252 research outputs found
Advantages and risks of nanotechnologies in cancer patients and occupationally exposed workers.
Introduction: In recent years, different nanotechnology platforms for drug delivery in the area of medical biology have gained remarkable attention. Areas covered: Nanoparticles (NPs) used as drug delivery vehicles consist of different materials such as natural or synthetic polymers, lipids or metals. They have an ultra-small size, large surface area-to-mass ratio and high reactivity. Although there are many data on the advantages in terms of both higher efficacy and less adverse effects of nanodrugs, several recent findings have reported unexpected toxicities giving origin to nanotoxicology. Expert opinion: Despite the great promise that NPs show, few studies have examined the human body's reaction due to NP exposure in both patients and workers. To perform this type of evaluation, it is necessary to define an adequate index of exposure, and the measure of this index is representative of what the worker is breathing. The properties of the nanomaterials used for designing NPs, such as in the case of poorly biocompatible materials (carbon nanotubes or heavy metals), and their chemical composition (as in the case of liposomes) largely contribute in determining potential side effects. Awareness of the levels of particles, which can cause health effects, is necessary for the workers and exposed patients
Extracellular vesicles. New endogenous shuttles for mirnas in cancer diagnosis and therapy?
Extracellular Vesicles (EVs) represent a heterogeneous population of membranous cell-derived structures, including cargo-oriented exosomes and microvesicles. EVs are functionally associated with intercellular communication and play an essential role in multiple physiopathological conditions. Shedding of EVs is frequently increased in malignancies and their content, including proteins and nucleic acids, altered during carcinogenesis and cancer progression. EVs-mediated intercellular communication between tumor cells and between tumor and stromal cells can modulate, through cargo miRNA, the survival, progression, and drug resistance in cancer conditions. These consolidated suggestions and EVs’ stability in bodily fluids have led to extensive investigations on the potential employment of circulating EVs-derived miRNAs as tumor biomarkers and potential therapeutic vehicles. In this review, we highlight the current knowledge about circulating EVs-miRNAs in human cancer and the application limits of these tools, discussing their clinical utility and challenges in functions such as in biomarkers and instruments for diagnosis, prognosis, and therapy
Essentially Negative News About Positive Systems
In this paper the discretisation of switched and non-switched linear positive systems using
Padé approximations is considered. Padé approximations to the matrix exponential
are sometimes used by control engineers for discretising continuous time systems and
for control system design. We observe that this method of approximation is not suited
for the discretisation of positive dynamic systems, for two key reasons. First, certain
types of Lyapunov stability are not, in general, preserved. Secondly, and more seriously,
positivity need not be preserved, even when stability is. Finally we present an alternative
approximation to the matrix exponential which preserves positivity, and linear and
quadratic stability
Wholegenome analysis suggesting probiotic potential and safety properties of Pediococcus pentosaceus DSPZPP1, a promising LAB strain isolated from traditional fermented sausages of the Basilicata region (Southern Italy).
Introduction: Many lactic acid bacteria (LAB) strains are currently gaining attention
in the food industry and various biological applications because of their harmless
and functional properties. Given the growing consumer demand for safe food,
further research into potential probiotic bacteria is beneficial. Therefore, we aimed
to characterize Pediococcus pentosaceus DSPZPP1, a LAB strain isolated from
traditional fermented sausages from the Basilicata region of Southern Italy.
Methods: In this study, we analyzed the whole genome of the P. pentosaceus
DSPZPP1 strain and performed in silico characterization to evaluate its
applicability for probiotics and use in the food industry.
Results and Discussion: The whole-genome assembly and functional
annotations revealed many interesting characteristics of the DSPZPP1 strain.
Sequencing raw reads were assembled into a draft genome of size 1,891,398 bp,
with a G + C content of 37.3%. Functional annotation identified 1930 proteinencoding
genes and 58 RNAs including tRNA, tmRNA, and 16S, 23S, and 5S
rRNAs. The analysis shows the presence of genes that encode water-soluble
B-group vitamins such as biotin, folate, coenzyme A, and riboflavin. Furthermore,
the analysis revealed that the DSPZPP1 strain can synthesize class II bacteriocin,
penocin A, adding importance to the food industry for bio-enriched food. The
DSPZPP1 genome does not show the presence of plasmids, and no genes
associated with antimicrobial resistance and virulence were found. In addition,
two intact bacteriophages were identified. Importantly, the lowest probability
value in pathogenicity analysis indicates that this strain is non-pathogenic to
humans. 16 s rRNA-based phylogenetic analysis and comparative analysis based
on ANI and Tetra reveal that the DSPZPP1 strain shares the closest evolutionary
relationship with P. pentosaceus DSM 20336 and other Pediococcus strains.
