Search Results (7,776)

Objectives: Obesity and related metabolic disorders, including insulin resistance, dyslipidemia, and non-alcoholic fatty liver disease, represent major global health challenges. Growing interest in complementary strategies has brought propolis, a resinous bee-derived product rich in phenolic and flavonoid compounds, into focus. This scoping review aimed to map and synthesize available in vitro, in vivo, and clinical evidence regarding the metabolic effects of whole propolis preparations and propolis-derived bioactive compounds in obesity-related contexts. Methods: The review was conducted in accordance with the PRISMA-ScR framework and included experimental and human studies evaluating adipogenesis, lipid and glucose metabolism, oxidative stress, inflammatory signaling, non-alcoholic fatty liver disease-related outcomes, and gut microbiota modulation. Results: Across preclinical models, propolis preparations have been associated with modulation of antioxidant defenses, attenuation of inflammatory signaling, regulation of adipogenic transcriptional programs, and alterations in gut microbiota composition and barrier integrity. Clinical evidence suggests modest improvements in selected metabolic and inflammatory biomarkers; however, effects on body weight and adiposity remain inconsistent. Interpretation is limited by heterogeneity in propolis type, extraction method, chemical standardization, dosing strategies, and study design. Full article

Background/Objectives: The anatomical variability of the human foot represents a subject of substantial interest, offering valuable insights in anthropological research as well as in clinical practice. The aim of this study is to document anatomical variants of the tarsal bones in a CISC//XXI skeletal sample (21st Century Identified Skeletal Collection), with a particular focus on the prevalence of accessory ossicles. Methods: The studied sample consisted of 163 individuals (83 females and 80 males). The prevalence of six accessory tarsal bones was recorded (os trigonum, calcaneum secundarium, the accessory navicular bone, os sustentaculum, os vesalianum and os intermetatarseum). Results: A total of 35 individuals (21.4%; 35/163) exhibited at least one accessory ossicle, with 13 females (15.7%; 13/83) and 22 males (27.5%; 22/80). The os trigonum and calcaneum secundarium were the most frequently observed accessory bones, respectively, in 9.3% (15/162) and 6.9% (11/159) of the individuals. No sex differences were observed. All accessory bones occurred more frequently unilaterally, and no co-occurrences of accessory bones were observed. Conclusions: These findings are crucial in both the biomedical and anthropological fields, where a detailed knowledge of foot anatomy and its variations is relevant. Full article

Background/Objectives: Molecular subtyping of pediatric B-cell acute lymphoblastic leukemia (B-ALL) has improved patient outcomes through stratification and selection of targeted therapies. Despite extensive genomic and transcriptomic profiling of this cancer, few studies to date have characterized the proteomic landscape, although proteins are the direct targets of many therapeutic agents. Methods: In this study, we demonstrate the utility of multi-omic integration of global transcriptomic, proteomic, and phosphoproteomic profiles of samples from patients diagnosed with either of two B-ALL subtypes—Ph-like (BCR::ABL1-like) and ETV6::RUNX1. Through individual and multi-omic analysis, we recapitulate known transcriptomic findings and identify novel subtype-specific proteomic and phosphoproteomic biomarkers. Conclusions: Our findings suggest a previously undescribed role for calcium-dependent signaling processes in Ph-like B-ALL, which has the potential to serve as a novel avenue for targeted treatments. By integrating multiple -omics modalities, we identify not only features of interest but also begin to unravel the regulatory interactions driving subtype-specific mechanisms of leukemogenesis. This integrated analytic approach paves the way for enhanced precision medicine for precise subtyping and treatment selection for pediatric leukemia patients. Full article

