Репозиторий Университета

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

© 2021, The Author(s). A crosstalk established between tumor microenvironment and tumor cells leads to contribution or inhibition of tumor progression. Mesenchymal stem cells (MSCs) are critical cells that fundamentally participate in modulation of the tumor microenvironment, and have been reported to be able to regulate and determine the final destination of tumor cell. Conflicting functions have been attributed to the activity of MSCs in the tumor microenvironment; they can confer a tumorigenic or anti-tumor potential to the tumor cells. Nonetheless, MSCs have been associated with a potential to modulate the tumor microenvironment in favouring the suppression of cancer cells, and promising results have been reported from the preclinical as well as clinical studies. Among the favourable behaviours of MSCs, are releasing mediators (like exosomes) and their natural migrative potential to tumor sites, allowing efficient drug delivering and, thereby, efficient targeting of migrating tumor cells. Additionally, angiogenesis of tumor tissue has been characterized as a key feature of tumors for growth and metastasis. Upon introduction of first anti-angiogenic therapy by a monoclonal antibody, attentions have been drawn toward manipulation of angiogenesis as an attractive strategy for cancer therapy. After that, a wide effort has been put on improving the approaches for cancer therapy through interfering with tumor angiogenesis. In this article, we attempted to have an overview on recent findings with respect to promising potential of MSCs in cancer therapy and had emphasis on the implementing MSCs to improve them against the suppression of angiogenesis in tumor tissue, hence, impeding the tumor progression.

© 2020 Elsevier B.V. Ecosystems are facing increased pressure due to the emission of many classes of emerging contaminants. However, very little is known about the interactions of these pollutants, such as bisphenols (BPs), plasticizers or pharmaceuticals. By employing bioluminescent bacteria (Microtox assay), we were able to define interactions between selected emerging pollutants (namely BPA, BPS, BPF, BADGE, BADGE·2HCl, DEP, DBP) in ternary mixtures, at environmentally relevant concentration levels (down to as low as 1.89, 1.42, 3.08, and 0.326 μM for, respectively, BPA, BPF, BPS and BADGE·2HCl). We provide the first systematic analysis of bisphenols and phthalates in three component mixtures. Using this system, we performed toxicity modelling with concentration addition (CA) and independent action (IA) approaches, followed by data interpretation using Model Deviation Ratio (MDR) evaluation. Interestingly, we mathematically and experimentally confirmed a novel synergy between BPA, BADGE and BADGE·2HCl. The synergy of BPA, BADGE and BADGE·2HCl is distinct, with both models suggesting these analytes have a similar mode of action (MOA). Moreover, we unexpectedly found a strong antagonistic impact with DEP, in mixtures containing BPA and BADGE analogues, which is confirmed with both mathematical models. Our study also shows that the impact of BPS and BPF in many mixtures is highly concentration dependent, justifying the necessity to perform mixture studies using wide concentration ranges. Overall, this study demonstrates that bioluminescent bacteria are a relevant model for detecting the synergistic and antagonist actions of environmental pollutants in mixtures, and highlights the importance of analyzing combinations of pollutants in higher order mixtures.

© 2021 Elsevier Ltd The objective of the present study was to assess the impact of cobalt (Co) exposure on tissue distribution of iron (Fe), copper (Cu), manganese (Mn), and zinc (Zn), as well as serum hepcidin levels in immature mice (18, 25, 30 days). Pregnant mice were exposed to 75 mg/kg b.w. cobalt chloride (CoCl2 × 6H2O) with drinking water starting from 3 days before delivery and during lactation. At weaning (day 25) the offspring were separated and housed in individual cages with subsequent exposure to 75 mg/kg b.w. CoCl2 until 30 days postnatally. Evaluation of tissue metal levels was performed by an inductively coupled plasma-mass spectrometry (ICP-MS). Serum hepcidin level was assayed by enzyme linked immunosorbent assay (ELISA). Cobalt exposure resulted in a time- and tissue-dependent increase in Co levels in kidney, spleen, liver, muscle, erythrocytes, and serum on days 18, 25, and 30. In parallel with increasing Co levels, CoCl2 exposure resulted in a significant accumulation of Cu, Fe, Mn, and Zn in the studied tissues, with the effect being most pronounced in 25-day-old mice. Cobalt exposure significantly increased serum hepcidin levels only in day18 mice. The obtained data demonstrate that Co exposure may alter essential metal metabolism in vivo.

