Search Results (999)

Bacterial cellulose (BC) has emerged as a structurally robust, biologically compatible, and highly adaptable biomaterial with significant potential for next-generation wound-care technologies. Its nanofibrillar, extracellular-matrix-like architecture provides exceptional moisture retention, mechanical stability, and conformability, enabling BC to function as an active scaffold rather than a traditional dressing. Advances in chemical modification, composite engineering, and bioactive functionalization, including antimicrobial metals, chitosan, biosurfactants, enzymes, and growth factors, have expanded BC’s therapeutic capabilities. Emerging smart BC dressings integrate biosensors, stimuli-responsive drug release, and 3D-printed architectures tailored to patient-specific wound geometries. Parallel developments in artificial intelligence (AI) are transforming BC production by optimizing bioprocessing, guiding genetic engineering, reducing culture media costs, and enabling real-time quality control, thereby improving scalability and industrial feasibility. These combined innovations position BC as a multifunctional, immunologically instructive, and digitally integrated platform for advanced regenerative wound care. This review reframes BC within the contemporary pathophysiology of chronic wounds, emphasizing its roles in immunomodulation, macrophage polarization, angiogenesis, mechanotransduction, and the disruption of mixed bacterial–fungal biofilms that characterize diabetic foot ulcers and other non-healing wounds. BC hydrogels typically contain >90–99% water and exhibit tensile strengths exceeding 200 MPa, enabling robust mechanical performance in wound environments. Advances in BC composites have demonstrated antimicrobial reductions of 3–5 log units against common chronic-wound pathogens. Full article

The increasing adoption of biopolymeric and nanostructured coatings for horticultural produce has emerged as a sustainable strategy to mitigate postharvest losses and extend shelf life. However, while their technological performance has been extensively documented, comprehensive and integrative assessments of biosafety, potential human health implications, and environmental risks profiles are still insufficiently explored. This review critically analyzes recent advances in polysaccharide, protein, and lipid-based coatings, including nanoenabled systems incorporating metallic nanoparticles and bioactive agents. The mechanisms underlying gas barrier properties, antimicrobial activity, and preservation efficacy are discussed alongside degradation pathways in composting, soil, and aquatic environments. Particular attention is given to nanoparticle release, migration potential, gastrointestinal fate, and toxicological endpoints such as oxidative stress, genotoxicity, endocrine disruption, and immunomodulation. Ecotoxicological evidence across trophic levels, from microorganisms and invertebrates to fish and amphibians, is examined, highlighting sublethal and mechanistic biomarkers relevant to environmental risk assessment. Regulatory frameworks from major agencies are also compared to contextualize current safety standards and limitations. Overall, although biopolymeric coatings represent promising alternatives to conventional plastics, their life-cycle impacts, transformation products, and nano-related uncertainties require comprehensive, multilevel risk evaluation to ensure truly sustainable and safe postharvest applications. Full article

Temporomandibular disorders (TMDs) are multifactorial conditions traditionally attributed to excessive mechanical loading on the temporomandibular joint, leading to clinical manifestations ranging from joint sounds to structural deformation. Contributing factors include trauma, occlusal abnormalities, psychological stress, and bruxism. However, immune and molecular alterations associated with early disease activity are not systematically integrated into structure-centered TMD frameworks. Emerging evidence indicates that temporomandibular joint osteoarthritis (TMJOA) involves activation of innate immunity caused by damage-associated molecular patterns (DAMPs) generated through mechanical loading, together with non-antigen-specific adaptive immune responses, including macrophage polarization and T helper 17 (Th17) and regulatory T (Treg) cell imbalance. Inflammatory and mechanical inputs converge through shared signaling modules and mechanoresponsive transcriptional programs, promoting extracellular matrix degradation, fibrotic remodeling, and subchondral bone remodeling. This review synthesizes the current immunopathological and mechanobiological evidence and introduces temporomandibular immunologic disease (TMID) as a mechanism-oriented framework, characterized by a reinforcing cycle between mechanically induced tissue damage and immune activation within the temporomandibular joint (TMJ) microenvironment. TMID complements TMJOA and Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) structural diagnostic categories while excluding antigen-specific autoimmune arthritides such as rheumatoid arthritis, thus functioning as a mechanistic overlay framework for the integration of immuno-mechanical signaling networks in immune-active, mechanically driven TMJ pathology. Full article

