Search Results (9,173)

Endometriosis, a chronic inflammatory condition affecting up to 10% of reproductive-age individuals, is characterized by the presence of endometrial-like tissue outside the uterine cavity. Current treatments are based primarily on hormonal therapy, analgesia, and surgery, while additional biologically targeted approaches remain under investigation. This review examines polyphenols in relation to endometriosis-associated redox dysregulation and inflammation. Rather than acting simply as antioxidants, individual polyphenols may function as context-dependent redox and signaling modulators. Preclinical studies suggest effects on NF-κB and MAPK signaling, Nrf2-related stress responses, angiogenesis, apoptosis, immune-cell activity, and hormone-related pathways, but the direction and magnitude of these effects differ substantially among compounds, doses, metabolites, and experimental models. Resveratrol and quercetin have generated the greatest clinical interest; however, human evidence remains sparse and heterogeneous, quercetin has been evaluated mainly in multicomponent formulations, and the only double-blind placebo-controlled randomized trial of resveratrol did not demonstrate superiority over placebo for pain reduction. Low and variable bioavailability, compound-specific metabolism, phytoestrogenic and pro-oxidant effects at some exposures, heterogeneous formulations, and limited long-term safety data remain major translational barriers. Polyphenols should therefore be regarded as potential adjunctive approaches whose clinical efficacy in endometriosis remains to be established. Full article

Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms show substantial developmental heterogeneity, yet less is known about how co-occurring psychopathology is associated with membership in different longitudinal symptom trajectories. This study examined developmental trajectories of parent-reported ADHD symptoms across seven annual assessment waves from late childhood through adolescence using data from the Adolescent Brain Cognitive Development (ABCD) Study. ADHD symptoms were assessed using the Child Behavior Checklist DSM-5-Oriented ADHD Problems scale and therefore represent dimensional symptom scores rather than clinical ADHD diagnoses. Growth mixture modelling was conducted in an analytic sample of 9718 participants and identified three trajectory classes: low/stable (79.87%), high/stable (10.77%), and remitting (9.36%). Baseline associations with class membership were subsequently examined using the R3STEP procedure in 9716 participants, preserving the identified class structure while accounting for classification uncertainty. Relative to the low/stable class, male sex and higher baseline affective, anxiety, conduct, and oppositional defiant problem scores were associated with greater odds of membership in both the remitting and high/stable classes, whereas age and somatic problems showed no clear associations. Comparisons between the remitting and high/stable classes were largely similar, although male sex was associated with greater odds of remitting-class membership. Overall, the findings demonstrate substantial heterogeneity in the developmental course of ADHD symptoms and suggest that baseline co-occurring psychopathology is associated primarily with differentiation between lower- and higher-symptom trajectories rather than clearly distinguishing persistent from remitting elevated-symptom pathways. Full article

Background/Objectives: Many ambulance-attended falls among older adults are not represented in hospital-based datasets. We used emergency medical service (EMS) records to describe residential and non-residential falls and identify factors associated with non-residential fall location and hospital transfer. Methods: We retrospectively analyzed records from Türkiye’s 112 EMS system from January 2023 through October 2025. The analytic sample comprised 685,666 records; no age-eligible records were excluded for missing study variables. Fall-location associations were examined using chi-square tests, Cramér’s V, and multivariable logistic regression; a multivariable model examined hospital transfer. Results: Residential falls accounted for 406,183 records (59.2%), increasing from 49.6% at ages 65–74 to 61.9% at 75–84 and 71.1% at ≥85 years, and occurring more often among women than men (65.4% vs. 50.8%). Adjusted odds ratios (ORs) for non-residential location were higher for daytime occurrence (08:00–16:59: OR = 2.871) and male sex (OR = 1.761) and lower with advancing age (≥85 years: OR = 0.424). Hospital transfer occurred in 527,881 records (77.0%). Adjusted odds were higher for yellow-coded (OR = 11.063) and red-coded (OR = 8.053) cases, lower for non-residential location (OR = 0.268) and age ≥85 years (OR = 0.739), and higher outside Istanbul (OR = 1.999). Conclusions: This is the first nationwide prehospital analysis of falls among older adults in Türkiye. Residential falls predominated, while fall location and hospital transfer showed demographic, temporal, triage, and geographic associations. These findings may inform research on fall prevention, prehospital assessment, and referral pathways. Full article

