Search Results (19,977)

Ultraviolet A (UVA) radiation induces oxidative stress and mitochondrial dysfunction in dermal fibroblasts, contributing to photodamage and skin aging. This study investigated the protective effects of Yeast/rice fermentation filtrate (RFF) and sialic acid (SA), both individually and in combination, against UVA-induced damage in human dermal fibroblasts. Cell viability, reactive oxygen species (ROS) levels, intracellular ATP and NAD⁺ contents, and mitochondrial membrane potential (ΔΨm) were evaluated following treatment. RFF, SA, and their combination significantly improved cell viability in UVA-damaged fibroblasts and reduced ROS generation. Notably, the combined treatment increased intracellular ATP levels by 201.2% (p < 0.05), with enhancements of 62.3% and 285.4% compared to RFF and SA alone, respectively. Additionally, the combined treatment significantly restored NAD⁺ levels and effectively preserved mitochondrial membrane potential. Transcriptomic analysis revealed modulation of pathways related to cellular energy metabolism, particularly AMPK, and upregulation of SIRT1, SIRT3, and SIRT5 expression. The RFF–SA combination confers robust UVA photoprotection by enhancing mitochondrial resilience, providing a foundation for the development of protective cosmetic formulations. Full article

Environmental exposure to particulate matter, including PM_2.5 and engineered nanomaterials, is a major global health concern. Although acute toxic effects have been widely documented, new evidence suggests that the retained particle burden arising from incomplete clearance, tissue retention, and redistribution plays a key role in long-term health outcomes. This review synthesizes knowledge on particle accumulation at multiple biological levels. It examines how particles are retained in pulmonary and lymphoid tissues, their uptake by immune cells, and their sequestration within organelles, particularly the endo-lysosomal system. The mechanisms by which lysosomal dysfunction can cause mitochondrial stress, redox and metabolic disturbances, and impaired autophagy are also discussed. These disruptions can alter the status of immune cells and disturb immune homeostasis. This review also examines how immune perturbation from accumulation may contribute to chronic lung diseases. Understanding these mechanisms explains the persistent health effects associated with low-dose exposure and supports more effective risk assessment and prevention. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes. Full article

Background: Ecuador is a genetically diverse population setting shaped by long-term interactions among Native American, European, and African populations across distinct ecological regions. Although multiple studies have examined ancestry patterns in Ecuadorian populations, the available evidence remains fragmented and methodologically heterogeneous. Objective: To systematically identify, critically appraise, and synthesize published studies on genetic ancestry and population structure in Ecuador. Methods: A systematic review was conducted in accordance with PRISMA 2020. Searches were performed in PubMed/MEDLINE, Scopus, Web of Science Core Collection, SciELO, and Google Scholar through 31 January 2026. Eligible studies reported extractable ancestry-related data from Ecuadorian populations using autosomal, mitochondrial DNA, Y-chromosomal, or other ancestry-relevant genetic markers. Methodological quality was assessed using an adapted Joanna Briggs Institute framework. Owing to substantial heterogeneity across marker systems, sampling strategies, and ancestry inference methods, findings were synthesized qualitatively rather than by meta-analysis. Results: Of 1243 records identified, 12 studies met the inclusion criteria. Across marker systems, the evidence consistently supported a three-way admixture framework involving Native American, European, and African ancestry components, together with substantial regional and population-specific heterogeneity. Autosomal studies generally showed higher Native American ancestry in Highland and Native American populations, whereas African ancestry was more prominent in Afro-Ecuadorian and some Coastal populations. Uniparental markers further supported persistent sex-biased admixture, with predominant Native American maternal lineages and comparatively greater European or African paternal contributions depending on region and population history. Conclusions: Ecuadorian populations share a broad three-way admixture framework, but with marked internal heterogeneity across regions and population groups. These findings highlight the importance of geographic and demographic context in ancestry interpretation and the need for larger, more balanced, and methodologically standardized genomic studies in Ecuador. Full article

