Search Results (548)

Umbilical cord mesenchymal stromal cells (UC-MSCs) are a key element of regenerative medicine due to their ability to secrete growth factors that stimulate proliferation and angiogenesis, and modulate the inflammatory response. Despite their widespread use, the influence of the perinatal microenvironment on their biological properties remains poorly understood. The aim of this study was to assess the influence of pH and blood gas parameters in umbilical cord blood on the global transcriptomic profile of UC-MSCs and to analyze the correlation between the metabolic status of the newborn and the expression of key trophic factors: EGF, FGF2, FGFR1, FGFR3, GDNF, HGF, IGF1, NES, NGF, and PGF. Methods: The study was conducted in two stages. In the first phase, transcriptomic screening was performed using Affymetrix HuGene 2.0 ST microarray on cells isolated from three environmental groups defined by cord blood pH: acidic (pH < 7.35), physiological (7.35–7.39), and alkaline (pH ≥ 7.4). In the second phase, the results were validated using qPCR on an expanded study group (N = 50). Gene expression levels (RQ) were related to blood gas parameters (pH, pCO₂, pO₂, cHCO₃) and the presence of clinical features of threatened neonatal asphyxia. Results: Microarray analysis revealed that environmental pH acts as a molecular phenotypic switch. Under low pH conditions (<7.35), a shift in cell profile from proliferative to structural–migratory was observed. Significant overexpression of genes responsible for extracellular matrix (ECM) organization and adhesion (e.g., COMP, DCN, LUM, FMOD) was observed, while pathways related to cell cycle and cell division (↓CDK1, AURKA, TOP2A) were downregulated. qPCR validation confirmed these observations, demonstrating a strong positive correlation between blood pH and the expression of regenerative mediators: FGFR1 (r = 0.28), EGF (r = 0.30), NGF (r = 0.39), and IGF1 (r = 0.30). A negative correlation was also found between carbon dioxide pressure (pCO₂) and the expression of NGF, FGFR1, and EGF. A significant clinical finding was that in newborns diagnosed with threatened asphyxia, EGF, FGFR1, and NGF gene expression was significantly reduced, indicating impaired trophic potential of the cells in response to metabolic stress. Conclusions: These results indicate that cord blood gas parameters are critical regulators of the genetic activity of UC-MSCs. Metabolic and respiratory acidosis not only inhibit the cells’ proliferative potential but also force them into a matrix remodeling mode, permanently modifying their transcriptomic profile. This suggests that the neonatal acid–base status may serve as an objective indicator of the “biological quality” of isolated stromal cells, which has significant implications for their future applications in cell therapies. Full article

Organoids are three-dimensional culture systems that self-organize and partially recapitulate the architecture, cellular composition, and functional properties of native tissues. In pediatric congenital hepatobiliary diseases, persistent cholestasis, bile duct maldevelopment, epithelial injury, and progressive fibrosis often lead to cirrhosis, liver failure, or the necessity for liver transplantation. Compared with conventional two-dimensional cell culture and animal models, hepatobiliary organoids provide patient-derived, human-relevant platforms for modeling disease mechanisms, evaluating therapeutic responses, and exploring regenerative strategies. Unlike previous reviews that mainly discuss general organoid culture systems or broad liver disease modeling, this review is organized around clinically oriented translational endpoints, including mechanistic target discovery, prognostic stratification, therapeutic validation, and regenerative reconstruction. We further discuss current barriers to clinical translation, including reproducibility, scalability, vascularization, immune integration, manufacturing standardization, and patient-specific genetic, environmental, and dietary modifiers. By integrating disease-specific mechanisms with translational applications, this review provides a framework for understanding how organoid-based platforms may contribute to future diagnosis, risk assessment, therapeutic decision-making, and regenerative medicine in pediatric congenital hepatobiliary disorders. Full article

