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1.
Mol Cell ; 46(1): 91-104, 2012 Apr 13.
Article in English | MEDLINE | ID: mdl-22424771

ABSTRACT

The association between hyperinflammatory states and numerous diseases is widely recognized, but our understanding of the molecular strategies that have evolved to prevent uncontrolled activation of inflammatory responses remains incomplete. Here, we report a critical, nontranscriptional role of GPS2 as a guardian against hyperstimulation of the TNF-α-induced gene program. GPS2 cytoplasmic actions are required to specifically modulate RIP1 ubiquitylation and JNK activation by inhibiting TRAF2/Ubc13 enzymatic activity. In vivo relevance of GPS2 anti-inflammatory role is confirmed by inhibition of TNF-α target genes in macrophages and by improved insulin signaling in the adipose tissue of aP2-GPS2 transgenic mice. As the nontranscriptional role is complemented by GPS2 functioning as positive and negative cofactor for nuclear receptors, in vivo overexpression also results in elevated circulating level of Resistin and development of hepatic steatosis. Together, these studies define GPS2 as a molecular guardian required for precise control of inflammatory responses involved in immunity and homeostasis.


Subject(s)
Adipose Tissue/metabolism , Homeostasis , Intracellular Signaling Peptides and Proteins/metabolism , Macrophages/metabolism , Adipose Tissue/immunology , Animals , Cell Line , GTPase-Activating Proteins/genetics , GTPase-Activating Proteins/immunology , GTPase-Activating Proteins/metabolism , Inflammation/genetics , Inflammation/immunology , Inflammation/metabolism , Insulin/genetics , Insulin/immunology , Insulin/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/immunology , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase 4/immunology , MAP Kinase Kinase 4/metabolism , Macrophages/immunology , Mice , Mice, Transgenic , Resistin/genetics , Resistin/immunology , Resistin/metabolism , Signal Transduction/genetics , Signal Transduction/immunology , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism , Ubiquitin-Conjugating Enzymes/genetics , Ubiquitin-Conjugating Enzymes/immunology , Ubiquitin-Conjugating Enzymes/metabolism , Ubiquitination/genetics , Ubiquitination/immunology
2.
Biochim Biophys Acta ; 1859(4): 627-38, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26921500

ABSTRACT

The heterotrimeric CCAAT-binding factor NF-Y controls the expression of a multitude of genes involved in cell cycle progression. NF-YA is present in two alternatively spliced isoforms, NF-YAs and NF-YAl, differing in 28 aminoacids in the N-terminal Q-rich activation domain. NF-YAs has been identified as a regulator of stemness and proliferation in mouse embryonic cells (mESCs) and human hematopoietic stem cells (hHSCs), whereas the role of NF-YAl is not clear. In the muscle system, NF-YA expression is observed in proliferating cells, but barely detectable in terminally differentiated cells in vitro and adult skeletal muscle in vivo. Here, we show that NF-YA inactivation in mouse myoblasts impairs both proliferation and differentiation. The overexpression of the two NF-YA isoforms differentially affects myoblasts fate: NF-YAs enhance cell proliferation, while NF-YAl boosts differentiation. The molecular mechanisms were investigated by expression profilings, detailing the opposite programs of the two isoforms. Bioinformatic analysis of the regulated promoters failed to detect a significant presence of CCAAT boxes in the regulated genes. NF-YAl activates directly Mef2D, Six genes, and p57kip2 (Cdkn1c), and indirectly the myogenic regulatory factors (MRFs). Specifically, Cdkn1c activation is induced by NF-Y binding to its CCAAT promoter and by reducing the expression of the lncRNA Kcnq1ot1, a negative regulator of Cdkn1c transcription. Overall, our results indicate that NF-YA alternative splicing is an influential muscle cell determinant, through direct regulation of selected cell cycle blocking genes, and, directly and indirectly, of muscle-specific transcription factors.


