Sviluppo di strategie per nuovi approcci terapeutici nelle malattie neurodegenerative

Development of strategies for new therapeutic approaches in neurodegenerative diseases Nowadays the causes of the onset of neurodegenerative diseases are not completely yet known, but it is confirmed that environmental, metabolic and nutritional factors contribute to their development. Among the involved mechanisms in neurodegeneration, the oxidative stress has been extensively studied in recent decades. In this regard in the present work, various drug delivery systems have been tested, as such or containing drugs, to evaluate their pharmacological effect in different cell models. Molecules of different nature, loaded to transferosomes or chitosan particles, protected PC12 cells from oxidative damage induced by hydrogen peroxide and from parkinsonism induced by the neurotoxin MPTP. A further study on MPTP damage was performed to measure glucose and lactate levels involved in the energy metabolism of cells using enzymatic biosensors. The cells were exposed to insulin, hormone known in literature to promote glucose internalization, which was able to restore aerobic metabolism interrupted by the damage induced by neurotoxin. The promising results obtained in this research allows to hypothesize new therapeutic approaches, based on drug delivery systems and drugs already known in several roles, able to protect as co-therapeutics in neurodegenerative diseases, such as Parkinson

Vertigo and Dizziness in Children: An Update

Background: Vertigo and dizziness are relatively infrequent in paediatric patients, but specific data on the prevalence of these disorders are limited and influenced by various factors, including the age of the examined population. These conditions often have a significant impact on patients' and parents' quality of life. The aim of this paper is to investigate the prevalence of different aetiologies of vertigo in the paediatric population through a systematic review. Methods: According to PRISMA guidelines, a systematic review of the literature was performed. Medline and Embase were searched from January 2011 through to 10 September 2021. The search yielded 1094 manuscripts, which were reduced to 7 upon the application of inclusion criteria. Results: A total of 2470 paediatric patients were evaluated by the selected papers. Vestibular Migraine was the most frequently diagnosed condition, occurring alone or in association with other diseases. Overall, audio-vestibular disorders represented the second cause of vertigo, and the prevalence appears to increase according to age growth. Over the years, even though we assisted in the amelioration of diagnostic rates, partially related to an improvement in diagnostic tools, the aetiology of vertigo remains still unclear in a variable percentage of patients. Conclusion: Vertigo in children, despite being an uncommon symptom, requires a multidisciplinary approach, often involving Paediatricians, Neurologists and Otorhinolaryngologists. A comprehensive evaluation of children suffering from vertigo is crucial for establishing a successful therapy and reducing parental worries

Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line.

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma

ViromeScan: a new tool for metagenomic viral community profiling

BACKGROUND: Bioinformatics tools available for metagenomic sequencing analysis are principally devoted to the identification of microorganisms populating an ecological niche, but they usually do not consider viruses. Only some software have been designed to profile the viral sequences, however they are not efficient in the characterization of viruses in the context of complex communities, like the intestinal microbiota, containing bacteria, archeabacteria, eukaryotic microorganisms and viruses. In any case, a comprehensive description of the host-microbiota interactions can not ignore the profile of eukaryotic viruses within the virome, as viruses are definitely critical for the regulation of the host immunophenotype. RESULTS: ViromeScan is an innovative metagenomic analysis tool that characterizes the taxonomy of the virome directly from raw data of next-generation sequencing. The tool uses hierarchical databases for eukaryotic viruses to unambiguously assign reads to viral species more accurately and >1000 fold faster than other existing approaches. We validated ViromeScan on synthetic microbial communities and applied it on metagenomic samples of the Human Microbiome Project, providing a sensitive eukaryotic virome profiling of different human body sites. CONCLUSIONS: ViromeScan allows the user to explore and taxonomically characterize the virome from metagenomic reads, efficiently denoising samples from reads of other microorganisms. This implies that users can fully characterize the microbiome, including bacteria and viruses, by shotgun metagenomic sequencing followed by different bioinformatic pipelines. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-016-2446-3) contains supplementary material, which is available to authorized users

The Role of Primary Mitochondrial Disorders in Hearing Impairment: An Overview

Background. Defects of mitochondrial DNA (mtDNA) involved in the function of the mitochondrial electron transport chain can result in primary mitochondrial diseases (PMDs). Various features can influence the phenotypes of different PMDs, with relevant consequences on clinical presentation, including the presence of hearing impairment. This paper aims to describe the hearing loss related to different PMDs, and when possible, their phenotype. Methods. A systematic review was performed according to PRISMA guidelines, searching Medline until December 2022. A total of 485 papers were identified, and based on specified criteria, 7 were included in this study. Results. A total of 759 patients affected by PMDs and hearing loss were included. The age of patients ranged from 2 days to 78 years old, and the male-to-female ratio was 1.3:1. The percentage of subjects affected by hearing loss was 40.8%, (310/759), and in most cases, hearing impairment was described as sensorineural, bilateral, symmetrical, and progressive, with different presentations depending on age and syndrome severity. Conclusions. PMDs are challenging conditions with different clinical phenotypes. Hearing loss, especially when bilateral and progressive, may represent a red flag; its association with other systemic disorders (particularly neuromuscular, ocular, and endocrine) should alert clinicians, and confirmation via genetic testing is mandatory nowadays

