Search Results (417)

Oral supplementation of the Hafnia alvei (H. alvei) HA4597 probiotic strain has been shown to reduce appetite, body weight and fat content in overweight humans and obese mice. However, it remains unknown if H. alvei may also influence the gut digestive function. Thus, in the present study, the structural parameters of the intestine and the activity of digestive enzymes of the brush border enterocytes were analyzed in mice after they received a suspension of live H. alvei bacteria or their total protein extract for 16 days. Using electron microscopy, bacteria resembling H. alvei were found on the surface of microvilli of colonic enterocytes of mice treated with H. alvei suspension. In the group receiving H. alvei protein, there was a trend toward an increase in the number of mucus-producing goblet cells on the villi of the jejunum, and in both groups receiving H. alvei preparations, the number of intraepithelial lymphocytes on the villi of the ileum increased (in the group receiving H. alvei protein, there was a tendency towards an increase; in the group receiving H. alvei suspension, there was a significant increase). Treatment with both H. alvei preparations led to an increased activity of alkaline phosphatase in the chyme of the duodenum and jejunum and also in the jejunal mucosa, correlating negatively with visceral body fat content. The use of both H. alvei preparations had no significant effect on the activity of glucoamylase, maltase and aminopeptidase N in the intestinal mucosa. Thus, the 16-day administration of H. alvei bacteria or their protein extract increases the protective properties of the intestine, including the mucous barrier. Moreover, increased activity of alkaline phosphatase, a fat absorption-limiting enzyme, may contribute to the known anti-obesity effects of H. alvei. Taken together, H. alvei preparations display beneficial effects on gut health. Full article

Background/Objectives: The administration of medicines via enteral feeding tubes presents unique challenges, including dose loss, tube blockage, and user-dependent variability. Although Quality by Design (QbD) frameworks provide a structured approach to product quality, administration-related quality attributes are rarely assessed in a systematic manner during pharmaceutical development. A conceptual framework, termed the Quality Target Administration Profile (QTAP), was developed to extend QbD principles to the administration stage. Methods: The framework comprises three phases: administration context characterization, administration attribute identification, and risk-based determination of Critical Administration Attributes (CAAs). QTAP was applied to three representative EFT administration scenarios: a ready-to-use oral suspension, a crushed tablet, and an oral solution. Results: Application of the framework identified 18–32 administration attributes across the three representative scenarios and prioritized 5–6 CAAs per scenario according to clinical impact, variability risk, and human-factor considerations. Administration quality requirements varied across scenarios, reflecting differences in administration context, including dosage form, patient population, clinical setting, and user characteristics. QTAP provides a structured approach for identifying and prioritizing administration-related quality considerations within pharmaceutical development. Conclusions: As a conceptual framework, QTAP is intended to complement rather than replace existing QbD approaches. Future prospective validation, including human-factor studies and real-world evaluations, is needed to establish its practical utility and predictive value. Full article

Bisphosphonates (BPs) and Denosumab (DMB) are antiresorptive agents (AA) commonly used in treatment of osteoporosis, multiple myeloma (8.0%), breast cancer (3.3%), prostate cancer (2.9%) and other malignancies (0.7%), bone metastases, and cancer-induced hypercalcemia. However, this therapy is associated with a significant risk of medication-related osteonecrosis of the jaw (MRONJ), particularly after tooth extraction. The aim of this narrative review was to summarize current evidence on measures aimed to reduce the risk of MRONJ after tooth extraction, and to critically discuss the strength of evidence supporting each of these measures. Articles published in the years 2013–2025 were reviewed using PubMed, Scopus, Web of Science databases. Available studies were categorized and compared with the use of selected prevention methods. The duration of the treatment, route of administration, dosage and type of AA have a significant impact on the risk of developing MRONJ. Antibiotic prophylaxis is considered in most published preventive protocols. However, the evidence supporting a single optimal regimen is limited. Patients from a high-risk group of MRONJ, demonstrating cancer, who were administered intravenous antiresorptive agents for longer than three years or zoledronic acid, or those with a history of jawbone necrosis or inflammation require prolonged antibiotic therapy (started before the procedure and continued up to 14 days after the procedure). Moreover, studies on the use of platelet-rich fibrin (PRF) and Concentrated Growth Factors (CGF) as a preventive measure have shown promising results in observational studies, along with antibiotic prophylaxis and optimal oral hygiene. Pentoxifylline with tocopherol and low-level laser therapy (LLLT) are recognized as potentially useful non-invasive preventions. However, evidence is limited due to the small sample sizes and heterogenous protocols. Vitamin D levels should be monitored, and oral supplementation should be considered if needed. AA therapy suspension prior to the surgical procedure must always be consulted with the attending physician. A multidisciplinary approach along with well-planned pre- and postoperative care is essential for safe tooth extraction in patients receiving AA therapy. Full article

