Search Results (3,163)

Marine lectins function as pattern recognition receptors in innate immunity through carbohydrate-binding mechanisms. However, mechanistic evidence detailing intracellular signaling cascades (e.g., MAPK/NF-κB/JAK-STAT activation linked to defined cytokine outputs) remains taxonomically uneven. Bivalve mollusks—particularly the Mytilectin family—represent the most extensively characterized group, whereas lectins from other marine phyla (echinoderms, cnidarians, fish, algae) have been studied primarily for structural and glycan-binding properties alongside phenotypic antimicrobial outcomes. Signaling-level resolution in native immune-cell contexts, while present in some cases, remains comparatively limited. This review synthesizes mechanistic insights dominated by bivalve-derived lectins, while integrating cross-taxa comparisons at evidence-supported levels. Specific bivalve lectins induce macrophage activation and pro-inflammatory cytokine production through reactive oxygen species-dependent activation of key signaling pathways including MAPK, NF-κB, and JAK-STAT cascades. These lectins exhibit context-dependent properties, promoting inflammatory responses in resting cells while inducing endotoxin tolerance in pre-activated macrophages through epigenetic reprogramming. Functional outcomes include broad-spectrum antiviral activity through viral envelope glycoprotein binding, anti-inflammatory effects in pain models, and cancer-associated immune responses through tumor glycan recognition and macrophage polarization. Critical gaps include uncharacterized effects on adaptive immunity, limited understanding of dendritic cell and natural killer cell interactions, and incomplete evaluation of cancer immunotherapy potential. Future research should prioritize mechanistic characterization of marine lectin-based immunotherapeutics. Full article

Articular cartilage, a highly specialised and avascular tissue, exhibits limited regenerative potential following trauma or degenerative conditions such as osteoarthritis (OA). Conventional surgical interventions, including microfracture and autologous chondrocyte implantation (ACI), have shown limited long-term efficacy due to donor site morbidity and restricted cell proliferation. In this context, mesenchymal stromal cells (MSCs) have emerged as a promising alternative owing to their multipotency, self-renewal capacity, and low immunogenicity. While bone marrow (BM) remains the traditional source of MSCs, recent studies have reported that peripheral blood-derived mesenchymal stromal cells (PB-MSCs) may possess chondrogenic, osteogenic, and adipogenic potential comparable to that of BM-derived MSCs. PB-MSCs can be harvested through minimally invasive methods, thereby avoiding the complications associated with BM aspiration. Experimental evidence indicates that PB-MSCs exhibit strong cell viability, proliferative potential, and the ability to synthesise cartilage-specific extracellular matrix proteins, such as type II collagen and sulphated glycosaminoglycans, within three-dimensional scaffolds. Immunophenotypically, PB-MSCs express mesenchymal markers including CD29, CD44, CD90, and CD105 while lacking hematopoietic markers CD34 and CD45. Flow cytometry analyses reveal that CD105⁺ populations increase following cryopreservation, highlighting their clinical utility. In contrast to these experimentally defined PB-MSCs, the term peripheral blood stem cells (PBSCs) is used in clinical studies to describe heterogeneous, non-cultured peripheral blood-derived cell preparations, typically enriched in hematopoietic stem and progenitor cells following granulocyte colony-stimulating factor (G-CSF) mobilisation, without full mesenchymal characterisation. In vitro studies confirm successful tri-lineage differentiation, whereas in vivo investigations have demonstrated effective cartilage regeneration using PB-based clinical approaches, including postoperative intra-articular administration of hyaluronic acid (HA) combined with PBSCs, as well as implantation of PBSCs covered with a collagen membrane. Furthermore, advancements in biomaterial engineering, such as poly(ethylene glycol)–cysteine–arginine–glycine–aspartic acid (PEG-CRGD) hydrogels, have enhanced PB-MSC adhesion, proliferation, and chondrogenic differentiation while promoting immunomodulation through M2 macrophage polarisation. Despite these promising outcomes, the available evidence remains limited and heterogeneous, with substantial variability in cell definitions, experimental models, and clinical study designs, which currently constrains definitive conclusions regarding clinical efficacy. Future research should focus on optimising isolation protocols, understanding molecular pathways governing PB-MSC chondrogenesis, and standardising clinical applications. Overall, PB-MSCs represent a viable, less invasive, and translationally relevant cell source for cartilage regeneration and regenerative orthopaedic therapies Full article

