Search Results (145)

Historically regarded as competitive modalities, pancreas and islet transplantation are increasingly recognized as complementary approaches to beta-cell replacement therapy. While whole-organ pancreas transplantation remains the established gold standard, islet transplantation has transitioned into an effective clinical alternative for selected cohorts of patients suffering from type 1 diabetes. This review provides a comprehensive evaluation of the clinical evolution characterizing these therapeutic modalities, tracing the shift from static cold storage (SCS) toward innovative dynamic preservation technologies, and exploring potential markers for predicting clinical outcomes. A focus on immunosuppression in islet transplantation is provided, emphasizing precise, tolerance-inducing strategies and investigating costimulation blockade, regulatory T-cell (Treg)-based therapies, and biomaterial-enabled local immunoprotection, with the aim of facilitating long-term graft survival while mitigating the metabolic and renal toxicities secondary to chronic calcineurin inhibitor exposure. Current evidence related to the transition from conventional SCS to advanced perfusion platforms, namely hypothermic machine perfusion (HMP), oxygenated hypothermic perfusion (HOPE), normothermic ex vivo perfusion (NEVP), and normothermic regional perfusion (NRP) is examined: the literature suggests that dynamic pancreas preservation platforms may improve metabolic recovery and some islet isolation outcomes; however, evidence that HOPE specifically reduces ischemia–reperfusion injury and consistently increases islet yield in the pancreas remains limited. Although normothermic perfusion provides significant utility for real-time viability assessment and graft reconditioning, its widespread clinical implementation remains constrained by technical impediments, notably interstitial edema. Ultimately, preservation efficacy is conceptualized not merely as a discrete preservation option, but as a multidimensional construct integrating biological integrity, graft usability, and recipient clinical outcomes. Full article

Ganoderma lucidum polysaccharide peptide (GLPP) is a food-derived macromolecule with immunomodulatory potential, but its gut-centered mechanisms under chemotherapy-associated immunosuppressive stress remain unclear. This study aimed to evaluate the protective effects of GLPP against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury in mice and to explore the associated microbiota–metabolite–gene interaction network using integrated foodomics. BALB/c mice were treated with CTX and then administered GLPP at 50, 100, or 200 mg/kg/day for 42 days, with levamisole as a positive control. High-dose GLPP restored spleen index from 1.592 ± 0.266 to 1.902 ± 0.212 mg/g and thymus index from 0.322 ± 0.146 to 0.656 ± 0.081 mg/g compared with the CTX group. It also enhanced lymphocyte proliferation (OD450: 1.529 ± 0.073 vs. 1.065 ± 0.051), increased carbon clearance index (3.403 ± 0.223 vs. 2.650 ± 0.164), elevated IL-2 and IgA levels, and reduced excessive IFN-γ and TNF-α responses. GLPP alleviated intestinal mucosal injury and reshaped gut microbial profiles, particularly taxa related to Bacteroidota and Bacteroides. Metabolomics revealed putatively annotated differential metabolites associated with amino acid, nicotinate–nicotinamide, and glycerophospholipid metabolism, while transcriptomics indicated modulation of PRR/MAPK-related immune signaling. Integrated correlation analysis suggested a microbiota–metabolite–gene–immune association network involving putative gamma-Glutamylleucine(γ-Glu-Leu), leukotriene D4(LTD4)-like lipid features, and hippuric acid. These findings support GLPP as a promising immune-supporting functional food ingredient, although metabolite assignments and causal mechanisms require further validation. Full article

Bacterial diseases occur frequently in freshwater aquaculture in China, highlighting the need for green immune preparations. Fucoidan and laminarin are commonly used feed additives in livestock and poultry industries; however, their application in freshwater aquaculture remains limited. In this study, juvenile Megalobrama amblycephala were fed diets supplemented with fucoidan or laminarin, each at 0.5% and 2% (w/w), for 8 weeks. After the feeding trial, fish were challenged with Aeromonas hydrophila. Cumulative mortality rate, tissue bacterial loads, innate immune and antioxidant enzyme activities, and immune-related gene and protein expression were evaluated. Dietary supplementation with 2% fucoidan significantly improved the growth performance and feed utilization of juvenile M. amblycephala, while 0.5% fucoidan and 2% laminarin groups only enhanced feed utilization. After A. hydrophila infection, cumulative mortality rates for the control, 0.5% and 2% fucoidan, and 0.5% and 2% laminarin groups were 76.67%, 67.78%, 57.78%, 62.22%, and 58.89%, respectively. Both supplements increased post-infection survival, reduced tissue bacterial loads, and enhanced host bactericidal and antioxidative abilities by elevating innate immune and antioxidant enzyme activities. Innate immunity of juvenile M. amblycephala was improved by regulation of immune-related gene and protein expression levels. Both additives demonstrated significant immunoprotective effects, markedly reducing mortality and tissue bacterial loads following infection. This study provides a theoretical foundation for developing green immunostimulants and antibiotic alternatives for bacterial diseases in fish. Full article

