Genome-Wide Transcriptional Reorganization Associated with Senescence-to-Immortality Switch during Human Hepatocellular Carcinogenesis

Cataloged from PDF version of article.Senescence is a permanent proliferation arrest in response to cell stress such as DNA damage. It contributes strongly to tissue aging and serves as a major barrier against tumor development. Most tumor cells are believed to bypass the senescence barrier (become "immortal") by inactivating growth control genes such as TP53 and CDKN2A. They also reactivate telomerase reverse transcriptase. Senescence-to-immortality transition is accompanied by major phenotypic and biochemical changes mediated by genome-wide transcriptional modifications. This appears to happen during hepatocellular carcinoma (HCC) development in patients with liver cirrhosis, however, the accompanying transcriptional changes are virtually unknown. We investigated genome-wide transcriptional changes related to the senescence-to-immortality switch during hepatocellular carcinogenesis. Initially, we performed transcriptome analysis of senescent and immortal clones of Huh7 HCC cell line, and identified genes with significant differential expression to establish a senescence-related gene list. Through the analysis of senescence-related gene expression in different liver tissues we showed that cirrhosis and HCC display expression patterns compatible with senescent and immortal phenotypes, respectively; dysplasia being a transitional state. Gene set enrichment analysis revealed that cirrhosis/senescence-associated genes were preferentially expressed in non-tumor tissues, less malignant tumors, and differentiated or senescent cells. In contrast, HCC/immortality genes were up-regulated in tumor tissues, or more malignant tumors and progenitor cells. In HCC tumors and immortal cells genes involved in DNA repair, cell cycle, telomere extension and branched chain amino acid metabolism were up-regulated, whereas genes involved in cell signaling, as well as in drug, lipid, retinoid and glycolytic metabolism were down-regulated. Based on these distinctive gene expression features we developed a 15-gene hepatocellular immortality signature test that discriminated HCC from cirrhosis with high accuracy. Our findings demonstrate that senescence bypass plays a central role in hepatocellular carcinogenesis engendering systematic changes in the transcription of genes regulating DNA repair, proliferation, differentiation and metabolism

How has internet addiction research evolved since the advent of internet gaming disorder? An overview of cyberaddictions from a psychological perspective

During the past two decades, Internet addiction (IA) has been the most commonly used term in research into online activities and their influence on the development of behavioral addictions. The aim of this review is to assess the impact of the concept of Internet gaming disorder (IGD), proposed by the American Psychiatric Association, on the scientific literature regarding IA. It presents a bibliometric analysis of the IA literature starting from the time IGD was first proposed, with the objective of observing and comparing the topics that have arisen during this period among the different IA themes researched. The findings demonstrate a steady evolution, particularly regarding publications related to the general aspects of IA: its clinical component, its prevalence and psychometric measures, the growing interest in the contextual factors promoting this addictive behavior, scientific progress in its conceptualization based on existing theoretical models, and neuropsychological studies. Nevertheless, many of the studies (22 %) focus on specific IA behaviors and show heterogeneity among the cyberaddictions, with online gaming (related to IGD) most common, followed by cybersex and social networking. Although research on the general concept of IA continues, investigators have begun to pay attention to the diverse spectrum of specific cyberaddictions and their psychological components

Chitosan/Octadecylamine-Montmorillonite Nanocomposite Containing Nigella arvensis Extract as Improved Antimicrobial Biofilm Against Foodborne Pathogens

The objective of this study was to develop inexpensive and facile nanocomposites based on chitosan and organo-clay with the antimicrobial affectivity that provide the serious challenges caused by bacterial infections in various products such as food packaging materials. The chitosan with octadecylamine montmorillonite (ODA-MMT) nanocomposites by supplementing 1, 2.5, and 5 w% Nigella arvensis seed (black cumin) extract (CMBC-1, CMBC-2.5, and CMBC-5) were prepared chitosan from ionic liquid solutions in the presence of ODA-MMT and black cumin extract suspension. The effect of black cumin with different content on the structure and antimicrobial activity of the nanocomposite have been investigated. The interactions between the chitosan matrix, ODA-MMT, and black cumin extract at different conditions were characterized both physicochemically (FT-IR, SEM, and XRD) and biologically (antimicrobial). The results indicated that the formation of exfoliated nanostructure of nanocomposites was provided by loading of nanodispersed clay in matrix. Antimicrobial activity of CMBC nanocomposite film was evaluated using disc diffusion method against Gram-negative bacteria Escherichia coli ATCC 25922 and Salmonella enterica serotype Typhimurium SL 1344 and Gram-positives Staphylococcus aureus ATCC 25923 and Streptococcus mutans ATCC 25175. The antimicrobial activity studies of the CMBCs illustrated that the nanocomposites could more strongly inhibit the growth of the tested Gram-negative bacteria than Gram-positive bacteria within increased content of black cumin from 1 to 5 w%. To our knowledge, this is the first report on the antimicrobial effect of CMBC nanocomposite film. Such biomaterials within nontoxic and inexpensive properties will thus have great potential applications in the development of new packing materials that can effectively prevent the antimicrobial formation. [Figure not available: see fulltext.] © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Rapid reduction of pentavalent antimony by trypanothione: Potential relevance to antimonial activation

The dithiol trypanothione can reduce an antiparasitic pentavalent antimony agent to trivalent rapidly; this reduction process is both pH and temperature dependent and trypanothione may therefore play an important role in the activation of the drug.link_to_subscribed_fulltex

Complexation of antimony (SbV) with guanosine 5′-monophosphate and guanosine 5′-diphospho-D-mannose: Formation of both mono- and bis-adducts

In spite of the extensive use of pentavalent antimony chemotherapy, the mechanism of its anti-leishmania action is still not clear. Here, we report the interactions of SbV, including the clinically used drug stibogluconate, with guanosine 5′-monophosphate (5′-GMP) and guanosine 5′-diphospho-d-mannose (5′-GDP-mannose) in aqueous solution. The deprotonated hydroxyl groups (-OH) of the ribose ring are shown to be the binding site for SbV, probably via chelation. Both mono- and bis-adducts were formed as determined by NMR, high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (ESI-MS), and both of them are stable in the pH range of 4 to around 9.5. The formation of the mono-adduct (k1 = 1.67 × 10-3 and 3.43 × 10-3 mM-1 min-1 for Sb(5′-GMP) and Sb(5′-GDP-mannose), respectively, at 298 K) was 10-fold faster than that of the bis-adduct (k2 = 0.16 × 10-3 and 0.21 × 10-3 mM-1 min-1, for Sb(5′-GMP) 2 and Sb(5′-GDP-mannose)2, respectively), and the mono-adduct was the major species in solution with the [bis-adduct]/[mono- adduct] < 0.5. The reactions of stibogluconate with 5′-GMP and 5′-GDP-mannose were slower than that of antimonate under similar conditions. © 2005 Elsevier Inc. All rights reserved.link_to_subscribed_fulltex