Psoriasis is a chronic inflammatory disease with a complex pathogenesis, and it is mainly driven by a dysregulation in immune responses. Therapeutic strategies constantly require novel compounds targeting immune modulation to substitute the current traditional drugs characterized by side effects and limited efficacy. In this study, we used a mannan-induced psoriasis-like inflammation mouse model to investigate the immunomodulatory potential of Iripin-3, a salivary serpin from the Ixodes ricinus ticks. Mice treated with Iripin-3 showed improvements in the severity of psoriasis-like lesions, as shown by the psoriasis area severity index (PASI) scores, epidermal thickness, and baker’s scores. Iripin-3 modulated the immune cascade by inhibiting dendritic cells and γδ T cells expression in secondary immune organs while increasing macrophages and neutrophils in skin. On the other hand, Iripin-3 exhibited significant reductions in the expression of inflammatory cytokines such as TNF-α, IL-22, IL-23, and IL-17 family cytokines, indicating broad immunomodulatory effects. Our findings suggest that Iripin-3 offers a unique and targeted mechanism of action through modulation of the IL-23/γδ T/IL-17 axis involved in mannan-induced psoriasis-like inflammation and thus could be a promising therapeutic candidate for treating psoriasis. Further studies are required to explore its translational potential in wider clinical settings. Full article

Advances in regenerative medicine have positioned platelets and their derivatives—including platelet-rich plasma, platelet-rich fibrin, platelet lysate, extracellular vesicles, and purified growth factors—as promising interventions specifically for skin and bone aging, two clinically accessible tissues with robust preclinical and clinical evidence for platelet-derived component-based rejuvenation and regeneration. Because much of the available evidence comes from injury models or age-associated inflammatory/degenerative diseases, we explicitly distinguish pathology-targeted inflammation resolution/repair from rejuvenation under physiological aging. This review summarizes the composition and core bioactivities of platelet-derived products and delineates their putative anti-aging mechanisms, encompassing proangiogenic signaling, immunomodulation, attenuation of oxidative stress, regulation of extracellular matrix turnover, and stimulation of osteogenesis. We further evaluate emerging applications that expand therapeutic performance, such as platelet-mimetic delivery vehicles, engineered and sustained-release formulations, and targeted use of subcellular structures. Evidence from recent preclinical and clinical studies indicates favorable safety profiles and signals of efficacy across cutaneous rejuvenation and skeletal regeneration, while underscoring persistent challenges related to product standardization, dosing, and outcome measures. Collectively, platelet-based therapeutics represent a versatile platform with broad applicability to anti-aging interventions in skin and bone and strong potential for translation through continued bioengineering and clinical validation. However, because most available evidence comes from injury models or age-associated diseases (e.g., photoaging, chronic wounds, osteoarthritis, osteoporosis), direct extrapolation to physiological aging is limited; throughout, we explicitly contrast these contexts, specify their indication-specific endpoints, and summarize the main translational limitations. Full article

