Search Results (484)

Despite significant advancements in understanding the pathogenesis and treatment of hematological malignancies, including leukemia and multiple myeloma, the majority of patients continue to experience poor long-term outcomes. This is partly due to the difficulty of accurately recapitulating the malignant microenvironment in vitro, particularly the bone marrow niche. The complexity of the bone marrow microenvironment poses a challenge for the in vitro examination of hematological malignancies. Traditionally, 2D culture and animal models have been utilized, but these representations are limited and have been criticized for their lack of human physiological relevance. In an attempt to overcome this, 3D models have been developed that more accurately recapitulate the in vivo microenvironment. Herein, we present an overview of recent developments in 2D and 3D models used for studying the bone marrow niche in hematological malignancies, highlighting their advantages and limitations. Full article

Red blood cell (RBC) production from bone marrow hematopoietic stem cells (BMHSCs) in vitro overlooks the mechanical signals of the bone marrow niche and overly relies on growth factors. Considering that the fate of hematopoietic stem cells (HSCs) is determined by the natural bone marrow microenvironment, differences in mechanical microenvironments provide a reference for the regulation of HSC differentiation. This study seek to reveal the role of mechanobiology cues in erythropoiesis and provide a new perspective for the design of in vitro erythropoiesis platforms. The hydrogel platforms we designed simulate the stiffness gradient of the bone marrow niche to culture HSCs and induce their differentiation into the erythroid system. Cells on the low-stiffness scaffold have higher potential for erythrocyte differentiation and faster differentiation efficiency and promote erythrocyte differentiation after erythropoietin (EPO) restriction. In vivo transplantation experiments demonstrated that these cells have the ability for continuous proliferation and differentiation into mature erythrocytes. By combining mechanical cues with in vitro erythrocyte production, this method is expected to provide insights for in vitro hematopoietic design and offer a scalable cell manufacturing platform for transfusion medicine. Full article

Skin aging is characterized by compromised epidermal homeostasis and dermo-epidermal junction (DEJ) integrity, resulting in reduced stem cell potential and impaired tissue regeneration. This study investigated the effects of Andrographis paniculata extract (APE) on keratinocyte stem cells (KSCs) and DEJ composition in human skin. Using human skin explants and cell culture models, we demonstrated that APE treatment enhances DEJ composition by increasing Collagen IV and Laminin production while decreasing MMP-9 expression, without altering epidermal structure or differentiation. In the same model, APE preserved stemness potential by upregulating markers related to niche components (collagen XVII and β1-integrin), proliferation (Ki-67 and KRT15), and stem cell capacity (Survivin and LRIG1). In vitro studies revealed that APE selectively stimulated KSC proliferation without affecting transit amplifying cells and promoted Collagen IV and Laminin secretion, particularly in KSCs. Furthermore, in a co-culture model simulating a compromised DEJ (UVB-induced), APE increased Laminin production in KSCs, suggesting a protective effect against photo-damage. These findings indicate that APE enhances DEJ composition and preserves stem cell potential, highlighting its promise as a candidate for skin anti-aging strategies targeting stem cell maintenance and extracellular matrix stability to promote skin regeneration and repair. Full article

Globalization and market saturation have led Portuguese textile companies to seek international markets not only for growth but also to contribute to their country’s international image. This study aims to explore how the internationalization of the Portuguese textile sector into the Chinese market contributes to Portugal’s destination image and identify the critical success factors in this process. The research follows an inductive, qualitative methodology based on semi-structured interviews with two groups of companies: those already operating in China (n = 5) and those preparing to enter the market (n = 5). The interviews were thematically analyzed to extract key patterns and insights. The findings reveal that successful companies operate in the luxury segment, rely on prior international experience, and often use local intermediaries. Firms planning to internationalize highlight quality differentiation, brand authenticity, and innovation as strategic advantages. These insights support the role of niche positioning and cultural adaptation in building both commercial success and a refined international image of Portugal. This study contributes to the literature by linking internationalization and destination branding through industry-specific case evidence and offers practical implications for managers targeting emerging markets like China. Full article

The fungal component of microbiota, known as the mycobiome, inhabits different body niches such as the skin and the gastrointestinal, respiratory, and genitourinary tracts. Much information has been gained on the bacterial component of the human microbiota, but the mycobiome has remained somewhat elusive due to its sparsity, variability, susceptibility to environmental factors (e.g., early life colonization, diet, or pharmacological treatments), and the specific in vitro culture challenges. Functionally, the mycobiome is known to play a role in modulating innate and adaptive immune responses by interacting with microorganisms and immune cells. The latter elicits anti-fungal responses via the recognition of specific fungal cell-wall components (e.g., β-1,3-glucan, mannan, and chitin) by immune system receptors. These receptors then regulate the activation and differentiation of many innate and adaptive immune cells including mucocutaneous cell barriers, macrophages, neutrophils, dendritic cells, natural killer cells, innate-like lymphoid cells, and T and B lymphocytes. Mycobiome disruptions have been correlated with various diseases affecting mostly the brain, lungs, liver and pancreas. This work reviews our current knowledge on the mycobiome, focusing on its composition, research challenges, conditioning factors, interactions with the bacteriome and the immune system, and the known mycobiome alterations associated with disease. Full article