© 2021, Advanced Scientific Research. All rights reserved. The state of human health is an important factor in the optimal for the existence in biological and social terms. It is now recognized that the best way to keep health – to lead healthy lives and avoid the negative influences of the environment. This is extremely important in the workplace and at home. The basis of life must be feasible rational muscular activity. Dosed physical loads provide balanced revitalizing effect on the body. They regulate the metabolism and have a pronounced training effect on motor and autonomic functions. Adequate and regular physical activity steadfastly increases the efficiency of the myocardium, improves blood flow to the brain and heart, improves the efficiency of peripheral circulation and venous return to the heart increases the body's tolerance to stress and the level of absorption of oxygen and nutrients to the tissues. In this regard, rational physical activity are considered the basis of healthy lifestyles, active aging, and high adaptation to the external environment.

© 2021, Advanced Scientific Research. All rights reserved. The state of human health is an important factor in the optimal for the existence in biological and social terms. It is now recognized that the best way to keep health – to lead healthy lives and avoid the negative influences of the environment. This is extremely important in the workplace and at home. The basis of life must be feasible rational muscular activity. Dosed physical loads provide balanced revitalizing effect on the body. They regulate the metabolism and have a pronounced training effect on motor and autonomic functions. Adequate and regular physical activity steadfastly increases the efficiency of the myocardium, improves blood flow to the brain and heart, improves the efficiency of peripheral circulation and venous return to the heart increases the body's tolerance to stress and the level of absorption of oxygen and nutrients to the tissues. In this regard, rational physical activity are considered the basis of healthy lifestyles, active aging, and high adaptation to the external environment.

© 2020, The Author(s). Background: Across the globe, diseases secondary to environmental exposures have been described, and it was also found that existing diseases have been modified by exposure to environmental chemicals or an environmental factor that has been found in their pathogenesis. The Institute of Medicine has shared a permanent concern related to the nations environmental health capacity since 1988. Main body: Contemporary imaging methods in the last 15 years started reporting alterations in different human systems such as the central nervous system, cardiovascular system and pulmonary system among others; evidence suggests the existence of a human environmental disease network. The primary anatomic regions, affected by environmental diseases, recently assessed with imaging methods include Brain (lead exposure, cerebral stroke, pesticide neurotoxicity), uses MRI, DTI, carotid ultrasonography and MRS; Lungs (smoke inhalation, organophosphates poisoning) are mainly assessed with radiography; Gastrointestinal system (chronic inflammatory bowel disease), recent studies have reported the use of aortic ultrasound; Heart (myocardial infarction), its link to environmental diseased has been proved with carotid ultrasound; and Arteries (artery hypertension), the impairment of aortic mechanical properties has been revealed with the use of aortic and brachial ultrasound. Conclusions: Environmental epidemiology has revealed that several organs and systems in the human body are targets of air pollutants. Current imaging methods that can assess the deleterious effects of pollutants includes a whole spectrum: radiography, US, CT and MRI. Future studies will help to reveal additional links among environmental disease networks.

