Search Results (3,293)

Background/Objectives: Metabolic syndrome (MetS) conditions lead to structural and functional alterations in cardiomyocytes, microvasculature, and extracellular matrix (ECM), leading to myocardial fibrosis and impaired diastolic function. Cardiac lymphatic vessels (LVs) are increasingly recognized as key regulators of myocardial homeostasis, yet their response to MetS remains poorly understood. Therefore, we aimed to investigate transcriptional changes in cardiac lymphatic endothelial cells (LECs) in db/db mice, a well-established model of MetS. Methods: Using flow cytometry-sorted LECs and RT-PCR, we analyzed mRNA expression of genes involved in lymphangiogenesis, metabolism, mechanotransduction, immune cell trafficking, and ECM interactions. Results: Our findings show the transcriptional plasticity of cardiac LECs in response to MetS. Conclusions: Although our study is limited by the lack of protein-level validation and functional assays, our approach provides a broader interpretative framework and identifies potential directions for future research, including functional studies and pathway-specific investigations of the identified genes to assess their impact on lymphatic flow and cardiac function. Understanding LEC responses to metabolic stress may uncover novel therapeutic targets for heart failure associated with MetS. Full article

Polydopamine (PDA) surface coatings are widely used in biomedical engineering to enhance cell–substrate interactions; however, their effects on cancer-cell behavior remain unclear. In this study, we investigated how PDA-coated two-dimensional (2D) culture surfaces influence oncogenic traits of human prostate cancer (PC) cells in vitro. Using LNCaP, DU145, and PC3 cell lines, we found that PDA-coated substrates markedly increased the adhesion, migration, invasion, proliferation, and colony formation in a dose- and time-dependent manner. PDA exposure also induced epithelial–mesenchymal transition (EMT), upregulated cancer stem cell markers (CD44, CD117, CD133, Sox2, Oct4, and Nanog), and elevated expression of metastasis- and chemoresistance-associated molecules (MMP-2, MMP-9, MDR1, and MRP1). Mechanistically, PDA coatings enhanced integrin α₂β₁-associated cell adhesion, accompanied by increased focal adhesion kinase (FAK) phosphorylation and downstream activation of JNK signaling. Pharmacological inhibition of integrin α₂β₁ (BTT-3033), FAK (PF573228) and JNK (SP600125) effectively abrogated PDA-induced malignant phenotypes and restored chemosensitivity to cabazitaxel, cisplatin, docetaxel, curcumin, and enzalutamide. Collectively, these findings identify PDA-coated surfaces as a simple, efficient, and reductionist in vitro platform for studying adhesion-mediated signaling and phenotypic plasticity in PC cells, while acknowledging that further validation in three-dimensional (3D) and patient-derived models will be required to establish in vivo relevance. Full article

Cell senescence is increasingly recognized as a key driver of atherosclerosis progression. Senescent smooth muscle cells (SMCs) lose their proliferative capacity and adopt a pro-inflammatory profile, contributing to impaired vessel repair and weakening of the fibrous cap. Moreover, senescence promotes SMC dedifferentiation and phenotypic modulation into unfavorable phenotypes associated with plaque destabilization. In this review, we will discuss how cell senescence is induced in atherosclerotic plaques, how this influences SMC plasticity, and how this impacts plaque stability. We will also evaluate the potential of current and experimental anti-atherosclerotic drugs to target SMC senescence and/or SMC phenotypic modulation. Full article

Chromatin architecture is highly dynamic, undergoing nanoscale rearrangements throughout the cell cycle and in response to environmental cues. In this study, we employed high-resolution stochastic optical reconstruction microscopy (STORM) to visualize chromatin organization and cellular plasticity at the nanoscale in two osteosarcoma cell lines, U2OS and MG63. To promote a tumor-suppressive bone microenvironment, we applied three biophysical modalities, namely mechanical vibration, electrical stimulation, and optical pulses, each previously linked to altered tumor behavior by reprogramming cells and generating induced tumor-suppressing (iTS) cells. These stimuli enlarged nuclear size and disrupted nuclear envelope integrity, as revealed by increased surface roughness. Critically, all three modalities transiently scattered nucleosome clusters, indicating chromatin decondensation as a hallmark of iTS cell generation. iTS cells exhibited elevated expression of histone demethylases lysine demethylase 3A (KDM3A) and lysine demethylase 4 (KDM4), accompanied by reduced levels of trimethylated histone H3 lysine 9 (H3K9me3). Consistently, pharmacological agents—Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor—induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment. Full article