Escherichia coli (E. coli) infection in poultry triggers severe diarrhea and intestinal damage, ultimately disrupting gut function. Alanyl-glutamine (Aln-Gln) dipeptide not only exhibits potent gut-repairing efficacy but also restores barrier integrity and counters E. coli pathology through mucosal healing and immune modulation. In this study, the effects of Aln-Gln on microbiome modulation and intestinal integrity in growing hens challenged with E. coli were evaluated. The 250 healthy, Hy-line brown pullets (42 days old) were randomly divided into 5 experimental groups, each having five replicates of 10 chicks. Five dietary groups include a basal diet without added Aln-Gln and no E. coli challenge (NC), a basal diet without added Aln-Gln and orally administered 2.0 × 10⁴ CFU/mL E. coli suspension (C), a basal diet added 0.1% Aln-Gln and orally administered 2.0 × 10⁴ CFU/mL E. coli suspension (G1), a basal diet added 0.2% Aln-Gln and orally administered 2.0 × 10⁴ CFU/mL E. coli suspension (G2) and a basal diet added 0.3% Aln-Gln and orally administered 2.0 × 10⁴ CFU/mL E. coli suspension (G3). The results showed that dietary supplementation with 0.2% or 0.3% Aln-Gln effectively mitigated the adverse effects of an E. coli challenge, restoring body weight and feed intake to levels comparable to non-challenged controls. Aln-Gln supplementation (0.2–0.3%) reduced diarrhea severity, restored ileal morphology (villus height, crypt depth), improved antioxidant enzyme activity (GSH-Px, SOD), and reduced oxidative markers (MDA) (p < 0.05). Aln-Gln decreased pro-inflammatory (IL-1β, IL-6, NO) and apoptotic (BAX) responses (p < 0.05) and enhanced barrier integrity. It rebalanced gut microbiota by suppressing pathogenic Clostridium (75% in C vs. 29.9% in G3) and increasing beneficial Lactobacillus in G2/G3 compared with C. These findings demonstrate Aln-Gln as a beneficial dietary additive that restores growth performance and gut integrity; reduces diarrhea severity, inflammation, and apoptosis; and improves antioxidant status as it rebalances gut microbiota. Full article

Background/Objectives: Pericoronitis is a polymicrobial, biofilm-associated odontogenic infection; however, selected facultative Gram-positive bacteria may contribute to oral infectious persistence. This study compared the residual antibacterial activity of chlorhexidine (CHX), low-level laser therapy (LLLT), injectable platelet-rich fibrin (i-PRF), and amoxicillin-loaded i-PRF against selected oral and odontogenic bacterial strains. Methods: Standardized planktonic suspensions of Streptococcus mutans ATCC 25175, Staphylococcus aureus ATCC 25923, and Enterococcus faecalis ATCC 29212 were prepared at 0.5 McFarland turbidity. Five conditions were evaluated: 0.2% CHX, i-PRF, amoxicillin-loaded i-PRF, 976 nm diode LLLT, and 0.9% sodium chloride as the negative control. Twelve independent tubes were used for each treatment and species, yielding 180 experimental units. After a residual 24-h exposure/incubation period, samples were serially diluted, plated on 5% sheep blood agar, and quantified as CFU/mL. Data were analyzed using non-parametric tests. Results: Significant treatment-dependent differences were observed for all species (p < 0.001). CHX showed the most consistent antibacterial activity, with median residual counts of 550 CFU/mL for S. mutans, 1 CFU/mL for S. aureus, and 5.5 CFU/mL for E. faecalis. i-PRF alone was comparable to the negative control. Amoxicillin-loaded i-PRF markedly reduced S. aureus counts, whereas S. mutans and E. faecalis remained at high residual levels. LLLT showed partial, variable inhibition mainly against S. aureus. Conclusions: CHX demonstrated the most consistent antibacterial effect in this planktonic residual 24-h in vitro model. i-PRF alone showed no measurable antibacterial activity, while amoxicillin-loaded i-PRF and LLLT exhibited limited, species-dependent effects. Full article