Glioblastoma (GBM) remains among the most treatment-refractory human malignancies. It is characterized by profound radioresistance and a highly immunosuppressive tumor microenvironment, limiting the durable efficacy of radiotherapy. Beyond direct cytotoxicity, ionizing radiation can induce immunogenic cell death and the release of damage-associated molecular patterns (DAMPs), including surface-exposed calreticulin, HMGB1, extracellular ATP/adenosine, and tumor-derived DNA. These signals engage pattern-recognition receptors and cGAS–STING–type I interferon pathways, transiently promoting antigen presentation and immune activation. In GBM, however, DAMP signaling frequently evolves toward chronic inflammation and immune suppression, characterized by myeloid cell recruitment, adenosine accumulation, and immune checkpoint upregulation, thereby contributing to tumor regrowth and radioresistance. This dual immune-regulatory role of DAMPs highlights the importance of temporal and contextual interpretation of radiation-induced immune responses. In this review, we summarize current mechanistic and translational evidence on DAMP-mediated immunomodulation in GBM radiotherapy; discuss modality-dependent considerations across photon, proton, and high-LET irradiation; and evaluate the emerging potential of DAMPs as dynamic biomarkers of treatment response. We further outline how integration of DAMP profiling with liquid biopsy, imaging, and nanotheranostic platforms may support biologically informed and adaptive radiotherapy strategies for glioblastoma. Full article

Fish allergy, mainly caused by Parvalbumin (PV), is a worldwide health issue with few effective mitigation options. This study investigated Maillard conjugation using chitosan (CS) and various saccharides to modify the structural, functional, and allergenic properties of turbot (Scophthalmus maximus) PV. Structural analyses, including SDS-PAGE, Western blotting, FTIR spectroscopy, and Circular dichroism, confirmed successful conjugation and significant changes in secondary structure, including decreases in α-helical content and increases in β-sheet and random-coil fractions. Glycation significantly boosted antioxidant activity, with total phenolic content (TPC) increasing up to 10.3 times and DPPH radical scavenging reaching 74.5% in the CS–xylose–PV conjugate (CXTPV). Indirect ELISA revealed notable (p < 0.05), sugar-dependent reductions in IgE-binding capacity, with reductions of up to approximately 72% for CXTPV. RBL-2H3 cell assays showed decreased β-hexosaminidase release (about 75% reduction), lowered IL-6 secretion, and strong inhibition of IL-4 production, indicating reduced allergenic potential and immune regulation. CXTPV demonstrated the best overall performance. These findings suggest that CS–saccharide Maillard conjugation is an effective approach for creating hypoallergenic marine ingredients with improved bioactive properties. Full article

Biological heterogeneity among different breast cancer (BC) subtypes results in markedly varying clinical outcomes. Identification and analysis of key gene biomarkers that are differentially regulated during radiation therapy (RT) may pose multiple clinical challenges for BC treatment. The purpose of the study is to identify and analyze the expression of key gene biomarkers and their networks that are differentially regulated after hypofractionated RT. Patients with BC (cT0-T2, N0, M0) were treated with hypofractionated whole breast RT 25 Gy in five fractions, 4 to 8 weeks before breast conservation surgery (BCS). Biopsy (pre-RT; n = 5) and surgical (post-RT; n = 14 or 15) BC tumor samples were used for NanoString targeted sequencing. We identified 165 and 244 differentially expressed genes (DEGs; p < 0.05) in BC tumor samples from BC patients post-RT using the nCounter BC360 and IO360 panels, respectively. Gene networks and pathway analysis revealed that RT increases the gene signature of tumor inflammation (TIS), cytotoxicity, and apoptosis, while downregulating the gene signatures of tumor cell proliferation, differentiation, and cell adhesion, and increases the claudin-low gene score. RT-induced mammary stemness and enhanced infiltration of stroma, mast, and macrophage cells in the BC tumor microenvironment (TME). Further, the nCounter IO360 (immuno-oncology) panel analysis validated the findings of BC360 and demonstrated that RT increased the myeloid inflammation signature and chemokine expression, modulated B, T, NK, and DC cell activities, and enhanced residual cancer burden (RCB) in BC tumors, thus creating an immunosuppressive TME. Collectively, RT sensitized BC tumors by increasing the gene signature of TIS, cytotoxicity, apoptosis, and mammary stemness. RT facilitated an immunosuppressive environment and increased RCB, suggesting that the therapeutic potential of RT is highly individualized for each patient based on their unique tumor biology, genetic makeup, and TME. Full article

