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The composite containing nanosilver uniformly deposited on matrix composed of CaHPO4 x 2H2O (brushite, ca 89 mass %), CaHPO4 (monteonite, ca 9.5 mass%), and Ag3PO4 (0.5 mas%) was obtained by addition of calcium nitrate and silver nitrate aqueous solution at 30:1 Ca:Ag molar ratio into excess of (NH4)2PO4 solution at pH 5.0 – 5.5. The isolated solid was characterized by STEM, XRD, and LDI mass spectrometry. It has been found that nanosilver was uniformly distributed within composite as

Abstract Background Heterozygosity of TP53 missense mutations is related to the phenomenon of the dominant-negative effect (DNE). To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene. This approach was based on the knowledge that genes with evident DNE, such as EGFR and IDH1, represent nearly 100% of single heterozygous mutations in tumour specimens and cell lines. Methods Genetic analyses (LOH and sequencing) performed for early and late passages of several cell lines originally described as showing single heterozygous TP53 mutations (H-318, G-16, PF-382, MOLT-13, ST-486 and LS-123). Statistical analysis of IARC TP53 and SANGER databases. Genetic analyses of N-RAS, FBXW7, PTEN and STR markers to test cross-contamination and cell line identity. Cell cloning, fluorescence-activated cell sorting and SSCP performed for the PF-382 cell line. Results A database study revealed TP53 single heterozygous mutations in 35% of in vivo (surgical and biopsy) samples and only 10% of cultured cells (in vitro), although those numbers appeared to be overestimated. We deem that published in vivo TP53 mutation analyses are not as rigorous as studies in vitro, and we did not find any cell line showing a stable, single heterozygous mutation. G16, PF-382 and MOLT-13 cells harboured single heterozygous mutations temporarily. ST-486, H-318 and LS-123 cell lines were misclassified. Specific mutations, such as R175H, R273H, R273L or R273P, which are reported in the literature to exert a DNE, showed the lowest percentage of single heterozygous mutations in vitro (about 5%). Conclusion We suggest that the currently reported percentage of TP53 single heterozygous mutations in tumour samples and cancer cell lines is overestimated. Thus, the magnitude of the DNE of TP53 mutations is questionable. This scepticism is supported by database investigations showing that retention of the wild-type allele occurs with the same frequency as either nonsense or missense TP53 mutations.

Abstract Background Recently published data showed discrepancies beteween P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers. Methods To this end, we analyzed 23 colorectal cancers for P53 mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry. Results We found P53 gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of P53 mRNA was present in samples with and without P53 mutations. Conclusion In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated P53 mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without P53 mutation (normal cells and cells showing K-RAS and/or APC but not P53 mutation) in samples presenting P53 mutation; 3, heterozygous or hemizygous mutations of P53 gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in P53 cDNA and DNA sequencing analysis.

Background: Recently published data showed discrepancies between P53 cDNA and DNA sequencing in glioblastomas. We hypothesised that similar discrepancies may be observed in other human cancers.Methods: To this end, we analyzed 23 colorectal cancers for P53 mutations and gene expression using both DNA and cDNA sequencing, real-time PCR and immunohistochemistry.Results: We found P53 gene mutations in 16 cases (15 missense and 1 nonsense). Two of the 15 cases with missense mutations showed alterations based only on cDNA, and not DNA sequencing. Moreover, in 6 of the 15 cases with a cDNA mutation those mutations were difficult to detect in the DNA sequencing, so the results of DNA analysis alone could be misinterpreted if the cDNA sequencing results had not also been available. In all those 15 cases, we observed a higher ratio of the mutated to the wild type template by cDNA analysis, but not by the DNA analysis. Interestingly, a similar overexpression of P53 mRNA was present in samples with and without P53 mutations.Conclusion: In terms of colorectal cancer, those discrepancies might be explained under three conditions: 1, overexpression of mutated P53 mRNA in cancer cells as compared with normal cells; 2, a higher content of cells without P53 mutation (normal cells and cells showing K-RAS and/or APC but not P53 mutation) in samples presenting P53 mutation; 3, heterozygous or hemizygous mutations of P53 gene. Additionally, for heterozygous mutations unknown mechanism(s) causing selective overproduction of mutated allele should also be considered. Our data offer new clues for studying discrepancy in P53 cDNA and DNA sequencing analysis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the leading cause of dementia in the aging population. Pathogenic processes related to the accumulation of amyloid plaques (Aβ) and intracellular neurofibrillary tangles (NFTs) begin during the asymptomatic stage long before the onset of deterioration in cognitive functions and neurodegeneration, which makes rapid diagnosis and treatment difficult. Although biochemical diagnostic markers isolated from the body fluids of AD patients are currently used, scientists are engaged in research into molecular biomarkers that will significantly accelerate the diagnosis long before the first clinical symptoms appear. The research presented here focused on microRNAs (miRNAs), small, non-coding RNA molecules that are involved in the regulation of the post-transcriptional expression of many genes. A review of the literature revealed that miRNAs play an important role in regulating the expression of genes involved in the pathophysiological mechanisms of AD. Changes in the levels of miRNAs in a patient's body fluids can be used for rapid diagnosis. Original scientific articles published between 2014 and 2023 describing clinical and experimental studies on the role and expression levels of various miRNAs were selected from scientific databases such as PubMed, NCBI, Science Direct, and Google Scholar. The selected miRNAs were divided into 2 groups based on their expression level in AD: those with increased expression and those with decreased expression. A review of the latest scientific reports confirms that miRNAs may be a promising source of non-invasive and widely available biomarkers. Additionally, their modulation may prove to be an effective therapeutic strategy in AD.

Worldwide, osteoarthritis (OA) is the most common cause of joint pain in older people. Many factors contribute to osteoarthritis' development and progression, including secondary osteoarthritis' underlying causes. It is important to note that osteoarthritis affects all four tissues: cartilage, bone, joint capsule, and articular apparatus. An increasingly prominent area of research in osteoarthritis regulation is microRNAs (miRNAs), a small, single-stranded RNA molecule that controls gene expression in eukaryotes. We aimed to assess and summarize current knowledge about the mechanisms of the action of miRNAs and their clinical significance. Osteoarthritis (OA) is affected by the interaction between miRNAs and inflammatory processes, as well as cartilage metabolism. MiRNAs also influence cartilage cell apoptosis, contributing to the degradation of the cartilage in OA. Studies have shown that miRNAs may have both an inhibitory and promoting effect on osteoporosis progression through their influence on molecular mechanisms. By identifying these regulators, targeted treatments for osteoarthritis may be developed. In addition, microRNA may also serve as a biomarker for osteoarthritis. By using these biomarkers, the disease could be detected faster, and early intervention can be instituted to prevent mobility loss and slow deterioration.

