Search Results (80)

Cyclodextrins (CDs) have traditionally been recognized as excipients that enhance solubility and stability of drugs. However, growing evidence shows that CDs themselves can act as active therapeutic agents. Their unique supramolecular properties enable them to interact with biological membranes, mobilize cholesterol, and modulate immune responses. This review highlights four therapeutic areas where CDs demonstrate particular promise. First, in gene and mRNA therapy, cationic CD derivatives form nanoparticles that protect nucleic acids, promote endosomal escape, and achieve targeted delivery. Second, in neurodegenerative disorders such as Niemann–Pick type C and Alzheimer’s disease, hydroxypropyl-β-CD facilitates cholesterol clearance and reduces pathological lipid accumulation. Third, in detoxification, the γ-CD derivative sugammadex exemplifies a clinically approved agent that encapsulates neuromuscular blockers to reverse anesthesia. Finally, CDs have emerged as safe vaccine adjuvants, inducing robust systemic and mucosal immunity with reduced IgE responses compared to alum. Together, these examples illustrate a paradigm shift: CDs are not only versatile excipients but also active molecules with direct therapeutic effects. Future translation will require careful optimization of safety, scalability, and regulatory compliance, but CDs are poised to contribute meaningfully to next-generation medicines. Full article

Nisin, a food preservative lantibiotic produced by Lactococcus lactis, exhibits potent antimicrobial activity against a wide range of Gram-positive pathogens, including antibiotic-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA). This study explores the development of a novel nano drug delivery platform comprising nisin-loaded niosomes, formulated via microfluidic mixing, and integrated into fast-dissolving oral films for targeted buccal administration. Microfluidic synthesis enabled the precise control of critical parameters including the flow rate ratio, surfactant composition, and lipid concentration, resulting in uniform niosomal vesicles with optimal size distribution (100–200 nm), low polydispersity index, and high encapsulation efficiency. Span 40 and Span 60 were employed as non-ionic surfactants, stabilized with cholesterol to improve bilayer rigidity and drug retention. The encapsulated nisin demonstrated improved physicochemical stability over time and protection against proteolytic degradation, thus preserving its antimicrobial potency. The niosomal suspensions were subsequently incorporated into polymer-based oral films as a final dosage form composed of polyvinyl alcohol (PVA) as the primary film-forming polymer, polyethylene glycol 400 (PEG400) as a plasticizer, and sucralose and mint as a sweetener and flavoring agent, respectively. A disintegrant was added to accelerate film dissolution in the oral cavity, facilitating the rapid release of niosomal nisin. The films were cast and evaluated for thickness uniformity, mechanical properties, disintegration time, surface morphology, and drug content uniformity. The dried films exhibited desirable flexibility, rapid disintegration (<30 s), and consistent distribution of nisin-loaded vesicles. In vitro antimicrobial assays confirmed that the bioactivity of nisin was retained post-formulation, showing effective inhibition zones (16 mm) against Bacillus subtilis. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments. Physicochemical characterization of the niosomes and niosome films was performed using Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) to evaluate thermal stability and scanning electron microscopy (SEM) to assess surface morphology. In vitro peptide release studies demonstrated sustained release from both niosomal suspensions and film matrices, and the resulting data were further fitted to established kinetic models to elucidate the underlying drug release mechanisms. This delivery system offers a promising platform for localized antimicrobial therapy in the oral cavity, potentially aiding in the treatment of dental plaque, oral infections, and periodontal diseases. Overall, the integration of microfluidic-synthesized nisin niosomes into oral films presents a novel, non-invasive strategy for enhancing the stability and therapeutic efficacy of peptide-based drugs in mucosal environments. Full article

