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排序方式: 共有207条查询结果,搜索用时 11 毫秒
11.
12.
Massimo Dal Monte Maurizio Cammalleri Valeria Pecci Monica Carmosino Giuseppe Procino Alessandro Pini Mario De Rosa Vincenzo Pavone Maria Svelto Paola Bagnoli 《Journal of cellular and molecular medicine》2019,23(2):1034-1049
The urokinase‐type plasminogen activator (uPA) receptor (uPAR) participates to the mechanisms causing renal damage in response to hyperglycaemia. The main function of uPAR in podocytes (as well as soluble uPAR ‐(s)uPAR‐ from circulation) is to regulate podocyte function through αvβ3 integrin/Rac‐1. We addressed the question of whether blocking the uPAR pathway with the small peptide UPARANT, which inhibits uPAR binding to the formyl peptide receptors (FPRs) can improve kidney lesions in a rat model of streptozotocin (STZ)‐induced diabetes. The concentration of systemically administered UPARANT was measured in the plasma, in kidney and liver extracts and UPARANT effects on dysregulated uPAR pathway, αvβ3 integrin/Rac‐1 activity, renal fibrosis and kidney morphology were determined. UPARANT was found to revert STZ‐induced up‐regulation of uPA levels and activity, while uPAR on podocytes and (s)uPAR were unaffected. In glomeruli, UPARANT inhibited FPR2 expression suggesting that the drug may act downstream uPAR, and recovered the increased activity of the αvβ3 integrin/Rac‐1 pathway indicating a major role of uPAR in regulating podocyte function. At the functional level, UPARANT was shown to ameliorate: (a) the standard renal parameters, (b) the vascular permeability, (c) the renal inflammation, (d) the renal fibrosis including dysregulated plasminogen‐plasmin system, extracellular matrix accumulation and glomerular fibrotic areas and (e) morphological alterations of the glomerulus including diseased filtration barrier. These results provide the first demonstration that blocking the uPAR pathway can improve diabetic kidney lesion in the STZ model, thus suggesting the uPA/uPAR system as a promising target for the development of novel uPAR‐targeting approaches. 相似文献
13.
Enrico Baria Simone Morselli Suresh Anand Riccardo Fantechi Gabriella Nesi Mauro Gacci Marco Carini Sergio Serni Riccardo Cicchi Francesco S. Pavone 《Journal of biophotonics》2019,12(11)
Urothelial carcinoma (UC) is the most common bladder tumour. Proper treatment requires tumour resection for diagnosing its grade (aggressiveness) and stage (invasiveness). White‐light cystoscopy and histopathological examination are the gold standard procedures for clinical and histopathological diagnostics, respectively. However, cystoscopy is limited in terms of specificity, histology requires long tissue processing, both procedures rely on operator's experience. Multimodal optical spectroscopy can provide a powerful tool for detecting, staging and grading bladder tumours in a fast, reliable and label‐free modality. In this study, we collected fluorescence, Raman and reflectance spectra from 50 biopsies obtained from 32 patients undergoing transurethral resection of bladder tumour using a multimodal fibre‐probe. Principal component analysis allowed distinguishing normal from pathological tissues, as well as discriminating tumour stages and grades. Each individual spectroscopic technique provided high specificity and sensitivity in classifying all tissues; however, a multimodal approach resulted in a considerable increase in diagnostic accuracy (≥95%), which is of paramount importance for tumour grading and staging. The presented method offers the potential for being applied in cystoscopy and for providing an automated diagnosis of UC at the clinical level, with an improvement with respect to current state‐of‐the‐art procedures. 相似文献
14.