© 2020, The Author(s). Background: Across the globe, diseases secondary to environmental exposures have been described, and it was also found that existing diseases have been modified by exposure to environmental chemicals or an environmental factor that has been found in their pathogenesis. The Institute of Medicine has shared a permanent concern related to the nations environmental health capacity since 1988. Main body: Contemporary imaging methods in the last 15 years started reporting alterations in different human systems such as the central nervous system, cardiovascular system and pulmonary system among others; evidence suggests the existence of a human environmental disease network. The primary anatomic regions, affected by environmental diseases, recently assessed with imaging methods include Brain (lead exposure, cerebral stroke, pesticide neurotoxicity), uses MRI, DTI, carotid ultrasonography and MRS; Lungs (smoke inhalation, organophosphates poisoning) are mainly assessed with radiography; Gastrointestinal system (chronic inflammatory bowel disease), recent studies have reported the use of aortic ultrasound; Heart (myocardial infarction), its link to environmental diseased has been proved with carotid ultrasound; and Arteries (artery hypertension), the impairment of aortic mechanical properties has been revealed with the use of aortic and brachial ultrasound. Conclusions: Environmental epidemiology has revealed that several organs and systems in the human body are targets of air pollutants. Current imaging methods that can assess the deleterious effects of pollutants includes a whole spectrum: radiography, US, CT and MRI. Future studies will help to reveal additional links among environmental disease networks.

© 2020 Elsevier GmbH Environmental factors have been severally established to play major roles in the pathogenesis of neurodevelopmental disorders including autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that is associated with symptoms that reduce the quality of life of affected individuals such as social interaction deficit, cognitive impairment, intellectual disabilities, restricted and repetitive behavioural patterns. ASD pathogenesis has been associated with environmental and genetic factors that alter physiologic processes during development. Here, we review literatures highlighting the environmental impact on neurodevelopmental disorders, and mechanisms by which environmental toxins may influence neurodevelopment. Furthermore, this review discusses reports highlighting neurotoxic metals (specifically, lead, mercury, cadmium, nickel and manganese) as environmental risk factors in the aetiology of ASD. This work, thus suggests that improving the environment could be vital in the management of ASD.

© 2020 Epithelial-to-mesenchymal transition (EMT) is an essential molecular and cellular process that is part of normal embryogenesis and wound healing, and also has a ubiquitous role in various types of carcinoma and glioblastoma. EMT is activated and regulated by specific microenvironmental endogenous triggers and a complex network of signalling pathways. These mostly include epigenetic events that affect protein translation-controlling factors and proteases, altogether orchestrated by the switching on and off of oncogenes and tumour-suppressor genes in cancer cells. The hallmark of cancer-linked EMT is that the process is incomplete, as it is opposed by the reverse process of mesenchymal-to-epithelial transition, which results in a hybrid epithelial/mesenchymal phenotype that shows notable cell plasticity. This is a characteristic of cancer stem cells (CSCs), and it is of the utmost importance in their niche microenvironment, where it governs CSC migratory and invasive properties, thereby creating metastatic CSCs. These cells have high resistance to therapeutic treatments, in particular in glioblastoma.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to elucidate the effect of perinatal cobalt chloride (CoCl2) exposure on extramedullary erythropoiesis in suckling mice in relation to iron (Fe) content and transferrin receptor (TfR) expression. Pregnant ICR mice were subjected to a daily dose of 75 mg CoCl2/kg body weight 2–3 days prior and 18 days after delivery. Co exposure significantly increased erythrocyte count (RBC), and reduced the erythrocytic parameters mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) in the offspring. Total iron-binding capacity (TIBC) was decreased while bilirubin values were ~ 1.2-fold higher in the metal-exposed mice. Perinatal CoCl2 treatment also induced pathohistological changes in target organs (spleen, liver, and kidneys) as altered organ weight indices, leukocyte infiltration, abundant Kupffer cells in the liver, increased mesangial cellularity, and reduced capsular space in the kidney. CoCl2 administration induced significant 68-, 3.8-, 41.3-, and 162-fold increase of Co content in the kidney, spleen, liver, and RBC, respectively. Fe content in the target organs of CoCl2-treated mice was also significantly elevated. Immunohistochemical analysis demonstrated that TfR1 was well expressed in the renal tubules, hepatocytes, the red pulp, and marginal zone of white pulp in the spleen. TfR2 showed similar expression pattern, but its expression was stronger in the spleen and liver samples of Co-treated mice compared with that of the untreated controls. The results demonstrate that exposure to CoCl2 during late pregnancy and early postnatal period affects body and organ weights and alters hematological and biochemical parameters, iron content, and TfR expression in target organs.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Here, I present the data testifying that the conversion of free radical NO molecules to nitrosonium ions (NO+), which are necessary for the realization of one of NO biological effects (S-nitrosation), may occur in living organisms after binding NO molecules to loosely bound iron (Fe2+ ions) with the subsequent mutual one-electron oxidation–reduction of NO molecules (their disproportionation). Inclusion of thiol-containing substances as iron ligands into this process prevents hydrolysis of NO+ ions bound to iron thus providing the formation of stable dinitrosyl iron complexes (DNIC) with thiol ligands. Such complexes act in living organisms as donors of NO and NO+, providing stabilization and transfer of these agents via the autocrine and paracrine pathways. Without loosely bound iron (labile iron pool) and thiols participating in the DNIC formation, NO functioning as one of universal regulators of diverse metabolic processes would be impossible.

