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21.
Multiple pathways of cell invasion are regulated by multiple families of serine proteases 总被引:5,自引:0,他引:5
Del Rosso M Fibbi G Pucci M D'Alessio S Del Rosso A Magnelli L Chiarugi V 《Clinical & experimental metastasis》2002,19(3):193-207
The complex process of tumor invasion requires the coordinated expression and activity of cell-substratum adhesive interactions
and of cell-associated protease systems, which destroy the extracellular matrix (ECM), in order to enable the invading cells
to simultaneously grip and destroy the anatomical barriers that control cell spreading. A number of data indicate that such
a `grip and go' process may be performed by an enlarging series of cell membrane-associated serine proteases and serine protease
receptors, which provide the invasive cells with a functional unit (the protease and its receptor), able to mediate cell-substratum
adhesion through specific receptor domains, to proteolytically degrade ECM and to deliver into the cell signals that up-regulate
the expression either of the protease/receptor complex, or of other adhesion molecules, such as integrins. There is evidence
that some proteases and protease receptor expression are under the control of tumor hypoxia, which is the result of an imbalance
in oxygen supply and demand. The urokinase-type plasminogen activator (u-PA) receptor (u-PAR) is under hypoxic control and
cooperates with other serine proteases of the blood coagulation pathways that may extravasate in the tumor milieu as a result
of hypoxia-simulated increase of vessel permeability. Other serine proteases and their receptors cooperate with the cell-associated
fibrinolytic system to promote cell invasion. Among these, tissue factor and its ligand coagulation factor VII, thrombin and
its protease-activated receptors, and type II trans-membrane serine proteases seem to play a crucial role. This Review takes
into consideration the complex scenario of the single serine proteases and related receptors that are involved in cell invasion,
as well as the protease receptor/adhesion molecule interplay which is necessary to focus the cell surface-driven proteolysis
where adhesion provides a grip to the invading cell.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
22.
Vignozzi L Vannelli GB Morelli A Mancina R Marini M Ferruzzi P Crescioli C Luconi M Donati S Fisher AD Baldi E Filippi S Forti G Maggi M 《Molecular human reproduction》2005,11(2):99-106
Although abnormalities of the male external genitalia (MEG) are a relatively common problem, little is known concerning the molecular mechanisms that finely regulate penile development. We report here the expression of the oxytocin receptor (OTR) gene by real-time RT-PCR in human fetal tissues (11th-12th week of gestation), including the MEG. The developing penis expressed a very high level of OTR mRNA, only a half log(10) unit lower than fetal central nervous system, used as a positive control. The OTR protein is also highly expressed (western, immunohistochemistry and binding studies) and immunolocalized both in the mesenchymal body and in the surrounding blood capillaries, which will later constitute penile trabeculae and sinusoids. Binding studies using [125I]oxytocin antagonist ([125I]OTA) in cultured human fetal penile smooth muscle cells (hfPSMC) revealed the presence of specific OTR with a high capacity and affinity for oxytocin (OT) and for OTA. Increasing concentrations of OT dose-dependently induced intracellular Ca2+ mobilization. Furthermore, OTR mediated an increase in the proliferation and the migration of hfPSMC. In conclusion, we demonstrate that in the developing human MEG, OTR is highly expressed and might be involved in coordinating timely and appropriate proliferation and migration of the penile cells. Thus, OTR might represent an additional target for investigating human fetal MEG organogenesis. 相似文献
23.
24.
