Search Results (2,918)

Poly(lactic-co-glycolic acid) (PLGA) is one of the most extensively investigated biodegradable polymers for biomedical applications, owing to its tunable degradation kinetics, established biocompatibility, and regulatory approval. In implantology, PLGA-based systems have emerged as versatile platforms for scaffolds, coatings, and localized drug delivery, aimed at enhancing osseointegration and tissue regeneration. This review provides a focused and up-to-date analysis of PLGA applications in dental and orthopedic implantology, with particular emphasis on advances reported over the past decade. Unlike previous reviews that predominantly address general drug delivery or broad tissue engineering applications, this work establishes a direct correlation between polymer composition (LA:GA ratio), processing strategies, and biological outcomes, including degradation behavior, mechanical performance, and host response. Special attention is given to multifunctional PLGA systems incorporating antibiotics, growth factors, and bioactive nanoparticles, highlighting their role in improving antibacterial efficacy and osteogenesis. Emerging technologies such as nanostructured composites, additive manufacturing, and stimuli-responsive delivery platforms are critically evaluated. Key limitations—including acidic degradation by-products, burst release kinetics, and translational barriers—are discussed in the context of clinical applicability. By integrating physicochemical design with biological performance and recent clinical trends (2024–2025), this review proposes a framework for the rational development of next-generation PLGA-based implant systems. Full article

Uridine diphosphate glucuronosyltransferases (UGTs) are critical phase II detoxification enzymes; however, their mutational landscape and protective roles against chemical carcinogenesis in hepatocellular carcinoma (HCC) remain poorly defined. Here, targeted sequencing of ten liver-enriched UGT genes in 38 paired tissues from a Chinese HCC cohort revealed striking mutation frequencies in UGT2B15 (44.74%), UGT2B10 (36.84%), and UGT2B17 (26.32%). This genomic instability was accompanied by a profound downregulation of UGT2B15 mRNA (9.02-fold decrease, p < 0.001) and protein levels (Z-score = 2.32, p = 0.0093) in tumors, with higher UGT2B15 expression correlating with improved overall survival in TCGA cohorts (HR = 1.724, p = 0.012). Mechanistically, we identified the androgen receptor (AR) as a direct transcriptional regulator of UGT2B15 and UGT2B17, with dihydrotestosterone (DHT) inducing dose-dependent increases in their expression, thereby linking endocrine signaling to hepatic detoxification. Transcriptomic profiling following UGT2B15 knockdown in HCC cells revealed a significant enrichment in chemical carcinogenesis-related pathways. Crucially, UGT2B15 deficiency severely exacerbated carbon tetrachloride (CCl₄)- and ethanol-induced hepatotoxicity both in vitro and in vivo. Our study uncovers a profound impairment of UGT-mediated detoxification in HCC and establishes the AR–UGT2B15 axis as a critical barrier against chemical-induced liver injury, highlighting its potential as a chemopreventive target in carcinogen-exposed populations. Full article

Purpose: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder strongly associated with intestinal microbial dysregulation. Although 5-aminosalicylic acid (5-ASA) is widely used in the clinical management of IBD, its therapeutic efficacy is often limited. To address this, the present study aimed to develop a bifidobacterium-derived extracellular vesicle-based drug delivery system (B-MVs@5-ASA) to enhance the therapeutic outcomes of IBD. Methods: B-MVs were isolated by PEG precipitation and loaded with 5-ASA via sonication to obtain B-MVs@5-ASA. Their morphology, particle size, zeta potential, and encapsulation efficiency were analyzed using TEM, DLS, and UV spectrophotometry. Cellular uptake, cytotoxicity (LDH and NO assays), and anti-inflammatory effects were assessed in RAW 264.7 and Caco-2 cells. A DSS-induced colitis mouse model was established to evaluate therapeutic efficacy. Cytokines (ELISA), colon histopathology (H&E), tight-junction proteins (IF), and gut microbiota composition (16S rRNA sequencing) were systematically analyzed. Results: B-MVs@5-ASA exhibited a particle size of 104.3 ± 2.81 nm and an encapsulation efficiency of 11.14% ± 3.63%. B-MVs@5-ASA exhibited the strongest anti-inflammatory effect in vitro and most effectively alleviated DSS-induced colitis in vivo, outperforming monotherapies in reducing inflammation, tissue damage, and enhancing barrier integrity. B-MVs@5-ASA further promoted goblet cell regeneration and beneficially modulated the gut microbiota by enriching Akkermansia and suppressing Escherichia, thereby restoring microbial homeostasis. Conclusions: B-MVs@5-ASA provides potent anti-inflammatory and mucosal-protective effects by modulating cytokine balance, enhancing epithelial barrier function, and reshaping gut microbiota. These findings highlight probiotic vesicle-based nanoplatforms as a safe and promising strategy for targeted IBD therapy. Full article

