Cadmium (Cd) is a ductile metal in the form of a blueish or silvery-white powder. It is naturally found in soil (about 0.2 mg/kg), minerals, and water. Cd belongs to the group of toxic, carcinogenic, ...and stimulating elements. Its biological half-life in the human body ranges from 16 to even 30 years on average. Some lung diseases (such as emphysema, asthma, and bronchitis) and high blood pressure are thought to be related to slow poisoning. The symptoms of cadmium poisoning may vary depending on the time of exposure, the type of diet, and the age and health status of the exposed people. For non-smokers and non-occupational exposures, the only source of exposure is diet. The FAO/WHO recommends that the tolerable cadmium intake for an adult is approximately 0.4–0.5 mg/week (60–70 µg per day). Cadmium is primarily absorbed through the respiratory system (about 13–19% of Cd from the air), but it can also enter through the digestive system (about 10–44%), when dust is mixed and swallowed with saliva. The amount of accumulated Cd ranges from 0.14 to 3.2 ppm in muscles, 1.8 ppm in bones, and 0.0052 ppm in the blood. People who are most frequently exposed to heavy metals should be continuously monitored in order to maintain a healthy lifestyle, as well as to implement effective preventive measures and improve public health.
The etiology and pathogenesis of miscarriage, which is the most common pregnancy complication, have not been fully elucidated. There is a constant search for new screening biomarkers that would allow ...for the early diagnosis of disorders associated with pregnancy pathology. The profiling of microRNA expression is a promising research area, which can help establish the predictive factors for pregnancy diseases. Molecules of microRNAs are involved in several processes crucial for the development and functioning of the body. These processes include cell division and differentiation, programmed cell death, blood vessel formation or tumorigenesis, and the response to oxidative stress. The microRNAs affect the number of individual proteins in the body due to their ability to regulate gene expression at the post-transcriptional level, ensuring the normal course of many cellular processes. Based on the scientific facts available, this paper presents a compendium on the role of microRNA molecules in the miscarriage process. The expression of potential microRNA molecules as early minimally invasive diagnostic biomarkers may be evaluated as early as the first weeks of pregnancy and may constitute a monitoring factor in the individual clinical care of women in early pregnancy, especially after the first miscarriage. To summarize, the described scientific data set a new direction of research in the development of preventive care and prognostic monitoring of the course of pregnancy. Summary Sentence: The expression of potential miRNA molecules as early minimally invasive diagnostic biomarkers may be evaluated in the first weeks of pregnancy and may constitute a monitoring factor in the individual clinical care of women in early pregnancy. Graphical Abstract
BPA has demonstrated enormous multisystem and multi-organ toxicity shown mainly in animal models. Meanwhile, the effects of its exposure in humans still require years of observation, research, and ...answers to many questions. Even minimal and short-term exposure contributes to disorders or various types of dysfunction. It is released directly or indirectly into the environment at every stage of the product life cycle, demonstrating its ease of penetration into the body. The ubiquity and general prevalence of BPA influenced the main objective of the study, which was to assess the toxicity and health effects of BPA and its derivatives based on the available literature. In addition, the guidelines of various international institutions or regions of the world in terms of its reduction in individual products were checked. Bisphenol A is the most widely known chemical and perhaps even the most studied by virtually all international or national organizations, but nonetheless, it is still controversial. In general, the level of BPA biomonitoring is still too high and poses a potential threat to public health. It is beginning to be widely argued that future toxicity studies should focus on molecular biology and the assessment of human exposure to BPA, as well as its substitutes. The effects of its exposure still require years of observation, extensive research, and answers to many questions. It is necessary to continue to deepen the knowledge and interest of many organizations, companies, and consumers around the world in order to make rational purchases as well as future choices, not only consumer ones.
