Search Results (3,500)

Endometriosis is characterized by enhanced cellular proliferation, migration, and resistance to apoptosis, contributing to lesion persistence and progression. Targeting cellular plasticity and mesenchymal-associated functions may therefore represent a promising therapeutic strategy. Here, we investigated the effects of Pelargonium graveolens essential oil (PGEO) on proliferation, apoptosis, migration, cytoskeletal organization, transcriptional regulation, and metabolic alterations in human endometriotic 12Z cells. PGEO treatment suppressed proliferative capacity in a concentration-dependent manner and significantly impaired cell migration, accompanied by reduced β-tubulin expression and decreased levels of mesenchymal-associated markers CD73 and CD105. Increased GRP78 expression together with ultrastructural alterations, including cytoplasmic vacuolization and mitochondrial and endoplasmic reticulum changes, indicated activation of cellular stress responses. Although transcriptional analysis revealed increased CCND1 and PIK3CA mRNA levels, these changes did not parallel the observed suppression of proliferation, suggesting compensatory regulatory responses. Untargeted metabolomic profiling revealed alterations in energy metabolism characterized by increased levels of glycolysis-related metabolites, reduced levels of several amino acids including glutamine and histidine, and changes in lipid-associated metabolites. Collectively, these findings demonstrate that PGEO suppresses proliferative and migratory behavior in endometriotic cells while modulating cytoskeletal, transcriptional, and metabolic pathways, highlighting its potential as a candidate for further investigation in endometriosis-targeted therapeutic strategies. Full article

Prostate cancer, particularly metastatic castration-resistant prostate cancer (mCRPC), presents therapeutic challenges rooted in adaptive lineage plasticity and neuroendocrine transdifferentiation. Conventional genome-based models fail to account for the divergent clinical trajectories observed among tumors that share identical driver mutations. This limitation requires reconceptualizing cancer as a dynamic system in which tumor cells can execute context-dependent molecular programs governed by epigenetic and transcriptional network remodeling. This review critically evaluates three convergent technological pillars reshaping prostate cancer research and clinical care. First, conditional reprogramming (CR) enables the rapid generation of patient-derived models that preserve genomic fidelity, intratumoral heterogeneity, and reversible phenotypic plasticity without genetic manipulation. Second, single-cell and spatial multi-omics approaches have clarified the cellular trajectories underlying luminal-to-neuroendocrine transdifferentiation, identifying a therapeutically actionable intermediate state. They have revealed the hierarchical transcription factor network (FOXA2–NKX2-1–p300/CBP) which orchestrates chromatin remodeling during this lethal transition. Third, physics-informed machine learning and digital twin architectures aim to move beyond correlative risk prediction toward mechanistically sound forecasting of tumor evolution, treatment response, and resistance emergence. We address unresolved challenges in prospective clinical validation, spatial heterogeneity capture, regulatory pathways for functional diagnostics, and the imperative for causal, as opposed to associative, inference from perturbational datasets. The integration of these three domains through closed-loop experimental–computational feedback cycles represents a paradigm shift from reactive to anticipatory precision oncology. Full article

Polysialic acid (PSA), a highly negatively charged glycan attached mainly to the neural cell adhesion molecule (NCAM), is emerging as a critical but underrecognized extracellular regulator of glutamatergic neurotransmission. While previous literature has focused on PSA’s developmental roles, increasing evidence indicates that PSA–NCAM also contributes to synaptic plasticity mechanisms in the mature brain. This review integrates evidence from structural biophysics, single-channel electrophysiology, and disease models to explain how PSA modulates glutamate receptor gating to control learning and memory. We synthesize findings from biochemical reconstitution, electrophysiological recordings, and in vivo studies to show that PSA can modulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor open probability, burst duration, and cooperative gating without affecting conductance, thereby promoting long-term potentiation. Conversely, PSA selectively suppresses GluN2B-containing extrasynaptic N-methyl D-Aspartate (NMDA) receptor activity by lowering open probability and calcium influx, maintaining an optimal balance between potentiation and depression while providing neuroprotection. Disruption of PSA–NCAM signaling in developmental and disease models, including prenatal cannabinoid exposure and neurodegeneration, produces cognitive deficits reversible by PSA restoration. Notably, much of the current evidence derives from in vitro systems, with relatively few studies conducted in vivo, and studies employing PSA mimetics mostly, which should be considered when interpreting physiological relevance. Collectively, the available evidence suggests that PSA functions as an extracellular modulator linking synaptic glycans to glutamate receptor regulation and plasticity related signaling pathways, highlighting the potential importance of extracellular glycan mechanisms in the control of synaptic function. Full article

