Ventricular septal defect (VSD) is the second most common congenital heart anomaly. In most cases, it closes spontaneously in the first year of life, but it sometimes requires surgical closure due to the risk of serious complications. This is why it is important to identify markers that could help predict its course. Findings that matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play an important role in the cleavage of the extracellular matrix were the reasons to investigate their role in cardiogenesis. In prior studies on this topic, their concentrations were studied in the blood. The aim of this prospective study was to investigate the role of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the etiology and pathophysiology of VSD using urine samples, as an innovative non-invasive approach, and the enzyme-linked immunosorbent assay (ELISA) method. It involved 52 children with isolated VSD and 20 healthy children up to one year of age. We found that these MMPs and TIMPs are significantly (P = 0.000) higher in children with VSD, and the correlations between their concentrations and the size of the defect are positive, especially for MMP-9 and TIMP-1. MMP-9 was significantly (P = 0.044) higher in cases in which VSD did not close in the first year of life compared to cases in which it closed. Our results suggest the role of MMP-2, MMP-9, TIMP-1, and TIMP-2 in the aetiopathogenesis of VSD and that their urinary concentrations, especially of MMP-9, in combination with echocardiographic and clinical monitoring, could be useful in predicting its natural course.

Objectives: Many polyphenols such as EGCG from green tea, curcumin, apigenin, resveratrol or the alkaloid berberine show in-vitro activity that is much higher than FDA and EU approved drugs. And yet, while mice studies show excellent results, human clinical trials have so far been quite disappointing.Methods: In this review paper we accordingly present data from scientific literature and publicly available databases that support further development of nanoformulations for enhanced natural antioxidants bioavailability and activity.Results: Nanobubbles, and nanoparticles may enhance the polyphenols bioavailability and special coatings can be used to avoid liver fast inactivation. Zeolites have also been tested as carriers for bioactive compounds from the Mediterranean food. Other polyphenols can be used with nanoemulsions for synergistic antioxidants treatment. Finally, nanobubbles in the presence of ferric or copper ions at low pH as in human stomach or lysosomes can produce small amount of hydroxyl radicals, stimulating activation of Nrf2 transcription factor and detox enzymes.Discussion: A number of nanoformulations, including nanobubbles loaded with natural antioxidants may be used with low carbs and protein diet as a support to chemotherapy or treatment of advanced tumors. Good results in animal studies of neurodegenerative diseases and type II diabetes were also observed.KEY POLICY HIGHLIGHTSNanobubbles and nanoparticles may enhance the polyphenols' bioavailabilityNanobubbles may stimulate the activation of Nrf2 and detox enzymesArmoured oxygen nanobubbles may enhance radiotherapy or chemotherapy effects

The aim of this study was to characterise the elemental and radiological composition of strawberry tree (Arbutus unedo L.) leaves and tea preparations and compare it with commercial Uvin H herbal mixture, widely used in treatment of urinary tract infections. The concentration of 17 elements and the activity concentration of selected radionuclides were measured in strawberry tree leaves/Uvin H herbal mixture, as well as in herbal tea prepared by infusion or decoction of leaves for 5 or 10 min. In both leaves and tea preparations, Ca, K, Mg, and Na were the most abundant elements, while the lowest levels were measured for As, Co, Mo, and Se. Only 137Cs and 40K were detected in analysed leaves/herbal mixture, while the activity of radionuclides in tea preparations was below the detection limit. The maximum possible health benefits can be obtained by a 10-min decoction of leaves, which resulted in the highest total phenolic content and antioxidant activity and levels of K, Ca, Mg, Na, Fe, Mn, and Se in comparison to the other preparation methods evaluated in this study. The calculated intake of potentially toxic elements and radionuclides does not represent a health risk to consumers.

Numerous scientific studies have been conducted in recent decades with the aim to study targeted application of zeolites in various industries, ecology, agronomy and medicine. The biggest advances, however, have been documented in medical and veterinary research of the natural zeolite, clinoptilolite. Although the exact biological mechanisms of action of the zeolite clinoptilolite are not completely elucidated, obtained results point to its antioxidative, immunomodulatory and detoxifying effects, the latter partially based on release of soluble and bioavailable silica forms from the surface material. The studied zeolite clinoptilolite materials have different geographical origins which confer to the physicochemical differences in the material. In addition, the production process of the material for oral applications differs between different producers which also accounts for different properties of the surface upon mechanical activation. Recently, a well-characterized zeolite clinoptilolite material, namely the PMA-zeolite, has been tested in different clinical applications and has shown potential as supportive therapy in inflammatory conditions, osteoporosis as well as during tumor chemotherapy. We accordingly present a comprehensive review of the PMA-zeolite effects in the clinical applications and discuss its probable mechanisms of effect in vivo.