Vertigo in the Elderly: A Systematic Literature Review

Background: Dizziness and vertigo are among the most prevalent complaints in the elderly and have a major negative influence on (i) the perception of the quality of life; and (ii) the risk of falling. Due to population aging, particularly in wealthy nations, vertigo represents a growing issue and a serious public health concern. In order to approach the patient correctly and to offer the best treatment options, it is mandatory to identify vertigo’s underlying causes. The aim of this paper was to identify the different etiologies of vertigo and possibly their frequency in the elderly population, by reviewing the scientific literature of the last decade (2012–2022). Methods: A systematic review was performed according to PRISMA guidelines, searching the Medline database from January 2012 through to December 2022. The search identified 1025 candidate papers, but after the application of specific selection criteria, only five were considered for further analysis. Results: A total of 2148 elderly patients (60–90 y old) presenting with vertigo were reported in the selected papers. A total of 3404 conditions were identified as the cause of vertiginous symptoms, (some patients presented multiple etiologies). All major diagnoses were categorized into different subgroups: the most common origin of vertigo was represented by audio-vestibular disorders (28.4%), followed by cardiovascular (20.4%) and neurological diseases (15.1%). Furthermore, 9.1% of patients were diagnosed with psychiatric conditions, whilst ophthalmologic and musculoskeletal disorders accounted for 7.5% and 6.3% of the cases respectively. Medication adverse effects and metabolic-related diseases were also considered among the causes. For 3.4% of cases the etiology remains unclear. Conclusions: Audio-vestibular disorders represent the most frequent cause of vertigo in the elderly. The etiologies affecting the vertigo patient must be defined in order to identify potential life-threatening conditions, such as cardiovascular and neurological disorders, which according to the data of this review constitute the second and third common causes of vertigo. A multidisciplinary strategy, involving different specialists (such as ENTs, Neurologists, Cardiologists, Geriatricians) is recommended for the correct assessment of these disorders

Management of Juvenile Otosclerosis: A Systematic Review

Background. Otosclerosis can occur during childhood, resulting in the early onset of conductive hearing loss. The approach to a child with otosclerosis can present some difficulties in terms of diagnosis and treatment, and the literature on juvenile otosclerosis (JO) is still relatively limited. Aim. To explore the current approaches to JO, in order to clear the management of this condition and evaluate the outcomes and the possible complications of surgical treatment. Methods. A systematic review was performed according to PRISMA guidelines, searching Medline and Embase from January 2002 through to 30 September 2022. A total of 759 papers were identified but based on specified criteria, nine were included in this study. Results. There were 94 children affected by JO and treated by stapes surgery. According to the available data, Male: Female ratio was 1:3-4, whilst the mean ages ranged from 10 to 16.3 years at the time of stapes surgery. After stapes surgery, the target of ABG < 10 dB was achieved in most of the patients. Overall, the 4 complications were reported (4/94= 4%): stenosis of the external ear canal, deterioration of hearing, anacusis with vertigo, tinnitus. Conclusions. The heterogeneity of the available studies does not allow us to draw straight conclusions on this topic, currently. More data about the natural history of the disease in children could help in approaching the treatment correctly, and possibly in drawing guidelines. Studies with a prolonged follow-up could be helpful for assisting clinicians and families in taking the most favorable decision about treatment

Intranasal Delivery of Genistein-Loaded Nanoparticles as a Potential Preventive System against Neurodegenerative Disorders

Genistein has been reported to have antioxidant and neuroprotective activity. Despite encouraging in vitro and in vivo results, several disadvantages such as poor water solubility, rapid metabolism, and low oral bioavailability limit the clinical application of genistein. The aim of this study was to design and characterize genistein-loaded chitosan nanoparticles for intranasal drug delivery, prepared by the ionic gelation technique by using sodium hexametaphosphate. Nanoparticles were characterized in vitro and their cytotoxicity was tested on PC12 cells. Genistein-loaded nanoparticles were prepared, and sodium hexametaphosphate was used as a valid alternative to well-known cross-linkers. Nanoparticle characteristics as well as their physical stability were affected by formulation composition and manufacturing. Small (mean diameters of 200–300 nm) and homogeneous nanoparticles were obtained and were able to improve genistein penetration through the nasal mucosa as compared to pure genistein. Nanoparticle dispersions showed a pH consistent with the nasal fluid and preserved PC12 cell vitality

Low-Temperature Storage Improves the Over-Time Stability of Implantable Glucose and Lactate Biosensors

Molecular biomarkers are very important in biology, biotechnology and even in medicine, but it is quite hard to convert biology-related signals into measurable data. For this purpose, amperometric biosensors have proven to be particularly suitable because of their specificity and sensitivity. The operation and shelf stability of the biosensor are quite important features, and storage procedures therefore play an important role in preserving the performance of the biosensors. In the present study two different designs for both glucose and lactate biosensor, differing only in regards to the containment net, represented by polyurethane or glutharaldehyde, were studied under different storage conditions (+4, −20 and −80 °C) and monitored over a period of 120 days, in order to evaluate the variations of kinetic parameters, as VMAX and KM, and LRS as the analytical parameter. Surprisingly, the storage at −80 °C yielded the best results because of an unexpected and, most of all, long-lasting increase of VMAX and LRS, denoting an interesting improvement in enzyme performances and stability over time. The present study aimed to also evaluate the impact of a short-period storage in dry ice on biosensor performances, in order to simulate a hypothetical preparation-conservation-shipment condition