A549 cells are widely used as an in vitro model of alveolar type II (ATII) epithelial cells; however, their phenotype and metabolic state are highly sensitive to culture conditions, cell density, and the duration of static, non-passaged cultivation. Here, we examined how prolonged static culture affects lipid metabolism, mitochondrial bioenergetics, and viability in A549 cells. A549 cultures were maintained without passaging for up to 25 days in DMEM or Ham’s F-12 and analyzed using lipid secretion assays, targeted lipidomics, [¹⁴C]-acetate incorporation, Seahorse bioenergetic profiling, and transcriptional analysis of stress-associated markers. Several surfactant-associated readouts were highest during early culture, peaking on day 7, as evidenced by elevated expression of ABCA3 and SP-A and maximal secretion of surfactant-associated phospholipids. With prolonged cultivation and increasing culture density, cellular phosphatidylglycerol levels declined progressively and became nearly undetectable by day 25, accompanied by reduced anabolic lipid metabolism, lower oxygen consumption, and impaired glycolytic activity. These changes coincided with increased reactive oxygen species, elevated intracellular Ca²⁺ levels, and increased expression of stress-associated transcripts, including CASP1, IL1B, and C3. Later stages were also associated with reduced mitochondrial respiration and decreased viability. Collectively, our findings show that prolonged static culture is associated with metabolic remodeling and reduced bioenergetic capacity in A549 cells. Full article

Oxidation of RNA has gained interest from the community due, in part, to a link in the progression/development of disease as well as other biological processes such as apoptosis, ageing, hibernation, and signalling, amongst others. Different types of RNA with varying functions and size have been shown to be oxidized in vivo, including ribosomal RNA (rRNA), transfer RNA (tRNA), microRNA (miRNA), messenger RNA (mRNA), and mitochondrial RNA (mtRNA). This process occurs from reactions between reactive oxygen species (ROS) and all biopolymers, including RNA, from endogenous as well as exogenous sources. As a consequence, mechanisms that handle oxidized RNA are important, and enzymatic degradation is the most commonly studied process to date. This review focuses on the ribonucleases that have been shown to play a role in the degradation of oxidized RNA. While emphasis is placed on, arguably, the most common oxidatively generated chemical modification, 8-oxo-7,8-dihydroguanosine (8-oxoG), the products that arise from the oxidation of other canonical nucleosides as well as naturally occurring modifications are also discussed in the context of RNA oxidation. Processing of oxidized RNA via its enzymatic degradation is likely the main route, but a potential role of other proteins involved in the handling of oxidized RNA is hypothesized, e.g., helicases, export proteins, and extracellular environments. We postulate that this is an area with great potential for discovery. Full article

Armillaria species hold significant ecological and economic importance and they play a vital role in the growth of traditional Chinese medicine Gastrodia elata (G. elata). In this study, we assembled and compared the mitochondrial genomes (mitogenomes) of six Armillaria mellea (Vahl) P. Kumm. (A. mellea) strains isolated from the main G. elata-producing region of Hanzhong, China. The internal transcribed spacer (ITS) sequencing confirmed that all six strains form a monophyletic clade. Their mitogenomes (120,775 to 120,839 bp) exhibit a highly conserved architecture, each containing 16 protein-coding genes (PCGs), 23 open reading frames (ORFs), 27 tRNAs, and two rRNAs. Codon usage and amino acid frequency were strikingly similar among the six strains, with a strong AT bias. In contrast, comparisons with other Armillaria species revealed marked differences in gene order, repeat structures, and selection pressures. Phylogenetic analyses based on PCGs further resolved the close relationship among the six strains while highlighting distinct molecular variation across species. On the whole, these findings demonstrate that A. mellea strains co-evolving with G. elata maintain a highly uniform mitochondrial genome architecture, suggesting strong purifying selection or recent divergence within this symbiotic population. The pronounced differences from other Armillaria species at the levels of gene arrangement and selection pressure imply that mitochondrial gene rearrangement may have accompanied species diversification in the genus. By providing the first complete mitogenomes of A. mellea from a major G. elata cultivation area, this study not only expands the genomic resources for Armillaria but also establishes a foundation for understanding how mitochondrial variation might influence fungal growth, adaptation, and symbiotic efficiency with G. elata. Full article

