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Given the strong associations between diet and cancer risk, there is considerable scientific interest in determining whether dietary factors associated with prostate cancer cell implantation may influence epigenetic alternations. The aim of the research was to assess impact of selected trace elements (selenium, zinc and copper) on the kinetics of changes (10-13-14-21 week of life cycle of rats) in the level of 7-methylguanine, 3-methyladenine, 1-methylguanine and 8-oxo-guanine in the urine of rats with implanted prostate cancer cells (LNCaP). Modified nucleobases were determined by validated high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method using multiple reaction monitoring (MRM) mode. In the presented model the implantation of rats with cancer cells did not affect the level of the examined biomarkers in the rats’ urine. The level of methyl derivatives was statistically significantly reduced with the age of the examined rats. The implantation of rats with cancer cells results in the appearance of tumors in 71% of the rats obtaining the standard diet and respectively in 25% of those supplemented with selenium. Supplementation with selenium affects both the effectiveness of tumor induction and the concentration of 7-MeG, 3-MeA, 1-MeG and 8-oxoG in urine of the examined rats. These findings show that modified nucleosides can play an important role in cancer prevention.

The aim of the research was to compare the impact of nano- and micro-sized-zinc on the kinetics of changes in the level of 3-methyladenine, 7-methylguanine, 7-methylguanosine, O-methylguanosine, 1-methyladenosine, N6-methyl-2’-deoxyguanosine in urine of rats with breast cancer. Female Sprague-Dawley rats divided into 3 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano and micro-sized zinc particles. To induce the mammary cancer (adenocarcinoma), rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a validated high performance liquid chromatography coupled to mass spectrometry method. In the first stage of investigations a synergistic activity of nanosized Zn with DMBA on the growth of the neoplastic process was found. During that time a statistically significant increase in the levels of all six examined markers in the rats’ urine was observed. However, as the experiment continued, the supplementation with nanosized zinc caused inhibition of tumour growth, being followed by regression and remission of tumours, as well as, a statistically significant systematic reduction of the levels of methyl derivatives in the urine. Biopsy images indicated grade 1 tumours with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, moderately-differentiated grade 2 adenocarcinoma was identified. It was found that the biological activity of zinc depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.

Abstract Background The aim of the study was to investigate the effect of dietary supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein, on the effectiveness of chemically induced mammary cancer and the changes in the content of selected elements (Zn, Cu, Mg, Fe, Ca) in tumors as compared with normal tissue of the mammary gland. Methods Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet and DMBA (7,12-dimethyl-1,2- benz[a]anthracene), were treated with zinc ions (Zn) or zinc ions + resveratrol (Zn + resveratrol) or zinc ions + genistein (Zn + genistein) via gavage for a period from 40 days until 20 weeks of age. The ICP-OES (inductively coupled plasma optical emission spectrometry) technique was used to analyze the following elements: magnesium, iron, zinc and calcium. Copper content in samples was estimated in an atomic absorption spectrophotometer. Results Regardless of the diet (standard; Zn; Zn + resveratrol; Zn + genistein), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn + resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. On the basis of quantitative analysis of selected elements we found - irrespectively of the diet applied - great accumulation of copper and iron, which are strongly prooxidative, with a simultaneous considerable decrease of the magnesium content in DMBA-induced mammary tumors. The combination of zinc supplementation with resveratrol resulted in particularly large differences in the amount of the investigated elements in tumors as compared with their content in normal tissue. Conclusions Diet supplementation with zinc and polyphenol compounds, i.e. resveratrol and genistein had no effect on the decreased copper level in tumor tissue and inhibited mammary carcinogenesis in the rat. Irrespectively of the applied diet, the development of the neoplastic process in rats resulted in changes of the iron and magnesium content in the cancerous tissue in comparison with the healthy mammary tissue. The application of combined diet supplementation with zinc ions and resveratrol considerably promoted the rate of carcinogenesis and increased the number of DMBA-induced mammary tumors.

Background/Objectives: This review summarizes the current knowledge about factors that affect the physical characteristics of urine. It highlights proper urine sample collection and displays factors like diet, hydration status, and medications that can alter urine color, odor, clarity, specific gravity and pH. Results: Urinalysis is a minimally invasive examination of a patient's health, especially concerning nephrological and endocrinological abnormalities, as well as dietary habits and stimulants used. Certain deviations in appearance, composition or frequency/pain during urination may indicate an ongoing disease process in the body. Based on laboratory results, further medical treatment is determined. The reason for a change in the color of the urine, for its clouding or intense odor may be a disease, as well as the consumption of food, medication, intensive physical exercise or inadequate hydration of the body. Well-standardized procedures for collecting, transporting, preparing and analyzing samples should become the basis for an effective diagnostic strategy in urinalysis. It is worth noting that pharmacists in pharmaceutical care are often the first people to whom a patient turns for health advice and for the interpretation of simple laboratory tests. Acquiring the ability to interpret the results of laboratory tests and the principles of proper sampling for laboratory tests is indispensable in the process of possible counseling and providing reliable answers to patients' questions. Conclusions: Although urinalysis is not recommended as a routine screening tool for the general population, it can prove to be a valuable source of patient health data in some cases as the data will be useful to physicians and pharmacists to more effectively diagnose and better care for patients.

The fruitbodies or sporocarps formed by mushrooms can accumulate mineral elements, such as selenium, zinc or copper, making them an important source of micronutrients essential to humans. However, the literature about environmental factors affecting mineral composition in mushrooms is scarce and limited to the ambiguous impact of soil properties and region. In our study, we investigated the effects of tree stand characteristics (tree species and tree canopy cover), understory cover, and soil properties (pH and C/N ratio of the soil) on the concentration of minerals in six edible mushroom species: Laccaria laccata, L. proxima, L. amethystina, Lepista nuda, Lycoperdon perlatum, and Calvatia excipuliformis, collected on 20 plots covered by stands of different tree species composition and varying in the understory cover. We estimated the concentration of eight elements (Zn, Se, Mg, Mn, Cu, Co, Cr, Mo) using the ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) technique and compared their concentration between the plots, using ordination and linear regression methods. Our research revealed that mushroom species identity, including its ecological role and phylogenetic affinity, had the greatest effect on the mineral composition of mushrooms. The effect of environmental factors depended also on the micronutrient identity. Some elements were not affected at all (Co, Cr), some only by soil reaction or C/N ratio (Mn, Mg, Cu), while others were influenced by both tree stand characteristics and soil properties (Se, Zn, Mo). This knowledge enables us to maximize the content of minerals in harvested mushrooms by collecting them in specific areas. For example, mushrooms, which are sources of Se and Zn, can be gathered in coniferous forests characterized by acid soils, low canopy cover, and minimal understory cover. This targeted collection approach can effectively increase the mineral content in harvested mushrooms, thereby enhancing their health benefits., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Food-drug interactions (FDIs) may alter drug pharmacokinetics and pharmacodynamics, modifying the whole therapy's effectiveness. Some of them cause the attenuation of drug effects, while others inhibit the medicines' metabolism resulting, in too high concentrations of the medicine in the body. Thus, some healthcare professionals-doctors, pharmacists or dieticians-should be aware of the possibility of food-drug interactions. This study aimed to assess knowledge of food-drug interactions among students of pharmacy, medicine, stomatology, medical analysis and dietetics and students of the college of further medical education for pharmacy technicians., Methods: Students (n = 820) completed a custom-made questionnaire. The relationships between the continuous variables were analysed on the basis of Pearson's correlation coefficient. To verify the predictors of objective students' knowledge about food-drug interactions, a multiple linear regression model with analysis of covariance (ANCOVA) was used. The Kruskal-Wallis test was performed to compare the total scores the respondents received for questions assessing their objective knowledge of FDI., Results: Students' objective knowledge of FDIs correlated positively with their year of study and their self-evaluation of it. It was also significantly influenced by the field and mode of studies and by the fact that the issue had been discussed during the courses., Conclusions: Most students of the medical university had serious deficiencies in their knowledge of food-drug interactions. This is of particular concern for future doctors and dentists. Among the respondents, pharmacy students stood out, as their FDI knowledge was greater. The issue of food-drug interactions should be more widely taught at medical universities, which was emphasised by the respondents themselves.

