Sex-Specific Effects of Cholesteryl Ester Transfer Protein (CETP) on the Perivascular Adipose Tissue.

Cholesteryl ester transfer protein (CETP) increases the atherosclerosis risk by lowering HDL-cholesterol levels. It also exhibits tissue-specific effects independent of HDL. However, sexual dimorphism of CETP effects remains largely unexplored.

The impact of cholesteryl ester transfer protein on the progression of cutaneous leishmaniasis.

Introduction: Pathogenesis of cutaneous leishmaniases involves parasite growth, persistent inflammation, and likely participation of lipoproteins (LP). The cholesteryl ester transfer protein (CETP), involved in LP remodeling, has been shown to participate in the inflammatory response and the evolution of infectious conditions.

Methods: We evaluated the impact of the presence of CETP on infection by in an experimental model of cutaneous leishmaniasis using C57BL6/J mice transgenic for human CETP (CETP), having as control their littermates that do not express the protein, wild-type (WT) mice.

Evaluation of oxidative stress in an experimental model of Crohn's disease treated with hyperbaric oxygen therapy.

Introduction: Treatments of Inflammatory Bowel Disease (IBD) are able to control symptoms in most cases, however, a fraction of patients do not improve or have a loss of response to treatments, making it important to explore new therapeutic strategies. Hyperbaric oxygen therapy (HBO) may represent one of them. The aim of this study was to evaluate the effects of HBO therapy in an experimental model of IBD.

ALX/FPR2 Activation by Stereoisomers of D1 Resolvins Elucidating with Molecular Dynamics Simulation.

Chronic inflammation contributes to several diseases, but its resolution is driven by specialized pro-resolving mediators (SPM) such as resolvin D1 (RvD1) and its epimer aspirin-triggered resolvin D1 (AT-RvD1), both biosynthesized from ω-3 fatty docosahexaenoic acid (DHA). RvD1 and AT-RvD1 have anti-inflammatory and pro-resolution potentials, and their effects could be mediated by formyl peptide receptor type 2 receptor ALX/FPR2, a G-protein-coupled receptor (GPCR). In this work, we performed 44 μs of molecular dynamics simulations with two complexes: FPR2@AT-RvD1 and FPR2@RvD1.

Increased plasma lipids in triple-negative breast cancer and impairment in HDL functionality in advanced stages of tumors.

The association between plasma lipids and breast cancer (BC) has been extensively explored although results are still conflicting especially regarding the relationship with high-density lipoprotein cholesterol (HDLc) levels. HDL mediates cholesterol and oxysterol removal from cells limiting sterols necessary for tumor growth, inflammation, and metastasis and this may not be reflected by measuring HDLc. We addressed recently diagnosed, treatment-naïve BC women (n = 163), classified according to molecular types of tumors and clinical stages of the disease, in comparison to control women (CTR; n = 150) regarding plasma lipids and lipoproteins, HDL functionality and composition in lipids, oxysterols, and apo A-I.

Monocyte-to-HDL ratio and non-HDL cholesterol were predictors of septic shock in newborns.

Background: The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis.

Methods: This prospective study included 49 septic neonates and 17 controls.

Plasma Campesterol Is Positively Associated with Carotid Plaques in Asymptomatic Subjects.

Background: Increased cholesterol absorption and reduced synthesis are processes that have been associated with cardiovascular disease risk in a controversial way. However, most of the studies involving markers of cholesterol synthesis and absorption include conditions, such as obesity, diabetes, dyslipidemia, which can be confounding factors. The present study aimed at investigating the relationships of plasma cholesterol synthesis and absorption markers with cardiovascular disease (CVD) risk factors, cIMT (carotid intima-media thickness), and the presence of carotid plaques in asymptomatic subjects.

Relationship between lipoprotein (a) and subclinical carotid atherosclerosis in asymptomatic individuals.

Background: This study aimed to evaluate the associations between Lipoprotein (a) ‒ Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data.

Methods: A total of 317 healthy normolipidemic subjects (20‒77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography.

Screening of and Genes for Sitosterolemia in a Familial Hypercholesterolemia Cascade Screening Program.

Background: Sitosterolemia is a rare autosomal recessive disorder caused by homozygous or compound heterozygous variants in . The disease is characterized by increased plasma plant sterols. Small case series suggest that patients with sitosterolemia have wide phenotypic heterogeneity with great variability on either plasma cholesterol levels or development of atherosclerotic cardiovascular disease.

Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration.

Objectives: Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol).

Method: The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study.

Plasma advanced glycation end products and soluble receptor for advanced glycation end products as indicators of sterol content in human carotid atherosclerotic plaques.

Advanced glycation end products (AGEs) are independently related to cardiovascular disease (CVD) and favor cholesterol and oxysterol accumulation in macrophage foam cells. Soluble RAGE (sRAGE) impairs cellular AGE signaling alleviating the deleterious effects of AGE in atherogenesis. The association between plasma AGEs and sRAGE with the content of cholesterol, markers of cholesterol synthesis and absorption, and oxysterols in atherosclerotic plaques was evaluated in subjects undergoing carotid endarterectomy.