Polygonatum sibiricum Red. is a medicinal and edible homologous plant whose rhizome quality determines its clinical efficacy and commercial value. However, conventional evaluations typically treat the entire rhizome as homogeneous, overlooking the intrinsic heterogeneity along age nodes, and the regulatory mechanisms governing such age-dependent quality variation remain largely unclear. In this study, four-year-old rhizomes were precisely segmented into four age nodes (HJ1–HJ4), and the contents of polysaccharides, flavonoids, and saponins were systematically determined alongside comparative transcriptome sequencing to dissect the age-dependent bioactive variation and underlying molecular mechanisms. The three bioactive components exhibited markedly asynchronous accumulation patterns, with polysaccharides peaking at HJ3, flavonoids at HJ4, and saponins at HJ1. Transcriptomic analysis identified 19,638 differentially expressed genes (DEGs), with KEGG enrichment pointing to starch and sucrose metabolism, flavonoid biosynthesis, and steroid biosynthesis as the pivotal pathways. A coordinated transcriptional reprogramming emerged across development, characterized by early upregulation of backbone-construction genes and progressive activation of modification-and-decoration genes—yet it manifested through pathway-specific regulatory logics, with Mantel tests further confirming that key genes, including β-amylase3, CYP75B11, and squalene epoxidase (SQLE), were significantly correlated with the accumulation of polysaccharides, flavonoids, and saponins, respectively. These findings challenge the conventional assumption that older nodes are universally superior and establish that age-node differentiation reflects fundamental metabolic reprogramming, supporting a node-targeted utilization strategy encompassing HJ3 for polysaccharide-based products, HJ4 for antioxidant applications, HJ1 for saponin extraction, and HJ2 for bulk materials, while providing both mechanistic insights and practical guidance for precision harvesting and quality-oriented management of P. sibiricum. Full article

Background: Dietary (poly)phenols have been proposed to protect against age-related cognitive decline through antioxidant, anti-inflammatory, and neuroprotective mechanisms. However, evidence specifically addressing mild cognitive impairment (MCI) remains limited. This study investigated the association between habitual dietary (poly)phenol intake, cognitive status, and circulating inflammatory biomarkers in older adults. Methods: In this cross-sectional study, Italian adults aged ≥65 years attending a memory clinic underwent standardized neuropsychological assessment for MCI diagnosis. Habitual dietary intake was assessed using a validated food frequency questionnaire, and dietary (poly)phenol intake was estimated using the Phenol-Explorer database. Plasma transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) concentrations were measured by ELISA. Logistic regression analyses were performed to evaluate associations between quartiles of (poly)phenol intake and MCI after adjustment for energy intake, age, sex, education, and smoking status. Results: Participants without MCI reported significantly higher intakes of total (poly)phenols and several subclasses, including flavonoids, anthocyanins, flavanones, flavones, hydroxycinnamic acids, and lignans. Higher intakes of flavanones, flavones, lignans, hesperetin, naringenin, lariciresinol, matairesinol, and pinoresinol were positively associated with cognitive performance. Individuals in the highest quartile of total (poly)phenol intake had substantially lower odds of MCI (adjusted OR = 0.08; 95% CI: 0.01–0.62), with similar inverse associations observed for flavonoids (OR = 0.16; 95% CI: 0.02–0.92), lignans (OR = 0.18; 95% CI: 0.04–0.89), flavones (OR = 0.18; 95% CI: 0.04–0.87), naringenin (OR = 0.19; 95% CI: 0.04–0.92), lariciresinol (OR = 0.18; 95% CI: 0.04–0.89), matairesinol (OR = 0.19; 95% CI: 0.04–0.93), and pinoresinol (OR = 0.16; 95% CI: 0.03–0.82), when compared to the lowest quartile. Total (poly)phenol intake was not associated with circulating inflammatory biomarkers, although biochanin A and caffeic acid were inversely associated with TNF-α concentrations. Conclusions: Higher habitual intake of selected dietary (poly)phenols, particularly flavonoids and lignans, was associated with a lower likelihood of MCI and better cognitive performance in older adults. However, the absence of consistent associations with inflammatory biomarkers does not support inference regarding an anti-inflammatory mechanism. Given the observational design, small sample size, and multiple statistical comparisons, these findings should be considered exploratory and hypothesis-generating. Prospective studies and randomized controlled trials are needed to confirm these associations and clarify the underlying biological pathways. Full article

