Biology and Life Sciences

Abstract: Taste buds are continuously renewed sensory organs in which development, adult maintenance, and repair share overlapping molecular circuitry. During embryogenesis, WNT/β-catenin signaling promotes taste placode formation and placodal Shh expression, whereas SHH refines papilla spacing and restricts neighboring papilla formation. SOX2 functions as a taste-competence and progenitor-maintenance factor. In adults, LGR5/LGR6-RSPO-WNT signaling sustains progenitor activity, and gustatory neurons provide RSPO2 as a niche signal that maintains epithelial renewal. HH signaling from epithelial and neuronal sources further supports SOX2-dependent progenitor homeostasis. Lineage allocation is controlled by transcriptional programs that include POU2F3/SKN-1a for sweet, umami, and bitter type II taste receptor cells and ASCL1 with posterior-field NKX2-2 for type III presynaptic/sour cells. After denervation or irradiation, regeneration depends primarily on LGR5+/KRT14+ progenitors and may be supplemented, in specific injury contexts, by plasticity of a subset of K8-lineage taste receptor cells that acquire KRT14/SOX2/PCNA progenitor-like features. Key unresolved issues include the direct chromatin targets of taste lineage regulators (which remain to be defined by ChIP-seq in native taste progenitors), the identity of the type I cell selector, the contribution of dedifferentiation across injury models, and the extent to which mouse-derived networks are conserved in human taste biology.

Abstract: Mid-stage embryos of different species often look more alike than early embryos or adults. Early and late development diverge, leading to a broad-narrow-broad hourglass pattern. I propose that mid-embryogenesis coincides with protocol waists, narrow interfaces that standardize communication between otherwise distinct processes. For example, continuous spatial geometry is translated into a morphogen gradient protocol readable by gene regulatory networks. This architecture arises because the physical space-time geometry of early development cannot directly instruct late gene regulatory programs. They require a translator. The need for domain translation distinguishes protocols from generic canalization and bottlenecks. Translation protocols explain the hourglass: a protocol screens off upstream inputs, allowing early diversification, and decouples downstream responses, enabling late radiation. A protocol waist often remains evolutionarily frozen as the essential common language that keeps these diverging halves compatible. Perturbations of protocol waists tend to cause widespread system failure, concentrating fragility. Protocol waists provide a framework to interpret domain translators, such as morphogen gradients for geometry-to-molecules, Notch/Delta lateral inhibition for topology-to-fates, the vertebrate segmentation clock for time-to-space, and Hox axial patterning for position-to-identity. Sequential domain translators form a protocol stack, matching the common architecture of robust complex systems in engineering.

Abstract: Human language continuously generates patterned mechanical vibrations, yet the cellular consequences of such structured sound remain largely unexplored. Here, we investigate whether acoustic vibration with different degrees of temporal and spectral organization modulates actin cable architecture and polarity in the non auditory eukaryote Saccharomyces cerevisiae. Using a direct contact stimulation setup, yeast cells expressing ABP140- GFP were exposed to sustained tonal sound, broadband white noise, or brief consonant like acoustic bursts designed to isolate speech relevant temporal structures without semantic content. Sustained tonal stimulation, characterized by rhythmic continuity and harmonic coherence similar to vowel like components of speech, increased ABP140- GFP signal intensity,actin branching and actin length and significantly enhanced shmoo formation. In contrast, broadband noise disrupted actin organization and suppressed shmooing, while transient consonant like bursts produced no measurable structural effects. These results indicate that language related acoustic structure, specifically sustained and coherent mechanical vibration, can modulate cytoskeletal organization in yeast, supporting the view of sound and speech as biologically active mechanical inputs rather than purely communicative signals.

