Search Results (7,650)

Background: In the Republic of Korea, a bivalent foot-and-mouth disease (FMD) vaccine covering serotypes O and A is administered to livestock, while antigens for the other serotypes are stockpiled in overseas antigen banks. To achieve self-reliance in FMD vaccine production, various vaccine strains have been developed using in-house technology. Although SAT 3 has historically been confined largely to Africa, preparedness against this serotype remains necessary, as the possibility of its introduction into Korea cannot be completely excluded. Methods: In this regard, we evaluated the commercial potential of the SAT 3 ZIM-R vaccine strain by assessing antigen productivity, scalability, inactivation kinetics, and immunogenicity. Results: Supplementation with 3 mM Ca²⁺ markedly increased antigen yield compared with that obtained in the absence of calcium. Further optimization showed that antigen yield was highest at pH 8.0–8.5. During scale-up, antigen yield was maintained at 9.2–9.8 μg/mL in flask cultures and remained high at approximately 7.8 μg/mL in a bioreactor, demonstrating robust scalability. Treatment with 2 mM binary ethylenimine at 26 °C achieved complete inactivation within 24 h. Vaccines formulated with the SAT 3 ZIM-R antigen produced either in flasks or in a bioreactor induced comparable neutralizing antibody responses in pigs following both the primary and booster immunizations. Conclusions: Collectively, these findings indicate that SAT 3 ZIM-R is a promising vaccine candidate for large-scale vaccine antigen production and the future establishment of a domestic FMD antigen bank in Korea. Full article

Background/Objectives: Ribosome-inactivating proteins (RIPs) are plant-derived enzymes with potent cytotoxic activity, widely studied as anticancer agents, particularly as toxic payloads in immunoconjugates. Despite numerous encouraging results reported, their clinical application has been limited by their immunogenicity. RIPs from edible plants have been proposed as potentially more suitable candidates due to their possible improved tolerability. However, this aspect still requires validation in vivo in animal models. This study investigated the cytotoxic activity, mechanisms of action and translational potential of sodin 5 (a recently characterized type 1 RIP derived from the edible plant Salsola soda L.) in human colon cancer models, comparing it to the well-known type 1 RIP saporin-S6. Methods: The effects of sodin 5 and saporin-S6 on cell viability, cell death mechanisms and epithelial barrier integrity were assessed on HT29 and Caco-2 cell lines. Sodin 5 cross-reactivity with other anti-type 1 RIP sera was evaluated by ELISA. Finally, its structural characteristics were analyzed. Results: Sodin 5 showed a cytotoxic effect comparable to that of saporin-S6 in HT29 and Caco-2 colon cancer cells, with time- and concentration-dependent reductions in viability. Both type 1 RIPs disrupted the integrity of the intestinal epithelial barrier in mono- and co-culture models and predominantly activated the apoptotic pathway, without inducing necrosis. Sodin 5 exhibited limited immunological cross-reactivity and a conserved catalytic core, supporting its potential relevance as a therapeutic payload for intestinal cancer therapy. Conclusions: Our results indicate that sodin 5 possesses promising characteristics for anticancer applications, particularly in the treatment of intestinal malignancies, where local exposure and repeated administration are often required. Full article

Although prebiotics and postbiotics support gastrointestinal health, evidence for their combined effects in dogs remains limited. This study evaluated a novel prebiotic and postbiotic supplement in healthy dogs undergoing a dietary transition. Thirty-six healthy adult dogs were randomly assigned to control group (CON, high-protein basal diet with placebo chew) or treatment group (TRT, the same basal diet with chew containing prebiotics [baobab fruit pulp and acacia gum] and postbiotics [inactivated Lactobacillus acidophilus and selected yeast fractions]) for a 28-day formal trial following a 7-day adaptation period. The primary outcomes evaluated included clinical fecal scores, specific biomarkers of intestinal barrier function and inflammation, fecal short-chain fatty acids, and microbiota structure. Following the 7-day adaptation, formal trial baseline, fecal scores were already within the healthy range and remained optimal without differing between groups throughout the study. Compared with CON, the TRT group showed lower fecal calprotectin and serum diamine oxidase levels, and higher fecal butyrate (p < 0.05). Metagenomic analysis revealed increased abundances of Bacteroidota, Oscillospiraceae, Prevotellaceae, and Prevotella in TRT (p < 0.05). Overall, in healthy dogs, this supplementation was associated with favorable microbiota modulation and modulated biomarkers of intestinal barrier and inflammation within normal ranges, without altering clinical fecal endpoints. Full article

