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This study aims to elaborate on a novel comprehensive CE-ICP-MS/MS method for liposome-based cisplatin delivery system characterization. The optimized method allows for direct monitoring of formation products, the drug loading efficiency, and the stability of systems under proteinaceous conditions.

Nucleic acid extraction and purification are crucial steps in sample preparation for multiple diagnostic procedures. Routine methodologies of DNA isolation require benchtop equipment (e.g., centrifuges) and labor-intensive steps. Magnetic nanoparticles (MNPs) as solid-phase sorbents could simplify this procedure. A wide range of surface coatings employs various molecular interactions between dsDNA and magnetic nano-sorbents. However, a reliable, comparative evaluation of their performance is complex. In this work, selected Fe3O4 modifications, i.e., polyethyleneimine, gold, silica, and graphene derivatives, were comprehensively evaluated for applications in dsDNA extraction. A family of single batch nanoparticles was compared in terms of morphology (STEM), composition (ICP-MS/MS and elemental analysis), surface coating (UV-Vis, TGA, FTIR), and MNP charge (ζ-potential). ICP-MS/MS was also used to unify MNPs concentration allowing a reliable assessment of individual coatings on DNA extraction. Moreover, studies on adsorption medium (monovalent vs. divalent ions) and extraction buffer composition were carried out. As a result, essential relationships between nanoparticle coatings and DNA adsorption efficiencies have been noticed. Fe3O4@PEI MNPs turned out to be the most efficient nano sorbents. The optimized composition of the extraction buffer (medium containing 0.1 mM EDTA) helped avoid problems with Fe3+ stripping, which improved the validity of the spectroscopic determination of DNA recovery.

Background: Metabolic derangements related to tissue energetics constitute an important pathophysiological feature of heart failure. We investigated whether iron deficiency and catabolic/anabolic imbalance contribute to decreased skeletal muscle performance in men with heart failure with reduced ejection fraction (HFrEF), and whether these pathologies are related to each other. Methods: We comprehensively examined 23 men with stable HFrEF (median age [interquartile range]: 63 [59–66] years; left ventricular ejection fraction: 28 [25–35]%; New York Heart Association class I/II/III: 17/43/39%). We analyzed clinical characteristics, iron status, hormones, strength and fatigability of forearm flexors and quadriceps (surface electromyography), and exercise capacity (6-minute walking test). Results: None of the patients had anemia whereas 8 were iron-deficient. Flexor carpi radialis fatigability correlated with lower reticulocyte hemoglobin content (CHR, p < 0.05), and there was a trend towards greater fatigability in patients with higher body mass index and lower serum ferritin (both p < 0.1). Flexor carpi ulnaris fatigability correlated with lower serum iron and CHR (both p < 0.05). Vastus medialis fatigability was related to lower free and bioavailable testosterone (FT and BT, respectively, both p < 0.05), and 6-minute walking test distance was shorter in patients with higher cortisol/FT and cortisol/BT ratio (both p < 0.05). Lower ferritin and transferrin saturation correlated with lower percentage of FT and BT. Men with HFrEF and iron deficiency had higher total testosterone, but lower percentage of FT and BT. Conclusions: Iron deficiency correlates with lower bioactive testosterone in men with HFrEF. These two pathologies can both contribute to decreased skeletal muscle performance in such patients.

The abnormal concentration of microRNAs (miRNAs) can be associated with occurrence of various diseases including cancer, cardiovascular and neurodegenerative, hence they can be considered as potential biomarkers. An attractive approach could be the application of electrochemical methods, particularly where hybridization event between single-stranded deoxyribonucleic acid (ssDNA) or peptide-nucleic acid (PNA) with miRNA strand happens. Recently, the use of various nanomaterials such as gold nanoparticles, graphene oxide, quantum dots as well as catalyzed hairpin assembly or hybridization chain reaction were proposed to further enhance the performance of elaborated sensors. Herein, we present the studies on selection of receptor layer composition for detection of miRNA 141. The possibility of formation of receptor layer and further duplex monolayer between ssDNA or PNA with miRNA was analyzed by atomic force microscopy (AFM) technique. The interaction of ssDNA and PNA probes with miRNA was further verified using surface plasmon resonance (SPR) and quartz - crystal microbalance (QCM) techniques. On the basis of impedance spectroscopy it was shown that the use of unlabelled ssDNA as receptor layer provided 0.1 pM detection limit. This shows that proposed biosensor that is simple in preparation and use is an attractive alternative to other recently presented approaches.

