Utility of 1.5 Tesla MRI Scanner in the Management of Small Sample Sizes Driven from 3D Breast Cell Culture.

The aim of this work was to use and optimize a 1.5 Tesla magnetic resonance imaging (MRI) system for three-dimensional (3D) images of small samples obtained from breast cell cultures in vitro. The basis of this study was to design MRI equipment to enable imaging of MCF-7 breast cancer cell cultures (about 1 million cells) in 1.5 and 2 mL glass tubes and/or bioreactors with an external diameter of less than 20 mm. Additionally, the development of software to calculate longitudinal and transverse relaxation times is described. Imaging tests were performed using a clinical MRI scanner OPTIMA 360 manufactured by GEMS. Due to the size of the tested objects, it was necessary to design additional receiving circuits allowing for the study of MCF-7 cell cultures placed in glass bioreactors. The examined sample's volume did not exceed 2.0 mL nor did the number of cells exceed 1 million. This work also included a modification of the sequence to allow for the analysis of T1 and T2 relaxation times. The analysis was performed using the MATLAB package (produced by MathWorks). The created application is based on medical MR images saved in the DICOM3.0 standard which ensures that the data analyzed are reliable and unchangeable in an unintentional manner that could affect the measurement results. The possibility of using 1.5 T MRI systems for cell culture research providing quantitative information from in vitro studies was realized. The scanning resolution for FOV = 5 cm and the matrix was achieved at a level of resolution of less than 0.1 mm/pixel. Receiving elements were built allowing for the acquisition of data for MRI image reconstruction confirmed by images of a phantom with a known structure and geometry. Magnetic resonance sequences were modified for the saturation recovery (SR) method, the purpose of which was to determine relaxation times. An application in MATLAB was developed that allows for the analysis of T1 and T2 relaxation times. The relaxation times of cell cultures were determined over a 6-week period. In the first week, the T1 time value was 1100 ± 40 ms, which decreased to 673 ± 59 ms by the sixth week. For T2, the results were 171 ± 10 ms and 128 ± 12 ms, respectively.

In Vitro MRS of Cells Treated with Trastuzumab at 1.5 Tesla.

The aim of the study was to investigate the effect of Trastuzumab on the MCF-7 and CRL-2314 breast cancer cell lines. Additionally, an attempt was made to optimize magnetic resonance spectroscopy (MRS) for cell culture studies, with particular emphasis on the impact of treatment with Trastuzumab. The research materials included MCF-7 and CRL-2314 breast cancer cell lines. The study examined the response of these cell lines to treatment with Trastuzumab. The clinical magnetic resonance imaging (MRI) system, OPTIMA MR360 manufactured by GEMS, with a magnetic field induction of 1.5 T, was used. Due to the nature of the tested objects, their size and shape, it was necessary to design and manufacture additional receiving coils. They were used to image the tested cell cultures and record the spectroscopic signal. The spectra obtained by MRS were confirmed by NMR using a 300 MHz NMR Fourier 300 with the TopSpin 3.1 system from Bruker. The designed receiving coils allowed for conducting experiments with the cell lines in a satisfactory manner. These tests would not be possible using factory-delivered coils due to their parameters and the size of the test objects, whose volume did not exceed 1 mL. MRS studies revealed an increase in the metabolite at 1.9 ppm, which indicates the induction of histone acetylation. Changes in histone acetylation play a very important role in both cell development and differentiation processes. The use of Trastuzumab therapy in breast cancer cells increases the levels of acetylated histones. MRS studies and spectra obtained from the 300 MHz NMR system are consistent with the specificity inherent in both systems.

Pushing boundaries in 3D printing: Economic pressure filament extruder for producing polymeric and polymer-ceramic filaments for 3D printers.

