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Simple Summary: Perillyl alcohol is a natural compound derived from plants, and it has shown promise as an anti-cancer agent in various types of cancer. This review explores how POH affects cancer cells by examining its impact on metabolic and regulatory pathways, such as those involved in cell cycle regulation and apoptosis. By understanding these mechanisms, researchers can identify new opportunities for cancer treatment and consider POH as a candidate for drug repurposing. The findings from this research may help develop novel therapies that are more effective and potentially less toxic, providing new avenues for cancer treatment. Background/Objectives: Perillyl alcohol (POH), a plant-derived compound, has demonstrated anti-tumor activity across various human cancers. Understanding the regulatory pathways through which POH exerts its effects is crucial for identifying new therapeutic opportunities and exploring potential drug repositioning strategies. Therefore, this scoping review aims to provide a comprehensive overview of the metabolic and regulatory pathways involved in the anticancer effects of POH, based on in vitro evidence. Methods: Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted in the PUBMED, Web of Science, and Scopus databases. Results: A total of 39 studies were included, revealing that POH exerts its biological effects by modulating several pathways, including the regulation of cyclins, CDKs, and p21, thereby affecting cell cycle progression. It inhibits growth and promotes cell death by attenuating AKT phosphorylation, reducing PARP-1 activity, increasing caspase activity and the FAS receptor and its ligand FASL. Additionally, POH reduces ERK phosphorylation, inhibits RAS protein isoprenylation, and decreases Na/K-ATPase activity. Conclusions: In conclusion, this review delineates the key regulatory pathways responsible for mediating the biological effects of POH in cancer. [ABSTRACT FROM AUTHOR]

This study sought to examine the coronavirus COVID-19 pandemic's impacts on local communities whose residents are directly or indirectly affected by city tourism. Qualitative research was conducted via in-depth interviews and Leximancer software analysis to explore locals' perceptions in two highly tourism-dependent southern European cities. While the crisis has had predominantly negative impacts on tourism, the pandemic's positive effects could contribute to cities' greater resilience and more sustainable tourism models. The results highlight the variables that residents perceive as having the most influence on city tourism, as well as providing insights into locals' expectations for the future. [ABSTRACT FROM AUTHOR]

This study focused on the unbalanced relationships that can arise in current public–private partnership (PPP) risk management frameworks, especially in developing countries' water sectors. Different stakeholders' perceptions of risk management were examined by analyzing 15 interviews in Portugal and Mozambique. The hybrid method included semantic, descriptive statistic, content, and narrative analyses. To achieve the research objectives, the semi-structured interview transcripts were processed using quantitative and qualitative techniques to collate relevant actors' opinions of risk management in PPP water projects. Five risk categories were identified. The interviewed experts ranked the financial risk category as the most crucial, followed by infrastructure, commercial, technical and operational, and context risks. However, when the transcripts were evaluated from a risk factor perspective, the context risk category unexpectedly jumped to first place. Twenty-five high-impact risk factors were isolated in the semi-structured interview contents. The top five most critical risk factors were political interference, no performance measurement baselines, an unfavorable private investment climate, nonpayment of bills, and water assets uncertain condition. The results comprise a fresh contribution to the existing knowledge about experts' perceptions of PPP contract risks, including that prior research and specialists categorize financial risks as the most important. The findings further reveal that experts consider managing context risks to be the key factor in PPPs success in developing countries, as well as highlighting the need to explore these risks more fully in emerging economies' water sectors. In addition, a complete risk management cycle is proposed based on the interviewed professionals' opinions, in which risk assessment and risk treatment or mitigation measures are dealt with simultaneously. [ABSTRACT FROM AUTHOR]

In vitro cell-based tests are an important preclinical step for the safety assessment of biomaterials and drugs. Three-dimensional cell culture models (3D) may improve the limitations of the usual 2D models, as they better simulate a physiological environment. This work describes the characterization of a 3D spheroid model of MC3T3-E1 murine preosteoblasts for the testing of bone-substitute materials and investigates its adequacy to some of the most employed cell viability tests. The spheroids presented structural stability for 28 days in culture, with a regular spheroidal aspect, compact surface, and dense inner structure, with high potential for mineralization, but a time-dependent reduction in size. The use of colorimetric tests (MTT, XTT, and NRU) did not achieve satisfactory optical densities and did not correlate with cell density in the 3D model, as the aggregates remain strongly stained even after dye extraction steps. On the other hand, the LDH test achieved appropriate optical density and a high correlation with cell density (r2 = 0.77) and identified a dose–response for a well-known cytotoxic polymer (latex), while no toxicity was identified for biocompatible PLA wires. These results indicate that material testing with 3D bone cell models requires a careful choice of test methods and parameters. [ABSTRACT FROM AUTHOR]