The epithelium represents the first line of defense against viral infection, yet the precise mechanisms by which viruses penetrate this complex barrier remain incompletely understood. Single-virus tracking (SVT) has emerged as a powerful fluorescence microscopy approach to directly visualize viral dynamics with nanometer spatial precision and millisecond temporal resolution. In this review, we survey recent progress in SVT methodologies, from image-based approaches to active feedback techniques, and assess their capacity to resolve viral behavior in physiologically relevant epithelial models. We further evaluate advances in virus labeling strategies—including fluorescent proteins, organic dyes, and nanoparticles—that enable prolonged observation while preserving infectivity. By integrating developments in optical instrumentation and molecular labeling, SVT is increasingly capable of capturing critical processes, including extracellular diffusion, receptor engagement, internalization, and trans-epithelial transport. Finally, we discuss current challenges, including limited penetration depth, photobleaching, and the complexity of 3D epithelial tissues, and outline future opportunities to extend SVT towards in situ and tissue-level studies. Together, these advances position SVT as a transformative tool to illuminate virus–epithelium interactions and guide therapeutic strategies. Full article

Micro- and nanoplastics (MNPs) have now been detected in human blood, placenta, and arterial tissue, yet the oral cavity has received strikingly little mechanistic attention despite serving as a primary portal of environmental exposure and a local site of polymer generation from dental and oral-care materials. This narrative review addresses that gap from an environmental microbiology perspective, synthesizing recent literature on periodontal disease, chronic low-grade inflammation, oral biofilms, dental materials, microbial–plastic interactions, and systemic chronic disease risk. Unlike prior reviews, we apply an explicit three-tier evidentiary framework (established, plausible, unproven) that distinguishes what is directly demonstrated from what is biologically plausible but unproven, and we situate the periodontal environment specifically as a particle-retention and inflammatory-amplification niche. The strongest direct oral evidence shows that human dental calculus harbors at least 26 microplastic types, dominated by polyamide (41.4%), polyethylene (32.7%), and polyurethane (7.0%). Polyethylene isolated from calculus induces cytotoxicity, apoptosis, impaired migration, NF-κB activation, and upregulation of IL-1β and IL-6 in human gingival fibroblasts. From a microbiological standpoint, oral organisms actively degrade methacrylate dental polymers, and the degradation products of these polymers reciprocally modulate oral bacterial virulence gene expression. Across experimental systems, MNPs activate oxidative stress, inflammasome signaling, macrophage polarization, and barrier dysfunction, pathways that overlap extensively with periodontal pathobiology. Adjacent environmental microbiology demonstrates that plastic-associated biofilms enhance extracellular polymeric substance production, quorum sensing, pathogen persistence, and antibiotic resistance gene transfer, supporting a plausible but not yet validated oral plastisphere within plaque and calculus. We argue that periodontitis should be reconceptualized as a chronically inflamed particle-processing interface that may increase local MNP retention, cellular reactivity, and systemic inflammatory spillover, with implications for cardiovascular, metabolic, and other chronic disease risk pathways. Current evidence does not yet prove that environmental MNP exposure causes human periodontitis, and that evidentiary boundary is maintained throughout. A priority research agenda is proposed, centered on contamination-controlled subgingival biomonitoring stratified by periodontal status, spatially resolved multi-species biofilm models, polymer source attribution, and longitudinal clinical studies linking oral plastic burden to inflammatory and systemic outcomes. Full article