Chiara Merlino Massimiliano Bergallo Giorgio Gribaudo Gabriella Gregori Giuseppe Paolo Segoloni Franca Giacchino Alessandro Negro Ponzi Rossana Cavallo 《Journal of clinical virology》2003,28(3):265-274
BACKGROUND: Several studies have disclosed a correlation between polyomavirus BK (BKV) and interstitial nephritis in renal transplant recipients and its quantification in urine and serum is therefore required to assess the role of BKV infection in nephropathy. OBJECTIVE: This paper describes a urine and serum BKV-DNA quantification protocol devised to evaluate the viral load. STUDY DESIGN: Screening of samples containing > or =10(3)/ml viral genome copies by a semi-quantitative polymerase chain reaction (PCR) assay is followed by precise quantification of the samples containing a high number of viral genomes in a quantitative-competitive (QC)-PCR assay. Generation of the competitor construct relied on the different sizes of wild-type and competitor amplicons. RESULTS AND CONCLUSIONS: Screening by semi-quantitative PCR selects samples with a high number of viral genomes for use in the more labor-intensive and -expensive QC-PCR assay and thus provides a handy means for quantitative DNA analysis of large numbers of samples. The results obtained in BKV-DNA quantification in urine and serum samples from 51 renal transplant recipients (22 on treatment with tacrolimus (FK506) and 29 on cyclosporine A (Cy A)) are interesting: BKV-DNA findings (43.1%) in urine samples are in agreement with the BKV urinary shedding reported in literature (5-45%). With regard to immunosuppressive treatment, the percentage of activation of the infection (revealed by BKV-DNA detection in urine samples) in the two groups of therapy is similar (40.9% vs 44.8%). The observation that the viral load in urine is dissociated with that of serum suggests that both parameters should be investigated in evaluation of the pathogenetic role of BKV reactivation in renal transplant recipients. Moreover, our BKV-DNA quantification protocol could be used to monitor viral load in urine and serum samples from renal transplant recipients so as to detect those at risk of nephropathy and monitor their response to immunosuppression reduction therapy if it occurs. 相似文献
25.
The CD31 antigen, a member of the immunoglobulin superfamily with a possible cell adhesion function, is expressed on approximately 50% of peripheral blood lymphoid cells at relatively low intensity (10-20% of the level on monocytes). In the accompanying paper we showed that a mAb, 5A2.G5, which identifies a glycosylation-dependent epitope of the CD31 antigen, bound to fewer lymphocytes than two other CD31 mAb, B2B1 and 2BD4, although the 3 antibodies bound equally well to monocytes. We have now analyzed the pattern of expression of epitopes of the CD31 antigen on lymphoid cell subpopulations using two-color immunofluorescence and flow cytometry. Large granular lymphocytes (CD16+), CD8-positive T cells and B cells (SMIg+) were mostly CD31-positive as indicated by the binding of mAb B2B1 and 2BD4. Single populations displaying some overlap with the negative control were obtained in each case. In contrast, CD4-positive T cells fell into two discrete populations with respect to CD31 antigen expression. mAb 5A2.G5 displayed weaker binding to all lymphoid cell types, indicating that the pattern of glycosylation of the CD31 antigen differs between lymphocytes (of all types) and cells of the myeloid lineages. The heterogeneity of CD31 antigen expression by CD4-positive cells was further examined by dual-labelling of purified CD4 cells with mAb B2B1 and CD45RA or CD29 mAb which identify naive and memory T cells respectively. The CD31 antigen was found to be preferentially expressed by the CD45RA-positive, naive cell population. 相似文献
26.
Bacteria of the genus Wolbachia constitute a group of intracellular and maternally inherited micro-organisms that are widespread in arthropods, inducing several reproductive disorders such as cytoplasmic incompatibility in their hosts. Considering relevant biological implications related to the presence of Wolbachia in several insect orders, for example its potential role as mechanism for rapid speciation and as vehicle to drive genetic markers in wild populations of vectors of medical and veterinary interest, we carried out an extensive polymerase chain reaction survey to detect Wolbachia in several species of mosquito belonging to genera involved in the transmission of pathogens. Five species out of 26 tested have shown to be infected; for four of them this is the first evidence of the Wolbachia infection. A phylogenetic analysis was also performed, positioning the five Wolbachia strains in the phyletic subdivision B. 相似文献
27.
The negative role exerted by cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in the regulation of T-cell activity, as induced by T-cell receptor (TCR)/CD3 and CD28 costimulation, has been widely described. In the present work we investigated the role of CTLA-4 in the control of cell activation, as induced by costimulation of the adhesion molecule lymphocyte function-associated antigen-1 (LFA-1) in murine CD4+ T cells. Results show that CTLA-4 engagement inhibits interleukin-2 (IL-2) production, not only when induced by CD3/CD28 costimulation, but also when CD4+ T cells are costimulated by anti-CD3 and anti-LFA-1 monoclonal antibodies (mAbs). LFA-1 has been described to induce Ca2+ mobilization also in the absence of TCR engagement. Moreover, we found that CTLA-4 engagement negatively affects Ca2+ mobilization and NF-AT activation, as induced by LFA-1 engagement alone. PLCgamma1 phosphorylation was also dampened within minutes after CTLA-4 engagement. Altogether these data indicate that through the control of signals induced by different receptors, CTLA-4 could be a global attenuator of T-cell activation. 相似文献
28.
