Search Results (1,920)

Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article

Current histological staining methods for intestinal tissue analysis face limitations in simultaneously visualizing multiple tissue components, often requiring multiple sequential stains that increase processing time and tissue consumption. This proof-of-concept study aimed to define and develop a pentachromatic staining method for enhanced visualization of gastrointestinal tissue architecture. We developed the Pentachroma O-H method, an original protocol using readily available histological reagents (Alcian Blue pH 2.5, Weigert’s resorcin–fuchsin, Mayer’s hematoxylin, and Van Gieson’s solution) applied in an optimized sequence. The protocol was tested on healthy human ileum tissue obtained from surgical specimens as proof of concept. Thirty serial sections were stained with Pentachroma O-H and compared to adjacent sections stained with conventional hematoxylin–eosin (H&E) to document the emerging morphological characteristics of this original stain. Pentachroma O-H achieved distinct five-color differentiation in approximately 45 min: acidic mucins appeared turquoise–blue, collagen fibers red, elastic fibers black–purple, smooth muscle and erythrocyte cytoplasm yellow, and nuclei blue–black. The method clearly delineated intestinal architecture, including mucosal goblet cells, muscularis mucosae, connective tissue vasculature (parietal smooth muscle and elastic laminae), fibers, and cellular components, as well as lymphoid tissue aggregates and infiltrates, with improved contrast compared to H&E. All tissue components were simultaneously visualized in single sections with excellent morphological preservation. This first description of Pentachroma O-H demonstrates its capability to provide comprehensive ileum tissue visualization equivalent to multiple traditional special stains in a single, efficient protocol, offering significant potential advantages for gastrointestinal pathology assessment and warranting future validation studies across diverse tissue types and pathological conditions. Full article

Background: Commercial oral care products commonly incorporate synthetic antimicrobials such as cetylpyridinium chloride (Cetyl Cl.), L-Arginine (L-arg.), and stannous fluoride (SnF₂). Although effective against oral pathogens, these agents are often associated with adverse effects including mucosal irritation, taste alteration, and disruption of the oral microbiome. These limitations have spurred growing interest in safer, plant-based alternatives. In this study, we present a two-pronged in vitro oral care testing model that integrates cell assays with machine-guided quantitative microscopy analyses to assess both antibacterial efficacy and host biocompatibility of botanical extracts. Methods: Using Miswak (Salvadora persica) and Neem (Azadirachta indica) as representative natural products, we conducted antibacterial and antibiofilm testing including the evaluation of the minimum inhibitory concentration (MIC), minimum biofilm inhibitory concentration (MBIC), and minimum biofilm eradication concentration (MBEC), alongside biocompatibility assessments via MTT cell viability assays on probiotic bacteria and mammalian oral cells. To evaluate biofilm structure and disruption, we employed scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM), augmented with machine-guided Weka segmentation and automated image analysis. Results: Our findings show that Miswak and Neem extracts exhibited 75–100% antibacterial and antibiofilm efficacy against all tested bacteria, as demonstrated by cell assays and microscopy analyses, comparable to synthetic oral care agents. They also maintained ~100% viability toward commensal microbes and mammalian oral cells, whereas Cetyl Cl. and SnF₂ showed dose-dependent cytotoxicity. Conclusions: This dual-assessment oral care testing model provides a comprehensive and biologically relevant framework for the discovery and screening of safe and effective natural herbal extracts in oral care applications. Full article

Injectable biomaterials for vocal fold disorders are being developed to provide not only mechanical reinforcement but also a regenerative microenvironment. Recent hydrogels based on hyaluronic acid (HA) derivatives, calcium hydroxylapatite and decellularized matrix scaffolds are designed to approximate the viscoelastic behavior of native tissue, allow controlled degradation, and modulate local immune responses. Rather than serving merely as space-filling agents, several of these materials deliver extracellular matrix (ECM)-like biochemical signals that help maintain pliability and overcome some limitations of conventional augmentation. Experimental and early clinical studies involving growth factor delivery, stem cell-based injections, and ECM-mimetic hydrogels have demonstrated improved mucosal wave vibration and reduced fibrosis in cases of scarring. In clinical series, benefits from basic fibroblast growth factor can persist for up to 12 months. Further progress will depend on correlating material properties with objective vibratory performance to achieve lasting restoration of phonation and advance true tissue-regenerative therapy. Full article