3D printing technology can deliver tailored, bioactive, and biodegradable bone implants. However, producing the new, experimental material for a 3D printer could be the first and one of the most challenging steps of the whole bone implant 3D printing process. Production of polymeric and polymer-ceramic filaments involves using costly filament extruders and significantly consuming expensive medical-grade materials. Commercial extruders frequently require a large amount of raw material for experimental purposes, even for small quantities of filament. In our publication, we propose a simple system for pressure filament extruding, which allows obtaining up to 1-meter-long filament suitable for fused filament fabrication-type 3D printers, requiring only 30 g of material to begin work. Our device is based on stainless steel pipes used as a container for material, a basic electric heating system with a proportional-integral-derivative controller, and a pressurised air source with an air pressure regulator. We tested our device on various mixes of polylactide and polycaprolactone with ß-tricalcium phosphate and demonstrated the possibility of screening production and testing of new materials for 3D-printed bone implants.

Assessment of steroid enzymes action in children and adolescents with obesity.

Rising prevalence of obesity has become an important impulse to investigate basic mechanisms involved in regulating the energy balance. It is widely accepted that steroids are potent factors affecting glucose, fat, and protein metabolism. Our study was aimed to analyze differences in the total amount of selected enzymes implicated in steroid metabolism in a group of children suffering from obesity and those with normal weight, further subdivided according to sex and pubertal stage. Data were obtained from 187 Caucasian children and adolescents, including 113 patients (63 girls, 50 boys) with obesity and 74 (34 girls, 40 boys) normal weight volunteers. Standard clinical examinations were performed in both groups. To evaluate the impact of puberty, preadolescent children and those with advanced puberty were assessed separately. Urine steroid excretion profiles were analyzed using gas chromatography/mass spectrometry method. Children with obesity revealed several changes in in the total amount of steroid enzymes as assessed by the relevant metabolite proportions, compared to their norm weight peers. Girls showed a significant increase in the activity of 11ßHSD1, while boys demonstrated a relevant elevation in 20αHSD action. Regardless of sex, children with obesity showed an increase in the activity of 5ß-reductase + 3αHSD complex and a decrease in the involvement of 11ßOH-lase. The effect is attenuated when consider pre- and pubertal subgroups. We hypothesize that changes in the activity levels of selected enzymes may be a compensatory mechanism to limit the glucocorticoid exposure of key target tissues as well as to improve metabolic control and reduce long-term complications of obesity.

Serum Levels of Hormones Regulating Appetite in Patients with Fetal Alcohol Spectrum Disorders.

Prenatal alcohol exposure is the cause of impaired growth and a wide range of developmental and behavioral disorders in the child. Improper eating patterns are commonly associated with fetal alcohol spectrum disorders (FASD) and may contribute to poor nutrition and growth restriction. To date, there have been only a few studies investigating the hormonal regulation of appetite in patients with FASD. We analyzed the levels of neuropeptide Y (NPY), Agouti signaling protein (ASP), alpha-melanocyte-stimulating hormone (α-MSH), and kisspeptin (KISS1) in 57 patients with FASD and 23 healthy controls. A comparison of the hormone levels studied was also performed in subgroups of fetal alcohol syndrome (FAS) and neurobehavioral disorder associated with prenatal alcohol exposure (ND PAE), as well as in males and females. We have found no differences in hormone levels tested between affected individuals and the controls and between FASD subgroups. In addition, sex had no effect on hormone levels. However, we identified some associations between hormone concentrations and parameters describing the clinical status of patients with FASD. Most of them concerned ASP, which has shown a positive correlation with age and hormones involved in appetite and metabolism, such as proopiomelanocortin (POMC) and adrenocorticotropic hormone (ACTH). We have also found a negative correlation of α-MSH with age, BMI percentile, and glycated hemoglobin (HbA1c). Furthermore, we found a weak negative correlation of NPY with HbA1c. Although FASD has been associated with impaired child growth and development, including nutrition and puberty onset, we did not identify differences in the levels of the hormones studied, which may suggest that prenatal alcohol exposure does not affect the levels of these metabolites.

Changes of androgen and corticosterone metabolites excretion and conversion in cystic fibrosis.

