middle-aged and old rats. Both NSL and NWS suppressed p-NF-κB expression in middle-aged and old rats. Docking studies demonstrated that Noni phytochemicals, damnacanthal, myricetin and ursolic acid, are potent inhibitors of ERK with binding sites in the catalytic and phosphorylation sites of the molecule. Conclusions: These results suggest that Noni fruit juices with or without seeds modulate cell-mediated immunity and antioxidant enzyme activities based on the phytochemicals that may differentially influence cell signaling and therefore, age-associated immunity.     

PHLDA1 Mediates Drug Resistance in Receptor Tyrosine Kinase-Driven Cancer

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The Burkholderia cenocepacia peptidoglycan‐associated lipoprotein is involved in epithelial cell attachment and elicitation of inflammation

The Burkholderia cepacia complex (Bcc) is a group of Gram‐negative opportunistic pathogens causing infections in people with cystic fibrosis (CF). Bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. The identification of novel targets for anti‐virulence therapies should improve therapeutic options for infected CF patients. We previously identified that the peptidoglycan‐associated lipoprotein (Pal) was immunogenic in Bcc infected CF patients; however, its role in Bcc pathogenesis is unknown. The virulence of a pal deletion mutant (Δpal) in Galleria mellonella was 88‐fold reduced (p < .001) compared to wild type. The lipopolysaccharide profiles of wild type and Δpal were identical, indicating no involvement of Pal in O‐antigen transport. However, Δpal was more susceptible to polymyxin B. Structural elucidation by X‐ray crystallography and calorimetry demonstrated that Pal binds peptidoglycan fragments. Δpal showed a 1.5‐fold reduced stimulation of IL‐8 in CF epithelial cells relative to wild type (p < .001), demonstrating that Pal is a significant driver of inflammation. The Δpal mutant had reduced binding to CFBE41o^? cells, but adhesion of Pal‐expressing recombinant E. coli to CFBE41o^? cells was enhanced compared to wild‐type E. coli (p < .0001), confirming that Pal plays a direct role in host cell attachment. Overall, Bcc Pal mediates host cell attachment and stimulation of cytokine secretion, contributing to Bcc pathogenesis.     

OmpA‐mediated rickettsial adherence to and invasion of human endothelial cells is dependent upon interaction with α2β1 integrin

Rickettsia conorii, a member of the spotted fever group (SFG) of the genus Rickettsia and causative agent of Mediterranean spotted fever, is an obligate intracellular pathogen capable of infecting various mammalian cell types. SFG rickettsiae express two major immunodominant s urface c ell a ntigen (Sca) proteins, OmpB (Sca5) and OmpA (Sca0). While OmpB‐mediated entry has been characterized, the contribution of OmpA has not been well defined. Here we show OmpA expression in Escherichia coli is sufficient to mediate adherence to and invasion of non‐phagocytic human endothelial cells. A recombinant soluble C‐terminal OmpA protein domain (954–1735) with predicted structural homology to the Bordetella pertussis pertactin protein binds mammalian cells and perturbs R. conorii invasion by interacting with several mammalian proteins including β1 integrin. Using functional blocking antibodies, small interfering RNA transfection, and mouse embryonic fibroblast cell lines, we illustrate the contribution of α2β1 integrin as a mammalian ligand involved in R. conorii invasion of primary endothelial cells. We further demonstrate that OmpA‐mediated attachment to mammalian cells is in part dependent on a conserved non‐continuous RGD motif present in a predicted C‐terminal ‘pertactin’ domain in OmpA.Our results demonstrate that multiple adhesin–receptor pairs are sufficient in mediating efficient bacterial invasion of R. conorii.     

After oxidation,zinc nanoparticles lose their ability to enhance responses to odorants

Electrical responses of olfactory sensory neurons to odorants were examined in the presence of zinc nanoparticles of various sizes and degrees of oxidation. The zinc nanoparticles were prepared by the underwater electrical discharge method and analyzed by atomic force microscopy and X-ray photoelectron spectroscopy. Small (1.2 ± 0.3 nm) zinc nanoparticles significantly enhanced electrical responses of olfactory neurons to odorants. After oxidation, however, these small zinc nanoparticles were no longer capable of enhancing olfactory responses. Larger zinc oxide nanoparticles (15 nm and 70 nm) also did not modulate responses to odorants. Neither zinc nor zinc oxide nanoparticles produced olfactory responses when added without odorants. The enhancement of odorant responses by small zinc nanoparticles was explained by the creation of olfactory receptor dimers initiated by small zinc nanoparticles. The results of this work will clarify the mechanisms for the initial events in olfaction, as well as to provide new ways to alleviate anosmia related to the loss of olfactory receptors.