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71.
Pompetti F Pilla D Giancola R 《BioEssays : news and reviews in molecular, cellular and developmental biology》2003,25(2):104-107
Cancer derives from a cell clone that has accumulated genetic and epigenetic changes that influence its phenotype and finally enable it to escape from the normal controls of proliferation. A recent paper shows that, in myc-induced tumours, the inactivation of this oncogene produces the regression of the tumours and the differentiation of the tumour cells into mature osteocytes.1 In addition, a further reactivation of myc in these cells does not restore the malignant phenotype but induces apoptosis. This discovery could lead to an innovative therapeutic strategy. 相似文献
72.
Monica Averna Roberta De Tullio Marco Pedrazzi Margherita Bavestrello Matteo Pellegrini Franca Salamino Sandro Pontremoli Edon Melloni 《PloS one》2015,10(1)
Here we demonstrate that heat shock protein 90 (HSP90) interacts with calpain-1, but not with calpain-2, and forms a discrete complex in which the protease maintains its catalytic activity, although with a lower affinity for Ca2+. Equilibrium gel distribution experiments show that this complex is composed by an equal number of molecules of each protein partner. Moreover, in resting cells, cytosolic calpain-1 is completely associated with HSP90. Since calpain-1, in association with HSP90, retains its proteolytic activity, and the chaperone is displaced by calpastatin also in the absence of Ca2+, the catalytic cleft of the protease is not involved in this association. Thus, calpain-1 can form two distinct complexes depending on the availability of calpastatin in the cytosol. The occurrence of a complex between HSP90 and calpain-1, in which the protease is still activable, can prevent the complete inhibition of the protease even in the presence of high calpastatin levels. We also demonstrate that in basal cell conditions HSP90 and calpain-1, but not calpain-2, are inserted in the multi-protein N-Methyl-D-Aspartate receptor (NMDAR) complex. The amount of calpain-1 at the NMDAR cluster is not modified in conditions of increased [Ca2+]i, and this resident protease is involved in the processing of NMDAR components. Finally, the amount of calpain-1 associated with NMDAR cluster is independent from Ca2+-mediated translocation. Our findings show that HSP90 plays an important role in maintaining a given and proper amount of calpain-1 at the functional sites. 相似文献
73.
Giuseppina Sandri Maria Cristina Bonferoni Silvia Rossi Franca Ferrari Cinzia Boselli Carla Caramella 《AAPS PharmSciTech》2010,11(1):362-371
The aim of this paper was to evaluate the penetration enhancement properties of nanoparticles (NP) based on N-trimethyl chitosan (TMC 35% quaternization degree) loaded with insulin. The permeation performances of TMC NP were compared
with those of chitosan (CS) NP and also with TMC and CS solutions. To estimate the mechanism of penetration enhancement, two
different approaches have been taken into account: an in vitro study (Caco-2 cells) and an ex vivo study (excised rat duodenum, jejunum, and ileum). Insulin-loaded CS and TMC NP had dimensions of about 250 nm and had high
yield and high encapsulation efficiency. The in vitro study evidenced that TMC and CS were able to enhance insulin permeation to the same extent. Penetration enhancement properties
of TMC NP seem to be prevalently related to endocytosis while the widening of tight junctions appeared more important as mechanism
in the case of CS NP. The ex vivo study put in evidence the role of mucus layer and of its microclimate pH. In duodenum (pH 5–5.5), CS and TMC solutions were
more effective than NP while TMC NP were more efficient towards jejunum tissue (pH 6–6.5) for their high mucoadhesive potential.
Confocal laser scanning microscopy study supported the hypothesis that penetration enhancement due to TMC NP was mainly due
to internalization/endocytosis into duodenum and jejunum epithelial cells. The good penetration enhancement properties (permeation
and penetration/internalization) make TMC NP suitable carriers for oral administration of insulin. 相似文献
74.
