Assessment of connective tissue metabolism in patients with head and neck malignancies treated with radiotherapy.

<br><b>Introduction:</b> Despite the use of highly specialized irradiation techniques in the treatment of head and neck tumors, it is still impossible to selectively destroy cancer cells without damaging normal structures, including connective tissue cells.</br> <br><b>Aim:</b> The aim of the study was to analyze the concentration of degradation markers such as collagen type I (carboxyterminal telopeptide of type I collagen; ICTP) and elastin (elastin-derived peptides; EDPs) as well as selected metalloproteinases (MMP-1, MMP-2, MMP-9) in patients with head and neck malignancies undergoing radiotherapy.</br> <br><b>Material and methods:</b> The test group consisted of 56 men, who underwent radical or palliative radiotherapy. The concentrations of ICTP, EDPs, MMP-1, MMP-2, MMP-9 were determined in three blood samples collected from patients prior to radiotherapy, immediately after its completion and 3 months after the therapy.</br> <br><b>Results</b>: Both radical and palliative radiotherapy contribute to a significant increase in the concentration of EDPs. At the time of healing of post-irradiation lesions, the level of EDPs was reduced in both groups. The ICTP concentration was not affected by radiotherapy. No significant differences were observed in the concentration of MMP-1 and MMP-2 before and after radiotherapy. Radical radiotherapy caused a statistically significant late reduction in the concentration of MMP-9. The lowest concentrations of MMP-1, MMP-2, MMP-9 in the serum of patients qualified for palliative radiotherapy were recorded in a samples collected three months post-irradiation.</br> <br><b>Conclusions:</b> The degradation markers of key extracellular matrix structural proteins may be helpful tools in the objective assessment of radiation-induced injuries to the connective tissue.</br>.

Electrospun fiber-based micro- and nano-system for delivery of high concentrated quercetin to cancer cells.

The anticancer potential of quercetin (Q), a plant-derived flavonoid, and underlining molecular mechanisms are widely documented in cellular models in vitro. However, biomedical applications of Q are limited due to its low bioavailability and hydrophilicity. In the present study, the electrospinning approach was used to obtain polylactide (PLA) and PLA and polyethylene oxide (PEO)-based micro- and nanofibers containing Q, namely PLA/Q and PLA/PEO/Q, respectively, in a form of non-woven fabrics. The structure and physico-chemical properties of Q-loaded fibers were characterized by scanning electron and atomic force microscopy (SEM and AFM), X-ray powder diffraction (XRD), differential scanning calorimetry (DSC), goniometry and FTIR and Raman spectroscopy. The anticancer action of PLA/Q and PLA/PEO/Q was revealed using two types of cancer and nine cell lines, namely osteosarcoma (MG-63, U-2 OS, SaOS-2 cells) and breast cancer (SK-BR-3, MCF-7, MDA-MB-231, MDA-MB-468, Hs 578T, and BT-20 cells). The anticancer activity of Q-loaded fibers was more pronounced than the action of free Q. PLA/Q and PLA/PEO/Q promoted cell cycle arrest, oxidative stress and apoptotic cell death that was not overcome by heat shock protein (HSP)-mediated adaptive response. PLA/Q and PLA/PEO/Q were biocompatible and safe, as judged by in vitro testing using normal fibroblasts. We postulate that PLA/Q and PLA/PEO/Q with Q releasing activity can be considered as a novel and more efficient micro- and nano-system to deliver Q and eliminate phenotypically different cancer cells.

Biodegradable and Non-Biodegradable Biomaterials and Their Effect on Cell Differentiation.

Biomaterials for tissue scaffolds are key components in modern tissue engineering and regenerative medicine. Targeted reconstructive therapies require a proper choice of biomaterial and an adequate choice of cells to be seeded on it. The introduction of stem cells, and the transdifferentiation procedures, into regenerative medicine opened a new era and created new challenges for modern biomaterials. They must not only fulfill the mechanical functions of a scaffold for implanted cells and represent the expected mechanical strength of the artificial tissue, but furthermore, they should also assure their survival and, if possible, affect their desired way of differentiation. This paper aims to review how modern biomaterials, including synthetic (i.e., polylactic acid, polyurethane, polyvinyl alcohol, polyethylene terephthalate, ceramics) and natural (i.e., silk fibroin, decellularized scaffolds), both non-biodegradable and biodegradable, could influence (tissue) stem cells fate, regulate and direct their differentiation into desired target somatic cells.

