Search Results (1,425)

Avian viruses formed the foundation of early retrovirology. The historical line extends from the discovery of the first sarcoma virus by Peyton Rous to the quantitative determination of oncogenic activity in cell culture by the focus assay. As a viral group, avian retroviruses offered exclusive advantages that allowed the assembly of a unique and powerful tool chest for the analysis of viral activity. Among the fundamental discoveries facilitated by these tools were viral and cellular oncogenes, cell surface receptors, virus-specific detection of inapparent infection, high-frequency genetic recombination between retroviruses, and the genetic maps of simple retroviruses. The work with avian viruses was soon complemented by research on mammalian retroviruses, and several oncogenes that became the basis of successful targeted therapies were defined. The field of cancer genes is at a point of transition. Future developments will be driven by new technologies and interpretations. They will also require a more comprehensive approach. Full article

Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal proliferation and survival of neoplastic plasma cells (PCs) within the bone marrow (BM), where disease progression is critically supported by interactions with the BM tumor microenvironment (TME). Despite significant advances in therapeutic strategies, MM remains incurable, underscoring the need for improved preclinical models to better understand the disease biology and therapeutic response. This review summarizes current and emerging MM treatment approaches and critically examines the development of models designed to more accurately recapitulate interactions between MM-PCs and the surrounding BM niche. We describe established and emerging modeling platforms, with emphasis on advanced three-dimensional (3D) culture systems and highlight their unique contributions to the preclinical assessment of both existing and novel therapies. The advantages of 3D models, including in vitro and in silico systems, over traditional two-dimensional (2D) models are discussed, alongside a comparative evaluation of scaffold-free and scaffold-based approaches. In addition, the benefits and recent advances in the customization of BM niche simulation using microfluidic technologies and organ-on-a-chip platforms are reviewed. The application of 3D models in MM research is increasingly enabling the study of disease pathogenesis, progression, drug resistance and precision-medicine approaches (informed by biomarker discovery). Although standardized preclinical approaches for evaluating MM therapeutics are currently lacking, the growing imperative to reduce reliance on preclinical animal models highlights the importance of alternate systems. Consequently, the development and adoption of physiologically relevant models that accurately recapitulate MM-PC interactions with the BM TME will be critical for advancing future therapeutic strategies in MM. Full article

Commercially mature products obtained by fractionation or extraction of phototrophic microalgal biomass remain concentrated in four categories: whole-cell Spirulina/Chlorella, C-phycocyanin, astaxanthin, and DHA-rich oils. Little diversification of these fractionated, mid-tier products has followed the decline in upstream costs. Whole-cell feed and live-culture markets, agricultural biostimulants, and fermentation-derived ingredients are commercially active but lie outside this phototrophic downstream-processing scope. Reported open-pond biomass production costs have fallen from ~US$10 kg⁻¹ in the 1990s to sub-US$1 kg⁻¹ nth-plant projections, yet no substantial product diversification has occurred. This review brings together three complementary lines of evidence: a bibliometric analysis of 1995–2025 publications showing that downstream fractionation, biorefinery, and integrated process design account for only 9.3% of food-core microalgal research; institutional surveys documenting the same four dominant categories across Europe, China, and global markets; and a meta-analysis of 53 whole-biomass cost rows from 16 techno-economic assessments. These sources indicate consistently that downstream processing is a necessary, though not sole, constraint on commercial diversification. A four-tier unit-operation roadmap is proposed-cell disruption at commodity energy cost, fractionation with functional ingredient preservation, decolorization and desalting at food-ingredient unit cost, and standardized transferable workflows-each linked to a quantitative threshold and to the product categories it would unlock. Closing the microalgal processing technology gap now depends less on demonstrating feasibility than on meeting these thresholds. Full article