Current wound healing strategies must confront numerous challenges. Helminth-induced immunomodulation offers a promising therapeutic avenue for inflammatory diseases and injury repair. However, research on the role of helminths in damage recovery remains limited. We utilized glycogen—a naturally occurring biomaterial—to encapsulate SJMHE1, a bioactive peptide derived from Schistosoma japonicum, and successfully developed a facilely prepared hydrogel formulation denoted as SJMHE1-gel. The properties of SJMHE1-gel, its effect on cell activity, and its performance in a murine full-thickness skin defect model were evaluated. The glycogen-based hydrogel exhibited a uniform pore size, excellent biocompatibility, and sustained release of SJMHE1. Topical application of SJMHE1-gel enhanced collagen deposition, promoted angiogenesis, facilitated the regeneration of hair follicles and sebaceous glands, and accelerated full-thickness wound healing. SJMHE1-gel also promoted M2 macrophage polarisation and suppressed inflammatory cytokine expression both in vivo and in vitro. Mechanistically, SJMHE1-treated macrophages upregulate TGF-β, which in turn promotes the migration of L929 fibroblasts and human umbilical vein endothelial cells (HUVECs) via the Smad3 pathway. Neutralization of TGF-β attenuates phosphorylated Smad3 (p-Smad3) levels and impairs the migratory capacity of both fibroblasts and HUVECs. Additionally, SJMHE1-treated macrophages upregulate VEGFA, thereby enhancing angiogenic tube formation in HUVECs. This easy-to-prepare hydrogel can regulate macrophage polarization, inhibit inflammation, promote angiogenesis, and accelerate collagen deposition, acting across wound healing stages to provide a novel therapeutic strategy. Full article

Background: Sepsis is one of the leading causes of early death after a liver transplant, with a frequency of up to 45% and a high death rate of 50% in more severe forms. Standard diagnostic and therapeutic algorithms are often not applicable to this specific population, where immunosuppression, reperfusion injury, and systemic inflammation overlap and generate a clinical picture that is significantly different from sepsis in immunocompetent patients. Methods: This paper analyzes the available literature and clinical experiences of characteristic immune and hemodynamic profiles of sepsis after liver transplants. Biomarkers (IL-6, IL-10, HLA-DR, lactate, and IgM) are discussed as tools for assessing immune status and guiding timely interventions, including the early application of continuous renal replacement therapy (CRRT) and the selective use of IgM-enriched immunoglobulins. Results: Sepsis after liver transplantation frequently unfolds in two phases, an initial hyper-inflammatory response driven by cytokine release and reperfusion injury and a second phase of secondary immunoparalysis characterized by reduced HLA-DR expression and increased anti-inflammatory signaling. The immunometabolic shift appears to influence the clinical course and may inform therapeutic decision-making. The immunoparalysis phase is accompanied by mitochondrial dysfunction and impaired vascular reactivity. This type of mechanism contributes to hemodynamic instability and a reduced response to standard therapy. Individualized monitoring and early use of hemofiltration and immunomodulatory measures can improve results in carefully selected patients. Conclusions: In this setting, an individualized immunometabolic approach may complement standard sepsis management in liver transplant recipients. The introduction of biomarkers of immune function into routine practice and the recognition of early signs of exhaustion of the immune response can assist in timely therapeutic decision-making and improve survival. Full article

Nerve injury often results in neuropathic pain, marked by spontaneous pain, hyperalgesia, and allodynia. Current treatments have moderate efficacy and have side effects, prompting interest in alternative approaches. Mesenchymal stem cell (MSC) therapy has shown promise in preclinical studies for reducing neuropathic pain and inflammation. However, the precise mechanisms underlying MSC-mediated pain reduction remain unclear. Investigating these mechanisms is crucial for optimizing MSC-based therapies for neuropathic pain. This article provides a brief overview of the MSC administration, animal models of neuropathic pain, and treatment regimens used in 25 preclinical studies, focusing on the potential mechanisms of action underlying the neuropathic pain-reducing effect of MSCs. Importantly, 23 out of the 25 studies demonstrated a reduction in neuropathic pain following MSC therapy, despite differences in MSC sources and treatment regimens. Neuropathic pain relief was associated with decreased inflammation, suggesting that MSCs may act through immune modulation. However, the resolution of inflammation does not always correlate with complete neuropathic pain relief, indicating the involvement of additional mechanisms. Full article

