1,721,000 research outputs found
The effects of histidine substitution of aromatic residues on the amyloidogenic properties of the fragment 264–277 of nucleophosmin 1
No full text: Histidine (His) plays a key role in mediating protein interactions and its unique side chain determines pH responsive self-assembling processes and thus in the formation of nanostructures. In this study, To identify novel self-assembling bioinspired sequences, we analyzed a series of peptide sequences obtained through the point mutation of aromatic residues of 264-277 fragment of nucleophosmin 1 (NPM1) with single and double histidines. Through several orthogonal biophysical techniques and under different pH and ionic strength conditions we evaluated the effects of these substitutions in the amyloidogenic features of derived peptides. The results clearly indicate that both the type of aromatic mutated residue and its position can have different effect on amyloid-like behaviors. They corroborate the crucial role exerted by Tyr271 in the self-assembling process of CTD of NPM1 in AML mutated form and add novel insights in the accurate investigation of how side chain orientations can determine successful design of innovative bioinspired materials
Peptides as therapeutic agents for inflammatory-related diseases
No full textInflammation is a physiological mechanism used by organisms to defend themselves against infection, restoring homeostasis in damaged tissues. It represents the starting point of several chronic diseases such as asthma, skin disorders, cancer, cardiovascular syndrome, arthritis, and neurological diseases. An increasing number of studies highlight the over-expression of inflammatory molecules such as oxidants, cytokines, chemokines, matrix metalloproteinases, and transcription factors into damaged tissues. The treatment of inflammatory disorders is usually linked to the use of unspecific small molecule drugs that can cause undesired side effects. Recently, many efforts are directed to develop alternative and more selective anti-inflammatory therapies, several of them imply the use of peptides. Indeed, peptides demonstrated as elected lead compounds toward several targets for their high specificity as well as recent and innovative synthetic strategies. Several endogenous peptides identified during inflammatory responses showed anti-inflammatory activities by inhibiting, reducing, and/or modulating the expression and activity of mediators. This review aims to discuss the potentialities and therapeutic use of peptides as anti-inflammatory agents in the treatment of different inflammation-related diseases and to explore the importance of peptide-based therapies
Modulation of hydrogel networks by metal ions
No full text: Self-assembling hydrogels are receiving great attention for both biomedical and technological applications. Self-assembly of protein/peptides as well as organic molecules is commonly induced in response to external triggers such as changes of temperature, concentration, or pH. An interesting strategy to modulate the morphology and mechanical properties of the gels implies the use of metal ions, where coordination bonds regulate the dynamic cross-linking in the construction of hydrogels, and coordination geometries, catalytic, and redox properties of metal ions play crucial roles. This review aims to discuss recent insights into the supramolecular assembly of hydrogels involving metal ions, with a focus on self-assembling peptides, as well as applications of metallogels in biomedical fields including tissue engineering, sensing, wound healing, and drug delivery
Editorial: Microencapsulation for Biomedical Applications
No full textThe systemic administration of drugs, such as chemotherapeutics, probiotics and anti-inflammatories, is known to be frequently associated to biomolecules short half-life, poor stability and side effects potentially harmful to functional tissues and organs. Advanced drug therapies require patient customization and targeting of drug formulation and dosage to warrant treatment efficacy and reduce possible undesired secondary effects. Nano- and microencapsulation strategies are generally defined as a set of technologies that allow to entrap active ingredients, namely small solid particles, liquid droplets or a gas, using a surrounding material (Silva and Meireles, 2014). These strategies may allow overcoming previous limitations as the encapsulating material protects the drugs, while their delivery can be tailored depending on the specific application by the careful modulation of carrier composition, size and architectural features. A variety of methods, including microfluidic emulsion, coacervation, antisolvent precipitation and soft lithography, have been used to produce drug delivery systems for precision medicine (Wang et al., 2006; Canelas et al., 2009; Liu et al., 2017). Overall, these methods offer control over basic parameters such as material-to-drug composition, carrier size, porosity and shape (Figure 1). In this vast and complex panorama, the aim of this Research Topic is to highlight and illustrate important knowledge in the field of micro- and nanoencapsulation and drug delivery systems as shared by experts in these research fields. Most notably, the nine articles collected in this issue, composed of five research articles and four reviews by different countries’ teams, are of interest to researchers looking for current drug delivery advances in biomedicine and biotechnology, as described following
