Effects of Animal-Assisted Therapy (AAT) in Alzheimer’s Disease: A Case Study

Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by cortical dementia and irreversibly progressive developments leading to a vegetative state and, finally, to death. Although many aspects of its etiology, diagnosis and treatment still remain obscure and the current approach to the disease mostly suffers from limited and low-efficiency therapeutic means, nevertheless, recent interventions have aimed at improving patients’ quality of life through nonpharmacological approaches, including animal-assisted therapy (AAT), arousing growing interest. In order to assess the physiological and neuropsychological effects of AAT on AD, 24 residents of a rest house in northern Italy were enrolled. The intervention consisted of one 45-minute AAT session per week over ten weeks. Twelve residents (six AD and six non-AD) received AAT and twelve (six AD and six non-AD) were controls. In order to evaluate the physiological and clinical effect of AAT on AD residents, three cardiac parameters, including the systolic and diastolic blood pressure and heart rate, were measured. Moreover, the neurocognitive and depressive states were assessed by the Mini Mental State Examination and the Geriatric Depression Scale, respectively. Analyses were performed by a four-way ANOVA model (including two ways for repeated measures) considering each main effect and interaction possible in the design. Our findings, despite the small sample size, suggest that AAT has a positive significant effect on physiological parameters and neurocognitive impairment, while no effect was observed on the depression level

Exosomal transfer of miR-126 promotes the anti-tumour response in malignant mesothelioma: Role of miR-126 in cancer-stroma communication

none11MiR-126 has been shown to suppress malignant mesothelioma (MM) by targeting cancer-related genes without inducing toxicity or histopathological changes. Exosomes provide the opportunity to deliver therapeutic cargo to cancer stroma. Here, a tumour stromal model composed of endothelial cells (HUVECs), fibroblasts (IMR-90 cells), non-malignant mesothelial cells (Met-5A cells) and MM cells (H28 and MM-B1 cells) was used. The cells were treated with exosomes from HUVECs carrying endogenous (exo-HUVEC) and enriched miR-126 (exo-HUVECmiR-126), and the uptake/turnover of exosomes; miR-126 distribution within the stroma; and effect of miR-126 on cell signalling, angiogenesis and cell proliferation were evaluated. Based on the sensitivity of MM cells to exo-HUVEC miR-126 treatment, miR-126 was distributed differently across stromal cells. The reduced miR-126 content in fibroblasts in favour of endothelial cells reduced angiogenesis and suppressed cell growth in an miR-126-sensitive environment. Conversely, the accumulation of miR-126 in fibroblasts and the reduced level of miR-126 in endothelial cells induced tube formation in an miR-126-resistant environment via VEGF/EGFL7 upregulation and IRS1-mediated cell proliferation. These findings suggest that transfer of miR-126 via HUVEC-derived exosomes represents a novel strategy to inhibit angiogenesis and cell growth in MM.noneMonaco, Federica; Gaetani, Simona; Alessandrini, Federica; Tagliabracci, Adriano; Bracci, Massimo; Valentino, Matteo; Neuzil, Jiri; Amati, Monica; Bovenzi, Massimo; Tomasetti, Marco; Santarelli, LoryMonaco, Federica; Gaetani, Simona; Alessandrini, Federica; Tagliabracci, Adriano; Bracci, Massimo; Valentino, Matteo; Neuzil, Jiri; Amati, Monica; Bovenzi, Massimo; Tomasetti, Marco; Santarelli, Lor

The role of melatonin in mood disorders

Melatonin (N-acetyl-5-methoxytryptamine) has been discovered as a hormone secreted by the pineal gland, even though it is also synthetized in various other organs, tissues, and cells. The circadian rhythm of melatonin is often used as an indicator phase position since it is a well-defined, high-amplitude rhythm controlled by the hypothalamic suprachiasmatic nuclei. Melatonin production is controlled by this endogenous circadian timing system. It peaks during the night and is suppressed by daylight. Mood spectrum disorders, including bipolar disorder (BD), major depressive disorder (MDD), and seasonal affective disorder (SAD), have been observed to be accompanied by circadian dysregulation as well as dysregulation in melatonin secretion. Simultaneously, it has also been documented that disruptions in circadian rhythms, including the sleep/wake cycle, though environmental means can produce mood-related problems in vulnerable individuals. These findings suggested that altered circadian rhythms might be biological markers of these disorders. As melatonin is considered a chronobiotic factor, ie, able to entrain the circadian rhythms of several biological functions (eg, activity/rest, sleep/wake, body temperature, endocrine rhythms, etc), its use may provide a new therapeutic approach for the treatment of affective disorders. However, the available evidence is controversial. This review summarizes the data published so far about reliable evidence on the role of melatonin in affective disorder

