Bioinformatic networks: molecular reticles for pinpointing pharmacological target selection.

Bridging centrality was developed as a novel metric to capitalize on rich biological networks and enable selection of therapeutically efficient, druggable candidates. Through incorporation of local and global network properties, targetable nodes are identified that harbor latent capacity to intercept informational flow without compromising systemic functionality. Translational implementation holds potential for increased therapeutic specificity and offers opportunities to add value to drug discovery and development through facilitation of individualized treatment.

Nuclear transport: target for therapy.

Drugs directed at plasma membrane receptors target environment-cell interactions and are the mainstay of clinical pharmacology. Decoding mechanisms that govern intracellular signaling has recently opened new therapeutic avenues for interventions at cytosol-organellar interfaces. The nuclear envelope and nuclear transport machinery have emerged central in the discovery and development of experimental therapeutics capable of modulating cellular genetic programs. Insight into nucleocytoplasmic exchange has unmasked promising anticancer, antiviral, and anti-inflammatory strategies.

Differential antioxidant properties of red wine in water soluble and lipid soluble peroxyl radical generating systems.

Red wine and its components have been shown to possess cardioprotective and anti-atherogenic effects. Additionally, red wine and many of its components like catechin, epicatechin, rutin, transresveratrol and quercetin possess antioxidant properties. Oxidized low density lipoprotein (LDL) is involved in the development of an atherosclerotic lesion. Red wine, therefore, may be anti-atherogenic because of its antioxidant effects on LDL modification. This study examined the antioxidant effects of catechin, epicatechin, rutin, transresveratrol, quercetin and Merlot wines on LDL oxidation. Merlot was chosen because although other red wines have been tested, limited information exists for this variety. Oxidation was carried out with AAPH (2,2'-Azo-bis(2-amidinopropane) dihydrochloride) and AMVN (2,2'-Azo-bis(2,4-dimethylvaleronitrile)), as water and lipid soluble peroxyl radical generating systems (FRGS), respectively. This allowed us to determine the lipophilic antioxidant characteristics of the wine and its components. Conjugated diene assays were used to measure LDL oxidation over 6 hrs. In an AAPH system, all polyphenolic compounds except transresveratrol displayed an antioxidant effect. LDL oxidation by AAPH was also inhibited by aliquots of Merlot wine. No antioxidant effects were observed in an AMVN environment except for a mild antioxidant effect by quercetin. Surprisingly, incubation of LDL with Merlot wine strongly protected against oxidation by AMVN. In summary, the five phenolic compounds displayed antioxidant effects in a water soluble free radical generating system, but only quercetin showed this in a lipid soluble one. However, red wine inhibited LDL oxidation by both water and lipid soluble free radical generating systems. Our data suggest, therefore, that red wines contain unidentified antioxidants that provide protection against LDL oxidation within a lipid soluble environment.

Differential antioxidant properties of red wine in water soluble and lipid soluble peroxyl radical generating systems.

Red wine and its components have been shown to possess cardioprotective and anti-atherogenic effects. Additionally, red wine and many of its components like catechin, epicatechin, rutin, transresveratrol and quercetin possess antioxidant properties. Oxidized low density lipoprotein (LDL) is involved in the development of an atherosclerotic lesion. Red wine, therefore, may be anti-atherogenic because of its antioxidant effects on LDL modification. This study examined the antioxidant effects of catechin, epicatechin, rutin, transresveratrol, quercetin and Merlot wines on LDL oxidation. Merlot was chosen because although other red wines have been tested, limited information exists for this variety. Oxidation was carried out with AAPH (2,2'-Azo-bis(2-amidinopropane) dihydrochloride) and AMVN (2,2'-Azo-bis(2,4-dimethylvaleronitrile)), as water and lipid soluble peroxyl radical generating systems (FRGS), respectively. This allowed us to determine the lipophilic antioxidant characteristics of the wine and its components. Conjugated diene assays were used to measure LDL oxidation over 6 hrs. In an AAPH system, all polyphenolic compounds except transresveratrol displayed an antioxidant effect. LDL oxidation by AAPH was also inhibited by aliquots of Merlot wine. No antioxidant effects were observed in an AMVN environment except for a mild antioxidant effect by quercetin. Surprisingly, incubation of LDL with Merlot wine strongly protected against oxidation by AMVN. In summary, the five phenolic compounds displayed antioxidant effects in a water soluble free radical generating system, but only quercetin showed this in a lipid soluble one. However, red wine inhibited LDL oxidation by both water and lipid soluble free radical generating systems. Our data suggest, therefore, that red wines contain unidentified antioxidants that provide protection against LDL oxidation within a lipid soluble environment. (Mol Cell Biochem 263: 211-215, 2004).

Comparative analysis of the phenolic content of selected Chilean, Canadian and American Merlot red wines.

Flavonoids are a group of naturally occurring antioxidant compounds found in wine that are thought to have therapeutic importance in cardiovascular disease. The flavonoid content of red wines can differ as a function of the variety of wine examined. Since there is a paucity of data on the content of these antioxidants in Merlot wine, we used high performance liquid chromatography to identify and compare catechin, epicatechin, rutin, transresveratrol and quercetin levels in selected Merlot wines from Canada, Chile and the United States. Additionally, antioxidant content was correlated with the price of the wine. Catechin content was the most abundant when compared to the other four phenolic compounds. The concentrations of each compound in the Merlot wines also varied as a function of the country of origin. Catechin and transresveratrol occurred in significantly lower concentrations in Merlots from the United States. The lowest levels of rutin were observed in Canadian Merlots. Quercetin occurred at significantly higher levels in Chilean Merlots. Wine prices were inversely correlated with catechin concentration. Merlot wine represents a source of antioxidants that may have an impact on cardiovascular disease.

Evidence for protection of nitrogenase from O(2) by colony structure in the aerobic diazotroph Gluconacetobacter diazotrophicus.

Gluconacetobacter diazotrophicus is an endophytic diazotroph of sugarcane which exhibits nitrogenase activity when growing in colonies on solid media. Nitrogenase activity of G. diazotrophicus colonies can adapt to changes in atmospheric partial pressure of oxygen (pO(2)). This paper investigates whether colony structure and the position of G. diazotrophicus cells in the colonies are components of the bacterium's ability to maintain nitrogenase activity at a variety of atmospheric pO(2) values. Colonies of G. diazotrophicus were grown on solid medium at atmospheric pO(2) of 2 and 20 kPa. Imaging of live, intact colonies by confocal laser scanning microscopy and of fixed, sectioned colonies by light microscopy revealed that at 2 kPa O(2) the uppermost bacteria in the colony were very near the upper surface of the colony, while the uppermost bacteria of colonies cultured at 20 kPa O(2) were positioned deeper in the mucilaginous matrix of the colony. Disruption of colony structure by physical manipulation or due to 'slumping' associated with colony development resulted in significant declines in nitrogenase activity. These results support the hypothesis that G. diazotrophicus utilizes the path-length of colony mucilage between the atmosphere and the bacteria to achieve a flux of O(2) that maintains aerobic respiration while not inhibiting nitrogenase activity.