The continuous accumulation of micro- and nanoplastics in the human living environment and their deposition in various organs of the body have become a global public health concern with the widespread use of plastic products. This review summarizes the main categories of micro- and nanoplastics entering the body through dietary intake and air inhalation, based on human exposure pathways. By integrating existing literature data, this study estimated the daily intake and excretion of micro- and nanoplastics in humans based on published data, summarized evidence regarding their potential deposition patterns in blood cells and hematopoietic-related organs, mainly inferred from animal and in vitro studies, and discussed the possible impacts of such deposition on hematopoietic function. Furthermore, the toxicity effects and potential hazards of micro- and nanoplastics on the human hematopoietic system at both cellular and animal levels, along with the underlying molecular mechanisms, were comprehensively reviewed. From the dual perspectives of environmental governance and bodily protection, exploratory research ideas are proposed, including biodegradation strategies and the application of medicinal and edible homologous substances. This aims to provide insights for reducing the risk of hematopoietic system diseases and preventing harm caused by micro- and nanoplastics to the human body in the future. Full article

Glioblastoma (GBM) is the most aggressive and prevalent primary brain tumor in adults, characterized by rapid growth, diffuse infiltration, and a dismal prognosis. Despite advances in conventional therapies, the median survival remains approximately one year, emphasizing the urgent need for novel therapeutic strategies. GD2, a disialoganglioside overexpressed in several malignancies, has been implicated in tumorigenesis and metastasis and has been identified as a cancer stem cell marker. While previous reports have identified high levels of GD2 expression in gliomas compared to normal brain tissue, its role in GBM stemness remains controversial. In this study, we revisited prior findings refuting GD2′s involvement in GBM stemness by replicating key tumorigenesis experiments and further explored its impact on stemness properties such as migration and metabolic plasticity. Additionally, a phytochemical screen was used to identify natural compounds as potential inhibitors targeting GD2-mediated tumorigenesis. Our findings aim to clarify GD2′s role in GBM and provide insights into novel therapeutic interventions. Full article

Inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn’s disease, are associated with an increased risk of colorectal cancer through mechanisms driven by persistent mucosal inflammation. Chronic inflammatory signaling, recurrent epithelial injury, and altered tissue repair processes progressively reshape the intestinal microenvironment, promoting genomic instability and facilitating the development of colitis-associated colorectal cancer (CAC). Despite the well-established link between inflammation and tumorigenesis, only a subset of patients with long-standing IBD develops malignancy, highlighting the complexity of the regulatory effects of the ongoing inflammation on the tumor initiation and progression. This review discusses the multifaceted roles of innate and adaptive immune responses in CAC pathogenesis. Innate immune signaling mediated by pattern recognition receptors, particularly Toll-like receptors, integrates microbial and damage-associated signals to activate inflammatory pathways that regulate epithelial proliferation, survival, and tumor-promoting cytokine networks. Tumor-associated macrophages, neutrophils, and myeloid-derived suppressor cells contribute to carcinogenesis by sustaining chronic inflammation, promoting immunosuppression, and remodeling the tumor microenvironment, although under specific conditions these cells can also support antitumor immunity. Innate lymphocyte subsets participate in immune surveillance and epithelial homeostasis, yet may also amplify inflammatory circuits that influence tumor development. Adaptive immune populations further shape CAC evolution, as CD4⁺ T-helper subsets, CD8⁺ cytotoxic T lymphocytes, regulatory T cells, and B cells exert divergent effects depending on cytokine milieu, immune context, and disease stage. Understanding immune-cell plasticity and the molecular pathways governing these processes may facilitate the identification of predictive biomarkers and the development of targeted immunomodulatory strategies aimed at preventing CAC. Full article