Cystic fibrosis (CF) is a life-threatening inherited disease related to a mutation in the CFTR gene, that leads to serious health complications such as chronic pulmonary infections, pancreatic insufficiency, dysfunction of the sweat glands and reproductive system. For the first time, we have described the profile of corticosterone and androgen metabolites in urine, as well as the activity of enzymes involved in steroid genesis and metabolism in people with CF, using gas chromatography/mass spectrometry. A significant reduction in the excretion of most of the measured metabolites in CF was found. These differences were observed in the group of progestagen metabolites, as well as among metabolites of corticosterone and androgens. We revealed higher activities of 17ß-hydroxysteroid dehydrogenase and 17,20-lyase in the Δ4 pathway compared with controls, what can promote the androgen synthesis through the backdoor androgen pathway. We have also found the increased conversion activity of 11-oxyganated steroids by 5a-reductase in backdoor pathway. Levels of the most potent and vital androgens (testosterone and dihydrotestosterone) are comparable in both groups. However, the excretion of dehydroepiandrosterone was lower in CF. Decreased cholesterol lipoprotein levels may contribute to limited intracellular cholesterol supply and reduced adrenal steroidogenesis in CF individuals. Changes in the activity of some steroidogenesis enzymes may suggest the presence of some peripheral adaptive mechanisms in CF to maintain androgen balance in the body despite the limited sufficiency of secretion by the adrenal cortex.

System for Patterning Polydopamine and VAPG Peptide on Polytetrafluoroethylene and Biodegradable Polyesters for Patterned Growth of Smooth Muscle Cells In Vitro.

Biomaterial's surface functionalization for selective adhesion and patterned cell growth remains essential in developing novel implantable medical devices for regenerative medicine applications. We built and applied a 3D-printed microfluidic device to fabricate polydopamine (PDA) patterns on the surface of polytetrafluoroethylene (PTFE), poly(l-lactic acid-co-D,l-lactic acid) (PLA), and poly(lactic acid-co-glycolic acid) (PLGA). Then, we covalently attached the Val-Ala-Pro-Gly (VAPG) peptide to the created PDA pattern to promote the adhesion of the smooth muscle cells (SMCs). We proved that the fabrication of PDA patterns allows for the selective adhesion of mouse fibroblast and human SMCs to PDA-patterned surfaces after only 30 min of in vitro cultivation. After 7 days of SMC culture, we observed the proliferation of cells only along the patterns on PTFE but over the entire surface of the PLA and PLGA, regardless of patterning. This means that the presented approach is beneficial for application to materials resistant to cell adhesion and proliferation. The additional attachment of the VAPG peptide to the PDA patterns did not bring measurable benefits due to the high increase in adhesion and patterned cell proliferation by PDA itself.

Low-density 3D-printed boluses with honeycomb infill in radiotherapy.

PURPOSE: Dosimetric characteristics of 3D-printed plates using different infill percentage and materials was the purpose of our study. METHODS: Test plates with 5%, 10%, 15% and 20% honeycomb structure infill were fabricated using TPU and PLA polymers. The Hounsfield unit distribution was determined using a Python script. Percentage Depth Dose (PDD) distribution in the build-up region was measured with the Markus plane-parallel ionization chamber for an open 10x10 cm2 field of 6 MV. PDD was measured at a depth of 1 mm, 5 mm, 10 mm and 15 mm. Measurements were compared with Eclipse treatment planning system calculations using AAA and Acuros XB algorithms. RESULTS: The mean HU for CT scans of 3D-printed TPU plates increased with percentage infill increase from -739 HU for 5% to -399 HU for 20%. Differences between the average HU for TPU and PLA did not exceed 2% for all percentage infills. Even using a plate with the lowest infill PDD at 1 mm depth increase from 44.7% (without a plate) to 76.9% for TPU and 76.6% for PLA. Infill percentage did not affect the dose at depths greater than 5 mm. Differences between measurements and TPS calculations were less than 4.1% for both materials, regardless of the infill percentage and depth. CONCLUSIONS: The use of 3D-printed light boluses increases the dose in the build-up region, which was shown based on the dosimetric measurements and TPS calculations.

The Impact of Obesity on the Excretion of Steroid Metabolites in Boys and Girls: A Comparison with Normal-Weight Children.