Comparison of Physicochemical, Mechanical, and (Micro-)Biological Properties of Sintered Scaffolds Based on Natural- and Synthetic Hydroxyapatite Supplemented with Selected Dopants.

The specific combinations of materials and dopants presented in this work have not been previously described. The main goal of the presented work was to prepare and compare the different properties of newly developed composite materials manufactured by sintering. The synthetic- (SHAP) or natural- (NHAP) hydroxyapatite serves as a matrix and was doped with: (i) organic: multiwalled carbon nanotubes (MWCNT), fullerenes C60, (ii) inorganic: Cu nanowires. Research undertaken was aimed at seeking novel candidates for bone replacement biomaterials based on hydroxyapatite-the main inorganic component of bone, because bone reconstructive surgery is currently mostly carried out with the use of autografts; titanium or other non-hydroxyapatite -based materials. The physicomechanical properties of the developed biomaterials were tested by Scanning Electron Microscopy (SEM), Dielectric Spectroscopy (BSD), Nuclear Magnetic Resonance (NMR), and Differential Scanning Calorimetry (DSC), as well as microhardness using Vickers method. The results showed that despite obtaining porous sinters. The highest microhardness was achieved for composite materials based on NHAP. Based on NMR spectroscopy, residue organic substances could be observed in NHAP composites, probably due to the organic structures that make up the tooth. Microbiology investigations showed that the selected samples exhibit bacteriostatic properties against Gram-positive reference bacterial strain S. epidermidis (ATCC 12228); however, the property was much less pronounced against Gram-negative reference strain E. coli (ATCC 25922). Both NHAP and SHAP, as well as their doped derivates, displayed in good general compatibility, with the exception of Cu-nanowire doped derivates.

Family-Based Cohort Association Study of PRKCB1, CBLN1 and KCNMB4 Gene Polymorphisms and Autism in Polish Population.

The aim of the study was to perform family-based association analysis of PRKCB1, CBLN1 and KCNMB4 gene polymorphisms and autism disorder. We comprised 206 Caucasian children with autistic spectrum disorder (ASD) and their biological parents. In transmission/disequilibrium test we observed that T-allele of the rs198198 polymorphism of the PRKCB1 gene was more often transmitted to affected children in the male subgroup (p = 0.010). Additionally, the T carrier state was significantly associated with hypotonia (p = 0.048). In the female subgroup, the T-allele carriers more often showed more mobile/vital behavior (p = 0.046). In conclusion, our study showed that the rs198198 of the PRKCB1 gene may be associated with ASD in men and with some features characteristic for the disorder.

Eating Behaviors of Children with Autism-Pilot Study, Part II.

Autism spectrum disorder is characterized by social communication deficit and non-normative behavior. The people with autism often experience troubles with feeding. The purpose of this study was to conduct evaluation of the feeding and eating behaviors among children with autism. PATIENTS AND METHODS: The study group included 41 high-functioning autistic children. The control group consisted of 34 children without the ASD. The questionnaire was used to assess the nutritional status. RESULTS: The children with ASD fuss during mealtimes more frequently, they require entertaining and diverting their attention, they are fed by parents, and they consume their meals away from the table. The significant difference found in the use of utensils and food selectivity works to the disadvantage of the Study Group. CONCLUSIONS: The food selectivity occurs significantly more frequently among children with ASD. The feeding and eating problems should be considered on a wider scale. The cooperation of the multidisciplinary and the parents teams should be proposed in the ASD patients care.

Casein Kinase-1-Alpha Inhibitor (D4476) Sensitizes Microsatellite Instable Colorectal Cancer Cells to 5-Fluorouracil via Authophagy Flux Inhibition.

