Search Results (1,306)

Background/Objectives: While excessive body fat is commonly linked to metabolic disorders (metabolically unhealthy obesity, MUO), a subset of individuals remain metabolic healthy despite obesity (metabolically healthy obesity, MHO). This work aims to determine how these phenotypes influence responses to lifestyle modification (LSM) in older adults. Methods: A 12-month lifestyle modification (LSM) intervention based on the Mediterranean Diet (MedDiet) and regular physical activity (PA) was conducted in 43 older adults (70% women) classified according to World Health Organization (WHO) criteria as MHO (22 subjects) or MUO (21 subjects). Clinical, dietary, and PA parameters were assessed at baseline and follow-up. Peripheral blood mononuclear cells were analyzed for mitochondrial fusion (OPA1, MFN2), mitophagy (PINK1), biogenesis (TFAM), and the respiratory chain (COX IV) using Western blot and RT-qPCR techniques. Results: At baseline, MUO showed significant lower OPA1-L, MFN2, and TFAM along with MFN2 degradation products and PINK1 accumulation. After 12 months of LSM, MUO participants exhibited greater metabolic profile improvements, such as significantly reduced MFN2 degradation products and higher COX IV. Changes in mitochondrial proteins were associated with nutrient intake and PA and clinical parameters with phenotype-specific patterns. In MUO, protein and cholesterol intake improved MFN2 fusion (rho = 0.446, p = 0.043; rho = 0.581, p = 0.006), while carbohydrates were negatively associated with OPA1 in MHO (rho = −0.596, p = 0.025). PA was positively related to fusion proteins in both phenotypes. Clinically, significant improvements in BMI, waist circumference, and HDL were found in MUO but not in MHO. Conclusions: Older adults with obesity show phenotype-specific mitochondrial impairments that shape distinct responses to LSM, highlighting the relevance of tailoring LSM interventions by metabolic phenotype. Full article

Advanced glycation end products (AGEs) are important biomarkers associated with diabetes and metabolic disorders; yet existing detection methods are invasive and unsuitable for frequent monitoring. This study aimed to develop a non-invasive and portable AGEs detection device, optimize strategies for mitigating pigmentation-related interference, and evaluate its feasibility for metabolic assessment. The proposed system employs a 365 nm ultraviolet LED excitation source, an optical filter assembly integrated into an ergonomic dark chamber, and an eyelid-signal-based algorithm to suppress ambient light and skin pigmentation interference. Simulation experiments were conducted to evaluate the influence of different pigment colors and skin tones on fluorescence measurements. A clinical study was performed in 200 participants, among whom 42 underwent concurrent serum AGEs measurement as the reference standard. Predictive models combining corneal fluorescence signals and body mass index (BMI) were constructed and evaluated. The results indicated that purple and blue pigments introduced greater interference, whereas green and pink pigments had minimal effects. Device-derived AGEs estimates demonstrated good agreement with serum AGEs, with a mean error below 8%. A hybrid model incorporating BMI achieved improved predictive accuracy compared with single-parameter models. Participants with high-AGE dietary habits exhibited elevated fluorescence signals and BMI. These findings suggest that the proposed device enables stable and accurate non-invasive AGEs assessment, with potential utility for metabolic monitoring. Incorporating lifestyle-related parameters may further enhance predictive performance and expand clinical applicability. Full article