Yeast β-glucans are bioactive polysaccharides derived primarily from the cell walls of Saccharomyces cerevisiae. They are widely recognized for their immunomodulatory, antioxidant, and anti-inflammatory actions as well as for their probiotic effects. Their addition to food products has gained growing interest owing to their ability to promote health as well as to enhance sensorial and technological attributes of foods. The aim of this narrative review is to present the health benefits of yeast β-glucans according to the mechanisms taking place, compare them to other biomolecules with analogous health-promoting effects, and summarize the existing knowledge on their incorporation into various food matrices. Focus is also given to clinical trials using foods enriched with yeast β-glucans as well as in vitro digestion studies of such foods. In addition, research interest extends to the methods of yeast β-glucan assessment in food products. Despite the promising results so far, significant challenges remain, including variability in study design, limited translational evidence from in vitro studies, and the lack of standardized protocols for determination across various food categories. Overall, the reviewed literature supports their growing potential as valuable components in the design of functional foods. Ongoing research and advancement should prioritize well-designed human trials, standardized production protocols and deeper structure–function relationship investigation in order to further reveal their contribution across a wide range of applications, reinforcing both consumer health and innovation within the food industry. Full article

Immunodeficiency is a global health concern, partly due to disrupted rhythms and drugs. Marine glycopeptides, with immunomodulatory and intestinal barrier protective activities, show great potential in dietary supplements and functional foods. Here, a marine glycopeptide, SC2-3, with a molecular weight of 5061 Da, was isolated and purified from Nereis succinea. Monosaccharide composition, NMR data, amino acid composition analysis, and SDS-PAGE analyses identified SC2-3 as a glycopeptide. The N-glycome results of SC2-3 collected by MALDI-TOF-MS revealed that SC2-3 contains fucosylated N-glycans with shorter glycan chains compared to human-derived N-glycans. SC2-3 exerted a significant immune-enhancing effect on macrophages in vitro. In vivo, in cyclophosphamide-induced immunocompromised mice, SC2-3 at different concentrations elevated organ indices, blood cell counts, and serum levels of IL-1β, TNF-α, and IL-6, while repairing cyclophosphamide-damaged/atrophied tissues. Mechanistically, SC2-3 induced the differentiation of RAW264.7 cells toward an M1-like activation profile, significantly promoting the release of NO and ROS, upregulating the secretion of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6), and activating the TLR4/NF-κB signaling pathway. Additionally, SC2-3 upregulated intestinal epithelial tight junction proteins and normalized the overexpression of MUC-2, thereby maintaining intestinal barrier integrity. These findings indicated the potential efficacy of the glycopeptide SC2-3 derived from natural marine sources in immunomodulation and protection of intestinal health. Full article

Ocular graft-versus-host disease (oGVHD) remains one of the most challenging complications of allogeneic hematopoietic stem cell transplantation (HSCT), often leading to severe ocular surface morbidity and irreversible vision loss if not properly managed. Diagnostic uncertainty persists due to variability in clinical presentation and a lack of universally accepted criteria, but the greatest clinical burden lies in establishing effective, durable treatment protocols. Current strategies range from lubricants and topical immunomodulators to advanced surgical interventions; however, outcomes remain inconsistent due to delayed recognition and heterogeneous practices across institutions. At institutions like MD Anderson Cancer Center (MDACC), a structured treatment strategy has been developed that emphasizes early recognition and targeted therapy based on the specific ocular tissues affected. This approach integrates patient-reported outcomes with objective ocular findings and applies stepwise therapeutic escalation aligned with tissue-specific pathology. This review offers a brief overview of the clinical burden and pathophysiology of oGVHD, outlines the key diagnostic challenges, and a more detailed discussion on therapeutic strategies with particular emphasis on the targeted tissue-based approaches. Full article