Background: This study aimed to construct a recombinant Pseudomonas aeruginosa outer membrane vesicle (OMV) vector vaccine delivering pcrV and compare the immunological impacts of OMVs as carriers versus as adjuvants. Methods: The recombinant plasmid pBBRMCS5-pcrV was constructed and transformed into P. aeruginosa. Recombinant OMVs (OMV_PcrV) were prepared via ultracentrifugation and characterized in terms of their morphology and particle size by means of transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). After a biosafety evaluation, mice were intramuscularly immunized with PcrV or OMV_PcrV, followed by a booster immunization on day 21. On day 42, the mice were challenged subcutaneously and intranasally with PAO1. Bacterial loads in tissues and blood, pulmonary T-cell subsets, and serum antibody levels were assessed. Results: The recombinant plasmid was successfully constructed, and Western blotting confirmed the delivery of PcrV into OMVs. TEM revealed typical spherical nanostructures, and NTA showed a median particle size of 127.4 ± 5.3 nm. Upon subcutaneous challenge, the OMV, OMV_PcrV, and OMV + PcrV groups all achieved 100% protection. Both the OMV_PcrV and OMV + PcrV groups exhibited increased CD4⁺ and CD8⁺ T-cell counts and higher induction levels of specific IgM, IgG1, and IgG2a antibodies. The OMV_PcrV group showed superior clearance of respiratory bacterial colonization and reduced inflammatory injury compared with the PBS control group. Conclusions: The constructed vector successfully delivered the PcrV antigen, and the OMVPcrV vaccine induced effective immune responses. Compared with wild-type outer membrane vesicles (OMVs) and the strategy of directly mixing free PcrV antigen with OMVs (OMV + PcrV), the recombinant OMV_PcrV vaccine exhibited superior immunoprotective efficacy in terms of bacterial clearance and tissue protection, providing experimental evidence for the development of a Pseudomonas aeruginosa vaccine. Full article

Mori Cortex Radicis (MCR), which is abundant in resources and low in cost, is a Chinese herbal medicine with antitussive, anti-inflammatory, analgesic, and hypoglycemic effects; however, its application in the prevention and control of aquatic pathogens remains understudied. In this study, a MCR water extract (MCR-WE) was prepared, and its contents of polysaccharides, polyphenols, and proteins were found to be 0.63%, 1.17%, and 2.79%, respectively. LC-MS metabolomics revealed that L(+)-Arginine, 9,12,13-Todea, Citric acid, 1-Deoxynojirimycin, and 4-Guanidinobutanoic acid were the most abundant compounds. Subsequently, by feeding the MCR-WE to crucian carp (Carassius auratus) and challenging them with Aeromonas veronii, it was found that the MCR-WE enhanced the activities of immune factors (AKP, ACP, LZM) and the phagocytic activity of leukocytes (p < 0.05). Furthermore, the MCR-WE improved the survival rate of crucian carp (p < 0.05), reduced the bacterial load in the kidneys (p < 0.05), decreased the mRNA expression of inflammatory factors (IL-6, IL-1β, TNF-α), and lowered the expression levels of antioxidant-related factors (CAT, GSH-Px, SOD, MDA) and the mRNAs of oxidative stress pathway factors (Nrf2, HO-1, Keap1) (p < 0.05). Histopathological sections and immunofluorescence assays showed that the MCR-WE maintained the structural integrity of internal organs and reduced renal cell apoptosis and DNA damage. Therefore, MCR-WE is rich in immunologically active substances, can activate the immune response of crucian carp, reduce fish mortality, exert anti-inflammatory and antioxidant activities, and maintain the structural and functional integrity of internal organs. Thus, the MCR-WE holds promise as a therapeutic agent against A. veronii infection in fish. Full article

