Work history and diagnosed hypertension among older adults in Ghana: evidence from WHO SAGE Wave2

Introduction There is limited knowledge in the context of Africa on how work history associates with hypertension at old age. Therefore, this paper analyses such an association using Ghana as a case study. Methods Data from the World Health Organisation Study on Global AGEing and Adult Health Wave 2 was used to explore the relationship between work history and diagnosed hypertension at old age. In the Wave2 study, a multistage cluster sampling was used to select participants at the household level across rural/urban areas in all administrative regions. A multifactor logit regression analysis was performed. The paper also estimated diagnosed hypertension prevalence across subgroups. Results The mean age of the total of 3564 participants examined was 64 years (SD = ±10years). The overall prevalence of hypertension was 10.3% [95% CI = 9.4–11.1]. The highest predicted rate was 41.1% [95% CI=38.0 – 49.2] among those who stopped working before the statutory retirement age 60 years, whereas it was only 4% [95% CI = 3.7 – 5.2] for those who retired from active work at age 60 years. Those who retired at age <60years recorded the highest risk of hypertension diagnosis [OR = 14.1; 95% CI=10.5-19.5]. There was also a significant association between diagnosed hypertension and a history of working <5 days per week [OR=1.6; 95% CI=1.1-2.3]. It emerged that those with a history of informal sector employment were at significant risk of hypertension at old age, if they worked <5days per week [OR=1.5; 95% CI=1.0-2.3]. Conclusions Overall, retirement age emerged as a significant risk factor for diagnosed hypertension at old age, followed by a history of less than five working days per week

HDL biodistribution and brain receptors in zebrafish, using HDLs as vectors for targeting endothelial cells and neural progenitors

High density lipoproteins (HDLs) display pleiotropic functions such as anti-inflammatory, antioxidant, anti-protease, and anti-apoptotic properties. These effects are mediated by four main receptors: SCARB1 (SR-BI), ABCA1, ABCG1, and CD36. Recently, HDLs have emerged for their potential involvement in brain functions, considering their epidemiological links with cognition, depression, and brain plasticity. However, their role in the brain is not well understood. Given that the zebrafish is a well-recognized model for studying brain plasticity, metabolic disorders, and apolipoproteins, it could represent a good model for investigating the role of HDLs in brain homeostasis. By analyzing RNA sequencing data sets and performing in situ hybridization, we demonstrated the wide expression of scarb1, abca1a, abca1b, abcg1, and cd36 in the brain of adult zebrafish. Scarb1 gene expression was detected in neural stem cells (NSCs), suggesting a possible role of HDLs in NSC activity. Accordingly, intracerebroventricular injection of HDLs leads to their uptake by NSCs without modulating their proliferation. Next, we studied the biodistribution of HDLs in the zebrafish body. In homeostatic conditions, intraperitoneal injection of HDLs led to their accumulation in the liver, kidneys, and cerebral endothelial cells in zebrafish, similar to that observed in mice. After telencephalic injury, HDLs were diffused within the damaged parenchyma and were taken up by ventricular cells, including NSCs. However, they failed to modulate the recruitment of microglia cells at the injury site and the injury-induced proliferation of NSCs. In conclusion, our results clearly show a functional HDL uptake process involving several receptors that may impact brain homeostasis and suggest the use of HDLs as delivery vectors to target NSCs for drug delivery to boost their neurogenic activity

Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood-brain barrier?

The blood-brain barrier (BBB) is a physical interface between the blood and the brain parenchyma, playing key roles in brain homeostasis. In mammals, the BBB is established thanks to tight junctions between cerebral endothelial cells, involving claudin, occludin, and zonula occludens proteins. Estrogens have been documented to modulate BBB permeability. Interestingly, in the brain of zebrafish, the estrogen-synthesizing activity is strong due to the high expression of Aromatase B protein, encoded by the cyp19a1b gene, in radial glial cells (neural stem cells). Given the roles of estrogens in BBB function, we investigated their impact on the expression of genes involved in BBB tight junctions. We treated zebrafish embryos and adult males with 17β-estradiol and observed an increased cerebral expression of tight junction and claudin 5 genes in adult males only. In females, treatment with the nuclear estrogen receptor antagonist (ICI182,780 ) had no impact. Interestingly, telencephalic injuries performed in males decreased tight junction gene expression that was partially reversed with 17β-estradiol. This was further confirmed by extravasation experiments of Evans blue showing that estrogenic treatment limits BBB leakage. We also highlighted the intimate links between endothelial cells and neural stem cells, suggesting that cholesterol and peripheral steroids could be taken up by endothelial cells and used as precursors for estrogen synthesis by neural stem cells. Together, our results show that zebrafish provides an alternative model to further investigate the role of steroids on the expression of genes involved in BBB integrity, both in constitutive and regenerative physiological conditions. The link we described between capillaries endothelial cells and steroidogenic neural cells encourages the use of this model in understanding the mechanisms by which peripheral steroids get into neural tissue and modulate neurogenic activity

Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions

Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (p = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. Conclusion: We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity

Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood–brain barrier?