Deregulated PI3K/AKT/mTOR signalling commonly exists in glioblastoma, making this axis an attractive target for therapeutic manipulation. Given that activation of PI3K/AKT/mTOR promotes tumour ...growth, metastasis, and resistance to anticancer therapies, mTOR inhibitors show promise in the treatment of cancer. The aim of this study was to investigate the underlying mechanism of novel dual PI3K/mTOR inhibitor, Apitolisib (GDC-0980), in A-172 and U-118-MG GBM tumour cell line suppression. It has been demonstrated that GDC-0980 induces time- and dose-dependent cytotoxicity and apoptosis in investigated glioma cell lines. In our study, the strongest induction of apoptosis was exhibited in the A-172 line after 48 h of incubation with 20 µM GDC-0980, where we observed 46.47% of apoptotic cells. In conclusion, we first discovered that dual PI3K/mTOR blockade by GDC-0980 markedly suppressed survival of human GBM cells and induced apoptosis, independent of the ER stress-mediated DR5 activation. We suggest that GDC-0980, by exerting an inhibitory effect on PERK expression, may thus block its inhibitory effect on protein synthesis, leading to intensification of translation, and this may result in an increase in apoptosis. On the other hand, CHOP stimulates protein synthesis and increases apoptosis. These findings suggest that GDC-0980 may be a candidate for further evaluation as a chemotherapeutic agent for anti-GBM therapy.
Objectives: The study aimed to evaluate the impact of aging on the formation of neutrophil extracellular traps (NETs). The impaired formation of NETs is the cause of an abnormal innate immune ...response. Material and Methods: The study included a total of 45 healthy male subjects of different age groups. Whole blood was collected from the subjects, and the concentration of myeloperoxidase (MPO), the main biocidal protein in NETs, was determined in serum using ELISA. The serum levels of circulating free DNA (cfDNA), which are the structural basis of NETs, were also measured by fluorescence. In addition, the white blood cell count was determined, whole blood smear was evaluated, and the neutrophil-lymphocyte ratio was calculated. The variations in the levels of NET biomarkers were analyzed in different age groups. Results: The low levels of MPO (243.70 ng/ml) and cfDNA (6.24 ng/100 microl) in boys indicated neutrophil insufficiency for NETosis in children. A progressive increase in the levels of MPO and cfDNA with age was observed among adolescents (420.91, p = 0.04; 13.55, p = 0.03, respectively), with the highest level noted in the healthy adult group (466.58, p = 0.01; 14.07, p = 0.01, respectively). The levels of the studied parameters were comparable in adolescents and young adults, which proved that the NETosis process was appropriate and suggested the attainment of neutrophil maturity for the release of NETs in adolescence. The levels of MPO and cfDNA were low in older men (225.46, p < 0.01; 5.19, p < 0.01, respectively) indicating impaired NET formation. Conclusions: Data on the generation of NETs in different age groups obtained in this study can allow a better understanding of the ontogenesis of the immune system in terms of the course of NETosis, and also indicate the need to support nonspecific responses in children and adults. Further research should be performed to determine the possibility of regulating the NETosis process. Key words: biomarkers, neutrophils, MPO, NETs, cfDNA, immunoaging
Background/Aims: The study was carried out to evaluate the changes in the eating habits and lipid parameters in a 21-year follow-up on a group of 435 men living in Poland. Methods: The studied ...population was composed of the same subjects: a group of men who were first studied in the years 1987–1989 and in 2008–2010. The following data was gathered: body mass, body mass index (BMI), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride concentration in blood serum. Results: The changes in the eating habits among the studied men registered throughout the 21-year period were positive since they showed a reduction in the caloric content of their diet (p < 0.001), lower total fat content (p < 0.001), total amount of carbohydrates (p < 0.001), sucrose (p < 0.001), iron (p < 0.001), and featured more vitamins: A (p < 0.002), B1 (p < 0.001), and C (p < 0.001). An adverse trend was observed in terms of constant calcium shortages in their food portions (ns). A 21-year follow-up of the studied group showed significant differences in terms of weight (p < 0.001), BMI (p < 0.001), and all cholesterol fractions (p < 0.001) in their blood serum, except cholesterol alone (ns). Conclusion: It is important to continue observing the dietary trends in the studied group, with the focus on the occurrence of potential changes in their bodies.
