Search Results (3,370)

Antioxidants are essential bioactive compounds widely recognized for their health benefits in preventing oxidative stress-related diseases. However, many lipophilic antioxidants suffer from poor aqueous solubility, low chemical stability, and limited bioavailability, restricting their application in food, nutraceutical, and pharmaceutical industries. Cyclodextrins (CDs), a class of cyclic oligosaccharides with a hydrophilic exterior and lipophilic interior, present an effective strategy to encapsulate and deliver these compounds by improving their solubility, stability, and therapeutic efficacy. This review critically examines the structural features and derivatives of cyclodextrins relevant for antioxidant encapsulation, mechanisms and thermodynamics of inclusion complex formation, and advanced characterization techniques. It evaluates the influence of CD encapsulation on the oral bioavailability and antioxidant activity of various lipophilic antioxidants supported by recent in vitro and in vivo studies. Moreover, sustainable preparation methods for CD complexes are discussed alongside safety and regulatory considerations. The comprehensive synthesis of current knowledge contributes to guiding the rational design and development of CD-based antioxidant nutraceuticals, addressing formulation challenges while promoting efficacy and consumer safety. Full article

Background: Amiodarone is a widely used class III antiarrhythmic agent, but its use can lead to peripheral neuropathy mediated by mitochondrial dysfunction, oxidative stress, and neuroinflammatory injury, while effective preventive options remain limited. Agents that support mitochondrial energy metabolism, sustain redox balance, and modulate inflammation, including adenosine triphosphate (ATP), melatonin, and thiamine pyrophosphate (TPP), may counteract these mechanisms; however, their relative neuroprotective potential in amiodarone-induced neuropathy remains unclear. This study aimed to comparatively evaluate the effects of ATP, melatonin, and TPP on amiodarone-induced peripheral neuropathy and neuropathic pain in rats. Methods: Thirty male albino Wistar rats were assigned to five groups: healthy; amiodarone (50 mg/kg/orally); amiodarone + ATP (5 mg/kg/intraperitoneally); amiodarone + melatonin (10 mg/kg/orally); or amiodarone + TPP (20 mg/kg/intraperitoneally). Treatments were given once daily for 14 days. Oxidative stress indices (malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT)) and proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1 Beta (IL-1β), interleukin-6 (IL-6)) were quantified in sciatic nerve by Enzyme-Linked Immunosorbent Assay (ELISA). Paw withdrawal thresholds were measured with the Randall-Selitto test before and after treatment. Histopathology was performed using Hematoxylin-eosin staining. Results: Amiodarone exposure resulted in pronounced elevations in MDA and proinflammatory cytokine levels, accompanied by significant reductions in tGSH, SOD, CAT activities, and paw withdrawal thresholds. ATP, melatonin and TPP ameliorated these alterations to varying degrees. Among them, TPP provided the most robust antioxidant and anti-inflammatory effects, followed by ATP and melatonin. Histopathological examination confirmed most severe axonal degeneration, interstitial edema and Schwann cell proliferation in the amiodarone group, with substantial amelioration in the TPP-treated rats. Conclusions: Amiodarone induces neuropathic pain through oxidative and inflammatory injury to peripheral nerves. TPP exhibited superior neuroprotective efficacy compared with ATP and melatonin, highlighting its potential as a candidate therapeutic agent for amiodarone-related neuropathy. Further clinical research is warranted to support translational application of these findings. Full article

This pilot study investigates the relationship between stress situations and speech fluency in virtual reality environments. It aims to analyze how different stress scenarios, classified into low-, medium-, and high-stress environments, can affect speech rate, increase syllable/word repetitions, and lead to hesitations in university students. Previous research has established connections between stress situations and speech fluency, highlighting that stress can negatively influence behavior, cognitive processes, and communicative performance across various contexts, including oral presentations. An experiment was conducted with 30 participants randomly divided into three groups. Each group was exposed to different virtual stress environments (low/medium/high) during simulated oral presentations. A virtual reality platform was created to establish controlled environments and monitor the participants’ fluency in real time. An Analysis of Variance (ANOVA) test revealed that participants in the low-stress virtual environment performed better, achieving higher word and syllable production. In contrast, the high-stress virtual environment demonstrated an increase in disfluencies and hesitations. Results emphasize the impact of stress situations on oral communication, advocating for the use of virtual reality technology as a means of preparing individuals for challenging speaking scenarios. This approach has the potential to enhance speech fluency as a result of targeted practice in stress-inducing environments; that is to say, alleviating anxiety and improving overall communicative efficacy. Full article