Cancer is still a leading cause of deaths worldwide, especially due to those cases diagnosed at late stages with metastases that are still considered untreatable and are managed in such a way that a lengthy chronic state is achieved. Nanotechnology has been acknowledged as one possible solution to improve existing cancer treatments, but also as an innovative approach to developing new therapeutic solutions that will lower systemic toxicity and increase targeted action on tumors and metastatic tumor cells. In particular, the nanoparticles studied in the context of cancer treatment include organic and inorganic particles whose role may often be expanded into diagnostic applications. Some of the best studied nanoparticles include metallic gold and silver nanoparticles, quantum dots, polymeric nanoparticles, carbon nanotubes and graphene, with diverse mechanisms of action such as, for example, the increased induction of reactive oxygen species, increased cellular uptake and functionalization properties for improved targeted delivery. Recently, novel nanoparticles for improved cancer cell targeting also include nanobubbles, which have already demonstrated increased localization of anticancer molecules in tumor tissues. In this review, we will accordingly present and discuss state-of-the-art nanoparticles and nano-formulations for cancer treatment and limitations for their application in a clinical setting.

Francisella tularensis is a gram-negative facultative intracellular bacterium that resists harsh environments. Several outbreaks of tularemia are linked to the consumption and contact with spring water. The number of F. tularensis in some waters is high, while in others, this bacterium does not survive. Except organic compounds, metals could be important for the survival of F. tularensis in water. Some Francisella strains showed the association with amoeba, which may act as the environmental reservoir. This study was aimed at following the role of metal ions and/or amoeba in the existence and replication of F. novicida in spring waters by growth kinetics, acquisition of metals, and ultrastructural analyses of bacteria. The bacteria showed a longer survival in water with higher initial concentrations of Mn and Zn. Although Mn and Zn were necessary for the survival of F. novicida, the results also showed that the bacterium does not grow in water with high levels of Zn. In contrast, high levels of Mn did not have such a negative effect on the survival of this bacterium in water. In addition, while F. novicida benefits presence of amoeba in spring water, the number of amoebae is decreasing in a coculture model with F. novicida.

European Journal of ImmunologyVolume 49, Issue S4 p. 1-75 Abstracts of MESIA 2019Free Access 4th Meeting of Middle European Societies for Immunology and Allergology, 28–30 November 2019, Samorin, Slovakia First published: 21 November 2019 https://doi.org/10.1002/eji.201970500AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume49, IssueS4Special Issue: 4th Meeting of Middle European Societies for Immunology and Allergology, 28–30 November 2019, Samorin, SlovakiaNovember 2019Pages 1-75 RelatedInformation

Alumosilicate materials zeolites are widely exploited due to porous structure and ion-exchange properties in several industrial, agriculture and veterinary applications. The mainly used zeolite for medical purposes in animals and humans is the natural zeolite clinoptilolite. Clinoptilolite may be prepared for medical applications by different methods that are usually based on mechanical or tribomechanical processing that increase specific surface area. Different processing procedures are known to cause substantial changes in the physical-chemical properties of the material that may affect biological properties as well. In this paper we therefore, (1) systematically analysed physical-chemical characteristics of three clinoptilolite materials obtained by different production methods and one synthetic zeolite to provide novel evidence on structural differences caused by production methods and (2) evaluated clinoptilolite materials detoxification properties in vitro and in AlCl3-intoxicated rats in vivo. We analysed a new clinoptilolite material as well, that was prepared by tribomechanical double micronization and oxygenation. Our results clearly show that each tested clinoptilolite material differs in physical chemical properties and that these are linked to the production method. Our results add knowledge on toxicology and safety properties of clinoptilolite materials as no aluminium leakage was observed from clinoptilolite materials into the blood or organs of tested animals. Presented results therefore, prove for the first time the efficiency of clinoptilolite in detoxification of aluminium in vivo, provide scientific data on clinoptilolite safety issues and usage for detoxification purposes. (C) 2017 Elsevier Inc. All rights reserved.