Pulmonary drug delivery has become a vital route for both local and systemic treatments because of the unique structure and function of the respiratory system. Unlike oral and injectable dosage forms, inhalation offers a non-invasive, direct route to deliver medicines to the lungs, bypassing gastric degradation and first-pass hepatic metabolism. Common forms such as aerosols, solutions, suspensions, and dry powders are frequently used to treat respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). However, their effectiveness is often limited by physiological and biopharmaceutical barriers, such as mucociliary clearance, enzymatic degradation, and nonspecific deposition, which reduce drug retention and bioavailability. These issues are especially critical for poorly soluble or sensitive molecules, leading to lower drug concentrations at the target site and necessitating frequent dosing. To address these challenges, advanced nanoparticle-based delivery systems are being developed to improve drug stability, targeting, and controlled release within the lungs. At the same time, computational methods, including deposition modeling, physiologically based pharmacokinetic (PBPK) simulations, and AI-driven optimization, are increasingly used in formulation development to predict in vivo performance and boost translational success. This review covers the physiological and biological barriers to pulmonary drug delivery, explores major inhalation routes and dosage forms, and discusses new therapeutic strategies and nanoparticle platforms. It also highlights the growing role of in silico modeling and AI in accelerating the design and optimization of pulmonary treatments, while addressing current challenges, limitations, and regulatory issues in translating pulmonary nanomedicine into clinical practice. Full article

Salvia guaranitica A.St.-Hil. Ex Benth. (Lamiaceae) is native from South America, traditionally used for releasing tension and treating gastrointestinal cramps. It was evaluated for the presence of flavonoids and isoflavones in the extract, and the hypothesis of being cardioprotective under ischemia and reperfusion (I/R), antidiarrheal, antispasmodic and anxyolitic in respective models. For phytochemistry, GC-MS and HPLC-DAD methodologies were used. Cardiac performance after subchronic oral administration of S. guaranitica tincture (S.g-T, 0.95 mg extract/mL) was evaluated in rat isolated perfused hearts exposed to I/R, and mechanisms were characterized. Antispasmodic effects of S.g-T were evaluated on contractile concentration–response curves (CRCs) of carbachol (CCh) and calcium (Ca²⁺) in rat isolated intestinal tissue. In vivo tests of ricin-oil diarrhea models, open-field (OFT), novel-suppressed feeding (NFT) and tail suspension (TST) tests were performed on mice. Phenolic acids, genistin, luteolin, kaempferol and quercetin glycosides, genins, loliolide, dodecane, farnesene, phytol and isochiapin B were identified. Post-ischemic cardiac recovery was improved by S.g.-T, associated to activation of phosphatidylinositol-3-kinase and β-estrogenic receptor. S.g.-T also induced antispasmodic effects, as a non-competitive inhibitor of the CCh-CRC and Ca²⁺-CRC in the intestine. In vivo, S.g.-T showed antidiarrheal activity (95 mg extract/kg) and anxiolytic-like effects (0.95–9.5 mg extract/kg) without sedation or antidepressant-like effects. Therefore, S. guaranitica leaves have potential therapeutic cardioprotective, antidiarrheal, antispasmodic and anxiolytic effects. Full article