Non-Hodgkin B-cell lymphomas are a heterogeneous group of lymphoid malignancies with variable biological behavior, clinical presentation and treatment response. While chemoimmunotherapy remains the cornerstone of their management, growing evidence implicates the gut microbiota as a critical modulator of both lymphomagenesis and therapeutic efficacy. Gut microbiota dysbiosis, characterized by reduced microbial diversity and pathogenic taxonomic shifts, has been observed also in newly diagnosed patients and not just after therapy. This microbial imbalance contributes to mucosal barrier disruption, systemic inflammation, and altered immune responses, affecting treatment outcomes and toxicity profiles. Antibiotic exposure, especially broad-spectrum agents, exacerbates dysbiosis and has been associated with inferior responses to immunochemotherapy and CAR T-cell therapy. Conversely, certain commensal taxa, like Faecalibacterium prausnitzii and Lactobacillus johnsonii, may exert protective effects by preserving mucosal homeostasis and promoting antitumor immunity. Targeted interventions, including prudent antibiotic stewardship, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation, are under investigation to restore eubiosis and improve clinical outcomes. Preliminary clinical trials suggest a strong correlation between baseline microbiome composition and therapeutic response. Further mechanistic studies and randomized trials are warranted to define the causal role of the microbiome in non-Hodgkin B-cell lymphomas pathophysiology and to develop personalized microbiome-modulating strategies as adjuncts to standard treatment. Full article

Background: Erosive gastritis has various causes, and severe damage to the mucosa can cause symptoms such as indigestion, abdominal pain, nausea, and vomiting. The condition is defined by visible erosions that emerge as discrete defects in the gastric mucosa. Stillen^® is a natural mucosal-protective agent derived from Artemisia asiatica, but its comparative efficacy versus rebamipide remains unclear. This systematic review and network meta-analysis evaluated whether Stillen^® leads to non-inferior endoscopic improvement outcomes compared to rebamipide in patients with acute or chronic gastritis. Methods: Databases including PubMed, EMBASE, Cochrane Library, RISS, KoreaMed, ClinicalTrials.gov, and ICTRP were searched through 15 August 2025. Eligible studies were randomized controlled trials (RCTs) comparing Stillen^® with rebamipide or other mucosal-protective agents in gastritis. Two reviewers independently screened studies, extracted data, and evaluated the risk of bias. The primary outcome was the improvement rate (≥50% erosion reduction); the secondary outcome was the cure rate (complete erosion resolution) and safety outcomes. Results: A total of 11 RCTs met the inclusion criteria, with 9 contributing to the primary network analysis. Stillen^® was non-inferior to rebamipide in terms of the improvement rate at 2 weeks (OR: 1.11, 95% CI: (0.88, 1.39) in FAS) and in pooled analysis across 2, 3, and 4 weeks. Cure rates showed no significant differences between the two agents. The safety outcomes were comparable, with no significant differences. Most studies were assessed as having a low risk of bias, and the certainty of evidence was rated as high for most efficacy outcomes. Conclusions: The network meta-analysis suggests that Stillen^® is non-inferior to rebamipide in improving erosions in patients with acute or chronic gastritis. Full article

Gastric ulcer (GU) is a common gastrointestinal disorder that impacts quality of life. Currently, several drugs are available for GU treatment, including proton pump inhibitors like omeprazole (OMP); however, their use is limited by numerous potential adverse effects. Glycyrrhizic acid (GLY), a natural anti-inflammatory agent, exhibits promising gastroprotective properties; however, its use is likewise limited by numerous potential adverse effects. This study aimed to synthesize GLY nanoparticles (GLY-NPs) to enhance their therapeutic potential and to comparatively evaluate their efficacy against OMP in an ethanol-induced GU in male Wistar rats. GLY-NPs were synthesized via a hydrothermal method and characterized using TEM, XRD, FTIR, and zeta potential analyses. In vivo, GLY-NPs significantly attenuated gastric mucosal damage compared to OMP, as evidenced by macroscopic and histopathological analyses. Biochemical assays revealed that GLY-NPs markedly improved antioxidant defenses by elevating SOD, catalase, and glutathione peroxidase activities while reducing MDA levels, surpassing the effects of OMP. Furthermore, GLY-NPs modulated inflammatory responses by downregulating p38 MAPK, NF-κB, and TNF-α expression, concomitant with upregulation of the anti-inflammatory cytokine IL-10. Mechanistic insights indicated that GLY-NPs favorably regulated key signaling pathways implicated in gastric mucosal protection, including suppression of the JAK2/STAT3 and TGF-β1/Smad3 pathways, alongside activation of the SIRT1/FOXO1/PGC-1α axis. In conclusion, these findings indicate that GLY-NPs offer higher gastroprotective effects relative to traditional OMP therapy through comprehensive modulation of oxidative stress, inflammation, and molecular signaling pathways. This study highlights GLY-NPs as a potent nanotherapeutic candidate for the effective management of GU. Full article

