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prof. dr hab. lek.med. Leszek Kalinowski
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total: 41
Catalog Publications
Year 2024
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Receptor for advanced glycation end‐products: Biological significance and imaging applications
PublicationThe receptor for advanced glycation end-products (RAGE or AGER) is a transmembrane, immunoglobulin-like receptor that, due to its multiple isoform structures, binds to a diverse range of endo- and exogenous ligands. RAGE activation caused by the ligand binding initiates a cascade of complex pathways associated with producing free radicals, such as reactive nitric oxide and oxygen species, cell proliferation, and immunoinflammatory...
Year 2023
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2-Methoxyestradiol and Hydrogen Peroxide as Promising Biomarkers in Parkinson’s Disease
PublicationEstrogens function in numerous physiological processes including controlling brain cell growth and differentiation. 2-Meth- oxestradiol (2-ME2), a 17β-estradiol (E2) metabolite, is known for its anticancer effects as observed both in vivo and in vitro. 2-ME2 affects all actively dividing cells, including neurons. The study aimed to determine whether 2-ME2 is a potentially cancer-protective or rather neurodegenerative agent in a...
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Activation of Metabotropic Glutamate Receptor (mGlu2) and Muscarinic Receptors (M1, M4, and M5), Alone or in Combination, and Its Impact on the Acquisition and Retention of Learning in the Morris Water Maze, NMDA Expression and cGMP Synthesis
PublicationThe Morris water maze (MWM) is regarded as one of the most popular tests for detecting spatial memory in rodents. Long-term potentiation and cGMP synthesis seem to be among the crucial factors involved in this type of learning. Muscarinic (M1, M4, and M5 receptors) and metabotropic glutamate (mGlu) receptors are important targets in the search for antipsychotic drugs with the potency to treat cognitive disabilities associated with...
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Butyrylcholinesterase signal sequence self-aggregates and enhances amyloid fibril formation in vitro
PublicationAlzheimer’s disease (AD) pathogenesis has been attributed to extracellular aggregates of amyloid β (Aβ) plaques and neurofibrillary tangles in the human brain. It has been reported that butyrylcholinesterase (BChE) also accumulates in the brain Aβ plaques in AD. We have previously found that the BChE substitution in 5′UTR caused an in-frame N-terminal extension of 41 amino acids of the BChE signal peptide. The resultant variant...
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Endothelial dysfunction due to eNOS uncoupling: molecular mechanisms as potential therapeutic targets
PublicationNitric oxide (NO) is one of the most important molecules released by endothelial cells, and its antiatherogenic properties support cardiovascular homeostasis. Diminished NO bioavailability is a common hallmark of endothelial dysfunction underlying the patho‑ genesis of the cardiovascular disease. Vascular NO is synthesized by endothelial nitric oxide synthase (eNOS) from the substrate L‑arginine (L‑Arg), with tetrahydrobiopterin...
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Environmental exposure to cadmium in breast cancer – association with the Warburg effect and sensitivity to tamoxifen
PublicationThe association between cadmium and breast cancer remains unexplained due to inconsistent epidemiological data and unknown underlying mechanisms. This study aimed to assess the relationship between environmental exposure to cadmium and the Warburg effect in breast cancer and, thus, its possible interference with breast cancer treatment. The observational study in two groups of breast cancer patients indicated a positive correlation between...
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Genome-Wide DNA Methylation and Gene Expression in Patients with Indolent Systemic Mastocytosis
PublicationMastocytosis is a clinically heterogenous, usually acquired disease of the mast cells with a survival time that depends on the time of onset. It ranges from skin-limited to systemic disease, including indolent and more aggressive variants. The presence of the oncogenic KIT p. D816V gene somatic mutation is a crucial element in the pathogenesis. However, further epigenetic regulation may also affect the expression of genes that...
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In Vitro and In Vivo Imaging-Based Evaluation of Doxorubicin Anticancer Treatment in Combination with the Herbal Medicine Black Cohosh
PublicationAs a substitution for hormone replacement therapy, many breast cancer patients use black cohosh (BC) extracts in combination with doxorubicin (DOX)-based chemotherapy. In this study, we evaluated the viability and survival of BC- and DOX-treated MCF-7 cells. A preclinical model of MCF-7 xenografts was used to determine the influence of BC and DOX administration on tumor growth and metabolism. The number of apoptotic cells after...
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Insights into oral microbiome and colorectal cancer – on the way of searching new perspectives
PublicationMicrobiome is a keystone polymicrobial community that coexist with human body in a beneficial relationship. These microorganisms enable the human body to maintain homeostasis and take part in mechanisms of defense against infection and in the absorption of nutrients. Even though microbiome is involved in physiologic processes that are beneficial to host health, it may also cause serious detrimental issues. Additionally, it has been...
