Transfected poly(I:C) activates different dsRNA receptors leading to apoptosis or immunoadjuvant response in androgen-independent prostate cancer cells

Background: Castration-resistant prostate cancer (CRPC) is refractory to chemo-radiotherapy. Results: Transfection of the synthetic analog of dsRNA poly(I:C) simultaneously stimulates apoptosis and IFN- expression through different pathways in androgen-independent prostate cancer (PCa) cells. Conclusion: Dual parallel pathways triggered by distinct receptors activate direct and immunologically mediated antitumor effects in advanced PCa. Significance: The proapoptotic/immunoadjuvant poly(I:C)-Lipofectamine complex may offer new therapeutic insights into CRPC

The adherent/invasive escherichia coli (AIEC) strain LF82 invades and persists in human prostate cell lineRWPE-1 activating a strong inflammatory response

Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect prostate cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 prostate cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within prostate epithelial cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-κB already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary trac

Tumor Necrosis Factor-α Induces Interleukin-6 Production and Integrin Ligand Expression by Distinct Transduction Pathways

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that elicits a large number of biological effects. However, the intracellular signaling mechanisms that are responsible for the TNF-alpha effects remain largely unknown. We have previously demonstrated that cultured mouse Sertoli cells, after TNF-alpha treatment, increase the surface expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and interleukin-6 (IL-6) production (Riccioli, A., Filippini, A., De Cesaris, P., Barbacci, E., Stefanini, M., Starace, G., and Ziparo, E. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 5808-5812). Here, we show that, in cultured Sertoli cells, TNF-alpha activates the mitogen-activated protein kinase pathway (p38, c-Jun N-terminal protein kinase/stress-activated protein kinase, and the p42/p44 mitogen-activated protein kinases) as revealed by an increased phosphorylation of p38, activating transcription factor-2, c-Jun, and Elk-1. Furthermore, our data indicate that the biological effects induced by TNF-alpha in Sertoli cells (enhancement of ICAM-1, VCAM-1, and IL-6 expression) depend on the activation of different signaling pathways. SB203580, a highly specific p38 inhibitor, does not affect ICAM-1 and VCAM-1 expression, but strongly inhibits IL-6 production. Moreover, interferon-gamma, which up-regulates adhesion molecule expression and reduces IL-6 production, does not induce phosphorylation of p38. Our data strongly support the hypothesis that, in response to TNF-alpha, activation of p38 leads to IL-6 production, whereas ICAM-1 and VCAM-1 expression could be induced by activation of the c-Jun N-terminal protein kinase/stress-activated protein kinase pathway

Circular RNAs in embryogenesis and cell differentiation with a focus on cancer development

In the recent years thousands of non-coding RNAs have been identified, also thanks to highthroughput sequencing technologies. Among them, circular RNAs (circRNAs) are a well-represented class characterized by the high sequence conservation and cell type specific expression in eukaryotes. They are covalently closed loops formed through back-splicing. Recently, circRNAs were shown to regulate a variety of cellular processes functioning as miRNA sponges, RBP binding molecules, transcriptional regulators, scaffold for protein translation, as well as immune regulators. A growing number of studies are showing that deregulated expression of circRNAs plays important and decisive actions during the development of several human diseases, including cancer. The research on their biogenesis and on the various molecular mechanisms in which they are involved is going very fast, however, there are still few studies that address their involvement in embryogenesis and eukaryotic development. This review has the intent to describe the most recent progress in the study of the biogenesis and molecular activities of circRNAs providing insightful information in the field of embryogenesis and cell differentiation. In addition, we describe the latest research on circRNAs as novel promising biomarkers in diverse types of tumors

The PI3K/AKT pathway is activated by HGF in NT2D1 non-seminoma cells and has a role in the modulation of their malignant behavior

Overactivation of the c-MET/HGF system is a feature of many cancers. We previously reported that type II testicular germ cell tumor (TGCT) cells express the c-MET receptor, forming non-seminomatous lesions that are more positive compared with seminomatous ones. Notably, we also demonstrated that NT2D1 non-seminomatous cells (derived from an embryonal carcinoma lesion) increase their proliferation, migration, and invasion in response to HGF. Herein, we report that HGF immunoreactivity is more evident in the microenvironment of embryonal carcinoma biopsies with respect to seminomatous ones, indicating a tumor-dependent modulation of the testicular niche. PI3K/AKT is one of the signaling pathways triggered by HGF through the c-MET activation cascade. Herein, we demonstrated that phospho-AKT increases in NT2D1 cells after HGF stimulation. Moreover, we found that this pathway is involved in HGF-dependent NT2D1 cell proliferation, migration, and invasion, since the co-administration of the PI3K inhibitor LY294002 together with HGF abrogates these responses. Notably, the inhibition of endogenous PI3K affects collective cell migration but does not influence proliferation or chemotactic activity. Surprisingly, LY294002 administered without the co-administration of HGF increases cell invasion at levels comparable to the HGF-administered samples. This paradoxical result highlights the role of the testicular microenvironment in the modulation of cellular responses and stimulates the study of the testicular secretome in cancer lesions