Endometrial cancer is one of the most common malignant tumours in women. The development of this tumour is associated with several genetic disorders, many of which are still unknown. One type of RNA molecules currently being intensively studied in many types of cancer are long non-coding RNAs (lncRNAs). LncRNA-coding genes occupy a large fraction of the human genome. LncRNAs regulate many aspects of cell development, metabolism, and other physiological processes. Diverse types of lncRNA can function as a tumour suppressor or an oncogene that can alter migration, invasion, cell proliferation, apoptosis, and immune system response. Recent studies suggest that selected lncRNAs are important in an endometrial cancer course. Our article describes over 70 lncRNAs involved in the development of endometrial cancer, which were studied via in vivo and in vitro research. It was proved that lncRNAs could both promote and inhibit the development of endometrial cancer. In the future, lncRNAs may become an important therapeutic target. The aim of this study is to review the role of lncRNAs in the development of carcinoma of uterine body.

MicroRNAs (miRNA) are involved in the process of carcinogenesis, including the development of endometrial cancer (EC). This study aimed to investigate the association between the expression of three miRNAs (miR-21-5p, miR-205-5p, and miR-222-3p) in endometrial cancer tissues. In addition, the stability of expression of SNORD48 and U6, which were initially planned to be used as reference miRNAs for normalization, was investigated. Endometrial tissue was obtained from 111 patients with EC during hysterectomy and from 19 patients undergoing surgery for uterine fibroids or pelvic organ prolapse as a control group without neoplastic changes. Our study was based on calculations made with a digital PCR method (Qiagen, Hilden, Germany) to measure the absolute expression. In the endometrial cancer tissue, miR-205-5p was upregulated, while miR-222-3p and SNORD48 were downregulated compared to the control group. We detected statistically significant correlation of miR-205-5p, U6, and SNORD48 expression with different histological grades; the expression of miR-205-5p increases with the histopathological grade advancement (intraepithelial neoplasia- EIN = 1590, G1 = 3367.2, G2 = 8067 and G3 = 20,360), while U6 and SNORD expression decreases from EIN to G2 and increases again in the G3 grade (U6: EIN = 19,032, G1 = 16,482.4, G2 = 13,642.4, G3 = 133,008; SNORD48: EIN = 97,088, G1 = 59,520, G2 = 43,544, G3 = 227,200). Our study suggests that upregulation of miR-205-5p and downregulation of miR-222-3p and SNORD48 may influence development of endometrial cancer. Moreover, miR-205-5p, U6, and SNORD48 expression changes may be associated with progression of endometrial cancer. The results also indicate that SNORD48 and U6, commonly used as internal references, may influence endometrial cancer development and progression; therefore, they should not be used as references. However, it is important to note that further research is required to understand their role in endometrial cancer.

Background: Micronutrients are important components for the homeostasis of the human body. The studies available in the literature of the subject on their impact on the risk of population diseases, including malignant neoplasms, are ambiguous. In this paper, the relationship between Cu and Zn serum levels and the occurrence of endometrial cancer have been analyzed., Methods: 306 patients (153 test group and 153 control group) matched for age were analyzed for Cu and Zn levels. Microelements levels were determined for sera collected during the hospitalization of patients by means of an inductively coupled plasma mass spectrometry. In addition, the Cu/Zn ratio in the population included in the study was analyzed. Univariable and multivariable analyzes were used to examine the relationship between the factors under study and the incidence of endometrial cancer., Results: Lower levels of elements were observed in the study group compared with the control group (Cu: 959.39 μg/L vs. 1176.42 μg/L, p < 0.001; Zn: 707.05 μg/L vs. 901.67 μg/L, p < 0.001). A statistically significant relationship with the occurrence of endometrial cancer was observed for Cu and Zn. The patients with the lowest Cu level had a significantly higher occurrence of endometrial cancer compared with reference tertile (OR 8.54; p < 0.001). Similarly, compared with the reference tertile, the patients with the lowest Zn levels had a significantly greater incidence of endometrial cancer (OR 15.0; p < 0.001)., Conclusion: The results of the study suggest an association of endometrial cancer occurrence with lower Cu and Zn serum levels.

The ADRB3 gene plays a role in energy expenditure by participating in lipolysis, which affects body composition and performance. The ADRB3 rs4994 polymorphism has been studied in groups of athletes, overweight individuals, and obese and diabetic patients, but it has not been studied in young and healthy adults so far. In the present study, we examined the association of ADRB3 rs4994 polymorphism with body composition, somatotype, cardiorespiratory fitness and physical activity in young, healthy adults ( N = 304). All subjects had anthropometric measurements, and somatotypes were assessed using the Heath-Carter method. In addition, cardiorespiratory fitness and physical activity levels were assessed. Genotyping for the ADRB3 gene was performed using a PCR-RFLP method. In the male group, body components were associated with the Trp64Trp genotype (waist circumference ( p = 0.035), hip circumference ( p = 0.029), BF (%) ( p = 0.008), and BF (kg) ( p = 0.010), BMI ( p = 0.005), WHtR ( p = 0.021), and BAI ( p = 0.006)). In addition, we observed that the Trp64Trp genotype was associated with somatotype components ( p = 0.013). In contrast, the Arg allele was associated with the ectomorphic components (0.006). We also observed a positive impact of the Trp64Trp genotype with maximal oxygen uptake ( p = 0.023) and oxygen pulse ( p = 0.024). We observed a negative relationship of the Trp64Trp genotype in the female group with reported moderate-intensity exercise ( p = 0.036). In conclusion, we found an association of the Trp64 allele with anthropometric traits, somatotype and parameters describing physical performance in the male group. In the female subpopulation, we only found an effect of the polymorphism Trp64Arg on the level of physical activity for moderate-intensity exercise.

Endometrial cancer is one of the most common cancers in developing and developed countries. Although the detection of this cancer is high at the early stages, there is still a lack of markers to monitor the disease, its recurrence, and metastasis. MiRNAs are in charge of the post-transcriptional regulation of genes responsible for the most important biological processes, which is why they are increasingly used as biomarkers in many types of cancer. Many studies have demonstrated the influence of miRNAs on the processes related to carcinogenesis. The characteristics of miRNA expression profiles in endometrial cancer will allow their use as diagnostic and prognostic biomarkers. This paper focuses on the discussion of selected miRNAs based on the literature and their role in the development of endometrial cancer.

Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival., Materials and Methods: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing., Results: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression., Conclusions: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

Leiomyomas, also referred to as fibroids, belong to the most common type of benign tumors developing in the myometrium of the uterus. Intravenous leiomyomatosis (IVL) tends to be regarded as a rare type of uterine leiomyoma. IVL tumors are characterized by muscle cell masses developing within the uterine and extrauterine venous system. The underlying mechanism responsible for the proliferation of these lesions is still unknown. The aim of the study was to investigate the expression of the two epigenetic factors, oncomiRs miR-182-5p and miR-103a-3p, in intravenous leiomyomatosis. This study was divided into two stages: initially, miR-182-5p and miR-103a-3p expression was assessed in samples coming from intravenous leiomyomatosis localized in myometrium (group I, n = 6), intravenous leiomyomatosis beyond the uterus (group II; n = 5), and the control group, i.e., intramural leiomyomas (group III; n = 9). The expression level of miR-182-5p was significantly higher in samples coming from intravenous leiomyomatosis (group I and group II) as compared to the control group ( p = 0.029 and p = 0.024, respectively). In the second part of the study, the expression levels of the studied oncomiRs were compared between seven samples delivered from one woman during a four-year observation. The long-term follow-up of one patient demonstrated significantly elevated levels of both studied oncomiRs in intravenous leiomyomatosis in comparison to intramural leiomyoma samples.

Asthma heterogeneity complicates the search for targeted treatment against airway inflammation and remodeling. We sought to investigate relations between eosinophilic inflammation, a phenotypic feature frequent in severe asthma, bronchial epithelial transcriptome, and functional and structural measures of airway remodeling. We compared epithelial gene expression, spirometry, airway cross-sectional geometry (computed tomography), reticular basement membrane thickness (histology), and blood and bronchoalveolar lavage (BAL) cytokines of n = 40 moderate to severe eosinophilic (EA) and non-eosinophilic asthma (NEA) patients distinguished by BAL eosinophilia. EA patients showed a similar extent of airway remodeling as NEA but had an increased expression of genes involved in the immune response and inflammation (e.g., KIR3DS1 ), reactive oxygen species generation ( GYS2 , ATPIF1 ), cell activation and proliferation ( ANK3 ), cargo transporting ( RAB4B , CPLX2 ), and tissue remodeling ( FBLN1 , SOX14 , GSN ), and a lower expression of genes involved in epithelial integrity (e.g., GJB1 ) and histone acetylation ( SIN3A ). Genes co-expressed in EA were involved in antiviral responses (e.g., ATP1B1 ), cell migration ( EPS8L1 , STOML3 ), cell adhesion ( RAPH1 ), epithelial-mesenchymal transition ( ASB3 ), and airway hyperreactivity and remodeling ( FBN3 , RECK ), and several were linked to asthma in genome- (e.g., MRPL14 , ASB3 ) or epigenome-wide association studies ( CLC , GPI , SSCRB4 , STRN4 ). Signaling pathways inferred from the co-expression pattern were associated with airway remodeling (e.g., TGF-β/Smad2/3, E2F/Rb, and Wnt/β-catenin).

Background: Available studies on the effect of serum selenium levels on the risk of malignancies show some conflicting results. In this study, we investigated the correlation between serum selenium levels and ovarian cancer occurrence., Methods: 314 women (157 diseased patients and 157 healthy ones) matched in terms of age and BMI were included in the study. The measurements of selenium in the collected blood samples were performed using an ICP mass spectrometer. Univariable and multivariable analyzes were performed to determine the relationship between the factors under the study and the occurrence of ovarian cancer., Results: The mean concentration of selenium was lower among diseased ones than among controls (53.31 μg/L vs. 78.99 μg/L). A decrease in selenium concentration was noticed with the advancement of ovarian cancer. In univariable and multivariable analyzes, a clear relationship between low selenium concentration and the occurrence of ovarian cancer was found (35.3 (95% CI: 11.2-111; p < 0.001) and 45.8 (95% CI: 12.8-164; p < 0.001))., Conclusion: The studied patients with ovarian cancer are characterized by statistically significant lower serum selenium levels than patients from the control group. Among the study group, a decrease in selenium concentration was observed with an increase in the FIGO stage. The determination of the role of selenium as a prophylactic factor in ovarian cancer requires further prospective studies.

More than 97% of patients with acute myeloid leukemia (AML) demonstrate genetic mutations leading to excessive proliferation combined with the evasion of regulated cell death (RCD). The most prominent and well-defined form of RCD is apoptosis, which serves as a defense mechanism against the emergence of cancer cells. Apoptosis is regulated in part by the BCL-2 family of pro- and anti-apoptotic proteins, whose balance can significantly determine cell survival. Apoptosis evasion plays a key role in tumorigenesis and drug resistance, and thus in the development and progression of AML. Research on the structural and biochemical aspects of apoptosis proteins and their regulators offers promise for new classes of targeted therapies and strategies for therapeutic intervention. This review provides a comprehensive overview of current AML treatment options related to the mechanism of apoptosis, particularly its mitochondrial pathway, and other promising concepts such as neddylation. It pays particular attention to clinically-relevant aspects of current and future AML treatment approaches, highlighting the molecular basis of individual therapies.

Triple negative breast cancer (TNBC) is regarded as the most aggressive breast cancer subtype with poor overall survival and lack of targeted therapies, resulting in many patients with recurrent. The insight into the detailed biochemical composition of TNBC would help develop dedicated treatments. Thus, in this study Fourier Transform Infrared microspectroscopy combined with chemometrics and absorbance ratios investigation was employed to compare healthy controls with TNBC tissue before and after chemotherapy within the same patient. The primary spectral differences between control and cancer tissues were found in proteins, polysaccharides, and nucleic acids. Amide I/Amide II ratio decrease before and increase after chemotherapy, whereas DNA, RNA, and glycogen contents increase before and decrease after the treatment. The chemometric results revealed discriminatory features reflecting a clinical response scheme and proved the chemotherapy efficacy assessment with infrared spectroscopy is possible., Competing Interests: The authors have declared that no competing interests exist.

