198,161 research outputs found
Simile, M.M., Pagnan, G., De Miglio, M.R., Muroni, M.R., Asara, G., Frau, M., Seddaiu M.A., Feo, F., Ponzoni, M., and Pascale, R.M
No full textAlterations of methionine metabolism as potential targets for the prevention and therapy of hepatocellular carcinoma
No full textSeveral researchers have analyzed the alterations of the methionine cycle associated with liver disease to clarify the pathogenesis of human hepatocellular carcinoma (HCC) and improve the preventive and the therapeutic approaches to this tumor. Different alterations of the methionine cycle leading to a decrease of S-adenosylmethionine (SAM) occur in hepatitis, liver steatosis, liver cirrhosis, and HCC. The reproduction of these changes inMAT1A-KO mice, prone to develop hepatitis and HCC, demonstrates the pathogenetic role of MAT1A gene under-regulation associated with up-regulation of the MAT2A gene (MAT1A:MAT2A switch), encoding the SAM synthesizing enzymes, methyladenosyltransferase I/III (MATI/III) and methyladenosyltransferase II (MATII), respectively. This leads to a rise of MATII, inhibited by the reaction product, with a consequent decrease of SAM synthesis. Attempts to increase the SAM pool by injecting exogenous SAM have beneficial effects in experimental alcoholic and non-alcoholic steatohepatitis and hepatocarcinogenesis. Mechanisms involved in hepatocarcinogenesis inhibition by SAM include: (1) antioxidative effects due to inhibition of nitric oxide (NO•) production, a rise in reduced glutathione (GSH) synthesis, stabilization of the DNA repair protein Apurinic/Apyrimidinic Endonuclease 1 (APEX1); (2) inhibition of c-myc, H-ras, and K-ras expression, prevention of NF-kB activation, and induction of overexpression of the oncosuppressor PP2A gene; (3) an increase in expression of the ERK inhibitor DUSP1; (4) inhibition of PI3K/AKT expression and down-regulation of C/EBPα and UCA1 gene transcripts; (5) blocking LKB1/AMPK activation; (6) DNA and protein methylation. Different clinical trials have documented curative effects of SAM in alcoholic liver disease. Furthermore, SAM enhances the IFN-α antiviral activity and protects against hepatic ischemia-reperfusion injury during hepatectomy in HCC patients with chronic hepatitis B virus (HBV) infection. However, although SAM prevents experimental tumors, it is not curative against already established experimental and human HCCs. The recent observation that the inhibition of MAT2A and MAT2B expression by miRNAs leads to a rise of endogenous SAM and strong inhibition of cancer cell growth could open new perspectives to the treatment of HCC
Diplosoma simile
No full textDiplosoma simile (Sluiter, 1909) Leptoclinum simile Sluiter, 1909: 77. Type locality: Indonesia. Diplosoma similis – Monniot F. & Monniot C. 1996: 170, Indonesia. MATERIAL EXAMINED. — Palau. Ngiwal, 7°31.43’N, 134°37.66’E, 1 m, 8. V.1996 (MNHN A 2 DIP. A 141). — Koror, Ngermeumangel Island, E side, 7°19.60’N, 134°30.84’E, 1 m, 27.XI.1996 (MNHN A 2 DIP. A 140).Published as part of Monniot, Françoise & Monniot, Claude, 2001, Ascidians from the tropical western Pacific, pp. 201-383 in Zoosystema 23 (2) on page 279, DOI: 10.5281/zenodo.539144
Induction by human interferon and murine h-2l(d) gene of the surface expression of endogenous hla class-I free heavy-chains in hct human colon-carcinoma cells, deficient in Beta-2-microglobulin
No full textLucifuga simile Nalbant 1981
No full text<p>Lucifuga simile Nalbant, 1981:</p> <p>ZMH 9518, 87.5 mm SL, male, Cuba.</p>Published as part of <i>Peter R. Møller, Werner Schwarzhans, Thomas M. Iliffe & Jørgen G. Nielsen, 2006, Revision of the Bahamian cave-fishes of the genus Lucifuga (Ophidiiformes, Bythitidae), with description of a new species from islands on the Little Bahama Bank., pp. 23-46 in Zootaxa 1223</i> on page 2
The warburg effect 97 years after its discovery
