Toxic effects of prolonged exposure to cadmium and /or polychlorinated biphenyls in rats

tokom prethodnih decenija, kadmijum (Cd), metal bez biološke funkcije, je zbog svoje toksičnosti i sposobnosti bioakumulacije postao predmet brojnih toksikoloških istraživanja...In previous decades, cadmium (Cd), a metal of no bioogical function, has gained attention due to its toxicity and ability to bioaccumulate..

MicroRNA-Regulated Signaling Pathways: Potential Biomarkers for Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer (PCa) and is expected to be the second most common cause of cancer-associated deaths. The high mortality rate is due to the asymptomatic progression of the clinical features until the advanced stages of the disease and the limited effectiveness of the current therapeutics. Aberrant expression of several microRNAs (miRs/miRNAs) has been related to PDAC progression and thus they could be potential early diagnostic, prognostic, and/or therapeutic predictors for PDAC. miRs are small (18 to 24 nucleotides long) non-coding RNAs, which regulate the expression of key genes by targeting their 3′-untranslated mRNA region. Increased evidence has also suggested that the chemoresistance of PDAC cells is associated with metabolic alterations. Metabolic stress and the dysfunctionality of systems to compensate for the altered metabolic status of PDAC cells is the foundation for cellular damage. Current data have implicated multiple systems as hallmarks of PDAC development, such as glutamine redox imbalance, oxidative stress, and mitochondrial dysfunction. Hence, both the aberrant expression of miRs and dysregulation in metabolism can have unfavorable effects in several biological processes, such as apoptosis, cell proliferation, growth, survival, stress response, angiogenesis, chemoresistance, invasion, and migration. Therefore, due to these dismal statistics, it is crucial to develop beneficial therapeutic strategies based on an improved understanding of the biology of both miRs and metabolic mediators. This review focuses on miR-mediated pathways and therapeutic resistance mechanisms in PDAC and evaluates the impact of metabolic alterations in the progression of PDAC

Bone mineral health is sensitively related to environmental cadmium exposure- experimental and human data

Exposure to cadmium (Cd) is recognised as one of the risk factors for osteoporosis, although critical exposure levels and exact mechanisms are still unknown. Here, we first confirmed that in male Wistar rats challenged orally with 6 different levels of Cd (0.3–10 mg/kg b.w.), over 28 days, there was a direct dose relationship to bone Cd concentration. Moreover, bone mineral content was significantly diminished by ∼15% (p < 0.0001) plateauing already at the lowest exposure level. For the other essential bone elements zinc (Zn) loss was most marked. Having established the sensitive metrics (measures of Cd exposure), we then applied them to 20 randomly selected human femoral head bone samples from 16 independent subjects. Bone Cd concentration was inversely proportional to trabecular bone mineral density and mineral (calcium) content and Zn content of bone, but not the donor's age. Our findings, through direct bone analyses, support the emerging epidemiological view that bone health, adjudged by mineral density, is extremely sensitive to even background levels of environmental Cd. Importantly, however, our data also suggest that Cd may play an even greater role in compromised bone health than prior indirect estimates of exposure could reveal. Environmental Cd may be a substantially determining factor in osteoporosis and large cohort studies with direct bone analyses are now merited

Research of features of professional self-actualization of civil servants through the determinants of information security

The article studies the features of professional self-actualization of civil servants through the determinants of information security. The essence and content of professional self-actualization are determined. The main theoretical approaches of scholars to the definition of professional self-realization of a specialist are described. Thus, professional self-actualization is a socialized direction of comprehensive development of the specialist's personality, which combines professional and spiritual experience in the process of obtaining professional qualifications and self-improvement in the process of performing professional tasks and functions, which is a necessary feature for disclosure and realization of personal and professional potential

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.publishedVersio

From Mechanisms to Implications: Understanding the Molecular Neurotoxicity of Titanium Dioxide Nanoparticles

Titanium dioxide nanoparticles (TiO2NPs) are widely produced and used nanoparticles. Yet, TiO2NP exposure may possess toxic effects to different cells and tissues, including the brain. Recent studies significantly expanded the understanding of the molecular mechanisms underlying TiO2NP neurotoxicity implicating a number of both direct and indirect mechanisms. In view of the significant recent progress in research on TiO2NP neurotoxicity, the objective of the present study is to provide a narrative review on the molecular mechanisms involved in its neurotoxicity, with a special focus on the studies published in the last decade. The existing data demosntrate that although TiO2NP may cross blood-brain barrier and accumulate in brain, its neurotoxic effects may be mediated by systemic toxicity. In addition to neuronal damage and impaired neurogenesis, TiO2NP exposure also results in reduced neurite outgrowth and impaired neurotransmitter metabolism, especially dopamine and glutamate. TiO2NP exposure was also shown to promote α-synuclein and β-amyloid aggregation, thus increasing its toxicity. Recent findings also suggest that epigenetic effects and alterations in gut microbiota biodiversity contribute to TiO2NP neurotoxicity. Correspondingly, in vivo studies demosntrated that TiO2NPs induce a wide spectrum of adverse neurobehavioral effects, while epidemiological data are lacking. In addition, TiO2NPs were shown to promote neurotoxic effects of other toxic compounds. Here we show the contribution of a wide spectrum of molecular mechanisms to TiO2NP-induced neurotoxicity; yet, the role of TiO2NP exposure in adverse neurological outcomes in humans has yet to be fully appreciated

