Angiotensin preconditioning of the heart

Angiotensin II (Ang II) has been found to exert preconditioning-like effect on mammalian hearts. Diverse mechanisms are known to exist to explain the cardioprotective abilities of Ang II preconditioning. The present study hypothesized, based on the recent report that Ang II generates reactive oxygen species (ROS) through NADPH oxidase, that Ang II preconditioning occurs through redox cycling. To test this hypothesis, a group of rat hearts was treated with Ang II in the absence or presence of an NADPH oxidase inhibitor, apocynin; or a cell-permeable ROS scavenger, N-acetyl cysteine (NAC). Ang II pretreatment improved postischemic ventricular recovery; reduced myocardial infarction; and decreased the number of cardiomyocyte apoptosis, indicating its ability to precondition the heart against ischemic injury. Both apocynin and NAC almost abolished the preconditioning ability of Ang II. Ang II resulted in increase in ROS activity in the heart, which was reduced by either NAC or apocynin. Ang II also increased both the NADPH oxidase subunits gp91 phox and p22phox mRNA expression, which was abolished with apocynin and NAC. Our results thus demonstrate that the Ang II preconditioning was associated with enhanced ROS activities and increased NADPH oxidase subunits p22phox and gp91phox expression. Both NAC and apocynin reduced ROS activities simultaneously abolishing preconditioning ability of Ang II, suggesting that Ang II preconditioning occurs through redox cycling. That both NAC and apocynin reduced ROS activities and abolished Ang II-mediated increase in p22phox and gp91phox activity further suggest that such redox cycling occurs via both NADPH oxidase-dependent and -independent pathways.     

Fibronectin–integrin mediated signaling in human cervical cancer cells (SiHa)

Interaction between cell surface integrin receptors and extracellular matrix (ECM) components plays an important role in cell survival, proliferation, and migration, including tumor development and invasion of tumor cells. Matrix metalloproteinases (MMPs) are a family of metalloproteinases capable of digesting ECM components and are important molecules for cell migration. Binding of ECM to integrins initiates cascades of cell signaling events modulating expression and activity of different MMPs. The aim of this study is to investigate fibronectin–integrin-mediated signaling and modulation of MMPs. Our findings indicated that culture of human cervical cancer cell (SiHa) on fibronectin-coated surface perhaps sends signals via fibronectin–integrin-mediated signaling pathways recruiting focal adhesion kinase (FAK) extracellular signal regulated kinase (ERK), phosphatidyl inositol 3 kinase (PI-3K), integrin-linked kinase (ILK), nuclear factor-kappa B (NF-κB), and modulates expression and activation of mainly pro-MMP-9, and moderately pro-MMP-2 in serum-free culture medium.     

Degradation of diesel oil by immobilized <Emphasis Type="Italic">Candida tropicalis</Emphasis> and biofilm formed on gravels

The performance of diesel oil degradation by Candida tropicalis immobilized on various conventional matrices (sodium alginate, carboxyl methyl cellulose, chitosan) and biowaste materials (wheat bran, sawdust, peanut hull powder) was investigated using the method of entrapment and physical adsorption. The yeast species immobilized in wheat bran showed enhanced efficiency in degrading diesel oil (98%) compared to free cells culture (80%) over a period of 7 days. Copious amount of exopolysaccharides were also produced in the presence of diesel oil. The biofilm forming ability of C. tropicalis on PVC strips was evaluated using XTT (2,3-bis[2-methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) reduction assay and monitored by scanning electron microscopy and atomic force microscopy. Yeast biofilm formed on gravels showed 97% degradation of diesel oil over a period of 10 days. The potential use of the biofilms for preparing trickling filters (gravel particles), for attenuating hydrocarbons in oily liquid wastes before their disposal in the open environment is suggested and discussed. This is the first successful attempt for ‘artificially’ establishing hydrocarbon degrading yeast biofilm on solid substrates.     

Yin Yang Gene Expression Ratio Signature for Lung Cancer Prognosis

Many studies have established gene expression-based prognostic signatures for lung cancer. All of these signatures were built from training data sets by learning the correlation of gene expression with the patients'' survival time. They require all new sample data to be normalized to the training data, ultimately resulting in common problems of low reproducibility and impracticality. To overcome these problems, we propose a new signature model which does not involve data training. We hypothesize that the imbalance of two opposing effects in lung cancer cells, represented by Yin and Yang genes, determines a patient’s prognosis. We selected the Yin and Yang genes by comparing expression data from normal lung and lung cancer tissue samples using both unsupervised clustering and pathways analyses. We calculated the Yin and Yang gene expression mean ratio (YMR) as patient risk scores. Thirty-one Yin and thirty-two Yang genes were identified and selected for the signature development. In normal lung tissues, the YMR is less than 1.0; in lung cancer cases, the YMR is greater than 1.0. The YMR was tested for lung cancer prognosis prediction in four independent data sets and it significantly stratified patients into high- and low-risk survival groups (p = 0.02, HR = 2.72; p = 0.01, HR = 2.70; p = 0.007, HR = 2.73; p = 0.005, HR = 2.63). It also showed prediction of the chemotherapy outcomes for stage II & III. In multivariate analysis, the YMR risk factor was more successful at predicting clinical outcomes than other commonly used clinical factors, with the exception of tumor stage. The YMR can be measured in an individual patient in the clinic independent of gene expression platform. This study provided a novel insight into the biology of lung cancer and shed light on the clinical applicability.     

Efficacy of Cyclin Dependent Kinase 4 Inhibitors as Potent Neuroprotective Agents against Insults Relevant to Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF) deprivation and oligomeric beta amyloid (Aβ) that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for AD.     

Toxicity of Essential Oil from a New Strain of Ocimum gratissimum (Clocimum) against Betelvine Pathogenic Fungi

The leaves of Ocimum gratissimum (Clocimum) exhibited strong volatile fungitoxicity against betelvine (Piper betle L.) pathogens—Alternaria alternata, Colletotrichum capsici and Sclerotium rolfsii. Fifteen compounds could be identified from the fungitoxic constituents—the essential oil. The oil at its minimum inhibitory concentrations of 50, 250 and 500 ppm against S. rolfsii, A. alternata and C. capsici, respectively, was fungistatic, although, fungicidal at higher concentrations. Eugenol was found to be the major fungitoxic principle in the oil. The oil was either equally effective or superior to synthetic commercial fungicides and was non-phytotoxic to the host plants. Thus, the oil can be used as a valuable indigenous and biodegradable agent against fungi that cause losses to the betelvine industry.     

N,O-Diacyl-4-benzoyl-N-phenylhydroxylamines as photoinduced DNA cleaving agents

Photoinduced homolytic fission of nitrogen–oxygen bond in N,O-diacyl-4-benzoyl-N-phenylhydroxylamines using ?310 nm UV light for 10 min produced acylaminyl and acyloxy radicals, which resulted in single strand cleavage of DNA at pH 7.0. Further the DNA cleaving ability of N,O-diacyl-4-benzoyl-N-phenylhydroxylamines found to depend both on its concentration and acyl substituents.