Alexithymia, responsibility attitudes and suicide ideation among outpatients with obsessive-compulsive disorder: An exploratory study

Abstract Aims Obsessive-compulsive disorder (OCD) is psychiatric disorder with a significant suicide risk, and the presence of alexithymia may increase this risk. As several studies attribute an important role, in OCD, to responsibility, the aims of this study were to evaluate possible clinical differences between patients positive or not for alexithymia concerning disorder severity, responsibility attitudes and suicide ideation and investigate which variables were associated with increased suicide ideation. Methods 104 adult outpatients with OCD were recruited. Alexithymia was measured with Toronto Alexithymia Scale (TAS-20), attitude about responsibility was tested with Responsibility Attitude Scale (RAS), suicide ideation was assessed with Scale of Suicide Ideation (SSI) and depressive symptoms were evaluated with Montgomery Asberg Depression Rating Scale (MADRS). Score of item #11 on the Y-BOCS was considered as a measure of insight. Results Patients positive for alexithymia showed higher responsibility attitudes and more severe suicide ideation. In a blockwise regression model, the presence of lower insight, higher RAS scores and difficulty in identifying feelings dimension of TAS-20 were associated with higher SSI scores. Conclusions OCD patients with alexithymia may show higher disorder severity, lower insight and inflated responsibility, all related to suicide ideation, independently from depressive symptoms. Implications were discussed and study limitations considered and reported

MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses

Background: Intestinal-type sinonasal adenocarcinomas (ITACs) are aggressive malignancies related to wood dust and leather exposure. ITACs are generally associated with advanced stage at presentation due to the insidious growth pattern and non-specific symptoms. Therefore, biomarkers that can detect the switch from the benign disease to malignancy are needed. Essential for tumour growth, angiogenesis is an important step in tumour development and progression. This process is strictly regulated, and MiR-126 considered its master modulator. Methods: We have investigated MiR-126 levels in ITACs and compared them to benign sinonasal lesions, such as sinonasal-inverted papillomas (SIPs) and inflammatory polyps (NIPs). The tumour-suppressive functions of MiR-126 were also evaluated. Results: We found that MiR-126 can significantly distinguish malignancy from benign nasal forms. The low levels of MiR- 126 in ITACs point to its role in tumour progression. In this context, restoration of MiR-126 induced metabolic changes, and inhibited cell growth and the tumorigenic potential of MNSC cells. Conclusions: We report that MiR-126 delivered via exosomes from endothelial cells promotes anti-tumour responses. This paracrine transfer of MiRs may represent a new approach towards MiR-based therapy

Association of MiR-126 with Soluble Mesothelin-Related Peptides, a Marker for Malignant Mesothelioma

BACKGROUND: Improved detection methods for diagnosis of malignant pleural mesothelioma (MPM) are essential for early and reliable detection as well as treatment. Since recent data point to abnormal levels of microRNAs (miRNAs) in tumors, we hypothesized that a profile of deregulated miRNAs may be a marker of MPM and that the levels of specific miRNAs may be used for monitoring its progress. METHODS AND RESULTS: miRNAs isolated from fresh-frozen biopsies of MPM patients were tested for the expression of 88 types of miRNA involved in cancerogenesis. Most of the tested miRNAs were downregulated in the malignant tissues compared with the normal tissues. Of eight significantly downregulated, three miRNAs were assayed in cancerous tissue and adjacent non-cancerous tissue sample pairs collected from 27 formalin-fixed, paraffin-embedded MPM tissues by quantitative RT-PCR. Among the miRNAs tested, only miR-126 significantly remained downregulated in the malignant tissues. Furthermore, the performance of the selected miR-126 as biomarker was evaluated in serum samples of asbestos-exposed subjects and MPM patients and compared with controls. MiR-126 was not affected by asbestos exposure, whereas it was found strongly associated with VEGF serum levels. Levels of miR-126 in serum, and its levels in patients' serum in association with a specific marker of MPM, SMRPs, correlate with subjects at high risk to develop MPM. CONCLUSIONS AND SIGNIFICANCE: We propose miR-126, in association with SMRPs, as a marker for early detection of MPM. The identification of tumor biomarkers used alone or, in particular, in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos

Ruolo antiossidante del coenzima Q10 nella prevenzione del danno ossidativo in macromolecole biologiche

Dottorato di ricerca in biochimica-biofisica. 11. ciclo. A.a. 1998-99. Coordinatore F. Rustichelli. Tutore G. P. LittarruConsiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome; Biblioteca Nazionale Centrale - P.za Cavalleggeri, 1, Florence / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

MicroRNA in Metabolic Re-Programming and Their Role in Tumorigenesis

The process of metabolic re-programing is linked to the activation of oncogenes and/or suppression of tumour suppressor genes, which are regulated by microRNAs (miRNAs). The interplay between oncogenic transformation-driven metabolic re-programming and modulation of aberrant miRNAs further established their critical role in the initiation, promotion and progression of cancer by creating a tumorigenesis-prone microenvironment, thus orchestrating processes of evasion to apoptosis, angiogenesis and invasion/migration, as well metastasis. Given the involvement of miRNAs in tumour development and their global deregulation, they may be perceived as biomarkers in cancer of therapeutic relevance

Vitamin E analogues and immune response in cancer treatment.

Chemotherapeutic drugs induce both proliferation arrest and apoptosis; however, some cancer cells escape drug toxicity and become resistant. The suppression of the immune system by chemotherapeutic agents and radiation promotes the development and propagation of various malignancies via "mimicry-induced" autoimmunity, and maintain a cytokine milieu that favors proliferation by inhibiting apoptosis. A novel, efficient approach is based on a synergistic effect of different anticancer agents with different modes of action. Recently, a redox-silent analogue of vitamin E, alpha-tocopheryl succinate (alpha-TOS), has come into focus due to its anticancer properties. alpha-TOS behaves in a very different way than its redox-active counterpart, alpha-tocopherol, since it promotes cell death. It exerts pleiotrophic responses in malignant cells leading to cell cycle arrest, differentiation, and apoptosis. Apart from its role in killing cancer cells via apoptosis, alpha-TOS affects expression of genes involved in cell proliferation and cell death in a "subapoptotic" manner. For example, it modulates the cell cycle machinery, resulting in cell cycle arrest. The ability of alpha-TOS to induce a prolonged S phase contributes to sensitization of cancer cells to drugs destabilizing DNA during replication. A cooperative antitumor effect was observed also when alpha-TOS was combined with immunological agents. alpha-TOS and TRAIL synergize to kill cancer cells either by upregulating TRAIL death receptors or by amplifying the mitochondrial apoptotic pathway without being toxic to normal cells. alpha-TOS and TRAIL in combination with dendritic cells induce INF-gamma production by CD4+ and CD8+ T lymphocytes, resulting in a significant tumor growth inhibition or in complete tumor regression. These findings are indicative of a novel strategy for cancer treatment that involves enhanced immune system surveillance

Biomarkers for Early Detection of Malignant Mesothelioma: Diagnostic and Therapeutic Application

Malignant mesothelioma (MM) is a rare and aggressive tumour of the serosal cavities linked to asbestos exposure. Improved detection methods for diagnosing this type of neoplastic disease are essential for an early and reliable diagnosis and treatment. Thus, focus has been placed on finding tumour markers for the non-invasive detection of MM. Recently, some blood biomarkers have been described as potential indicators of early and advanced MM cancers. The identification of tumour biomarkers alone or in combination could greatly facilitate the surveillance procedure for cohorts of subjects exposed to asbestos, a common phenomenon in several areas of western countries