Abstract: The retina and optic nerve rely on a tightly regulated neurovascular unit that sustains the highly dynamic and metabolically demanding neural tissues required for vision. Adequate oxygen and nutrient delivery are essential for maintaining tissue function and cellular survival. Over the past decades, extensive research within and beyond the field of ophthalmology has sought to elucidate the mechanisms that govern neurovascular regulation in health and disease. Growing evidence indicates that neurovascular dysfunction plays an important role in both the initiation and progression of glaucoma, a leading cause of irreversible blindness worldwide. Alterations in vascular architecture and blood flow may compromise the metabolic support required by retinal ganglion cells, increasing their vulnerability to injury and degeneration. While neurons possess limited regenerative capacity, the vascular system retains a remarkable degree of plasticity and is therefore amenable to repair. This vascular plasticity presents an opportunity to develop therapeutic strategies aimed at restoring vascular architecture and improving blood flow, complementing existing approaches focused on intraocular pressure reduction, neuroprotection, axonal regeneration, and/or neuronal transplantation. In this review, we summarize the current understanding of neurovascular function in the healthy eye, discuss mechanisms that contribute to vascular compromise in glaucoma, and highlight emerging avenues for promoting vascular regeneration and blood flow recovery. By identifying key knowledge gaps and future research priorities, we aim to outline promising directions for targeting the ocular neurovasculature to preserve retinal ganglion cell function and slow or stop progressive vision loss.

Abstract:

Background: Mesangiogenic Progenitor cells (MPCs) were first described in 2008 in cultures of human bone marrow mononuclear cells (hBM-MNCs) aimed at isolating mesenchymal stromal cells (MSCs) using human autologous serum. A selective culture method was subsequently developed to isolate MPCs with a high degree of purity, yielding approximately 1% of the total plated cells. Since their initial description, MPCs have demonstrated the ability to differentiate into highly clonogenic MSCs while retaining early vasculogenic potential. Gene expression profiling of MPCs revealed constitutive expression of pluripotency-associated transcription factors such as OCT-4 and NANOG, as well as SOX15 instead of SOX2, suggesting a possible molecular mechanism that sustains MPC plasticity, defined as the “adult Oct-4 circuit”. Although the expression of these pluripotency-associated markers has been hypothesized to represent a distinctive adult molecular circuit, concerns regarding the tumorigenic potential of MPCs are reasonable and have not yet explored. Methods: Here, we present data from the tumorigenicity test in partial compliance with WHO recommendations of two different MPC-derived cell products in athymic nude mice. Results: Histomorphometric analysis of nodules excised from animals at 6, 8, or 12 weeks post-cell transplantation excluded tumor formation and demonstrated the ability of MPCs to generate homogeneous and organized tissue through distinct phases: an “early” vasculogenic phase, followed by remodeling of the newly formed microvascular network and the deposition of structured, aligned collagen fibers. Conclusions: MPCs do not possess intrinsic tumorigenic potential and spontaneously form vascularized xenogenic tissue four weeks after injection into the subcutaneous space.

Abstract: Circadian rhythms are fundamental regulators of bone remodeling, orchestrating the co-ordinated actions of osteoblasts, osteocytes, and osteoclasts. Recent studies have high-lighted how core clock genes, such as Bmal1, Clock, Per1/2, and Cry1/2, exhibit rhythmic expression in bone tissue and modulate key markers of bone formation and resorption. Disruptions in circadian regulations, whether caused by environmental factors or genetic alterations, have been linked to osteoporosis, impaired fracture healing, and increased risk of bone fragility. This review provides a comprehensive evaluation of current experi-mental models used to study circadian regulation in skeletal biology, including in vivo, ex vivo, and in vitro approaches. We summarize their respective advantages and limitations and outline the molecular and cellular markers employed to assess circadian function in bone cells. We also discuss the emerging co-culture models and human-relevant plat-forms, for their potential to bridge the gaps between mechanistic research and transla-tional applications. By comparing model characteristics and highlighting integrated re-search strategies, this review aims to advance circadian bone research and inform future investigations into potential temporal aspects of skeletal health.