To address the lack of a commercially available vaccine for goose circovirus (GoCV), we developed and evaluated a prokaryotically expressed subunit vaccine targeting the viral capsid (Cap) protein. A truncated Cap protein (GoCV-ΔCap) was expressed in Escherichia coli (E. coli) and formulated with aluminum hydroxide as a subunit vaccine (GoCVsubvac). Goslings were primed intramuscularly (i.m.) with high (75 µg) or low (15 µg) doses GoCVsubvac, followed by a boost 14 days later. At 14 days post-boost, goslings were challenged with GoCV and were administered a bivalent inactivated vaccine against Newcastle disease virus (NDV) and H9-subtype Avian influenza virus (AIV). Using our established gosling pathogenicity model, vaccine efficacy was evaluated via body weight, lesions, viral load, antibody titers, cytokine responses, and interference with NDV/AIV immunity. Results demonstrated that the GoCV-ΔCap vaccine, especially the high-dose formulation, provided effective immunoprotection. It elicited robust humoral and cellular immune responses, reduced lymphoid pathology, and decreased the viral detection rate in lymphoid tissues from 100% (5/5) in infected controls to 40% (2/5). Importantly, it alleviated GoCV-induced immunosuppression and preserved the immunogenicity of co-administered vaccines. This novel subunit vaccine is a promising candidate for controlling GoCV disease (GoCVD). Full article

Pasteurella multocida serotype A (P. multocida) is frequently associated with severe respiratory disease in swine (Sus scrofa), highlighting the need for effective preventive strategies. To identify protective antigens suitable for a subunit vaccine targeting porcine P. multocida infection, six recombinant proteins (rAspA, rLolA, rOmpP6, rOppA, rRps6, rSmpA) were expressed in a prokaryotic system, and their efficacy was evaluated in a Mus musculus (Kunming) mouse model. All proteins were purified using His-tag affinity chromatography, and SDS-PAGE analysis confirmed expression with bands at the expected molecular weights (61, 26, 21, 63, 19, and 17 kDa). Each protein, formulated with ISA 201 adjuvant, was administered to mice in two immunizations. Indirect ELISA of sera collected at multiple time points demonstrated that all vaccines induced high antigen-specific IgG levels. rOppA, rLolA, rOmpP6, and rRps6 were expressed in soluble form, whereas rAspA and rSmpA formed inclusion bodies. In a lethal challenge model, rLolA and rRps6 conferred the highest protection (60% each), followed by rAspA and rOmpP6 (30%), rOppA (20%), and rSmpA (10%). Under the conditions tested, the highest protection observed was 60%, and none of the six antigens achieved complete protection against homologous A7 challenge in mice. This first head-to-head comparison under identical conditions provides a reference framework for future antigen screening studies. Full article

Avibacterium paragallinarum (A. paragallinarum) is the primary causative agent of infectious coryza in chickens. Infection often leads to growth retardation in broilers and a 10% reduction in egg production, reaching over 40% in laying hens. The problem is particularly severe under intensive farming conditions, significantly jeopardizing global poultry health and farming profitability. From a ‘One Health’ perspective, this not only disrupts the stability of the food supply chain, but also increases antibiotic usage due to disease prevention and control needs, thereby aggravating antimicrobial resistance (AMR) and posing a global public health challenge. This review systematically summarizes advances in the pathogenesis of A. paragallinarum and the protective immunity induced by subunit vaccines. It focuses on the infection mechanisms of A. paragallinarum, emphasizing its colonization strategies in the infraorbital sinus and nasal epithelium of chickens, and analyzes the roles of key virulence factors such as hemagglutinin and capsule in adhesion, colonization, and immune evasion. We integrate the tissue-specific pathogenesis of A. paragallinarum with the role of respiratory commensal microbiota in facilitating infection, providing an in-depth analysis of the bacterium’s key immune evasion strategies, thus offering novel insights into host–pathogen-microbiome interactions. Concurrently, to the best of our knowledge, this review provides the first comprehensive overview of current developments in subunit vaccines and their immunoprotective properties, with special attention to limitations in eliciting mucosal immune responses. By delving into the pathogen-host interaction mechanisms, this review aims to inform the optimization of subunit vaccine design and immunization strategies. Ultimately, it seeks to establish a theoretical basis and practical framework for precise control of A. paragallinarum. Full article

