87,033 research outputs found
Anti-mullerian hormone is expressed by endometriosis tissues and induces cell cycle arrest and apoptosis in endometriosis cells
No full textBackground: The anti-mullerian hormone (AMH) is a member of the transforming growth factor β (TGF-β) superfamily, which is responsible of the regression of the mullerian duct. AMH is expressed in the normal endometrium, where, acting in a paracrine fashion, negatively regulates cellular viability. Our objective was to evaluate the in vitro effects of the treatment with AMH of endometriosic cells. Methods. AMH expression in human endometriosis glands was evaluated by immunohistochemistry. RT-PCR has been used to quantify the expression levels of AMH and AMH RII isoforms, as well as of cytochrome P450 in both endometriosis epithelial and stromal cells Effects of AMH and AMH-cleaved treatment in endometriosis cells were evaluated by flow-cytometry analysis. Finally, it has been evaluated the effect of plasmin-digested AMH on cytochrome P450 activity. Results: AMH and AMH RII isoforms, as well as cytochrome P450, were expressed in both endometriosis epithelial and stromal cells. Treatment of endometriosis stromal and epithelial cell growth with AMH was able to induce a decrease in the percentage of cells in S phase and increase percentage of cells in G1 and G2 phase; coherently, decreased cell viability and increased percentage of cells death fraction was observed. The plasmin-digested AMH was able to suppress most of the cytochrome P450 activity, causing an increase of pre-G1 phase and of apoptosis induction treating with plasmin-digested AMH in both cell lines, most marked in the epithelial cells. Conclusions: The data produced suggest a possible use of AMH as therapeutic agents in endometriosis. © 2014 Signorile et al.; licensee BioMed Central Ltd
p38α, the β-catenin chromatin associated kinase, as promising target in colorectal cancer stem cells for personalized therapy
No full textColorectal cancer (CRC) is the third most frequent malignancy, but the second cause of death for tumor in the western population. Only 14% of patients with advanced and metastatic disease survive five years from diagnosis. Recently, it has been shown that tumor relapse and chemoresistance depend on a small population of cells, called cancer stem cells (CSCs). Current evidence indicates that the Wnt cascade is the main driver in controlling CSC fate; the key player in this pathway is β-catenin, a cytoplasmic protein whose stability is regulated by the so-called “destruction complex”. During carcinogenesis, the increasing amount of β-catenin resulting from APC inactivation translocates into the nucleus, causing the transcriptional activation of several mitogenic genes, including c-Myc. c-Myc is one of the most important factors involved in CRC initiation and progression; indeed, it functions as a link connecting malignancy with stemness. During colorectal carcinogenesis, c-Myc is maintained upregulated through β-catenin-mediated transcriptional activation and ERK-mediated post-translational stabilization. Our data showed that p38α, a kinase involved in CRC metabolism and survival, contributes to both mechanisms. Previous reports in other tissues provided evidence that Wnt3a can activate p38, and the p38 pathway feeds into the canonical Wnt/β-catenin pathway at least at the level of GSK3β. Our findings also highlighted that CRC cells and colorectal cancer stem cells (CRC-SCs) have higher levels of activated p38 than their normal counterparts, and experiments using kinase-specific inhibitors revealed that these cells are “addicted” to p38 activity. Importantly, we found that p38α co-immunoprecipitates with β-catenin in both normal and cancer cells; however, these proteins are confined to the cytoplasm in colonocytes, while they significantly occupy discrete nuclear regions in CRC cells, CRC-SCs, and in vivo models. These data were further corroborated by the inhibitory effect of p38α blockade on several β-catenin-responsive genes (i.e. c-Myc, cyclin D1/2, survivin, and others). This functional interaction was further characterized by chromatin immunoprecipitation experiments, which demonstrated that p38α is a chromatin-associated β-catenin kinase required for the transcriptional induction of several Wnt target genes, including c-Myc. Additionally, we demonstrated that p38α, like ERK, stabilizes c-Myc protein levels by preventing its ubiquitination. The finding that the phenotypes arising after APC loss in the intestine are fully dependent on c-Myc target gene expression suggests that c-Myc inhibition may be a good target for chemoprevention in CRC. These considerations underline the relevance of molecular profiling and preclinical investigation in order to achieve more efficient and accurate therapies. Indeed, our study identifies p38α as a promising therapeutic target acting directly on c-Myc and CRC-SCs, which are thought to be responsible for tumor proliferation, metastatic dissemination, and chemoresistance
Supplement_Table_2 – Supplemental material for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis
No full textSupplemental material, Supplement_Table_2 for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis by Meng Ni, Joseph B. Hazzard, Joseph F. Signorile and Corneliu Luca in Neurorehabilitation and Neural Repair</p
Supplement_Table_1 – Supplemental material for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis
No full textSupplemental material, Supplement_Table_1 for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis by Meng Ni, Joseph B. Hazzard, Joseph F. Signorile and Corneliu Luca in Neurorehabilitation and Neural Repair</p
PRISMA_Flow – Supplemental material for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis
No full textSupplemental material, PRISMA_Flow for Exercise Guidelines for Gait Function in Parkinson’s Disease: A Systematic Review and Meta-analysis by Meng Ni, Joseph B. Hazzard, Joseph F. Signorile and Corneliu Luca in Neurorehabilitation and Neural Repair</p
Il tempo dei castelli: popolamento, assetto dei poteri aristocratici e sviluppo signorile nel comitatus di Arezzo tra X e XII secolo
No full textIl tempo dei castelli: popolamento, assetto dei poteri aristocratici e sviluppo signorile nel comitatus di Arezzo tra X e XII secol
A fresh look at the nested soft-collinear subtraction scheme: NNLO QCD corrections to N-gluon final states in q q ¯ annihilation
No full textAbstract We describe how the nested soft-collinear subtraction scheme [1] can be used to compute the next-to-next-to-leading order (NNLO) QCD corrections to the production of an arbitrary number of gluonic jets in hadron collisions. We show that the infrared subtraction terms can be combined into recurring structures that in many cases are simple iterations of those terms known from next-to-leading order. The way that these recurring structures are identified and computed is fairly general, and can be applied to any partonic process. As an example, we explicitly demonstrate the cancellation of all singularities in the fully-differential cross section for the q q ¯ → X + Ng process at NNLO in QCD. The finite remainder of the NNLO QCD contribution, which arises upon cancellation of all ϵ-poles, is expressed via relatively simple formulas, which can be implemented in a numerical code in a straightforward way. Our approach can be extended to describe arbitrary processes at NNLO in QCD; the largest remaining challenge at this point is the combinatorics of quark and gluon collinear limits
LIVELLI DI TOSSICITà NELLE ACQUE REFLUE URBANE DEPURATE E NEI RELATIVI CORPI RECETTORI MARINI
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Oxidative damages to ocular structures in diabetic patients are related to retinal free radical production
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