Search Results (1,677)

Background/Objectives: Percutaneous coronary intervention (PCI) effectively restores coronary flow in acute myocardial infarction (AMI), but myocardial ischemia–reperfusion injury (MIRI) remains a major prognostic determinant. Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) has shown cardiovascular protective effects, yet its association with MIRI is unclear. This study aimed to investigate the relationship between serum MOTS-c levels and MIRI in AMI patients. Methods: Seventy-two AMI patients undergoing PCI were enrolled and divided into MIRI (n = 34) and non-MIRI (n = 38) groups. Clinical data and MOTS-c levels in peripheral serum and intracoronary blood were compared. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed to identify MIRI predictors. Results: The MIRI group exhibited lower systolic blood pressure, preoperative thrombolysis in myocardial infarction (TIMI) grade, and HDL-C, but higher total ischemic time, door-to-balloon time, culprit vessel stenosis severity, Killip grade and adverse event incidence (all p < 0.05). Postoperative peripheral serum MOTS-c levels were significantly lower in the MIRI group than in the non-MIRI group (p < 0.05), while preoperative peripheral and intracoronary MOTS-c levels showed no significant differences between groups. Multivariate logistic regression identified postoperative peripheral MOTS-c levels (OR = 0.986, 95%CI: 0.976–0.996) and preoperative TIMI grade ≥ 1 (OR = 0.036, 95%CI: 0.004–0.309) as independent protective factors for MIRI, whereas serum creatinine was identified as an independent risk factor. ROC analysis demonstrated that postoperative peripheral MOTS-c levels predicted MIRI with an area under the curve of 0.648. Conclusions: Postoperative peripheral serum MOTS-c levels represent an independent protective factor against MIRI in patients with acute myocardial infarction and suggest a potential predictive value for MIRI, although its clinical utility as a standalone predictor requires further validation through dynamic monitoring and larger-scale studies. This finding may offer a potential novel biomarker and therapeutic direction for MIRI. Full article

The reproductive caste of higher termites exhibits remarkable longevity, but the mechanisms by which they manage age-related oxidative stress during lifespan extension remain insufficiently understood. This study investigated the dynamic regulation of the insulin/IGF (IIS)–FOXO axis, a key anti-aging regulatory pathway that integrates insulin signaling with downstream processes, including antioxidant defense and DNA repair, as well as the superoxide dismutase (SOD) system in female Odontotermes formosanus reproductives at various life stages (Swarming Queen (SQ), 1-Year Queen (1YQ), 8-Year Queen (8YQ)) through transcriptomic, qRT-PCR, and enzyme activity analyses. Age-dependent upregulation of IIS pathway components (InR, chico, PDK1, Akt, Sirt1, FOXO) was observed, alongside the identification of six SOD transcripts, including two SOD1, two SOD2, and two SOD3 isoforms. Notably, mitochondrial SOD2 (particularly SOD2_b) showed a progressive increase with age, exhibiting the highest enzymatic activity and being associated with reduced mitochondrial oxidative stress and the disruption of reactive oxygen species (ROS) amplification cycles. These findings suggest that O. formosanus reproductives counteract the potential lifespan-reducing effects of chronic IIS activation by maintaining or enhancing FOXO activity, thereby supporting DNA repair, antioxidant defenses, and cellular homeostasis. The IIS–FOXO–SOD2 axis is identified as a key regulator of reproductive longevity in higher termites, offering new insights into the molecular mechanisms behind lifespan extension in social insects. Full article

