Search Results (31,732)

Macrophage-mediated inflammation is known to be involved in the epithelial–mesenchymal transition (EMT) of various types of cancer. This makes macrophage-derived inflammatory factors prime targets for the development of new treatments. This study uncovers the therapeutic potential and action mechanism of DAB-2-28, a small-molecule derived from para-aminobenzoic acid, in the treatment of breast cancer. The luminal MCF-7 and the triple-negative MDA-MB-231 cancer cell lines used in this study represent, respectively, breast cancers in which the differentiation states are related to the epithelial phenotype of the mammary gland and breast cancers expressing a highly aggressive mesenchymal phenotype. In MCF-7 cells, soluble factors from macrophage-conditioned media (CM-MØ) induce a characteristic morphology of mesenchymal cells with an upregulated expression of Snail1, a mesenchymal marker, as opposed to a decrease in the expression of E-cadherin, an epithelial marker. DAB-2-28 does not affect the differential expression of Snail1 and E-cadherin in response to CM-MØ, but negatively impacts other hallmarks of EMT by decreasing invasion and migration capacities, in addition to MMP9 expression and gelatinase activity, in both MCF-7 and MDA-MB-231 cells. Moreover, DAB-2-28 inhibits the phosphorylation of key pro-EMT transcriptional factors, such as NFκB, STAT3, SMAD2, CREB, and/or AKT proteins, in breast cancer cells exposed to different EMT inducers. Overall, our study provides evidence suggesting that inhibition of EMT initiation or maintenance is a key mechanism by which DAB-2-28 can exert anti-tumoral effects in breast cancer cells. Full article

Social anxiety is a prevalent mental health concern among college students, often intensified by academic and interpersonal pressures on campus. This study investigated the relationship between physical activity, loneliness, and social anxiety among college students, aiming to examine the mediating role of loneliness in the process of physical activity affecting social anxiety, as well as the moderating role of gender in this mediating effect. A cross-sectional research design was adopted, and data on physical activity levels, loneliness, and social anxiety were collected through questionnaires completed by 638 students at a university in China. This study conducted a single-factor Harman test, descriptive statistical analysis, reliability analysis, correlation analysis, and independent-samples t-tests, and it modeled the moderated mediation effect. The results showed that physical activity was significantly and negatively correlated with both loneliness and social anxiety. Loneliness played a mediating role in the influence of physical activity on social anxiety, and this mediating effect was moderated by gender, being more pronounced in the female group. This study concluded that physical activity can help alleviate social anxiety, but the mechanism involving the reduction of loneliness is more apparent in women, indicating the need to consider gender differences when developing interventions, as there may be other, more significant reasons for men. Full article

Improving construction site safety remains a critical challenge in Saudi Arabia’s rapidly growing construction sector, where high accident rates and diverse labor forces demand evidence-based managerial interventions. This study investigated the influence of Managers’ Safety Perceptions and Practices (MSP) on Workers’ Safety Behaviors (WSB) in the Saudi construction industry, emphasizing the mediating roles of Workers’ Safety Awareness (WSA), Safety Competency (WSC), and Safety Actions (SA). The conceptual framework integrates these three mediators to explain how managerial attitudes and practices translate into frontline safety outcomes. A quantitative, cross-sectional design was adopted using a structured questionnaire distributed among construction workers, supervisors, and project managers. A total of 352 from 384 valid responses were collected, and the data were analyzed using Partial Least Squares Structural Equation Modeling (PLS-SEM) via SmartPLS 4. The findings revealed that MSP does not directly influence WSB but has significant indirect effects through WSA, WSC, and SA. Among these, WSC emerged as the most powerful mediator, followed by WSA and SA, indicating that competency is the most critical driver of safe worker behavior. These results provide robust empirical support for a multidimensional mediation model, highlighting the need for managers to enhance safety behaviors not merely through supervision but through fostering awareness and competency, providing technical training, and implementing proactive safety measures. Theoretically, this study contributes a novel and integrative framework to the occupational safety literature, particularly within underexplored Middle Eastern construction contexts. Practically, it offers actionable insights for safety managers, industry practitioners, and policymakers seeking to improve construction safety performance in alignment with Saudi Vision 2030. Full article