Obesity in childhood is associated with several steroid changes, which result from excess body mass. The aim of this study was to evaluate steroid metabolism in children with obesity compared with those with normal weight, especially in relation to sex and puberty progress. We analyzed the clinical data of 191 children, aged between 5 and 18 years, with 115 affected (64 girls and 51 boys) and 76 unaffected (35 girls and 41 boys) by obesity. Routine clinical assessment and pubertal stage evaluation based upon Tanner's scale were performed. In addition, to evaluate the impact of puberty, children with pre-adolescence and advanced puberty were divided into separate subgroups. Then, 24 h urine steroid excretion profiles were analyzed by gas chromatography/mass spectrometry. Significant differences in the excretion of steroid metabolites were found between normal weight children and children with obesity, especially in the prepubertal cohort. In this group, we observed enhanced activity in all the pathways of adrenal steroidogenesis. Raised excretion of mineralocorticoid derivatives such as tetrahydro-11-deoxycorticosterone, tetrahydrocorticosterone, and 5α-tetrahydrocorticosterone supported increased activity of this track. No significant differences were detected in the excreted free forms of cortisol and cortisone, while the excretion of their characteristic tetrahydro-derivatives was different. In pre-adolescent children with obesity, α-cortol and especially α-cortolone appeared to be excreted more abundantly than ß-cortol or ß-cortolone. Furthermore, in children with obesity, we observed elevated androgen excretion with an enhanced backdoor pathway. As puberty progressed, remarkable reduction in the differences between adolescents with and without obesity was demonstrated.

Polytrimethylenimines: Highly Potent Antibacterial Agents with Activity and Toxicity Modulated by the Polymer Molecular Weight.

Cationic polymers have been extensively investigated as a potential replacement for traditional antibiotics. Here, we examined the effect of molecular weight (MW) on the antimicrobial, cytotoxic, and hemolytic activity of linear polytrimethylenimine (L-PTMI). The results indicate that the biological activity of the polymer sharply increases as MW increases. Thanks to a different position of the antibacterial activity and toxicity thresholds, tuning the MW of PTMI allows one to achieve a therapeutic window between antimicrobial activity and toxicity concentrations. L-PTMI presents significantly higher antimicrobial activity against model microorganisms than linear polyethylenimine (L-PEI) when polymers with a similar number of repeating units are compared. For the derivatives of L-PTMI and L-PEI, obtained through N-monomethylation and partial N,N-dimethylation of linear polyamines, the antimicrobial activity and toxicity were both reduced; however, resulting selectivity indices were higher. Selected materials were tested against clinical isolates of pathogens from the ESKAPE group and Mycobacteria, revealing good antibacterial properties of L-PTMI against antibiotic-resistant strains of Gram-positive and Gram-negative bacteria but limited antibacterial properties against Mycobacteria.

Serum Appetite-Regulating Hormone Levels in Cystic Fibrosis Patients: Influence of the Disease Severity and the Type of Bacterial Infection-A Pilot Study.

Cystic fibrosis (CF) belongs to the most common inherited diseases. The severity of the disease and chronic bacterial infections are associated with a lower body index, undernutrition, higher number of pulmonary exacerbations, more hospital admissions, and increased mortality. The aim of our study was to determine the impact of the severity of the disease and the type of bacterial infection in 38 CF patients on the serum level of appetite-regulating hormones including leptin, ghrelin, neuropeptide Y, agouti-signaling protein, proopiomelanocortin, kisspeptin, putative protein Y, and α-melanocyte-stimulating hormone. The patients were divided according to the severity of the disease according to spirometry and the type of chronic bacterial infection. We found that leptin level was significantly higher in patients with severe CF than in patients with mild disease (20.02 ± 8.09 vs. 12.38 ± 6.03 ng/mL, p = 0.028). Furthermore, leptin level was elevated in patients with chronic infection with Pseudomonas aeruginosa compared to uninfected participants (15.74 ± 7.02 vs. 9.28 ± 1.72 ng/mL, p = 0.043). The severity of the disease and the type of bacterial infection did not affect the levels of other appetite-regulating hormones. Moreover, we found a positive correlation between pro-inflammatory interleukin-6 and leptin level (p = 0.0426, R = 0.333). Taken together, our results indicate that both the severity of the disease and the type of bacterial infection are associated with elevated leptin levels in CF patients. Future CF treatment strategies should consider possible disturbances in the hormones that regulate appetite and the factors that influence their levels.

