Search Results (1,697)

Cholangiocarcinoma (CCA) is highly prevalent in the Greater Mekong sub-region, especially northeastern Thailand, where infection with the liver fluke Opisthorchis viverrini is a major etiological factor. Limited therapeutic options and the absence of reliable early diagnosis tools impede effective disease control. Atractylodes lancea (Thunb.) DC.—long used in Thai and East Asian medicine, contains atractylodin (ATD), a potent bioactive compound with anticancer potential. Here, we developed ATD-loaded poly(lactic co-glycolic acid) nanoparticles (ATD PLGA NPs) and evaluated their antitumor efficacy against CCA. The formulated nanoparticles had a mean diameter of 229.8 nm, an encapsulation efficiency of 83%, and exhibited biphasic, sustained release, reaching a cumulative release of 92% within seven days. In vitro, ATD-PLGA NPs selectively reduced the viability of CL-6 and HuCCT-1 CCA cell lines, with selectivity indices (SI) of 3.53 and 2.61, respectively, outperforming free ATD and 5-fluorouracil (5-FU). They suppressed CL-6 cell migration and invasion by up to 90% within 12 h and induced apoptosis in 83% of cells through caspase-3/7 activation. Micronucleus assays showed lower mutagenic potential than the positive control. In vivo, ATD-PLGA NPs dose-dependently inhibited tumor growth and prolonged survival in CCA-xenografted nude mice; the high-dose regimen matched or exceeded the efficacy of 5-FU. Gene expression analysis revealed significant downregulation of pro-tumorigenic factors (VEGF, MMP-9, TGF-β, TNF-α, COX-2, PGE₂, and IL-6) and upregulation of the anti-inflammatory cytokine IL-10. Collectively, these results indicate that ATD-PLGA NPs are a promising nanotherapeutic platform for targeted CCA treatment, offering improved anticancer potency, selectivity, and safety compared to conventional therapies. Full article

The aim of this study was to verify whether comprehensive and inclusive pro-safety education contributes to building a strong safety culture in food companies. The study was conducted in 612 Polish companies, where special attention was paid to modern forms of education during pro-safety education, as well as the frequency and duration of this education. The results of the study showed that safety culture is poorly developed, even when it is consciously and formally implemented in the company. One of the identified problems was the discrepancy between the company’s declared commitment to pro-safety education and the actual behavior of employees. This indicates that formal company strategies may not be effectively embedded in the attitudes and actions of employees. The research emphasizes the importance of adapting pro-safety efforts to the organizational culture in order to ensure significant results and avoid superficial implementation. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Polymerase-coupled nanopore sequencing requires DNA polymerases with strong strand displacement activity and high processivity to sustain continuous signal generation. In this study, we characterized two novel B family DNA polymerases, SRHS and BBum, isolated from Bacillus phages SRT01hs and BeachBum, respectively. Both enzymes exhibited robust strand displacement, 3′→5′ exonuclease activity, and maintained processivity under diverse reaction conditions, including across a broad temperature range (10–45 °C) and in the presence of multiple divalent metal cofactors (Mg²⁺, Mn²⁺, Fe²⁺), comparable to the well-characterized Phi29 polymerase. Through biochemical analysis of mutants designed using AlphaFold3-predicted structural models, we identified key residues (G96, M97, D486 in SRHS; S97, M98, A493 in BBum) that modulated exonuclease activity, substrate specificity and metal ion utilization. Engineered variants SRHS_F and BBum_Pro_L efficiently incorporated unnatural nucleotides in the presence of Mg²⁺—a function not observed in Phi29 and other wild-type strand-displacing B family polymerases. These combined biochemical features highlight SRHS and BBum as promising enzymatic scaffolds for nanopore-based long-read sequencing platforms. Full article

