Search Results (254)

Background: With the evolving paradigm of vaccine development, microcapsules have attracted considerable research interest as particulate adjuvants over the past decades. However, the rational engineering design of microcapsule-based composite adjuvant systems to elicit robust immune responses remains a significant challenge. Methods: This study developed polylactic acid (PLA) microcapsules with spatiotemporally coupled delivery and immunopotentiator properties. The resulting formulations were assessed for humoral and cellular immune responses in mice. Results: We prepared uniform-sized microcapsules (MC) and formulated them with monophosphoryl lipid A (MPLA) as a composite component (MPLA@MC), with hydrodynamic diameters of 4.58 μm and 4.12 μm, respectively. Such composite adjuvants, when loaded with ovalbumin (OVA) to form OVA@MC and OVA&MPLA@MC, promoted cellular uptake and activation, exhibiting preferred lysosomal escape advantages. For in vivo experiments, microcapsule-based vaccines elevated serum levels of IgG antibody, and OVA&MPLA@MC induced Th1-biased antibody responses. Specifically, OVA&MPLA@MC also elicited strong cellular immune responses compared to other vaccines, as evidenced by increased secretion of Interferon-γ (IFN-γ) in mouse splenocytes and Granzyme B (Gzmb) in T cells. Mechanistically, muscle tissues at the injection site showed that microcapsule-based vaccines enhanced the recruitment for phagocytosis. Meanwhile, bulk RNA sequencing (RNA-seq) confirmed extensive activation of immune responses and related signaling pathways. Conclusions: This rationally designed composite strategy for spatiotemporally coupled delivery serves as a potent platform for orchestrating synergistic immune responses, opening up new avenues for the development of effective therapeutic and anti-infectious vaccines. Full article

Background: Disease outbreaks remain a major constraint on aquaculture production, making vaccination essential for disease management in farmed fish. However, injectable oil-adjuvanted vaccines can be costly and may induce adverse inflammatory reactions and welfare concerns, motivating investigations into alternative injectable adjuvant materials. Methods: We conducted an in vivo safety evaluation of shear-thinning, amidated TEMPO-oxidized cellulose nanofiber (TO-CNF) hydrogels formulated with an inactivated Vibrio anguillarum bacterin. Formulations were administered intraperitoneally to Atlantic salmon (Salmo salar L.) using a common garden design with cohabitated treatment groups across triplicate tanks. Fish were monitored and sampled at pre-injection baseline and at 300-, and 600-degree days post-injection. Safety endpoints included mortality, macroscopic and histopathological outcomes, and growth evaluated relative to sham controls, unmodified TO-CNF, and a commercial oil-adjuvanted vaccine. Results: Amidated TO-CNF formulations were associated with increased mortality (up to 16–18% in higher reagent-loading groups) compared to commercial oil-adjuvanted vaccine, material, and sham controls. Affected fish exhibited adverse outcomes, including adhesions, proliferative lesions, ascites, edema, hemorrhage, and secondary opportunistic infections. In contrast, controls showed minimal mortality and pathology. Growth and immune response endpoints were variable and did not demonstrate consistent treatment-associated effects. Physicochemical analyses indicated differences in formulation stability and qualitative compositional differences across modification levels, but these were not quantified nor linked to specific causal mechanisms in this study. Conclusions: The amidated TO-CNF formulations tested here were associated with formulation-dependent safety risks under the conditions evaluated and are not yet suitable as injectable vaccine adjuvants in Atlantic salmon. These findings define important safety constraints for this material class and highlight the need for improved modification and purification strategies. More broadly, this work underscores the importance of establishing in vivo safety boundaries prior to efficacy optimization for emerging biomaterial-based vaccine adjuvants. Full article

