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Orally administrable barrier selective nanoparticle for managing hyperlipidemia by maintaining extra and intracellular cholesterol homeostasis and reducing reactive oxygen species: Liver samples

ABSTRACT: Heart disease causes the most death worldwide primarily caused by coronary artery disease (CAD). CAD is caused by atherosclerotic plaques in blood vessels supplying blood, oxygen and nutrients to the heart tissue. These plaques are buildups of oxidized lipoproteins in the arterial walls, which can eventually lead to the occlusion of blood vessels resulting in heart attack or stroke. Here, we report the development of a therapeutic lipid nanoparticle (NP) mimicking high density lipoproteins (HDL), which can clear the plaque build-up in the arteries, while also treating the root cause of the plaque build-up – dysfunction in the endothelial cells of the blood vessel. Our lipid NP contains the natural anti-oxidant coenzyme Q10 (CoQ10) to alleviate the reactive oxygen species (ROS) which cause endothelial dysfunction in the blood vessels. Further, given the current trend of increased age in pregnant women, it is prudent to develop therapy which considers this population as well. Current treatment options such as statins are not recommended for pregnant women as they can cross the placental barrier a cause potential harm to the fetus. We report that our nanoparticle is capable of (i) improving the lipid profile in vivo, (ii) reducing plaque formation and lipid droplet deposits in the liver and aorta and (iii) does not cross the placental barrier, making it a safe option for pregnant women dealing with hyperlipidemia

ORGANISM(S): Mus musculus

PROVIDER: GSE269837 | GEO | 2026/09/16

REPOSITORIES: GEO

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Orally administrable barrier selective nanoparticle for managing hyperlipidemia by maintaining extra and intracellular cholesterol homeostasis and reducing reactive oxygen species: Aorta samples

Project description:Heart disease causes the most death worldwide primarily caused by coronary artery disease (CAD). CAD is caused by atherosclerotic plaques in blood vessels supplying blood, oxygen and nutrients to the heart tissue. These plaques are buildups of oxidized lipoproteins in the arterial walls, which can eventually lead to the occlusion of blood vessels resulting in heart attack or stroke. Here, we report the development of a therapeutic lipid nanoparticle (NP) mimicking high density lipoproteins (HDL), which can clear the plaque build-up in the arteries, while also treating the root cause of the plaque build-up – dysfunction in the endothelial cells of the blood vessel. Our lipid NP contains the natural anti-oxidant coenzyme Q10 (CoQ10) to alleviate the reactive oxygen species (ROS) which cause endothelial dysfunction in the blood vessels. Further, given the current trend of increased age in pregnant women, it is prudent to develop therapy which considers this population as well. Current treatment options such as statins are not recommended for pregnant women as they can cross the placental barrier a cause potential harm to the fetus. We report that our nanoparticle is capable of (i) improving the lipid profile in vivo, (ii) reducing plaque formation and lipid droplet deposits in the liver and aorta and (iii) does not cross the placental barrier, making it a safe option for pregnant women dealing with hyperlipidemia

2026-09-16 | GSE311003 | GEO

Gene expression in the spleen; effect of maternal exposure to carbon black nanoparticle

Project description:The aim of this study was to investigate the effects of administration of carbon black nanoparticle (CB-NP) to pregnant mice on the development of lymphoid tissues in infantile mice. Pregnant ICR mice were treated with a suspension of CB-NP 95 microg/kg/time) by intranasal instillation, twice, on gestational day 5 and 9. Spleen and thymus were collected from offspring mice at 5 days post-partum. RNA sample was taken from spleen of 5-day-old mouse prenatally received carbon black nanoparticle, while control RNA was taken from control counterpart prenatally received distilled water. Comparisons among groups were made by one-color method with normalized data from Cy3 channels for data analysis.

2013-08-30 | E-GEOD-50432 | biostudies-arrayexpress

Impact of pregnancy on composition of human high density lipoproteins (SEC fractions)

Project description:Pregnancy results in significant physiological changes which can impact the health and development of the fetus and mother. Pregnancy-induced changes in plasma lipoproteins are well-documented with modest to no impact observed on the generic measure of high-density lipoprotein (HDL) cholesterol. However, no studies have taken a deeper look at the impact of pregnancy on the concentration and composition of HDL subspecies. In this prospective study, we collected plasma from 24 non-pregnant and 19 pregnant women in their second trimester. Using nuclear magnetic resonance (NMR) we quantified 11 different lipoprotein size subspecies from plasma including 3 in the HDL class. We observed a profound increase in the number of larger HDL particles in pregnant women. These findings were confirmed by tracking phospholipid across lipoproteins using high-resolution gel-filtration chromatography. Using liquid chromatography-mass spectrometry (LC-MS) we identified 87 lipid-associated proteins across size speciated fractions. We report drastic shifts in multiple protein clusters across different HDL sized fractions in pregnant females compared to their non-pregnant controls. In summary, we have shown that pregnancy results in major alterations in HDL subspecies concentrations and compositions that would have otherwise been missed using traditional lipid measurements. These findings significantly elevate our understanding of how changes in lipoprotein metabolism due to pregnancy could impact the health of both the fetus and the mother.