This study explores the role of egoistic and altruistic values on green real estate purchase intention among young consumers in Canada aged between 20 and 40 years. In addition, this study examines the mediating effects of pro-environmental self-identity between social consumption motivation and green real estate purchase intention. A quantitative cross-sectional research design with an explanatory nature is employed. A total of 432 participating consumers in Canada, comprising 44% men and 48% women, with a graduate educational background accounting for 46.7%, and the ages between 24 and 35 contributing 75.2%, were part of the study, and the data collection used a survey method with a purposive sampling, followed by a respondent-driven method. Descriptive and inferential statistics were performed on the scales used for the study variables. A structural equational model and path analysis were conducted to derive the results, and the relationships were positive and significant. The study results infer the factors contributing to green real estate purchase intention, including altruistic value, egoistic value, social consumption motivation, and pro-environmental self-identity, with pro-environmental self-identity mediating the relationship. This study emphasizes the relevance of consumer values in real estate purchasing decisions, urging developers and marketers to prioritize ethical ideas, sustainable practices, and building a feeling of belonging and social connectedness. Offering eco-friendly amenities and green construction methods might attract clients, but creating a secure area for social interaction is critical. To the best of the authors’ knowledge, this research is the first to explore the role of egoistic and altruistic values on purchase intention, mainly in the housing and real estate sector, with the target consumers being young consumers in Canada. Full article

Understanding the social drivers of pro-environmental behavior in urban forests and green spaces is critical for addressing sustainability challenges. Subjective norms serve as a key pathway through which social expectations influence individuals’ behavioral intentions. Despite mixed findings in the literature regarding the impact of subjective norms on individuals’ intentions, there is a research gap about the determinants of this construct. This study was conducted to explore how social expectations shape perceived subjective norms among visitors of urban forests. A theoretical model was developed with subjective norms at its center, incorporating their predictors including social identity, media influence, interpersonal influence, and institutional trust, personal norms as a mediator, and behavioral intention as the outcome variable. Using structural equation modeling, data was collected and analyzed from a sample of visitors of urban forests in Tehran, Iran. The results revealed that subjective norms play a central mediating role in linking external social factors to behavioral intention. Social identity emerged as the strongest predictor of subjective norms, followed by media and interpersonal influence, while institutional trust had no significant effect. Subjective norms significantly influenced both personal norms and intentions, and personal norms also directly predicted intention. The model explained 50.9% of the variance in subjective norms and 39.0% in behavioral intention, highlighting its relatively high explanatory power. These findings underscore the importance of social context and internalized norms in shaping sustainable behavior. Policy and managerial implications suggest that strategies should prioritize community-based identity reinforcement, media engagement, and peer influence over top-down institutional messaging. This study contributes to environmental psychology and the behavior change literature by offering an integrated, empirically validated model. It also provides practical guidance for designing interventions that target both social and moral dimensions of environmental action. Full article

Ozone (O₃) occurs in nature as a chemical compound made of three oxygen atoms. It is an unstable, highly oxidative gas that rapidly decomposes into oxygen. The therapeutic use of O₃ dates back to the beginning of the 20th century and is currently based on the application of low doses, inducing a moderate oxidative stress that stimulates the antioxidant cellular defenses without causing cell damage. Low O₃ doses also induce anti-inflammatory and regenerative effects, and their anticancer potential is under investigation. In addition, the oxidative properties of O₃ make it an excellent antibacterial, antimycotic, and antiviral agent. Thanks to these properties, O₃ is currently widely used in several medical fields. However, its chemical instability represents an application limit, and ozonated oil is the only stabilized form of medical O₃. In recent years, novel O₃ formulations have been proposed for their sustained and more efficient administration, based on nanotechnology. This review offers an overview of the nanocarriers designed for the delivery of medical O₃, and of their therapeutic applications. The reviewed articles demonstrate that research is active and productive, though it is a rather new entry in the nanotechnological field. Liposomes, nanobubbles, nanoconstructed hydrogels, polymeric nanoparticles, and niosomes were designed to deliver O₃ and have been proven to exert antiseptic, anticancer, and pro-regenerative effects when administered in vitro and in vivo. Improving the therapeutic administration of O₃ through nanocarriers is a just-started challenge, and multiple prospects may be foreseen. Full article