Heparan sulfate proteoglycans (HSPGs) within the neuronal niche are expressed during brain development, contributing to multiple aspects of neurogenesis, yet their roles in glial lineage commitment remain elusive. This study utilised three human cell models expanded under basal culture conditions followed by media-induced lineage induction to identify a reproducible and robust model of gliogenesis. SH-SY5Y human neuroblastoma cells (neuronal control), ReNcell CX human neural progenitor cells (astrocyte inductive) and ReNcell VM human neural progenitor (mixed neural induction) models were examined. The cultures were characterised during basal and inductive states via Q-PCR, Western Blotting, immunocytochemistry (ICC) and calcium signalling activity analyses. While the ReNcell lines did not produce fully mature or homogeneous astrocyte cultures, the ReNcell CX cultures most closely resembled an astrocytic phenotype with ReNcell VM cells treated with platelet-derived growth factor (PDGF) biased toward an oligodendrocyte lineage. The glycated variant of surface-bound glypican-2 (GPC2) was found to be associated with lineage commitment, with GPC6 and 6-O HS sulfation upregulated in astrocyte lineage cultures. Syndecan-3 (SDC3) emerged as a lineage-sensitive proteoglycan, with its cytoplasmic domain enriched in progenitor-like states and lost upon differentiation, supporting a role in maintaining neural plasticity. Conversely, the persistence of transmembrane-bound SDC3 in astrocyte cultures suggest continued involvement in extracellular signalling and proteoglycan secretion, demonstrated by increased membrane-bound HS aggregates. This data supports HSPGs and HS GAGs as human neural lineage differentiation and specification markers that may enable better isolation of human neural lineage-specific cell populations and improve our understanding of human neurogenesis. Full article

Templestay programs in South Korea represent a unique convergence of Buddhist ritual, cultural immersion, and wellness tourism. While often treated as niche cultural experiences, their broader significance within sustainable wellness tourism remains underexplored. This study examines participant reflections from the Beomeosa Templestay program through thematic analysis of over 600 reviews sourced from TripAdvisor, Google Reviews, and handwritten guestbooks. Using a triangulated framework combining Grounded Theory, Symbolic Interactionism, and the Wellness Tourism Model, the research identifies four recurring experiential themes: spiritual development, emotional healing, cultural immersion, and conscious consumption. Findings reveal cross-cultural variations: non-Korean participants emphasized spiritual exploration and cultural learning, while Korean participants prioritized emotional renewal and reconnection with heritage. Yet, across all groups, participants reported transformative outcomes, including heightened clarity, inner calm, and enhanced self-awareness. These results suggest that Templestays serve as accessible, culturally grounded wellness retreats that align with rising global demand for intentional, mindful travel. This study contributes to sustainable tourism scholarship by framing Templestays as low-impact, spiritually resonant alternatives to commercialized wellness retreats. Practical recommendations are offered to expand participation while maintaining program authenticity and safeguarding the spiritual and cultural integrity of monastic hosts in an increasingly globalized wellness landscape. Full article

Eccrine sweat glands play a vital role in human thermoregulation; however, their self-repair function is minimal. Therefore, developing methods to regenerate and improve sweat gland function that use cultured sweat gland cells presents an urgent issue. The tissue microenvironment, especially hypoxic niches, essentially maintain cell stemness, highlighting the importance of oxygen concentration in the culture environment. Therefore, we evaluated the effects of different oxygen environments on human sweat glands and their regulatory mechanisms. Human eccrine sweat glands express HIF-1α and HIF-2α, suggesting that they respond to hypoxia in vivo. Primary human-derived eccrine sweat gland cells were cultured for two weeks using the spheroid culture method at 0.5%, 2%, 10%, and 21% O₂ concentration. HIF-1, Wnt/β-Catenin, and TGFβ1 signaling increased in sweat gland cells cultured in 0.5% O₂ conditions, along with increased undifferentiated cell marker expression. The results of this study will contribute to in vitro research models of sweat glands and treatment development for damage to sweat glands, including burns. Full article