Laser toners appear as attractive materials for barriers and easily laminated interphases for Lab-on-a-Foil microfluidics, due to the excellent adhesion to paper and various membranes or foils. This work shows for the first time a comprehensive study on the adsorption of antibodies on toner-covered poly(ethylene terephthalate) (PET@toner) substrates, together with assessment of such platforms in rapid prototyping of disposable microdevices and microarrays for immunodiagnostics. In the framework of presented research, the surface properties and antibody binding capacity of PET substrates with varying levels of toner coverage (0–100%) were characterized in detail. It was proven that polystyrene-acrylate copolymer-based toner offers higher antibody adsorption efficiency compared with unmodified polystyrene and PET as well as faster adsorption kinetics. Comparative studies of the influence of pH on the effectiveness of antibodies immobilization as well as measurements of surface ζ-potential of PET, toner, and polystyrene confirmed the dominant role of hydrophobic interactions in adsorption mechanism. The applicability of PET@toner substrates as removable masks for protection of foil against permanent hydrophilization was also shown. It opens up the possibility of precise tuning of wettability and antibody binding capacity. Therefore, PET@toner foils are presented as useful platforms in the construction of immunoarrays or components of microfluidic systems.

Spherical gold nanoparticles (GNPs), whose unique properties regarding biomedical applications were broadly investigated, are an object of interest as nanocarriers in drug targeted delivery systems (DTDSs). The possibility of surface functionalization, especially in enabling longer half-life in the bloodstream and enhancing cellular uptake, provides an opportunity to overcome the limitations of popular anticancer drugs (such as cisplatin) that cause severe side effects due to their nonselective transportation. Herein, we present investigations of gold nanoparticle–cisplatin systems formation (regarding reaction kinetics and equilibrium) in which it was proved that the formation efficiency and stability strongly depend on the nanoparticle surface functionalization. In this study, the capillary electrophoresis hyphenated with inductively coupled plasma tandem mass spectrometry (CE-ICP-MS/MS) was used for the first time to monitor gold–drug nanoconjugates formation. The research included optimizing CE separation conditions and determining reaction kinetics using the CE-ICP-MS/MS developed method. To characterize nanocarriers and portray changes in their physicochemical properties induced by the surface’s processes, additional hydrodynamic size and ζ-potential by dynamic light scattering (DLS) measurements were carried out. The examinations of three types of functionalized GNPs (GNP-PEG-COOH, GNP-PEG-OCH3, and GNP-PEG-biotin) distinguished the essential differences in drug binding efficiency and nanoconjugate stability.

Iron deficiency (ID) constitutes an important comorbidity affecting symptoms and outcomes in patients with heart failure (HF). Recent experimental studies and randomized clinical trials have demonstrated important novel data regarding either the mechanisms of this comorbid condition or the beneficial effects of intravenous iron therapy in patients with HF. In this review we summarize new developments regarding ID in patients with HF with either reduced or preserved ejection fraction, along with brief description of ongoing morbidity and mortality trials in this field-4 years after the release of the 2016 European Society of Cardiology guidelines that clearly recommend to screen for, and consider treatment of, ID in patients with HF with reduced ejection fraction.

Although heart failure (HF) is considered as a cardiogeriatric syndrome, elderly and very elderly patients are under-represented in the vast majority of clinical trials investigating novel drugs and therapies in this population. The homoeostatic systems of elderly subjects are very fragile, and the management of HF accompanied by numerous comorbidities requires a holistic approach towards the patient, with special emphasis not only on psychosomatic problems but also on the individual (including social) needs of each particular patient, along with the support for the family and/or caregivers. In this article, we summarize current evidence regarding pharmacotherapy of elderly patients with HF and summarize the clinical problems occurring in this population.

