Search Results (4,628)

This study investigates the therapeutic potential of grape skin polysaccharides (GSP) for type 2 diabetes (T2D). Employing a T2D model developed via a high-fat diet combined with STZ, three intervention groups were established: low-dose GSP (25 mg/kg), high-dose GSP (100 mg/kg), and metformin control (300 mg/kg). Following a 30-day oral administration period, marked enhancements in body weight and glucose/lipid metabolic parameters were noted in both the high-dose GSP group and the metformin-treated cohort. Specifically, compared with the model group, high-dose GSP improved insulin resistance by 48.48%, increased hepatic glycogen content by 63.38% and HDL–C levels by 13.16%, while reducing TG, TC, and LDL–C by 65.5%, 20.80%, and 32.63%, respectively. GSP also enhanced GSH–Px activity by 10.15% and SOD activity by 26.48%, while reducing MDA levels by 30.91%, thereby alleviating pathological damage in the liver, kidneys, and intestines. These results suggested that the regulatory effect of GSP is concentration-dependent. GSP also regulated gut microbiota by not only reducing Thermodesulfobacteriota and increasing Bacillota/Bacteroidetes abundance, but also enhancing acid-producing bacteria to elevate short-chain fatty acid (SCFA) levels, thereby further improving insulin sensitivity. Collectively, these preclinical data support the potential of GSP as a functional food ingredient or adjunct therapy for T2D management, pending further clinical validation. Full article

Background: Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) of the oral cavity is a chronic, rapidly developing mucosal lesion with an unclear pathogenesis, manifesting as a solitary ulcer. Given the malignant clinical appearance of the lesions, it is crucial to ensure the accuracy of the diagnosis to avoid unnecessary invasive surgical interventions. Methods: We present a case involving a 69-year-old female affected by a wide, painful ulcer on the left margin of the tongue. An incisional biopsy was performed, and histopathological examination confirmed the diagnosis, revealing a neutrophilic inflammatory infiltrate with components of eosinophils and lymphocytes. Considering the condition’s reactive and inflammatory nature, we planned a corticosteroid treatment with intralesional injections of triamcinolone acetonide. This therapy delivers the active principle directly to the tissues beneath the ulcerative lesion. Results: In three treatment sessions, we achieved the complete regression of the lesion’s signs and symptoms. During a one-year follow-up period, no recurrences were reported. Conclusions: The scarcity of documented cases and the ambiguity of definitions in the scientific literature highlight the importance of clinical reports, which refine scientific knowledge about this condition. At the same time, we record an effective and non-invasive treatment that could facilitate healthcare professionals in managing these types of oral pathologies. Full article

Alzheimer’s disease (AD), the most prevalent form of dementia, still lacks a clearly defined pathogenesis and effective disease-modifying therapies, prompting growing interest in peripheral drivers of neurodegeneration. Among these, chronic oral dysbiosis has emerged as a potential risk factor. Disruption of the oral ecosystem in periodontitis promotes systemic inflammation and the circulation of bacterial products capable of influencing brain homeostasis. By integrating molecular findings with epidemiological data linking periodontitis, tooth loss, and poor oral health to increased AD risk, this review examines how oral dysbiosis contributes to systemic inflammation as part of a broader network of interacting factors involved in AD pathophysiology. It describes how inflammatory, gut-microbial, genetic, and barrier-related processes intersect with oral dysbiosis and jointly contribute to the acceleration of AD progression. Building on this systemic perspective, the review highlights emerging oral biomarkers and oral–gut microbiota-targeted therapies as potential tools to address current gaps in early diagnosis and intervention. Overall, this work advances current understanding by integrating previously fragmented evidence and highlighting the key conceptual and methodological gaps that must be addressed to clarify causality and to guide the development of preventive and therapeutic approaches targeting oral health in the context of AD. 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

Diabetes mellitus represents a global health concern, which is expected to worsen over the years. The prevalence is estimated to increase up to 642 million people by 2040. Almost half of diabetic patients are at a high risk of developing kidney involvement up to dialysis; moreover, macrovascular complication could be an obstacle to kidney transplant. Besides the classic albuminuric phenotype, non-albuminuric diabetic kidney disease was also discovered recently. Fortunately, compared with classic therapy with diet, oral hypoglycemic drugs, and insulin, current clinicians can rely on several new drugs that act with different pathways characterized by kidney and heart protection, as shown by several clinical trials and confirmed in clinical practice. Herein, we will review the therapies that nephrologist and diabetologist have available today and the future perspective. Full article

