Search Results (5,674)

Gastrointestinal malignant tumors account for approximately one-third of global cancer-related deaths, primarily including colorectal, gastric, pancreatic ductal adenocarcinoma, and hepatocellular carcinomas. These tumors have a high incidence, are often asymptomatic, and are prone to metastasis and recurrence, posing a significant public health burden. Although traditional methods such as radiotherapy and chemotherapy can delay disease progression, their nonspecific effects often lead to severe side effects and drug resistance, resulting in limited efficacy. Therefore, developing novel treatment strategies with high target specificity and favorable biological safety is a critical scientific issue in this field. Peptide drugs offer advantages such as good biocompatibility, low immunogenicity, diverse structures, and ease of modification, collectively demonstrating unique potential for tumor treatment. They can not only achieve precise delivery by specifically recognizing tumor receptors but can also directly interfere with signal transduction, metabolism, and immune regulation, producing multi-target antitumor effects. This article systematically reviews the research progress of peptide drugs in gastrointestinal tumors, focusing on their molecular mechanisms, delivery modification strategies, and the latest applications. It also summarizes the challenges and future directions for clinical translation, providing a theoretical foundation and future perspectives for the precise treatment of gastrointestinal tumors and the design of new drugs. Full article

The α-gal epitope is synthesized in non-primate mammals and New-World monkeys by the glycosylation enzyme α1,3galactosyltransferase (α1,3GT), encoded by the GGTA1 gene. Ancestral Old-World monkeys and apes synthesizing α-gal epitopes underwent extinction 20–30 million years ago. Their mutated offspring, with the inactivated GGTA1 gene, survived and produced the natural anti-Gal antibody, specifically binding α-gal epitopes. Anti-Gal protected the surviving offspring from lethal viruses presenting α-gal epitopes, which killed α-gal-synthesizing parental primates. Anti-Gal constitutes ~1% of human immunoglobulins and is also produced in Old-World monkeys and apes. α-Gal epitopes can serve as therapeutic agents in several clinical disciplines: 1. Cancer immunotherapy: Engineering cancer cells to express α-gal epitopes results in anti-Gal binding to these cells and localized activation of the complement system that kills these cancer cells and recruits the antigen-presenting cells (APCs) dendritic cells and macrophages. Anti-Gal bound to cancer cells targets them for robust uptake by APCs, which process internalized tumor antigens (TAs) and transport them to lymph nodes for activation of cytotoxic T-cells. These T-cells kill TA-presenting metastatic tumor cells. Clinical trials demonstrated that such engineering is achieved by intra-tumoral injection of α-gal glycolipids, the use of recombinant α1,3GT, or the use of oncolytic viruses containing the GGTA1 gene. 2. Viral vaccines: Inactivated whole-virus vaccines presenting α-gal epitopes bind anti-Gal, which targets them for extensive uptake by APCs, thereby increasing their immunogenicity by ~100-fold. 3. Injured-tissue regeneration: Anti-Gal binding to α-gal-presenting nanoparticles administered to wounds, into the post-myocardial infarction (MI) injured myocardium and into injured spinal cord, activates the complement system that recruits pro-regenerative macrophages, which orchestrate regeneration by recruiting stem cells and the secretion of pro-regenerative cytokines. All these findings suggest that α-gal/anti-Gal antibody interaction can serve as a novel therapeutic approach, applicable to various clinical settings. Full article

Equine Infectious Anemia (EIA) is a retroviral disease of equids, for which there is no vaccine particularly adapted to American viral strains. In this work we searched for possible epitope regions for the surface proteins gp90 and gp45, rationally employing the latest available bioinformatics tools that constitute the state of the art in the field. We selected eight regions that contain numerous overlapping epitopes that have a high coverage amongst American viral strains and designed a chimeric envelope protein with those proteins fused in tandem as a novel vaccine candidate. In silico predictors were used to analyze chimeric protein physicochemical and immunogenic properties, as well as its allergenicity and toxicity. Protein structure was predicted and validated, and its ability to trigger cytotoxic immune responses was predicted by molecular docking to ELA alleles. The proposed sequence is predicted to be highly immunogenic and sets the base for a novel EIAV vaccine that could be used to protect against several American field strains. 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