Subject(s)
CCAAT-Binding Factor/genetics , Cell Differentiation/genetics , Muscle Development/genetics , Muscle, Skeletal/growth & development , Protein Isoforms/genetics , Animals , CCAAT-Binding Factor/biosynthesis , Cell Proliferation/genetics , Cyclin B/biosynthesis , Gene Expression Regulation, Developmental , Hematopoietic Stem Cells/metabolism , Humans , Mice , Myoblasts/metabolism , Promoter Regions, Genetic , Transcription Factors/biosynthesis , Transcription Factors/genetics
3.
Proc Natl Acad Sci U S A ; 111(13): 4892-7, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24639548

ABSTRACT

Estrogen receptor-α (ERα) has central role in hormone-dependent breast cancer and its ligand-induced functions have been extensively characterized. However, evidence exists that ERα has functions that are independent of ligands. In the present work, we investigated the binding of ERα to chromatin in the absence of ligands and its functions on gene regulation. We demonstrated that in MCF7 breast cancer cells unliganded ERα binds to more than 4,000 chromatin sites. Unexpectedly, although almost entirely comprised in the larger group of estrogen-induced binding sites, we found that unliganded-ERα binding is specifically linked to genes with developmental functions, compared with estrogen-induced binding. Moreover, we found that siRNA-mediated down-regulation of ERα in absence of estrogen is accompanied by changes in the expression levels of hundreds of coding and noncoding RNAs. Down-regulated mRNAs showed enrichment in genes related to epithelial cell growth and development. Stable ERα down-regulation using shRNA, which caused cell growth arrest, was accompanied by increased H3K27me3 at ERα binding sites. Finally, we found that FOXA1 and AP2γ binding to several sites is decreased upon ERα silencing, suggesting that unliganded ERα participates, together with other factors, in the maintenance of the luminal-specific cistrome in breast cancer cells.


Subject(s)
Breast Neoplasms/genetics , Estrogen Receptor alpha/metabolism , Genome, Human/genetics , Binding Sites , Breast Neoplasms/pathology , Cell Proliferation , Chromatin Immunoprecipitation , Female , Gene Ontology , Humans , Ligands , MCF-7 Cells , Polymerase Chain Reaction , RNA, Small Interfering/metabolism
4.
Implant Dent ; 24(1): 77-82, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25621553

ABSTRACT

PURPOSE: The aim of this multicenter human clinical trial was to radiographically evaluate the marginal bone loss and to assess implant survival rate in patients treated using 2 different implant systems (Bio-Plant and Tuber-Plant) after 10 years of loading. METHODS: Ninety-seven patients were selected, and 160 implants were inserted (72 Bio-Plant and 88 Tuber-Plant). Ten years later, 20 patients were lost at follow-up and 77 patients (126 implants; 67 Bio-Plant and 59 Tuber-Plant) were recalled. After 10-year, the periimplant bone resorption was significantly lower (P = 0.0039) for Tuber-Plant (0.74 ± 0.12 mm) than for Bio-Plant (1.31 ± 0.09 mm). The cumulative survival rate was 99.11%. CONCLUSION: Both implant systems demonstrated to be suitable for a long-term successful rehabilitation because of stable marginal bone levels and high survival rates after 10 years of functional loading.


Subject(s)
Alveolar Bone Loss/diagnostic imaging , Dental Implants/adverse effects , Aged , Aged, 80 and over , Alveolar Process/diagnostic imaging , Dental Implantation, Endosseous/adverse effects , Dental Implantation, Endosseous/instrumentation , Dental Implantation, Endosseous/methods , Female , Humans , Male , Middle Aged , Prospective Studies , Radiography, Panoramic
5.
Odontology ; 101(2): 133-9, 2013 Jul.
Article in English | MEDLINE | ID: mdl-22678711

ABSTRACT

Coating characteristics of dental implants such as composition and topography regulate cell response during implant healing. The aim of this study was to assess how surface topography can affect osteogenic differentiation of mesenchymal stem cells (MSCs) by analyzing the expression levels of bone-related genes and MSCs marker. Thirty disk-shaped, commercially pure Grade 2 titanium samples (10 × 2 mm) with 3 different surface topographies (DENTSPLY-Friadent GmbH, Mannheim, Germany) were used in the present study: 10 Ti machined disks (control), 10 Ti sandblasted and acid-etched disks (DPS(®)) and 10 sandblasted and acid-etched disks at high temperature (Plus(®)). Samples were processed for real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. By comparing machined and Plus(®) disks, quantitative real-time RT-PCR showed a significant reduction of the bone-related genes osteocalcin (BGLAP) and osteoblast transcriptional factor (RUNX2). The comparison between DPS(®) and Plus(®) disks showed a slight induction of all the genes examined (RUNX2, ALPL, COL1A1, COL3A1, ENG, FOSL1, SPP1, and SP7); only the expression of BGLAP remained stable. The present study, demonstrated that implant surface topography affects osteoblast gene expression. Indeed, Plus(®) surface produces an effect on MSCs in the late differentiation stages.