The 2016 ESC/HFA heart failure (HF) guidelines emphasize the importance of identifying and treating iron deficiency (ID) in patients with HF. Iron deficiency can occur in half or more of HF sufferers, depending on age and the phase of the disease. Iron deficiency can be a cause of anaemia, but it is also common even without anaemia, meaning that ID is a separate entity, which should be screened for within the HF population. Although assessment of iron stores in bone marrow samples is the most accurate method to investigate iron status, it is not practical in most HF patients. Levels of circulating iron biomarkers are an easily available alternative; especially, ferritin and transferrin saturation (Tsat). In patients with HF serum ferritin level

AIMS Abnormal endogenous erythropoietin (EPO) constitutes an important cause of anaemia in chronic diseases. We analysed the relationships between iron deficiency (ID) and the adequacy of endogenous EPO in anaemic heart failure (HF) patients, and the impact of abnormal EPO on 12-month mortality. METHODS AND RESULTS We investigated 435 anaemic HF patients (age: 74 ± 10 years; males: 60%; New York Heart Association class I or II: 39%; left ventricular ejection fraction: 43 ± 17%). Patients with EPO higher than expected for a given haemoglobin were considered EPO-resistant whereas those with EPO lower than expected - EPO-deficient. ID was defined as serum ferritin

The presented work concerns pattern-based sensing with quantum dots for the identification and quantification of neurotransmitters by means of excitation-emission fluorescence spectroscopy (2D fluorescence). In the framework of this study, glutathione capped CdSeS/ZnS nanocrystals were used as non-specific nanoreceptors capable of differentiated interaction with neurotransmitters. The pattern-based sensing with QDs was realized by using excitation-emission fluorescence spectroscopy to provide analyte-specific multidimensional optical information. These characteristic fluorescent response patterns were processed by unfolded partial least squares–discriminant analysis, showing that satisfactory identification of all investigated neurotransmitters: dopamine, norepinephrine, epinephrine, serotonin, GABA, and acetylcholine, can be achieved through the proposed sensing strategy. The impact of the considered fluorescence signal (datum, i.e. zeroth-order data acquired per sample; spectrum, i.e. first-order data acquired per sample; excitation-emission matrix, i.e. second-order data acquired per sample) on the sensing capability of glutathione capped QDs was also verified. The best performance parameters such as accuracy, precision, sensitivity, and specificity were obtained using excitation-emission matrices (88.9–93.3%, 0.93–0.95, 0.89–0.93, and 0.99–1.00, respectively). Thus, it was revealed that excitation-emission fluorescence spectroscopy may improve the recognition of neurotransmitters while using only one type of nanoreceptor. Furthermore, is was demonstrated that the proposed excitation-emission fluorescence spectroscopy assisted QD assay coupled with unfolded partial least squares regression can be successfully utilized for quantitative determination of catecholamine neurotransmitters at the micromolar concentration range with R2 in the range 0.916–0.987. Consequently, the proposed sensing strategy has the potential to significantly simplify the sensing element and to expand the pool of bioanalytes so far detectable with the use of QDs. Graphical abstract

The purpose of the presented work was to modify the surface of core/shell-type CdSexS1–x/ZnS quantum dots (QDs) with an anticancer drug to form bifunctional nanoconjugate for imaging and drug delivery. 6-Thioguanine (6-TG) which is used to treat acute myeloid and lymphoblastic leukemia was applied for this aim. The modification of the nanocrystals was carried out using a biphasic method, based on transferring of QDs from the organic phase to the aqueous one with the simultaneous exchange of hydrophobic ligand to the hydrophilic one. To enable a complex evaluation of 6-TG bioactivity, the surface of quantum dots was also modified using mercaptoacetic acid (MAA). Mercaptoacetic acid was chosen as a biologically neutral ligand; so, it was possible to evaluate the effect of nanocrystals toxicity without the participation of the drug (6-TG ligand versus neutral ligand). Moreover, the effect of 6-TG itself on cells was also studied. The studies were carried out on three cell lines: K562 (human myeloid leukemia), A549 (human lung cancer cells) and MRC-5 (normal human lung cells). Evaluation of the cytotoxicity of nanostructures, at various concentrations, was carried out after 24- and 48-h incubation of the cell culture with nanoparticles/drug solutions. MTT and the Alamar Blue assays were used to determine cell viability. Based on the cytotoxicity measurements, it was found that quantum dots modified with 6-TG are more toxic than the drug itself or QDs modified with 3-mercaptoacetic acid. Images taken using fluorescence and confocal microscopy allowed to define the location of examined QDs inside cells.