Andreassi MG Botto N Cocci F Battaglia D Antonioli E Masetti S Manfredi S Colombo MG Biagini A Clerico A 《Human genetics》2003,112(2):171-177
Elevated levels of plasma homocysteine (Hcy), a risk factor for coronary artery disease (CAD), can result from genetic errors, e.g., the methylenetetrahydrofolate reductase (MTHFR) polymorphism, or nutritional deficiencies, e.g., in vitamin B12 and folate. The mechanism by which Hcy induces atherosclerosis is not fully understood. Recently, Hcy has also been observed to induce DNA damage. In this study, we have investigated whether DNA damage is related to the C677T variant in the MTHFR gene and to plasma levels of Hcy, B12, and folate in patients with CAD. Patients ( n=46) with angiographically proven CAD were studied by using the micronucleus (MN) test, an accepted method for evaluating genetic instability. TT patients had plasma Hcy levels higher than those with the CT or CC genotypes (27.8+/-5.2 vs 13.7+/-2.2 and 12.9+/-1.9 micro mol/l, respectively; P=0.02). Patients with multi-vessel disease had higher plasma Hcy levels (11.6+/-1.2, 22.0+/-4.7, 19.3+/-3.9 micromol/l for one-, two- and three-vessel disease, respectively; P=0.05). The MN index increased with the number of affected vessels (8.4+/-0.7, 11.1+/-2.0, 14.2+/-1.7 for one-, two-, and three-vessels disease, respectively; P=0.02) and was significantly higher in subjects with the TT genotype compared with the CC or CT genotypes (15.7+/-2.4 vs 8.9+/-1.7 and 9.9+/-0.8; P=0.02). The MN index was also correlated negatively with plasma B12 concentration ( r=-0.343; P=0.019) and positively with plasma Hcy ( r=0.429, P=0.005). These data indicate that the MN index is associated with the severity of CAD and is related to the MTHFR polymorphism, suggesting an interesting link between coronary atherosclerosis and genetic instability in humans. 相似文献
75.
Gianni Bonadonna Silvio Monfardini Mario de Lena Franca Fossati-Bellani 《BMJ (Clinical research ed.)》1969,3(5669):503-506
Adriamycin, a new antitumour antibiotic of the anthracycline group with a structural formula very similar to daunorubicin, has proved to have potent tumour-growth-inhibiting properties, and to be particularly effective in childhood malignancies. Though adriamycin produces a higher percentage of side-effects than daunorubicin—namely, stomatitis and alopecia—a lower dosage may be used for therapy. 相似文献
76.
Rodríguez-Argüelles MC Tourón-Touceda P Cao R García-Deibe AM Pelagatti P Pelizzi C Zani F 《Journal of inorganic biochemistry》2009,103(1):35-42
Cobalt, nickel, copper and zinc coordination compounds of two thiosemicarbazones with general composition ML2 (L: monodeprotonated ligand corresponding to 2-acetyl-γ-butyrolactone thiosemicarbazone, HL1, and 2-furancarbaldehyde thiosemicarbazone, HL2) and also complexes with general composition MCl2(HL2) were synthesized (except [NiCl2(HL2)] and [Co(L2)2]). The interaction of CuCl2 with HL2 gave [CuCl(HL2)], a copper(I) complex. The ligands and metal complexes were characterized by IR, 1H and 13C NMR spectroscopy, and magnetic susceptibility measurements. The crystal structure of [Ni(L2)2] · 2dmso was determined and a trans-square planar coordination of the two κ2-N,S chelate rings forming polymeric strips through H-bonds with dmso was observed. Actually, in all the reported complexes both ligands behaved as κ2-N,S chelates, except in the case of [Co(L1)2] in which HL1 is tridentate κ3-N,S,O. The antimicrobial properties of all compounds were studied using a wide spectrum of bacterial and fungal strains. The copper complexes of HL2 were the most active against all strains, including dermatophytes and phytopathogenic fungi. Most of the studied compounds, especially [Cu(L1)2], presented good activity against Haemophilus influenzae, a very harmful bacterium to humans. 相似文献
77.