Analysis of carbohydrate active enzymes (CAZymes) identified glycosyl
transferases (GT) as a main class of enzymes followed by glycoside hydrolases (GH). Our study shows several interesting characteristics of the isolated DSPZPP1 strain from fermented Italian sausages, suggesting its potential use as a promising probiotic candidate and making it more appropriate for selection as a future additive in biopreservation
Hybrid lipid self-assembling nanoparticles for brain delivery of microRNA
Hybrid self-assembling nanoparticles (SANPs) have been previously designed as novel drug delivery system that overcomes stability issues following long-term storage and with an easy scale-up. This system has been successfully used to deliver anionic-charged agents, e.g. bisphosphonates, in different types of tumors, such glioblastoma (GBM). Here, SANPs were tested and optimized for the delivery of nucleic acids, in particular of a specific microRNA, e.g. miR603, used for its potential role in controlling the chemoresistance in different forms of cancer, e.g. (GBM). To this aim, SANPs with different lipids were prepared and characterized, in terms of size, polydispersity index, zeta potential, miRNA encapsulation, stability in BSA, serum and hemolytic activity. Then, SANPs were tested in vitro on two different cell lines of GBM. Finally, miRNA biodistribution was tested in vivo in an orthotopic model of GBM. The majority of the formulations showed good technological characteristics and were stable in BSA and serum with a low hemolytic activity. The intracellular uptake studies on GBM cell lines showed that SANPs allow to achieve a higher miRNA delivery compared to others transfection agents, e.g. lipofectamine. Finally, in vivo biodistribution studies in an orthotopic of GBM demonstrated that the optimized SANP formulations, were able to deliver miRNA in different organs, e.g. the brain
Insight toward the microRNA profiling of laryngeal cancers: Biological role and clinical impact
Head and neck squamous cell carcinoma (HNSCC), a heterogeneous disease arising from various anatomical locations including the larynx, is a leading cause of death worldwide. Despite advances in multimodality treatment, the overall survival rate of the disease is still largely dismal. Early and accurate diagnosis of HNSCC is urgently demanded in order to prevent cancer progression and to improve the quality of the patient’s life. Recently, microRNAs (miRNAs), a family of small non-coding RNAs, have been widely reported as new robust tools for prediction, diagnosis, prognosis, and therapeutic approaches of human diseases. Abnormally expressed miRNAs are strongly associated with cancer development, resistance to chemo-/radiotherapy, and metastatic potential through targeting a large variety of genes. In this review, we summarize on the recent reports that emphasize the pivotal biological roles of miRNAs in regulating carcinogenesis of HNSCC, particularly laryngeal cancer. In more detail, we report the characterized miRNAs with an evident either oncogenic or tumor suppressive role in the cancers. In addition, we also focus on the correlation between miRNA deregulation and clinical relevance in cancer patients. On the basis of intriguing findings, the study of miRNAs will provide a new great opportunity to access better clinical management of the malignancies
Molecular and preclinical models enhancing anti-tumour activity of zoledronic acid
AbstractZoledronic acid (ZOL) is an aminobisphosphonate able to inhibit the prenylation of intracellular proteins through the inhibition of farnesylpyrophosphate synthase. Prenylation is essential for the maintenance of the activation of components of signal transduction pathways regulating apoptosis and proliferation such as Ras and Ras-related proteins. ZOL has demonstrated a direct anti-tumour effect in vitro and in preclinical models, and its ability in preventing skeletal-related events is proven in patients with bone metastases from different origins. Clinical evidence on its direct anti-proliferative effects is emerging. We describe several strategies in order to improve the anti-tumour activity of ZOL. In detail, we illustrate new combinations between ZOL and cytotoxic drugs or other biological agents such as the farnesyltransferase inhibitor tipifarnib focusing on the sequence of administration of these drugs. Moreover, the efforts to find new molecular targets of ZOL through the use of technological platforms such as DNA microarrays are described
Effect of restriction vegan diet's on muscle mass, oxidative status, and myocytes differentiation: A pilot study
This study was conceived to evaluate the effects of three different diets on body composition, metabolic parameters and serum oxidative status. We enrolled three groups of healthy men (omnivores, vegetarians and vegans) with similar age, weight and BMI and we observed a significant decrease in muscle mass index and lean body mass in vegan compared to vegetarian and omnivore groups, and higher serum homocysteine levels in vegetarians and vegans compared to omnivores. We studied whether serum from omnivore, vegetarian and vegan subjects affected oxidative stress, growth and differentiation of both cardiomyoblast cell line H9c2 and H-H9c2 (H9c2 treated with H2 O2 to induce oxidative damage). We demonstrated that vegan sera treatment of both H9c2 and H-H9c2 cells induced an increase of TBARS values and cell death and a decrease of free NO2- compared to vegetarian and omnivorous sera. Afterwards, we investigated the protective effects of vegan, vegetarian and omnivore sera on the morphological changes induced by H2 O2 in H9c2 cell line. We showed that the omnivorous sera had major antioxidant and differentiation properties compared to vegetarian and vegan sera. Finally, we evaluated the influence of the three different groups of sera on MAPKs pathway and our data suggested that ERK expression increased in H-H9c2 cells treated with vegetarian and vegan sera and could promote cell death. The results obtained in this study demonstrated that restrictive vegan diet could not prevent the onset of metabolic and cardiovascular diseases nor protect by oxidative damage. This article is protected by copyright. All rights reserved
Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer
NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT
elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the
regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing,
NF-YAl and NF-YAs, which differ in the transactivation domain.
Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a
significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer
(CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’
survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by
the worst prognosis.
Through the analysis of 3D cellular models, we demonstrated that altered expression of genes
related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced
migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of
metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl
in metabolic flexibility of cancer cells that adjust their metabolism in response to
environmental changes to potentiate migration. The zebrafish xenograft model confirmed the
metastatic potential triggered by NF-YAl in CRC cells.
Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and
suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination
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