Genome-edited (GE) crops are reaching consumers faster than the analytical infrastructure designed to monitor them. Unlike transgenic crops, most GE products carry only small sequence changes and no foreign DNA, making conventional element-based polymerase chain reaction (PCR) screening, which has underpinned genetically modified organism (GMO) enforcement for two decades, largely ineffective. This review critically evaluates detection technologies not by listing them sequentially, but by comparing their performance against a shared set of enforcement-relevant criteria: sensitivity at regulatory thresholds, allele discrimination capacity, prior target knowledge requirement, and validation maturity. Building on detection/discrimination distinctions already present in ENGL guidance documents and the DETECT project, we formalize a two-axis framework separating detectability (technically achievable for most known targets in defined seed or DNA mixtures at or near the 0.1% MRPL) from identifiability (rarely achievable without developer disclosure), with detection as a necessary precondition for identification, and apply it product by product to each commercialized GE crop for which public molecular data are available. The sulfonylurea-tolerant canola (SU Canola) case, in which analytical specificity is established but forensic event specificity is contested, and the German DETECT project are examined as contrasting case studies of analytical success and attribution failure, extracting generalizable lessons for the field. A technology comparison table, a product-specific feasibility matrix, and a tiered enforcement workflow are provided as practical tools. We conclude with five research priorities for closing the detection–identification gap across near-term, mid-term and longer-term horizons. Full article

Cancer is attributed to being caused by multiple genetic, epigenetic, and various direct and indirect environmental factors. Microplastics are defined as pieces of plastic that are smaller than five millimeters. Microplastics have been emphasized as ubiquitous environmental contaminants found in terrestrial and aquatic systems, food webs, and the human body. Moreover, microplastics can bind to environmentally harmful pollutants, heavy metals, and refractory organic pollutants that can aggravate the biological effects of these pollutants. Microplastics are suggested to induce chronic inflammation, oxidative stress, and genotoxicity by adsorbing and modifying the biomolecules in the biological systems. Oxidative stress, inflammation, and chemical-induced genetic and epigenetic changes in cancer cells and cancer-associated cells are considered as crucial processes in the development, progression, and therapeutic outcome of cancer. Among numerous tumor-promoting environmental factors, preclinical and clinical evaluations of how microplastics contribute to cellular and non-cellular pro-tumorigenic mechanisms like inflammation, genomic instability, and epigenetic modulation are emerging. This review will contribute to a better understanding of microplastics as additional environmental components apart from established carcinogens and genotoxic substances that directly or indirectly influence the pro-tumor microenvironment. Full article

Lithofacies characterization of organic-rich shales constitutes the essential foundation for sweet spot evaluation in lacustrine shale oil systems. This study targets the first member of the Upper Cretaceous Qingshankou Formation (K₂qn¹) in the southern Songliao Basin. Based on systematic core description of 908 m of core from eight cored wells, combined with 123 total organic carbon (TOC) measurements, 47 whole-rock X-ray diffraction (XRD) analyses, 29 major- and trace-element analyses, and six maceral identification datasets (≥500 organic particles counted per sample), together with conventional well log data from 75 wells (measured vitrinite reflectance $R_o$ = 0.34%–1.38%, mean = 0.94%), we establish an integrated lithofacies classification scheme incorporating the TOC as a classification parameter and develop a log-based lithofacies identification workflow. Eight lithofacies are recognized within K₂qn¹ across the study area, of which three are organic-rich. The high-TOC clay-rich mudstone-grade laminated shale deposited in a deep lake setting (LF-A; mean TOC = 3.18%, clay minerals ≥50%, formed under saline and strongly anoxic-euxinic conditions; mean paleosalinity = 8.06‰, V/(V + Ni) = 0.75–0.97) and the high-to-moderate-TOC felsic mudstone-grade laminated shale deposited in a semi-deep lake setting (LF-B; mean TOC = 2.18%, felsic minerals ≥50%, formed under brackish-to-saline anoxic conditions; mean paleosalinity = 5.10‰, V/(V + Ni) = 0.70–0.84) constitute the dominant organic-rich lithofacies. From Y1 to Y3, the cumulative thickness of organic-rich lithofacies expands from approximately 10 m to approximately 25 m. Areally, the mean TOC increases systematically from 1.65% in the southern delta-front zone to 2.74% in the northern deep lake center, reflecting an enrichment pattern governed primarily by paleoproductivity and modulated jointly by preservation conditions and terrigenous dilution. The log-based identification workflow, established by integrating a modified ΔlogR method with multiple linear regression, achieves a TOC prediction coefficient of determination of $R^2=0.86$ in the calibration well and lithofacies identification accuracies ranging from 64.6% to 94.0% in validation wells, with the highest performance observed in the delta-front facies zone. These results provide quantitative constraints for the genetic interpretation and log-based identification of organic-rich lacustrine shales. Full article

