Genomic organization and cytokine-mediated inducibility of the human TRIM-8/Gerp gene.

Cytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appear rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family, interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in-vitro and in-vivo. Trim-8/Gerp, transcribes a 3.0-kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-γ in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor, and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling

Autophagy processes are dependent on EGF receptor signaling

Autophagy is a not well-understood conserved mechanism activated during nutritional deprivation in order to maintain cellular homeostasis. In the present study, we investigated the correlations between autophagy, apoptosis and the MAPK pathways in melanoma cell lines. We demonstrated that during starvation the EGF receptor mediated signaling activates many proteins involved in the MAPK pathway. Our data also suggest a previously unidentified link between the EGFR and Beclin-1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key inhibitory role in the early stage of starvation, possibly through the Beclin-1 sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of the autophagic process. Interestingly enough, when the EGFR pathway was blocked by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho-EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax was observed with a decreased activation of the stress-induced JNK kinase, thus avoiding the transduction pathways that activate autophagy and apoptosis, respectively. For this reason, we advance the hypothesis that the activation of the EGFR is a necessary event that allows the ignition and progression of the autophagic process, at least in melanoma cells

differential tbxa2 receptor transcript stability is dependent on the c924t polymorphism

Abstract Background In order to better characterize the molecular mechanisms involved in processing mutated transcripts, we investigated the post-transcriptional role of the C924T polymorphism (rs4523) located in the 3′ region of the TBXA2R gene. Methods and Results Experiments of dose response with Actinomycin D on MEG-01 human cell line showed a significant decrease on cell viability that was more evident on cells treated for 24 h. In addition, we showed that treatments with 5–10 μM, 15 μM and 20 μM of actinomycin D reduced cell viability by 44%, 72% and 75%, respectively, compared to the control group. Conversely, the samples treated with 1 μM of actinomycin D did not show significant difference on cell viability as compared to the control group. Analysis of the steady state mRNA level of TBXA2R by qRT-PCR evidenced an increase in mRNA stability for the wild type (C) compared to the mutant (T) allele. Furthermore, the expression levels of TBXA2R on wild type (CC) and mutant type (TT) patients, based on C924T polymorphism, were analyzed. The wild type showed a higher expression of TBXA2 receptor also with two different degrees of glycosylation (55 and 64 kDa), when compared to the mutant. These observations correlated with platelet aggregation, which was reduced in TT, independently of the platelet aggregation stimuli. Conclusions The instability of the TBXA2R transcript and the lack of effect on platelet aggregation might suggest a protective role for the TBXA2R TT genotype against atherothrombosis and its complications in high-risk aspirin-treated patients

Impact of neuropeptide substance P an inflammatory compound on arachidonic acid compound generation

There is much evidence that neuropeptide substance P is involved in neurogenic inflammation and is an important neurotransmitter and neurmodulator compound. In addition, substance P plays an important role in inflammation and immunity. Macrophages can be activated by substance P which provokes the release of inflammatory compounds such as interleukins, chemokines and growth factors. Substance P is involved in the mechanism of pain through the trigeminal nerve which runs through the head, temporal and sinus cavity. Substance P also activates mast cells to release inflammatory mediators such as arachindonic acid compound, cytokines/chemokines and histamine. The release of these chemical mediators is crucial for inflammatory response. Among these mediators there are prostoglandins and leukotrines. Here we review the impact of substance P on inflammatory compounds

Midpalatal Suture Density as a Function of Sex and Growth-Pattern-Related Variability via CBCT Evaluations of 392 Adolescents Treated with a Rapid Maxillary Expander Appliance

Background and objectives. This paper aimed to evaluate the changes in mean bone density values of the midpalatal suture (MPS) in 392 young patients treated with a rapid palatal expander (RPE) appliance, depending on sex and vertical and sagittal skeletal patterns. Materials and Methods. Evaluations were performed using a low-dose protocol for cone beam computed tomography scans at T0 (preoperative) and T1 (1 year after the beginning of the therapy). The region of interest was used to calculate bone density in Hounsfield units (HU) for the area between the maxillary incisors. Results. CBCT scan data of 196 females and 196 males (mean age of 11.7 years) showed homogeneous and similar density values of the MPS at T0 (550.17–563.70 HU) and T1 (541.92–553.85 HU). Class III skeletal individuals showed significantly higher BD than the Class II group at T0, but not at T1. Females showed significant and substantially higher BD than males at T0 and T1. No significant differences were found between the other groups and between the two time points in terms of the bone density values of the MPS. Conclusions. Females and the Class III group showed significantly higher bone density values than males and Class II, respectively. No statistically significant differences were found from T0 to T1 in any groups, suggesting that a similar rate of suture reorganization occurs after the use of an RPE, causing reorganization and bone deposition along the MPS