Abstract: Caspases orchestrate metazoan apoptosis, regulating processes such as embryogenesis, the death of old and infected cells and immune tolerance. Structural orthologs of caspases have been identified in bacteria, plants, protists and fungi and regulated cell death has been demonstrated in these organisms. This led some researchers to conclude that fungal metacaspases might perform a similar function to caspases. This review discusses regulated cell death, beginning with an account of RCD and the central role of caspases in mammalian RCD. It goes on to give examples of RCD in fungi, compares the structure and activity of caspase orthologs and outlines examples of metacaspase-dependent and metacaspase-independent cell death in fungi, focusing on S. cerevisiae. Finally, it addresses the question “are metacaspases caspases?”, identifies alternative cell death proteases and recommends future research objectives.

Abstract: Background: Primary cells derived from connective tissues contain mesenchymal stem/stromal cell (MSC)–like progenitors with chondrogenic potential relevant for cartilage repair. However, donor‑ and tissue‑specific variability and the lack of robust, high‑throughput analytical methods limit their translational use. Objectives: This study aimed to develop and optimize a fast, reproducible high‑content imaging workflow for quantitative evaluation of chondrogenesis in three‑dimensional (3D) spheroids derived from primary cells. Methods: Primary human cells isolated from cartilage were chondrogenically differentiated in vitro. A systematic optimization of immunofluorescence staining parameters was performed, including staining platform, enzymatic matrix digestion, non‑specific site blocking, membrane permeabilization, and nuclear counterstaining. Type II collagen was detected using an Alexa Fluor 488–conjugated antibody, and spheroids were analyzed using high‑content non-confocal imaging. Fluorescence intensities were normalized to spheroid area to account for size‑dependent effects. Results: Staining directly in imaging plates enabled streamlined high‑content analysis. Controlled pepsin‑mediated matrix digestion markedly enhanced antibody penetration, while excessive digestion compromised spheroid integrity. Extended bovine serum albumin blocking improved type II collagen signal intensity and homogeneity. Triton X‑100 permeabilization increased detection sensitivity but occasionally induced structural disruption in weakly organized control spheroids. The optimized protocol enabled clear discrimination between chondrogenic spheroids and controls, with approximately threefold higher type II collagen signal in chondrogenic samples. Conclusions: This study establishes a standardized, high‑content imaging–based workflow for quantitative assessment of 3D chondrogenesis from primary cells. The approach provides a rapid, scalable platform with direct relevance for in vitro screening, potency testing, and quality control in cartilage‑oriented advanced therapy development.

Abstract: Rho GTPases—including RhoA, Rac1, and Cdc42—are key molecular switches that regulate cytoskeletal dynamics and transduce biochemical and mechanical signals essential for skeletal and dental tissue development. These small GTPases orchestrate fundamental cellular processes such as proliferation, migration, polarity, and differentiation, thereby guiding the morphogenesis, homeostasis, and regeneration of bone and teeth. In bone, Rho GTPases modulate osteoblast proliferation and matrix mineralization, osteoclast-mediated bone resorption, and mechanotransductive responses to physical stimuli. They are also critical for the behavior and fate specification of skeletal stem cells, integrating environmental cues to balance self-renewal and lineage commitment. In dental tissues, Rho GTPases regulate epithelial–mesenchymal interactions, odontoblast and ameloblast polarization, and the formation of enamel and dentin. Additionally, they play vital roles in craniofacial suture development, where their spatially and temporally controlled activity maintains suture patency and regulates ossification. Dysregulation of Rho GTPase signaling is implicated in a variety of pathological conditions, including osteoporosis, craniosynostosis, and dentinogenesis and amelogenesis imperfecta. Despite their therapeutic potential, targeting Rho GTPases remains challenging due to their pleiotropic functions and broad tissue distribution. This review highlights the mechanistic roles, regulatory networks, and developmental relevance of RhoA, Rac1, and Cdc42 in skeletal and dental biology, and discusses emerging strategies for modulating their activity in regenerative and disease contexts.