Background: Aberrant DNA methylation is an important mechanism by which the normal patterns of microRNA expression are disrupted in human cancers including B-cell precursor acute lymphoblastic leukemia (BCP ALL), the most common pediatric malignancy., Objectives: To characterize the methylation profile landscape of microRNA genes in BCP ALL patients., Material and Methods: We employed Infinium® MethylationEPIC BeadChip Arrays to measure the methylation of microRNA genes from bone marrow samples of children with BCP ALL (n = 38) and controls without neoplasms (n = 4)., Results: This analysis revealed differential methylation of the microRNA genes in the pediatric BCP ALL when compared to the control. A subcluster amongst BCP ALL patients with TCF3-PBX1 genetic subtype was also observed. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-related phenotypes are enriched by the genes with hyperand hypomethylated sites located in promoters as well as gene bodies. The top 3 miRNA genes, promoters of which were the most statistically significantly hypermethylated in BCP ALL were MIR1273G, MIR1304 and MIR663, and the top 3 hypomethylated were MIR4442, MIR155 and MIR3909., Conclusions: In this study, a different microRNA genes methylation landscape was shown in pediatric BCP ALL compared to children without neoplasms. A visible subcluster among BCP ALL samples consisted of individuals with TCF3-PBX1 genetic subtype. No other differences were observed in association with age, gender or risk group. Several interesting leukemia-connected phenotypes were found, associated with genes with hyperand hypomethylated sites located on promoters as well as gene bodies.

Background: Numerous studies have shown a relationship between low serum selenium levels and an increased risk of developing cancer. Methods: A total of 306 women participated in the study: 153 patients diagnosed with endometrial cancer and 153 healthy women who were matched, in terms of birth year (+/−3 years), to the patients from the study group. The quantitative measurement of selenium content in the collected blood samples was performed using a mass spectrometer with excitation in inductively coupled plasma. In order to determine the relationship between the risk factors and the incidence of endometrial cancer, analyses based on single- and multi-factor conditional logistic regression models were performed. Results: The mean concentration of selenium was lower in patients with endometrial cancer than in healthy controls (60.63 µg/L (0.77 µmol/L) vs. 78.74 µg/L (0.99 µmol/L), respectively). When compared in quartiles, a significant association of lower selenium concentration with the incidence of endometrial cancer was recorded. The highest OR was observed in the first and second quartiles (OR-22.0, p-value < 0.001; medium selenium level 46.95 µg/L (0.59 µmol/L), and OR-5.94; p-value < 0.001; medium selenium level 63.60 µg/L (0.80 µmol/L), respectively). Conclusion: A strong correlation between the level of selenium in the blood serum and the risk of endometrial cancer indicates that patients with low levels should be a candidate group requiring appropriate preventive examinations. Further research on a larger group of patients is required.

Background: Numerous studies indicate a relationship between the presence of GPX1 (rs1050450), DIO2 (rs225014) and SEPP1 (rs7579) gene polymorphisms and the development of chronic or neoplastic diseases. However, there are no reports on the influence of these polymorphisms on the development of endometrial cancer., Methods: 543 women participated in the study. The study group consisted of 269 patients with diagnosed endometrial cancer. The control group consisted of 274 healthy women. Blood samples were drawn from all the participants. The PCR-RFLP method was used to determine polymorphisms in the DIO2 (rs225014) and GPX1 (rs1050450) genes. The analysis of polymorphisms in the SEPP1 (rs7579) gene was performed by means of TaqMan probes., Results: There was a 1.99-fold higher risk of developing endometrial cancer in CC homozygotes, DIO2 (rs225014) polymorphism (95% Cl 1.14-3.53, p = 0.017), compared to TT homozygotes. There was no correlation between the occurrence of GPX1 (rs1050450) and SEPP1 (rs7579) polymorphisms and endometrial cancer., Conclusion: Carriers of the DIO2 (rs225014) polymorphism may be predisposed to the development of endometrial cancer. Further research confirming this relationship is recommended.

Early detection of the most common pediatric neoplasm, B-cell precursor lymphoblastic leukemia (BCP-ALL), is challenging and requires invasive bone marrow biopsies. The purpose of this study was to establish new biomarkers for early screening to detect pediatric leukemia. In this small cohort study, Fourier transform infrared (FTIR) spectra were obtained from blood sera of 10 patients with BCP-ALL and were compared with the control samples from 10 children with some conditions other than neoplasm. Using various analytical approaches, including a new physical model, some significant differences were observable. The most important include: the different peak area ratio 2965/1645 cm -1 ( p = 0.002); the lower average percentage of both β-sheet and β-turn protein structures in the sera of BCP-ALL patients ( p = 0.03); an AdaBoost-based predictive model for classifying healthy vs. BCP-ALL patients with 85% accuracy; and the phase shift of the first derivative in the spectral range 1050-1042 cm -1 correlating with white blood cell (WBC) and blast cell count in BCP-ALL patients contrary to the samples obtained from healthy controls. Although verification in larger groups of patients will be necessary, these promising results suggest that FTIR spectroscopy may have future potential for the early screening of BCP-ALL.

Airway remodeling in asthma is characterized by reticular basement membrane (RBM) thickening, likely related to epithelial structural and functional changes. Gene expression profiling of the airway epithelium might identify genes involved in bronchial structural alterations. We analyzed bronchial wall geometry (computed tomography (CT)), RBM thickness (histology), and the bronchial epithelium transcriptome profile (gene expression array) in moderate to severe persistent ( n = 21) vs. no persistent ( n = 19) airflow limitation asthmatics. RBM thickness was similar in the two studied subgroups. Among the genes associated with increased RBM thickness, the most essential were those engaged in cell activation, proliferation, and growth (e.g., CDK20 , TACC2 , ORC5 , and NEK5 ) and inhibiting apoptosis (e.g., higher mRNA expression of RFN34 , BIRC3 , NAA16 , and lower of RNF13 , MRPL37 , CACNA1G ). Additionally, RBM thickness correlated with the expression of genes encoding extracellular matrix (ECM) components ( LAMA3 , USH2A ), involved in ECM remodeling ( LTBP1 ), neovascularization ( FGD5 , HPRT1 ), nerve functioning ( TPH1 , PCDHGC4 ), oxidative stress adaptation ( RIT1 , HSP90AB1 ), epigenetic modifications ( OLMALINC , DNMT3A ), and the innate immune response ( STAP1 , OAS2 ). Cluster analysis revealed that genes linked with RBM thickness were also related to thicker bronchial walls in CT. Our study suggests that the pro-fibrotic profile in the airway epithelial cell transcriptome is associated with a thicker RBM, and thus, may contribute to asthma airway remodeling.

