66 research outputs found
Phase II study of ‘high-dose’ celecoxib and metronomic ‘low-dose’ cyclophosphamide and methotrexate in patients with relapsed and refractory lymphoma
An Investigation of Gene Action on Different Traits of Barley (Hordeum Vulgare L.) Using Partial Diallel Crosses System
Abstract: The present study was carried out to investigate the genetic structure of 10 hybrids generated by crossing five cultivars of barley with their first (F 1 ) and Second (F 2 ) progeny in growing season 2011-2012 to evaluate these genotypes under normal (0.0 g l -1 sea salt) and salinity stress (7 g l -1 sea salt) conditions in form of randomized complete block design with three replications in a half diallel fashion. The studied traits included spike length (cm), no. of kernels/spike, no. of spikelets/spike, no. of spikes/plants, chlorophyll a, b contents, calcium and magnesium content. The analysis of variance revealed significant differences among genotypes (5 parents + 10 F 1 's+ 10 F 2 's) and for all the studied traits, except chlorophyll b. The results showed that components additive and dominance effects of genes were significant for all studied traits. The estimated value of average degree of dominance (H 1 /D) 0.5 revealed that non-additive genetic effects was more pronounced in the inheritance of the chlorophyll a, b contents, calcium and magnesium in all the two generations (F 1 and F 2 crosses) and spike length (cm), no. of kernels/spike, no. of spikelets/spike and no. of spikes/plants for F 1 crosses. . On contrary, additive genetic effects was evident for spike length (cm), no. of kernels/spike, no. of spikelets/spike and no. of spikes/plants for F 2 crosses. The traits including, chlorophyll a, b and calcium were controlled by over dominance in all the two generations (F 1 and F 2 crosses). The traits including spike length (cm), no. of kernels/spike, no. of spikelets/spike and no. of spikes/plants controlled by over dominance in F 1 crosses and partial dominance in F 2 .While, magnesium were controlled by partial dominance effects of genes. The genetic component (H 2 ) was recorded with low magnitude than (H 1 ) for all traits in both F 1 and F 2 under 0.0 and 7 gl -1 sea salt. The f value was positive for most traits of F 1 and F 2 generations, while it was negative for magnesium in both of F 1 and F 2 generations in all cases of sea salt treatments. The narrow sense heritability was high to moderate for most the studied traits. Moreover, the lowest value was also detected in some cases
Tamarindus indica Extract Alters Release of Alpha Enolase, Apolipoprotein A-I, Transthyretin and Rab GDP Dissociation Inhibitor Beta from HepG2 Cells
Background: The plasma cholesterol and triacylglycerol lowering effects of Tamarindus indica extract have been previously described. We have also shown that the methanol extract of T. indica fruit pulp altered the expression of lipid-associated genes including ABCG5 and APOAI in HepG2 cells. In the present study, effects of the same extract on the release of proteins from the cells were investigated using the proteomics approach. Methodology/Principal Findings: When culture media of HepG2 cells grown in the absence and presence of the methanol extract of T. indica fruit pulp were subjected to 2-dimensional gel electrophoresis, the expression of seven proteins was found to be significantly different (p<0.03125). Five of the spots were subsequently identified as alpha enolase (ENO1), transthyretin (TTR), apolipoprotein A-I (ApoA-I; two isoforms), and rab GDP dissociation inhibitor beta (GDI-2). A functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects the three latter proteins with the interactomes was identified using the Ingenuity Pathways Analysis software. Conclusion/Significance: The methanol extract of T. indica fruit pulp altered the release of ENO1, ApoA-I, TTR and GDI-2 from HepG2 cells. Our results provide support on the effect of T. indica extract on cellular lipid metabolism, particularly that of cholesterol
Hemokinin-1 Gene Expression Is Upregulated in Microglia Activated by Lipopolysaccharide through NF-κB and p38 MAPK Signaling Pathways