Modeling the influence of alternative forest management scenarios on wood production and carbon storage: A case study in the Mediterranean region

Forest ecosystems are fundamental for the terrestrial biosphere as they deliver multiple essential ecosystem services (ES). In environmental management, understanding ES distribution and interactions and assessing the economic value of forest ES represent future challenges. In this study, we developed a spatially explicit method based on a multi-scale approach (MiMoSe-Multiscale Mapping of ecosystem services) to assess the current and future potential of a given forest area to provide ES. To do this we modified and improved the InVEST model in order to adapt input data and simulations to the context of Mediterranean forest ecosystems. Specifically, we integrated a GIS-based model, scenario model, and economic valuation to investigate two ES (wood production and carbon sequestration) and their trade-offs in a test area located in Molise region (Central Italy). Spatial information and trade-off analyses were used to assess the influence of alternative forest management scenarios on investigated services. Scenario A was designed to describe the current Business as Usual approach. Two alternative scenarios were designed to describe management approaches oriented towards nature protection (scenario B) or wood production (scenario C) and compared to scenario A. Management scenarios were simulated at the scale of forest management units over a 20-year time period. Our results show that forest management influenced ES provision and associated benefits at the regional scale. In the test area, the Total Ecosystem Services Value of the investigated ES increases 85% in scenario B and decreases 82% in scenario C, when compared to scenario A. Our study contributes to the ongoing debate about trade-offs and synergies between carbon sequestration and wood production benefits associated with socio-ecological systems. The MiMoSe approach can be replicated in other contexts with similar characteristics, thus providing a useful basis for the projection of benefits from forest ecosystems over the futureL'articolo è disponibile sul sito dell'editore www.elsevier.com/locate/envre

Modeling the influence of alternative forest management scenarios on wood production and carbon storage: A case study in the Mediterranean region

Forest ecosystems are fundamental for the terrestrial biosphere as they deliver multiple essential ecosystem services (ES). In environmental management, understanding ES distribution and interactions and assessing the economic value of forest ES represent future challenges. In this study, we developed a spatially explicit method based on a multi-scale approach (MiMoSe-Multiscale Mapping of ecosystem services) to assess the current and future potential of a given forest area to provide ES. To do this we modified and improved the InVEST model in order to adapt input data and simulations to the context of Mediterranean forest ecosystems. Specifically, we integrated a GIS-based model, scenario model, and economic valuation to investigate two ES (wood production and carbon sequestration) and their trade-offs in a test area located in Molise region (Central Italy). Spatial information and trade-off analyses were used to assess the influence of alternative forest management scenarios on investigated services. Scenario A was designed to describe the current Business as Usual approach. Two alternative scenarios were designed to describe management approaches oriented towards nature protection (scenario B) or wood production (scenario C) and compared to scenario A. Management scenarios were simulated at the scale of forest management units over a 20-year time period. Our results show that forest management influenced ES provision and associated benefits at the regional scale. In the test area, the Total Ecosystem Services Value of the investigated ES increases 85% in scenario B and decreases 82% in scenario C, when compared to scenario A. Our study contributes to the ongoing debate about trade-offs and synergies between carbon sequestration and wood production benefits associated with socio-ecological systems. The MiMoSe approach can be replicated in other contexts with similar characteristics, thus providing a useful basis for the projection of benefits from forest ecosystems over the futureL'articolo è disponibile sul sito dell'editore www.elsevier.com/locate/envre

Mapping and assessment of forest ecosystems and their services - Applications and guidance for decision making in the framework of MAES

The aim of this report is to illustrate by means of a series of case studies the implementation of mapping and assessment of forest ecosystem services in different contexts and geographical levels. Methodological aspects, data issues, approaches, limitations, gaps and further steps for improvement are analysed for providing good practices and decision making guidance. The EU initiative on Mapping and Assessment of the state of Ecosystems and their Services (MAES), with the support of all Member States, contributes to improve the knowledge on ecosystem services. MAES is one of the building-block initiatives supporting the EU Biodiversity Strategy to 2020.JRC.H.3-Forest Resources and Climat