Search Results (196)

Oral wound healing is a robust process; however, complications from surgery, systemic diseases, and aging can impair healing. While some treatments exist, regenerative therapies to promote mucosal wound healing remain limited. In recent years, there has been a significant rise in FDA-approved cell-based therapies; however, extracellular vesicles represent an emerging cell-free alternative that may mitigate risks associated with cellular therapies, including tumorigenesis and immunogenicity. These lipid-encapsulated nanovesicles can deliver therapeutic cargo, such as proteins, lipids, nucleic acids, or drugs, to the wound site. Extracellular vesicles can be derived from mesenchymal stromal cells, immune cells, bodily fluids, or bacteria, and engineered through genetic modification, preconditioning, or direct cargo loading to enhance therapeutic potency. Furthermore, advanced delivery platforms, including hydrogels, microneedles, and aerosols, allow for sustained and localized EV delivery to the oral wound site. This review examines differences between cutaneous and oral wound healing; factors that impair oral repair; extracellular vesicle sources and engineering strategies; and delivery strategies for developing EV-based therapeutics for oral wound healing. Full article

Background: The management of pediatric inflammatory bowel disease (PIBD) has evolved significantly over the past two decades, transitioning from corticosteroids and immunomodulators to biologic and small-molecule therapies. These advances have aimed not only to control inflammation but also to promote mucosal healing, improve growth, and enhance long-term quality of life. Objectives: This narrative review summarizes current evidence on the efficacy, safety, and clinical applications of biologic and novel small-molecule therapies in PIBD, highlighting emerging trends in personalized and precision-based management. Methods: A literature search was performed across PubMed, Embase, and the Cochrane Library, focusing on studies published within the last five years. Additional data were retrieved from key guidelines and position papers issued by ECCO–ESPGHAN, SIGENP, the FDA, and the EMA. Results: Anti–tumor necrosis factor (TNF) agents such as infliximab and adalimumab remain first-line biologics with proven efficacy in remission induction and maintenance. Newer biologics—vedolizumab, ustekinumab, risankizumab, and mirikizumab—offer alternatives for anti-TNF-refractory cases, showing encouraging short-term results and favorable safety profiles. Although many are approved only for adults with limited pediatric evidence, emerging small molecules—including Janus kinase (JAK) inhibitors (tofacitinib, upadacitinib) and sphingosine-1-phosphate (S1P) modulators (etrasimod)—provide oral, rapidly acting, and non-immunogenic treatment options for refractory disease. Furthermore, the gut microbiome is increasingly recognized as an emerging therapeutic target in PIBD, with growing evidence that host–microbiome interactions can influence both the efficacy and safety of biologics and small-molecule therapies. Conclusions: While biologics and small molecules have transformed PIBD management, challenges remain, including high treatment costs, limited pediatric trial data, and variable access worldwide. Future directions include multicenter pediatric studies, integration of pharmacogenomics, and biomarker-guided precision medicine to optimize early, individualized treatment and improve long-term outcomes. Full article

The COVID-19 pandemic accelerated vaccine innovation but also exposed weaknesses in global access and manufacturing. Yeast-based platforms, particularly Saccharomyces cerevisiae and Pichia pastoris, also known as Komagataella phaffii, offer a practical complement to vector systems. These eukaryotic microorganisms combine safety, scalability, and cost-effectiveness with the ability to express complex antigens and assemble virus-like particles. Building on the success of the recombinant hepatitis B vaccine, recent advances in glycoengineering, CRISPR-based host optimization, and surface display technologies have expanded the utility of yeast-based platforms for the rapid development of vaccines. Yeast-derived SARS-CoV-2 receptor-binding domain (RBD) subunit vaccines, such as Corbevax and Abdala (CIGB-66), demonstrate that affordable, immunogenic, and thermostable products are feasible at scale. Emerging innovations in glycan humanization, thermostable formulations, and oral or mucosal delivery highlight the potential of yeast-based vaccines for decentralized manufacturing and equitable pandemic preparedness. This review summarizes recent technical and clinical progress in yeast-based vaccine research, positioning these platforms as accessible and adaptable tools for future outbreak responses and global immunization strategies. Full article

