A class of discretely defined positive linear operators satisfying DeVore-Gopengauz inequalities

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Metformin plus PIAF combination chemotherapy for hepatocellular carcinoma

Objectives: Metformin, the most used oral antidiabetic drug for the treatment of type 2 diabetus mellitus, has proved encouraging results when used in the treatment of various types of cancer such as triple-negative breast cancer. Despite compelling evidence of a role of metformin as an anticancer drug, the mechanisms by which metformin exerts its oncostatic actions are not fully understood yet. Therefore, we tried to bring new insights by analyzing the anti-neoplastic effect of metformin for hepatocellular carcinoma-derived stem-like cells treated with conventional combination chemotherapy. Methods: Cancer stem-like cells previusly isolated from a hepatocellular carcinoma biopsy were treated with metformin, PIAF chemotherapy regimen and the combination of these two protocols. Measurements of lipid peroxidation, reduced glutathione, fluorescein diacetate and proliferation rates were determined, apart from the autophagy assay and apoptosis determination by chip flow cytometry. Results: Metformin alone and especially metformin in association with PIAF increases oxidative stress within the cells by increasing the levels of lipid peroxids as well as decreasing the levels of reduced glutathione. The MTT cell proliferation assay showed decreased prolife­ration rates for the arm treated with metformin and with the combination of drugs in comparison with the control arm, proving high correlation with the oxidative stress results. The autophagy assay and determination of apoptosis by chip flow cytometry confirmed the results obtained in the previous assays. Conclusion: Metformin could be used in chemotherapy treatments to induce reactive oxygen species and increase the cytostatics effects within the tumor cell. Still, further experiments must be carried out on murine models before we can move on and use this drugs in the adjuvant setting for unresectable primary liver cancer

Metformin delivery using chitosan-capped gold nanoparticles in glioblastoma cell lines

Introduction: Metformin (MET), an old anti-diabetic drug, has proven unexpected anti-glioblastoma effects, by impacting cell proliferation, migration and invasion. However, its remarkable anti-cancer efficacy is mainly limited to the use of high millimolar concentrations in in vitro studies, which are hard to be attained in the clinical setting. Aim: The aim of this paper was to synthetize gold nanoparticles loaded with MET and to test if an enhanced drug delivery via nanotechnology could overcome the limitations of small drug concentrations. Materials and Methods: Gold nanoparticles were functionalized with chitosan (GNPc) and loaded with 80 µM of MET. Their size, zeta potential and stability were characterized and their internalization within tumor cells was assayed through dark field microscopy. Three primary glioblastoma stem cell lines were treated with 5, 10 and 20 µg/mL concentrations of nanoparticles and irradiated. The anti-tumoral effect was evaluated through the MTT cell viability assay. Results: MET-GNPc are easily synthetized and have a positive zeta potential, spherical shape and a median size of 26 nm. MET-GNPc have an increased cell internalization and affect the viability of all three glioblastoma cell lines used compared to control and free MET. However, their anti-cancer effect is not statistically different when compared to GNPc, although a slight tendency to a better response may be observed. Conclusion:Despite an increased cell internalization, the small micromolar concentrations of metformin does not bring an additional benefit to chitosan-based GNPs. Novel delivery methods being able to carry a higher drug concentration of metformin should be tested

Two transgenic mouse models for beta subunit components of succinate-CoA ligase yielding pleiotropic metabolic alterations

Succinate-CoA ligase is a heterodimer enzyme composed of Suclg1 -alpha- and a substrate-specific Sucla2 or Suclg2 -beta- subunit yielding ATP or GTP, respectively. In humans, the deficiency of this enzyme leads to encephalomyopathy with, or without methylmalonyl aciduria, in addition to resulting in mitochondrial DNA depletion. We generated mice lacking either one Sucla2 or Suclg2 allele. Sucla2 heterozygote mice exhibited tissue- and age-dependent decreases in Sucla2 expression associated with decreases in ATP-forming activity, but rebound increases in cardiac Suclg2 expression and GTP-forming activity. Bioenergetic parameters including substrate-level phosphorylation were not different between wild type and Sucla2 heterozygote mice unless a submaximal pharmacological inhibition of succinate-CoA ligase was concomitantly present. mtDNA contents were moderately decreased, but blood carnitine esters were significantly elevated. Suclg2 heterozygote mice exhibited decreases in Suclg2 expression but no rebound increases in Sucla2 expression or changes in bioenergetic parameters. Surprisingly, deletion of one Suclg2 allele in Sucla2 heterozygote mice still led to a rebound but protracted increase in Suclg2 expression, yielding double heterozygote mice with no alterations in GTP-forming activity or substrate-level phosphorylation, but more pronounced changes in mtDNA content and blood carnitine esters, and an increase in succinate dehydrogenase activity. We conclude that a partial reduction in Sucla2 elicits rebound increases in Suclg2 expression which is sufficiently dominant to overcome even a concomitant deletion of one Suclg2 allele, pleiotropically affecting metabolic pathways associated with succinate-CoA ligase. These results as well as the availability of the transgenic mouse colonies will be of value in understanding succinate-CoA ligase deficiency

Scapegoat Pathology

Is it possible to live without conflicts? Individuals and groups of individuals are often scapegoated to resolve conflicts and crisis. Based on previous research, it is argued that when a person or group is scapegoated (bullied) for a significant period of time, the individual or group is in danger of developing a certain pathology, named scapegoat pathology in this dissertation. A Global Assessment of Scapegoat Health (GASH) is proposed. It is also argued that there is a high risk that scapegoat pathology permeates the culture of the scapegoated group, and if the individuals of the group do not develop and maintain a healthy (collective) identity and (master) narrative(s), then they will develop a maladaptive and pathological culture. Scapegoated cultures were contrasted and used as examples to illustrate the arguments of the dissertation. Special attention was paid to Hungarians and Hungarian culture. Finally, an argument is made for specific interventions to address scapegoat pathology and maladaptive (pathological) cultures resulting from scapegoating, bullying, and mobbing

The sociolinguistic reality of writers from the Expanding Circle: A new English literature

Nowadays, poets and novelists from all over the world might choose to write in English, regardless of their native tongues, and those in the Expanding Circle of World Englishes are no exception. This study proposes that a new branch of English literature is currently forming through the works of authors who live and work in contexts in which English is taught as a foreign language (EFL) and who choose English as their creative communication tool. This claim is based on extended interviews with eight writers (representing Argentina, Indonesia, Israel, Italy, Mongolia, and Thailand) who differ from their English-using counterparts in the post-colonial contexts of the Outer Circle in such concerns as themes, audience, goals; choice of English over another language or translation; venues for publication; attitudes toward English; and style and code-switching. Given the resulting map of the sociolinguistic reality of these writers, it is argued that yet another distinctive branch of new literatures in English is emerging that further studies will show to be deserving of recognition and inclusion among known English literatures

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Master in Business Administration (MBA) - Nord universitet 202