Pancreatic β-cell dysfunction is the key driver of type 2 diabetes, and anthocyanins have been proposed as dietary compounds that may help preserve β-cell health. This systematic review aimed to synthesise evidence on the direct effects of anthocyanins on β-cell viability, apoptosis, oxidative stress, and insulin secretion across in vitro models. Four databases were searched in March–April 2025, and eighteen studies met the inclusion criteria. Purified anthocyanins—including cyanidin-3-glucoside (C3G), cyanidin-3-rutinoside (C3R), malvidin-3-glucoside (M3G), and delphinidin-3-glucoside (D3G)—as well as anthocyanin-rich berry extracts, were tested in INS-1, MIN6, RIN-m5F cells and primary mouse or human islets under glucotoxic, lipotoxic, oxidative, cytokine, and amyloidogenic stress. Anthocyanins consistently improved β-cell viability, reduced apoptosis, and lowered reactive oxygen species (ROS), nitric oxide (NO), and thiobarbituric acid reactive substances (TBARSs) levels while enhancing antioxidant enzyme activities. Multiple studies showed upregulation of insulin secretion-related genes and proteins, and both acute and chronic treatments increased glucose-stimulated insulin secretion under normal and stressed conditions. Mechanistic pathways involved modulation of mitogen-activated protein kinase (MAPK) signalling, endoplasmic reticulum (ER) stress responses, inflammatory mediators, and mitophagy (PINK1/PARKIN). While effective in vitro concentrations were higher than typical circulating levels, the collective evidence highlights anthocyanins as promising β-cell protective agents and underscores the need for studies examining their metabolites and physiologically relevant exposure. Full article

Apatite is a widespread accessory mineral, which can provide information on the geochemical characteristics of magma and the conditions of hydrothermal alteration of the rocks in magmatic–hydrothermal deposits. This study aims to understand the relationships between the geochemical and textural features of apatites from diorite porphyries that have undergone different degrees of hydrothermal alteration in the Sharlo Dere area, Chelopech epithermal Cu-Au deposit, Bulgaria. The apatites were characterized by laser ablation–inductively coupled plasma mass spectrometry, scanning electron microscopy with energy-dispersive X-ray spectroscopy, electron probe microanalysis with wave-dispersive spectroscopy, optical cathodoluminescence and multi-element mapping. Magmatic apatites from “hematitic”, propylitic and propylitic-sericitic zones of alteration are distinguished by euhedral crystals with oscillatory zoning and brown luminescence in CL images. In quartz-sericitic alteration zones, apatite has a yellow CL response. Hydrothermally altered apatites in the diorite porphyries overprinted by advanced argillic alteration have corroded, irregular forms and pink-green luminescence. Apatite crystals of magmatic origin reveal high contents of chlorine, strontium, light rare earth elements (LREE), negative Eu anomalies and high La_N/Sm_N and Ce_N/Yb_N ratios. Hydrothermally altered or hydrothermal apatites are distinguished by their higher contents of Na₂O, F, SO₃, Y and middle rare earth elements (MREEs) and their low La_N/Sm_N and Ce_N/Yb_N ratios. The intensity of hydrothermal alteration affects the luminescence and major and trace element contents, including the rare earth element patterns in the apatites, implying apatite can be used as a geochemical indicator to study magmatic–hydrothermal ore deposits. Full article

Mitophagy, as a critical form of selective autophagy, plays a central role in maintaining cellular homeostasis. While the canonical PTEN-Induced Kinase 1 (PINK1)–Parkin pathway is well established, mitophagy can still be effectively induced in Parkin-deficient cells such as HeLa, indicating the existence of Parkin-independent alternative pathways. The mitochondrial matrix proteins 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) acts as a key effector in such pathways, yet its regulatory mechanisms remain incompletely understood. Here, we identify Ubiquitination Factor E4B (UBE4B) as an E3 ubiquitin ligase for NIPSNAP1 and demonstrate that it catalyzes NIPSNAP1 ubiquitination in both Human Embryonic Kidney 293 cells (HEK293T) and HeLa cells. Under mitochondrial depolarization, UBE4B not only promotes NIPSNAP1 ubiquitination and subsequent lysosome-dependent degradation, but also significantly enhances its interaction with the autophagy adaptors Nuclear Dot Protein 52 kDa (NDP52) and Sequestosome 1 (p62/SQSTM1). Notably, while Parkin does not ubiquitinate NIPSNAP1, UBE4B-mediated ubiquitination facilitates mitophagy in Parkin-null HeLa cells by strengthening the binding between NIPSNAP1 and NDP52. Collectively, this study unveils a novel mitophagy pathway regulated by the UBE4B-NIPSNAP1 axis, offering new insights into mitochondrial quality control. Full article