Background and aim: Advanced Therapy Medicinal Products (ATMPs) are innovative drugs based on genes, tissues, or cells that target rare and severe diseases. ATMPs have shown promising clinical outcomes but are associated with high costs, raising questions about cost-effectiveness. Hence, this systematic review aims to analyze the cost-effectiveness and cost-utility profiles of the European Medicines Agency-authorized ATMPs for treating rare diseases. Methods: A systematic review was conducted following PRISMA guidelines. Studies were identified by searching PubMed, Embase, Web of Science, and ProQuest scientific databases. Economic evaluations reporting incremental cost-effectiveness/utility ratios (ICERs/ICURs) for ATMPs were included. Costs were standardized to 2023 Euros, and a cost-effectiveness plane was constructed to evaluate the results against willingness-to-pay (WTP) thresholds of EUR 50,000, EUR 100,000, and EUR 150,000 per QALY, as part of a sensitivity analysis. Results: A total of 61 studies met the inclusion criteria. ATMPs for rare blood diseases, such as tisagenlecleucel and axicabtagene ciloleucel, were found to be cost-effective in a majority of studies, with incremental QALYs ranging from 1.5 to 10 per patient over lifetime horizon. Tisagenlecleucel demonstrated a positive cost-effectiveness profile in the treatment of acute lymphoblastic leukemia (58%), while axicabtagene ciloleucel showed a positive profile in the treatment of diffuse large B-cell lymphoma (85%). Onasemnogene abeparvovec for spinal muscular atrophy (SMA) showed uncertain cost-effectiveness results, and voretigene neparvovec for retinal diseases was not cost-effective in 40% of studies, with incremental QALYs around 1.3 and high costs exceeding the WTP threshold set. Conclusions: ATMPs in treating rare diseases show promising economic potential, but cost-effectiveness varies across indications. Policymakers must balance innovation with system sustainability, using refined models and the long-term impact on patient outcomes. Full article

Sprouted grains are gaining attention as a natural and sustainable source of bioactive compounds with potential benefits in managing insulin resistance (IR), a hallmark of obesity-related metabolic disorders. This review aims to synthesize current findings on the biochemical changes induced during grain germination and their relevance to metabolic health. We examined recent in vitro, animal, and human studies focusing on how germination enhances the nutritional and functional properties of grains, particularly through the synthesis of compounds such as γ-aminobutyric acid, polyphenols, flavonoids, and antioxidants, while reducing anti-nutritional factors. These bioactive compounds have been shown to modulate metabolic and inflammatory pathways by inhibiting carbohydrate-digesting enzymes, suppressing pro-inflammatory cytokines, improving redox balance, and influencing gut microbiota composition. Collectively, these effects contribute to improved insulin sensitivity and glycemic control. The findings suggest that sprouted grains serve not only as functional food ingredients but also as accessible dietary tools for preventing or alleviating IR. Their role in delivering multiple bioactive molecules through a simple, environmentally friendly process highlights their promise in developing future nutrition-based strategies for metabolic disease prevention. Full article

In an ever-evolving digital environment, organizations must adopt advanced technologies for real-time big data processing to maintain their competitiveness and growth. However, selecting appropriate technologies is a challenge, particularly for small and medium-sized enterprises (SMEs). This study develops a literature review to analyze the methodologies used in the selection of technologies, with a special focus on those associated with the Industry 4.0. Knowledge Development Process-Constructivist (ProKnow-C) method, which was used to build a bibliographic portfolio, examining approximately 3400 articles published between 2005 and 2024, from which 80 were selected for a detailed analysis. The main methodological contributions come from research articles, the ScienceDirect database, the Expert Systems with Applications Journal, studies conducted in Turkey, and publications from the year 2023. The results highlight the predominant use of multi-criteria techniques, emphasizing hybrid approaches that combine various decision-making methodologies. In particular, the analytic hierarchy process (AHP) and TOPSIS methods were employed in 51.25% of the analyzed cases, either individually or in combination. It is concluded that technology selection should be based on flexible and adaptive approaches tailored to the organizational context, aligning long-term strategic objectives to ensure business sustainability and success. Full article

Identifying predictors of pro-environmental behaviors (PEBs) can not only figure out who concerns about the environment most but also inform possible pathways that advance or inhabit such prosocial actions. Most past studies and theories focus on factors that reside within personal characteristics or sociopsychological mechanisms rather than taking a holistic view that integrates these two elements into a framework. This study investigates how socioeconomic status (SES) correlates with PEBs, integrating both structural and psychological mechanisms. Drawing on the Stimulus–Organism–Response (SOR) theoretical framework, this paper examines the paradox whereby individuals with higher SES exhibit more frequent environmental actions yet demonstrate lower willingness to pay (WTP)—a form of economic sacrifice. Using nationally representative data from the 2021 Chinese General Social Survey (CGSS), our structural equation modeling reveals that adulthood SES positively correlates with environmental values and behaviors but negatively correlates with WTP. This challenges the traditional linear assumption that greater willingness necessarily leads to greater action. Additionally, while childhood SES predicts adult SES, it shows no direct effect on environmental engagement. These findings highlight multidimensional pathways by which SES shape environmental actions, necessitating differentiated policy approaches to build a sustainable world. Full article