Angela Lombardi Michele Saviano Flavia Nastri Ornella Maglio Marco Mazzeo Carla Isernia Livio Paolillo Vincenzo Pavone 《Biopolymers》1996,38(6):693-703
In the present paper we describe the solution nmr structural analysis and restrained molecular dynamic simulation of the cyclic pentapeptide cyclo-(Pro-Phe-Phe-β-Ala-β-Ala). The conformational analysis carried out in CD3CN and dimethylsulfoxide (DMSO) solutions by nmr spectroscopy was based on interproton distances derived from rotating frame nuclear Overhauser effect spectroscopy spectra and homonuclear coupling constants. A restrained molecular dynamic simulation in vacuo was also performed to build refined molecular models. The molecule is present in both solvent systems as two slowly interconverting conformers, characterized by a cis-trans isomerism around the β-Ala5-Pro1 peptide bond. In CD3CN solution, the conformer with a cis peptide bond is quite similar to that observed in the solid state, while the conformer containing all trans peptide bonds is characterized by an intramolecular hydrogen bond stabilizing a C10- and a C13-ring structure. In DMSO solution, the trans isomer is partly similar to that observed in CD3CN solution while the cis isomer is different from that observed in the solid state. The effect of the solvent in stabilizing different conformations was also investigated in DMSO-CD3CN solvent mixtures. © 1996 John Wiley & Sons, Inc. 相似文献
15.
Villani GR Balzano N Vitale D Saviano M Pavone V Di Natale P 《Biochimica et biophysica acta》1999,1453(2):185-192
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is an autosomal recessive disorder due to the deficiency of the lysosomal enzyme N-acetylgalactosamine-4-sulfatase (arylsulfatase B, ASB). Mutation analysis in Maroteaux-Lamy syndrome resulted in the identification of approximately 40 molecular defects underlying a great genetic heterogeneity. Here we report five novel mutations in Italian subjects: S65F, P116H, R315Q, Q503X, P531R; each defect was confirmed by restriction enzyme or amplification refractory mutation system (ARMS) analysis. We also performed a three-dimensional (3-D) structure analysis of the alterations identified by us, and of an additional 22 point mutations reported by other groups, in an attempt to draw helpful information about their possible effects on protein conformation. 相似文献
16.
Mastroberardino PG Iannicola C Nardacci R Bernassola F De Laurenzi V Melino G Moreno S Pavone F Oliverio S Fesus L Piacentini M 《Cell death and differentiation》2002,9(9):873-880
By crossing Huntington's disease (HD) R6/1 transgenic mice with 'tissue' transglutaminase (TG2) knock-out mice, we have demonstrated that this multifunctional enzyme plays an important role in the neuronal death characterising this disorder in vivo. In fact, a large reduction in cell death is observed in R6/1, TG2(-/-) compared with R6/1 transgenic mice. In addition, we have shown that the formation of neuronal intranuclear inclusions (NII) is potentiated in absence of the 'tissue' transglutaminase. These phenomena are paralleled by a significant improvement both in motor performances and survival of R6/1, TG2(-/-) versus R6/1 mice. Taken together these findings suggest an important role for tissue transglutaminase in the regulation of neuronal cell death occurring in Huntington's disease. 相似文献
17.
Long-term treatment with low doses of interleukin-2 and interferon-α: immunological effects in advanced renal cell cancer 总被引:2,自引:0,他引:2
Pavone L Andrulli S Santi R Majori M Buzio C 《Cancer immunology, immunotherapy : CII》2001,50(2):82-86
We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-α
(rIFN-α) in patients bearing advanced renal cell carcinoma.
Methods: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular
rIFN-α twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients.
rIL-2 (1 × 106 IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3–5 of each week; rIFN-α (1.8 × 106 IU/m2) was given on days 3 and 5.
In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets,
and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months
of follow-up).
Results: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P=0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+)
(28%, P=0.011).
No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R
(P=0.036 and P=0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively
thereafter.
Conclusions: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important
lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3–CD56+ cells.
Received: 8 November 2000 / Accepted: 11 January 2001 相似文献
18.