Adjuvant chemotherapy with 5-fluorouracil (5-FU) does not improve survival of patients suffering from a form of colorectal cancer (CRC) characterized by high level of microsatellite instability (MSI-H). Given the importance of autophagy and multi-drug-resistant (MDR) proteins in chemotherapy resistance, as well as the role of casein kinase 1-alpha (CK1α) in the regulation of autophagy, we tested the combined effect of 5-FU and CK1α inhibitor (D4476) on HCT116 cells as a model of MSI-H colorectal cancer. To achieve this goal, the gene expression of Beclin1 and MDR genes, ABCG2 and ABCC3 were analyzed using quantitative real-time polymerase chain reaction. We used immunoblotting to measure autophagy flux (LC3, p62) and flow cytometry to detect apoptosis. Our findings showed that combination treatment with 5-FU and D4476 inhibited autophagy flux. Moreover, 5-FU and D4476 combination therapy induced G2, S and G1 phase arrests and it depleted mRNA of both cell proliferation-related genes and MDR-related genes (ABCG2, cyclin D1 and c-myc). Hence, our data indicates that targeting of CK1α may increase the sensitivity of HCT116 cells to 5-FU. To our knowledge, this is the first description of sensitization of CRC cells to 5-FU chemotherapy by CK1α inhibitor.

Eating Behaviors of Children with Autism-Pilot Study.

Autism Spectrum Disorder (ASD) is the most recognized neuropsychiatric disorder of childhood. Comorbid conditions (such as feeding disorders) are more common among people with autism than among the general population. The most frequent somatic disorders in autistic children include the gastrointestinal disorders observed in 46-91% of patients. The purpose of this study was the evaluation of the nutrition of children with autism, with particular emphasis placed on feeding in the first year of life, in comparison to the group of healthy peers. Participants included 75 Caucasian children (41 children diagnosed with pure autism, and the control group consisting of 34 children without autistic traits). The analysis was performed based on a questionnaire of own design with the first part devoted to the eating practices of the early infancy. Results: Autistic children, as compared to the healthy peers, presented a shortened time of breastfeeding (the children fell asleep at the breast) (p = 0.04), a delayed introduction of dairy products (p = 0.001), the need of more trials to introduce new foods (p = 0.006), a delayed introduction of foods with solid and lumpy structure (p = 0.004), a longer duration of bottle feeding (p = 0.005), delayed attempts to eating using own hands (p = 0.006) and needed a greater support of parents to divert their attention from food during eating (p = 0.05). Conclusions: 1. The dietary problems are more common among children with the autism spectrum disorder than among the population of healthy children, during the first year of life from the time of introducing the complementary foods. 2. The autistic children experience difficulties with eating and require their parents' additional involvement significantly more often than their healthy peers.

Orbital reconstruction - applied materials, therapeutic agents and clinical problems of restoration of defects.

Reconstruction of large cavities in the skull and facial regions is important not only to restore health but also for the correction of facial distortions. Every visible deformity in the facial region of the patient affects their mental wellness and perception by society, entailing both, deterioration of health, but also a decrease in the performance in society, which translates into its productivity. With the progressive degradation of the natural environment, cancer, in the coming years, will be on the leading causes of morbidity and mortality. The review focuses on two main aspects: (i) the causes of injuries leading to the necessity of removal of orbital cavities occupied by the tumor and then their reconstruction, with the focus on the anatomical structure of the orbital cavity, (ii) the materials used to reconstruct the orbital cavities and analyze their advantages and disadvantages. The manuscript also underlines the not yet fully met challenges in the area of facial- and craniofacial reconstruction in people affected by cancer.

What would you like to print? Students' opinions on the use of 3D printing technology in medicine.

BACKGROUND: Recent advances in 3D printing technology, and biomaterials are revolutionizing medicine. The beneficiaries of this technology are primarily patients, but also students of medical faculties. Taking into account that not all students have full, direct access to the latest advances in additive technologies, we surveyed their opinion on 3D printing and education in this area. The research aimed to determine what knowledge about the use of 3D printing technology in medicine, do students of medical faculties have. METHODS: The research was carried out in the form of a questionnaire among 430 students of the Medical University of Silesia in Katowice (Poland) representing various fields of medicine and health sciences. The questions included in the survey analyzed the knowledge of the respondents for 3D printing technology and the opportunities it creates in medicine. RESULTS: The results indicate that students do have knowledge about 3D printing obtained mainly from the internet. They would be happy to deepen their knowledge at specialized courses in this field. Students appreciated the value of 3D printing in order to obtain accurate anatomical models, helpful in learning. However, they do not consider the possibility of complete abandonment of human cadavers in the anatomy classes. Their knowledge includes basic information about current applications of 3D printing in medicine, but not in all areas. However, they have no ethical doubts regarding the use of 3D printing in any form. The vast majority of students deemed it necessary to incorporate information regarding 3D printing technology into the curriculum of different medical majors. CONCLUSION: This research is the first of its kind, which allows for probing students' knowledge about the additive technologies in medicine. Medical education should be extended to include issues related to the use of 3D printing for medical applications.

