Search Results (94)

Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder associated with gut microbiota dysbiosis and impaired intestinal barrier function. Probiotic interventions have shown potential in alleviating intestinal inflammation and restoring microbial balance. This study explores the protective effects of Lacticaseibacillus paracasei (L. paracasei) E10 in mice. L. paracasei E10 demonstrated strong gastrointestinal transit tolerance, high mucosal adhesion, and probiotic properties such as hydrophobicity and aggregation ability (p < 0.05). The oral administration of L. paracasei E10 significantly alleviated colitis symptoms by reducing the disease activity index, preserving colonic architecture, increasing goblet cell density, and upregulating tight junction proteins, thereby enhancing intestinal barrier integrity. 16S rRNA sequencing revealed that L. paracasei E10 supplementation enriched microbial diversity, increased the abundance of Muribaculaceae, and modulated the Firmicutes/Bacteroidetes ratio, contributing to gut homeostasis. These findings indicate that L. paracasei E10 is a potential candidate for IBD management. Full article

Background: Cachexia worsens prognosis, quality of life and chemotherapy treatment compliance of patients with lung cancer. Chemotherapy-induced cachexia has also been implicated in lowered mortality. This study aimed to evaluate the frequency of cachexia-related measures and symptoms as outcomes in lung cancer chemotherapy trial protocols and to examine how key trial characteristics influence them. Method: We conducted a cross-sectional data analysis of randomised controlled chemotherapy trials of lung cancer registered in four public trial registries between 2012 and 2023. Trial outcome measures included overall survival, treatment toxicity/side effects and cachexia-related indicators such as physical activity, weight/body mass index (BMI), dietary limitations, caloric intake and lean muscle mass. Symptom-related outcomes, including appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, dysphagia, dyspnoea and oral mucositis, were also extracted. Additionally, the number and type of performance status and assessment tool were recorded. Data were summarised descriptively. Chi-square tests were used to examine associations between trial outcomes and characteristics including cancer type, trial location, lead investigator/funding source, assessment tools and trial commencement year. A p < 0.05 was considered statistically significance. Results: Of the 335 trial protocols (non-small cell (87.2%) and small cell (12.8%)), most were from Europe (50.4%). The trial lead investigator was from industry (56.7%) followed by academia (25.1%). Allied health professional involvement was minimal (0.6%). Trial protocols mostly recorded overall survival (96.4%) and toxicity (83.9%). However, physical activity, weight/BMI, dysphagia, dyspnoea and oral mucositis were recorded in <30%, with dietary limitations, caloric intake and lean muscle mass recorded in <3% of the trials. Measures and symptoms were not associated with cancer type. Trial location was associated with the measures toxicity, physical activity and caloric intake and all symptoms. Lead investigator was associated with the measures toxicity and weight/BMI and all symptoms except for dyspnoea. Performance status and assessment tools were mentioned in 93.4% and 41.8% of the trials, respectively, with significant associations between assessment tools and outcomes, except for weight/BMI, dietary limitations, lean muscle mass, dysphagia and oral mucositis. There was a significant trend with trial commencement year for the measures physical activity (p = 0.002) and weight/BMI (p = 0.000) and all symptoms, except for appetite loss (p = 0.115) and pain (p = 0.433). Conclusions: While the reporting of measures and outcomes was generally higher compared to gastrointestinal chemotherapy cancer trials, it still faced significant under-reporting. Assessment tools should include cachexia-specific symptoms to accurately assess the quality of life in patients with lung cancer undergoing chemotherapy clinical trials. Full article