Background/Objectives: As antimicrobial dental treatments, based on chemical products, long tested for their efficacy, have been lately associated with developing antimicrobial resistance, there is a growing interest to identify and develop efficient alternatives. The aim of this paper is to assess the antimicrobial potential of eight selected essential oils (EOs): Cinnamon (Cinnamomum verum), Tea tree (Melaleuca alternifolia), Spearmint (Mentha spicata), Rosemary (Rosmarinus officinalis), Clove (Eugenia caryophyllata), Eucalyptus (Eucalyptus radiata), Cedarwood (Juniperus virginiana), and Lemongrass (Cymbopogon flexuosus), more or less recognized and investigated for this particular therapeutic effect, on Streptococcus mutans (S. mutans), a key pathogen involved in oral pathology. Materials and methods: The chemical constituents of the EOs were identified and quantified by Gas Chromatography-Mass Spectrometry (CG-MS) method. Saliva samples, collected from nine patients with active dental caries, were tested in vitro. To assess the bacterial susceptibility of the selected EOs against S. mutans, the inhibition zones (IZ), minimum inhibitory concentrations (MIC), and minimum bactericidal concentrations (MBC) were determined. Results: All EOs tested showed antimicrobial activity against S. mutans, with IZs over 20 mm. The highest antimicrobial efficacy was observed for spearmint, followed by Eucalyptus, Tea tree, and Lemongrass. The next in descending order were Cinnamon Bark, Clove, Rosemary, and Cedarwood. Considering the mean MIC and MBC values, the spearmint EO proved to be the most effective in inhibiting the growth of S. mutans, as well as in annihilating it, followed by the Eucalyptus EO, Tea tree EO and Lemongrass EO. The less effective were determined to be Cinnamon, Clove, Rosemary and Cedarwood EOs. Conclusions: The eight selected EOs demonstrated antimicrobial activity against S. mutans, with Spearmint and Eucalyptus showing the most significant effects, advocating for their potential in dental caries prevention and treatment, and their potential role in oral hygiene applications. Full article

Pediatric drug delivery presents unique challenges due to physiological and pharmacological differences across age groups, requiring specialized formulation approaches beyond simple dose adjustments of adult medications. This review synthesizes recent advances in polysaccharide-based pediatric drug delivery and highlights novel findings that may accelerate clinical translation. It summarizes how chitosan, alginate, hyaluronic acid, dextran, modified starches, and other polysaccharides are engineered into nanoparticles, hydrogels, films, and orodispersible/mini-tablet formulations to improve stability, bioavailability, taste masking, and controlled release across neonates to adolescents. These systems can accommodate developmental variations in absorption, distribution, metabolism, and excretion processes across pediatric subpopulations, with particular emphasis on oral and alternative administration routes. Evidence supporting unexpectedly high acceptability of mini-tablets, successful integration of modified polysaccharides in 3D-printed personalized low-dose therapies, and the emergence of blood–brain barrier-penetrating and RGD-functionalized polysaccharide nanocarriers for pediatric oncology are emphasized as novel, clinically relevant trends. This review also addresses regulatory considerations, safety profiles, and future perspectives. By integrating developmental insights with innovative formulation strategies, polysaccharide polymers offer promising solutions to improve medication adherence, safety, and efficacy across the pediatric age spectrum. Full article

Periodontitis is a multifactorial disease that is primarily driven by bacterial biofilm and oral dysbiosis. Listerine^® is a widely used essential-oil-based mouthwash that is well established for its safety and anti-plaque efficacy. However, limited evidence exists regarding its impact on oral microbial composition or its potential effects on gut microbiota. This pilot study aimed to investigate changes in subgingival microbiota and periodontal indices after Listerine^® use and to explore modulation of the gut microbiota. Twelve healthy adults were enrolled, and oral plaque and stool samples were collected at baseline and after a 28-day treatment period. Microbial profiling was performed using next-generation sequencing (NGS) to assess shifts in oral and gut microbiota. The α-diversity and β-diversity indices were computed, and differential abundance analyses were conducted to identify taxa modulated by treatment. NGS-based profiling revealed that oral microbial α-diversity and β-diversity remained stable. Several oral taxa were significantly modulated, including reductions in Gemella haemolysans, Streptococcus oralis and Granulicatella sp., along with increases in Actinomyces viscosus. In the gut microbiota, a modest trend toward reduced Shannon and Simpson diversity indices was observed. Taxonomic shifts included enrichment of the Bacteroides, Phocaeicola and Alistipes species, and decreases in Lachnospiraceae, Intestinibacter sp. and Blautia luti. Despite the limited cohort size and short observation period, these findings suggest that essential-oil-based mouthwash use can transiently modulate both oral and intestinal microbial ecosystems. Full article

