The (endo)cannabinoid signaling in female reproduction: What are the latest advances?

Cannabis extracts like marijuana have the highest consumption rate worldwide. Yet, their societal acceptance as recreational and therapeutic drugs could represent a serious hazard to female human reproduction, because cannabis ingredients [termed (phyto)cannabinoids] can perturb an endogenous system of lipid signals known as endocannabinoids. Accumulated evidence on animal models and humans has demonstrated a crucial role of these endogenous signals on different aspects of female reproduction, where they act through an ensamble of proteins that synthesize, transport, degrade and traffic them. Several reports have recently evidenced the potential role of endocannabinoids as biomarkers of female infertility for disease treatment and prevention, as well as their possible epigenetic effects on pregnancy. The purpose of this review is to provide an update of data collected in the last decade on the effects of cannabinoids and endocannabinoids on female reproductive events, from development and maturation of follicles and oocytes, to fertilization, oviductal transport, implantation and labor. In this context, a particular attention has ben devoted to the ovary and the production of fertilizable oocytes, because recent studies have addressed this hot topic with conflicting results among species

Stage-variations of anandamide hydrolase activity in the mouse uterus during the natural oestrus cycle

Recent studies have demonstrated that the endogenous cannabinoids are important modulators of fertility in mammals. In particular, a role of the endocannabinoid system in early stages of embryo development, oviductal transport of embryos, pregnancy maintenance and labour has been demonstrated in rodents and/or in humans. In the present paper, we report the analysis of FAAH activity and protein content in the mouse uterus as a function of the natural oestrus cycle stages. Variations of FAAH activity are discussed in relationship to changes in sex steroid levels and to the possible action of AEA on remodelling of uterine tissues

Anti-inflammatory effects of fatty acid amide hydrolase inhibition in monocytes/macrophages from alzheimer’s disease patients

Growing evidence shows that the immune system is critically involved in Alzheimer’s disease (AD) pathogenesis and progression. The modulation and targeting of peripheral immune mechanisms are thus promising therapeutic or preventive strategies for AD. Given the critical involvement of the endocannabinoid (eCB) system in modulating immune functions, we investigated the potential role of the main elements of such a system, namely type-1 and type-2 cannabinoid receptors (CB1 and CB2), and fatty acid amide hydrolase (FAAH), in distinct immune cell populations of the peripheral blood of AD patients. We found that, compared to healthy controls, CB1 and CB2 expression was significantly lower in the B-lymphocytes of AD patients. Moreover, we found that CB2 was significantly lower and FAAH was significantly higher in monocytes of the same subjects. In contrast, T-lymphocytes and NK cells did not show any variation in any of these proteins. Of note, monocytic CB2 and FAAH levels significantly correlated with clinical scores. Furthermore, the pharmacological inactivation of FAAH in monocytes and monocyte-derived macrophages obtained from AD patients was able to modulate their immune responses, by reducing production of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-12, and enhancing that of the anti-inflammatory cytokine IL-10. Furthermore, FAAH blockade skewed AD monocyte-derived macrophages towards a more anti-inflammatory and pro-resolving phenotype. Collectively, our findings highlight a central role of FAAH in regulating AD monocytes/macrophages that could be of value in developing novel monocyte-centered therapeutic approaches aimed at promoting a neuroprotective environment

Plasma fibrinogen: now also an antidepressant response marker?

Major depressive disorder (MDD) is one of the leading causes of global disability. It is a risk factor for noncompliance with medical treatment, with about 40% of patients not responding to currently used antidepressant drugs. The identification and clinical implementation of biomarkers that can indicate the likelihood of treatment response are needed in order to predict which patients will benefit from an antidepressant drug. While analyzing the blood plasma proteome collected from MDD patients before the initiation of antidepressant medication, we observed different fibrinogen alpha (FGA) levels between drug responders and nonresponders. These results were replicated in a second set of patients. Our findings lend further support to a recently identified association between MDD and fibrinogen levels from a large-scale study

Performance of Optically Readout GEM-based TPC with a 55Fe source

Optical readout of large Time Projection Chambers (TPCs) with multiple Gas Electron Multipliers (GEMs) amplification stages has shown to provide very interesting performances for high energy particle tracking. Proposed applications for low-energy and rare event studies, such as Dark Matter search, ask for demanding performance in the keV energy range. The performance of such a readout was studied in details as a function of the electric field configuration and GEM gain by using a $^{55}$Fe source within a 7 litre sensitive volume detector developed as a part of the R\&D for the CYGNUS project. Results reported in this paper show that the low noise level of the sensor allows to operate with a 2~keV threshold while keeping a rate of fake-events lesser than 10 per year. In this configuration, a detection efficiency well above 95\% along with an energy resolution ($\sigma$) of 18\% is obtained for the 5.9 keV photons, demonstrating the very promising capabilities of this technique

The faah gene is the first direct target of estrogen in the testis: role of histone demethylase LSD1