Sam domain-based stapled peptides: Structural analysis and interaction studies with the Sam domains from the EphA2 receptor and the lipid phosphatase Ship2
No full textEffects of surface nanopatterning on internalization and amyloid aggregation of the fragment 264-277 of Nucleophosmin 1
No full textThe mechanical interpretation of the plethora of factors that governs cellular localization of amyloid aggregates is crucial for planning novel therapeutical interventions in neurodegenerative diseases since these aggregates exert a primary role in the proteostasis machinery. The uptake of Cell Penetrating Peptides (CPPs) conjugated with different amyloid polypeptides occurs via different endocytic processes regulated by cytoskeleton organization and cell morphology. Herein, we deepened the internalization of an amyloid system in cells cultured on nanopatterned surfaces that represent a powerful tool to shape cell and regulate its contractility. We analyzed the behavior of an amyloid model system, employing NPM1264-277 sequence, covalently conjugated to Tat fragment 48-60 as CPP. To investigate its internalization mechanism, we followed the formation of aggregates on two kinds of substrates: a flat and a nanopatterned surface. Herein, investigations during time were carried out by employing both confocal and second harmonic generation (SHG) microscopies. We showed that modifications of cellular environment affect peptide localization, its cytoplasmic translocation and the size of amyloid aggregates
Engineered PLGA-PVP/VA based formulations to produce electro-drawn fast biodegradable microneedles for labile biomolecule delivery
No full textBiodegradable polymer microneedles (MNs) are recognized as non-toxic, safe and stable systems for advanced drug delivery and cutaneous treatments, allowing a direct intradermal delivery and in some cases a controlled release. Most of the microneedles found in the literature are fabricated by micromolding, which is a multistep thus typically costly process. Due to industrial needs, mold-free methods represent a very intriguing approach in microneedle fabrication. Electro-drawing (ED) has been recently proposed as an alternative fast, mild temperature and one-step strategy to the mold-based techniques for the fabrication of poly(lactic-co-glycolic acid) (PLGA) biodegradable MNs. In this work, taking advantage of the flexibility of the ED technology, we engineered microneedle inner microstructure by acting on the water-in-oil (W/O) precursor emulsion formulation to tune drug release profile. Particularly, to promote a faster release of the active pharmaceutical ingredient, we substituted part of PLGA with poly(1-vinylpyrrolidone-co-vinyl acetate) (PVP/VA), as compared to the PLGA alone in the matrix material. Moreover, we introduced lecithin and maltose as emulsion stabilizers. Microneedle inner structural analysis as well as collagenase entrapment efficiency, release and activity of different emulsion formulations were compared to reach an interconnected porosity MN structure, aimed at providing an efficient protein release profile. Furthermore, MN mechanical properties were examined as well as its ability to pierce the stratum corneum on a pig skin model, while the drug diffusion from the MN body was monitored in an in vitro collagen-based dermal model at selected time points
MICROSCOPIC TECHNIQUES AND A MULTI-ANALYTICAL APPROACH TO CHARACTERIZE THE MATERIALS OF TWO RUSSIAN ICONS
No full textTwo 19th century Russian icons, from the Museo Diocesano of Palermo, were analysed by UV photography, X-ray fluorescence, energy-dispersive X-ray fluorescence (ED-XRF), optical microscopy, micro-Raman spectroscopy and Scanning Electron Microscopy, combined with energy dispersive x-ray analysis, (SEM/EDS).
The multi-analytical study of the icons “Protezione della Madre di Dio” (Pokrov’s Icon, Protection of Holy Mother of God) and ‘’Madre di Dio Gioia di Tutti gli Afflitti’’, (Holy Mother of God, Joy of all the afflicted), have been performed to reveal materials and technological features of the original painting of the 19th century as well as the materials used during past restoration works.
The obtained results suggest the use of traditional manufacturing techniques and materials such as: paper and cloths for ’impannatura’, gypsum and glue for preparatory layer and lead/tin yellow, cinnabar/vermilion, red lead, carbon black, Prussian blue, red iron oxide, yellow ochre, and lead white as painting pigments
Levels of 24-hydroxycholesteryl esters in cerebrospinal fluid and plasma from patients with amyotrophic lateral sclerosis
No full textObjective
In this context, our study aimed to ascertain whether the esterification of 24-hydroxycholesterol, a process heavily affected by oxidative stress, is altered in ALS.
Methods
The study examined the level of 24-hydroxycholesteryl esters in cerebrospinal fluid and plasma of 18 ALS patients by spectroscopic technique as Ultra-high performance liquid chromatography mass spectrometry (UPLC-MS).
Results
The level of 24-hydroxycholesteryl esters in cerebrospinal fluid was found to be lower as the brain-blood barrier was damaged. Such a level was positively correlated with the level of esters in plasma. Both cerebrospinal fluid (CSF) level and plasma level were lower in ALS patients (60.05 ± 4.24 % and 54.07 ± 20.37 % respectively) than in controls (79.51 ± 2.47 % and 80.07 ± 10.02 % respectively).
Conclusions
The data suggest that the level 24-hydroxycholesteryl esters might be a new biomarker of ALS and can be measured for monitoring the disease progression
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