Numerous edible mushrooms accumulate Potentially Toxic Elements (PTE), such as cadmium, mercury, and lead, within their sporocarps. This accumulation poses a potential risk of poisoning for humans and is influenced by factors such as the mushroom species, type of element, and the level of industrialization in the region. In our study, we investigated how soil and tree stand characteristics, including C/N ratio, pH, tree diversity, canopy cover, and the proportion of deciduous trees, influence PTE concentration in mushrooms. We collected edible mushrooms from 20 plots situated in the Białowieża Primeval Forest, one of Europe's best-preserved lowland forests. Plots varied in terms of tree species composition, with other factors minimized. We used ICP-MS (Inductively Coupled Plasma - Mass Spectrometry) technique to analyze the concentration of eight PTE (Ag, As, Cd, Ni, Pb, Sb, Sr, Tl) in eight edible mushroom species (M.procera, L.perlatum, R. butyracea, R.cyanoxantha, R.heterophylla, L.vellereus, A.mellea, and Xerocomellus chrysenteron). Our research revealed that the presence of the effect of specific factors on concentration of PTE and its direction depends on mushroom species and type of PTE. The proportion of deciduous tree species and pH of the topsoil layer emerged as the most influential factors affecting PTE concentration in mushroom samples. Tree species richness in the canopy layer did not affect PTE concentration in mushrooms, except for the concentration of Pb in X. chrysenteron. We observed a consistent profile of PTE concentration in mushrooms with similar ecological roles (ectomycorrhizal, saprotrophic, parasite mushrooms) and from comparable phylogenetic affinities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

All over the world, birds' eggs are an important and valuable component of the human diet. This study aimed to compare the content of lipid components and their nutritional value as well as iron and zinc levels in chicken and quail eggs commonly available on the market. In egg lipids, unsaturated fatty acids were dominant, especially oleic acid, the content of which was about 40% of the total fatty acids (TFAs). Linoleic acid was the major polyunsaturated fatty acid. Compared to other products of animal origin, eggs were characterized by favorable values of lipid quality indices, especially the index of atherogenicity, thrombogenicity, and the hypocholesterolemic-to-hypercholesterolemic ratio. In the present study, no differences were found in the content of tested nutrients between eggs from different production methods (organic, free-range, barn, cages). Based on linear discriminant analysis, inter-breed differences were noticed. Cluster analysis showed that eggs enriched in n3 PUFAs (according to the producers' declarations) differed from other groups of chicken eggs. However, in eggs from one producer only, the amount of EPA and DHA exceeds 80 mg per 100 g, entitling the use of the nutrition claim on the package. Quail eggs differed from chicken eggs in FA profile and cholesterol and iron levels., Competing Interests: The authors declare no conflict of interes.

The importance of mushrooms as a food source is continually increasing. To investigate how environmental factors affect the nutritional value of mushrooms, we harvested them in eastern Poland, south-central Germany, and northwestern Belgium in plots with similar environmental conditions but varying in tree species composition and richness. We used gas chromatography-mass spectrometry (GC-MS) to analyze the fatty acid (FA) content of the mushrooms. Fungal species identity explained the largest part (40%) of the total variation in FA concentration and composition. Environmental factors accounted for 1-12% of variation. The concentration of FA, especially saturated fatty acids, decreased with increasing understory cover and increasing nitrogen concentration in the topsoil. The effect of tree species richness or tree species identity was negligible. Our results suggest that the nutritional value of mushrooms depends mainly on the species identity of fungi, but that their FA content is slightly higher in forests with less undergrowth and in nitrogen-poor soils.

Cholesterol oxidation products (COPs) are contaminants of food of animal origin. Increased levels of these compounds in the human body are associated with an increased risk of many non-communicable diseases. Dairy products are mentioned among the main sources of these compounds in the diet. The objective of this study was to evaluate the contents of cholesterol and its oxidized derivatives in eleven groups of dairy products, willingly consumed in European countries. The levels of COPs were determined by applying the GC-TOF/MS method. In the tested products, cholesterol and its oxidation derivatives, such as 7-ketocholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, 5,6β-epoxycholesterol and 5,6α-epoxycholesterol, were determined. The studied dairy products differed in their contents and profiles of oxysterols. The highest contents of COPs were found in cheese with internal mold (13.8 ± 2.5 mg kg -1 ) and Cheddar (11.7 ± 3.5 mg kg -1 ), while the lowest levels were detected in yoghurt (0.94 ± 0.30 mg kg -1 ) and kefir (0.57 ± 0.11 mg kg -1 ). 7-ketocholesterol and 5,6β-epoxycholesterol were the dominant oxysterols. The ratio of oxidized derivatives to total cholesterol was on average 1.7%. Our results confirmed that dairy products are an important dietary source of COPs. Their levels should be monitored in dairy products to provide the best health quality.

The aim of our study was to analyse the effect of supplementation with various forms of genistein (nano-, micro-, and macro-) on the mineral status of rat femurs in conditions of DMBA-induced mammary gland neoplasia. Thirty-two 30-day-old Sprague Dawley rats were used in the study. The rats were divided into four experimental groups: a control group (without supplementation) and groups supplemented with nanosized (92 ± 41 nm), microsized (587 ± 83 nm), and macrosized genistein. Micromorphometric and histological examination of the rat femurs were performed, as well as analysis of the weight and mineral composition (17 elements). Quadrupole ICP-MS was used for analysis of all trace elements. Supplementation with genistein (nano-, micro-, and macro-) was shown to cause changes in the mineral composition of the bones. In the rats receiving nanogenistein, disintegration of the bone tissue was observed. The femurs of these animals had higher content of calcium (by nearly 300%) and potassium (by 25%) than the other groups, while the level of magnesium was about 22% lower. In the case of microelements, there were increases in copper (by 67%), boron (48%), manganese (13%), and nickel (100%), and a 16% decrease in strontium compared to the bones of rats without genistein supplementation. Changes in micromorphometric parameters, resulting in increased bone fragility, were observed. Administration of genistein was found to have an effect on the amount of trace elements in the bone tissue of rats with breast cancer.

The purpose of this study was to evaluate the effect of genistein in nano, micro, and macro forms on the intensity of the DMBA-induced tumor process in rats and to understand the mechanisms of this action. The effect of genistein supplementation on the content of selected eicosanoids (HETEs, HODE, and HEPE) in the serum of rats was evaluated. The levels and expression of genes encoding various pro-inflammatory cytokines (IL-1, IL-6) and MMP-9 in the blood of rats were also investigated. The biological material for the study was blood obtained from female rats of the Sprague Dawley strain (n = 32). The animals were randomly divided into four groups: animals without supplementation, and animals supplemented at a dose of 0.2 mg/kg b.w. (0.1 mg/mL) with macro, micro (587 ± 83 nm), or nano (92 ± 41 nm) genistein. To induce mammary neoplasia (adenocarcinoma), rats were given 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The content of selected eicosanoids was determined by liquid chromatography with UV detection. An immunoenzymatic method was used to determine the content of cytokines and MMP-9. The expression of the IL-6, IL-1beta, and MMP-9 genes was determined with quantitative real-time PCR (qRT-PCR) using TaqMan probes. Based on the study, it was shown that supplementation of animals with genistein in macro, micro, and nano forms increased the intensity of the tumor process in rats. It was shown that the content of 12-HEPE, HODE, and 12-HETE in the serum of genistein-supplemented rats was statistically significantly lower with respect to the content of the aforementioned markers in the serum of rats receiving only a standard diet, devoid of supplementation. It was found that animals supplemented with nano-, micro-, and macrogenistein had higher levels of metalloproteinase-9, MMP-9, compared to animals without supplementation. There was a significant increase in MMP-9 gene expression in the blood of macrogenistein-supplemented animals, relative to the other groups of rats. On the basis of the study, it was shown that supplementation of animals with nano-, micro-, and macrogenistein had an effect on the development of the tumor process. Dietary supplementation with genistein significantly decreased the level of selected eicosanoids, which may have significant impacts on cancer development and progression.

