Contrast-Free FLIM Reveals Metabolic Changes in Pathological Islets of Langerhans

FLIM (Fluorescence Lifetime Imaging Microscopy) is a powerful tool that could be used in the future to diagnose islet cell recovery after therapy. The identification of appropriate FLIM parameters is required to determine islet quality and islet cell metabolism throughout the organ under various conditions of insulin deficiency. The aim of the work was to identify key FLIM parameters, changes of which are characteristic of pancreatic pathologies. The τm, τ1, τ2, α1, α2 and α1/α2 of free and bound forms of NAD(P)H of the islet cells of animals (rats and pigs) and of humans with and without pathologies were measured and analyzed. The data were confirmed by IHC and histological studies. We identified three FLIM parameters in islet cells from animals with streptozotocin (STZ)-induced diabetes mellitus (DM) and from humans with chronic pancreatitis + type 2 diabetes (T2D), which differ in the same way: τm and α2 take lower values compared to the nonpathological islet cells, while α1/α2 takes higher values. In islet cells from patients with adenocarcinoma (PDAC) and chronic pancreatitis, these parameters had reverse tendency relative to the norm or did not differ. Thus, minimally invasive and non-contrast FLIM methods may, in the future, be used to diagnose pathological islet cells.     

Esterase Activity of Serum Albumin Studied by 1H NMR Spectroscopy and Molecular Modelling

Serum albumin possesses esterase and pseudo-esterase activities towards a number of endogenous and exogenous substrates, but the mechanism of interaction of various esters and other compounds with albumin is still unclear. In the present study, proton nuclear magnetic resonance (¹H NMR) has been applied to the study of true esterase activity of albumin, using the example of bovine serum albumin (BSA) and p-nitrophenyl acetate (NPA). The site of BSA esterase activity was then determined using molecular modelling methods. According to the data obtained, the accumulation of acetate in the presence of BSA in the reaction mixture is much more intense as compared with the spontaneous hydrolysis of NPA, which indicates true esterase activity of albumin towards NPA. Similar results were obtained for p-nitophenyl propionate (NPP) as substrate. The rate of acetate and propionate release confirms the assumption that there is a site of true esterase activity in the albumin molecule, which is different from the site of the pseudo-esterase activity Sudlow II. The results of molecular modelling of BSA and NPA interaction make it possible to postulate that Sudlow site I is the site of true esterase activity of albumin.     

Candidate Genes and Proteomic Biomarkers of Serum and Urine in Medication-Overuse Headache

Chronic headache is a topical problem of neurology, psychiatry and general practice. The medication-overuse headache (MOH) is one of the leading pathologies in the structure of chronic headache. However, early diagnosis of the MOH is challenging. We analyzed potential proteomic biomarkers of serum and urine in patients with MOH. Methods: We searched PubMed, Springer, Scopus, Web of Science, ClinicalKey, and Google Scholar databases for English publications over the past 10 years using keywords and their combinations. Results: We found and analyzed seven studies that met the search criteria for the purpose of the review, including 24 serum proteomic biomarkers and 25 urine proteomic biomarkers of MOH. Moreover, the candidate genes and locus of the studied serum (vitamin D-binding protein, lipocalin-type prostaglandin D2 synthase, apolipoprotein E, etc.) and urine proteomic biomarkers (uromodulin, alpha-1-microglobulin, zinc-alpha-2-glycoprotein, etc.) of MOH are presented in this review. Conclusions: The serum and urine proteomic biomarkers of MOH can potentially help with the identification of patients with MOH development. Due to the relevance of the problem, the authors believe that further investigation of the MOH proteomic biomarkers in different ethnic and racial groups of patients with primary headache is necessary. In addition, it is important to investigate whether medications of different drug classes influence the levels of serum and urine proteomic biomarkers.     

Reinforcing thermosets using crystalline desoxyanisoin structures

This article presents results on the potential of using crystalline flame retardants for thermoset reinforcement. The approach involves introducing reinforcement in thermosetting polymers through low molecular weight crystallizable additives. Thermally induced phase separation (TIPS) and crystallization of desoxyanisoin in diglycidylether of bisphenol‐A (DGEBA) epoxy monomer were investigated. Small angle light scattering and polarized optical microscopy were utilized to monitor phase separation and the crystallization of desoxyanisoin in DGEBA at different concentrations. Reaction induced phase separation (RIPS) with polyetheramine was carried out under isothermal and temperature gradient curing conditions. Altering the cure schedule resulted in a rich range of morphologies due to the competition between TIPS and RIPS. During isothermal cure, straight fiber‐like anisotropic crystals on a centimeter length scale developed. In contrast, thermal gradients frustrated the crystal growth and resulted in complex and rich morphologies. Desoxyanisoin provided marginal epoxy thermoset reinforcement at 10 vol %. However, the additive did not increase the thermoset flammability retardancy. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39853.     