Successful biomaterials for bone tissue therapy must present different biocompatible properties, such as the ability to stimulate the migration and proliferation of osteogenic cells on the implantable surface, to increase attachment and avoid the risks of implant movement after surgery. The present work investigates the applicability of a three-dimensional (3D) model of bone cells (osteospheres) in the evaluation of osteoconductive properties of different implant surfaces. Three different titanium surface treatments were tested: machined (MA), sandblasting and acid etching (BE), and Hydroxyapatite coating by plasma spray (PSHA). The surfaces were characterized by Scanning Electron Microscopy (SEM) and atomic force microscopy (AFM), confirming that they present very distinct roughness. After seeding the osteospheres, cell–surface interactions were studied in relation to cell proliferation, migration, and spreading. The results show that BE surfaces present higher densities of cells, leaving the aggregates towards than titanium surfaces, providing more evidence of migration. The PSHA surface presented the lowest performance in all analyses. The results indicate that the 3D model allows the focal analysis of an in vitro cell/surfaces interaction of cells and surfaces. Moreover, by demonstrating the agreement with the clinical data observed in the literature, they suggest a potential use as a predictive preclinical tool for investigating osteoconductive properties of novel biomaterials for bone therapy. [ABSTRACT FROM AUTHOR]

In the context of football's globalisation, some of the most important football clubs (FCs) can currently be classified as 'entertainment multinationals'. Sport hospitality provides opportunities to maximise club stadiums' use so that they can increase clubs' annual turnover and function as branding platforms. This study sought to identify the main narratives shared online about—and the dimensions of—visitors' experiences with top football brands in stadium tours. The data collected for this research comprised 400 text reviews for 10 European FCs' stadiums (i.e., 4000 reviews) written by visitors in the post-experience phase. Content analysis of these Web reviews was conducted using Leximancer software. The results confirm the existence of 15 themes: fan, tour, stadium, team, museum, room, staff, game, (best) place, ticket, seating, recommend(ation), food, shop and attraction. Most researchers have examined stadium tours from a supply-side perspective. The present study's aim was, therefore, to contribute to the existing literature by analysing stadium tours' dimensions from the visitors' point of view. Stadium tours and museum visits are important sources of revenue that contribute to FCs' economic sustainability. Offering outstanding customer experiences is thus of utmost importance to maximise club stadiums' usage and strengthen fans' engagement. [ABSTRACT FROM AUTHOR]

Good laboratory practices (GLP) increase the quality and traceability of results in health sciences research. However, factors such as high staff turnover, insufficient resources, and a lack of training for managers may limit their implementation in research and academic laboratories. This Scoping Review aimed to identify digital tools for managing academic health sciences and experimental medicine laboratories and their relationship with good practices. Following the PRISMA-ScR 2018 criteria, a search strategy was conducted until April 2021 in the databases PUBMED, Web of Sciences, and Health Virtual Library. A critical appraisal of the selected references was conducted, followed by data charting. The search identified twenty-one eligible articles, mainly originated from high-income countries, describing the development and/or implementation of thirty-two electronic management systems. Most studies described software functionalities, while nine evaluated and discussed impacts on management, reporting both improvements in the workflow and system limitations during implementation. In general, the studies point to a contribution to different management issues related to GLP principles. In conclusion, this review identified evolving evidence that digital laboratory management systems may represent important tools in compliance with the principles of good practices in experimental medicine and health sciences research. [ABSTRACT FROM AUTHOR]

This study aimed to assess the response of 3D printed polylactic acid (PLA) scaffolds biomimetically coated with apatite on human primary osteoblast (HOb) spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution to promote apatite deposition, and characterized by physical-chemical, morphological, and mechanical properties. PLA-CaP scaffolds with interconnected porous and mechanical properties suitable for bone repairing were produced with reproducibility. The in vitro biological response was assessed with human primary osteoblast spheroids. Increased cell adhesion and the rise of in vitro release of growth factors (Platelet-Derived Growth Factor (PDGF), Basic Fibroblast Growth Factor (bFGF), Vascular Endothelial Growth Factor (VEGF) was observed for PLA-CaP scaffolds, when pre-treated with fetal bovine serum (FBS). This pre-treatment with FBS was done in a way to enhance the adsorption of serum proteins, increasing the number of bioactive sites on the surface of scaffolds, and to partially mimic in vivo interactions. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, coated with apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 on critical-sized defects (8 mm) of rat calvaria. PLA-CaP+rhBMP2 presented higher values of newly formed bone (NFB) than other groups at all in vivo experimental periods (p < 0.05), attaining 44.85% of NFB after six months. These findings indicated two new potential candidates as alternatives to autogenous bone grafts for long-term treatment: (i) 3D-printed PLA-CaP scaffold associated with spheroids, since it can reduce the time of repair in situ by expression of biomolecules and growth factors; and (ii) 3D-printed PLA-CaP functionalized rhBMP2 scaffold, a biocompatible, bioactive biomaterial, with osteoconductivity and osteoinductivity. [ABSTRACT FROM AUTHOR]