Despite major advances in early breast cancer detection and therapeutic strategies, locoregional and distant recurrences, as well as the development of a second primary breast cancer, remain major clinical challenges. Current prognostic tools primarily rely on tumor-specific features, such as the histological grade, hormone receptor status, and proliferative index, and, more recently, on molecular signatures aimed at improving risk stratification and predicting recurrence. However, these approaches remain imperfect, and there is an urgent need to develop complementary strategies. Growing attention has been focused on the tumor microenvironment and the surrounding non-tumoral tissue, which may harbor clinically relevant molecular alterations. Emerging evidence suggests that DNA methylation changes can be detected in the adjacent and contralateral breast tissue and reflect early steps of carcinogenesis or predisposition to tumor development. This phenomenon, often referred to as field cancerization, raises new questions about the dynamics of cancer development. The aim of this work is to provide an integrative overview of DNA methylation alterations in normal breast tissue, including peritumoral and contralateral areas, and to examine their potential as predictive biomarkers of recurrence, based on the available data from tumoral tissue. In theory, these applications seem promising, but their role needs to be confirmed in large prospective trials, in order to overcome barriers to clinical implementation. The currently available evidence does not support a role for DNA methylation in the selection of locoregional and systemic treatment strategies, particularly with a view to reducing the rising number of uni- and bilateral mastectomies performed without any demonstrated survival benefit. Full article

Urinary cancers present a severe clinical challenge due to high recurrence rates. Standard intravesical therapies suffer from limited efficacy because of the urinary tract’s robust physiological defenses, namely, the dynamic washout effect during voiding and highly restrictive urothelial barriers, such as the anti-adhesive glycosaminoglycan layer and intercellular tight junctions. This review aims to explore how biomimetic engineering can overcome these obstacles by transitioning drug delivery from passive carriers to active, nature-inspired systems. We conducted a comprehensive review of the recent literature focusing on biomimetic strategies for intravesical drug delivery and urinary cancer theranostics. The analyzed approaches are categorized into chemical biomimicry (such as adhesion and camouflage) and structural/functional biomimicry (including adaptive devices and microrobots). Biomimetic strategies significantly enhance targeted drug retention and tissue penetration. Chemical biomimicry, utilizing mussel-inspired catechol chemistry and cell membrane camouflage, effectively bypasses the urothelial anti-adhesive defenses and reduces the immune clearance. Structural and functional biomimicry, such as naturally derived carriers and actively propelled magnetic or biohybrid microrobots, enables the precise spatial localization and controlled payload release in dynamic fluid environments. Furthermore, lab-on-a-chip technologies and patient-derived organoids (PDOs) offer scalable platforms for screening cargo-specific efficacies and tailoring treatments, providing a crucial bridge to personalized precision medicine. Integrating nature-inspired designs with advanced nanotechnologies provides a highly promising pathway with which to overcome the mechanical and biological barriers of the urinary tract. These biomimetic innovations hold the potential to shift the therapeutic paradigm for urinary oncology, paving the way for more efficient, targeted, and personalized precision medicine. Full article

The mammalian intestinal epithelium is a rapid self-renewal tissue in the body, serving as a critical interface between the host and the external environment. Maintaining the intestinal epithelium homeostasis requires precise coordination of cellular processes, including proliferation, migration, differentiation, autophagy, and cell-to-cell interaction. An increasing body of evidence has unveiled circular RNAs (circRNAs) as abundant and stable regulatory molecules that play pivotal roles in the intestinal epithelial biology and are intimately involved in many aspects of gut mucosal pathologies. Unlike linear RNAs, circRNAs form covalently closed loop structures through back-splicing events, conferring remarkable stability and resistance to exonucleolytic degradation. circRNAs regulate the growth of the intestinal mucosa, injury-induced epithelial regeneration, and gut barrier function via diverse mechanisms, including interactions with microRNAs and RNA-binding proteins. Deregulated circRNAs are implicated in the pathogenesis of various gut mucosal disorders such as inflammatory bowel disease and malignancies. In this review, we highlight pathobiological functions and mechanisms of intestinal epithelium-enriched circRNAs, particularly circHIPK3, Cdrlas, and circPABPN1, in the epithelium homeostasis and pathologies and also discuss potential clinical application of circRNAs as diagnostic biomarkers and therapeutic targets in patients with critical diseases. Full article

