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Animals and humans are exposed each day to a multitude of chemicals in the air, water and food. They have developed a battery of enzymes and transporters that facilitate the biotransformation and elimination of these compounds. Moreover, a majority of these enzymes and transporters are inducible due to the activation of xenobiotic receptors which act as transcription factors for the regulation of their target genes (such as xenobiotic metabolizing enzymes, see below §4 for the AhR). These receptors include several members of the nuclear/steroid receptor family (CAR for Constitutive Androstane Receptor, PXR for Pregnane X Receptor) but also the Aryl hydrocarbon Receptor or AhR, a member of the bHLH-PAS family (basic Helix-Loop-Helix - Period/ARNT/Single minded). In addition to the regulation of xenobiotic metabolism, numerous alternative functions have been characterized for the AhR since its discovery. These alternative functions will be described in this review along with its endogenous functions as revealed by experiments performed on knock-out animals.

An infectious retroviral particle contains 1000–1500 molecules of the nucleocapsid protein (NC) that cover the diploid RNA genome. NC is a small zinc finger protein that possesses nucleic acid chaperone activity that enables NC to rearrange DNA and RNA molecules into the most thermodynamically stable structures usually those containing the maximum number of base pairs. Thanks to the chaperone activity, NC plays an essential role in reverse transcription of the retroviral genome by facilitating the strand transfer reactions of this process. In addition, these reactions are involved in recombination events that can generate multiple drug resistance mutations in the presence of anti-HIV-1 drugs. The strand transfer reactions rely on base pairing of folded DNA/RNA structures. The molecular mechanisms responsible for NC-mediated strand transfer reactions are presented and discussed in this review. Antiretroviral strategies targeting the NC-mediated strand transfer events are also discussed.

Vanadate, a protein tyrosine phosphatase inhibitor which elicits insulin-like effects, has previously been shown to inhibit expression of the insulin receptor gene at the transcriptional level in rat hepatoma cells. In an attempt to identify the DNA sequence and transcription factors potentially involved in this effect, a fragment of the proximal 5′flanking region of the IR gene (−1143/−252 upstream the ATG codon) has been cloned and functionally characterized. RNase protection allowed the identification of several transcription start sites in the conserved region of the gene, among which two major sites at −455 and −396. Upon fusion to the luciferase gene and transient transfection into hepatoma cells, the −1143/−252 fragment showed promoter activity. This was unaffected by deletion of the −1143/−761 sequence, but markedly decreased (90%) by additional deletion of the −760/−465 sequence. Treatment of hepatoma cells with vanadate led to a dose-dependent decrease in promoter activity of the 1143/−252, −760/−252 and −464/−252 constructs (change relative to untreated cells, 40, 55 and 23% at 125 μM, and 70, 85 and 62% at 250 μM, respectively). These data suggest that although the entire DNA sequence upstream the transcription start sites is probably involved in vanadate-induced inhibition, the short sequence downstream of position −464 and is sufficient for inhibition. Potential targets of vanadate are the transcription factors FoxO1 and HMGA1, two downstream targets of the insulin signaling pathway which have been shown to mediate the inhibitory effect of insulin on IR gene expression.

Introduction

Production of isoprostanes (IsoPs) is enhanced after acute, intense, and prolonged exercise, in untrained subjects. This effect is greater in older subjects. The present study aims to delineate the profile of acute-exercise-induced IsoPs levels in young and older endurance-trained subjects.

Methods

All included subjects were male, young (n = 6; 29 yrs ± 5.7) or older (n = 6; 63.7 yrs ± 2.3), and competitors. The kinetics of F₂-IsoPs in blood-sera was assessed at rest, for the maximal aerobic exercise power (MAP) corresponding to the cardio-respiratory fitness index and after a 30-min recovery period.

Results

No significant time effect on F₂-IsoPs kinetics was identified in young subjects. However, in older athletes, F₂-IsoPs blood-concentrations at the MAP were higher than at rest, whereas these blood-concentrations did not differ between rest and after the 30-min recovery period.

Conclusion

Because plasma glutathione (GSH) promotes the formation of some F₂-IsoPs, we suggest that the surprising decrease in F₂-IsoPs levels in older subjects would be caused by decreased GSH under major ROS production in older subjects. We argue that the assessment F₂-IsoPs in plasma as biomarkers of the aging process should be challenged by exercise to improve the assessment of the functional response against reactive oxygen species in older subjects.

