Circulating fatty acids and endocannabinoidome-related mediator profiles associated to human longevity

To evaluate whether a peculiar plasma profile of fatty acids and endocannabinoidome (eCBome)-related mediators may be associated to longevity, we assessed them in octogenarians (Old; n=42) living in the east-central mountain area of Sardinia, a High-Longevity Zone (HLZ), compared to sexagenarian (Young; n=21) subjects from the same area, and to Olds (n=22) from the Northern Sardinia indicated as Lower-Longevity Zone (LLZ). We found significant increases in conjugated linoleic acid (CLA) and heptadecanoic acid (17:0) levels in Old-HLZ with respect to younger subjects and Old-LLZ subjects. Young-HLZ subjects exhibited higher circulating levels of pentadecanoic acid (15:0) and retinol. Palmitoleic acid (POA) was elevated in both Young and Old subjects from the HLZ. eCBome profile showed a significantly increased plasma level of the two endocannabinoids, N-arachidonoyl-ethanolamine (AEA) and 2-arachidonoyl-glycerol (2-AG) in Old-HLZ subjects compared to Young-HLZ and Old-LLZ respectively. In addition, we found increased N-oleoyl-ethanolamine (OEA), 2-linoleoyl-glycerol (2-LG) and 2-oleoyl-glycerol (2-OG) levels in Old-HLZ group with respect to Young-HLZ (as for OEA an d 2-LG) and both the Old-LLZ and Young-HLZ for 2-OG. The endogenous metabolite of docosahexaenoic acid (DHA), N-docosahexaenoyl-ethanolamine (DHEA) was significantly increased in Old-HLZ subjects. In conclusion, our results suggest that in the HLZ area, Young and Old subjects exhibited a favourable, albeit distinctive, fatty acids and eCBome profile that may be indicative of a metabolic pattern potentially protective from adverse chronic conditions. These factors could point to a suitable physiological metabolic pattern that may counteract the adverse stimuli leading to age-related disorders such as neurodegenerative and metabolic diseases

Modificazioni dei livelli di acido arachidonico e vitamina A in relazione alla attività anticancerogena attribuita all'apporto alimentare di burro naturalmente arricchito in acido linoleico a dieni coniugati (CLA)

Considerable attention has recently been directed to the naturally occurring trace fatty acid conjugated linoleic acid (CLA), based on its dual ability to act both as a preventive and therapeutic agent in a number of rodent and human tumor model systems. CLA, which is synthesized by rumen bacteria, is found in meat and dairy products, and is of particular interest since it is effective at low levels in the diet. Our research interest is to explore whether the mechanism of the anticarcinogenic activity of CLA may be reconductible to its metabolism and influence on tissue lipid metabolism. CLA is a polyunsaturated fatty acid (PUFA) with two singular properties: 1) Its metabolism is alike that of linoleic acid and thus competes with the latter for the elongation and desaturation enzyme systems, leading on one hand to a decreased generation of eicosatrienoic and arachidonic acids for eicosanoid synthesis, and on the other to a replacement of the natural substrates with CLA metabolites known to inhibit the cyclooxigenase (COX) and lipooxygenase (LPOX) pathways; and 2) It increases the retinol content of different tissues, an effect that may be due to β-oxidation of CLA by peroxisomes with consequent activation of peroxisome proliferator activated receptor a (PPARα). The effects of CLA on eicosanoid synthesis may be the key factor of a common mechanism underlying its pleiotropic activities, and our current working hypothesis is that this factor along with tissue retinol increase, mediate the anticarcinogenic action of CLA

Human breast milk cells are positive for the pioneer transcription factor ISL1

Objective: ISL1 is a pioneer transcription factor that plays important roles in cell lineage specification and differentiation, by programming the epigenome and recruiting additional regulatory factors. The aim of this study is to determine whether the human breastmilk contains ISL1-positive stem cells, and, if so, to describe the subcellular localization of ISL1. Materials and methods: Breast milk was obtained from fourteen healthy females during the first 2-6 months of lactation. Cell morphology was examined in the breast milk with the automatic ThinPrep® processor (Hologic® Inc.) in commercial Cytological ThinPrep® solution (Hologic® Inc.), followed by standard immunohistochemical staining of ISL1. Results: ISL1 had a granular diffuse cytoplasmic localization, with varying intensity of staining in both single and grouped cells. Nuclear staining was also present, as was staining of intracellular and extracellular vesicles with ISL1 antibody. Conclusions: These preliminary results suggest that ISL1 could distinguish a readily available source of putative stem cells in human breast milk. These stem cells may complete the network created between the mother and the newborn during gestation, thereby improving the efficiency of programming and reprogramming postnatal events