Portable Surface Plasmon Resonance Detector for COVID-19 Infection.

Methods based on nucleic acid detection are currently the most commonly used technique in COVID-19 diagnostics. Although generally considered adequate, these methods are characterised by quite a long time-to-result and the necessity to prepare the material taken from the examined person-RNA isolation. For this reason, new detection methods are being sought, especially those characterised by the high speed of the analysis process from the moment of sampling to the result. Currently, serological methods of detecting antibodies against the virus in the patient's blood plasma have attracted much attention. Although they are less precise in determining the current infection, such methods shorten the analysis time to several minutes, making it possible to consider them a promising method for screening tests in people with suspected infection. The described study investigated the feasibility of a surface plasmon resonance (SPR)-based detection system for on-site COVID-19 diagnostics. A simple-to-use portable device was proposed for the fast detection of anti-SARS-CoV-2 antibodies in human plasma. SARS-CoV-2-positive and -negative patient blood plasma samples were investigated and compared with the ELISA test. The receptor-binding domain (RBD) of spike protein from SARS-CoV-2 was selected as a binding molecule for the study. Then, the process of antibody detection using this peptide was examined under laboratory conditions on a commercially available SPR device. The portable device was prepared and tested on plasma samples from humans. The results were compared with those obtained in the same patients using the reference diagnostic method. The detection system is effective in the detection of anti-SARS-CoV-2 with the detection limit of 40 ng/mL. It was shown that it is a portable device that can correctly examine human plasma samples within a 10 min timeframe.

The Association of the Hypothalamic-Pituitary-Adrenal Axis with Appetite Regulation in Children with Fetal Alcohol Spectrum Disorders (FASDs).

Prenatal alcohol exposure causes growth impairment and a wide range of developmental, physical, and cognitive disorders in children, collectively referred to as fetal alcohol spectrum disorders (FASDs). In the course of FASDs, abnormalities can also affect eating behavior and nutritional status, but these problems have received little attention. Therefore, the aim of our study was to determine the levels of hormones involved in the action of the hypothalamic-pituitary-adrenal axis: proopiomelanocortin (POMC), cortisol, and adrenocorticotropic hormone (ACTH), in the serum of patients with FASDs. To our knowledge, none of these hormones studied have yet been evaluated in FASDs to date. We investigated 62 FASD patients and 23 healthy controls by applying an enzyme-linked immunosorbent method (ELISA). Fasting POMC levels were significantly lower in patients with FASDs (10.97 vs. 18,57 ng/mL, p = 0.039) compared to controls. However, there were no differences in cortisol concentrations. Additionally, the sex and subgroup status (fetal alcohol syndrome (FAS), neurobehavioral disorder associated with prenatal alcohol exposure (ND-PAE), and FASD risk) did not affect hormone levels. POMC was positively correlated with some clinical parameters such as age, BMI percentile, carbohydrate biomarkers, and ACTH. A positive correlation was observed between ACTH and cortisol levels, as well as ACTH and cholesterol levels. Data analysis showed no HPA axis abnormalities in the form of elevated serum cortisol and ACTH levels. Differences in POMC concentration may indicate the involvement and/or impairment of central nervous system structures in hormonal alterations in FASD individuals, caused by prenatal alcohol exposure. Hormonal dysregulation in FASDs can contribute to reduced growth and development, as well as many other disturbed processes, including neurological/neurodevelopmental dysfunctions. Further insightful studies involving a larger group of patients are needed to determine the potential impact of the measured hormones.

Cellular 1H MR Relaxation Times in Healthy and Cancer Three-Dimensional (3D) Breast Cell Culture.

