Enhancing Solubility and Bioefficacy of Stilbenes by Liposomal Encapsulation-The Case of Macasiamenene F.

Stilbenes in food and medicinal plants have been described as potent antiphlogistic and antioxidant compounds, and therefore, they present an interesting potential for the development of dietary supplements. Among them, macasiamenene F (MF) has recently been shown to be an effective anti-inflammatory and cytoprotective agent that dampens peripheral and CNS inflammation . Nevertheless, this promising molecule, like other stilbenes and a large percentage of drugs under development, faces poor water solubility, which results in trickier administration and low bioavailability.

Dietary fatty acid composition drives neuroinflammation and impaired behavior in obesity.

Nutrient composition in obesogenic diets may influence the severity of disorders associated with obesity such as insulin-resistance and chronic inflammation. Here we hypothesized that obesogenic diets rich in fat and varying in fatty acid composition, particularly in omega 6 (ω6) to omega 3 (ω3) ratio, have various effects on energy metabolism, neuroinflammation and behavior. Mice were fed either a control diet or a high fat diet (HFD) containing either low (LO), medium (ME) or high (HI) ω6/ω3 ratio.

Unlocking Therapeutic Synergy: Tailoring Drugs for Comorbidities such as Depression and Diabetes through Identical Molecular Targets in Different Cell Types.

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people.

Linotrins: Omega-3 oxylipins featuring an E,Z,E conjugated triene motif are present in the plant kingdom and alleviate inflammation in LPS-challenged microglial cells.

Alpha-linolenic acid (ALA), an essential omega-3 polyunsaturated fatty acid found in plants, exerts neuroprotection and anti-inflammatory effects in chronic and acute CNS disease models. However, the underlying mechanisms are not yet understood. Since ALA is not incorporated into the brain, the observed health benefits may result from some of its metabolites.

The eukaryotic initiation factor 5A (eIF5A1), the molecule, mechanisms and recent insights into the pathophysiological roles.

Since the demonstration of its involvement in cell proliferation, the eukaryotic initiation factor 5A (eIF5A) has been studied principally in relation to the development and progression of cancers in which the isoform A2 is mainly expressed. However, an increasing number of studies report that the isoform A1, which is ubiquitously expressed in normal cells, exhibits novel molecular features that reveal its new relationships between cellular functions and organ homeostasis. At a first glance, eIF5A can be regarded, among other things, as a factor implicated in the initiation of translation.

Targeting oxidative stress, a crucial challenge in renal transplantation outcome.

Disorders characterized by ischemia/reperfusion (I/R) are the most common causes of debilitating diseases and death in stroke, cardiovascular ischemia, acute kidney injury or organ transplantation. In the latter example the I/R step defines both the amplitude of the damages to the graft and the functional recovery outcome. During transplantation the kidney is subjected to blood flow arrest followed by a sudden increase in oxygen supply at the time of reperfusion.

Sortilin-derived peptides promote pancreatic beta-cell survival through CREB signaling pathway.

Deterioration of insulin secretion and pancreatic beta-cell mass by inflammatory attacks is one of the main pathophysiological features of type 2 diabetes (T2D). Therefore, preserving beta-cell mass and stimulating insulin secretion only in response to glucose for avoiding the hypoglycemia risks, are the most state-of-the-art option for the treatment of T2D. In this study we tested two correlated hypothesis that 1/ the endogenous peptide released from sortilin, known as PE, that stimulates insulin secretion only in response to glucose, protects beta-cells against death induced by cytokines, and 2/ Spadin and Mini-Spadin, two synthetic peptides derived from PE, that mimic the effects of PE in insulin secretion, also provide beneficial effect on beta-cells survival.

Inhibition of eIF5A hypusination reprogrammes metabolism and glucose handling in mouse kidney.

Inhibition of the eukaryotic initiation factor 5A activation by the spermidine analogue GC7 has been shown to protect proximal cells and whole kidneys against an acute episode of ischaemia. The highlighted mechanism involves a metabolic switch from oxidative phosphorylation toward glycolysis allowing cells to be transiently independent of oxygen supply. Here we show that GC7 decreases protein expression of the renal GLUT1 glucose transporter leading to a decrease in transcellular glucose flux.

Therapeutic potential of prenylated stilbenoid macasiamenene F through its anti-inflammatory and cytoprotective effects on LPS-challenged monocytes and microglia.

Ethnopharmacological Relevance: Macaranga Thou. (Euphorbiaceae) is a large genus that comprises over 300 species distributed between Western Africa and the islands of the South Pacific. Plants of this genus have a long-standing history of use in traditional medicine for different purposes, including the treatment of inflammation.

Dietary fat exacerbates postprandial hypothalamic inflammation involving glial fibrillary acidic protein-positive cells and microglia in male mice.

In humans, obesity is associated with brain inflammation, glial reactivity, and immune cells infiltration. Studies in rodents have shown that glial reactivity occurs within 24 hr of high-fat diet (HFD) consumption, long before obesity development, and takes place mainly in the hypothalamus (HT), a crucial brain structure for controlling body weight. Here, we sought to characterize the postprandial HT inflammatory response to 1, 3, and 6 hr of exposure to either a standard diet (SD) or HFD.

Inhibition of eIF5A hypusination pathway as a new pharmacological target for stroke therapy.

In eukaryotes, the polyamine pathway generates spermidine that activates the hypusination of the translation factor eukaryotic initiation factor 5A (eIF5A). Hypusinated-eIF5A modulates translation, elongation, termination and mitochondrial function. Evidence in model organisms like drosophila suggests that targeting polyamines synthesis might be of interest against ischemia.

An acute coronary syndrome in Antarctica.