Cholesterol present in food of animal origin is a precursor of oxysterols (COPs), whose high intake through diet can be associated with health implications. Evaluation of the content of these contaminants in food is associated with many analytical problems. This work presents a GC-TOF/MS method for the simultaneous determination of squalene, cholesterol and seven COPs (7-ketocholesterol, 7α-hydroxycholesterol, 7β-hydroxycholesterol, 25-hydroxycholesterol, 5,6α-epoxycholesterol, 5,6β-epoxycholesterol, cholestanetriol). The sample preparation procedure includes such steps as saponification, extraction and silylation. The method is characterized by high sensitivity (limit of quantification, 0.02-0.25 ng mL -1 for instrument, 30-375 μg kg of sample), repeatability (RSD 2.3-6.2%) and a wide linearity range for each tested compound. The method has been tested on eight different animal-origin products. The COP to cholesterol content ratio in most products is about 1%, but the profile of cholesterol derivatives differs widely (α = 0.01). In all the samples, 7-ketocholesterol is the dominant oxysterol, accounting for 31-67% of the total COPs level. The levels of the other COPs range between 0% and 21%. In none of the examined products are cholestanetriol and 25-hydroxycholesterol present. The amount of squalene, which potentially may inhibit the formation of COPs in food, ranges from 2 to 57 mg kg -1 .

Metabolic disorders and nutritional deficiencies in ASD children may be identified by the determination of urinary-modified compounds. In this study, levels of selected seven modified compounds: O-methylguanosine, 7-methylguanosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine, 3-methyladenine, and 8-hydroxy-2`-deoxyguanosine in the group of 143 ASD children and 68 neurotypical controls were analyzed. An ancillary aim was to verify if the reported levels differed depending on the pathogenetic scoring of ASD (mild deficit, moderate deficit, severe deficit). Elevated O-methylguanosine and 7-methylguanosine levels and significantly lower levels of 3-methyladenine, 1-methylguanine, 1-methyladenosine, 7-methylguanine, and 8-hydroxy-'2'-deoxyguanosine were observed in ASD children compared to controls. O-methylguanosine levels were elevated in the mild and moderate groups, while the levels of 1-methylguanine, 1-methyladenosine, 7-methylguanine, and 8-hydroxy-'2'-deoxyguanosine in the same groups were lower than in neurotypical controls. The reported evidence shows that modified nucleosides/bases can play a potential role in the pathophysiology of ASD and that each nucleoside/base shows a unique pattern depending on the degree of the deficit.

Autism spectrum disorder (ASD) is a complex developmental disorder in which communication and behavior are affected. A number of studies have investigated potential biomarkers, including uremic toxins. The aim of our study was to determine uremic toxins in the urine of children with ASD (143) and compare the results with healthy children (48). Uremic toxins were determined with a validated high-performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method. We observed higher levels of p-cresyl sulphate (pCS) and indoxyl sulphate (IS) in the ASD group compared to the controls. Moreover, the toxin levels of trimethylamine N-oxide (TMAO), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) were lower in ASD patients. Similarly, for pCS and IS in children classified, according to the intensity of their symptoms, into mild, moderate, and severe, elevated levels of these compounds were observed. For mild severity of the disorder, elevated levels of TMAO and comparable levels of SDMA and ADMA for ASD children as compared to the controls were observed in the urine. For moderate severity of ASD, significantly elevated levels of TMAO but reduced levels of SDMA and ADMA were observed in the urine of ASD children as compared to the controls. When the results obtained for severe ASD severity were considered, reduced levels of TMAO and comparable levels of SDMA and ADMA were observed in ASD children.

Background: The aim of this study was to determine changes in the mineral composition of the bones of rats with chemically induced mammary gland cancer and to attempt to establish whether a specific diet modification involving the inclusion of zinc ions in two forms-nano and micro-will affect the mineral composition of the bones., Methods: Female Sprague-Dawley rats were used for the research. The animals were randomly assigned to three experimental groups. All animals were fed a standard diet (Labofeed H), and selected groups additionally received zinc nanoparticles or microparticles in the amount of 4.6 mg/mL. To induce mammary cancer, the animals were given 7,12-dimethyl-1,2-benz[a]anthracene. The content of Ag, As, B, Ba, Cd, Cr, Cu, Mn, Ni, Pb, Rb, Se, Sr, Tl, U, and V was determined using ICP-MS, while that of Ca, Fe, K, Mg, Na, and Zn was determined using FAAS., Results: The use of a diet enriched with zinc nano- or microparticles significantly influenced the content of the elements tested. In the bones of rats fed a diet with zinc nanoparticles, changes were found in the content of Ca, Mg, Zn, Cd, U, V, and Tl, while in the case of the diet supplemented with zinc microparticles, there were differences in six elements-Ca, Mg, B, Cd, Ag, and Pb-compared to animals receiving an unsupplemented diet., Conclusions: The content of elements in the bone tissue of rats in the experimental model indicates disturbances of mineral metabolism in the tissue at an early stage of mammary cancer.

The aim of the study was to evaluate the effect of selected polyphenolic compounds: epicatechin, apigenin, and naringenin, administered separately or in combination with zinc (Zn), on the growth and development of the neoplastic process induced by 7,12-dimethylbenz[a]anthracene (DMBA) in rats. The impact of supplementation with the above-mentioned compounds on the content of modified derivatives: 1-methyladenosine, N6-methyl-2'-deoxyadenosine, O-methylguanosine, 7-methylguanine, 3-methyladenine, 1-methylguanine, 2-amino-6,8-dihydroxypurine, and 8-hydroxy-2'-deoxyguanosine in the urine of rats with mammary cancer was also assessed. Female Sprague-Dawley rats divided into 7 groups were used in the study: animals without supplementation and animals supplemented with apigenin, epicatechin, and naringenin separately or in combination with zinc. To induce mammary cancer, rats were treated with DMBA. Modified derivatives were determined by a validated high-performance liquid chromatography coupled to mass spectrometry method. Based on the obtained results, it can be said that supplementation of the animals with naringenin inhibits the development and progression of the neoplastic process in rats treated with 7,12-dimethylbenzanthracene. Neoplastic tumors were found in only 2 of 8 rats (incidence: 25%) and were considered to be at most grade 1 malignancy. The first palpable tumors in the group of animals receiving naringenin appeared two-three weeks later when compared to other groups. The combination of zinc with flavonoids (apigenin, epicatechin, and naringenin) seems to stimulate the process of carcinogenesis. The level of N6-methyl-2'-deoxyadenosine and 3-methyladenine in the urine of rats was statistically significantly higher in the groups supplemented with apigenin, epicatechin, and naringenin administered in combination with Zn than in the groups receiving only polyphenolic compounds. In conclusion, supplementation of rats with selected flavonoids administered separately or in combination with Zn has an impact on the development of neoplasms and the level of modified nucleosides in the urine of rats with breast cancer. Our results raise the question of whether simultaneous diet supplementation with more than one anti-cancer agent may reduce/stimulate the risk of carcinogenesis.