Background/Objectives: In pregnancy, beta-cell function is of interest since not only insulin resistance but also beta-cell dysfunction is common, especially when gestational diabetes mellitus (GDM) occurs. Typically, model-based beta-cell function is assessed with (at least) five-sample oral glucose tolerance test (OGTT). The aim of this study was to investigate whether the clinically common three-sample OGTT is sufficient for model-based beta-cell function assessment in pregnancy. Methods: We studied a group of pregnant women undergoing a 2 h five-sample OGTT with glucose, insulin, and C-peptide measurement at early and/or mid-pregnancy, for a total of 152 OGTTs. The five-sample OGTT was used for model-based beta-cell function assessment, yielding three beta-cell function parameters, i.e., glucose sensitivity (GSENS), potentiation factor ratio (PFR), and rate sensitivity (RSENS). GSENS, PFR, and RSENS assessment was repeated with the three-sample OGTT (at 0, 60, 120 min) and related values were compared to those from the five-sample OGTT (reference). Results: We found that, for GSENS, regression and Bland–Altman analyses showed satisfactory results (conditional and marginal R² values: 0.56 and 0.75, p < 0.0001, and limits of agreement containing 94.2% of samples). Moreover, five-sample and three-sample OGTT GSENS versions were fully consistent in patient subgroup analyses. Results for PFR were less satisfactory but acceptable, whereas those for RSENS were not reliable. Conclusions: The three-sample OGTT is acceptable for model-based beta-cell function assessment in pregnancy, although not for all parameters. Our methodology may be used to explore the effect of time sample reduction in other in-silico models. Full article

Background: There is increasing interest in cosmeceuticals—cosmetic regimes incorporating a specific probiotic or postbiotic strain, fully characterized genetically and phenotypically—which, when topically applied, have the ability to modulate the skin microbiome, exhibit anti-inflammatory properties and improve the overall skin appearance by reducing signs of aging. In addition, claims have been made that emotional and psychological well-being can be improved by neuroactive substances released by the probiotics in cosmeceuticals, acting via the skin–brain axis. However, claims are somewhat generalized and imprecise, and we deemed it important to look more precisely at published research relating to cosmeceuticals. There have been very few research publications on these products, identified as neurocosmetics, and they immediately provoked strong reactions from dermatologists and psychiatrists, mainly with regard to the ethical and safety aspects of their use. Objectives/Method: The present strain-centered literature evaluation aimed to select from peer-reviewed publications referring to cosmeceuticals only those dealing with fully characterized, specific probiotic strains with documented beneficial skin properties. Eligible strains found were subsequently subjected to a secondary search to ascertain whether they also demonstrated clinical, or even experimental, evidence of strain-specific psychobiotic properties. Results: From 33 strain-specific cosmeceuticals identified, only three strains—Lactococcus lactis subsp. cremoris H61, Limosilactobacillus reuteri DSM 17938, and Weizmannia coagulans MTCC 5856—demonstrated reproducible evidence of psychobiotic potential. Conclusions: Current evidence does not support the notion that cosmeceuticals are likely to directly modulate emotional states through topical application, since the coexistence of cosmeceutical and psychobiotic properties within the same probiotic strain seems to be both uncommon and highly strain-specific and therefore of little practical, generalized use. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder for which no disease-modifying therapy that halts or substantially slows disease progression is currently available. Although antibody therapies targeting amyloid β (Aβ) have recently received FDA approval, their high cost, limited efficacy, and potential adverse effects highlight the need for alternative solutions. Therefore, the development of low-molecular-weight compounds capable of reducing toxic Aβ aggregates is of considerable interest. In this study, we investigated the effects of 2,3,4-trihydroxybenzophenone (THB) on the inhibition and disassembly of Aβ_1–42 aggregates through in vitro and in vivo experiments. Methods: In vitro assays were performed to evaluate the effects of THB on Aβ_1–42 aggregation and fibril disassembly. Cell viability assays and hippocampal slice electrophysiology were conducted to assess neurotoxicity and synaptic function. In vivo effects were examined in Aβ_1–42 aggregate-injected mice and in 5 Familial AD mutations (5XFAD) mice using behavioral, histological, and electrophysiological analyses. Results: THB inhibited Aβ_1–42 aggregation in a concentration-dependent manner and promoted the disassembly of preformed fibrils. THB attenuated Aβ_1–42-induced Neuro2a cell death and restored Aβ_1–42 aggregate-associated long-term potentiation (LTP) deficits in hippocampal slices. In Aβ_1–42 aggregate-injected and 5XFAD mice, THB reduced amyloid pathology and neuroinflammatory markers and improved synaptic function and memory performance. Conclusions: These findings suggest that THB modulates pathogenic Aβ_1–42 assemblies and provides a structural basis for the development of small-molecule modulators of Aβ_1–42 aggregation with potential preventive or disease-modifying applications in AD. Full article

