Stachyonic Acid: A Dengue Virus Inhibitor from Basilicum polystachyon

Stachyonic acid A, arising from the first in-depth phytochemical investigation of the herb Basilicum polystachyon, was found to display potent inhibitory activity against dengue virus, with limited cytotoxicity. Andrographolide, a known dengue virus inhibitor and closely related labdane-type diterpene, is structurally more complex but displayed poor antiviral activity in the PRNT assay, and increased cytotoxicity in comparison. Furthermore, a Diels–Alder reaction with PTAD identified the active pharmacophore of stachyonic acid to be the conjugated diene.     

Magnetic properties of Al-based icosahedral alloys

One of the fundamental questions which has not been answered sufficiently well till today is whether a nonclassical symmetry such as an icosahedral one would induce any special and distinctive features in the physical properties of the systems. Most theoretical investigations indicate that there are unique features in the electronic structure on account of icosahedral symmetry which could for example, influence the magnetic properties significantly. Experimental studies, particularly, on Al-based icosahedral alloys, have shown a large variation in magnetic properties ranging from diamagnetic to Curie like and Pauli paramagnetism on one hand and ferromagnetic and spin glass like behaviour on the other. In the present article, we will concentrate on some aspects of moment formation and variation in magnetic properties in Al-Mn based icosahedral systems and their dependence on the method of preparation which presumably controls and introduces the variable disorder. We will also try to answer some pertinent questions related to magnetism in icosahedral systems such as extent and origin of moment formation existence of magnetic and nonmagnetic Mn sites and distribution of interatomic distances reponsible for variation in magnetic properties.     

Quasicrystalline and related phases in titanium based alloy systems

Amongst the non-aluminium based quasicrystalline alloys, investigations of titanium containing alloys in regard to the occurrence and stability of quasicrystalline phases have aroused considerable interest in recent years. Employing X-ray and TEM techniques a systematic investigation of the influence of substitution for Fe by Si and Ni on the stability of icosahedral phase in rapidly quenched Fe-Ti alloy has been carried out. The occurrence of metastable phases including commensurately modulated phase and the decagonal phase in Fe-Ti-Si system have been found. In addition, the occurrence ofstructural disorder manifested by arcs of diffuse scattering in diffraction patterns and anisotropy in the shape of idffraction spots has also been pointed out. It has been observed that 6 at.% of Si in Fe-Ti-Si system results in the formation of single-phase icosahedral quasicrystals. We have shown that contrary to some earlier reported results on Ti₂Ni, Ti₂Ni(Si) and Ti₅₆Ni₂₃Fe₅Si₁₆ alloys do not possess the icosahedral phase. In Ti₆₈Fe_26−xNi_xSi₆ alloy system, icosahedral phase formation ability is limited to the value of x < 9. The occurrence of icosahedral phase in these alloy systems has been analysed in terms of e/a ratio.     

A mathematical model of combined therapies against cancer using viruses and inhibitors

This paper deals with a procedure for combined therapies against cancer using oncolytic viruses and inhibitors. Replicating genetically modified adenoviruses infect cancer cells, reproduce inside them and eventually cause their death (lysis). As infected cells die, the viruses inside them are released and then proceed to infect other tumor cells. The successful entry of virus into cancer cells is related to the presence of the coxsackie-adenovirus receptor (CAR). Mitogen-activated protein kinase kinase (known as MEK) inhibitors can promote CAR expression, resulting in enhanced adenovirus entry into cancer cells. However, MEK inhibitors can also cause G1 cell-cycle arrest, inhibiting reproduction of the virus. To design an effective synergistic therapy, the promotion of virus infection must be optimally balanced with inhibition of virus production. We introduce a mathematical model to describe the effects of MEK inhibitors and viruses on tumor cells, and use it to explore the reduction of the tumor size that can be achieved by the combined therapies. Furthermore, we find an optimal dose of inhibitor: P _optimal = 1 − μ/δ for a certain initial density of cells (where μ is the removal rate of the dead cells and δ is the death rate of the infected cells). The optimal timing of MEK inhibitors is also numerically studied. This work was supported by the National Natural Science Foundation of China (Grant No. 10571023)     

New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS‐6620, remdesivir and pyrazofurin) are C‐nucleosides, and two of them (GS‐6620, remdesivir) also contain a phosphoramidate part. The C‐nucleoside and phosphoramidate (and for the adenine analogues the 1′‐cyano group as well) may be considered as essential attributes for their antiviral activity.     

T4 virus-based toolkit for the direct synthesis and 3D organization of metal quantum particles

One of the challenges in building superstructures based on small metal particles is producing stable interparticle separation. Herein, we present a novel assembly method based on the use of the T4 bacteriophage capsid as a scaffold for the construction of 3D monodisperse metal–particle arrays. The highly regular and symmetrical protein surface of the T4 capsid allows the site‐directed adsorption and subsequent reduction of metal ions, thus permitting the growth of metal particles in situ to enable them to exist at a quantum size with a high degree of monodispersity. Both these characteristics contribute to a great improvement in the electrocatalytic activity of the patterned noble‐metal particles. Organized magnetic particles as small as 2–4 nm still maintain an observable ferromagnetic behavior, which makes them promising for a variety of possible biomedical applications.     

Role of inducible nitric oxide synthase on the development of virus-associated asthma exacerbation which is dependent on Th1 and Th17 cell responses

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.