The increasing prevalence of obesity and Alzheimer’s disease (AD) in the aging population underscores an urgent need to understand the common cellular and metabolic mechanisms they share. Accumulated evidence suggests that overlapping metabolic disturbances contribute to the pathogenesis of these two conditions. In this review, we highlight key underlying interconnecting metabolic pathways: (1) adipose-brain crosstalk mediated by adipokines and adipose tissue-derived extracellular vesicles that can modulate neuronal function and amyloid pathology, (2) dysregulated lipid metabolism affecting cholesterol, sphingolipids, and phospholipids and thereby promoting inflammation, amyloid precursor protein processing, and tau hyperphosphorylation, (3) impaired glycolysis and insulin resistance, which accelerate both obesity and neurodegenerative processes, (4) mitochondrial dysfunction marked by disrupted tricarboxylic acid cycle enzymes and electron transport chain complexes, leading to elevated reactive oxygen species and driving both obesity and AD pathology, and (5) gut microbiota dysbiosis, which can trigger inflammation as well as amyloid and tau aggregation. Together, these mechanisms show that metabolic alterations appear early, preceding clinical disease, and that understanding these underlying connections can provide strategies to protect metabolic health and prevent disease progression. Full article

Viral infections of grapevines reduce plantation productivity and planting material quality, necessitating the development of effective sanitization methods and comprehensive systems for monitoring plant physiological status. This study conducted a comprehensive analysis of the physiological–biochemical status of grapevine microplants (morphometric parameters, activity of key antioxidant enzymes, dehydrogenase activity, pigment composition, and relative copy number of mitochondrial and chloroplast DNA) in microclones of the rootstock Vitis riparia × Vitis berlandieri ‘Kober 5 BB’ in vitro, depending on the presence of viral infection and sanitization using thermo- and cryotherapy. Four plant variants were investigated: healthy (VIRUS FREE), infected (VIRUS), sanitized via thermotherapy (V.F.T.), and cryotherapy (V.F.K.). It was shown that, despite the absence of pronounced suppression of morphometric parameters, viral infection causes a significant increase in total protein content, catalase, polyphenol oxidase, and total dehydrogenase activity in tissues, as well as pigment imbalance (changes in the chlorophyll coefficient) and modulation of the carotenoid profile, along with alterations in the relative copy number of mitochondrial and chloroplast DNA. The relative copy number of mitochondrial and chloroplast DNA decreased in infected plants and was restored to a greater extent after cryotherapy rather than after thermotherapy. The results indicate the formation of stress-related changes (stress imprint) that persist in sanitized microclones and can serve as a multilevel marker system for assessing sanitization efficacy and monitoring the physiological status of grapevine microplants in vitro. Full article

Physical integration between endosymbiotic algae and host mitochondria is a recurring feature across photosynthetic symbioses, yet the structural nature of this association has remained unresolved. In the ciliate Paramecium bursaria, each endosymbiotic Chlorella cell is enclosed by a perialgal vacuole (PV) membrane consistently surrounded by host mitochondria, suggesting a conserved architecture for metabolic interaction. Although transmission electron microscopy has shown close membrane apposition, it has remained unclear whether this reflects incidental proximity or a reinforced adhesion. Here, we provide direct evidence that the PV membrane and host mitochondrial membrane form a stable physical association. Using discontinuous Percoll centrifugation, we isolated intact units in which Chlorella and mitochondria co-sedimented, indicating that their association withstands mechanical disruption. By fluorescently labeling the PV and mitochondrial membranes with BODIPY FL C₅-ceramide (BC₅C), together with a mitochondria-specific monoclonal antibody and DAPI, we visualized the PV membrane under light microscopy and demonstrated that the mitochondrial–PV membrane complex persists after homogenization and centrifugation. As expected from the membrane-insertion behavior of BC₅C, this fluorescent labeling revealed that the PV–mitochondrial membrane association is structurally reinforced rather than incidental, providing a mechanistic framework for understanding how Chlorella cells are stably positioned beneath the host cortex. Full article