Background: Endometrial cancer is the most common malignant neoplasm of the female reproductive organs. A dysfunctional endometrial renin-angiotensin system (RAS) might contribute to the growth and spread of endometrial cancer. The RAS-related gene polymorphisms, including the polymorphism of insertion/deletion (I/D) in the angiotensin-converting enzyme (ACE) gene, influence RAS activity., Objectives: In the present study, we examined the association between the I/D polymorphism of the ACE gene and endometrial cancer risk in Polish women., Material and Methods: Genotype analysis of the ACE I/D polymorphism was carried out using polymerase chain reaction (PCR) on 142 endometrial cancer type 1 patients and 68 cancer-free subjects. The results of the analyses were correlated with clinical data., Results: The frequency of DD, DI and II ACE genotypes did not vary significantly between the experimental group and the control group (40 (28%), 61 (43%) and 41 (29%) vs 18 (26%), 31 (46%), and 19 (28%), respectively; p = 0.935). In addition, the incidence of the DD, DI and II polymorphisms in the ACE gene did not vary significantly between the experimental subgroups when stratified by cancer grade - G1, G2 and G3 endometrioid carcinoma - and the control group. Furthermore, the ACE polymorphism was not significantly associated with hypertension, diabetes or lymph node metastasis., Conclusions: The ACE I/D gene polymorphism was not associated with endometrial cancer risk or the clinicopathological features in Polish women.

Mantle cell lymphoma (MCL) is regarded as an incurable neoplasm, even to the novel drug strategies. It is known MCL has two morphological variants- classic and aggressive. Aggressive MCL is characterized by a higher mitotic index and proliferation rate, and poor overall survival in comparison to classic subtype. The insight into the detailed biochemical composition of MCL is crucial in the further development of diagnostic and treatment guidelines for MCL patients; therefore Synchrotron radiation Fourier Transform Infrared (S-FTIR) microspectroscopy combined with Principal Component Analysis (PCA) was used. The major spectral differences were observed in proteins and nucleic acids content, revealing a classification scheme of classic and aggressive MCLs. The results obtained suggest that FTIR microspectroscopy has reflected the histopathological discrimination of both MCL subtypes.

Breast cancer accounts for 22%-25% of all female cancers diagnosed worldwide. The aim of study was to compare the 5-year relative survival rates for breast cancer patients treated in the years 2008-2010, 2000-2002, and 2005-2007, and to determine their relationships with the methods and costs of treatment. Data were collected from the National Cancer Registry and the Narodowy Fundusz Zdrowia (National Health Fund) data bases. An increase in the 5-year survival rate was observed. The results show the impact of some factors on the survival and treatment costs. It is necessary to create data bases being a platform for further comprehensive analyses., (© 2019 Wiley Periodicals, Inc.)

ACTN3 encodes the protein α-actinin-3, which affects the muscle phenotype. In the present study, we examined the association of ACTN3 R577X polymorphism with body somatotype and cardiorespiratory fitness in young, healthy adults. The study group included 304 young adults, in whom cardiorespiratory fitness was evaluated and the maximum oxygen uptake was determined directly. The somatotype components were calculated according to the Heath-Carter method. Genotyping for the ACTN3 gene was performed using a polymerase chain reaction followed by high-resolution melting analysis. In the female group, a lower maximal heart rate (HRmax) was more strongly associated with the RR genotype ( p = 0.0216) than with the RX and XX genotypes. In the male group, the ACTN3 RX genotype, as compared with other genotypes, tended to be associated with a lower percentage of adipose tissue ( p = 0.0683), as also reflected by the body mass index ( p = 0.0816). ACTN3 gene polymorphism may affect cardiorespiratory fitness. Our analysis of ACTN3 gene polymorphism does not clearly illustrate the relationships among genotype, body composition, and somatotype in young, healthy adults.