Interindividual variability in L1CAM expression in the human kidney during development: are there implications for fetal programming of kidney diseases presenting in adulthood?

L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

<p>Abstract</p> <p>Background</p> <p>Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of <it>Pistacia lentiscus </it>L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma.</p> <p>Methods</p> <p>Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone.</p> <p>Results</p> <p>BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA).</p> <p>Conclusions</p> <p>Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.</p

Expression of l1 cell adhesion molecule (l1cam) in extracellular vesicles in the human spinal cord during development

OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry. MATERIALS AND METHODS: Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks. RESULTS: L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth. CONCLUSIONS: The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors

Validation of the Italian version of the &quot;Mood Disorder Questionnaire&quot; for the screening of bipolar disorders.

The study measured the accuracy of the Italian version of the Mood Disorder Questionnaire (MDQ) as a screening instrument for bipolar disorders in a psychiatric setting. Methods: 154 consecutive subjects attending the Division of Psychiatry of the University of Cagliari (Italy), were screened for bipolar disorders using the Italian translation of the MDQ, and diagnostically interviewed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) by physicians. Results: On the basis of the SCID: 51 (33.1%) received a diagnosis of bipolar or schizoaffective bipolar type disorders, 63 (40.9%) were diagnosed as having at least one psychiatric disorder in Axis I (other than bipolar or schizoaffective bipolar type disorders), whilst 40 (25.9%) were unaffected by any type of psychiatric disorder. MDQ showed a good accuracy for bipolar or schizoaffective bipolar type disorders: the cut-off 4 had sensitivity 0.90 and specificity 0.58; the cut-off 5 had sensitivity 0.84 and specificity 0.70; and the cut-off 6 had sensitivity 0.76 and specificity 0.86. The accuracy for bipolar II disorders was sufficient but not excellent: the cut-off 4 had sensitivity 0.80 and specificity 0.45; the cut-off 5 had sensitivity 0.70 and specificity 0.55; and the cut-off 6 had sensitivity 0.55 and specificity 0.65. Conclusion: Our results seem to indicate a good accuracy of MDQ, and confirm the results of recent surveys conducted in the USA. Moreover the instrument needs to be validated in other settings (e.g. in general practice)

Spontaneous and deliberate future thinking: A dual process account

© 2019 Springer Nature.This is the final published version of an article published in Psychological Research, licensed under a Creative Commons Attri-bution 4.0 International License. Available online at: https://doi.org/10.1007/s00426-019-01262-7.In this article, we address an apparent paradox in the literature on mental time travel and mind-wandering: How is it possible that future thinking is both constructive, yet often experienced as occurring spontaneously? We identify and describe two ‘routes’ whereby episodic future thoughts are brought to consciousness, with each of the ‘routes’ being associated with separable cognitive processes and functions. Voluntary future thinking relies on controlled, deliberate and slow cognitive processing. The other, termed involuntary or spontaneous future thinking, relies on automatic processes that allows ‘fully-fledged’ episodic future thoughts to freely come to mind, often triggered by internal or external cues. To unravel the paradox, we propose that the majority of spontaneous future thoughts are ‘pre-made’ (i.e., each spontaneous future thought is a re-iteration of a previously constructed future event), and therefore based on simple, well-understood, memory processes. We also propose that the pre-made hypothesis explains why spontaneous future thoughts occur rapidly, are similar to involuntary memories, and predominantly about upcoming tasks and goals. We also raise the possibility that spontaneous future thinking is the default mode of imagining the future. This dual process approach complements and extends standard theoretical approaches that emphasise constructive simulation, and outlines novel opportunities for researchers examining voluntary and spontaneous forms of future thinking.Peer reviewe