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The behavior of a cell is strongly influenced by the physical properties and stimuli in its microenvironment. Furthermore, the activation and modulation of mechanotransduction pathways are involved in tissue development and homeostasis and even pathological processes. Thus, when developing materials aimed at mimicking the extracellular matrixes of healthy or pathological tissues, their mechanical features should be closely considered. In this context, nanoindentation represents a powerful technique for mechanically characterizing biological tissues and hydrogels at the cell-length scale. However, standardized experimental protocols and data analysis techniques are lacking. Here, we proposed a methodological approach based on the nanoindentation technique for quantitatively analyzing and comparing the time-dependent load relaxation responses of soft biological tissues and hydrogels. As this was an explanatory study, stress-relaxation nanoindentation tests were performed on samples of pig and human lung tissues and of a specific gelatin-methacryloyl (GelMA) hydrogel to quantify and compare their viscoelastic properties. The proposed method allowed for identifying the characteristic parameters needed for describing the behavior of each sample, permitting us to quantitatively compare their mechanical behaviors. All samples showed load relaxation at a defined indentation depth because of their intrinsic viscoelastic behaviors, and the GelMA samples showed the highest relaxation capabilities. The distribution of the characterization parameters showed that the biological samples presented similar time-dependent responses, while differences were observed in the GelMA samples. Overall, the proposed methodological approach allows for providing key insights into the time-dependent behaviors of soft biological tissues and hydrogels at the cell-length scale in view of supporting tissue engineering and pathophysiological investigations. [ABSTRACT FROM AUTHOR]

Abstract Background Aurora kinase A (AURKA) is a member of serine/threonine kinase family. Several kinases belonging to this family are activated in the G2/M phase of the cell cycle being involved in mitotic chromosomal segregation. AURKA overexpression is significantly associated with neoplastic transformation in several tumors and deregulated Aurora Kinases expression leads to chromosome instability, thus contributing to cancer progression. The purpose of the present study was to investigate the expression of AURKA in non small cell lung cancer (NSCLC) specimens and to correlate its mRNA or protein expression with patients' clinico-pathological features. Materials and methods Quantitative real-time PCR and immunohistochemistry analysis on matched cancer and corresponding normal tissues from surgically resected non-small cell lung cancers (NSCLC) have been performed aiming to explore the expression levels of AURKA gene. Results AURKA expression was significantly up-modulated in tumor samples compared to matched lung tissue (p < 0.01, mean log2(FC) = 1.5). Moreover, AURKA was principally up-modulated in moderately and poorly differentiated lung cancers (p < 0.01), as well as in squamous and adenocarcinomas compared to the non-invasive bronchioloalveolar histotype (p = 0.029). No correlation with survival was observed. Conclusion These results indicate that in NSCLC AURKA over-expression is restricted to specific subtypes and poorly differentiated tumors.

Objectives: Somatic mosaicism of PIK3CA gene is currently recognized as the molecular driver of Klippel–Trenaunay syndrome. However, given the limitation of the current technologies, PIK3CA somatic mutations are detected only in a limited proportion of Klippel–Trenaunay syndrome cases and tissue biopsy remains an invasive high risky, sometimes life-threatening, diagnostic procedure. Next generation sequencing liquid biopsy using cell-free DNA has emerged as an innovative non-invasive approach for early detection and monitoring of cancer. This approach, overcoming the space-time profile constraint of tissue biopsies, opens a new scenario also for others diseases caused by somatic mutations. Methods: In the present study, we performed a comprehensive analysis of seven patients (four females and three males) with Klippel–Trenaunay syndrome. Blood samples from both peripheral and efferent vein from malformation were collected and cell-free DNA was extracted from plasma. Tissue biopsies from vascular lesions were also collected when available. Cell-free DNA libraries were performed using Oncomine™ Pan-Cancer Cell-Free Assay. Ion Proton for sequencing and Ion Reporter Software for analysis were used (Life Technologies, Carlsbad, CA, USA). Results: Cell-free circulating DNA analysis revealed pathogenic mutations in PIK3CA gene in all patients. The mutational load was higher in plasma obtained from the efferent vein at lesional site (0.81%) than in the peripheral vein (0.64%) leading to conclude for a causative role of the identified variants. Tissue analysis, available for one amputated patient, confirmed the presence of the mutation at the malformation site at a high molecular frequency (14–25%), confirming its causative role. Conclusions: Our data prove for the first time that the cell-free DNA-next generation sequencing–liquid biopsy, which is currently used exclusively in an oncologic setting, is indeed the most effective tool for Klippel–Trenaunay syndrome diagnosis and tailored personalized treatment. [ABSTRACT FROM AUTHOR]