Inflammation plays an important role in the pathogenesis of many diseases, including cardiovascular diseases, atherosclerosis, diabetes, asthma, and cancer. An appropriate diet and the active compounds contained in it can affect various stages of the inflammatory process and significantly affect the course of inflammatory diseases. Recent reports indicate that polyphenolic acids, vitamins, minerals, and other components of fruits may exhibit activity stimulating an anti-inflammatory response, which may be of importance in maintaining health and reducing the risk of disease. The article presents the latest data on the chemical composition of fruits and the health benefits arising from their anti-inflammatory and antioxidant effects. The chemical composition of fruits determines their anti-inflammatory and antioxidant properties, but the mechanisms of action are not fully understood.

Lesniowski-Crohn's disease (CD) is a type of chronic inflammatory bowel disease (IBD) of uncertain etiology. Initially, pharmacological management is undertaken; however, surgical intervention is necessary to improve life quality and relieve symptoms in most cases. Here changes are reported in blood metabolome that occurred three days after the ileo-colic region resection in the case of seven patients. Alterations are observed in levels of metabolites associated with multiple mitochondrial pathways, based on the Metabolite Set Enrichment Analysis, reflecting a high energy demand in the post-operative period. As most of these metabolites are also essential nutrients supplied from foods, we believe that our results might contribute to the discussion on perioperative nutrition's role in enhanced recovery.

A study was conducted to determine the effect of long-term supplementation with selenium and copper, administered at twice the level used in the standard diet of rats, on the content of selected elements in the femoral bones of healthy rats and rats with implanted LNCaP cancer cells. After an adaptation period, the animals were randomly divided into two experimental groups. The rats in the experimental group were implanted with prostate cancer cells. The rats in the control group were kept in the same conditions as those in the experimental group and fed the same diet, but without implanted cancer cells. The cancer cells (LNCaP) were intraperitoneally implanted in the amount of 1 × 10 6 (in PBS 0.4 mL) at the age of 90 days. The content of elements in the samples was determined by a quadrupole mass spectrometer with inductively coupled plasma ionization (ICP-MS). In the femoral bones of rats with implanted LNCaP cells, in the case of the standard diet and the copper-enriched diet, there was a marked decreasing trend in the content of the analysed elements relative to the control rats. This may indicate slow osteolysis taking place in the bone tissue. Contrasting results were obtained for the diet enriched with selenium; there was no significant reduction in the level of these elements, and there was even an increase in the concentrations of Fe and K in the bones of rats with implanted LNCaP cells. Particularly, numerous changes in the mineral composition of the bones were generated by enriching the diet with copper. The elements that most often underwent changes (losses) in the bones were cobalt, iron, manganese and molybdenum. The changes observed, most likely induced by the implantation of LNCaP cells, may indicate a disturbance of mineral homeostasis.

The intake of selected minerals, especially zinc, calcium and selenium, and high consumption of dietary isoflavones are recognised as factors influencing prostate cancer risk. Moreover, changes in levels of some essential elements are characteristic of the disease. Here, we examined the combined effects of main dietary isoflavonoids (genistein, daidzein and its metabolite, equol) and minerals implicated in prostate cancer, namely zinc, selenium, copper, iron and calcium, on LNCaP prostate cancer cells proliferation. Secondly, we evaluated the influence of the combinations on genotoxicity of model mutagens, 4-nitroquinoline oxide (4NQO) and 2-aminoanthracene (2AA), in the umu test. All combinations of isoflavonoids and minerals inhibited prostate cancer cells growth. However, only mixtures with iron ions had significantly stronger effect than the phytochemicals. Interestingly, we observed that only genistein attenuated genotoxicity of 4NQO. The addition of any tested mineral abolished this effect. All tested isoflavonoids had anti-genotoxic activity against 2AA, which was significantly enhanced in the presence of copper sulphate. Our results indicate that the tested minerals in physiological concentrations had minimal influence on the anti-proliferative activity of isoflavonoids. However, they significantly modulated the anti-genotoxic effects of isoflavonoids against both metabolically activated and direct mutagens. Thus, the minerals intake and nutritional status may modulate protective action of isoflavonoids.

The aim of this study was to assess the effect of genistein on the level of cholesterol, oxysterols, and composition of fatty acids, as well as enzymatic activity of desaturases, in rats with breast cancer. The animals were supplemented with nano-, micro-, and macrogenistein. Rats were treated with 7,12-dimethylbenz[a]anthracene to induce mammary adenocarcinoma. In the case of animals supplemented with genistein, an increase in the intensity of the carcinogenesis process was observed. Genistein supplementation also affected the cholesterol and oxysterols levels, as well as the composition of fatty acids, in the serum of rats with neoplastic disease. Dietary supplementation with nanogenistein significantly increased the level of cholesterol ( p = 0.02) and cholesterol oxidation products ( p = 0.02), which may have significant impacts on cancer development and progression.

Purpose: Fatty acids (FA), particularly polyunsaturated (PUFA) ones, are involved in the regulation of glycemic control, lipid metabolism, and inflammation. The aim of the study was to assess patient FA profile in relation to obesity, lipid and carbohydrate metabolism disturbances, and weight loss., Materials and Methods: The studied group consisted of 51 patients with extreme obesity, 23 of whom achieved radical weight reduction within 1 year after a laparoscopic sleeve gastrectomy (LSG). FA levels were determined using gas chromatography with flame ionization detection., Results: Patients with extreme obesity and higher serum PUFA content have lower serum levels of SFA and MUFA (especially myristic, palmitic, lignoceric acids and palmitoleic, oleic acids), as well as lower triglyceride and higher HDL-cholesterol concentrations and it was not influenced by CEPT Taq1B variant. At baseline, the fatty acid profile of patients with type II diabetes differ from patients with dyslipidemia. In patients who had lost weight, significantly lower levels of selected saturated FA and major trans-fatty acid, elaidic, were found. Moreover, the proportion of PUFA was increased., Conclusion: In extreme obesity, higher PUFA exert their favorable effects on serum lipids. Significant weight reduction after the bariatric surgery is associated with beneficial changes in the fatty acid profile., (© 2021. The Author(s).)

The aim of this study was to investigate the effect of zinc supplementation (in the form of nano or microparticles) on the profile and metabolism of fatty acids in the liver microsomes of rats with induced breast cancer. The activity of desaturases (Δ5, Δ6, Δ9) and the level of cholesterol and its oxidized derivatives were measured. The aim of this study was also to determine the effect of various forms of zinc supplements on rats that were on 5-, 12- and 15-hydroxyeicosatetraenoic (5-, 12- and 15-HETE) and hydroxyoctadecadienoic (HODE) acids, and the level of prostaglandin E2 (PGE2). Female Spraque-Dawley rats ( n = 24) were divided into 2 groups that were supplemented with zinc in the micro form (342 nm) or nano form (99 nm) particles, respectively, and a group with a standard diet (control group). All animals received 7,12-dimethylbenz[a]anthracene twice for the induction of breast cancer. Dietary nano-Zn supplementation increased vaccenic acid content ( p = 0.032) and decreased Δ6-desaturase activity ( p = 0.006), whereas micro-Zn increased cholesterol ( p = 0.006), ∑COPs (total cholesterol-oxidation products) ( p = 0.019) and PGE2 ( p = 0.028) content. Dietary enrichment with Zn microparticles resulted in lower concentrations of the metabolites 15-, 12- and 5-HETE and HODE. Our study indicates that the effect of zinc supplementation on the metabolism of fatty acids in the liver microsomes under neoplastic conditions depends on the form in which it is administered.

The virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the disease coronavirus disease 2019 (COVID-19). The cumulative number of cases reported globally is now nearly 197 million and the number of cumulative deaths is 4.2 million (26 July to 1 August 2021). Currently we are focusing primarily on keeping a safe distance from others, washing our hands, and wearing masks, and the question of the effects of diet and diet-dependent risk factors remains outside the center of attention. Nevertheless, numerous studies indicate that diet can play an important role in the course of COVID-19. In this paper, based on select scientific reports, we discuss the structure and replication cycle of SARS-CoV-2, risk factors, dietary standards for sick patients, and the roles of the microbiome and dietary components supporting the immune system in preventing COVID-19.

Background/aim: The aim of the study was to assess the impact of nano-, micro-, and macro-sized-genistein on the growth and development of neoplasms in rats with mammary cancer. Additionally, the effect on the kinetics of changes (9-11-17-20 week of a rat's life) in the levels of methyl derivatives: 1-methyladenine, 3-methyladenine, 7-methylguanine, 1-methylguanine, 1-methyladenosine, 7-methylguanosine, O-methyl-guanosine and N6-methyl-2'-deoxyguanosine in the urine of rats was analyzed., Materials and Methods: Female Sprague-Dawley rats divided into 4 groups were used in the study. Animals were fed only a control diet or diets supplemented with the nano-, micro- and macro-sized genistein. To induce the mammary adenocarcinoma, rats were treated with 7,12-dimethylbenz[a]anthracene (DMBA). Modified nucleosides were determined by a high-performance liquid chromatography coupled to mass spectrometry method (LC-MS/MS)., Results: The supplementation of the diet of animals with genistein resulted in an increase in the excretion of methylated derivatives in the urine of rats. In the animals receiving standard diet, the levels of methyl derivatives increased during the study or remained relatively low. In the case of animals whose diet was supplemented with the various forms of genistein, the levels of methylated derivatives were very high from the beginning., Conclusion: High levels of methyl derivatives can influence carcinogenesis., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The purpose of this work was to evaluate the effect of the nanosized or microsized zinc (Zn) particles on fatty acid profile, enzyme activity and the level of cholesterol, squalene and oxysterols in rats with breast cancer. Rats (female, n = 24) were divided into the following groups: control, and two test groups, whose diets were enriched with either Zn microparticles (342 nm) or Zn nanoparticles (99 nm). All rats were treated twice with the carcinogenic agent; 7,12-dimethylbenz[a]anthracene. In rats whose diet was enriched with zinc (especially in the form of nanoparticles), the number and sizes of tumors were lower. Diet supplementation also significantly reduced the cholesterol ( p = 0.027) and COPs (cholesterol oxidation products) levels ( p = 0.011) in rats serum. Enriching the diet with Zn microparticles decreased the Δ6-desaturase activity ( p < 0.001). Zn influences fatty acids' profile in rats' serum as well as inhibiting desaturating enzymes. A reduced amount of pro-inflammatory arachidonic acid derivatives may be the expected effect.

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch ( Perca fluviatilis ); flounder ( Platichthys flesus ); turbot ( Scophthalmus maximus ); plaice ( Pleuronectes platessa ); cod ( Gadus morhua callarias ); bream ( Abramis brama ); crucian ( Carassius carassius ). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7β-hydroxycholesterol; 5β,6β-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) μg/g-4.18 μg/g (perch), which corresponded to 0.7-1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14-1.79 ± 0.06 μg/g), 7β-hydroxycholesterol (0.50 ± 0.04-3.20 ± 2.95 μg/g) and 5β,6β-epoxycholesterol (0.66 ± 0.03-1.53 ± 0.66 μg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.

Background/aim: The aim of the study was to determine the effect of various diets with zinc or zinc in combination with resveratrol or genistein on mineral contents of the serum, urine, liver, kidney and heart in rats with chemically-induced mammary carcinoma., Materials and Methods: The manuscript presents the tissues and body fluids content of iron, calcium, zinc, magnesium and copper in control rats or rats treated with 7,12-dimethyl-1,2-benz[a]anthracene to induce mammary carcinogenesis, under four dietary conditions: standard feed, Zn supplemented feed (6.9 mg Zn/ml), Zn and resveratrol (0.2 mg/kg body) supplemented feed, or Zn and genistein (0.2 mg/kg body) supplemented feed., Results: The content of calcium and copper highly varied depending on the tissue and the type of dietary supplement (no change for zinc and magnesium). Irrespective of the diet used, the chemical induction of mammary cancer caused a decrease in iron concentration in most samples analysed. Only supplementation of the rats' diet with zinc and genistein induced no changes in iron distribution in the serum, urine, liver, kidney and heart., Conclusion: Further research using various levels of zinc and genistein in the diet should be conducted to determine how the development and progression of cancer is linked to iron content in cells and its ability to accumulate in tumour tissue., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Prostate cancer (PCa) is the second most frequent cancer in men and the fifth most common cause of death worldwide, with an estimated 378,553 deaths in 2020. Prostate cancer shows a strong tendency to form metastatic foci in the bones. A number of interactions between cancer cells attacking bones and cells of the bone matrix lead to destruction of the bone and growth of the tumour. The last few decades have seen increased interest in the precise role of minerals in human health and disease. Tumour cells accumulate various minerals that promote their intensive growth. Bone, as a storehouse of elements, can be a valuable source of them for the growing tumour. There are also reports suggesting that the presence of some tumours, e.g., of the breast, can adversely affect bone structure even in the absence of metastasis to this organ. This paper presents the effect of chronic dietary intake of calcium, iron and zinc, administered in doses corresponding maximally to twice their level in a standard diet, on homeostasis of selected elements (Ca, K, Zn, Fe, Cu, Sr, Ni, Co, Mn and Mo) in the femoral bones of healthy rats and rats with implanted cancer cells of the LNCaP line. The experiment was conducted over 90 days. After the adaptation period, the animals were randomly divided into four dietary groups: standard diet and supplementation with Zn, Fe and Ca. Every dietary group was divided into experimental group (with implanted cancer cells) and control group (without implanted cancer cells). The cancer cells (LnCaP) were implanted intraperitoneally in the amount 1 × 10 6 to the rats at day 90 of their lifetime. Bone tissue was dried and treated with microwave-assisted mineral digestation. Total elemental content was quantified by ICP-MS. Student's t -test and Anova or Kruskal-Wallis tests were applied in order to compare treatment and dietary groups. In the case of most of the diets, especially the standard diet, the femoral bones of rats with implanted LNCaP cells showed a clear downward trend in the content of the elements tested, which may be indicative of slow osteolysis taking place in the bone tissue. In the group of rats receiving the standard diet, there were significant reductions in the content of Mo (by 83%), Ca (25%), Co (22%), Mn (13%), K (13%) and Sr (9%) in the bone tissue of rats with implanted LNCaP cells in comparison with the control group receiving the same diet but without LNCaP implantation. Supplementation of the rat diet with calcium, zinc and iron decreased the frequency of these changes relative to the standard diet, which may indicate that the diet had an inhibitory effect on bone resorption in conditions of LNCaP implantation. The principal component analysis (PCA) score plot confirms the pronounced effect of implanted LNCaP cells and the standard diet on bone composition. At the same time, supplementation with calcium, zinc and iron seems to improve bone composition. The microelements that most often underwent quantitative changes in the experimental conditions were cobalt, manganese and molybdenum.