Transmissible gastroenteritis (TGE), caused by the TGE virus (TGEV), is a highly contagious enteric disease characterized by vomiting, dehydration, and watery diarrhea. It mainly endangers piglets within two weeks of age, with a 100% mortality rate, inflicting severe economic losses on the global swine industry. Since enteric tropism of the virus and mucosa serves as the first line of defense against viral invasion, an oral vaccine inducing sufficient secretory immunoglobulin A (SIgA) antibodies in animals should be developed. Being a generally recognized as safe (GRAS) microorganism, Bacillus subtilis can form endospores under extreme environmental conditions, which confer resistance to the hostile gastric environment and have been widely employed as delivery vehicles for oral vaccines owing to their immunoadjuvant activity and non-specific antidiarrheal effects. In this study, the AD antigenic epitope of the TGEV S protein was selected as the immunogen. The mature peptide of the B subunit of the heat-labile enterotoxin from enterotoxigenic Escherichia coli served as a mucosal adjuvant, and B. subtilis WB800N was used as the delivery host to construct the recombinant strain pHT43-LTB-AD/WB800N. After confirming the successful expression of the target protein, oral immunization was performed using mice as a model. The results demonstrated that this recombinant strain induced robust mucosal, humoral, and cellular immunity, along with considerable levels of neutralizing antibodies. These findings indicate that recombinant B. subtilis could serve as an oral vaccine candidate to combat TGEV infections. Full article

Diseases associated with yeast pathogens have become an increasingly serious global health issue. The range of virulence factors and the development of mechanisms of resistance have posed a significant challenge in the fight against these types of infections. Lectins, proteins capable of reversibly binding to carbohydrates and glycoconjugates, have been assessed as antifungal agents. This review shows that lectins have demonstrated versatility and significant potential as therapeutic agents against Candida, Nakaseomyces and Cryptococcus. These molecules act through diverse mechanisms, including disruption of fungal cell membranes, induction of oxidative stress, inhibition of ergosterol biosynthesis, and interference with mitochondrial and lysosomal functions. Some lectins have been shown to inhibit yeast-to-hyphae morphological transitions and biofilm formation, which are critical virulence factors for pathogenic yeasts. Moreover, some lectins have shown potential to enhance the efficacy of conventional antifungal drugs through synergistic interactions, though these effects can depend on the fungal isolate. Beyond in vitro activity, translational considerations remain underdeveloped in the context of antifungal applications of lectins. Some lectins exhibit minimal toxicity, while others require careful dosing due to potential toxicity or undesired immunogenicity. Delivery and stability also present challenges, though strategies such as chemical modifications and topical, mucosal, or nanoparticle-based formulations show promise. Overall, the multifaceted antifungal activities of lectins highlight their promising role as innovative candidates in the development of novel therapies to address the growing challenge of yeast pathogen resistance. However, significant knowledge gaps persist, highlighting the urgent need for coordinated research that bridges in vitro findings with practical pharmacological applications. Full article

