mCICR is required for As2O3-induced permeability transition pore opening and cytochrome c release from mitochondria.

The permeability transition pore (PTP) is central for apoptosis by acting as a good candidate pathway for the release of Cyt. c and apoptosis induction factors (AIF). Arsenite induces apoptosis via a direct effect on PTP.

Oxidative mechanisms contributing to the developmental neurotoxicity of nicotine and chlorpyrifos.

Nicotine and chlorpyrifos are developmental neurotoxicants that, despite their differences in structure and mechanism of action, share many aspects for damage to the developing brain. Both are thought to generate oxidative radicals; in the current study, we evaluated their ability to produce lipid peroxidation in two in vitro models of neural cell development (PC12 and SH-SY5Y cells) and for nicotine, with treatment of adolescent rats in vivo. Nicotine and chlorpyrifos, in concentrations relevant to human exposures, elicited an increase in thiobarbituric-acid-reactive species (TBARS) in undifferentiated cells, an effect that was prevented by addition of the antioxidant, Vitamin E.

Modeling the developmental neurotoxicity of nicotine in vitro: cell acquisition, growth and viability in PC12 cells.

Although nicotine is a developmental neurotoxicant, it also can exert neuroprotective effects. In the current study, we used PC12 cells to determine the developmental phases in which these disparate actions are expressed and to compare the concentrations required for each. In undifferentiated cells, 1 or 10 microM nicotine had little or no effect on cell number (assessed by measuring DNA) but exerted positive trophic actions, characterized by transient enhancement of cell growth (increased total protein/DNA ratio) and persistent enhancement of cell viability (decreased proportions of cells stained with trypan blue).

[Congenital absence of the vas deferens].

Congenital absence of the vas deferens (CAVD) is an important factor that contributes to obstructive azoospermia and male infertility. The etiology of CAVD is associated with the cystic fibrosis transmembrane conductance regulator (CFTR) gene and defects in the Wolffian duct, and frequently complicated by renal agenesis and other urogenital abnormalities. Physical examination may reveal nonpalpable scrotal vas deferentia, while vasography intrinsic vasal absence.

Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues.

14-3-3 Proteins play important roles in a wide range of vital regulatory processes, including signal transduction, apoptosis, cell cycle progression and DNA replication. In mammalian cells, 7 14-3-3 isoforms (beta, gamma, epsilon, eta, sigma, theta and zeta) have been identified and each of these seems to have distinct tissue localizations and isoform-specific functions. Previous studies have shown that 14-3-3 protein levels are higher in human lung cancers as compared to normal tissues.

Effects of prenatal nicotine exposure on primate brain development and attempted amelioration with supplemental choline or vitamin C: neurotransmitter receptors, cell signaling and cell development biomarkers in fetal brain regions of rhesus monkeys.

Studies in developing rodents indicate that nicotine is a neuroteratogen that disrupts brain development by stimulating nicotinic acetylcholine receptors (nAChRs) that control neural cell replication and differentiation. We administered nicotine to pregnant Rhesus monkeys from gestational day 30 through 160 by continuous infusion, achieving maternal plasma levels comparable to those in smokers (30 ng/ml). Fetal brain regions and peripheral tissues were examined for nAChR subtypes, other neurotransmitter receptors, and indices of cell signaling and cell damage.

Behavioral alterations in adolescent and adult rats caused by a brief subtoxic exposure to chlorpyrifos during neurulation.

The widely used organophosphate insecticide, chlorpyrifos (CPF), elicits neurobehavioral abnormalities after apparently subtoxic neonatal exposures. In the current study, we administered 1 or 5 mg/kg/day of CPF to pregnant rats on gestational days 9-12, the embryonic phase spanning formation and closure of the neural tube. Although there were no effects on growth or viability, offspring showed behavioral abnormalities when tested in adolescence and adulthood.

Does pharmacotherapy for preterm labor sensitize the developing brain to environmental neurotoxicants? Cellular and synaptic effects of sequential exposure to terbutaline and chlorpyrifos in neonatal rats.

It is increasingly clear that environmental toxicants target specific human subpopulations. In the current study, we examined the effects of prior developmental exposure to a beta(2)-adrenoceptor agonist used to arrest preterm labor, terbutaline, on the subsequent effects of exposure to the organophosphate insecticide, chlorpyrifos (CPF). Neonatal rats were given terbutaline on postnatal day (PN) 2-5, followed by CPF on PN11-14.

Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.

The developmental neurotoxicity of chlorpyrifos (CPF) involves multiple mechanisms, thus rendering the immature brain susceptible to adverse effects over a wide window of vulnerability. Earlier work indicated that CPF exposure at the neural tube stage elicits apoptosis and disrupts mitotic patterns in the brain primordium but that rapid recovery ensues before birth. In the current study, we assessed whether defects in cholinergic synaptic activity emerge later in development.

Nicotine is a developmental neurotoxicant and neuroprotectant: stage-selective inhibition of DNA synthesis coincident with shielding from effects of chlorpyrifos.

Although nicotine is now well recognized as a developmental neurotoxicant, it also may have neuroprotectant properties. In the current study, we used PC12 cells to characterize the specific developmental phases in which these effects are expressed. In undifferentiated cells, nicotine had a modest effect on DNA synthesis (10% reduction), which was nevertheless selective, as no significant reductions were seen for RNA or protein synthesis.

The sea urchin embryo as a model for mammalian developmental neurotoxicity: ontogenesis of the high-affinity choline transporter and its role in cholinergic trophic activity.

Embryonic development in the sea urchin requires trophic actions of the same neurotransmitters that participate in mammalian brain assembly. We evaluated the development of the high-affinity choline transporter, which controls acetylcholine synthesis. A variety of developmental neurotoxicants affect this transporter in mammalian brain.