The adult pig intestinal microbiota boosts piglet intestinal and microbiome development, thereby improving growth. However, the functional bacteria, metabolites, and their region-specific intestinal roles remain to be characterized. Administration of adult colon microbiota (CM; devoid of metabolites) to piglets promoted intestinal development post-weaning, as indicated by increased intestinal mucosal weight, villus-to-crypt ratio of the ileum (p < 0.05), and stimulated mucin secretion (p < 0.05). This effect was potentially mediated by modulating beneficial microbiota, including ASV50_Prevotella 7, ASV52_Prevotella 1, and ASV81_Coprococcus 1. Adult colon-derived microbiota was found to preferentially colonize the piglet colon, supported by significantly higher bacterial loads in colonic contents. Piglets receiving adult colon supernatant (CS; without bacterial cells) showed improved feed efficiency (FE; p < 0.05), with numerically higher body weight (BW) and average daily gain (ADG) compared to the control (CON) group. Additionally, CS transplantation (CST) promoted intestinal development, potentially by modulating abundances of beneficial bacteria species, including ASV95_Turicibacter, and ASV109_Ruminococcaceae, which correlated with increased production of antioxidant and anti-inflammatory chemicals, including protocatechuic acid (PCA, p < 0.01). Adult colon-derived microbiota and metabolites enhanced intestinal development in piglets. CS supplementation improved growth and immunity, mitigating post-weaning stress potentially through enriching growth-linked bacteria (e.g., Turicibacter and Ruminococcaceae) and metabolites production (e.g., prephenate and PCA). These findings highlight these functional microbiota and metabolites as promising direct-fed microbial or metabolite additives for piglet growth and intestinal health post-weaning. Full article

Primary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive bile duct inflammation and fibrosis. Its strong association with inflammatory bowel disease (IBD) highlights the possible role of the gut–liver axis in disease pathogenesis. Here, we review the mechanisms that may contribute to the disruption of the gut–liver axis, leading to liver injury and the development of PSC. In particular, disruption of the intestinal barrier allows microbial products to enter the portal circulation, stimulating hepatic immune cells and triggering biliary inflammation. Concurrently, gut-primed lymphocytes expressing mucosal homing receptors migrate aberrantly to the liver, where they may contribute to biliary epithelial cell injury. Dysbiosis, characterized by reduced microbial diversity and the expansion of bile-tolerant and pro-inflammatory taxa, amplifies this immune activation and disturbs gut–liver homeostasis. Moreover, bile acids act as signaling molecules, regulating metabolism and immune responses through receptors such as FXR and TGR5. Dysregulation of these pathways may promote cholestasis, inflammation, and fibrosis. By understanding these interactions, we may identify novel therapeutic targets for PSC. Full article

Background: Intranasal (I.N.) vaccination holds promise to elicit mucosal immunity that counters respiratory pathogens at the site of infection. For subunit protein vaccines, immunostimulatory adjuvants are typically required. Methods: We screened a panel of 22 lipid-phase adjuvants to identify which ones elicited antigen-specific IgA with I.N. immunization of liposome-displayed SARS-CoV-2 receptor-binding domain (RBD). Results: Initial screening showed the TLR-4 agonist Kdo2-Lipid A (KLA) effectively elicited RBD-specific IgA. A second round of screening identified further inclusion of the invariant NKT cell ligands α-Galactosylceramide (α-GalCer) and its synthetic analog 7DW8-5 as complementary adjuvants for I.N. immunization, resulting in orders-of-magnitude-greater mucosal IgA response relative to intramuscular (I.M.) immunization. The inclusion of cationic lipids conferred capacity for mucosal adhesion and maintained immune responses. In K18 hACE2 transgenic mice, vaccination significantly reduced viral replication and prevented mortality from SARS-CoV-2 challenge. Conclusions: These results point towards the potential for the use of KLA and α-GalCer for I.N. subunit vaccines. Full article