International audienceThe blood-brain barrier (BBB) is a physical interface between the blood and brain parenchyma, playing key roles in homeostasis. In mammals, BBB established thanks to tight junctions cerebral endothelial cells, involving claudin, occludin, zonula occludens proteins. Estrogens have been documented modulate permeability. Interestingly, of zebrafish, estrogen-synthesizing activity strong due high expression Aromatase B protein, encoded by cyp19a1b gene, radial glial cells (neural stem cells). Given estrogens function, we investigated their impact on genes involved junctions. We treated zebrafish embryos adult males with 17β-estradiol observed an increased junction claudin 5 only. females, treatment nuclear estrogen receptor antagonist (ICI182,780 ) had no impact. telencephalic injuries performed decreased gene that was partially reversed 17β-estradiol. This further confirmed extravasation experiments Evans blue showing estrogenic limits leakage. also highlighted intimate links neural suggesting cholesterol peripheral steroids could be taken up used as precursors for synthesis cells. Together, our results show provides alternative model investigate role integrity, both constitutive regenerative physiological conditions. link described capillaries steroidogenic encourages use this understanding mechanisms which get into tissue neurogenic activity

Lactic Fermentation as an Efficient Tool to Enhance the Antioxidant Activity of Tropical Fruit Juices and Teas

International audienceTropical fruits like pineapple, papaya, mango, and beverages such as green or black teas, represent an underestimated source of antioxidants that could exert health-promoting properties. Most food processing technologies applied to fruit beverages or teas result in an impairment of inherent nutritional properties. Conversely, we hypothesise that lactic acid fermentation may constitute a promising route to maintain and even improve the nutritional qualities of processed fruits. Using specific growth media, lactic acid bacteria were selected from the fruit phyllosphere diversity and fruit juice, with the latter undergoing acidification kinetics analyses and characterised for exopolysaccharide production. Strains able to ferment tropical fruit juices or teas into pleasant beverages, within a short time, were of particular interest. Strains Weissella cibaria 64 and Leuconostoc mesenteroides 12b, able to increase antioxidant activity, were specifically studied as potential starters for lactic fermented pineapple juice

ApoA-I Nanoparticles as Curcumin Carriers for Cerebral Endothelial Cells: Improved Cytoprotective Effects against Methylglyoxal

Methylglyoxal (MGO) is a highly reactive metabolite of glucose present at elevated levels in diabetic patients. Its cytotoxicity is associated with endothelial dysfunction, which plays a role in cardiovascular and cerebrovascular complications. Although curcumin has many therapeutic benefits, these are limited due to its low bioavailability. We aimed to improve the bioavailability of curcumin and evaluate a potential synergistic effect of curcumin and reconstituted high-density lipoprotein (rHDL) nanoparticles (Cur-rHDLs) on MGO-induced cytotoxicity and oxidative stress in murine cerebrovascular endothelial cells (bEnd.3). Cur-rHDL nanoparticles (14.02 &plusmn; 0.95 nm) prepared by ultracentrifugation and containing curcumin were quantified by LC&ndash;MS/MS. The synergistic effect of cur-rHDL nanoparticles was tested on bEnd.3 cytotoxicity, reactive oxygen species (ROS) production, chromatin condensation, endoplasmic reticulum (ER) stress, and endothelial barrier integrity by impedancemetry. The uptake of curcumin, alone or associated with HDLs, was also assessed by mass spectrometry. Pretreatment with Cur-rHDLs followed by incubation with MGO showed a protective effect on MGO-induced cytotoxicity and chromatin condensation, as well as a strong protective effect on ROS production, endothelial cell barrier integrity, and ER stress. These results suggest that Cur-rHDLs could be used as a potential therapeutic agent to limit MGO-induced dysfunction in cerebrovascular endothelial cells by enhancing the bioavailability and protective effects of curcumin

Aging and glycation promote erythrocyte phagocytosis by human endothelial cells: Potential impact in atherothrombosis under diabetic conditions

International audienceBackground and aims: Atherothrombotic plaques of type 2 diabetic (T2D) patients are characterized by an increased neovascularization and intraplaque hemorrhage. The clearance of erythrocytes may be carried out by vascular cells. We explored the potential of human endothelial cells to bind and phagocyte in vitro aged and/or glycated erythrocytes as well as erythrocytes obtained from diabetic patients.Methods: Fresh, aged and glycated-aged erythrocytes from healthy volunteers and T2D patients were tested for their binding and phagocytosis capacity as well as the potential functional consequences on endothelial cells (viability, proliferation and wound healing capacity). Immunohistochemistry was also performed in human carotid atherothrombotic samples (from patients with or without T2D).Results: Aging and glycation of erythrocytes induced phosphatidylserine (PS) exposure and oxidative stress leading to enhanced endothelial cell binding and engulfment. Phagocytosis by endothelial cells was more pronounced with aged and glycated erythrocytes than with fresh ones. Phagocytosis was enhanced with T2D versus healthy erythrocytes. Furthermore, endothelial wound healing potential was significantly blunted after exposure to glycated-aged versus fresh erythrocytes. Finally, we show that interactions between erythrocytes and endothelial cells and their potential phagocytosis may occur in vivo, in atherothrombotic conditions, in neovessels and in the luminal endothelial lining.Conclusions: Endothelial cells may play an important role in erythrocyte clearance in an atherothrombotic environment. Under diabetic conditions, erythrocyte glycation favors their engulfment by endothelial cells and may participate in endothelial dysfunction, thereby promoting vulnerable atherothrombotic plaques to rupture

Development, synthesis, and 68Ga-Labeling of a Lipophilic complexing agent for atherosclerosis PET imaging

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Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated albumin

International audienceIncreased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively. Our data reveal increased oxidative stress biomarkers and lipid accumulation in plasma and livers of diabetic mice, together with albumin glycoxidation. Purified mouse albumin modifications resembled those typically found in diabetic patients, i.e. degree of glycation, carbonylation, AGE levels and in terms of chemical composition. Receptor for AGE expression and reactive oxygen species production were upregulated in db/db mouse livers, together with impaired proteolytic, antioxidant and mitochondrial respiratory activities. In parallel, acute exposure of HepG2 cells to glycated albumin also elicited intracellular free radical formation. Together this study demonstrates that AGE-modified albumin can trigger damaging effects on the liver, i.e. by increasing oxidative stress, attenuating antioxidant capacity, and by impairment of hepatic proteolytic and respiratory chain enzyme activities