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Isolation of Citrus lemon extracellular vesicles: Development and process control using capillary electrophoresis
PublicationA new and scalable method for the isolation of extracellular vesicles (EV) from Citrus lemon juice samples was developed. The methodology included preliminary preconcentration of the sample using ultrafiltration (UF) followed by size-exclusion chromatography (SEC) purification and final preconcentration of the eluates. Transmission electron microscopy and proteomic analysis showed that isolates contained exosome-like vesicles, exocyst-positive...
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Microbiota-derived metabolites in colorectal cancer patients in preoperative period
PublicationShort-chain fat-ty acids (SCFAs) are microbial derived metabo-lites, which have multiple beneficial properties. The amount of SCFAs depends on several fac-tors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In col-orectal cancer (CRC) patients, microbiota alter-ations have been shown. Consequently,...
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Nanoparticle Tracking Analysis of Urinary Extracellular Vesicle Proteins as a New Challenge in Laboratory Medicine
PublicationUrinary extracellular vesicle (uEV) proteins may be used as specific markers of kidney damage in various pathophysiological conditions. The nanoparticle-tracking analysis (NTA) appears to be the most useful method for the analysis of uEVs due to its ability to analyze particles below 300 nm. The NTA method has been used to measure the size and concentration of uEVs and also allows for a deeper analysis of uEVs based on their protein...
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Novel Tools for Comprehensive Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants
PublicationFamilial hypercholesterolemia (FH) is an autosomal-dominant disorder caused mainly by substitutions in the low-density lipoprotein receptor (LDLR) gene, leading to an increased risk of premature cardiovascular diseases. Tremendous advances in sequencing techniques have resulted in the discovery of more than 3000 variants of the LDLR gene, but not all of them are clinically relevant. Therefore, functional studies of selected variants...
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Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs – is it a new perspective for personalized treatment of cancer patients?
PublicationIntestinal bacteria are equipped with an enzyme apparatus that is involved in the active biotrans-formation of xenobiotics, including drugs. Pharmacomicrobiomics, a new area of pharmacology, analyses interactions between bacteria and xenobiotics. However, there is another side to the coin. Pharmacotherapeutic agents can significantly modify the microbiota, which consequently affects their efficacy. In this review, we comprehensively...
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Postbiotics in oncology: science or science fiction?
PublicationThe gut microbiome has been increasingly understood to play a critical role in carcinogenesis and cancer disease progression. The most recent research advancements have shown that different tools of microbiota manipulation contribute to gut microbiome–immune–oncology axis modulation, offering exciting opportunities for targeted interventions aimed at improving the efficacy of established anti-cancer therapy. Postbiotics are a new...
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Protein overproduction alters exosome secretion in Chinese hamster ovary cells
PublicationDespite the abundance of available cell lines, nearly 70% of all recombinant therapeutic proteins today are produced in Chi-nese hamster ovary (CHO) cells. The impact of protein overproduction on the secretion of exosomes by CHO cells has been investigated here. Increased secretion of extracellular vesicles (EVs) by protein overexpressing CHO cells was demonstrated with protein content assay, nanoparticle tracking analysis, and...
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Proteomic and Metabolomic Changes in Psoriasis Preclinical and Clinical Aspects
PublicationSkin diseases such as psoriasis (Ps) and psoriatic arthritis (PsA) are immune-mediated inflammatory diseases. Overlap of autoinflammatory and autoimmune conditions hinders diagnoses and identifying personalized patient treatments due to different psoriasis subtypes and the lack of verified biomarkers. Recently, proteomics and metabolomics have been intensively investigated in a broad range of skin diseases with the main purpose...
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RAGE as a Novel Biomarker for Prostate Cancer: A Systematic Review and Meta-Analysis
PublicationThe receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects....
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The Unfolded Protein Response: A Double-Edged Sword for Brain Health
PublicationEfficient brain function requires as much as 20% of the total oxygen intake to support normal neuronal cell function. This level of oxygen usage, however, leads to the generation of free radicals, and thus can lead to oxidative stress and potentially to age-related cognitive decay and even neurodegenerative diseases. The regulation of this system requires a complex monitoring network to maintain proper oxygen homeostasis. Furthermore,...
Year 2022
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Fluorescence Imaging Using Methylene Blue Sentinel Lymph Node Biopsy in Melanoma
PublicationIntroduction: Fluorescence imaging of sentinel node biopsy in melanoma is a novel method. Both indocyanine green (ICG) and methylene blue (MB) have fl uorescent properties. The aim of this study was to present, for the fi rst time in a clinical series of patients, the possible usage of MB as a fl uorescent dye for sentinel node biopsy during surgery for melanoma. Material and methods: Twenty patients with...
