Emerging roles for HMGB1 protein in immunity, inflammation, and cancer

High-mobility group box 1 (HMGB1) protein is a member of the highly conserved non-histone DNA binding protein family. First identified in 1973, as one of a group of chromatin-associated proteins with high acidic and basic amino acid content, it was so named for its characteristic rapid mobility in polyacrylamide gel electrophoresis. HMGB1 was later discovered to have another function. It is released from a variety of cells into the extracellular milieu to act on specific cell-surface receptors. In this latter role, HMGB1 is a proinflammatory cytokine that may contribute to many inflammatory diseases, including sepsis. Therefore, HMGB1 regulates intracellular cascades influencing immune cell functions, including chemotaxis and immune modulation. The bioactivity of the HMGB1 is determined by specific posttranslational modifications that regulate its role in inflammation and immunity. During tumor development, HMGB1 has been reported to play paradoxical roles in promoting both cell survival and death by regulating multiple signaling pathways. In this review, we focus on the role of HMGB1 in physiological and pathological responses, as well as the mechanisms by which it contributes to immunity, inflammation, and cancer progression

Scaffold functionalization to support a tissue biocompatibility

The aim of this chapter is to illustrate the most applied methods for covalent and non-covalent functionalization of scaffold surface with biomimetic molecules, including bioactive proteins, peptides, and polysaccharides to improve scaffold biocompatibility. Additionally, the main techniques for surface physicochemical characterization are presented together with the commonly used approaches for in vitro testing of biocompatibility. Finally, new perspectives in scaffold surface functionalization and application of functionalized scaffolds are discussed in the conclusions

Targeting Calcium Signalling in Malignant Mesothelioma

Calcium ions (Ca2+) are central in cancer development and growth, serving as a major signaling system determining the cell\u2019s fate. Therefore, the investigation of the functional roles of ion channels in cancer development may identify novel approaches for determining tumor prognosis. Malignant mesothelioma is an aggressive cancer that develops from the serosal surface of the body, strictly related to asbestos exposure. The treatment of malignant mesothelioma is complex and the survival outcomes, rather than the overall survival data are, to date, disappointedly daunting. Nevertheless, conventional chemotherapy is almost ineffective. The alteration in the expression and/or activity of Ca2+ permeable ion channels seems to be characteristic of mesothelioma cells. In this review, we explore the involvement of the Ca2+toolkit in this disease. Moreover, the established sensitivity of some Ca2+channels to selective pharmacological modulators makes them interesting targets for mesothelioma cancer therapy

Protein-enriched Platelet-Rich Plasma (PEF-PRP) a New Products for Tissue Regeneration Developed Through the Ultrafiltration of PRP - Preclinical Study

Background: Platelet-Rich Plasma (PRP) is a blood component used for the biological treatment in many fields of regenerative medicine. The term PRP is currently applied to numerous blood components with different cellular and protein compositions. The optimal platelet concentration and the best technique for preparing PRP have not yet been defined and it is, therefore, important to understand the specific biological roles of the individual components. The aqueous part of PRP is plasma, which is an acellular component with containing proteins that are important for tissue regeneration. Objective: This preclinical study evaluated the biological characteristics and effects on proliferation (in an in vitro model) of a blood component Protein-Enriched Filtered PRP (PEFPRP) obtained through the ultrafiltration of low-concentration PRP and compared these effects with those of a standard PRP and other blood components preparation. Method: PEFPRP is a plasma enriched obtained by ultrafiltration of a plasma with low concentration platelets and its effects have been compared with those of a standard PRP and other blood components preparation. Result and Conclusion: PEFPRP provides a high concentration of proteins which have an important accessory function in in-vitro proliferation and could be highly significant in-vivo, accelerating tissue regeneration

Novel polyurethane-based thermosensitive hydrogels as drug release and tissue engineering platforms: design and in vitro characterization