Background: Up to one-third of patients with gastroesophageal reflux disease (GERD) have persistent symptoms despite proton-pump inhibitor (PPI) therapy. E-Gastryal^® + MgAlg (Aurora Biofarma, Italy) is a mucosal protective agent that enhances barrier function against acid and non-acidic reflux. This study assessed its efficacy in combination with omeprazole versus omeprazole alone and as maintenance therapy. Methods: Patients with symptomatic GERD and Grade A reflux esophagitis confirmed by endoscopy were randomized to receive omeprazole 20 mg plus E-Gastryal^® + MgAlg or omeprazole 20 mg alone. The primary endpoint was the number of rescue medications used over 28 days. Secondary endpoints included symptom relief and quality-of-life assessments using the Reflux Symptom Index (RSI), Gastroesophageal Reflux Disease Impact Scale (GIS), GERD-Health-Related Quality of Life (GERD-HRQL), and Global Assessment of Performance (IGAP). Results: Ninety-six patients were included. The combination group used significantly fewer rescue medications (mean: 21 vs. 40.9 tablets; p = 0.002). At week 4, the combination group showed greater improvement in RSI, GIS, and GERD-HRQL scores (p < 0.001). Symptom relief was sustained during weeks 5–26 with E-Gastryal^® + MgAlg alone. Conclusions: E-Gastryal^® + MgAlg combined with omeprazole improves symptom control compared to PPI monotherapy. Continued use as maintenance therapy supports its role in long-term GERD management (NCT04130659). Full article

Respiratory syncytial virus (RSV) is a major etiological agent of lower respiratory tract infections, particularly among infants and the elderly. Activation of B cells in the mucosa and the production of specific neutralizing antibodies are essential for protective immunity against pulmonary infection. B-cell activating factor (BAFF) is a critical survival factor for B cells and has been associated with antiviral responses; however, its regulation during RSV infection remains poorly understood. This study examined BAFF regulation in BEAS-2B cells exposed to RSV or IFN-β. The treatments resulted in a progressive increase in gene expression over time, accompanied by higher protein levels. BAFF mRNA peaked at 12 h post-infection and declined by 48 h, coinciding with the release of soluble BAFF protein into the culture supernatant. Pre-treatment with anti-IFN-β antibodies prior to RSV infection reduced both BAFF mRNA and protein levels, indicating that IFN-β plays a regulatory role in BAFF production by airway epithelial cells. Western blot analysis revealed membrane-bound BAFF (~31 kDa) in non-infected cells, with elevated expression at 24 h post-infection. By 48 h, this form was cleaved into a soluble ~17 kDa form, which was detected in the supernatant. Immunostaining further demonstrated reduced surface expression of membrane-bound BAFF in RSV-infected cells compared to uninfected controls, suggesting that RSV infection promotes the cleavage and release of BAFF into the extracellular environment. Additionally, the release of BAFF was not affected by furin convertase inhibition or ER–Golgi transport blockade, indicating a potentially novel cleavage mechanism. Co-culturing BAFF produced by BEAS-2B cells with isolated B cells enhanced B cell viability. Overall, these results indicate that RSV infection stimulates BAFF production in airway epithelial cells through a pathway involving IFN-β, potentially contributing to B cell activation and promoting local antibody-mediated immunity. Understanding this mechanism may offer valuable insights for improving mucosal vaccine strategies and enhancing immunity against respiratory pathogens. Full article