Selenium-sand melon (Cucumis melo L.) juice (SSJ) is valued for its lycopene and organic selenium content, but its shelf-life is limited by heat-labile nutrients and postharvest microbial spoilage. Non-thermal strategies that combine UV-C with natural antioxidants are therefore of interest. This study quantified the individual and interactive effects of UV-C alone or with four antioxidant systems on microbial safety, bioactive retention, and the flavor stability of SSJ under extreme contamination conditions (Escherichia coli D25015 at 5.19 log₁₀ CFU/mL; Mucor circinelloides D11624 at 4.36 log₁₀ CFU/mL). For this, we evaluated the efficacy of five treatments: UV-C alone (Group Z) and UV-C combined with catechin (Group EC, 0.01%), sodium erythorbate (Group K, 0.01%), ascorbic acid (Group VC, 0.1%), and catechin-ascorbic acid (Group HH, 0.005% + 0.05%). Conventional pasteurization (high-temperature short-time, HTST; low-temperature long-time, LTLT) served as controls. UV-C alone (Group Z) preserved lycopene and volatile flavor compounds better than HTST or LTLT. The combined use of UV-C and antioxidants exhibited synergistic effects, with no viable bacteria detected in Group K (sodium erythorbate) within four weeks. UV-C combined with antioxidants offer a scalable, non-thermal strategy that maintains nutritional and sensory quality while achieving pathogen reduction. These findings provide a quantitative framework for clean-label preservation of functional melon beverages. Full article

Dickkopf-1 (DKK1) is a 266-amino-acid secreted glycoprotein originally identified as a high-affinity antagonist of the canonical Wnt/β-catenin signaling pathway and has emerged as a complex regulator in oncology. While historically considered as a tumor suppressor due to its ability to abrogate Wnt-driven proliferation, recent discoveries highlight a paradoxical pro-oncogenic role across various malignancies. The molecular mechanisms by which DKK1 promotes tumor progression, metastasis, and immune evasion are driven by its interaction with cell-surface receptors, specifically LRP5/6 and CKAP4. The DKK1-CKAP4 axis independently activates PI3K/AKT signaling, facilitating epithelial–mesenchymal transition (EMT), chemoresistance, and the formation of osteolytic bone lesions. Furthermore, DKK1 serves as a critical orchestrator of the tumor microenvironment (TME) by driving comprehensive immune reprogramming. It mediates the recruitment of myeloid-derived suppressor cells (MDSCs) and inactivates cytotoxic CD8⁺ T cells and natural killer (NK) cells, thereby fostering an immunosuppressive tumor microenvironment and resistance to checkpoint inhibitors. Interestingly, cancer-associated fibroblasts (CAFs) are a primary source of DKK1 in the stroma, where they facilitate immune evasion. Clinically, elevated circulating DKK1 levels correlate with advanced disease stages, increased metastatic potential, and poor overall survival in solid and hematological tumors. When used in combination with established biomarkers, serum DKK1 levels demonstrate significant utility for early detection and therapeutic monitoring. Given its intricate impact on malignancy, DKK1 has become a promising therapeutic target, with ongoing clinical trials investigating neutralizing antibodies such as DKN-01 to disrupt its oncogenic and immunosuppressive signaling. Understanding the context-dependent nature of DKK1 signaling remains essential for refining its application as both a biomarker and a component of emerging precision immunotherapy strategies. By prioritizing the literature from the last decade, this review characterizes DKK1 as a key mediator of tumor progression and immune reprogramming, while assessing its clinical potential as a biomarker and therapeutic target. Full article

