Management of 10 Children With Inflammatory Rosacea With Topical Ivermectin.

Rosacea diagnosis and treatment in children are challenging, due to its rarity and to the lack of approved pharmacological agents for its treatment in this age group. In this case series, response to treatment with once daily applications of ivermectin (IVM) 1% cream for 12 weeks in 10 children affected by mild to severe inflammatory rosacea was evaluated clinically by Investigator Erythema Severity Assessment (IESA), Investigator Global Assessment of Severity (IGA-S), Investigator Global Assessment score of Global Efficacy (IGA-GE), and instrumentally by dermoscopy and Erythema-Directed Digital Photography (EDDP). Clinical improvement was achieved at the end of treatment compared to baseline (IESA: 2.

Plasma-treated collagen functionalized with chondroitin sulfate as bioactive and nanostructured extracellular matrix mimics.

Cell microenvironment contains a plethora of information that influences cell modulation. Indeed, the extracellular matrix plays a central role in tissue development. Reproducing the cell-extracellular matrix crosstalk able to recapitulate both physical and biochemical signals is crucial to obtain functional tissue models or regenerative strategies.

Tyrosine glucosylation of collagen films exploiting Horseradish Peroxidase (HRP).

The development of human tissue models for regenerative medicine and animal-free drug screening requires glycosylated biomaterials such as collagen. An easy and fast biomaterial glycosylation method exploiting Horseradish Peroxidase (HRP) phenol coupling reaction is proposed. The protocol is adaptable to any polymer functionalized with phenol residues or tyrosine containing proteins.

Alginate-Gelatin Self-Healing Hydrogel Produced via Static-Dynamic Crosslinking.

Alginate-gelatin hydrogels mimicking extracellular matrix (ECM) of soft tissues have been generated by static-dynamic double crosslinking, allowing fine control over the physical and chemical properties. Dynamic crosslinking provides self-healing and injectability attributes to the hydrogel and promotes cell migration and proliferation, while the static network improves stability. The static crosslinking was performed by enzymatic coupling of the tyrosine residues of gelatin with tyramine residues inserted in the alginate backbone, catalyzed by horseradish peroxidase (HRP).

3D printed tissue models: From hydrogels to biomedical applications.

The development of new advanced constructs resembling structural and functional properties of human organs and tissues requires a deep knowledge of the morphological and biochemical properties of the extracellular matrices (ECM), and the capacity to reproduce them. Manufacturing technologies like 3D printing and bioprinting represent valuable tools for this purpose. This review will describe how morphological and biochemical properties of ECM change in different tissues, organs, healthy and pathological states, and how ECM mimics with the required properties can be generated by 3D printing and bioprinting.

3D bioprinted colorectal cancer models based on hyaluronic acid and signalling glycans.

In cancer microenvironment, aberrant glycosylation events of ECM proteins and cell surface receptors occur. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) crosslinking hyaluronic acid and gelatin functionalized with three signalling glycans characterized in CRC, 3'-Sialylgalactose, 6'-Sialylgalactose and 2'-Fucosylgalactose. The crosslinking, performed exploiting azide functionalized gelatin and hyaluronic acid and 4arm-PEG-dibenzocyclooctyne, resulted in biocompatible hydrogels that were 3D bioprinted with commercial CRC cells HT-29 and patient derived CRC tumoroids.

Preventing extrinsic mechanisms of bioprosthetic degeneration using polyphenols.

Objectives: The purpose of this study was to evaluate the impact of a polyphenols-based treatment on the extrinsic mechanisms responsible for early bioprosthetic heart valve (BHV) degeneration. Structural degeneration can be driven by both extrinsic and intrinsic mechanisms. While intrinsic mechanisms have been associated with inherent biocompatibility characteristics of the BHV, the extrinsic ones have been reported to involve external causes, such as chemical, mechanical and hydrodynamic, responsible to facilitate graft damage.

Home management of COVID-19 symptomatic patients: a safety study on COVID committed home medical teams.