During tendon healing, collagen III expression precedes that of collagen I. The collagen I-to-III ratio at a certain time point post-laceration serves as an indicator of the healing status. Consequently, it is crucial to understand how different therapeutic approaches to support tendon healing affect the collagen I-to-III ratio in the extracellular matrix of a healing tendon, particularly across distinct anatomical zones. We compared the impact of a platelet-derived growth factor-BB (PDGF-BB) treatment via controlled release from coaxially electrospun DegraPol^® (Ab medica, Cerro Maggiore, Italy) hollow-fiber mesh with a treatment by the vehicle alone (no PDGF-BB) in the rabbit Achilles tendon full transection model and provide data on the collagen I-to-III ratio 3 weeks post-operation. For this purpose, we compared a dual-color Herovici staining to two single IHC labeling, for collagen I and collagen III, respectively. Herovici staining (HV) was expected to offer a more precise approach (pink-to-blue histogram) than the two separately labeled IHC stainings, both with chromogenic DAB labeling (red-to-green histogram), despite an anticipated positive correlation of the data assessed by these methods. Different zones were compared, i.e., native tendon tissue, reactive zone at interface to implant, hot zone within the core of the healing tendon and the zone within the scaffold, meaning the collagen deposited within the fibers of the implanted DegraPol^® tube, respectively. The analysis revealed that the ratios obtained via HV correlated weakly with the ratios obtained by IHC. Based on HV, PDGF-BB therapy led to higher collagen I-to-III ratios in all zones, except for the zone within the scaffold pores, while IHC did not reveal significant differences. Notably, collagen I-to-III ratios were not higher in immediate proximity, but rather distal from the PDGF-BB releasing implant, specifically in the core of the healing tendon tissue. Hence, a PDGF-BB therapy is suggestive of greater collagen maturation in specific zones of the healing tendon. Full article

Biosurfactants produced by halophilic bacteria are gaining attention as eco-friendly and biocompatible alternatives to synthetic surfactants due to their high surface activity, stability under extreme conditions, and intrinsic antimicrobial properties. These amphiphilic biomolecules hold great promise for bioremediation, biomedical, and pharmaceutical applications. In this study, moderately halophilic bacteria capable of biosurfactant production were isolated from saline mud collected at the Burgas solar salterns (Bulgaria). The halophilic microbiota was enriched in Bushnell–Haas (BH) medium containing 10% NaCl amended with different carbon sources. Primary screening in BH liquid medium evaluated the isolates’ ability to degrade n-hexadecane while at the same time producing biosurfactants. Thirty halophilic bacterial strains were isolated on BH agar plates supplemented with 2% n-hexadecane, 2% olive oil, or 2% glycerol. Four isolates—BS7OL, BS8OL, BS9GL, and BS10HD—with strong emulsifying activity (E₂₄ = 56%) and reduced surface tension in the range of 27.3–45 mN/m were derived after 7 days of batch fermentation. Strain BS10HD was chosen as the most potent biosurfactant producer. Its phylogenetic affiliation was determined by 16S rRNA gene sequence analysis; according to the nucleotide sequence, it was assigned to Halomonas ventosae. The extract material was analysed by thin-layer chromatography (TLC) and Fourier transform infrared spectroscopy (FTIR). Upon spraying the TLC plate with ninhydrin reagent, the appearance of a pink spot indicated the presence of amine functional groups. FTIR analysis showed characteristic peaks for both lipid and peptide functional groups. Based on the observed physicochemical properties and analytical data, it can be suggested that the biosurfactant produced by Halomonas ventosae BS10HD is a lipopeptide compound. Full article