Increasing evidence suggests pancreatic cancer develops within a host–microbe ecosystem in which microbial communities across anatomical niches interact with tumour biology, immune regulation, metabolism, and therapeutic response. This review examines pancreatic cancer through the lens of humans as holobionts, integrating evidence from the oral, gut, biliary, and intratumoural microbiomes. Epidemiological and sequencing studies demonstrate consistent microbial alterations across these niches in pancreatic cancer, including oral dysbiosis associated with periodontal pathogens, gut microbial shifts toward pro-inflammatory taxa, disease-specific biliary microbial signatures, and the presence of distinct intratumoural microbial communities. Mechanistic studies indicate that intestinal barrier disruption, microbial translocation, immune and metabolite signalling can influence tumour immune architecture, macrophage polarisation, T-cell infiltration, oncogenic signalling pathways, and chemotherapeutic metabolism, particularly inactivation by tumour-associated bacteria. Microbiome-driven shifts in immunometabolism can reprogramme immune-cell metabolic pathways, impairing effective T-cell activation, promoting tumour-supportive macrophage phenotypes. Emerging therapeutic strategies aim to modulate the microbiome–tumour axis, including dietary interventions, probiotics and immunonutrition, faecal microbiota transplantation, engineered microbial therapies, and microbiome-informed antibiotic strategies. While pre-clinical findings are compelling and early-phase clinical studies suggest feasibility, most evidence remains associative and heterogeneous across cohorts and methodologies. Understanding pancreatic cancer as a multi-site ecological system may help explain inter-patient variability in disease progression and treatment response. This could usher in a new era for therapeutic manipulation where future progress will depend on longitudinal, multi-omic, and interventional studies to determine whether microbiome-targeted strategies can produce clinically meaningful improvements in pancreatic cancer outcomes. Full article

Background: Methylthioadenosine phosphorylase (MTAP) deficiency caused by homozygous deletion is prevalent in solid tumors and contributes to malignant progression, thereby rendering cancer cells vulnerable to dysfunction of protein arginine methyltransferase 5 (PRMT5). This study aimed to investigate whether Poly (ADP-ribose) polymerase (PARP) inhibitors could exploit this vulnerability through PRMT5 inactivation in MTAP-deficient tumors. Methods: PRMT5 activity was assessed in vitro and in vivo following PARP inhibitor treatment. The antitumor effects of PARP inhibitors alone or in combination with either the MTAP inhibitor MTDIA or the PRMT5 inhibitor EPZ015666 were evaluated in solid tumor models, including MTAP-deficient tumor models in vivo. Results: PARP inhibitors effectively inactivated PRMT5 in vitro and in vivo and exacerbated DNA double-strand breaks induced by PARP inhibition. Moreover, PARP inhibitors showed significant synergistic effects when combined with either MTDIA or EPZ015666 in solid tumor models. MTAP-deficient tumors exhibited increased vulnerability to olaparib in vivo, and combined treatment with olaparib plus MTDIA or EPZ015666 produced improved therapeutic outcomes compared with olaparib alone. Conclusions: These findings identify PARP inhibitors as a potential therapeutic strategy for MTAP-deficient tumors through targeted inactivation of PRMT5 and support further evaluation of PARP inhibitor-based combination therapies in this molecular context. Full article

Background/Objectives: The efficacy of inactivated foot-and-mouth disease virus (FMDV) vaccines depends on the structural integrity of the 146S virions. However, instability of 146S antigens during vaccine manufacturing and storage can compromise vaccine quality. Despite its high immunogenicity, the Korean serotype O strain O Jincheon (O JC) exhibits poor physical stability. Methods: To enhance antigenic stability while preserving strain-specific antigenicity, we engineered a VP1-substituted recombinant virus, (R) O1 M–O JC_VP1, by integrating the VP1 coding region of O JC into the O1 Manisa (O1 M) backbone. Results: The resulting chimeric virus exhibited significantly improved capsid stability, as demonstrated by an increased melting temperature and enhanced resistance to thermal stress, chloroform exposure, and long-term storage. Importantly, the recombinant antigen maintained its immunogenicity and induced antibody responses comparable to those induced by the parental O JC strain in vaccinated pigs. Conclusions: These findings demonstrate that VP1-direct chimeric engineering can improve capsid stability without compromising antigenicity and provide a practical approach for developing a stable FMDV vaccine. Full article

Background: Lumpy skin disease (LSD) is caused by a Capripoxvirus. Live attenuated vaccines, which are commercially available, could be not safe because of the side effects. The aim of this study was the evaluation of the safety, immunogenicity, and effects on the qualitative and quantitative parameters of milk. The feasibility of identifying vaccinated animals using our inactivated vaccine in dairy cows was analysed. The vaccine was tested in guinea pigs as an immunogenicity predictive model. Methods: LSD virus was propagated on Madin–Darby Bovine Kidney (MDBK) cells, then inactivated and supplemented with keyhole limpet hemocyanin (KLH) protein, obtaining a positive marker vaccine. This was inoculated in guinea pigs and in dairy cows, and animal sera were analysed using enzyme-linked immunosorbent assay (ELISA) and a serum neutralisation (SN) test. Quantitative and qualitative analyses were performed on milk. Results: The vaccine was previously tested for efficacy in vaccinated calves, showing a pronounced reduction in clinical symptoms after challenge. The safety and immunogenicity obtained in calves were also confirmed in dairy cows in this study. In fact, high values of the SN test (1:20 to 1:80) and ELISA (90 and 240 S/P%) were obtained after vaccination. Moreover, high immunogenicity of the vaccine was also assessed in guinea pigs. In addition, the results of the milk analyses did not show any differences between vaccinated and control groups. The KLH was able to elicit an immune response detectable using an ELISA (3.0 and 3.5 optical density values). Finally, our vaccine could be used to reduce LSD symptoms and identify vaccinated animals. Full article