Atherosclerosis is a chronic, multifactorial vascular disease and the leading global cause of cardiovascular morbidity. Its development reflects interconnected disturbances in lipid metabolism, endothelial function, inflammation, smooth muscle cell (SMC) phenotypic switching, and extracellular matrix remodeling. Genetic predisposition, including monogenic disorders such as familial hypercholesterolemia and polygenic risk variants, modulates disease susceptibility by altering lipid homeostasis as well as inflammatory and thrombotic pathways. Epigenetic regulators and noncoding RNAs, such as histone modifications, microRNAs, and long noncoding RNAs, further shape gene expression and link environmental cues to vascular pathology. Endothelial injury promotes lipoprotein retention and oxidation, triggering monocyte recruitment and macrophage-driven foam cell formation, cytokine secretion, and necrotic core development. Persistent inflammation, macrophage heterogeneity, and SMC plasticity collectively drive plaque growth and destabilization. Emerging insights into immune cell metabolism, intracellular signaling networks, and novel regulatory RNAs are expanding therapeutic possibilities beyond lipid-lowering. Current and evolving treatments include statins, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, anti-inflammatory agents targeting interleukin-1 beta (IL-1β) or NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), and advanced approaches such as gene editing, siRNA, and nanoparticle-based delivery. Integrating multi-omics, biomarker-guided therapy, and precision medicine promises improved risk stratification and next-generation targeted interventions. This review summarizes recent molecular advances and highlights translational opportunities for enhancing atherosclerosis prevention and treatment. Full article

Human microbiota, a complex consortium of microorganisms co-evolved with the host, profoundly influences tissue development, immune regulation, and disease progression. Growing evidence shows that microbial metabolites and signaling molecules modulate key stem cell pathways—such as Hedgehog, Wnt/β-catenin, and Notch—thereby reprogramming stem cell fate toward tumor-suppressive or tumor-promoting outcomes. Specific taxa within oral, intestinal, and urogenital niches have been linked to cancer initiation, therapy resistance, and recurrence. In parallel, clinical studies reveal that microbiota composition affects infection dynamics: bacterial isolates from symptomatic urinary tract infections inhibit commensal growth more strongly than the reverse, with Gram-positive and Gram-negative strains displaying distinct interaction profiles. Collectively, these findings highlight microbiota’s dual role in regulating cellular plasticity and pathogenicity. Elucidating host–microbe and microbe–microbe mechanisms may guide microbiota-targeted interventions to improve cancer and infectious disease management. Full article

The growing concern over plastic pollution and the widespread presence of micro- and nanoplastics has renewed interest in polyhydroxybutyrate (PHB) as a biodegradable alternative; however, its industrial deployment remains constrained by costly recovery operations with a high environmental burden. This study examines how PHB biosynthesis and intracellular organization, physicochemical properties, and the characteristics of the producing microorganism influence the performance of conventional recovery routes, including extraction with organic solvents, alkaline/oxidative chemical digestion, and enzymatic–physical schemes coupled with mechanical disruption. Based on this foundation, quantitative data are analyzed for PHB content in bacteria, mixed microbial cultures, cyanobacteria, and microalgae, along with extraction yields, polymer purity, and solvent recyclability in processes employing chlorine-free solvents, green solvents, and hydrophobic natural deep eutectic solvents (NaDESs) formulated with terpenes and organic acids. The analysis integrates mechanistic perspectives on NaDES–cell and NaDES–PHB interactions with solvent design criteria, biorefinery configurations, and preliminary evidence from technoeconomic and life cycle assessments. The findings identify NaDES as an up-and-coming platform capable of reconciling biopolymer quality with the principles of green chemistry while delineating critical gaps in recovery efficiency, viscosity management, solvent recycling, and pilot-scale validation. Full article

Neuroinflammation is a defining feature of many neurological disorders, including neurodegenerative diseases, traumatic brain injury, and demyelinating conditions. Glial cells play a central role in this process by initiating, modulating, and resolving inflammatory responses in the CNS. This review examines the diverse roles of glial cells in neuroinflammation, focusing on their molecular and cellular interactions, context-dependent activation states, and phenotypic plasticity. It discusses how microglial activation can result in both neuroprotective and neurotoxic effects, while astrocytes contribute to immune regulation, blood–brain barrier integrity, and neuronal survival. The review also highlights interactions between glial cells and peripheral immune components, which may exert synergistic or antagonistic effects. Finally, it outlines emerging preclinical and clinical strategies targeting glial pathways to modulate several neuroinflammatory outcomes, emphasizing that a detailed understanding of glial dynamics is essential for developing effective CNS therapies. Full article