Oocytes cultured in vitro are exposed to high oxygen tension and lack follicular antioxidants, leading to redox imbalance. Eicosapentaenoic acid (EPA), a marine long-chain n-3 polyunsaturated fatty acid, possesses strong antioxidant activity. Here, using pigs as a model, we examined the effects of EPA on oocyte in vitro maturation (IVM) and subsequent developmental competence. Cumulus–oocyte complexes were cultured with EPA, followed by assessment of nuclear and cytoplasmic maturation and embryonic development; transcriptomic and proteomic analyses were conducted to explore underlying mechanisms. Supplementation with 10 µM EPA significantly improved maturation and blastocyst rates by reducing spindle defects, facilitating a more uniform organization of cortical granules and mitochondria. EPA increased resolvin E1 accumulation and reduced cumulus-cell apoptosis through downregulation of TNF-α and BAX and upregulation of BCL2. In MII oocytes, EPA lowered apoptosis, DNA damage, and ROS levels while enhancing SOD2 and GPX4 expression. Mitochondrial quality and turnover were improved via upregulation of PPARGC1A, NDUFS2, PINK1, LC3, FIS1, MUL1, and OPA1, alongside strengthened ER–mitochondria contacts. These findings demonstrate that EPA alleviates oxidative stress, optimizes mitochondrial function, and enhances porcine oocyte maturation and developmental competence in a parthenogenetic model, highlighting its potential as a marine-derived functional additive for reproductive biotechnology. Future studies will be required to validate these effects under fertilization-based embryo production systems and to further refine dose–response relationships using expanded embryo-quality endpoints. Full article

Mitochondrial dysfunction is a key early pathological process in neurodegenerative diseases (NDs), leading to oxidative stress, impaired energy metabolism, and neuronal apoptosis prior to the onset of clinical symptoms. Although mitochondria represent important therapeutic targets, effective interventions targeting mitochondrial function remain limited. This review summarizes current evidence regarding the mechanisms by which melatonin protects mitochondria and evaluates its therapeutic relevance, with a primary focus on Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease—the major protagonists of NDs—while briefly covering other NDs such as amyotrophic lateral sclerosis, multiple sclerosis, and prion diseases. Melatonin selectively accumulates in neuronal mitochondria and exerts neuroprotection through multiple pathways: (1) direct scavenging of reactive oxygen species (ROS); (2) transcriptional activation of antioxidant defenses via the SIRT3 and Nrf2 pathways; (3) regulation of mitochondrial dynamics through DRP1 and OPA1; and (4) promotion of PINK1- and Parkin-mediated mitophagy. Additionally, melatonin exhibits context-dependent pleiotropy: under conditions of mild mitochondrial stress, it restores mitochondrial homeostasis; under conditions of severe mitochondrial damage, it promotes pro-survival autophagy by inhibiting the PI3K/AKT/mTOR pathway, thereby conferring stage-specific therapeutic advantages. Overall, melatonin offers a sophisticated mitochondria-targeting strategy for the treatment of NDs. However, successful clinical translation requires clarification of receptor-dependent signaling pathways, development of standardized dosing strategies, and validation in large-scale randomized controlled trials. Full article

Nitrite, as a widely present nitrogen oxide compound in nature, and is extensively distributed in production and daily life; precise and rapid detection of it is of great significance for ensuring human health. This study developed nitrogen-doped carbon dots (N-CDs) using malic acid and 3-diethylaminophenol as precursors by one-step hydrothermal treatment. The obtained N-CDs exhibited strong green fluorescence with a high quantum yield of 20.86%. More importantly, they served as a highly effective fluorescent probe for NO₂⁻ sensing, demonstrating a low detection limit of 28.33 μM and a wide linear response range of 400 to 1000 μM. The sensing mechanism was attributed to an electrostatic interaction-enhanced dynamic quenching process. Notably, the probe enabled dual-mode detection: a distinct color change from light pink to dark brown under daylight for visual semi-quantification, and quantitative fluorescence quenching. The N-CDs showed excellent selectivity over common interfering ions. Furthermore, their low cytotoxicity and good biocompatibility allowed for successful bioimaging of exogenous and endogenous NO₂⁻ fluctuations in live HeLa cells. This work presents a facile green strategy to synthesize multifunctional N-CDs that realized the sensitive, selective, and visual detection of NO₂⁻ in environmental and biological systems. Full article

