Fatty Acid Profile and Genetic Variants of Proteins Involved in Fatty Acid Metabolism Could Be Considered as Disease Predictor.

Circulating fatty acids (FA) have an endogenous or exogenous origin and are metabolized under the effect of many enzymes. They play crucial roles in many mechanisms: cell signaling, modulation of gene expression, etc., which leads to the hypothesis that their perturbation could be the cause of disease development. FA in erythrocytes and plasma rather than dietary FA could be used as a biomarker for many diseases. Cardiovascular disease was associated with elevated trans FA and decreased DHA and EPA. Increased arachidonic acid and decreased Docosahexaenoic Acids (DHA) were associated with Alzheimer's disease. Low Arachidonic acid and DHA are associated with neonatal morbidities and mortality. Decreased saturated fatty acids (SFA), increased monounsaturated FA (MUFA) and polyunsaturated FA (PUFA) (C18:2 n-6 and C20:3 n-6) are associated with cancer. Additionally, genetic polymorphisms in genes coding for enzymes implicated in FA metabolism are associated with disease development. FA desaturase (FADS1 and FADS2) polymorphisms are associated with Alzheimer's disease, Acute Coronary Syndrome, Autism spectrum disorder and obesity. Polymorphisms in FA elongase (ELOVL2) are associated with Alzheimer's disease, Autism spectrum disorder and obesity. FA-binding protein polymorphism is associated with dyslipidemia, type 2 diabetes, metabolic syndrome, obesity, hypertension, non-alcoholic fatty liver disease, peripheral atherosclerosis combined with type 2 diabetes and polycystic ovary syndrome. Acetyl-coenzyme A carboxylase polymorphisms are associated with diabetes, obesity and diabetic nephropathy. FA profile and genetic variants of proteins implicated in FA metabolism could be considered as disease biomarkers and may help with the prevention and management of diseases.

sHLA-G1 and HLA-G5 levels are decreased in Tunisian women with multiple abortion.

Pregnancy is associated with increased levels of soluble (s) human leukocyte antigen (HLA)-G molecules, while during abortion these molecules are decreased. To date, little is known about the role of sHLA-G isoforms during abortion. In this study, we investigated the levels of total sHLA-G and its isoforms: HLA-G1 (membrane shedded isoform) and alternative spliced HLA-G5 in plasma samples obtained from 55 women who had experienced spontaneous abortion, 108 pregnant healthy women and 56 non pregnant healthy women. We found that pregnant women exhibited higher amounts of sHLA-G compared to either non pregnant women or women with abortion. Among women who had experienced spontaneous abortion, women with recurrent abortions (RSA) had lower sHLA-G than women with only one abortion. In particular, RSA women were characterized by the absence of sHLA-G1 isoform, suggesting a possible implication in abortion event.

Pregnancy and breastfeeding: a new theory for sHLA-G in breast cancer patients?

It is now widely recognized that HLA-G molecule is implicated in immune tolerance and particularly in immune subversion of tumor cells. In this study, we explored levels of soluble HLA-G (sHLA-G) in plasma samples obtained from women with breast cancer (BC). Additionally, we correlated sHLA-G concentration with pregnancy and breastfeeding history. We reported in this preliminary work significant differences in sHLA-G levels between BC patients with/without breastfeeding experience (p = 0.04). Interestingly, among women with BC, only those without previous pregnancy experience present significant increase in sHLA-G (p = 0.02). Of relevance, we demonstrated that patients without both pregnancy and breastfeeding history have advanced SBR III grade, associated with significant enhancement in tumor size compared with patients who had both experiences (p = 0.028). Taken together, our results indicate the potential implication of previous pregnancy and breastfeeding experience in sHLA-G expression during BC. We theorized that having pregnancy and breastfeeding history may protect against advanced BC stages.

Effect of endocrine disruptor pesticides: a review.

Endocrine disrupting chemicals (EDC) are compounds that alter the normal functioning of the endocrine system of both wildlife and humans. A huge number of chemicals have been identified as endocrine disruptors, among them several pesticides. Pesticides are used to kill unwanted organisms in crops, public areas, homes and gardens, and parasites in medicine. Human are exposed to pesticides due to their occupations or through dietary and environmental exposure (water, soil, air). For several years, there have been enquiries about the impact of environmental factors on the occurrence of human pathologies. This paper reviews the current knowledge of the potential impacts of endocrine disruptor pesticides on human health.

Golimumab and malignancies: true or false association?

Malignancy is one of the comorbidities linked to golimumab, a biological TNF-α blocker. In this systematic review and meta-analysis, we searched different databases and analyzed original publications to elucidate the remaining open question about the real association of malignancies with golimumab therapy. The most frequent cancer in patients treated with golimumab, in association or not with methotrexate, is the lung adenocarcinoma. However, lymphoma is not very commonly represented in these patients. We show that there is no major and evident risk of malignancies associated with golimumab in current scientific literature. An increased risk of malignancies may be associated with golimumab, but this warrants further clinical confirmation. Also, this risk mentioned in different studies must be taken with caution because of number of limits and biases.