Juliana F. W. Cohen Amelie A. Hecht Gabriella M. McLoughlin Lindsey Turner Marlene B. Schwartz 《Nutrients》2021,13(3)
The school environment plays an important role in children’s diets and overall health, and policies for universal free school meals have the potential to contribute to positive child health outcomes. This systematic review evaluates studies examining the association between universal free school meals and students’ school meal participation rates, diets, attendance, academic performance, and Body Mass Index (BMI), as well as school finances. The search was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). A search for studies published in economically developed countries published through December 2020 was performed in PubMed, Education Resources Information Center (ERIC), Thomson Reuters’ Web of Science, and Academic Search Ultimate, followed by examining the references in the resultant literature. A total of 47 studies were identified and the Newcastle-Ottawa Scale (NOS) was applied to assess bias. Nearly all studies examining universal free school meals found positive associations with school meal participation. Most studies examining universal free school meals that included free lunch found positive associations with diet quality, food security, and academic performance; however, the findings of studies examining only universal free breakfast were mixed. Research findings were similarly mixed when examining attendance as an outcome. Concerns about adverse outcomes on student BMI were not supported by the literature; in fact, several studies detected a potentially protective effect of universal free school meals on BMI. Research examining the impact of universal free meals on school finances was limited, but suggest that lower-income school districts in the U.S. may have positive financial outcomes from participation in universal free school meal provisions. Additionally, providing free meals to students may be associated with improved household incomes, particularly among lower-income families with children. Further research is needed to examine the financial implications of universal free meals for both school districts and families. Overall, universal free school meals may have multiple benefits for students and countries should consider universal free school meal provisions with strong nutrition guidelines. (PROSPERO registration: CRD42020221782). 相似文献
29.
Vincenzo Di Stefano Raffaele Ornello Andrea Gagliardo Angelo Torrente Elisa Illuminato Valeria Caponnetto Ilaria Frattale Raffaella Golini Chiara Di Felice Fabiola Graziano Maria Caccamo Davide Ventimiglia Salvatore Iacono Gabriella Matarazzo Francesco Armetta Giuseppe Battaglia Alberto Firenze Simona Sacco Filippo Brighina 《Nutrients》2021,13(4)
Background: The restrictions taken to control the rapid spread of COVID-19 resulted in a sudden, unprecedented change in people’s lifestyle, leading to negative consequences on general health. This study aimed to estimate the impact of such changes on migraine severity during 2020 March–May lockdown. Methods: Patients affected by migraine with or without aura, diagnosed by expert physicians, completed a detailed interview comprehensive of: assessment of migraine characteristics; measure of physical activity (PA) levels; measure of the intake frequency of main Italian foods; the Insomnia Severity Index (ISI) questionnaire investigating sleep disorders. Results: We included 261 patients with a mean age of 44.5 ± 12.3 years. During social distancing, 72 patients (28%) reported a headache worsening, 86 (33%) an improvement, and 103 (39%) a stable headache frequency. A significant decrease of the PA levels during COVID-19 quarantine in the whole study sample was observed (median total metabolic equivalent task (METs) decreased from 1170 to 510; p < 0.001). Additionally, a significant difference was reported on median ISI scores (from 7 to 8; p < 0.001), which were increased in patients who presented a stable or worsening headache. Conclusions: Our study confirmed that the restrictions taken during the pandemic have affected the practice of PA levels and sleep quality in migraine. Hence, PA and sleep quality should be assessed to find strategies for an improvement in quality of life. 相似文献
30.
Luigi Barrea Giovanna Muscogiuri Gabriella Pugliese Chiara Graziadio Maria Maisto Francesca Pivari Andrea Falco Gian Carlo Tenore Annamaria Colao Silvia Savastano 《Nutrients》2021,13(5)
Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference (p < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet (p < 0.001) and the lowest circulating TMAO concentrations (p < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = −0.627, p < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = −0.479, t = −12.08, and p < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 (p < 0.001, R2 = −0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD. 相似文献