In this work core/shell cadmium-free zinc‑copper‑indium sulfide ZnCuInS/ZnS quantum dots (QDs) originally stabilized with hydrophilic alkanethiol were modified with 3-mercaptopropionic acid (MPA) or 6-mercaptohexanoic acid (MHA) via two-step ligand exchange method. The obtained QDs were further characterized by TEM, UV Vis, and fluorescence spectroscopy. Both types of QDs were non-toxic in a wide range of concentrations. To our knowledge, our studies are the first attempt to determine the type of cell death and reactive oxygen species production level as a result of incubation of cell cultures with ZnCuInS/ZnS QDs. Furthermore, the accumulation of QDs in vitro was examined on three human cell lines by fluorescence intensity measurements and visualized by confocal microscopy. The modification of QDs with a ligand characterized by slightly longer aliphatic chain (MHA), instead of typically used MPA turns out to be beneficial both from the point of colloidal stability, preservation of optical properties during ligand exchange as well as reflects in a higher cellular uptake. This contribution can be beneficial from the point of view of the selection of the optimal ligands and concentrations in the case of ZnCuInS/ZnS core-shell QDs for biological applications.

This article describes the work on synthesis, surface functionalization and characterization of hollow gold nanoshells (HGNs), and their application in a photothermal tumor therapy. The studied gold nanoshells were synthesized using a method based on a reduction of HAuCl4 onto silver nanoparticle templates. A selected aptamer - AS1411 – selective towards nucleolin, with a terminal thiol group was conjugated to HGNs. Surface functionalization of synthesized nanoparticles was necessary to gain the affinity to tumor cells, thus allowing the selective delivery of the modified nanoparticles to target cells. As expected, an increased selectivity of nanoconjugates towards tumor cells (A375) in a comparison to normal ones (HaCaT) was observed (2.67 times). In the framework of our studies the biological activity of the obtained nanoconjugates was evaluated using MTT assay. For this aim, both normal and tumor cell cultures respresenting skin tissue were exposed to gold nanoparticles solutions. It was found, that HGN-AS1411 conjugates cause less than 10% loss in a cell viability in the case of both cell lines at the highest tested concentration. The potential of the developed nanoconjugates as agents in PTT of skin cancer was investigated in a subsequent stage of our research. It was found, that A375 cell viability amounted to less than 40% for 75μM of nanoconjugates (expressed as a concentration of Au atoms) as a result of the laser irradiation of this cell culture after desired accumulation of the tested nanoconjugates inside A375 cells.

Interactions of proteins with nanomaterials draw attention of many research groups interested in fundamental phenomena. However, alongside with valuable information regarding physicochemical aspects of such processes and their mechanisms, they more and more often prove to be useful from a point of view of bioanalytics. Deliberate use of processes based on adsorption of proteins on nanoparticles (or vice versa) allows for a development of new analytical methods and improvement of the existing ones. It also leads to obtaining of nanoparticles of desired properties and functionalities, which can be used as elements of analytical tools for various applications. Due to interactions with nanoparticles, proteins can also gain new functionalities or lose their interfering potential, which from perspective of bioanalytics seems to be very inviting and attractive. In the framework of this article we will discuss the bioanalytical potential of interactions of proteins with a chosen group of nanoparticles, and implementation of so driven processes for biosensing. Moreover, we will show both positive and negative (opportunities and challenges) aspects resulting from the presence of proteins in media/samples containing metal-based nanoparticles or their precursors.

Cardiac fibroblasts and cardiomyocytes are the main cells involved in the pathophysiology of myocarditis (MCD). These cells are especially sensitive to changes in iron homeostasis, which is extremely important for the optimal maintenance of crucial cellular processes. However, the exact role of iron status in the pathophysiology of MCD remains unknown. We cultured primary human cardiomyocytes (hCM) and cardiofibroblasts (hCF) with sera from acute MCD patients and healthy controls to mimic the effects of systemic inflammation on these cells. Next, we performed an initial small-scale (n = 3 per group) RNA sequencing experiment to investigate the global cellular response to the exposure on sera. In both cell lines, transcriptomic data analysis revealed many alterations in gene expression, which are related to disturbed canonical pathways and the progression of cardiac diseases. Moreover, hCM exhibited changes in the iron homeostasis pathway. To further investigate these alterations in sera-treated cells, we performed a larger-scale (n = 10 for controls, n = 18 for MCD) follow-up study and evaluated the expression of genes involved in iron metabolism. In both cell lines, we demonstrated an increased expression of transferrin receptor 1 (TFR1) and ferritin in MCD serum-treated cells as compared to controls, suggesting increased iron demand. Furthermore, we related TFR1 expression with the clinical profile of patients and showed that greater iron demand in sera-treated cells was associated with higher inflammation score (interleukin 6 (IL-6), C-reactive protein (CRP)) and advanced neurohormonal activation (NT-proBNP) in patients. Collectively, our data suggest that the malfunctioning of cardiomyocytes and cardiofibroblasts in the course of MCD might be related to alterations in the iron homeostasis.