Astrocytes are critical for maintaining brain homeostasis through metabolic support, neurotransmitter regulation, and blood–brain barrier integrity. In the aging brain and neurodegenerative conditions, astrocytes undergo functional and morphological changes that culminate in a state of cellular senescence. Astrocytic senescence—characterized by irreversible cell-cycle arrest and a pro-inflammatory senescence-associated secretory phenotype (SASP)—is emerging as a key contributor of chronic neuroinflammation and synaptic dysfunction in aging. This review examines the molecular mechanisms underlying astrocyte senescence, highlighting how persistent DNA damage responses (DDR), oxidative stress, and mitochondrial dysfunction disrupt essential astrocytic functions (e.g., glutamate uptake, K⁺ buffering, and metabolic coupling with neurons). These senescent changes in astrocytes lead to impaired synaptic plasticity and contribute to age-related cognitive decline. Collectively, astrocytic senescence represents a pivotal and targetable mechanism in age-related neurodegeneration, and therapeutic strategies aimed at eliminating senescent cells or modulating the SASP hold promise for restoring synaptic function and promoting healthy brain aging. Full article

Brain tumors, particularly glioblastoma, remain among the most lethal cancers, with limited survival benefits from current genetic and molecular-targeted approaches. Emerging evidence reveals that beyond oncogenes and mutations, neuronal plasticity, long-term potentiation, synaptic remodeling, and neurotransmitter-driven signaling play a pivotal role in shaping tumor progression and therapeutic response. This convergence of neuroscience and oncology has given rise to the field of cancer neuroscience, which explores the bidirectional interactions between neurons and malignant cells. In this review, we summarize fundamental principles of neuronal plasticity, contrasting physiological roles with pathological reprogramming in brain tumors. We highlight how tumor cells exploit synaptic input, particularly glutamatergic signaling, to enhance proliferation, invasion, and integration into neural circuits. We further discuss how neuronal-driven feedback loops contribute to therapy resistance, including chemoresistance, radioresistance, and immune evasion, mediated through pathways such as mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase/protein kinase B (PI3K/AKT), and calcium influx. The tumor microenvironment, including astrocytes, microglia, and oligodendrocyte-lineage cells, emerges as an active participant in reinforcing this neuron-tumor ecosystem. Finally, this review explores therapeutic opportunities targeting neuronal plasticity, spanning pharmacological interventions, neuromodulation approaches (transcranial magnetic stimulation (TMS), deep brain stimulation (DBS), optogenetics), and computational/artificial intelligence frameworks that model neuron tumor networks to predict personalized therapy. Also, we propose future directions integrating connect omics, neuroinformatics, and brain organoid models to refine translational strategies. Full article

Oral squamous cell carcinoma (OSCC) remains a highly prevalent and aggressive malignancy with limited improvements in survival rates. One of the major obstacles to successful treatment is the development of chemoresistance, which contributes to recurrence, metastasis, and treatment failure. This narrative review aims to integrate current evidence on the molecular and cellular mechanisms that drive chemoresistance in OSCC and to delineate how these processes converge under therapeutic pressure. A structured search was performed to identify relevant studies addressing chemoresistance in OSCC, focusing on preclinical and translational evidence. Multiple interconnected mechanisms have been implicated in driving resistance in OSCC, including epigenetic alterations, deregulated signaling pathways, cancer stem cell plasticity, epithelial–mesenchymal transition (EMT), interactions with the tumor microenvironment (TME), drug efflux mediated by ATP-binding cassette (ABC) transporters, and enhanced DNA damage response. In combination, these mechanisms support tumor persistence and limit effective antitumor immunity. Emerging strategies such as epigenetic modulators, signaling pathway inhibitors, immunomodulation, and nanomedicine-based delivery systems have shown promising results in preclinical models. By highlighting convergent resistance networks, this integrative perspective supports the rational design of combination therapies and biomarker-guided strategies aimed at overcoming chemoresistance in OSCC. Full article

Mesothelial cells line serosal cavities and internal organs, playing a vital role in maintaining serosal integrity and homeostasis. Their remarkable plasticity and ability to undergo mesothelial-to-mesenchymal transition (MMT) position them as key regulators of tissue repair. However, when normal repair processes fail, mesothelial cells can acquire a profibrotic phenotype. They actively contribute to all stages of fibrosis development, including inflammation, fibrin accumulation, myofibroblast differentiation, and extracellular matrix (ECM) remodeling. Fibrotic progression involves multiple cell types, and communication among them is essential for its perpetuation. Mesothelial cells are implicated in bidirectional crosstalk with fibroblasts, macrophages, lymphocytes, and endothelial cells of the serosal microenvironment through direct contact, paracrine signaling, and extracellular vesicle exchange. These interactions regulate immune cell recruitment, cytokine balance, endothelial permeability, and ECM deposition, while, in turn, immune and endothelial cells modulate mesothelial activation, proliferation, and transition. Understanding this complex network of intercellular communication provides new insights into fibrosis pathogenesis and reveals promising targets for antifibrotic therapies. Full article