Rodríguez-Argüelles MC Mosquera-Vázquez S Tourón-Touceda P Sanmartín-Matalobos J García-Deibe AM Belicchi-Ferrari M Pelosi G Pelizzi C Zani F 《Journal of inorganic biochemistry》2007,101(1):138-147
Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl and isonicotinoyl hydrazones of 3-(N-methyl)isatin (HL(1) and HL(2), respectively) were synthesized and characterized, being the crystal structures of HL(1), HL(2) and [Ni(L(1))(2)].2CHCl(3) elucidated by X-ray diffraction techniques. The in vitro antimicrobial activity of all these compounds was tested against several bacteria and fungi. HL(1)and its complexes exhibited a strong inhibition of the growth of Haemophilus influenzae (MIC 0.15-1.50microg/mL) and good antibacterial properties towards Bacillus subtilis (MIC 3-25microg/mL). The minimal inhibitory concentration (MIC) was defined as the lowest concentration of compound inhibiting the growth of each strain. The antibacterial effectiveness was confirmed against a number of Gram positive bacteria, including methicillin-resistant Staphylococcus aureus. Yeasts and moulds showed a low susceptibility, except the dermatophyte mould Epidermophyton floccosum that is inhibited at concentrations ranging from 6 to 50microg/mL. In general, the antimicrobial activity of the thiophene derivatives was greater than that of the isonicotinic analogues. 相似文献
78.
Galli U Oliaro-Bosso S Taramino S Venegoni S Pastore E Tron GC Balliano G Viola F Sorba G 《Bioorganic & medicinal chemistry letters》2007,17(1):220-224
New dimethylamino truncated squalene ether derivatives containing a different aromatic moiety (phenyl, naphthyl, and biphenyl) or a simple alkyl (n-hexylic) group were synthesized as inhibitors of the oxidosqualene cyclase (OSC) and of the sterol biosynthetic pathway. The activity against human OSC was compared with the activity against the OSCs of pathogenic organisms such as Pneumocystis carinii and Trypanosoma cruzi. The phenyl derivative was the most potent inhibitor of T. cruzi OSC. 相似文献
79.
Raucci F Di Fiore MM 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2011,879(29):3268-3276
We investigated the involvement of D-Aspartic acid (D-Asp) on ovarian and testicular morphology of the green frog, Rana esculenta, and its effect on the testosterone production. The study has been performed throughout the reproductive cycle. In both ovary and testis a substantial amount of D-Asp is endogenously present and its concentration varies as function of reproduction. In the frog, D-Asp content is differently correlated with gonadal and plasmatic levels of testosterone, depending on the sex. In fact, the amount of the D-Asp is inversely linked with that of the testosterone in the ovary, while this correlation directly matched in the testis. In vivo short-term experiments, consisting of a single intra-peritoneal injection of D-Asp (2.0 μmol/g body weight), demonstrated that the enantiomer is significantly accumulated by both the ovary and testis, reaching after 3 h the highest uptake and thereafter decreasing to baseline values within 24 h. Furthermore, D-Asp influences the synthesis and/or the release of testosterone, causing a decrease of its level in the female, and an increase in the male, respectively. In vivo long-term experiments, D-Asp, chronically administered to the frogs of both sexes, enhances the maturation of both gonads, determining in the oocytes an higher accumulation of carbohydrate yolk plates in the ooplasm, and stimulating the spermatogenesis in the testis. Taken altogether, our results show that D-Asp operates differently in female and male frog gonads, indicating that it has different targets in the reproductive machinery depending on the sex. 相似文献
80.
Cattani F Gallese A Mosca M Buanne P Biordi L Francavilla S Coletti G Pellegrini L Melillo G Bertini R 《European cytokine network》2006,17(1):42-48
The recruitment of polymorphonuclear neutrophil leukocytes (PMN) into a challenge site, and their subsequent activation, are thought to play a role in the elicitation of the contact hypersensitivity (CHS) response. The present study investigated the role played by CXCR2 activity in tissue PMN infiltration and subsequent triggering of CHS. Our results show that the cutaneous infiltration by PMN, induced by hapten challenge was dramatically inhibited in sensitized, CXCR2-deficient (CXCR2(-/-)) mice. Inhibition of PMN recruitment into the hapten-challenged ears of CXCR2(-/-) mice was associated with a consistent reduction of the CHS response (ear swelling) in CXCR2(-/-) mice as compared with that observed in neutropenic, wild-type (CXCR2(+/+)) mice. Prevention of skin PMN infiltration and the ear swelling response by the absence of functional CXCR2 was observed regardless of the hapten used. These data clearly suggest that CXCR2 activity plays an essential role in mediating cutaneous recruitment and activation of PMN, and thus indirectly regulates recruitment of hapten-primed T cells into challenge sites, with the subsequent elicitation of the CHS response. The role played by CXCR2 activity in the CHS response provides the rationale for testing CXCR2 inhibitors as a new therapeutic approach to skin diseases. 相似文献