Fetal therapy has evolved into a rapidly advancing field with the potential to alter the natural history of many severe congenital and genetic disorders before irreversible injury occurs. Progress in prenatal imaging, molecular diagnostics, and fetal intervention techniques now enables the earlier identification of disease and, in select settings, targeted prenatal treatment. This review synthesizes the current landscape of fetal therapies, spanning established surgical interventions for structural anomalies and emerging biologic and molecular approaches, including enzyme replacement therapy, stem cell-based strategies, gene therapy, and gene editing. The intrauterine environment provides a distinct therapeutic context, with developmental plasticity, immune immaturity, enhanced tissue accessibility, and relatively permissive central nervous system exposure that together define a time-sensitive window for intervention. Preclinical studies and early clinical experience across both structural anomalies and genetic disorders, including lysosomal storage disorders, osteogenesis imperfecta, and spinal muscular atrophy, support the premise that prenatal treatment can preserve organ development and improve pediatric outcomes. However, translation remains constrained by procedural risks, uncertainty regarding long-term safety and durability, ethical and regulatory complexities, and challenges with equitable access, alongside the need for robust comparative evidence versus early postnatal therapy. As the field advances, multidisciplinary collaboration, rigorous trial design with meaningful developmental endpoints, and ethically grounded implementation frameworks will be essential to guide responsible clinical adoption and maximize benefit for children and families. Full article

Transposable elements (TEs) are major contributors to genome plasticity and can reshape gene regulation through stress-responsive activation and the formation of TE-gene chimeric transcripts. Although therapeutic stress is known to perturb transcriptional networks in cancer cells, its impact on canonical TE transcription and TE-gene chimera formation in esophageal squamous cell carcinoma (ESCC) remains poorly defined. To address this, we performed a comprehensive transcriptome-wide analysis of TE expression and TE-gene chimeric transcripts in KYSE150 ESCC cells following combined 125I radiation and carfilzomib treatment. The TE analysis showed 148 dysregulated TEs, characterized by ERV1 LTR element enrichment and distinct treatment-control sample separation, indicating structured remodeling of the TE transcriptome. We identified 301 significant TE-gene chimeric events, indicating category-specific remodeling with an increase in TE-initiated and TE-exonic chimeras and a decrease in TE-terminal events. The TE families that underwent the most transcriptional changes were not those that drove chimeric events, indicating that global TE activation does not passively cause chimera remodeling. The gene repression was strongly associated with chimeric transcripts, and gene expression changes were negatively correlated with chimerism frequency. SPANXN1, IL1RL1, and RSAD2, strongly downregulated genes, produced novel TE-derived isoforms and were high-potential functional candidates. Epigenetic context analysis showed considerable overlap between exonized chimeras and candidate cis-regulatory elements, suggesting a potential association with regulatory genomic contexts. Pathway enrichment analysis showed synchronized transcriptomic reprogramming and cell cycle and DNA repair pathway activation and autophagy inhibition. In esophageal cancer cells, concurrent genotoxic and proteotoxic stress causes complex TE remodeling, linking traditional TE transcriptional alterations to structured TE-gene chimera development and stress-related transcriptome reprogramming. Full article

Colorectal cancer (CRC) is a heterogeneous disease driven by complex genetic, epigenetic, and microenvironmental alterations. Members of the PR domain-containing (PRDM) protein family have emerged as context-dependent regulators of CRC initiation, progression, tumor cell plasticity, immune modulation, and therapeutic response. Accumulating evidence highlights divergent roles for PRDM proteins as tumor suppressors, oncogenes, or isoform-dependent dual-function regulators. Collectively, PRDM family members represent a central node of transcriptional/epigenetic control in CRC biology, with significant potential as biomarkers for early detection, prognosis, and treatment stratification, as well as promising candidates for epigenetic and pathway-directed therapeutic strategies. Full article