Poloxamer P407 (P407) is a Food and Drug Administration approved triblock copolymer; its hydrogels show fast dissolution in aqueous environment and weak mechanical strength, limiting their in vivo application. In this work, an amphiphilic poly(ether urethane) (NHP407) was synthesized from P407, an aliphatic diisocyanate (1,6-hexanediisocyanate) and an amino acid derived diol (N-Boc serinol). NHP407 solutions in water-based media were able to form biocompatible injectable thermosensitive hydrogels with a lower critical gelation temperature behavior, having lower critical gelation concentration (6% w/v versus 18% w/v), superior gel strength (G′ at 37 °C about 40 000 Pa versus 10 000 Pa), faster gelation kinetics (<5 min versus 15–30 min) and higher stability in physiological conditions (28 days versus 5 days) compared to P407 hydrogels. Gel strength and PBS absorption at 37 °C increased whereas dissolution rate (in phosphate-buffered saline (PBS) at 37 °C) and permeability to nutrients (studied using fluorescein isothiocyanate–dextran model molecule) decreased as a function of NHP407 hydrogel concentration from 10% to 20% w/v. By varying the concentration, NHP407 hydrogels were thus prepared with different properties which could suit specific applications, such as in situ drug/cell delivery or bioprinting of scaffolds. Moreover, deprotected amino groups in NHP407 could be exploited for the grafting of bioactive molecules obtaining biomimetic hydrogels

Role of nutraceuticals in cancer therapy.

Nutraceuticals are natural bioactive products with food value and promising therapeutic properties in several diseases. Current cancer treatments, such as chemotherapy, radiotherapy and surgery, induce unintended side effects compromising also health and well-being of patients. Emerging studies suggest that some plant-based agents may impact cellular and molecular processes underlying tumor progression. However, some of these molecules might also play an antagonistic activity against classic therapeutic agents. The aim of this article is to review the current knowledge underpinning the use of nutraceuticals in cancer prevention and therapy.</p

Multidisciplinary analysis of Italian Alpine wildflower honey reveals criticalities, diversity and value

Wildflower honeys produced in mountain grasslands are an expression of the biodiversity of these fragile habitats. Despite its importance, the botanical origin of honey is often defined without performing formal analysis. The aim of the study was to characterize six wildflower mountain honeys produced in the Italian Alps with different analytic techniques (SPME–GC–MS, HPLC-Orbitrap, cicatrizing and antioxidant activity) alongside melissopalynological analysis and botanical definition of the production area. Even though the apiaries were in mountain grasslands rich in Alpine herbaceous species, the honey could be defined as rhododendron/raspberry unifloral or raspberry and rhododendron bifloral while the honey produced at the lowest altitude differed due to the presence of linden, heather and chestnut. The non-compliance of the honey could be due to habitat (meadows and pastures) fragmentation, but also to specific compounds involved in the plant–insect relationship, such as kynurenic acid, present in a high quantity in the sample rich in chestnut pollen. 255 volatile compounds were detected as well as some well-known markers of specific botanic essences, in particular chestnut, linden and heather, also responsible for most of the differences in aroma profiling. A high correlation between nicotinaldehyde content and percentage of raspberry pollen (r = 0.853, p < 0.05) was found. Phenolic acid and hydroxy-fatty acid were predominant in the chestnut pollen dominant honey, which presented the highest antioxidant activity and the lowest cicatrizing activity, while the flavonoid fraction was accentuated in one sample (rhododendron pollen prevalent), that was also the one with the highest effect on wound closure, although all samples had similar cicatrizing effects apart from the chestnut pollen dominant honey (lowest cicatrizing activity). Our study highlighted the difficulty of producing mountain wildflower honey and the importance of a thorough characterization of this product, also to encourage its production and valorisation.Fil: Leoni, Valeria. Università degli Studi di Milano; ItaliaFil: Giupponi, Luca. Università degli Studi di Milano; ItaliaFil: Pavlovic, Radmila. Università degli Studi di Milano; ItaliaFil: Gianoncelli, Carla. Università degli Studi di Milano; ItaliaFil: Cecati, Francisco Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Investigaciones en Tecnología Química. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: Ranzato, Elia. Università degli Studi di Milano; ItaliaFil: Martinotti, Simona. Università degli Studi di Milano; ItaliaFil: Pedrali, Davide. Università degli Studi di Milano; ItaliaFil: Giorgi, Annamaria. Università degli Studi di Milano; ItaliaFil: Panseri, Sara. Università degli Studi di Milano; Itali