The mammalian tachykinins, substance P (SP) and hemokinin-1 (HK-1), are widely distributed throughout the nervous system and/or peripheral organs, and function as neurotransmitters or chemical modulators by activating their cognate receptor NK1. The TAC1 gene encoding SP is highly expressed in the nervous system, while the TAC4 gene encoding HK-1 is uniformly expressed throughout the body, including a variety of peripheral immune cells. Since TAC4 mRNA is also expressed in microglia, the resident immune cells in the central nervous system, HK-1 may be involved in the inflammatory processes mediated by these cells. In the present study, we found that TAC4, rather than TAC1, was the predominant tachykinin gene expressed in primary cultured microglia. TAC4 mRNA expression was upregulated in the microglia upon their activation by lipopolysaccharide, a well-characterized Toll-like receptor 4 agonist, while TAC1 mRNA expression was downregulated. Furthermore, both nuclear factor-κB and p38 mitogen-activated protein kinase intracellular signaling pathways were required for the upregulation of TAC4 mRNA expression, but not for the downregulation of TAC1 mRNA expression. These findings suggest that HK-1, rather than SP, plays dominant roles in the pathological conditions associated with microglial activation, such as neurodegenerative and neuroinflammatory disorders
Expression and function of human hemokinin-1 in human and guinea pig airways
<p>Abstract</p> <p>Background</p> <p>Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the <it>TAC4 </it>gene. <it>TAC4 </it>and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study.</p> <p>Methods</p> <p>RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages.</p> <p>Results</p> <p>In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK<sub>1</sub>-and NK<sub>2</sub>-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK<sub>2</sub>-receptors, which blockade unmasked a NK<sub>1</sub>-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK<sub>1</sub>-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages.</p> <p>Conclusions</p> <p>We demonstrate endogenous expression of <it>TAC4 </it>in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.</p
Protective Effector Memory CD4 T Cells Depend on ICOS for Survival
Memory CD4 T cells play a vital role in protection against re-infection by pathogens as diverse as helminthes or influenza viruses. Inducible costimulator (ICOS) is highly expressed on memory CD4 T cells and has been shown to augment proliferation and survival of activated CD4 T cells. However, the role of ICOS costimulation on the development and maintenance of memory CD4 T cells remains controversial. Herein, we describe a significant defect in the number of effector memory (EM) phenotype cells in ICOS−/− and ICOSL−/− mice that becomes progressively more dramatic as the mice age. This decrease was not due to a defect in the homeostatic proliferation of EM phenotype CD4 T cells in ICOS−/− or ICOSL−/− mice. To determine whether ICOS regulated the development or survival of EM CD4 T cells, we utilized an adoptive transfer model. We found no defect in development of EM CD4 T cells, but long-term survival of ICOS−/− EM CD4 T cells was significantly compromised compared to wild-type cells. The defect in survival was specific to EM cells as the central memory (CM) ICOS−/− CD4 T cells persisted as well as wild type cells. To determine the physiological consequences of a specific defect in EM CD4 T cells, wild-type and ICOS−/− mice were infected with influenza virus. ICOS−/− mice developed significantly fewer influenza-specific EM CD4 T cells and were more susceptible to re-infection than wild-type mice. Collectively, our findings demonstrate a role for ICOS costimulation in the maintenance of EM but not CM CD4 T cells
Prospect of vasoactive intestinal peptide therapy for COPD/PAH and asthma: a review
There is mounting evidence that pulmonary arterial hypertension (PAH), asthma and chronic obstructive pulmonary disease (COPD) share important pathological features, including inflammation, smooth muscle contraction and remodeling. No existing drug provides the combined potential advantages of reducing vascular- and bronchial-constriction, and anti-inflammation. Vasoactive intestinal peptide (VIP) is widely expressed throughout the cardiopulmonary system and exerts a variety of biological actions, including potent vascular and airway dilatory actions, potent anti-inflammatory actions, improving blood circulation to the heart and lung, and modulation of airway secretions. VIP has emerged as a promising drug candidate for the treatment of cardiopulmonary disorders such as PAH, asthma, and COPD. Clinical application of VIP has been limited in the past for a number of reasons, including its short plasma half-life and difficulty in administration routes. The development of long-acting VIP analogues, in combination with appropriate drug delivery systems, may provide clinically useful agents for the treatment of PAH, asthma, and COPD. This article reviews the physiological significance of VIP in cardiopulmonary system and the therapeutic potential of VIP-based agents in the treatment of pulmonary diseases
Identification of different resting state networks under anesthesia in neurosurgical patients operated under intraoperative MRI control
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