Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.

Abstract Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression

Mathematical Phase Model of Neural Populations Interaction in Modulation of REM/NREM Sleep

Aim of the present study is to compare the synchronization of the classical Kuramoto system and the reaction - diffusion space time Landau - Ginzburg model, in order to describe the alternation of REM (rapid eye movement) and NREM (non-rapid eye movement) sleep across the night. These types of sleep are considered as produced by the cyclic oscillation of two neuronal populations that, alternatively, promote and inhibit the REM sleep. Even if experimental data will be necessary, a possible interpretation of the results has been proposed

Plasmonic nanowires for wide wavelength range molecular sensing

In this paper, we propose the use of a standing nanowires array, constituted by plasmonic active gold wires grown on iron disks, and partially immersed in a supporting alumina matrix, for surface-enhanced Raman spectroscopy applications. The galvanic process was used to fabricate nanowires in pores of anodized alumina template, making this device cost-effective. This fabrication method allows for the selection of size, diameter, and spatial arrangement of nanowires. The proposed device, thanks to a detailed design analysis, demonstrates a broadband plasmonic enhancement effect useful formany standard excitationwavelengths in the visible andNIR. The trigonal pores arrangement gives an efficiency weakly dependent on polarization. The devices, tested with 633 and 830 nm laser lines, show a significant Raman enhancement factor, up to around 6 × 104, with respect to the flat gold surface, used as a reference for the measurements of the investigated molecules

Superhydrophobic lab-on-chip measures secretome protonation state and provides a personalized risk assessment of sporadic tumour

Secretome of primary cultures is an accessible source of biological markers compared to more complex and less decipherable mixtures such as serum or plasma. The protonation state (PS) of secretome reflects the metabolism of cells and can be used for cancer early detection. Here, we demonstrate a superhydrophobic organic electrochemical device that measures PS in a drop of secretome derived from liquid biopsies. Using data from the sensor and principal component analysis (PCA), we developed algorithms able to efficiently discriminate tumour patients from non-tumour patients. We then validated the results using mass spectrometry and biochemical analysis of samples. For the 36 patients across three independent cohorts, the method identified tumour patients with high sensitivity and identification as high as 100% (no false positives) with declared subjects at-risk, for sporadic cancer onset, by intermediate values of PS. This assay could impact on cancer risk management, individual’s diagnosis and/or help clarify risk in healthy populations

Fabrication and Applications of Micro/Nanostructured Devices for Tissue Engineering

Nanotechnology allows the realization of new materials and devices with basic structural unit in the range of 1–100 nm and characterized by gaining control at the atomic, molecular, and supramolecular level. Reducing the dimensions of a material into the nanoscale range usually results in the change of its physiochemical properties such as reactivity, crystallinity, and solubility. This review treats the convergence of last research news at the interface of nanostructured biomaterials and tissue engineering for emerging biomedical technologies such as scaffolding and tissue regeneration. The present review is organized into three main sections. The introduction concerns an overview of the increasing utility of nanostructured materials in the field of tissue engineering. It elucidates how nanotechnology, by working in the submicron length scale, assures the realization of a biocompatible interface that is able to reproduce the physiological cell–matrix interaction. The second, more technical section, concerns the design and fabrication of biocompatible surface characterized by micro- and submicroscale features, using microfabrication, nanolithography, and miscellaneous nanolithographic techniques. In the last part, we review the ongoing tissue engineering application of nanostructured materials and scaffolds in different fields such as neurology, cardiology, orthopedics, and skin tissue regeneration

An Overview of Lipid Droplets in Cancer and Cancer Stem Cells

For decades, lipid droplets have been considered as the main cellular organelles involved in the fat storage, because of their lipid composition. However, in recent years, some new and totally unexpected roles have been discovered for them: (i) they are active sites for synthesis and storage of inflammatory mediators, and (ii) they are key players in cancer cells and tissues, especially in cancer stem cells. In this review, we summarize the main concepts related to the lipid droplet structure and function and their involvement in inflammatory and cancer processes

Microfluidic platforms for cell cultures and investigations

This review covers several aspects of microfluidic devices used for culturing and monitoring of both adherent and non-adherent cells, including a multitude of applications. A comparison of available platforms with high throughput analysis, automation capability, interface to sensors and integration, is reported. Aspects, such as operational versatility of the devices, are scrutinized in terms of their analytical efficacy. It is found that due to multi-functionality capability of modern microfluidics, there is big amount of experimental data obtainable from a single device, allowing complex experimental control and efficient data correlation, particularly important when biomedical studies are considered. Hence several examples on cell culture and monitoring are given in this review, including details on design of microfluidic devices with their distinctive technological peculiarities

Clinical, pathological and microbiological profiles of spontaneous enteropathies in growing rabbits