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Genetic and pharmacologic proteasome augmentation ameliorates Alzheimer’s-like pathology in mouse and fly APP overexpression models
PublicationThe proteasome has key roles in neuronal proteostasis, including the removal of misfolded and oxidized proteins, presynaptic protein turnover, and synaptic efficacy and plasticity. Proteasome dysfunction is a prominent feature of Alzheimer’s disease (AD). We show that prevention of proteasome dysfunction by genetic manipulation delays mortality, cell death, and cognitive deficits in fly and cell culture AD models. We developed...
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Higher platelet counts correlate to tumour progression and can be induced by intratumoural stroma in non-metastatic breast carcinomas
PublicationBackground Platelets support tumour progression. However, their prognostic significance and relation to circulating tumour cells (CTCs) in operable breast cancer (BrCa) are still scarcely known and, thus, merit further investigation. Methods Preoperative platelet counts (PCs) were compared with clinical data, CTCs, 65 serum cytokines and 770 immune-related transcripts obtained using the NanoString technology. Results High normal...
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Methylene Blue Near-Infrared Fluorescence Imaging in Breast Cancer Sentinel Node Biopsy
PublicationIntroduction: Fluorescence-based navigation for breast cancer sentinel node biopsy is a novel method that uses indocyanine green as a fluorophore. However, methylene blue (MB) also has some fluorescent properties. This study is the first in a clinical series presenting the possible use of MB as a fluorescent dye for the identification of sentinel nodes in breast sentinel node biopsy. Material and methods: Forty-nine patients with...
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Molecular Imaging and Nanotechnology—Emerging Tools in Diagnostics and Therapy
PublicationPersonalized medicine is emerging as a new goal in the diagnosis and treatment of diseases. This approach aims to establish differences between patients suffering from the same disease, which allows to choose the most effective treatment. Molecular imaging (MI) enables advanced insight into molecule interactions and disease pathology, improving the process of diagnosis and therapy and, for that reason, plays a crucial role in personalized...
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Multispectral Imaging Using Fluorescent Properties of Indocyanine Green and Methylene Blue in Colorectal Surgery—Initial Experience
PublicationIntroduction: Image-guided surgery is becoming a new tool in colorectal surgery. Intraoperative visualisation of different structures using fluorophores helps during various steps of operations. In our report, we used two fluorophores—indocyanine green (ICG), and methylene blue (MB)— during different steps of colorectal surgery, using one camera system for two separate near-infrared wavelengths. Material and methods: Twelve patients...
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Procognitive activity of nitric oxide inhibitors and donors in animal models
PublicationNitric oxide is a small gaseous molecule that plays important roles in the majority of biological functions. Impairments of NO-related pathways contribute to the majority of neurological disorders, such as Alzheimer’s disease (AD), and mental disorders, such as schizophrenia. Cognitive decline is one of the most serious impairments accompanying both AD and schizophrenia. In the present study, the activities of NO donors, slow (spermine...
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Quality Control of Bacterial Extracellular Vesicles with Total Protein Content Assay, Nanoparticles Tracking Analysis, and Capillary Electrophoresis
PublicationExtracellular vesicles (EVs) were isolated from Pectobacterium zantedeschiae culturing media using direct ultracentrifugation (UC), iodixanol cushion ultracentrifugation (ICUC), and iodixanol density gradient ultracentrifugation (IDGUC) techniques. The isolates were characterized with total protein content assay (bicinchoninic acid assay, BCA), nanoparticles tracking analysis (NTA), and capillary electrophoresis (CE). A satisfactory...
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The Digital Tissue and Cell Atlas and the Virtual Microscope
PublicationWith the cooperation of the CI TASK (Center of lnformatics Tri-Citry Academic Supercomputer and network) and the Gdańsk University of Technology, the Medical University of Gdańsk undertook the creation of the Digital Tissue and Cell Atlas and the Virtual Microscope for the needs of the Bridge of Data project. In the beginning, an extensive collection of histological and cytological slides was carefully selected and prepared by...
Year 2021
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Comprehensive Review of Fluorescence Applications in Gynecology
PublicationSince the introduction of indocyanine green (ICG) as a fluorophore in near-infrared imaging, fluorescence visualization has become an essential tool in many fields of surgery. In the field of gynecology, recent new applications have been proposed and found their place in clinical practice. Different applications in gynecology were investigated, subcategorized, and overviewed concerning surgical applications and available dyes....
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Endothelial Dysfunction Driven by Hypoxia—The Influence of Oxygen Deficiency on NO Bioavailability
PublicationCardiovascular diseases (CVDs) are the leading cause of death worldwide. The initial stage of CVDs is characterized by endothelial dysfunction, defined as the limited bioavailability of nitric oxide (NO). Thus, any factors that interfere with the synthesis or metabolism of NO in endothelial cells are involved in CVD pathogenesis. It is well established that hypoxia is both the triggering factor as well as the accompanying factor...