Education is a complex process because of its influence in child's personality development. Above all subjects, Religion is the queen, the spring of all values the students can learn. Romanian society was separated from every religious act because of communism atheism. During the communism period, it was forbidden to speak about God and Religion within the school. Beginning from 1990, the things changed and the exuberance of the freedom of language and thought continued, as was normal, with the re-introduction of Religion into school. the icons resumed their place in classrooms, the teachers started to transfer the values. Everybody agrees that this subject influence beyond the classroom. Religion must be seen and treated as a link between school and family, the values go within the family and change behaviors, attitudes and lives. Many student's families transformed only as a influence of their children' life changing through orthodox values learned from school, from Religion hour, from Religion's teachers. A lot of mothers and fathers started to fast because of their children, started to go to church to pray. It was a blooming of spiritual life. Both the parents and children reinvent their life through Orthodoxy's values. This phenomenon was supported by orthodox literature and by mass media. [ABSTRACT FROM AUTHOR]

ATF2 is a transcription factor involved in stress and DNA damage. A correlation between ATF2 JNK-mediated activation and resistance to damaging agents has already been reported. The purpose of the present study was to investigate whether ATF2 may have a role in acquired resistance to cisplatin in non-small cell lung cancer (NSCLC). mRNA and protein analysis on matched cancer and corresponding normal tissues from surgically resected NSCLC have been performed. Furthermore, in NSCLC cell lines, ATF2 expression levels were evaluated and correlated to platinum (CDDP) resistance. Celastrol-mediated ATF2/cJUN activity was measured. High expression levels of both ATF2 transcript and proteins were observed in lung cancer specimens ( p << 0.01, Log2(FC) = +4.7). CDDP-resistant NSCLC cell lines expressed high levels of ATF2 protein. By contrast, Celastrol-mediated ATF2/cJUN functional inhibition restored the response to CDDP. Moreover, ATF2 protein activation correlates with worse outcome in advanced CDDP-treated patients. For the first time, it has been shown NSCLC ATF2 upregulation at both mRNA/protein levels in NSCLC. In addition, we reported that in NSCLC cell lines a correlation between ATF2 protein expression and CDDP resistance occurs. Altogether, our results indicate a potential increase in CDDP sensitivity, on Celastrol-mediated ATF2/cJUN inhibition. These data suggest a possible involvement of ATF2 in NSCLC CDDP-resistance. [ABSTRACT FROM AUTHOR]

Background: Aurora kinase A (AURKA) is a member of serine/threonine kinase family. Several kinases belonging to this family are activated in the G2/M phase of the cell cycle being involved in mitotic chromosomal segregation. AURKA overexpression is significantly associated with neoplastic transformation in several tumors and deregulated Aurora Kinases expression leads to chromosome instability, thus contributing to cancer progression. The purpose of the present study was to investigate the expression of AURKA in non small cell lung cancer (NSCLC) specimens and to correlate its mRNA or protein expression with patients' clinico-pathological features.Materials and Methods: Quantitative real-time PCR and immunohistochemistry analysis on matched cancer and corresponding normal tissues from surgically resected non-small cell lung cancers (NSCLC) have been performed aiming to explore the expression levels of AURKA gene.Results: AURKA expression was significantly up-modulated in tumor samples compared to matched lung tissue (p<0.01, mean log2(FC)=1.5). Moreover, AURKA was principally up-modulated in moderately and poorly differentiated lung cancers (p<0.01), as well as in squamous and adenocarcinomas compared to the non-invasive bronchioloalveolar histotype (p=0.029). No correlation with survival was observed.Conclusion: These results indicate that in NSCLC AURKA over-expression is restricted to specific subtypes and poorly differentiated tumors. [ABSTRACT FROM AUTHOR]