Mesenchymal stromal cells of the tumor microenvironment (TME) play a significant role in the progression of multiple myeloma (MM). The cells of the TME demonstrate resistance to treatment, thereby creating a favorable environment for disease relapse. The status of the TME during remission is poorly understood. An association between treatment response and TME status (including signaling pathways) has been suggested. One of the key players in the establishment of the MM TME is WNT signaling. In this study, we evaluated the expression of WNT family proteins in the TME and MM cells to assess their potential as TME markers and predictors of treatment response. A bioinformatic analysis of normal and malignant plasma cells, combined with an analysis of published data, revealed the following differentially expressed WNT genes: WNT5A, WNT10B, CTNNB1, and WNT3A. Immunohistochemical staining with the antibodies against the proteins encoded by the genes was conducted on trephine biopsy samples of bone marrow from healthy donors and patients with different responses to therapy. A quantitative analysis of the immunohistochemical data revealed differences in the amounts of WNT3A, WNT5A, WNT10B, and β-catenin proteins in the bone marrow before treatment depending on the subsequent responses of the patients to therapy. Multiplex fluorescent immunohistochemical staining with tyramide signal amplification revealed that WNT3A was predominantly present in mesenchymal stromal cells, whereas WNT5A and WNT10B were primarily observed in plasma cells. β-catenin was detected in both cell types. We analyzed the mRNA levels of the WNT gene family and CTNNB1 in MSC cultures from healthy donors and patients using qPCR. These genes were differentially expressed in MSC cultures derived from patients and healthy donors, as well as between patients grouped according to their response to therapy. Therefore, WNT proteins and β-catenin can be considered potential markers to assess the state of the tumor niche. Full article

Multiple myeloma is a hematologic malignancy characterized by the clonal proliferation of plasma cells within the bone marrow. The tumor microenvironment plays a crucial role in multiple myeloma pathogenesis, progression, and drug resistance. Traditional two-dimensional cell culture models have been instrumental in multiple myeloma research. However, they fail to recapitulate the complex in vivo bone marrow microenvironment, leading to limited predictive value for clinical outcomes. Three-dimensional cell culture models emerged as more physiologically relevant systems, offering enhanced insights into multiple myeloma biology. Scaffold-based systems (e.g., hydrogels, collagen, and Matrigel), scaffold-free spheroids, and bioprinted models have been developed to simulate the bone marrow microenvironment, incorporating key components like mesenchymal stromal cells, osteoblasts, endothelial cells, and immune cells. These models enable the functional assessment of cell adhesion-mediated drug resistance, cytokine signaling networks, and hypoxia-induced adaptations, which are often lost in 2D cultures. Moreover, 3D platforms demonstrated improved predictive value in preclinical drug screening, facilitating the evaluation of novel agents and combination therapies in a setting that better mimics the in vivo tumor context. Hence, 3D cultures represent a pivotal step toward bridging the gap between basic myeloma research and translational applications, supporting the development of more effective and patient-specific therapies. Full article

Moniliophthora roreri (MR, frosty pod rot) and M. perniciosa (MP, witches’ broom disease) pose critical threats to cacao production in Latin America. This study explores the biocontrol potential of Trichoderma spp. strains against these pathogens through exploratory analysis of mycoparasitism, chitinolytic activity, and volatile organic compound (VOC) production. Dual-culture assays revealed species-specific antagonism, but C2A/C4B showed a dual-pathogen efficacy (>93% of Monioliopthora inhibition). Chitinase activity revealed C4A/C1 strains as exceptional producers (72 mg/mL NAGA vs. MR and 94 mg/mL vs. MP, respectively). GC-MS analysis identified pathogen-modulated VOC dynamics: hexadecanoic acid dominated in 80% Trichoderma solo-cultures (up to 26.65% peak area in C3B). MP showed 18.4-fold higher abundance of hexadecanoic acid than MR (0.23%). In 90% of dual-culture with MR and MP, HDA was detected as the most abundant. Functional specialization was evident. C4A and C1 prioritized chitinase production growing on MR and MP cell walls (respectively), whereas C9 excelled in antifungal hexadecanoic acid synthesis in confrontation with both pathogens. Complementary strengths among strains—enzymatic activity in C4A/C4B versus volatile-mediated inhibition in C9—suggest niche partitioning, supporting a consortium-based approach for robust biocontrol. This study provides preliminary evidence for the biocontrol potential of several Trichoderma strains, showing possible complementary modes of action. Full article