This study aimed to investigate the ameliorative effects of glucuronolactone (GL) as a dietary additive on high-fat diet (HFD)-induced growth suppression and metabolic disorders in turbot. A 10-week feeding trial was conducted using juvenile turbot (16.7 ± 0.03 g). Two diets with different protein (%)/lipid (%) levels were formulated: PC (54/12) and NC (47/17). Based on the NC diet, three experimental diets were prepared by supplementing 200 (G200), 400 (G400), and 600 (G600) mg/kg of GL. The present results show that compared to the PC group, HFDs significantly inhibited the growth performance of turbot and induced severe metabolic disorders, hepatointestinal damage, and gut microbiota dysbiosis. Dietary GL supplementation effectively reversed these adverse effects. Specifically, compared to the NC group, GL supplementation significantly restored growth performance, enhanced non-specific immunity, and systematically improved metabolic health. In the liver, GL notably ameliorated tissue damage and downregulated key lipogenic genes (SREBP1, ACC, FAS, PPARγ), while upregulating genes involved in lipid oxidation and catabolism (PPARα1, CPT1, ACOX1, HSL, LPL) and lipid transport (ApoB100, MTP), thereby alleviating hepatic lipid deposition. Furthermore, GL activated the Nrf2/Keap1 antioxidant pathway, up-regulating the expression of genes such as SOD, CAT, GPX, and HO-1. It also suppressed the NF-κB-mediated inflammatory response (downregulation of IL-1β, IFN-γ and TNF-α2; upregulation of IL-10 and TGF-β2) and the mitochondrial apoptosis pathway (increased Bcl-2/Bax ratio; downregulation of Caspase3/7/9), collectively mitigating oxidative damage and cellular apoptosis. Moreover, GL restored intestinal morphology, enhanced the expression of tight junction proteins (Claudin-3, Claudin-7, ZO-1, Occludin) and MUC2, and inhibited MLCK signaling. These improvements led to a reduction in serum D-LA levels, indicating strengthened intestinal barrier function. Concurrently, GL reshaped the gut microbiota composition by enriching beneficial bacteria such as Akkermansia and suppressing potential pathogens like Listeria. In summary, GL effectively alleviated HFD-induced growth suppression and metabolic damage in turbot by improving lipid metabolism and alleviating hepatic injury, while concurrently restoring intestinal barrier integrity and microbiota homeostasis. Full article

Conventional therapies for rheumatoid arthritis (RA) are limited by poor selectivity, insufficient modulation of the oxidative inflammatory microenvironment, and systemic side effects. Oxidative stress and macrophage-driven immune dysregulation represent critical therapeutic targets. Cinnamaldehyde (CA) and arginine (Arg) possess antioxidant, anti-inflammatory, and anti-osteoclastogenic activities, but their poor solubility, instability, and lack of targeting restrict clinical application. Here, we report a pH-responsive cinnamaldehyde–arginine nanoprodrug (Arg-CA NPs), synthesized via Schiff base reaction, that spontaneously self-assembles into uniform nanoparticles capable of acid-triggered dual-drug release. Arg-CA NPs enhanced the solubility and stability of CA, exhibited excellent dispersibility and circulatory stability, and demonstrated intrinsic antioxidant and anti-inflammatory properties. Mechanistically, Arg-CA NPs attenuated intracellular ROS accumulation, preserved mitochondrial function, and reprogrammed macrophages toward an anti-inflammatory M2 phenotype by suppressing hypoxia-inducible factor-1α (HIF-1α), cyclooxygenase-2 (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. In an adjuvant-induced arthritis (AIA) rat model, Arg-CA NPs selectively accumulated in inflamed joints and significantly alleviated joint swelling, synovial inflammation, cartilage erosion, and bone destruction. These findings identify Arg-CA NPs as a promising redox-active nanoplatform for RA therapy by targeting oxidative stress and immune dysregulation. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is the most common chronic liver disease in the world. The disease progresses from steatosis to metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The modern concept of “multiple parallel hits” interprets disease progression as the result of the synergistic action of lipotoxicity, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, proinflammatory signals, and gut–liver axis dysfunction. Against the background of the limited translation of preclinical data from animal models due to interspecies differences, the importance of human-oriented in vitro platforms compatible with controlled design and high-throughput screening is increasing. The current review analyzes MASLD models based on the HepG2 cell line, systematizing steatosis induction protocols, evaluating the metabolic characteristics and limitations of this cell, and comparing 2D monocultures, 3D systems, and co-cultures. HepG2 has been shown to demonstrate a predictable steatogenic response to free fatty acids (FFAs) and is convenient for reproducing early stages of pathogenesis and primary pharmacological selection of compounds. At the same time, key limitations of the model are highlighted, namely tumor origin, glycolytic shift (Warburg effect), reduced β-oxidation, impaired very-low-density lipoprotein (VLDL) assembly and secretion, and sharply reduced cytochrome P450 (CYP450) activity, as well as limited reproducibility of fructose-induced de novo lipogenesis (DNL). Comparative analysis demonstrates an increase in physiological relevance with the transition from 2D to 3D and multicomponent co-cultures, accompanied by increased complexity and cost, but allowing for the modeling of inflammation and fibrogenesis. The review justifies approaches to selecting the appropriate platform based on the specific research task. Full article