Oral infections are common health problems in companion animals, often associated with bacterial colonization, biofilm formation, and inflammation. This study investigates the efficacy of hypertonic salt tablets as an antibacterial approach and their effect on bacteria-associated inflammatory stimulation against important oral pathogens, Staphylococcus aureus and Pasteurella canis. Agar well diffusion showed that 0.3 g salt tablets exhibited antibacterial activity, with inhibition zones of 13.33 ± 0.89 mm for S. aureus and 28.75 ± 1.18 mm for P. canis, compared with 23.10 ± 0.87 mm and 31.43 ± 0.81 mm for 0.12% chlorhexidine, respectively. In vitro cytotoxicity assessment demonstrated that 1% v/v and 10% v/v released salt solutions maintained high cell viability (>80%), while morphology assays confirmed non-cytotoxicity of 1% v/v 24 h released salt solution. The 1% v/v and 10% v/v 10 min-released salt solution reduced relative biofilm formation in S. aureus to approximately 61% and 45%, respectively, and in P. canis to approximately 89% and 52%, respectively. Salt-treated bacterial suspensions induced lower NO production in RAW264.7 macrophages, decreasing NO levels from 33.17 ± 2.01 to 4.34 ± 0.65 µM for S. aureus and from 60.73 ± 0.99 to 36.33 ± 0.69 µM for P. canis, suggesting attenuation of bacteria-associated inflammatory stimulation. In a preliminary mouse oral mucosal wound model, local application of NaCl crystals for 30 min reduced total bacterial counts from 8.9 × 10² to 2.0 × 10² CFU/mL, corresponding to a 77.5% reduction. These findings suggest that hypertonic sodium chloride tablets may provide a simple localized approach for short-term reduction in oral bacterial burden and bacteria-associated inflammatory stimulation; however, further validation is required in clinically relevant oral disease models and companion animals. Full article

Essential oils are multicomponent natural products with potential neurobehavioral activity, but integrated comparative studies remain limited. This study compared the essential oils of Satureja brevicalyx, Peperomia dolabriformis, and Rosmarinus officinalis in relation to their chemical profiles, predicted target interactions, preliminary acute oral safety, anxiolytic-like and antidepressant-like effects, antagonist-sensitive behavioral patterns, and exploratory serum biomarkers. Oils were characterized by GC-MS, and their constituents were screened by molecular docking against anxiety-, depression-, sleep-, and stress-related targets. Independent cohorts of male BALB/c mice received oral essential oils (25–100 mg/kg) and were assessed in anxiety-related, depression-related, and locomotor behavioral paradigms, including the elevated plus maze, light–dark box, marble burying, tail suspension, forced swim, and open field tests. Flumazenil and WAY-100635 were used to examine whether the behavioral responses were sensitive to γ-aminobutyric acid type A (GABA-A)/benzodiazepine- and serotonin 1A (5-HT1A)-related pharmacological modulation, respectively. In a preliminary 24-h acute oral toxicity screen, no mortality was observed up to 5000 mg/kg. The three oils produced anxiolytic-like and antidepressant-like effects without reducing spontaneous locomotor activity. Within its experimental block, S. brevicalyx showed the most consistent flumazenil-sensitive anxiolytic-like pattern and FDR-significant reductions in corticosterone and TNF-α, together with increased IL-4. P. dolabriformis showed a broader predicted multitarget docking profile and antagonist-sensitive behavioral attenuation compatible with mixed pathway participation. R. officinalis produced significant but more moderate behavioral effects. WAY-100635 partially attenuated the antidepressant-like effects of all three oils. These findings support differentiated but convergent functional neurobehavioral profiles among the oils. The docking, antagonist, and biomarker results should be interpreted as hypothesis-generating evidence of possible pathway involvement, supporting further validation in chronic stress models, receptor-specific assays, pharmacokinetic studies, and expanded safety evaluations. Full article