Cannabidiol (CBD) has transitioned from anecdotal use to an evidence-based adjunctive therapy for Lennox–Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This review integrates knowledge on CBD’s pharmacology, pharmacokinetics, and clinical implementation, with focus on metabolism, therapeutic drug monitoring (TDM), and clinically relevant interactions with antiseizure medications. CBD exerts CB1/CB2-independent mechanisms—prominently GPR55 antagonism, TRP-channel desensitization, and adenosine-mediated network dampening—supporting efficacy across heterogeneous seizure phenotypes. Its pharmacokinetic profile is characterized by low and variable oral bioavailability, a pronounced food effect, extensive tissue distribution, and phase I/II biotransformation to the active 7-hydroxy-CBD and abundant 7-carboxy-CBD, resulting in substantial inter-individual variability and liability for drug–drug interactions. Clinically salient interactions include CYP2C19-mediated elevation of N-desmethylclobazam and increased transaminases in valproate co-therapy. We summarize emerging TDM practices—standardized fed-state trough sampling with paired measurement of CBD and 7-hydroxy-CBD—and discuss how preliminary interpretive ranges can support dose optimization, adherence assessment, and safety surveillance. Practical recommendations emphasize interaction-aware titration within evidence-based dose bands, liver function monitoring, and standardized documentation of formulation and sampling conditions. Future work should align pharmacogenomics with TDM, refine bioavailability through advanced delivery systems, and tighten analytical and product-quality standards to consolidate CBD as a precision-ready component of modern epilepsy care. Full article

Background/Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can naturally infect a broad spectrum of animal species, with cats, minks, and ferrets being highly susceptible. There is a potential risk that infected animals could transmit viruses to humans. Moreover, SARS-CoV-2 continues to evolve via mutation and genetic recombination, resulting in the continuous emergence of new variants that have triggered a wave of reinfection. Therefore, safe and effective corona virus disease 2019 (COVID-19) vaccines for animals are still being sought. Methods: We generated three recombinant Modified vaccinia virus Ankara (MVAs) expressing the prefusion-stabilized S proteins, S6P, DS6P, and BA2S6P, targeting the full-length S protein genes of the ancestral, Delta, and Omicron BA.2 strains of SARS-CoV-2. Subsequently, the safety, immunogenicity, and protective efficacy of these MVA-based oral COVID-19 vaccine candidates were assessed in mice, minks, and cats. Results: These recombinant MVAs are safe in mice, minks, and cats. Oral or intramuscular vaccination with rMVA-S6P induced a robust SARS-CoV-2 neutralizing antibody (NA) response and conferred complete protection against the SARS-CoV-2 challenge in mice. Meanwhile, oral or intramuscular administration of these recombinant MVAs in combination induced a potent and durable NA response against homotypic SARS-CoV-2 pseudovirus in mice, minks, and cats, respectively. Conclusions: These findings suggest that the MVA-vectored vaccines are promising oral COVID-19 vaccine candidates for animals, and that the combined vaccination approach is an effective administration strategy for such vaccines. Full article

(1) Background: Whether anticoagulation can be resumed in atrial fibrillation (AF) combined with intracranial hemorrhage (ICH), and which anticoagulation modality is used with better efficacy and safety, is unknown. (2) Method: Randomized controlled trials (RCTs) and observational studies on relevant topics were included by searching five databases: PubMed, EMBASE, EBSCO, Cochrane Central Register of Controlled Trial and ClinicalTrials. Bayesian network meta-analysis was performed to analyze the effect of oral anticoagulant (OAC), new oral anticoagulant (NOAC), warfarin, antiplatelet, left atrial appendage occlusion (LAAO) and no therapy in patients with AF after intracranial hemorrhage. (3) Results: We included 16 studies involving 25,483 patients. Compared with no antithrombotic therapy, the risk of thromboembolism and all-cause mortality were both reduced with OAC (OR: 0.38, 95% CI: 0.21–0.67; OR: 0.45, 95% CI: 0.25–0.8) and LAAO (OR: 0.11, 95% CI: 0.01–0.76; OR: 0.11, 95% CI: 0.01–0.88), and there was no increased risk of recurrent intracranial hemorrhage. Regarding thromboembolism, OAC (OR: 0.28, 95% CI: 0.11–0.69) was superior to antiplatelet therapy, and antiplatelet therapy (OR: 12.59, 95% CI: 1.57–133.50) was associated with a higher risk of thromboembolism than LAAO. There were no significant differences in recurrent intracranial hemorrhage between the interventions. LAAO appeared to be the best option for reducing thromboembolism (SUCRA: 0.96), recurrent intracranial hemorrhage (SUCRA: 0.75) and all-cause mortality (SUCRA: 0.94). (4) Conclusions: Based on this network meta-analysis, we hypothesize that LAAO has the highest likelihood of reducing the risk of thromboembolism and recurrent intracranial hemorrhage, as well as all-cause mortality in patients with AF after intracranial hemorrhage, followed by OAC. Full article