The recombinant fucolectin-related protein (FRP) of unknown function, encoded by the SP2159 gene of Streptococcus pneumoniae, was expressed in E. coli. In this study, its glycan-recognition epitopes and their binding potencies were examined by enzyme-linked lectinosorbent and inhibition assays. The results indicate that FRP reacted strongly with human blood group ABH and l-Fucα1→2-active glycotopes and in their polyvalent (super) forms. When expressed by mass relative potency, the binding affinities of FRP to poly-l-Fucα1→glycotopes were about 5.0 × 10⁵ folds higher than that of the mono-l-Fucα1→glycotope form. This unique binding property of FRP can be used as a special tool to differentiate complex forms of l-Fucα1→2 and other forms of glycotopes.

Herbal drugs, on which 80% of the world's population rely, are relatively safe over conventional drugs. Conventional drugs are costly, have serious side effects and hence over the past few decades researchers have focused on drug discovery from herbal medicines or botanical sources. The majority of new herbal drugs have been generated from secondary metabolites (alkaloids, terpenoids and phenolic compounds) of plant metabolism. Till date, only a small fraction of the vast diversity of plant metabolism has been explored for the production of new medicines and other products. The emergence of new herbal genomics research, medicinal plant genomics consortium, together with advances in other omics information may help for the speedy discovery of previously unknown metabolic pathways and enzymes. This review highlights the importance of genomics research in the discovery of some previously unknown enzymes/pathways which may make significant contributions in plant metabolic biology and may be used for the future discovery of many new pharmaceutical agents.

The sodium leak channel NALCN is poorly understood, but is reported as a Na⁺-permeable, nonselective cation leak channel which regulates resting membrane potential and electrical excitability. Previous work has indicated that NALCN currents can be stimulated by activation of several G protein coupled receptors, including the M3 muscarinic receptor. We undertook a study using voltage clamp electrophysiology to investigate NALCN currents. We compared currents elicited from untransfected control HEK239 cells in response to M3R agonists muscarine or Oxotremorine M to currents elicited from cells transfected with M3R only or the M3R plus NALCN and cDNA encoding accessory proteins UNC-80 and Src. Currents with similar properties were observed in all three groups of cells in response to muscarine agonists, in similar proportions of cells tested, from all three groups of cells. Our findings do not support previous electrophysiological studies suggesting that heterologously expressed NALCN functions as a Na⁺ leak channel in HEK293 cells. More research will be required to determine the molecular requirements for successful expression of the NALCN channel.

Research on the biological effects of essential oils on human skin cells is scarce. In the current study, we primarily explored the biological activities of 10 essential oils (nine single and one blend) in a pre-inflamed human dermal fibroblast system that simulated chronic inflammation. We measured levels of proteins critical for inflammation, immune responses, and tissue-remodeling processes. The nine single oils were distilled from Citrus bergamia (bergamot), Coriandrum sativum (cilantro), Pelargonium graveolens (geranium), Helichrysum italicum (helichrysum), Pogostemon cablin (patchouli), Citrus aurantium (petitgrain), Santalum album (sandalwood), Nardostachys jatamansi (spikenard), and Cananga odorata (ylang ylang). The essential oil blend (commercial name Immortelle) is composed of oils from frankincense, Hawaiian sandalwood, lavender, myrrh, helichrysum, and rose. All the studied oils were significantly anti-proliferative against these cells. Furthermore, bergamot, cilantro, and spikenard essential oils primarily inhibited protein molecules related to inflammation, immune responses, and tissue-remodeling processes, suggesting they have anti-inflammatory and wound healing properties. Helichrysum and ylang ylang essential oils, as well as Immortelle primarily inhibited tissue remodeling-related proteins, suggesting a wound healing property. The data are consistent with the results of existing studies examining these oils in other models and suggest that the studied oils may be promising therapeutic candidates. Further research into their biological mechanisms of action is recommended. The differential effects of these essential oils suggest that they exert activities by different mechanisms or pathways, warranting further investigation. The chemical composition of these oils was analyzed using gas chromatography–mass spectrometry.