Search Results (7,685)

Recently developed quantitative structure–activity relationship (QSAR) prediction uses machine learning techniques with analytical signals from the full scan of mass spectra as input, and does not need exhaustive structural determination to assess unknown compounds. The QSAR approach assumes that a mass spectral pattern reflects the structure of a target chemical. However, the relationship between the spectrum and structure is complex, and requirement of its interpretation could restrict further development of QSAR prediction methods based on analytical signals. In this study, whether gas chromatography-electron-impact ionization-mass spectrometry (GC-EI-MS) data contain meaningful structural information that assists QSAR prediction was determined by comparing it with the traditional molecular descriptor used in QSAR prediction. Four molecular descriptors were used: ECFP6, topological descriptor in CDK, MACCS key, and PubChem fingerprint. The predictive performance of QSAR based on analytical and molecular descriptors was evaluated in terms of molecular weight, log K_o-w, boiling point, melting point, water solubility, and two oral toxicities in rats and mice. The influential variables were further investigated by comparing analytical-descriptor-based and linear regression models using simple indicators of the mass spectrum. The investigation indicated that the analytical and molecular descriptors preserved structural information differently. However, their performance was comparable. The analytical-descriptor-based approach predicted the physicochemical properties and toxicities of structurally unknown chemicals, which was beyond the scope of the molecular-descriptor-based approach. The QSAR approach based on analytical signals is valuable for evaluating unknown chemicals in many scenarios. Full article

Background: Angle’s dental class asymmetries not associated with crossbite are malocclusions that are often underestimated in pediatric patients. However, they may be associated with alterations in the development of the stomatognathic system. Objective: The objective of this study was to evaluate the prevalence of Angle’s class asymmetries without crossbite in primary-school-aged children and to investigate possible associations with perinatal, clinical, and functional variables. Materials and Methods: This cross-sectional observational study analyzed a sample of 391 children aged 6 to 11 years, attending a primary school in the metropolitan area of Milan, Italy. Data were systematically collected through both clinical examination and patient history, with the aim of identifying significant correlations with the occurrence of dental asymmetries in the absence of crossbite. Results. The results revealed a higher prevalence of occlusal asymmetries associated with factors such as oral breathing, low tongue posture, type of delivery, formula feeding, and systemic diseases during the first three years of life. Advanced carious lesions and inclination of the occlusal plane were significantly associated with asymmetry. Conclusions: The study highlights the importance of early diagnosis and a multidisciplinary approach to prevent malocclusions and complex craniofacial dysfunctions later in life. Full article

Dental caries remains one of the most prevalent chronic diseases worldwide, driven by complex interactions among dietary, hygienic, and biological factors. This study introduces a hybrid predictive framework that integrates mathematical modelling and artificial intelligence (AI) to estimate individual caries risk based on daily sugar intake, oral hygiene index, salivary pH, fluoride exposure, age, and sex. A first-order balance differential equation was applied to simulate demineralisation–remineralisation dynamics, while a feed-forward artificial neural network (ANN) was trained on simulated and literature-derived datasets. The hybrid model demonstrated strong predictive performance, achieving 91.2% accuracy and an AUC of 0.98 in classifying individuals into low-, moderate-, and high-risk categories. Sensitivity analysis identified sugar intake and oral hygiene as dominant determinants, while fluoride and salivary pH showed protective effects. These findings highlight the feasibility of combining mechanistic and data-driven approaches to enhance early risk assessment and support the development of intelligent, personalised screening tools in preventive dentistry. Full article