The Amazonian açaí waste is promising for producing charcoal through pyrolysis and bioenergy through combustion, but the property losses from its poor disposal in the environment remain unknown. Therefore, this work aimed to analyze how different storage conditions of the açaí waste over time, which mimic the reality throughout the Amazon, modify its bioenergetic properties. The samples were stored in a covered greenhouse for nine months in the following conditions: immersed in water, on the soil, and in open plastic bags. The biomass was analyzed by Fourier-transformed near-infrared spectroscopy, physical properties, stereomicroscopy, proximate composition, and thermogravimetry. The degraded waste showed endocarp attack and fungi proliferation. The chemical groups of primary cell wall components were concentrated, unlike water-soluble materials, raising the fixed carbon from 22% to 25% after 30 days. Consequently, higher heating values were kept (≈19 MJ/kg). However, water immersion storage sharply decreased the waste basic density from 0.81 g/cm³ to 0.56 g/cm³, dropping the energy density from 12 GJ/m³ to 8 GJ/m³. Moreover, storage raised ash content from 1.1% up to 1.9%. The storage hindered the start of the main phases of combustion and pyrolysis, which were later intensified, especially for soil-stored waste. Therefore, more stable combustion and pyrolysis require fresh waste. Besides natural drying, plastic bag storage over time kept the waste quality closer to that of the fresh waste. Full article

Ribosomes are widely recognized as large intracellular macromolecular complexes responsible for protein synthesis. However, in recent years, numerous studies have revealed that ribosomal proteins possess non-canonical functions beyond translation, including roles in cell fate regulation, development, and disease. This review outlines emerging concepts surrounding the extracellular functions of ribosomes, with a particular focus on ribosome-induced cellular plasticity and transdifferentiation. Our studies have demonstrated that the incorporation of exogenous ribosomes reprograms somatic cells into a multipotent state and promotes differentiation into multiple lineages. These findings represent an alternative perspective to the conventional view of ribosomes as merely translational components. Furthermore, we discuss the biological significance of factors secreted by ribosome-incorporated cells by integrating the paracrine hypothesis with ribosome-mediated cell fate conversion. Finally, we explore the potential applications of ribosomes in regenerative medicine and cell-cultured food production. By redefining ribosomes as active regulators of cellular identity, this review provides a conceptual framework for understanding ribosome-driven cell fate regulation and its potential applications in sustainable biotechnology. Full article

Brain-Derived Neurotrophic Factor (BDNF), a key member of the neurotrophin family, is critically involved in neuronal survival, synaptic plasticity, learning, and memory. While its roles in mammals have been extensively documented, the molecular regulatory mechanisms governing BDNF expression and its causal contributions to complex cognitive behaviors remain poorly understood in non-mammalian vertebrates—particularly for the domestic pigeon (Columba livia domestica), a species distinguished by its remarkable spatial navigation and homing capabilities. This review synthesizes the current evidence on BDNF in the pigeon central nervous system across five thematic domains: molecular structure and isoform diversity, transcriptional and epigenetic regulatory networks, involvement in neural development, associations with cognitive and navigational behaviors, and potential translational applications. A particular emphasis is placed on the region-specific and activity-dependent expression patterns of BDNF in brain structures such as the hippocampal formation (HF), optic tectum, and striatum, and their functional relevance to visual processing, homing behavior, and stress adaptation. To date, most findings remain correlational; therefore, establishing a mechanistic understanding necessitates the integration of advanced methodologies—including single-cell omics, CRISPR-based gene editing, and high-resolution behavioral phenotyping—to causally link BDNF dynamics, neural circuit modulation, and spatial cognition. This synthesis aims to bridge gaps in comparative neurobiology, inform molecular approaches to avian cognitive enhancement, and support evidence-based strategies for racing pigeon breeding and welfare assessment. Full article