Background/Objectives: New vaccine platforms that rapidly yield low-cost, easily manufactured vaccines are highly desired, yet current approaches lack key features. We developed the Killed Whole-Cell/Genome-Reduced Bacteria (KWC/GRB) platform, which uses a genome-reduced Gram-negative chassis to enhance antigen exposure and modularity via an autotransporter (AT) system. Integrated within a Design–Build–Test–Learn (DBTL) framework, KWC/GRB enables rapid iteration of engineered antigens and immunomodulatory elements. Here, we applied this platform to the HIV-1 fusion peptide (FP) and tested multiple antigen engineering strategies to enhance its immunogenicity. Methods: For a new vaccine, we synthesized DNA encoding the antigen together with selected immunomodulators and cloned the constructs into a plasmid. The plasmids were transformed into genome-reduced bacteria (GRB), which were grown, induced for antigen expression, and then inactivated to produce the vaccines. We tested multiple strategies to enhance antigen immunogenicity, including multimeric HIV-1 fusion peptide (FP) designs separated by different linkers and constructs incorporating immunomodulators such as TLR agonists, mucosal-immunity-promoting peptides, and a non-cognate T-cell agonist. Vaccines were selected based on structure prediction and confirmed surface expression by flow cytometry. Mice were vaccinated, and anti-FP antibody responses were measured by ELISA. Results: ELISA responses increased nearly one order of magnitude across design rounds, with the top-performing construct showing an ~8-fold improvement over the initial 1mer vaccine. Multimeric antigens separated by an α-helical linker were the most immunogenic. The non-cognate T-cell agonist increased responses context-dependently. Flow cytometry showed that increased anti-FP-mAb binding to GRB was associated with greater induction of antibody responses. Although anti-FP immune responses were greatly increased, the sera did not neutralize HIV. Conclusions: Although none of the constructs elicited detectable neutralizing activity, the combination of uniformly low AlphaFold pLDDT scores and the functional data suggests that the FP region may not adopt a stable native-like structure in this display context. Importantly, the results demonstrate that the KWC/GRB platform can generate highly immunogenic vaccines, and when applied to antigens with well-defined native tertiary structures, the approach should enable rapidly produced, high-response, very low-cost vaccines. Full article

Background/Objectives: Advanced drug delivery systems (DDSs) are essential for targeted delivery, controlled release, and reduced systemic toxicity, but their clinical adoption is limited by biological barriers, manufacturing complexities, and cost. The aim of this systematic review is to critically evaluate the quantitative relationships between platform design, overcoming biological barriers, and clinical translation outcomes for DDS developed between 2016 and 2025. Methods: A comprehensive literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science (January 2016–April 2025) in accordance with the PRISMA 2020 guidelines. Included studies focused on experimental or clinical data for nanocarrier platforms (liposomes, lipid nanoparticles, polymer systems, biomimetic carriers, extracellular vesicles). Data on platform characteristics, interactions with barriers, pharmacokinetics, manufacturing, and clinical outcomes were extracted and synthesized in narrative form due to the significant methodological heterogeneity. Results: An analysis of 77 included studies confirms that successful clinical translation depends on matching the physicochemical properties of the carrier (size, surface chemistry, material) to specific biological barriers. Liposomes and lipid nanoparticles (LNPs) remain the most clinically validated platforms, exploiting the EPR effect and liver tropism, respectively. Key engineering solutions include stealth coatings, ligand-mediated targeting, and stimulus-responsive materials to overcome barriers such as mononuclear phagocyte system clearance, the blood–brain barrier, and mucosal barriers. Microfluidic and continuous manufacturing processes enable reproducibility, but scalability, cost, and immunogenicity (e.g., anti-PEG responses) remain key translational challenges. Engineered extracellular vesicles, biomimetic carriers, and 3D/4D-printed systems combined with AI-driven design demonstrate the potential for personalized, adaptive delivery. Conclusions: Cutting-edge DDSs have validated their clinical value, but realizing their full potential requires a holistic, patient-centered design approach integrating barrier-specific engineering, scalable manufacturing, and rigorous safety assessment from the earliest stages of development. Further progress will depend on standardizing methods for new platforms (e.g., extracellular vesicles), implementing digital and AI tools, and ensuring translational feasibility as a fundamental principle. Full article