Mucosal immunization represents a promising strategy for preventing enteric infections. Rotavirus (RV), a leading gastrointestinal pathogen distinguished by its remarkable stability and segmented double-stranded RNA genome, has been engineered into a versatile oral vaccine vector through advanced reverse genetics systems. The clinical efficacy of live-attenuated RV vaccines highlights their unique capacity to concurrently induce mucosal IgA responses and systemic neutralizing antibodies, positioning them as a multiple action vector for multiple immune protection. In this review, we summarize the RV colonization of the intestine and stimulation of intestinal immunity, as well as recent advancements in RV reverse genetics, and focus on their application in the rational design of a multivalent mucosal vaccine vector targeting enteric pathogens considering the advantages and challenges of RV as a vector. We further propose molecular strategies to overcome genetic instability in recombinant RV vectors, including the codon optimization of heterologous inserts. These insights provide a theoretical foundation for developing next-generation mucosal immunization platforms with enhanced safety, stability, and cross-protective efficacy. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent, recurrent, and relapsing inflammation of the mucosal layer. Its pathogenesis is complex and not yet fully understood, with current treatments mainly focused on alleviating symptoms through pharmacological methods. Direct drug administration for UC often leads to poor intestinal bioavailability, suboptimal targeting, and an increased risk of resistance. Therefore, there is an urgent need for effective drug delivery systems. Lipid nanoparticles (LNPs) are promising candidates for UC drug delivery due to their high biocompatibility, stability, and customizable properties. Oral administration, as a preferred treatment approach for UC, offers benefits such as convenience, cost-effectiveness, and better patient compliance. However, oral drug delivery systems must navigate the complex gastrointestinal tract to effectively target colonic lesions, posing significant challenges for LNP-based systems. Researchers are exploring ways to enhance oral delivery efficiency by adjusting LNP composition, surface functionalization, and coating. This article reviews recent advancements in oral LNP research aimed at improving drug delivery efficiency for UC treatment and discusses future prospects. Full article

Ulcerative colitis (UC) is a chronic inflammation disease with severe impact on quality of life, with limited treatment options. Ramulus Mori alkaloids (SZ-A) from Morus alba show promise for UC treatment due to their safety and pharmacological effects, including anti-inflammation and barrier repair. However, their clinical use has been limited by gastrointestinal flatulence as a side effect due to their pharmacological action as an α-glucosidase inhibitor targeting the small intestine following oral administration. Therefore, constructing a colon-targeted formulation to deliver SZ-A is an advantageous strategy to improve UC therapy. In this study, we used the complex formed by thiolated hyaluronic acid, which has mucosal adhesion and inflammation-targeting properties, and SZ-A as an intermediate carrier and prepared sodium alginate-modified PLGA microspheres (SZ-A@MSs) with the double emulsion method to achieve efficient encapsulation of SZ-A. Specifically, sodium alginate serves as a gastric acid protectant and microbiota-responsive material, enabling the precise and responsive release of microspheres in the colonic region. SZ-A@MSs have a particle size of about 30 µm, a drug loading of about 12.0%, and an encapsulation efficiency of about 31.7% and function through intestinal adhesion to and targeting of inflammatory sites. SZ-A@MSs showed antioxidant and anti-inflammatory abilities in Raw264.7 cells. In vivo imaging results suggest that SZ-A@MSs have good colon site retention and sustained-release effect. Pharmacodynamic results show that SZ-A@MSs display good efficacy, including the ability to inhibit weight loss, inhibit colonic atrophy, and inhibit the secretion of inflammatory factors. In conclusion, SZ-A@MSs have good colon-targeting properties, can improve therapeutic effects, and provide a potential treatment method for UC. Full article

Background/Objectives: Porcine epidemic diarrhea (PED) is a highly contagious enteric infectious disease that causes severe morbidity and mortality in piglets, posing significant economic losses to the swine industry worldwide. Oral vaccines based on Lactococcus lactis offer a promising approach due to their safety and genetic manipulability. This study aims to develop and evaluate an oral L. lactis-based vaccine expressing the full-length PEDV S protein. Methods: A recombinant L. lactis strain expressing the PEDV S protein was constructed and encapsulated in alginate–chitosan microcapsules. Vaccine stability was tested in simulated digestive fluids, and mice were orally immunized. Immune responses were evaluated by measuring specific antibodies, cytokines, and lymphocyte proliferation. Results: The recombinant L. lactis NZ3900/pNZ8149-S strain successfully expressed the full-length PEDV S protein and maintained stable plasmid inheritance. Oral immunization in mice induced detectable PEDV-specific immune responses. Both encapsulated and non-encapsulated vaccines stimulated the production of IgG and sIgA antibodies, as well as cytokines associated with Th1 and Th2 responses. Notably, encapsulation with alginate–chitosan significantly enhanced bacterial survival in digestive conditions and further amplified immune responses, including higher antibody titers, elevated levels of IFN-γ, IL-4, and IL-10, and greater lymphocyte proliferation, indicating improved immune memory. Conclusions: The oral L. lactis NZ3900/pNZ8149-S vaccine expressing the PEDV S protein effectively induced systemic and mucosal immunity in mice. Encapsulation with alginate–chitosan further enhanced its immunogenicity and stability in gastrointestinal conditions. These results suggest that both the engineered L. lactis strain and the encapsulation strategy contribute to the development of a promising oral vaccine platform for controlling PEDV in swine populations. Full article