Background Large randomized clinical trials have demonstrated that intravenous (IV) iron therapy in iron-deficient patients with heart failure with reduced ejection fraction (HFrEF) brings clinical benefits related to symptoms of the disease and exercise capacity. Mechanisms underlying beneficial effects of such repletion are still the subject of interest as this is not solely related to improved haematopoiesis (IV iron works also in non-anaemic subjects). In patients with chronic heart failure iron deficiency (ID) is linked with inflammatory processess but data regarding the impact of IV iron on inflammation is scarce. Purposes We evaluated whether IV iron therapy affects circulating biomarkers of pro-inflammatory state in men with HFrEF and concomitant ID. Methods This is the sub-analysis of the study to investigate the effects of IV ferric carboxymaltose (FCM) on the functioning of skeletal muscles in men with HFrEF. For the purposes of current research we analyzed data of 20 men with HFrEF (median age 68 (62, 75 – in brackets interquartile ranges, respectively) years, LVEF: 30 (25, 35) %, ischaemic HF aetiology: 85%, NYHA class I/II/III: 30%/50%/20%) and ID (definition according to ESC guidelines - ferritin Results IV FCM therapy repleted iron stores in men with HFrEF as reflected by an increase in serum ferritin and TSAT, which was not seen in a control group. IV FCM therapy (as well as the saline administration) affected neither haemoglobin concentration nor parameters reflecting iron stores in red cells. Baseline serum ferritin was not related to hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 (all p>0.23). Baseline TSAT was related to hs-CRP (r=−0.47, p=0.02) but not other inflammatory biomarkers. Levels of hs-CRP, TNF-α, IL-6, IL-1β, and IL-22 at week 0 were similar in subjects who received IV iron and controls (all p>0.22). Change from week 0 to week 24 adjusted for baseline value (delta W24-W0 as the percentage of W0) regarding IL-22 was lower in an active treatment arm as compared with saline (p=0.049) and there was a trend towards lower delta TNF-α in FCM group compared to saline (p=0.067). These findings were not valid for other measured pro-inflammatory biomarkers. Conclusions In men with HFrEF and concomitant ID intravenous iron therapy with FCM affects biomarkers of pro-inflammatory state. Clinical relevance of this finding requires further translational research. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This research was funded by the National Science Centre (Poland) grant allocated on the basis of the decision number DEC-2012/05/E/NZ5/00590

Reactive oxygen species (ROS) play an important role in various physiological processes of living organisms. However, their increased concentration is usually considered as a threat for our health. Plants, invertebrates, and vertebrates including humans have various enzymatic and non-enzymatic defence systems against ROS. Unfortunately, both bad condition of surrounding environment and unhealthy lifestyle can interfere with an activity of enzymes responsible for a regulation of ROS levels. Therefore, it is important to look for alternative ROS scavengers, which could be administrated to chosen tissues to prevent pathological processes such as distortion of DNA or RNA structures and oxidation of proteins and lipids. One of the most recently proposed solutions is the application of nanozymes, which could mimic the activity of essential enzymes and prevent excessive activity of ROS. In this work, nanoparticles of Au, Pt, Pd, Ru and Rh were synthesized and studied in this regard. Peroxidase-, catalase (CAT)- and superoxide dismutase (SOD)-like activity of obtained nanoparticles were tested and compared using different methods. The influence of bovine and human albumins on CAT- and peroxidase-like activity was examined. Moreover, in the case of CAT-like activity, an influence of pH and temperature was examined and compared. Determination of SOD-like activity using the methods described for the examination of the activity of native enzyme was not fully successful. Moreover, cytotoxicity of chosen nanoparticles was studied on both regular and tumor cells.