Noninvasive measurements of 1H Magnetic Resonance Imaging (MR) relaxation times in a three-dimensional (3D) cell culture construct are presented. Trastuzumab was used as a pharmacological component delivered to the cells in vitro. The purpose of this study was to evaluate the Trastuzumab delivery by relaxation times in 3D cell cultures. The bioreactor has been designed and used for 3D cell cultures. Four bioreactors were prepared, two with normal cells and two with breast cancer cells. The relaxation times of HTB-125 and CRL 2314 cell cultures were determined. An immunohistochemistry (IHC) test was performed before MRI measurements to confirm the amount of HER2 protein in the CRL-2314 cancer cells. The results showed that the relaxation time of CRL2314 cells is lower than normal HTB-125 cells in both cases, before and after treatment. An analysis of the results showed that 3D culture studies have potential in evaluating treatment efficacy using relaxation times measurements with a field of 1.5 Tesla. The use 1H MRI relaxation times allows for the visualization of cell viability in response to treatment.

A simple and fast method for screening production of polymer-ceramic filaments for bone implant printing using commercial fused deposition modelling 3D printers.

3D printing is a promising technique for obtaining bone implants. However, 3D printed bone implants, especially those printed using fused deposition modelling, are still in the experimental phase despite decades of work. Research on new materials faces numerous limitations, such as reagents' cost and machines' high prices to produce filaments for 3D printing polymer-ceramic composites for fused deposition modelling. This paper presents a simple, low-cost, and fast method of obtaining polymer-ceramic filaments using apparatus consisting of parts available in a hardware store. The method's versatility for producing the filaments was demonstrated on two different biodegradable polymers - polylactic acid and polycaprolactone - and different concentrations of calcium phosphate - ß-tricalcium phosphate - in the composite, up to 50 % by weight. For screening purposes, numerous scaffolds were 3D printed from the obtained filaments on a commercial 3D printer. Structural, mechanical, and biological tests show that the 3D printed scaffolds are suitable for bone implants, as their structure, mechanical, and non-cytotoxic properties are evident. Moreover, the proposed method of composite forming is a simplification of the processes of manufacturing and researching 3D printed materials with potential applications in the regeneration of bone tissue.

Alteration in glucocorticoids secretion and metabolism in patients affected by cystic fibrosis.

Cystic fibrosis (CF) is an inherited syndrome associated with a mutation in a cystic fibrosis transmembrane conductance regulator gene, composed of exocrine gland dysfunction involving multiple systems that may result in chronic respiratory infections, pancreatic enzyme deficiency, and developmental disorders. Our study describes for the first time the urinary profile of glucocorticoid metabolites and the activity of the enzymes involved in the development and metabolism of cortisol in patients with CF, using a gas chromatography/mass spectrometry method. Data were obtained from 25 affected patients and 70 sex- and age- matched healthy volunteers. We have shown a general decrease in the activity of enzymes involved in the peripheral metabolism of cortisol, such as 11ß-hydroxysteroid dehydrogenase type 2, 5α- and 5ß-reductases. In contrast, the activity of 11ß-hydroxysteroid dehydrogenase type 1, the enzyme that converts cortisone to cortisol, increased. Furthermore, our study found a significant decrease in glucocorticoid excretion in patients with CF. This may suggest adrenal insufficiency or dysregulation of the HPA axis and the development of peripheral mechanisms to counteract cortisol degradation in the case of reduced synthesis of glucocorticoids by the adrenal glands. Furthermore, the activity of 5α-reductase seems to be enhanced only through the backdoor pathway, especially when we taking into consideration 11ß-hydroxyandrosterone/11ß-hydroxyetiocholanolone ratio which has been shown to be the best differential marker for enzyme activity. CF impairs nutritional effects and energetic balance in patients; thus, our findings suggest the existence of adaptive mechanisms due to limited secretion of adrenal steroids and subsequent diminished amounts of their metabolites in urine. On the other hand, local control of cortisol availability is maintained by enhanced 11ßHSD1 activity and its recovery from cortisone in organs and tissues which need this. Steroid hormone dysregulation might be another important factor in the course of CF that should be taken into account when planning an effective and comprehensive therapy.

Serum levels of hormones regulating appetite in patients with cystic fibrosis - a single-center, cross-sectional study.

Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients' clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF.

Serum kisspeptin and proopiomelanocortin in cystic fibrosis: a single study.