Short-term adolescent nicotine exposure has immediate and persistent effects on cholinergic systems: critical periods, patterns of exposure, dose thresholds.

In adolescents, the symptoms of nicotine dependence can appear well before the onset of habitual smoking. We investigated short-term nicotine exposure in adolescent rats for corresponding cholinergic alterations. Beginning on postnatal day 30, rats were given a 1-week regimen of nicotine infusions or twice-daily injections, at doses (0.

Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood.

Fetal and childhood exposures to widely used organophosphate pesticides, especially chlorpyrifos (CPF), have raised concerns about developmental neurotoxicity. Previously, biomarkers for brain cell number, cell packing density, and cell size indicated that neonatal rats were more sensitive to CPF than were fetal rats, yet animals exposed prenatally still developed behavioral deficits in adolescence and adulthood. In the present study, we administered CPF to pregnant rats on gestational days 17-20, using regimens devoid of overt fetal toxicity.

Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 signaling in brain endothelial cells. Specific role for glypican-1 in glioma angiogenesis.

Fibroblast growth factor-2 (FGF2) is a potent angiogenic factor in gliomas. Heparan sulfate promotes ligand binding to receptor tyrosine kinase and regulates signaling. The goal of this study was to examine the contribution of heparan sulfate proteoglycans (HSPGs) to glioma angiogenesis.

[Research on the regulation of glucoamylase gene(glaA) expression in A. niger. II. Analysis of the function of 5'-regulatory region of A. niger T21 and 3.795 glaA gene].

Two plasmid vectors pXH2 and pGH1 were constructed through the fusion of E. coli hph gene, the report gene and the 5' upstream regions of A. niger T21 and 3.

Developmental toxicity of terbutaline: critical periods for sex-selective effects on macromolecules and DNA synthesis in rat brain, heart, and liver.

beta-Adrenoceptors (betaARs) control cell replication/differentiation, and during development, signaling is not subject to desensitization. We examined the effects of terbutaline, a beta(2)AR agonist used as a tocolytic, on development in rat brain regions and peripheral tissues with high betaAR concentrations. Prenatal terbutaline (gestational days 17-20) decreased cell numbers (DNA content) in the fetal brain and liver.

Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period?

Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) produced brain cell damage and loss, with resultant abnormalities of synaptic development. We used the same biomarkers to examine prenatal CPF treatment so as to define the critical period of vulnerability. One group of pregnant rats received CPF (subcutaneous injections in dimethyl sulfoxide vehicle) on gestational days (GD) 17-20, a peak period of neurogenesis; a second group was treated on GD9-12, the period of neural tube formation.

Degradation of human hair keratin scaffold implanted for repairing injured skeletal muscles.

Objective: To observe the in vivo degradation process of human hair keratin (HHK) scaffold after implantation in rabbits.

Methods: Seven New Zealand rabbits were divided into 4 groups including a control group and 3 operation groups. HHK scaffold was implanted, after partial resection of the skeletal muscles, in rabbits of the 3 operation groups, followed by observation 1, 3, and 6 weeks later respectively.

[The mechanism and application of posttranscriptional gene silencing].

The purpose of this review is to confirm the reason resulted the gene silence and explore the countermeasure avoiding the gene silence in transgene plant. The method is to divide the gene silencing into transcriptional gene silencing(TGS) and posttranscriptional gene silencing(PTGS). Several models resulted PTGS were analyzed by RNA threshold model, ectopic pairing and aberrant RNA model and ds-RNA model.

Activator protein-1 and CCAAT/enhancer-binding protein mediated GADD153 expression is involved in deoxycholic acid-induced apoptosis.

Studies have demonstrated bile acids, principally deoxycholic acid (DCA), to be colon tumor promoters. DCA is cytotoxic and increasing evidence suggests a role for DCA-induced apoptosis in colon tumorigenesis. Although the precise mechanism by which DCA induces apoptosis remains unclear, DCA may affect cell growth and cell death via altering intracellular signaling and gene expression.

Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas.

The piwi family genes are highly conserved during evolution and play essential roles in stem cell self-renewal, gametogenesis, and RNA interference in diverse organisms ranging from Drosophila melanogaster and C. elegans to Arabidopsis. Here we report the molecular characterization of hiwi, a human member of the piwi gene family.

Perinatal exposure to environmental tobacco smoke upregulates nicotinic cholinergic receptors in monkey brain.

In humans, perinatal exposure to environmental tobacco smoke (ETS) is associated with neurobehavioral deficits. In the current study, we exposed Rhesus monkeys to ETS in late gestation and in the early neonatal period, and examined changes in neurotransmitter receptors in the brainstem and caudal portion of the cerebral cortex. Nicotinic acetylcholine receptors were markedly upregulated and the effect was selective in that there were no changes in m(2)-muscarinic acetylcholine receptors or in beta-adrenergic receptors.

Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein.

The organophosphate pesticide, chlorpyrifos (CPF), is a developmental neurotoxicant. In cell cultures, CPF affects gliotypic cells to a greater extent than neuronotypic cells, suggesting that glial development is a specific target. We administered CPF to developing rats and examined the levels of glial fibrillary acidic protein (GFAP), an astrocytic marker.

Caffeine induces TP53-independent G(1)-phase arrest and apoptosis in human lung tumor cells in a dose-dependent manner.

Caffeine is a model radiosensitizing agent that is thought to work by abrogating the radiation-induced G(2)-phase checkpoint. In this study, we examined the effect that various concentrations of caffeine had on cell cycle checkpoints and apoptosis in cells of a human lung carcinoma cell line and found that a concentration of 0.5 mM caffeine could abrogate the G(2)-phase arrest normally seen after exposure to ionizing radiation.