A newly isolated red-pigmented yeast, Sporobolomyces reniformis EMCC1691, was evaluated for its biotechnological potential in an integrated case study aimed at developing an efficient microbial cell factory for the valorization of delactosed whey. Fermentation trials in 5 L bioreactors demonstrated robust yeast growth on this dairy by-product, with complete consumption of glucose (21.86 g/L) and galactose (20.36 g/L), leading to the accumulation of approximately 6172 mg/L of lipids and 5634 µg/L of total carotenoids. Fatty acid analysis revealed a final concentration of 3924 mg/L, mainly represented by oleic (2037 mg/L), palmitic (779 mg/L), stearic (403 mg/L), and linoleic (362 mg/L) acids. HPLC analysis showed a pigment profile dominated by torularhodin, torulene, γ-carotene, and β-carotene. To complement downstream processing, the fermented culture was spray-dried into a stable powder and subsequently subjected to a simple, cost-effective, and unconventional mechanical pretreatment using a hydraulic press. This post-drying operation ensured extensive cell-wall disruption without the use of chemical agents or specialized equipment, thereby significantly enhancing the recoverability of intracellular lipids and carotenoids through supercritical CO₂ extraction. Under optimized conditions, SFE-CO₂ with ethanol recovered 92.18 ± 1.61 µg/g of total carotenoids, achieving an extraction efficiency of 84% relative to organic solvent extraction (109.17 ± 2.10 µg/g). Importantly, fermentation also reshaped the fatty acid composition of delactosed whey, shifting it toward a profile enriched in monounsaturated and polyunsaturated fatty acids, thereby further highlighting the metabolic impact and bioconversion potential of S. reniformis EMCC1691. Overall, this work highlights the technological relevance of a recently characterized yeast species and its potential to convert dairy by-products into high-value compounds within a proof-of-concept microbial cell factory framework, paving the way for future scale-up investigations. Full article

iPSC technology is well established in mammals but remains underdeveloped in non-mammalian species. A major barrier to generating avian iPSCs has been the lack of species-specific reprogramming factors and culture conditions capable of supporting self-renewal in avian pluripotent stem cells. Here, we report the generation of chicken iPSCs (ciPSCs) using a cocktail of seven chicken transcription factors (T7: Oct4, Sox2, Sox3, Klf4, c-Myc, Nanog, and Lin28B) combined with an optimized avian culture system. Transcriptomic and functional analyses identified Sox3, rather than Sox2, as the predominant SoxB1 factor in avian reprogramming. The resulting ciPSCs exhibited stable self-renewal for over 40 passages, expressed core pluripotency markers, differentiated into all three germ layers, and were transcriptionally similar to chicken ESCs. In chimera assays, ciPSCs contributed to somatic, extra-embryonic, and germline lineages, giving rise to gonadal PGC-like cells that did not acquire full germline competence. We further demonstrate that the T7 system generates iPSCs from quail, duck, peacock, zebra finch, and pigeon, and that duck iPSCs can form interspecies chimeras with donor cells detected in the host gonads. These findings establish a generalizable platform for avian iPSC generation with applications in developmental biology and germline preservation of endangered species. Full article

Radiotherapy is one of the most effective methods of cancer treatment. New, more effective, and safer radiotherapy methods can be developed thanks to selective radioprotectors. In our study, we investigated the antioxidant and radiomodulatory activity of sodium aminodihydrophthalazinedione (the drug Tameron^®) on human mesenchymal stem cells (MSCs) and human osteosarcoma cells of the MNNG/Hos line in vitro. We have shown that sodium aminodihydrophthalazinedione effectively scavenged radiation-induced hydrogen peroxide in aqueous solution in a concentration-dependent manner after X-ray irradiation. We also showed that sodium aminodihydrophthalazinedione (0.25 mM and above) effectively protects human MSCs from the damaging effects of X-rays, reducing the level of intracellular ROS and the number of apoptotic cells after irradiation, enhancing the restoration of double-stranded DNA breaks and clonogenic activity. Meanwhile, the effect of sodium aminodihydrophthalazinedione on human osteosarcoma MNNG/Hos cells was different: it increased the number of apoptotic cells and reduced the rate of repair of double-stranded DNA breaks. Transcriptomic studies on both cell culture types using nanopore sequencing technology after X-ray irradiation and sodium aminodihydrophthalazinedione pretreatment revealed a significant level of modulation of key genes responsible for DNA repair, antioxidant activity, and genome stability. Our data show that sodium aminodihydrophthalazinedione may be a promising therapeutic agent for modulating the cellular effects of radiation exposure. Full article