Toxoplasma gondii is the most common infectious cause of posterior uveitis in immunocompetent adults. While the parasite is typically acquired through ingestion of undercooked meat or contaminated food and water, unpasteurized goat milk has been identified as a less frequent but plausible source of infection. Coinfections in ocular toxoplasmosis are rare, and the role of Epstein–Barr virus (EBV) in these coinfections remains poorly understood. We report the case of a 70-year-old immunocompetent male presenting with severe, refractory panuveitis in the left eye. Initial serologic testing confirmed acquired Toxoplasma gondii infection, and treatment was initiated with systemic antimicrobials and corticosteroids. Intraocular inflammation persisted despite sequential therapy with trimethoprim–sulfamethoxazole, clindamycin, and azithromycin, eventually requiring pars plana vitrectomy with intravitreal clindamycin and dexamethasone due to non-clearing vitreous hemorrhage. Vitreous PCR testing revealed intraocular concurrent detection of EBV DNA, prompting combined antimicrobial and antiviral therapy. Epidemiological history revealed recent consumption of unpasteurized goat milk, suggesting a potential oral transmission route for Toxoplasma gondii. Although visual acuity improved following surgical intervention and targeted therapy, it remained markedly compromised due to the severity of the disease. This case illustrates the diagnostic value of multiplex PCR in refractory uveitis, enabling the detection of Toxoplasma gondii and the concurrent detection of EBV DNA in an immunocompetent patient. It highlights the importance of early molecular testing and detailed epidemiological assessment, including atypical transmission routes such as unpasteurized goat milk. 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: β-galactosidase (lactase) is a transformative enzyme used in many different fields. Its significance spans from biotechnology to food and pharmaceutical industries. β-galactosidase catalyzes the hydrolysis of lactose into glucose and galactose. In medicine, β-galactosidase has gained attention and has many applications, mainly in enzyme replacement therapy. β-galactosidase is the main active ingredient of medications for lactose intolerance. Industrially β-galactosidase is typically produced by the Aspergillus oryzae filamentous fungus. Therapeutic interventions involving β-galactosidase aim to mitigate symptoms and improve the patients’ quality of life. In the food industry, it plays a crucial role in the production of lactose-free products, improving accessibility to dairy products. However, despite its versatility and wide use, challenges connected to β-galactosidase still exist, such as the need for cost-effective and more efficient methods for administering the enzyme. Additionally, there are several ongoing studies that seek to enhance stability and optimize the performance of β-galactosidase in various applications. The aim of this manuscript is to summarize current knowledge about β-galactosidase as an active ingredient and to present some preparations that are commercially available or mentioned in the literature. Methods: A systematic search was conducted in PubMed, Scopus, Embase and Web of Science to identify relevant articles on formulations related to β-galactosidase, focusing on original research articles published between 1895 and 2025 that exclusively examine the use of oral drug delivery. Results: After a rigorous search across multiple databases, 45 relevant studies out of 1633 initial results were selected for analysis. Conclusions: β-galactosidase remains a highly versatile enzyme with broad industrial and medical relevance. While current formulations offer significant benefits, further innovation is needed to improve delivery efficiency, stability, and cost-effectiveness. The findings of this review contribute to a deeper understanding of β-galactosidase as an active ingredient and outline opportunities for advancing its application in oral drug delivery systems. Full article

Spotty liver disease (SLD), primarily caused by Campylobacter hepaticus and (less frequently) by Campylobacter bilis, significantly impacts commercial layer hens by causing liver lesions, reducing egg production, and increasing mortality, meaning it can result in serious economic losses for farmers. This study explored the relationship between infection, liver dysfunction, and reproduction, aiming to identify host genetic markers for tracking SLD progression. Hens were orally inoculated with the C. hepaticus strain NSW44L and monitored over a seven-day period. Pathogen colonisation was quantified using qPCR across the liver, bile, caeca, spleen, and ovarian follicles, while liver lesions were scored and hepatic transcriptomes analysed using RNA-seq. C. hepaticus was detected in the liver, caeca, and spleen from one day post-inoculation (dpi) (1.44–1.68 log₁₀ CFU/mL), appeared in bile by the third dpi (3.64 log₁₀ CFU/mL), and reached the follicles by the fourth dpi (3.25 log₁₀ CFU/mL). The highest bacterial loads were found in bile on days six and seven (up to 7.18 CFU/mL). Liver lesions were first observed on the fourth dpi, reaching their peak at the sixth and seventh dpi. Gene expression analysis in liver tissue revealed a notable downregulation of yolk-precursor and metabolic genes, such as prolactin receptor (PRLR), 7-dehydrocholesterol reductase (DHCR7), and malic enzyme 1 (ME1). In contrast, from days three to seven post-infection, there was significant upregulation of avidin (AVD), a biotin-binding protein, and versican (VCAN), which is linked to tissue remodelling and inflammation. These findings correlate with the disease’s progression from initial liver infection to widespread bacterial presence, suggesting value as host biomarkers for effective SLD monitoring and the development of targeted therapies. Full article