Avian colibacillosis, caused by Escherichia coli, remains a significant threat to poultry health and production, particularly in the context of rising antimicrobial resistance. Efficient and scalable vaccination strategies are needed to reduce economic losses and reliance on antibiotics. This study investigated the safety and immunogenicity of a novel single-dose in ovo vaccine candidate based on three inactivated E. coli strains formulated with cationic maltodextrin nanoparticles. The vaccine was evaluated in broilers under commercial hatchery conditions. In ovo administration was well tolerated and did not adversely affect hatchability, survival, growth performance, or feed efficiency. Vaccinated birds mounted a measurable serum immunoglobulin Y (IgY) response against E. coli from 14 days post-hatch, which persisted until slaughter age. Furthermore, when co-administered with routinely used live-attenuated viral vaccines, no interference with the immunogenicity of these vaccines was observed. These results demonstrate that the inactivated nanovaccine is safe, immunogenic, and compatible with an industrial-scale in ovo vaccination. The findings support its potential as a practical prophylactic approach to prevent avian colibacillosis in broiler production. Full article

Background: Plant-derived nanovesicles (PDNVs), a class of naturally occurring nanoparticles with a phospholipid bilayer structure, have attracted significant attention in biomedicine, particularly in anti-tumor research, due to their broad source availability, low production cost, high biocompatibility, and low immunogenicity. Methods: This review systematically summarizes and analyzes the isolation methods, composition, anti-tumor mechanisms, and clinical translation potential of PDNVs based on literature retrieved from PubMed and Web of Science, with clinical trials identified and categorized using ClinicalTrials.gov. Results: Current research has made impressive progress in the application of PDNVs, both as direct therapeutic agents and as drug delivery systems. Their remarkable stability, ability to cross physiological barriers (e.g., the gastrointestinal tract and blood–brain barrier), and engineerability underpin their versatile potential. Conclusions: This review comprehensively outlines the compositional characteristics of PDNVs and explores their multi-dimensional mechanisms and application prospects as natural therapeutics and drug delivery platforms in cancer therapy. Despite challenges such as standardization in preparation, PDNVs represent a highly promising class of novel nanobiomaterials. Full article

Background/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) as an alternative viral vector boost vaccine. Methods: A recombinant VSV-GP vector co-expressing HBV surface and core antigens (VSV-GP-HBs/c) was generated and characterized for antigen expression. Its immunogenicity, antiviral efficacy, and durability were assessed in HBV-naïve and HBV-carrier mice, using protein primed, viral vector-primed, and multi-viral vector boost regimens. Results: VSV-GP-HBs/c efficiently expressed both HBV antigens in vitro. A single immunization with VSV-GP-HBs/c induced only weak HBV-specific immune responses in vivo. Replacing protein priming with VSV-GP-HBs/c resulted in modest immune activation and limited antiviral effects in HBV-carrier mice. In contrast, substituting the modified vaccinia virus Ankara (MVA)-HBs/c boost in the TherVacB regimen with VSV-GP-HBs/c elicited robust HBV-specific antibody responses and strong CD4 and CD8 T-cell immunity, assessed by intracellular IFN-γ staining after peptide stimulation. This regimen achieved a substantial reduction in serum HBsAg levels, numbers of HBV-positive hepatocytes, and intrahepatic HBV-DNA, with antiviral efficacy comparable to that of the classical TherVacB regimen. Notably, a second viral vector boost did not enhance HBV-specific immunity or antiviral efficacy; instead, it promoted dominant vector-specific CD8 T-cell responses. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime/VSV-GP-HBs/c boost was sufficient to achieve sustained antiviral control. Conclusions: These findings identify VSV-GP-HBs/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity. Full article