Rafael Torres Martin de Rosales Marina Faiella Erik Farquhar Lawrence Que Jr Concetta Andreozzi Vincenzo Pavone Ornella Maglio Flavia Nastri Angela Lombardi 《Journal of biological inorganic chemistry》2010,15(5):717-728
The design, synthesis, and metal-binding properties of DF3, a new de novo designed di-iron protein model are described (“DF”
represents due ferri, Italian for “two iron,” “di-iron”). DF3 is the latest member of the DF family of synthetic proteins. They consist of helix–loop–helix
hairpins, designed to dimerize and form an antiparallel four-helix bundle that encompasses a metal-binding site similar to
those of non-heme carboxylate-bridged di-iron proteins. Unlike previous DF proteins, DF3 is highly soluble in water (up to
3 mM) and forms stable complexes with several metal ions (Zn, Co, and Mn), with the desired secondary structure and the expected
stoichiometry of two ions per protein. UV–vis studies of Co(II) and Fe(III) complexes confirm a metal-binding environment
similar to previous di-Co(II)- and di-Fe(III)-DF proteins, including the presence of a μ-oxo-di-Fe(III) unit. Interestingly,
UV–vis, EPR, and resonance Raman studies suggest the interaction of a tyrosine adjacent to the di-Fe(III) center. The design
of DF3 was aimed at increasing the accessibility of small molecules to the active site of the four-helix bundle. Indeed, binding
of azide to the di-Fe(III) site demonstrates a more accessible metal site compared with previous DFs. In fact, fitting of
the binding curve to the Hill equation allows us to quantify a 150% accessibility enhancement, with respect to DF2. All these
results represent a significant step towards the development of a functional synthetic DF metalloprotein. 相似文献
19.
Pavone LM Mithbaokar P Mastellone V Avallone L Gaspar P Maharajan V Baldini A 《Genesis (New York, N.Y. : 2000)》2007,45(11):689-695
Serotonin regulates cardiovascular functions during embryogenesis and adulthood. However, the source of serotonin in the cardiovascular system and the role of circulating serotonin and serotonin transporter (SERT) in the regulation of cardiovascular functions are still unclear. We used a cell fate approach to map the regions of the mouse heart expressing SERT, utilizing a Cre/loxP system driven by SERT gene expression. Cell labelling was first detected at E10.5 and was mapped until E18.5. We found labelling in the outflow tract, part of right ventricle and to a very limited extent in the left ventricle. Interestingly, the distribution pattern of SERT-fated cells was remarkably similar to that obtained with markers of the second heart field lineage. In addition, we observed staining of atrioventricular valves, consistent with valvular abnormalities observed in SERT-/-animals. Overall, our data reveal specific and regionally restricted distribution of SERT-expressing cells in the developing heart of mouse. 相似文献
20.
Pavone LM Cattaneo F Rea S De Pasquale V Spina A Sauchelli E Mastellone V Ammendola R 《Cellular signalling》2011,23(12):1961-1971
Hepatocyte Growth Factor (HGF)/c-MET signaling has an emerging role in promoting cell proliferation, survival, migration, wound repair and branching in a variety of cell types. HGF plays a crucial role as a mediator of stromal–epithelial interactions in the normal prostate but the precise biological function of HGF/c-Met interaction in the normal prostate and in prostate cancer is not clear. HGF has two naturally occurring splice variants and NK1, the smallest of these HGF variants, consists of the HGF amino terminus through the first kringle domain. We evaluated the intracellular signaling cascades and the morphological changes triggered by NK1 in human prostate epithelial cell line PNT1A which shows molecular and biochemical properties close to the normal prostate epithelium. We demonstrated that these cells express a functional c-MET, and cell exposure to NK1 induces the phosphorylation of tyrosines 1313/1349/1356 residues of c-MET which provide docking sites for signaling molecules. We observed an increased phosphorylation of ERK1/2, Akt, c-Src, p125FAK, SMAD2/3, and STAT3, down-regulation of the expression of epithelial cell–cell adhesion marker E-cadherin, and enhanced expression levels of mesenchymal markers vimentin, fibronectin, vinculin, α-actinin, and α-smooth muscle actin. This results in cell proliferation, in the appearance of a mesenchymal phenotype, in morphological changes resembling cell scattering and in wound healing. Our findings highlight the function of NK1 in non-tumorigenic human prostatic epithelial cells and provide a picture of the signaling pathways triggered by NK1 in a unique cell line. 相似文献