Decellularization and Delipidation Protocols of Bovine Bone and Pericardium for Bone Grafting and Guided Bone Regeneration Procedures

The combination of bone grafting materials with guided bone regeneration (GBR) membranes seems to provide promising results to restore bone defects in dental clinical practice. In the first part of this work, a novel protocol for decellularization and delipidation of bovine bone, based on multiple steps of thermal shock, washes with detergent and dehydration with alcohol, is described. This protocol is more effective in removal of cellular materials, and shows superior biocompatibility compared to other three methods tested in this study. Furthermore, histological and morphological analyses confirm the maintenance of an intact bone extracellular matrix (ECM). In vitro and in vivo experiments evidence osteoinductive and osteoconductive properties of the produced scaffold, respectively. In the second part of this study, two methods of bovine pericardium decellularization are compared. The osmotic shock-based protocol gives better results in terms of removal of cell components, biocompatibility, maintenance of native ECM structure, and host tissue reaction, in respect to the freeze/thaw method. Overall, the results of this study demonstrate the characterization of a novel protocol for the decellularization of bovine bone to be used as bone graft, and the acquisition of a method to produce a pericardium membrane suitable for GBR applications

CD4(+) and CD4(-) CD1D-restricted natural killer T cells in perinatally HIV-1 infected children receiving highly active antiretroviral therapy.

We conducted a cross-sectional study on 43 Italian perinatally human immunodeficiency virus-type 1 (HIV-1) infected children receiving highly active antiretroviral therapy (HAART) and 26 age-matched healthy controls to explore CD1d-restricted NKT subsets. CD4+CD1d-rectricted natural killer (NKT) cell depletion was evidenced in 26 HIV-1 infected children with active viral replication despite HAART. Conversely, no alteration was evidenced in 17 children with undetectable viral load, suggesting full recovery in both CD4+ and CD4− CDld-rectricted NKT cell subsets. The loss of CD4+ NKT cells in unresponsive children may have clinical consequences, including autoimmune disorders or cancer development. Future therapeutic perspectives are suggested

Regulation of the microtubular cytoskeleton by Polycystin-1 favors focal adhesions turnover to modulate cell adhesion and migration.

BACKGROUND: Polycystin-1 (PC-1) is a large plasma membrane receptor, encoded by the PKD1 gene, which is mutated in most cases of Autosomal Dominant Polycystic Kidney Disease (ADPKD). The disease is characterized by renal cysts. The precise function of PC-1 remains elusive, although several studies suggest that it can regulate the cellular shape in response to external stimuli. We and others reported that PC-1 regulates the actin cytoskeleton and cell migration. RESULTS: Here we show that cells over-expressing PC-1 display enhanced adhesion rates to the substrate, while cells lacking PC-1 have a reduced capability to adhere. In search for the mechanism responsible for this new property of PC-1 we found that this receptor is able to regulate the stability of the microtubules, in addition to its capability to regulate the actin cytoskeleton. The two cytoskeletal components are acting in a coordinated fashion. Notably, we uncovered that PC-1 regulation of the microtubule cytoskeleton impacts on the turnover rates of focal adhesions in migrating cells and we link all these properties to the capability of PC-1 to regulate the activation state of Focal Adhesion Kinase (FAK). CONCLUSIONS: In this study we show several new features of the PC-1 receptor in modulating microtubules and adhesion dynamics, which are essential for its capability to regulate migration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-015-0059-3) contains supplementary material, which is available to authorized users

Negative effects of a high tumour necrosis factor-α concentration on human gingival mesenchymal stem cell trophism: The use of natural compounds as modulatory agents

Background: Adult mesenchymal stem cells (MSCs) play a crucial role in the maintenance of tissue homeostasis and in regenerative processes. Among the different MSC types, the gingiva-derived mesenchymal stem cells (GMSCs) have arisen as a promising tool to promote the repair of damaged tissues secreting trophic mediators that affect different types of cells involved in regenerative processes. Tumour necrosis factor (TNF)-α is one of the key mediators of inflammation that could affect tissue regenerative processes and modify the MSC properties in in-vitro applications. To date, no data have been reported on the effects of TNF-α on GMSC trophic activities and how its modulation with anti-inflammatory agents from natural sources could modulate the GMSC properties. Methods: GMSCs were isolated and characterized from healthy subjects. The effects of TNF-α were evaluated on GMSCs and on the well-being of endothelial cells. The secretion of cytokines was measured and related to the modification of GMSC-endothelial cell communication using a conditioned-medium method. The ability to modify the inflammatory response was evaluated in the presence of Ribes nigrum bud extract (RBE). Results: TNF-α differently affected GMSC proliferation and the expression of inflammatory-related proteins (interleukin (IL)-6, IL-10, transforming growth factor (TGF)-β, and cyclooxygenase (COX)-2) dependent on its concentration. A high TNF-α concentration decreased the GMSC viability and impaired the positive cross-talk between GMSCs and endothelial cells, probably by enhancing the amount of pro-inflammatory cytokines in the GMSC secretome. RBE restored the beneficial effects of GMSCs on endothelial viability and motility under inflammatory conditions. Conclusions: A high TNF-α concentration decreased the well-being of GMSCs, modifying their trophic activities and decreasing endothelial cell healing. These data highlight the importance of controlling TNF-α concentrations to maintain the trophic activity of GMSCs. Furthermore, the use of natural anti-inflammatory agents restored the regenerative properties of GMSCs on endothelial cells, opening the way to the use and development of natural extracts in wound healing, periodontal regeneration, and tissue-engineering applications that use MSCs