Purpose: Diabetes mellitus type 2 (T2DM) and its vascular complications are a serious world health problem. For this reason it is important to look for new diabetes complication risk factors. The aim of this study was to determine whether 18-bp insertion/deletion (I/D) polymorphism at -2549 position of the vascular endothelial growth factor (VEGF) gene is associated with diabetic vascular complications (DVC)., Material and Methods: Caucasian subjects (n = 100) with T2DM were recruited for this study. Genotyping of the VEGF gene I/D polymorphism was done by the polymerase chain reaction (PCR) method. The results were correlated with laboratory and clinical data., Results: In our population heterozygous of the VEGF gene polymorphism was observed most frequently (57%). DVC were observed in 53 patients. Heterozygous T2DM patients significantly more often suffered from heart failure (HF) and stroke (p = 0.05). Amongst all the DVC, D allele of the VEGF polymorphism had a significantly increased risk of diabetic retinopathy (DR) (OR = 1.31; p = 0.033) irrespective of the duration of diabetes, BMI, the glycemia control expressed by HbA1c, renal function, lipid values or applied treatment. The studied polymorphism did not correlate with coronary heart disease, peripheral vascular disease, cardiovascular death, diabetic kidney disease or applied treatment., Conclusions: The multivariate logistic regression analysis showed that the D allele in the promoter region of the VEGF gene is an independent risk factor of DR irrespective of other laboratory and clinical variables in T2DM patients. Our study suggests that I/D allele in the studied gene is associated with HF and strokes., (Copyright © 2018 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Introduction: TP53 and MGMT alterations play a crucial role in glioblastoma (GB) pathogenesis. TP53 and MGMT function is affected by several pathologic mechanisms, such as point mutations or promoter methylation, which are well characterized. Expression of both genes can be regulated by other mechanisms as well, e.g., microRNAs (miRNAs). Moreover, cross-talk among various pathologic processes may occur, further affecting MGMT and TP53 functionality., Material and Methods: In 49 GB patients, we analyzed the possible associations between TP53 and its miRNA regulators miR-125b , miR-21 , and miR-34a , as well as MGMT and its miRNA regulators miR-181d and miR-648 . We evaluated the possible influence of mutational and methylation status on the pre-identified associations., Results: In patients with immunohistochemistry-detected TP53 overexpression, expression levels of miR-34a and TP53 were negatively correlated ( r = -0.56, p = 0.0195), and in patients with TP53 mutations, expression levels of TP53 and miR-21 were negatively correlated ( r = -0.67, p = 0.0330). In patients with MGMT methylation, expression levels of MGMT were negatively correlated with miR-648 and miR-125b expression levels ( r = -0.61, p = 0.0269 and r = -0.34, p = 0.0727, respectively)., Conclusions: Our findings demonstrate that selected miRNAs are significantly correlated with MGMT and TP53 levels, but the extent of this correlation differs regarding the TP53 and MGMT mutational and promoter methylation status., Competing Interests: The authors declare no conflict of interest. References1LouisDNPerryAReifenbergerGThe 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summaryActa Neuropathol201613180320271579312HongYShiYShangCInfluence of far upstream element binding protein 1 gene on chemotherapy sensitivity in human U251 glioblastoma cellsArch Med Sci20161215662269251323StuppRMasonWPvan den BentMJRadiotherapy plus concomitant and adjuvant temozolomide for glioblastomaN Engl J Med200535298796157580094StuppRHegiMEMasonWPEffects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trialLancet Oncol20091045966192698955AlifierisCTrafalisDTGlioblastoma multiforme: pathogenesis and treatmentPharmacol Ther20151526382259445286VlachostergiosPJPapandreouCNEfficacy of low dose temozolomide in combination with bortezomib in U87 glioma cells: a flow cytometric analysisArch Med Sci20151130710259957457HegiMEDiserensACGorliaTMGMT gene silencing and benefit from temozolomide in glioblastomaN Engl J Med20053529971003157580108PreusserMde RibaupierreSWöhrerACurrent concepts and management of glioblastomaAnn Neurol201170921217862969OhgakiHKleihuesPThe definition of primary and secondary glioblastomaClin Cancer Res201319764722320903310Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature2008455106181877289011OhgakiHKleihuesPEpidemiology and etiology of gliomasActa Neuropathol2005109931081568543912McLendonRFriedmanABignerDComprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature2008455106181877289013AmatyaVJNaumannUWellerMOhgakiHTP53 promoter methylation in human gliomasActa Neuropathol2005110178841602528714Jesionek-KupnickaDSzybkaMMalachowskaBTP53 promoter methylation in primary glioblastoma: relationship with TP53 mRNA and protein expression and mutation statusDNA Cell Biol201433217262450654515FengZZhangCWuRHuWTumor suppressor p53 meets microRNAsJ Mol Cell Biol2011344502127845116DunnJBaborieAAlamFExtent of MGMT promoter methylation correlates with outcome in glioblastomas given temozolomide and radiotherapyBr J Cancer2009101124311953609617Jesien-LewandowiczEJesionek-KupnickaDZawlikIHigh incidence of MGMT promoter methylation in primary glioblastomas without correlation with TP53 gene mutationsCancer Genet Cytogenet200918877821910050918CrinièreEKaloshiGLaigle-DonadeyFMGMT prognostic impact on glioblastoma is dependent on therapeutic modalitiesJ Neurooncol20078317391721905619KrethSLimbeckEHinskeLCIn human glioblastomas transcript elongation by alternative polyadenylation and miRNA targeting is a potent mechanism of MGMT silencingActa Neuropathol2013125671812334098820FanYNMeleyDPizerBSeeVMir-34a mimics are potential therapeutic agents for p53-mutated and chemo-resistant brain tumour cellsPLoS One20149e1085142525081821FreemanJAEspinosaJMThe impact of post-transcriptional regulation in the p53 networkBrief Funct Genomics20131246572324217822ShiLZhangSFengKMicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide through the mitochondrial pathway of apoptosisInt J Oncol201240119292187925723BradleyBSLoftusJCMielkeCJDinuVDifferential expression of microRNAs as predictors of glioblastoma phenotypesBMC Bioinformatics201415212443817124KarsyMGelbmanMShahPBalumbuOMoyFArslanEEstablished and emerging variants of glioblastoma multiforme: review of morphological and molecular featuresFolia Neuropathol201250301212331918725DongHSiuHLuoLFangXJinLXiongMInvestigating gene and microRNA expression in glioblastomaBMC Genomics200911172226ChangTCWentzelEAKentOATransactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosisMol Cell200726745521754059927HeLHeXLoweSWHannonGJSuppression puzzleNat Rev Cancer20077819221791440428TazawaHTsuchiyaNIzumiyaMNakagamaHTumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cellsProc Natl Acad Sci USA20071041547271787598729LeMTNTehCShyh-ChangNMicroRNA-125b is a novel negative regulator of p53Genes Dev200923862761929328730HaemmigSBaumgartnerUGlückAmiR-125b controls apoptosis and temozolomide resistance by targeting TNFAIP3 and NKIRAS2 in glioblastomasCell Death Dis20145e12792490105031ZhangWZhangJHoadleyKMiR-181d: predictive glioblastoma biomarker that downregulates MGMT expressionNeuro Oncol20121471292257042632LouisDNOhgakiHWiestlerODThe 2007 WHO classification of tumours of the central nervous systemActa Neuropathol2007114971091761844133NagpalJJamoonaAGulatiNDRevisiting the role of p53 in primary and secondary glioblastomasAnticancer Res200626463391721431934PreusserMMGMT analysis at DNA, RNA and protein levels in glioblastoma tissueHistol Histopathol20092451181922445435CapperDMittelbronnMMeyermannRSchittenhelmJPitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approachActa Neuropathol2008115249591796586536YunqingLGuessousFYingZMicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenesCancer Res2009697569761977344137GaoHZhaoHXiangWExpression level of human miR-34a correlates with glioma grade and prognosisJ Neurooncol201311322182352979838TsudaHHirohashiSAssociation among p53 gene mutation, nuclear accumulation of the p53 protein and aggressive phenotypes in breast cancerInt J Cancer199457498503791015139EsrigDSpruckCHNicholsPWp53 nuclear protein accumulation correlates with mutations in the p53 gene, tumor grade, and stage in bladder cancerAm J Pathol1993143138997790199440RenFZhangXLiangHPrognostic significance of MiR-34a in solid tumors: a systemic review and meta-analysis with 4030 patientsInt J Clin Exp Med2015817377912677032941MrazMMalinovaKKotaskovaJmiR-34a, miR-29c and miR-17-5p are downregulated in CLL patients with TP53 abnormalitiesLeukemia2009231159631915883042VoliniaSCalinGALiuCGA microRNA expression signature of human solid tumors defines cancer gene targetsProc Natl Acad Sci USA20061032257611646146043SilberJLimDAPetritschCmiR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cellsBMC Med20086141857721944SlabyOLakomyRFadrusPMicroRNA-181 family predicts response to concomitant chemoradiotherapy with temozolomide in glioblastoma patientsNeoplasma20105726492035327945RaoSASantoshVSomasundaramKGenome-wide expression profiling identifies deregulated miRNAs in malignant astrocytomaMod Pathol2010231404172071117146YangCHYueJPfefferSRMicroRNA-21 promotes glioblastoma tumorigenesis by down-regulating insulin-like growth factor-binding protein-3 (IGFBP3)J Biol Chem201428925079872505966647BarbanoRPalumboOPasculliBA miRNA signature for defining aggressive phenotype and prognosis in gliomasPLoS One20149e1089502527946148KushwahaDRamakrishnanVNgKA genomewide miRNA screen revealed miR-603 as a MGMT-regulating miRNA in glioblastomasOncotarget201454026392499411949StarkAMvan de BerghJHedderichJMehdornHMNabaviAGlioblastoma: clinical characteristics, prognostic factors and survival in 492 patientsClin Neurol Neurosurg201211484052237733350FilippiniGFalconeCBoiardiAPrognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastomaNeuro Oncol20081079871799363451ZawlikIVaccarellaSKitaDMittelbronnMFranceschiSOhgakiHPromoter methylation and polymorphisms of the MGMT gene in glioblastomas: a population-based studyNeuroepidemiology2009322191899747452Jesionek-KupnickaDSzybkaMPotemskiPAssociation of loss of heterozygosity with shorter survival in primary glioblastoma patientsPol J Pathol2013642687524375041