Background/Objectives: Oral mucosal injury is a frequent complication in oncologic and surgical settings, significantly affecting patient quality of life. Zinc L-carnosine (ZnC) is a cytoprotective compound with anti-inflammatory, antioxidant, and epithelial reparative properties. This systematic review evaluated its protective and healing effects on oral mucosa. Methods: A systematic search followed PRISMA guidelines was conducted across PubMed, Scopus, Web of Science, and Cochrane Library (2015–2026). Randomized and non-randomized controlled studies assessing ZnC in patients with or at risk of oral mucosal injury were included. Risk of bias was evaluated using RoB 2 and ROBINS-I tools. Meta-analyses were conducted under both common- and random-effects models. The certainty of evidence was evaluated according to the GRADE guidelines. Results: Eight studies (n = 544) were included. Six non-randomized studies showed moderate or serious risk of bias, while randomized trials presented some concerns. ZnC was administered in different formulations, including mouthwashes, lozenges, and mucoadhesive suspensions based on sodium alginate, polyacrylic acid, and carboxyvinyl polymer, and across different clinical settings. Meta-analysis showed a reduced incidence of severe oral mucositis (grade ≥ 3) under the Common Effect model (OR 0.48; 95% CI 0.32–0.72), although statistical significance was not maintained under random-effects models (OR 0.44; 95% CI 0.18–1.06). Similar results were observed for grade ≥ 2 mucositis. According to the GRADE assessment, the certainty of evidence was low for oral mucositis outcomes and very low for oral mucosal healing. Only one study suggested improved surgical wound healing. No serious adverse events were reported. Conclusions: ZnC may support oral mucosal protection and healing, particularly in preventing oral mucositis. However, substantial heterogeneity and limited high-quality randomized evidence restrict the strength of conclusions. Further well-designed randomized trials are needed. Full article

Background/Objectives: Implant-associated infections are challenging conditions in orthopedic surgery. This experimental study aimed to evaluate phage localization within infected tissues following different routes of administration. Methods: An implant-related infection model was created using methicillin-resistant Staphylococcus aureus (MRSA) in twenty-four rats. Subjects were randomly divided into four groups depending on the bacteriophage administration route. Three rats were designated as the control group. Phage suspension was applied intraperitoneally, intravenously, orally and locally at 0.1 mL/day of 1 × 10⁸ PFU/mL suspension for three consecutive days. In the control group, intravenous, intraperitoneal and oral phage suspensions were administered separately at the same dose for 3 days. After completion of the experiment, tibia samples were taken in the experimental group. Additionally, liver, kidney, stomach, brain, heart muscle and striated muscle tissue samples were taken from the three subjects in the control group. Results: In the control group, unconfirmed phage-like structures were incidentally observed in some mitochondria of renal proximal tubular epithelial cells on transmission electron microscopy. In the experimental group, there was a strong positive linear relationship between the total number of bacteria and the number of bacteriophage clusters, independent of the groups. Conclusions: Bacteriophage clusters were detected in infected tibial tissues after all administration routes, suggesting phage localization at the infection site. Unexpected phage-like clusters were observed within mitochondria of proximal tubular epithelial cells in the control animals. This finding should be regarded as an unconfirmed incidental finding requiring further validation. Full article

Background/Objectives: The aim of this study was to investigate primary colonizers adhering to the oral biofilm on five adhesive restorative materials. Methods: For each material (Admira Fusion, Clearfil AP-X, Durafill VS, Filtek Supreme XTE, and Venus Diamond), sixteen test specimens were prepared according to a standardized protocol. For pellicle formation, the specimens were incubated for two hours at 37 °C with sterile-filtered inactivated human saliva. The bacteria (Streptococcus oralis (S. oralis), Streptococcus gordonii (S. gordonii), Streptococcus sanguinis (S. sanguinis), Streptococcus mitis (S. mitis), and Actinomyces naeslundii (A. naeslundii)) were cultivated and suspended. A bacteria mix was prepared from the suspensions. The specimens with pellicles were wetted with the bacterial mix and incubated at 37 °C for 8 h. The total genomic DNA of the adhered bacteria was isolated and subsequently quantified using SYBR Green qPCR. Results: For S. gordonii, S. oralis, and A. spp., no significant differences in the amount of adhered bacterial DNA were found between the different materials. S. mitis DNA concentration was significantly higher on Filtek Supreme XTE compared to the other materials. Significantly higher DNA concentrations of S. sanguinis could also be detected on Filtek Supreme XTE compared to Clearfil AP-AX and Durafill VS. Conclusions: The investigated restorative materials showed species-specific differences in bacterial adhesion, with Filtek Supreme XTE exhibiting higher adhesion of S. mitis and S. sanguinis, whereas no differences were observed for the other tested species. Full article

