Search Results (394)

Background: Triple-negative breast cancer (TNBC) is more likely to metastasise to the lungs than other breast cancer (BrCa) types, yet the molecular interactions within the tumour microenvironment (TME) at secondary sites remain poorly understood. Methods: This pilot study aimed to explore the metabolic crosstalk between MDA-MB-231 TNBC cells and MRC-5 lung fibroblasts within a co-culture system to replicate the lung metastatic TME. Co-cultures were also treated with Vitamin D or Vitamin E to evaluate the effects of these nutraceuticals on the metabolic crosstalk between TNBC cells and fibroblasts. Results: Our findings demonstrate that co-culture induced the activation of fibroblasts into cancer-associated fibroblasts (CAFs), evidenced by increased α-SMA and FAP expression. Metabolic profiling revealed that TNBC cells in co-culture displayed increased expression of enzymes associated with oxidative phosphorylation (OXPHOS) and glutamine metabolism, while fibroblasts exhibited a metabolic profile consistent with glycolysis and lactate metabolism. Vitamin D inhibited lactate metabolism and HIF-1α expression in fibroblasts while suppressing TCA cycle activity in cancer cells, suggesting a potential role in disrupting oncogenic metabolic crosstalk. Conversely, Vitamin E treatment was associated with increased expression of TCA cycle and oxidative metabolism-related markers in BrCa cells without significantly affecting fibroblast glycolysis. Such differential metabolic responses may contribute to metabolic heterogeneity within the tumour microenvironment. Conclusions: These results provide valuable insights into the metabolic dynamics of TNBC metastases in the lung TME and demonstrate that Vitamins D and E exert distinct effects on metabolic crosstalk between cancer cells and fibroblasts. These findings may have significant implications for the potential supplementation of Vitamins D and E in patients with metastatic TNBC and justify further in-depth analysis. Full article

This study examines how Green Human Resource Management (GHRM) is linked to sustainable organizational performance, encompassing environmental, economic, and social outcomes through the capability-building mechanisms of green innovation (GI) and green organizational culture (GOCL) in emerging manufacturing systems. Drawing on the Resource-Based View and capability-based sustainability perspectives, GHRM is conceptualized as a strategic organizational capability that enables firms in developing economies to beyond short-term regulatory compliance toward measurable and integrated sustainability performance outcomes. Survey data were collected from 446 managerial and technical respondents in Ethiopia’s garment and textile industrial parks, one of Africa’s fastest-growing industrial sectors facing significant sustainability challenges. Using Partial Least Squares Structural Equation Modeling (PLS-SEM) with bootstrapping-based mediation analysis, the results show that GHRM is positively associated with sustainable organizational performance, with GI and GOCL operating as key mediating mechanisms that translate HR-related practices into measurable sustainability outcomes. The findings highlight the role of GHRM in strengthening firms’ adaptive and developmental sustainability capabilities by fostering pro-sustainability mindsets and innovation-oriented behaviors, which are particularly critical in resource-constrained and weak-institutional contexts. The study contributes to sustainability and management literature by explicitly linking Green HRM to triple-bottom-line performance through a capability-building framework and by providing rare firm-level empirical evidence from a low-income emerging economy. Practically, the results provide guidance for managers and policy makers to design, monitor, and evaluate HRM systems that intentionally cultivate human, cultural, and innovative capabilities to support long-term organizational sustainability transitions. Full article