Subject(s)
Cell Differentiation , Hematopoietic Stem Cells/cytology , Surface Properties , Titanium/chemistry , Base Sequence , DNA Primers , Humans , In Vitro Techniques , Middle Aged , Real-Time Polymerase Chain Reaction
6.
Clin Exp Rheumatol ; 30(5): 799-804, 2012.
Article in English | MEDLINE | ID: mdl-23020938

ABSTRACT

OBJECTIVES: Kawasaki syndrome (KS) is an acute systemic vasculitis of unknown origin predominantly affecting young children. Early diagnosis is crucial to prevent cardiac complications. However, the differential diagnosis of patients with the incomplete or atypical form of the disease poses a heavy challenge for the paediatrician. Our aim was to evaluate the prevalence of incomplete and atypical cases among children with KS and to identify clinical and laboratory variables that may help differentiate incomplete and atypical KS from other febrile diseases at this age. METHODS: We established an international registry to recruit patients with KS, including those with incomplete and atypical forms. The control group included age-matched febrile children admitted to the hospital with a variety of diseases mimicking KS. The aim was to define clinical or laboratory clues to help in the discrimination of incomplete and atypical KS patients from others. RESULTS: Two hundred and twenty-eight patients with incomplete KS (78%) and atypical KS (22%) were compared to 71 children with other febrile diseases. Patients with incomplete and atypical KS presented a statistically significant higher frequency of mucosal changes, conjunctivitis, extremity abnormalities and perineal desquamation compared to the group of other febrile diseases. In addition, C-reactive protein and platelet counts were significantly higher in incomplete and atypical KS compared to the other group. CONCLUSIONS: This is the largest series of incomplete and atypical KS patients of non East-Asian ancestry: we suggest that in patients with the aforementioned clinical features and laboratory evidence of systemic inflammation in terms of increased C-reactive protein and platelet counts an echocardiogram should be performed and diagnosis of KS considered.


Subject(s)
Fever/diagnosis , Mucocutaneous Lymph Node Syndrome/diagnosis , Analysis of Variance , Biomarkers/blood , C-Reactive Protein/analysis , Case-Control Studies , Chi-Square Distribution , Child , Child, Preschool , Diagnosis, Differential , Early Diagnosis , Europe/epidemiology , Female , Fever/blood , Fever/epidemiology , Fever/immunology , Humans , Infant , Infant, Newborn , Inflammation Mediators/blood , Israel/epidemiology , Male , Mucocutaneous Lymph Node Syndrome/blood , Mucocutaneous Lymph Node Syndrome/epidemiology , Mucocutaneous Lymph Node Syndrome/immunology , Platelet Count , Predictive Value of Tests , Prevalence , Prognosis , Registries , South America/epidemiology , Turkey/epidemiology
7.
Clin Exp Rheumatol ; 29(1 Suppl 64): S121-5, 2011.
Article in English | MEDLINE | ID: mdl-21385556

ABSTRACT

BACKGROUND: Microparticles (MPs) are increased in diseases characterised by endothelial injury. Kawasaki disease (KD) damages the endothelium provoking life-threatening involvement of coronary arteries. OBJECTIVES: To compare KD MPs vs. controls. METHODS. Thirty KD and 20 controls were enrolled. MPs were stained with monoclonal antibodies against platelets, endothelial cells (EC), monocytes, T and B cells, neutrophils, and quantified by FACS. RESULTS: The total number of MPs was significantly increased in KD versus controls (193x105±0.6x105 vs. 94x105±0.9x105 million/ml plasma p=0.01) and vs. KD after IVIG therapy (132x105±0.4x105million/ml plasma p=0.01). EC and T cells were the major source of MPs in KD (72x105±1x105 vs. 3x105±0.9x105million/ml plasma for T cells p=0.005; 76x105±0.7x105 vs. 45x105±0.4x105 million/ml plasma for EC p<0.02) followed by MPs derived from platelets (13x105±0.3x105 vs. 3x105±0.9x105 million/ml plasma p=0.028). Cell-derived MPs B were 17x105±0.4x105 vs. 20x105±0.8x105million/ml plasma in controls (p=0.7). No significant differences were observed in KD MPs derived from monocytes and neutrophils. After IVIG administration, a significant decrease of MPs derived from platelets (3x105±0.2x105 million/ml plasma p=0.03), EC (9x105±0.4x105 million/ml plasma p=0.01), T cells (72x105±1x105 million/ml plasma p=0.02) and B cells (7x105±0.3x105 million/ml plasma p=0.02) was observed. CONCLUSIONS: The number of KD MPs is significantly increased and EC and T cells are the major source. MPs may develop from endothelial damage and cell activation. Their role as markers of disease activity or as contributors to endothelial derangement in KD has to be further investigated.