Background and objectives: Early recovery after major head-and-neck reconstruction is shaped by nutritional vulnerability and functional decline. We evaluated whether preoperative CT-defined low skeletal muscle mass—considered here as an imaging-derived muscle-depletion phenotype rather than the full consensus syndrome of sarcopenia—predicts swallowing milestones, weight trajectory, and patient-reported outcomes at 12 weeks. Methods: In a prospective longitudinal cohort of 74 adults undergoing oncologic resection with reconstruction, low skeletal muscle mass was derived from preoperative cervical CT-based skeletal muscle measurements and nutritional risk was screened with NRS-2002. Outcomes included FOIS, PEG dependence, percent weight loss, MDADI, and European Organisation for Research and Treatment of Cancer QLQ-C30/QLQ-H&N35 at 12 weeks. A multivariable logistic regression explored a composite poor-recovery endpoint (PEG at 12 weeks and/or FOIS ≤ 3 and/or MDADI < 55). Results: Low skeletal muscle mass (32/74, 43.2%) was associated with longer length of stay (13.4 ± 4.1 vs. 10.3 ± 3.3 days; p < 0.001) and more major complications (31.2% vs. 11.9%; p = 0.04). At 12 weeks, affected patients had greater weight loss (10.9 ± 3.4% vs. 8.6 ± 2.6%; p = 0.003), lower FOIS (3.9 ± 1.1 vs. 4.6 ± 1.1; p = 0.01), lower MDADI (57.1 ± 10.9 vs. 66.6 ± 11.9; p = 0.001), and higher PEG dependence (31.2% vs. 9.5%; p = 0.018). Low skeletal muscle mass remained associated with poor recovery after adjustment (aOR 5.4; 95% CI 1.4–24.0; p = 0.016); adjuvant radiotherapy was also associated (aOR 4.3; p = 0.049). Model discrimination was good (AUC 0.81). Conclusions: Preoperative CT-defined low skeletal muscle mass was associated with impaired early recovery after major head-and-neck reconstruction, particularly when adjuvant radiotherapy was anticipated; however, these findings should be interpreted as exploratory and hypothesis-generating. Full article

Background/Objectives: Breast cancer remains the leading cause of cancer-related death among women worldwide. While tools such as Adjuvant Online, PREDICT, OncotypeDx and Mammoprint identify patients at higher risk of relapse who should therefore be offered chemotherapy, there are currently no tools to accurately predict response to chemotherapy, with varied response rates (regardless of subtypes, etc.) of 8–70% reported. Accurately stratifying patients based on their likelihood of benefiting from SoC chemotherapy is therefore critical to guide personalised treatment decisions. Methods: A retrospective cohort of 293 breast cancer patients treated with SoC adjuvant anthracycline-based regimen was analysed. Five biomarkers (TOP2A, PTEN, EGFR, IGF1R, and phospho-mTOR), selected for their prognostic and therapeutic relevance, were assessed using immunohistochemistry (IHC) combined with digital pathology. Results: Biomarker expression was quantified using the digital pathology platform, QuPath, with each marker, when stratified based on high/low expression, demonstrating a significant association with relapse-free survival following SoC chemotherapy in specific subtypes of breast cancer. A composite five-biomarker signature was then generated by integrating the individual biomarker scores to improve prognostic precision. Patients with a five-biomarker signature score greater than zero exhibited a significantly higher likelihood of favourable outcomes following anthracycline-based chemotherapy compared with those with a score of zero or below. Conclusions: This study establishes a novel IHC-based five-biomarker signature capable of predicting patient outcome in the context of SoC chemotherapy. As the signature relies exclusively on IHC, it is simple, cost-effective and readily integratable into routine diagnostic workflows. In addition to its prognostic value, several biomarkers within the panel are potentially actionable, offering opportunities to guide targeted therapies in patients predicted to have poor response to conventional chemotherapy. Full article