Introduction: Osteoarthritis (OA) is a widely prevalent joint disease leading to motor disability and pain. Appropriate indicators for identifying patients at risk for this progressive disease, identifying molecular events for detecting early phases of the disease, or biomarkers to screen for treatment responses, however, are lacking. Micro RNAs (miRNAs), which play crucial roles in OA, could be potential biomarkers of OA. Because circulating miRNA levels reflect the disease state, they may be useful for OA screening and as diagnostic tools, reducing the need for invasive procedures and minimizing the cost of current diagnostic methods., Materials and Methods: The expression levels of 18 microRNAs (let-7e-5p, miR-21-5p, miR-93-5p, miR-101-3p, miR-103a-3p, miR-130a-3p miR-146a-5p, miR-16-5p, miR-193b-3p miR-199a-3p, miR-210-3p, miR-222-3p, miR-22-3p, miR-27a-3p, miR-27b-3p, miR-335-5p, miR-454-3p, and miR-98-5p) were analyzed by quantitative real-time polymerase chain reaction in the cartilage tissues and serum samples of 28 OA patients and were compared to those of 2 healthy controls., Results: Expression of microRNA-146a-5p was significantly upregulated in the cartilage (p=0.006) and serum (p=0.002) of OA patients. The expression levels of miR-146a-5p in the serum were positively correlated with those in the cartilage (Pearson correlation coefficient R=0.32; p=0.002)., Conclusion: miR-146a-5p was significantly overexpressed in patients with OA, both in the articular cartilage tissue and serum, with a positive correlation between the levels in both types of samples. Therefore, the miR-146a-5p serum level could reflect the molecular processes in the cartilage, suggesting its clinical utility as a biomarker for OA management. Implementing noninvasive biomarker using serum miRNAs involves the analysis of the misregulated miRNAs linked to the cartilage pathology.

Alzheimer's disease (AD) is a disease of advanced civilization and a common form of dementia in people over 65 years of age. We used Fourier transform infrared (FTIR) spectroscopy combined with principal component analysis (PCA) to determine changes in the quantity and quality of the cerebrospinal fluid from AD patients at three different stages of the disease (ADI, ADII, and ADIII), as well as from patients with mild cognitive impairment (MCI). Moreover, based on the FTIR spectra, we calculated the ratio of α-helix and β-sheet secondary protein structures as well as the lipid-protein balance as potential AD markers. The FTIR spectra of cerebrospinal fluid obtained from MCI, ADI, ADII, and ADIII patients showed that peaks corresponding to protein and deoxyribonucleic acid (DNA), and phospholipid and lipid vibrations were shifted in comparison with those of control subjects. Furthermore, the levels of these chemical compounds were lower in the patients than in the control subjects. The β-sheet secondary protein structure levels were increased in the MCI and AD patients compared with the control subjects. In addition, significant changes in the lipid-protein balance were observed. Interestingly, as the disease progressed, the lipid-protein balance became further disrupted, that is, the lipid amount decreased with disease progression. PCA analysis of lipid-protein FTIR regions revealed that the spectra could be used to distinguish between controls and patients with MCI, ADI, ADII, and ADIII.

Rationale: A prolonged, prodromal phase before definitive paediatric precursor B acute lymphoblastic leukaemia (BCP ALL) diagnosis is rarely observed., Patients Concerns: In the first, the patient presented with an aplastic preleukemic phase, whilst the second presented with a rheumatic-like preliminary phase., Diagnoses: The case reports of two patients with BCP ALL with a prodromal phase lasting a few weeks are presented., Interventions and Outcomes: DNA whole genome profile methylation analysis of bone marrow cells obtained at diagnosis revealed a pattern of methylation that was readily distinguishable from both healthy and standard course BCP ALL bone marrow samples., Lessons: The biological implication of this observation remains unclear, with many differentially methylated loci involved in many processes like neurogenesis, cell projection organization and adhesion along with leucocyte activation and apoptosis. The prevalence and clinical significance of these methylation changes is unknown but this data indicates that the epigenetic basis of BCP ALL with a prolonged, prodromal phase requires a more detailed assessment.

In addition to genetic alterations, epigenetic abnormalities have been shown to underlie the pathogenesis of acute lymphoblastic leukemia (ALL)-the most common pediatric cancer. The purpose of this study was to characterize the whole genome DNA methylation profile in children with precursor B-cell ALL (BCP ALL) and to compare this profile with methylation observed in normal bone marrow samples. Additional efforts were made to correlate the observed methylation patterns with selected clinical features. We assessed DNA methylation from bone marrow samples obtained from 38 children with BCP ALL at the time of diagnosis along with 4 samples of normal bone marrow cells as controls using Infinium MethylationEPIC BeadChip Array. Patients were diagnosed and stratified into prognosis groups according to the BFM ALL IC 2009 protocol. The analysis of differentially methylated sites across the genome as well as promoter methylation profiles allowed clear separation of the leukemic and control samples into two clusters. 86.6% of the promoter-associated differentially methylated sites were hypermethylated in BCP ALL. Seven sites were found to correlate with the BFM ALL IC 2009 high risk group. Amongst these, one was located within the gene body of the MBP gene and another was within the promoter region- PSMF1 gene. Differentially methylated sites that were significantly related with subsets of patients with ETV6-RUNX1 fusion and hyperdiploidy. The analyzed translocations and change of genes' sequence context does not affect methylation and methylation seems not to be a mechanism for the regulation of expression of the resulting fusion genes.