The murine p202 protein, an IFN-Inducible modulator of transcription, is activated by the mitogen platelet-derived growth factor

p202 is a murine interferon (IFN)-inducible protein belonging to a cluster of IFN-inducible genes (the 200 family) located in a segment of chromosome I. It is a nuclear DNA-binding protein that is able to modulate transcription by interacting with a heterogeneous set of transcription factors, including NF-kappaB, (p50/p65), AP-1, c-fos, c-jun, and RB-1, The p202 protein is believed to attenuate cell growth/proliferation, mainly through the activation of IFN-stimulated of gene factor 3 (ISGF3), which binds IFN-stimulated response elements (ISRE) located in the promoters of type I IFN genes. In this report, we show that the p202 gene can also be induced by platelet-derived growth factor (PDGF), a mitogen known to drive G(o)-arrested cells toward reentry into the cell cycle, PDGF transiently enhances the steady-state mRNA level of p202 and increases the p202 protein level independently from IFN signaling, by acting at the transcriptional level on its promoter. The kinetics of p202 induction by PDGF are faster and more transient than those of IFN, These data identify p202 as a member of the IFN-inducible gene family that can be directly regulated by mitogenic stimuli

Oxidative stress and cardiovascular risk: the role of vascular NAD(P)H oxidase and its genetic variants

Several risk factors for coronary artery disease (CAD) induce atherosclerosis through endothelial activation and dysfunction, and ample evidence now suggests that the balance between production and removal of reactive oxygen species (ROS) - a condition termed oxidative stress - is implicated in such processes. A main source of ROS in vascular cells is the reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase system. This is a membrane-associated enzyme, composed of five subunits, catalyzing the one-electron reduction of oxygen, using NADH or NADPH as the electron donor. One of the system subunits, termed p22-phox, has a polymorphic site on exon 4, associated with variable enzyme activity. This polymorphism is generated by a point mutation (C(242)T) producing a substitution of histidine with tyrosine at position 72, which affects one of the heme binding sites essential for the NAD(P)H enzyme activity. The consequent decrease of superoxide production thus characterizes a phenotype candidate for conferring to the carrier a reduced susceptibility to CAD. At present, however, the body of evidence from current literature is not yet sufficient to confirm or exclude the hypothesis that the C(242)T polymorphism protects from CAD. The functional effects of this polymorphism and the potential and its pathophysiological consequences also need further investigatio

Measurement of Airflow Resistivity Variation Due to Temperature and Its Impact on Simulated Sound Absorption Inside a Vehicle’s Passenger Compartment

Airflow resistivity is one of the most important parameters in the study of the physical properties of porous acoustic materials. This parameter is fundamental for the correct evaluation of sound absorption of acoustic materials and is needed in all the theoretical models. In the present work, airflow resistivity of porous materials is determined under effective operating conditions inside a vehicle (temperature, compression of the panels). Starting from the discussion on the measurement uncertainty, experimental data of airflow resistivity, measured as a function of temperature and applied static loads, are presented. By introducing the measured values in a SEA model of a typical vehicle panel, the foreseen values of acoustic absorption due to variation of temperature and static load are determined and presented

Metabolic Alterations, Aggressive Hormone-Naïve Prostate Cancer and Cardiovascular Disease: A Complex Relationship

Background: Epidemiological studies suggest a possible relationship between metabolic alterations, cardiovascular disease and aggressive prostate cancer, however, no clear consensus has been reached. Objective: The aim of the study was to analyze the recent literature and summarize our experience on the association between metabolic disorders, aggressive hormone-naïve prostate cancer and cardiovascular disease. Method: We identified relevant papers by searching in electronic databases such as Scopus, Life Science Journals, and Index Medicus/Medline. Moreover, we showed our experience on the reciprocal relationship between metabolic alterations and aggressive prostate cancer, without the influence of hormone therapy, as well the role of coronary and carotid vasculopathy in advanced prostate carcinoma. Results: Prostate cancer cells have an altered metabolic homeostatic control linked to an increased aggressivity and cancer mortality. The absence of discrimination of risk factors as obesity, systemic arterial hypertension, diabetes mellitus, dyslipidemia and inaccurate selection of vascular diseases as coronary and carotid damage at initial diagnosis of prostate cancer could explain the opposite results in the literature. Systemic inflammation and oxidative stress associated with metabolic alterations and cardiovascular disease can also contribute to prostate cancer progression and increased tumor aggressivity. Conclusions: Metabolic alterations and cardiovascular disease influence aggressive and metastatic prostate cancer. Therefore, a careful evaluation of obesity, diabetes mellitus, dyslipidemia, systemic arterial hypertension, together with a careful evaluation of cardiovascular status, in particular coronary and carotid vascular disease, should be carried out after an initial diagnosis of prostatic carcinoma