The critical raw materials issue between scarcity, supply risk, and unique properties

ABSTRACT: This editorial reports on a thorough analysis of the abundance and scarcity distribution of chemical elements and the minerals they form in the Earth, Sun, and Universe in connection with their number of neutrons and binding energy per nucleon. On one hand, understanding the elements’ formation and their specific properties related to their electronic and nucleonic structure may lead to understanding whether future solutions to replace certain elements or materials for specific technical applications are realistic. On the other hand, finding solutions to the critical availability of some of these elements is an urgent need. Even the analysis of the availability of scarce minerals from European Union sources leads to the suggestion that a wide-ranging approach is essential. These two fundamental assumptions represent also the logical approach that led the European Commission to ask for a multi-disciplinary effort from the scientific community to tackle the challenge of Critical Raw Materials. This editorial is also the story of one of the first fulcrum around which a wide network of material scientists gathered thanks to the support of the funding organization for research and innovation networks, COST (European Cooperation in Science and Technology).info:eu-repo/semantics/publishedVersio

Capacity for the management of kidney failure in the International Society of Nephrology Western Europe region:Report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA)

Western Europe boasts advanced healthcare systems, robust kidney care guidelines, and a well-established healthcare workforce. Despite this, significant disparities in kidney replacement therapy incidence, prevalence, and transplant access exist. This paper presents the third International Society of Nephrology Global Kidney Health Atlas’s findings on kidney care availability, accessibility, affordability, and quality in 22 Western European countries, representing 99% of the region's population. The known chronic kidney disease (CKD) prevalence across Western Europe averages 10.6%, slightly above the global median. Cardiovascular diseases account for a substantial portion of CKD-related deaths. Kidney failure incidence varies. Government health expenditure differs, however, most countries offer government-funded acute kidney injury, dialysis, and kidney transplantation care. Hemodialysis and peritoneal dialysis are universally available, with variations in the number of dialysis centers. Kidney transplantation is available in all countries (except for three microstates), with variable transplant center prevalence. Conservative kidney management is increasingly accessible. The region's kidney care workforce is substantial, exceeding global averages, however, workforce shortages are reported. Barriers to optimal kidney care include limited workforce capacity, lack of surveillance mechanisms, and suboptimal integration into national non-communicable disease strategies. Policy recognition of CKD as a health priority varies across countries. While Western Europe exhibits strong kidney care infrastructure, opportunities for improvement exist, particularly in CKD prevention, surveillance, awareness, and policy implementation. Efforts to improve CKD care should include automated detection, educational support, and enhanced workflows. Based on these findings, healthcare professionals, stakeholders, and policymakers are called to act to enhance kidney care across the region

Nanostructured modifications of titanium surfaces improve vascular regenerative properties of exosomes derived from mesenchymal stem cells: Preliminary in vitro results

© 2021 by the authors. Licensee MDPI, Basel, Switzerland.(1) Background: Implantation of metal-based scaffolds is a common procedure for treating several diseases. However, the success of the long-term application is limited by an insufficient endothelialization of the material surface. Nanostructured modifications of metal scaffolds represent a promising approach to faster biomaterial osteointegration through increasing of endothelial commitment of the mesenchymal stem cells (MSC). (2) Methods: Three different nanotubular Ti surfaces (TNs manufactured by electrochemical anodization with diameters of 25, 80, or 140 nm) were seeded with human MSCs (hMSCs) and their exosomes were isolated and tested with human umbilical vein endothelial cells (HUVECs) to assess whether TNs can influence the secretory functions of hMSCs and whether these in turn affect endothelial and osteogenic cell activities in vitro. (3) Results: The hMSCs adhered on all TNs and significantly expressed angiogenic-related factors after 7 days of culture when compared to untreated Ti substrates. Nanomodifications of Ti surfaces significantly improved the release of hMSCs exosomes, having dimensions below 100 nm and expressing CD63 and CD81 surface markers. These hMSC-derived exosomes were efficiently internalized by HUVECs, promoting their migration and differentiation. In addition, they selectively released a panel of miRNAs directly or indirectly related to angiogenesis. (4) Conclusions: Preconditioning of hMSCs on TNs induced elevated exosomes secretion that stimulated in vitro endothelial and cell activity, which might improve in vivo angiogenesis, supporting faster scaffold integration

