Investigation of the Impact of L-Phenylalanine and L-Tyrosine Pre-Treatment on the Uptake of 4-Borono-L-Phenylalanine in Cancerous and Normal Cells Using an Analytical Approach Based on SC-ICP-MS.

Boron has gained significant attention in medical research due to its B-10 isotope's high cross section for the reaction with thermal neutrons, generating ionizing particles that can eliminate cancer cells, propelling the development of boron neutron capture therapy (BNCT) for cancer treatment. The compound 4-borono-L-phenylalanine (BPA) has exhibited potential in BNCT clinical trials. Enhancing BPA uptake in cells involves proposing L-amino acid preloading. This study introduces a novel analytical strategy utilizing ICP-MS and single cell ICP-MS (SC-ICP-MS) to assess the effectiveness of L-tyrosine and L-phenylalanine preloading on human non-small cell lung carcinoma (A549) and normal Chinese hamster lung fibroblast (V79-4) models, an unexplored context. ICP-MS outcomes indicated that L-tyrosine and L-phenylalanine pre-treatment increased BPA uptake in V79-4 cells by 2.04 ± 0.74-fold (p = 0.000066) and 1.46 ± 0.06-fold (p = 0.000016), respectively. Conversely, A549 cells manifested heightened BPA uptake solely with L-tyrosine preloading, with a factor of 1.24 ± 0.47 (p = 0.028). BPA uptake remained higher in A549 compared to V79-4 regardless of preloading. SC-ICP-MS measurements showcased noteworthy boron content heterogeneity within A549 cells, signifying diverse responses to BPA exposure, including a subset with notably high BPA uptake. This study underscores SC-ICP-MS's utility in precise cellular boron quantification, validating cellular BPA uptake's heterogeneity.

Molecularly Imprinted Polymers Specific towards 4-Borono-L-phenylalanine-Synthesis Optimization, Theoretical Analysis, Morphology Investigation, Cytotoxicity, and Release Studies.

The aim of this study was to create molecularly imprinted polymers (MIPs) that are specific towards 4-borono-L-phenylalanine (BPA) to serve as boron compound carriers. The honeycomb-like MIPs were characterized in the matter of adsorption properties, morphology, structure, and cytotoxicity towards A549 and V79-4 cell lines. The honeycomb-like MIP composed from methacrylic acid and ethylene glycol dimethacrylate was characterized by a binding capacity of 330.4 ± 4.6 ng g-1 and an imprinting factor of 2.04, and its ordered, porous morphology was confirmed with scanning electron microscopy. The theoretical analysis revealed that the coexistence of different anionic forms of the analyte in basic solution might lower the binding capacity of the MIP towards BPA. The release profiles from the model phosphate buffer saline showed that only 0 to 4.81% of BPA was released from the MIP within the time frame of two hours, furthermore, the obtained material was considered non-cytotoxic towards tested cell lines. The results prove that MIPs can be considered as effective BPA delivery systems for biomedical applications and should be investigated in further studies.

Factors associated with quality of life in systemic sclerosis: a cross-sectional study.

INTRODUCTION: Systemic sclerosis (SSc) is a connective tissue disease characterized by progressive fibrosis of the skin and internal organs, leading to their failure and disturbances in the morphology and function of blood vessels. The disease affects people in different ways, and identifying how the difficulties and limitations are related to quality of life may contribute to designing helpful interventions. The aim of this study was to identify factors associated with quality of life in people with SSc. METHODS: This was a cross-sectional study conducted in 11 rheumatic centres in Poland. Patients diagnosed with SSc were included. Quality of life was measured using the SSc Quality of Life Questionnaire (SScQoL). The following candidate factors were entered in preliminary multivariable analysis: age, place of residence, marital status, occupational status, disease type, disease duration, pain, fatigue, intestinal problems, breathing problems, Raynaud's symptoms, finger ulcerations, disease severity, functional disability, anxiety and depression. Factors that achieved statistical significance at the 10% level were then entered into a final multivariable model. Factors achieving statistical significance at the 5% level in the final model were considered to be associated with quality of life in SSc. RESULTS: In total, 231 participants were included. Mean age (SD) was 55.82 (12.55) years, disease duration 8.39 (8.18) years and 198 (85.7%) were women. Factors associated with quality of life in SSc were functional disability (ß = 2.854, p < 0.001) and anxiety (ß = 0.404, p < 0.001). This model with two factors (functional disability and anxiety) explained 56.7% of the variance in patients with diffuse SSc and 73.2% in those with localized SSc. CONCLUSIONS: Functional disability and anxiety are significantly associated with quality of life in SSc. Interventions aimed at improving either of these factors may contribute towards improving the quality of life of people with SSc.

