Apigenin inhibits PMA-induced expression of pro-inflammatory cytokines and AP-1 factors in A549 cells

Acute and chronic alveolar or bronchial inflammation is thought to be central to the pathogenesis of many respiratory disorders. Cytokines and granulocyte macrophage colony-stimulating factors (GM-CSF) play an important role in chronic inflammation. Activator protein-1 (AP-1) the superfamily of transcription factors is involved in proliferation, differentiation, apoptosis, and transformation including inflammation. Understanding the function and regulation of proinflammatory factors involved in inflammation may provide the novel therapeutic strategies in the treatment of inflammatory diseases. Our aim of the present study is to investigate the pro-inflammatory cytokines and pattern of AP-1 factors expressed during activation of lung adenocarcinoma A549 cells by Phorbol-12-myristate-13-acetate (PMA) and to understand the anti-inflammatory effect of apigenin. A549 cells were treated with and without PMA or apigenin, and the cell viability was assessed by MTT assay. Expressions of inflammatory mediators and different AP-1 factors were analyzed by semi-quantitative RT-PCR. IL-6 protein secreted was analyzed by ELISA, and expressions of IL-1β, c-Jun, and c-Fos proteins were analyzed by Western blotting. Activation of A549 cells by PMA, induced the expression of pro-inflammatory cytokine (IL-1β, IL-2, IL-6, IL-8, and TNF-α) mRNAs and secretion of IL-6 and the expression of specific AP-1 factors (c-Jun, c-Fos, and Fra-1). Treatment of cells with apigenin, significantly inhibited PMA-stimulated mRNA expression of above pro-inflammatory cytokines, AP-1 factors, cyclooxygenase-2, and secretion of IL-6 protein. Results suggested that the AP-1 factors may be involved in inflammation and apigenin has anti-inflammatory effect, which may be useful for therapeutic management of lung inflammatory diseases. © 2015, Springer Science+Business Media New York

Interplay of nuclear receptors (ER, PR, and GR) and their steroid hormones in MCF-7 cells

Steroid hormones and their nuclear receptors play a major role in the development and progression of breast cancer. MCF-7 cells are triple-positive breast cancer cells expressing estrogen receptor (ER), progesterone receptor (PR), and glucocorticoid receptor (GR). However, interaction and their role in expression pattern of activator protein (AP-1) transcription factors (TFs) are not completely understood. Hence, in our study, MCF-7 cells were used as an in vitro model system to study the interplay between the receptors and hormones. MCF-7 cells were treated with estradiol-17β (E2), progesterone (P4), and dexamethasone (Dex), alone or in combination, to study the proliferation of cells and expression of AP-1 genes. MTT assay results show that E2 or P4 induced the cell proliferation by more than 35 %, and Dex decreased the proliferation by 26 %. E2 and P4 are found to increase ERα by more than twofold and c-Jun, c-Fos, and Fra-1 AP-1 TFs by more than 1.7-fold, while Dex shows opposite effect of E2- or P4-induced effect as well as effect on the expression of nuclear receptors and AP-1 factors. E2 antagonist Fulvestrant (ICI 182,780) found to reduce proliferation and E2-induced expression of AP1-TFs, while P4 or Dex antagonist Mifepristone (RU486) is found to block GR-mediated expression of NRs and AP-1 mRNAs. Results suggest that E2 and P4 act synergistically, and Dex acts as an antagonist of E2 and P4

Aqueous areca nut extract induces oxidative stress in human lung epithelial A549 cells: Probable role of p21 in inducing cell death

Areca nut a well-known masticator used across globe. Habitual chewing of areca nut is associated with serious oral health effects. However, the role of areca nut in oxidative stress induction and cell death is less understood. Hence, in the present study we aimed to evaluate the toxic mechanism of areca nut extract on human lung epithelial A549 cells. Cells were treated with or without aqueous areca nut extract and cell viability was measured by MTT assay. Cells treated with areca nut extract show reduced viability in a dose dependent manner with the IC50 of 0.5 concentration. Areca nut extract induced the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with leakage of lactate dehydrogenase (LDH) enzyme. Cells with continuous exposure of areca nut extract depletes the free radical neutralizing anti-oxidant enzymes like superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) and Glutathione-S-transferase (GST). Further, the analysis of mRNA expression of apoptotic genes and cell cycle regulators show decreased expression of anti-apoptotic gene (Bcl-2), Cyclin E1, Cyclin D1, CDK4, Rb and p53 whereas induced expression of p21 and marginal increase of pro-apoptotic gene (Bax) confirms the toxic nature of areca nut. Thus, cell death due to areca nut exposure may be through different mechanism rather than the conventional apoptotic pathway, where p21 induction might be independent of p53 action, which possibly suggests that there may be a role of p21 in oxidative stress induced cell death. Further FACS analysis confirms cell death in areca nut treated cells. © 2016 Elsevier Inc

Fermionic Molecular Dynamics for nuclear dynamics and thermodynamics

A new Fermionic Molecular Dynamics (FMD) model based on a Skyrme functional is proposed in this paper. After introducing the basic formalism, some first applications to nuclear structure and nuclear thermodynamics are presentedComment: 5 pages, Proceedings of the French-Japanese Symposium, September 2008. To be published in Int. J. of Mod. Phys.