Background: This study aimed to evaluate the efficacy and safety of off-label use of non-vitamin K antagonist oral anticoagulants (NOACs) compared with antiplatelet therapy (APT) in patients with AF-related acute ischemic stroke (AIS) and a glomerular filtration rate (GFR) below 15 mL/min/1.73 m². Methods: We used a multicenter prospective stroke registry to identify patients with AF-related AIS and GFR < 15 mL/min/1.73 m² who were treated with either APT alone or NOAC alone at discharge. Primary outcomes were ischemic stroke recurrence, major bleeding, and all-cause mortality within one year. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression. Results: Among 311 eligible patients, 135 (43.4%) received APT and 176 (56.6%) received low-dose NOACs. Compared to APT, NOAC use was associated with a significantly lower risk of ischemic stroke recurrence (aHR 0.54, 95% CI 0.29–0.99) but higher risks of major bleeding (aHR 3.25, 95% CI 1.84–5.73) and all-cause mortality (aHR 2.65, 95% CI 1.60–4.38). The most common causes of death were non-vascular events such as sepsis and respiratory failure. Conclusions: In patients with AF-related stroke and ultra-low GFR, off-label use of NOACs may offer a benefit in stroke prevention but is associated with increased risks of bleeding and mortality. These findings suggest the need for individualized treatment strategies and careful monitoring when prescribing NOACs in this vulnerable population. Full article

Background/Objectives: Pulmonary fibrosis (PF) is a progressive interstitial lung disease with limited therapeutic options. Lepidium sativum (cress seeds) possess recognized antioxidant and anti-inflammatory properties, yet its potential antifibrotic activity has not been investigated. This study evaluated the phytochemical composition and antifibrotic efficacy of cress seed extract (CSE) and examined whether its effects are associated with modulation of the ncNRFR/let-7d pathway in methotrexate (Mtx)-induced PF. Methods: Comprehensive metabolite profiling was performed using GC–MS, HPLC, and UPLC–T-TOF–MS/MS. Antioxidant capacity and antiproliferative effects were assessed in vitro. Network pharmacology was used to identify CSE-related PF targets and regulatory pathways. In vivo, PF was induced in adult male Wistar rats by Mtx, followed by oral CSE administration (50–150 mg/kg). Biochemical markers of inflammation, oxidative stress, extracellular matrix deposition, EMT, and ncRNA expression (ncNRFR and let-7d) were quantified alongside histopathology and immunohistochemistry. Results: CSE contained diverse terpenes, phenolics, flavonoids, glucosinolates, and amino acid derivatives. It exhibited potent antioxidant activity and antiproliferative effects against A549 and Hep2 lung cancer cells. Network analysis identified 997 overlapping CSE–PF targets and highlighted IL6 and MMP1 as relevant miR-let-7d–associated nodes. In vivo, Mtx-induced marked fibrosis characterized by increased ncNRFR, reduced let-7d, elevated IL6, HMGB1, TGF-β, MMP1, collagen, and hydroxyproline, and reduced antioxidant enzyme activity. CSE treatment dose-dependently mitigated these alterations, improved histoarchitecture, and reduced collagen deposition. Conclusions: CSE showed antifibrotic, antioxidant, and anti-inflammatory activity in MTX-induced PF in rats and modulated the reciprocal expression patterns of ncNRFR and let-7d. These findings support CSE as a potential source of bioactive constituents for PF management and identify the putative ncNRFR–let-7d regulatory relationship as a novel pathway in fibrotic lung disease, warranting further mechanistic investigation. Full article