Porcelain-fused-to-metal (PFM) crowns continue to serve as a cornerstone of restorative dentistry owing to their strength, affordability, and esthetics. However, late-onset complications such as oral burning and lichenoid reactions have been observed in long-serving PFMs, suggesting complex host–material interactions that extend beyond simple mechanical wear. This Perspective introduces the Nallan–Nickel Effect, a theoretical model proposing that a host- and environment-dependent threshold of bioavailable nickel ions (Ni²⁺), once exceeded, may trigger a neuro-immune cascade culminating in a burning phenotype. Within this framework, slow corrosion at exposed PFM interfaces releases Ni²⁺ into saliva and crevicular fluid, facilitating epithelial uptake and activation of innate immune sensors such as TLR4 and NLRP3. The resulting cytokine milieu (IL-1β, IL-6, TNF-α) drives NF-κB, mediated inflammation and T-cell activation, while neurogenic mediators—including nerve growth factor (NGF), substance P, and CGRP—sensitize TRPV1/TRPA1 nociceptors, establishing feedback loops of persistent burning and neurogenic inflammation. Modifying factors such as low salivary flow, acidic oral pH, mixed-metal galvanic coupling, and parafunctional stress can lower this threshold, whereas replacement with high-noble or all-ceramic materials may restore tolerance. The model generates testable predictions: elevated local free Ni²⁺ levels and increased expression of TLR4 and TRPV1 in symptomatic mucosa, along with clinical improvement following substitution of nickel-containing restorations. Conceptually, the Nallan–Nickel Effect reframes PFM-associated burning and lichenoid lesions as threshold-governed, neuro-immune phenomena rather than nonspecific irritations. By integrating corrosion chemistry, mucosal immunology, and sensory neurobiology, this hypothesis offers a coherent, testable framework for future translational research and patient-centered management of PFM-related complications. Full article

Oral mucosal wound healing is a rapid, precisely regulated process distinct from cutaneous repair due to the specialized anatomical, microbial, and physiological features of the oral cavity. This review outlines the sequential healing phases—hemostasis, inflammation, proliferation, and remodeling—and examines the coordinated roles of keratinocytes, fibroblasts, endothelial cells, and immune cell subsets in tissue restoration. Central molecular pathways, including PI3K/Akt, JAK/STAT, Ras/MAPK, TGF-β/SMAD, and Wnt/β-catenin, along with growth factors such as TGF-β, FGF, EGF, and VEGF, are discussed in relation to their regulatory influence on cell behavior and extracellular matrix dynamics. Unique intraoral factors—namely saliva-derived histatins and a distinct resident microbiota—promote accelerated re-epithelialization and attenuated fibrosis. Systemic conditions such as diabetes, aging, and tobacco exposure are identified as key modulators that compromise repair efficiency. Emerging therapeutic strategies, including stem-cell-based interventions, microbiota modulation, bioengineered scaffolds, and photobiomodulation, offer translational potential to enhance clinical outcomes in oral tissue regeneration. Full article

NPs have become a concerning global environmental problem. Dietary exposure to NPs can cause microbial dysbiosis. However, the risks of NPs to animals, particularly poultry species such as chickens, remain poorly understood. In this study, chickens were continuously exposed to 100 nm NPs via dietary inclusion from 18 weeks of age for 120 days to evaluate the effects of NPs on intestinal health. We found that NPs accumulated in chicken intestinal tissues, leading to adverse alterations in the intestinal mucosal structure, such as villus atrophy and goblet cell depletion, and significantly altering intestinal length. The 16S rRNA sequencing revealed significant gut microbiota dysbiosis, characterized by a loss of diversity and shifts in key bacterial groups. Functional predictions of the microbiota revealed impairments in metabolic pathways, especially carbohydrate and amino acid metabolism. Furthermore, network analysis showed that microbial interactions were disrupted and key functional hubs were lost. Most importantly, NPs exposure led to a significant decline in egg quality parameters, including eggshell thickness and strength, yolk color, weight, shape index, and Haugh units. Correlation analyses connected specific taxa, such as Methanobrevibacter, Rikenellaceae_RC9_gut_group, and Prevotellaceae_UCG-001, to intestinal damage and declines in egg quality. These findings provide a scientific basis for assessing the health risks of NPs in animals and offer insights into the development of gut health interventions. Full article

