A novel process for transcellular hemoglobin transport from macrophages to cancer cells.

Hemoglobin (Hb) performs its physiological function within the erythrocyte. Extracellular Hb has prooxidative and proinflammatory properties and is therefore sequestered by haptoglobin and bound by the CD163 receptor on macrophages. In the present study, we demonstrate a novel process of Hb uptake by macrophages independent of haptoglobin and CD163.

Challenges in Exploiting Human H Ferritin Nanoparticles for Drug Delivery: Navigating Physiological Constraints.

Over the past two decades, ferritin has emerged as a promising nanoparticle for drug delivery, catalyzing the development of numerous prototypes capable of encapsulating a wide array of therapeutic agents. These ferritin-based nanoparticles exhibit selectivity for various molecular targets and are distinguished by their potential biocompatibility, unique symmetrical structure, and highly controlled size. The hollow interior of ferritin nanoparticles allows for efficient encapsulation of diverse therapeutic agents, enhancing their delivery and effectiveness.

Ferritin-based disruptor nanoparticles: A novel strategy to enhance LDL cholesterol clearance via multivalent inhibition of PCSK9-LDL receptor interaction.

Hypercholesterolemia, characterized by elevated low-density lipoprotein (LDL) cholesterol levels, is a significant risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in cholesterol metabolism by regulating LDL receptor degradation, making it a therapeutic target for mitigating hypercholesterolemia-associated risks. In this context, we aimed to engineer human H ferritin as a scaffold to present 24 copies of a PCSK9-targeting domain.

Ferritin at different iron loading: From biological to nanotechnological applications.

The characterization of the structure of ferritin in solution and the arrangement of iron stored in its cavity are intriguing subjects for both cell biology and applied science, since the protein structure, stability, and easiness of production make it an ideal tool for biomedical applications. We characterized the ferritin structure over a wide range of iron loadings by visible light, X-ray, and neutron scattering techniques. We found that the arrangement of iron ions inside the protein cage resulted in a more disposable arrangement at lower loading factors and then in a crystalline structure.

Combined Delivery of miR-15/16 through Humanized Ferritin Nanocages for the Treatment of Chronic Lymphocytic Leukemia.

Chronic lymphocytic leukemia (CLL) is a widespread type of leukemia that predominantly targets B lymphocytes, undermining the balance between cell proliferation and apoptosis. In healthy B cells, miR-15/16, a tandem of microRNAs, functions as a tumor suppressor, curbing the expression of the antiapoptotic B cell lymphoma 2 protein (Bcl-2). Conversely, in CLL patients, a recurring deletion on chromosome 13q14, home to the miR15-a and miR16-1 genes, results in Bcl-2 overexpression, thereby fostering the onset of the pathology.

Lactoferrins in Their Interactions with Molecular Targets: A Structure-Based Overview.

Lactoferrins and lactoferrin-derived peptides display numerous functions linked to innate immunity in mammalians, spanning from antimicrobial to anti-inflammatory and immunomodulatory actions, and even demonstrate antitumor properties. To date, the proposed mechanisms for their biological actions are varied, although the molecular basis that governs lactoferrin interactions with molecular targets has been clarified only in a limited number of specific cases. However, key in silico methods have recently moved the topic to the fore, thus greatly expanding the possibilities of large-scale investigations on macromolecular interactions involving lactoferrins and their molecular targets.

Design of protein-binding peptides with controlled binding affinity: the case of SARS-CoV-2 receptor binding domain and angiotensin-converting enzyme 2 derived peptides.

The development of methods able to modulate the binding affinity between proteins and peptides is of paramount biotechnological interest in view of a vast range of applications that imply designed polypeptides capable to impair or favour Protein-Protein Interactions. Here, we applied a peptide design algorithm based on shape complementarity optimization and electrostatic compatibility and provided the first experimental proof of the efficacy of the design algorithm. Focusing on the interaction between the SARS-CoV-2 Spike Receptor-Binding Domain (RBD) and the human angiotensin-converting enzyme 2 (ACE2) receptor, we extracted a 23-residues long peptide that structurally mimics the major interacting portion of the ACE2 receptor and designed five mutants of such a peptide with a modulated affinity.

Hydrophobicity-enhanced ferritin nanoparticles for efficient encapsulation and targeted delivery of hydrophobic drugs to tumor cells.