Menopause represents a key transitional phase in women’s health, characterized by declining estrogen levels and increased risk for cardiometabolic, musculoskeletal, and urogenital disorders. Beyond its endocrine roots, emerging evidence highlights the gut microbiome as a critical modulator of systemic hormonal balance. This review synthesizes current understanding of the bidirectional relationship between estrogen and the gut microbiome and its implications for women’s health during menopause. Evidence from current studies reveals distinct findings across populations, reflecting the complexity of estrogen regulation in part by the gut microbiome (i.e., estrobolome). While no ideal gut microbial composition has been identified for women across stages of perimenopause, likely due to geographically unique gut microbiome profiles among healthy women, greater microbial diversity has been positively associated with improved estrogen regulation. Conversely, reduced diversity and altered Firmicutes/Bacteroidetes ratios have been linked to biomarkers of inflammation during perimenopause, which is a key driver across many perimenopausal symptoms. Although hormone replacement therapy remains the primary clinical intervention during perimenopause, we highlight emerging evidence on the adjuvant potential of diet, synbiotics, phytoestrogens, and strain-specific probiotics in modulating the estrogen–gut microbiome axis for improved health span trajectories and better symptom management. Future longitudinal studies integrating diet, gut microbiome profiles and symptom trajectories are essential to clarify these mechanisms across ethnicity and geography. Ultimately, understanding localized diet–microbiome interactions will enable the development of accessible, personalized, and non-hormonal strategies to complement and increase agency in proactive management during the perimenopausal transition. Full article

Type 2 diabetes mellitus (T2DM) has become a global metabolic disorder, and sprouted wheat (SW) exhibits potential for alleviating metabolic syndromes, although its mechanism remains unclear. This study aimed to investigate the effects and underlying mechanisms of SW on T2DM using a high−fat diet−induced T2DM mouse model. SW intervention significantly improved glycolipid metabolism disorders (p < 0.05), attenuated hepatic mitochondrial injury (p < 0.05) and maintained hepatic homeostasis. SW also reshaped the gut microbiota structure and inhibited the TLR4/NF−κB inflammatory pathway (p < 0.05). Untargeted metabolomics combined with network pharmacology identified five key functional metabolites and four core targets involved in the protective effects of SW. Germination optimized the nutritional composition of wheat, and SW regulated the microbe–liver axis through a multi−component, multi−target and multi-pathway mode. These results reveal the mechanism of SW in improving T2DM−related metabolic disorders and provide experimental support for its application. In the future, SW can be further developed as a dietary nutritional supplement for the prevention and adjuvant treatment of metabolic diseases. Full article

Background/Objectives: Diffuse midline glioma (DMG), H3 K27M-altered, represents a rare group of gliomas arising in midline structures of the central nervous system. Historically regarded as a pediatric entity, it is now increasingly recognized in adults. Although its relative prevalence among all midline diffuse gliomas and its clinical-radiological characteristics are well defined in children, these tumors remain less characterized in adults, and comparative evaluations with H3 K27 wildtype midline diffuse gliomas are limited. Methods: Consecutive adult patients with histopathologically confirmed diffuse glioma (WHO grade ≥ 2) diagnosed between 2016 and 2025 were retrospectively screened for midline tumor location, with systematic revision of imaging and pathology. For identified midline diffuse gliomas, comprehensive clinical, imaging, and immunohistochemical data were collected, and a detailed morphometric analysis was performed. H3 K27 alteration status was established immunohistochemically, with supplementary immunostaining when necessary. Descriptive and comparative analyses were conducted. Results: A total of 5% of the 541 adult diffuse gliomas were midline, and 23% of IDH wildtype midline gliomas were consistent with DMG, H3 K27-altered (all H3 K27M-mutant). The affected patients were significantly younger, and these tumors predominantly involved the thalamus and mesencephalon. Morphometric analyses revealed trends toward fewer high-grade features in H3 K27-altered tumors, with composite scores demonstrating significant discriminatory ability. The overall survival was not significantly different between groups but showed associations with ring-like enhancement as well as adjuvant and salvage therapies in the overall midline cohort. Conclusions: This study provides population-based prevalence estimates for DMG, H3 K27M-altered, and complements the limited literature with comparative clinical-radiological and morphometric data of potential prognostic relevance. Full article