Toxoplasmosis, caused by the obligate intracellular parasite T. gondii, is one of the most prevalent parasitic infections worldwide, affecting approximately one-third of the global population. Despite decades of intensive research, no effective human vaccine exists. The only commercially available vaccine, Toxovax, is restricted to veterinary use in sheep and is unsuitable for human application due to safety concerns. Beyond summarizing the literature, this review offers a critical appraisal of why translation has stalled and where the field should focus next. Live-attenuated vaccines remain the most immunogenic in preclinical models but face significant translational barriers for human use. Key antigenic targets include surface antigens (SAG), dense granule antigens (GRA), rhoptry proteins (ROP), and microneme proteins (MIC). Protective immunity relies critically on Th1-type immune responses characterized by interferon-gamma production. Major obstacles include the parasite’s complex life cycle, strain diversity, and difficulty achieving sterile immunity. Subunit and mRNA-based platforms offer more favorable safety profiles and established clinical precedents, representing the most viable pathway toward a human vaccine. Recent advances in CRISPR/Cas9 gene editing and emerging mRNA vaccine platforms offer promising new directions. This review advances the field in three ways. (i) It prioritizes mRNA and adjuvanted subunit formulations targeting multistage conserved antigens as the most realistic near-term human candidates. (ii) It identifies the limited targeting of bradyzoite-stage biology as a principal, under-addressed gap. (iii) It argues that future development must be differentiated into three complementary One Health goals—prevention of congenital disease in humans, reduction in tissue-cyst burden in livestock, and interruption of environmental transmission by vaccinating cats. In practice, a veterinary-first deployment strategy is the most immediate and impactful pathway to reducing the human and zoonotic burden of toxoplasmosis. Full article

Dietary polyunsaturated fatty acids (PUFAs) are vital for brain health and cognitive function. The dorsal raphe nucleus (DRN) regulates mood via serotonin, while the hypothalamus (HYP) controls energy homeostasis. Flaxseed oil (FLAX) is rich in omega-3 PUFAs like α-linolenic acid (ALA), and has been reported to influence serotonergic signaling in mammals, but data in poultry are scarce. This study investigated the effects of FLAX on metabolites crossing the blood-brain barrier (BBB) to serotonergic brain regions and on growth performance in broiler chickens. Day-old chicks (n = 160) were assigned to two diets (5 replicates/treatment): control (CON; poultry fat-based diet) or FLAX (3% inclusion level). Growth performance was recorded, and DRN, HYP, and plasma were analyzed using HPLC-MS metabolomics. Serotonin and its metabolite 5-HIAA were quantified using LC-MS/MS. FLAX-fed birds had higher body weight gain (p < 0.0055) and better feed conversion ratio (p < 0.0049) than CON. Metabolomics identified 2271 features, of which 650 were annotated as metabolites. Of 35 differentially abundant plasma metabolites, eight were also differentially abundant in brain tissues. In the DRN, tryptophan (serotonin precursor) and corydaline (neuroprotective) were upregulated. Serotonin levels were significantly higher in both the DRN and HYP of FLAX-fed birds compared to CON. This suggest that dietary flaxseed oil may modulate stress responses, behavior, and welfare in broilers. In the HYP, dethiobiotin (energy), galanthamine (neuroprotective), and gambogic acid (antioxidative) were upregulated, while xanthoxyletin (anti-inflammatory) was downregulated. In conclusion, flaxseed oil improved growth and elevated serotonin in the DRN and HYP via enhanced tryptophan availability, suggesting potential benefits for stress resilience and welfare. Full article