Wavy stripes and squares in zero P number convection

A simple model to explain numerically observed behaviour of chaotically varying stripes and square patterns in zero Prandtl number convection in Boussinesq fluid is presented. The nonlinear interaction of mutually perpendicular sets of wavy rolls, via higher mode, may lead to a competition between the two sets of wavy rolls. The appearance of square patterns is due to the secondary forward Hopf bifurcation of a set of wavy rolls.Comment: 8 pages and 3 figures, late

Cadmium induces oxidative stress and apoptosis in lung epithelial cells

Cadmium (Cd) is one of the well-known highly toxic environmental and industrial pollutants. Cd first accumulates in the nucleus and later interacts with zinc finger proteins of antiapoptotic genes and inhibit the binding of transcriptional factors and transcription. However, the role of Cd in oxidative stress and apoptosis is less understood. Hence, the present study was undertaken to unveil the mechanism of action. A549 cells were treated with or without Cd and cell viability was measured by MTT assay. Treatment of cells with Cd shows reduced viability in a dose-dependent manner with IC50 of 45 μM concentration. Cd significantly induces the reactive oxygen species (ROS), lipid peroxidation followed by membrane damage with the leakage of lactate dehydrogenase (LDH). Cells with continuous exposure of Cd deplete the antioxidant super oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzymes. Further, analysis of the expression of genes involved in apoptosis show that both the extrinsic and intrinsic apoptotic pathways were involved. Death receptor marker tumor necrosis factor-α (TNF-α), executor caspase-8 and pro-apoptotic gene (Bax) were induced, while antiapoptotic gene (Bcl-2) was decreased in Cd-treated cells. Fluorescence-activated cell sorting (FACS) analysis further confirms the induction of apoptosis in Cd-treated A549 cells

Differential expression of AP-1 transcription factors in human prostate LNCaP and PC-3 cells: role of Fra-1 in transition to CRPC status

Androgen receptor (AR) signaling axis plays a vital role in the development of prostate and critical in the progression of prostate cancer. Androgen withdrawal initially regresses tumors but eventually develops into aggressive castration-resistant prostate cancer (CRPC). Activator Protein-1 (AP-1) transcription factors are most likely to be associated with malignant transformation in prostate cancer. Hence, to determine the implication of AR and AP-1 in promoting the transition of prostate cancer to the androgen-independent state, we used AR-positive LNCaP and AR-negative PC-3 cells as an in vitro model system. The effect of dihydrotestosterone or anti-androgen bicalutamide on the cell proliferation and viability was assessed by MTT assay. Expression studies on AR, marker genes-PSA, TMPRSS2, and different AP-1 factors were analyzed by semi-quantitative RT-PCR and expressions of AR and Fra-1 proteins were analyzed by Western blotting. Dihydrotestosterone induced the cell proliferation in LNCaP with no effect on PC-3 cells. Bicalutamide decreased the viability of both LNCaP and PC-3 cells. Dihydrotestosterone induced the expression of AR, PSA, c-Jun, and Fra-1 in LNCaP cells, and it was c-Jun and c-Fos in case of PC-3 cells, while bicalutamide decreased their expression. In addition, constitutive activation and non-regulation of Fra-1 by bicalutamide in PC-3 cells suggested that Fra-1, probably a key component, involved in transition of aggressive androgen-independent PC-3 cells with poor prognosis. © 2017, Springer Science+Business Media New York

Impact Sensitivity of RDX and Viton Compositions Prepared by Co-precipitation Method

Desensitisation of explosive materials using polymers is an important area in safe utilisation of explosives in various applications. The RDX/viton composition has been developed using co-precipitation method with varying content of viton, ranging from 5 to 35 wt per cent. RDX and viton were dissolved in acetone which is a common solvent for RDX and viton, and then the acetone was extracted from the solution by distillation resulting in homogeneous RDX/viton composition. Infrared spectroscopy studies indicated presence of RDX and viton in the resulting compositions. Thermogravimetric and differential thermal analysis studies made on yielded compositions confirmed that RDX is present in the composition in desired content. The shift in exotherm of RDX/viton composition as compared to RDX showed that polymer-bonded RDX compositions are more stable. The impact sensitivity studies showed that sensitivity of RDX/viton composition decreased with increasing content of viton. The similar trend was observed for friction sensitivity. The co-precipitation method has been found to be advantages to obtain homogeneous composition of RDX and viton (with viton content up to 25 wt per cent) as revealed by linear trend in sensitivity data measurements. It has been demonstrated that the sensitivity of RDX can be tailored within a wide range using viton so as to suit in desired applications.Defence Science Journal, Vol. 65, No. 4, July 2015, pp. 287-291, DOI: http://dx.doi.org/10.14429/dsj.65.864

Solving order constraints in logarithmic space.

We combine methods of order theory, finite model theory, and universal algebra to study, within the constraint satisfaction framework, the complexity of some well-known combinatorial problems connected with a finite poset. We identify some conditions on a poset which guarantee solvability of the problems in (deterministic, symmetric, or non-deterministic) logarithmic space. On the example of order constraints we study how a certain algebraic invariance property is related to solvability of a constraint satisfaction problem in non-deterministic logarithmic space

Quasiparticle vanishing driven by geometrical frustration

We investigate the single hole dynamics in the triangular t-J model. We study the structure of the hole spectral function, assuming the existence of a 120 magnetic Neel order. Within the self-consistent Born approximation (SCBA) there is a strong momentum and t sign dependence of the spectra, related to the underlying magnetic structure and the particle-hole asymmetry of the model. For positive t, and in the strong coupling regime, we find that the low energy quasiparticle excitations vanish outside the neighbourhood of the magnetic Goldstone modes; while for negative t the quasiparticle excitations are always well defined. In the latter, we also find resonances of magnetic origin whose energies scale as (J/t)^2/3 and can be identified with string excitations. We argue that this complex structure of the spectra is due to the subtle interplay between magnon-assisted and free hopping mechanisms. Our predictions are supported by an excellent agreement between the SCBA and the exact results on finite size clusters. We conclude that the conventional quasiparticle picture can be broken by the effect of geometrical magnetic frustration.Comment: 6 pages, 7 figures. Published versio