The cytotoxic properties of zinc nanoparticles have been evaluated in vitro against several types of cancer. However, there is a lack of significant evidence of their activity in vivo, and a potential therapeutic application remains limited. Herein we report the effective inhibition of tumor growth by zinc nanoparticles in vivo, as the effect of the dietary intervention, after the chemical induction in a rodent model of breast cancer. Biopsy images indicated grade 1 tumors with multiple inflammatory infiltrates in the group treated with zinc nanoparticles, whereas, in the other groups, a moderately differentiated grade 2 adenocarcinoma was identified. Moreover, after the supplementation with zinc nanoparticles, the levels of several metabolites associated with cancer metabolism, important to its survival, were found to have been altered. We also revealed that the biological activity of zinc in vivo depends on the size of applied particles, as the treatment with zinc microparticles has not had much effect on cancer progression.

Pomegranate seed oil (PSO) and bitter melon dried fruits (BME) are used as natural remedies in folk medicine and as dietary supplements. However, the exact mechanism of their beneficial action is not known. The aim of study was to assess how the diet supplementation with PSO and/or with an aqueous solution of Momordica charantia affects the metabolism of fatty acids, fatty acids composition and the level of prostaglandin E 2 (PGE 2 ) in rat liver. Animals (Sprague-Dawley female rats, n = 48) were divide into four equinumerous groups and fed as a control diet or experimental diets supplemented with PSO, BME or both PSO and BME for 21 weeks. Fatty acids were determined using gas chromatography with flame ionization detection. PSO added to the diet increased the rumenic acid content ( p < 0.0001) and increased accumulation of n -6 fatty acids ( p = 0.0001) in hepatic tissue. Enrichment of the diet either with PSO or with BME reduced the activity of Δ 6 -desaturase (D6D) ( p = 0.0019), whereas the combination of those dietary factors only slightly increased the effect. Applied dietary supplements significantly reduced the PGE 2 level ( p = 0.0021). No significant intensification of the influence on the investigated parameters resulted from combined application of PSO and BME. PSO and BME have potential health-promoting properties because they influence fatty acids composition and exhibit an inhibiting effect on the activity of desaturases and thus they contribute to the reduction in the metabolites of arachidonic acid (especially PGE 2 ).

Epigenetic modifications play a key role in gene regulation and expression and are involved in numerous cellular processes. Due to the limited research on nucleosides in Parkinson's disease (PD), it is very important to consider epigenetic factors and their role in the development of PD. The aim of this study was to investigate and compare the levels of modified nucleosides, such as O -methylguanosine, N 6 -methyl-2'-deoxyadenosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine, 3-methyladenine and 7-methylguanosine in the urine of Parkinson's disease (PD) patients and the control group, and to verify that the results obtained differ in a subgroup of patients with parkinsonian syndromes. The study group comprised 18 patients with diagnosed idiopathic Parkinson's disease and four parkinsonian syndromes. The control group consisted of 30 age- and sex-matched neurological patients without confirmation by neuroimaging brain damage and extrapyramidal symptoms. The levels of nucleosides were determined by validated liquid chromatography coupled with the mass spectrometry (LC-MS/MS) method using the multiple reaction monitoring (MRM) mode. Lower levels of O -methylguanosine, 3-methyladenine, 1-methylguanine, N 6 -methyl-2'-deoxyadenosine and a higher level of 7-methylguanine in the urine of 22 PD patients were observed. Moreover, elevated levels of 1-methyladenosine, 7-methylguanine, and O -methylguanosine were observed in the parkinsonian syndrome subgroup. These preliminary results may indicate that modified nucleosides describe metabolic disturbances in the metabolism of purine, which was the most severely affected pathway that mediated the detrimental effects of neuroinflammation on PD.

5-Hydroxymethylfurfural (5-HMF) is a cyclic aldehyde formed during non-enzymatic browning reactions. In milk, it is, on the one hand, a contaminant, on the other, a quality indicator. The objective of this study was to evaluate the content and selected factors affecting the concentration of 5-HMF in cows' milk and first infant milk. The content of 5-HMF in market milk varied widely, the average was 54.8 μg L -1 (3.3-136.8). There was no significant difference in the concentration of this contaminant between UHT, HTST pasteurised and micro-filtered milk. It was also shown that the content of lipid components did not affect the concentration and kinetics of the 5-HMF formation in milk subjected to thermal treatment. Lactose-free milk was characterised by a level of this compound much higher than regular products. The 5-HMF average contents in powder cows' milk and first infant milk were respectively 642 and 2315 μg kg -1 .

Bromhexine (BH), expectorant used in the treatment of respiratory disorders associated with viscid or excessive mucus, is not permitted for use in the competing horse by many authorities in horseracing and Olympic disciplines. Metabolic studies are of the great importance in anti-doping field because they allow for updating the selection of the most appropriate markers for prohibited substances, such as metabolites present at higher concentration levels and/or lasted for a longer period of time in biological samples than a parent drug. This study describes LC-MS/MS-based method for simultaneous determination of BH and its metabolites, including 4-(2-amino-3,5-dibromobenzylamino)cyclohexanol (4-HDMB), 3-(2-amino-3,5-dibromobenzylamino)cyclohexanol (3-HDMB), in equine serum samples. The 2-(2-amino-3,5-dibromobenzylamino)cyclohexanol (2-HDMB) was monitored as well. The assay was validated in terms of linearity (R 2  greater than 0.9951), intra- and inter-assay accuracy (91.6 - 109.1%) and precision (CV < 9.6%) as well as recovery (94.8 - 105.65%). The LODs were 0.0052, 0.0053, 0.0056 and 0.0043 ng/mL for BH, 2-HDMB, 3-HDMB and 4-HDMB, respectively. The developed method was applied to determine the time curses of BH and its metabolites concentrations in equine serum collected for 95.25 h following a single oral administration of BH to two healthy mares (in dose of 0.8 mg/kg). The parent drug was found at higher concentration levels than 3-HDMB (major metabolite) and 4-HDMB (minor metabolite), however, both BH metabolites lasted for a longer period of time in equine serum than the parent drug. Thus, both metabolites of BH can be considered as BH abuse markers., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The aim of the study was to evaluate the effect of dietary supplementation with chosen minerals (Zn, Se, Fe) on expression of selected cytokines (IL-1, IL-6, TNFα) in spleen of rats and on their concentrations in rat serum under inflammatory and pathological conditions obtained by implantation of prostate cancer cells (LnCaP). Serum levels of metabolites of arachidonic, eicosapentaenoic and linoleic acids (hydroxyeicosatetraenoic, hydroxyeicosapentaenoic and hydroxyoctadecadienoic acids, respectively), as compounds involved in inflammation and cancer development, were also investigated. Male rats were randomised into dietary groups supplemented with Zn, Se or Fe. Prostate cancer cells were implanted to some rats in each group. The study demonstrated that minerals supplemented with the diet may exert various effects on an organism. Selenium, zinc and iron influence pro-inflammatory cytokine expression, what leads to stimulation of inflammation. They also affect synthesis of arachidonic and linoleic acid metabolites that exert pro-inflammatory action and enable cancer development and metastasis., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Fatty acids, especially polyunsaturated, and their metabolites (eicosanoids) play many pivotal roles in human body, influencing various physiological and pathological processes. The aim of the study was to evaluate the effect of supplementation with edible oils diverse in terms of fatty acid composition on fatty acid contents, activities of converting their enzymes, and on lipoxygenase metabolites of arachidonic and linoleic acids (eicosanoids) in rat serum. Female Sprague-Dawley rats divided into seven groups were used in the study. Animals from six groups were fed one of oils daily (carotino oil, made up by combining of red palm oil and canola oil, linseed oil, olive oil, rice oil, sesame oil, or sunflower oil). One group received a standard diet only. Fatty acids were determined using gas chromatography with flame ionization detection. Eicosanoids-hydroxyeicosatetraenoic (HETE) and hydroxyoctadecadienoic acids (HODE) were extracted using a solid-phase extraction method and analyzed with HPLC. Vegetable oils given daily to rats caused significant changes in serum fatty acid profile and eicosanoid concentrations. Significant differences were also found in desaturases' activity, with the linseed and olive oil supplemented groups characterized by the highest D6D and D5D activity. These findings may play a significant role in various pathological states., Competing Interests: The authors declare no conflict of interest.