Abstract: Regulation of the cell cycle is critical for maintaining genomic integrity. Therefore, cells have adapted several mechanisms to ensure that cell cycle events occur in a precise order. Some mechanisms regulate cell cycle progression by inhibiting cell cycle drivers, cyclin dependent kinases (CDKs). The Wee1/Myt1 family of kinases regulate the G2 to M phase transition by phosphorylating and inactivating Cdk1. Investigations of Wee1/Myt1 have mainly focused on its regulation of mitosis; the role of Wee1/Myt1 kinases in the meiotic cell cycle is less well understood. However, misregulation of Wee1/Myt1 during meiosis can have a range of fertility consequences from mild to severe, including human fertilization failure and infertility. Studies from several organisms reveals that the meiotic functions of Wee1/Myt1 kinases differ from mitosis depending on the species and sex. Here, we review how Wee1/Myt1 kinases regulate cell-cycle progression in meiosis across species. We highlight current knowledge of Wee1/Myt1 in meiosis and discuss unanswered questions and new directions to advance the fields of meiosis, reproduction, and development. Understanding the molecular and cellular functions of Wee1/Myt1 homologs in these various systems may contribute to the discovery of the mechanisms underlying human infertility cases, better diagnoses, and clinical treatments.

Abstract: This study proposes a mechanobiological model explaining how the multilayered retroperitoneal fascia forms through the interplay of local and systemic tension fields. The classical peritoneal fusion hypothesis (Toldt, 1879) cannot account for the regular lamellar architecture observed in this region, nor for the 10-week temporal lag between early visceral fixation (gestational week 10) and definitive fascial lamination (gestational week 20). We hypothesize that early local tension at gestational weeks 10–12 forms the inner layer of the renal fascia, while a "systemic tension field"—driven by axial skeletal ossification, pelvic expansion, and exponential volumetric growth, converging near gestational week 20—establishes a fetal-scale tensegrity-like network. This systemic tension triggers orthogonal Poisson effect compression, poroelastic fluid exudation, and lysyl oxidase (LOX)-mediated cross-linking, the integration of which generates the multilayered outer fascial layers. To provide empirical grounding for this theoretical framework, we identified a cohort of adults with pure renal absence (empty renal fossa; n = 3) from 5,509 consecutive CT scans. Despite the absence of a sustained, expanding renal mass (due to true agenesis or severe involution), continuous outer fascial layers were unambiguously preserved in all cases, demonstrating that their formation is tension-driven rather than organ-dependent. This natural "subtraction experiment" resolves a long-standing discrepancy between classical gross anatomy and modern cross-sectional imaging, supporting a mechanobiological origin for retroperitoneal fascial lamination.

Abstract: Background: Integrins and other cell adhesion molecules play a critical role in migration and homing of leukocytes. This study investigates whether metastatic tumor cells can exploit leukocyte-like rolling and arrest mechanisms during early vascular steps of metastatic dissemination. Methods: B16 melanoma cell adhesion to activated bEnd.3 endothelial monolayers or immobilized VCAM-1 was analyzed under defined shear flow using a parallel-plate chamber. Function-blocking antibodies, divalent cation modulation, pertussis toxin, and low-temperature conditions were used as classical controls. Results: B16-BL6 melanoma cells exhibited robust VLA-4-dependent rolling and arrest on activated endothelial monolayers and on immobilized VCAM-1 under physiological shear stresses (0.7–2 dyn/cm²), independent of chemokine-related Gαi signaling. Conclusions: These findings identify a chemokine-independent mechanism of VLA-4-mediated vascular capture by melanoma cells under shear flow, providing a potential mechanistic basis for early steps in metastatic dissemination.