Objectives: This study was designed to investigate the gastroprotective effects of Citrus reticulata ‘Chachi’ polysaccharide (CRP) against alcohol-induced gastric ulcers (GUs) and to elucidate its underlying mechanisms. Methods: CRP was extracted, purified, and structurally characterized. BALB/c mice (50/250 mg/kg CRP) and GES-1 cells (1 mg/mL CRP) were subjected to alcohol-induced injury. Oxidative stress (SOD, MDA, ROS), inflammation (TNF-α, IL-1β, NLRP3 inflammasome), mucosal barrier proteins (ZO-1, occludin, Claudin-5), and Nrf2/HO-1 signaling were analyzed via histopathology, Western blot, flow cytometry, and immunohistochemistry. Results: CRP pretreatment significantly alleviated gastric lesions, decreased oxidative stress, and suppressed inflammatory responses in alcohol-induced mice. Mechanistically, CRP induced the Nrf2/HO-1 antioxidant pathway while inhibiting the activation of the NLRP3 inflammasome. CRP also restored tight junction protein expression, enhanced mucosal repair, and reduced epithelial apoptosis. In vitro, CRP promoted cell proliferation, migration, and survival of GES-1 cells under alcohol stress. Conclusions: CRP mitigated alcohol-induced GU via dual antioxidant, anti-inflammatory, and barrier-protective mechanisms, positioning it as a considerable agent for GU. Full article

The intestinal epithelium, which is protected by mucosal surfaces composed of mucins and other glycoproteins, functions as a selective barrier that absorbs nutrients while preventing the translocation of harmful substances. To understand the mechanisms between mucosal disruption and tissue inflammation, we orally administrated a mucus-disrupting agent, dextran sodium sulfate, to Drosophila melanogaster and screened 63 differentially expressed genes (DEGs). Through a database search using bioinformatics tools (CHEA3 and WebGestalt), we identified ELK1 as a potential key transcription factor for the selected DEGs, and among the 63 DEGs, ELK1-related genes, B3GAT3, FIBP, and TENT2 (GlcAT-S, Fibp, and Wisp in Drosophila), were selected as the relevant genes that respond to mucus disruption. We confirmed that enterocyte (EC)-specific GlcAT-S knockdown by RNAi significantly reduced gut length and increased intestinal stem cell proliferation in Drosophila. Additionally, in EC-specific GlcAT-S-knockdown flies, it was observed that the mucus-production-related genes, Muc68D and Mur29B, were specifically reduced, whereas the inflammatory cytokines egr and upd3 were overexpressed. This study provides evidence that GlcAT-S is involved in the regulation of intestinal inflammation in Drosophila and plays a protective role against mucus disruption. Our findings suggest that GlcAT-S may be a potential therapeutic target for the treatment of intestinal inflammatory diseases such as IBD. Full article