Modern Trends in ELT Through E-Learning Platforms

This article provides an overview of the modern trends in online learning and the use of e-learning tools since the field of English Language Teach- ing (ELT) has seen a significant shift in recent years with the introduction of e-learning plat- forms. The study aims to examine the range of tools and the flexibility these platforms provide to learn English. However, technical students face unique challenges when using these platforms. These students require specialized language instruction that caters to their specific field of study, making it difficult to find suitable content on e-learning platforms. Additionally, balancing the combination of synchronous and asynchronous teaching can be challenging, as technical stu- dents may have other commitments that require flexibility in their learning schedule.Дана стаття містить огляд сучасних тенденцій в онлайн-освіті та використанні засобів електронного навчання, оскільки сфера викладання англійської мови зазнала значних змін за останні роки з впровадженням платформ для електронного навчання. Дослідження має на меті вивчити доступні інструменти та гнучкість, яку надають ці платформи для вивчення англійської мови. Проте студенти технічних факультетів стикаються з різними проблемами під час використання цих платформ. Студентам потрібне спеціальне підхід до вивчення мови відповідно до напрямку їх навчання, що ускладнює пошук відповідного контенту на платформах для електронного навчання. Крім того, важливою задачею є збалансу- вати використання синхронного та асинхронного викладання

PHYSICAL AND CHEMICAL CHARASTERISTIC OF URBAN AEROSOL OF CENTRAL BALKANS (BELGRADE)

Size-segregated urban aerosol of Belgrade center (44049'14''N, 20027'44''E) was studied during the summer-autumn 2008. The representative location in traffic area Studentski trg was chosen for investigating physical and chemical characteristics of collected particles. Particle size distribution in the size range Dp £ 0.49 µm, 0.49 £ Dp £ 0.95 µm, 0.95 £ Dp £ 1.5 µm, 1.5 £ Dp £ 3.0 µm, 3.0 £ Dp £ 7.2 µm and Dp ³ 7.2 µm were measured. Aerosol samples were submitted to gravimetric SEM analysis. The shape, size and chemical composition of the fine and coarse particles were analyzed. The imaging was carried out by SEM (Nova NanoSEM 230, FEI, USA). The same SEM was also used for the EDX measurements performed. The particles collected on fiber filters for SEM imaging were further on coated with 4 nm Pt layer to improve conductivity of the samples. The morphological and chemical composition suggested that the most abundant particles were carbonaceous soot but also microbes and natural and anthropogenic inorganic mineral materials. The chemical characterization was performed on a semi-quantitative level. The contents of the carbon were up to 70% or higher. In the samples were dominating next others elements: O, Mo, Si, Fe, Ca, Al, K, Mg

Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer

Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)-mediated toxicity in hTERT-HPNE and AsPC-1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0-100 M) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 M was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 M compared to 42 M in the AsPC-1 cells (P lt 0.01). The CdCl2-mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC-1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell-dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development

Cu2Se and Cu Nanocrystals as Local Sources of Copper in Thermally Activated in Situ Cation Exchange

Among the different synthesis approaches to colloidal nanocrystals, a recently developed toolkit is represented by cation exchange reactions, where the use of template nanocrystals gives access to materials that would be hardly attainable via direct synthesis. Besides, postsynthetic treatments, such as thermally activated solid-state reactions, represent a further flourishing route to promote finely controlled cation exchange. Here, we report that, upon in situ heating in a transmission electron microscope, Cu2Se or Cu nanocrystals deposited on an amorphous solid substrate undergo partial loss of Cu atoms, which are then engaged in local cation exchange reactions with Cu “acceptor” phases represented by rod- and wire-shaped CdSe nanocrystals. This thermal treatment slowly transforms the initial CdSe nanocrystals into Cu2−xSe nanocrystals, through the complete sublimation of Cd and the partial sublimation of Se atoms. Both Cu “donor” and “acceptor” particles were not always in direct contact with each other; hence, the gradual transfer of Cu species from Cu2Se or metallic Cu to CdSe nanocrystals was mediated by the substrate and depended on the distance between the donor and acceptor nanostructures. Differently from what happens in the comparably faster cation exchange reactions performed in liquid solution, this study shows that slow cation exchange reactions can be performed at the solid state and helps to shed light on the intermediate steps involved in such reactions