Background and Clinical Significance: Simultaneous, multiple infections coinfections caused by zoonotic or fecal-orally transmitted diseases are common in tropical and subtropical regions. Published data report that leptospirosis may coexist with other infections, complicating the clinical presentation and trajectory due to overlapping symptoms and leading to more severe clinical progress. Case Presentation: We describe a clinical case of a 34-year-old female diagnosed with a triple infection caused by Leptospira, Hepatitis A Virus, and Hepatitis E Virus. To our knowledge, this is the first case described in the literature in a non-endemic area without travel history to tropical or subtropical regions. The patient presented with one-week history of influenced clinical status, myalgia, headaches, nausea, high fever, bloody diarrheas, and abdominal pain. During the last two days, she also developed jaundice. Swimming in the rock pools of the island where she lives was indicated as the source of the infection. The laboratory tests revealed increased values of inflammatory markers, thrombocytopenia, and severe abnormalities of liver function. Serological and PCR tests for a wide range of pathogens proved an acute infection caused by Leptospira interogans, Hepatitis A virus, and Hepatitis E Virus. The patient received intravenous fluids and antibiotic treatment with ceftriaxone for seven days leading to gradual clinical improvement and normalization of liver function tests with subsequent reduction in jaundice within 30 days. Conclusions: This case report suggests that clinical suspicion and laboratory investigation should include the probability of coinfections even in non-endemic areas based on medical history of the patients. An early diagnosis of a zoonotic disease and other infective agents of acute hepatitis are vital in order to choose the appropriate treatment option and avoid severe complications. Full article

Kratom (Mitragyna speciosa (Korth.) Havil.) is a medicinal plant containing bioactive alkaloids, notably mitragynine and 7-hydroxymitragynine, which are psychoactive compounds with analgesic and stimulant properties. Due to safety concerns, the use of Kratom leaves and mitragynine in oral pharmaceutical products is restricted. Therefore, their potential as topical cosmeceutical agents merits further exploration. This study aimed to investigate the antioxidant and anti-adipogenic activities of Kratom ethanolic (Et-MS) and alkaloid-rich (Alk-MS) extracts, as well as purified mitragynine, to determine whether mitragynine is the major bioactive compound responsible for lipid reduction in 3T3-L1 adipocytes. The antioxidant properties were assessed using DPPH, ABTS, and FRAP assays, yielding EC₅₀ values of 0.06 mg/mL, 0.29 mg/mL, and 55 g Fe²⁺/100 g for Et-MS, respectively. In comparison, ascorbic acid (positive control) showed a DPPH EC₅₀ value of 0.002 mg/mL. Both Alk-MS and mitragynine significantly inhibited lipid accumulation in 3T3-L1 adipocytes by up to 50–70% at non-cytotoxic concentrations (≤25 µg/mL), as determined by Oil Red O staining. These findings provide preliminary in vitro evidence that phenolic constituents contribute to antioxidant capacity, while mitragynine is the principal anti-adipogenic constituent in Kratom extracts. Collectively, the results support the potential for further development of Kratom-derived extracts and mitragynine as plant-based candidates for topical or cosmeceutical applications targeting subcutaneous fat and oxidative skin damage. Full article

Background/Objectives: Grape seed oil (GSO) is a potent source of dietary phytochemicals, particularly polyphenols and flavonoids, known for their health-promoting properties. This study aims to investigate the anticancer and hepatoprotective effects of a nanoemulsion formulation of grape seed oil (GSONE), to enhance the efficacy and bioavailability of its phytochemical constituents against solid tumors. Methods: Ninety female Swiss albino mice were divided into six groups: control, alone, GSONE alone, Ehrlich solid tumor (EST), EST treated with GSO, and EST treated with GSONE. Tumor development, growth performance, serum biochemistry, antioxidant status, hepatic histopathology, apoptotic gene expression, and flow cytometry analyses were assessed following 30 days of daily oral treatment. Results: GSONE significantly reduced tumor weight and volume (52.9%) and more effectively counteracted tumor-induced body weight loss than crude GSO. Treatment with GSONE normalized serum protein levels and improved liver function markers (AST, ALT, ALP, total bilirubin) to near-control values. Tumor markers (AFP, CEA) and oxidative stress indices (MDA, 8-OHdG) were markedly decreased, while activities of hepatic antioxidants (SOD, CAT, GPx, GSH) were restored. GSONE enhanced gene expression of pro-apoptotic markers (Bax, TP53, caspase-3, caspase-9), suppressed anti-apoptotic Bcl-2, and significantly increased the proportion of p53- and cleaved caspase-3-positive tumor cells. Liver histopathology and ultrastructure demonstrated normalized morphology and reduced damage in GSONE-treated mice. Multivariate analyses confirmed GSONE’s restorative effect compared to raw GSO. Conclusions: The delivery of dietary phytochemicals via nanoemulsion significantly enhances antitumor and hepatoprotective actions in a preclinical solid tumor model. These findings support the potential of phytochemical-rich edible oils, enhanced by nanotechnology, for dietary prevention and adjunctive management of cancer. Full article