Modified nucleosides and nucleobases serve as potential diagnostic and prognostic markers of various diseases, including cancer. These compounds are hydrophilic, but are determined mainly using columns with C18 stationary phase. Moreover, these compounds require purification due to the presence of high amounts of isotopomers in the sample matrix and risk of matrix interferences. The most commonly used method for analyte extraction (i.e. solid-phase extraction on phenylboronic acid sorbent) is not appropriate for all the analytes since compounds with cis-diol groups (e.g. 7-methylguanine) are not absorbed. Thus, the aim of this study was to develop and validate a simple and fast method for the simultaneous determination of the methylated nucleosides and nucleobases (derivatives of adenine and guanine including those with cis-diol groups) in urine. The method was based on hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry (HILIC-MS/MS). The sample preparation involved only dilution with acetonitrile and centrifugation. The method was validated for selectivity, calibration curve, precision, accuracy, stability, matrix effect, dilution integrity, and carryover, according to the guidelines of the European Medicines Agency (EMA). All the analyzed validation criteria were fulfilled. The method was applied to the urine of rats and humans (adults and children). To our best knowledge, HILIC-MS/MS method established by our team is the first method that does not require the extraction step as well as this method enables simultaneously determination of 1-methylguanine, 2'-O-methylguanosine, 3-methyladenine, and N 6 -methyl-2'-deoxyadenosine in urine. The method is reliable and can be applied to determine the concentrations of the modified nucleosides and nucleobases in the urine of humans and rats. Because the method is cost-effective, fast, and easy to perform, it may be considered as a routine tool in clinical laboratories., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.

Vitamin D, or more precisely its active metabolite calcitriol (1,25-(OH) 2 D 3 ), plays a fundamental role in bone metabolism and differentiation as well as in intestinal absorption of calcium and regulation of calcium-phosphate metabolism. Recent decades have brought about the discovery of the role of calcitriol in processes regulating cell differentiation, proliferation, angiogenesis and apoptosis. This creates the potential for numerous therapeutic applications of vitamin D in diseases associated with autoaggressive immune responses or in cancer. This study presents selected issues regarding current knowledge of the anti-cancer mechanisms of vitamin D., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The objective of the present study was to determine the influence of dietary supplementation with pomegranate seed oil (PSO) and/or an aqueous extract of dried bitter melon fruits (BME) on breast cancer risk and fatty acid profile in serum of female rats with chemical carcinogen-inflicted mammary tumours. Sprague-Dawley rats (n = 96) were fed control diet or experimental diets supplemented with 0.15 ml PSO/day, BME or jointly PSO and BME. After 21 weeks mammary tumours were subjected to histopathological examination and in serum fatty acids, 8-isoprostaglandin F 2α content and indices of desaturases activity were analysed. Supplementation of the diet with PSO and BME did not inhibit the breast cancer formation. Conjugated linolenic acids (CLnA), present in PSO, were converted into cis-9, trans-11 conjugated linoleic acid (CLA), however, its content was lower in groups treated with a carcinogen. A similar tendency was observed for the content of SFA, MUFA, PUFA, 8-iso PGF 2α and the activity of Δ 6 -desaturase. Enhanced pro-carcinogenic effect of 7,12-dimethylbenz[a]anthracene (DMBA), caused by applied supplements, may be a result of their influence on DMBA metabolism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Prostate cancer continues to be a major cause of morbidity and mortality in men around the world. The data concerning the antioxidant status and the degree of lipid peroxidation at the moment of the initiation of cancer is limited. The aim of this research is to assess the effect of selected minerals (zinc, selenium, iron, copper and calcium) on the growth of the neoplastic process and the concentrations of selected biomarkers of the oxidative damage in rats with implanted prostate cancer cells. It was found that the diet supplementation with selected minerals (zinc, selenium, iron, copper and calcium) affect the occurrence of prostate tumor growth in the examined rats. The intraperitoneal implantation of prostate cancer cells resulted in the occurrence of prostatic adenoma in 71% of the examined rats. In the rats that were additionally supplemented with selenium and with copper, the cancer cell aggregates constituted, respectively, 25% and 38% of the cases. As a result of implantation of cancer cells, the level of biomarkers of lipid peroxidation increased both in the urine and in tissues of the examined animals (rat group without supplementation). No relationship was found between the process of lipid peroxidation due to the supplementation with selenium and copper, and the lower incidence of cancer and the induction of apoptosis. The reduced activity of antioxidative enzymes (catalase, superoxide dismutase and glutathione peroxidase) creates favorable conditions for the formation of cancer cell aggregates, which was shown in the rats whose diet was supplemented with iron. In summary, we conclude that lipid peroxidation represents a fruitful approach to early stage cancer prevention. Supplementation of rats with trace elements correlated with the risk of developing cancer, but the mechanisms of this action is complicated and dose-dependent.

The aim of this study was to investigate and compare the levels of concentration of modified nucleosides in the urine of autistic and healthy children. The compounds have never been analyzed before. The levels of nucleosides in the urine of both groups were determined by validated high performance liquid chromatography coupled to mass spectrometry (LC-MS/MS) method using multiple reaction monitoring (MRM) mode. Chromatographic separation was achieved with HILIC column and tubercidin was used as the internal standard for the quantification of urinary nucleosides. The within run accuracy and precision ranged from 89 to 106% and from 0.8% to 4.9%, respectively. Lower levels of O-methylguanosine, 7-methylguanosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine and 3-methyladenine in the urine of 22 children with autism, aged 3 to 16 were observed. The differences were not observed in 20 healthy volunteers, in a similar age group. These findings show that modified nucleosides there are metabolic disturbances and nutritional deficiencies in autistic children., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The aim of the present study was to assess the effect of zinc and copper, separately or in combination with resveratrol, on the concentration of 15-hydroxyeicosatetraenoic acid (15-HETE) in urine of rats with mammary cancer (adenocarcinoma) induced with 7,12- dimethyl-1,2-benz[a]anthracene (+ DMBA). The research focused on the kinetics of alterations in urinary 15-HETE at the early stage of carcinogenesis, as well as on the influence of dietary factors on the process. The content of 15-hydroxyeicosatetraenoic acid in the rats' urine was determined by enzyme-linked immunosorbent assay (ELISA). The 15-HETE level was standardized by conversion to the creatinine level. Regardless of the diet (standard, Zn, Zn+resveratrol, Cu, Cu+resveratrol), DMBA-induced breast carcinogenesis was not inhibited. On the contrary, in the Zn+resveratrol supplemented group, tumorigenesis developed at a considerably faster rate. It was found that the supplementation of the rats' diet with zinc only or zinc plus resveratrol resulted in a reduction of the 15-HETE level in urine of rats with mammry cancer (+ DMBA) as compared with control rats (- DMBA). A statistically lower concentration of 15-HETE was found in urine of rats supplemented with zinc or copper with resveratrol when compared with the animals that received only zinc or copper (p=0.02; p=0.0001). Summing up the obtained results, it can be concluded that the level of 15-HETE in urine of the examined animals depended on the applied supplementation.

