Chitosan Nanoparticles, a Novel Drug Delivery System to Transfer Squalene for Hepatocyte Stress Protection.

The Mediterranean diet is a well-known dietary pattern that has gained considerable popularity worldwide for its ability to prevent the progression of nonalcoholic fatty liver disease. This is largely attributed to the use of virgin olive oil as the primary source of fat, which contains a substantial amount of squalene, a natural antioxidant. In order to enhance the delivery of squalene and amplify its effects due to its highly hydrophobic nature, herein, squalene has been incorporated into chitosan nanoparticles.

TXNDC5 Plays a Crucial Role in Regulating Endoplasmic Reticulum Activity through Different ER Stress Signaling Pathways in Hepatic Cells.

The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by a number of variables, including endoplasmic reticulum stress (ER). Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family and acts as an endoplasmic reticulum (ER) chaperone. Nevertheless, the function of TXNDC5 in hepatocytes under ER stress remains largely uncharacterized.

Effect of virgin olive oil as spreadable preparation on atherosclerosis compared to dairy butter in Apoe-deficient mice.

Unlabelled: Olive oil is the main source of lipid energy in the Mediterranean diet and there is strong evidence of its health benefits. The effect of extra virgin olive oil (EVOO) in the form of a preparation of spreadable virgin olive oil (S-VO) on the progression of atheroma plaques was investigated in Apoe-deficient mice, a model of accelerated atherosclerosis.

Methods: Two isocaloric Western purified diets containing 20% fat, either as S-VO or as dairy butter, were used to feed 28 males and 16 females of two-month-old Apoe-deficient mice for 12 weeks.

Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?

This review focuses on the thioredoxin domain containing 5 (TXNDC5), also known as endoplasmic reticulum protein 46 (ERp46), a member of the protein disulfide isomerase (PDI) family with a dual role in multiple diseases. TXNDC5 is highly expressed in endothelial cells, fibroblasts, pancreatic β-cells, liver cells, and hypoxic tissues, such as cancer endothelial cells and atherosclerotic plaques. TXNDC5 plays a crucial role in regulating cell proliferation, apoptosis, migration, and antioxidative stress.

Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line.

Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5).

Thioredoxin domain containing 5 is involved in the hepatic storage of squalene into lipid droplets in a sex-specific way.

Hepatic thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family found associated with anti-steatotic properties of squalene and located in the endoplasmic reticulum and in lipid droplets. Considering that the latter are involved in hepatic squalene accumulation, the present research was aimed to investigate the role of TXNDC5 on hepatic squalene management in mice and in the AML12 hepatic cell line. Wild-type and TXNDC5-deficient (KO) mice were fed Western diets with or without 1% squalene supplementation for 6 weeks.

Dietary proteins modulate high-density lipoprotein characteristics in a sex-specific way in Apoe-deficient mice.

Objectives: The type and amount of dietary protein have become a topic of renewed interest, considering their involvement in several diseases. However, little attention has been devoted to the effect of avian proteins despite their wide human consumption. In a previous study, we saw that compared with soybean protein, the consumption of avian proteins, depending on sex, resulted in similar or lower atherosclerosis with a higher paraoxonase 1 activity, an antioxidant enzyme carried by high-density lipoproteins (HDL).

Pulsed electric field increases the extraction yield of extra virgin olive oil without loss of its biological properties.

Introduction: Pulsed electric field (PEF) has been used for improving extraction of extra virgin olive oil (EVOO). However, the biological changes induced by the consumption of pulsed electric field-obtained extra virgin olive oil (PEFEVOO) have not been studied yet.

Materials And Methods: EVOO oils from Empeltre variety were prepared by standard (STD) cold pressure method involving crushing of the olives, malaxation and decanting and by this procedure including an additional step of PEF treatment.

Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins.

Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic expression was observed. To study the role of TXNDC5 in the liver, we generated -deficient mice.

Dietary Avian Proteins Are Comparable to Soybean Proteins on the Atherosclerosis Development and Fatty Liver Disease in -Deficient Mice.