Beyond their classical role as “cellular powerhouses”, mitochondria are increasingly recognized as dynamic and interconnected networks whose architecture, quality control, and intercellular communication influence cellular and organismal homeostasis. Mitochondrial dynamics—including fusion–fission balance, mitophagy–biogenesis coupling, intracellular organization, and intercellular transfer via tunneling nanotubes, extracellular vesicles, or transient cell fusion—contribute to tissue adaptation and functional decline during aging. Focusing on cardiac muscle, skeletal muscle, and the nervous system, this narrative review synthesizes current evidence describing how aging disrupts mitochondrial network integrity through altered dynamics, impaired organelle positioning and transport, reduced mitophagy, mtDNA instability, and compromised metabolic coupling between cells. These alterations propagate across tissues, limiting energetic flexibility, stress resilience, and regenerative capacity. Building on these mechanisms, we discuss a systems-level perspective in which aging is associated with progressive loss of mitochondrial network coherence rather than solely cumulative molecular damage. Within this framework, mitochondrial connectivity functions as an integrative descriptor of cellular resilience: well-organized networks counteract metabolic perturbations, whereas functionally decoupled networks amplify stress and promote maladaptive aging trajectories. Emerging evidence indicates that physiological and pharmacological interventions, including endurance exercise, caloric restriction or mimetics, fusion-supporting pathways, and mitophagy-enhancing strategies, can partially restore network organization even later in life. Molecular, cellular, and tissue-level insights are integrated to highlight mitochondrial network dynamics as both a mechanistic contributor to aging and a potentially modifiable target for future preventive and therapeutic interventions. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by cholinergic dysfunction, amyloid-β aggregation, mitochondrial stress, and aberrant kinase activity. Carotenoids, naturally occurring pigments with antioxidant and neuroprotective properties, have emerged as promising candidates for AD intervention. In this study, we performed a systematic stepwise computational screening of a large carotenoid library (n = 1191) to identify multitarget candidates against AD–related proteins. The workflow consisted of predefined ADMET filtering (oral absorption > 90%, Caco-2 > 0.9, logBB > −1, and absence of major CYP inhibition and toxicity alerts), reducing the dataset to 61 compounds, followed by multi-target molecular docking against AChE, BChE, BACE-1, MAO-B, and GSK3-β. Compounds were ranked using an aggregated mean docking score across all five targets, and the top-performing candidate was subjected to detailed mechanistic analyses. Hopkinsiaxanthin emerged as the highest-ranked multitarget carotenoid and was further evaluated using frontier molecular orbital (FMO) analysis, pharmacophore modeling, 100 ns molecular dynamics (MD) simulations, MM/PBSA binding free energy calculations, and per-residue decomposition. Docking predicted favorable estimated binding affinities toward all targets. MD simulations confirmed stable receptor–ligand complexes with low RMSD values (0.278–0.285 nm). MM/PBSA analysis indicated favorable binding free energies, particularly for GSK3-β (−22.73 kcal/mol) and AChE (−21.50 kcal/mol). Per-residue decomposition identified key hotspot residues driving stabilization. Overall, this structured computational framework identifies Hopkinsiaxanthin as a promising multitarget scaffold and supports its prioritization for experimental validation in AD models. Full article

Leucine-rich repeat kinase 2 (LRRK2) is a multidomain serine/threonine kinase and a major genetic contributor to Parkinson’s disease (PD). Although LRRK2 has been extensively studied in neurodegeneration, emerging evidence indicates that it also plays a critical role in systemic metabolism. LRRK2 regulates glucose homeostasis through modulation of insulin signaling, vesicle trafficking, mitochondrial function, and inflammatory responses. Studies using LRRK2 knockout and knock-in models, including the pathogenic G2019S mutation, have revealed abnormalities in insulin sensitivity, adipose tissue inflammation, hepatic glucose production, and skeletal muscle metabolism. Mechanistically, LRRK2 phosphorylates Rab GTPases, thereby controlling insulin receptor trafficking and GLUT4 translocation. In addition, LRRK2 influences mitochondrial dynamics and reactive oxygen species production, linking metabolic stress to inflammatory signaling. Importantly, LRRK2 also regulates innate immune pathways, including TLR4–NFκB signaling and inflammasome activation, thereby connecting peripheral metabolic dysfunction to neuroinflammation. Here, we propose an integrated metabolic–neuroinflammatory crosstalk model in which LRRK2 functions as a molecular coordinator linking peripheral metabolic dysfunction to central neurodegeneration. In this framework, systemic metabolic stress—characterized by insulin resistance, chronic inflammation, advanced glycation end product (AGE) accumulation, and blood–brain barrier disruption—drives microglial activation and neurodegenerative processes. Understanding this systemic axis may provide new therapeutic opportunities targeting both metabolic dysfunction and neurodegeneration in PD. Full article