Diabetes mellitus affects over 530 million adults globally, with current therapies limited by frequent dosing, <20% oral bioavailability, and poor long-term glycemic control. Nanomedicine, particularly self-assembled peptide nanostructures (nanofibrils), offers sustained, glucose-responsive drug release and extended peptide bioactivity for several days per dose. This review critically evaluates recent advances in smart antidiabetic nanomedicine, focusing on quantitative improvements in pharmacokinetics, controlled release, and patient compliance compared with conventional treatments. It also outlines remaining challenges in large-scale synthesis, safety validation, and regulatory translation. Collectively, these insights highlight the potential of reversible peptide nanofibrils as long-acting, cost-effective therapeutics for improved diabetes management. 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: The incidence of endometrial cancer (EC) is rising globally across all age groups. Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion that may progress to EC if untreated. A clinical model is needed to efficiently identify women requiring prompt evaluation while avoiding unnecessary invasive procedures. Obesity is a major risk factor, but whether Asian women require a lower body mass index (BMI) cutoff than the World Health Organization (WHO) definition remains debated. This study aimed to develop a multivariable risk prediction model to guide biopsy decisions and determine an appropriate BMI cutoff for predicting EIN/EC risk among Asian women. Methods: This study retrospectively reviewed 1192 women aged ≥18 years who underwent hysteroscopy between 2010 and 2023 at a tertiary hospital. Candidate predictors included patient age, parity, BMI, postmenopausal status, symptom of abnormal uterine bleeding (AUB), diabetes mellitus, hypertension, polycystic ovary syndrome (PCOS), use of oral contraceptives, intrauterine devices, or menopausal hormone therapy, tamoxifen treatment, presence of multiple polyps, and endometrial thickness (EMT) measured by transvaginal ultrasonography. Multivariable logistic regression with stepwise selection identified independent predictors, and model stability and calibration were assessed using 1000 bootstrap resamples. Results: EIN/EC was diagnosed in 55 patients (4.6%). Six independent predictors were identified: postmenopausal status (adjusted odds ratio [aOR] 5.93, 95% CI 2.92–12.04), AUB (aOR 4.07, 1.51–10.97), multiple polyps (aOR 2.49, 1.33–4.66), PCOS (aOR 2.37, 1.08–5.22), BMI (aOR 1.13 per kg/m²; 1.84 per +5 kg/m²), and EMT (aOR 1.07 per mm, 1.02–1.11). When using categorical cutoffs, Obese II (BMI ≥ 30 kg/m²) and markedly increased EMT (≥20 mm) remained significant. Predicted probabilities ranged from 0.3% with no risk factors to 90.9% with all six risk factors present. The final model demonstrated good discrimination (AUC 0.79, 95% CI 0.73–0.86) and excellent calibration on bootstrap validation (mean absolute error 0.005). Conclusions: This six-factor clinical model stratifies individual EIN/EC risk using readily available variables and may guide timely, risk-based biopsy decisions by identifying high-risk patients while minimizing unnecessary procedures in low-risk cases. BMI ≥ 30 kg/m² (WHO obesity threshold) was confirmed as a meaningful cutoff, but external validation is warranted to confirm its generalizability and clinical applicability. Full article

Oral diseases pose a major public health challenge, especially in low-income countries where dental care is limited due to high costs. In this context, phytotherapy has gained attention as a complementary approach due to its bacteriostatic, anti-inflammatory, healing, and analgesic properties. These therapeutic effects are mainly attributed to plant-derived bioactive metabolites, which interact with cellular structures, especially the plasma membrane, to modulate inflammation, stimulate tissue regeneration, and support antimicrobial defense. This review systematically examined the scientific literature to identify Latin American medicinal plants with therapeutic potential in dentistry. Based on their clinical and ethnobotanical applications, the analysis focused on species with anti-inflammatory, healing, analgesic, and relaxing effects, particularly in conditions such as dental pain, gingivitis, and periodontitis. Given the close relationship between pain, inflammation, and periodontal disease, these conditions cannot be studied in isolation. Gingivitis and periodontitis often present with painful symptoms and inflammatory responses that overlap with mechanisms of tissue damage and repair. Therefore, broadening the scope of this review allows for a more comprehensive understanding of how Latin American medicinal plants can contribute not only to pain relief but also to periodontal health, inflammation control, and wound healing. Fifty plant species were identified. Among these, 35 exhibited anti-inflammatory activity, 28 had healing properties, 20 showed analgesic effects, and 12 were associated with relaxing properties. Mexico accounted for the highest proportion of species (60%), followed by Colombia and Peru (54%) and then Brazil (32%). These percentages represent the proportion of plant species reported in studies originating from each country, relative to the total number of species identified in the review. The most studied species were Salvia rosmarinus Spenn. (Lamiaceae), Moringa oleifera Lam. (Moringaceae), Aloe vera (L.) Burm.f. (Asphodelaceae), and Ocimum basilicum L. (Lamiaceae). Latin American medicinal plants demonstrate strong potential not only in dental therapy but also in the management of periodontal inflammation and oral diseases. However, further research and clinical validation are needed to ensure their safe integration into conventional treatments. 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