Ferritin, a naturally occurring iron storage protein, has gained significant attention as a drug delivery platform due to its inherent biocompatibility and capacity to encapsulate therapeutic agents. In this study, we successfully genetically engineered human H ferritin by incorporating 4 or 6 tryptophan residues per subunit, strategically oriented towards the inner cavity of the nanoparticle. This modification aimed to enhance the encapsulation of hydrophobic drugs into the ferritin cage.

Ferritin-Coated SPIONs as New Cancer Cell Targeted Magnetic Nanocarrier.

Superparamagnetic iron oxide nanoparticles (SPIONs) may act as an excellent theragnostic tool if properly coated and stabilized in a biological environment, even more, if they have targeting properties towards a specific cellular target. Humanized Ferritin (HumAfFt) is an engineered ferritin characterized by the peculiar salt-triggered assembly-disassembly of the hyperthermophile ferritin and is successfully endowed with the human H homopolymer recognition sequence by the transferrin receptor (TfR1 or CD71), overexpressed in many cancer cells in response to the increased demand of iron. For this reason, HumAfFt was successfully used in this study as a coating material for 10 nm SPIONs, in order to produce a new magnetic nanocarrier able to discriminate cancer cells from normal cells and maintain the potential theragnostic properties of SPIONs.

Response to the first awake prone positioning relates with intubation rate in SARS-CoV-2 patients suffering from acute respiratory failure with moderate to severe hypoxaemia: a retrospective study.

Aims Of The Study: Awake prone positioning (aPP) in non-intubated patients with severe SARS-CoV-2-related pneumonia improves oxygenation and reduces the intubation rate, but no early predictors for success or failure of the strategy have been described. The main objective of this study was to assess whether response to the first aPP in terms of PaO2/FiO2, alveolar-arterial gradient (Aa-O2), respiratory rate and PaCO2 could predict the need for intubation. As secondary objective, we assessed the effects of aPP on the same parameters for all the sessions considered together.

Immobilization of Amine Oxidase on Magnetic Microparticles for Biocatalytic Applications.

Amine oxidases are enzymes belonging to the class of oxidoreductases that are widespread, from bacteria to humans. The amine oxidase from has recently appeared in the landscape of biocatalysis, showing good potential in the green synthesis of aldehydes. This enzyme catalyzes the oxidative deamination of a wide range of primary amines into the corresponding aldehydes but its use as a biocatalyst is challenging due to the possible inactivation that might occur at high product concentrations.

Lactoferrin Inhibition of the Complex Formation between ACE2 Receptor and SARS CoV-2 Recognition Binding Domain.

The present investigation focuses on the analysis of the interactions among human lactoferrin (LF), SARS-CoV-2 receptor-binding domain (RBD) and human angiotensin-converting enzyme 2 (ACE2) receptor in order to assess possible mutual interactions that could provide a molecular basis of the reported preventative effect of lactoferrin against CoV-2 infection. In particular, kinetic and thermodynamic parameters for the pairwise interactions among the three proteins were measured via two independent techniques, biolayer interferometry and latex nanoparticle-enhanced turbidimetry. The results obtained clearly indicate that LF is able to bind the ACE2 receptor ectodomain with significantly high affinity, whereas no binding to the RBD was observed up to the maximum "physiological" lactoferrin concentration range.

Rational design and synthesis of a novel BODIPY-based probe for selective imaging of tau tangles in human iPSC-derived cortical neurons.

Numerous studies have shown a strong correlation between the number of neurofibrillary tangles of the tau protein and Alzheimer's disease progression, making the quantitative detection of tau very promising from a clinical point of view. However, the lack of highly reliable fluorescent probes for selective imaging of tau neurofibrillary tangles is a major challenge due to sharing similar β-sheet motifs with homologous Amyloid-β fibrils. In the current work, we describe the rational design and the in silico evaluation of a small-size focused library of fluorescent probes, consisting of a BODIPY core (electron acceptor) featuring highly conjugated systems (electron donor) with a length in the range 13-19 Å at C3.

Inferring the stabilization effects of SARS-CoV-2 variants on the binding with ACE2 receptor.