Oxidative stress markers in saliva and plasma differ between diet-controlled and insulin-controlled gestational diabetes mellitus.

OBJECTIVES: The aims of the study were as follows: to investigate possible differences between plasma oxidative status (OS) in late-onset GDM and well-characterized healthy pregnant women (oral health, diet); to verify the existence of possible differences between GDMG1 (diet-treated) and GDMG2 (insulin-treated GDM); to determine whether oxidative stress markers could be detected in saliva. MATERIAL AND METHODS: A total of 89 pregnant women (n = 89; 59 with GDM and 30 controls) were evaluated. Malondialdehyde (MDA), total antioxidant capacity (ORAC), inactivation of aldehyde dehydrogenase (IALDH), activity of glutathione peroxidase (GPx) and glutathione transferase (GST)) in plasma and/or saliva were analyzed. RESULTS: The activity of GPx and GST in plasma was higher in GDMG2 as compared to GDMG1 and controls. Also, in GDMG2, elevated concentrations of salivary MDA and higher IALDH were observed. In contrast, GDMG1 had higher plasma ORAC and lower GPx activity as compared to controls, probably due to low-energy diet, high in antioxidants and fibers. Salivary and plasma OS were correlated and most significant for ORAC. CONCLUSION: Oxidative stress were not observed in GDMG1 but were confirmed to be moderate in GDMG2. However, large variability of the analyzed markers in GDM groups encourages screening of all patients, regardless of the treatment option. Saliva may be considered useful for the estimation of oxidative stress levels in GDM populations.

Effects of Selol 5% supplementation on tissue antioxidant enzyme levels and peroxidation marker in healthy mice.

BACKGROUND: Selenium (Se) is an essential micronutrient for animals and humans used in the prevention or treatment of cancer. Selol is a mixture of selenitetriglycerides, containing Se(IV). It does not exhibit mutagenic activity and is less toxic than inorganic sodium selenite containing Se(IV). The antioxidant properties of the Selol were demonstrated using the blood of healthy animals. The aim of the study was to evaluate Selol as a Se supplement by determining the effect of its administration on the Se level and the antioxidant status in the tissues. METHODS: We examined the effect of long-term (28-day) Selol 5% supplementation on the activity of antioxidant enzymes, including the main selenoenzymes in healthy mice organs, such as liver, brain, lungs, and testis. Enzyme activities of the tissue homogenates and the concentration of malondialdehyde (MDA) as a biomarker of oxidative stress were measured using spectrophotometric methods. The selenium concentrations in the tissues were determined by inductively coupled plasma mass spectrometer (ICP-MS) as well. RESULTS: A significant increase in glutathione peroxidase, thioredoxin reductase, and glutathione S-transferase activity as well as the MDA concentration was observed in most of the studied tissues during the Selol 5% supplementation. CONCLUSIONS: Long-term supplementation with the new Se(IV) compound - Selol 5% significantly affects the activity of antioxidant enzymes and the redox state in healthy mice organs. In the healthy population Selol 5% seems to be a promising new antioxidant compound.

Assessment of education requirements for patients with rheumatoid arthritis, based on the Polish version of the Educational Needs Assessment Tool (Pol-ENAT), in the light of some health problems - A cross-sectional study.

