The tumor suppressor p53 is a negative regulator of the carcinoma-associated transcription factor FOXQ1.

The forkhead box family transcription factor FOXQ1 is highly induced in several types of carcinomas, where it promotes epithelial-to-mesenchymal transition and tumor metastasis. The molecular mechanisms that lead to FOXQ1 deregulation in cancer are incompletely understood. Here, we used CRISPR-Cas9-based genomic locus proteomics and promoter reporter constructs to discover transcriptional regulators of FOXQ1 and identified the tumor suppressor p53 as a negative regulator of FOXQ1 expression.

The oncogenic transcription factor FOXQ1 is a differential regulator of Wnt target genes.

The forkhead box transcription factor FOXQ1 contributes to the pathogenesis of carcinomas. In colorectal cancers, FOXQ1 promotes tumour metastasis by inducing epithelial-to-mesenchymal transition (EMT) of cancer cells. FOXQ1 may exacerbate cancer by activating the oncogenic Wnt/β-catenin signalling pathway.

Protocol for Prevention and Monitoring of Surgical Site Infections in Implant-Based Breast Reconstruction: Preliminary Results.

Surgical site infection in implant-based breast reconstruction is a complication with variable incidence reported in the literature. Due to potential loss of implant and reconstruction, it can have a strong psychological impact on patients. This study aimed primarily at analyzing the current status of the surgical site infection (SSI), (type, time of onset, clinical presentation, pathogens and management) in patients who underwent implant-based breast reconstruction at our Breast Unit.

A human minisatellite hosts an alternative transcription start site for NPRL3 driving its expression in a repeat number-dependent manner.

Minisatellites, also called variable number of tandem repeats (VNTRs), are a class of repetitive elements that may affect gene expression at multiple levels and have been correlated to disease. Their identification and role as expression quantitative trait loci (eQTL) have been limited by their absence in comparative genomic hybridization and single nucleotide polymorphisms arrays. By taking advantage of cap analysis of gene expression (CAGE), we describe a new example of a minisatellite hosting a transcription start site (TSS) which expression is dependent on the repeat number.

Wnt activator FOXB2 drives the neuroendocrine differentiation of prostate cancer.

The Wnt signaling pathway is of paramount importance for development and disease. However, the tissue-specific regulation of Wnt pathway activity remains incompletely understood. Here we identify FOXB2, an uncharacterized forkhead box family transcription factor, as a potent activator of Wnt signaling in normal and cancer cells.

Single-cell RNA sequencing unveils the shared and the distinct cytotoxic hallmarks of human TCRVδ1 and TCRVδ2 γδ T lymphocytes.

γδ T lymphocytes represent ∼1% of human peripheral blood mononuclear cells and even more cells in most tissues of vertebrates. Although they have important anticancer functions, most current single-cell RNA sequencing (scRNA-seq) studies do not identify γδ T lymphocytes because their transcriptomes at the single-cell level are unknown. Here we show that high-resolution clustering of large scRNA-seq datasets and a combination of gene signatures allow the specific detection of human γδ T lymphocytes and identification of their T cell receptor (TCR)Vδ1 and TCRVδ2 subsets in large datasets from complex cell mixtures.

Different Circulating Trace Amine Profiles in De Novo and Treated Parkinson's Disease Patients.

Early diagnosis of Parkinson's disease (PD) remains a challenge to date. New evidence highlights the potential clinical value of circulating trace amines (TAs) in early-stage PD and their involvement in disease progression. A new ultra performance chromatography mass spectrometry (UPLC-MS/MS) method was developed to quantify plasmatic TAs, and the catecholamines and indolamines pertaining to the same biochemical pathways.

γδ T Cells and Tumor Microenvironment: From Immunosurveillance to Tumor Evasion.

