Cadmium Toxicity and Health Effects-A Brief Summary.

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.

Immunoaging - the effect of age on serum levels of NET biomarkers in men: a pilot study.

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 neutrophillymphocyte 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 µl) 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. Int J Occup Med Environ Health. 2023;36(3):333-48.

The role of miRNA molecules in the miscarriage process.

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.

Bisphenol A: Potential Factor of Miscarriage in Women in the Context of the Phenomenon of Neutrophil Extracellular Traps.

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.

Novel Dual PI3K/mTOR Inhibitor, Apitolisib (GDC-0980), Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells.

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.

Profile of new vascular damage biomarkers in middle-aged men with arterial hypertension.

PURPOSE: Normal endothelial function is important for the homeostasis of the cardiovascular (CV) system. The aim of the present study was to determine the profile of key parameters of endothelial dysfunction in middle-aged men that play a significant role in the functioning of endothelial vessels, which seems to be crucial for the early diagnosis of cardiovascular disorders. MATERIALS AND METHODS: The study included 53 men, 20 with hypertension (HTN), 18 with HTN and related diseases, 15 healthy controls Apart from general testing (BMI, biochemical analysis, SBP, DBP), we used the Griess reaction to assess the total amount of nitric oxide (NO), and used ELISA to verify the concentrations of malondialdehyde (MDA), nitrotyrosine (NT), asymmetric dimethylarginine (ADMA), tumor necrosis factor-alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1), and myeloperoxidase (MPO). Furthermore, we assessed the concentration of circulating free DNA (cfDNA) using the fluorescence method. RESULTS: The values of MDA, ADMA, cfDNA, and MPO observed in samples from men with HTN were determined to be higher compared to those from men without HTN. In the group of men with HTN and other concomitant cardiovascular disorders, we observed low concentrations of NO, MDA, and ADMA with high concentrations of cfDNA. CONCLUSIONS: The results obtained for parameters selected for the study, should be considered by cardiologists as a prompt to include in the diagnostic profile the assessment of NO and cfDNA concentrations for risk evaluation and/or diagnosis of endothelial dysfunction in patients suffering from HTN or related complications.

Biomarkers of neutrophil extracellular traps (NETs) and nitric oxide-(NO)-dependent oxidative stress in women who miscarried.

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.

Concentration of Selected Elements and Antioxidative Potential in a Group of Males Working in the Metal Industry: Elements And Antioxidative Potential In Men.

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 Bialystok, 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.

Changes in Dietary Patterns and the Nutritional Status in Men in the Metallurgical Industry in Poland Over A 21-Year Period.

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.