Changes in immune and inflammatory responses may play a crucial role in the development and progression of atherosclerosis, as an autoimmune, chronic and progressive inflammatory disease. Immunological activity and vascular inflammation during atherosclerosis can be modulated by autoimmune responses against self-antigens, according to changeable risk factors (cholesterol, oxidized low-density lipoprotein (ox-LDL) in the vascular wall, fatty acids, etc.), and accompanied by accumulation of leucocytes and proinflammatory cytokines, which stimulate the transcription of matrix metalloproteinases (MMPs), whose concentration are increased in foam cell-rich regions. Regulatory T cells (Tregs) represent a unique subpopulation of T cells specialized in the regulation of immune response and in the suppression of proatherogenic T cells. The aim of our study was to examine the interactions between the concentration of enzyme matrix metalloproteinases 2 and 9 (MMP-2 and 9) in urine and the percentage of Tregs in peripheral blood of two groups of patients: with carotid artery stenosis (CAS), undergoing surgery and with mild atherosclerosis (A) from general practice. The method of enzyme immunoassay (ELISA) was used to determine enzyme MMP expression, and Tregs was examined by flow cytometric analysis. Our data have showed a large increase in the enzyme MMP-2 and 9 in the urine of CAS and A patients in comparison with healthy controls and indicated this method as an easy marker for the monitoring of the development of atherosclerosis. Simultaneously, the diminished number of Tregs in the same patients pointed the importance of these regulatory mechanisms in the etiopathogenesis of atherosclerosis and possible Tregs-mediated therapy.

Ivana Sutic, Aleksandar Bulog, Ingrid Sutic, Valentino Pavisic, Ines Mrakovcic-Sutic Department of Family Medicine, Medical Faculty, University of Rijeka, Croatia Department of Public Health, Medical Faculty, University of Rijeka, Croatia Medical Faculty, University of Rijeka, Croatia Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Croatia e-mail: ines.mrakovcic.sutic@uniri.hr Abstract—Nowadays, the prevalence of environmental diseases is increasing worldwide and these diseases are an onerous burden both to the individual and to the public health. Urban air pollution represents a common and difficult problem in the majority of metropolises, which contain high levels of traffic congestion generating great amounts of genotoxic substances. Volatile organic compounds (VOCs) play an important role in ecological damages, disturbing the ecosystem and human health. Although the association between COPD and urban air pollution is well established, the relationship between the concentration of BTEX (benzene, toluene, ethyl benzene, isomeric xylenes) and occupational and environment risk factors has not been investigated. The objectivities and methods of our study were to determine the concentration of BTEX in urine in inhabitants from urban and rural areas, as well as in workers in shipyard, who are occupationally exposed to volatile aromatic hydrocarbons. Results: people living in urban industrial fields have significantly augmented the concentration of BTEX in urine, as well as the occupationally exposed workers in shipyards. Conclusion: BTEX-analyze in urine, as an important and easy method represents a good marker in environmental monitoring which contributes better protection of air pollutants and quicker diagnosis of occupationally exposed individuals.

Benzene, toluene, ethylbenzene, and isomeric xylenes (BTEX) are by-products of tobacco smoke and traffic emissions. The aim of this study was to determine the contribution of cigarette smoking to urinary levels of BTEX present in humans. Nicotine and cotinine, biomarkers of exposure to tobacco smoke, as well as BTEX, were measured in urine of smokers (n = 70) and nonsmokers (n = 65) using headspace solid-phase microextraction (HS-SPME) followed by gas chromatography-mass spectrometry (GC-MS). In smokers, a significant correlation was found between urinary BTEX levels and nicotine and cotinine. In addition, significant regression models with nicotine and cotinine as predictors showed that BTEX in smokers' urine was predominantly derived from exposure to tobacco smoke. In nonsmokers a weak correlation between BTEX and nicotine and cotinine was found in urine. Further, there was a lack of significant contribution of BTEX to urinary nicotine and cotinine concentrations in nonsmokers. Thus, it was presumed that vehicle exhaust was the main source of exposure to BTEX in nonsmokers.

BACKGROUND:Heavy metals naturally occur in the marine environment and ecosystems. Due to anthropogenic influence they became common waters and coastal regions pollutants in particular where their concentrations remain hazardously high. We therefore tested a protocol for combined analysis of 6 heavy metal (Pb, Cd, Cr, Zn, Fe and Hg) concentrations in mussels Mytilus galloprovincialis collected from a coastal industrial zone (shipyard locality) and mariculture facilities in combination with expression analysis of multi xenobiotic resistance related genes and stress-related gene (HSC-70).FINDINGS:In this paper we tested a protocol for heavy-metal levels assessment by use of a highly sensitive analytical method, ICP-OES, combined with expression analysis of multi xenobiotic resistance related genes, including the stress-related gene encoding 70-kDa heat shock cognate protein on mussels (Mytillus Galloprovincialis). Mussels from the shipyard locality had higher heavy metal concentrations, except Fe. Higher metal concentrations did not influence expression of multi xenobiotic resistance related genes with exception of stress-related gene (HSC-70) encoding 70-kDa heat shock cognate protein.CONCLUSIONS:Our results indicate that mussels sampled in the industrial area have increased metal concentrations in comparison with the aquaculture locality, that are accompanied by increased transcript levels of HSC-70.