Bone integrity is maintained through continuous remodeling, orchestrated by the coordinated actions of osteocytes, osteoblasts, and osteoclasts. Once considered passive bystanders, osteocytes are now recognized as central regulators of this process, mediating biochemical signaling and mechanotransduction. Malfunctioning osteocytes contribute to serious skeletal disorders such as osteoporosis. Mesenchymal stromal cells (MSCs), multipotent stem cells capable of differentiating into osteoblasts, have emerged as promising agents for bone regeneration, primarily through the paracrine effects of their secreted exosomes. MSC-derived exosomes are nanoscale vesicles enriched with proteins, lipids, and nucleic acids that promote intercellular communication, osteoblast proliferation and differentiation, and angiogenesis. Notably, they deliver osteoinductive microRNAs (miRNAs) that influence osteogenic markers and support bone tissue repair. In vivo investigations validate their capacity to enhance bone regeneration, increase bone volume, and improve biomechanical strength. Additionally, MSC-derived exosomes regulate the immune response, creating pro-osteogenic and pro-angiogenic factors, boosting their therapeutic efficacy. Due to their cell-free characteristics, MSC-derived exosomes offer benefits such as diminished immunogenicity and minimal risk of off-target effects. These properties position them as promising and innovative approaches for bone regeneration, integrating immunomodulatory effects with tissue-specific regenerative capabilities. Full article

Background: Workplace mobbing is a widespread phenomenon with serious psychological and emotional consequences on employees’ emotional well-being. Psychological resilience has been identified as a potential protective factor against such adverse outcomes. Aim: This study investigates the relationship between workplace mobbing and emotional well-being, as expressed through positive and negative affect, and examines the mediating role of psychological resilience in this association. Methods: Ninety nurses participated in this cross-sectional study. Data were collected using the Connor–Davidson Resilience Scale (CD-RISC), the Workplace Psychologically Violent Behaviors (WPVB) scale, and the Positive and Negative Affect Schedule (PANAS). Statistical analyses included correlation, multiple regression, and mediation using bootstrapped confidence intervals. Results: Resilience was strongly associated with positive affect (r = 0.74, p < 0.001) and inversely with negative affect (r = −0.46, p < 0.001). Mobbing was significantly related to increased negative affect (β = 0.12, p < 0.001) but not to positive affect. Resilience emerged as the strongest predictor of emotional outcomes and partially mediated the relationship between “Attack on professional role” and negative affect. Conclusions: Psychological resilience plays a key protective role in moderating the emotional impact of workplace mobbing. Enhancing resilience in healthcare professionals may mitigate the negative emotional effects of mobbing, although it does not fully buffer against all its consequences. Full article

This review explores the biofilm architecture and drug resistance of Enterococcus faecalis in clinical and environmental settings. The biofilm in E. faecalis is a heterogeneous, three-dimensional, mushroom-like or multilayered structure, characteristically forming diplococci or short chains interspersed with water channels for nutrient exchange and waste removal. Exopolysaccharides, proteins, lipids, and extracellular DNA create a protective matrix. Persister cells within the biofilm contribute to antibiotic resistance and survival. The heterogeneous architecture of the E. faecalis biofilm contains both dense clusters and loosely packed regions that vary in thickness, ranging from 10 to 100 µm, depending on the environmental conditions. The pathogenicity of the E. faecalis biofilm is mediated through complex interactions between genes and virulence factors such as DNA release, cytolysin, pili, secreted antigen A, and microbial surface components that recognize adhesive matrix molecules, often involving a key protein called enterococcal surface protein (Esp). Clinically, it is implicated in a range of nosocomial infections, including urinary tract infections, endocarditis, and surgical wound infections. The biofilm serves as a nidus for bacterial dissemination and as a reservoir for antimicrobial resistance. The effectiveness of first-line antibiotics (ampicillin, vancomycin, and aminoglycosides) is diminished due to reduced penetration, altered metabolism, increased tolerance, and intrinsic and acquired resistance. Alternative strategies for biofilm disruption, such as combination therapy (ampicillin with aminoglycosides), as well as newer approaches, including antimicrobial peptides, quorum-sensing inhibitors, and biofilm-disrupting agents (DNase or dispersin B), are also being explored to improve treatment outcomes. Environmentally, E. faecalis biofilms contribute to contamination in water systems, food production facilities, and healthcare environments. They persist in harsh conditions, facilitating the spread of multidrug-resistant strains and increasing the risk of transmission to humans and animals. Therefore, understanding the biofilm architecture and drug resistance is essential for developing effective strategies to mitigate their clinical and environmental impact. Full article