Subject(s)
Cell-Derived Microparticles/pathology , Endothelial Cells/pathology , Mucocutaneous Lymph Node Syndrome/diagnosis , T-Lymphocytes/pathology , B-Lymphocytes/pathology , Blood Platelets/pathology , Case-Control Studies , Cell-Derived Microparticles/drug effects , Cell-Derived Microparticles/immunology , Child, Preschool , Endothelial Cells/immunology , Female , Flow Cytometry , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Infant , Italy , Linear Models , Male , Monocytes/pathology , Mucocutaneous Lymph Node Syndrome/immunology , Mucocutaneous Lymph Node Syndrome/pathology , Mucocutaneous Lymph Node Syndrome/therapy , Neutrophils/pathology , Severity of Illness Index , T-Lymphocytes/immunology , Treatment Outcome
8.
IEEE Access ; 9: 37936-37950, 2021.
Article in English | MEDLINE | ID: mdl-34812382

ABSTRACT

Several blockchain projects to help against COVID-19 are emerging at a fast pace, showing the potential of this disruptive technology to mitigate the multi-systemic threats the pandemic is posing on all phases of the emergency management and generate value for the economy and society as a whole. This survey investigates how blockchain technology can be useful in the scope of supporting health actions that can reduce the spread of COVID-19 infections and allow a return to normality. Since the prominent use of blockchains to mitigate COVID-19 consequences are in the area of contact tracing and vaccine/immunity passport support, the survey mainly focuses on these two classes of applications. The aim of the survey is to show that only a proper combination of blockchain technology with advanced cryptographic techniques can guarantee a secure and privacy preserving support to fight COVID-19. In particular, this article first presents these techniques, i.e. zero-knowledge, Diffie Hellman, blind signatures, and proxy re-encryption, then describes how they are used in combination with blockchains to define robust and privacy-preserving solutions. Finally, a brief description of blockchain applications beyond contact tracing and vaccine certification is presented.

9.
Article in English | MEDLINE | ID: mdl-33671417

ABSTRACT

BACKGROUND: Guidelines recommend limiting melanoma screening in a population with known risk factors, but none indicates methods for efficient recruitment. The purpose of this study is to compare three different methods of recruiting subjects to be screened for melanoma to detect which, if any, is the most efficient. METHODS: From 2010 to 2019, subjects were recruited as follows: (1) regular skin examinations (RS), mainly conducted through the Associazione Contro il Melanoma network; (2) occasional melanoma screening (OS), during annual public campaigns; (3) and selective screening (SS), where people were invited to undergo a skin check after filling in a risk evaluation questionnaire, in cases where the assigned outcome was intermediate/high risk. Melanoma risk factors were compared across different screening methods. Generalized Linear Mixed Models were used for multivariable analysis. RESULTS: A total of 2238 subjects (62.7% women) were recruited, median age 44 years (2-85), and 1094 (48.9 %) records were collected through RS, 826 (36.9 %) through OS, and 318 (14.2 %) through SS. A total of 131 suspicious non-melanoma skin cancers were clinically diagnosed, 20 pathologically confirmed, and 2 melanomas detected. SS performed significantly better at selecting subjects with a family history of melanoma and I-II phototypes compared to OS. CONCLUSIONS: Prior evaluation of melanoma known risk factors allowed for effective selection of a population to screen at higher risk of developing a melanoma.


Subject(s)
Melanoma , Skin Neoplasms , Adult , Female , Humans , Male , Mass Screening , Melanoma/diagnosis , Melanoma/epidemiology , Melanoma/prevention & control , Physical Examination , Risk Factors , Skin Neoplasms/diagnosis , Skin Neoplasms/epidemiology , Skin Neoplasms/prevention & control
10.
Clin Neurophysiol ; 131(3): 734-743, 2020 03.
Article in English | MEDLINE | ID: mdl-32007920