Introduction: It has been proved that genetic and epigenetic changes play a significant role in the development and progression of acute leukemia. The aim of our study was to evaluate the frequency and prognostic implications of genetic and epigenetic alterations in p15 , MGMT , DNMT3A and TP53 genes in acute leukemias., Material and Methods: We included in the study 59 patients with acute leukemia. Evaluation of TP53 and DNMT3A mutations was performed using sequencing analysis and PCR-RFLP, respectively. Methylation status of MGMT and p15 genes was evaluated using MSP and COBRA, respectively. For assessment of global DNA methylation ELISA-based kit was used., Results: We found that overall survival was higher for ALL patients. MGMT promoter methylation was significantly associated with patients age at the time of diagnosis ( p = 0.03). TP53 and DNMT3A mutations were observed only in AML patients (16.67% and 8.8%, respectively). Patients with acute leukemia and p15 promoter methylation had significantly more frequently mutated TP53 gene ( p = 0.04) and AML patients with p15 promoter methylation had significantly more frequently detected global hypomethylation of DNA ( p = 0.009). In the group of ALL patients we noted an opposite trend: only patients negative for p15 promoter methylation were characterized by global DNA hypomethylation., Conclusions: Our findings demonstrate that MGMT promoter methylation can have a considerable impact on the development of acute leukemia in older patients. DNMT3A and TP53 mutations may play a significant role in AML development. However, further studies conducted in a larger cohort of patients are needed to determine its clinical utility., Competing Interests: The authors declare no conflict of interest.

Background: Osteoarthritis (OA), the most prevalent disease of articulating joints, is a complex multifactorial disease caused by genetic, mechanical, and environmental factors. In this research, we evaluated miRNA expression in OA., Methods: Forty tissue samples from 29 patients undergoing joint replacement for OA were evaluated. Tissue from two control patients undergoing hip replacement not related to OA was used as a control. Total RNA (containing miRNA species) from cartilage was isolated using a miRCURYTM [corrected] Isolation Kit. Expression of 19 miRNAs was assessed by real-time quantitative polymerase chain reaction., Results: Expression of four miRNAs, miR-138-5p, miR-146a-5p, miR-335-5p, and miR-9-5p, was significantly upregulated in OA tissues (patients vs. control group)., Conclusions: These findings may contribute to disease prevention and the development of therapeutic targets for OA.

Objectives: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. TNBC is usually diagnosed at a relatively young age and is characterized by high risk of developing metastases. Some epigenetic regulation of gene expression is associated with TNBC. Expression of microRNAs (miRNAs) can serve as a potential tool for identifying critical biomarkers in TNBC. The aim of our study is to examine expression of selected miRNAs in TNBC and to assess the relationship between miRNA expression and clinicopathological factors., Material and Methods: Expression levels of 19 selected miRNAs were compared between cancerous and normal breast tissues by use of qPCR method. We have evaluated the relationship between the expression level of miRNAs and clinicopathological factors such as: age, tumor size and lymph node status., Results: We found that in TNBC tissues, when compared with normal breast tissues, the expression of miR-190a, miR- 136-5p and miR-126-5p was significantly reduced (p = 0.0041, p = 0.0007, p = 0.0007, respectively) whereas expression of miR-135b-5p and miR-182-5p was significantly increased (p = 0.0194, p = 0.0041, respectively). We found a linear trend for tumor size and expression of miR-126-5p (p = 0.0296) and miR-135b-5p (p = 0.0241)., Conclusions: Our study confirms that miRNA expression profile is dysregulated in TNBC patients compared to healthy controls. MiR-190a, miR-136-5p, miR-126-5p, miR-135b-5p and miR-182-5p may be associated with development and progression of TNBC.

The paper presents experimental studies of dielectric properties of nanofluids based on ethylene glycol and SC-TiO2 nanoparticles with average size of 15-40 nm with various mass concentrations. The dielectric permittivity both real part and imaginary part as a function of temperature and frequency were measured. Also, dependence ac conductivity on frequency, temperature, and mass concentration were investigated. Based on the curves of ac conductivity, dc conductivity was calculated, and 400 % enhancement in dc conductivity was exposed.

Triple-negative breast cancer is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. Approximately 70% of triple-negative breast cancer patients fail to achieve a pathologic complete response (pCR) after chemotherapy due to the lack of targeted therapies for this subtype. We report here the development of a focal-plane-array Fourier transform infrared (FPA-FTIR) microspectroscopic technique combined with principal component analysis (PCA) for monitoring chemotherapy effects in triple-negative breast cancer patients. The PCA results obtained using the FPA-FTIR spectral data collected from the same patients before and after the chemotherapy revealed discriminatory features that were consistent with the pathologic and clinical responses to chemotherapy, indicating the potential of the technique as a monitoring tool for observing chemotherapy efficacy.

Raman spectroscopy and infrared (IR) spectroscopy are both techniques that allow for the investigation of vibrating chemical particles. These techniques provide information not only about chemical particles through the identification of functional groups and spectral analysis of so-called "fingerprints", these methods allow for the qualitative and quantitative analyses of chemical substances in the sample. Both of these spectral techniques are frequently being used in biology and medicine in diagnosing illnesses and monitoring methods of therapy. The type of breast cancer found in woman is often a malignant tumor, causing 1.38 million new cases of breast cancer and 458 000 deaths in the world in 2013. The most important risk factors for breast cancer development are: sex, age, family history, specific benign breast conditions in the breast, ionizing radiation, and lifestyle. The main purpose of breast cancer screening tests is to establish early diagnostics and to apply proper treatment. Diagnoses of breast cancer are based on: (1) physical techniques (e.g., ultrasonography, mammography, elastography, magnetic resonance, positron emission tomography [PET]); (2) histopathological techniques; (3) biological techniques; and (4) optical techniques (e.g., photo acoustic imaging, fluorescence tomography). However, none of these techniques provides unique or especially revealing answers. The aim of our study is comparative spectroscopic measurements on patients with the following: normal non-cancerous breast tissue; breast cancer tissues before chemotherapy; breast cancer tissues after chemotherapy; and normal breast tissues received around the cancerous breast region. Spectra collected from breast cancer patients shows changes in amounts of carotenoids and fats. We also observed changes in carbohydrate and protein levels (e.g., lack of amino acids, changes in the concentration of amino acids, structural changes) in comparison with normal breast tissues. This fact verifies that Raman spectroscopy and IR spectroscopy are very useful diagnostic tools that will shed new light in understanding the etiology of breast cancer., (© The Author(s) 2016.)