Abstract: Biological execution depends on the multiplicative convergence of four jointly necessary domains — Archetype (A), Drive (D), Context (C), and Gating Field (Φ) — as formalized in the ARCH × Φ framework. Prior applications of this framework treated the A-domain as a given structural substrate and focused primarily on sterol-dependent mechanisms underlying Φ. The present paper addresses this gap by proposing that the Bauplan — the conserved topological architecture of an organism’s organs and appendages — is proposed as the physical instantiation of the A-domain. Bauplan is not a description of morphological outcome, but an upstream structural prerequisite that determines the ceiling of what any combination of D, C, and Φ can execute. We propose a four-tier hierarchy of A-domain constraint (phylotypic, ontogenetic, functional, and state), in which Tiers I–III define the Bauplan and Tier IV represents the configuration gated in real time by ARCH × Φ. Four lines of published empirical evidence are integrated. The fin-to-limb appendage system demonstrates conserved Bauplan specification via the ZRS enhancer across approximately 400 million years. Organ-level topology — including cardiac extracellular matrix architecture, hepatic lobular organization, and renal nephron geometry — shows that disruption of structural topology produces categorical execution failure independent of cellular viability. Minimal model systems, including the Caenorhabditis elegans connectome and the zebrafish Mauthner circuit, provide direct examples of Bauplan-as-circuit. Finally, pathological cardiac hypertrophy demonstrates that sustained Φ activation can drive partially irreversible Tier III A-domain remodeling through extracellular matrix fibrosis that persists after Φ normalization. We further propose that sterol derivatives may contribute to Φ regulation at both membrane and epigenetic levels. Oxysterols act as agonists of DNA methyltransferase 1, and steroid hormones activate nuclear receptor pathways that recruit chromatin-remodeling complexes, suggesting a potential linkage between membrane gating and chromatin state. Finally, we introduce Topological Connectivity Density (TCD), a metric derivable from second-harmonic generation microscopy of standard biopsy sections, as an operational measure of A-domain state. The framework predicts distinct failure modes in cirrhosis, dilated cardiomyopathy, and congenital malformations that are not reducible to D, C, or Φ deficits, but instead reflect irreversible disruption of underlying topological constraints.

Abstract: Oxidative stress is one of the few defined causes of male infertility affecting at least one third of patients attending infertility clinics. Human spermatozoa are vulnerable to this form of attack because their stripped-down architecture means that they possess limited antioxidant protection and little capacity for biochemical repair. They also compound their vulnerability by being active generators of reactive oxygen species (ROS) and possessing multiple substrates for oxidative damage. The major sources of ROS in these cells are their mitochondria, an L-amino acid oxidase (IL4I1) and a calcium-dependent NADPH oxidase (NOX 5). Spermatozoa tolerate the risks associated with ROS generation because their biology is heavily dependent on redox regulation. ROS are important mediators of sperm capacitation, stimulating the generation of cAMP and prostaglandins, inhibiting protein phosphatases and encouraging removal of cholesterol from the plasma membrane. Furthermore, during fertilization, the ability of ROS to activate metalloproteinases facilitates penetration of the zona pellucida and sperm-oocyte fusion. While ROS are physiologically important for sperm function, the over-production of these metabolites can impair sperm function. Antioxidants have therefore assumed some importance as a possible therapy for the infertile male. However, before this potential can be realized, we need to optimize the composition and dose of reagents used in such formulations and develop improved methods of diagnosing oxidative stress within the patient population.