© 2019 Elsevier GmbH Introduction: Eastern and North-Eastern regions of Kazakhstan are considered to be environmentally disadvantaged due to industrial pollution and activity of the former Semipalatinsk Nuclear Test Site. Ferrous metallurgy is represented by the world's largest ferroalloy plant located in Aksu. In addition to a ferroalloy plant, Aksu is the home for the largest thermal power plant in Kazakhstan. Objective: Biomonitoring of 31 hair and blood trace elements (Ag, Ba, Be, Bi, Cs, Co, Ce, Cr, Cu, Eu, Gd, Hf, In, La, Li, Mn, Mo, Nb, Nd, Pb, Sc, Sn, Tl, Th, U, V, W, Y, Yb, Zn, and Zr) in non-occupationally exposed population residing in polluted areas of East Kazakhstan and Pavlodar regions. Methods: Five case groups, residing in the vicinity to the former Semipalatinsk Nuclear Test Site (Akzhar, Borodulikha, and Karaul) or in proximity to industrial plants (Aksu and Ust-Kamenogorsk) have been assessed vs. controls from a rural settlement in Kurchum. In total, 204 hair and blood samples were analyzed by inductively coupled plasma mass spectrometry. Results: The observed blood concentrations of trace elements were in agreement with earlier studies on residents of industrially polluted areas. Elevated levels of blood Ba, Mn, Pb, V, and Zn were detected in residents of Aksu and Ust-Kamenogorsk. The elemental composition of head hair was characterized by greater stability between the study sites. Conclusion: Residency near the former Semipalatinsk Test Site could be considered as safe, while the environmental status of industrial settlements appears to be rather adverse.

© 2019 Elsevier Inc. Loss of dopaminergic neurons in the substantia nigra is one of the pathogenic hallmarks of Parkinson's disease, yet the underlying molecular mechanisms remain enigmatic. While aberrant redox metabolism strongly associated with iron dysregulation and accumulation of dysfunctional mitochondria is considered as one of the major contributors to neurodegeneration and death of dopaminergic cells, the specific anomalies in the molecular machinery and pathways leading to the PD development and progression have not been identified. The high efficiency and relative simplicity of a new genome editing tool, CRISPR/Cas9, make its applications attractive for deciphering molecular changes driving PD-related impairments of redox metabolism and lipid peroxidation in relation to mishandling of iron, aggregation and oligomerization of alpha-synuclein and mitochondrial injury as well as in mechanisms of mitophagy and programs of regulated cell death (apoptosis and ferroptosis). These insights into the mechanisms of PD pathology may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Diet plays an important role in the development of obesity and may contribute to dysregulated iron metabolism (DIM). A cross-sectional survey of 208 adults was conducted in Taipei Medical University Hospital (Taipei, Taiwan). A reduced-rank regression from 31 food groups was used for a dietary pattern analysis. DIM was defined as at least four of the following criteria: serum hepcidin (men >200 ng/mL and women >140 ng/mL), hyperferritinemia (serum ferritin of >300 ng/mL in men and >200 ng/mL in women), central obesity, non-alcoholic fatty liver disease, and two or more abnormal metabolic profiles. Compared to non-DIM patients, DIM patients were associated with an altered body composition and had a 4.52-fold (95% confidence interval (CI): (1.95–10.49); p < 0.001) greater risk of metabolic syndrome (MetS) after adjusting for covariates. A DIM-associated dietary pattern (high intake of deep-fried food, processed meats, chicken, pork, eating out, coffee, and animal fat/skin but low intake of steamed/boiled/raw foods and dairy products) independently predicted central obesity (odds ratio (OR): 1.57; 95% CI: 1.05–2.34; p < 0.05) and MetS (OR: 1.89; 95% CI: 1.07–3.35; p < 0.05). Individuals with the highest DIM pattern scores (tertile 3) had a higher visceral fat mass (%) (β = 0.232; 95% CI: 0.011–0.453; p < 0.05) but lower skeletal muscle mass (%) (β = −1.208; 95% CI: −2.177–−0.239; p < 0.05) compared to those with the lowest DIM pattern scores (tertile 1). In conclusion, a high score for the identified DIM-associated dietary pattern was associated with an unhealthier body composition and a higher risk of MetS.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO.