Fetal alcohol spectrum disorders (FASD) encompass a continuum of developmental abnormalities caused by prenatal alcohol exposure, resulting in persistent neurodevelopmental and structural defects. Accumulating evidence indicates that redox dysregulation plays a central role in the pathogenesis of FASD. Ethanol disrupts cellular redox homeostasis by promoting excessive reactive oxygen species production and depleting endogenous antioxidants, thereby perturbing key redox-sensitive molecular networks. Dysregulation of these pathways leads to mitochondrial dysfunction, endoplasmic reticulum stress, lysosome dysfunction, and disrupted cellular processes, including proliferation, differentiation, and migration, while also promoting apoptosis and neuroinflammation, ultimately leading to the developmental abnormalities characteristic of FASD. Recent studies demonstrate that antioxidant supplementation or targeted modulation of redox-sensitive signaling can mitigate these deleterious effects in preclinical models. This review synthesizes current knowledge of the molecular networks underlying redox dysregulation in FASD and discusses emerging antioxidant and dietary interventions with therapeutic potential. Elucidating these mechanisms provides critical insight into the pathogenesis of FASD and may inform the development of effective strategies for the prevention and treatment of FASD. Full article

Elm (Ulmus pumila), an ecologically and economically valuable tree, exhibits significant tolerance to abiotic stress. However, the physiological and molecular mechanisms underlying its stress adaptabilities are largely unknown. Here, two elm salt-tolerant cultivars (ST-Y and ST-Q) and two salt-sensitive cultivars (SS-J and SS-JX) were identified in the 13 elm accessions collected from Shandong province, China via phenotypic salt tolerance screening. The key salt tolerance mechanisms were explored in ST-Y and SS-J via transcriptomic (RNA-Seq) assays, and subsequently validated in ST-Q and SS-JX via quantitative real-time polymerase chain reaction (RT-qPCR) analyses. Under salt treatment, ST-Y maintained leaf intactness and enhanced activation of antioxidant enzymes with a reduction in reactive oxygen species (ROS) accumulation, while SS-J suffered leaf defoliation and showed compromised antioxidant capacity with higher ROS levels. KEGG pathway analysis revealed that ST-Y leaves exhibited a unique enrichment of differentially expressed genes (DEGs) in the “oxidative phosphorylation (OXPHOS)” pathway after salt stress treatment. Both ST-Y and SS-J exhibited significant enrichment in the “metabolic pathway”, but the number of DEGs in the “arachidonic acid (AA) metabolism” pathway was much higher in ST-Y than in SS-J. Further RT-qPCR analysis verified the accuracy of the RNA-Seq data and revealed that genes related to the “OXPHOS” pathway were significantly up-regulated in ST-Y and ST-Q, but down-regulated in SS-J and SS-JX. Our results suggested that OXPHOS efficiency is critical to antioxidant capacity in elm salt tolerance, suggesting new avenues for forest tree improvement for climate change. Full article