Background/Objectives: Tumor-induced immune reprogramming is increasingly recognized as a key mechanism by which cancers evade surveillance and promote disease progression. The interaction between cancer and immune cells within the tumor microenvironment (TME) can drive phenotypic and functional changes in immune populations, facilitating metastasis and immune evasion. Methods: In this study, we used co-culture models to expose THP1 monocytes to triple-negative breast cancer (TNBC) cells, MDA-MB-231 and BT-549, either directly or indirectly via tumor-conditioned media, to mimic tumor–immune cell communication. Transcriptomic and pathway analyses revealed that cancer-exposed monocytes adopt a reprogrammed phenotype marked by activation of pro-tumorigenic signaling pathways, enhanced proliferative capacity, and elevated expression of pro-inflammatory cytokines such as IL6. Results: Functional assays confirmed a significant increase in monocyte proliferation under both direct and indirect tumor exposure. Importantly, we demonstrated that this tumor-driven proliferation of THP1 cells could be suppressed by the STAT3 inhibitor STAT3-IN-12. This highlights the critical role of STAT3 signaling in mediating immune cell transformation and supporting a novel immunomodulatory approach for therapeutic intervention. Conclusions: These findings support the potential for targeting tumor-educated transcriptional programs as a novel immunomodulatory strategy in cancer treatment. Restoring immune cell homeostasis and suppressing pro-tumor phenotypes through pharmacological inhibition of the key signaling nodes such as STAT3 may complement existing cancer therapies. This study provides new insights into immune cell plasticity in cancer and identifies actionable strategies to counteract tumor-driven immune dysregulation. Full article

The genus Streptomyces is the largest group within the phylum Actinobacteria, recognized for producing antibiotics and enzymes, with wide applications in medicine and biological control for crop protection against phytopathogens. In this study, the Streptomyces sp. Caat 5-35 strain, isolated from soil of the Caatinga biome in Brazil, and identified by analysis of the 16S rRNA gene, demonstrated its antagonistic effect in vitro in dual cultures against Phytophthora palmivora, Colletotrichum acutatum, Fusarium oxysporum, Rhizoctonia solani, Sclerotinia sclerotiorum, and Fusarium graminearum. Caat 5-35 inhibited mycelial growth ranging from 19% to 73.3%. Compounds purified by prep-HPLC from extracts were identified by spectral data analysis using UHPLC-triple-TOF-MS/MS, or nuclear magnetic resonance (NMR). This work demonstrated for the first time the anti-oomycete activity of albofungin, its derivatives, and albonoursin against P. palmivora. Moreover, the growth inhibition of Colletotrichum gloeosporioides by albonoursin and the antibacterial effect of 2-chloroadenosine and 5′-O-sulfamoyl-2-chloroadenosine against Pectobacterium carotovorum were demonstrated as novel findings. Caat 5-35 exhibited the ability to solubilize phosphates and produce cellulases on CMC agar. The findings of this study, in combination with in vitro bioassays on cacao pods (Theobroma cacao L.) inoculated with the antagonist strain and P. palmivora APB-35, demonstrate that Streptomyces sp. Caat 5-35 is a source of natural products with applications in agriculture and could serve as an alternative for crop protection. Full article

The enormous applications of various nanoparticles (NPs) have raised the possibility that humans may be simultaneously exposed to mixtures of them in real life. Realistically, this situation may apply to plastic NPs, mainly derived from the breakdown of larger plastics, and to silver NPs, both of which are among the most frequently detected NPs in the envirnment due to their applications in healthcare, consumer products, and water purification. Although numerous studies have examined the toxicity of plastic and silver NPs individually, knowledge of their combined toxicity remains limited. Hence, the main objective of our study was to investigate the toxicity of high-density polyethene nanoparticles (HDPE NPs), thermally isolated from food-cooking bags, in combination with citrate-stabilised silver nanoparticles (AgNPcit) to Caco-2 and HT29MTX cells growing in 2D monoculture or in 3D triple-culture with Raji cells. Cellular uptake of NPs was quantified from the side-scatter (SSC) signal in flow cytometry; toxicity was evaluated by the neutral red assay; apoptosis was evaluated by the Annexin V method; and induction of oxidative stress was evaluated by a fluorescent method using DCFDA and DHR probes. Both cell lines took up both types of NPs; however, HT29MTX cells were more effective in the NPs’ uptake. Interestingly, HDPE NPs and AgNPcit mutually inhibited each other’s uptake, which suggests a similar mechanism of entry. Both types of NPs were toxic to both cell lines growing in monoculture; Caco-2 cells were more susceptible than HT29MTX. The toxicity was attributed to the induction of oxidative stress and associated apoptosis. In line with the mutual inhibition of the NPs’ uptake, the toxic effect of both NPs in the mixture was less than that expected as the sum of individual treatments. The toxic effects of both NPs or their mixture were less pronounced in the triple-culture Caco-2/HT29MTX/Raji, than in Caco-2 and HT29MTX growing in monoculture. Full article