Objectives: To investigate the efficacy and underlying mechanisms of IBCar’s biological activity in breast cancer models, both in cell culture and in mice, and to compare its effects on cancer versus normal cells. Methods: The cytotoxicity of IBCar was evaluated using the MTS assay to assess metabolic activity and the clonogenic assay to determine reproductive integrity. The impact of IBCar on microtubule integrity, mitochondrial function, and multiple signaling pathways was analyzed using Western blotting, microarray analysis, and live cell imaging. The therapeutic effectiveness of orally administered IBCar was assessed in a transgenic mouse model of Luminal B breast cancer and in mice implanted with subcutaneous triple-negative breast cancer xenografts. Results: IBCar demonstrated potent cytotoxicity across a diverse panel of breast cancer cell lines, including those with mutant or wild-type TP53, and cell lines with short and long doubling times. Comparative analysis revealed distinct responses between normal and cancer cells, including differences in IBCar’s effects on the mitochondrial membrane potential, endoplasmic reticulum stress and activation of cell death pathways. In breast cancer cells, IBCar was cytotoxic at nanomolar concentrations, caused irreversible microtubule depolymerization leading to sustained mitochondrial dysfunction, endoplasmic reticulum stress, and induced apoptosis. In normal cells, protective mechanisms included reversible microtubule depolymerization and activation of pro-survival signaling via the caspase-8 and riptosome pathways. The therapeutic potential of IBCar was confirmed in mouse models of Luminal B and triple negative BC, where it exhibited strong antitumor activity without detectable toxicity. Conclusions: These findings collectively support IBCar as a promising, effective, and safe therapeutic candidate for breast cancer treatment. Full article

Background: This study explores the potential of outdoor physical activity (OPA) to support physical, mental, and social health, while contributing to the One Health strategy. Methods: Based on Eurobarometer 97.3 data, 570 physically active individuals were compared by activity setting using descriptive statistics, chi-square tests with odds ratios, and the Mann–Whitney U test. Results: The analysis reveals that OPA is often driven by personal beliefs and a strong connection to nature, yet participants may overlook their environmental and social impact. Conclusions: The findings underscore the need for intersectoral cooperation and civic education to realise OPA’s role in promoting health, inclusion, and sustainability. Full article

The growing disconnection between humans and nature—particularly in urban environments—has been associated with declining well-being and lower engagement in pro-environmental behavior. Although the Connectedness with Nature Scale (CNS) has been widely used internationally to measure this relationship, there is a lack of evidence on its validity and reliability in Latin American contexts, especially in urban and rural settings. This study aims to address this gap by examining the psychometric properties of the CNS in a sample of 956 Colombian participants. Using exploratory and confirmatory factor analyses, we tested two versions of the scale (14-item and 12-item models), both showing good fit and high internal consistency (α > 0.90). Convergent validity was confirmed through strong correlations with the Environmental Identity and Pro-environmental Behavior Scales. These findings support the CNS as a valid and reliable tool to assess the human–nature connection in Colombia and highlight its potential for informing urban sustainability initiatives, environmental education, and public policy in diverse sociocultural contexts. Full article

Platelets have long been known to be critically involved in hemostasis and thrombosis. However, platelets are also recognized as metabolically active cells that require well-regulated mitochondrial function to support their multiple functions in hemostasis, thrombosis, and inflammation. Mitochondrial activity has also recently been shown to play a crucial role in determining platelet activation, survival, and pro-inflammatory potential. A key nexus in these processes is the mitochondrial permeability transition pore (mPTP), a high-conductance channel in the inner mitochondrial membrane. Sustained mPTP opening triggers mitochondrial depolarization, the cessation of ATP synthesis, osmotic swelling, and, finally, platelet dysfunction or clearance. However, its transient opening might play physiological signaling roles. This review summarizes the current understanding of the molecular components and regulatory factors governing the platelet mPTP, explores its physiological and pathological relevance, and evaluates its potential as a therapeutic target in cardiovascular disease, inflammation, cancer, and potentially neurodegenerative diseases. We also highlight the ongoing challenges and crucial future directions in deciphering the complexities of platelet mitochondrial dynamics and mPTP functions. Full article