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Abstract Background Osteoarthritis (OA) is a degenerative musculoskeletal disease that significantly impacts the quality of life. Currently, no validated biomarkers for early detection of OA are defined. The possibility of discovering OA biomarkers is the focus of this study. Methods Human primary OA synovial cells (SVs), isolated from discarded joint tissue of patients with Kellgren & Lawrence score (KL)

Abstract Osteosarcoma (OS) is the most frequent primary malignant bone tumour, whose heterogeneity represents a major challenge for common antitumour therapies. Inflammatory cytokines are known to be necessary for OS progression. Therefore, to optimise therapy, it is important to discover reliable biomarkers by identifying the mechanism generating OS and investigating the inflammatory pathways that support the undifferentiated state. In this work, we highlight the differences of epigenetic activities of IL-1β and TNFα, and the susceptibility of TET-1 enzymatic inhibition, in tumour progression of three different OS cell lines. Investigating DNA methylation of IL-6 promoter and determining its expression, we found that TET enzymatic inhibition influences proliferation induced by inflammatory cytokines in OS cell lines. Moreover, Bobcat 339 treatment blocks IL-1β epigenetic action on IL-6 promoter, while only partially those of TNFα as well as inhibits IL-1β-dependent epithelial–mesenchymal transition (EMT) process, but only partially those of TNFα. In conclusion, this work highlights that IL-1β and TNFα have different effects on DNA demethylation in OS cell lines, making DNA methylation a potential biomarker of disease. Specifically, in IL-1β treatment, TET-1 inhibition completely blocks tumour progression, while in TNFα actions, it is only partially effective. Given that these two inflammatory pathways can be therapeutic targets for treating these tumours, knowledge of their distinct epigenetic behaviours can be useful for developing precise and specific therapeutic strategies for this disease.

Magnesium and its alloys represent promising candidates for biomedical implants due to their biodegradability and mechanical properties, which are similar to natural bone. However, their rapid degradation process characterized by dynamic pH fluctuations and significant hydrogen gas evolution during biocorrosion adversely affects both in vitro and in vivo assessments. While the ISO 10993-5 and 12 standards provide guidelines for evaluating the in vitro biocompatibility of biodegradable materials, they also introduce testing variability conditions that yield inconsistent results. To address these inherent characteristics of Mg alloys, developing improved methods that accurately simulate the physiological environment for in vitro biocompatibility testing is essential. This study introduces two novel extraction approaches for evaluating Mg alloys: a buffered solution utilizing PBS/DMEM with quaternary dilutions and a modified ISO standard protocol employing decuple dilution of conventional unbuffered extracts. The present findings establish that controlled optimization of extraction conditions, specifically buffer composition and dilution parameters, enables reliable in vitro cytotoxicity assessment of Mg alloys, providing a robust methodology that advances the preclinical evaluation of these promising biodegradable materials.

Introduction: The development of reliable treatments for infected or potentially infected bone loss resulting from open fractures and non-unions is extremely urgent, especially to reduce the prolonged courses of antimicrobial therapy to which affected patients are subjected. Numerous bone graft substitutes have been used over the years, but there are currently no effective solutions to treat critical bone loss, especially in the presence of infection. The present study evaluated the use of the biomorphic calcium phosphate bone scaffold b. Bone™, based on a next-generation resorbable biomimetic biomaterial, in bone reconstruction surgery in cases of infection.Methods: Using an “in vitro 3D bone fracture model” to predict the behavior of this drug delivery system during critical bone loss at an infected (or potentially infected) site, the effects of scaffolds loaded with gentamicin or vancomycin on the viability and differentiation capacity of human mesenchymal stem cells (hMSCs) were evaluated.Results: This scaffold, when loaded with gentamicin or vancomycin, exhibits a typical drug release curve that determines the inhibitory effects on the growth of Staphylococcus aureus, Enterococcus faecalis, and Escherichia coli, as well as relative biofilm formation.Discussion: The study demonstrates that b.bone scaffolds can effectively address key challenges in orthopedic surgery and patient care by inhibiting bacterial growth and biofilm formation through rapid, potent antibiotic release, reducing the risk of treatment failure due to resistance, and providing a promising solution for bone infections and improved patient outcomes. Future studies could explore the combination of different antibiotics on these scaffolds for more tailored and effective treatments against post-traumatic osteomyelitis pathogens.

The COVID-19 pandemic was a health, economic, and financial crisis. The aviation sector was one of the most severely hit. Despite the extensive literature on this, COVID-Finance has been focused on stock returns, neglecting what could be learnt from the spreads of airlines’ credit default swaps (CDSs). This would seem of the utmost importance, given the epicenter of the crisis within the credit market. In this paper, an in-depth analysis of airlines’ CDS spreads is conducted. It is found that they were severely hit, for all airlines studied. However, the results of the PSY test showed that speculative trading led the surge, as explosive roots were found in the spreads of all these aviation firms. The dramatic increase in CDS spreads has contributed to already high borrowing costs for airlines. Our results suggest that aviation bail outs have helped to mitigate spreads’ explosiveness. Monetary policy measures have also limited, albeit indirectly, the funding risk posed by the government bail outs. By the end of March 2021, spreads were no longer explosive, and were approaching, at highly heterogeneous paces, their pre-pandemic values. Notwithstanding, airlines’ stock prices have been notably resistant to recovery.

Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and inflammation. The current treatments mainly concern pain control and reduction of inflammation, but no therapeutic strategy has been identified as a disease-modifying treatment. Therefore, identifying specific biomarkers useful to prevent, treat or distinguish the stages of OA disease has become an immediate need of clinical practice. The role of microRNAs (miRNAs) in OA has been investigated in the last decade, and increasing evidence has emerged that the influence of the environment on gene expression through epigenetic processes contributes to the development, progression and aggressiveness of OA, in particular acting on the microenvironment modulations. The effects of epigenetic regulation, particularly different miRNA methylation during OA disease, were highlighted in the present systematic review. The evidence arising from this study of the literature conducted in three databases (PubMed, Scopus, Web of Science) suggested that miRNA methylation state already strongly impacts OA progression, driving chondrocytes and synoviocyte proliferation, apoptosis, inflammation and ECM deposition. However, the possibility of understanding the mechanism by which different epigenetic modifications of miRNA or pre-miRNA sequences drive the aggressiveness of OA could be the new focus of future investigations.

Osteosarcoma (OS) is the most common primary bone sarcoma affecting the life of pediatric patients. The clinical treatment faces numerous difficulties, including the adverse effects of chemotherapies, chemoresistance, and recurrences. In this study, the effects of resveratrol (RSV), a natural polyphenol, on OS cell lines were investigated to evaluate its action as an adjuvant therapy to the current chemotherapy regimens. RSV exhibited multiple tumor-suppressing activities on OS cell lines, inducing a series of critical events. We found (1) a cell growth inhibition due to an increase in cell distress, which was, in part, due to the involvement of the AKT and caspase-3 pathways, (2) an increase in cellular differentiation due to major gene expression levels of the osteoblastic differentiation genes, (3) an inhibition of IL-6 secretion due to an epigenetic effect on the IL-6 promoter, and (4) an inhibition of OS cells migration related to the decrease in IL-8 secretion levels due to an epigenetic effect on its promoter. Finally, the cotreatment of RSV with doxorubicin and cisplatin increased their cytotoxic effect on OS cells. Although further investigations are mandatory, it seems RSV might be a promising therapeutic adjuvant agent for OS cell treatment, exerting an antitumor effect when combined with chemotherapy.

Abstract Background Bone tissue is one of the main sites for breast metastasis; patients diagnosed with advanced breast cancer mostly develop bone metastasis characterized by severe osteolytic lesions, which heavily influence their life quality. Low Intensity Pulsed Ultrasound (LIPUS) is a form of mechanical energy able to modulate various molecular pathways both in cancer and in health cells. The purpose of the present study was to evaluate for the first time, the ability of LIPUS to modulate osteolytic capability of breast cancer cells. Methods Two different approaches were employed: a) Indirect method -conditioned medium obtained by MDA-MB-231 cell line treated or untreated with LIPUS was used to induce osteoclast differentiation of murine macrophage Raw264.7 cell line; and b) Direct method -MDA-MB-231 were co-cultured with Raw264.7 cells and treated or untreated with LIPUS. Results LIPUS treatment impaired MDA-MB-231 cell dependentosteoclast differentiation and produced a reduction of osteoclast markers such as Cathepsin K, Matrix Metalloproteinase 9 and Tartrate Resistant Acid Phosphatase, suggesting its role as an effective and safe adjuvant in bone metastasis management. Conclusion LIPUS treatment could be a good and safety therapeutic adjuvant in osteolyitic bone metastasis not only for the induction properties of bone regeneration, but also for the reduction of osteolysis.

Abstract Osteosarcoma (OS) is the most common primary malignant tumor of bone, which preferentially develops lung metastasis. Although standard chemotherapy has significantly improved long-term survival over the past few decades, the outcome for patients with metastatic or recurrent OS remains dramatically poor. Novel therapies are therefore required to slow progression and eradicate the disease. Furthermore, to better understand the cellular and molecular mechanisms responsible for OS onset and progression, the development of novel predictive culture systems resembling the native three-dimensional (3D) tumor microenvironment are mandatory. ‘Tumor engineering’ approaches radically changed the previous scenario, through the development of advanced and alternative 3D cell culture in vitro models able to tightly mimic the in vivo tumor microenvironment. In this review, we will summarize the state of the art in this novel area, illustrating the different methods and techniques employed to realize 3D OS cell culture models and we report the achieved results, which highlight the efficacy of these models in reproducing the tumor milieu. Although data need to be further validated, the scientific studies reviewed here are certainly promising and give new insights into the clinical practice.

Here, we presented new original data on the effects of iron depletion on the circulating lipid profile in B6HCV mice, a murine model of HCV-related dyslipidemia. Male adult B6HCV mice were subjected to non-invasive iron depletion by low iron diet. Serum iron concentration was assessed for evaluating the effects of the dietary iron depletion. Concentrations of circulating triglycerides, total cholesterol, Low Density Lipoproteins (LDLs), High Density Lipoproteins (HDLs) were analyzed and reported by using stacked line charts. The present data indicated that low serum iron concentration is associated to i) lower serum triglycerides concentrations and ii) increased circulating LDLs. The presented original data have not been published elsewhere.