Background/Objectives: Tick-borne encephalitis (TBE) is the most important tick-borne viral central nervous system (CNS) infection in Europe and Asia. Since the introduction of a vaccine in Austria in the late 1970s, sero-epidemiological studies on the true incidence of tick-borne encephalitis virus (TBEV) infection in the population have been difficult, because it was not possible to distinguish between vaccine- and infection-induced antibodies. The goal of our study has been to analyze the sero-epidemiology of TBEV infections, vaccination protection rate, and manifestation index of the disease in the region of interest. Methods: Applying a newly developed anti-TBEV-NS1-IgG assay and the neutralization test, the protection and infection rates in blood donors of the Austrian Federal State of Upper Austria.It is one of the first areas in Austria, where the TBEV vaccine had been rolled out and broadly used. Samples from blood donors of all districts of the Federal State of Upper Austria were screened for anti-TBEV-IgG. Positive sera were differentiated for infection- and vaccine-induced antibodies. The results were matched with donor age, gender, and geographical origin. Results: 2162 samples were analyzed. A total of 87.0% of the blood donors tested showed anti-TBEV-IgG related to past TBEV vaccination. Within the unvaccinated group, a total of 13.3% of male and 9.9% of female blood donors exhibited anti-TBEV-NS1-IgG, indicating a past TBEV infection. The anti-TBE-NS1-IgG seroprevalence was determined at 74/100,000 for the whole population and at 594/100,000 in the non-vaccinated population. The manifestation index (MI) was calculated at 2.8%. The MI is defined as the probability or percentage of infected individuals who develop clinical symptoms of a disease. Conclusions: Our data provide evidence of a continuing high risk of TBEV infection in the Federal state of Upper Austria. The non-vaccinated population has an eightfold higher infection prevalence compared to the whole population. The MI of TBEV for severe infection seems lower as detailed in previous reports. Full article

Background/Objectives: Metformin, a widely used antidiabetic drug, has recently gained attention in dermatology due to its pleiotropic effects. Given the high prevalence, chronicity, and therapeutic challenges of several dermatological conditions, there is growing interest in repurposing metformin as a topical agent with anti-inflammatory, antioxidant, metabolic, and regenerative properties. This narrative review aimed to synthesize and critically analyze the available preclinical and clinical evidence regarding the mechanisms of action, efficacy, safety, and therapeutic potential of topical metformin across different skin disorders. Methods: A literature search was conducted in PubMed and complementary databases for studies published between 2015 and 2025 addressing topical metformin in dermatology, including experimental, observational, interventional, and review articles. Results: The findings indicate that topical metformin has been associated with beneficial biological effects in conditions such as melasma, photoaging, wound healing, psoriasis, acne, skin cancer, and hair disorders, largely through AMPK activation, modulation of inflammation and oxidative stress, inhibition of melanogenesis, enhancement of tissue regeneration, and regulation of immune and metabolic pathways, although evidence remains predominantly preclinical and methodologically heterogeneous. Conclusions: Topical metformin represents a promising investigational multifunctional dermatological agent; however, its clinical translation depends on well-designed randomized controlled trials with standardized formulations, adequate sample sizes, and long-term follow-up to establish its efficacy, safety, and optimal therapeutic protocols. Full article

Background/Objectives: Osmotic demyelination syndrome (ODS) causes marked myelin loss with relative axonal preservation. We used diffusion tensor imaging (DTI) to longitudinally assess white matter (WM) changes, hypothesizing that radial diffusivity (RD) would show dynamic recovery alongside clinical improvement. Methods: A 40-year-old woman with ODS and five age-matched female controls underwent DTI at 7 weeks and 6 months post-onset. Metrics were extracted from 27 WM tract categories using atlas-based regions of interest. Lesions were defined by directional dual thresholds (RD_d ≥ 2.0, axial diffusivity [AD] ≤ −2.0, or fractional anisotropy [FA] ≤ −2.0) and confirmed using the Crawford–Howell test with Benjamini–Hochberg FDR correction (q ≤ 0.05). Longitudinal percent change (Δ%) was compared using the Friedman test with Bonferroni-corrected Wilcoxon post hoc tests (α = 0.017). Results: Serum sodium increased from 126 to 138 mmol/L within 24 h, followed by a severe neurological deficit; near-complete recovery by 6 months. At 7 weeks, RD-defined lesions were detected in 10/27 tracts (37.0%)—1/6 brainstem-related and 9/21 non-brainstem—indicating widespread myelin-predominant injury. No AD- or FA-based lesions met criteria, although AD increase in the cingulate gyrus was significant. From 7 weeks to 6 months, the mean Δ% was −0.40 ± 9.38% (AD), −4.73 ± 9.73% (RD), and +7.94 ± 7.53% (FA). Changes differed across metrics (χ²(2) = 24.07, p = 5.92 × 10⁻⁶), with greater RD and FA changes than AD. Conclusions: Early RD-predominant abnormalities preceded RD reduction and FA increase during recovery, consistent with restoration of myelin-related microstructure. Larger studies are warranted. Full article