Background: Moral harassment (mobbing) in healthcare, particularly among nurses, remains a persistent issue with detrimental effects on mental health, resilience, and quality of life. Aim: We examine the relationship between the resilience of nurses working in Emergency Departments (EDs) and how these factors influence experiences of workplace mobbing. Methods: This cross-sectional study included 90 nurses from four public hospitals in Greece’s 5th Health District. Data were collected between October 2023 and March 2024 using the WHOQOL-BREF, Workplace Psychologically Violent Behaviors (WPVB) scale and the Connor–Davidson Resilience Scale (CD-RISC). The sample consisted primarily of full-time nurses (84.3% female; mean age = 43.1 years), with 21.1% reporting chronic conditions. Most participants were married (80.0%) and had children (74.4%), typically two (56.1%). Statistical analyses—conducted using SPSS version 27.0—included descriptive statistics, Pearson and Spearman correlations, multiple linear regression, and mediation analysis, with significance set at p < 0.05. Results: Resilience was moderate (mean = 66.38%; Cronbach’s α = 0.93) and positively correlated with all WHOQOL-BREF domains—physical, psychological, social, and environmental (r = 0.30–0.40)—but not with the overall WHOQOL-BREF. The mean overall WHOQOL-BREF score was 68.4%, with the lowest scores observed in the environmental domain (mean = 53.76%). Workplace mobbing levels were low to moderate (mean WPVB score = 17.87), with subscale reliabilities ranging from α = 0.78 to 0.95. Mobbing was negatively associated with social relationships and the environmental WHOQOL-BREF (ρ = –0.23 to –0.33). Regression analysis showed that cohabitation and higher resilience significantly predicted better WHOQOL-BREF outcomes, whereas mobbing was not a significant predictor. Mediation analysis (bootstrap N = 5000) indicated no significant indirect effect of resilience in the relationship between mobbing and WHOQOL-BREF. Conclusions: Resilience was identified as a key protective factor for nurses’ quality of life in emergency care settings. Although workplace mobbing was present at low-to-moderate levels, it was negatively associated with specific WHOQOL-BREF domains. Enhancing mental resilience among nurses may serve as a valuable strategy to mitigate the psychological effects of moral harassment in healthcare environments. Full article

Virtual influencers (VIs) on e-commerce platforms are becoming increasingly popular, enhancing the consumer experience. This study examines the consumer–brand relationship (CBR) with VIs through the perspective of social presence. Data from 1041 e-commerce platform users (e.g., Douyin, RED, Weibo) were collected and analyzed using Structural Equation Modeling (SEM). The findings reveal that both the visual and mental human-likeness of VIs significantly strengthen CBR, with social presence acting as a mediator. Additionally, the interaction between visual and mental human-likeness positively impacts social presence, which in turn enhances CBR. Moreover, consumers’ need for uniqueness moderates the relationship between social presence and CBR, providing valuable insights for virtual influencer strategies in e-commerce. This research suggests the feasibility of leveraging VI design both visually and mentally to capture new trends in developing effective virtual campaigns with digitization and metaverse technologies. This study extends the stream of research VIs use for interactive marketing, highlighting the role of parasocial relationships in interactive marketing. These findings can provide managers with a better understanding of VI design from both visual and mental aspects. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article