LigiLactobacillus saerimneri (L. sae) has shown considerable promise as a probiotic in recent years, particularly in poultry production. Comprehensive evaluation of its genetic functions, safety profile, and immunogenicity is essential prior to practical application. Our previous study demonstrated that the chicken-derived strain L. sae M-11 colonizes effectively and exhibits a favorable safety profile at adequate dosages. In this study, we further evaluated the potential of L. sae M-11 by analyzing its genetic basis for intestinal adaptation, metabolic features, safety risks, and suitability as a delivery vector. Comparative genomic analysis revealed that L. sae has evolved distinctive genetic features and functional specialization that may facilitate host adaptation. Genomic stability assessments and virulence factor screening confirmed that L. sae M-11 poses no substantial health risks. Furthermore, based on transmembrane protein predictions, the LPQTGE-motif protein was identified as a cell wall anchor in genetically engineered L. sae M-11 using immunoelectron microscopy. Notably, this delivery system selectively activated peripheral blood monocyte-derived dendritic cells (PB-MoDCs) in vitro, as evidenced by the up-regulation of maturation markers (CD83, CD80), pro-inflammatory cytokines (IL-1β, IL-6), Th1-associated IL-12, and the chemokine CXCLi1. However, it exhibited a limited antigen presentation capacity, indicated by low expression levels of CD40, MHCII, DEC205, TNF-α, and IFN-γ. The prospects and challenges associated with the application of L. sae M-11 have been discussed. Overall, these findings support the potential development of L. sae M-11 as a microbial cell factory and mucosal delivery vector. Full article

Background: Adjuvants enhance the immune response to antigens incorporated in vaccine formulations. Given that the majority of infectious agents enter the body through mucosal surfaces, efficacious vaccines must generate protective immunity at these sites, which serve as the first line of defense. There is a need for mucosal adjuvants; hence, we explored the potential of repurposing existing drugs with established safety profiles in humans. Polymyxins are a class of clinically used antibiotics. They are cationic peptides and mast cell activators, which are a novel class of vaccination adjuvants. The goal was to assess the adjuvant properties of Polymyxin B microparticles in combination with vaccine candidates previously developed in our laboratory, such as microparticulate gonorrhea, influenza, measles, Zika, and canine coronavirus vaccines, and to compare their performance with FDA-licensed adjuvants, such as MF59 and Alum. Methods: Polymyxin microparticles were formulated using a double emulsion method, and the toxicity profile and autophagosome generation of Polymyxin B microparticles were assessed. The immunogenic potential of Polymyxin B in these vaccines was studied using multiple parameters such as nitric oxide release using Griess assay and immune profiling using flow cytometry for markers such as MHC I, MHC II, CD40, and CD80. Results: Polymyxin B microparticles were found to be non-cytotoxic to dendritic cells up to 500 μg/mL. Polymyxin B promoted autophagosome formation and nitric oxide release, and showed the upregulation of MHC I, MHC II, CD80, and CD40 pathways. Conclusions: The adjuvant activity of Polymyxin B across various vaccine platforms is significantly comparable to FDA-approved adjuvants, which is a critical requirement for generating T cell responses such as helper T cell and cytotoxic CD8+ T cell responses. Full article

Hypertension is a major public health problem worldwide, and high-salt diets are one of the main causes of hypertension. The intestinal mucosal immune system is the largest immune organ in vertebrates. Hypertension was associated with increased intestinal permeability and an inflammatory state. The bacterial communities attached to the intestinal mucosa played a significant role in the development and maturation of the autoimmune system, as well as inflammation and immunity to disease. In this review, we focused on the relationship between the impaired intestinal barrier and the development and progression of hypertension under the high-salt dietary pattern. We systematically reviewed how a high-salt diet caused hypertension by disrupting the intestinal mechanical, chemical, and microbial barriers, interacting with immunogenic isolevuglandin (IsoLG)-protein adducts and microbiota, and activating the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Meanwhile, this review also summarizes the dietary therapy for hypertension, which involves supplementing natural antihypertensive substances and adjusting dietary patterns to repair the intestinal barrier and assist in lowering blood pressure. Such measures included supplementing plant-based foods, polyunsaturated fatty acids (PFAs), probiotics, prebiotics, food–medicine homologous substances (FMHS), vitamins, and minerals, as well as transforming high-salt dietary patterns into the dietary approaches to stop hypertension (DASH), the Mediterranean diet (MD), and the ketogenic diet (KD), with the aim of providing a reference for the occurrence, development, and dietary prevention and control of high-salt hypertension. Full article