Malignant gliomas, including glioblastoma multiforme (GBM) and grade 4 astrocytoma, are the most common types of brain tumors in adults. Standard treatment for gliomas includes adjuvant chemotherapy, typically based on temozolomide, combined with radiotherapy. However, its effectiveness is severely hindered by the limited ability of drugs to cross the blood–brain barrier and by the hyperactivation of the canonical Wnt signaling pathway, which drives tumor cell survival. Therefore, innovative drug combinations and novel delivery strategies are crucial for overcoming these barriers. Polymeric micelles represent a promising approach for enhancing drug delivery to brain tumors. This study aimed to obtain micelles containing cannabidiol (CBD), celecoxib (CELE), and temozolomide (TMZ), as well as their combinations, and to verify their anti-glioma properties. The study involved optimizing the micelle composition, incorporating active ingredients, and assessing the temporal stability of the resulting nanocarriers under varying temperature conditions. The GBM cell line U-138 MG and astrocytoma cell line U-87 MG were used to evaluate the biologic effects of the tested micelles. Cytotoxicity was assessed using the MTT assay, and flow cytometry was used to analyze the effect of the micelles on apoptosis. Western blot analysis was employed to assess the impact of the tested nanoformulations on the Wnt/β-catenin signaling pathway. The optimized micelles demonstrated strong cytotoxic and proapoptotic effects, accompanied by attenuation of the Wnt/β-catenin pathway. These preliminary findings support the therapeutic potential of polymeric micelles for treating malignant gliomas; however, further in vitro and in vivo studies are required to confirm their clinical applicability. Full article

Celiac disease (CeD) is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals which also entails intestinal dysbiosis. This hallmark microbial imbalance provides a rationale for exploring interventions that could modulate the gut ecosystem. Cocoa is a bioactive food rich in polyphenols, theobromine, and fiber, compounds known to have an influence on both immune function and gut microbiota composition. Here, we investigated the effects of cocoa supplementation on the gut microbial profile and predicted functionality in DQ8-D^d-villin-IL-15tg mice, genetically predisposed to CeD. Animals were assigned to a reference group receiving a gluten-free diet (GFD), a gluten-containing diet group (GLI), or the latter supplemented with defatted cocoa (GLI + COCOA) for 25 days. The cecal microbiota was analyzed via 16S rRNA sequencing, and functional pathways were inferred using PICRUSt2. Goblet cell counts and CeD-relevant autoantibodies were measured and correlated with microbial taxa. Cocoa supplementation partially attenuated gluten-induced dysbiosis, preserving beneficial taxa such as Akkermansia muciniphila and Lactobacillus species while reducing opportunistic and pro-inflammatory bacteria. Functional predictions suggested differences in the predicted microbial metabolic potential related to amino acid, vitamin, and phenolic compound metabolism. Cocoa also mitigated goblet cell loss and was inversely associated with anti-gliadin IgA levels. These findings suggest that cocoa, as an adjuvant to a GFD, could be of help in maintaining microbial homeostasis and intestinal health in CeD, supporting further studies to assess its translational potential. Full article

Candida albicans is a major opportunistic fungal pathogen whose increasing resistance to antifungal agents requires new alternative therapies. This study evaluated the antifungal potential of Lippia graveolens (Mexican oregano) essential oil, with particular emphasis on its effects on key C. albicans virulence factors. The chemical composition of the essential oil was determined by GC–MS, identifying carvacrol and thymol as abundant components. Antifungal activity was assessed via disk diffusion, broth microdilution, and time-kill kinetics against clinical and reference Candida strains. The essential oil showed potent fungicidal activity, with MIC and MFC values of 2 mg/mL and 3 mg/mL, respectively. In addition to demonstrating antifungal potency, this work focused on C. albicans virulence factors, revealing that L. graveolens essential oil significantly inhibited germ tube formation at 1 mg/mL and completely suppressed both germ tube and biofilm development at concentrations ≥ 2 mg/mL, along with dose-dependent disruption of fungal membrane integrity. These findings highlight the multifactorial mechanisms by which L. graveolens essential oil affects C. albicans pathogenicity. This study supports its potential as a natural antifungal agent and a valuable adjuvant in the treatment of resistant candidiasis. Full article