The purpose of this study was to show that some elements have a proven
antioxidative effect and are essential for the proper development and
functioning of the human body. The study also assessed the ...concentration of
selected elements and total antioxidant status (TAS) in a group of male
inhabitants of Białystok, Poland, who are professionally active in the metal
industry. The study group comprised 163 men aged 55–64 years. The concentration
of the analyzed elements was determined using flame (Zn and Cu) and
electrothermal (Se, Cd, and Pb) atomic absorption spectrometry.
Spectrophotometric test kits were used to assay the TAS and glutathione
reductase (GR) activity in serum. The results suggested the mean concentration
of Se in serum was 54.04 ± 12.10 μg/L, which was below the reference range. A
significant negative correlation was observed between the concentration of Se in
the serum and Pb and Cd concentrations in the whole blood of the studied men.
The concentrations of the other elements, antioxidant potential, and GR activity
were within the reference range. A statistically significant positive
correlation was observed between Pb and Cd, indicating combined exposure and a
considerable negative correlation between lead and selenium as well as between
lead and TAS. Selenium and TAS are likely to modify the adverse effects of Pb in
the bodies of the studied men. The results indicate that it is necessary to
constantly monitor men who are occupationally exposed to heavy metals, maintain
a healthy lifestyle, and introduce effective preventive measures at a local
level.
Pregnancy loss is a multidisciplinary problem which concerns researchers from the fields of medicine, epidemiology, psychology, and public health. The primary objective of the present study was to ...explain the potential role of neutrophil extracellular traps (NETs) in the process of spontaneous miscarriage. Enzyme-linked immunosorbent assay to assess the levels of biomarkers of NETs in the serum of examined women was conducted. Furthermore, levels of nitric oxide (NO) and late markers of its action were measured in serum samples. Analyses results demonstrated the existence of NETs in the placental tissue of women who miscarried as well as a simultaneous increase in the levels of myeloperoxidase and pentraxin 3. This clearly confirms the participation of NETs in the course of pregnancy loss. Women who have had a miscarriage but did not show the presence of NETs in their placenta exhibited the highest contents of NO, nitrotyrosine, and malondialdehyde suggesting a different pathway leading to pregnancy loss associated with disturbed oxidative-antioxidative processes. Although study results demonstrate new aspects associated with the formation of NETs they are not, however, sufficient to unambiguously determine the role of NETs in the course of miscarriage.
Humans are exposed to a number of environmental pollutants every day. Among them, endocrine disruptors are particularly harmful to human health. Bisphenol A (BPA) is a xenoestrogen that has been ...shown to disrupt the endocrine system and cause reproductive toxicity. In this study, we aimed to verify the potential relationship between BPA and miscarriage involving the formation of neutrophil extracellular traps (NETs). Blood samples were collected from healthy women and women who had miscarriage in the first trimester of pregnancy. The serum levels of cytoplasmic anti-PR3 antibody and perinuclear anti-MPO antibody were determined using an immunoenzymatic method. The concentrations of key proinflammatory proteins TNF-α and MCP-1, as well as NADPH oxidase subunits NOX1 and NCF2, were also measured in the serum samples. The serum concentration of BPA was determined using gas chromatography. The results showed that the concentrations of BPA were significantly elevated in the serum of women who had miscarriage compared to the control group, with the highest concentration found in the “NETs-positive” group. The levels of MCP-1 and TNF-α were significantly higher in the “NETs-positive” group compared to the “NETs-negative” and control group. The levels of NOX1 and NCF2 were also higher in the “NETs-positive” group compared to the “NETs-negative” group. The study showed that BPA could play a role in the course of miscarriage through the formation of NETs. The results indicate the need to limit the exposure of women planning pregnancy to xenoestrogens, including BPA.
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