Background: Increasing evidence identifies intratumoral bacteria as key modulators of tumor progression, chemoresistance, and immunosuppression, presenting major obstacles to conventional cancer therapies. Recent advances in nanotechnology have enabled new strategies for selective targeting bacteria within the tumor microenvironment, potentially improving anticancer efficacy. Methods: A scoping review was conducted to outline the current landscape of nano-based therapeutic approaches aimed at the simultaneous elimination of intratumoral bacteria and cancer. Preclinical research publications involving in vivo antitumor efficacy evaluations were retrieved from three databases, Web of Science, PubMed, and Scopus, using the key words “(kill* OR eradicate* OR eliminate*) AND intratumoral AND (bacteria OR infection)”. Key information from the eligible studies was extracted and analyzed. Results: The diversity of bacterial species, cancer models, and evaluation methodologies employed in these preclinical studies were summarized, followed by critical examination of the design principles, therapeutic outcomes, and translational challenges of various nanomedicine platforms, including passive and active targeting drug delivery systems, phototherapy, phage therapy, and emerging modalities. Nano-based therapeutics functionalized with both antibacterial and anticancer properties were shown to effectively overcome bacteria-induced treatment resistance. Conclusions: Targeting intratumoral bacteria may significantly enhance the efficacy of existing treatments and contribute to the evolution of precision oncology. The insights gained from this review are expected to guide future systematic reviews and inform research directions in the development of dual-functional nanomedicines for cancer therapy. Full article

Emodin, a trihydroxy-methyl anthraquinone abundant in rhubarb, Polygonum species, and other medicinal plants, exemplifies the therapeutic potential and translational complexity of the broader anthraquinone scaffold. Anthraquinone derivatives have demonstrated antiproliferative, anti-inflammatory, metabolic, cardiovascular, antifibrotic, and immunomodulatory effects, consistently reported across diverse preclinical models, targeting pathways such as NF-κB, PI3K/AKT, MAPKs, AMPK, PPARs, NLRP3, and ferroptosis-related axes. Despite strong preclinical efficacy, clinical development has been limited by unfavorable absorption, distribution, metabolism, and excretion (ADME) characteristics, including poor aqueous solubility, extensive first-pass glucuronidation, and active efflux via intestinal and hepatic transporters. These features result in low and variable systemic exposure, while high local concentrations, particularly in the gastrointestinal tract, contribute to context-dependent toxicity signals that complicate risk assessment. The present review integrates pharmacological, toxicological, and formulation-focused evidence to provide a unified assessment of emodin and the anthraquinone scaffold. Particular emphasis is placed on bidirectional, dose- and context-dependent effects on the liver and kidney; the modulation of cytochrome P450 enzymes, UGTs, and transporters; and emerging preclinical formulation strategies that aim to decouple intrinsic bioactivity from pharmacokinetic limitations. Full article

Solid-state and submerged fermentation (SSF and SmF) were evaluated as bioprocessing strategies to enhance the recovery and bioactivity of phenolic compounds from blueberry bagasse. Fermentation was performed using Aspergillus niger ATCC 6275 and Rhizopus oryzae BIOTEC018, alongside non-inoculated controls. Extracts (SmF filtrate, buffer, methanol, and buffer-methanol) were obtained and analyzed for total phenolic content (TPC), total anthocyanins, and antioxidant capacity over 0–60 h. Methanolic extracts obtained after 24 h of SSF were further selected for profiling of individual phenolics and for intracellular reactive oxygen species (ROS), nitric oxide (NO), and cytokine responses. Compared with SmF and non-inoculated controls, SSF—particularly when combined with methanolic extraction—was associated with modified phenolic recovery patterns at 24 h, including increases in TPC and differences in anthocyanin preservation. SSF promoted the accumulation of phenolic acids and flavan-3-ols, together with improved preservation of major anthocyanins. These compositional changes translated into higher antioxidant capacity and a marked reduction in ROS and NO levels (≈40–60% of oxidant or LPS controls). Cytokine responses were strain-dependent, indicating regulated immune modulation rather than generalized inflammation. Overall, fungal SSF combined with methanolic extraction modulated the phenolic profile and associated biological responses of blueberry bagasse under laboratory conditions. Full article