Objectives: This study aimed to assess the effects of voluntary exercise on type 1 diabetes mellitus (T1D) development and splenic immunological profiles in non-obese diabetic (NOD) mice, a spontaneous model of human T1D. Methods: Prediabetic female NOD mice were randomly assigned to sedentary or exercise groups, with mice in the exercise group given 10-week wheel access and sedentary mice receiving none. Late-time mice were monitored to diabetes onset or 24 weeks of age; early-time mice were analyzed immediately post-intervention. Blood glucose, food intake, water consumption, and body mass were monitored weekly. At the endpoints, splenocyte counts, T and B cell subsets, and mitogen-stimulated cytokine production were analyzed using flow cytometry. Results: Mice in the exercise group ran an average of 20.76 ± 0.22 km/day. By the late-time endpoint, 75% of mice in the exercise group remained non-diabetic versus 35% of sedentary mice (p = 0.006). Mice in the exercise group demonstrated lower blood glucose (p = 0.015), visceral fat mass (p = 0.035), and water intake (p < 0.001) but higher food intake (p = 0.001), with no difference in body mass (p = 0.389) compared to sedentary mice. No differences were observed in splenocyte counts or Th, Tc, Treg, or B cell populations at either time point (p ≥ 0.185). Early-time point cytokines also did not differ between groups (p ≥ 0.08). Conclusions: Voluntary exercise reduces T1D incidence and mitigates hyperglycemia in NOD mice, suggesting a protective effect against disease progression. Despite the benefits, physical activity did not alter splenic Tcell subsets or inflammatory cytokines, demonstrating systemic immunomodulation may not be the primary driver of benefit. Our results indicate that voluntary exercise protects against T1D through tissue-specific or metabolic mechanisms, which warrant further mechanistic investigation. Full article

Sulfated polysaccharides (SPs), biologically active macromolecules from marine and terrestrial organisms, hold significant potential in revolutionizing cancer therapy. Characterized by their unique sulfate ester groups and structural diversity, SPs exhibit a broad spectrum of bioactivities, including immunomodulation, apoptosis induction, metastasis suppression, and angiogenesis inhibition. Prominent SPs, such as fucoidan from brown algae and carrageenan from red algae, have shown remarkable anticancer properties, either as standalone agents or in synergy with conventional therapies like chemotherapy and radiotherapy. Their mechanisms of action involve targeting critical pathways such as NF-kB, VEGF, and PI3K/Akt, disrupting cancer cell proliferation, invasion, and tumor microenvironment dynamics. SPs also enhance immune system responses, reduce chemotherapy-induced side effects, and exhibit antioxidant properties, making them versatile candidates in cancer treatment. Innovations like SP-based nanoparticles are addressing bioavailability and drug delivery challenges, providing targeted and sustained therapeutic effects while minimizing off-target toxicity. Despite their promise, challenges such as structural complexity, scalability, and clinical validation hinder their widespread adoption. This review provides a comprehensive analysis of SPs’ therapeutic potential, mechanisms, and emerging applications in oncology. It emphasizes the need for advanced extraction, characterization techniques, and clinical research to unlock their full potential, paving the way for novel, efficient, and safer cancer therapies. Full article

Dang Gui (Radix Angelica sinensis), a classic Chinese medicinal herb, is renowned for nourishing blood, promoting blood circulation, regulating meridians, and relieving pain, and widely used clinically for anemia, cancer, rheumatoid arthritis, ulcerative colitis, and other diseases. Studies have confirmed that Dang Gui and its major bioactive components (e.g., polysaccharides, ferulic acid, (Z)-ligustilide) exert diverse pharmacological activities including immunomodulation, neuroprotection, and hepatoprotection. Based on a systematic literature search, this review summarizes the traditional applications and main chemical constituents of A. sinensis, with a focused analysis of its immunomodulatory effects. Evidence shows that A. sinensis exerts bidirectional immunoregulation by improving immune organ indices, promoting the proliferation and activation of immune cells, including T/B lymphocytes (T/B cells), macrophages, and regulating cytokine secretion. Furthermore, it reviews its immunomodulatory mechanisms in immune-related diseases (e.g., cancer, aplastic anemia, chronic pain), analyzes its quality control standards from regulatory and pharmacopeial perspectives and summarizes relevant safety research. This review comprehensively integrates the immunoregulatory effects and underlying mechanisms of A. sinensis, aiming to provide a scientific basis for its future research and clinical application. Full article