Oral vaccines are currently the focus of vaccine development because they are convenient to administer, easy to distribute, and capable of activating mucosal immunity. However, the complexity of the gastrointestinal environment and the lack of delivery vehicles severely limit the stability and effectiveness of oral vaccines. This study established a novel platform for developing oral vaccines based on the surface display system of yeast spores. As a specific example, oral vaccines for COVID-19, designed by displaying the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein on the surface of three Saccharomyces cerevisiae spore types, including AN120, osw2Δ, and dit1Δ, were constructed and evaluated. The displayed RBD showed perfect gastrointestinal stability in vitro and was validated in animal studies to produce effective humoral immunity and significant mucosal immune responses after the vaccination. Notably, the displayed RBD elicited a cellular immune response skewed towards a T-helper type 1 (Th1) cell direction in a mouse model. Our findings proved that the oral vaccines of S. cerevisiae spores could rapidly induce a comprehensive and protective immune response to SARS-CoV-2. This study aims to provide a promising and potentially useful system that can be used to develop other oral vaccines. Full article

All parts of Alocasia × amazonica (A. amazonica, Araceae) pose a toxicological risk due to oxalate production. Ingestion of the plant extract may cause multi-organ damage and fatal outcomes. Given the rarity of poisoning cases, its toxicological profile and systemic effects remain insufficiently characterized. This study aimed to investigate and report an appropriate approach to managing a patient intoxicated with A. amazonica (Araceae). A case of intentional self-poisoning with A. amazonica is presented. The patient, a 63-year-old woman, ingested approximately 200–300 mL of liquid prepared from the grated root of the plant. The initial clinical presentation involved localized injuries to the oral cavity and gastrointestinal tract, including severe pain, hoarseness, aphonia, dysphagia, mucosal erosions, and necrosis. Additional symptoms included hematinic vomiting, hemorrhagic diarrhea, and abdominal discomfort. These superficial and mucosal lesions resolved without the development of adhesions. Systemic effects comprised impaired consciousness indicative of encephalopathy, early metabolic acidosis, pulmonary edema with acute respiratory insufficiency, mild liver dysfunction, and hematuria. The therapeutic protocol for oral poisoning management was appropriate, leading to the patient’s discharge after 20 days of hospitalization. Full article