Zanthoxylum bungeanum leaves (ZBL) are a phytogenic feed resource, but their energy value and functional effects in laying hens are not well defined. Two experiments were conducted. In Exp. 1, 96 healthy 38-week-old Roman Pink laying hens were allotted to either a control diet or a diet containing 5% ZBL (eight replicates, six hens per replicate) to determine apparent metabolizable energy (AME) using an indicator method (7 d adaptation, 3 d collection). The AME and nitrogen-corrected AME of ZBL were 5.46 and 5.33 MJ/kg, respectively. In Exp. 2, 832 healthy 41-week-old hens were randomly assigned to diets supplemented with 0, 1%, 2%, or 3% ZBL (8 replicates, 26 hens per replicate) for 8 weeks after 1 week adaptation. Dietary ZBL at 1% to 3% did not affect production performance (p > 0.05), but increased albumen height linearly (p < 0.05) and improved yolk color at 2% and 3% (p < 0.05). ZBL increased serum albumin (p < 0.05) with a linear tendency (p = 0.065), and elevated serum IgA and IgM linearly (p < 0.05). Serum total antioxidant capacity and total superoxide dismutase were increased (p < 0.05) with significant linear and quadratic responses (p < 0.05), while serum malondialdehyde was reduced (p < 0.05). In the liver, 3% ZBL increased total antioxidant capacity (p < 0.05), hepatic catalase activity was decreased in all ZBL groups (p < 0.05), and hepatic malondialdehyde was reduced (p < 0.05). Cecal acetate increased linearly (p < 0.05), and propionate and butyrate increased with both linear and quadratic dose responses (p < 0.05). ZBL improved small intestinal morphology, especially duodenal villus height (p < 0.05). Gut microbiota was remodeled, with a marked reduction in norank_o__WCHB1-41 and increases in Ruminococcus, Pseudoflavonifractor, and several Coriobacteriales and Erysipelatoclostridiaceae taxa. Overall, ZBL provides usable energy and, at 2–3% inclusion, enhances egg quality, antioxidant status, humoral immunity, short-chain-fatty-acid production, and intestinal health without compromising laying performance. Full article

The purpose of this research was to investigate whether music empirically associated with therapeutic effects contains intrinsic informational structures that differentiate it from other sound sequences. Drawing on ontology, phenomenology, nonlinear dynamics, and complex systems theory, we hypothesize that therapeutic relevance may be linked to persistent structural patterns embedded in musical signals rather than to stylistic or genre-related attributes. This paper introduces the Discriminating Music Sequences (DiMuSes) method, an unsupervised, structure-oriented analytical framework designed to detect such patterns. The method applies 24 scalar evaluators derived from statistics, fractal geometry, nonlinear physics, and complex systems, transforming sound sequences into multidimensional vectors that characterize their global temporal organization. Principal Component Analysis (PCA) reduces this feature space to three dominant components (PC1–PC3), enabling visualization and comparison in a reduced informational space. Unsupervised k-Means clustering is subsequently applied in the PCA space to identify groups of structurally similar sound sequences, with cluster quality evaluated using Silhouette and Davies–Bouldin indices. Beyond clustering, DiMuSe implements ranking procedures based on relative positions in the PCA space, including distance to cluster centroids, inter-item proximity, and stability across clustering configurations, allowing melodies to be ordered according to their structural proximity to the therapeutic cluster. The method was first validated using synthetically generated nonlinear signals with known properties, confirming its capacity to discriminate structured time series. It was then applied to a dataset of 39 music and sound sequences spanning therapeutic, classical, folk, religious, vocal, natural, and noise categories. The results show that therapeutic music consistently forms a compact and well-separated cluster and ranks highly in structural proximity measures, suggesting shared informational characteristics. Notably, pink noise and ocean sounds also cluster near therapeutic music, aligning with independent evidence of their regulatory and relaxation effects. DiMuSe-derived rankings were consistent with two independent studies that identified the same musical pieces as highly therapeutic.The present research remains at a theoretical stage. Our method has not yet been tested in clinical or experimental therapeutic settings and does not account for individual preference, cultural background, or personal music history, all of which strongly influence therapeutic outcomes. Consequently, DiMuSe does not claim to predict individual efficacy but rather to identify structural potential at the signal level. Future work will focus on clinical validation, integration of biometric feedback, and the development of personalized extensions that combine intrinsic informational structure with listener-specific response data. Full article