Marine biofouling presents a persistent challenge for maritime industries, necessitating the development of eco-friendly and intelligent antifouling strategies. In this work, an ATP-responsive nanocontainer was developed by encapsulating a natural organic compound (CS106-10), isolated from Talaromyces trachyspermus in cold seep sediments, together with D-phenylalanine (D-Phe) into ZIF-90 nanoparticles (D-Phe/CS106-10@ZIF-90). These nanoparticles were incorporated into zinc acrylate resin to fabricate a novel self-polishing antifouling coating. CS106-10, as a natural antifoulant, provided efficient and environmentally sustainable bactericidal activity, while D-Phe acted as a synergistic adjuvant to inhibit and disrupt biofilm formation. More importantly, the ATP-responsive ZIF-90 framework enabled controlled, on-demand release of antifouling agents in response to local metabolic signals associated with biofilm growth. Laboratory and real-sea evaluations confirmed that the composite coating effectively suppressed biofilm formation and significantly reduced the required dosage of conventional toxic antifoulants. This study integrates a natural antifoulant with an ATP-responsive metal–organic framework, providing new insight for developing antifouling coatings. Full article

Background/Objective: Alzheimer’s disease (AD) is a neurodegenerative condition characterized by oxidative stress, neuroinflammation, amyloidogenesis, and tau-related pathology. This study investigated the macronutrient and phytochemical composition of strawberry (S), lemon (L), and lemon juice-assisted strawberry (S/L) extracts and evaluated their neuroprotective efficacy relative to selenium (Se) in an aluminum chloride (AlCl₃)-induced rat model of AD. Methods: Macronutrients and phenolics were quantified in S, L, and S/L, and the extracts were profiled using high-performance liquid chromatography and electrospray ionization tandem mass-spectrometry. Male Sprague–Dawley rats received AlCl₃ with or without S, L, S/L, or Se, and their cognitive performance was assessed using the Morris water maze, Y-maze, and conditioned avoidance tests. Markers of oxidative status, inflammation, cholinergic function, apoptotic signaling, and Wnt3/β-catenin pathway activity were quantified in the brain tissue, and cortico-hippocampal morphology was examined. Results: The S/L extract showed the highest carbohydrate, protein, and lipid content. The total phenolic content was highest in S/L (60.46 mg gallic acid equivalents/g), followed by L (55.08) and S (44.75), with S/L also being the richest in gallic, ellagic, and chlorogenic acids. S/L attenuated AlCl₃-induced cognitive deficits, restored antioxidant status, suppressed neuroinflammation, improved cholinergic indices, modulated apoptotic signaling, and downregulated amyloidogenic and NLRP3 inflammasome markers, consistent with histological evidence of neuronal preservation. Conclusions: Lemon juice-assisted extraction enhanced the macronutrient and phenolic richness and multitarget neuroprotection of strawberries. S/L co-extracts represent promising functional food–derived adjuvants for AD management and support integrative compositional–mechanistic profiling to optimize natural product–based interventions. Full article

