Tear samples collected from patients with central retinal vein occlusion (CRVO; n = 28) and healthy volunteers (n = 29) were analyzed using a proteomic label-free absolute quantitative approach. A ...large proportion (458 proteins with a frequency > 0.6) of tear proteomes was found to be shared between the study groups. Comparative proteomic analysis revealed 29 proteins (p < 0.05) significantly differed between CRVO patients and the control group. Among them, S100A6 (log (2) FC = 1.11, p < 0.001), S100A8 (log (2) FC = 2.45, p < 0.001), S100A9 (log2 (FC) = 2.08, p < 0.001), and mesothelin ((log2 (FC) = 0.82, p < 0.001) were the most abundantly represented upregulated proteins, and β2-microglobulin was the most downregulated protein (log2 (FC) = −2.13, p < 0.001). The selected up- and downregulated proteins were gathered to customize a map of CRVO-related critical protein interactions with quantitative properties. The customized map (FDR < 0.01) revealed inflammation, impairment of retinal hemostasis, and immune response as the main set of processes associated with CRVO ischemic condition. The semantic analysis displayed the prevalence of core biological processes covering dysregulation of mitochondrial organization and utilization of improperly or topologically incorrect folded proteins as a consequence of oxidative stress, and escalating of the ischemic condition caused by the local retinal hemostasis dysregulation. The most significantly different proteins (S100A6, S100A8, S100A9, MSLN, and β2-microglobulin) were applied for the ROC analysis, and their AUC varied from 0.772 to 0.952, suggesting probable association with the CRVO.
Background: Tracking the migration pathways of living cells after their introduction into a patient’s body is a topical issue in the field of cell therapy. Questions related to studying the ...possibility of long-term intravital biodistribution of mesenchymal stromal cells in the body currently remain open. Methods: Forty-nine laboratory animals were used in the study. Modeling of local radiation injuries was carried out, and the dynamics of the distribution of mesenchymal stromal cells labeled with 89ZrZr-oxine in the rat body were studied. Results: the obtained results of the labelled cell distribution allow us to assume that this procedure could be useful for visualization of local radiation injury using positron emission tomography. However, further research is needed to confirm this assumption. Conclusions: intravenous injection leads to the initial accumulation of cells in the lungs and their subsequent redistribution to the liver, spleen, and kidneys. When locally injected into tissues, mesenchymal stromal cells are not distributed systemically in significant quantities.
Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early ...diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation.
Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant (
< 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression.
The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in ...mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.
Food Intolerance: The Role of Histamine Shulpekova, Yulia O.; Nechaev, Vladimir M.; Popova, Irina R. ...
Nutrients,
09/2021, Letnik:
13, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Histamine is a natural amine derived from L-histidine. Although it seems that our knowledge about this molecule is wide and diverse, the importance of histamine in many regulatory processes is still ...enigmatic. The interplay between different types of histamine receptors and the compound may cause ample effects, including histamine intoxication and so-called histamine intolerance or non-allergic food intolerance, leading to disturbances in immune regulation, manifestation of gastroenterological symptoms, and neurological diseases. Most cases of clinical manifestations of histamine intolerance are non-specific due to tissue-specific distribution of different histamine receptors and the lack of reproducible and reliable diagnostic markers. The diagnosis of histamine intolerance is fraught with difficulties, in addition to challenges related to the selection of a proper treatment strategy, the regular course of recovery, and reduced amelioration of chronic symptoms due to inappropriate treatment prescription. Here, we reviewed a history of histamine uptake starting from the current knowledge about its degradation and the prevalence of histamine precursors in daily food, and continuing with the receptor interactions after entering and the impacts on the immune, central nervous, and gastrointestinal systems. The purpose of this review is to build an extraordinarily specific method of histamine cycle assessment in regard to non-allergic intolerance and its possible dire consequences that can be suffered.
An athlete's diet is influenced by external and internal factors that can reduce or exacerbate exercise-induced food intolerance/allergy symptoms. This review highlights many factors that influence ...food choices. However, it is important to remember that these food choices are dynamic, and their effectiveness varies with the time, location, and environmental factors in which the athlete chooses the food. Therefore, before training and competition, athletes should follow the recommendations of physicians and nutritionists. It is important to study and understand the nutritional strategies and trends that athletes use before and during training or competitions. This will identify future clinical trials that can be conducted to identify specific foods that athletes can consume to minimize negative symptoms associated with their consumption and optimize training outcomes.