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by a lack of targetable receptors, leading to limited treatment options and a critical need for novel therapeutic strategies. This study aimed to evaluate the potential of azelastine, a clinically approved H1-antihistamine, for drug repositioning against TNBC and to elucidate its underlying HRH1-independent mechanism of action. Cell viability assays (CCK-8) were performed on TNBC cell lines (MDA-MB-231 and BT-549) following treatment with azelastine and its major metabolite, desmethyl azelastine. After observing ambiguous clinical associations between HRH1 expression and patient prognosis, HRH1 dependency was assessed through histamine stimulation and HRH1 knockdown (siRNA). Subsequently, the role of ADP-ribosylation factor 1 (ARF1), found to be overexpressed in TNBC and linked to poor prognosis, was investigated using ARF1 knockdown (siRNA), co-treatment with the Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) inhibitor golgicide A (GCA), and co-treatment with the Drp1 inhibitor M-divi 1. Azelastine and desmethyl azelastine potently reduced MDA-MB-231 cell viability in a dose- and time-dependent manner, achieving cell survivals of 61.3 ± 6.1% (30 µM) and 34.9 ± 3.7% (50 µM) for azelastine, and 52.4 ± 12.5% (30 µM) for desmethyl azelastine, respectively, after 72 h, with an IC₅₀ of 35.93 µM determined for azelastine in MDA-MB-231 cells. Additionally, azelastine significantly reduced the viability of BT-549 cells. Bioinformatic analysis of clinical datasets revealed HRH1 downregulation in tumors and, functionally, neither histamine stimulation nor HRH1 knockdown mediated azelastine cytotoxicity in cell culture. Importantly, ARF1 expression was significantly upregulated in TNBC and associated with poor prognosis. Co-treatment with GCA, preventing ARF1 activation, restored viability to near-control levels, supporting dependence on the GBF1–ARF1 activation axis of azelastine, whereas the Dynamic-related protein 1 (Drp1) inhibitor M-divi 1 not only partially rescued CCK-8-based cell viability but also normalized azelastine-induced loss of MitoTracker™ Red CMXRos signal and partially preserved (4′,6-diamidino-2-phenylindole) DAPI-based cell density, indicating Drp1-dependent mitochondrial dysfunction. Furthermore, azelastine selectively reduced p-ERK phosphorylation in the cell signaling pathway. Azelastine exerts potent anticancer effects in TNBC cells via an HRH1-independent, ARF1-dependent mechanism that attenuates the Extracellular signal-regulated kinase (ERK)–Drp1 axis, and induces Drp1-dependent mitochondrial dysfunction, independent of its canonical HRH1 receptor function. This ARF1-dependent mechanism provides strong scientific rationale for the drug repositioning of azelastine as an effective therapeutic agent for ARF1-driven TNBC. Full article