[EN] In a rabbit production facility, health monitoring for enteropathies was performed in 15 production cycles for 20 mo. For each cycle, up to a hundred 35 d old rabbits weaned the same day were randomly selected, reared in the same fattening unit, but separately from the source batch and fed with the same feed except for antimicrobial supplementation. Clinical symptoms and enteric lesions of the selected group were recorded, using two checklists with binomial response (yes/no answer to a list of 54 clinical and enteric variables). The day after weaning, one week later, at the beginning of the enteric symptoms and 4-5 d after the start of the symptoms, inocula from the small intestine and caecum of selected animals were subjected to microbiological, C. spiroforme, Eimeria oocyst and rotavirus antigen detection tests. Representative samples of E. coli and C. perfringens isolates were tested, respectively, for serotype, biotype, eae, afr/2 genes and for a, b1, b2, e, i and enterotoxin toxin genes. The answers to the clinical-pathological variables were subjected to statistical analysis with a cluster analysis programme in order to obtain homogeneous, statistically significant groups of diseased animals (clusters). Then, the clusters were statistically associated with the laboratory outcomes. The cluster to which the enterotyphlitis lesions significantly contributed was associated with E. coli detection, E. coli O103 serotype detection and C. spiroforme ("several elements" variable). C. spiroforme ("rare elements" variable) was significantly associated with a cluster, characterised by a pathological profile consisting of bloating/rumbling noise and liquid content in stomach and caecum, without enteric inflammation. C. perfringens was significantly associated with a cluster, characterised by a pathological profile consisting of dilation/liquid content of small intestine, caecal impaction and mucoid content in the colon. Eighteen out of twenty-fi ve C. perfringens strains, examined for their toxin genotypes, proved to be toxin type A, while 7 out of 25 strains showed the a and b2 toxin genes in combination. The rotavirus antigen and Eimeria oocysts were detected from healthy rabbits (specimens of the day after weaning and one week later) in about 15% of specimens examined, but their presence in the sick animals was not significantly associated with any cluster.This study was supported by a financial contribution from Avitalia, Unione Nazionale Associazioni di Produttori Avicunicoli, Forlì, Italy, as part of the programme entitled “Miglioramento della qualità, della gestione dell’offerta delle produzioni cunicole e di rafforzamento dei rapporti di filiera. Azione 4.3”. Our thanks go to breeder Leta Covelli and Dasco srl for supplying the rabbits, to our colleague Romolo Salini and to Fabrizio Agnoletti of the Istituto Zooprofilattico Sperimentale del Veneto, Trevise, ItalyBadagliacca, P.; Letizia, A.; Candeloro, L.; Di Provvido, A.; Di Gennaro, A.; Scattolini, S.; Pompei, G.... (2010). Clinical, pathological and microbiological profiles of spontaneous enteropathies in growing rabbits. World Rabbit Science. 18(4):187-198. doi:10.4995/wrs.2010.77518719818

Micro/nanopatterned superhydrophobic surfaces fabrication for biomolecules and biomaterials manipulation and analysis

Superhydrophobic surfaces display an extraordinary repulsion to water and water-based solutions. This effect emerges from the interplay of intrinsic hydrophobicity of the surface and its morphology. These surfaces have been established for a long time and have been studied for decades. The increasing interest in recent years has been focused towards applications in many different fields and, in particular, biomedical applications. In this paper, we review the progress achieved in the last years in the fabrication of regularly patterned superhydrophobic surfaces in many different materials and their exploitation for the manipulation and characterization of biomaterial, with particular emphasis on the issues affecting the yields of the fabrication processes and the quality of the manufactured devices

Waveguiding and SERS simplified Raman spectroscopy on biological samples

Biomarkers detection at an ultra-low concentration in biofluids (blood, serum, saliva, etc.) is a key point for the early diagnosis success and the development of personalized therapies. However, it remains a challenge due to limiting factors like (i) the complexity of analyzed media, and (ii) the aspecificity detection and the poor sensitivity of the conventional methods. In addition, several applications require the integration of the primary sensors with other devices (microfluidic devices, capillaries, flasks, vials, etc.) where transducing the signal might be difficult, reducing performances and applicability. In the present work, we demonstrate a new class of optical biosensor we have developed integrating an optical waveguide (OWG) with specific plasmonic surfaces. Exploiting the plasmonic resonance, the devices give consistent results in surface enhanced Raman spectroscopy (SERS) for continuous and label-free detection of biological compounds. The OWG allows driving optical signals in the proximity of SERS surfaces (detection area) overcoming spatial constraints, in order to reach places previously optically inaccessible. A rutile prism couples the remote laser source to the OWG, while a Raman spectrometer collects the SERS far field scattering. The present biosensors were implemented by a simple fabrication process, which includes photolithography and nanofabrication. By using such devices, it was possible to detect cell metabolites like Phenylalanine (Phe), Adenosine 5-triphosphate sodium hydrate (ATP), Sodium Lactate, Human Interleukin 6 (IL6), and relate them to possible metabolic pathway variation