Melanoma is a highly heterogeneous disease, with unique genetic subtypes that influence clinical behavior and treatment response. While targeted therapies and immunotherapy have transformed care for more common types of melanoma, optimal strategies for KIT-mutant melanoma are less well-defined. In this review, we summarize the associations between KIT mutations and specific clinico-pathologic patterns, including their enrichment in acral, mucosal, and chronically sun-damaged melanomas. We detail the spectrum of KIT mutations across relevant exons, noting how mutation subtype influences sensitivity to targeted therapies. We will then analyze several therapeutic trials and case reports that describe the use of c-KIT inhibitors as well as immune checkpoint inhibitors in melanoma treatment. We also discuss early findings supporting combination strategies that may enhance therapeutic outcomes. Finally, we identify critical gaps in understanding the mechanisms of resistance, CNS progression, and the immunogenic landscape of KIT-driven melanoma. Deeper insight into the function of KIT and its interaction with therapeutic pathways is essential to optimizing treatment sequencing and tailoring personalized strategies that improve outcomes in this patient population. Full article

Background/Objectives: Melanoma is a malignant tumour of melanocytes. Cutaneous melanoma accounts for the vast majority of cases and has benefitted from advances in targeted and immune checkpoint inhibitor therapies, leading to substantial improvements in survival. In contrast, mucosal and vulvovaginal melanomas are rare, aggressive subtypes with distinct molecular and immune profiles and poor prognoses. This review synthesises evidence comparing cutaneous, mucosal, and vulvovaginal melanoma, with emphasis on biology, treatment, and outcomes Methods: A narrative comparative review was undertaken, examining the published literature on the epidemiology, molecular and immune characteristics, and treatment outcomes of cutaneous, mucosal, and vulvovaginal melanoma, including systemic therapies and surgical approaches. Results: Cutaneous melanoma demonstrates high tumour mutational burden and frequent BRAF and NRAS mutations, underpinning the success of targeted therapy and immunotherapy. Mucosal and vulvovaginal melanomas exhibit lower mutational burden, distinct mutation patterns, and reduced immunogenicity, correlating with poorer treatment responses. Surgery remains the mainstay of management, though optimal margins in vulvovaginal melanoma are unclear. Recurrence rates are high, and five-year survival remains poor. Evidence for systemic therapy is limited to small retrospective cohorts and subgroup analyses, showing lower response and survival rates compared with cutaneous melanoma. Chemotherapy has minimal benefit. Conclusions: Mucosal and vulvovaginal melanomas are biologically and clinically distinct from cutaneous melanoma and continue to have poor survival outcomes. Their rarity restricts high-quality evidence, highlighting the need for collaborative, innovative research to inform effective treatment strategies. Full article

Background: Celiac disease (CeD) is a chronic, immune-mediated enteropathy triggered by gluten ingestion in genetically predisposed individuals. While a lifelong gluten-free diet (GFD) remains the cornerstone of treatment, inadequate follow-up can lead to persistent symptoms, nutritional deficiencies, and long-term complications. Aim: This narrative review summarizes best practices in celiac disease follow-up, with emphasis on multidisciplinary, nutritional, clinical, and preventive care strategies to optimize long-term outcomes. Main Findings: High-quality follow-up requires coordinated care involving gastroenterologists, dietitians, primary care providers, and other specialists. Nutritional challenges of the GFD include high cost, limited fortification, suboptimal nutrient content, and increased risk of obesity and metabolic dysfunction. Patients also face psychosocial and behavioral burdens such as anxiety, social isolation, and disordered eating. Evidence-based strategies for follow-up include structured clinical and serologic monitoring, laboratory assessments, bone health evaluation, cancer risk reduction, and preventive care. Novel tools such as gluten immunogenic peptide testing, digital health platforms, and artificial intelligence are emerging as adjuncts to clinical management. Implications: Structured, patient-centered follow-up that integrates medical, nutritional, and psychosocial dimensions is essential to achieving mucosal healing, maintaining long-term health, and improving quality of life in individuals with CeD. Full article