INTRODUCTION: Patients with chronic rheumatoid arthritis (RA) need advice in order to face the problems of everyday life, as well as suffering associated with the disease. Health professionals should attempt to raise the level of resourcefulness and independence of the patient. OBJECTIVE: To assess the relationship between the deficit of knowledge about RA and the degree of pain, fatigue, morning stiffness, assessment of disease activity as well as functional efficiency. MATERIALS AND METHOD: The study was conducted on 277 patients with RA in 7 rheumatologic centres in Poland. The method applied was the questionnaire Pol-ENAT (0-156); HAQ DI (0-3); analog scales (0-100). RESULTS: Mean (SD) age was 53.28 (13.01) and disease duration 13.70 (10.63) years. The mean (SD) value was 54.93 (23.17) for pain, 52.97 (21.98) for fatigue, 48.28 (24.76) for morning stiffness (0-100 mm). HAQ DI was 1.40 (0.66), with an upward trend with duration of disease (p<0.001). There was a positive correlation between the demand for knowledge about the movement (r=0.194; p=0.001), self-care (r=0.134; p=0.026), assistance/support(r =0.163; p=0.006) and morning stiffness experienced. There was a negative correlation between the need for knowledge concerning managing pain, feelings and the arthritis process and daily ability assessed with HAQ DI. CONCLUSIONS: The study shows that health education should be targeted at young patients with early RA. In the case of the severity of morning joints stiffness, there is a need to increase knowledge about the methods of mobility aids, self-care and the possibility of obtaining support.

THE MEASUREMENT OF ANTIOXIDANT CAPACITY AND POLYPHENOL CONTENT IN SELECTED FOOD SUPPLEMENTS.

Oxidative stress (OS), defined as a disturbance in the balance between the production of reactive oxygen species (ROS) and antioxidant defenses, can result in the development of many serious diseases like diabetes or cancer. Moreover, the role of oxidative stress in the acceleration of the aging process is also confirmed. ROS are constantly produced in the natural biochemical processes, mainly during cellular respiration. Their enhanced production may be the result of e.g., an inappropriate diet high in saturated fats, low in fiber, fruits and vegetables, insufficient physical activity or smoking. To prevent oxidative stress, besides changes in life style, the additional supplementation of antioxidants is proposed. On the Polish market, the number of food supplements with declared antioxidant activity is still increasing. However, their antioxidant properties are rarely confirmed experimentally. The aim of our study was to determine the antioxidant potential of selected dietary supplements available on the market and recommended in chronic fatigue syndrome. The antioxidant potential was measured using four methods: FRAP, ORAC, HORAC, EPR/DPPH. Moreover, the content of polyphenols in the dietary supplements was also determined.

Selenitetriglycerides-Redox-active agents.

BACKGROUND: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. MATERIALS AND METHODS: The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. RESULTS AND CONCLUSIONS: The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.

Effects of Selol 5% supplementation on the activity or concentration of antioxidants and malondialdehyde level in the blood of healthy mice.

BACKGROUND: Selol is a novel organoselenium Se(IV) compound. It reveals lower potential of toxicity than sodium selenite and does not exhibit mutagenic activity. Its antioxidant and anticancer properties including overcoming cancer cell resistance to standard therapy of the drug were proven. This is the first publication describing the influence of Selol 5% on the activity of blood antioxidant status in vivo. MATERIALS AND METHODS: We investigated the influence of Selol 5% short-term (24h) and long-term (28 days) administration on the activity of antioxidant enzymes, including the main selenoenzymes, in healthy mice plasma and erythrocytes. Plasma oxygen radical absorbance capacity value (ORAC) and the concentration of malonyldialdehyde (MDA) in plasma as a biomarker of oxidative stress as well as the value of selenium (Se) concentration in erythrocytes were shown. RESULTS: A significant increase of the selenium dependent glutathione peroxidase (Se-GSHPx) activity in plasma and erythrocytes, plasma selenoprotein P concentration, ORAC values, and Se concentration were observed during long-term supplementation as well as after Selol 5% single-dose administration, with two distinct increases of activity a few hours after the beginning of the experiment and before its end. We found a decreased thioredoxin reductase (THRR) activity and an increased MDA level during Selol 5% long-term supplementation. Glutathione S-transferase activity (GST) remained unchanged. CONCLUSION: Selol 5% supplementation in vivo affects the selenoenzymes activities as well as the antioxidant status of plasma and erythrocytes. Selol 5% is an inhibitor of thioredoxin reductase activity, which can be important in anticancer therapy.