Neuroinflammation is the major contributor to the pathology of neonatal hypoxic–ischemic (HI) brain injury. Our previous studies have demonstrated that microRNA210 (miR210) inhibition with antisense locked nucleic acid (LNA) inhibitor mitigates neuroinflammation and provides neuroprotection after neonatal HI insult. However, the underlying mechanisms remain elusive. In the present study, using miR210 knockout (KO) mice and microglial cultures, we tested the hypothesis that miR210 promotes microglial activation and neuroinflammation through suppressing mitochondrial function in microglia after HI. Neonatal HI brain injury was conducted on postnatal day 9 (P9) wild-type (WT) and miR210 knockout (KO) mouse pups. We found that miR210 KO significantly reduced brain infarct size at 48 h and improved long-term locomotor functions assessed by an open field test three weeks after HI. Moreover, miR210 KO mice exhibited reduced IL1β levels, microglia activation and immune cell infiltration after HI. In addition, in vitro studies of microglia exposed to oxygen–glucose deprivation (OGD) revealed that miR210 inhibition with LNA reduced OGD-induced expression of Il1β and rescued OGD-mediated downregulation of mitochondrial iron–sulfur cluster assembly enzyme (ISCU) and mitochondrial oxidative phosphorylation activity. To validate the link between miR210 and microglia activation, isolated primary murine microglia were transfected with miR210 mimic or negative control. The results showed that miR210 mimic downregulated the expression of mitochondrial ISCU protein abundance and induced the expression of proinflammatory cytokines similar to the effect observed with ISCU silencing RNA. In summary, our results suggest that miR210 is a key regulator of microglial proinflammatory activation through reprogramming mitochondrial function in neonatal HI brain injury. Full article

Background/Objectives: Extracellular vesicles (EVs) are involved in cell-to-cell communication and delivery of signaling molecules and represent an interesting approach in targeted therapy. This project focused on EV-mediated facilitation and cell-specific delivery of effector antimiR molecules carried by biologically produced gold nanoparticles (AuNPs). Methods: First, we loaded EVs derived from cancer cells 4T1 with AuNPs-antimiR. The AuNPs were also decorated with or without transferrin (Tf) molecules. We examined parental cell-specific delivery of the AuNPs-Tf-antimiR within monocultures as well as co-cultures in vitro. Subsequently, we used autologous EVs containing AuNPs-Tf-antimiR to target tumor cells in a xenograft tumor model in vivo. Efficacy of the antimir transfer was assessed by qPCR and apoptosis assessment. Results: In vitro, EVs loaded with AuNPs-antimiR were internalized only by the parental cells and the AuNPs-antimiR transfer was successful and effective only in EVs that were decorated with Tf. We achieved effective delivery of the antimiR molecule into cancer cells in vivo, which was proved by specific silencing of the target oncogenic miRNA as well as induction of cancer cells apoptosis. Conclusions: EVs represent an interesting and potent way for targeted cargo delivery and personalized medicine. On the other hand, there are various safety and efficacy challenges that remain to be addressed. Full article

Multiple sclerosis (MS) and allergic diseases, traditionally considered immunologically opposing entities, may share pathogenic mechanisms rooted in immune dysregulation. While MS is predominantly mediated by Th1 and Th17 responses and allergies by Th2 responses, emerging evidence suggests overlapping immunological pathways, including the involvement of histamine, regulatory T cells, and innate lymphoid cells. This review synthesizes current knowledge on the epidemiological and immunopathological associations between MS and allergies. Epidemiological studies have yielded inconsistent results, with some suggesting a protective role for respiratory and food allergies against MS onset, while others find no significant correlation. Clinical studies indicate that food allergies in adults may be associated with increased MS inflammatory activity, whereas childhood atopy might exert a protective effect. In addition, we review hypersensitivity reactions to disease-modifying treatments for MS, detailing their immunological mechanisms, clinical presentation, and management, including desensitization protocols where applicable. Finally, we explore how treatments for allergic diseases—such as clemastine, allergen immunotherapy, montelukast, and omalizumab—may modulate MS pathophysiology, offering potential therapeutic synergies. Understanding the interplay between allergic and autoimmune processes is critical for optimizing care and developing innovative treatment approaches in MS. Full article

