Selective Hyper-responsiveness of the Interferon System in Major Depressive Disorders and Depression Induced by Interferon Therapy

Though an important percentage of patients with chronic hepatitis C virus (HCV) undergoing interferon (IFN) therapy develop depressive symptoms, the role of the IFN system in the pathogenesis of depressive disorders is not well understood.50 patients with HCV infection were treated with standard combination therapy (pegylated IFN-α2a/ribavirin). IFN-induced gene expression was analyzed to identify genes which are differentially regulated in patients with or without IFN-induced depression. For validation, PBMC from 22 psychiatric patients with a severe depressive episode (SDE) and 11 controls were cultivated in vitro with pegylated IFN-α2a and gene expression was analyzed.IFN-induced depression in HCV patients was associated with selective upregulation of 15 genes, including 6 genes that were previously described to be relevant for major depressive disorders or neuronal development. In addition, increased endogenous IFN-production and selective hyper-responsiveness of these genes to IFN stimulation were observed in SDE patients.Our data suggest that selective hyper-responsiveness to exogenous (IFN therapy) or endogenous (depressive disorders) type I IFNs may lead to the development of depressive symptoms. These data could lead to the discovery of novel therapeutic approaches to treat IFN-induced and major depressive disorders

Fizikalni mehanizmi i metode u tumorskim terapijama i prijenosu lijekova do tumora

In addition to several well-known drug delivery strategies developed to facilitate effective chemotherapy with anticancer agents, some new approaches have been recently established, based on specific effects arising from the applications of ultrasound, magnetic and electric fields on drug delivery systems. This paper gives an overview of newly developed methods of drug delivery to tumors and of the related anticancer therapies based on the combined use of different physical methods and specific drug carriers. The conventional strategies and new approaches have been put into perspective to revisit the existing and to propose new directions to overcome the threatening problem of cancer diseases.Osim dobro poznatih metoda prijenosa lijekova u kemoterapijskom pristupu liječenja tumora, nedavno su otkriveni novi načini prijenosa koji se zasnivaju na specifičnim mehanizmima uzrokovanim upotrebom ultrazvuka, magnetskih i električnih polja. Članak sadrži prikaz fizikalnih mehanizama na kojima se temelje ove nove metode, kao i pregled novootkrivenih prijenosnika lijekova (Pluronske micele, magnetoliposomi, magnetski fluidi), novih terapija tumora (magnetska hipertermija, elektrokemoterapija) i najnovijih istraživanja temeljenih na fizikalnom pristupu ovoj problematici

Ancient pigs reveal a near-complete genomic turnover following their introduction to Europe

Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process