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Coronary heart disease (CHD) is a prevalent cardiovascular disease characterized by coronary artery blood flow reductions caused by lipid deposition and oxidation within the coronary arteries. Dyslipidemia is associated with local tissue damage by oxidative stress/inflammation and carotid bodies (CB) peripheral chemoreceptors are heavily modulated by both reactive oxygen species and pro-inflammatory molecules (i.e., cytokines). Despite this, it is not know whether CB-mediated chemoreflex drive may be affected in CHD. In the present study, we evaluated peripheral CB-mediated chemoreflex drive, cardiac autonomic function, and the incidence of breathing disorders in a murine model of CHD. Compared to age-matched control mice, CHD mice showed enhanced CB-chemoreflex drive (twofold increase in the hypoxic ventilatory response), cardiac sympathoexcitation, and irregular breathing disorders. Remarkably, all these were closely linked to the enhanced CB-mediated chemoreflex drive. Our results showed that mice with CHD displayed an enhanced CB chemoreflex, sympathoexcitation, and disordered breathing and suggest that CBs may be involved in chronic cardiorespiratory alterations in the setting of CHD.

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Radiotherapy (RT) is an essential part of breast cancer (BC) treatments. Unfortunately, heart exposure to radiation can also impair the long-term survival of patients. Our study aimed to quantify the oncological benefit and the cardiovascular (CV) risk associated with modern RT in a real-world cohort of BC patients. Our descriptive study enrolled BC patients who received adjuvant RT. Ten-year overall survival (OS) was estimated using Predict® version 2.1 (National Health Service, London, UK). The basal risk of CV events was estimated using the American Heart Association (ACC/AHA) CV score. Treatment volumes and mean cardiac doses were obtained from RT treatment plan records. The increased risk of CV events due to RT was estimated using a model proposed by Darby. The risk of acute myocardial infarction or stroke mortality was estimated using HeartScore® (European Society of Cardiology, Brussels, Belgium). A total of 256 BC patients were included in the study. The average age of patients was 57 years old (range: 25-91); 49.6% had left BC. The mean cardiac dose was 166 cGy (interquartile range (IQR) 94-273); the estimated hazard ratio (HR) for CV disease was HR 1.12 (confidence interval (CI) 1.04-1.24). The estimated baseline 10-year CV risk was 5.6% (0.2 to 51.2); CV risk increased by 0.9% (range 0.02-35.47%) after RT. The absolute risk of 10-year mortality from CV disease was 2.5% (0.1-9); RT was associated with an estimated 4.9% survival benefit (3.73-6.07) against BC death and a 0.23% (0.17-0.29) estimated increase in CV mortality. Modern RT decreased 10-year BC mortality by 4% but increased CV mortality by 0.2% in this cohort. Our findings encourage the implementation of personalized adjuvant RT treatments that balance risks and benefits to improve long-term BC patient survival.

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Extracellular vesicles (EVs) are particles naturally released from cells that are delimited by a lipid bilayer and are unable to replicate. How the EVs cross the Blood-Brain barrier (BBB) in a bidirectional manner between the bloodstream and brain parenchyma remains poorly understood. Most in vitro models that have evaluated this event have relied on monolayer transwell or microfluidic organ-on-a-chip techniques that do not account for the combined effect of all cellular layers that constitute the BBB at different sites of the Central Nervous System. There has not been direct transcytosis visualization through the BBB in mammals in vivo, and evidence comes from in vivo experiments in zebrafish. Literature is scarce on this topic, and techniques describing the mechanisms of EVs motion through the BBB are inconsistent. This review will focus on in vitro and in vivo methodologies used to evaluate EVs transcytosis, how EVs overcome this fundamental structure, and discuss potential methodological approaches for future analyses to clarify these issues. Understanding how EVs cross the BBB will be essential for their future use as vehicles in pharmacology and therapeutics.

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Chickpeas are rich sources of bioactive compounds such as phenolic acids, flavonoids, and isoflavonoids. However, the contribution of insoluble-bound phenolics to their antioxidant properties remains unclear. Four varieties of chickpeas were evaluated for the presence of soluble (free and esterified) and insoluble-bound phenolics as well as their antiradical activity, reducing power and inhibition of peroxyl-induced cytotoxicity in human HuH-7 cells. In general, the insoluble-bound fraction showed a higher total phenolic content. Phenolic acids, flavonoids, and isoflavonoids were identified and quantified by UPLC-MS/MS. Taxifolin was identified for the first time in chickpeas. However, m-hydroxybenzoic acid, taxifolin, and biochanin A were the main phenolics found. Biochanin A was mostly found in the free fraction, while m-hydroxybenzoic acid was present mainly in the insoluble-bound form. The insoluble-bound fraction made a significant contribution to the reducing power and antiradical activity towards peroxyl radical. Furthermore, all extracts decreased the oxidative damage of human HuH-7 cells induced by peroxyl radicals, thus indicating their hepatoprotective potential. This study demonstrates that the antioxidant properties and bioactive potential of insoluble-bound phenolics of chickpeas should not be neglected.