This study emphasizes overcoming the challenges of targeted drug delivery in colon cancer therapy by developing gastrointestinal (GI) stable, pectin-coated nanoliposomes for the oral delivery of Apigenin-Cyclodextrin Complex as an in situ gel formation. Initially, the formulation was strategically designed using design expert software for formulation optimization. FTIR and XRD studies were conducted to ensure physical compatibility and to confirm the encapsulation of apigenin within the formulation. In process optimization, among all seventeen formulations run tested, PNL (Api-Cy)-13 was identified for the highest drug loading, favourable size dimension of particle with zeta potential, and spherical external morphology through SEM analysis. The metered drug release during an in vitro study for PNL (Api-Cy)-13 was remarkably high (more than 75% of drug availability in the colonic environment, precisely in contrast to only 20% in the gastric phase in a sustained release manner), focused on colon drug targeting as an in situ gel. Furthermore, apigenin release from PNL (Api-Cy)-13 in an ex vivo chick ileum permeability study was observed both in the absence and presence of 1% vancomycin. An incremental apigenin release in the absence of the antibiotic (1% vancomycin) indicated gut microbial-associated and pectinase-mediated drug release. Here, pectin degradation materializes by the colonic microbial environment, which facilitates desirable incremental colonic drug permeation. Finally, an in vitro MTT assay and a competitive flowcytometric cell uptake study with PNL (Api-Cy)-13 using HCT-116 cells proved significant superiority in cytotoxicity profile for apigenin when delivered as an optimized coated nanoliposome in comparison to free apigenin or other non-modified nano-formulation. Also, the inhibition of the cell efflux process was validated by Multidrug Resistance 1 (MDR1) gene regulation. These observations establish an undoubted promise for the novel biopolymer, pectin-based apigenin-cyclodextrin nanoliposomes as targeted therapy in colon cancer with significant in vivo pharmacokinetics and safety profile. Full article

Objective: This study aimed to explore the direct relationships between social determinants and behavioral clusters, as well as their potential indirect associations mediated by edentulism. Methods: Information on social variables (collected in Wave 3, 2006/07), edentulism (Wave 5, 2010/11), and health-related behaviors (Wave 7, 2014/15) was drawn from the English Longitudinal Study of Ageing (ELSA). Baseline sociodemographic characteristics, including age, gender, ethnicity, education, and wealth, were accounted for. Latent class analysis (LCA) was applied to four behavioral indicators—smoking status, alcohol consumption, fruit and vegetable intake, and physical activity—to identify behavioral clusters. A confirmatory factor analysis (CFA) was then used to construct a latent variable representing social support and social networks. Two structural equation models (SEM) were developed to examine both the direct associations between social support/network and behavioral clusters, and the indirect associations mediated by edentulism. Results: In LCA, the two-class model was the best fit for the data. Class 1 (risky behaviors) had 7%, while Class 2 (healthy behaviors) had 93%. In SEM Model 1, higher social support/network levels predicted being in the healthy cluster directly (SC = 0.147) and indirectly (SC = 0.009). In Model 2, accounting for wealth and education, higher levels of social support/network maintained the direct association with the healthy cluster (SC = 0.132), but the indirect path lost significance. Conclusions: This study found that greater social support was associated with healthier behaviors, and this relationship may be mediated by edentulism. Health policies that encourage social interaction could therefore improve both general and oral health. Full article