In this study, we propose the Integrated Developmental Entrepreneurship Resiliency Framework (IDERF), a conceptual model positioning universities as orchestrators of stakeholder networks for entrepreneurial resilience and sustainability. Review and analysis of historical and contemporary research revealed gaps in existing approaches to sustainable entrepreneurship. Entrepreneurship education has evolved from isolated curricula to formal programs that incorporate experiential learning and multilateral institutional access, which appreciably enhance entrepreneurial resilience and venture longevity. The integration of resilience theory with entrepreneurship research has identified multi-level sustainment factors across the disciplines of psychology, organizational theory, and structural economic development. The IDERF addresses this limitation by adapting the triple helix model to a quadruple helix framework that encompasses academia, government, industry, and community stakeholders. Our proposed conceptual framework was developed through conceptual synthesis based on a structured literature review of 212 publications on university-led entrepreneurship programs and entrepreneur sustainability and resilience since 1940. Our findings revealed the need for more resiliency-focused entrepreneurship program designs, synthesis between resilience and sustainability education, analysis of educational program impacts on business development sustainability, and practical entrepreneur training in real-world economic contexts. The resulting IDERF encompasses five dimensions of adaptive entrepreneurial capacity, stakeholder governance, economic transformation, social–environmental integration, and institutional reform as novel components of entrepreneurial resilience and sustainability. We propose an integrated mixed-methods research agenda that includes proposed research questions to instigate the development of measurement frameworks and cross-cultural validation to empirically test the IDERF’s effectiveness in fostering entrepreneurial resilience across diverse contexts and economic regions. Full article

Background: In Saudi Arabia, rising multi-drug-resistant (MDR) fungal infections from broad-spectrum antifungal overuse highlight the urgent need for epidemiological and susceptibility research. Methods: This cross-sectional study analyzed fungal isolates from 55 patients with positive blood cultures in a Riyadh tertiary hospital, with identification and antifungal susceptibility tested via the VITEK-2 compact system. Results: Candida albicans and non-albicans Candida (NAC) were isolated from 11 and 38 patients, respectively. In the NAC group, C. glabrata and C. parapsilosis spp. were predominant. C. glabrata exhibited the highest resistance to antifungals. Increased rates of resistance were shown by fluconazole and itraconazole, whereas voriconazole was the most effective azole with the lowest resistance. No evidence of resistance was found against non-azole antifungals. A single case of triple resistance to ketoconazole, fluconazole, and itraconazole was observed in C. parapsilosis. A single isolate of C. albicans was resistant to all tested azoles. A rare instance of coinfection with C. glabrata and C. albicans was identified in a single male patient with a dual-resistance pattern against posaconazole and itraconazole. Conclusions: The high prevalence of NAC, including tolerant isolates of C. parapsilosis and C. glabrata, along with multi-azole-resistant C. albicans and unique coinfection scenarios, urgently requires robust antifungal resistance surveillance. Full article

The aim of this study is to investigate the A_2BAR-dependence of okhotoside A₁-1 cytotoxic and antiproliferative action on triple-negative MDA-MB-231 breast cancer cells using monolayer and 3D culture approaches. Earlier triterpene glycoside okhotoside A₁-1 (Okh) was isolated from the sea cucumbers Cucumaria djakonovi and C. conicospermium and its selective cytotoxicity against MDA-MB-231 vs. non-tumorigenic MCF-10A cells was reported. Now it has been found that the A_2B adenosine receptor (A_2BAR) is one of the molecular targets for Okh and its antiproliferative effect is A_2BAR-dependent. Molecular docking studies suggested a unique behavior for Okh demonstrating two highly probable binding modes with comparable affinity, when the aglycone is immersed in the binding pocket, or alternatively, the carbohydrate moiety occupies the site. The glycoside modulated cAMP and intracellular Ca²⁺ levels in an A_2BAR-dependent manner, which accompanied by the suppression of p38 MAPK and ERK1/2 phosphorylation, and blocked cell cycle progression. Okh induced mitochondrial dysfunction, characterized by increased ROS production and loss of the mitochondrial membrane potential (ΔΨm), which led to the upregulation of APAF-1 and cytochrome C, activation of caspases-9 and -3, and initiation of apoptosis. The antitumor potential of Okh was confirmed in a 3D culture of MDA-MB-231 cells and was more significant than those of another A_2BAR-targeted triterpene glycoside cucumarioside A₀-1 and cisplatin. Full article