A major challenge in research on cognitive decline and dementia is the identification of at-risk populations in the preclinical phase. In this context, there is growing interest in language markers as early indicators of cognitive impairment. Objectives: This study aims to identify early linguistic markers that may facilitate the detection of individuals at risk of cognitive decline and dementia during the preclinical stage. Additionally, it seeks to evaluate the effectiveness of various assessment techniques and instruments for detecting such language impairments. Methods: A systematic review was conducted in accordance with the PRISMA guidelines, encompassing studies published between 2014 and 2025. A total of 109 articles were included in the qualitative synthesis. Results: The findings indicate that syntactic–structural features—particularly complexity, discourse coherence, and global organization—together with acoustic parameters such as pause duration, exhibit a higher accuracy and predictive value for the early diagnosis of cognitive decline and its progression to dementia. Furthermore, narrative-based tasks analyzed through automated methods demonstrate significant advantages for the assessment of language impairments. Conclusions: The analysis of language markers—particularly through the examination of syntactic complexity, acoustic features, and automated narrative assessments—represents a promising and effective approach for the early identification of cognitive impairment and the prediction of subsequent dementia onset. Full article

Background/Objectives: Gastric ulcer is a prevalent global gastrointestinal disorder influenced by multiple factors, including excessive alcohol consumption, poor dietary habits, psychological stress, smoking, and the chronic use of non-steroidal anti-inflammatory drugs. Among these, alcohol plays a critical role in gastric mucosal injury by enhancing gastric acid secretion, triggering inflammatory responses, inducing oxidative stress, and promoting epithelial cell apoptosis while simultaneously depleting key protective mediators such as nitric oxide and prostaglandin E₂. Growing interest has focused on medicinal plants as promising sources of novel therapeutic agents for the management of peptic ulcer disease. Methods: This review summarizes commonly used medicinal plants documented in both Ayurvedic and modern medical systems that exhibit ulcer-healing potential. Experimental and preclinical studies indicate that various herbal drugs and plant extracts derived from different plant parts exert significant anti-ulcer effects through multiple mechanisms, including antioxidant activity, modulation of inflammatory pathways, enhancement of mucosal defense, and inhibition of gastric acid secretion. Results: The review further highlights the gastroprotective effects of these herbal remedies as demonstrated in established experimental ulcer models. Conclusions: Exploring plant-based therapies for gastric ulcers offers valuable insights into alternative and complementary treatment strategies. Continued research aimed at identifying bioactive compounds, elucidating their molecular mechanisms, and developing improved formulations may contribute to safer, more effective, and patient-friendly therapeutic options for peptic ulcer management. Full article

Background/Objectives: Autism Spectrum Disorder (ASD) diagnosis is difficult due to heterogeneity. Current Time-series Transformer (TST) methods cannot capture both dynamic and global brain connectivity simultaneously, which limits ASD classification performance. Methods: We propose TwoTST, a dual-stream Transformer that combines raw Region of Interest(ROI) time series and Pearson correlation matrices(PCC).We pre-train the two TST branches via self-supervised learning by randomly masking ROIs and PCC, use contrastive learning and fine-tuning for feature alignment, evaluate five fusion strategies, and analyze relative parameter changes during fine-tuning. Results: Experiments were conducted on the ABIDE I dataset using the CC200 atlas. Contrastive learning, pre-training, and the dual-stream structure improve mean AUC by 3–6%, 3–7%, and 3–4% respectively. Attention Pooling is the optimal fusion strategy. Relative parameter changes are 0.32–0.44 for TST modules and 0.31–1.45 for contrastive projection heads. Conclusions: TwoTST effectively integrates dynamic and global connectivity for ASD identification. The proposed design outperforms single-stream models and provides a reliable approach for neuroimaging-based disorder classification. Full article