Background/Objectives: Multidrug-resistant (MDR) Enterobacter spp. are critical pathogens within the ESKAPE group, frequently exhibiting resistance to carbapenems. Antimicrobial photodynamic therapy (aPDT) represents a promising non-antibiotic strategy to circumvent these resistance mechanisms. This scoping review aims to map the current evidence regarding the efficacy of aPDT in inactivating Enterobacter spp., identifying the most effective photosensitizers (PS), light parameters, and existing research gaps. Methods: A systematic search was performed across PubMed, Scopus, and Google Scholar (2013–2025) following PRISMA-ScR guidelines and registered on OSF. Studies were included if they evaluated aPDT against Enterobacter spp. (in vitro or in vivo) and provided quantitative data on microbial reduction. Data was extracted using a standardized charting form covering bacterial strains, PS type, light source, and viability reduction. The results from the eligible sources of evidence were synthesized narratively to address the review objectives. Results: Despite the clinical priority of Enterobacter, only seven studies met the eligibility criteria. Methylene Blue remains the most frequently studied PS, achieving reductions of 3–8 log₁₀. Emerging evidence highlights the synergistic efficacy of monocationic chlorins and graphene-based nanomaterials in enhancing the bactericidal effect of light-based treatments. Notably, aPDT demonstrated the ability to inactivate carbapenemases, the bacterial enzymes responsible for carbapenem resistance. However, only two studies evaluated in vivo applications, primarily within dental settings. Conclusions: aPDT is a promising method against MDR Enterobacter spp. and bypasses traditional resistance mechanisms. However, the limited number of studies indicates a significant knowledge gap. Future research should focus on standardized in vivo protocols and the synergy between aPDT and conventional antibiotics to support clinical translation. Full article

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases. Full article

Arbuscular mycorrhizal fungi (AMF) are widely applied as bioinoculants to enhance crop performance, yet their broader ecological effects on rhizosphere microbial assembly under field conditions remain insufficiently understood. Here, we evaluated the impact of a commercial AMF inoculant and its carrier material on lettuce performance and rhizosphere microbial communities in an open-field experiment. We hypothesized that both viable AMF propagules and formulation components contribute to shifts in rhizosphere processes. Active AMF inoculation significantly increased root colonization and fresh biomass at harvest, confirming successful establishment and enhanced plant performance under field conditions. Colonization levels in the heat-inactivated carrier treatment were comparable to the non-inoculated control, indicating that the carrier did not inhibit indigenous AMF activity or induce nutrient-mediated suppression of symbiosis. Plant physiological responses were stage-dependent, supporting the context-dependent nature of AMF effects in dynamic field environments. High-throughput sequencing revealed no significant treatment effects on bacterial or fungal alpha diversity. However, beta-diversity analyses demonstrated significant compositional restructuring of rhizosphere communities, particularly within the bacterial domain. A stable core microbiome persisted across treatments, yet relative abundances and community evenness were altered by both active inoculation and carrier application. These results suggest that AMF inoculation reorganizes microbial community structure predominantly via shifts in ecological niche occupation. Collectively, our results show that AMF inoculation functions not only as a symbiotic nutrient-acquisition strategy but also as a driver of rhizosphere microbial reorganization under field conditions. Integrating plant performance with microbiome dynamics provides a more comprehensive framework for understanding and optimizing microbial inoculants in sustainable agricultural systems. Full article