No full textThe deregulation of the oxidative metabolism in cancer, as shown by the increased aerobic glycolysis and impaired oxidative phosphorylation (Warburg effect), is coordinated by genetic changes leading to the activation of oncogenes and the loss of oncosuppressor genes. the understanding of the metabolic deregulation of cancer cells is necessary to prevent and cure cancer. in this review, we illustrate and comment the principal metabolic and molecular variations of cancer cells, involved in their anomalous behavior, that include modifications of oxidative metabolism, the activation of oncogenes that promote glycolysis and a decrease of oxygen consumption in cancer cells, the genetic susceptibility to cancer, the molecular correlations involved in the metabolic deregulation in cancer, the defective cancer mitochondria, the relationships between the Warburg effect and tumor therapy, and recent studies that reevaluate the Warburg effect. Taken together, these observations indicate that the Warburg effect is an epiphenomenon of the transformation process essential for the development of malignancy
S-Adenosylmethionine: From the Discovery of Its Inhibition of Tumorigenesis to Its Use as a Therapeutic Agent
No full textAlterations of methionine cycle in steatohepatitis, cirrhosis, and hepatocellular carcinoma induce MAT1A decrease and MAT2A increase expressions with the consequent decrease of S-adenosyl-L-methionine (SAM). This causes non-alcoholic fatty liver disease (NAFLD). SAM administration antagonizes pathological conditions, including galactosamine, acetaminophen, and ethanol intoxications, characterized by decreased intracellular SAM. Positive therapeutic effects of SAM/vitamin E or SAM/ursodeoxycholic acid in animal models with NAFLD and intrahepatic cholestasis were not confirmed in humans. In in vitro experiments, SAM and betaine potentiate PegIFN-alpha-2a/2b plus ribavirin antiviral effects. SAM plus betaine improves early viral kinetics and increases interferon-stimulated gene expression in patients with viral hepatitis non-responders to pegIFN alpha/ribavirin. SAM prevents hepatic cirrhosis, induced by CCl4, inhibits experimental tumors growth and is proapoptotic for hepatocellular carcinoma and MCF-7 breast cancer cells. SAM plus Decitabine arrest cancer growth and potentiate doxorubicin effects on breast, head, and neck cancers. Furthermore, SAM enhances the antitumor effect of gemcitabine against pancreatic cancer cells, inhibits growth of human prostate cancer PC-3, colorectal cancer, and osteosarcoma LM-7 and MG-63 cell lines; increases genomic stability of SW480 cells. SAM reduces colorectal cancer progression and inhibits the proliferation of preneoplastic rat liver cells in vivo. The discrepancy between positive results of SAM treatment of experimental tumors and modest effects against human disease may depend on more advanced human disease stage at moment of diagnosis
Cognitive translation analysis of fiction simile
No full textThis paper introduces a method of cognitive translation analysis of English-Ukrainian translation of fiction simile. Our analysis of Ukrainian and foreign research on fiction simile translation has revealed that such papers are mostly based on traditional structural-semantic translation analysis. Cognitive translation analysis of fiction simile, which allows identifying cognitive models that underpin simile functioning in speech and affect its translation, has been done in very few papers and therefore it requires developing. This paper aims at establishing correlations between linguacultural specificity or, conversely, similarity of cognitive models of English fiction similes and a choice of a translation strategy to render English similes into Ukrainian. The research sample consists of 1200 English similes, collected from D. Tartt’s novels, The Goldfinch and The Secret History, and M. Atwood’s novel, The Blind Assassin, and their Ukrainian translations, performed, respectively, by V. Shovkun, B. Stasiuk and O. Oksenych. Achieving this goal involves fulfilling the following tasks: 1) identifying and comparing cognitive models of English similes and their Ukrainian translations; 2) revealing translation procedures used to render fiction similes – retention, replacement, reduction, omission or addition; 3) establishing correlations between translation procedures and translation strategies – the foreignization strategy and the domestication strategy. A fiction simile is addressed as an explicit conceptual metaphor structured by a propositional model (A is