Immunotherapy, particularly effective in tumors with a high mutational burden, is very often administered in combination with chemotherapy. Several tumor types with a high mutational rate include melanoma and non-small cell lung cancer (NSCLC), which are particularly sensitive to immunotherapy. For NSCLC, conventional platinum-based doublet chemotherapy has been extended with drugs targeting signaling pathways (such as the epidermal growth factor receptor) and immune checkpoint inhibitors (ICI) directed against PD-1 and PD-L1. This review highlights the potential role of the membrane antigens CD73 and CD39 in enhancing the efficacy of combined immuno-chemotherapy. These ecto-nucleotidases catalyze the degradation of extracellular ATP to AMP and subsequently to adenosine (Ado), a potent immunosuppressive metabolite that acts through adenosine receptors. Consequently, CD73 and CD39 function as key downregulators of immunogenic signaling. Both CD73 and CD39 are highly expressed not only on tumor cells but also on immune and endothelial cells within the tumor microenvironment. Conventional chemotherapy may further upregulate their expression, contributing to drug resistance and impaired immune responses. To counteract these effects, inhibitors of CD73 and CD39, both monoclonal antibodies and small molecules, are currently under clinical evaluation, with early results indicating potential therapeutic benefit. Although this evidence supports the involvement of CD73 and CD39 in modulating responses to immunotherapy, particularly in combination with chemotherapy, the precise mechanisms underlying these interactions remain unclear. Elucidating these pathways will be critical for optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC. This review highlights the critical role of these pathways in optimizing treatment strategies and improving clinical outcomes in malignancies such as NSCLC. Full article

Plant-derived extracellular vesicles (PDEVs), engineered phytosomes, bioinspired polymeric plant-based nanoparticles (PBNPs), hybrid phyto-inorganic nanocomposites, green-synthesized metal nanoparticles, self-assembled nanoarchitectures, and multifunctional composites represent a rapidly advancing class of sustainable, nature-inspired nanocarriers. These platforms combine exceptional biocompatibility, negligible immunogenicity, and renewable sourcing with tunable drug loading, targeted delivery, and controlled release properties. This review synthesizes translational advances from 2020 to 2026, covering scalable isolation/bioprocessing (bioreactors, elicitation), multi-parametric physicochemical/multi-omics characterization, rational engineering/hybridization, and rigorous in vitro/in vivo assessments of uptake, biodistribution, pharmacokinetic (PK), and efficacy. Phytosomes and PBNPs markedly enhance oral bioavailability and targeted delivery of lipophilic phytochemicals, while PDEVs offer unique immunomodulatory, anti-inflammatory, and gene-regulatory activities. Hybrid and green-synthesized systems provide structural stability, redox modulation, and synergistic effects, and self-assembled/multifunctional composites address solubilization barriers with stimuli-responsive design. Early-phase human studies on grapefruit-, ginger-, turmeric-, and ginseng-derived PDEVs report excellent short-term safety, favorable PK, and preliminary bioactivity signals, with no observed immunogenicity or dose-limiting toxicities; however, these trials remain exploratory, constrained by small sample sizes and safety-focused endpoints. Despite challenges, including methodological heterogeneity, variable yields, long-term safety uncertainties (notably for inorganic hybrids), and regulatory ambiguities, emerging strategies such as clustered regularly interspaced short palindromic repeats (CRISPR)-engineered plant line; artificial-intelligence-driven process optimization; standardized guidelines, and integrated clinical, intellectual property, and commercialization frameworks are progressively addressing these barriers. Collectively, these advances position plant-derived nanocarriers as immunologically privileged, eco-friendly alternatives to synthetic and mammalian platforms, laying the foundation for a sustainable era of precision phytomedicine. Full article

Celiac disease (CD) is an autoimmune disorder triggered by immunogenic gluten peptides that resist gastrointestinal digestion. The only current treatment is a strict gluten-free diet, which is challenging to maintain. Lactic acid bacteria (LAB) with specific proteolytic systems offer a promising strategy for gluten hydrolysis and potential reduction of immunogenicity. This study aims to isolate and characterize gluten-degrading LAB from traditional Spanish and Algerian dairy products. A total of 27 artisanal dairy samples were collected. LAB were isolated on MRS and Elliker agar. Gluten-degrading activity was screened using a well diffusion assay with cell-free supernatants and a spot assay with live cultures. Active isolates were identified by 16S rRNA gene sequencing. Out of 123 isolates, 40 (32.5%) were positive in the well assay, while 67 (54.5%) were positive in the spot assay, indicating the latter’s higher sensitivity for detecting cell-associated proteases. Halo diameters ranged from 6 to 16 mm. Algerian isolates exhibited significantly stronger activity (mean halo: 12.6 ± 2.1 mm) compared to Spanish isolates (10.2 ± 2.0 mm; p < 0.001). Molecular identification of the 32 most active isolates revealed the following dominant species: Lactiplantibacillus plantarum, L. pentosus, Levilactobacillus brevis, and Enterococcus faecium. This study confirms that artisanal dairy fermentations are rich sources of LAB with robust gluten-degrading potential. The superior activity of Lactiplantibacillus spp. aligns with their complex peptidase systems. The geographical variation highlights the influence of local fermentation practices. Selected strains represent excellent candidates for developing adjunct cultures to produce gluten-reduced foods and warrant further investigation as potential probiotics, pending safety and efficacy validation in vivo and in clinical studies. Full article