To estimate the risk of all‐cause mortality and hospitalization in frail patients with chronic heart failure (HF), a systematic search and meta‐analysis was carried out to identify all prospective cohort studies conducted among adults with HF where frailty was quantified and related to the primary endpoints of all‐cause mortality and/or hospitalization. Twenty‐nine studies reporting the link between frailty and all‐cause mortality in 18 757 patients were available for the meta‐analysis, along with 11 studies, with 13 525 patients, reporting the association between frailty and hospitalization. Frailty was a predictor of all‐cause mortality and hospitalization with summary hazard ratios (HRs) of 1.48 [95% confidence interval (CI): 1.31–1.65, P

The concept of frailty syndrome (FS) was first described in the scientific literature three decades ago. For a very long time, we understood it as a geriatric problem, recently becoming one of the dominant concepts in cardiology. It identifies symptoms of FS in one in 10 elderly people. It is estimated that in Europe, 17% of elderly people have FS. The changes in FS resemble and often overlap with changes associated with the physiological aging process of the body. Although there are numerous scientific reports confirming that FS is age correlated, it is not an unavoidable part of the aging process and does not apply only to the elderly. FS is a reversible clinical condition. To maximize benefits of frailty-reversing activities for patient with frailty, identification of its determinants appears to be fundamental. Many of the determinants of the FS have already been known: reduction in physical activity, malnutrition, sarcopenia, polypharmacy, depressive symptom, cognitive disorders, and lack of social support. This review shows that insight into FS determinants is the starting point for building both the comprehensive definition of FS and the adoption of the assessment method of FS, and then successful clinical management.

Background Recent evidence suggests that iron depletion may be involved in the pathophysiology of acute myocarditis (MCD), however no data on the contribution of this mechanism to the MCD-associated cardiac performance abnormalities are available. The decrease in longitudinal deformation is an early manifestation of left ventricular (LV) dysfunction. Nonetheless, global longitudinal strain (GLS) is afterload-dependent, and the estimation of myocardial work correcting GLS for changes in systolic blood pressure may permit a more adequate assessment of LV contractility. Aim We sought to investigate the association between iron status and LV function in patients with MCD. Methods We prospectively included 30 patients (age 32 ± 8 years; 97% male) hospitalized for acute MCD in a tertiary cardiology center. MCD was diagnosed based on the following criteria: 1) new onset symptoms suggestive of myocarditis (exercise intolerance, dyspnea, palpitations or chest pain), 2) elevated high sensitivity cardiac troponin I (hscTnI), 3) exclusion of obstructive coronary artery disease, 4) confirmation of myocardial oedema based on T2 mapping in cardiac magnetic resonance. On admission, each participant underwent echocardiography with LV strain and myocardial work (global work index [GWI], global constructive work [GCW], global wasted work [GWW], global work efficiency [GWE]) analysis, and laboratory assessment including the iron status markers: ferritin and transferrin saturation (TSAT). Iron deficiency (ID) was defined as transferrin saturation (TSAT) Results ID was found in 16 (53%) enrollees. Patients with reduced TSAT demonstrated lower GCW and GWI than their peers with normal TSAT (Table). No significant between-group differences were found for GLS, LV ejection fraction, early diastolic tissue velocity (e’) and E/e’ ratio. Both subsets did not significantly differ with respect to hemoglobin, creatinine, NT-proBNP, hscTnI and CRP. Both GWI and GCW significantly correlated with TSAT (r = 0.39, p = 0.03, and r = 0.37, p = 0.04, respectively). In multivariable analysis, after adjustment for patient age, body mass index, creatinine, hscTnI and CRP, TSAT was an independent predictor of GWI (beta = 0.40; p = 0.02) and GCW (beta = 0.38; p = 0.02). Conclusion In patients with MCD, ID defined as low TSAT is associated with a worse LV longitudinal performance as assessed by GCW and GWI, which might suggest a role of this pathophysiological pathway in the development of cardiac dysfunction. Myocardial work parameters seem to outperform GLS in diagnosing LV functional impairment in this clinical setting. Abstract P1392 Figure.

Background Skeletal and respiratory muscle dysfunction constitutes an important pathophysiological feature of heart failure (HF). We assessed the relationships between respiratory muscle function, skeletal muscle mass, and physical fitness in men with HF with reduced left ventricular ejection fraction (HFrEF), and investigated the hypothesis of whether iron deficiency (ID) contributes to respiratory muscle dysfunction in these patients. Methods We examined 53 male outpatients with stable HFrEF without asthma or chronic obstructive pulmonary disease (age: 64 ± 10 years; New York Heart Association [NYHA] class I/II/III: 36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction ≤40%) and 10 middle-aged healthy men (control group). We analysed respiratory muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was measured using dual-energy X-ray absorptiometry), physical fitness (components of Functional Fitness Test for Older Adults), and iron status. Results MIP, MEP, and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs. healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower in men with HFrEF with vs. without ID. In a multivariable linear regression model lower serum ferritin (but not transferrin saturation) was associated with lower MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In multivariable linear regression models, lower MIP was associated with worse results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and haemoglobin concentration). Conclusions In men with HFrEF, low ferritin reflecting depleted iron stores is associated with inspiratory muscle weakness independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates with worse physical fitness independently of either skeletal muscle mass or disease severity.