The receptor for advanced glycation end-products (RAGE) is a lung-enriched pattern recognition receptor implicated in inflammatory responses. Its role in ferroptosis-mediated lung injury during viral infection, however, remains unclear. Here, we combined bioinformatics analysis with in vitro and in vivo experimental validation to investigate the RAGE–ferroptosis axis in influenza virus infection. Cross-analysis of RAGE- and ferroptosis-related genes identified overlapping candidates, suggesting functional crosstalk. Influenza-infected A549 cells exhibited ferroptotic cell death, characterized by Fe²⁺ accumulation, reactive oxygen species (ROS) elevation, and lipid peroxidation, which was markedly attenuated by the RAGE inhibitor FPS-ZM1. In A/PR/8/34 (H1N1)-infected female C57BL/6J mice, FPS-ZM1 treatment improved survival, reduced lung injury, restored redox balance, and modulated key ferroptosis regulators ACSL4, POR, and GPX4. Moreover, RAGE inhibition decreased M1 macrophage and neutrophil infiltration and reduced pro-inflammatory cytokines. Collectively, these findings reveal that RAGE activation drives ferroptosis and amplifies oxidative stress–associated lung injury, whereas RAGE inhibition mitigates tissue damage via the ACSL4/POR/GPX4 pathway and immunomodulation. This study identifies the RAGE–ferroptosis axis as a potential therapeutic target for severe pulmonary inflammation. Full article

Polysaccharides are natural polymers that are widely found in medicinal plants. Structurally, they are complex molecules composed of long chains of monosaccharide units linked by glycosidic bonds. Modern pharmacological research shows that the bioactivity of polysaccharides is closely related to their monosaccharide composition. This review summarises the monosaccharide composition of 210 polysaccharides from 72 medicinal plants. They were classified into 10 types through principal component analysis (glucans; homogalacturonan; galactans; arabinogalactans; mannans; glucomannans; arabinans; xylans; fructans; rhamnogalacturonan-I). The relationship between monosaccharide composition and biological activity was further analysed. The results are as follows: glucans make significant contributions to immunomodulation, antioxidant activity, and gut microbiota regulation; galactans are crucial for antioxidant effects, immunomodulation, and gut microbiota regulation; mannans play a key role in immunomodulation, antitumor activity, and neuroprotection; fructans are vital for gut microbiota regulation, immunomodulation, and antioxidant effects; and pectins exhibit notable immunomodulatory, antioxidant, and hypoglycaemic properties. Consequently, developing polysaccharides from medicinal plant resources based on their monosaccharide composition is expected to speed up the search for polysaccharides with high biological activity and provide a theoretical reference for polysaccharide research. Full article

Bone defects have become a leading cause of disability and mortality. The pro-inflammatory state and impaired vascularization are major factors hindering bone defect repair. However, current bone regeneration materials lack the ability to regulate the osteoimmune microenvironment and promote vascularized bone regeneration. In this study, we employed clinically used fat emulsion (FE), which is intravenously administered to provide nutrition and energy for patients, to investigate the effect of immunomodulation on promoting angiogenesis and osteogenesis. Results from RT-qPCR analysis and immunofluorescence staining demonstrated that FE exhibited potent anti-inflammatory effects by reducing the expression of the pro-inflammatory marker inducible nitric oxide synthase (iNOS) and upregulating the expression of the anti-inflammatory marker transforming growth factor-beta (TGF-β). Endothelial tube formation and scratch assays demonstrated that FE promoted angiogenesis and cell migration by releasing vascular endothelial growth factor (VEGF) within the inflammatory microenvironment. Alkaline phosphatase (ALP) and alizarin red S (ARS) staining revealed that FE facilitated ALP activity and calcium nodule formation by releasing bone morphogenetic protein-2 (BMP-2) within the inflammatory microenvironment. These findings may prove promising and cost-effective for the clinical treatment of bone defects. Full article

Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared richness in polysaccharides and secondary metabolites relevant to immune engineering and regenerative medicine. This review critically synthesizes current evidence on plant-derived polysaccharides and phytochemicals, including algal sulfated polysaccharides (fucoidan, alginate, carrageenan, and ulvan), terrestrial plant polysaccharides (e.g., Lycium barbarum and Aloe vera derivatives), polyphenols, and other secondary metabolites such as terpenoids and alkaloids, highlighting their roles as immunomodulators in biomedical contexts. Key mechanisms include macrophage polarization along an M1–M2 continuum, pattern recognition receptor engagement, redox and metabolic regulation, and crosstalk between innate and adaptive immunity, with emphasis on context-dependent signaling and structural heterogeneity. Material design parameters, including molecular weight and chemical functionalization, are critical determinants of immune responses. Advanced delivery systems, such as hydrogels, nanocomposites, phytosomes, and plant-derived extracellular vesicles (EVs), enable improved stability and spatiotemporal control. Applications in wound and musculoskeletal regeneration are discussed alongside translational challenges, including variability, reproducibility, regulatory issues, and the need for standardized characterization and immune validation. Full article

Background: Orthodontic tooth movement is traditionally explained through mechanical deformation of the periodontal ligament (PDL); however, increasing evidence indicates that immune mechanisms critically shape bone remodeling outcomes. Mechanical stimuli influence immune cell recruitment, cytokine release, and phenotypic polarization, but these components are rarely integrated into a unified framework. Conceptual framework: We propose the Osteoimmune Axis Model, a conceptual framework describing how mechanical loading may bias immune polarity and thereby gate periodontal remodeling. Compressive loading appears to favor an M1 macrophage/Th17-dominant program associated with pro-inflammatory cytokines and enhanced RANKL-mediated osteoclastogenesis. In contrast, tensile or physiological strains may favor M2 macrophages and regulatory T cells (Treg), supporting IL-10, TGF-β, angiogenesis, extracellular-matrix repair, and osteoblastic activity. Stromal cells are proposed to act as mechanosensors and immune amplifiers that shape cytokine gradients and feedback loops. Predictions: The model predicts that identical forces may produce divergent outcomes depending on immune baseline; load duration may be more destructive than peak magnitude; tensile strain may stabilize M2/Treg pathways; thin periodontal phenotypes may shift toward the catabolic pole at lower mechanical loads; ROS may amplify immune-mediated bone loss; and immunomodulation may raise the threshold for pathological remodeling. Conclusion: The Osteoimmune Axis integrates mechanobiology and immunology into a testable framework for explaining variability in orthodontic periodontal remodeling and for generating hypothesis-driven, immune-aware risk assessment. Full article

This study investigates the immunomodulatory effects and underlying mechanisms of KEMPFPK, a peptide derived from bovine β-casein, using integrated in vitro, in silico, and in vivo approaches. In RAW264.7 macrophages, KEMPFPK enhanced proliferation, phagocytosis, and migration and selectively upregulated the chemokine MCP-1. Under LPS-induced inflammation, KEMPFPK suppressed pro-inflammatory cytokines (IL-1β, TNF-α) and NO production while promoting the anti-inflammatory cytokine IL-10. These effects were mediated through the inhibition of NF-κB and MAPK signaling pathways. Molecular docking predicted high-affinity binding of KEMPFPK to Toll-like receptors (TLR2 and TLR4), suggesting a potential mechanism for its immunomodulatory activity. In cyclophosphamide (CTX)-induced immunosuppressed mice, KEMPFPK administration restored immune organ indices, rebalanced serum cytokine levels, and modulated humoral immunity. Importantly, KEMPFPK was associated with a significantly reshaped gut microbiota profile, characterized by the promotion of beneficial genera (e.g., Ligilactobacillus, Adlercreutzia) and the suppression of opportunistic pathogens (e.g., Escherichia–Shigella). These findings establish KEMPFPK as a dual-phase immunomodulator and suggest that its effects may involve direct immune cell regulation coupled with indirect microbiota remodeling. This study provides a scientific foundation for the application of KEMPFPK in immunomodulatory functional foods. Full article