Conventional drug delivery systems often suffer from problems such as limited targeting specificity, short half-lives, poor biocompatibility, and systemic toxicity, which significantly limit their therapeutic efficacy against major diseases like cancer. Blood cells, as native components of the human circulatory system, offer distinct advantages including low immunogenicity, long circulation times, remarkable mechanical flexibility, and innate ability to home to disease sites. These attributes make blood cells a promising platform for next-generation targeted drug carriers. In this review, we examine the biological and mechanical properties of red blood cells, white blood cells, platelets, and cell-derived membrane vesicles. We highlight recent advances in how these cells are engineered and loaded with drugs, and their application in tumor-targeted therapy, while also considering their potential in other diseases. We also discuss current technical challenges and outline future directions for clinical translation, offering a practical perspective on advancing blood cell-based delivery technologies. Full article

Background: In South Korea, foot-and-mouth disease (FMD), a highly contagious viral infection that affects cloven-hoofed animals, has led to the implementation of a bivalent FMD vaccination program. The current FMD vaccination strategy involves intramuscular (IM) administration to the shoulder region of the swine. However, this method is associated with adverse reactions at injection sites. Our previous studies have demonstrated that intradermal (ID) vaccination eliminates these side effects while maintaining immunogenicity comparable to that of IM vaccination. This study aimed to assess the early immune response induced by ID vaccination and compare its protective ability against FMDV serotype O with that of a commercial IM vaccine recently used in South Korea. Methods: An ID FMD vaccine was evaluated using two adjuvants, ISA 207 (50%) and EMULSIGEN-D (15%). Virus neutralization (VN) titers and structural protein levels were measured to compare efficacy across groups. To assess the early protective efficacy of ID vaccination, viral challenge experiments were conducted at 7 and 14 days post-vaccination (dpv). Results: Swine vaccinated via the ID route exhibited no clinical symptoms at 14 dpv, indicating effective early protection against FMD (O/AS/SKR/2019). In addition, no side effects of FMD ID vaccination were observed. Conclusions: These results suggest that ID vaccination could serve as a viable alternative to conventional IM vaccination, which is frequently associated with adverse effects. Importantly, this study demonstrates that ID vaccination can provide effective early protection within 7–14 days post-vaccination, highlighting its potential utility for emergency outbreak control. Full article

Background: Cervical carcinoma remains a widespread cancer worldwide, primarily caused by persistent infection with high-risk human papillomavirus (HPV). HPV types 16 and 18 account for approximately 70% of cervical cancer cases. Although prophylactic HPV vaccines are commercially available, their high cost and reliance on expensive expression platforms limit their accessibility in developing countries. Objectives: This study aimed to develop a cost-effective, plant-based HPV vaccine candidate by expressing capsomeric HPV-16 and HPV-18 L1 antigens in Brassica oleracea (broccoli). Methods: Modified L1 from HPV types 16 and 18 were designed to retain capsomeric assembly and fused with heat-labile enterotoxin B subunit (LTB). Immunoinformatics analyses were used to assess antigenicity, epitope distribution, and structural characteristics. Codon-optimized genes were cloned using Gateway^® technology and expressed in broccoli via Agrobacterium-mediated transformation. Transgenic plants were validated by PCR and qRT-PCR. Protein accumulation was quantified, and immunogenicity was evaluated in mice. Results: PCR and qRT-PCR confirmed the stable integration of two copies of the LTB-L1 transgenes in broccoli plants. Western blotting detected L1 protein at ~56.5 kDa, indicating the cleavage of the LTB-L1 fusion protein. The correct folding of L1 capsomeres was verified by antigen-capture ELISA. The recombinant proteins accumulated to approximately 0.33% and 0.35% of total soluble protein for HPV-16 and HPV-18, respectively. The immunization of mice with transgenic L1 induced significant humoral immune responses, comparable to those elicited by purified VLPs. Conclusions: The results demonstrate broccoli as a promising platform for the expression of immunogenic HPV L1 capsomeres and highlight its potential for the development of affordable, plant-based HPV vaccines. Full article