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This study aimed to evaluate if the changes in oxygen saturation levels at intercostal muscles (SmO2-m.intercostales) assessed by near-infrared spectroscopy (NIRS) using a wearable device could determine the respiratory compensation point (RCP) during exercise. Fifteen healthy competitive triathletes (eight males; 29 ± 6 years; height 167.6 ± 25.6 cm; weight 69.2 ± 9.4 kg; V˙O2-máx 58.4 ± 8.1 mL·kg−1·min−1) were evaluated in a cycle ergometer during the maximal oxygen-uptake test (V˙O2-máx), while lung ventilation (V˙E), power output (watts, W) and SmO2-m.intercostales were measured. RCP was determined by visual method (RCPvisual: changes at ventilatory equivalents (V˙E·V˙CO2−1, V˙E·V˙O2−1) and end-tidal respiratory pressure (PetO2, PetCO2) and NIRS method (RCPNIRS: breakpoint of fall in SmO2-m.intercostales). During exercise, SmO2-m.intercostales decreased continuously showing a higher decrease when V˙E increased abruptly. A good agreement between methods used to determine RCP was found (visual vs NIRS) at %V˙O2-máx, V˙O2, V˙E, and W (Bland-Altman test). Correlations were found to each parameters analyzed (r = 0.854; r = 0.865; r = 0.981; and r = 0,968; respectively. p < 0.001 in all variables, Pearson test), with no differences (p < 0.001 in all variables, Student's t-test) between methods used (RCPvisual and RCPNIRS). We concluded that changes at SmO2-m.intercostales measured by NIRS could adequately determine RCP in triathletes.

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The IL-1 superfamily of cytokines is a central regulator of immunity and inflammation. The family is composed of 11 cytokines (with agonist, antagonist, and anti-inflammatory properties) and 10 receptors, all tightly regulated through decoy receptor, receptor antagonists, and signaling inhibitors. Inflammation not only is an important physiological response against infection and injury but also plays a central role in atherosclerosis development. Several clinical association studies along with experimental studies have implicated the IL-1 superfamily of cytokines and its receptors in the pathogenesis of cardiovascular disease. Here, we summarize the key features of the IL-1 family, its role in immunity and disease, and how it helps shape the development of atherosclerosis.

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BACKGROUND: Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. METHODOLOGY: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. DISCUSSION: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

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INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). METHODS: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. RESULTS: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. CONCLUSION: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.

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ETHNOPHARMACOLOGICAL RELEVANCE: Chilean population relies on medicinal plants for treating a wide range of illnesses, especially those of the gastrointestinal system. Junellia spathulata (Gillies & Hook.) Moldenke var. spathulata (Verbenaceae), called as "verbena-azul-de-cordilleira", is a medicinal plant native to Argentina and Chile traditionally used for treating digestive disorders. Although the species of the genus are important as therapeutic resources for the Andean population, the plants are very scarcely studied. AIMS OF THE STUDY: The purpose of the present study was to find out the main constituents and investigate the protective effect of J. spathulata against oxidative stress induced by the potent oxidant 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in human hepatoblastoma cells. MATERIALS AND METHODS: The crude methanol extract of J. spathulata and an iridoid obtained by chromatographic processes were tested to access the hepatoprotective effect and cytotoxicity in HepG2 cell. In addition, the reducing power of the samples and their ability to scavenge free radicals were evaluated using FRAP and ORAC assay systems. RESULTS: The iridoid asperuloside, the main compound of the crude methanol extract of J. spathulata, was isolated and identified by means of NMR analysis. The crude methanol extract of J. spathulata and asperuloside protected HepG2 cells against oxidative damage triggered by AAPH-derived free radicals. This effect can be credited to the ability of the extract and asperuloside to protect the liver cells from chemical-induced injury, which might be correlated to their free radical scavenging potential. CONCLUSIONS: This study experimentally evidenced the ethnopharmacological usefulness of J. spathulata as a treatment of digestive disorders. Our result could stimulate further investigations of hepatoprotective agents in other Chilean Junellia species.

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