Abstract: Here, we review the history, advancements, and broad utility of the NTR/prodrug system, and suggest future strategies for developing versatile ablation models. As a chemogenetic tool, the nitroreductase (NTR)/prodrug system enables precise spatiotemporal control over cell ablation. The technology leverages bacterial nitroreductase enzymes (e.g., nfsB) to convert inert prodrugs into cytotoxic agents, thereby allowing researchers to induce targeted cell death. Although the NTR/prodrug approach was first implemented in transgenic mice, it was subsequently adapted to zebrafish, where it has been extensively optimized and applied. Consequently, zebrafish remain the primary focus of this review. Nevertheless, the utility of the NTR/prodrug system has expanded to other important model organisms, including Drosophila, Nematostella, Xenopus, medaka, and rats, enabling detailed studies of tissue damage and regenerationThis review highlights how the NTR system has been deployed to model a spectrum of human diseases, including Parkinson's disease, retinal degeneration, demyelinating disorders, and kidney disease. These models provide valuable platforms to study pathogenesis in vivo. Furthermore, the precise and controllable nature of NTR ablation makes it an ideal tool for high-throughput chemical and genetic screens aimed at discovering pro-regenerative and protective compounds.The development of NTR2.0, an enzyme variant with over 100-fold greater activity, along with more potent prodrugs such as ronidazole (RNZ), has dramatically broadened experimental possibilities. These improvements permit chronic ablation and long-term disease modeling at well-tolerated drug concentrations. Here we present some key considerations including transgenic design for optimal cell-type specificity, calibrating expression levels for desired ablation kinetics, and suitable controls to allow interpretation. These best practices will allow the researcher to develop a precise, reproducible, and versatile platform for either modeling human disease or dissecting regenerative mechanisms.

Abstract: Cells of higher organisms express numerous cell surface proteins, and their spectrum and level of expression are directly related to cells’ functions. The technology of mass cell selection based on the surface protein expression levels may be highly important both for basic research and cell therapy applications. We have previously developed a method of magnetic selection of cells differing in surface marker expression levels, which we term here MACS-MEL (Magnetic Assisted Cell Selection by Marker Expression Levels). The method demonstrated its effectiveness in the artificial model system, namely retrovirally transduced NIH 3T3 cells. However, whether it was also applicable to complex natural cell populations remained unclear. In the current study, we validated the MACS-MEL approach by separating mouse bone marrow (BM) cells into fractions according to the expression of pan-hematopoietic marker CD45. In the basic protocol, two-stage fractionation of CD45⁺ cells from BM was performed using selection of cells consecutively with 2 μl and 8 μl of anti-CD45 magnetic beads, resulting in isolation of CD45^high and CD45^int cell populations. To explore in full the potential of the method, the extended protocol was also tested, where a third selection stage with 30 μl of anti-CD45 beads was added. The isolated cell fractions were analyzed by flow cytometry for CD45 expression, as well for CD11b, Gr-1, CD117, CD115 and CD19 markers, while their progenitor function was assessed by quantitating colony-forming units (CFUs) in methyl cellulose. The results of analysis demonstrate that the isolated cell fractions significantly differed both in their surface phenotypes and CFU potential. In particular, cell fractions with progressively reduced CD45 expression were characterized by decreasing expression of myeloid differentiation markers CD11b and Gr-1, as well as B-lymphoid marker CD19. The expression of stem/progenitor cell marker CD117, on the contrary, significantly increased. The CFU frequency also strongly correlated with decrease in CD45 expression, while differentiation potential of CFUs differed substantially in various cell fractions. In general, our results demonstrate that more primitive, less differentiated cells in mouse BM are characterized by lower CD45 expression levels, in full accordance with data obtained in human system. Successful validation of MACS-MEL in a BM system characterized by existence of multiple cell types and high phenotypic and functional heterogeneity, demonstrated the effectiveness, simplicity and affordability of this method. The MACS-MEL approach can be applied for mass selection of cells based on differential marker expression and may yield cell subsets suitable for advanced cell therapy applications.