Background: Low birth weight (LBW) is correlated with gut microbiota dysbiosis and intestinal barrier function disruption, increasing susceptibility to enteric diseases. These alterations underscore the critical need to identify key regulators of gut homeostasis, among which bile acids are increasingly recognized as pivotal for barrier integrity, microbial ecology, and host metabolism. Methods: Eight pairs of LBW (the initial BW was 0.850 ± 0.053 kg) and normal-birth-weight (NBW; 1.488 ± 0.083 kg) piglets were compared to evaluate cecal morphology and bile acid profiles. Subsequently, sixteen LBW piglets and eight NBW piglets were allocated into three groups: NBW (1.563 ± 0.052 kg), LBW control (LBW-CON; 0.950 ± 0.120 kg), and LBW with bile acid supplementation (LBW-bile powder; 0.925 ± 0.116 kg). Piglets in the LBW-bile powder group received 25 mg/kg BW of bile powder (hyodeoxycholic acid-enriched) by daily oral gavage for 14 days. Results: LBW piglets exhibited retarded cecal development and lower abundance of hyocholic acid species (p = 0.006). Importantly, bile powder supplementation significantly improved cecal length (p = 0.009) and mucosal thickness (p = 0.020) compared with LBW-CON piglets. Microbial analysis showed that the microbial dysbiosis index was restored to near-normal levels. Transcriptomic analysis revealed impaired extracellular matrix structure and mucus secretion in LBW piglets. Notably, bile powder supplementation markedly upregulated the protein expression of WNT8B (p < 0.001) and the bile acid receptors (i.e., GPBAR1 and FXR), alongside enhanced tight junctions and the goblet cell marker mucin-2 expression (p < 0.05). Conclusions: These findings suggest that specific bile acid supplementation improves gut barrier function and partially supports cecal development in LBW piglets. Full article

Background/Objectives: The aim of this study was to investigate the cytotoxic, genotoxic, apoptotic, and anti-inflammatory effects of the antiseptic agent octenidine dihydrochloride (OCT-D) on the RPMI-2650 cell line derived from human nasal mucosa in vitro. Methods: RPMI-2650 cells and Human Umbilical Cord Endothelial Cells (HUVECs) were treated with various concentrations of OCT-D (0.00625–0.4%) for 12 and 24 h. Cell viability was assessed using the WST-1 assay, while DNA damage was assessed using the comet and micronucleus (MN) assays. Apoptotic activity was determined using Annexin V flow cytometry and fluorescence microscopy. Intracellular reactive oxygen species (ROS) levels were measured, and inflammatory cytokines (IL-1β, IL-6, TNF-α, and IFN-γ) were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of genes associated with apoptosis, oxidative stress, and inflammation was analyzed using RT-PCR. Results: OCT-D caused dose- and time-dependent cytotoxicity, and RPMI-2650 cells showed greater resistance compared to HUVECs. While a strong apoptotic response was observed in HUVECs, RPMI-2650 cells exhibited limited apoptosis. OCT-D was found to cause dose-dependent DNA damage and an increase in MN in both cell lines. OCT-D significantly reduced cytokine levels and ROS production in both cell types. RT-PCR results supported its anti-inflammatory and antioxidant effects at the molecular level. Conclusions: In conclusion, this study demonstrated that OCT-D exhibited minimal cytotoxic and apoptotic effects in RPMI-2650 cells, but affected vascular structure by inducing apoptosis in endothelial cells. These findings provide important evidence that OCT-D can be used as a potential adjunctive agent in nasal treatments, and these data need to be supported by preclinical and clinical studies. Full article