Obesity, a major risk factor for cardiometabolic diseases, arises from chronic energy imbalance and ectopic lipid deposition. This study investigated the anti-obesity potential of Coral dealbatus crude polysaccharides (CDP), a previously uncharacterized bioactive fraction from a hybrid vegetable cultivar developed by the Chinese Academy of Agricultural Sciences. CDP, obtained via hydroalcoholic extraction, was structurally characterized as amorphous with heterogeneous molecular weights (87,813 Da, 4158 Da, and 728 Da) and glucose-dominant monosaccharide composition (FT-IR, XRD, and HPLC). In a high-fat diet (HFD)-induced murine obesity model, oral CDP administration significantly attenuated body weight gain (p < 0.05) and reduced ectopic lipid deposition. Histopathological analysis confirmed CDP’s efficacy in ameliorating hepatic steatosis, evidenced by diminished lipid droplet accumulation. Furthermore, CDP reversed HFD-induced gut microbiota dysbiosis, modulating beneficial bacterial taxa. These findings demonstrate CDP’s therapeutic potential against diet-induced metabolic disorders, likely mediated through lipid metabolism regulation and intestinal microbiota modulation, supporting its development as a novel functional food ingredient for dietary intervention. Full article

Background/Objectives: Paediatric patients continue to lack access to age-appropriate oral medicines for their treatment and have to depend on the off-label use of medicines approved for adults, which compromises dosing accuracy and exposes children to unpleasant bitterness. Building on previous proof-of-concept work with flucloxacillin sodium, this study investigated the effects of fatty-acid chain length on the formation, stability, dissolution, and sensory acceptability of diclofenac sodium (DS)–Eudragit® EPO (EE)–fatty acid (FA) polyelectrolyte complexes (PECs). Four saturated fatty acids, lauric (C12), myristic (C14), palmitic (C16), and stearic acid (C18), were evaluated at stoichiometric equimolar DS:EE:FA ratio (1:1:1). Methods: PEC microparticles were prepared by solvent evaporation. A stability-indicating RP-HPLC assay was developed and validated according to ICH guidelines to quantify DS content. Drug content and stability were monitored over 3 months at ambient storage. In vitro dissolution was performed in pH 5.5 medium at 37 °C. Taste acceptability and willingness to take again was assessed with 25 healthy adult volunteers using 11-point scale. Results: All PECs retained >90% of expected drug content after 3 months. Compared with neat DS, PECs markedly suppressed early drug release (32–39% vs. 94% at 2 min) but achieved >87% cumulative drug release in 60 min. Sensory evaluation showed significant differences across samples (p < 0.001): neat DS was least acceptable (20.8% willing to take again), while DS-EE-PA was most acceptable (92%), followed by DS-EE-SA and DS-EE-MA. DS-EE-LA was least favoured among PECs. Conclusions: Fatty-acid chain length influenced PEC formation and taste acceptability, but not the PEC stability and drug dissolution profile. Palmitic acid (DS-EE-PA) offered the best overall profile and represents a promising candidate for further development of paediatric-appropriate diclofenac formulations. 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