Silver nanoparticles (AgNPs) have gained significant interest across various areas arising from their multifunctional mechanisms. Biomedical applications are one of the areas where the therapeutic and diagnostic potential of AgNPs are highlighted. Considering the expansion of biomedical use of AgNPs, nervous system-based applications, including neuroimaging, neural implant coatings and development of neural tissue-targeted drug delivery systems are some of the potential applications of AgNPs in the current research. However, growing interest in these nervous system related applications and the limited regenerative capacity of neural tissues make it essential to carefully evaluate the potential neurotoxic effects of AgNPs. AgNP-induced responses in neural tissues may differ according to key physicochemical and exposure-related parameters, specifically particle size, shape, surface chemistry, coating properties, protein corona formation, exposure route, dose, and duration. Among the possible mechanisms that may contribute to these responses are blood–brain barrier (BBB) disruption, mitochondrial dysfunction and oxidative stress, neuroinflammation and glial activation, and cell death processes such as apoptosis, autophagy, and ferroptosis. In this review, in the context of the potential neurotoxic effects of AgNPs on the nervous system, the main parameters that determine AgNP neurotoxicity and the possible mechanisms involved are examined in detail, where recent scientific developments in this field are evaluated based on current in vitro and in vivo studies. Full article

Brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin receptor kinase B (TrkB) are classically associated with neuroplasticity, but increasing evidence suggests a broader role for BDNF/TrkB signaling in systemic stress adaptation beyond the central nervous system. Strenuous exercise is a model of functional stress that may become a clinically relevant renal challenge under conditions such as dehydration, heat stress, vascular vulnerability, and repeated exposure. Neuroendocrine stress activation, hemodynamic perturbations, and cytoskeletal instability are key factors that may contribute to glomerular barrier dysfunction in this setting. BDNF biogenesis is complex, and circulating BDNF largely reflects platelet-associated pools and context-dependent release. At the tissue level, BDNF/TrkB signaling can activate actin-regulatory pathways involved in cellular resilience. The podocyte is of particular interest because its actin-dependent architecture functionally parallels that of neurons and is essential for maintenance of the glomerular filtration barrier. Within this framework, BDNF/TrkB signaling may stabilize podocyte actin dynamics, reduce foot process effacement, and attenuate proteinuria. The present review focuses on the brain–kidney axis and the potential renoprotective role of BDNF/TrkB signaling, while highlighting major knowledge gaps regarding BDNF availability to glomerular cells, isoform-specific TrkB actions, and causal inference in humans exposed to repeated exercise-related renal stress. However, current human evidence is insufficient to define the dominant source and delivery route of BDNF to glomerular cells during exercise-related renal stress. Therefore, BDNF/TrkB is discussed here as a candidate modulatory/resilience pathway rather than an established causal driver. Full article

Background/Objectives: Glucagon-like peptide-1 (GLP-1) is a nutritionally regulated incretin involved in the coordination of intestinal, hepatic, and adipose metabolic responses. Although plant-derived extracts are increasingly investigated for their metabolic effects, mechanistic evidence integrating multiple metabolic tissues remains limited. This study aimed to investigate the molecular effects of a combination of plant-derived extracts in an integrated in vitro gut–liver–adipose model. Methods: Differentiated Caco-2 monolayers were exposed to a standardised combination of plant-derived extracts obtained from Gastrodia elata, Morus alba, and Paeonia lactiflora. GLP-1 secretion and epithelial barrier integrity were assessed. Conditioned media from intestinal cells were applied to HepG2 hepatocytes, and downstream effects on lipid metabolism-related pathways were evaluated. Subsequently, conditioned media from hepatic cells were applied to differentiated 3T3-L1 adipocytes to assess lipid accumulation and metabolic signalling. Results: Exposure of intestinal cells to the extract combination significantly increased GLP-1 secretion without altering epithelial barrier integrity. Intestinal conditioned media were associated with reductions in intracellular triglyceride levels in hepatocytes and with modulation of markers linked to lipid handling, including resistin, FGF21, SREBP-1c, NRF2, Src, AMPK, SIRT1, and PGC1α, suggesting GLP-1-associated effects. In adipocytes, hepatic conditioned media decreased lipid accumulation and increased the levels of metabolic markers associated with adipocyte browning-related signalling, including UCP1, NOS, SIRT1, and STAT3. Conclusions: Within the limitations of this in vitro multi-organ model, these findings suggest that the tested combination of plant-derived extracts modulates cellular pathways related to GLP-1-associated metabolic signalling across intestinal, hepatic, and adipose systems. These results should be interpreted as mechanistic and hypothesis-generating, and further in vivo and clinical studies are required to confirm their physiological relevance. Full article