Adolescence is a metabolically vulnerable period, during which rapid physiological maturation coincides with the dynamic remodelling of the gut microbiome. This narrative review summarises evidence from 2015 to 2025 to clarify how disturbances to the gut–liver axis driven by dysbiosis contribute to the development and progression of non-alcoholic fatty liver disease (NAFLD) in young people. Based on a systematic search of the databases PubMed, Scopus and Web of Science, we outline the basis of bidirectional communication between the gut and liver and emphasise how microbial imbalance alters the handling of lipids in the liver by enhancing de novo lipogenesis, impairing fatty acid oxidation and disrupting AMPK signalling and mitochondrial function. Consistent findings from clinical and experimental studies show that adolescents with NAFLD exhibit reduced microbial diversity, the enrichment of ethanol- and LPS-producing taxa, and altered short-chain fatty acid profiles. Each of these is associated with hepatic inflammation and metabolic reprogramming. Microbial molecules, including LPS, secondary bile acids and branched-chain amino acid metabolites, activate TLR4–NF-κB pathways, promote Kupffer cell activation and intensify oxidative stress. These mechanisms intersect with factors specific to adolescence, such as increased adiposity, hormonal shifts and diet-induced metabolic strain. Dietary patterns emerge as key modulators of these processes. Westernised diets promote dysbiosis and endotoxemia, whereas Mediterranean, fibre-rich and plant-based diets enhance SCFA production, strengthen epithelial integrity and modulate adiponectin-dependent hepatic metabolism. Micronutrient-sensitive epigenetic regulation, particularly that involving folate, choline and polyphenols, also plays a role in shaping lipid homeostasis and inflammatory tone. We also highlight emerging evidence that the activation of cytoprotective pathways, especially Nrf2, is dependent on lifestyle factors and links antioxidant-rich functional foods and physical activity to improved mitochondrial resilience and microbiome stability. We evaluate therapies targeting the microbiome, including probiotics, prebiotics, synbiotics and postbiotics, which reduce endotoxemia, restore microbial balance and complement dietary strategies. Thus, these findings emphasise the importance of age-specific, mechanistically informed interventions that integrate diet quality, microbial ecology, and the molecular pathways that govern metabolic health in adolescents with NAFLD. Full article

Nutrient-sensing nuclear receptors (NSNRs), including PPARs, FXR, LXRs, RAR/RXR, VDR, and related orphan receptors, integrate a molecular interface that allows diet to communicate directly with the genome. By binding fatty acids, bile acids, sterols, vitamins, polyphenols, and other food-derived metabolites, NSNRs translate qualitative and quantitative features of the diet into coordinated transcriptional programmes across metabolically active organs. This ligand-dependent signalling network integrates dietary information to orchestrate inter-organ lipid and glucose metabolism, mitochondrial function, thermogenesis, and immune response, thereby enabling the organism to adapt dynamically to fasting–feeding cycles. In this review, we synthesise current evidence on the integrated roles of major NSNRs in the liver, skeletal muscle, white and brown adipose tissue, and kidney, emphasising how receptor networks within and between metabolic organs collectively govern energy expenditure, substrate partitioning, and systemic metabolic flexibility. We propose a conceptual framework in which diet functions as an “external endocrine organ”, acting as the primary source of chemically diverse NSNR ligands, while metabolic tissues serve as secondary signal amplifiers and integrators. Through circulating lipid species, bile acids, oxysterols, and other metabolites, these organs engage in continuous bidirectional communication that reprograms NSNR activity across tissues. We then examine how the global shift from minimally processed, nutrient-rich foods to nutrient-poor, energy-dense ultra-processed diets leads to a reduction in NSNR ligand diversity, promoting hepatic steatosis, muscle metabolic inflexibility, adipose tissue dysfunction, renal lipotoxicity, and chronic low-grade inflammation, ultimately causing obesity, type 2 diabetes, and cardiometabolic disease. Finally, we explore strategies to restore NSNR function, including Mediterranean and plant-based dietary patterns, as well as diets enriched with ω-3 polyunsaturated fatty acids, monounsaturated fats, and polyphenols. By integrating molecular, physiological, and clinical evidence, this review aims to clarify how NSNR networks translate dietary cues into coordinated inter-organ metabolism and how nutrient-poor diets lead to metabolic diseases trough a loss of metabolic information, rather than merely by energy excess. This framework supports a paradigm shift from calorie-centred nutrition to diet quality as the main therapeutic target for preventing metabolic diseases and promoting health. Full article