ABSTRACT

OBJECTIVE: To localize the seizure onset zone (SOZ) and irritative zone (IZ) using electric source imaging (ESI) on intracranial EEG (iEEG) and assess their clinical value in predicting epilepsy surgery outcome in children with focal cortical dysplasia (FCD). METHODS: We analyzed iEEG data from 25 children with FCD-associated medically refractory epilepsy (MRE) who underwent surgery. We performed ESI on ictal onset to localize SOZ (ESI-SOZ) and on interictal discharges to localize IZ (ESI-IZ). We tested whether resection of ESI-SOZ and ESI-IZ predicted good surgical outcome (Engel 1). We further compared the prediction performance of ESI-SOZ and ESI-IZ to those of SOZ and IZ defined using conventional methods, i.e. by identifying iEEG-contacts showing ictal onsets (conventional-SOZ) or being the most interictally active (conventional-IZ). RESULTS: The proximity of ESI-SOZ (p = 0.043, odds-ratio = 3.9) and ESI-IZ (p = 0.011, odds-ratio = 7.04) to resection has higher effect on patients' outcome than proximity of conventional-SOZ (p = 0.17, odds-ratio = 1.7) and conventional-IZ (p = 0.038, odds-ratio = 2.6). Resection of ESI-SOZ and ESI-IZ presented higher discriminative power in predicting outcome (68% and 60%) than conventional-SOZ and conventional-IZ (48% and 53%). CONCLUSIONS: Localizing SOZ and IZ via ESI on iEEG offers higher predictive value compared to conventional-iEEG interpretation. SIGNIFICANCE: iEEG-ESI may help surgical planning and facilitate prognostic assessment of children with FCD-associated MRE.


Subject(s)
Brain/physiopathology , Drug Resistant Epilepsy/physiopathology , Epilepsy/physiopathology , Malformations of Cortical Development, Group I/physiopathology , Adolescent , Brain/diagnostic imaging , Brain/surgery , Brain Mapping , Child , Child, Preschool , Drug Resistant Epilepsy/diagnostic imaging , Drug Resistant Epilepsy/surgery , Electroencephalography , Epilepsy/diagnostic imaging , Epilepsy/surgery , Female , Humans , Magnetic Resonance Imaging , Male , Malformations of Cortical Development, Group I/diagnostic imaging , Malformations of Cortical Development, Group I/surgery , Preoperative Period , Prognosis , Retrospective Studies , Treatment Outcome
11.
Oncotarget ; 9(18): 14580-14596, 2018 03 06.
Article in English | MEDLINE | ID: mdl-29581865

ABSTRACT

Circular RNAs are highly stable molecules present in all eukaryotes generated by distinct transcript processing. We have exploited poly(A-) RNA-Seq data generated in our lab in MCF-7 breast cancer cells to define a compilation of exonic circRNAs more comprehensive than previously existing lists. Development of a novel computational tool, named CircHunter, allowed us to more accurately characterize circRNAs and to quantitatively evaluate their expression in publicly available RNA-Seq data from breast cancer cell lines and tumor tissues. We observed and confirmed, by ChIP analysis, that exons involved in circularization events display significantly higher levels of the histone post-transcriptional modification H3K36me3 than non-circularizing exons. This result has potential impact on circRNA biogenesis since H3K36me3 has been involved in alternative splicing mechanisms. By analyzing an Ago-HITS-CLIP dataset we also found that circularizing exons overlapped with an unexpectedly higher number of Ago binding sites than non-circularizing exons. Finally, we observed that a subset of MCF-7 circRNAs are specific to tumor versus normal tissue, while others can distinguish Luminal from other tumor subtypes, thus suggesting that circRNAs can be exploited as novel biomarkers and drug targets for breast cancer.

12.
Front Cell Neurosci ; 10: 147, 2016.
Article in English | MEDLINE | ID: mdl-27313512

ABSTRACT

Estrogens are neuroprotective factors in several neurological diseases. Neuroglobin (NGB) is one of the estrogen target genes involved in neuroprotection, but little is known about its transcriptional regulation. Estrogen genomic pathway in gene expression regulation is mediated by estrogen receptors (ERα and ERß) that bind to specific regulatory genomic regions. We focused our attention on 17ß-estradiol (E2)-induced NGB expression in human differentiated neuronal cell lines (SK-N-BE and NT-2). Previously, using bioinformatics analysis we identified a putative enhancer in the first intron of NGB locus. Therefore, we observed that E2 increased the enrichment of the H3K4me3 epigenetic marks at the promoter and of the H3K4me1 and H3K27Ac at the intron enhancer. In these NGB regulatory regions, we found estrogen receptor alpha (ERα) binding suggesting that ERα may mediate chromatin remodeling to induce NGB expression upon E2 treatment. Altogether our data show that NGB expression is regulated by ERα binding on genomic regulatory regions supporting hormone therapy applications for the neuroprotection against neurodegenerative diseases.