Evaluation of subarachnoid space and subarachnoid cisterns in children and teenagers based on computed tomography studies.

PURPOSE: The aim of the study was to develop the normative values of linear indices to the diagnosis of changes in size of the subarachnoid space. MATERIAL AND METHODS: Retrospective studies were conducted based on 507 head computed tomography (CT) examinations in children from 0-18 years of age. In total 381 tests were selected for correct reference values. Patients were divided into age groups. For each group, linear indices were calculated, taking into account the size of the fluid spaces in relation to the size of the skull and then the mean with standard deviation, median, as well as 10th and 90th percentile were calculated. The range between the 10th and the 90th percentiles was defined as the reference value. RESULTS: Obtained normative values, minimum and maximum for all groups: index of basal cistern size to the size of the skull - 0.129-0.197; index of basal cistern transverse dimension to the size of the skull - 0.173-0.255; index of basal cistern sagittal dimension to the size of the skull - 0.086-0.150; index of prepontine cistern - 0.034-0.067; index of interhemispheric fissure width - 0.044-0.127; index of Sylvian fissure - 0.036-0.085; index of insular cistern width - 0.020-0.074; index of subarachnoid space - 0.017-0.081. CONCLUSIONS: The linear indices can be calculated based on images achieved during routine CT examination. The reference values allow us to determine if the size of the subarachnoid space is within the normal range for a given age group. The results from the oldest age group can also be referred to the adults.

Composite Nanofibers Containing Multiwall Carbon Nanotubes as Biodegradable Membranes in Reconstructive Medicine.

We have tested titanium (Ti) plates that are used for bone reconstruction in maxillofacial surgery, in combination with five types of novel long-resorbable biomaterials: (i) PCL0-polycaprolactone without additives, (ii) PCLMWCNT-polycaprolactone with the addition of multiwall carbon nanotubes (MWCNT), (iii) PCLOH-polycaprolactone doped with multiwall carbon nanotubes (MWCNT) containing ⁻OH hydroxyl groups, (iv) PCLCOOH-polycaprolactone with the addition of multiwall carbon nanotubes (MWCNT) containing carboxyl groups, and (v) PCLTI-polycaprolactone with the addition of Ti nanoparticles. The structure and properties of the obtained materials have been examined with the use of Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), and/or X-ray powder diffraction (XRD). Titanium BR plates have been covered with: (i) PCL0 fibers (PCL0BR-connection plates), (ii) PCLMWCNT fibers (PCLMWCNTBR-plates), (iii) PCLOH fibers (PCLOHBR-plates), (iv) PCLCOOH (PCLCOOHBR-plates), (v) PCLTI fiber (PCLTIBR-connection plates). Such modified titanium plates were exposed to X-ray doses corresponding to those applied in head and neck tumor treatment. The potential leaching of toxic materials upon the irradiation of such modified titanium plates, and their effect on normal human dermal fibroblasts (NHDF) have been assessed by MTT assay. The presented results show variable biological responses depending on the modifications to titanium plates.

Galectin-1 and -3 contents in primary and reccurent nasal and paranasal sinus polyps.