Background/Objectives: Benign prostatic hyperplasia (BPH) is a multifactorial condition associated with androgen imbalance, oxidative stress, and chronic inflammation, leading to growing interest in food-derived bioactive compounds with multitarget activity. This study aimed to investigate the biological effects of a nutraceutical combination of Gastrodiae elata Blume extract and coenzyme Q10 (Q10), focusing on mechanisms relevant to prostate physiological balance using food-relevant in vitro models. Methods: An intestinal epithelial barrier model (Caco-2) was employed to assess intestinal tolerance and permeability of the tested compounds. Subsequently, a prostate epithelial–stromal co-culture exposed to dihydrotestosterone (DHT) was used to reproduce BPH-like cellular conditions. Oxidative stress, inflammatory mediators, androgen-related pathways, and markers of proliferation and apoptosis were evaluated following simulated intestinal passage. Results: The combined formulation showed no cytotoxic effects and demonstrated efficient intestinal permeability. After intestinal passage, the combination significantly reduced oxidative stress and inflammatory responses in the prostate co-culture, decreasing reactive oxygen species and pro-inflammatory mediators, including NF-κB, TNF-α, and IL-1β. In parallel, the formulation modulated androgen-related pathways by reducing 5-α-reductase activity and DHT levels while supporting testosterone homeostasis. Across some of the evaluated endpoints, the combined formulation tended to show more pronounced protective effects compared with the individual components. Conclusions: These results suggest that a combination of Gastrodiae elata and coenzyme Q10 may have a positive effect on prostate health. In the nutraceutical field, this food-based formulation could help support prostate health, probably through antioxidant, anti-inflammatory, and hormonal control mechanisms. Further studies using advanced experimental models are warranted. Full article

Conifer bark extracts have attracted growing interest for their potential to protect and support endothelial function. The objective of this study was to evaluate the effects of Abies alba Mill. and Cedrus brevifolia (Hook. f.) Henry bark extracts on vascular endothelial function. The bark extracts were characterized by liquid chromatography coupled to high-resolution mass spectrometry. Bioactivity studies were first conducted in EA.hy926 endothelial cells to investigate the effects of bark extracts on cell viability and proliferation, nitric oxide production, oxidative stress, and angiogenesis. The vasorelaxant effects of bark extracts in rat aortic rings, as well as their impact on in vitro arginase activity, were further assessed. Abies alba bark extract was more effective in enhancing nitric oxide production (8.8-fold vs. 7.4-fold at 0.1 mg/mL), reducing oxidative stress (by 33% vs. 26% at 0.1 mg/mL), and inhibiting angiogenesis in EA.hy926 endothelial cells. It also exhibited stronger arginase inhibitory activity (IC₅₀ = 68.30 µg/mL vs. 115.31 µg/mL). Both bark extracts showed marked vasorelaxant activity (EC₅₀ < 15 µg/mL), mainly mediated by an endothelial nitric oxide synthase-related mechanism, with the Cedrus brevifolia bark extract being more active. Overall, our findings indicate that both bark extracts are promising candidates for supporting endothelial function. Full article

Background/Objectives: Health-related quality of life (HRQoL) is a critical indicator of developmental progress, educational engagement, and psychosocial resilience. By identifying both shared and context-specific differences in HRQoL, we aim to contribute to a more nuanced understanding of well-being that can inform the development of assessment approaches and future research tailored to the diverse contexts in which children with disabilities live and learn. Thus, the purpose of this study is to explore HRQoL and its putative influencing factors among youth with multiple disabilities across two distinct cultural settings, the United States and Iceland. Methods: Participants (N = 26; Icelandic = 50%; Mage = 16.34 ± 2.33 years) completed height, weight, the Test of Perceived Physical Competence (TPPC), Supine-to-Stand (STS), Rapid Assessment of Physical Activity (RAPA), and VISIONS QL. We conducted five, 2 group × 2 sex ANOVA and several independent samples t-tests within groups by sex for our variables of interest. Results: There was a significant difference between Icelandic boys and girls for BMI (p = 0.087, d = 0.65) and STS (p = 0.027, d = 1.04). Conversely, a significant difference was found in the American group between boys and girls for RAPA (p = 0.092, d = 0.81) and TPPC (p = 0.068, d = 0.92). Conclusions: Preliminary findings suggest that patterns in objective and self-reported health indicators may vary by context. These results highlight the importance of considering both measured performance and self-perceived health when examining HRQoL among adolescents with multiple disabilities, while underscoring the need for further research in larger samples to clarify these relationships. Full article