Background/Objectives: Natural plant-based compounds, especially black pepper extract, are known to have anti-inflammatory, antibacterial, and antioxidant qualities that promote procollagen formation and wound healing. This study focused on developing a collagen-based composite enriched with P. nigrum extract in powder form, designed to enhance the efficacy of the antibiotic cefazolin while promoting the healing of chronic wounds. Methods: The polyphenolic P. nigrum extract was obtained by ultrasound-assisted extraction and was characterised by UHPLC-MS/MS and spectrophotometry. Antimicrobial and antioxidant activities were assessed using conventional methods. Pharmacokinetic and pharmacodynamic parameters were evaluated for the specific taxon compounds using Deep-RK. P. nigrum extract was incorporated into a collagen hydrogel with arginine and freeze-dried. The powders were characterised by FTIR, SEM, TGA-DSC, and DLS. The antimicrobial activity and potential synergistic effects with cefazolin were evaluated on reference microbial strains and isolates from infected wounds. Biocompatibility and hemocompatibility were evaluated, as well as wound closure in vitro. Results: Polyphenols, including phenolic acids, stilbenes, anthocyanins, and flavonoids, which provide a potent antioxidant capacity through electron transfer mechanisms (FRAP, CUPRAC), were abundant in the P. nigrum extract. FTIR and SEM analyses confirmed the integration of phenolic compounds into the collagen–arginine matrix without protein denaturation. TGA–DSC data showed thermal stabilisation at moderate extract concentrations. The extract exhibited predominantly bacteriostatic antibacterial activity and antibiofilm effects, with synergy/additivity with cefazolin, especially at medium doses. Tests on keratinocytes confirmed biocompatibility, and hemocompatibility demonstrated an excellent safety profile, with protection against AAPH-induced oxidative stress. Conclusions: Overall, collagen powders with P. nigrum extract at moderate/low concentrations combine stability, antibiotic-enhanced activity, and cellular compatibility, making them promising adjuvants for the topical treatment of chronically infected wounds. Full article

Dandelion is an edible and medicinal plant that has beneficial effects in various complex disorders. In this study, we investigated the regulatory effects of dandelion leaf aqueous extract (DAE) on mice with hyperuricemia (HUA) and explored its underlying mechanisms. DAE exhibited a high total phenolic content (363.31 ± 0.61 mg GAC/g) and contained 20 identified polyphenolic compounds. The administration of DAE significantly reduced serum uric acid levels and exerted protective effects on both liver and kidney function in mice with HUA. Mechanistically, DAE inhibited the NLRP3/Caspase-1 and TLR4/MyD88/NF-κB signaling pathways, leading to the downregulated mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), thereby alleviating renal inflammation. Additionally, DAE modulated the gut microbiota composition and increased SCFA-producing bacteria, along with increases in fecal SCFA contents. These findings suggest that DAE effectively mitigates HUA and its associated renal complications by regulating uric acid metabolism, suppressing renal inflammation, and restoring gut microbial homeostasis. Thus, DAE holds promise as a natural adjuvant therapy for HUA and related kidney inflammation. Full article

Nutrition is being increasingly recognized as a modifiable adjuvant factor in symptom management, yet few studies have examined the direct contribution of fruit consumption to chronic disease outcomes. The existing research largely emphasizes broad dietary patterns or isolated nutrients, rather than specific fruit species and their complex bioactive profiles. This gap is particularly evident in conditions lacking disease-specific pharmacological treatments, such as fibromyalgia syndrome (FMS), where patients often depend on lifestyle adjustments and complementary strategies for symptom relief. The therapeutic use of fruits presents methodological challenges, as their biochemical composition is strongly influenced by abiotic and biotic stresses, seasonal and regional variations, as well as post-harvest handling and storage. Such variability complicates reproducibility and obscures causal links in clinical research. While reductionist approaches that isolate single compounds offer dose control, they risk losing synergistic effects inherent to whole fruits. Conversely, whole-fruit consumption preserves integrative complexity but introduces variability. Overcoming these limitations requires rigorous standardization across agricultural, nutritional, and clinical domains, accurate species and cultivar identification, controlled cultivation conditions, chemical fingerprinting, and biomarker validation. In this context, cacti fruits such as Opuntia ficus-indica (prickly pear), which is rich in betalains and polyphenols, emerge as promise adjuvant agents for FMS symptom management. We propose a protocol designed to systematically evaluate their efficacy and feasibility in clinical application, aiming to strengthen the reliability and accuracy of research outcomes. Full article