The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration.

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group.

Epidemiological analysis of stroke patients with emphasis on access to acute-phase therapies.

Background: Stroke is a public health problem. For patients with ischemic stroke, venous thrombolysis and mechanical thrombectomy are effective therapeutic options. However, even after the National Stroke Treatment Guidelines were published in 2012, the number of cases treated is still lower than expected.

Cholesterol metabolism in aging simultaneously altered in liver and nervous system.

In humans, aging, triggers increased plasma concentrations of triglycerides, cholesterol, low-density lipoproteins and lower capacity of high-density lipoproteins to remove cellular cholesterol. Studies in rodents showed that aging led to cholesterol accumulation in the liver and decrease in the brain with reduced cholesterol synthesis and increased levels of cholesterol 24-hydroxylase, an enzyme responsible for removing cholesterol from the brain. Liver diseases are also related to brain aging, inducing changes in cholesterol metabolism in the brain and liver of rats.

HISTOPATHOLOGICAL, CLINICAL AND EPIDEMIOLOGICAL FEATURES OF HEPATOPORTAL SCLEROSIS IN A REFERRAL CENTER FOR LIVER DISEASE IN NORTHEASTERN BRAZIL.

Background: Hepatoportal sclerosis HPS or obliterative portal venopathy (OPV), one of the differential diagnoses for non-cirrohtic portal hypertension, is characterized by the disappearance of the portal branches, portal and septal fibrosis, perisinusoidal fibrosis and regenerative nodular hyperplasia (RNH). It is a spectral disease that may progress to severe portal hypertension. Its etiopathogenesis is still little understood, especially in Brazil, it has been probably misdiagnosed due to its histopatological similarities with the hepatosplenic form of schistosomiasis.

Supplementation of omega-3 and dietary factors can influence the cholesterolemia and triglyceridemia in hyperlipidemic Schnauzer dogs: A preliminary report.

Primary hyperlipidaemia in Schnauzer is characterized by increased plasma triglycerides (TG) and/or total cholesterol (TC) concentration and is associated with an increased risk of developing pancreatitis, insulin resistance and seizures. In humans, omega-3 fatty acids in addition to a low-fat diet can be used to reduce TG and TC. This study evaluated the therapeutic efficacy of omega-3 fatty acids associated to a diet management with two different fat content in Schnauzer with primary hyperlipidaemia.

Cholesterol-Ester Transfer Protein Alters M1 and M2 Macrophage Polarization and Worsens Experimental Elastase-Induced Pulmonary Emphysema.

Cholesterol-ester transfer protein (CETP) plays a role in atherosclerosis, the inflammatory response to endotoxemia and in experimental and human sepsis. Functional alterations in lipoprotein (LP) metabolism and immune cell populations, including macrophages, occur during sepsis and may be related to comorbidities such as chronic obstructive pulmonary disease (COPD). Macrophages are significantly associated with pulmonary emphysema, and depending on the microenvironment, might exhibit an M1 or M2 phenotype.

Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial.

Background: COVID-19 is associated with a prothrombotic state leading to adverse clinical outcomes. Whether therapeutic anticoagulation improves outcomes in patients hospitalised with COVID-19 is unknown. We aimed to compare the efficacy and safety of therapeutic versus prophylactic anticoagulation in this population.

Antivirals virtual screening to SARS-CoV-2 non-structural proteins.

In March 2020, the World Health Organization (WHO) declared coronavirus disease-19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Since then, the search for a vaccine or drug for COVID-19 treatment has started worldwide. In this regard, a fast approach is the repurposing of drugs, primarily antiviral drugs.

Novel role of cholesteryl ester transfer protein (CETP): attenuation of adiposity by enhancing lipolysis and brown adipose tissue activity.

Objective: The systemic function of CETP has been well characterized. CETP plasma activity reduces HDL cholesterol and thus increases the risk of atherosclerosis. Here, we investigated whether CETP expression modulate adiposity.

DISTINCT PHENOTYPE OF NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH LOW LEVELS OF FREE COPPER AND OF CERULOPLASMIN.

Background: Copper deficiency has been linked to alterations in lipid metabolism and hepatic steatosis. Oxidative stress plays a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). One of the enzymes that neutralize oxidative stress is Cu/Zn superoxide dismutase, which depends on the availability of adequate amounts of copper.

The coronary artery calcium score is linked to plasma cholesterol synthesis and absorption markers: Brazilian Longitudinal Study of Adult Health.

It is controversial whether atherosclerosis is linked to increased intestinal cholesterol absorption or synthesis in humans. The aim of the present study was to relate atherosclerosis to the measurements of plasma markers of cholesterol synthesis (desmosterol, lathosterol) and absorption (campesterol, sitosterol). In healthy male (n=344), non-obese, non-diabetics, belonging to the city of São Paulo branch of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), we measured in plasma these non-cholesterol sterol markers, together with their anthropometric, dietary parameters, traditional atherosclerotic risk factors, and blood chemistry, coronary arterial calcium score (CAC), and ultrasonographically measured common carotid artery intima-media thickness (CCA-IMT).