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global population, poses a significant yet underappreciated threat to reproductive health in both sexes. Although this parasite has long been linked to birth defects caused by infection during pregnancy, new research shows that it also reduces fertility in both sexes through different but related mechanisms. This review synthesizes knowledge on T. gondii-induced reproductive pathology across females and males, examining shared mechanistic themes while respecting tissue-specific differences, and evaluates emerging therapeutic strategies. In females, the parasite establishes persistent uterine reservoirs, triggers decidual immune dysregulation characterized by NK cell cytotoxicity, M1 macrophage polarization, Treg apoptosis, and inflammasome-mediated pyroptosis, while disrupting estrogen and progesterone signaling through both host receptor modulation and intrinsic parasite steroidogenic enzymes (TgCYP450mt, TgMAPR, Tg-HSD). In males, T. gondii breaches the blood–testis barrier, induces germ cell and Leydig cell apoptosis via ER stress and caspase pathways, impairs sperm quality parameters across acute and chronic infection, and disrupts the hypothalamic–pituitary–gonadal axis. Conserved molecular mechanisms—including NLRP3 inflammasome activation, PERK/eIF2α/ATF4/CHOP-mediated ER stress, and oxidative stress—operate in both reproductive tissues. The parasite’s intrinsic steroidogenic capability and bidirectional hormonal manipulation represent a paradigm shift in understanding host–parasite interactions. Conventional antiparasitics face limitations due to poor reproductive sanctuary penetration. Immunomodulatory approaches targeting Trem2, Tim-3, and the NLRP3 inflammasome show promise, along with natural products including Inonotus obliquus polysaccharide and ginseng polysaccharide. Nanomedicine platforms and mRNA vaccine candidates offer new directions for overcoming tissue barrier limitations. Toxoplasma gondii represents a fundamental threat to fertility and pregnancy outcomes rather than merely a risk for congenital infection. Integrated therapeutic strategies addressing direct parasitism, immunopathology, and endocrine disruption are needed. Longitudinal cohort studies, strain-specific mechanistic comparisons, and clinical trials of immunomodulatory adjuncts are urgently required. Full article

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), has long been characterized as a neoplasm of mature memory T cells, based on monoclonal T-cell receptor (TCR) rearrangements and tissue-resident memory (TRM)/central memory (TCM) T-cell phenotypes. This review synthesizes converging population-genetic, multi-omic, and single-cell evidence to argue that this characterization is incomplete and that a progenitor-based model better accounts for the full spectrum of disease biology. We present evidence that initiating mutations arise in hematopoietic stem or early lymphoid progenitor survive thymic selection, and diversify after TCR assembly, resulting in branched evolution across both blood and skin. In SS, paired analyses reveal > 200 shared variants between CD34⁺ progenitors and Sézary cells, as well as signal-joint T-cell receptor excision circle (sjTREC) positivity, providing direct progenitor-level evidence. In MF, convergent signals, multiple malignant clonotypes per lesion, greater blood–skin than skin–skin clonotype overlap, and compartment-specific CNV subclones, implicate hematogenous seeding and reseeding. Population-scale lymphoid clonal hematopoiesis and lymphoid-pattern mosaic chromosomal alterations define a compatible antecedent state. Spatial single-cell atlases and trajectory analyses map site-conditioned programs in skin, including Th2-skewed cytokines, microbial responses, and UV signatures, that select and expand subclones and explain inter- and intra-patient heterogeneity. This framework reconciles mature immunophenotypes with upstream initiation and clarifies why compartment-focused therapies often reshape rather than eradicate disease. It yields testable predictions and actionable implications: trials should pair multicompartment cytoreduction with strategies that attenuate progenitor-derived reservoirs, restore immune balance, and repair skin barrier dysfunction. A progenitor-initiated, niche-adapted model provides a coherent scaffold for more durable control in CTCL. Full article