This paper presents a modification of the surface of CdS/ZnS and CdSexS1−x/ZnS quantum dots (QDs) with 3-mercaptopropionic and 6-mercaptohexanoic acid. The obtained QDs were characterized using TEM, DLS, UV–Vis, and fluorescence spectroscopy. Flow cytometry was applied to evaluate the cytotoxicity of QDs and examine the type of death caused by the tested nanoparticles. In addition, the generation of reactive oxygen species after incubation of the tested cells with CdSexS1−x/ZnS–MPA and CdSexS1−x/ZnS–MHA QDs was evaluated. The study was conducted on three cell lines: adherent (A549 and MRC-5) and suspension ones (K562). The conducted research demonstrated that the tested nanoparticles exhibit concentration-dependent toxicity. It was observed that the surface modification influences the toxicity level of the examined QDs, and modification of their surface with the use of the ligand of longer carbon chain (MHA) reduces the toxicity in comparison with QDs–MPA. It was also found that all tested QDs caused the death of cells in the course of necrosis. Based on obtained results, it was concluded that the cytotoxicity of QDs is to a large extent related to reactive oxygen species (ROS) generation.

In our work, the cytotoxicity of selected, cadmium-based quantum dots with various surface architectures was studied on 3D spheroids. A specially designed microsystem as a tool for three-dimensional cell culture and nanoparticle toxicity evaluation was used for this aim. Two types of hydrophilic quantum dots with different surface charges at physiological pH were examined: CdTe-capped with ω-mercaptocarboxylic acid (COO−-terminated) and CdSeS/ZnS-glucosamine (–OH-terminated). We studied the influence of five different concentrations of nanoparticles within the range of 5 to 100 μM in order to assess dose-dependent toxic effects of the selected quantum dots on cellular spheroids as a more realistic (in vivo-like) model of human tissue. The obtained results of cytotoxicity were compared with the results for a standard, two-dimensional model – a cell monolayer. In the case of three-dimensional structures of various cell lines (normal MRC-5 and tumor A549) no significant differences in cytotoxicity caused by the tested nanoparticles have been noticed. The comparative studies revealed the enhanced biocompatibility of CdSeS/ZnS-OH quantum dots resulting from the presence of an uncharged ligand of biomimetic character on their surface. It was also found that the cytotoxicity of the same quantum dots depends on the cell culture model on which the tests were conducted. Significantly higher cytotoxicity of the tested nanomaterial was observed when experiments were carried out with the use of cell monolayers. Based on the obtained results, we claim that cytotoxicity studies of nanomaterials conducted on standard 2D cell monolayers are overestimated. In our opinion, reliable in vitro studies on the biological activity of nanoparticles require application of 3D cell cultures.

In patients with heart failure (HF), iron deficiency (ID) correlates with decreased exercise capacity and poor health-related quality of life, and predicts worse outcomes. Both absolute (depleted iron stores) and functional (where iron is unavailable for dedicated tissues) ID can be easily evaluated in patients with HF using standard laboratory tests (assessment of serum ferritin and transferrin saturation). Intravenous iron therapy in iron-deficient patients with HF and reduced ejection fraction has been shown to alleviate HF symptoms and improve exercise capacity and quality of life. In this paper, we provide information on how to diagnose ID in HF. Further we discuss pros and cons of different iron preparations and discuss the results of major trials implementing iron supplementation in HF patients, in order to provide practical guidance for clinicians on how to manage ID in patients with HF.

Iron deficiency (ID) is one of the most common co-morbidities in patients with heart failure (HF). It has its highest prevalence in elderly subjects, women, decompensated subjects, and patients with numerous co-morbidities. ID is associated with worse symptoms, poorer quality of life, reduced exercise capacity, and a high morbidity and mortality. Both ID and the anaemia it can lead to can be harmful in HF. Repletion of iron stores has been shown to be effective in HF and detection and treatment of ID are now recommended in major HF guidelines. This paper summarises iron therapy for ID in HF patients.