INTRODUCTION: Nasal and paranasal sinus polyps are one of the most common laryngological problems. Often, despite surgical treatment of nasal and paranasal sinus polyps, they grow back and require surgical retreatment. It is very difficult to predict which patients are particularly exposed to it. Markers are still being sought to predict which patients are particularly exposed to regrowth of polyps and thus require increased clinical surveillance. Galectins are a group of glycoproteins that have been intensively studied recently. The sugar part of these proteins can play a role in transmitting intercellular signals. Laryngologists are especially interested in galectins-1 and-3. The determination of their increased content in cancer tissue is considered as a marker of malignancy, which worsens prognosis in patients. Recently, more and more attention has been paid to the role of galectins in benign lesions, and such are the nasal and paranasal sinus polyps. MATERIALS AND METHODS: In our work, the contents of galectin-1 and-3 were determined in the tissue of the surgically removed primary (n = 35) and recurrent polyps (n = 15). RESULTS: The content of galectin-1 and-3 showed no statistically significant differences between primary and recurrent polyps. CONCLUSIONS: The content of galectin-3 was lower in recurrent polyps, however the observed difference did not reach statistical significance (p = 0.07). Since the obtained "p" value is close to the significance limit, it is advisable to broaden the submitted studies to a larger group of patients in order to be able to fully assess whether the determination of the content of galectin-3 may be helpful in assessing the risk of recurrence of nasal and paranasal sinus polyps.

Chemoprevention of Head and Neck Cancers: Does It Have Only One Face?

Head and neck squamous cell cancer (HNSCC) represents a significant burden worldwide. Chemoprevention of HNSCC is a means of cancer control with a use of drugs or natural agents in order to hinder or delay the cancer development. The purpose of this article is to review mechanism of action of different chemopreventive agents' groups and results of most important researches concerning them. The safety issues of HNSCC chemoprevention are also discussed. In case of HNSCC there is currently no agent, which would give positive result in the third phase of clinical trials. Promising results of preclinical trials are not always confirmed by further tests. Main problems are low effectiveness, high toxicity, and lack of highly specificity biomarkers for monitoring the research. New trials concerning many agents, as well as novel technologies for provision of pharmaceutical forms of them, including drug nanocarriers, are currently underway, which gives hope for finding the perfect chemopreventive agent formula.

How does nonsyndromic craniosynostosis affect on bone width of nasal cavity in children? - Computed tomography study.

Craniosynostosis is caused by premature fusion of one or more cranial sutures, restricting skull, brain and face growth. Nonsyndromic craniosynostosis could disturb the proportions of face. Although morphometric diameters of nasal cavity in healthy children are already known, they have not been established yet in children with nonsyndromic craniosynostosis. The aim our study was to check whether diameters of bone structures of nasal cavity in children with nonsyndromic craniosynostosis measured in CT are within normal range. 249 children aged 0-36 months (96 with clinical diagnosis of nonsyndromic craniosynostosis and 153 in control group) were included into the study. The following diameters were measured on head CT scans: anterior bony width (ABW), bony choanal aperture width (BCAW), right and left posterior bony width (between bone sidewall and nasal cavity septum-RPBW and LPBW). The study group has been divided into 4 categories, depending on child's age. The dimensions measured between bone structures of nasal cavity were statistically significantly lower in comparison to the control group. They did not depend on the sex for ABW, nor on age in groups 7-12 months and < 2 years for BCAW, RPBW and LPBW. The measured dimensions increased with age. In children with nonsyndromic craniosynostosis the diameter of pyriform aperture and bony choanal aperture were lower than in controls, what may be described as fronto-orbital anomalies. Morphometric measurements of anthropometric indicators on CT scans could be used as standards in the clinical identification of craniosynostosis type and may help in planning surgical procedures, particularly in the facial skeleton in children.

Collagen Type III Metabolism Evaluation in Patients with Malignant Head and Neck Cancer Treated with Radiotherapy.

Ionizing radiation affects the metabolism of key proteins of extracellular matrix including type III collagen, an important component of human skin. The aim of the work is an analysis of the impact of radical and palliative radiotherapy on collagen type III synthesis in patients with head and neck cancer. The test group consisted of 56 males with histopathologically confirmed head and neck cancer, for whom radiotherapy was applied as a form of radical or palliative treatment. The level of procollagen III aminoterminal propeptide (PIIINP), which is a marker of collagen type III synthesis, was determined in blood serum before radiotherapy, immediately following radiotherapy, and 3 months after it was finished. As a result of radical radiotherapy a statistically significant decrease of PIIINP levels in serum (p < 0.0001) was observed, both immediately after the radiotherapy and 3 months after the end of the treatment. Also the palliative radiotherapy caused a significant decrease of PIIINP right after the treatment (p = 0.0052), as well as during the examination performed 3 months later (p = 0.0004). The achieved results suggest that PIIINP can be used as a marker helpful in assessing radiation damage to connective tissue.