Acidic-store depletion is required for human platelet aggregation.

Platelet stimulation with thrombin induces an elevation in cytoplasmic free Ca(2+) concentration ([Ca(2+)]c) due to Ca(2+) release from intracellular stores and entry from the extracellular medium. Two different intracellular Ca(2+) stores have been described in human platelets: the dense tubular system and the lysosomal-like acidic stores. In the present study, we investigated the contribution of the acidic stores in thrombin-induced platelet aggregation. We have found that platelet aggregation induced by thrombin is reduced in a Ca(2+)-free medium. Discharge of the acidic Ca(2+) stores by treatment with the sarcoendoplasmic Ca(2+)-ATPase (SERCA)3 selective inhibitor 2,5-di-(tert-butyl)-1,4-hydroquinone reduced thrombin-evoked platelet aggregation. In the presence of 2,5-di-(tert-butyl)-1,4-hydroquinone, platelet aggregation induced by the protease-activated receptor (PAR)-1 and PAR-4 agonist peptides, SFLLRN and AYPGKF, respectively, was significantly reduced. In cells with depleted acidic stores, activation of GPIb-IX-V by thrombin resulted in reduced or no platelet aggregation in a medium containing 1 mmol/l Caor in a Ca(2+)-free medium, respectively. This finding suggests that Ca(2+) accumulation in the acidic Ca(2+) compartments is required for platelet aggregation induced by activation of the G-coupled PAR-1 and PAR-4 thrombin receptors and, by the occupation of the leucine-rich glycoprotein GPIb-IX-V and provide evidence supporting a functional role of the lysosomal-like acidic Ca(2+) stores in human platelets.

Tyrosine phosphorylation / dephosphorylation balance is involved in thrombin-evoked microtubular reorganisation in human platelets.

We have investigated the intracellular mechanisms involved in microtubular remodelling by thrombin and its possible involvement in platelet aggregation and secretion. Platelet stimulation with thrombin induces a time- and concentration-dependent regulation of the microtubular content, which was found to be maximally effective at the concentration 0.1 U/ml. Thrombin (0.1 U/ml) evoked an initial decrease in the microtubule content detectable at 5 seconds (sec) and reached a minimum 10 sec after stimulation. The microtubular content then increased, exceeding basal levels again approximately 30 sec after stimulation. Inhibition of tyrosine phosphatases using vanadate abolished thrombin-induced microtubular depolymerisation while inhibition of tyrosine kinases by methyl-2,5-dihydroxycinnamate prevented microtubule polymerisation. Thrombin activates the cytosolic Bruton's tyrosine kinase (Btk) and Src proteins. Inhibition of Btk or Src by LFM-A13 or PP1, respectively, abolished thrombin-induced microtubular polymerisation, while maintaining intact its ability to induce initial depolymerisation. Microtubular disruption by colchicine significantly reduced thrombin-induced platelet aggregation and ATP secretion. Similar results were observed after inhibition of microtubular disassembly by paclitaxel. These findings indicate that thrombin induces microtubular remodelling by modifying the balance between protein tyrosine phosphorylation and dephosphorylation. The former seems to be required for microtubular polymerisation, while tyrosine dephosphorylation is required for microtubular depolymerisation. Both, initial microtubular disassembly and subsequent polymerisation are required for thrombin-induced platelet aggregation and secretion in human platelets.

Characterization of the intracellular mechanisms involved in the antiaggregant properties of cinnamtannin B-1 from bay wood in human platelets.

Cinnamtannin B-1, a natural A-type proanthocyanidin recently identified as a radical scavenger component of Laurus nobilis L., exerts antiaggregant and antiapoptotic effects in human platelets. Here, we have investigated the intracellular mechanisms involved in the antiaggregant effects of cinnamtannin B-1. Cinnamtannin B-1 showed a greater free radical scavenging activity than vitamin C, vitamin E, or Trolox, among other antioxidants and reduced thrombin-evoked tubulin reorganization and platelet aggregation. Thrombin-evoked activation of Btk and pp60(src) was also inhibited by cinnamtannin B-1. In conclusion, we show that cinnamtannin B-1 is a powerful oxygen radical scavenger that reduces thrombin-evoked microtubular remodeling and activation of the tyrosine kinases Btk and pp60(src), which leads to inhibition of platelet aggregation. These observations suggest that cinnamtannin B-1 may prevent thrombotic complications associated to platelet hyperaggregability and hyperactivity, although further studies are necessary to establish appropriate therapeutic strategies.