Sea fennel (Crithmum maritimum L.) is an emerging crop valued for its nutritional and sensory properties and has been reported to exert health-promoting effects, including antioxidant, anti-inflammatory, antimicrobial, and cardioprotective activities, as well as potential benefits for gut health and metabolic regulation. Building on these features, the present study aimed to unlock the potential of sea fennel to produce novel pickles. Two independent batches were prepared using young leaves and stems of sea fennel fermented in brine. After fermentation, salt concentration was standardized in all prototypes, and two types of vinegar (apple and wine) were added at four acetic acid levels (0.05%, 0.2%, 0.5%, and 0.7%). All prototypes were subsequently subjected to mild pasteurization. During fermentation, physicochemical and microbiological parameters were monitored, while after pasteurization additional physicochemical, microbiological, volatile organic compound (VOCs), and sensory analyses were performed during storage. In both batches and across all prototypes, fermentation resulted in a significant pH decrease, dominance of lactic acid bacteria, inhibition of Enterobacteriaceae, and a gradual increase in yeasts. Following vinegar addition and pasteurization, pH, titratable acidity, and salt content remained stable over six months of storage in most prototypes, particularly those with 0.2% acetic acid. Pasteurization effectively inactivated lactic acid bacteria and Enterobacteriaceae in all prototypes, whereas yeasts and mesophilic bacteria persisted in low-acidity samples (0.05%). Therefore, the 0.05% acidity samples were later excluded due to mid-stage microbial spoilage. Batch-dependent differences were observed in color and sensory attributes, with batch 2 showing higher overall stability mainly in acidic flavor and aroma, particularly in prototypes with 0.2% acidity. VOCs analysis revealed profiles primarily driven by batch variation, with secondary modulation by vinegar type: sesquiterpenes remained stable, while γ-terpinene, limonene, and p-cymene were the dominant compounds, with greater stability observed in batch 2. Overall, the combined use of lactic acid fermentation, vinegar pickling, and mild pasteurization represents a promising strategy for preserving sea fennel and supports its potential as a vegetable crop. Full article

Background: Atypical teratoid/rhabdoid tumors (AT/RT) are rare, highly aggressive pediatric central nervous system (CNS) malignancies. AT/RT of the lateral ventricle is an exceptionally rare subgroup, with only 11 reported cases. SMARCB1 inactivation is the primary molecular feature of AT/RT. Current consensus is to classify AT/RT based on methylation and molecular profiles into the following subgroups: AT/RT-TYR, AT/RT-SHH, AT/RT-MYC, and a potentially distinct SMARCA4-deficient subtype. AT/RT-MYC exhibits high levels of CD8⁺ tumor-infiltrating lymphocytes, indicating immunogenic potential. Case presentation: We report three pediatric cases presenting with intracranial hypertension and seizures. Diagnosis was confirmed via histopathology and molecular profiling. Interventions included gross total resection, chemotherapy, radiotherapy, and combined immune checkpoint inhibitors (pembrolizumab and ipilimumab). Outcomes varied from rapid progression to 3-year recurrence-free survival. A cohort of 14 pediatric patients with lateral ventricle AT/RT, comprising 3 institutional cases and 11 cases identified from the PubMed database, was evaluated through a narrative synthesis. Conclusions: These advancements highlight the crucial role of molecular subtyping in tailoring personalized treatments, including epigenetic modifiers and immune-based regimens. However, clinical validation is essential to establish standardized protocols. Integrating genomic, epigenetic, and immune microenvironment profiling may enhance risk assessment and treatment precision, ultimately improving survival and quality of life in pediatric patients. Full article

Toxoplasma gondii is an intracellular protozoan transmitted via environmentally resistant oocysts present in food and water, as well as through the consumption of meat containing infective bradyzoites. This study evaluated the inactivation of T. gondii oocysts and bradyzoites (ME-49 strain) by Pulsed Electric Field technology (PEF). Treatment efficacy was determined by mouse bioassay combining brain qPCR and indirect immunofluorescence (IFA), with complementary qPCR in Hs27 cells. The infectious dose (ID₅₀) of T. gondii was estimated at 34.6 oocysts. PEF-treated oocysts (15 kV/cm; 50 kJ/kg; 225 µs) showed a significant reduction in infectivity compared with untreated controls; accordingly, the dose required to establish infection increased to 85.3 oocysts after PEF treatment. Brain qPCR and IFA were highly correlated, whereas heart tissue was less sensitive. Bradyzoites recovered from PEF-treated meat (3.3 kV/cm; 27 kJ/kg; 1600 µs) showed a 50% infectivity reduction compared with untreated samples. In vitro assays confirmed an in vivo reduction in infectivity, indicating that cell cultures can serve as an ethical and efficient tool for preliminary viability assessment. This is the first evidence of T. gondii inactivation by PEF, highlighting its potential as a non-thermal strategy. Further studies are needed to optimize treatment parameters. Full article