This article discusses rheumatoid arthritis (RA) as a chronic, systemic autoimmune disease leading to progressive joint damage and multi-organ complications. The complex pathogenesis of the disease is presented, involving the interaction of environmental, genetic, and immunological factors, including the role of autoantibodies and proinflammatory cytokines. Particular attention is paid to leflunomide, a disease-modifying antirheumatic drug (DMARD), which primarily works by inhibiting the DHODH enzyme, leading to reduced T and B cell proliferation. The additional anti-inflammatory properties of the drug’s active metabolite, teriflunomide, and its impact on signaling pathways related to the immune response are also discussed. This article examines the variability in patient responses to leflunomide treatment in terms of both efficacy and toxicity, with particular emphasis on the potential role of pharmacogenetic factors. It was pointed out that polymorphisms in genes related to drug metabolism, transport, and mechanism of action may influence the pharmacokinetics and safety of the therapy. It was also emphasized that the available data are primarily derived from observational studies and small cohorts, and the results are often inconsistent. Although some genetic variants and plasma teriflunomide concentrations show potential as predictors of treatment response, the current level of evidence does not support the routine use of pharmacogenetic testing in clinical practice. The article emphasizes that the pharmacogenetics of leflunomide represents a promising, yet still exploratory, avenue of research in the context of personalized RA therapy. It emphasizes the need for larger, well-designed clinical trials and the development of standardized guidelines, which would be necessary before the potential implementation of such strategies in routine clinical practice. Full article

The autoantibody reactome refers to the multidimensional repertoire of antibody reactivities against self-antigens across the human proteome or selected antigenic compartments. This offers a scalable systemic layer for precision immunology across spontaneous autoimmunity and treatment-induced immune toxicity. Autoimmune diseases and immune-related adverse events (irAEs) share major features of dysregulated immunity, yet clinically useful tools for risk stratification, early detection, endotyping, and treatment guidance remain limited and slow. A central challenge is that tissue pathology is highly informative but not uniformly accessible across diseases and organ systems, whereas routine serology captures only a narrow fraction of immune heterogeneity. In this perspective, I argue that a global autoantibody reactome can serve as a central unifying framework linking systemic immune history, tissue pathology, and clinical trajectories across autoimmune disorders and irAEs. Rheumatoid arthritis (RA) provides a strong prototype because its serological diversity, major role of post-translationally modified autoantigens, and marked synovial heterogeneity allow reactome features to be interpreted against tissue biology. Immune checkpoint inhibitor-associated inflammatory arthritis serves as an illustrative rheumatic irAE and a model of treatment-induced immune dysregulation with clear opportunities for longitudinal blood-based profiling. Spatial transcriptomics and proteomics are therefore positioned not as stand-alone solutions, but as mechanistic tools that can decode reactome-defined immune states within tissue microenvironments where tissue is accessible. Clinical translation will require integration of autoantibody reactomes with tissue, circulating proteomic, imaging, genetic, and clinical data through transparent multimodal models, as well as a shift from exploratory resources such as AAgAtlas toward analytically validated and clinically interpretable biomarker panels for risk prediction, endotyping, monitoring, and biomarker-guided intervention. This perspective outlines technical and strategic steps toward clinically actionable decision support, including risk stratification before ICI initiation and treatment guidance for patients who develop ICI-induced inflammatory arthritis, through integration of autoantibody reactome profiling, spatial omics and transparent multimodal AI. Full article