like B), where A is the target concept / domain representing the entity that is compared, B is source the concept / domain representing the entity to which the target is compared (its language / speech instantiation is called a vehicle). Simile can also explicate the characteristic, which is the basis for comparison (A (target) is like B (source / conductor) by characteristic B). Conducting the translation analysis, we take into account the type of fiction simile. We distinguish between conventional simile, grounding on universal knowledge, and original simile, reflecting individual knowledge and creative imagination of an author. Among conventional similes, we differentiate between allusive similes that are mostly based on subcultural knowledge, and idiomatic similes that can be based on both universal and culturally specific knowledge embodied in idioms. Our cognitive translation analysis led to the following conclusions. Retention of similes realizes different translation strategies depending on the type of the simile and the presence / absence of its linguacultural specificity. Retention of conventional and original similes correlates with neutral translation strategy, as neither the former nor the latter has linguacultural specificity that would indicate the inconsistency of their cognitive models and thus constrain the translator's choice, causing a translation problem. Retention of allusive similes can also correlate with neutral strategy if the allusion is part of universal knowledge although more often retention of allusive simile realizes foreignization strategy as such similes are based on subculturally specific knowledge and thus rest on cognitive models that are unestablished in the minds of most representatives of both cultures. If a translator adds a commentary, foreignization is neutralized by domestication. Replacement, reduction, omission or addition of similes correlate with domestication, which can be compulsory if English and Ukrainian similes are based on different cultural cognitive models, or optional if they are based on similar cognitive models. Moreover, domestication can be complete if the simile cognitive model is replaced or partial if the concepts of the model are specified or explained, but the model remains unchanged. These results call for further research, specifically, conducting a quantitative analysis to establish quantitative correlations between the procedures and strategies of English-Ukrainian translation of fiction similes
Genetic Predisposition to Hepatocellular Carcinoma
No full textLiver preneoplastic and neoplastic lesions of the genetically susceptible F344 and resistant BN rats cluster, respectively, with human HCC with better (HCCB) and poorer prognosis (HCCP); therefore, they represent a valid model to study the molecular alterations determining the genetic predisposition to HCC and the response to therapy. The ubiquitin-mediated proteolysis of ERK-inhibitor DUSP1, which characterizes HCC progression, favors the unrestrained ERK activity. DUSP1 represents a valuable prognostic marker, and ERK, CKS1, or SKP2 are potential therapeutic targets for human HCC. In DN (dysplastic nodule) and HCC of F344 rats and human HCCP, DUSP1 downregulation and ERK1/2 overexpression sustain SKP2-CKS1 activity through FOXM1, the expression of which is associated with a susceptible phenotype. SAM-methyl-transferase reactions and SAM/SAH ratio are regulated by GNMT. In addition, GNMT binds to CYP1A, PARP1, and NFKB and PREX2 gene promoters. MYBL2 upregulation deregulates cell cycle and induces the progression of premalignant and malignant liver. During HCC progression, the MYBL2 transcription factor positively correlates with cells proliferation and microvessel density, while it is negatively correlated to apoptosis. Hierarchical supervised analysis, regarding 6132 genes common to human and rat liver, showed a gene expression pattern common to normal liver of both strains and BN nodules, and a second pattern is observed in F344 nodules and HCC of both strains. Comparative genetics studies showed that DNs of BN rats cluster with human HCCB, while F344 DNs and HCCs cluster with HCCP
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