Corneal endothelial dysfunction is a major cause of corneal blindness worldwide. This is primarily due to the limited regenerative capacity of human corneal endothelial cells (CECs) and the global shortage of donor tissues. Corneal endothelial cell therapy (CECT), which involves injecting cultured CECs into the anterior chamber, has emerged as a promising alternative to conventional transplantation. However, its clinical efficacy remains limited by several factors, including rapid cell loss, non-uniform distribution, and insufficient long-term adhesion following injection. Recent advances in biomaterials and regenerative engineering have led to the development of emerging biomaterial-assisted strategies aimed at addressing these challenges. In this review, we provide a mechanistic and translational overview of next-generation CECT, highlighting a range of biomaterial-assisted strategies aimed at improving cell retention, spatial localization, and long-term adhesion following injection. These emerging approaches aim to mitigate key limitations of conventional cell injection therapy, including variability in cell distribution and retention. However, their effectiveness and translational feasibility remain under active investigation. In addition, we analyze recent global patent trends, regulatory frameworks, and market dynamics to highlight emerging opportunities for innovation and development in this field. Although many of these technologies remain at the preclinical or early translational stage, these approaches may provide a promising direction to improve engraftment efficiency, reduce surgical variability, and enable more scalable, minimally invasive treatment options. This review highlights the potential of biomaterial-assisted CECT as a next-generation regenerative strategy and outlines key challenges that must be overcome for successful clinical translation. Full article

Foodborne pathogens pose a major challenge for public health, food safety regulation, and industrial quality control. Effective surveillance, outbreak tracing, and early warning for foodborne microbial contamination require rapid, reliable detection methods. Conventional culture-based methods are still essential for regulatory confirmation since they recover viable isolates and support downstream verification. However, their long turnaround time, labor-intensive procedures, and limited throughput restrict their use in rapid screening and on-site testing. In recent years, immunological assays, nucleic acid amplification and recognition methods, biosensors, microfluidic systems, CRISPR-Cas platforms, mass spectrometry, sequencing technologies, and artificial intelligence-assisted analysis have expanded the detection toolbox. These methods improve speed, sensitivity, portability, and multiplexing capacity, but their performance still depends on food-matrix properties, sample pretreatment, and application conditions. This review compares representative methods in terms of analytical principle, sample pretreatment, sensitivity, specificity, assay time, viable-cell discrimination, field applicability, and standardization potential. In our opinion, culture-based methods are central for confirmation, while emerging technologies are better suited for rapid screening, integrated analysis, and point-of-need testing. Nevertheless, matrix interference, limited validation in naturally contaminated samples, insufficient viable/dead-cell discrimination, and weak cross-platform consistency remain key barriers to routine use. Full article

Tissue engineering using the self-assembly approach represents a promising technology. However, age-related reductions in extracellular matrix deposition by stromal cells limit the mechanical robustness of reconstructed tissues what can be critical for midurethral sling reconstruction. Indeed, stress urinary incontinence predominantly affects women over 50 years of age and is commonly treated by implantation of midurethral slings, whose synthetic versions have raised concerns regarding safety and long-term tolerance. In this study, we investigated whether biochemical modulation could enhance collagen deposition and mechanical properties of self-assembled dermal tissues reconstructed from female donors of different ages. Dermal fibroblasts were cultured in the presence of ascorbic acid, and the effects of hormonal supplementation, metabolic and hypoxia-related stimuli, and insulin signaling activation were evaluated using collagen quantification, histological analyses, and mechanical testing. Fibroblasts derived from younger donors deposited significantly more collagen than those from older female donors. Among all tested conditions, insulin like growth factor 1 (IGF 1) markedly increased collagen deposition in a dose-dependent manner, including in fibroblasts from women over 50 years of age, whereas β-estradiol and progesterone had no significant effect on collagen content. Although β-estradiol slightly increased tissue thickness, only IGF-1 supplementation resulted in substantial improvements in perforation strength, stiffness, displacement at break, and toughness. These results demonstrate that IGF-1 is a potent enhancer of extracellular matrix production and mechanical performance in dermal tissues reconstructed by the self-assembly approach, and represents a promising strategy to improve the development of biological midurethral slings. Full article