Although there have been advancements in stroke treatment (reperfusion) therapy, and it has been shown that many individuals continue to suffer from partial recoveries and continuing decline in their neurological status as a result of suffering a stroke, a primary barrier to providing precise care to patients with stroke continues to be the inability to capture changes in molecular and cellular programs over time and in biological compartments. This review synthesizes evidence that represents the entire continuum of ischemia, beginning with acute metabolic failure and excitotoxicity, and ending with immune response in the nervous system, reprogramming of glial cells, remodeling of vessels, and plasticity at the level of networks, and organizes this evidence in a temporal framework that includes three biological compartments:central nervous system tissue, cerebrospinal fluid, and peripheral blood. Additionally, this review discusses new technologies which enable researchers to discover biomarkers at an extremely high resolution, including single-cell and spatial multi-omics, profiling of extracellular vesicles, proteoform-resolved proteomics, and glymphatic imaging, as well as new computational methods and machine-learning algorithms to integrate data from multiple modalities and predict trajectories of disease progression. The final section of this review will provide an overview of translationally relevant and ethically relevant issues regarding the deployment of predictive biomarkers, such as privacy, access, equity, and fairness, and emphasize the importance of global coordination of research efforts in order to ensure the clinical applicability and global equity of biomarker-based diagnostics and treatments. Full article

Microalgae are an evolutionarily ancient and morphologically diverse group of photosynthetic eukaryotes, with taxonomic resolution complicated by environmentally driven phenotypic plasticity. This study merges deep learning and explainable artificial intelligence (XAI) to establish a transparent, reliable, and biologically meaningful framework for green microalgae (Chlorophyta) classification. Microscope images from three morphologically distinct algal species—Desmodesmus flavescens, Desmodesmus subspicatus, and Tetradesmus dimorphus representing the genera Desmodesmus and Tetradesmus within Chlorophyta—were analyzed using twelve convolutional neural networks, including EfficientNet-B0–B7, DenseNet201, NASNetLarge, Xception, and ResNet152V2. A curated dataset comprising 3624 microscopic images from three Chlorophyta species was used, split into training, validation, and test subsets. All models were trained using standardized preprocessing and data augmentation procedures, including grayscale conversion, CLAHE-based contrast enhancement, rotation, flipping, and brightness normalization. The model’s performance was assessed using accuracy and loss metrics on independent test datasets, while interpretability was evaluated through saliency maps and Gradient-weighted Class Activation Mapping (Grad-CAM) visualizations. ResNet152V2 achieved the highest overall performance among all evaluated architectures, outperforming EfficientNet variants, NASNetLarge, and Xception in terms of macro F1-score. Visualization analysis showed that both Grad-CAM and saliency mapping consistently highlighted biologically relevant regions—including cell walls, surface ornamentation, and colony structures—confirming that the models relied on taxonomically meaningful features rather than background artifacts. The findings indicate that the integration of deep learning and XAI can attain consistently high test accuracy for microalgal species, even with constrained datasets. This approach enables automated taxonomy and supports biodiversity monitoring, ecological assessment, biomass optimization, and biodiesel production by integrating interpretability with high predictive accuracy. Full article

Background: Aging brains are shaped by a persistent dialogue between declining neurogenesis and rising neuroinflammation. Neural stem cells progressively lose regenerative capacity, while microglia and astrocytes shift toward maladaptive states that erode synaptic plasticity and cognition. This convergence defines inflammaging, a slow yet relentless process that undermines resilience. However, the field remains hampered by critical gaps: incomplete mapping of microglial heterogeneity, poorly understood epigenetic scars from inflammasome signaling, lack of longitudinal data, unclear niche-specific immune mechanisms, and uncertain cross-species relevance. This review addresses these pressing barriers, aiming to transform fragmented insights into actionable strategies. Summary: I chart how neurogenesis and neuroinflammation operate in continuous dialogue, identify five major knowledge gaps, and evaluate strategies to reprogram this interaction. Approaches include longitudinal imaging, niche-focused immunomodulation, glial subtype reprogramming, brain-penetrant inflammasome inhibitors, and CRISPR-based epigenetic editing. Each strategy is mapped against translational potential, short-term feasibility, and long-term vision, with emphasis on how mechanistic precision can guide clinical innovation. Conclusions: Here I highlight that neurogenic potential is not entirely lost with age but may be preserved or restored by tuning immune and epigenetic environments. This review proposes a roadmap for reshaping the aging brain’s fate, offering mechanistically grounded strategies to delay cognitive decline. Beyond neurology, the work underscores a broader principle: by integrating cellular plasticity with immune modulation, science edges closer to re-engineering resilience across the lifespan. Full article