IN-VITRO CYTOTOXICITY ANALYSIS OF TAMOXIFEN CITRATE LOADED CROSS-LINKED GUAR GUM NANOPARTICLES ON JURKAT (HUMAN T-CELL LEUKEMIA) CELL LINE

The present investigation was aimed to study the antiproliferative action of tamoxifen citrate (TMX), a non steroidal antiestrogen, on a human T-cell leukemia cell line, Jurkat, as free drug and TMX loaded guar gum nanoparticles. For this we developed a new formulation containing chemically cross-linked guar gum nanoparticles (GG NPs) loaded with tamoxifen citrate (TMX). Single step (oil in water) emulsion and in-situ polymer cross-linking technique was employed to prepare spherical and smooth surfaced nanoparticles in the size range of 200-300nm. Nanoparticle size and shape was confirmed from observation in transmission electron microscope (TEM) analysis. Cytotoxicity on Jurkat (human T-cell leukemia) cell lines as determined by cell growth inhibition after 48 hrs of incubation indicated that tamoxifen citrate loaded guar gum nanoparticles were as efficient as the free drug when applied to the cancer line. However, the crosslinked guar gum nanoparticles loaded with tamoxifen citrate exhibited sustained release of the drug and delayed apoptosis over a long period of time making it suitable for cancer treatment. Keywords: Nanoparticles, guar gum, tamoxifen citrate, Jurkat (human T-cell leukemia) cell line, cytotoxicity, cell death, WST-1 assay

Environmental toxicity, redox signaling and lung inflammation:the role of glutathione

Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is the most abundant intracellular antioxidant thiol and is central to redox defense during oxidative stress. GSH metabolism is tightly regulated and has been implicated in redox signaling and also in protection against environmental oxidant-mediated injury. Changes in the ratio of the reduced and disulfide form (GSH/GSSG) can affect signaling pathways that participate in a broad array of physiological responses from cell proliferation, autophagy and apoptosis to gene expression that involve H(2)O(2) as a second messenger. Oxidative stress due to oxidant/antioxidant imbalance and also due to environmental oxidants is an important component during inflammation and respiratory diseases such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, acute respiratory distress syndrome, and asthma. It is known to activate multiple stress kinase pathways and redox sensitive transcription factors such as Nrf2, NF-κB and AP-1, which differentially regulate the genes for pro-inflammatory cytokines as well as the protective antioxidant genes. Understanding the regulatory mechanisms for the induction of antioxidants, such as GSH, versus pro-inflammatory mediators at sites of oxidant-directed injuries may allow for the development of novel therapies which will allow pharmacological manipulation GSH synthesis during inflammation and oxidative injury. This article features the current knowledge about the role of GSH in redox signaling, GSH biosynthesis and particularly the regulation of transcription factor Nrf2 by GSH and downstream signaling during oxidative stress and inflammation in various pulmonary diseases. We also discussed the current therapeutic clinical trials using GSH and other thiol compounds, such as N-acetyl-L-cysteine, fudosteine, carbocysteine, erdosteine in environment-induced airways disease

Anisotropic strange star with Tolman–Kuchowicz metric under

In the current article, we study anisotropic spherically symmetric strange star under the background of f(R, T) gravity using the metric potentials of Tolman–Kuchowicz type (Tolman in Phys Rev 55:364, 1939; Kuchowicz in Acta Phys Pol 33:541, 1968) as $$\lambda (r)=\ln (1+ar^2+br^4)$$ and $$\nu (r)=Br^2+2\ln C$$ which are free from singularity, satisfy stability criteria and also well-behaved. We calculate the value of constants a, b, B and C using matching conditions and the observed values of the masses and radii of known samples. To describe the strange quark matter (SQM) distribution, here we have used the phenomenological MIT bag model equation of state (EOS) where the density profile ($$\rho$$) is related to the radial pressure ($$p_r$$) as $$p_r(r)=\frac{1}{3}(\rho -4B_g)$$. Here quark pressure is responsible for generation of bag constant $$B_g$$. Motivation behind this study lies in finding out a non-singular physically acceptable solution having various properties of strange stars. The model shows consistency with various energy conditions, TOV equation, Herrera’s cracking condition and also with Harrison–Zel$$'$$dovich–Novikov’s static stability criteria. Numerical values of EOS parameter and the adiabatic index also enhance the acceptability of our model

Curcumin Restores Corticosteroid Function in Monocytes Exposed to Oxidants by Maintaining HDAC2

Oxidative stress as a result of cigarette smoking is an important etiologic factor in the pathogenesis of chronic obstructive pulmonary disease (COPD), a chronic steroid-insensitive inflammatory disease of the airways. Histone deacetylase-2 (HDAC2), a critical component of the corticosteroid anti-inflammatory action, is impaired in lungs of patients with COPD and correlates with disease severity. We demonstrate here that curcumin (diferuloylmethane), a dietary polyphenol, at nanomolar concentrations specifically restores cigarette smoke extract (CSE)- or oxidative stress–impaired HDAC2 activity and corticosteroid efficacy in vitro with an EC50 of approximately 30 nM and 200 nM, respectively. CSE caused a reduction in HDAC2 protein expression that was restored by curcumin. This decrease in HDAC2 protein expression was reversed by curcumin even in the presence of cycloheximide, a protein synthesis inhibitor. The proteasomal inhibitor, MG132, also blocked CSE-induced HDAC2 degradation, increasing the levels of ubiquitinated HDAC2. Biochemical and gene chip analysis indicated that curcumin at concentrations up to 1 μM propagates its effect via antioxidant-independent mechanisms associated with the phosphorylation-ubiquitin-proteasome pathway. Thus curcumin acts at a post-translational level by maintaining both HDAC2 activity and expression, thereby reversing steroid insensitivity induced by either CSE or oxidative stress in monocytes. Curcumin may therefore have potential to reverse steroid resistance, which is common in patients with COPD and asthma