Tumor heterogeneity and microenvironmental complexity remain fundamental barriers to genomics-centered precision oncology, frequently causing discordance between molecular alterations and real-world therapeutic responses. Here, we reviewed patient-derived organoid (PDO) technologies as functional platforms that complement molecular profiling by directly investigating patient-specific sensitivity, resistance, and microenvironment dependent vulnerability. We first summarize why conventional preclinical systems, two-dimensional cell lines and patient-derived xenografts, are limited by reduced biological fidelity, impractical turnaround time, and scalability for clinical decision support. We then synthesized organoid-based evidence across three representative disease malignancies with distinct precision-medicine bottlenecks. Across these settings, we highlight advances that extend the PDO capability beyond the tumor epithelium alone, including air–liquid interface cultures, immune and stromal co-cultures, and microfluidic organoid-on-chip systems, as well as integration with multi-omics and artificial intelligence for scalable analytics. Finally, we discuss the key translational requirements, standardization of culture matrices and assay readouts, quality control, automation to reduce turnaround time, and regulatory/ethical frameworks, required to transition organoid-guided testing from proof-of-concept to routine implementation. Collectively, this review reframes organoids as functional stratification platforms supporting the integration of functional response profiling alongside genomics-guided precision oncology approaches. Full article

Currently, the most commonly used methods for detecting Mycoplasma are the culture method and the indicator cell culture method. However, both approaches exhibit low sensitivity and are incapable of detecting low-concentration contamination. In addition, the detection period may extend up to 28 days, which is unsuitable for rapid screening and may delay timely contamination control measures. To address these limitations, a Mycoplasma detection method based on nucleic acid amplification technology (NAT) was developed following a comparative analysis of gene sequences from various Mycoplasma species. The method was validated with respect to its detection performance and its applicability to biological product samples. DNA was extracted from Mycoplasma-contaminated samples using a magnetic bead-based nucleic acid extraction method. Universal primers were designed based on the highly conserved 16S rRNA gene sequence of Mycoplasma, and amplification was performed using multiplex quantitative PCR (qPCR) with fluorescent probes. The limit of detection (LOD) was established based on statistics of 24 replicates. Method specificity and robustness were evaluated according to the guidelines set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH Q2), while sample applicability was assessed in accordance with the European Pharmacopoeia (EP) <2.6.7>. The NAT-based Mycoplasma detection method enabled rapid, qualitative identification of Mycoplasma contamination. The validated LOD was 10 CFU/mL, and the method met predefined requirements for sensitivity, specificity, and robustness. To assess applicability, real biological product samples, including monoclonal antibodies, antibody fusion proteins, bispecific antibodies, and trispecific antibodies, were spiked with 10 CFU/mL of standard Mycoplasma strains. All spiked samples tested positive. These findings confirm that the NAT-based Mycoplasma detection method is suitable for process control and product release testing in the production of biological products. Full article

In the fields of cell engineering, bio-fabrication, and targeted therapy, achieving high-precision manipulation of microparticles and cells remains a technical challenge. Although acoustic tweezers based on surface acoustic waves (SAWs) offer a promising solution, the structural complexity of conventional SAW devices has limited their practical applications. This work proposes a symmetric interdigitated transducer (IDT)-based acoustic tweezers device featuring a simple structure and high flexibility for modulating acoustic pressure field patterns and enabling particle manipulation. Theoretical investigations into the particle manipulation mechanism of the proposed device were conducted using the finite element method. A detachable polymethyl methacrylate (PMMA) assembly chamber was also designed. The effectiveness of the device was validated through dynamic and reconfigurable manipulation experiments using fluorescent polystyrene microspheres. Experimental results demonstrate that the proposed device can rapidly and precisely modulate SAW to achieve array-based manipulation of particle clusters, forming corresponding array patterns. Compared with conventional sorting methods, this device offers advantages including low cost, high precision, ease of operation, and good biocompatibility, making it suitable for large-scale manipulation of microparticles and biological cells. This technology has the potential to expand the application landscape of SAW and may emerge as a cutting-edge approach for directed cell assembly and culture. Full article