Background: Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders caused by impaired adrenal steroidogenesis, most frequently due to pathogenic variants in the CYP21A2 gene leading to 21-hydroxylase deficiency (21-OHD). Epidemiology and management vary across the Mediterranean Basin as a result of genetic and healthcare differences. Objective: To provide an overview of the epidemiology, diagnostic approaches and treatment patterns of CAH in Mediterranean countries. Methods: A structured review of the literature was performed using PubMed, using combined disease-related, geographic and methodological terms. Eligible studies reporting on epidemiology, diagnosis, or management of CAH were included. Data on study design, population characteristics, incidence, diagnostics, genetics and treatment availability were extracted. Results: Data were collected from 23 Mediterranean and neighboring regions covering over 8.7 million screened newborns. In countries with established newborn screening (e.g., Spain, Italy, France, Greece), the incidence of classic CAH ranged from 1:10,000 to 1:25,000 live births. Higher rates were reported in parts of North Africa and the Eastern Mediterranean. Diagnostic set-up and access to biochemical and genetic confirmation varied widely. Hydrocortisone remains the primary therapy, while access to mineralocorticoids and modified-release glucocorticoids differed across settings. Conclusions: Overall, considerable heterogeneity in CAH epidemiology and care exists across the Mediterranean region. Genetic factors such as founder effects, consanguinity and healthcare organization contribute to these differences. Expanding newborn screening, improving diagnostics and availability to treatments are critical to reducing disparities in CAH care. Full article

Plants in agricultural systems rarely face single stressors; instead, they encounter concurrent biotic (pathogen, pests) and abiotic (drought, salinity, heavy metals) stresses that causes severely reduce crop yields and endanger food security. The traditional methods of breeding, genetic engineering, and agrochemicals tend to target individual stresses and still do not suffice in the complex field conditions. Compared to these approaches, nanotechnology offers distinct advantages: nanoparticles (NPs) can be applied as foliar sprays or seed treatments without lengthy breeding cycles or regulatory hurdles associated with genetically modified organisms. However, nanotechnology is not inherently “better” but rather complementary to crop engineering; each approach has specific strengths. Breeding and genetic engineering provide heritable, long-term solutions, while nanotechnology offers immediate, season-specific, and reversible interventions. Cross-tolerance, the phenomenon whereby exposure to one stress enhances tolerance to another, offers a promising alternative. This review critically examines how NPs act as stress-priming agents that induce cross-tolerance by activating overlapping defense networks, including antioxidant systems (SOD, CAT, APX), phytohormonal crosstalk (ABA, SA, JA), osmolyte homeostasis, and stress-responsive gene expression. We synthesize current evidence on NP uptake, translocation, and cellular interactions, and evaluate their dual role in directly suppressing pathogens while simultaneously enhancing plant immune responses and physiological resilience. However, efficacy is highly dose-dependent: low, subtoxic doses prime defense through hermetic ROS signaling, whereas supraoptimal doses cause phytotoxicity. The current challenges in nano-mediated stress alleviation include: (i) a persistent laboratory-to-field translation gap, with field outcomes averaging only 60–70% of greenhouse efficacy; (ii) dose-dependent phytotoxicity; (iii) poor reproducibility across studies; (iv) scalability and formulation stability issues; and (v) insufficient understanding of long-term environmental fate, including soil accumulation, non-target organism effects, and food chain safety. Future research should consider field-validated formulations (e.g., SiNPs, ZnONPs, Fe₃O₄NPs) across major staple crops); integrating nanotechnology with precision agriculture through nanosensors, remote sensing, and artificial intelligence for site-specific, dose-optimized applications;developing smart, biodegradable nanoparticles with stimuli-responsive release; and establishing harmonized regulatory frameworks for nano-agrochemical approval. When deployed responsibly, nanoparticle-induced cross-tolerance represents a sustainable approach to improve crop resistance against multifactorial stress, with significant implications for climate-resilient agriculture and global food security. Full article