Microneedle array-based drug delivery offers a minimally invasive and safe approach for breaching the skin barrier, enabling localized and targeted treatment—an advantage particularly valuable in chronic condition management, such as rheumatoid arthritis (RA). RA presents a multifaceted pathophysiology, often necessitating long-term pharmacological management. However, conventional oral administration may lead to systemic drug distribution, increasing the likelihood of adverse effects, and ultimately undermining therapeutic efficacy. In this study, a hollow microneedle array was employed for effective delivery of Tofacitinib and the antioxidant N-acetylcysteine (NAC). A comprehensive evaluation was conducted across multiple levels, in which inflammation and cartilage degradation were assessed histologically using hematoxylin-eosin (H&E) and Safranin O–Fast Green staining. Radiologically, micro-computed tomography (micro-CT) was employed to visualize bone structure alterations. On the molecular level, enzyme-linked immunosorbent assay (ELISA) was used to quantify inflammatory cytokines and oxidative stress markers. Furthermore, differentially expressed genes and enriched signaling pathways were identified through transcriptomic profiling pre- and post-treatment. And the potential regulatory targets and mechanistic insights into the therapeutic response were elucidated through correlation analyses between gene expression profiles and pathological indicators. This study provides a mechanistic and computational basis for precision targeted therapy, validates the efficacy and safety of microneedle delivery in a rheumatoid arthritis (RA) model, and demonstrates its potential application in local drug delivery strategies. Full article

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment. Full article

Background: Acne vulgaris is a multifactorial disease with significant clinical and psychosocial impacts. Methods: The purpose of this study was to evaluate the efficacy of a combination therapy including oral isotretinoin and a non-ablative 675 nm red-light laser compared with laser monotherapy. Thirteen young patients with active facial acne of varying severity were enrolled and divided into two groups: Seven subjects received laser monotherapy treatment (RT group), while six underwent combined laser and isotretinoin therapy (RTI group). The laser protocol consisted of six weekly sessions, with a 5-point pain scale used to monitor tolerability. Standardized photographs were obtained at baseline and at a 3-month follow-up after the last treatment. Each patient completed the Acne Radar Questionnaire, and lesion severity was assessed using the Global Evaluation Acne (GEA) scale. Results: All patients completed the study without adverse events. Scores from the Acne Radar Questionnaire improved in both groups, while the GEA scale demonstrated a significant reduction in lesion severity, confirmed by photographic comparison. Pain was reported as mild in most cases, and no discontinuations occurred. Conclusions: These findings indicate that the 675 nm laser is a safe and effective therapeutic option for acne vulgaris, with isotretinoin addition resulting in more rapid and pronounced clinical improvement. Full article

Introduction/Objective: Dental extractions are among the most common oral surgical procedures worldwide, with postoperative pain representing a significant clinical concern. Cannabidiol (CBD), a non-intoxicating phytocannabinoid with analgesic and anti-inflammatory properties, has recently gained attention as a potential adjunct for managing acute dental pain. To explore its clinical utility to generate preliminary feasibility, we conducted the Simple Tooth Extraction with Analgesic Phytocannabinoid (SWAP) pilot trial to evaluate the preliminary efficacy and safety of oral CBD at two concentrations (17 mg/mL and 37 mg/mL) compared with placebo and standard ibuprofen/acetaminophen therapy following simple extractions. Materials and Methods: Eight adults were randomized equally to four arms (n = 2 per arm) CBD 17 mg/mL, CBD 37 mg/mL, placebo, or treatment-as-usual (TAU; ibuprofen/acetaminophen). CBD/placebo groups received 0.5 mL every 4–6 h as needed for 7 days, while TAU followed the non-opioid regimen. The primary endpoint was pain intensity (0–10 Numeric Rating Scale) captured via ecological momentary assessment (EMA) over 72 h. Secondary endpoints included worst pain, rescue medication use, adherence, tolerability, and qualitative feedback. Results: All participants completed follow-up with >75% EMA adherence. Because of the very small sample (n = 8), results are descriptive only. Baseline imbalance was observed; the CBD 17 mg/mL group reported substantially lower pre-extraction pain than other groups, limiting interpretability. Pain trajectories diverged by group: CBD 37 mg/mL showed the lowest ratings, paralleling TAU; CBD 17 mg/mL and placebo showed limited efficacy. Conclusions: This pilot suggests that higher-concentration CBD (37 mg/mL) may provide analgesia comparable to standard non-opioid therapy. Within this small feasibility cohort, higher-concentration CBD (37 mg/mL) appeared to produce pain patterns qualitatively similar to standard non-opioid therapy. Findings should be interpreted as exploratory only. A fully powered randomized trial incorporating biomarker endpoints and a taste-matched placebo is warranted. Full article