TIMP-1 Protects Tight Junctions of Brain Endothelial Cells From MMP-Mediated Degradation.

Objective: The blood-brain barrier (BBB) plays a critical role in central nervous system homeostasis, and the integrity of BBB is disrupted in many neurodegenerative diseases. Matrix metalloproteinases (MMPs) degrade the tight junctions (TJs) of endothelial cells and basement membrane components essential to BBB integrity, which leads to increased BBB permeability and allows inflammatory cells and neurotoxic substances to enter the brain. Tissue inhibitors of metalloproteinases (TIMPs), endogenous inhibitors of MMPs, regulate MMP activity, thereby maintaining BBB integrity.

Cannabinoid and Opioid Receptor Affinity and Modulation of Cancer-Related Signaling Pathways of Machaeriols and Machaeridiols from Pers.

Machaeriols and machaeridiols are unique hexahydrodibenzopyran-type aralkyl phytocannabinoids isolated from Pers. Earlier studies of machaeriol A () and B () did not show any affinity for cannabinoid receptor 1 (CB1 or CNR1), although they are structural analogs of psychoactive hexahydrocannabinol. This study comprehensively reports on the affinities of isolated Pers.

In Vitro and In Silico Studies of Neolignans from L. Seeds against Human Cannabinoids and Opioid Receptors.

L. (Magnoliaceae) is a plant of considerable medicinal significance; its flowers and seeds have been used in various traditional remedies. Radioligand binding assays of -hexane seeds extract showed displacement of radioligand for cannabinoid (CB1 and CB2) and opioid δ (delta), κ (kappa), and µ (mu) receptors.

Novel Machaeriol Analogues as Modulators of Cannabinoid Receptors: Structure-Activity Relationships of (+)-Hexahydrocannabinoids and Their Isoform Selectivities.

Machaeriols are an important class of compounds that structurally resemble tetrahydrocannabinol (Δ-THC), with the major differences being inverted stereochemistry at the ring junction as [6a, 10a] and an additional stereocenter at the C9 position of the A-ring due to saturation. A previous study reported that machaeriols did not show any cannabinoid receptor activity, even though these hexahydrodibenzopyran analogues mimic a privileged (+)-tetrahydrocannabinoid scaffold. To unravel structural requisites for modulation of cannabinoid receptors, a simple late-stage divergent approach was undertaken to functionalize the machaeriol scaffold using the Suzuki coupling reaction.

In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower.

Ethnopharmacological Relevance: Nelumbo nucifera Geartn., known as sacred lotus, has been used traditionally in South East Asia as a traditional medicine for various CNS disorders including stress, fever, depression, insomnia, and cognitive conditions.

Aim Of The Study: To investigate the in vitro cannabinoid and opioid receptor binding affinities, and in vivo behavioral actions of Nelumbo flower extracts and to isolate the potential compounds to treat CNS associated disorders.

Flavonoids from Perovskia atriplicifolia and Their in Vitro Displacement of the Respective Radioligands for Human Opioid and Cannabinoid Receptors.

Bioassay-guided fractionation of the leaves of Perovskia atriplicifolia (Russian sage) resulted in the isolation of four previously known flavonoid derivatives, 5-hydroxy-6,7,3',4'-tetramethoxyflavone (1), 5,7-dihydroxy-6,3',4'-trimethoxyflavone (2), 5-hydroxy-6,7,4'-trimethoxyflavone (3), and 5,7-dihydroxy-6,4'-dimethoxyflavone (4). Compounds 1, 3, and 4 showed displacement of the radioligand for the cloned human δ opioid receptor with Ki values ranging from 3.1 to 26.

Longitudinal analysis of vaginal microbiome dynamics in women with recurrent bacterial vaginosis: recognition of the conversion process.

Bacterial vaginosis (BV) affects ∼ 30% of women of reproductive age, has a high rate of recurrence, and is associated with miscarriage, preterm birth, and increased risk of acquiring other sexually transmitted infections, including HIV-1. Little is known of the daily changes in the vaginal bacterial composition as it progresses from treatment to recurrence, or whether any of these might be useful in its prediction or an understanding of its causes. We used phylogenetic branch-inclusive quantitative PCR (PB-qPCR) and Lactobacillus blocked/unblocked qPCR (Lb-qPCR) to characterize longitudinal changes in the vaginal microbiota in sequential vaginal self-swabs from five women with recurrent BV, from diagnosis through remission to recurrence.

Novel PCR-based methods enhance characterization of vaginal microbiota in a bacterial vaginosis patient before and after treatment.

Deep characterization, even by next-generation sequencing, of the vaginal microbiota in healthy women or posttreatment bacterial vaginosis patients is limited by the dominance of lactobacilli. To improve detection, we offer two approaches: quantitative PCR (qPCR) using phylogenetic branch-inclusive primers and sequencing of broad-spectrum amplicons generated with oligomers that block amplification of lactobacilli.

Current micronutrient recommendations in Europe: towards understanding their differences and similarities.

Background: Nowadays most countries in Europe have established their own nutrient recommendations to assess the adequacy of dietary intakes and to plan desirable dietary intakes. As yet there is no standard approach for deriving nutrient recommendations, they may vary from country to country. This results in different national recommendations causing confusion for policy-makers, health professionals, industry, and consumers within Europe.

How we will produce the evidence-based EURRECA toolkit to support nutrition and food policy.

Background: There is considerable variation in the recommended micronutrient intakes used by countries within Europe, partly due to different methodologies and concepts used to determine requirements and different approaches used to express the recommendations. As populations become more mobile and multi-national, and more traditional foods become available internationally, harmonised recommendations based on up to date science are needed. This was recognised by the European Commission's (EC) Directorate-General (DG) Research in their 2005 call for proposals for a Network of Excellence (NoE) on 'nutrient status and requirements of specific vulnerable population groups'.

Eight strategies to engage industry in biosecurity.

A significant portion of the domestic bio-research base-and the one most likely to provide translational research-is not engaged in biodefense. Despite the fact that more than one-third of all life science researchers are employed in commercial bio-research, fewer than 3% of the 1,500 U.S.

Physiological and metabolic aspects of very prolonged exercise with particular reference to hill walking.

Hill walking is a popular recreational activity in the developed world, yet it has the potential to impose severe stress simultaneously upon several regulatory systems. Information regarding the physiological strain imposed by prolonged walking outdoors in adverse climatic conditions was reported almost four decades ago and recent research has extended some of this work. These data indicate that once the walker fatigues and starts to slow or stops walking altogether, the rate of heat production falls dramatically.

Public health aspects of food fortification: a question of balance.

Micronutrient malnutrition is widespread throughout the world, with important health and economic consequences. Tools to address this situation include food fortification, supplementation and dietary diversification, each having different and complementary roles. Fortification (mandatory and voluntary) has been practised over several decades in Western countries as well as in developing countries.

Dietary intake and nutritional status of children and adolescents in Europe.

The objective of this project was to collect and evaluate data on nutrient intake and status across Europe and to ascertain whether any trends could be identified. Surveys of dietary intake and status were collected from across Europe by literature search and personal contact with country experts. Surveys that satisfied a defined set of criteria -- published, based on individual intakes, post-1987, adequate information provided to enable its quality to be assessed, small age bands, data for sexes separated above 12 years, sample size over 25 and subjects representative of the population -- were selected for further analysis.