To reduce the overburden in the hospital, during the COVID-19 pandemic, some "COVID Committed Home Medical Teams" (CCHTs) were created in Italy. These units consist of a small pool of general practitioners who aim to evaluate all patients with COVID-19 who require a medical examination directly at home. After the first visit (which can end with patient hospitalisation or home management), CCHTs periodically monitor the patients' clinical conditions and vital signs (usually a revaluation every 24-48 hours, except for a sudden worsening).

Multivalent γ-PGA-Exendin-4 Conjugates to Target Pancreatic β-Cells.

Targeting of glucagon-like peptide 1 receptor (GLP-1R), expressed on the surface of pancreatic β-cells, is of great interest for the development of advanced therapies for diabetes and diagnostics for insulinoma. We report the conjugation of exendin-4 (Ex-4), an approved drug to treat type 2 diabetes, to poly-γ-glutamic acid (γ-PGA) to obtain more stable and effective GLP-1R ligands. Exendin-4 modified at Lysine-27 with PEG4-maleimide was conjugated to γ-PGA functionalized with furan, in different molar ratios, exploiting a chemoselective Diels-Alder cycloaddition.

Combined Analytical Approaches to Standardize and Characterize Biomaterials Formulations: Application to Chitosan-Gelatin Cross-Linked Hydrogels.

A protocol based on the combination of different analytical methodologies is proposed to standardize the experimental conditions for reproducible formulations of hybrid hydrogels. The final hybrid material, based on the combination of gelatin and chitosan functionalized with methylfuran and cross-linked with 4-arm-PEG-maleimide, is able to mimic role, dynamism, and structural complexity of the extracellular matrix. Physical-chemical properties of starting polymers and finals constructs were characterized exploiting the combination of HP-SEC-TDA, UV, FT-IR, NMR, and TGA.

Differential glycosylation of collagen modulates lung cancer stem cell subsets through β1 integrin-mediated interactions.

In lung cancer, CD133+ cells represent the subset of cancer stem cells (CSC) able to sustain tumor growth and metastatic dissemination. CSC function is tightly regulated by specialized niches composed of both stromal cells and extracellular matrix (ECM) proteins, mainly represented by collagen. The relevance of collagen glycosylation, a fundamental post-translational modification controlling several biological processes, in regulating tumor cell phenotype remains, however, largely unexplored.

Design and Synthesis of Chitosan-Gelatin Hybrid Hydrogels for 3D Printable Models.

The development of 3D printable hydrogels based on the crosslinking between chitosan and gelatin is proposed. Chitosan and gelatin were both functionalized with methyl furan groups. Chemical modification was performed by reductive amination with methyl furfural involving the lysine residues of gelatin and the amino groups of chitosan to generate hydrogels with tailored properties.

Integration of nano- and biotechnology for beta-cell and islet transplantation in type-1 diabetes treatment.

Regenerative medicine using human or porcine β-cells or islets has an excellent potential to become a clinically relevant method for the treatment of type-1 diabetes. High-resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell-derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre-clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology-based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole-body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans.

3D Extracellular Matrix Mimics: Fundamental Concepts and Role of Materials Chemistry to Influence Stem Cell Fate.

Synthetic 3D extracellular matrices (ECMs) find application in cell studies, regenerative medicine, and drug discovery. While cells cultured in a monolayer may exhibit unnatural behavior and develop very different phenotypes and genotypes than , great efforts in materials chemistry have been devoted to reproducing behavior in cell microenvironments. This requires fine-tuning the biochemical and structural actors in synthetic ECMs.

Coupling quaternary ammonium surfactants to the surface of liposomes improves both antibacterial efficacy and host cell biocompatibility.

By functionalizing the surface of PEG-liposomes with linkers bearing quaternary ammonium compounds (QACs), we generated novel bacteria disruptors with anti-adhesive properties and reduced cytotoxicity compared to free QACs. Furthermore, QAC-functionalized liposomes are a promising platform for future drug encapsulation. The QAC (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide (MTAB) was attached to maleimide-functionalized liposomes (DSPE-PEG) via thiol linker.

A New Approach for Glyco-Functionalization of Collagen-Based Biomaterials.