γδ T cells possess cytotoxic antitumor activity mediated by production of proinflammatory cytokines, direct cytotoxic activity, and regulation of the biological functions of other cell types. Hence, these features have prompted the development of therapeutic strategies in which γδ T cells agonists or -expanded γδ T cells are administered to tumor patients. Several studies have shown that γδ T cells are an important component of tumor-infiltrating lymphocytes in patients affected by different types of cancer and a recent analysis of ~18,000 transcriptomes from 39 human tumors identified tumor-infiltrating γδ T cells as the most significant favorable cancer-wide prognostic signature.

γδ cells and tumor microenvironment: A helpful or a dangerous liason?

γδ T cells are a subset of T lymphocytes that have been implicated in immunosurveillance against infections and tumors. γδ T cells are endowed with antitumor activities, and hence several γδ T cell-based small-scale clinical trials have been conducted either by in vivo activation by intravenous administration of aminobiphosphonates or by adoptive transfer of in vitro expanded γδ T cells. Although both these strategies have yielded promising results, there are a number of limitations associated with each of them which, if overcome may help to further improve efficacy.

Current Advances in γδ T Cell-Based Tumor Immunotherapy.

γδ T cells are a minor population (~5%) of CD3 T cells in the peripheral blood, but abound in other anatomic sites such as the intestine or the skin. There are two major subsets of γδ T cells: those that express Vδ1 gene, paired with different Vγ elements, abound in the intestine and the skin, and recognize the major histocompatibility complex (MHC) class I-related molecules such as MHC class I-related molecule A, MHC class I-related molecule B, and UL16-binding protein expressed on many stressed and tumor cells. Conversely, γδ T cells expressing the Vδ2 gene paired with the Vγ9 chain are the predominant (50-90%) γδ T cell population in the peripheral blood and recognize phosphoantigens (PAgs) derived from the mevalonate pathway of mammalian cells, which is highly active upon infection or tumor transformation.

Expression of the Endocannabinoid Receptor 1 in Human Stroke: An Autoptic Study.

Objective: Stroke is one of the leading causes of disability and death in the world. The endocannabinoid (eCB) system is upregulated in several neurological diseases including stroke. A previous animal study demonstrated an increased expression of the endocannabinoid receptor 1 (CB1R) in the penumbra area surrounding the ischemic core, suggesting a crucial role in inflammation/reperfusion after stroke.

Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.

Background: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD.

Amino acid supplementation in l-dopa treated Parkinson's disease patients.

Background: The correlation between Parkinson disease and malnutrition is well established, however a protein-restricted diet is usually prescribed because of potentially negative interactions between dietary amino acids and l-dopa pharmacokinetics. This strategy could increase the risk of further nutritional deficits.

Methods: A monocentric, prospective, randomized, double-blind pilot study was performed on two groups of Parkinson-affected, protein-restricted, patients: Intervention (n = 7; amino acid supplementation twice daily) and Placebo (n = 7; placebo supplementation twice daily).

Clinical usefulness of dopamine transporter SPECT imaging with 123I-FP-CIT in patients with possible dementia with Lewy bodies: randomised study.

Background: Dementia with Lewy bodies (DLB) is underrecognised in clinical settings.

Aims: To investigate whether performing a (123)I-ioflupane injection ((123)I-FP-CIT also called DaTSCAN™) single photon emission computed tomography (SPECT) scan in patients with possible DLB would lead to a more certain diagnosis (probable DLB or non-DLB dementia).

Method: We randomised 187 patients with possible DLB 2:1 to have a scan or not (control group).

Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development.

The p53 tumor suppressor is a potent transcription factor that plays a key role in the regulation of cellular responses to stress. It is controlled by its negative regulator MDM2, which binds directly to p53 and inhibits its transcriptional activity. MDM2 also targets p53 for degradation by the proteasome.

Long-range neural activity evoked by premotor cortex stimulation: a TMS/EEG co-registration study.

The premotor cortex is one of the fundamental structures composing the neural networks of the human brain. It is implicated in many behaviors and cognitive tasks, ranging from movement to attention and eye-related activity. Therefore, neural circuits that are related to premotor cortex have been studied to clarify their connectivity and/or role in different tasks.