13.
PLoS One ; 11(12): e0168639, 2016.
Article in English | MEDLINE | ID: mdl-27992601

ABSTRACT

Tab2, originally described as a component of the inflammatory pathway, has been implicated in phenomena of gene de-repression in several contexts, due to its ability to interact with the NCoR corepressor. Tab2 interacts also with steroid receptors and dismisses NCoR from antagonist-bound Estrogen and Androgen Receptors on gene regulatory regions, thus modifying their transcriptional activity and leading to pharmacological resistance in breast and prostate cancer cells. We demonstrated previously that either Tab2 knock-down, or a peptide mimicking the Estrogen Receptor alpha domain interacting with Tab2, restore the antiproliferative response to Tamoxifen in Tamoxifen-resistant breast cancer cells. In this work, we map the domain of Tab2 responsible of Estrogen Receptor alpha interaction. First, using both co-immunoprecipitation and pull-down with recombinant proteins, we found that the central part of Tab2 is primarily responsible for this interaction, and that this region also interacts with Androgen Receptor. Then, we narrowed down the essential interaction region by means of competition assays using recombinant protein pull-down. The interaction motif was finally identified as a small region adjacent to, but not overlapping, the Tab2 MEKK1 phosphorylation sites. A synthetic peptide mimicking this motif efficiently displaced Tab2 from interacting with recombinant Estrogen Receptor alpha in vitro, prompting us to test its efficacy using derivatives of the MCF7 breast carcinoma cell lines that are spontaneously resistant to Tamoxifen. Indeed, we observed that this mimic peptide, made cell-permeable by addition of the TAT minimal carrier domain, reduced the growth of Tamoxifen-resistant MCF7 cells in the presence of Tamoxifen. These data indicate a novel functional domain of the Tab2 protein with potential application in drug design.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Breast Neoplasms/metabolism , Estrogen Receptor alpha/metabolism , Neoplasm Proteins/metabolism , Adaptor Proteins, Signal Transducing/genetics , Amino Acid Motifs , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Resistance, Neoplasm/drug effects , Drug Resistance, Neoplasm/genetics , Estrogen Receptor alpha/genetics , Female , Humans , MCF-7 Cells , Neoplasm Proteins/genetics , Peptides/genetics , Peptides/pharmacology , Protein Domains , Tamoxifen/pharmacology
14.
Oncotarget ; 7(3): 3201-16, 2016 Jan 19.
Article in English | MEDLINE | ID: mdl-26621851

ABSTRACT

Estrogen Receptor alpha (ERα) activation by estrogenic hormones induces luminal breast cancer cell proliferation. However, ERα plays also important hormone-independent functions to maintain breast tumor cells epithelial phenotype. We reported previously by RNA-Seq that in MCF-7 cells in absence of hormones ERα down-regulation changes the expression of several genes linked to cellular development, representing a specific subset of estrogen-induced genes. Here, we report regulation of long non-coding RNAs from the same experimental settings. A list of 133 Apo-ERα-Regulated lncRNAs (AER-lncRNAs) was identified and extensively characterized using published data from cancer cell lines and tumor tissues, or experiments on MCF-7 cells. For several features, we ran validation using cell cultures or fresh tumor biopsies. AER-lncRNAs represent a specific subset, only marginally overlapping estrogen-induced transcripts, whose expression is largely restricted to luminal cells and which is able to perfectly classify breast tumor subtypes. The most abundant AER-lncRNA, DSCAM-AS1, is expressed in ERα+ breast carcinoma, but not in pre-neoplastic lesions, and correlates inversely with EMT markers. Down-regulation of DSCAM-AS1 recapitulated, in part, the effect of silencing ERα, i.e. growth arrest and induction of EMT markers. In conclusion, we report an ERα-dependent lncRNA set representing a novel luminal signature in breast cancer cells.