The cell microenvironment plays a pivotal role in mediating cell adhesion, survival, and proliferation in physiological and pathological states. The relevance of extracellular matrix (ECM) proteins in cell fate control is an important issue to take into consideration for both tissue engineering and cell biology studies. The glycosylation of ECM proteins remains, however, largely unexplored.

Glycans in nanomedicine, impact and perspectives.

Glycans have been selected by nature for both structural and 'recognition' purposes. Taking inspiration from nature, nanomedicine exploits glycans not only as structural constituents of nanoparticles and nanostructured biomaterials but also as selective interactors of such glyco-nanotools. Surface glycosylation of nanoparticles finds application in targeting specific cells, whereas recent findings give evidence that the glycan content of cell microenvironment is able to induce the cell fate.

Phage-displayed peptides targeting specific tissues and organs.

Phage display is a powerful and widely used technique to find novel peptide ligands. A massive amount of peptide sequences have been identified for all kinds of materials, and peptides that may have targeting capabilities towards specific cells and tissues have received special attention in biomedical sciences. As a result, it is increasingly harder to follow all the work that has been done, which sometimes leads to many promising ligands receiving little attention, together with the publication of false positives that have already been found.

Multifunctional LUV liposomes decorated for BBB and amyloid targeting. A. In vitro proof-of-concept.

Multifunctional LUV liposomes (mf-LIPs) were developed, having a curcumin-lipid ligand (TREG) with affinity towards amyloid species, together with ligands to target the transferrin and the LDL receptors of the blood-brain-barrier (BBB), on their surface. mf-LIPs were evaluated for their brain targeting, on hCMEC/D3 monolayers, and for their ability to inhibit Aβ-peptide aggregation. The transport of mf-LIP across hCMEC/D3 monolayers was similar to that of BBB-LIPs, indicating that the presence of TREG on their surface does not reduce their brain targeting potential.

Flavonoids and Their Glycosides as Anti-amyloidogenic Compounds: Aβ1-42 Interaction Studies to Gain New Insights into Their Potential for Alzheimer's Disease Prevention and Therapy.

Combining NMR spectroscopy, transmission electron microscopy, biochemical and in vitro toxicity assays, we characterized the effect of flavonoid glycosylation, a chemical modification found very frequently in nature, on their ability to recognize and bind Aβ1-42 oligomers, preventing their aggregation and their neurotoxicity. Our data allow the elucidation of their structure-activity relationships, showing that glycosylation has a modest impact on flavonoid affinity for Aβ oligomers but, at the same time, increases both solubility and chemical stability, thus promoting their beneficial properties against Alzheimer's disease (AD). As flavonoids and their glycosides are widely available in natural foods, our results provide important information for the evaluation of the role of a flavonoid-rich diet for the prevention of AD.

Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study.

Objectives: To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs.

Design: Nested case-control study.

Setting: Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom).

A probabilistic bias analysis for misclassified categorical exposures, with application to oral anti-hyperglycaemic drugs.

Purpose: The effect of drug exposure misclassification generally receives little attention in pharmacoepidemiological research. In this paper, we illustrate a probabilistic bias analysis approach for misclassified categorical exposures and apply it in a database study of oral anti-hyperglycaemic drugs (OADs).

Methods: A cohort study based on the Health Search Database general-practice database was carried out by including 12 640 adult (≥40 years) patients newly treated with OADs during 2003-2010.

Metformin, other antidiabetic drugs, and endometrial cancer risk: a nested case-control study within Italian healthcare utilization databases.

Metformin may reduce the risk of endometrial cancer whereas other drugs for the treatment of type 2 diabetes mellitus appear to increase it, although the evidence is still limited. We investigated this issue using data from a nested case-control study within the healthcare utilization databases of the Lombardy Region, Italy. This study included 376 diabetic women with endometrial cancer and 7485 diabetic controls matched for cases on age, date at cohort entry, and duration of follow-up.

Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma: A real-world investigation.

Background And Objective: Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study.

Methods: The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18-40 years and newly treated with ICS during 2005-2008, was followed from their first ICS dispensation until 2010.