Absolute quantification of choline-related biomarkers in breast cancer biopsies by liquid chromatography electrospray ionization mass spectrometry.

It has been repeatedly demonstrated that choline metabolism is altered in a wide variety of cancers. In breast tumours, the choline metabolite profile is characterized by an elevation of phosphocholine and total choline-compounds. This pattern is increasingly being exploited as biomarker in cancer diagnosis.

The incidence of amyotrophic lateral sclerosis in Friuli Venezia Giulia, Italy, from 2002 to 2009: a retrospective population-based study.

Background: We conducted a retrospective population-based study to estimate the incidence of amyotrophic lateral sclerosis (ALS) in Friuli Venezia Giulia, Italy, from 2001 to 2009.

Methods: Multiple sources were used for case ascertainment: Health databases, archives of the neurology departments and of the regional chapter of the Italian ALS Association. The diagnosis was validated through clinical documentation review.

Smooth muscle cells of human intracranial aneurysms assume phenotypic features similar to those of the atherosclerotic plaque.

Objectives: Characterize the phenotypic features of smooth muscle cells (SMCs) in the wall of human saccular intracranial aneurysms (sIAs).

Methods And Results: We investigated by means of immunohistochemistry the expression of the cytoskeletal differentiation markers α-smooth muscle actin (α-SMA), smooth muscle myosin heavy chains (SMMHCs), and smoothelin in 26 sIAs and 15 nonaneurysmal cerebral arteries. In addition, S100A4, a recently identified marker of dedifferentiated SMCs in atherosclerotic plaques, was also investigated.

Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors.

A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead compound 1 have been synthesized and evaluated for their effects on mitosis and angiogenesis. Described herein is the design, synthesis, SAR, and antitumor activity of these compounds leading to the identification of R1530, which was selected for clinical evaluation.

Optic nerve and its arterial-venous vascularization: an ultrasonologic study in multiple sclerosis patients and healthy controls.

Background: Recent studies suggest that alterations in the cerebrospinal venous system may play a role in multiple sclerosis (MS) and that chronic cerebrospinal venous insufficiency correlates with clinical features of MS patients.

Objectives: To evaluate the vascularization of optic nerve (ONr) and measure ONe thickness by color Doppler ultrasonography in MS patients with and without previous optic neuritis (ONe).

Subjects And Methods: We assessed flow variables in the ophthalmic artery, central retinal artery, and central retinal vein and measured the diameter of ONe in 46 relapsing-remitting MS patients and 37 healthy controls (HC).

Transcranial magnetic stimulation and preparation of visually-guided reaching movements.

To better define the neural networks related to preparation of reaching, we applied transcranial magnetic stimulation (TMS) to the lateral parietal and frontal cortex. TMS did not evoke effects closely related to preparation of reaching, suggesting that neural networks already identified by our group are not larger than previously thought. We also replicated previous TMS/EEG data by applying TMS to the parietal cortex: new analyses were performed to better support reliability of already reported findings (Zanon et al.

Altered serum content of brain-derived neurotrophic factor isoforms in multiple sclerosis.

In multiple sclerosis (MS), brain-derived neurotrophic factor (BDNF) provides neuroprotection, but can also promote disease through the maintenance of autoreactive T cells. One aspect that has not been explored yet in MS is related to the opposite functions of BDNF protein isoforms consisting of the pro-BDNF precursor, which has pro-apoptotic effects, and two proteolytic isoforms, the mature BDNF with pro-survival effects and truncated BDNF, with unknown functions. Using ELISA and semi-quantitative Western-blot we determined the relative serum levels of BDNF isoforms in 20 relapsing-remitting MS patients without any disease modifying therapy and 20 age and gender-matched healthy controls and searched for clinical correlates.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue.

Purpose: This study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue.

Materials And Methods: We enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.