Background/Objectives: Developing effective therapies for patients with triple-negative breast cancer (TNBC) remains an urgent clinical priority. Compared with other subtypes, the basal B type of TNBC exhibits a less differentiated and mesenchymal-like phenotype that models highly invasive and metastatic breast malignancies. To target metastatic TNBC, our current study sought to identify effective therapeutic drugs and the underlying mechanisms. Methods: A systematic screening of 140 FDA-approved drugs was conducted for repurposing using live-cell imaging-based wound-healing assays. Candidate efficacy was validated by in vitro transwell invasion assays, in vivo allograft/xenograft models, and ex vivo three-dimensional air–liquid interface (ALI) and patient-derived organoid (PDO) cultures. Results: Dasatinib emerged as a promising anti-cancer agent in aggressive TNBC, particularly in the basal B type, with high ETS proto-oncogene 1 (ETS1) expression. Mechanistically, dasatinib disrupts the actin cytoskeleton, impairing cell motility and migration while concurrently suppressing the expression of ETS1 and matrix metalloproteinase-3 (MMP3) to remodel the extracellular matrix (ECM) and inhibit invasion. Moreover, the combination of dasatinib with an anti-programmed cell death protein-1 (PD-1) antibody represents a potential therapeutic strategy. Conclusions: These findings highlight dasatinib as a potential therapeutic option for metastatic TNBC and suggest that selecting patients with high ETS1 expression may optimize treatment response. Full article

Conventional cancer treatments have limited efficacy for aggressive subtypes such as triple-negative breast cancer (TNBC), which points to the importance of new therapeutic strategies. Functionalized nanoparticles in conjunction with photodynamic therapy (PDT) represent a promising alternative. Additionally, 3D cell culture emerges as a more effective model, as it better replicates the structural and functional characteristics of the tumor microenvironment. In this study, 3D microtumors of TNBC were cultivated and treated with PDT using gold nanoparticles functionalized with Chlorin e6 (AuNPs@Ce6). Cell viability was assessed using the MTT colorimetric assay, combined with histological analysis using hematoxylin-eosin staining. The MTT assay and histological evaluation of the 3D spheroids demonstrated that PDT with AuNPs@Ce6 effectively reduced cell viability and induced necrotic morphological changes, while maintaining biocompatibility with the non-irradiated control group. These findings reinforce the potential of this approach for further investigation in TNBC models and underscore the value of 3D cultures as physiologically relevant and ethical alternatives to animal testing. Full article

The cultural heritage of the Liao dynasty in Chifeng encompasses significant historical and cultural information that requires systematic digital preservation and management. However, heterogeneous data sources across museums, archives, and research institutions lack semantic interoperability, creating barriers for cross-system integration and knowledge discovery. This study proposes a standardized knowledge graph construction method by integrating the CIDOC Conceptual Reference Model version 7.2 with large language models. A unified ontology framework enables semantic consistency across diverse heritage data, while Generative Pre-trained Transformer-based models automatically extract structured triples from unstructured texts through prompt engineering and entity disambiguation, with the resulting knowledge graph implemented in Neo4j graph database. The constructed knowledge graph integrates 106 immovable cultural heritage records from Chifeng City with approximately 20 types of semantic relationships, forming a comprehensive semantic network covering people, places, events, time, and materials. K-means clustering reveals five cultural value themes, including “Nomadic Imperial Power System” and “Multi-Capital Governance Network”, while geospatial mapping identifies a “dual-core and ring-belt” distribution pattern for heritage protection zoning. This research demonstrates how international semantic standards can be integrated with artificial intelligence technologies to enable interoperable cultural heritage knowledge systems, providing practical implications for cross-institutional heritage management and archaeological survey planning. Full article