Cruise tourism to Antarctica is constantly growing. Passengers and crewmembers may experience illnessesor injuries while traveling to remote areas with harsh weather conditions from where prompt evacuationis mostly unavailable. While a small explorer ship was at Wilhelmina bay (64°39' South and 62°08' West)in the Antarctic Peninsula, a 73-year-old male passenger presented with acute chest pain after two shortexcursions off the vessel in cold weather conditions.

Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets.

Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies.

Sortilin in Glucose Homeostasis: From Accessory Protein to Key Player?

The pharmacological properties and physiological roles of the type I receptor sortilin, also called neurotensin receptor-3, are various and complex. Sortilin is involved in important biological functions from neurotensin and pro-Nerve Growth Factor signaling in the central nervous system to regulation of glucose and lipid homeostasis in the periphery. The peripheral functions of sortilin being less extensively addressed, the focus of the current review is to discuss recent works describing sortilin-induced molecular mechanisms regulating blood glucose homeostasis and insulin signaling.

Ionic Homeostasis Maintenance in ALS: Focus on New Therapeutic Targets.

Amyotrophic lateral sclerosis (ALS) is one of the most threatening neurodegenerative disease since it causes muscular paralysis for the loss of Motor Neurons in the spinal cord, brainstem and motor cortex. Up until now, no effective pharmacological treatment is available. Two forms of ALS have been described so far: 90% of the cases presents the sporadic form (sALS) whereas the remaining 10% of the cases displays the familiar form (fALS).

Cruise ship pathologies in remote regions.

Background: Navigations on cruise ships are rising and tend to spread to remote areas like polar regions. Our aim was to assess the prevalence of pathologies encountered on a cruise ship navigating in remote areas including Polar Seas.

Materials And Methods: A prospective observational, descriptive and cross-sectional study was conducted aboard a cruise ship with an overall capacity of 200-264 passengers and 140 crewmembers, sailing in remote areas as the Arctic Ocean and the Antarctic Peninsula over a period of 205 days.

Hypothalamic Inflammation and Energy Balance Disruptions: Spotlight on Chemokines.

The hypothalamus is a key brain region in the regulation of energy balance as it controls food intake and both energy storage and expenditure through integration of humoral, neural, and nutrient-related signals and cues. Many years of research have focused on the regulation of energy balance by hypothalamic neurons, but the most recent findings suggest that neurons and glial cells, such as microglia and astrocytes, in the hypothalamus actually orchestrate together several metabolic functions. Because glial cells have been described as mediators of inflammatory processes in the brain, the existence of a causal link between hypothalamic inflammation and the deregulations of feeding behavior, leading to involuntary weight loss or obesity for example, has been suggested.

Tackling issues in the path toward clinical translation in brain conditioning: Potential offered by nutraceuticals.

Brief periods of ischemia have been shown in many experimental setups to provide tolerance against ischemia in multiple organs including the brain, when administered before (preconditioning) or even after (postconditioning) the normally lethal ischemia. In addition to these so-called ischemic conditionings, many pharmacological and natural agents (e.g.

Central CCL2 signaling onto MCH neurons mediates metabolic and behavioral adaptation to inflammation.

Sickness behavior defines the endocrine, autonomic, behavioral, and metabolic responses associated with infection. While inflammatory responses were suggested to be instrumental in the loss of appetite and body weight, the molecular underpinning remains unknown. Here, we show that systemic or central lipopolysaccharide (LPS) injection results in specific hypothalamic changes characterized by a precocious increase in the chemokine ligand 2 (CCL2) followed by an increase in pro-inflammatory cytokines and a decrease in the orexigenic neuropeptide melanin-concentrating hormone (MCH).

Targeting eIF5A Hypusination Prevents Anoxic Cell Death through Mitochondrial Silencing and Improves Kidney Transplant Outcome.

The eukaryotic initiation factor 5A (eIF5A), which is highly conserved throughout evolution, has the unique characteristic of post-translational activation through hypusination. This modification is catalyzed by two enzymatic steps involving deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH). Notably, eIF5A may be involved in regulating the lifespan of during long-term hypoxia.

Alpha-linolenic acid given as enteral or parenteral nutritional intervention against sensorimotor and cognitive deficits in a mouse model of ischemic stroke.

Stroke is a leading cause of disability and death worldwide. Numerous therapeutics applied acutely after stroke have failed to improve long-term clinical outcomes. An emerging direction is nutritional intervention with omega-3 polyunsaturated fatty acids acting as disease-modifying factors and targeting post-stroke disabilities.

Failure and rescue of preconditioning-induced neuroprotection in severe stroke-like insults.

Preconditioning is a well established neuroprotective modality. However, the mechanism and relative efficacy of neuroprotection between diverse preconditioners is poorly defined. Cultured neurons were preconditioned by 4-aminopyridine and bicuculline (4-AP/bic), rendering neurons tolerant to normally lethal (sufficient to kill most neurons) oxygen-glucose deprivation (OGD) or a chemical OGD-mimic, ouabain/TBOA, by suppression of extracellular glutamate (glutamateex) elevations.

The complex contribution of chemokines to neuroinflammation: switching from beneficial to detrimental effects.

Inflammation is an innate mechanism that defends organisms against harmful stimuli. Inflammation leads to the production and secretion of proinflammatory mediators that activate and recruit immune cells to damaged tissues, including the brain, to resolve the cause of inflammation. In the central nervous system, inflammation is referred to as neuroinflammation, which occurs in various pathological conditions of the brain.

The nutraceutical potential of omega-3 alpha-linolenic acid in reducing the consequences of stroke.

Stroke is a worldwide major cause of mortality and morbidity. Preclinical studies have identified over 1000 molecules with brain-protective properties. More than 200 clinical trials have evaluated neuroprotective candidates for ischemic stroke yet, to date almost all failed, leading to a re-analysis of treatment strategies against stroke.