Chemotherapy resistance remains a major obstacle to durable cancer control, yet its underlying mechanisms cannot be fully explained by genetic mutations alone. Increasing evidence suggests that therapeutic stress induces dynamic adaptive programs that reshape tumor phenotypic landscapes. Here, we propose a systems-level framework in which chemotherapy resistance emerges from the stabilization of interconnected stress-response circuits integrating redox signaling, metabolic reprogramming, and transcriptional plasticity. In this model, cytotoxic therapies function as state-generating perturbations that elevate oxidative stress and activate adaptive buffering systems, including NADPH-dependent redox homeostasis, replication stress tolerance, and integrated stress response (ISR)-mediated translational reprogramming. These adaptive modules collectively expand the accessibility of therapy-tolerant phenotypic states within tumor cell populations. Importantly, these circuits coordinate mitochondrial redox homeostasis, metabolic NADPH regeneration, and epigenetic–transcriptional plasticity to sustain cellular survival under persistent oxidative pressure. Such adaptive redox networks not only stabilize stress-tolerant phenotypes but also create vulnerabilities that can be therapeutically exploited. From a translational perspective, this framework suggests that effective strategies to overcome chemotherapy resistance should move beyond single-target inhibition and instead focus on circuit-guided therapeutic interventions that simultaneously destabilize redox buffering systems, constrain phenotypic plasticity, and disrupt metabolic stress adaptation. By conceptualizing therapy resistance as a dynamic redox-regulated state-space phenomenon, this model provides a mechanistic foundation for the development of evolution-aware and plasticity-constraining therapeutic strategies. Targeting the coordinated redox–metabolic–translational circuits that maintain tumor adaptability may therefore represent a promising direction for next-generation redox therapeutics in cancer. Full article

Adult acute lymphoblastic leukemia (ALL) is a highly heterogeneous hematologic malignancy where treatment response and relapse risk do not exclusively rely on the identification of genetic lesions but also on dynamic biological states sustained by specific transcriptional and epigenetic programs. Although the integrated application of multi-omics approaches has significantly expanded our knowledge of oncogenic dependencies, cellular plasticity, and mechanisms of therapeutic resistance, its systematic translation into the clinical practice of adult ALL is yet to become a reality. The aim of this review is to provide a critical and focused synthesis on how the integration of genomics, transcriptomics, and epigenetics enables the interpretation of disease biological behaviors and may guide personalized therapeutic strategies while simultaneously addressing the major limitations that hinder clinical implementation. Genomics allows for the identification of driver events and pharmacologically actionable vulnerabilities, whereas transcriptomics, including single-cell analyses, reveals functional states associated with clonal persistence, glucocorticoid resistance, and therapeutic adaptation, even in the absence of new mutations. In parallel, epigenetic signatures emerge as key elements in stabilizing oncogenic programs and resistant phenotypes, contributing to the biological plasticity of leukemic cells and representing potentially reversible therapeutic targets. Taken together, multi-omics signatures provide an integrated functional readout of adult ALL and support a dynamic precision-medicine model. However, adaptive therapeutic decisions aimed at relapse prevention require the full integration of these approaches through standardized strategies, longitudinal studies, and a sustainable implementation of molecular profiling and minimal residual disease monitoring. Full article

Bisphenol A (BPA) has long been used in plastics, resins, and food packaging materials; however, extensive research has demonstrated its reproductive, developmental, and endocrine-disrupting effects. Consequently, BPA has been increasingly restricted and replaced with structural analogues. Among these, tetramethyl bisphenol F (TMBPF) has emerged as one of the most widely used substitutes, particularly in epoxy resins and food-can coatings. Although initially regarded as a safer alternative, accumulating evidence suggests that TMBPF may exert multiple toxicological effects, raising concerns about its potential developmental neurotoxicity. The present study aimed to investigate the neurodevelopmental effects of TMBPF using both in vitro and in vivo approaches. First, a developmental neurotoxicity assay employing Sox1−GFP mouse embryonic stem cells was used to evaluate cytotoxicity using the cell counting kit-8 assay and neural differentiation based on green fluorescent protein (GFP) fluorescence intensity. The results indicated developmental neurotoxic potential according to the established discrimination index. Subsequently, pregnant and lactating mice were exposed to TMBPF daily from gestational day 10.5 to postnatal day 20, and their offspring were assessed for behavioral performance as well as changes in the expression of neurodevelopment-related genes in the brain. Behavioral analyses encompassed multiple domains, including memory and learning, social behavior, anxiety-related responses, and spontaneous locomotor activity, suggesting alterations in these functional outcomes. Molecular analyses further demonstrated changes associated with dopaminergic and cholinergic signaling, synaptic plasticity, neuronal activity markers, neuropeptides, and inflammatory pathways. Collectively, these findings provide the first evidence in a mammalian model that maternal exposure to TMBPF may influence offspring neurodevelopment. These findings suggest potential implications for human exposure to TMBPF, particularly through food-contact materials, and warrant further mechanistic and dose–response studies. Full article