Glioblastoma and chemoresistance to alkylating agents: Involvement of apoptosis, autophagy, and unfolded protein response.

Despite advances in neurosurgical techniques and radio-/chemotherapy, the treatment of brain tumors remains a challenge. This is particularly true for the most frequent and fatal adult brain tumor, glioblastoma (GB). Upon diagnosis, the average survival time of GB patients remains only approximately 15months. The alkylating drug temozolomide (TMZ) is routinely used in brain tumor patients and induces apoptosis, autophagy and unfolded protein response (UPR). Here, we review these cellular mechanisms and their contributions to TMZ chemoresistance in brain tumors, with a particular emphasis on TMZ chemoresistance in glioma stem cells and GB.

Notch signaling pathway and gene expression profiles during early in vitro differentiation of liver-derived mesenchymal stromal cells to osteoblasts.

Notch signaling is a key signaling pathway for cell proliferation and differentiation. Therefore, we formulated a working hypothesis that Notch signaling can be used to detect early osteoblastic differentiation of mesenchymal stromal cells. Changes in expression and distribution of Notch 1, 2, 3, and Delta1 in the cytoplasm and nuclei of rat liver-derived mesenchymal stromal cells differentiating into osteoblasts were investigated, together with the displacement of intracellular domains (ICDs) of the receptors. In addition, an oligonucleotide microarray was used to determine the expression of genes known to be linked to selected signaling pathways. Statistically significant changes in the number of cells expressing Notch1, Notch2, and Delta1, but not Notch3, and their activated forms were detected within 24 h of culture under osteogenic conditions. Although the number of cells expressing Notch3 remained unchanged, the number of cells with the activated receptor was significantly elevated. The number of cells positive for Notch3 was higher than that for the other Notch receptors even after 48 h of differentiation; however, a smaller fraction of cells contained activated Notch3. Culture mineralization was detected on day 4 of differentiation, and all analyzed receptors were present in the cells at that time, but only Delta1 was activated in twice as many cells than that before differentiation. Thus, the three analyzed receptors and ligand can serve as markers of very early stages of osteogenesis in stromal cells. These early changes in activation of the Notch signaling pathway were correlated with the transcription of several genes linked to osteogenesis, such as Bmps, Mmps, and Egfr, and with the regulation of cell cycle and apoptosis.

Oral and oropharyngeal papillomas are not associated with high-risk human papillomavirus infection.

The role of different types of human papillomavirus (HPV) in the development of oral and oropharyngeal papillomas remains unclear. High-risk HPV (HR-HPV) was shown to be involved in the pathogenesis of significant proportion of squamous cell carcinomas of the oropharynx. In this study, we hypothesized that in some oropharyngeal papillomas, low-risk HPV (LR-HPV) and HR-HPV infection could co-exist, similar to what is observed in genital warts, and thus contribute to the elevated risk of malignancy. To test this hypothesis, we used real-time PCR to assess the presence of HPV DNA of 16 types (2 LR-HPV and 14 HR-HPV), in 75 formalin-fixed and paraffin-embedded histopathological samples of oral and oropharyngeal papillomas and in 57 squamous cell carcinomas from the same regions. We investigated the biological activity of HPV by demonstrating accumulation of P16(INK4A) protein in the viral-infected tissue samples. The presence of the LR-HPV genome from the HPV6 or HPV11 types was confirmed in 42 (56%) papillomas and in no carcinomas. HPV6/HPV11 co-infection was detected in 17 (22.7%) of the papillomas. HR-HPV DNA presence and HR-HPV activity hallmarks were not observed in any of the investigated papillomas. Thus, a causative role for HR-HPV or its contribution to LR/HR-HPV co-infection in the pathogenesis of oral or oropharyngeal papillomas is unlikely. Additionally, HR-HPV and LR-HPV infections seem to be mutually exclusive in papillomas and squamous cell carcinomas of the oral cavity and oropharynx.