Abstract: Histiocytic sarcoma (HS) is an aggressive hematological malignancy whose trans-formed cells exhibits morphological and immunophenotypic characteristics similar to macrophages, and arise de novo, or as part of a clonal ‘‘evolution’’ of other pre-existing hematological neoplasms. This study investigates the potential use of the J774A.1 cell line (a line derived from murine tumor cells, commonly used in macrophage research) as a research model for the role of polydisperse extracellular vesicles (PEVs) secreted by the HS cells, considering that bacterial infections are common in patients with cancer, including HS. The influences of bacterial components on tumor progression are still not fully understood. We stimulated the J774A.1 cell line in vitro with a fraction of E. coli and our results show that the bacterial stimulation increases the secretion of PEVs by these cells. Comparative results of J774A.1 cells with PEVs using confocal and scanning electron microscopy with micrographic reports of HS histological slides (from several cited mammal species, including humans) suggest a possible relationship of large PEVs with marks, footprints or traces of possible large PEVs disrupted in the HS of these reports. A subsequent proteomic analysis of these PEVs revealed a diverse subcellular origin of its components such as proteins as including: Triosephosphate isomerase (TPI), Heat shock cognate 71 kDa, Apolipoprotein A-1, Rho GDP-dissociation inhibitor 1, GAPDH, Galectin, Moesin, globular Actin and Annexin. These results highlight the importance of studying the interplay between the HS, others hematological cancers, and bacterial infections to better understand progression of this cancer, identify new therapeutic targets and emphasize the importance of preventing bacterial infections in cancer patients. Furthermore, the results demonstrate the potential use of the stimulated J774A.1 cell line for research of the HS-related PEVs.

Abstract: Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis.

Abstract: Vascular endothelial cells (ECs) coordinate with osteogenic processes to establish the specialized vasculature of bone tissue, where endothelial cells and bone cells interact, and bone cells regulate EC proliferation and differentiation. However, it remains unclear how ECs and bone cells are coordinated during early bone formation and whether these interactions differ between endochondral ossification (e.g., femur) and intramembranous ossification (e.g., skull). To address this question, we analyzed endothelial and osteogenic marker expression in the femur and skull between postnatal days 3 and 39. We identified distinct expression patterns of endothelial markers (Endomucin, VE-cadherin and CD31) and osteogenic markers (Osterix, Cbfa1 and BGLP) during osteogenesis in these tissues. In the femurs, endothelial marker expression alternated with the expression of osteogenic markers, suggesting potential reciprocal regulation. In contrast, in the skull, endothelial and osteogenic markers exhibited similar temporal expression patterns without alternation. We also analyzed the expression of VEGF and its receptor FLK1. In the femur, VEGF expression paralleled osteogenic marker expression, whereas in the skull VEGF expression differed from both osteogenic and endothelial marker patterns. Together, these results demonstrate that the coordination of endothelial and osteogenic marker expression, as well as VEGF signaling, differs between endochondral and intramembranous ossification, suggesting distinct modes of interaction between endothelial and bone cells during the formation of long and flat bones.

Abstract: Epigenomic regulation, particularly DNA methylation, plays a critical role in gene expression control and has emerged as an important source of biomarkers for disease diagnosis, risk prediction, and longitudinal health monitoring. As high-throughput sequencing technologies have expanded, epigenomic research has rapidly grown, producing a large and complex body of biomedical literature. This review presents an AI-driven literature-level analysis aimed at uncovering structural patterns and research trends related to epigenomic biomarker discovery. Using a large corpus of full-text articles collected from PubMed and PubMed Central, we applied text mining techniques including keyword frequency analysis, document-level co-occurrence analysis, topic clustering, contextual concordance analysis, and temporal trend analysis. Rather than evaluating individual experiments, this approach examines the broader research landscape to identify recurring conceptual structures and methodological patterns. The analysis reveals that epigenomic biomarker research is organized into several interconnected domains, including disease-focused epigenomics, chromatin regulation studies, transcriptomic integration research, and cancer-related epigenomic investigations. The rapid growth of publications since 2010 further reflects the increasing importance of high-throughput epigenomic profiling and biomarker-driven research. These findings demonstrate that AI-driven literature mining provides a scalable framework for uncovering epigenomic biomarker knowledge and translating it toward AI-enabled health monitoring systems. Such approaches may support biomarker prioritization, early disease detection, and data-driven health monitoring within precision health environments.