Background/Objectives: Ursodeoxycholic acid (UDCA) is a bile acid widely used for the treatment of cholestatic liver diseases; however, its poor aqueous solubility represents a major limitation for the development of oral liquid formulations, particularly in pediatric patients requiring accurate and flexible dosing. This study aimed to develop and characterize a fully solubilized extemporaneous UDCA oral formulation using the ready-to-use vehicle Wagner, with particular emphasis on the role of hydroxypropyl-β-cyclodextrin (HP-β-CD) as a solubilizing excipient. Methods: Phase-solubility studies, Job’s plot analysis, and ¹H NMR spectroscopy were performed to investigate the host–guest interaction between UDCA and HP-β-CD, confirming the formation of a stable 1:1 inclusion complex responsible for a marked increase in drug solubility. The aqueous solubility of UDCA increased from approximately 0.02 mg/mL in water to 31 ± 1 mg/mL in the Wagner base containing HP-β-CD, compared to ~10 mg/mL in the corresponding cyclodextrin-free vehicle. Chemical stability was evaluated using an HPLC method adapted from the European Pharmacopoeia, employing dual detection (refractive index and photodiode array detector) to ensure specificity and stability-indicating capability. Results: The UDCA solution (20 mg/mL) remained chemically stable for at least 4 months under refrigerated (4–8 °C) and room temperature (25 °C) conditions, with only moderate degradation observed at 40 °C. Physical stability studies confirmed the absence of precipitation, phase separation, or significant pH variations under all storage conditions. Conclusions: Wagner-based formulation enabled the development of a stable and homogeneous UDCA oral solution, providing a complementary formulation strategy to conventional suspension-based preparations. This approach represents a robust and patient-oriented strategy for extemporaneous compounding, particularly suitable for pediatric use. Full article

The oral cavity harbors a complex microbial community where pathogens implicated in dental caries and periodontitis can heavily colonize toothbrushes, transforming them into persistent sources of contamination that threaten both oral and systemic health. Consequently, this study evaluated the bactericidal efficacy of 275 nm ultraviolet light-emitting diode (UV-LED) irradiation against common oral bacteria in vitro and its practical utility for extraoral toothbrush sanitization. Suspensions of Streptococcus mutans, Streptococcus sanguinis, Porphyromonas gingivalis, and Fusobacterium nucleatum were irradiated for 3 min, 6 min, and 9 min. Bacterial growth and bactericidal effects were measured using growth curve and colony-forming unit assays, respectively. LIVE/DEAD staining and crystal violet staining were used to evaluate the bacterial viability and multispecies biofilm formation after irradiation. Additionally, the sanitization effects of a 275 nm UVC-based portable device on used toothbrushes were investigated. Direct UVC irradiation at 275 nm exhibited strong bactericidal effects against common oral bacteria in vitro. UVC irradiation also showed great sanitization effects on used toothbrushes. In summary, the vulnerability of common oral bacteria to 275 nm UVC, combined with its sanitizing efficacy on used toothbrushes, establishes a solid basis for extraoral sanitization, offering a reliable strategy to mitigate the risk of oral pathogen transmission from contaminated toothbrushes. Full article

Halitosis is caused by volatile sulfur compounds (VSCs) produced by periodontopathogens. The aim of this study is to examine the mechanism by which Ligilactobacillus salivarius WB21 inhibits halitosis. A susceptibility assay for Porphyromonas gingivalis was conducted using spent culture media (SCM) from L. salivarius WB21, and VSCs from the suspension of P. gingivalis were analyzed in the presence or absence of the SCM. After co-cultivating P. gingivalis and L. salivarius, P. gingivalis growth and VSC levels were measured using a spectrophotometer and a gas chromatograph, respectively. Additionally, levels of methyl mercaptan in the suspension and in the mgl gene of P. gingivalis were investigated. The SCM from L. salivarius WB21 significantly inhibited growth of P. gingivalis (p < 0.05) and significantly reduced emission of VSCs from the suspension of P. gingivalis (p < 0.05). When L. salivarius WB21 was present in a co-culture condition, P. gingivalis growth was significantly inhibited, and levels of methyl mercaptan in the culture medium were also reduced (p < 0.05). Finally, expression of the mgl gene of P. gingivalis was significantly reduced under co-cultivation with L. salivarius WB21 (p < 0.05). L. salivarius WB21 may inhibit colonization of periodontopathogens in the oral cavity and suppress production and emission of VSCs. Therefore, L. salivarius WB21 may be effective in treating halitosis when applied to the oral cavity. Full article