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Mitochondrial DNA copy number and trimethylamine levels in the blood: New insights on cardiovascular disease biomarkers
PublicationAmong cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine-N-oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO, and mtDNAcn in a population of 389 coronary artery disease...
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Molecularly targeted nanoparticles: an emerging tool for evaluation of expression of the receptor for advanced glycation end products in a murine model of peripheral artery disease
PublicationAbstract Background: Molecular imaging with molecularly targeted probes is a powerful tool for studying the spatio-temporal interactions between complex biological processes. The pivotal role of the receptor for advanced glycation end products (RAGE) in numerous pathological processes, aroused the demand for RAGE targeted imaging in various diseases. In the study, we evaluated the use of a diagnostic imaging agent for RAGE quantification...
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Neurochemical changes underlying cognitive impairment in olfactory bulbectomized rats and the impact of the mGlu5-positive allosteric modulator CDPPB
PublicationThe olfactory bulbectomized (OBX) rat model is a well-established model of depression in which antidepressant drugs reverse deficits in the passive avoidance test 14 days after administration. Recently, the olfactory bulbectomized rat model has been proposed to be a model of Alzheimer’s disease (AD), and the available data indicate similarities between the changes that typically occur in AD and those observed in OBX animals. In...
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Nitric Oxide-Dependent Pathways as Critical Factors in the Consequences and Recovery after Brain Ischemic Hypoxia
PublicationBrain ischemia is one of the leading causes of disability and mortality worldwide. Nitric oxide (NO), a molecule that is involved in the regulation of proper blood flow, vasodilation, neuronal and glial activity constitutes the crucial factor that contributes to the development of pathological changes after stroke. One of the early consequences of a sudden interruption in the cerebral blood flow is the massive production of reactive...
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Serotonergic–Muscarinic Interaction within the Prefrontal Cortex as a Novel Target to Reverse Schizophrenia-Related Cognitive Symptoms
PublicationRecent studies revealed that the activation of serotonergic 5-HT1A and muscarinic M1, M4, or M5 receptors prevent MK-801-induced cognitive impairments in animal models. In the present study, the effectiveness of the simultaneous activation of 5-HT1A and muscarinic receptors at preventing MK-801-induced cognitive deficits in novel object recognition (NOR) or Y-maze tests was investigated. Activators of 5-HT1A (F15599), M1 (VU0357017),...
Year 2020
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Gender-Related Differences in Trimethylamine and Oxidative Blood Biomarkers in Cardiovascular Disease Patients
PublicationGender differences in the burden of cardiovascular disease (CVD) have been observed worldwide. In this study, plasmatic levels of trimethylamine (TMA) and blood oxidative biomarkers have been evaluated in 358 men (89 controls and 269 CVD patients) and 189 women (64 control and 125 CVD patients). The fluorescence technique was applied to determine erythrocyte membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) and Laurdan,...
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Genetic and Epigenetic Aspects of Atopic Dermatitis
PublicationAtopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications...
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Pathogenesis of psoriasis in the “omic” era. Part II. Genetic, genomic and epigenetic changes in psoriasis
PublicationPsoriasis is a multifactorial disease in which genetic, environmental and epigenetic factors regulating gene expression play a key role. In the “genomic era”, genome-wide association studies together with target genotyping platforms performed in different ethnic populations have found more than 50 genetic susceptible markers associated with the risk of psoriasis which have been identified so far. Up till now, the strongest association...
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Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis
PublicationPsoriasis is a systemic disease that is strictly connected with metabolic disorders (insulin resistance, atherogenic dyslipidemia, arterial hypertension, and cardiovascular diseases). It occurs more often in patients with a more severe course of the disease. Obesity is specially an independent risk factor and it is associated with a worse treatment outcome because of the high inflammatory activity of visceral fatty tissue and...
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Results from a Genome-Wide Association Study (GWAS) in Mastocytosis Reveal New Gene Polymorphisms Associated with WHO Subgroups
PublicationMastocytosis is rare disease in which genetic predisposition is not fully understood. The aim of this study was to analyze associations between mastocytosis and single nucleotide polymorphisms (SNPs) by a genome-wide association study (GWAS) approach. A total of 234 patients were enrolled in our study, including 141 with cutaneous mastocytosis (CM; 78 children and 63 adults) and 93 with systemic mastocytosis (SM, all adults)....
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Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study
PublicationThe early atherosclerotic lesions develop by the accumulation of arterial foam cells derived mainly from cholesterol-loaded macrophages. Therefore, cholesterol and cholesteryl ester transfer protein (CETP) have been considered as causative in atherosclerosis. Moreover, recent studies indicate the role of trimethylamine N-oxide (TMAO) in development of cardiovascular disease (CVD). The current study aimed to investigate the association...
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