Subject(s)
Breast Neoplasms/genetics , Breast Neoplasms/pathology , Estrogen Receptor alpha/genetics , Gene Expression Regulation, Neoplastic , RNA, Long Noncoding/genetics , Biomarkers, Tumor/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Cell Survival/genetics , Down-Regulation , Enzyme Activation , Epithelial-Mesenchymal Transition/genetics , Estrogens/metabolism , Female , HEK293 Cells , Humans , Ligands , MCF-7 Cells , RNA Interference , RNA, Small Interfering/genetics
15.
Clin Implant Dent Relat Res ; 17 Suppl 1: e35-44, 2015 01.
Article in English | MEDLINE | ID: mdl-23879771

ABSTRACT

PURPOSE: The purpose of the present preliminary in vitro study on bovine ribs was to validate a new intraoperative site-specific classification of bone Density Index (IDI), obtained by an innovative computerized implant motor, by correlating these data with the data obtained by the histomorphometrical evaluation of the same samples. MATERIALS AND METHODS: Five segments of bovine ribs were used, and a total of 22 perforations were performed. A computerized implant motor ("Torque Measuring Motor") was used to evaluate the bone density, which was classified into four classes: ID1, ID2, ID3, and ID4. Histomorphometrical analysis of bone density, expressed as percentage of bony trabeculae over the total biopsy area, was also performed. The data of bone density obtained by the implant motor were statistically correlated with the histomorphometrical results. RESULTS: A significant positive correlation was found between the bone density measured by the implant motor and the bone density assessed by histomorphometry (r = 0.89, p < .0001). Moreover, a significant positive correlation in D1, D2, and D4, whereas a negative, not significant correlation in D3 was found. CONCLUSION: Within the limitations of this in vitro study, the intraoperative site-specific classification of bone density, obtained with this innovative system, could be helpful for the clinician to tailor the surgical protocol to the different situations in implant dentistry.


Subject(s)
Bone Density/physiology , Ribs/physiology , Torque , Animals , Cattle , In Vitro Techniques
16.
Clin Implant Dent Relat Res ; 16(3): 394-400, 2014 Jun.
Article in English | MEDLINE | ID: mdl-22967171

ABSTRACT

BACKGROUND: Implant stability is one of the key factors for a successful osseointegration. At present, several techniques are available to regenerate bone tissue, but it is not clear whether implants placed in grafted bone are as stable as implants in native bone over time. PURPOSE: The aim of the present study was to compare, by means of resonance frequency analysis (RFA), the stability of implants placed in sinus-grafted and -nongrafted sites during 12-month follow-up. METHODS: Twenty-five patients received a total of 38 implants. Nineteen implants were placed in maxillary native bone (group A) and 19 implants following maxillary sinus floor augmentation using anorganic bovine bone and autogenous bone (group B) in a 50:50 ratio. Group B was divided into groups B1 and B2 depending on the timing of implant insertion, that is, B1 simultaneously and B2 6 months after sinus lift. The implants were inserted according to a two-stage procedure. RFA values were collected at baseline, 6 and 12 months after implant placement. RESULTS: Between the tested groups, no statistically significant difference was found in RFA values of implants placed in sinus-grafted and -nongrafted sites after the surgery as well as at 6 and 12 months, while a significant difference was recorded in group B1 (p = .0297) when RFA values were compared over time. CONCLUSIONS: The results of the present study suggest that regenerated bone can offer good stability for dental implants.


Subject(s)
Dental Implants , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Surgery, Oral
17.
Ann Stomatol (Roma) ; 4(3-4): 273-7, 2013.
Article in English | MEDLINE | ID: mdl-24611094

ABSTRACT

The aim of the present clinical report was to describe the use of a patient's extensive fixed prosthesis, where the supporting teeth were hopeless, for fabricating an interim immediate complete denture. The present procedure was used to replicate the vertical dimension, phonetic and aesthetic of the existing fixed prostheses as part of an immediate denture and a final complete denture.

18.
Article in English | MEDLINE | ID: mdl-23377047

ABSTRACT

PURPOSE: To evaluate the clinical and histologic aspects of bone formation in maxillary sinus augmentation using macroporous biphasic calcium phosphate (MBCP) comprising hydroxyapatite/tricalcium phosphate (HA/TCP) 60/40 as bone-grafting material. MATERIALS AND METHODS: A total of 10 patients and 12 sinuses grafted with MBCP in two-stage sinus augmentation were included in the present study. After a healing period of 6 months, bone core biopsies were harvested during implant insertion and evaluated under light microscopy. RESULTS: The histologic examination showed that the MBCP particles were in close contact with new bone in all biopsies. Histomorphometric evaluation demonstrated that newly formed bone constituted 28.3% ± 2.7%, residual grafted material 27.3% ± 1.2%, and marrow spaces 45.9% ± 1.9%. CONCLUSIONS: Histologic investigation showed that the MBCP grafted particles were embedded and integrated in the newly formed bone; this bone was in close and tight contact with the biomaterial particles. Data from the preliminary results demonstrated that MBCP is a biocompatible and osteoconductive material that can be successfully used as a grafting material for sinus floor augmentation.