Background: Telemedicine may improve access to care and streamline patient pathways, but real-world uptake in otorhinolaryngology remains uncertain. This single-center study evaluated an online appointment module with an option for video consultation at ENT University Hospital Freiburg and compared real-world utilization with patients’ hypothetical willingness to use telemedicine. Materials and Methods: The online module was implemented from March to June 2021. We recorded symptom category, age, gender, distance to the clinic, insurance status, type of consultation requested, and preference for video versus face-to-face consultation. Video consultations were evaluated separately in March and April. In addition, an independent survey was conducted in February 2021 among patients presenting with otological symptoms to assess hypothetical willingness to substitute an equivalent telemedical consultation for an in-person visit. Results: Of 7435 outpatient contacts, 507 (6.8%) used the online appointment module. Among these, 35 (6.9%) requested a video consultation and 472 (93.1%) requested a face-to-face appointment; video requests therefore represented 0.47% of all outpatient contacts. By contrast, 35 of 55 survey respondents (63.6%) stated that they would forgo an in-person visit if equivalent telemedical care were available. In March and April, 29 video consultations were scheduled or requested after telephone counseling, of which 11 were completed. Nine of the 11 completed video consultations (81.8%) did not require a subsequent in-person visit, whereas two (18.2%) required additional audiometry or nasal endoscopy. Because only 11 video consultations were completed, these findings are descriptive and exploratory. Conclusions: Hypothetical willingness to use telemedicine was substantially higher than real-world video consultation utilization. This gap indicates that stated acceptance does not necessarily translate into actual use and may reflect clinical suitability, awareness, organizational or technical barriers, or patient preference. ENT departments considering telemedicine should therefore use targeted patient selection and pre-consultation triage, particularly for follow-up visits, counseling, and second opinions that do not require immediate examination or diagnostic testing. Generalizability is limited by the single-center design, the short observation period, the small number of completed video consultations, and the COVID-19 pandemic context. Full article

Ocimum gratissimum L. (OGL) is a medicinal plant known for various therapeutic properties, yet its potential in genetic-level skin anti-aging remains underexplored. This study aimed to evaluate the phytochemical profiles, antioxidant activities, and anti-aging potential of OGL leaf extracts obtained via aqueous boiling (OGL-B) and ethanolic maceration (OGL-M). Total phenolic and flavonoid contents were quantified using colorimetric assays, while rutin, catechin, and quercetin were analyzed using HPLC. Biological activities were assessed using antioxidant models, tyrosinase inhibition, and B₁₆F₁₀ anti-melanogenesis assays, while skin regenerative potential was evaluated through collagen biosynthesis and expression of longevity-related genes (SIRT1, FOXO1, TERT, and KLOTHO) in human skin fibroblasts. OGL-B provided a significantly higher extraction yield (14.70%) and superior multifunctional antioxidant capacity than OGL-M. OGL-M showed higher phenolic content and cell-free tyrosinase inhibition, whereas OGL-B demonstrated greater cellular anti-melanogenic efficacy and more than twofold higher collagen stimulatory effects than L-ascorbic acid. OGL-B significantly upregulated mRNA expression (271.25 ± 0.21%), exceeding the reference activator resveratrol, and enhanced fibroblast viability to 121.53 ± 3.85% at 1 mg/mL, indicating high biocompatibility. These findings suggest that OGL-B is a multifunctional extract capable of modulating longevity-related pathways, with potential for advanced anti-aging food supplement and cosmeceutical applications. Full article