Background And Aim: The type and amount of dietary protein has become a topic of renewed interest in light of their involvement in metabolic diseases, atherosclerosis and thrombosis. However, little attention has been devoted to the effect of avian proteins despite their wide human consumption. The aim was to investigate the influence of chicken and turkey as sources of protein compared with that of soybean on atherosclerosis and fatty liver disease.

Dietary Erythrodiol Modifies Hepatic Transcriptome in Mice in a Sex and Dose-Dependent Way.

Erythrodiol is a terpenic compound found in a large number of plants. To test the hypotheses that its long-term administration may influence hepatic transcriptome and this could be influenced by the presence of APOA1-containing high-density lipoproteins (HDL), Western diets containing 0.01% of erythrodiol (10 mg/kg dose) were provided to - and -deficient mice.

Dietary Squalene Induces Cytochromes Cyp2b10 and Cyp2c55 Independently of Sex, Dose, and Diet in Several Mouse Models.

Scope: To investigate the effects of squalene, the main hydrocarbon present in extra virgin olive oil, on liver transcriptome in different animal models and to test the influence of sex on this action and its relationship with hepatic lipids.

Methods And Results: To this purpose, male C57BL/6J Apoe-deficient mice are fed a purified Western diet with or without squalene during 11 weeks and hepatic squalene content is assessed, so are hepatic lipids and lipid droplets. Hepatic transcriptomic changes are studied and confirmed by RT-qPCR.

Hepatic Synaptotagmin 1 is involved in the remodelling of liver plasma- membrane lipid composition and gene expression in male Apoe-deficient mice consuming a Western diet.

Background And Aims: The molecular mechanisms by which the liver develops steatotic disease still remain unclear. Previous studies using nutritional and genetic models of hepatic steatosis in mice showed that liver synaptotagmin 1 (Syt1) expression was associated with lipid droplet area. Hepatic Syt1 overexpression was used as a tool to explore its effect on hepatic and plasma lipids.

is responsible for the sex differences in hepatic mRNA expression in hepatic steatosis of mice fed a Western diet.

Hepatic fat-specific protein 27 [cell death-inducing DNA fragmentation effector protein C ()/] mRNA levels have been associated with hepatic lipid droplet extent under certain circumstances. To address its hepatic expression under different dietary conditions and in both sexes, apolipoprotein E ()deficient mice were subjected to different experimental conditions for 11 wk to test the influence of cholesterol, Western diet, squalene, oleanolic acid, sex, and surgical castration on mRNA expression. Dietary cholesterol increased hepatic expression, an effect that was suppressed when cholesterol was combined with saturated fat as represented by Western diet feeding.

Identification and validation of common molecular targets of hydroxytyrosol.

Hydroxytyrosol (HT) is involved in healthful activities and is beneficial to lipid metabolism. Many investigations focused on finding tissue-specific targets of HT through the use of different omics approaches such as transcriptomics and proteomics. However, it is not clear which (if any) of the potential molecular targets of HT reported in different studies are concurrently affected in various tissues.

Prenylcysteine oxidase 1, a pro-oxidant enzyme of low density lipoproteins.

Elevated levels of low density lipoproteins (LDLs) cause atherosclerotic disease, and proteomic analyses have found that these lipoproteins are endowed with prenylcysteine lyase. This systematic review summarizes current understanding of this enzyme, now known as prenylcysteine oxidase 1 (PCYOX1), which hydrolyzes the thioether bond of prenylcysteines in the final step in the degradation of prenylated proteins, releasing hydrogen peroxide, cysteine and the isoprenoid aldehyde. Despite the high variability of the gene, no polymorphism has yet been associated with any disease.

Lysyl oxidase overexpression accelerates cardiac remodeling and aggravates angiotensin II-induced hypertrophy.