Background/Objectives: Sublingual vaccination offers a non-invasive route for inducing both systemic and mucosal immunity, yet the formulation properties that govern its success remain poorly defined. This study investigated the relationships among key formulation parameters for sublingual vaccines, such as viscosity, mucoadhesion, and mucosal residence, to understand their impact on in vivo immune responses in the sublingual delivery context. Methods: Ovalbumin (OVA)-based vaccine formulations containing cholera toxin B (CTB) adjuvant and mucoadhesive excipients such as hydroxypropyl methylcellulose (HPMC) or methylglycol chitosan (MGC), were evaluated for: (1) their respective rheological properties—characterized by viscosity and mucoadhesion parameters, as well as (2) in situ mucosal retention (assessed using Cy7-labeled formulations tracked by IVIS in vivo imaging system) and (3) in vivo immunogenicity via systemic (IgG) and mucosal (IgA) responses measured by ELISA, following sublingual administration to mice. Correlations between rheology, in situ/ex situ mucosal residence, and in vivo immune outcomes were determined. Results: Sublingual vaccine formulations containing HPMC exhibited the highest viscosity, mucoadhesion, and mucosal retention profiles, but paradoxically elicited the weakest systemic and mucosal antibody responses. In contrast, chitosan-based formulations enhanced immune responses even at reduced antigen and adjuvant doses, likely due to its permeation-enhancing and adjuvant effects. Correlation analyses revealed that while formulation viscosity and mucoadhesive strength were positively associated with mucosal retention, both rheological and retentive properties showed a significant inverse relationship with immunogenicity in the context of sublingual vaccine delivery. Conclusions: While viscosity and mucoadhesion are essential for in situ retention of sublingual vaccines, prolonged residence driven by excipient’s excessive rheological strength was found to reduce vaccine immunogenicity—likely due to restricted antigen release and mucosal uptake. Accordingly, HPMC appears suboptimal as a sublingual vaccine excipient, while chitosan shows promise for sublingual delivery as a permeation-enhancing adjuvant. These findings may shift the design paradigm for sublingual vaccine formulations, highlighting the need to balance mucosal retention with efficient antigen absorption for maximizing immune responses. Full article

Vaccines have emerged as one of the most effective biomedical strategies for the eradication of diseases. However, a significant limitation remains in their ability to induce comprehensive humoral and cellular immune responses. Recently, nanoparticles (NPs) have been advanced as a novel vaccine delivery approach to address reduced immunogenicity. Several nanoparticle-based agents have now been approved for human use, and NP-based formulations have shown remarkable potential to enhance immunogenicity and stability, supporting targeted delivery and controlled release either through co-encapsulation of adjuvants such as Toll-like receptor (TLR) agonists or the inherent immune-stimulatory properties of NP materials in minimizing cytotoxicity. Despite these advances, there remains a pressing need for vaccines capable of addressing complex and multifactorial diseases such as neurological disorders and cancer. Nanotechnology could be a viable solution to this challenge. The use of lipid-based NPs, particularly those encapsulating mRNA, has garnered attention for its adaptability in vaccine delivery. Current studies indicate that NP composition, surface charge and size may play a crucial role in modulating biodistribution, delivering immune-stimulatory molecules, targeting antigens and trafficking antigen-presenting cells (APCs), which enhance immune responses across mucosal and systemic tissues. This review highlights recent advancements in NP-based vaccines and delivery systems, and adjuvants for cancer and neurological disorders. The review also covers an overview of NP-based and alternative delivery systems, focusing on the mechanisms and innovations related to NP-based systems for immunotherapeutic applications in cancer and neurological disorders. Full article