Type II toxin–antitoxin (TA) systems are significantly expanded in the Mycobacterium tuberculosis complex; however, the functional role of the VapBC40 system in Mycobacterium bovis (M. bovis) pathogenesis remains poorly characterized. This study aimed to investigate the role of VapBC40 in mycobacterial virulence and evaluate its potential as a target for rational vaccine attenuation. We performed evolutionary analysis and yeast two-hybrid assays to characterize VapBC40 system specificity, conducted in vitro macrophage infection models and in vivo murine studies to assess virulence contribution, and evaluated the immunoprotective efficacy of a VapC40 knockout strain. Evolutionary analysis revealed progressive sequence conservation and stringent homologous pairing specificity within the VapBC40 system. The VapC40 toxin correlates with enhanced intracellular bacterial survival, increased host cell death, and more severe pulmonary pathology with systemic dissemination. Based on these findings, we evaluated the vaccine potential of a vapC40 knockout strain. Immunization with this attenuated strain elicited a Th1 cellular immune response, characterized by enhanced IFN-γ production and increased frequency of CD4⁺IFN-γ⁺ T cells. Upon challenge with virulent M. bovis, the knockout strain conferred superior protection compared to the conventional BCG vaccine, significantly reducing lung pathology and restricting extrapulmonary bacterial dissemination. Although the molecular mechanisms underlying VapC40-mediated effects remain to be fully elucidated, our findings suggest an important role of the VapBC40 system in mycobacterial-host interactions and support its potential as a target for next-generation tuberculosis vaccine development. Full article

Parathyroid allotransplantation is a promising treatment for hypoparathyroidism, yet immune rejection and fibrosis remain significant barriers. This study evaluates a novel immunoprotective culture system utilizing a moderate-intensity static magnetic field (SMF) to modulate lymphocyte migration without compromising graft functionality. Human parathyroid cells were encapsulated and divided into 10 experimental groups, co-cultured with Jurkat T-lymphocytes, and either exposed to SMF or maintained as controls. Over 72 h, we analyzed parathormone (PTH) secretion, cell viability (via proliferation assays), and molecular expression patterns of key markers (VitDR, PTH, GCM2, and CaSR). Lymphocyte dynamics were monitored through comparative imaging and cytokine profiling (IL-1α, IL-1β, and IL-2). SMF exposure significantly altered Jurkat cell behavior; while lymphocytes in unexposed groups aggregated around microcapsules, they were effectively repelled and migrated away from the graft interface under SMF exposure. Crucially, this biophysical manipulation was safe: no significant differences in PTH secretion or viability were observed across groups. All groups maintained essential genetic markers. Our findings demonstrate that SMF exposure induces lymphocyte migration away from the capsule without compromising parathyroid cell characteristics or functionality. Integrating encapsulation with SMF represents a novel, non-pharmacological, non-invasive immunoprotective strategy for parathyroid allotransplantation, offering a technological alternative to systemic immunosuppression. Full article

The moderate pathogenicity coupled with high host susceptibility of Eimeria maxima has precipitated substantial economic losses in the poultry industry. Addressing challenges such as emerging drug resistance underscores the imperative for innovative vaccine strategies. This study developed a novel DNA vaccine to solve this challenge by fusing E. maxima elongation factor-1α (EmEF1α) with chicken chemokine XCL1 (ChXCL1) in the pVAX1 vector. The recombinant plasmid, designated pVAX1-ChXCL1-EmEF1α, was successfully constructed and confirmed to express the ChXCL1-EmEF1α fusion protein in vitro. Immunization of chickens with this DNA vaccine elicited a robust and balanced immune response, characterized by significantly increased proportions of CD4⁺ (11.76%) and CD8⁺ (5.58%) T lymphocytes, elevated levels of Th1-associated cytokines (IFN-γ and IL-12), and strong antigen-specific IgG and IgA antibody responses. Following experimental challenge with E. maxima, vaccinated birds exhibited substantial protection: a 66.4% reduction in oocyst shedding, a 71.7% improvement in relative weight gain, marked attenuation of intestinal lesions, and an anticoccidial index (ACI) of 170. These findings demonstrate that the ChXCL1-EmEF1α DNA vaccine effectively enhances both cellular and humoral immunity. Collectively, this study validates ChXCL1 as a potent molecular adjuvant and establishes the “antigen–adjuvant” fusion DNA platform as a promising strategy for developing next-generation vaccines against avian coccidiosis. Full article

Static magnetic fields (SMFs) are underexplored as biophysical tools for transplant immunomodulation. This study investigated a 300 mT SMF as a non-pharmacological adjuvant to enhance graft survival in parathyroid xenotransplantation. Human parathyroid tissues were transplanted into Sprague-Dawley rats (n = 20) across four groups: control (G1), SMF-only (G2), transplantation-only (G3), and SMF-assisted transplantation (G4). Following 30-day continuous SMF exposure, functional and immunological assessments were performed. G4 achieved the highest systemic PTH recovery (p = 0.009) without altering intrinsic secretory capacity. Systemic cytokine profiling revealed significant IFN-gamma suppression in G4 (p = 0.0024), suggesting downregulation of Th1-mediated rejection pathways. While G2 showed pro-inflammatory increases (TNF-alpha, GM-CSF), G4 maintained baseline levels, confirming biocompatibility. IHC confirmed that SMF exposure sequestered lymphocytes to the graft periphery, preventing the diffuse infiltration observed in G3. In conclusion, continuous SMF exposure modulates the immune microenvironment by altering lymphocyte migration and IFN-gamma signaling. This biophysical strategy provides localized immunoprotection, potentially offering a drug-free alternative to systemic immunosuppression in endocrine tissue transplantation. Full article