Lysyl oxidase (LOX) controls matrix remodeling, a key process that underlies cardiovascular diseases and heart failure; however, a lack of suitable animal models has limited our knowledge with regard to the contribution of LOX to cardiac dysfunction. Here, we assessed the impact of LOX overexpression on ventricular function and cardiac hypertrophy in a transgenic LOX (TgLOX) mouse model with a strong cardiac expression of human LOX. TgLOX mice exhibited high expression of the transgene in cardiomyocytes and cardiofibroblasts, which are associated with enhanced LOX activity and HO production and with cardiofibroblast reprogramming.

Transcriptomics and the Mediterranean Diet: A Systematic Review.

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases and cancer and in decreasing overall mortality. Nowadays, transcriptomics is gaining particular relevance due to the existence of non-coding RNAs capable of regulating many biological processes. The present work describes a systematic review of current evidence supporting the influence of the Mediterranean diet on transcriptomes of different tissues in various experimental models.

The Search for Dietary Supplements to Elevate or Activate Circulating Paraoxonases.

Low levels of paraoxonase 1 (PON1) have been associated with the development of several pathological conditions, whereas high levels have been shown to be anti-atherosclerotic in mouse models. These findings suggest that PON1 could be a good surrogate biomarker. The other members of the family, namely PON2 and PON3, the role of which has been much less studied, deserve more attention.

Diet and sexual hormones regulate hepatic synaptotagmin 1 mRNA in mice.

The expression of Synaptotagmin 1 (Syt1) has been found to be associated with the lipid droplets in liver. Here, we studied the expression of Syt1 in Apoe-deficient mice receiving cholesterol, Western diet, squalene, and oleanolic acid. We also studied the influence of sex and impact of surgical castration.

Airborne measurements of organic bromine compounds in the Pacific tropical tropopause layer.

Very short-lived brominated substances (VSLBr) are an important source of stratospheric bromine, an effective ozone destruction catalyst. However, the accurate estimation of the organic and inorganic partitioning of bromine and the input to the stratosphere remains uncertain. Here, we report near-tropopause measurements of organic brominated substances found over the tropical Pacific during the NASA Airborne Tropical Tropopause Experiment campaigns.

PON1 and Mediterranean Diet.

The Mediterranean diet has been proven to be highly effective in the prevention of cardiovascular diseases. Paraoxonase 1 (PON1) has been implicated in the development of those conditions, especially atherosclerosis. The present work describes a systematic review of current evidence supporting the influence of Mediterranean diet and its constituents on this enzyme.

Dietary squalene increases high density lipoprotein-cholesterol and paraoxonase 1 and decreases oxidative stress in mice.

Background And Purpose: Squalene, the main hydrocarbon in the unsaponifiable fraction of virgin olive oil, is involved in cholesterol synthesis and it has been reported to own antiatherosclerotic and antiesteatosic effects. However, the squalene's role on lipid plasma parameters and the influence of genotype on this effect need to be addressed.

Experimental Approaches: Three male mouse models (wild-type, Apoa1- and Apoe- deficient) were fed chow semisynthetic diets enriched in squalene to provide a dose of 1 g/kg during 11 weeks.

Lysyl oxidase (LOX) in vascular remodelling. Insight from a new animal model.

Lysyl oxidase (LOX) is an extracellular matrix-modifying enzyme that seems to play a critical role in vascular remodelling. However, the lack of viable LOX-deficient animal models has been an obstacle to deep in LOX biology. In this study we have developed a transgenic mouse model that over-expresses LOX in vascular smooth muscle cells (VSMC) to clarify whether LOX could regulate VSMC phenotype and vascular remodelling.

[The nuclear receptor NOR-1 regulates the activation of vascular cells and vascular remodelling in response to hemodynamic stress].

Introduction: Previous studies have shown that the loss of NOR-1 function modulates the activation of vascular smooth muscle cells (VSMC). In this study we use a mouse that over-expresses human NOR-1 in VSMC to analyze the effect of a gain of NOR-1 function on the activation of VSMC and in the hyperplasia of the intima induced by hemodynamic stress.

Methods: To generate the transgenic animal the human NOR-1 cDNA was placed under the control of the SM22α promoter.