Chemotherapy remains a cornerstone in the treatment of esophageal cancer (EC), yet chemoresistance remains a critical challenge, leading to poor outcomes and limited therapeutic success. Mitochondrial DNA (mtDNA) has emerged as a pivotal player in mediating these responses, influencing cellular metabolism, oxidative stress regulation, and apoptotic pathways. This review provides a comprehensive overview of the mechanisms by which mtDNA alterations, including mutations and copy number variations, drive chemoresistance in EC. Specific focus is given to the role of mtDNA in metabolic reprogramming, including its contribution to the Warburg effect and lipid metabolism, as well as its impact on epithelial–mesenchymal transition (EMT) and mitochondrial bioenergetics. Recent advances in targeting mitochondrial pathways through novel therapeutic agents, such as metformin and mitoquinone, and innovative approaches like CRISPR/Cas9 gene editing, are also discussed. These interventions highlight the potential for overcoming chemoresistance and improving patient outcomes. By integrating mitochondrial diagnostics with personalized treatment strategies, we propose a roadmap for future research that bridges basic mitochondrial biology with translational applications in oncology. The insights offered in this review emphasize the critical need for continued exploration of mtDNA-targeted therapies to address the unmet needs in EC management and other diseases associated with mitochondria. Full article

Loneliness is a significant challenge for millions worldwide, with chronic loneliness having harmful effects on physical health, mental well-being, and relationships. Cognitive distortions play an important role in perpetuating loneliness. Psychological interventions targeting such distortions have been effective at alleviating feelings of loneliness. However, less is known about which cognitive distortions are most prevalent among lonely individuals and how these distortions relate to loneliness and mental well-being. This exploratory study prescreened a Census-matched sample of 1000 U.S. adults for loneliness, then asked those in the top quartile (N = 237) to rate multiple patterns of cognitive distortion related to loneliness. Factor analyses identified six common and influential patterns of cognitive distortion (mindreading, future reward, catastrophizing, essentializing, deservedness, and externalizing). Essentializing was the most strongly endorsed factor, followed by mindreading and catastrophizing. Essentializing also evidenced the strongest correlation with loneliness. Additionally, the relationship between loneliness and participants’ stress was completely mediated by mindreading, catastrophizing, and essentializing. These findings highlight the importance of targeting specific cognitive distortions in loneliness interventions to effectively improve the mental well-being of lonely individuals. Full article

This study aims to clarify how different types of motivation influence employee retention by identifying the distinct roles of intrinsic and extrinsic factors in shaping job satisfaction, particularly under varying levels of urban stress and generational identity. Drawing on Herzberg’s Two-Factor Theory and Self-Determination Theory, we distinguish between intrinsic drivers (e.g., autonomy, achievement) and extrinsic hygiene factors (e.g., pay, stability). Using survey data from 356 Chinese employees and applying PLS-SEM with a moderated mediation design, we investigate how urbanization and Generation Z moderate these relationships. Results show that intrinsic motivation enhances satisfaction, especially in urban settings, while extrinsic factors negatively affect satisfaction when perceived as insufficient or unfair. Job satisfaction mediates the relationship between motivation and retention, although this effect is weaker among Generation Z employees. These findings refine motivational theories by demonstrating how environmental pressure and generational values jointly shape employee attitudes. The study contributes a context-sensitive framework for understanding retention by integrating individual motivation with macro-level moderators, offering practical implications for managing diverse and urbanizing labor markets. Full article