Dogs can develop chronic inflammatory diseases that induce progressive tissue damage and illness. Delphinidin is a component of maqui (Aristotelia chilensis) and has anti-inflammatory and antioxidant effects. This study evaluated the immunomodulatory effects of delphinidin chloride (DC) and delphinidin-3-glucoside (D3G) on neutrophils and peripheral blood mononuclear cells (PBMCs) in dogs. Leukocytes were isolated from 20 clinically healthy dogs and treated with DC and D3G at concentrations of 50, 100, and 150 µM. The cells were then stimulated with lipopolysaccharide (LPS), platelet-activating factor (PAF), or phorbol 12-myristate 13-acetate (PMA) to evaluate cell viability, reactive oxygen species (ROS) production, neutrophil extracellular trap (NET) formation, phagocytosis, chemotaxis, matrix metalloproteinase 9 (MMP-9) activity, and cytokine production. The results showed that both compounds preserved cell viability, significantly reducing ROS production and NET formation. DC significantly increased chemotaxis and D3G significantly reduced MMP-9 activity. Both compounds reduced the secretion of interleukin (IL) 1β (IL-1β) and tumor necrosis factor α (TNF-α) in neutrophils. In PBMCs, they decreased the production of IL-4 and IL-6 and modulated the production of interferon γ (IFN)-γ. In conclusion, delphinidin exerts selective anti-inflammatory activities in canine leukocytes, promoting inflammation resolution, suggesting its potential role as a nutraceutical for managing inflammatory pathologies in dogs. Full article

Background: Immunomodulatory compounds can modify or regulate the immune responses. Given that vaccine-induced immune responses can vary in magnitude and durability depending on antigen properties and adjuvant selection. Immunomodulators that enhance antigen-specific immune responses with low toxicity may complement existing adjuvant systems. Recent studies indicate that adenosine receptor–mediated signaling can modulate dendritic cell (DC) function through mechanisms distinct from classical pathogen-associated molecular pattern (PAMP)-driven Toll-like receptor pathways. Methods: In this context, the present study comparatively evaluates poly-(lactic-co-glycolic acid) (PLGA) microparticle–encapsulated β-L-adenosine (BLA MPs) alongside established FDA-approved adjuvants to assess their immunomodulatory potential under limited-antigen conditions. FDA-approved PLGA was used to encapsulate BLA in combination with multiple viral antigens, including H1N1 influenza, Zika virus, and canine coronavirus, to enable sustained delivery, antigen protection, and efficient uptake by antigen-presenting cells. Results: Physicochemical characterization demonstrated uniform particle size distribution, a low polydispersity index, and a stable negative surface charge. Release studies showed more than 50% payload release within 12 h, with release kinetics best described by the Korsmeyer–Peppas model. Cytotoxicity evaluation using DC2.4 cells confirmed that BLA MPs were non-cytotoxic at concentrations up to 250 μg/mL. Comparative in vitro immunological assessments revealed that BLA MPs induced dendritic cell activation, including upregulation of antigen-presenting and co-stimulatory molecules, at levels largely comparable to those observed with Alum- and MF59-based formulations across multiple antigen groups. Nitric oxide production remained within comparable ranges, indicating balanced immunostimulatory activity without excessive inflammatory signaling. In select conditions, co-formulation of BLA MPs with MF59 further enhanced DC activation, supporting its role as a complementary immunomodulatory component. Conclusion: These findings align with previously reported adenosine-dependent pathways involved in DC maturation and antigen presentation. Overall, this comparative study demonstrates that PLGA-encapsulated β-L-adenosine functions as an effective immunomodulatory agent, with performance comparable to that of established FDA-approved adjuvants across diverse vaccine antigens. Further in vivo studies are warranted to evaluate dose dependency, cytokine profiles, and antibody responses to define its role within combinatorial vaccine adjuvant strategies. Full article