The determination of hormonal biomarkers is of increasing interest in many diseases, including cystic fibrosis (CF). Hormones that have not been estimated and described so far in CF include kisspeptin (KISS) and proopiomelanocortin (POMC), which are involved in the regulation of many processes, including appetite and fertility. Therefore, the aim of our study was to estimate the level of KISS and POMC in sera from CF patients and to determine the correlation between these hormones and clinical parameters. For this purpose, we estimated the levels of KISS and POMC in 38 CF patients and 16 healthy participants with enzyme-linked immunosorbent assay. We found significantly reduced levels of KISS and POMC in people with CF compared to healthy subjects (1.76 ± 0.46 vs. 2.27 ± 0.56 ng/mL, p < 0.05 and 6.25 ± 4.36 vs. 14.74 ± 6.24 ng/mL, p < 0.001, respectively). Furthermore, the level of both hormones was negatively correlated with age. The hormones studied did not correlate with the results of spirometry and each other. Thus, decreased KISS and POMC levels may be associated with lower body weight and delayed puberty in patients with CF.

Serum leptin and neuropeptide Y in patients with cystic fibrosis-A single center study.

Along with the significant elongation in the average life expectancy of patients with cystic fibrosis (CF), there are still significant discrepancies in the height, weight, and body mass index (BMI) of patients compared to controls without CF. The correlation between hormones that regulate appetite and body fat mass may be an additional factor in weight loss or poor weight gain in CF patients. Our objective was to estimate serum concentrations of leptin and neuropeptide Y in patients with CF as well as to assess correlations between studied hormones and the clinical parameters of CF. Leptin and neuropeptide Y serum concentrations after an overnight fast were measured using an enzyme-linked immunosorbent assay. All study participants had anthropometric tests and spirometry. In addition, fasting serum lipid profile was also analyzed. Fasting leptin levels in CF were significantly higher in patients with CF patients (13.9 ± 6.9 vs. 6.5 ± 2.6 ng/mL, p < 0.001) compared to controls. There were no differences in leptin concentration between female and male CF participants (15.7 ± 7.8 vs. 12.2 ± 5.6 ng/mL, p = 0.13). Leptin was correlated with age (R = 0.64, p < 0.001), BMI (R = 0.65, p < 0.001), spirometry results (R = -0.49, p < 0.01), and body fat (R = 0.5, p < 0.05). There were no differences in neuropeptide Y concentration between participants with CF and controls as well as neuropeptide Y was not correlated with any studied parameters. The results of our study suggest that weight loss may be associated with a decreased level of leptin, while reduced pulmonary function in CF may be related to an elevated level of leptin.

Multifunctional Nanoparticles Based on Iron Oxide and Gold-198 Designed for Magnetic Hyperthermia and Radionuclide Therapy as a Potential Tool for Combined HER2-Positive Cancer Treatment.

Iron oxide nanoparticles are commonly used in many medical applications as they can be easily modified, have a high surface-to-volume ratio, and are biocompatible and biodegradable. This study was performed to synthesize nanoparticles designed for multimodal HER2-positive cancer treatment involving radionuclide therapy and magnetic hyperthermia. The magnetic core (Fe3O4) was coated with a gold-198 layer creating so-called core-shell nanoparticles. These were then further modified with a bifunctional PEG linker and monoclonal antibody to achieve the targeted therapy. Monoclonal antibody-trastuzumab was used to target specific breast and nipple HER2-positive cancer cells. The nanoparticles measured by transmission electron microscopy were as small as 9 nm. The bioconjugation of trastuzumab was confirmed by two separate methods: thermogravimetric analysis and iodine-131 labeling. Synthesized nanoparticles showed that they are good heat mediators in an alternating magnetic field and exhibit great specific binding and internalization capabilities towards the SKOV-3 (HER2 positive) cancer cell line. Radioactive nanoparticles also exhibit capabilities regarding spheroid degradation without and with the application of magnetic hyperthermia with a greater impact in the case of the latter. Designed radiobioconjugate shows great promise and has great potential for in vivo studies regarding magnetic hyperthermia and radionuclide combined therapy.