© 2019 Elsevier Inc. Climate change is one of the biggest and most urgent challenges for the 21st century. Rising average temperatures and ocean levels, altered precipitation patterns and increased occurrence of extreme weather events affect not only the global landscape and ecosystem, but also human health. Multiple environmental factors influence the onset and severity of human diseases and changing climate may have a great impact on these factors. Climate shifts disrupt the quantity and quality of water, increase environmental pollution, change the distribution of pathogens and severely impacts food production – all of which are important regarding public health. This paper focuses on brain health and provides an overview of climate change impacts on risk factors specific to brain diseases and disorders. We also discuss emerging hazards in brain health due to mitigation and adaptation strategies in response to climate changes.

© 2019 Elsevier B.V. Human populations are chronically exposed to mixtures of toxic chemicals. Predicting the health effects of these mixtures require a large amount of information on the mode of action of their components. Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on human health. Our review aims to explore the literature for studies looking to characterize the different modes of action and outcomes of major chemical pollutants, and some components of cosmetics and food additives, on gut microbial communities in order to facilitate an estimation of their potential mixture effects. We identified good evidence that exposure to heavy metals, pesticides, nanoparticles, polycyclic aromatic hydrocarbons, dioxins, furans, polychlorinated biphenyls, and non-caloric artificial sweeteners affect the gut microbiome and which is associated with the development of metabolic, malignant, inflammatory, or immune diseases. Answering the question ‘Who is there?’ is not sufficient to define the mode of action of a toxicant in predictive modeling of mixture effects. Therefore, we recommend that new studies focus to simulate real-life exposure to diverse chemicals (toxicants, cosmetic/food additives), including as mixtures, and which combine metagenomics, metatranscriptomics and metabolomic analytical methods achieving in that way a comprehensive evaluation of effects on human health.

© 2019, Pleiades Publishing, Ltd. Abstract: It is shown that the efficacy of the photosensitized oxidation of organic substrates in aqueous media (with the oxidation of tryptophan being used as an example) does not depend on adding biologically active dinitrosyl iron complexes (DNICs) with thiol-containing ligands to the reaction medium if it contains Pluronic F127, a poly(ethylene oxide)–poly(propylene oxide)– poly(ethylene oxide) triblock copolymer, at concentrations higher than the critical micelle concentration. Photosensitizer molecules are localized in Pluronic micelles and are shielded from the damaging impact of NO• radicals that form upon the photodegradation of DNIC molecules. Photodynamic therapy (PDT) sessions (the photoinduced necrosis and apoptosis of cells in pathologically altered tissues and the simultaneous initiation of regeneration and repair of the treated tissues due to the photodecomposition of DNIC molecules) thus become fundamentally possible.