31 research outputs found

    Genetic variants on chromosome 19 (rs439401 and rs4420638) are associated with obesity and high blood pressure in the Algerian population

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    Metabolic syndrome (MetS) represents a combination of at least three primary metabolic abnormalities from among obesity, hyperglycemia, dyslipidemia, and high blood pressure, once combined, they increase significantly the cardiovascular risk. The APOE gene is considered as a genetic risk factor for cardiovascular diseases, it has been linked to MetS or its traits in several populations. Our study aimed to analyze the association of three APOE gene polymorphisms with MetS risk and its components in a general population sample, and to highlight the potential influence of these polymorphisms on individual susceptibility to MetS. We performed this work using a population-based, cross-sectional study of a representative sample of 787 individuals (378 men and 409 women, aged between 30 and 64 years) recruited in the city of Oran, Algeria (the ISOR Study); the subjects were genotyped for four polymorphisms, rs7412, rs429358, rs4420638 and rs439401, located in the APOE gene, using the KASPar technology. rs439401 showed a significant association with hypertension (HBP). The T allele confers a high risk of hypertension with an odds ratio (OR) of 1.46 (95 % CI [1.12–1.9], p = 0.006). rs4420638 was significantly associated with obesity in the general population. The G allele provides protection against obesity, the resulting OR is 0.48 (95 % CI [0.29–0.81], p = 0.004). Although APOE variants were not associated with the risk of MetS, the APOE polymorphism alleles were associated with some of the metabolic parameters in Algerian subjects. The relation of APOE rs439401 alleles with a HBP is likely to be indicative of a state of stress of the population

    Molecular definition of group 1 innate lymphoid cells in the mouse uterus

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    Determining the function of uterine lymphocytes is challenging because of the rapidly changing nature of the organ in response to sex hormones and, during pregnancy, to the invading fetal trophoblast cells. Here we provide the first genome-wide transcriptome atlas of mouse uterine group 1 innate lymphoid cells (g1 ILCs) at mid-gestation. The composition of g1 ILCs fluctuates throughout reproductive life, with Eomes-veCD49a+ ILC1s dominating before puberty and specifically expanding in second pregnancies, when the expression of CXCR6, a marker of memory cells, is upregulated. Tissue-resident Eomes+CD49a+ NK cells (trNK), which resemble human uterine NK cells, are most abundant during early pregnancy, and showcase gene signatures of responsiveness to TGF-β, connections with trophoblast, epithelial, endothelial and smooth muscle cells, leucocytes, as well as extracellular matrix. Unexpectedly, trNK cells express genes involved in anaerobic glycolysis, lipid metabolism, iron transport, protein ubiquitination, and recognition of microbial molecular patterns. Conventional NK cells expand late in gestation and may engage in crosstalk with trNK cells involving IL-18 and IFN-γ. These results identify trNK cells as the cellular hub of uterine g1 ILCs at mid-gestation and mark CXCR6+ ILC1s as potential memory cells of pregnancy.This work was funded by a Wellcome Trust Investigator Award 200841/Z/16/Z, the Centre for Trophoblast Research (CTR), and the Cambridge NIHR BRC Cell Phenotyping Hub to FC, the Associazione Italiana Ricerca per la Ricerca sul Cancro (AIRC) - Special Project 5x1000 no. 9962, AIRC IG 2017 Id.19920 and AIRC 2014 Id. 15283 to LM, and Ministero della Salute RF-2013, GR-2013-02356568 to PV. IF was funded by a CTR PhD fellowship

    Haloxylon Scoparium: An Ethnopharmacological Survey, Phytochemical Screening and Antibacterial Activity against Human Pathogens Causing Nosocomial Infection

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    Nosocomial infections occur worldwide, both in the developed and developing world. They are a major cause of death and increased morbidity in hospitalized patients. This study deals with the valorization of medicinal plants of southwest Algeria, in order to find new bioactive natural productsagainst human pathogens causing nosocomial infection. Haloxylon Scoparium (Chenopodiaceae family) is a local medicinal plant, which has been used extensively in the southwestern part of Algeria. It was subjected to an ethnopharmacological survey,phytochemical screening and antinosocomial activity. The ethnopharmacological survey revealed that the H. Scopariumis used to treat numerous human diseasesespecially the infectious one such as skin infections, urinaryandgenitalinfections.Therefore, the H. scoparium aerial part was subjected to a phytochemical screening. Then its crude extracts, including, acetone, ethanol, methanol, chloroform, dichloromethane, chlorohydric and water extracts were tested against three pathogens causing nosocomial infectionusing the disc diffusion method. As a result, all the phytochemical constituents were found to be present in the aerial part of H. scoparium. The methanolic extract was found more bioactive comparing to the other extracts

    Genetic determinants of dyslipidemia in African-based populations: a systematic review

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    Identification of genetic/genomic factors contributing to dyslipidemia is of great interest to prevention and reduction of the onset and burden of cardiovascular diseases in Africa. This systematic review summarizes available data on genetic variants associated with dyslipidemia in populations within Africa. A PubMed and EMBASE database search was conducted to identify all studies published until June 2018 on genetic susceptibility to dyslipidemia in African-based populations, excluding familial hypercholesterolemia. All studies on genetic predispositions of dyslipidemia and respecting the preestablished inclusion criteria were included in this systematic review. Because of high heterogeneity, the data were summarized narratively. Twenty-two studies investigated mostly the targeted genetic variants. A total of 51 polymorphisms in 28 susceptibility genes to dyslipidemia have been associated with a particular trait in the African populations, and through variable effects. Most polymorphisms investigated in Northern Africa seemed to have consistent effects on increasing the level of low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides in patients with diabetes, myocardial infarction, coronary artery disease, and metabolic syndrome. By contrast, only Ser447Ter and C49620T variants were associated with increased LDL-C in sub-Saharan Africa. Despite few studies available in this context in the literature, certain genetic variants were consistently associated with dyslipidemia especially in Northern Africa as highlighted in this analysis. Further data, particularly from genome-wide association studies, would help establish an African-specific reference for genetic susceptibility markers of dyslipidemia.Jean Jacques Noubiap, Edith Pascale M. Mato, Magellan Guewo-Fokeng, Arnaud D. Kaze, Houssam Boulenouar, and Ambroise Wonka

    Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth

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    The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal–fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction
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