Background/Objectives: Fruit and vegetable purchase intention may reflect personal, normative, and access-related factors, yet evidence from Peru remains limited. This study aimed to examine associations of health consciousness, family influence, perceived behavioral control, and perceived convenience and availability with attitude and fruit and vegetable purchase intention, including indirect statistical associations through attitude. Methods: This cross-sectional study used non-probability convenience sampling to recruit 458 adults residing in Peru; 73.8% were female, 76.9% had university education, and 66.2% resided in Lima. Standardized composite scores were analyzed in a path model adjusted for sex, age group, education, marital status, household income, and region. HC3 robust standard errors and 5000 bootstrap resamples were used. Results: Health consciousness (β = 0.331), perceived behavioral control (β = 0.228), and perceived convenience and availability (β = 0.096) were positively associated with attitude, whereas family influence was not. Attitude was positively associated with purchase intention (β = 0.568), while direct associations of the four antecedents with purchase intention were not supported. Positive indirect statistical associations through attitude were observed for health consciousness (β = 0.188, 95% CI: 0.117–0.265), perceived behavioral control (β = 0.130, 95% CI: 0.073–0.190), and perceived convenience and availability (β = 0.055, 95% CI: 0.010–0.104). The model explained 29.4% of attitude and 43.2% of purchase-intention variance. Conclusions: Health consciousness and perceived behavioral control showed the most consistent associations. Given the non-random and demographically imbalanced sample, findings should not be generalized to all Peruvian adults or interpreted as causal pathways or actual purchasing behavior. Full article

Aging and cancer form a biological continuum influenced by epigenomic changes, metabolic dysfunction, inflammation, cellular senescence, and loss of tissue homeostasis. Age-related epigenetic alterations can promote cancer, which exploits plasticity for evolution, immune evasion, metastasis, and resistance. Nutrition and metabolism affect this process through one-carbon metabolism, methyl-donor availability, acetyl-CoA and NAD⁺ balance, redox status, microbiome metabolites, and chromatin enzyme activity. Circulating biomarkers such as cell-free DNA methylation, mutation-based ctDNA, fragmentomic features, and non-coding RNAs can detect tumor and host changes linked to aging, inflammation, nutrition, and treatment with minimal invasiveness. This review explores the epigenetic aging–cancer link, how nutrition and metabolism modify pathways, and the potential of circulating biomarkers for diagnosis, prognosis, prediction, and monitoring. The focus is on epigenetic plasticity, drug-tolerant states, resistance, epigenetic drugs, metabolic targeting, and nutritional interventions. New technologies, including single-cell and spatial epigenomics, long-read sequencing, and multimodal computational approaches, aid biomarker discovery and clinical use. Challenges include variability, misclassification, heterogeneity, confounding, reverse causality, overfitting, and limited validation. Clinical applications need standard workflows, representative cohorts, transparent models, and proof that biomarker-guided strategies improve outcomes. Full article

Alzheimer’s disease (AD) involves not only the neural parenchyma but also brain-border interfaces in which border-associated macrophages (BAMs) regulate amyloid-β (Aβ) handling, vascular function, and immune surveillance. This review focuses on a pathological axis in which persistent vascular Aβ40 and aging-related stress shift clearance-competent BAMs toward oxidative-stress and senescent-like states. Two experimentally supported but incompletely connected branches are emphasized. In one, Aβ engages macrophage CD36–NOX2 signaling and generates reactive oxygen species that impair neurovascular function. In the other, Aβ40 internalization promotes TSPAN4-dependent migrasome formation and enrichment of CD5L/AIM; vascularly deposited CD5L/AIM lowers endothelial CD59, facilitates C5b–9 formation, and damages the blood–brain barrier. A separate aging study indicates that CD5L/AIM-rich BAM migrasomes can transmit apoptosis resistance and senescence-like dysfunction to microglia. Human evidence is currently strongest for CAA rather than parenchymal AD: a small CAA cohort showed increased circulating CD14-positive migrasomes and monocyte TSPAN4, with an exploratory area under the ROC curve of approximately 0.91 for TSPAN4-positive monocytes versus healthy controls, whereas AD patients selected to lack imaging evidence of CAA did not show increased circulating migrasome counts. Accordingly, the Aβ40–TSPAN4–CD5L/AIM vascular branch should presently be regarded as a CAA-enriched mechanism that may be especially relevant to AD with prominent CAA, not as a universal mechanism of Aβ42-dominant sporadic AD without substantial vascular amyloid. Direct demonstration of BAM-derived migrasomes in human AD brain tissue is still lacking, and neither TSPAN4 nor CD5L/AIM is sufficiently specific to serve as a stand-alone biomarker. We therefore distinguish peer-reviewed human observations, experimental causal evidence, preprint findings, and proposed cross-pathway interactions and outline biomarker validation and pathway-selective therapeutic strategies that preserve beneficial BAM functions. Full article