Background: Porcine epidemic diarrhoea virus (PEDV) is a highly contagious pathogen causing severe diarrhoea and high mortality in neonatal piglets. Methods: In this study, consensus sequences encoding the N-terminal domain of spike subunit 1 (S1-NTD) and nucleocapsid (N) protein of PEDV were cloned into a eukaryotic expression vector pJHL204 and transformed into an attenuated Salmonella Typhimurium strain JOL2500. Antigen expression was confirmed by Western blot and immunofluorescence analyses. The recombinant strains were evaluated in vivo for safety, persistence, and immunogenicity. Immunogenicity was characterised by measuring antibody response, virus neutralising assays, cytokine profiling, and flow cytometric analysis of T cell subpopulation. Protective efficacy against salmonellosis in dams and passive transfer of neutralising antibodies to suckling mice were evaluated. Results: Vaccinated mice exhibited no adverse effects or bacterial persistence in major organs, confirming the vaccine’s safety. Immunisation elicited robust PEDV- and Salmonella-specific humoral and cell-mediated immune responses. Upon Salmonella challenge, vaccinated mice showed significantly reduced bacterial loads in splenic tissues. Furthermore, vaccinated dams and their offspring induced detectable anti-PEDV neutralising antibodies, indicating successful passive antibody transfer. Conclusion: Our findings indicate that the designed vaccine constructs provide a promising platform for inducing multifaceted immuno-protectivity against PEDV and salmonellosis. Full article

Diabetes mellitus remains a leading cause of morbidity worldwide, driven in type 1 diabetes by autoimmune destruction of pancreatic β-cells and in advanced type 2 diabetes by progressive β-cell dysfunction and failure. Diabetes affects around 830 million people globally, with the vast majority residing within low- and middle-income nations. Over the last few decades, the numbers of people who have diabetes and those with untreated diabetes have consistently increased. Although current pharmacologic therapies improve glycemic control, they do not restore functional β-cell mass. Consequently, strategies aimed at protecting, regenerating, or replacing insulin-producing cells have emerged as a major focus of regenerative medicine. Stem cell-based approaches offer the potential to generate renewable sources of glucose-responsive β-like cells, but challenges remain in achieving full functional maturation, immune protection, scalable manufacturing, and durable clinical engraftment. This review examines advances in engineering stem cell-derived insulin-producing cells for islet replacement therapy, with an emphasis on differentiation strategies, immunoprotective approaches, and the translational barriers that must be addressed for durable β-cell replacement. Full article

The ontological categorization of the cellular elements of the brain was proposed over a century ago by Santiago Ramón y Cajal (neurons, astroglia) and Pío del Río-Hortega (oligodendroglia, microglia). It combines histochemical observations of morphology with allied inferences about the specialized functions and origins (ectoderm or mesoderm) of each cellular element. This ontology shapes modern neuroscience, with the main non-neuronal cells—astroglia, oligodendroglia and microglia—viewed as having distinct primary roles relating respectively to the metabolic support, myelination and immunoprotection of neurons, the information signaling cells. Yet contemporary techniques, ranging from electrophysiology to single-cell transcriptomics and ultrahigh resolution spectroscopy, are revealing intersecting molecular profiles and functional capacities of these cell groups, for example metabolic support, neuroimmune and signaling functions in oligodendroglia. Here we identify discrepancies in current glial paradigms, from empirical, evolutionary and pragmatic perspectives. We suggest a subset of small, iron-rich glial cells, usually with few processes, often viewed as oligodendroglia with myelin-related primary functions, instead have iron-related primary functions that are central to all aspects of brain activity. We call these ‘ferriglia’. We discuss implications for pathogenesis across the spectrum of neuropsychiatric and neurological disorders, including neurodegenerative conditions such as Alzheimer’s disease and other less common cognitive, movement and neurobehavioral disorders, stroke and cerebrovascular disease, glioblastoma and other brain cancers and neuroimmune conditions. We also briefly address the question of where ferriglia may reside within existing glial compartments and lineages, implications for the ontological classification of other glial cells, and research challenges that must be overcome going forward. Full article