Chemotherapy resistance remains a major obstacle to durable cancer control, yet its underlying mechanisms cannot be fully explained by genetic mutations alone. Increasing evidence suggests that therapeutic stress induces dynamic adaptive programs that reshape tumor phenotypic landscapes. Here, we propose a systems-level framework in which chemotherapy resistance emerges from the stabilization of interconnected stress-response circuits integrating redox signaling, metabolic reprogramming, and transcriptional plasticity. In this model, cytotoxic therapies function as state-generating perturbations that elevate oxidative stress and activate adaptive buffering systems, including NADPH-dependent redox homeostasis, replication stress tolerance, and integrated stress response (ISR)-mediated translational reprogramming. These adaptive modules collectively expand the accessibility of therapy-tolerant phenotypic states within tumor cell populations. Importantly, these circuits coordinate mitochondrial redox homeostasis, metabolic NADPH regeneration, and epigenetic–transcriptional plasticity to sustain cellular survival under persistent oxidative pressure. Such adaptive redox networks not only stabilize stress-tolerant phenotypes but also create vulnerabilities that can be therapeutically exploited. From a translational perspective, this framework suggests that effective strategies to overcome chemotherapy resistance should move beyond single-target inhibition and instead focus on circuit-guided therapeutic interventions that simultaneously destabilize redox buffering systems, constrain phenotypic plasticity, and disrupt metabolic stress adaptation. By conceptualizing therapy resistance as a dynamic redox-regulated state-space phenomenon, this model provides a mechanistic foundation for the development of evolution-aware and plasticity-constraining therapeutic strategies. Targeting the coordinated redox–metabolic–translational circuits that maintain tumor adaptability may therefore represent a promising direction for next-generation redox therapeutics in cancer. Full article

Postglacial expansion dynamics strongly influence the genetic structure of temperate species; however, mitochondrial data from the Baltic region are limited. To assess diversity, phylogenetic origins, and regional structuring, we analyzed mitochondrial cytochrome b (726 bp) and control region (421–422 bp) sequences of the common vole (Microtus arvalis Pallas, 1779) from Lithuania. Of the 91 cytb sequences and 70 control region sequences analyzed, five and four haplotypes were identified, respectively. Markedly low haplotype and nucleotide diversity compared with most European populations were detected. Phylogenetic Maximum Likelihood and network analyses revealed that all Lithuanian haplotypes belong to the eastern European lineage and are most closely related to Polish and central European samples, which supports recolonization from a Carpathian refugium. Despite the overall low variation, we detected two distinct mitochondrial groups: a highly differentiated western group and a second group encompassing eastern, northern, and central–southern populations. This strong regional structuring suggests limited maternal gene flow on a small geographic scale. There was no evidence of introgression from related taxa, such as Microtus obscurus. Our findings refine the phylogeographic context of Baltic M. arvalis and highlight the region’s role in shaping postglacial diversity patterns. Full article