Background: Agarwood has been widely used for the treatment of gastrointestinal diseases. Our research group has suggested that agarwood alcohol extracts (AAEs) provide good gastric mucosal protection. However, the exact mechanisms underlying this effect remain unclear. Objectives: This study aimed to investigate the ameliorative effect of agarwood chromone on gastric ulcers and its mechanism. Methods: Network pharmacology was used to predict the disease spectrum and key therapeutic targets of 2-(2-phenylethyl)chromone (CHR1) and 2-(2-(4-methoxyphenyI)ethyl)chromone (CHR2). Mice were orally administered CHR1 (20 and 40 mg/kg) and CHR2 (20 and 40 mg/kg) and the positive drug omeprazole as an enteric-coated capsule (OEC, 40 mg/kg) orally. After 7 days of pretreatment with the CHRs, gastric ulcers were induced using absolute ethanol (0.15 mL/10 g). The ulcer index, gastric histopathology, biochemical parameters, and inflammatory and apoptotic proteins were evaluated. Finally, binding of the core compounds to the key targets was verified via molecular docking and visualized. Results: The pharmacological results show that the CHRs reduced the gastric occurrence and ulcer inhibition rates by up to more than 70% in a dose-dependent manner. The CHRs decreased the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), and improved the severity of the pathological lesions in the gastric tissue. The expression of ATP-binding box transporter B1 (ABCB1), arachidonic acid-5-lipoxygenase (ALOX5), nuclear factor kappa B (NF-κB), cysteinyl aspartate specific proteinase 3 3 (Caspase3), and cysteinyl aspartate specific proteinase 9 (Caspase9) was inhibited, but the expression of B-cell lymphoma-2 (Bcl-2) was enhanced. The CHRs bound stably to the key targets via hydrogen bonding, van der Waals forces, etc. These results demonstrate that agarwood chromone compounds exert alleviative effects against the occurrence and development of gastric ulcers by inhibiting the NF-κB and caspase pathways. The CHRs have a therapeutic effect on gastric ulcers through anti-inflammation and anti-apoptosis mechanisms. Conclusions: This study suggests that agarwood may have a potential role in drug development and the prevention and treatment of gastrointestinal inflammation, and tumors. Full article

Porcine epidemic diarrhea (PED) is a severe gastrointestinal disease caused by the porcine epidemic diarrhea virus (PEDV), a virus that spreads through the intestinal tract, leading to significant economic losses in the global swine industry. Therefore, compared to traditional injection method, developing vaccines that effectively stimulate the mucosal immune system to induce a protective immune response is crucial for PED prevention. This study evaluated the immunogenicity of recombinant Lactococcus lactis (L. lactis) strains expressing the PEDV S1 and M proteins (MG1363/pMG36e-S1 and MG1363/pMG36e-M) via oral administration in BALB/c mice and neonatal piglets, assessing cellular, humoral, and mucosal immune responses in the host. The results demonstrated that the recombinant strains significantly stimulated lymphocyte proliferation in mice and increased the proportion of CD3+, CD4+, and CD3+, CD8+ double-positive cells in the spleens of mice and the peripheral blood of piglets (p < 0.05). Furthermore, the recombinant strains significantly increased serum IgG, IgA, and mucosal SIgA levels in piglets (p < 0.05). Meanwhile, serum cytokine levels, including IL-4 and IFN-γ, were significantly elevated in piglets when compared to the control group (p < 0.05). In conclusion, the recombinant L. lactis demonstrated promising potential as a novel live vector vaccine against PEDV. Full article

The oral mucosa is a versatile surface for drug administration, supporting both local and systemic therapies. Many active substances are effectively absorbed in the oral cavity, offering an alternative to enteral administration by bypassing the harsh gastrointestinal environment and hepatic first-pass metabolism. This has made oral mucosal drug delivery a growing area of research. Enhancing the bioavailability of active ingredients is a key focus in pharmaceutical technology, especially given the challenges of developing new drugs. Numerous strategies to improve bioavailability are compatible with oral mucosal delivery, with the unique anatomy of the oral cavity enabling specialized applications. A variety of dosage forms tailored for oral mucosal delivery meet therapeutic needs while addressing biopharmaceutical and patient compliance challenges. Proper formulation can achieve controlled release, improved bioavailability, and patient convenience. This review highlights the potential of oral mucosal drug delivery, focusing on bioavailability enhancement methods and the types and production technologies of dosage forms optimized for use in the oral cavity. Full article