Fears and perception of the impact of COVID-19 on patients with lung cancer. A mono-institutional survey

In February 2020, Italy became one of the first countries to be plagued by the SARS-CoV-2 pandemic, COVID-19. In March 2020, the Italian government decreed a lockdown for the whole country, which overturned communication systems, hospital organization, and access to patients and their relatives and carers. This issue had a particular regard for cancer patients. Our Thoracic Oncology Division therefore reorganized patient access in order to reduce the risk of contagion and, at the same time, encourage the continuation of treatment. Our staff contacted all patients to inform them of any changes in treatment planning, check that they were taking safety measures, and ascertain their feelings and whether they had any COVID-19 symptoms. To better understand patients’ fears and expectations of during the pandemic period, we created a nine-question interview, administered from April to May 2020 to 156 patients with lung cancer. Patients were classified by age, sex, comorbidity, disease stage, prior treatment, and treatment type. The survey showed that during the pandemic period some patients experienced fear of COVID-19, in particular: women (55% vs. 33%), patients with comorbidities (24% vs. 9%), and patients who had already received prior insult (radiotherapy or surgery) on the lung (30% vs. 11%). In addition, the patients who received oral treatment at home or for whom intravenous treatment was delayed, experienced a sense of relief (90% and 72% respectively). However, only 21% of the patients were more afraid of COVID-19 than of their cancer, in particular patients with long-term (> 12 months) vs. short-term cancer diagnosis (28% vs. 12.5%, respectively). Furthermore, the quarantine period or even just the lockdown period alone, worsened the quality of life of some patients (40%), especially those in oral treatment (47%). Our data demonstrate how lung cancer patients are more afraid of their disease than of a world pandemic. Also this interview indirectly highlights the clinician’s major guiding principle in correctly and appropriately managing not just the patient’s expectations of their illness and its treatment, but also and especially of the patient’s fears

The emerging role of cancer nanotechnology in the panorama of sarcoma

In the field of nanomedicine a multitude of nanovectors have been developed for cancer application. In this regard, a less exploited target is represented by connective tissue. Sarcoma lesions encompass a wide range of rare entities of mesenchymal origin affecting connective tissues. The extraordinary diversity and rarity of these mesenchymal tumors is reflected in their classification, grading and management which are still challenging. Although they include more than 70 histologic subtypes, the first line-treatment for advanced and metastatic sarcoma has remained unchanged in the last fifty years, excluding specific histotypes in which targeted therapy has emerged. The role of chemotherapy has not been completely elucidated and the outcomes are still very limited. At the beginning of the century, nano-sized particles clinically approved for other solid lesions were tested in these neoplasms but the results were anecdotal and the clinical benefit was not substantial. Recently, a new nanosystem formulation NBTXR3 for the treatment of sarcoma has landed in a phase 2-3 trial. The preliminary results are encouraging and could open new avenues for research in nanotechnology. This review provides an update on the recent advancements in the field of nanomedicine for sarcoma. In this regard, preclinical evidence especially focusing on the development of smart materials and drug delivery systems will be summarized. Moreover, the sarcoma patient management exploiting nanotechnology products will be summed up. Finally, an overlook on future perspectives will be provided

Evaluation of Endometrial Urocortin Secretion for Prediction of Pregnancy after Intrauterine Insemination

Abstract Background: Urocortin is a neuropeptide produced by the human endometrium and has biological effects putatively important for promoting blastocyst implantation. We measured urocortin concentrations in samples of endometrial wash fluid collected from women with unexplained infertility who underwent intrauterine insemination (IUI). Methods: Patients 28–42 years of age (n = 71) were consecutively enrolled after a complete clinical evaluation. Endometrial wash fluid was retrieved before IUI, at the time of ultrasound evaluation of endometrial thickness. Urocortin concentrations were assayed with a specific ELISA. Results: After IUI, 28 patients (39%) became pregnant. Urocortin concentrations were significantly higher in women who became pregnant than in those who did not (0.38 μg/L vs 0.13 μg/L, P <0.0001). At a cutoff of 0.321 μg/L, urocortin results were positive in 61% [95% confidence interval (CI), 41%–78%] of women who had successful implantation and negative in 98% (95% CI, 88%–99.6%) of those who did not. The pregnancy rate for women with urocortin concentrations >0.32 μg/L was 94%, which differed significantly (P <0.05) from the overall pregnancy rate of 39% in the study population. Conclusions: Urocortin is measurable in endometrial wash fluid, and its concentrations before IUI are higher in women who subsequently achieve pregnancy. These data suggest that the probability of having a successful pregnancy-producing IUI may be better estimated by measuring urocortin in endometrial wash fluid