In the European Union, mandatory labeling of food and feed products is required when authorized genetically modified organisms (GMOs) exceed 0.9% per ingredient, necessitating reliable analytical methods for official control laboratories. Event-specific PCR assays validated according to ISO/IEC 17025 are the reference approach for GMO detection, identification, and quantification. The growing use of digital PCR (dPCR) has encouraged the adaptation of real-time PCR methods to dPCR-based strategies, as dPCR enables absolute quantification without calibration standards, shows reduced sensitivity to inhibitors, and allows for the design of a multiplex assay. In this study, an in-house validation of a duplex dPCR assay targeting the maize GM event NK603 and the HMG reference gene was performed on three platforms: Bio-Rad QX200™ (Pleasanton, CA, USA), Qiagen QIAcuity (Venlo, The Netherlands), and Thermo Fisher QuantStudio Absolute Q (Waltham, MA, USA). All validation parameters met the Joint Research Centre (JRC) acceptance criteria. In particular, this assay demonstrated high specificity, sensitivity (limit of quantification or LOQ < 35 copies per reaction), precision, and trueness (RSDr and bias <25%). The data indicate that the duplex dPCR assay can be used for routine GMO analysis and future collaborative validation studies. Full article

Kopi Luwak (civet coffee), produced from coffee beans recovered from the feces of the Asian palm civet, is among the most expensive specialty coffees worldwide for its unique sensory characteristics. In this study, a multi-omics strategy was employed to elucidate the impact of drying on the microbial community structure and metabolic profiles of Typica Kopi Luwak beans. Drying induced pronounced shifts in the microbial composition, with a significant enrichment of Sphingobacterium and depletion of Streptococcus at the genus level. Concurrently, drying resulted in substantial metabolic remodeling, characterized by increased levels of prenol lipids, fatty acyls, carboxylic acids and derivatives, steroids and steroid derivatives, and organooxygen compounds, accompanied by a marked reduction in flavonoids. KEGG pathway analysis indicated that both altered microbial taxa and metabolites were associated with lipid metabolism, carbohydrate metabolism, amino acid metabolism, and the biosynthesis of other secondary metabolites. Correlation network analysis further revealed the associations between key microbial genera and specific classes of differential metabolites. Collectively, these findings suggest the potential role of post-excretion sun-drying in shaping the microbiome and metabolome of Typica Kopi Luwak beans, offering a scientific basis for controlled or in vitro fermentation strategies to produce coffees with reproducible quality attributes. Full article

A quartz crystal microbalance-based biosensor for the specific detection of the first transgenic common bean (L.) cultivar (BRS FC401 RMD) with resistance to Bean golden mosaic virus (BGMV) was developed. The immobilization chemistry relies on the strong bond between the thiolated probe and the gold electrode surface. The probe sequence is internal to a region of the BGMV rep gene that was introduced into the common bean genome. The sensor’s analytical performance was determined using synthetic oligonucleotides. Real samples of transgenic and wild-type bean seeds were also tested. Sample pretreatment consisted only of enzymatic fragmentation, followed by a thermal denaturation step combined with blocking oligonucleotides. Different biosensor regeneration approaches were studied. Immobilization showed good reproducibility (CV% of 5.8%). The biosensor proved specific for both synthetic oligonucleotides and non-amplified genomic DNA. A linear detection range of 0–1.4 ng/µL was observed, with a detection limit of 0.18 ng/µL. Three sequential detections were performed without loss of surface activity. The results demonstrate the biosensor’s potential for direct, real-time, label-free detection of DNA samples for field screening of transgenic common bean cultivars. Full article