Subject(s)
Bone Substitutes/therapeutic use , Ceramics/therapeutic use , Hydroxyapatites/therapeutic use , Osseointegration/physiology , Osteogenesis/physiology , Sinus Floor Augmentation/methods , Adult , Aged , Bone Regeneration , Durapatite , Female , Humans , Male , Maxillary Sinus/cytology , Middle Aged , Wound Healing
19.
J Periodontol ; 84(9): 1234-42, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23205918

ABSTRACT

BACKGROUND: The aim of the present study is to perform a systematic review of the literature on the use of titanium grids for implant surgery before and simultaneously with implant placement and to assess the success rate of the procedure, as well as survival and success rates of implants placed in the regenerated areas. METHODS: Medline was used to identify studies in English published from 1996 to 2011. An additional hand search was performed of the relevant journals and of the bibliographies of the papers identified. Articles retrieved by two independent authors were screened using specific inclusion criteria: randomized controlled trials (RCTs), controlled clinical trials, and prospective clinical studies regarding vertical and/or horizontal regeneration of the alveolar ridge using titanium grids, in association or not with biomaterials, before and simultaneously with implant placement. RESULTS: Six articles were selected, including a total of 79 patients, 87 titanium grids, and 141 implants. Twenty-four implants were placed simultaneously with titanium grids, and 117 implants were inserted after a period of 4 to 9 months. Titanium grids in combination with autogenous bone were used in 43 cases, 25 in combination with a mixture of autogenous bone and bone substitutes, 14 in association with bone substitutes, five using only titanium grids. The overall success rate of the regenerative procedures was 98.86%; the overall survival and success rates of implants were 100% and 93.2%, respectively. CONCLUSIONS: The main limit of the present systematic review is the scarcity of papers with an adequate and consistent methodology regarding the data collection and analysis and the lack of RCTs and large well-designed long-term trials. Survival and success rates of implants placed in the areas treated with titanium grids were comparable to those of implants placed in native, non-regenerated bone and of implants placed in bone regenerated with resorbable and non-resorbable membranes.


Subject(s)
Alveolar Ridge Augmentation/instrumentation , Biocompatible Materials/chemistry , Dental Implantation, Endosseous/methods , Guided Tissue Regeneration, Periodontal/instrumentation , Surgical Mesh , Titanium/chemistry , Alveolar Ridge Augmentation/methods , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Guided Tissue Regeneration, Periodontal/methods , Humans
20.
Int J Periodontics Restorative Dent ; 32(6): e182-8, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23057061

ABSTRACT

The aim of this study was to evaluate the performance of piezoelectric devices during sinus elevation to determine the percentage of sinus membrane perforation and the time required to perform the antrostomy and elevation of the membrane. A total of 35 patients and 40 grafted sinuses were included. The parameters recorded were bony window length and height, bone thickness, osteotomy area, operative time, and number of perforations. Seven (17.5%) membrane perforations were observed, which were repaired with resorbable membranes. The mean length, height, and thickness of the osteotomy were 13.8 ± 2.9 mm, 6.9 ± 1.4 mm, and 1.4 ± 0.4 mm, respectively. The mean osteotomy area was 96.8 ± 32.2 mm(2), and the mean operative time was 10.3 ± 2.1 minutes. This study demonstrated that a piezoelectric device could be an attractive alternative for successful sinus augmentation.


Subject(s)
Nasal Mucosa/injuries , Piezosurgery/instrumentation , Sinus Floor Augmentation/instrumentation , Absorbable Implants , Adult , Aged , Bone Substitutes/therapeutic use , Bone Transplantation/methods , Female , Follow-Up Studies , Humans , Intraoperative Complications , Jaw, Edentulous/surgery , Male , Maxillary Sinus/pathology , Maxillary Sinus/surgery , Membranes, Artificial , Middle Aged , Nasal Mucosa/surgery , Operative Time , Osteotomy/instrumentation , Piezosurgery/adverse effects , Radiography, Panoramic , Sinus Floor Augmentation/adverse effects , Surgical Flaps/surgery , Tomography, X-Ray Computed , Treatment Outcome
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