Guided bone regeneration membranes are essential for bone formation. While non-resorbable membranes require removal surgery, resorbable membranes such as poly (lactic-co-glycolic acid) PLGA are widely used; however, issues with animal-derived components and degradation control have been identified. A novel bilayer membrane composed of synthetic poly (L-lactic acid-co-ε-caprolactone) (PBM) was developed, offering prolonged degradability and elasticity. This study compared the wound-healing effects of PBM and PLGA membranes in vivo and in vitro experiments. In vivo, maxillary molars were extracted from rats, and membranes were placed over the sockets. Healing was evaluated histologically at 1, 2, 3, 4 and 8 weeks. In vitro, oral epithelial cells and fibroblasts were seeded on both sides of PBM. Adhesion and permeability of the membranes were assessed. In vivo, both groups displayed similar mucosal healing. However, PBM preserved a clear bone-soft tissue boundary. In vitro, the surface of PBM supported significantly greater oral epithelial cell adhesion than the reverse side, with no differences for fibroblasts. Both sides of PBM exhibited better protein permeability compared to PLGA. PBM maintained distinct bone-soft tissue separation in rat extraction sockets, suggesting its potential as an effective space maintainer in guided bone regeneration. Further studies are warranted to investigate the mechanisms underlying these favorable properties. Full article

Mycotoxins are toxic secondary metabolites produced by filamentous fungi that contaminate agricultural commodities, posing risks to food safety, animal productivity, and human health. The gastrointestinal tract is the first and most critical site of exposure, where the intestinal epithelium functions as both a physical and immunological barrier against luminal toxins and pathogens. While extensive research has demonstrated that mycotoxins disrupt epithelial integrity through tight junction impairment, oxidative stress, apoptosis, and inflammation, their effects on the intestinal stem cell (ISC) compartment and epithelial regeneration remain insufficiently understood. This review integrates recent findings from in vivo, cell culture, and advanced 3D intestinal organoid and gut-on-chip models to elucidate how mycotoxins such as deoxynivalenol and zearalenone impair ISC proliferation, alter Wnt/Notch signaling, and compromise mucosal repair. We also discuss dose relevance, species differences, and the modulatory roles of the microbiome and short-chain fatty acids, as well as emerging evidence of additive or synergistic toxicity under co-exposure conditions. By bridging well-established mechanisms of barrier disruption with the emerging concept of ISC-driven regenerative failure, this review identifies a critical knowledge gap in mycotoxin toxicology and highlights the need for integrative models that link epithelial damage to impaired regeneration. Collectively, these insights advance understanding of mycotoxin-induced intestinal dysfunction and provide a foundation for developing nutritional, microbial, and pharmacological strategies to preserve gut integrity and repair. Full article

Inflammation drives the development of multiple inflammatory enterohepatic diseases. The recruitment of immune cells to inflammatory tissues is essential for maintaining immune homeostasis, mediating immune responses and regulating inflammation. MAdCAM-1/α4β7 is a pair of homing ligand and receptor that plays important roles in lymphocyte migration. Their binding induces lymphocytes to cross endothelial structures into corresponding lymphoid tissues, contributing to the inflammatory response. Aberrant lymphocyte migration due to excessive binding is closely related to the occurrence and development of inflammatory bowel disease and liver inflammation. In this review, we focus on the activation of α4β7 and binding to MAdCAM-1 how to induce the migration of multiple kinds of lymphocytes. Additionally, we describe the intestinal microbiota and its metabolites associated with MAdCAM-1/α4β7 in inflammatory enterohepatic diseases. We also discuss the current status of the development of monoclonal antibodies and small molecule drugs targeting MAdCAM-1/α4β7 for the remission and treatment of inflammatory enterohepatic disease. Future research should focus on enhancing hepatic specificity and conducting well-designed clinical trials for inflammatory liver diseases to confirm therapeutic efficacy. Full article