Oral squamous cell carcinoma (OSCC) is an aggressive epithelial malignancy with high local invasiveness and a tendency for early cervical lymph node metastasis. Conventional prognostic markers often lack precision. This study evaluated the expression of putative cancer stem cell markers—CD44, CD133, and CD166—in OSCC tissues and explored their associations with clinical parameters, including salivary flow rates. Twelve patients with histologically confirmed OSCC (9 males, 3 females; mean age: 65 years) were included. Clinical TNM staging and tumor dimensions were recorded. Depth of invasion was measured histologically. Tumor tissues were enzymatically dissociated to establish primary cell cultures, and flow cytometry was used to quantify putative cancer stem cell markers expression. Unstimulated salivary flow rates were measured using sialometry. CD44 expression was uniformly high (median: 96.4%) and CD166 showed moderate to high expression (median: 85.5%), while CD133 was low (median: 1.5%). Co-expression levels were the highest for CD44+/CD166+ (median: 86.6%). Triple-marker co-expression had a median of 2.0%. Depth of invasion was positively correlated with CD133+ and its co-expression with CD44+ and CD166+ (p ≤ 0.05). Salivary flow rates were negatively correlated with CD166+ and CD44+/CD166+ expression (p ≤ 0.01). These findings suggest putative cancer stem cell markers, particularly CD133, may have prognostic value in OSCC and warrant further investigation. Full article

Destinations such as Bali face intensifying overtourism, which undermines ecological integrity, cultural authenticity, and local livelihoods. Traditional sustainable tourism approaches have proven insufficient, leading to calls for regenerative tourism that restores ecosystems and strengthens communities. This study examines how Penta-Helix collaboration can drive regenerative tourism, mitigate overtourism, and deliver sustainability outcomes. A mixed-methods design was employed. Survey data from 220 domestic and international visitors were analyzed using structural equation modeling (SEM–PLS) to test relationships among Penta-Helix collaboration, regenerative tourism, overtourism mitigation, and sustainability outcomes. To complement these findings, an analytic hierarchy process (AHP) was conducted with 30–40 key stakeholders drawn from 100 informants (government, businesses, communities, academia, and media) to prioritize mitigation strategies. SEM–PLS results indicate that Penta-Helix collaboration significantly enhances regenerative tourism practices (β = 0.62), which strongly reduce overtourism impacts (β = 0.58). Mediation tests reveal that overtourism mitigation is a key mechanism linking regenerative tourism to triple bottom line outcomes (economic, socio-cultural, environmental). AHP results show that carrying capacity enforcement and participatory governance emerge as the top-priority strategies, underscoring the dual importance of institutional policy and community empowerment. The findings advance theoretical debates by positioning regenerative tourism as a systemic innovation enabled by networked governance and operationalized through overtourism mitigation strategies. Practically, the study highlights the need for policy enforcement, participatory governance, and adaptive destination management to embed regenerative principles in overtourism hotspots. Full article

Hepatocellular carcinoma (HCC) ranks as the second most lethal malignancy worldwide, presenting formidable therapeutic challenges including tumor heterogeneity, complex microenvironment, and inefficient drug delivery. Conventional therapies such as surgery, chemotherapy, and immunotherapy are limited by systemic toxicity, drug resistance, and poor targeting specificity. Mesenchymal stem cells (MSCs) have emerged as promising drug delivery vehicles, leveraging their innate tumor-homing capacity, immunomodulatory properties, and exosome-mediated cargo transport. Preclinical studies demonstrate that MSC-based systems triple drug accumulation in tumors and synergize with immunotherapy, extending survival in HCC models. This review systematically examines recent advances in MSC-based delivery systems for HCC, focusing on engineering strategies to enhance targeting precision and controlled drug release, including genetic modification, exosome engineering, and stimuli-response systems. Despite progress, challenges such as MSC heterogeneity and scalable production persist. Emerging solutions like single-cell RNA sequencing for subpopulation selection and 3D bioprinting for standardized culture are highlighted. This work provides a roadmap for developing MSC-based precision therapies, bridging translational gaps in HCC treatment. Full article