This study explores the dynamics of motorcycle tourism in rural areas and its potential contribution to sustainable and regenerative development. A bibliometric analysis of management-related publications was conducted using the Web of Science Core Collection, focusing on topics such as tourism, motivation, rurality, and motorcycling. VOSviewer software (version 1.6.20) was employed to support this analysis. Based on the literature, a theoretical framework was developed, leading to four research hypotheses that aimed to empirically examine the relationships between cultural motivation, community interaction, type of accommodation, event location, and tourist behaviour. To test these hypotheses, structured questionnaires were distributed in person during rural motorcycling events in Portugal, yielding a valid sample of 233 respondents. The data were analysed using SPSS 28 software via statistical methods to reduce dimensionality and identify latent structures, chi-square tests, and logistic regression. The results confirmed all four hypotheses, highlighting the importance of cultural motivation for return intentions, community interaction for perceived authenticity, accommodation type for destination recommendations, and event location for overall satisfaction. The study also identifies gender-related differences and reinforces the value of immersive, co-created experiences in enhancing the competitiveness of rural destinations. This theoretical contribution supports the advancement of motorcycle tourism as a sustainable niche while offering practical guidance for inclusive and regenerative tourism planning. Full article

Campus living labs (CLLs) foster sustainability within higher education institutions (HEIs), yet their institutional embedding remains challenging. Relying on the idea of strategic niche management (SNM), this paper examines three processes key to protected space development: vision articulation, social network building, and learning. This research explores the factors that enable the development of protected spaces for successful CLLs. Using an embedded case study approach, seven sustainability initiatives were analysed at Utrecht University, the Netherlands. We found that the perceived success in CLLs is related to sustainability outcomes, scaling pathways, and process outcomes. In addition, different groups of factors driving the development of protected spaces were identified: broad factors that contribute to all or multiple key processes, specific factors that support only one process, and peripheral factors that were less frequently mentioned. ‘Organisational culture’ appeared to be an important broad factor contributing to all key processes. ‘Resources’ and ‘Coordination’ were also important, specifically for social network building, but also mentioned as currently being absent by many. Finally, this paper contributes by incorporating a new factor, ‘Orchestration’, a subtle yet strategic form of coordination. It offers insights for HEIs aiming to develop CLLs as part of their sustainability strategy. Full article

Breast cancer (BC) frequently metastasizes to bone, leading to poor patient prognosis. The infiltration of cancer cells in bone impairs its homeostasis, triggering a pathological interaction between tumors and resident cells. Preclinical models able to mimic the bone microenvironment are needed to advance translational findings on BC mechanisms and treatments. We designed strontium-doped calcium phosphate cement to be employed for culturing cancer and bone cells and developed an in vitro bone metastasis model. The platform was established step by step, starting with the monoculture of cancer cells, mature osteoblasts (OBs) differentiated from mesenchymal stem cells, and mature osteoclasts (OCs) differentiated from Peripheral Blood Mononuclear Cells. The model was implemented with the co-culture of cancer cells with OBs or OCs, or the co-culture of OBs and OCs, allowing us to discriminate the interaction between the actors of the bone metastatic niche. The biomimetic material was further challenged with bone metastasis patient-derived material, showing good versatility and biocompatibility, suggesting its potential use as bone substitute. Overall, we developed a bone-mimicking model able to reproduce reciprocal interactions between cancer and bone cells in a biomimetic environment suitable for studying the biomolecular determinants of bone metastasis and, in the future, as a drug efficacy platform. Full article

Tumour-associated angiogenesis plays a key role at all stages of cancer development and progression by providing a nutrient supply, promoting the creation of protective niches for therapy-resistant cancer stem cells, and supporting the metastatic cascade. Therapeutic strategies aimed at vascular targeting, including vessel disruption and/or normalisation, have yielded promising but inconsistent results, pointing to the need to set up reliable models dissecting the steps of the angiogenic process, as well as the ways to interfere with them, to improve patients’ outcomes while limiting side effects. Murine models have successfully contributed to both translational and pre-clinical cancer research, but they are time-consuming, expensive, and cannot recapitulate the genetic heterogeneity of cancer inside its native microenvironment. Non-animal technologies (NATs) are rapidly emerging as invaluable human-centric tools to reproduce the complex and dynamic tumour ecosystem, particularly the tumour-associated vasculature. In the present review, we summarise the currently available NATs able to mimic the vascular structure and functions with progressively increasing complexity, starting from two-dimensional static cultures to the more sophisticated tri-dimensional dynamic ones, patient-derived cultures, the perfused engineered microvasculature, and in silico models. We emphasise the added value of a “one health” approach to cancer research, including studies on spontaneously occurring tumours in companion animals devoid of the ethical concerns associated with traditional animal studies. The limitations of the present tools regarding broader use in pre-clinical oncology, and their translational potential in terms of new target identification, drug development, and personalised therapy, are also discussed. Full article