Halogenated derivatives of polycyclic aromatic hydrocarbons (PAHs), such as chlorinated PAHs (ClPAHs), are an emerging class of contaminants that are being detected in the environment as well as in wildlife and human populations. Previous studies have shown that chemical substitution of PAHs, including chlorination, may alter the toxicity of parent PAHs; however, whether chlorination affects their endocrine-disrupting potential remains unexplored. In this study, we examined the effects of phenanthrene (Phe), one of the most prevalent PAHs, and its chlorinated congeners, 9-chlorophenanthrene (9ClPhe) and 9,10-dichlorophenanthrene (9,10Cl₂Phe), on hormone production in granulosa cells, key hormone-secreting cells of the ovary. We observed that Phe and its chlorinated congeners differentially altered anti-Müllerian hormone (AMH), estradiol (E2), and progesterone (P4) secretion. Since mitochondria are central to steroidogenesis, we further evaluated mitochondrial function. While Phe increased ATP production, both 9ClPhe and 9,10Cl₂Phe increased ROS, decreased mitochondrial membrane potential, and reduced the expression of markers for mitochondrial dynamics and mitophagy without altering ATP levels. We further tested impacts on cell fate and found that neither Phe nor its chlorinated congeners altered granulosa cell apoptosis. Together, these results suggest that chlorination of Phe leads to dose-dependent, differential effects on hormone production and mitochondrial pathways without inducing cell death in granulosa cells. This study highlights the potential adverse impacts of ClPAH exposure on ovarian follicle development and female fertility by disrupting steroidogenesis and mitochondrial quality control. Full article

Horizontal Gene Transfer (HGT) is a hallmark of the evolution of parasitic plants, facilitated by the haustorial connection. While mitochondrial HGT is widespread, the extent of nuclear HGT and the long-term retention of foreign genetic material in holoparasitic lineages remain poorly understood. This study explores the genomic architecture of Prosopanche americana (Hydnoraceae), a non-photosynthetic holoparasite currently specialized on Fabaceae. Through a comparative phylogenomic approach integrating draft mitochondrial genomes (mtDNA) and nuclear transcriptomes of P. americana, we identified a multi-layered landscape of foreign DNA. The mtDNA of P. americana contains 18 foreign regions (>500 bp) primarily derived from Solanales, Malvales, and Fabales. Notably, 13 of these regions are shared with P. panguanensis, indicating they were acquired in their common ancestor before speciation and ecological shift. In the nuclear genome, we identified 303 horizontally acquired transcripts (99 orthogroups) with high confidence. Functional analysis revealed an enrichment of foreign genes involved in metabolic pathways and plastid functions (e.g., photosystems and thylakoids) exclusively derived from the ancestral host order Solanales. Our results demonstrate that the genome of P. americana acts as a “molecular fossil,” preserving evidence of past ecological interactions with diverse host lineages. The disparity in HGT footprints between the current host (Fabaceae) and ancestral hosts suggests a period of high genomic plasticity followed by host specialization, providing new insights into the timing and dynamics of horizontal gene flow in holoparasitic Piperales. Full article

Understanding salmonid spawning dynamics is critical for conserving cold-water river ecosystems amid increasing human and climate pressures. This study developed and validated a species-specific eDNA (Salmo cf. trutta and Thymallus thymallus) and evaluated its performance for seasonal spawning activity monitoring using droplet digital PCR (ddPCR). Species-specific primers and probes targeting mitochondrial nd5 (S. trutta) and cytb (T. thymallus) genes were designed and optimized as a duplex assay. Performance assessments included in vitro validation, cross-amplification testing, and determining the LOB, LOD, and LOQ. Field validation over a year at two spawning sites in the Gradac River, Serbia, involved seasonal eDNA sampling, filtration, extraction, and ddPCR analysis. Fish community composition was also assessed with electrofishing and metabarcoding. The assay showed high specificity and sensitivity, with LODs of 0.14 cp/µL and LOQs of 0.99 and 1.25 cpµL for S. trutta and T. thymallus. S. trutta eDNA peaked in late autumn during spawning, while T. thymallus remained at or below detection limits, reflecting its lower abundance and different spawning season. Filter type affected filtration efficiency but not eDNA yield. These findings confirm ddPCR-based eDNA as a powerful, non-invasive tool for monitoring salmonid spawning and seasonal changes, supporting adaptive fisheries management and conservation amid environmental changes. Full article

