Epigenetic regulation of processes related to high level of fibroblast growth factor 21 in obese subjects

We hypothesised that epigenetics may play an important role in mediating fibroblast growth factor 21 (FGF21) resistance in obesity. We aimed to evaluate DNA methylation changes and miRNA pattern in obese subjects associated with high serum FGF21 levels. The study included 136 participants with BMI 27–45 kg/m2. Fasting FGF21, glucose, insulin, GIP, lipids, adipokines, miokines and cytokines were measured and compared in high serum FGF21 (n = 68) group to low FGF21 (n = 68) group. Human DNA Methylation Microarrays were analysed in leukocytes from each group (n = 16). Expression of miRNAs was evaluated using quantitative PCR-TLDA. The study identified differentially methylated genes in pathways related to glucose transport, insulin secretion and signalling, lipid transport and cellular metabolism, response to nutrient levels, thermogenesis, browning of adipose tissue and bone mineralisation. Additionally, it detected transcription factor genes regulating FGF21 and fibroblast growth factor receptor and vascular endothelial growth factor receptor pathways regulation. Increased expression of hsa-miR-875-5p and decreased expression of hsa-miR-133a-3p, hsa-miR-185-5p and hsa-miR-200c-3p were found in the group with high serum FGF21. These changes were associated with high FGF21, VEGF and low adiponectin serum levels. Our results point to a significant role of the epigenetic regulation of genes involved in metabolic pathways related to FGF21 action

Glucagon-like peptide-1 receptor agonist stimulates mitochondrial bioenergetics in human adipocytes

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are relatively new pharmacological agents used to normalize glucose level in type 2 diabetes. Recently, GLP-1RAs have been approved for the treatment of obesity to reduce body weight in non-diabetic patients. The extra-pancre-atic effects of GLP-1RAs, as well as their molecular mechanism of action, are still poorly understood. Thus this study was aimed to verify the hypothesis that the mechanism of action of the GLP-1RAs involves mitochondria and that GLP-1RAs administration can improve mitochondrial functions. For this purpose, preadipocytes CHUBS7 were differentiated to mature adipocytes and then stimulated with GLP-1RA, exendin-4 at 100 nM for 24 h. Oxygen consumption rates, mitochondrial membrane potential, intracellular ATP (adenosine triphosphate) level, SIRT1 and SIRT3 gene expression and the histone deacetylases' activity were measured. Exendin-4 was found to uncouple mitochondrial electron transport from ATP synthesis, slightly decreasing mitochondrial membrane potential in mature adipocytes. Routine respiration and uncoupled oxy- gen consumption rates were higher in exendin-4 treated adipocytes than in the non-treated cells. The ATP level remained unchanged. Exendin-4 enhanced SIRT1 and SIRT3 genes expression. Histone deacetylases' activity in the nuclear fraction was not affected by exendin-4, although the activity of class III histone deacetylases was increased. All of the effects on mitochondrial bioenergetics induced by exendin-4 were abolished by addition of glucagon-like peptide 1 receptor antagonist. In conclusion, exendin-4 activates the sirtuin pathway and increases energy expenditure in human adipocytes. Our results suggest another mechanism that may be responsible for body weight reduction observed in patients using GLP-1RAs

Apoptosis-related gene expression in glioblastoma (LN-18) and medulloblastoma (Daoy) cell lines

The expression of apoptosis genes in a commercial pre-designed low-density array from Applied Biosystems was evaluated in two human brain cancer cell models, LN-18 and Daoy (HTB-186™) in comparison to the reference human primary endothelial cells under basic conditions. Analysis of the gene expression in the cancer cell lines compared to the normal control revealed features reflecting anti-apoptotic and inflammatory characteristics of the former. There was an overall downregulation of apoptosis-stimulating genes in both cancer cell lines, along with an upregulation of certain apoptosis inhibitors. A number of genes demonstrated statistically significant changes in their expressions, including BAX (BCL2-associated X protein); the CARD4/NLR family, CARD domain containing 4; CASP10 (caspase 10, apoptosis-related cysteine peptidase); DAP1 (death-associated protein kinase 1), and BIRC5 (baculoviral IAP repeat-containing 5). Anti-apoptotic potential in both cell lines was demonstrated by changes in the Bax:Bcl-2 ratio and downregulation of the APAF1 gene in LN18 cells. There was also significant downregulation of extrinsic signals and the TNF/FADD/inflammatory cascade, and upregulation of caspase inhibitors (IAPs). These results provided a novel molecular characterization of important human cancer cell lines, which might provide a useful research tool for investigating the experimental model of the CNS cell