Germline stem cells (GSCs) are crucial for gametogenesis, genetic conservation, and molecular breeding. Although GSCs lines have been well studied in mammals and several model teleost species, progress in commercial marine teleosts remains limited. In this study, we report a successful establishment of a long-term stable ovarian cell line derived from the Asian seabass (Lates calcarifer), designated the Seabass Ovarian (SBO) cell line. Ovaries were dissociated using a combined collagenase–trypsin digestion protocol; the cells were propagated and maintained in DMEM supplemented with bFGF, LIF, and fish serum. The SBO cells exhibited strong alkaline phosphatase activity. Furthermore, the cultured cells robustly expressed both germ-cell specific markers (Vasa) and pluripotency associated proteins (Nanog, SSEA-1). These findings indicate the successful isolation and long-term maintenance of an ovarian cell line expressing female germline stem cell markers from Asian seabass ovaries. The established cell line not only provides a valuable in vitro model for elucidating the mechanisms behind germ cell differentiation but also serves as a crucial cellular resource for advancing genetic breeding, germplasm preservation, and surrogate broodstock technologies in marine teleosts. Full article

Spectral monitoring combined with chemometrics models resulting from machine learning approaches allows cell culture to be monitored almost in real time. This process analytical technology offers to drastically reduce the amount of hands-on time and laboratory testing needed to monitor this crucial biomanufacturing step. In this article, we propose a method to anticipate future spectra. The method is based on extrapolation of the spectra in a reduced-dimensionality space, followed by retroprojection in the original space. Passed to regular chemometrics models already fitted, these anticipated spectra enable predictive cell culture monitoring up to several dozen hours with satisfactory quality. This anticipation paves the way for course-correction and enhanced operations such as reduced need for night shifts. Full article

Glioblastoma multiforme (GBM) remains the most aggressive and therapeutically intractable primary brain tumor, with many patients experiencing rapid relapse despite maximal surgical resection followed by standard chemoradiation. This persistent failure reflects the convergence of profound tumor-intrinsic genetic heterogeneity and a highly dynamic, spatially structured, and immunosuppressive tumor microenvironment (TME). Together, these forces create strong selective pressures that fuel tumor evolution, intratumoral diversity, phenotype plasticity, diffuse invasion, and robust resistance to therapy. The TME of GBM is orchestrated through a complex interplay between diverse cellular constituents, including tumor-associated macrophages, reactive astrocytes, endothelial cells, pericytes, and GBM stem cells, and non-cellular components such as extracellular matrix remodeling, hypoxia, metabolic and nutrient gradients, and spatially patterned cytokine and chemokine signaling networks. Additionally, heterogeneity in blood–brain barrier (BBB) and blood–tumor barrier (BTB) complicates drug delivery and immune surveillance, reinforcing therapeutic resistance and regional tumor adaptation. Conventional two-dimensional cell cultures and animal models fail to sufficiently capture these multiscale, patient-specific interactions, limiting their translational predictive power. In this narrative review, we synthesize recent advances in GBM organoid technologies as physiologically relevant, three-dimensional platforms that more faithfully recapitulate TME for driving tumor evolution and treatment resistance. We compare complementary organoid strategies, including patient-derived GBM organoids that preserve native cytoarchitecture, cerebral organoid co-culture systems that reconstruct tumor–brain interactions, and advanced platforms incorporating immune and vascular features such as air–liquid interface cultures, microglia-enriched systems, and BBB/BTB-integrated models. Finally, we highlight emerging innovations such as spatial transcriptomics, organoid-on-a-chip systems, live imaging coupled with lineage tracing, genome engineering, and artificial intelligence integration that collectively position GBM organoids at the forefront of precision neuro-oncology, reproducing TME, enabling dynamic mapping of tumor evolution, and accelerating patient-specific therapeutic discovery. Full article