Cardiovascular diseases have been one of the leading causes of death worldwide for over 30 years and coronary artery disease occupies a prominent place among them. Predicting the long-term outcome after coronary artery bypass graft (CABG) is still a challenging task; however, since platelets are directly involved in the course of the disease, their functional status can help predict postoperative complications. The objective was to evaluate the dynamics of platelet apoptosis before and after CABG. The study involved 30 patients with a scheduled CABG suffering from coronary artery disease. Flow cytometry, Western blot and polymerase chain reaction were used to evaluate apoptosis and the activation of platelets. Changes in platelet membranes and the depolarization of mitochondrial membranes were observed, as well as the expression of active caspase 8 and BCL-2, indicating the activation of apoptosis through an extrinsic receptor-dependent signaling pathway. The data obtained suggest significant changes in platelet metabolic processes, which could play a crucial role in the development of coronary artery disease and atherosclerosis as well as being associated with postoperative complications. Full article

Cellular homeostasis is a dynamic process which balances anabolic processes with catabolic and recycling processes. These processes require nutrients, which are converted to energy to fuel the complex interactions of intracellular signalling. Cellular health requires that, on average, energy input and energy requirements are matched. Cells contain a nutrient-sensing mechanism which controls the balance between anabolism and catabolism. Normal intracellular functions generate products which regulate signalling pathways, and health at a cellular level requires a fluctuation between relative nutrient abundance and relative nutrient scarcity. This allows clearance of damaged intracellular molecules and organelles. When nutrient supply exceeds cellular requirements, adaptations to intracellular signalling occur, resulting in energy being stored as glycogen in muscle and the liver and fatty acids in adipose tissue. Overfuelling and aberrant fuelling of mitochondria result in oxidative stress, which not only disrupts cellular homeostasis but can alter epigenetic expression, with intergenerational effects. If the recycling mechanisms of the cell are insufficient to clear metabolic products, apoptosis may result or expression of Damage-Associated Molecular Patterns (DAMPs) on the cell surface may occur, activating immunity and inflammation at a systemic level. Disrupted cellular signalling affects cells with different “professional” functions in different organs, and it is the mechanism which underlies the associations between chronic non-communicable diseases such as cancer, type 2 diabetes, cardiovascular disease, neurodegenerative disease, autoimmune diseases, and macular degeneration. Mitochondria are the controllers of energy production and are pivotal in cell signalling. Mitochondrial function governs health at cellular and organismal levels. This paper reviews the influence of nutrition on mitochondrial function, nutrient sensing, autophagy, insulin signalling, and apoptosis—the key pathways in cellular homeostasis. Full article

Graphene oxide (GO)–lipid hybrid nanostructures represent a promising class of multifunctional platforms for drug delivery and fluorescence-guided cellular imaging. In this study, we developed a graphene oxide-supported lipid bilayer system composed of rhodamine-labeled phosphatidylcholine (POPC-Rhod) for the delivery of the repurposed antispasmodic drug alverine citrate (ALV) to neuroblastoma cells. The hybrid nanostructures were assembled using two drug-loading strategies and characterized by UV–Vis spectroscopy, fluorescence analysis, dynamic light scattering, and atomic force microscopy to evaluate molecular interactions, vesicle size distribution, and nanomechanical properties. In vitro studies were performed using human neuroblastoma SH-SY5Y cells and their retinoic acid-differentiated neuronal-like counterparts. Confocal microscopy confirmed efficient cellular uptake of the fluorescent lipid–graphene hybrids, while viability and mitochondrial reactive oxygen species assays revealed differentiation-dependent cellular responses. ALV-loaded hybrids induced cytotoxic effects in proliferating neuroblastoma cells, whereas differentiated neuron-like cells exhibited greater tolerance and, at moderate concentrations, preserved viability despite increased oxidative stress. These findings demonstrate that graphene oxide–lipid hybrids can act as fluorescence-traceable drug delivery platforms and highlight the potential of alverine as a candidate for repurposing in neural cancer models. The system presented here provides a proof-of-concept framework for the development of multifunctional nanocarriers integrating therapeutic delivery with imaging capabilities. Full article