Sanghuang (Sanghuangporus sanghuang, SS) is a medicinal fungus with multiple pharmacological effects, including antioxidant, anti-inflammatory, immune-boosting, and anti-cancer activities. 5-fluorouracil (5-FU) is a commonly used chemotherapeutic agent for the treatment of colorectal cancer. It primarily exerts its antitumor effect by inhibiting DNA and RNA synthesis, leading to cell apoptosis. However, it frequently induces adverse effects These issues limit the clinical application of 5-FU. This research aims to determine the potential of SS as a therapeutic agent in reducing 5-FU-induced intestinal mucositis in a mouse model. The results indicated that 5-FU administration significantly increased diarrhea severity, reduced colon length, caused small intestinal villus atrophy, disrupted intestinal architecture, led to insufficient crypt cell proliferation, and resulted in weight loss. It also significantly upregulated inflammatory responses, apoptosis, oxidative stress, and epithelial–mesenchymal transition (EMT) pathways, and disrupted the integrity of intestinal mucosal tight junction, while elevating pro-inflammatory cytokines and reducing antioxidant capacity. However, SS significantly ameliorating alleviating the adverse impacts of the chemotherapeutic agent on the intestinal mucosa. In conclusion, this investigation provides the first evidence of the protective effects of SS on 5-FU-induced mucositis. These findings suggest SS as a potential therapeutic application, offering a promising strategy for reducing the adverse effects of 5-FU chemotherapy and improving the treatment and quality of life for colorectal cancer patients. Full article

Upper gastrointestinal bleeding from erosive gastritis remains associated with high mortality in septic or postoperative patients. While stress ulcer bleeding has declined, it still occurs in septic patients and is considered a manifestation of intestinal failure within multi-organ failure syndrome. The integrity of the gastric mucosal barrier plays a crucial role in protection against this condition. Somatostatin (SS) appears as a biomolecule with cytoprotective properties. We aimed to investigate whether SS treatment protected the gastric mucosa in a rat model of lipopolysaccharide (LPS)-induced sepsis. Rats received LPS (10 mg/kg) intraperitoneally, followed by saline or SS (200 μg/kg; 5 mL/kg) treatment after 30 min (early treatment group) or 120 min (late treatment group). Control rats received only saline. Two hours after saline or SS administration (total procedure duration of 150 or 240 min), gastric lavage, gastric mucosa, and plasma samples were collected for analysis. SS treatment mitigated the LPS-induced gastric mucosal barrier disruption preserving phosphatidylcholine (PC) levels, as well as decreasing leukocyte infiltration marker myeloperoxidase (MPO), inflammation-related enzyme phospholipase A2 (PLA2), and lipid peroxidation indicator malondialdehyde (MDA). SS also reduced arachidonic acid-related metabolites thromboxane B2 (TXB2) and leukotriene B4 (LTB4) while increasing prostaglandin I2 (PGI2). SS treatment effectively maintained gastric mucosal integrity, reducing inflammation, and modulating arachidonic acid metabolites. These findings suggest that SS may serve as a therapeutic agent for preserving gastric mucosal integrity and reducing inflammation in LPS-induced gastric injury. Full article

Gastric ulcer (GU) is a prevalent gastrointestinal disorder impacting millions worldwide, with complex pathogenic mechanisms that may progress to severe illnesses. Conventional therapies relying on anti-secretory agents and antibiotics are constrained by drug abuse and increased bacterial resistance, highlighting the urgent need for safer therapeutic alternatives. Natural medicinal compounds, particularly triterpenoids derived from plants and herbs, have gained significant attention in recent years due to their favorable efficacy and reduced toxicity profiles. Emerging evidence indicates that triterpenoids exhibit potent anti-ulcer properties across various experimental models, modulating key pathways involved in inflammation, oxidative stress, apoptosis, and mucosal protection. Integrating current knowledge of these bioactive compounds facilitates the development of natural triterpenoids, addresses challenges in their clinical translation, deepens mechanistic understanding of GU pathogenesis, and drives innovation of therapeutic strategies for GU. This review comprehensively evaluates the progress of research on triterpenoids in GU treatment since 2000, discussing their biological sources, structural characteristics, pharmacological activities, and mechanisms of action, the animal models employed in the studies, current limitations, and the challenges associated with their clinical application. Full article