Estrogen (E(2)) regulates spermatogenesis, yet its direct target genes have not been identified in the testis. Here, we cloned the proximal 5' flanking region of the mouse fatty acid amide hydrolase (faah) gene upstream of the luciferase reporter gene, and demonstrated its promoter activity and E(2) inducibility in primary mouse Sertoli cells. Specific mutations in the E(2) response elements (ERE) of the faah gene showed that two proximal ERE sequences (ERE2/3) are essential for E(2)-induced transcription, and chromatin immunoprecipitation experiments showed that E(2) induced estrogen receptor β binding at ERE2/3 sites in the faah promoter in vivo. Moreover, the histone demethylase LSD1 was found to be associated with ERE2/3 sites and to play a role in mediating E(2) induction of FAAH expression. E(2) induced epigenetic modifications at the faah proximal promoter compatible with transcriptional activation by remarkably decreasing methylation of both DNA at CpG site and histone H3 at lysine 9. Finally, FAAH silencing abolished E(2) protection against apoptosis induced by the FAAH substrate anandamide. Taken together, our results identify FAAH as the first direct target of E(2)

KOMPETENSI PROFESIONAL GURU BK DALAM IMPLEMENTASI ASSESMEN BK (SUATU PENELITIAN PADA GURU BK DI SMA FAVORIT KOTA BANDA ACEH)

Banda Ace

Cryotolerance of equine spermatozoa correlates with specific fatty acid pattern: A pilot study

Sperm cryopreservation represents a powerful tool for horse breeding. To improve the efficiency of artificial insemination in the horse using cryopreserved spermatozoa, an adequate understanding of the underlying biophysical properties that affect sperm cryosurvival needs to be reached yet. In this pilot study, we described isolation and analysis of the main fatty acids from sperms of stallions classified as good and poor freezers (7 GF and 5 PF, according to sperm motility and viability, before and after cryopreservation). Fatty acid profiles were only assessed in pre-thaw sperms. Eight main fatty acids were identified, using gas chromatography, and their contents were expressed as percentage of the total lipid content. We found that lauric, myristic and oleic acid (C12:0, C14:0 and C18:1n9c) turned out to be about 2-fold more abundant in the sperm cells of the GFs compared with PFs. Moreover, we described for the first time the presence of a very high amount of a trans geometrical isomer of linoleic acid, linolelaidic acid (C18:2n6t), in pre-thaw PF spermatozoa. Notably, we found in fresh sperms of PF stallions a ratio of unsaturated fatty acids to saturated fatty acids which was twice that of those of GF group, suggesting a positive effect of a high saturated-to-unsaturated fatty acid ratio for the “freezability” of equine spermatozoa. Finally, principal component analysis (PCA) confirmed the relationships between specific fatty acids and cryotolerance of equine spermatozoa, also providing a graphical classification and additional information about the dominant variables governing the classification process

GLP-1 receptor agonists and renal outcomes in patients with diabetes mellitus type 2 and diabetic kidney disease: State of the art

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are highly effective in improving glycaemic control either as monotherapy or in combination with other hypoglycaemic drugs, and have low incidence of side effects, such as hypoglycaemia, nausea and weight gain, thus increasing patients' adherence to therapy. Methods: In this review we report the most recent studies demonstrating the beneficial effects of GLP-1RAs on renal outcomes, and also discuss the direct and indirect mechanisms through which they confer kidney protection. Finally, we discuss the metabolic and anti-inflammatory effects of GLP-1RAs in diabetic patients with COVID-19 disease. Results: GLP-1RAs have a nephroprotective action, which is expressed through both indirect (improvement of blood pressure and glycaemic control, weight loss) and direct (restoration of normal intrarenal haemodynamics, prevention of ischaemic and oxidative damage) effects. They have shown also metabolic and anti-inflammation beneficial effects in patients with COVID-19 disease. Conclusions: GLP-1RAs prevent albuminuria and slow the decline of renal function towards end stage renal disease in patients with diabetic kidney disease. They might be an opportunity to break the typical inflammation processes of COVID-19 disease

Behavioural and biochemical stress responses of Palinurus elephas after exposure to boat noise pollution in tank

This study examined the effects of boat noise on the behavioural and biochemical parameters of the Mediterranean spiny lobster (Palinurus elephas).The experiment was conducted in a tank equipped with a video and audio recording system. 18 experimental trials, assigned to boat noise and control conditions, were performed using lobsters in single and group of 4 specimens. After a 1. h habituation period, we audio- and video-recorded the lobsters for 1. h. During the experimental phase, the animals assigned to the boat groups were exposed to boat noise pollution (a random sequence of boat noises). Exposure to the noise produced significant variations in locomotor behaviours and haemolymphatic parameters. Our results indicate that the lobsters exposed to boat noises increased significantly their locomotor activities and haemolymphatic bioindicator of stressful conditions such as glucose, total proteins, Hsp70 expression and THC when tested both singly and in groups. © 2014 Elsevier Ltd