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by the death of motor neurons leading to paralysis and death generally 3–5 years post-symptom onset. ALS is a cell- and non-cell-autonomous disease, with glia such as astrocytes influencing disease pathology and progression. Our laboratory has previously identified purine metabolism dysfunction in induced neural progenitor cell-derived astrocytes (iAstrocytes) from sporadic ALS (SALS) cases, driven by loss of the enzyme adenosine deaminase (ADA). Here, we have demonstrated that loss of ADA, along with changes to ecto-5′-nucleotidase and hypoxanthine-guanine phosphoribosyl transferase led to disruption in purine metabolite levels, linked to the level of the ADA enzyme. These alterations were recapitulated in SALS CSF and post-mortem tissue, with ageing and sex affecting purine metabolite levels downstream of ADA and positively correlating with disease progression. Loss of ADA led to reduced 53BP1-mediated DNA repair and increased P16 levels, which was recapitulated in control iAstrocytes via ADA inhibition. Our findings indicate that TDP43 dysfunction drives impairment of ADA-mediated purine metabolism in vitro, leading to downstream effects that include DNA damage, likely through inhibition of DNA repair mechanisms, and the induction of cellular senescence. Furthermore, these results suggest that therapeutic targeting of the ADA pathway may help slow ALS disease progression. Full article

The low temperature electrocatalysis of CO₂ to CO typically requires purified CO₂, adding complexity, cost, and energy penalties due to the need for separate CO₂ capture and purification processes. Electrochemical reactive capture (e-RCC) is emerging as a simplification of the process. The method combines CO₂ capture with amines to form ammonium carbamates which are then reduced to produce CO and H₂. Heterometallic polyoxometalate catalysts were evaluated for e-RCC by cyclic voltammetry showing that [SiCu₂^IIGa^III(H₂O)₃W₉O₃₇]⁹⁻ had the lowest overpotential and highest turnover frequency. A combination of cyclic voltammetry and controlled potential electrolysis and transport measurements of carbamates through Nafion membranes revealed that commonly used small-molecule carbamates easily traversed membranes and were oxidized at the anode to CO and CO₂. To avoid anodic amine oxidation, polyammonium carbamates were prepared, and the method provides an efficient way to convert CO₂ captured into valuable carbon monoxide. Controlled potential electrolysis confirmed that [SiCu₂^IIGa^III(H₂O)₃W₉O₃₇]⁹⁻ reduced polyammonium carbamate at a negative potential of −1 V vs. Ag/AgCl, forming CO and H_2, while other polyoxometalate catalysts yield CO and H₂ at more negative potentials of −1.3 V. This research combines the use of polyoxometalates for electrocatalysts for e-RCC and provides a potential pathway to avoid detrimental amine/carbamate anodic oxidation. Full article

Maternal immune activation (MIA) during pregnancy is a recognized risk factor for neurodevelopmental and neurodegenerative disorders, including Alzheimer’s disease. Although the long-term consequences of prenatal inflammation have been extensively investigated, the influence of biological sex on age-related behavioral and hippocampal alterations remains insufficiently understood. MIA was induced in pregnant Wistar rats by the intraperitoneal administration of lipopolysaccharide (100 μg/kg) on gestational day 17. Male and female offspring were examined at 12 months of age. Behavioral patterns were assessed using the Morris water maze and elevated plus maze. Hippocampal neuronal morphology and microglial and astrocytic phenotypes were evaluated by histology and IHC, while the expression of genes associated with inflammation, neurodegeneration, neuroplasticity, oxidative stress, and neurogenesis was determined by RT-qPCR. Prenatal LPS exposure produced persistent behavioral alterations in both sexes but with distinct phenotypes. Both male and female offspring exhibited increased anxiety-like behavior, whereas females showed reduced exploratory activity during spatial memory testing. Female offspring demonstrated more pronounced hippocampal pathology, including an increased relative number of pyknotic hyperchromic neurons, a reduced ramified-to-amoeboid microglia ratio, decreased Bdnf, and selective upregulation of Bace1 and Usp11, potentially indicating enhanced susceptibility to neurodegenerative processes. In contrast, males maintained predominantly ramified microglia morphology and showed increased expression of the neuronal progenitor gene Pax6, possibly suggesting the activation of compensatory mechanisms. Both sexes exhibited hippocampal upregulation of Il18, Arg1, Mmp9, Ntrk2, and Gpx4, consistent with chronic pro-inflammatory background accompanied by adaptive antioxidant and anti-inflammatory responses. Prenatal immune activation induces long-lasting behavioral, morphological, and molecular alterations that persist into middle age and exhibit marked sexual dimorphism. Female offspring appear more vulnerable to pro-neurodegenerative changes, whereas male offspring activate compensatory neuroprotective pathways that might partially preserve hippocampal function despite sustained pro-inflammatory reactions. These findings highlight sex as a critical biological variable in the long-term consequences of prenatal inflammation and may facilitate the identification of early biomarkers and therapeutic targets for MIA-associated neuropsychiatric and neurodegenerative disorders. Full article