Norovirus is a major etiological agent of nonbacterial gastroenteritis around the world. Due to its in vitro culture complexity, high genome diversity, and the lack of cross-reactive immunity between genogroups, there is an unmet urgent need for polyvalent norovirus vaccines that provide broad-spectrum protection, and no vaccine has gained global approval to date. In this study, we constructed a bivalent norovirus vaccine, based on the highly attenuated poxvirus [strain VG9] vector, expressing the major capsid protein VP1 from genotypes GII.4 and GII.17. VG9-NOR exhibited a comparable replication ability to the authentic virus while preserving good safety. After the intramuscular and intranasal immunization of mice, VG9-NOR induced high IgG- and IgA-binding antibody (Ab) titers against GII.4 and GII.17, increased the secretion of GII.4 and GII.17-specific HGBA-blocking antibodies, and enhanced GII.17-specific mucosal immunity. Furthermore, VG9-NOR also induced a Th1-mediated cellular response. These results demonstrate that the polyvalent poxvirus vector vaccine expressing VP1 variants from different subtypes is able to elicit effective protection. Our study highlights the VG9 vector as a highly promising candidate for the development of polyvalent norovirus vaccines. Full article

When the protective mechanisms of the gastroesophageal mucosa are overwhelmed by injurious factors, the structural and functional mucosal integrity is compromised, resulting in a wide spectrum of disorders. Poliprotect has recently been shown to be non-inferior to standard-dose omeprazole for the treatment of endoscopy-negative patients with heartburn and/or epigastric pain or burning. Here, we provide preclinical data describing the mechanism of action of the Poliprotect formulation, a 100% natural, biodegradable, and environmental friendly medical device according to EU 2017/745 and containing UVCB (unknown or variable composition, complex-reaction products, or biological materials) substances of botanical and mineral origin, according to the REACH and European Chemical Agency definitions. Different in vitro assays demonstrated the capability of Poliprotect to adhere to mucus-secreting gastric cells and concomitantly deliver a local barrier with buffering and antioxidant activity. In studies conducted in accordance with systems biology principles, we evaluated the effects of this barrier on human gastric cells exposed to acidic stress. Biological functions identified via Ingenuity Pathway Analysis highlighted the product’s ability to create a microenvironment that supports the mucosal structural and functional integrity, promotes healing, and restores a balanced mucosal inflammatory status. Additionally, transepithelial electrical resistance and an Ussing chamber showed the product’s capability of preserving the integrity of the gastric and esophageal epithelial barriers when exposed to an acid solution. Two in vivo models of erosive gastropathy further highlighted its topical protection against ethanol- and drug-induced mucosal injury. Overall, our findings sustain the feasibility of a paradigm shift in therapeutics R&D by depicting a very innovative and desirable mode of interaction with the human body based on the emerging biophysical, rather than the pharmacological properties of these therapeutic agents. Full article

The integrity of esophageal epithelial cells in patients with gastroesophageal reflux disease (GERD) or GERD-like symptoms is the first mechanism of protection to decrease the sensitivity to gastric reflux and heartburn symptoms. We investigated the protective effects of Poliprotect^® (PPRO), a CE-marked medical device, on esophageal epithelial integrity using in vitro and ex vivo models. In vitro, the protective effects of PPRO were tested on Caco-2 cells. PPRO demonstrated safety and protection against oxidative damage induced by hydrogen peroxide. It also preserved epithelial integrity by maintaining transepithelial electrical resistance (TEER) against damage from calcium removal or bile acid exposure (taurodeoxycholic acid, TDCA). Ex vivo, esophageal biopsies from patients subjected to endoscopy were mounted in Ussing chambers and exposed to damaging agents (HCl or HCl + TDCA). Untreated biopsies (control) showed significant loss of epithelial resistance (up to −33%). In contrast, low concentrations of PPRO (50–100 µg/mL) provided strong protection against these damages (p < 0.001), even after 60 min of washing. Histological analysis confirmed the barrier-enhancing effect of PPRO. Overall, PPRO effectively protected the esophageal epithelium from damage in both models, suggesting its potential role in alleviating GERD or GERD-like symptoms by strengthening mucosal barriers and reducing epithelial sensitivity to reflux. Full article