Background/Objectives: Obstructive sleep apnea (OSA) affects approximately 1 billion adults worldwide with extensive comorbidities, including cardiovascular disease, metabolic disorders, and cognitive decline, yet pharmacological therapies remain limited. Conventional bottom-up omics approaches identify numerous genes overlapping with other diseases, hindering therapeutic translation. This study introduces a top-down, comorbidity-driven approach to identify actionable molecular targets and develop rational dual kinase inhibitors for OSA management. Methods: We implemented a five-tier modeling workflow: (1) comorbidity network analysis, (2) disease module identification through NetworkAnalyst, (3) mechanistic pathway reconstruction of the CK1δ-(HIF1A)-PINK1 signaling cascade, (4) molecular docking analysis of Nigella sativa alkaloids and reference inhibitors (IC261, PF-670462) against CK1δ (PDB: 3UYS) and PINK1 (PDB: 5OAT) using AutoDock Vina, and (5) rational design and computational validation of novel dual inhibitors (ICL, PFL) integrating pharmacophoric features from natural alkaloids and established kinase inhibitors. Results: Extensive network analysis revealed a discrete OSA disease module centered on two interconnected protein kinases—CK1δ and PINK1—that mechanistically bridge circadian disruption and neurodegeneration. Among natural alkaloids, Nigellidine showed strongest CK1δ binding (−8.0 kcal/mol) and Nigellicine strongest PINK1 binding (−8.6 kcal/mol). Rationally designed dual inhibitors demonstrated superior binding: ICL (−7.2 kcal/mol PINK1, −8.9 kcal/mol CK1δ) and PFL (−10.8 kcal/mol CK1δ, −11.2 kcal/mol PINK1), representing −2.6–2.8 kcal/mol improvements over reference compounds. Conclusions: This study establishes a comorbidity-driven translational framework identifying the CK1δ-PINK1 axis as a therapeutic target in OSA. The rationally designed dual inhibitors represent third-generation precision therapeutics addressing OSA’s multi-dimensional pathophysiology, while the five-tier workflow provides a generalizable template for drug discovery in complex multimorbid diseases. Full article

Rhodoliths (from Greek etymology meaning red + stone) are spheroidal accretions composed of various types of crustose coralline red algae that dwell in relatively shallow waters where sunlight allows for photosynthesis. Unlike most other kinds of algae that are attached to the seabed by a holdfast, rhodoliths are free to roll about by circumrotary movements stimulated mainly by gentle wave action and bottom currents, as well as by disruptions by associated fauna. Frequent movement exposes every part of the algal surface to an equitable amount of sunlight, which generally results in an evenly concentric pattern of growth over time. Individual structures may attain a diameter of 10 to 20 cm, representing 100 years of growth or more. Initiation typically involves encrustation by founder cells on a rock pebble or shell fragment. In life, the functional outer surface is red or pink in complexion, whereas the structure’s inner core amounts to dead weight. Chemically, rhodoliths are composed of high magnesium calcite [(Ca,Mg)CO₃], with examples known around many oceanic islands and virtually all continental shelves in the present world. The oldest fossil rhodoliths appeared during the early Cretaceous, 113 million years ago. Geologically, rhodoliths may occur in massive limestone beds composed of densely packed accumulations. Living rhodoliths commonly occur in waters as shallow as −2 to −10 m, as well as seaward in mesophotic waters up to −100 m under exceptional conditions of water clarity. Especially in shallower waters, rhodoliths are vulnerable to transfer by storm waves to supratidal settings, which result in bleaching under direct sunlight and death. Increasingly, marine biologists recognize that rhodolith beds represent a habitat that offers shelter to a community of other algae and diverse marine invertebrates. Full article