Background Cardiac myocytes, which are particularly sensitive to disordered iron homeostasis, are the main cells affected in the course of myocarditis. Iron is essential for the proper maintenance of energy metabolism but also plays key role in inflammation and ROS production. We hypothesize that iron homeostasis might be involved in the pathophysiology of myocarditis. Purpose The aim of the study was to assess differences in the expression of key genes and proteins involved in iron homeostasis, cardiac malfunctioning, and protection against ROS in human cardiomyocytes (HCMs) cultured in the indirect model of myocarditis. Methods HCMs were cultured for 48 hours with 10% of sera from patients with acute myocarditis (n=11) and after 6 weeks of recovery, and also with sera from healthy controls (n=7). We analyzed expression of light and heavy ferritin chains [FTL, FTH], transferrin receptor 1 [TfR1], galectin 3 [LGALs3], TGFβ signaling [TGFβ1, TGFβ2, TGFβ3], glutathione peroxidase [GPX] and superoxide dismutase [SOD1] at the mRNA level using RTqPCR and at the protein level using Western bloting. We compared obtained data with the clinical characteristics of patients. Results In HCMs exposed to sera from myocarditis patients, in comparison to those treated with sera from healthy controls, we found a significant increase in an expression of TfR1 both at mRNA and protein level (p Moreover, we observed elevated expression of FTH and FTL at the mRNA level (both p Interestingly, we noticed detrimental effects of myocarditis sera on HCMs reflected by augmented expression of galectin 3 (p In addition, HCMs treated with sera from myocarditis patients showed an increase in expression of ROS protective genes such as SOD1 and GPX (both p We noticed that gene expression profile was similar in HCMs treated with sera collected after 6 weeks of clinical recovery, suggesting that the negative impact of sera was preserved. Conclusions Malfunctioning of cardiomyocytes in course of myocarditis might be related to disturbances in the iron homeostasis. Acknowledgement/Funding The present study was financially supported by the National Science Centre (Krakow, Poland; grant no. 2014/13/B/NZ5/03146)

Introduction Acute myocarditis (MCD) can progress to post-myocarditis cardiomyopathy. Immune response is the major pathophysiological trigger leading to MCD. Optimal iron status is essential for the functioning of immune cells, cardiomyocytes and cardiofibroblasts. Therefore, there are premises to consider iron metabolism as a significant modulator of complex pathophysiology of MCD. Purpose We aimed to assess iron status in the course of MCD and relate it with clinical and laboratory measures. Methods We prospectively enrolled consecutive patients hospitalized for acute MCD in 2 tertiary referral cardiology centers during 2015–2018 and followed them up for 30 weeks. MCD was diagnosed based on the following criteria: 1) new onset symptoms suggestive of myocarditis (effort intolerance, dyspnea, palpitations or chest pain), 2) elevated high sensitivity cardiac troponin I (hs-cTnI), 3) exclusion of obstructive coronary artery disease. Results Study group comprised 41 patients with confirmed MCD [age: 31 (26–34) years, men: 95%] and 15 healthy age- and gender-matched subjects [age: 30 (28–33) years, men: 87%]. All patients survived hospitalization and follow-up, no subject needed ventricular assist device. Patients with MCD had lower LVEF (56±10% vs. 69±14%) and higher CRP [32 (14–8754) vs. 3 (3–3) mg/l], NT-proBNP [452 (240–877) vs. 33 (18–46) pg/ml], hs-cTnI [7.3 (3.3–12.8) vs. 0,01 (0.01–0.01) μg/l] than the control group (all p0.02). Patients with MCD and NT-proBNP >1000 pg/ml had lower TSAT (16±8 vs. 23±9%; p0.2). 46% of patients during acute phase of MCD had LVEF≤55% – these patients presented lower TSAT (17±8% vs. 24±10%) and higher NT-proBNP – [577 (436–1657) vs. 358 (167–499) pg/ml] (all p0.2). After 6 weeks of follow-up patients with MCD already presented higher LVEF (61±8%; p0.2). Conclusions Iron status is deranged in acute MCD. Serum ferritin is an indicator of inflammatory response, whereas TSAT relates to neurohormonal activation and cardiac dysfunction. Iron status normalizes within 6 weeks after acute phase of MCD. Acknowledgement/Funding This research was financially supported by the National Science Centre (Poland) grant number 2014/13/B/NZ5/03146.