The review covers some research conducted in the field of medical and biomedical application of devices based on silicon sensor elements (Si-NW-sensors). The use of Si-NW-sensors is one of the key ...methods used in a whole range of healthcare fields. Their biomedical use is among the most important ones as they offer opportunities for early diagnosis of oncological pathologies, for monitoring the prescribed therapy and for improving the people's quality of life.
Prostate cancer (PC) is one of the major causes of death among elderly men. PC is often diagnosed later in progression due to asymptomatic early stages. Early detection of PC is thus crucial for ...effective PC treatment. The aim of this study is the simultaneous highly sensitive detection of a palette of PC-associated microRNAs (miRNAs) in human plasma samples. With this aim, a nanoribbon biosensor system based on “silicon-on-insulator” structures (SOI-NR biosensor) has been employed. In order to provide biospecific detection of the target miRNAs, the surface of individual nanoribbons has been sensitized with DNA oligonucleotide probes (oDNA probes) complementary to the target miRNAs. The lowest concentration of nucleic acids, detectable with our biosensor, has been found to be 1.1 × 10−17 M. The successful detection of target miRNAs, isolated from real plasma samples of PC patients, has also been demonstrated. We believe that the development of highly sensitive nanotechnology-based biosensors for the detection of PC markers is a step towards personalized medicine.
Despite of multiple systematic studies of schizophrenia based on proteomics, metabolomics, and genome-wide significant loci, reconstruction of underlying mechanism is still a challenging task. ...Combination of the advanced data for quantitative proteomics, metabolomics, and genome-wide association study (GWAS) can enhance the current fundamental knowledge about molecular pathogenesis of schizophrenia. In this study, we utilized quantitative proteomic and metabolomic assay, and high throughput genotyping for the GWAS study. We identified 20 differently expressed proteins that were validated on an independent cohort of patients with schizophrenia, including ALS, A1AG1, PEDF, VTDB, CERU, APOB, APOH, FASN, GPX3, etc. and almost half of them are new for schizophrenia. The metabolomic survey revealed 18 group-specific compounds, most of which were the part of transformation of tyrosine and steroids with the prevalence to androgens (androsterone sulfate, thyroliberin, thyroxine, dihydrotestosterone, androstenedione, cholesterol sulfate, metanephrine, dopaquinone, etc.). The GWAS assay mostly failed to reveal significantly associated loci therefore 52 loci with the smoothened p < 10
were fractionally integrated into proteome-metabolome data. We integrated three omics layers and powered them by the quantitative analysis to propose a map of molecular events associated with schizophrenia psychopathology. The resulting interplay between different molecular layers emphasizes a strict implication of lipids transport, oxidative stress, imbalance in steroidogenesis and associated impartments of thyroid hormones as key interconnected nodes essential for understanding of how the regulation of distinct metabolic axis is achieved and what happens in the conditioned proteome and metabolome to produce a schizophrenia-specific pattern.
The development and improvement of methods for comparing and searching for three-dimensional protein structures remain urgent tasks in modern structural biology. To solve this problem, we developed a ...new tool, SAFoldNet, which allows for searching, aligning, superimposing, and determining the exact coordinates of fragments of protein structures. The proposed search and alignment tool was built using neural networking. Specifically, we implemented the integrative synergy of neural network predictions and the well-known BLAST algorithm for searching and aligning sequences. The proposed method involves multistage processing, comprising a stage for converting the geometry of protein structures into sequences of a structural alphabet using a neural network, a search stage for forming a set of candidate structures, and a refinement stage for calculating the structural alignment and overlap and evaluating the similarity with the starting structure of the search. The effectiveness and practical applicability of the proposed tool were compared with those of several widely used services for searching and aligning protein structures. The results of the comparisons confirmed that the proposed method is effective and competitive relative to the available modern services. Furthermore, using the proposed approach, a service with a user-friendly web interface was developed, which allows for searching, aligning, and superimposing protein structures; determining the location of protein fragments; mapping onto a protein molecule chain; and providing structural similarity metrices (expected value and root mean square deviation).
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