Background/Objectives: Helicobacter pylori is the leading cause of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosal-associated lymphoma. Due to the emerging problems with antibiotic treatment against H. pylori in clinical practice, H. pylori vaccination has gained more interest. Oral immunization is considered a promising approach for preventing initial colonization of this bacterium in the gastrointestinal tract, establishing a first line of defense at gastric mucosal surfaces. Chitosan nanoparticles can be exploited effectively for oral vaccine delivery due to their stability, simplicity of target accessibility, and beneficial mucoadhesive and immunogenic properties. Methods: In this study, new multi-epitope pDNA- and recombinant protein-based vaccines incorporating multiple H. pylori antigens were produced and encapsulated in chitosan nanoparticles for oral and intramuscular administration. The induced immune response was assessed through the levels of antigen-specific IgGs, secreted mucosal SIgA, and cytokines (IL-2, IL-10, and IFN-γ) in immunized BALB/C mice. Results: Intramuscular administration of both pDNA and recombinant protein-based vaccines efficiently stimulated the production of specific IgG2a and IgG1, which was supported by cytokines levels. Oral immunizations with either pDNA or recombinant protein vaccines revealed high SIgA levels, suggesting effective gastric mucosal immunization, contrasting with intramuscular immunizations, which did not induce SIgA. Conclusions: These findings indicate that both pDNA and recombinant protein vaccines encapsulated into chitosan nanoparticles are promising candidates for eradicating H. pylori and mitigating associated gastric diseases in humans. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30–50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) —DNA-based structures with cytotoxic proteins—that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly—without systemic absorption—could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients. Full article

Background and Objectives: Acute gastric injury is a prevalent gastrointestinal disorder characterized by inflammation and damage to the stomach lining. In this study, we investigated the therapeutic potential effects of broccoli stem extract (BSE) against acute gastritis in a rat model. Materials and Methods: The antioxidant properties of BSE were evaluated through DPPH and ABTS radical scavenging activity assays and total polyphenol content analysis. Acute gastric injury was induced using 150 mM HCl/60% EtOH, and male SD rats (6-weeks old, n = 6/group) were administered BSE by oral gavage at concentrations of 50, 125, and 250 mg/kg. Results: The BSE 250 mg/kg group exhibited significant relief of clinical signs compared to the negative control group. In addition, the BSE 250 mg/kg group showed significant improvements in gastric tissue, including macroscopic reductions in ulcer size and improved overall gastric morphology as assessed through gross examination, as well as microscopic improvements such as reduced inflammation and the restoration of mucosal integrity observed in histopathological analysis. BSE modulated NF-κB signaling, decreased inflammatory cytokines (TNF-α, IL-1β, and IL-6), and increased PGE₂ levels. Pyloric ligation experiments demonstrated reduced pepsin and gastric acid secretion. Improvements in gastric emptying and gastrointestinal motility were also observed in the BSE-treated group. Conclusions: These findings highlight the potential of BSE as an effective therapeutic agent for acute gastritis in rats, offering significant improvements in gastric damage, inflammation, and motility. Full article

Background/Objectives: Recurrent aphthous stomatitis is a common oral mucosal disorder characterized by painful ulcerations and frequent recurrences, which can significantly impair quality of life. This study explores the efficacy of zinc-enriched multivitamin supplementation (ZnVita, containing 22.5 mg of elemental zinc) for the treatment of recurrent aphthous stomatitis in treatment-naïve patients, aiming to diminish the reliance on immunomodulatory drugs. Methods: Conducted as a retrospective observational study at a tertiary referral hospital from 2013 to 2023, we analyzed 201 patients who received ZnVita daily for a minimum duration of one month as their initial management. Patients who were using systemic immunomodulating agents or met the diagnostic criteria for Behçet’s disease were excluded. Results: Of the 201 patients, 95 presented with an oral ulcer alone and 106 exhibited additional symptoms associated with Behçet’s disease. Efficacy analysis was conducted on 155 patients due to follow-up loss or incomplete data. Among them, 58.7% (91/155) showed partial or significant responses. Patients with BD-related symptoms were significantly more prevalent among non-responders (64.1%, 41/64) compared to responders (42.9%, 39/91), with a statistically significant difference (p = 0.009). Treatment was well-tolerated, with mild gastrointestinal adverse events reported in only 2.5% of cases. Conclusions: These results suggest that zinc-enriched multivitamin supplementation offers a beneficial and safe initial treatment alternative for a considerable proportion of treatment-naïve recurrent aphthous stomatitis patients, especially those without concurrent symptoms of Behçet’s disease, showcasing its potential in reducing the future need for immunomodulatory treatments. Full article