As the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic continues to spread, several variants of the virus, with mutations distributed all over the viral genome, are emerging. While most of the variants present mutations having little to no effects at the phenotypic level, some of these variants are spreading at a rate that suggests they may present a selective advantage. In particular, these rapidly spreading variants present specific mutations on the spike protein.

Biocatalytic Production of Aldehydes: Exploring the Potential of Amine Oxidase.

Aldehydes are a class of carbonyl compounds widely used as intermediates in the pharmaceutical, cosmetic and food industries. To date, there are few fully enzymatic methods for synthesizing these highly reactive chemicals. In the present work, we explore the biocatalytic potential of an amino oxidase extracted from the etiolated shoots of for the synthesis of value-added aldehydes, starting from the corresponding primary amines.

Right ventricular time intervals - Comparison between pulsed wave Doppler and tissue Doppler imaging.

Background: Cardiac time intervals are used as indices of systolic and diastolic function. Echocardiographic assessment of these intervals is based on either pulsed wave Doppler (PWD) or tissue Doppler imaging (TDI). We investigated the agreement between the two techniques in the evaluation of right ventricular (RV) time intervals in healthy adults.

Self-assembling ferritin-dendrimer nanoparticles for targeted delivery of nucleic acids to myeloid leukemia cells.

Background: In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells.

Computational optimization of angiotensin-converting enzyme 2 for SARS-CoV-2 Spike molecular recognition.

Since the beginning of the Covid19 pandemic, many efforts have been devoted to identifying approaches to neutralize SARS-CoV-2 replication within the host cell. A promising strategy to block the infection consists of using a mutant of the human receptor angiotensin-converting enzyme 2 (ACE2) as a decoy to compete with endogenous ACE2 for the binding to the SARS-CoV-2 Spike protein, which decreases the ability of the virus to enter the host cell. Here, using a computational framework based on the 2D Zernike formalism we investigate details of the molecular binding and evaluate the changes in ACE2-Spike binding compatibility upon mutations occurring in the ACE2 side of the molecular interface.

Design and Synthesis of Piperazine-Based Compounds Conjugated to Humanized Ferritin as Delivery System of siRNA in Cancer Cells.

Gene expression regulation by small interfering RNA (siRNA) holds promise in treating a wide range of diseases through selective gene silencing. However, successful clinical application of nucleic acid-based therapy requires novel delivery options. Herein, to achieve efficient delivery of negatively charged siRNA duplexes, the internal cavity of "humanized" chimeric Archaeal ferritin (HumAfFt) was specifically decorated with novel cationic piperazine-based compounds (PAs).

Exciplex Formation in Lipid-bound Escherichia coli Flavohemoglobin.

Flavohemoglobins have the particular capability of binding unsaturated and cyclopropanated fatty acids as free acids or phospholipids. Fatty acid binding to the ferric heme results in a weak but direct bonding interaction. Ferrous and ferric protein, in presence or absence of a bound lipid molecule, have been characterized by transient absorption spectroscopy.

Molecular Mechanisms Behind Anti SARS-CoV-2 Action of Lactoferrin.

Despite the huge effort to contain the infection, the novel SARS-CoV-2 coronavirus has rapidly become pandemic, mainly due to its extremely high human-to-human transmission capability, and a surprisingly high viral charge of symptom-less people. While the seek for a vaccine is still ongoing, promising results have been obtained with antiviral compounds. In particular, lactoferrin is regarded to have beneficial effects both in preventing and soothing the infection.

A novel strategy for molecular interfaces optimization: The case of Ferritin-Transferrin receptor interaction.

Protein-protein interactions regulate almost all cellular functions and rely on a fine tune of surface amino acids properties involved on both molecular partners. The disruption of a molecular association can be caused even by a single residue mutation, often leading to a pathological modification of a biochemical pathway. Therefore the evaluation of the effects of amino acid substitutions on binding, and the design of protein-protein interfaces, is one of the biggest challenges in computational biology.

Ethylchloroformate Derivatization for GC-MS Analysis of Resveratrol Isomers in Red Wine.

Resveratrol (3,5,4'-trihydroxystilbene) is a natural compound that can be found in high concentrations in red wine and in many typical foods found in human diet. Over the past decades, resveratrol has been widely investigated for its potential beneficial effects on human health. At the same time, numerous analytical methods have been developed for the quantitative determination of resveratrol isomers in oenological and food matrices.