2022-02-17 | PXD026683 | Pride

Impact of pregnancy on composition of human high density lipoproteins (apoB-depleted plasma)

2022-02-17 | PXD026543 | Pride

Gene expression in the spleen; effect of maternal exposure to carbon black nanoparticle

2013-08-30 | GSE50432 | GEO

Gene expression in the placenta, and cerebral cortex of the brain of offspring mice; effect of maternal exposure to carbon black nanoparticle and ascorbic acid pre-treatment

Project description:To investigate the effects of administration of carbon black nanoparticle (CB-NP) to pregnant mice on the brain development in infantile mice, we have employed whole-genome microarray expression profiling to identify genes which show dose-dependent differential expression with astrogliosis in the frontal cortex of offspring mice. Some pregnant mice were pretreated with ascorbic acid to investigate the mechanism underlying the CB-NP effect. In addition to the frontal cortex of offspring mice who were exposed to CB-NP maternally, placenta was also subjected to the analysis to investigate the mechanism. Pregnant mice were intranasally exposed to 0, 2.9, 15, 73, or 95 micro gram of CB-NP (Printex 90) per kg (body weight) on gestational days　(GDs) 5 and 9. Some pregnant mice were treated with intraperitoneal injection of ascorbic acid (500 mg/kg) at 1 h before the CB-NP instillation (95 μg/kg). Placentae were collected from pregnant dams on GD 13. Dissected cerebral cortex were collected from 6- and 12-week-old offspring mice.

2023-12-20 | GSE250286 | GEO

Proteomic profile of plasma-derived extracellular vesicles from Colombian pregnant women with Plasmodium-soil transmitted helminths coinfection

Project description:Background: Knowledge about extracellular vesicles (EV) and their molecular cargo in gestational parasitic infections, particularly by Plasmodium and soil-transmitted helminths (STH), is almost non-existent. Objective: To perform isolation and molecular characterization of plasma-derived EVs from Colombian pregnant women and compare quantity, size, concentration and protein cargo of those EVs according to the infectious status. Methodology: Five study groups were formed: 1), Pregnant women with Plasmodium infection. 2), Pregnant women with STH infection. 3), Pregnant women with coinfection Plasmodium and STH. 4), Pregnant women without infection with Plasmodium nor STH. 5), Non-pregnant women without infection with Plasmodium nor STH. Plasma-derived EVs were isolated by size exclusion chromatography (SEC) and fractions containing EVs identified by a bead-based flow cytometric assay for tetraspanin CD9; the size and concentration of EVs were quantified by nanoparticle tracking analysis, and proteins associated with EVs were identified by liquid chromatography-mass spectrometry (LC-MS) in a pool of samples per study group.

2024-11-26 | PXD051270 | Pride

Whole-blood transcriptional profiles early predict the presence of coronary atherosclerosis and high-risk plaque features at coronary CT angiography

Project description:This study aims at identifying gene expression patterns in the whole blood that could differentiate patients with severe coronary atherosclerosis from subjects without detectable coronary artery disease (CAD), and assess associations of gene expression patterns with plaque features at coronary CT angiography (CCTA). Patients undergoing CCTA for suspected CAD, with no cardiovascular history, were enrolled. Coronary stenosis was quantified and CCTA plaque features were assessed. The whole-blood transcriptome was analyzed by RNA-Sequencing. We detected highly significant differences in the circulating transcriptome between patients with high-degree coronary stenosis (> 70%) at CCTA and subjects with the absence of coronary plaques. Noteworthy, regression analysis revealed expression signatures associated with Leaman score, segment involved score, segment-stenosis score, and plaque volume with density <150 HU at CCTA. This pilot study shows that patients with significant coronary stenosis are characterized by whole blood transcriptome profiles that may discriminate them from patients without CAD. Furthermore, our results suggest that whole blood transcriptional profiles may predict plaque characteristics.

2022-06-29 | GSE202625 | GEO

CSF immune cell alterations in women with neuropsychiatric Long COVID

Project description:Background: Women are disproportionately affected by neuropsychiatric symptoms following recovery from acute COVID-19, commonly termed neuropsychiatric long COVID (NP-long COVID). However, whether there are central nervous system-specific changes in gene expression in women with NP-long COVID remains unknown. Methods: Twenty-two women with and ten women without NP-long COVID were enrolled from New Haven, CT, and the surrounding region and consented to a blood draw and large volume lumbar puncture. Total RNA was extracted from cerebrospinal fluid (CSF) cells and peripheral blood mononuclear cells (PBMC). Polyadenylated RNA was then sequenced, and differential expression analyses were performed using DESeq2. Results: Both CSF and PBMC samples showed differential gene expression associated with long COVID status. While some pathways were dysregulated in both the CSF and PBMC of long COVID compared to controls, including those related to androgen response, MTORC1 signaling, and lipid metabolism, these are likely driven by different suites of genes. Moreover, there were also CSF-specific differentially expressed genes in people with long COVID, indicating compartment-specific immune responses. Notably, oxidative stress, reactive oxygen species, and P53 response were all enriched in the CSF of women with long COVID but not PBMC. Conclusions: Women with NP-long COVID show distinct, compartment-specific, transcriptional profiles in the CSF.

2026-01-21 | GSE297499 | GEO

B cells acquire a unique and differential transcriptomic profile during pregnancy in mice

Project description:Pregnancy significantly alters B cells development and function. B cell activation is initiated by antigens specific binding to the BCR, leading to an intricate signaling pathway responsible for B cell survival, proliferation, antigen processing/presentation and antibody production. We performed a genome-wide transcriptome profiling in splenic B cells from pregnant (P) and non-pregnant (NP) mice. We identified 1136 genes with differential expression in B cells from P mice (625 up- and 511 down-regulated) compared to NP animals. In silico analysis showed that B cell activation through BCR-signaling pathway as well as antigen processing/presentation and TLR cascades seems to be lowered during pregnancy. Further RT-qPCR analysis confirmed these data. In addition, B cells from pregnant women stimulated in vitro through BCR in combination with CpG, produced significantly lower levels of cytokines compared to non-pregnant women. Our results suggest that B cells acquire a state of hypo-responsiveness during gestation, probably as part of the maternal immune strategy for fetal tolerance. However, our results also open new avenues to understand why pregnant women are at highest risk for some infections.

2021-07-27 | GSE174290 | GEO

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