The tolerance of proton radiotherapy — preliminary results

Introduction. Because the specific proton beam dose distribution (i.e. the so-called ’Bragg curve’), proton radiotherapy ensures that the high-dose region is precisely confined to the target volume while minimizing the dose delivered to healthy tissues/critical organs surrounding the tumour or to those lying in the path of the proton beam. This method has been used for patients in Kraków since November 2016. Aim. To report the early tolerance outcomes to proton radiotherapy in patients completing their treatment just before the end of August 2017. Materials and methods. Study subjects were 47 patients who had completed their treatment before the end of August 2017 with a mean age of 41.6 years (range: 16–76, median: 40). The most frequent diagnoses were skull base tumours (22 pts. — 46.8%) and brain G1 or G2 gliomas (17 pts. — 36.2%), whereas the most frequent histological types were chordomas (17 pts. — 36.2%). Proton radiotherapy was administered by pencil beam scanning and consisted of using the intensity modulated proton therapy (IMPT) technique. The total dose given per cancer type averaged as follows: (i) 70 and 74 Gy(RBE), for respectively chodrosarcomas and chordomas, (ii) 54 Gy(RBE) for brain gliomas and (iii) 70 Gy(RBE) for paranasal sinuses tumours. Early tolerance was prospectively evaluated and measured according to the CTCAE scale, version 4.03. Results. In all, 91 side effects (SE) were recorded in 44 patients. The intensity of SEs were as following: 62 SEs (68.1%) were of grade 1 intensity, 21 SEs (23.1%) were of grade 2 and 8 SEs (8.8%) were of grade 3. The most frequently developed SEs were skin reactions (29 pts. — 61.7%) or oral/pharyngeal mucositis (20 pts. — 42.6%). Because the patient follow-up period was short, presented results only describes the early tolerance to this therapy. Our findings of mild intensities for the most early side effects, at (grades 1 or 2) are consistent with other published studies.

The tolerance of proton radiotherapy — preliminary results

Introduction. Because the specific proton beam dose distribution (i.e. the so-called ’Bragg curve’), proton radiotherapy ensures that the high-dose region is precisely confined to the target volume while minimizing the dose delivered to healthy tissues/critical organs surrounding the tumour or to those lying in the path of the proton beam. This method has been used for patients in Kraków since November 2016. Aim. To report the early tolerance outcomes to proton radiotherapy in patients completing their treatment just before the end of August 2017. Materials and methods. Study subjects were 47 patients who had completed their treatment before the end of August 2017 with a mean age of 41.6 years (range: 16–76, median: 40). The most frequent diagnoses were skull base tumours (22 pts. — 46.8%) and brain G1 or G2 gliomas (17 pts. — 36.2%), whereas the most frequent histological types were chordomas (17 pts. — 36.2%). Proton radiotherapy was administered by pencil beam scanning and consisted of using the intensity modulated proton therapy (IMPT) technique. The total dose given per cancer type averaged as follows: (i) 70 and 74 Gy(RBE), for respectively chodrosarcomas and chordomas, (ii) 54 Gy(RBE) for brain gliomas and (iii) 70 Gy(RBE) for paranasal sinuses tumours. Early tolerance was prospectively evaluated and measured according to the CTCAE scale, version 4.03. Results. In all, 91 side effects (SE) were recorded in 44 patients. The intensity of SEs were as following: 62 SEs (68.1%) were of grade 1 intensity, 21 SEs (23.1%) were of grade 2 and 8 SEs (8.8%) were of grade 3. The most frequently developed SEs were skin reactions (29 pts. — 61.7%) or oral/pharyngeal mucositis (20 pts. — 42.6%). Because the patient follow-up period was short, presented results only describes the early tolerance to this therapy. Our findings of mild intensities for the most early side effects, at (grades 1 or 2) are consistent with other published studies

Thermal Barrier Coating Analysis of Remaining Life and Contaminant Composition

A novel inorganic nanocomposite material, called BOA, which has the form of small building blocks composed of gold nanoparticles embedded in a polyoxoborate matrix, is presented. It is demonstrated that cotton wool decorated with the BOA nanocomposite displays strong antibacterial activity toward both Gram-positive and -negative bacteria strains. Importantly, the modified cotton does not release any toxic substances, and the bacteria are killed upon contact with the fibers coated with the BOA. Toxicity tests show that the nanocomposite–in spite of its antiseptic properties–is harmless for mammalian cells. The presented method of surface modification utilizes mild, environmentally friendly fabrication conditions. Thus, it offers a facile approach to obtain durable nontoxic antiseptic coatings for biomedical applications