Ibuprofen is widely used in human and veterinary medicine for the treatment of chronic pain as well as rheumatic and musculoskeletal disorders. However, the analgesic and anti-inflammatory properties of Ibuprofen have contributed to frequent drug abuse in equestrian sports. A sensitive and rapid gas chromatography with tandem mass spectrometry based method with a simple liquid-liquid extraction and derivatization requiring 200 μL volume of sample and 2 mL of extraction solvent for the simultaneous determination of ibuprofen and its metabolites was developed. The proposed procedure was optimized and validated according to the principles for bioanalytical methods. The assay achieved satisfactory validation parameters, namely, recovery (92.2-105%), interday accuracy (92.5-106%), and precision (0.3-4.4%) for all investigated compounds as well as limits of quantification of 50 ng/mL for ibuprofen, 2-hydroxyibuprofen, and carboxyibuprofen, 25 ng/mL for 1-hydroxyibuprofen and 100 ng/mL for 3-hydroxyibuprofen. The applicability of the method was evaluated by the analysis of five real urine samples collected from different horses after drug administration. In view of the low limits of quantification, high selectivity, repeatability, and recovery, the procedure can be utilized for laboratory applications, including the control of ibuprofen abuse in equestrian sports for anti-doping purposes and drug/pharmaceutical mentality investigations., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Epilobium sp. are commonly used in traditional medicine in the treatment of early stages of benign prostatic hyperplasia and inflammation. It is suggested that a dominating constituent, oenothein B, is responsible for the extracts therapeutic effects. Several bioactivities were established for extracts and oenothein B in various in vitro models, but due to the questionable bioavailability of this dimeric macrocyclic ellagitannin, their significance in the in vivo effects remains unresolved. We have thus focused our attention on a complex comparative investigation of the in vitro and in vivo activities of phytochemically characterized Epilobium angustifolium aqueous extract and oenothein B on prostate cancer cells proliferation.Incubation of different cell lines with E. angustifolium aqueous extract resulted in a significant reduction of proliferation of PZ-HPV-7 and LNCaP cells, which was partly associated with antiandrogenic activity. These effects were fully congruent with oenothein B, examined in parallel. Oral supplementation of rats implanted with LNCaP cells with E. angustifolium aqueous extract 50-200 mg/kg b. w. resulted in a reduction of the occurrence of prostatic adenoma up to 13 %. Oenothein B was not detected in the urine and feces of the E. angustifolium aqueous extract-treated group, however, conjugates of nasutins gut microbiota metabolites of ellagitannins were detected in the urine, while in human volunteers supplemented with Epilobium tea, only urolithin conjugates were present.Despite observing significant and consistent effects in vitro and in vivo , we were unable to point out unequivocally the factors contributing to the observed E. angustifolium aqueous extract activity, facing the problems of an unknown metabolic fate of oenothein B and interspecies differences in E. angustifolium aqueous extract gut microbiota metabolism., Competing Interests: Conflict of Interest: The authors declare no conflict of interest., (Georg Thieme Verlag KG Stuttgart · New York.)

Prostate cancer significantly affects the overall morbidity and mortality of malignant tumours in highly developed countries. Important risk factors include family predisposition and regional, racial and dietary determinants. The scientific literature contains a great deal of data on the role of calcium and dairy products in general in the process of neoplastic transformation of the prostate. This is most likely linked to the fact that changes in the concentration of calcium ions control such varied life processes as secretion of hormones and neurotransmitters, the level of cyclic nucleotides, and cell growth, division and differentiation. Research is conducted to demonstrate that disorders of cell cycle control due to differences in calcium ion concentrations may be crucial for the development and prevention of cancer. Disturbances of calcium homeostasis in the body can be caused by various mechanisms, such as excessive calcium intake in the diet, vitamin D deficiency, structural and functional changes in vitamin D receptor (VDR), Calcium-Sensing Receptor (CaSR), and parathyroid hormone receptor (PTH-1-R), changes in calcium ion channels, phosphate metabolism disorders (phosphatonin and the Klotho protein), changes in the level of parathyroid hormone-related protein (PTHrP), and others. The article presents data on the mechanisms maintaining calcium homeostasis at the molecular level and genetic aspects playing a role in the pathogenesis of prostate cancer. The data cited on the occurrence of abnormal mechanisms of calcium metabolism in prostate cancer suggest the need for individualized intake of this element in the diet, especially in the case of patients with a family history of PCa., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The aim of the present study was to assess the effect of dietary supplementation (with zinc or zinc and polyphenolic compounds - resveratrol or genistein) on antioxidant enzymes (glutathione peroxidase - GPx, catalase - CAT and superoxide dismutase - SOD) and the frequency of microsatellite instability (MSI) in a widely used model of mammary carcinogenesis induced in the rat by treatment with 7,12-dimethyl-1,2-benz[a]anthracene (DMBA). The impact of selected compounds on the intensity of DMBA-induced carcinogenesis was also assessed. Sixty four Sprague-Dawley female rats were divided into study groups which, apart from the standard diet and DMBA, were treated with zinc, zinc and resveratrol or zinc and genistein via gavage for a period ranging from 40 days to 20 weeks of age. On the basis of the obtained results it can be said that synergistic reaction between Zn(II) and genistein causes a delay in cancer development as compared with the animals treated with DMBA but with no food supplementation. Supplementation with Zn(II) and polyphenolic compounds resulted in the occurrence of microsatellite instabilities in tumors. LOH (loss of heterozygosity) was found in tumor samples at microsatellite D1Mgh6 and D3Mgh9. DMBA treatment increased significantly the glutathione peroxidase activity whereas it had no effect on the SOD and CAT activities, as compared with control rats. Diet supplementation has an effect on the activity of selected antioxidant enzymes. Diet supplementation has an effect on the occurrence of microsatellite instabilities as well as on the intensity of the neoplastic process. The intensity of occurrence of microsatellite instabilities does not depend on the activity of selected antioxidant enzymes.

In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p < 0.05) or copper plus resveratrol (p < 0.001) in comparison with the control groups that received the same diets. In cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p < 0.001). The mean serum copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p < 0.001). The characteristic changes in iron content and the zinc/copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.

Background: Epigenetic alterations have been identified as promising new targets for cancer prevention strategies as they occur early during carcinogenesis and represent potentially initiating events for cancer development., Objective: The aim of the present study was to assess the effect of zinc and copper on the DNA methylation in rats whose breast adenocarcinoma was simultaneously induced with 7, 12 dimethylbenz[a]anthracene (DMBA). The research focused on the kinetics of alterations in urinary 5-MedC (5-methyl-2'-deoxycytidine) at the early and late stages of carcinogenesis, as well as the influence of dietary factors on the process., Methods: The content of 5-methyl-2'-deoxycytidine in the rats' urine was determined by the ELISA (enzyme-linked immunosorbent assay) method. The 5-MedC level was standardized by conversion to the creatinine level., Results: It was found that in the rats fed only the standard diet and DMBA-treated the urinary levels of 5-MedC collected after the 10th week were considerably lower in comparison with the content of this biomarker in urine starting from the 19th week (43.56 ± 14.34 vs. 71.84 ± 42.64). The animals treated with DMBA and additionally obtaining copper were characterized by a much higher content of the examined biomarker in urine, both in the early phase of carcinogenesis (10th week) and later (19th week), as compared with the animals fed only the standard diet or the zinc-supplemented diet. In the rats with a fully developed tumor (100% incidence of the disease) the applied dose of resveratrol (0.2 mg/kg bw) was too low to prevent the intensive formation and increase of 5-MedC level in urine, additionally stimulated by the presence of Cu in the diet as well as by the active, ongoing neoplastic process., Conclusions: Summing up the obtained results of investigations it can be said that the urinary level of 5-MedC depends on the applied supplementation.