The increasing frequency and severity of natural disasters attributable to climate change have placed growing pressure on farmers’ livelihoods in ecologically fragile areas. Reducing livelihood vulnerability and strengthening resilience are therefore essential for disaster risk reduction and sustainable development. Previous research has predominantly focused on assessing livelihood vulnerability and its influencing factors, leaving gaps in understanding regarding the formation mechanisms. Therefore, this study aimed to develop a framework based on exposure, sensitivity, and adaptability, drawing on survey data from 312 farmers in the Hehuang Valley. This research examined the characteristics of farmers’ livelihood vulnerability and employed structural equation modeling to explore its formation mechanism. Monte Carlo simulation was applied to assess how different scenarios affected the farmers’ livelihood vulnerability index (LVI). The LVI differed markedly across regions, age, education, and income. Pathway analysis identified a dual pattern of association from natural disasters to the LVI: they were positively associated with livelihood vulnerability through certain pathways while showing negative associations through other pathways that may reflect coping responses associated with reductions in the LVI. Within the formation mechanism, natural capital appeared more frequently in the long pathways from natural disasters to the LVI with negative action intensity, whereas housing security appeared more frequently in those with positive action intensity. Scenarios combining improvements in education and household income were associated with clear reductions in the LVI, irrespective of other variables. Accordingly, this study proposes measures to reduce livelihood vulnerability by lowering exposure and sensitivity while improving adaptability, thereby supporting resilience building and risk management in vulnerable areas. Full article

Breast cancer remains the most prevalent malignancy among middle-aged and elderly women with underlying health conditions, with triple-negative breast cancer (TNBC) representing a notably aggressive subtype associated with poorer clinical outcomes. Prunus africana (P. africana) has been reported to contain bioactive compounds with notable antioxidant and anticancer properties. Bark extracts obtained using water, as well as single (100%) and binary (50% v/v) solvents of methanol and ethanol (MeOH-100, EtOH-100, MeOH-50, and EtOH-50), were evaluated for their antioxidant activity, apoptosis-inducing effects, and modulation of signaling pathways in selected breast cancer cell lines. Antioxidant activity was measured via FRAP, DPPH radical scavenging, and TEAC assays; cytotoxic activity and pathway modulation were assessed using MTS, human apoptosis, and phospho-RTK array assays. While the EtOH-100 extract presented the lowest extraction yield of 3.22%, it showed the highest total phenolic (505.96 mg GAE/g) and total flavonoid (2.53 mg RU/g) contents and antioxidant activities (2.25 mM Fe²⁺/g and 311.68 mM TE/g), and the lowest EC₅₀ (0.21 mg/mL), comparable to ascorbic acid (0.18 mg/mL). EtOH-100 also notably induced apoptosis in HCC1806 as shown by increased cleaved caspase-3, HSP60, and HSP27 expression, and sustained catalase levels. Phospho-RTK array analysis revealed early silencing of HGF and transient upregulation of EGF and Insulin R following EtOH-100 extract treatment, suggesting modulation of oncogenic signaling. These findings highlight the therapeutic potential of P. africana, particularly the EtOH-100 extract, as a viable treatment for TNBC. Full article