Background/Objectives: The integration of molecular classification has significantly refined prognostic stratification in endometrial carcinoma (EC). However, a tumor subset harboring more than one molecular classifier challenges the current hierarchical classification systems, and their biological and clinical significance remains incompletely defined. Methods: We analyzed an expanded cohort of 150 EC patients using next-generation sequencing and immunohistochemistry, integrating molecular and clinicopathological data. Multiple-classifier ECs were identified and compared with those of single-classifier tumors sharing at least one molecular feature. A systematic review and meta-analysis including our cohort were also performed to estimate the incidence and distribution of multiple-classifier ECs. Results: In our cohort, 6% of ECs harbored molecular multiple-classifiers. POLEmut-MMRd/MSI tumors generally retained POLE-mutated features, including ultrahigh tumor mutational burden (TMB), early-stage disease, and favorable clinicopathological characteristics, consistent with a highly immunogenic phenotype. In contrast, MMRd/MSI-p53abn/TP53mut tumors were more frequently associated with adverse clinicopathological features and showed lower and heterogeneous TMB values, suggesting that the coexistence of TP53 alterations may modify the typical intermediate-risk of MMRd/MSI-only tumors. Triple-classifier tumors were exceedingly rare, precluding definitive conclusions regarding prognosis. The meta-analysis demonstrated an overall prevalence of multiple-classifier ECs of approximately 5.4%, with substantial inter-study heterogeneity largely attributable to differences in molecular testing strategies, analytical sensitivity, and variant interpretation criteria. Conclusions: Multiple-classifier ECs represent a small but clinically relevant subset encompassing biologically heterogeneous entities. Our findings highlight the limitations of current molecular classification hierarchies and underscore the need for harmonized molecular testing and standardized reporting to improve risk stratification and the management of multiple-classifier ECs. Full article

Background: Triple-negative breast cancer lacks established targeted therapies, and only a subset of patients achieves a pathologic complete response to neoadjuvant chemotherapy. We aimed to integrate bulk cohorts with an exploratory single-cell multi-omic dataset from only five patients to identify tumor and immune-related features associated with chemotherapy response. Methods: Bulk analyses were performed in two public breast cancer cohorts (GSE76275 and GSE25065) to compare triple-negative versus non-triple-negative tumors and to relate pretreatment transcriptional and inferred immune infiltration patterns to neoadjuvant chemotherapy response. Separately, in a hypothesis-generating single-cell cohort of five triple-negative breast cancers (n = 5; four responders, one non-responder), we performed single-cell RNA sequencing, T cell and B cell receptor sequencing, single-cell ATAC sequencing, and glycosylation tag profiling. Results: In bulk data, triple-negative tumors showed a loss of luminal estrogen receptor-associated programs, higher proliferation, and CIBERSORT-estimated enrichment of myeloid-associated immune fractions compared with non-triple-negative tumors. Chemotherapy response was associated with modest transcriptional shifts and inferred immune composition differences in triple-negative tumors and more pronounced epithelial, stromal, and inflamed immune changes in non-triple-negative disease. Single-cell data suggested that responder tumors were enriched for T and natural killer cells, antigen-presenting myeloid cells, expanded and diverse T and B cell clonotypes, and immune-associated glycosylation signals, whereas the non-responder sample was dominated by epithelial and fibroblast compartments with secretory, adhesion, and potential immune evasion programs. Checkpoint-related analyses reflected expression patterns and predicted ligand–receptor communication, nominating TIGIT–NECTIN2 as a candidate axis for further investigation. Conclusions: Integrating public bulk cohorts with exploratory single-cell multi-omics supports a model in which chemotherapy sensitivity in triple-negative breast cancer is linked to inflamed, antigen-presenting microenvironments and adaptable antitumor immunity, whereas resistance is associated with stromal and tumor dominance. These candidate biomarkers and pathways require validation in larger independent cohorts, and clinical translation is premature given the exploratory single-cell cohort. Full article