Phosphatidylglycerol provides short-term prophylaxis against respiratory syncytial virus infection

Respiratory syncytial virus (RSV) causes respiratory tract infections in young children, and significant morbidity and mortality in the elderly, immunosuppressed, and immunocompromised patients and in patients with chronic lung diseases. Recently, we reported that the pulmonary surfactant phospholipid palmitoyl-oleoyl-phosphatidylglycerol (POPG) inhibited RSV infection in vitro and in vivo by blocking viral attachment to epithelial cells. Simultaneous application of POPG along with an RSV challenge to mice markedly attenuated infection and associated inflammatory responses. Based on these findings, we expanded our studies to determine whether POPG is effective for prophylaxis and postinfection treatment for RSV infection. In vitro application of POPG at concentrations of 0.2–1.0 mg/ml at 24 h after RSV infection of HEp-2 cells suppressed interleukin-8 production up to 80% and reduced viral plaque formation by 2–6 log units. In vivo, the turnover of POPG in mice is relatively rapid, making postinfection application impractical. Intranasal administration of POPG (0.8–3.0 mg), 45 min before RSV inoculation in mice reduced viral infection by 1 log unit, suppressed inflammatory cell appearance in the lung, and suppressed virus-elicited interferon-γ production. These findings demonstrate that POPG is effective for short-term protection of mice against subsequent RSV infection and that it has potential for application in humans.     

Verrucarin A, a protein synthesis inhibitor, induces growth inhibition and apoptosis in breast cancer cell lines MDA-MB-231 and T47D

Verrucarin A (VA), a protein synthesis inhibitor, derived from the pathogen fungus Myrothecium verrucaria, inhibits growth of leukemia cell lines and activates caspases and apoptosis and inflammatory signaling in macrophages. We have investigated VA-induced growth inhibition in breast cancer cells MDA-MB-231 and T47D and, particularly, the mechanism of VA-induced apoptosis. VA treatment brought about apoptotic cell death in a dose- and time-dependent manner which was associated with chromatin condensation, cell shrinkage, nuclear fragmentation and intracellular ROS production. Mitochondrial membrane depolarization, activation of caspase-3, down-regulation of Bcl-2 expression and up-regulation of Bax and p53 expression were observed. VA thus affects the viability of both the breast cancer cells by triggering ROS-mediated intrinsic mechanism of apoptosis.     

Engineering Escherichia coli with acrylate pathway genes for propionic acid synthesis and its impact on mixed-acid fermentation

Fermentation-derived products are in greater demand to meet the increasing global market as well as to overcome environmental problems. In this work, Escherichia coli has been metabolically engineered with acrylate pathway genes from Clostridium propionicum for the conversion of d-lactic acid to propionic acid. The introduced synthetic pathway consisted of seven genes encoding the enzymes propionate CoA-transferase (Pct), lactoyl-CoA dehydratase (Lcd) and acryloyl-CoA reductase (Acr). The engineered strain synthesised propionic acid at a concentration of 3.7?±?0.2 mM upon fermentation on glucose. This low production level could be attributed to the low activity of the recombinant enzymes in particular the rate-limiting enzyme, Acr. Interestingly, the recombinant pathway caused an increased lactate production in E. coli with a yield of 1.9 mol/mol of glucose consumed along with a decrease in other by-products. Down-regulation of the pfl (pyruvate formate lyase) genes and a possible inhibition of Pfl activity by the acrylate pathway intermediate, acryloyl-CoA, could have reduced carbon flow to the Pfl pathway with a concomitant increase in lactate production. This study reports a novel way of synthesising propionic acid by employing a non-native, user-friendly organism through metabolic engineering.     

An Insight for Potent In-Vitro Antioxidant Status of Short-Chain Peptides

International Journal of Peptide Research and Therapeutics - Peptides test drug 1, 2, 3 and 4 coded as RK, KH, RRH, and RRK were subjected to in-vitro antioxidant screening methods for the...     

Multifarious Pharmacological Applications of Green Routed Eco-Friendly Iron Nanoparticles Synthesized by Streptomyces Sp. (SRT12)

Biological Trace Element Research - A simple, eco-friendly, green routine co-precipitation method was experimented to synthesize iron nanoparticles (Fe-NPs) using the cell-free supernatant of...     

A role for F-actin in hexokinase-mediated glucose signaling

HEXOKINASE1 (HXK1) from Arabidopsis (Arabidopsis thaliana) has dual roles in glucose (Glc) signaling and in Glc phosphorylation. The cellular context, though, for HXK1 function in either process is not well understood. Here we have shown that within normal experimental detection limits, AtHXK1 is localized continuously to mitochondria. Two mitochondrial porin proteins were identified as capable of binding to overexpressed HXK1 protein, both in vivo and in vitro. We also found that AtHXK1 can be associated with its structural homolog, F-actin, based on their coimmunoprecipitation from transgenic plants that overexpress HXK1-FLAG or from transient expression assays, and based on their localization in leaf cells after cryofixation. This association might be functionally important because Glc signaling in protoplast transient expression assays is compromised by disruption of F-actin. We also demonstrate that Glc treatment of Arabidopsis seedlings rapidly and reversibly disrupts fine mesh actin filaments. The possible roles of actin in HXK-dependent Glc signaling are discussed.     

Actin-related proteins in chromatin-level control of the cell cycle and developmental transitions

Regulating developmental transitions, cell proliferation and cell death through differential gene expression is essential to the ontogeny of all multicellular organisms. Chromatin remodeling is an active process that is necessary for managing the genome-wide suppression of gene activities resulting from DNA compaction. Recent data in plants suggest a general theme, whereby chromatin remodeling complexes containing nuclear actin-related proteins (ARPs) potentiate the activities of crucial regulatory genes involved in plant growth and development, in addition to their basal activities on a much larger set of genes.     

Bio-efficacy potential of seaweed Gracilaria firma with copepod,Megacyclops formosanus for the control larvae of dengue vector Aedes aegypti

Mosquitoes are the most critical group of insects in the context of public health, because they transmit numerous diseases, causing millions of deaths annually. The frequent use of systemic insecticides to manage insect pests leads to the destabilization of ecosystems and enhanced resistance to insecticides by pests, suggesting a clear need for alternatives. Marine organisms are a rich source of structurally novel and biologically active metabolites, and cyclopoid copepods are prominent predators in many aquatic ecosystems and have been used as biological agents in successful programs to control mosquito larvae. In this study, we determine the effectiveness of the Taiwanese seaweed Gracilaria firma and different solvent extracts combined with the copepod Megacyclops formosanus for controlling Aedes aegypti. A significant larvicidal potential was recorded after seaweed extract treatment against the dengue vector A. aegypti. Larval mortality was observed after 24 h of exposure in laboratory. All extracts exhibited larvicidal effects; however, the highest larval mortality was observed in the methanol extract of G. firma against A. aegypti larvae (LC₅₀ = 0.251%). The methanol extract of G. firma was more effective than the other extracts and is an ideal eco-friendly approach for the control larvae of the dengue vector A. aegypti.