Novel Biocompatible Magnetoelectric MnFe2O4 Core@BCZT Shell Nano–Hetero-Structures with Efficient Catalytic Performance

Magnetoelectric (ME) small-scale robotic devices attract great interest from the scientific community due to their unique properties for biomedical applications. Here, novel ME nano hetero-structures based on the biocompatible magnetostrictive MnFe₂O₄ (MFO) and ferroelectric Ba_0.85Ca_0.15Zr_0.1Ti_0.9O₃ (BCZT) are developed solely via the hydrothermal method for the first time. An increase in the temperature and duration of the hydrothermal synthesis results in increasing the size, improving the purity, and inducing morphology changes of MFO nanoparticles (NPs). A successful formation of a thin epitaxial BCZT-shell with a 2–5 nm thickness is confirmed on the MFO NPs (77 ± 14 nm) preliminarily treated with oleic acid (OA) or polyvinylpyrrolidone (PVP), whereas no shell is revealed on the surface of pristine MFO NPs. High magnetization is revealed for the developed ME NPs based on PVP- and OA-functionalized MFO NPs (18.68 ± 0.13 and 20.74 ± 0.22 emu g⁻¹, respectively). Moreover, ME NPs demonstrate 95% degradation of a model pollutant Rhodamine B within 2.5 h under an external AC magnetic field (150 mT, 100 Hz). Thus, the developed biocompatible core–shell ME NPs of MFO and BCZT can be considered as a promising tool for non-invasive biomedical applications, environmental remediation, and hydrogen generation for renewable energy sources.     

Composite ZrO2 fibre-based materials with double ammonium-cobalt and ammonium-magnesium diphosphates

The mechanism of solid-state interface interaction in systems of pure and stabilized zirconia fibres with ammonium-magnesium and ammonium-cobalt diphosphates has been studied. The investigation conducted makes it possible to control the preparation process of the composites. The optimal composition of dry slip was found to be 70 wt% of fibre and 30 wt% binder. The properties of the developed composite materials are presented.     

Endometriosis and Cancer: Exploring the Role of Macrophages

Endometriosis and cancer have much in common, notably their burgeoning of cells in hypoxic milieus, their invasiveness, and their capacity to trigger remodeling, vascularization, and innervation of other tissues. An important role in these processes is played by permissive microenvironments inhabited by a variety of stromal and immune cells, including macrophages. Remarkable phenotypical plasticity of macrophages makes them a promising therapeutic target; some key issues are the range of macrophage phenotypes characteristic of a particular pathology and the possible manners of its modulation. In both endometriosis and cancer, macrophages guard the lesions from immune surveillance while promoting pathological cell growth, invasion, and metastasis. This review article focuses on a comparative analysis of macrophage behaviors in endometriosis and cancer. We also highlight recent reports on the experimental modulation of macrophage phenotypes in preclinical models of endometriosis and cancer.     

A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells

Endocrine Disrupting Chemicals (EDCs) are man-made compounds that alter functions of the endocrine system. Environmental mixtures of EDCs might have adverse effects on human health, even though their individual concentrations are below regulatory levels of concerns. However, studies identifying and experimentally testing adverse effects of real-life mixtures are scarce. In this study, we aimed at evaluating an epidemiologically identified EDC mixture in an experimental setting to delineate its cellular and epigenetic effects. The mixture was established using data from the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study where it was associated with lower birth weight, an early marker for prenatal metabolic programming. This mixture was then tested for its ability to change metabolic programming of human mesenchymal stem cells. In these cells, we assessed if the mixture induced adipogenesis and genome-wide DNA methylation changes. The mixture increased lipid droplet accumulation already at concentrations corresponding to levels measured in the pregnant women of the SELMA study. Furthermore, we identified differentially methylated regions in genes important for adipogenesis and thermogenesis. This study shows that a mixture reflecting human real-life exposure can induce molecular and cellular changes during development that could underlie adverse outcomes.     

MicroRNA and Hemostasis Profile of Carotid Atherosclerosis

Carotid atherosclerosis (CA) is an important risk factor for ischemic stroke. We described the miRNA and hemostasis profile of patients with moderate and advanced stages of carotid atherosclerosis and elucidated potential correlations with hemostatic activation. A prospective case-control study included 61 patients with evidence of carotid atherosclerosis (via ultrasound). The study population was divided into groups depending on the degree of carotid artery stenosis: 60% or more (advanced) and <60% (moderate). All patients underwent the following blood tests: general blood test, hemostatic parameters and microRNA. Extraction of microRNA was performed using Leukocyte RNA Purification Kit (NORGEN Biotec Corp., Thorold, ON, Canada); miRNA quantification was performed via RT-PCR. Statistical analysis was performed in R programming language (v. 4.1.0) using RSudio. MicroRNA expression profile was different depending on CA degree. MiR-33a-5p/3p levels were higher in patients with ≥60% carotid stenosis (42.70 and 42.45 versus 38.50 and 38.50, respectively, p < 0.05). Almost complete separation can be visualized with the levels of miR-126-5p: 9.50 in the moderate CA group versus 5.25 in the advanced CA (p < 0.001). MiR-29-5p was higher in the moderate CA group: 28.60 [25.50;33.05] than in advanced CA group: 25.75 [24.38;29.50] (p = 0.086); miR-29-3p was also higher in the moderate CA group: 10.36 [8.60;14.99] than in advanced CA group: 8.46 [7.47;10.3] (p = 0.001). By-group pairwise correlation analyses revealed at least three clusters with significant positive correlations in the moderate CA group: miR-29-3p with factors V and XII (r = 0.53 and r = 0.37, respectively, p < 0.05); miR-21-5p with ADAMTS13, erythrocyte sedimentation rate and D-dimer (r = 0.42, r = 0.36 and r = 0.44, respectively, p < 0.05); stenosis degree with miR-33a-5p/3p and factor VIII levels (r = 0.43 (both) and r = 0.62, respectively, p < 0.05). Hemostasis parameters did not reveal significant changes in CA patients: the only statistically significant differences concerned factor VIII, plasminogen and (marginally significant) ADAMTS-13 and protein C. Down-regulation of miR-126-5p expression has been identified as a promising biomarker of advanced carotid atherosclerosis with high specificity and sensitivity. Correlation cluster analysis showed potential interplay between miRNAs and hemostatic activation in the setting of carotid atherosclerosis.