Lumbar spine disorders often require surgical intervention using medical implants to stabilize or replace damaged structures. As the prevalence of these surgeries increases due to an aging population, rigorous preclinical evaluation is critical. This narrative review aims to summarize current testing methods, identify gaps in clinical translatability, and explore the role of emerging computational technologies. Mechanical testing protocols established by the American Society for Testing and Materials (ASTM) and the International Organization for Standardization (ISO) provide essential standardized data on structural integrity but fail to replicate the complex biological interactions of the human spine. Similarly, animal models offer insights into biological responses like osseointegration but are limited by quadrupedal biomechanics and anatomical differences. Recent advancements in Artificial Intelligence (AI) and Finite Element Analysis (FEA) enable rapid, patient-specific modeling and high-throughput screening, significantly reducing the time and cost of physical testing. Future innovations include 3D-printed personalized implants, bio-responsive materials, and genetically modified animal models to bridge existing translatability gaps. In conclusion, improving the clinical success of lumbar spine implants requires an integrated framework that combines mechanical, biological, and computational approaches. This interdisciplinary collaboration is vital for developing safer and more effective treatments for patients. Full article

Acinetobacter baumannii has emerged as one of the most challenging opportunistic pathogens in modern healthcare due to its remarkable ability to acquire and disseminate antimicrobial resistance determinants. Carbapenem-resistant A. baumannii (CRAB) is now recognized by the World Health Organization as a critical priority pathogen, highlighting the urgent need for improved diagnostic, surveillance, and therapeutic strategies. This review synthesizes current evidence on the relationship between phenotypic antimicrobial susceptibility patterns and underlying genetic determinants of resistance in A. baumannii. A structured literature search was conducted across major biomedical databases (PubMed/MEDLINE, Scopus, Web of Science, and the Cochrane Library), supplemented by citation tracking and relevant institutional sources, focusing on studies published between 2016 and 2026. The analysis integrates findings from studies examining phenotypic antimicrobial susceptibility testing (AST) with molecular and genomic investigations of resistance mechanisms, including carbapenemases, aminoglycoside-modifying enzymes, efflux pumps, and resistance-associated genomic islands. Particular attention is given to the complex and sometimes discordant relationship between genotype and phenotype, where the presence of resistance genes does not always translate directly into phenotypic resistance due to regulatory mechanisms, gene expression variability, and genomic context. The review further discusses methodological differences in AST standards and genomic prediction approaches that may contribute to variability across studies. Collectively, the evidence supports a multidimensional interpretation of antimicrobial resistance in A. baumannii, emphasizing the necessity of integrating phenotypic and genotypic data for accurate diagnostics, surveillance, and clinical decision-making. This integrated perspective may contribute to improved understanding of resistance evolution and support the development of more effective strategies for managing multidrug-resistant A. baumannii infections. Full article

Background: Infectious hematopoietic necrosis virus (IHNV), a rhabdovirus classified within the genus Novirhabdovirus, continues to be one of the most detrimental pathogens impacting salmonid aquaculture on a global scale. Notable for inducing high mortality rates among fry and fingerlings, IHNV represents a substantial threat to the economic stability of the aquaculture industry. This review offers an in-depth analysis of the contemporary advancements in IHNV vaccine development. Methods: We assess the efficacy and immunological mechanisms of traditional vaccine platforms, including inactivated and live-attenuated vaccines, while emphasizing the groundbreaking success of DNA vaccines, particularly those encoding the viral glycoprotein (G). Although nucleic acid-based therapies provide high levels of protection, they face logistical challenges related to delivery and regulatory obstacles associated with Genetically Modified Organisms (GMOs). Additionally, we examine emerging “next-generation” platforms, such as viral vector vaccines, subunit proteins produced in yeast or plant systems, and RNA-based technologies. We critically analyze technical bottlenecks, including the lack of efficient mucosal delivery systems and the limited understanding of long-term cellular memory in teleosts. Results: We propose future research directions that emphasize the development of multivalent formulations and the incorporation of molecular adjuvants to augment mucosal immunity. Conclusions: This synthesis seeks to integrate fundamental viral pathogenesis with applied immunology to develop a strategic framework for the sustainable, long-term management of IHNV in global salmonid populations. Full article