Digital twins (DTs), virtual replicas that integrate mechanistic modeling with real-time clinical data, are emerging as powerful tools in healthcare with particular promise in pediatrics, where age-dependent physiology and ethical considerations complicate infectious disease management. This narrative review examines current and potential applications of DTs across antimicrobial stewardship (AMS), diagnostics, vaccine personalization, respiratory support, and system-level preparedness. Evidence indicates that DTs can optimize antimicrobial therapy by simulating pharmacokinetics and pharmacodynamics to support individualized dosing, enable Bayesian therapeutic drug monitoring, and facilitate timely de-escalation. They also help guide intravenous-to-oral switches and treatment durations by integrating host-response markers and microbiological data, reducing unnecessary antibiotic exposure. Diagnostic applications include simulating host–pathogen interactions to improve accuracy, forecasting clinical deterioration to aid in early sepsis recognition, and differentiating between viral and bacterial illness. Immune DTs hold potential for tailoring vaccination schedules and prophylaxis to a child’s unique immune profile, while hospital- and system-level DTs can simulate outbreaks, optimize patient flow, and strengthen surge preparedness. Despite these advances, implementation in routine pediatric care remains limited by challenges such as scarce pediatric datasets, fragmented data infrastructures, complex developmental physiology, ethical concerns, and uncertain regulatory frameworks. Addressing these barriers will require prospective validation, interoperable data systems, and equitable design to ensure fairness and inclusivity. If developed responsibly, DTs could redefine pediatric infectious disease management by shifting practice from reactive and population-based toward proactive, predictive, and personalized care, ultimately improving outcomes while supporting AMS and health system resilience. 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

Sapindus mukorrosi (Sm) seeds have been used in Chinese medicine for treating gingival disease, suggesting that Sm may modulate oral bacteria and alleviate gingival inflammation. However, the hydrophobicity of seed oil limits its use in the aqueous oral environment. Therefore, the artificial saliva-infused Sm seed aqueous extract (SMa) was developed and applied to our ex vivo model to test its anti-bacterial effect. Unstimulated whole saliva from seven patients with Stage III/IV, Grade C periodontitis was cultured for 8 h with or without SMa. The bacterial count was measured based on the optical density and bacterial DNA concentration. The salivary microbiome was sequenced via next-generation sequencing over the 16S rRNA gene V3-V4 hypervariable regions. The bacterial DNA concentration in the SMa group was significantly lower than the Without-SMa group after 6 to 8 h of culture. No significant difference in alpha and beta diversity was observed between the two groups. The relative abundance of Porphyromonas was reduced, while that of Veillonella was elevated in the SMa group compared to the Without-SMa group. The findings indicated that the antibacterial effects of SMa are manifested primarily through bacterial growth inhibition, with the minor modulation of specific taxa. Full article

Background/Objectives: Children with autism spectrum disorder (ASD) frequently experience poor compliance with oral medication due to bitterness, unpleasant taste, and unsuitable dosage forms such as large tablets or capsules. Risperidone, a widely prescribed antipsychotic for managing ASD symptoms, is particularly challenging in this regard. The present study aimed to develop a novel sucrose-based microfiber drug delivery system to improve the palatability, acceptance, and bioavailability of risperidone in pediatric patients with ASD. Methods: Risperidone was incorporated into sucrose microfibers using centrifugal spinning technology. Fiber morphology was characterized by scanning electron microscopy (SEM). Drug loading (DL), encapsulation efficiency (EE%), and disintegration time were measured. In vitro drug release and cytotoxicity assays were performed using human foreskin fibroblast cells (HFF-1). An in vivo palatability and preference study was conducted in male BALB/c mice to evaluate the acceptability of the formulation compared with a commercial risperidone oral solution. Results: SEM analysis revealed smooth, bead-free, non-porous fibers with uniform morphology and size distribution. The formulation showed a rapid disintegration time of ~3 s, DL of 30 ± 5 µg/mg, and EE% of 60 ± 10%. Approximately 50% of risperidone was released within 15 min. Cytotoxicity testing confirmed that concentrations ≤ 125 µg/mL maintained high cell metabolic activity, indicating biocompatibility. In vivo, the microfiber solution demonstrated a strong preference (93%) compared with the commercial oral solution (30%). Conclusions: Risperidone-loaded sucrose microfibers represent a promising fast-dissolving oral delivery system for children with ASD. This child-friendly formulation improves palatability and compliance while maintaining safety and drug release performance. Full article